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PROCEEDINGS
59. OG(ta)Ka
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OF THE
SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE
VOLUME VI
1908-1909
EDITED BY THE SECRETARY
NEW YORK
1909
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PRESS OF
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CONTENTS:
SCIENTIFIC PROCEEDINGS (30th—34th meetings) :
Communications of the thirtieth meeting, October 21, 1908
Communications of the thirty first meeting, December 16, 1908.
Communications of the thirty second meeting, February 17,
1909 . 5 ¢ é ‘ : : é 3
Communications of the thirty third meeting, April 21, 1009
Communications of the thirty fourth meeting, May 26, 1909
Recapitulation of the names of the authors and of the titles of the
communications : 3 :
EXECUTIVE PROCEEDINGS (30th—34th meetings)
REGISTER OF NAMES AND ADDRESSES OF THE MEMBERS
LIST OF OFFICERS :
CLASSIFIED LIST OF MEMBERS ‘
INDEX OF THE SCIENTIFIC PROCEEDINGS
(iii)
PaGE.
MOEUN TARTANA |
YAPVEIN SANIT AE 4g
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SCIEN MEIC PROCEEDINGS.
ABSTRACTS OF THE COMMUNICA'TIONS,
Thirtieth meeting.
College of Physicians and Surgeons, Columbia University.
October 21, 1908. President Lee in the char,
I (339)
Studies on the chemistry of anaphylaxis.
By H. GIDEON WELLS.
[From the Pathological Laboratory of the University of Chicago. |
Egg albumin, freed from the other proteins of egg white by
repeated crystallization, produces typically the anaphylaxis re-
action. It sensitizes in doses as small as one twenty-millionth of
a gram, fatally in doses of one millionth of a gram, The mini-
mum lethal dose for sensitized pigs is about one half a milligram
by intraperitoneal injection, and about one tenth to one twentieth
of a milligram when injected into the circulation, The unpurified
proteins of egg white are much less active, the minimum sensitiz-
ing dose being about one hundred times greater and the minimum
lethal dose being five times greater than with purified egg albumin.
This suggests that inhibiting substances are possibly present in
crude egg white.
The minuteness of the minimum sensitizing and intoxicating
dose of pure protein seems to indicate conclusively that both the
sensitizing and the intoxicating agent are one and the same kind
of protein molecule, or else two different constituents of the same
molecule.
Gelatin seems to be devoid of the power of participating in the
anaphylaxis reaction, either with itself or with other proteins,
This may be due to its poverty in aromatic radicals ; it probably
is not due to the heating that is necessary for the conversion of
collagen into gelatin. Addition of tyrosin to gelatin (without
(1)
iS)
SCIENTIFIC PROCEEDINGS (30),
chemical combination) does not modify gelatin in respect to the
anaphylaxis reaction.
Milk does not lose its sensitizing or intoxicating power when
heated to 100° for 30 minutes. If large enough doses of serum
heated to the same degree are used they will sensitize guinea pigs
to unheated serum. Coagulation with alcohol destroys or reduces
greatly the toxicity of proteins which it renders insoluble in water
(egg albumin) but not proteins that it does not render insoluble
(serum albumin).
Pure zein is actively and specifically toxic to guinea pigs sensi-
tized with zein, although it is devoid of tryptophane and lysine.
Gliadin, which contains a less quantity of aromatic radicals than
almost any other protein except gelatin, has but slight power to
intoxicate pigs previously injected with gliadin.
lodization of different specimens of serum by a constant method
did not yield constant results. The partially saturated serum
proteins suffered no modification in specificity analogous to that
found by Obermayer and Pick in the case of the precipitin re-
action, When most nearly saturated they may lose the power of
sensitizing’for the unaltered serum, but this is uncertain. Pure
crystallized egg albumin may be saturated with iodine quite
readily, the iodine saturating the unsaturated carbon atoms of the
benzene ring. Such iodized albumin retains its specificity un-
altered, but seems to lose much of its toxicity for sensitized guinea
pigs, nor does it sensitize well to egg albumin.
Tryptic digestion of serum furnishes further evidence of the
protein nature of the substances concerned in the anaphylaxis re-
action. Both sensitizing and intoxicating principles are attacked,
and slowly decrease in strength as the coagulable protein disap-
pears. After 59 days’ digestion of a sample of serum so that but
4.7 per cent, of the nitrogen was in a coagulable form, the sensi-
tizing dose had been changed from one one-thousandth of a cubic
centimeter to one fiftieth of a cubic centimeter, while 5 cubic centi-
meters intraperitoneally did not intoxicate pigs previously sensi-
tized to bovine serum. Digestion of serum does not affect its
specificity for species, but the digested serum sensitizes much
better to itself than to bovine serum, and conversely.
OBSERVATIONS ON THE CLINICAL ASPECTS OF HEMOLYSIS. 3
2 (340)
Further observations on the clinical aspects of hemolysis.
By GEORGE W. CRILE.
[From the Laboratory of the Private Ward Service of Lakeside
Flospital, Cleveland, O. |
All cases of tuberculosis showed reverse hemolysis, 7. ¢.,
normal serum hemolyzed the patient's corpuscles. In all cases
serum heated to 55° C. for ten minutes prevented hemolysis.
Sudden chilling of the blood according to the method of Hoover
and Stone caused a marked increase in the hemolytic action.
Plasma obtained by immediately centrifugalizing the serum caused
little or no hemolysis in hemolytic cases.
The hemolytic property reaches its. maximum about 24 hours
after the blood is drawn.
In the cancer group the cases in which the disease was entirely
removed lost their hemolytic property in from 12 to 21 days after
operation.
In cases in which an incomplete operation was performed the
hemolysins continued indefinitely.
Yotal number of cases studied 591.
Per cent.
NO NMA Sis opageencaewe, ssectonarsecers 211 iINoshentolyisissessreeteenss see fo)
yo cemicilinitine sa cecseseeneternses ese 70 7mbemoliysis wen eece asst Io
BenitonestinmonSerecties-sceisccessen see 55 INo®hemolysisynsscecceresece: fo)
Gane en Merc: see was assitan.ceasseloe satin 153 Tig OMbiemolySismemsaene cess 85
Post operative cancer cases with
climicalixeemmrenGe@sesesse-see sees as II Piehentolysiseaieessa= 4) sees 100
Post operative cases without clinical
recurrence 3 weeks to I5 years
BNF Gyo AWOI9n25, coco ocatooos6 soo0uE 37 INohemolysisierscscsn esctee fe)
MiubenculOsissemincesceceemesseecscs ses 52 48 hemolysis ., .......- fice 192
Our conclusion is that hemolysis occurs in a number of diseases.
It occurs in great frequency in cancer and tuberculosis. The re-
action in tuberculosis is the reverse of that of cancer. From the
clinical standpoint hemolysis offers additional evidence which may
be used in the diagnosis of cancer and tuberculosis. This evidence
is not as yet specific.
4 SCIENTIFIC PROCEEDINGS (30).
3 (341)
The behavior of alanin in metabolism.
By A. I. RINGER and GRAHAM LUSK.
[from the Physiological Laboratory of the University and Bellevue
Hospital Medical Collcge.|
Injection of 20 grams of z-alanin ina completely phlorhizinized
dog resulted in the elimination of ‘‘ extra sugar” in the urine to an
amount equalling 18.8 grams, or 93 per cent. of that theoretically
possible, Although z-alanin is almost completely convertible into
dextrose, preliminary respiration experiments indicate that it does
not spare fat metabolism as effectually as does dextrose itself.
This may be due to heat loss in the breaking down of alanin into
simpler molecules (formic aldehyde?) and heat absorption in its
construction into dextrose. A similar reasoning would serve to
explain Rubner’s “ specific dynamic action ”’ of protein.
4 (342)
An important source of error in Heller’s test for urinary
protein.
By WILLIAM WEINBERGER. (By invitation.)
[from the Laboratory of Biological Chemistry of Columbia Univer-
sity, at the College of Physicians and Surgeons. |
Heller’s test for urinary protein is a fairly reliable one if care
is taken in its application, but several urinary protein constituents
give uncertain results with it. Thus, mucin fails to yield true pre-
cipitation — the ‘‘ ring” is more or less opalescent and disappears
on mixing. With nucleoalbumin the ring is not quite typical and
is indistinct in undiluted urine. On the other hand various mis-
leading factors, such as resinous acids, must be taken into account.
Resinous acids may be ignored, however, if such products as
Balsamum Copaive, or Santal Oil, have not been administered,
or if the specific HCl test for resinous acids shows their absence.
The turbidity formed with resinous acids dissolves on warming.
The acids themselves may be removed by extraction with ether.
In concentrated urine, as is well known, a uric acid ring may ap-
pear just above the line of junction of the urine and acid, and urea
IMPORTANT SOURCE OF ERROR IN HELLER’S TEST. 5
may be precipitated in the form of glittering nitrate crystals; but
dilution of the urine prevents these effects.
In the course of our investigation of another problem, an ad-
ditional source of error has been found in urines preserved with
thymol in any of the usual ways. If Heller’s test is applied to
such urine after filtration, a ring will invariably appear even in the
absence of protein. The ring is most marked, all other things
being equal, in urines that have been treated with a solution of
thymol, although it is very conspicuous in urines that have been
preserved with powdered thymol.
The characteristics of this ring may be briefly stated as fol-
lows: A few seconds after the urine has been carefully poured
upon the acid, there forms, precisely on the line of junction, a
grayish white ring about 0.5 mm. high, resembling the albumin
ring given by a faint trace of albumin, and gradually becoming
more and more distinct, until, in some urines under conditions to
be mentioned later, it presents the appearance of a heavy thick
precipitate, the height of which increases continuously and renders
the lower portion of the urine completely opaque. At this stage
the color is somewhat different from that of a protein ring, in that
it is more yellowish. Below the ring there is a greenish zone ex-
tending somewhat into the acid; above it, a reddish zone smaller
than the former and more contracted. The white ring is seen
best in daylight reflected from a dark background, the color rings
are seen best if the test-tube is held against a white surface.
On slightly disturbing the layers of urine and acid the ring, if
a delicate one, disappears but reappears immediately. These ef-
fects can be obtained a few times in the same mixture. <A heavy
ring, however, will not completely disappear on slightly shaking
but will gradually widen and extend into the upper urinary layer ;
and it depends on the volume-relation between urine and acid
whether complete mixing will remove the precipitate. On thor-
oughly shaking an excess of acid with little urine, a clear yellow
solution results. If an excess of urine has been used, the mixture
will not clear, but will remain turbid. Warming the mixture
will not prevent the formation of this ring, nor will it clear the
liquid, but, if anything, will make the reaction more distinct ; nor
has dilution of the urine with three to four times its volume of water
any marked effect.
6 SCIENTIFIC PROCEEDINGS (30).
This reaction is caused by the fact that thymol dissolves in
urine when the latter is treated with it even in solid form, and it is
noteworthy that more thymol is dissolved if the urine is neutral
or alkaline, than when acid. Accordingly, an alkaline thymolized
urine will give Heller’s test more pronouncedly than a strongly
acid one. But while the thick and heavy ring in the first case will
have an appearance somewhat different from the protein ring and
thus will hardly mislead one, the delicate thymol ring in the acid
urine closely resembles a protein ring and is therefore more apt to
cause confusion.
In urine containing both albumin and thymol in various amounts
each ring may be discerned. The albumin ring is somewhat the
wider of the two (about 2-3 mm.), and is whitish; whereas the
thymol ring forms directly underneath and is grayer and thinner.
The albumin ring may be completely covered by the thick thy-
mol ring, so that the detection of protein may be seriously inter-
fered with.
Further investigation proved that this ring is first formed by
the precipitation of thymol by the concentrated acid. At this
stage it closely resembles the albumin ring. Nitration of the thy-
mol soon occurs, resulting in the formation of nitroso- and pos-
sibly nitro-thymol. This accounts for the gradual color-change
from white to yellowish white, which the precipitate undergoes.
A partially successful attempt has been made to isolate the nitro-
substance or substances produced. With the aid of chloroform
as the solvent, crystals of a yellowish brown color were obtained
that gave Liebermann’s nitroso reaction. These crystals melt at a
temperature slightly above 50° C., whereas nitroso-thymol melts at
160°C. Thymol melts at 50°. It is quite probable, therefore,
that very incomplete nitration occurred and that the brown crys-
talline product referred to was a mixture of thymol and a small
amount of nitroso-thymol. Besides, some chloroform may have
been occludedin the crystals. Work in this direction is proceeding.
To guard against this source of error, Heller’s test cannot be
directly applied to urine preserved with thymol. The latter must
first be removed by extraction. Petroleum ether is very suitable
for this purpose. Gentle agitation of the urine with an equal vol-
ume of petroleum ether in a test-tube for 2 minutes suffices to re-
move all traces of thymol.
IMPORTANT SOURCE OF ERROR IN HELLER’S TEST. 7
When 5 grams of thymol were administered per os to a medium
sized dog, the urine excreted during the succeeding 24 hours
showed the familiar brownish yellow color. On standing it grad-
ually became black. Heller’s test was positive but, as the result-
ant precipitate had the same color as the urine, the exact signifi-
cance of the result was uncertain. Thereupon different metabolic
derivatives of thymol — thymo-sulfuric, thymo-hydrochinon sul-
furic and thymo-glucuronic acids were isolated from the urine in
the form of their chlorin substitution products. A small quantity
of each of these substances was then individually added to xormal
urine, which in turn was subjected to Heller’s test and invariably
showed a positive reaction.
Agitation of such treated urine with petroleum ether in the
manner above indicated did ot extract thymol-glycuronic acid.
This fact is of some importance; for while petroleum ether readily
extracts thymol from urine to which thymol has been added as a
preservative, it does not quantitatively extract from urine thymol
that has been given internally and which is excreted in combined
forms through the kidneys.
5 (343)
A clamp for direct transfusion of blood.
A demonstration.
By ISAAC LEVIN.
[From the Department of Pathology of Columbia University, at the
College of Physicians and Surgeons. |
The clamp is similar in its construction to an artery forceps
without the grooves. At the tip of each blade there is attached a
small cannula with a smooth bore. At the inner edge of each can-
nula four small pin points are attached, and on the outer surface of
the cannula four grooves are cut. When the clamp is closed, the
pins of one cannula lie in the grooves of the other. The pins are
bent outward and therefore the cannulas have a pyramidal form,
so that each pin can lie snugly in its groove. At the beginning
of the operation, both halves of the clamp are separated. The
vein is pushed through one cannula and its wall is hooked on the
pins. The same is done with the artery and the other half of the
8 SCIENTIFIC PROCEEDINGS (30).
clamp. Then both halves of the clamp are united and clamped.
I believe that when we deal with small blood vessels it is easier to
hook the walls on the pins than to turn them back like a cuff as
is done in Crile’s cannula. When the clamp is closed, both blood
vessels are connected with the endothelial surfaces.
I have performed several operations on dogs, uniting the
femoral or cervical vein of one dog to the femoral artery of an-
other. The transfusion was kept up for over half an hour, until
the donor was practically exsanguinated. There was no clotting,
leakage, or any other defect in the clamp.
6 (344)
The further separation of antitoxin from its associated proteins
in horse serum.
By EDWIN J. BANZHAF.
[from the Research Latoratory of the Department of Health, New
York City. |
The literature concerning means of purification of anti-bodies
and their chemical characteristics has been thoroughly reviewed
by Gibson,’ Ledingham,? Banzhaf and Gibson,* and Brieger and
Kraus.*
Stark ° was the first to report that by heating for one hour at
56° C., ovalbumin could be converted into a body, which, because
of its precipitation and solution reactions, and also its composi-
tion, was obviously a globulin. Later Noll® showed the same to
be true of albumin in rabbit, dog and horse serum.
My experiments were to ascertain the resulting conditions after
heating antitoxic horse serum, citrated plasma, and Gibson’s con-
centrated and partially purified antitoxic globulin solution.
An antitoxic serum by the Gibson method" gave the following :
An elimination of 23 per cent. protein and an increase of antitoxic
units per gram protein of 30 per cent. over the native serum. A
1 Journal of Biolog. Chem., 1, p. 161, 1906.
2 Journal of Hyg., vii, p. 65, 1907.
8 Journal of Biolog. Chem., iii, p. 253, 1907.
4 Berl. klin. Woch., xliv, p. 946, 1907.
5 Zeitschr. f. Biol., xl, p. 494, 1900 (new series, vol. 22).
6 Hofmeister’s Beitrage, iv, p. 563, 1904.
SEPARATION OF ANTITOXIN FROM ITS ASSOCIATED PROTEINS. 9
series of the same antitoxic serum was heated for from 6 to 72
hours in closed containers, at a temperature of 57°C. After cool-
ing to room temperature, the series was saturated with sodium
chloride and brought up to a dilution of 1:10 with saturated
sodium chloride solution. Twelve hours later the resulting pre-
cipitations were filtered off. Potency tests on these filtrates showed
a loss of 5 per cent. after heating 6 hours and an increasing loss
up to 22 per cent. after heating 72 hours. The protein converted
into an insoluble condition (in saturated sodium chloride solution)
was 30 per cent. for the 6-hour period, increasing up to 48 per
cent. for the 72-hour period. The increase of antitoxic units, per
gram protein, was 35 per cent. after 6 hours heating, increasing
up to 53 per cent. after 48 hours.
Owing to the larger per cent. destruction of antitoxin at the 72-
hour heating than the per cent. increase on conversion, the potency
per gram protein dropped to 52 per cent. increase over the native
serum. On separating the remaining unconverted albumin from
this series, the increase of antitoxic units, per gram protein, was
60 per cent. after 6 hours heating, increasing to 78 per cent.
after 48 hours. The 72-hour heating showed an increase of 73
per cent. over the native serum.
Citrated plasma under the same conditions gave practically the
same results. Gibson’s antitoxic globulin solution (blood alka-
linity) containing only that globulin soluble in saturated sodium
chloride solution was heated under the same conditions. The
potency loss was 5 per cent. for the 6-hour period, and an increas-
ing loss up to 23 per cent. for the 72-hour period. The soluble
globulin converted into an insoluble condition (in saturated sodium
chloride solution) was 30 per cent. after 6 hours’ heating, in-
creasing to 47 per cent. after 72 hours. The increase of anti-
toxic units, per gram of protein, was 37 per cent. after 6 hours’ heat-
ing, increasing to 54 per cent. for the 24 hours. Here again
the 72-hour heating period caused a larger per cent. destruction
of antitoxin than per cent. globulin converted into an insoluble
condition (in saturated sodium chloride solution), dropping to an in-
crease of 46 per cent., per gram protein, over Gibson’s antitoxin
globulin solution. This work which is being carried out further is
practically and scientifically important, and may throw some light
on the chemical characteristics and the nature of antitoxins.
fe) SCIENTIFIC PROCEEDINGS (30).
7 (345)
Multiple tumors in mice.
By J. W. JOBLING.
[from the Rockefeller Institute tor Medical Research. |
During about two years we have obtained twenty-six mice with
spontaneously developed tumors. Of the twenty-six mice, five
showed two or more tumors of different types.
In two, the superficial and larger tumor of the two was situated
on the chest wall; they were spindle cell sarcoma.
In one, in addition to the sarcoma, both ovaries were much en-
larged by papillary cyst-adenomata. The other mouse with the
sarcoma showed a 3 mm. wedge-shaped mass in the left lung
which was not a metastasis, but a papillary cyst-adenoma.
In three other mice, the large superficial tumors were adeno-
carcinoma and the primary lung tumors, cyst-adenomata. It might
be supposed that the lung tumors were metastases, but a study of
sections showed great differences between the superficial and lung
growths. Metatases show, as a rule, many mitotic figures, while
the tumor of the lung, regarded as primary, show karyokinesis ex-
ceptionally. Next, the type of cell in the matastases corresponds
with that of the primary tumor, besides which the cells are usually
packed so closely that the cell outlines are lost, while other differ-
ences in protoplasm and nuclei occur. Again, there is little stroma
in metastases, unless acini are present, in which case they are easily
distinguished, while in the primary papillary growths there is a
definite supporting framework. And finally, metastases tend to be
invasive, while primary growths do not. The last statement is
based on the point noticed that in every instance the primary
growth projected from the surface and there was atelectasis of the
surrounding tissue, while in metastasic nodules the growth can
usually be seen extending into the alveoli without compressing the
lung, or else it is confined to blood vessels. These primary lung
tumors correspond very closely with those described by Tyzzer.
On PLASTEIN. iat
8 (346)
On plastein.
By D. D. VAN SLYKE and P. A. LEVENE.
[From the Rockefeller Institute for Medical Research. |
“ Plastein ’” is the name usually applied to the protein-like sub-
stance or substances precipitated from concentrated albumose
solutions by the action of enzymes. Of those who have investi-
~ gated the nature of plasteins, some have agreed that they are
resynthesized proteins, resulting from the reversibility of the hy-
drolytic reaction ; others view them merely as albumoses separating
from the concentrated solutions because of a lack of proper condi-
tions to maintain solubility ; while still others regard them as the
insoluble simple products of further digestion of the albumoses.
Because, probably, of the small yields in which plasteins are
obtained, no investigator has hitherto performed a systematic esti-
mation of the hydrolytic products, although such estimations fur-
nish at present our most significant data concerning the nature of
proteins. We have hydrolyzed 130 g. of plastein obtained by the
action of pepsin upon Witte peptone. For comparison we tabulate
with our results those obtained by Brunner in Fischer’s laboratory
from fibrin, the mother protein of the plastein.
From 100 g. plastein
From 100 g. fibrin ( Brunner )
AD YROSIN Cb ce wasieccieeseceste sacs 3.03 B25
Givicocolliivarcdccseseserccrsrs 0.50 2.2
Alanine sccccetene ceasceaeen ? 3.1
WONG \ hes eae 15.59 Bresent
Leucine 13.0
Phenylalanine esse eccesss 1.20 eZ
Glutaminic acid............ 10.02 6.8
Aspartic acid..............- 2atis 4)
IBroline?secsestavceccccorscstes 2.55 2.4
ELIStIGING se.cs0 0) sesesccs ers 0.43 Not determined
ASOININ Ghssastecanecescsasete 2.06 <e
WeySINC}.cussesecesn ccvensss cs 1.42 “6
Tryptophane............... Present Present
Total determined.......... 38.95 33-5
Of the thirteen amino-acids tested for in plastein the presence
was proved of all except alanine, which was not isolated in pure
12 SCIENTIFIC PROCEEDINGS (30).
condition. The proportions otherwise were not greatly different
from those found in fibrin. It is evident that the plastein ranks
with either the complex native proteins or their higher decompo-
sition products.
In order to obtain evidence indicating with which of the above
classes the plastein is to be ranked, viscosity measurements were
employed. It has been shown that digestion of a protein solu-
tion is accompanied by a rapid decrease in viscosity. Conse-
quently it appears that, under similar conditions, even its primary
decomposition products form markedly less viscous solutions than
the mother protein.
On comparison of equally concentrated solutions of plastein
and fibrin in normal NaOH (400 mg. of dry substance to 10 c.c.
solvent), it was found that the plastein solution showed much the
lower viscosity. The fibrin was gradually hydrolyzed by the
alkali, however, and the viscosity of its solution fell finally even
below that of the plastein, which had changed but little.
For further comparison, viscosity measurements were per-
formed upon similar solutions of hetero-albumose, and of the
proteins casein, gliadin, glutein and edestine. The hetero-albu-
mose gave a solution of viscosity similar to that of the plastein,
while the native proteins all showed, like fibrin, markedly higher
viscosities, and also less stability in the presence of alkali.
These results indicate that the plastein is related to the higher
albumoses, and apparently, from its resistance to alkali, to the
anti-albumoses rather than to the native proteins.
For the determinations, the proteins were dissolved by shaking
on a machine at room temperature. All solutions were clear ex-
cept that of glutein, which was cloudy. The viscosity of each
was determined as soon as solution became complete, and the
determination repeated at intervals. The time intervals were not
regular, but figures for roughly comparable intervals are tabulated
on the same line. The figures under “ Hrs.” indicate the time in
hours between the mixing of substance and alkali, and the vis-
cosity determination opposite. The viscosity figures indicate the
rate of flow of the solutions through an Ostwald viscosimeter at
23° +0.1°, the rate of flow of water at the same temperature be-
ing taken as 100.
On PLASTEIN. 13
VISCOSITY OF SOLUTIONS OF PLASTEIN AND HETERO-ALBUMOSE,
Plastein Hetero-albumose
Hrs. Viscosity Hrs. Viscosity
% 160.7 y% 166.7
2% 156.5 134 161.6
8 156.0 8 154.8
20 156.3 18 150.7
Sot et 30 146.9
—- — 42 146.8
52 156.1
VISCOSITY OF VARIOUS PROTEIN SOLUTIONS.
Fibrin Casein Gliadin Glutein Edestin
Hrs. Viscosity Hrs. Viscosity Hrs. Viscosity Hrs. Viscosity Hrs. Viscosity
YK =-266.8 —
a —_ S—— —— —— 2 175.9
4 223.1 5 178.0 —_>= —- 3 169.1
8% 179.2 ——- — 8% 181.4 9 247.8 10% 153.0
23 158.3 18 LOZs3i ze! LOSs Tee 20 220nl Zo 146.3
54 151.3 52 154.6 47 DSS Sti eS TAS AT
The viscosity determinations were made at the Laboratory of the U. S. Fish
Commission, Woods Holl, Mass.
9 (347)
The action of bile and some of its constituents upon intestinal
peristalsis and the circulation.
By ISAAC OTT and JOHN C. SCOTT.
[From the Laboratory of the Medico-Chirurgical College of
Philadelphia. |
In their experiments with a Vella fistula, Fubini and Luzzati
found that a pea, fastened to a thread, passed along the bowel
more quickly when ten to fifteen minutes previously they had in-
jected two grams of bile. C. Eckhard,’ of Giessen, also studied
the influence of the bile upon the peristaltic movement of the
small intestine.
Eckhard experimented upon rabbits. He used a sodium chloride
bath and studied the movements of the intestine 27 seta after opening
the abdomen. After the injection into the duodenum of one cubic
centimeter of bile of the rabbit the duodenum remained for ten
minutes in absolute rest. He injected three c.c. of bile of rabbit,
calf and sheep in different parts of the small intestine with the
1 Eckhard: Centralblatt fiir Physiologie, 1889, p. 49.
14 SCIENTIFIC PROCEEDINGS (30).
same result, the intestine remaining quiet fifteen to twenty minutes.
If, however, the intestine remained for some time in the salt
solution, it became more:sensitive to the irritant. With the injec-
tion of large quantities of bile there was more frequently than before
little wave-like movements, although Eckhard does not feel sure
that this was the result of the bile injected.
Drs. Hallion and Netter’ have studied the influence of bile on
the peristalsis of the intestine. They operated on dogs curarized
or narcotized by chloralose or by morphine and chloral. By a
small button hole in the small (mainly in the duodenum) intestine
they introduced a balloon which was connected with a water
manometer by means of rubber tubing. The balloon was flexible
rubber and mounted upon a metal tube perforated by a large
number of lateral openings, which prevented bends of the balloon
upon itself. The water manometer was connected with a Marey
tambour which inscribed the movements. After the balloon was
inserted the abdomen was closed by a suture and the movements
registered for more than an hour, so that subsequent curves pro-
duced by the bile could be closely compared. The bile was
injected either into the blood or into the intestine. Ox bile was
used, concentrated by desiccation at a low temperature, but sub-
sequently when used diluted to its original volume by water.
Then 10 c.c. of bile was injected into the rectum. At the end of
four minutes repeated movements of defecation ensued, followed
by an irregular rhythm for eight minutes. The intravenous
injection of bile (3-7 c.c.) was by the saphenous vein. There was
produced a marked diminution of peristalsis and a relaxation of
tonus in the smellintestine. Immediately afterwards the contrac-
tions and the tonus considerably increased. Bile put in contact
with the intestinal mucous membrane exercises a local excito-motor
effect upon the small intestine. Intravenously it produces the
same effect, a result that is due, in part at least, to an augmented
secretion of bile by the liver, induced by the cholagogue influ-
ences of the injected bile.
Dr. Albert Schiipbach,? working in the Hallerianum under
Professor Asher, has studied the effect of bile on the movements of
1 Hallion and Netter; Comptes Rendus de Biologie, 1907, pp. 182 and 254.
2 Schiipbach : Zeztschrift fiir Biologie, xxx, pp. I-41.
AcTION OF BILE AND SOME OF ITS CONSTITUENTS. 15
the small intestine. Dr. Schiipbach made experiments witha Vella
fistula in two dogs; also upon the rabbit’s large intestine in situ,
and by the Magnus method with the isolated intestine of the cat
and also upon the rectum in dogs.
In the dogs with Vella fistula he made experiments with a ball
of sealing wax, with a thread attached to a little weight. The bile
was injected into the intestine. He also found that psychic irrita-
tions by holding ham near the nose of the animal excited increased
peristalsis. When the bile was injected he noted how fast the ball
moved in the intestine. The bile was mixed with physiological
salt solution, or with milk, or with water. He also used the Mag-
nus method of excised intestine.
He concludes that bile in the dog either has no special influence
upon the small intestine in normal conditions or in many of the
cases has an inhibitory effect. In the case of the implantation of
the gall bladder into a Vella fistula, the gall of the dog had no
special effect upon the peristalsis of the small intestine. In a state
of hunger and at different hours after taking nourishment, the ac-
tion of the bile was indifferent or a weak inhibition of peristalsis
ensued.
In rabbits under ether and morphine, with the small intestine 27
situ, the bile acted in an inhibitory manner. The excised cat’s in-
testine was inhibited by bile. The large intestine of the rabbit zz
situ had its peristalsis increased by bile. When through an injec-
tion of gall the large intestine had increased peristalsis, the small
intestine remained quiet. Bile injected into the rectum of the dog
called out defecation.
Our experiments were made upon etherized rabbits and cats.
They were thirty-eight in number. We used two methods in the
study of intestinal peristalsis. The first one was that of Magnus
on the excised intestine in a modified Ringer solution with oxygen
bubbling through it. The other was the insertion of a rubber
balloon into about the middle of the jejunum in the small intestine
and in the ascending colon of the large intestine. This was con-
nected with the delicate piston recorder of Dr. Schlayer, of Tibin-
gen. The bile used was that of cats and of rabbits.
Effect of bile on small intestine. — With the method of Magnus
small and large doses locally applied decreased peristalsis. In one
16 SCIENTIFIC PROCEEDINGS (30).
case, a cat, there was with one eighth of a drop an increase of tonus
and a slight augmentation of peristalsis. In the balloon method,
bile given per jugular or injected into the lumen of the intestinal
part experimented upon decreased peristalsis. In the rabbit, with
one eighth of a drop by the Magnus method a temporary, well
marked inhibition of peristalsis was seen with a decrease of extent
of peristalsis. In a cat by the balloon method, one half a drop
per jugular increased peristalsis. In a rabbit, one quarter of a
drop by the jugular produced an increased peristalsis with the
balloon method.
Effect of bile on the large intestine. — The effect of bile on the
large intestine by the Magnus method was to decrease tonus and
peristalsis of the intestine. In rabbits there was occasionally,
after a =; to a 34, of a drop of bile by the Magnus method, greatly
increased peristalsis. In the balloon method, bile in the cat per
jugular in doses of a drop, decreased tonus and peristalsis at first,
and afterwards greatly increased them.
Effect of glycocholic acid upon the small intestine. —In the cat,
by the balloon method, three quarters of a grain of glycocholic
acid per jugular increased the tonus and the extent of the per-
istaltic movements. In other cats, one half grain of glycocholic
acid decreased peristalsis, using the balloon method and injecting
the acid per jugular.
In the rabbit, 3 of a grain of glycocholic acid by the Magnus
method greatly decreased the tonus and peristalsis.
Effect of glycochole acid upon the large intestine. —In the
rabbit, glycocholic acid by the balloon method in one half grain
doses per jugular decreased peristalsis. In a rabbit and a cat it
increased peristalsis producing quite large waves.
Effect of taurocholic acid on the small intestine. —In the cat,
one half grain of taurocholic acid greatly increased peristalsis by
the Magnus method. In the rabbit there was a momentary in-
crease of tonus by the Magnus method.
In the rabbit, with =, to } grain of taurocholic acid there was
with the Magnus method a great decrease of tonus and peris-
talsis.
In the balloon method, } of a grain of taurocholic acid per
jugular in the cat increased peristalsis after a temporary decrease.
17
ACTION OF BILE AND SOME OF ITS CONSTITUENTS.
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18 SCIENTIFIC PROCEEDINGS (30).
Liffect of taurocholic acid on the large intestine.—By the Magnus
method, 3 grain of taurocholic acid decreased peristalsis and the
tonus of the large intestine. In the rabbit, } to } grain of tauro-
cholic acid by the Magnus method greatly decreased the tonus
and peristalsis.
There is no doubt that either with the excised intestine or with
the balloon method, where the nerves of the intestine are attached,
that bile from 3', of a drop up to 4 c.c. primarily inhibits peri-
talsis and afterwards may or may not increase peristalsis. The
taurocholic and glycocholic acids have the same action as the bile
itself. The experiments upon the pulse-rate and arterial tension
show that bile after a few doses reduces the tension and the heart
beat. Taurocholic acid reduces the heart beat and the blood pres-
sure. Glycocholic acid reduces the blood pressure, but did not
materially alter the pulse-rate.
From an examination of our results it is apparent that bile has
contradictory effects upon the small and large intestine. It is
evident that with either the Magnus method or the balloon
method results are antagonistic. Dr. Schtipbach believes that
this may in part be explained by a psychic reaction on the intes-
tine in his experiments. It will not, however, explain the con-
tradictory effect in the case of the excised intestine. In 1884,
in a paper on intestinal peristalsis, Ott called the ganglia in the
intestine intestino-motor and intestino-inhibitory. It is probable
that these ganglia have a varying antagonistic effect, and as one or
the other is in the ascendant we have an increase or a decrease of
peristalsis by the bile. It is evident that the circulatory changes
did not have any part in the changes in intestinal persitalsis.
10 (348)
The uric acid excretion of normal men.
By PAUL J. HANZLIK and P. B. HAWK.
[from the Laboratory of Physiological Chemistry of the Department
of Animal Husbandry of the University of Illinois. |
The purpose of the investigation was to observe the course of
the excretion of uric acid in normal men living on an ordinary
mixed diet. Each subject was allowed to select his own diet and
THE Uric Acip Excrerion oF Norma MEn, 19
then was required to ingest the diet selected during the course of
six periods of four days each. Ten university students served as
subjects. Quarters were provided where the men could easily be
observed as to certain regulations of sleep and diet. The body
weights of the subjects ranged from 53.1 kg. to 76.7 kg. and
their ages varied from 19 to 29 years. There were no athletes
among the subjects so that no individual took excessive or violent
exercise, but all lived the life of the average, normal university
student. The Folin-Shaffer method for the determination of uric
acid was employed.
CONCLUSIONS.
1. The average daily excretion of uric acid for ten men rang-
ing in age from 1g to 29 years, and fed a normal mixed diet, was
0.597 gram, a value somewhat lower than the generally accepted
average of 0.7 gram for such a period.
2. The average daily protein ingestion for these same subjects,
when permitted to select their diet, was 91.2 grams or 1.33 gram
per kilogram of body weight.
TI (349)
Hemolysins in the sera of carcinoma and syphilis.
By 8. PESKIND. (By invitation.)
[From Dr. Peskind’s Private Laboratory, Cleveland, Oho. |
A few years ago the writer commenced a research, the object
of which was to determine in what diseases hemolysins commonly
occurred and whether or not they were specific for these diseases.
The ultimate purpose was to obtain data that one could use in
diagnosis.
A preliminary report was published.'. The work had to be
abandoned shortly thereafter. Since then, other investigators —
notably Kelling — have taken up the study of hemolysins in con-
nection with their use in diagnosis.
It occurred to the writer that it would be very desirable to
determine the question as to the specific nature of the hemolysins
found in various diseases. With this object in view, a study of
1 Peskind: American Medicine, 1903, v, p. 918.
20 SCIENTIFIC PROCEEDINGS (30).
the serum in several diseases has been undertaken. In this brief
report are given the results obtained in carcinoma and syphilis.
The sera and corpuscles of 12 cases of carcinoma and 7 cases
of tertiary syphilis were examined. In Io other cases of tertiary
syphilis, the corpuscles alone were examined.
The experiments were planned in groups. In each group, the
corpuscles of at least one normal person, and several cases of
syphilis and carcinoma were exposed to the action of sera derived
from syphilitic and carcinomatous patients.
The customary technic was employed, special care being taken
to use only fresh specimens of blood. Equal parts of serum and
of a one per cent. saline suspension of corpuscles (washed four
times) were incubated at 37° C. for one or two hours, sedimented
on ice over night, and compared with control tubes of the serum.
In all 290 serum-corpuscle combinations were made.
In this way were studied the actions of syphilitic and carcino-
matous sera on their own corpuscles, on normal corpuscles, and
on the corpuscles of other cases of syphilis and carcinoma.
The following results were obtained :
SUMMARY OF RESULTS.
Out of the 12 cases of carcinoma, 4 showed the presence of
hemolysins in their sera, which caused laking of the erythrocytes
derived from normal human individuals.
Out of the 7 cases of tertiary syphilis whose sera were ex-
amined, 6 showed the presence of hemolysins which dissolved the
corpuscles of normal persons.
The corpuscles showed the following behavior :
The corpuscles belonging to a hemolytic carcinomatous blood
were found to be immune to the action of the hemolysins in its
own serum or any other carcinomatous serum.
The corpuscles belonging to a non-hemolytic carcinomatous
blood were readily laked by a hemolytic carcinomatous serum.
Similarly the corpuscles of a hemolytic luetic blood were
found to be immune to the action of its own serum or any other
syphilitic serum.
The corpuscles of a syphilitic blood, whose serum did not
contain hemolysins were laked by any hemolytic syphilitic serum.
HEMOLYSINS IN THE SERA OF CARCINOMA AND SYPHILIS. 21
In every instance, it was found that the corpuscles belonging
to a hemolytic carcinomatous blood were immune to the action
of the hemolysins found in syphilitic serum. Conversely, the
corpuscles present in a hemolytic syphilitic blood were immune
to the action of the hemolysin present in carcinomatous serum.
However, the corpuscles of a non-hemolytic carcinomatous
blood were readily laked by hemolytic syphilitic serum and simi-
larily the corpuscles of a non-hemolytic syphilitic blood were laked
by a hemolytic carcinomatous serum.
Judging from the behavior of the sera towards the corpuscles
derived from various normal and diseased persons, one could not
distinguish a hemolytic syphilitic serum from a hemolytic carcino-
matous serum.
This would suggest that the hemolysin found in syphilitic serum
is identical with one found in carcinomatous serum.
It would seem, from the above results, that there is some con-
nection between the presence of a hemolysin in the blood and the
immunity of the corpuscles contained in that blood.
The corpuscles found in hemolytic bloods —whether from
cases of carcinoma or syphilis — are immune to the action of the
hemolysins in those sera. The corpuscles of non-hemolytic bloods
are vulnerable and are readily laked by the hemolysins contained
in either carcinomatous or syphilitic sera.
The reverse proposition could be argued from the results of
the above experiments. That is, if the corpuscles of a given blood
are immune to the action of a hemolytic serum, then the blood in
question contains a hemolysin. If the corpuscles are laked by a
hemolytic serum, then the blood in question does not contain hem-
olysin.
The corpuscles of 10 other cases of tertiary lues (whose serum
was not obtained) were tested against the hemolysins in carcino-
matous and syphilitic sera.
The corpuscles of 3 of these cases were easily laked by hem-
olytic sera derived from carcinomatous or syphilitic persons.
The corpuscles of the other 7 cases were found to be immune
to the action of the hemolysins.
It is reasonable to suppose that the 3 bloods with the vulner-
able corpuscles did not contain hemolysins, while the 7 bloods
containing immune or resisting corpuscles did contain hemolysins.
22 SCIENTIFIC PROCEEDINGS (30).
It was found that the addition of 30 per cent. of normal serum
was sufficient to inhibit the action of the hemolysins in both the
syphilitic and carcinomatous sera.
Normal serum seems to possess protective substances which
inhibit the action of the hemolysins. Hemolytic sera also may
possibly contain the same protective substances as normal sera.
These substances, if present, would neutralize a certain amount of
the hemolysin existing in the serum.
If only a small amount of hemolysin be present, it would, if
the above conditions actually exist, be neutralized and rendered
incapable of detection by the technique used at present. The
corpuscles belonging to such a serum, however, would still be im-
mune to hemolytic carcinomatous and syphilitic serum.
The serum of one case of tertiary lues was found to contain so
little hemolysin as to be barely demonstrable. The corpuscles of
this blood, however, were perfectly immune to either carcinoma-
tous or syphilitic sera.
The results of this research have some bearing on the subject
of transfusion. Inasmuch as some cases of carcinoma possess
hemolytic sera, we could not transfuse such cases with normal blood:
If transfusion of such a carcinoma case be found necessary — as
a preliminary to operation or for other reasons — it will be neces-
sary to secure as donor a person whose blood corpuscles are im-
mune to the serum of the carcinoma case and vice versa.
According to our observations, the desired blood could be found
in cases of tertiary lues that have just recovered from their
lesions.
The hemolysins found in syphilis and carcinoma appear to be
true isolysins. In experimental isolysin-formation the isolysin is
a reaction product of the organism in which it is formed. The
corpuscles of the animal in whom the isolysin is produced are im-
mune to that isolysin. No anti-hemolysins are present in the sera
of such animals.
The evident immunity of the corpuscles in the hemolytic syphi-
litic and carcinomatous bloods towards the hemolysins in their sera
indicates that the hemolysin is a true isolysin, and, like the experi-
mental isolysins, is probably a reaction product of the organism in
which it occurs. Some toxic substances absorbed from the dis-
HEMOLYSINS IN THE SERA OF CARCINOMA AND SYPHILIS. 23
eased focus could be assumed as the exciting cause of such an iso-
lysin formation.
In conclusion, the writer wishes to acknowledge his indebted-
ness to Dr. J. E. Tuckerman, who collaborated in the research.
12 (350)
The effect of instilling adrenalin chloride into the mammalian
eye.
By W. H. SCHULTZ. (By invitation.)
[From the Division of Pharmacology, Hygienic Laboratory,
Washington, D. C.]
Certain writers have concluded that mydriasis cannot be pro-
duced by instilling adrenalin into the eye of higher animals except
under pathological conditions such as lesions of the pancreas or
the removal of the superior cervical ganglion. Perhaps this con-
clusion results from an oversight of the antagonism existing be-
tween the influence of instilled adrenalin and light stimuli when
simultaneously acting upon the intact eye. At any rate the con-
clusion is not supported by more recent experiments and is mis-
leading when used as a basis for diagnosing certain pathological
conditions.
I have found that mydriasis can be produced in these animals
with relative ease and certainty. In making a comparative study,
however, of different degrees of susceptibility to adrenalin, due
care must be taken to keep the intensity of light stimuli constant.
This is essential, since in the eyes of higher mammals where the
light reflex is well developed, strong light may cause the pupil to
constrict to such an extent that any antagonism of this process by
adrenalin may be lost sight of. For instance, by instilling adren-
alin into the normal cat eye for some minutes and then examin-
ing the eye in light bright enough to constrict the untreated eye
to a small slit-like aperture, no difference in the drugged and un-
drugged eyes can be detected ; but the same eyes examined in a
dark corner may show a distinct difference in the pupils, the
drugged pupil dilating more than the normal one. Thus the early
dilating effect of adrenalin can be detected more easily by reduc-
ing the intensity of the light stimuli. In this preliminary com-
24 SCIENTIFIC PROCEEDINGS (30).
munication, however, it is not so much the time of initial dilation
as it is the time required for complete antagonism of the light
stimuli by adrenalin that is considered. The degree of resistance
to this antagonism is perhaps best illustrated by the appended
protocols, each taken from a series of experiments. Here it is
shown that maximal dilation and loss of light reflex in the guinea
pig results within 23 minutes after instilling 6 drops of I: 1000
solution of adrenalin chloride. After instilling 2 drops every 2
minutes into the eyes of the following, maximal dilation and loss
of light reflex results: In the rabbit, within 56 minutes; the dog,
96; the cat 101 ; whereas in the monkey it requires 148 minutes ;
and in normal man even longer.
From the protocols it will be seen that adrenalin not only di-
lates the pupil of the mammalian eye, but that in each case the
stimulating effect of light of moderate intensity can be completely
overcome by it. Furthermore the ease with which this antagonism
is accomplished seems to depend upon the degree of development
attained by the light reflex mechanism, since in animals that have
a sensitive light accommodating mechanism most highly developed
the period of instillation and amount of solution must be increased
to produce mydriasis, whereas in animals with a reflex mechanism
less sensitive to light stimuli, mydriasis is relatively easy. In con-
clusion it seems that these facts must be considered in formulating
a theory dealing with the dilator mechanism of the eye or with the
value of the adrenalin test for certain pathological conditions.
1. Normal guinea pig. Sept. 5. Park, Davis & Co.’s 1: 10000 adrenalin chloride.
10.30 A, M. Before instillation, diameter of right and left pupil about 5 mm.
10.32 ‘* two drops instilled in right eye.
10.36 ‘* right pupil 5.8 mm., left pupil 5 mm.
TO:30))) SS cc «6 mm., left pupil 5 mm.
10.43 ‘* two drops instilled into right eye.
10.45 ‘* right pupil 7 mm., left pupil 5 mm.
10.50 * cc «ee 7.8 mm., left pupil 5 mm.
10.51 ‘‘ two drops instilled into right eye.
10.55 ‘* right pupil 9 mm., left pupil 5 mm.
iM igiig ty) GC <¢ « g mm., practically dilated to a maximum.
12.32 P.M. ‘ ‘* about same as at II.II.
Hispiis, 09 «oe 7% mm.,, left about 5 mm.
12a «c «¢ about same as left.
Maximum dilation brought on by six drops. Time required was about 23 min.,
at the end of which time the pupil no longer reacted to light.
EFFECT OF INSTILLING ADRENALIN CHLORIDE. 25
2. Normal gray rabbit. Sept. 3. Two drops of P., D. & Co.’s adrenalin chloride in-
stilled every 2 minutes.
3.40 P. M. Right pupil 6.6x 9 mm,, left 6.6 x 9.0 mm.
4.025) 6 SS Se eb. Ox 2 5mm.
AsI2 *6 eee k 2. O-x 02.5),
ARG Syn ace ee 13.5 x 14mm. Lastinstillation: left 7x 10.4 mm., pupil
scarcely reacted to light.
3. Large adult female cat. Aug. 20, P., D. & Co, 1:1000. Instilled every 2
minutes.
10.30 A. M. Right and left pupils alike ; transverse diameter about 114 mm.
Fo: 345) <6 first instillation,
ringyksy slight dilation of right eye, 214 mm., left 114 mm.
12.45 P. M. maximum dilation 11.2 mm., left 114 mm., practically no reaction
to light after IoI minutes,
4. Young adult female dog. Aug. 21. P., D. & Co.’s 1: 1000 sol. of adrenalin
chloride; two drops every two minutes.
10.00 A, M. Right and left pupils of same diameter — about 4.2 mm,
10.04 ‘ _ first instillation.
10.40 ‘* right pupil about 5 mm., left 4.2 mm.
II.oo <6 OG COMNIG"SsmmepnsS 4c SE
11.16 <* “ 66 “c 9 mm.,, “cs 4.2 “é
Mfige ke) Ch GO «Tr mm., “ 4.2 * Last instillation.
4.30 12) 91 Ge SGC oe sé 2 mm., “é 5 “6
Maximum dilation was reached after about 96 minutes at which time the pupil
ceased to react to fairly bright light from a skylight. By 4.30 the right pupil had not
only ceased to dilate, but even in such a light as one might secure in a well-lighted
room at 4.30 P. M., the drugged eye constricted much more than did the normal one.
5. Monkey. P., D. & Co.’s adrenalin chloride, 1: 1000. Two drops every two minutes.
10.30 A. M. Both pupils of the same diameter, about 2.4 mm.
10.32 ‘ first instillation.
10.46 ‘* right pupil 2.6 mm., left 2.4 mm,
10.49 “cc “ 6 3.0 mm., 6c 2.4 ‘é
Onn: GE $B Hingis, CEP pe MG
1 tay id CC OG LS) abrigg, “CO Bayt UC
Tinea | GG CF G0) ASA iets, UO en ie G6
LIE4O) 16° «6.0 mm., ‘ 3.0 ‘ pupils turned toward bright light.
12.00 P.M. ‘ ** 6.5 mm., ‘* 2.8 ‘* constricted to about I mm.
125200 pce Gt OS Gioia, Cpe} © GC
T2240m iss cee 8.4mm., “ 3.2 ** When turned toward bright light,
the left pupil constricted to less than I mm. in diameter while the right constricted
but little (8.2 mm.).
1.00 P. M. Last instillation, practically maximum dilation.
5.00 ‘* In dim light, right and left pupils about the same.
Maximum dilation was reached after 148 minutes at the end of which time the
pupil no longer responded to bright light. Greater constriction of the right eye than
the left was noticed the following morning.
In normal men, the resistance is still greater than in the monkey.
26 SCIENTIFIC PROCEEDINGS (30).
13 (351)
Successful canine infection with cultures of Leishmania
infantum (Ch. Nicolle).
By F. G. Novy.
[from the Hygienic Laboratory, University of Michigan,
Ann Arbor, Mich. |
By the collective term Lezshmaniasis we may designate three
apparently distinct diseases (1) Kala-azar or tropical splenomegaly
of India and the East; (2) Oriental sore, otherwise known as
Delhi, Biskra, Aleppo, etc., boil ; and (3) infantile splenic anemia.
These are characterized by the presence of peculiar intracellular
parasites commonly knownasthe Leishman-Donovan bodies. The
work of Rogers and others has shown that the parasite of Kala-
azar develops in a citrate solution, into flagellate or trypanosome-
like organisms, but attempts at cultivation on blood agar have
given negative results. The recent investigations of Ch. Nicolle
on the parasites of Oriental sore and of infantile splenic anemia
establish the important fact that the Leishman bodies found in these
two diseases can be cultivated on blood agar with the same ease
as in the case of many trypanosomes. Nicolle has further shown
that the infantile splenic anemia can be transmitted to dogs and
monkeys by injection of suspensions of the diseased tissues, but
attempts to produce an infection by inoculation of the cultures
of the flagellate failed.
Having received through the courtesy of M. Mesnil, of the
Pasteur Institute, transplants of the eighth generation of Nicolle’s
flagellate, it was decided, first of all, to test in a severe way the
question as to the possibility of inducing an experimental infection
in animals by means of such cultures. Accordingly a dog was
given, in the interval from April 13 to Sept. 21, fifteen intraperi-
toneal injections of fresh vigorous cultures. The organism was
grown on blood-agar at 20°, and for each inoculation the growth
from a large number of tubes (8—40) was taken up in citrate solu-
tion and injected. A total of 270 cultures were thus utilized in
the course of five months. The dog apparently showed no effect,
other than occasional leucocytosis, and microscopic examination of
the peripheral blood gave negative results.
CANINE INFECTION WITH LEISHMANIA INFANTUM. 27
The dog was bled and when autopsied on October 9 presented
evidence of a prolonged chronic infection. The spleen was small
and tough and weighed but 33 grams, the dog weighing 11.7
kilos. The liver and kidney likewise were found to be unusually
hard. Microscopical examination of the spleen, liver, kidneys,
lungs, and bone-marrow showed enormous numbers of typical
Leishman-Donovan bodies, free and intracellular, with no sign of
the flagellate form. Cultures made from the spleen and liver gave
at the end of five days exceedingly rich growths of the flagellated
organism.
Tubes inoculated with the peripheral blood likewise gave good
cultures though somewhat later, that is, on the tenth day. The
latter fact indicates the value of the cultural method as a diagnostic
means.
It will be seen therefore that, starting out with the flagellate
form, it has been possible to produce a typical infection in the dog
and to recover from the infected animal, by cultural means, the
parasite in the flagellated stage. Undoubtedly this result can also
be obtained by employing less massive doses than was deemed
necessary in this preliminary experiment.
14 (352)
New apparatus designed especially to facilitate the preserva-
tion of food for use in metabolism experiments.'
A demonstration.
By WILLIAM J. GIES.
[From the Laboratory of Biological Chemistry of Columbia Unt-
versity, at the College of Physicians and Surgeons. |
The writer exhibited a new form of apparatus that has been
very serviceable in the preservation of fresh food by refrigeration.
The apparatus consists in the main of a galvanized “angle iron”’
frame constructed to support glass trays specially designed as food
containers. Fresh food, ¢. g., hashed meat, may be very satis-
factorily preserved, without change of general composition, by
1This method further improves the process described by the author some years ago
in the American Journal of Physiology (1901, v, p. 235). See also Gies and col-
laborators : Biochemical Researches, 1903, i, p. 69 (Reprint No. 1).
28 SCIENTIFIC PROCEEDINGS (30).
placing it in covered trays of the kind referred to and transferring
them immediately to such a frame in a freezing room. The gen-
eral characters and relationships of the main parts of the apparatus
are clearly shown in Figure 1. The structure and dimensions of
the glass trays are indicated in detail in Figures 2 and 3. See
pages 30 and 31.
In the form of this apparatus now in use in this laboratory, each
“angle iron” skeleton is 20 inches high, 21 inches wide and 10
inches deep. Twenty five glass trays fit snugly into as many
stalls," which are just a trifle wider and longer than the trays, and
are arranged in five tiers. The removable horizontal rods at the
front are so arranged as to prevent the trays from falling from the
frame if the latter happens to be tilted forward. The “angle
iron” fixtures at the rear prevent movement of the trays in that
direction when the frame is tilted backward.
The glass trays are the essential parts of the apparatus and are
excellent food containers. Plates of ordinary glass furnish very
satisfactory covers for the contents of the trays. Such a glass
lid, trimmed to fit intimately, can easily be put in place and can
readily be elevated with a finger at the depression in the edge of
the tray, at one end, Air tight closure may be secured by plac-
ing over the tray a full-width strip of paraffined muslin before the
closely fitting lid is pressed down tight upon the ledge in the tray
which supports it. Paraffined muslin will not appreciably absorb
moisture from the contents, nor freeze fast to the latter, and can
be washed free from the slight amounts of food that may adhere
to it. If sucha paraffined muslin strip is allowed to extend a
little beyond one end of the tray, the protruding portion serves as
a means of drawing the tray from the frame and also of lifting the
lid of the tray. Such paraffined muslin strips may be used again
and again.
The trays are composed of thick flint-glass and therefore are
able to withstand unusally rough treatment. Neither the lids nor
the trays have been cracked by alternate cooling and warming
between the extremes of temperature to which they have com-
1 Five additional trays may conveniently be placed directly underneath the lower
tier of trays in the frame.
2Such closed trays full of meat may be kept weeks at a time in a refrigeration
room without losing weight.
APPARATUS TO FACILITATE PRESERVATION OF Foop. 29
monly been subjected, z. ¢., 5° C. and room temperature, nor have
the lower temperatures made the glass brittle.
The covered trays hold about 550 grams of hashed, expressed,
lean meat, or 325 grams of cracker meal.’ The freezing of a closed
trayful of lean meat is devoid of any appreciable expansive effects.
This method of food preservation, where the necessary refrigera-
tion facilities are at hand, offers the following special advantages :
The trays are in effect bottles that rest on one side and open on
the opposite side. The paraffined muslin cover and the glass lid
may be removed together as easily as a stopper may be taken from
a bottle. The trays can be filled or emptied easily and quickly.
The thick side of the tray furnishes a very stout fulcrum for
strong leverage with a heavy knife through frozen food, such as
hashed meat. Consequen‘ly, frozen food in such a tray may easily
be sectioned with a knife into blocks without any risk of breaking
the tray.
The trays are comparatively shallow. Therefore, percolation
of liquid in fresh food (such as the juice in hashed meat) before
freezing sets in must be very slight, if it occurs at all.*_ The influ-
ence of such possible percolation on the uniformity of composition
of portions removed daily is negligible, especially if the food is used
in sections cut from top to bottom.
The uniformity of the dimensions of the tray makes it easy to
mark off very accurately given quantities of any relatively homo-
geneous product. Upright partitions, of paraffined card-board
for example, may be used between weighed quantities of food,
placed side by side, without any danger of admixture or difficulty
of removal,
Since the trays can easily be marked for identification, many dif-
ferent dietary mixtures can be systematically preserved at the same
time in the apparatus described, and may be used separately with-
out confusion, After fresh food has been frozen, trays containing
it may safely be kept in an ordinary refrigerator for a day or more,
thus increasing the convenience of handling material preserved in
this way.
1 The covered trays hold about 575 c.c. of water.
? Thus far no visible percolation has occurred, in such trays, in meat previously ex-
ressed in an ordinary ‘¢ tincture press,”’
y P
30 SCIENTIFIC PROCEEDINGS (30).
5)
Fic. 1. A view of the ‘‘angle iron’
frame holding seven glass trays. Two
additional trays in different positions, with their glass lids leaning against them, are
shown, The white objects in the foreground are paraffined muslin strips, which are
used with the glass lids to effect air tight closure of the trays.
Tray I in the second stall of the first tier has a glass lid in place, which shows
distinctly in the picture. The trays in the stalls diagonally downward to the right of
Tray I, and also the tray in the second stall of the lowest tier, are empty and without
lids, The two covered trays in the fourth and fifth stalls of the second tier contain
frozen hashed meat and show the usual appearance of full trays in reserve in the frame.
Trays II and III outside the frame show clearly the inside appearance of the
trays.
The removable horizontal rods are in position to prevent forward movement of the
trays. The special turns on the ends of the rods should be noted.
APPARATUS TO FACILITATE PRESERVATION OF FoopD. 31
It is needless to dwell upon the obvious fact that the apparatus
described may be used very satisfactorily for many other purposes.
The trays are excellent crystallization dishes, for example, and
serial recrystallizations may be effected in them very conveniently.
Fic. 2. A diagram of a tray with the lid out of place, to show especially the
ledge upon which the lid rests when the tray is covered. The depression in the edge
of the tray at one end, where the lid may readily be lifted with a finger, is also indi-
cated sharply. This depression does not extend to the surface of the ledge. There-
fore, when the lid is in place, the tray is completely closed.
The general structure of the apparatus permits its placement in
out of the way positions. The whole of it can readily be pro-
tected by an easily removable impervious covering.
Fic. 3. A diagram showing the relationships of the parts of the tray, including
the lid, and giving the main dimensions.
I am indebted to my assistants, Mr. Walter H. Eddy and Dr.
Archibald FE. Olpp, for the photograph and drawings of the
apparatus. Mr. Christian Seifert, of this laboratory, executed
admirably the plans for the frame. The glass trays were made to
order by the Whitall Tatum Co.
Thirty first meeting.
Rockefeller Institute for Medical Research. December 16, 1908.
President Lee in the chair.
15 (353)
Reply and explanation to recent criticism of my experimental
study on effects of extirpation of the salivary glands
on the gastric secretion.
By JOHN C, HEMMETER. (By invitation.)
[From the Physiologic Laboratory of the University of Maryland,
Baltimore. |
It is not always a congenial task to have to reply to a criticism
of one’s experimental work. To many a conservative thinker, the
policy contained in a remark attributed to Ludwig under a similar
circumstance, “‘ Schweigen ist gold,’ may appeal as more expedient.
But yet, the dignified silence may be interpreted, by the one who
has advanced the criticism and even by the research worker and
general student of physiology, as a tacit approval to the fault find-
ing —in other words, as signifying that the criticism was deserved
and the work criticised defective. I find myself in this embar-
rassing position with regard to an article published in the “ Pro-
ceedings of the Society for Experimental Biology and Medicine,
1908, v, pp. 114-117,’ New York, by Dr. A. S. Loevenhart and
Dr. D. R. Hooker, entitled : ‘Note on the supposed presence of a
gastric hormon in the salivary glands.”
Although the physiology and pathology of digestion has been
my life work, yet, as one of the results of many years of labora-
tory teaching and training, I am loathe to insist dogmatically on
any of my opinions and am ready at any moment to be corrected and
to advance another step in the attainment oftruth. (‘‘ Experientia
fallax, Experimenta mendax.’’)!
1 But rather than dwell upon the moral side of scientific controversy I prefer to
refer to Sir Thomas Browne’s ‘‘ Religio medici,’’ 1904 edition, p. 98.
(33)
34 SCIENTIFIC PROCEEDINGS (31).
Especially welcome are such corrections when they emenate
from such an esteemed friend and talented worker as Dr. Loeven-
hart. The original worker whose results are criticised has the
right, however, to demand that his special point of inquiry (‘‘ Frage-
stellung’’) and all the methods of experimentation, operative, phys-
iologic and chemic, shall be conscientiously repeated on, at least,
an equal number of the same kind of animals, successfully nursed
through the identical operative procedures. He has a right to
demand a scrupulous regard for detail, and for all the finer distinc-
tions made in his application of methods, some of which may have
required years for their perfection in his hands and those of his
associates.
Let us investigate whether my friend, Dr. Loevenhart, has ful-
filled these indispensable, fundamental conditions that should pre-
cede destructive criticism.
I sought to ascertain the effect of salivary gland extract in
dogs deprived of all four pairs of salivary glands, whose gastric
juice had been carefully studied before any operation of removing
the glands was undertaken. Sometimes the removal had no very
marked effect ; but in those dogs in which it did, I tried to ascer-
tain whether the depressed gastric secretion could be restored or
not by salivary gland extract. I tried to study the effect on a
secretion already abnormally depressed in three series of dogs —
thoroughly recovered from the operation, allowing ten days to two
weeks, at least, for recovery.
Dr. Loevenhart starts with normal dogs, as he supposes, and
expects to raise the gastric secretion qualitatively and quantitatively
above the normal. He seeks the effect of salivary gland extract
in raising a supposedly normal gastric secretion to a higher acidity
and proteolysis — an entirely different problem from mine.
I have never published anything on the effect of salivary gland
extract on the normal gastric secretion of dogs. It is not asserted
that this extract can raise the gastric secretion above normal, but
only that it may, under certain conditions, partially restore a gas-
tric secretion that is depressed de/ow normal. Dr. Loevenhart is
attempting to change a normal secretion to an abnormal (higher)
one. I studied the effect in restoring an abnormal secretion to a
normal one.
EFFECTS OF EXTIRPATION OF THE SALIVARY GLANDS. 35
When there are four different procedures for obtaining gastric
juice on the same dog within thirty minutes, and the jugular vein
exposed, a cannula inserted and submaxillary extract injected in-
travenously, it must not be overlooked that, with every additional
interference, the animal becomes more and more disturbed and that
this seriously influences his gastric secretion. The chemico-phys-
ical and the neuro-physical processes of secretion are thoroughly
upset unless a long time for recovery is given. This is shown in Dr.
Loevenhart’s results, page 4 of his reprint, in which the total acid-
ity and free HCl and the proteolytic power became less and less
in specimens A, B and C; only when the psychic secretion was
aroused, granting that this was not a delayed effect of injection
sal. gl. extr. specimen D, was there any notable proteolysis with-
out addition of acid. The notes of the beginning of experimen-
tation on this dog bear the date of April 6, and the qualitative
studies bear the date of April 8 — not near time enough to permit
dog No. 2 to entirely recover.
To expect salivary gland extract to raise the gastric secretion
qualitatively and quantitatively above what is the regular standard
for the average dog is to expect something abnormal —for an un-
usually abundant and unusually active gastric juice is logically
as abnormal as one that is unusually diminished or inactive.
1. What Dr. Loevenhart presumes is that the salivary gland
extract should change a normal gastric juice to an abnormal one
(from the regular amount to an unusually high amount and activity).
2. What I attempted to ascertain was whether or not an abnor-
mal gastric juice could be restored to the normal (from diminished
and weakened secretion to the normal). The “ Fragestellung”’ is
not the same, in fact, it is highly digressing.
Dr. Loevenhart observed only two animals. Nowhere does
he give the date of operations, nor state the time that elapsed
between the operation and first day of experimentation, nor the
amount of proteolysis in millimeters of Mett tubes. Both animals
were abnormal. The first dog, No. 1, he admits had distemper
and was feverish, was thin and would not eat. The first observa-
tions are dated November 11, 1907, and this animal died within
48 hours,
36 SCIENTIFIC PROCEEDINGS (31).
All of our results were gained from dogs that lived for three
to six months and then had to be killed in most cases because we
had no room or facilities for keeping them during the summer vaca-
tion — excepting the series of the summer of 1907 when I kept
four dogs at our country home.
What Dr. Loevenhart aimed at |
6 Secretion expected to rise above normal
ne
Line of normal gastri BE
ine of n ee Sout
e of normal gastric secretion ‘5 >, no extirpation
3g 4 of salivary glands
—= 8
42) 5)
=}
n
What Dr. Hemmeter attempted to
ascertain.
=
ag
Line representing nor- ‘6 8
mal gastr. secret. 8 "on
pe || $a sevcceeenesnnnceneene nnnnnneensoncereneneeeneseit
gE Fs 5 i gradually re-
‘BE Sie 5 stored to
as ac = nearly normal
oss
gee
Zz oa
gastric \juice > -= 5
decidedly reduced qualitatively
and quantitatively
Dog No. 2 of Dr. Loevenhart was also abnormal. This is evi-
dent from the feeble proteolysis as indicated by Mett tubes (in Dr.
Loevenhart’s article they are called “‘ Metz” tubes) and the low
acidity, and Dr. Loevenhart gravely states that the fluid gained by
catheterization, 8.6 c.c., specimen A, contained much dark mucus
(blood? and mucus). Mucus in a fasting dog’s stomach is one
of the most reliable indications of gastritis. Dog No. 2 had a dis-
eased stomach also.
We made our salivary extract from maceration of all four pairs
of canine salivary glands, even the orbital — and it is all important
that this extract should be made only from salivary glands that
have been functionally active immediately before their excision
EFFECTS OF EXTIRPATION OF THE SALIVARY GLANDS. 37
(the dog must be made to chew bread and then rapidly etherized).
I have worked with extracts of inactive glands, but so far have
refrained from publishing anything concerning their effects or non-
effect. In nota single instance, has the operative plan and tech-
nique used by us, nor the physiologic routine of preparing the
glands by functional work, nor the chemic discipline of ascertaining
the proteolytic activity been punctiliously carried out by Doctors
Loevenhart and Hooker.
Both of the animals had diseased stomachs. In neither were
the salivary glands extirpated. The entire plan of experimentation
and aspect of physiologic inquiry is so fundamentally different from
mine, that comparison of their work with ours is not logical, and
any deductions from their work as used to interpret our results
are unfortunately misapplied.
It is only fair that the work of an experimentor should be
judged from his most recent publication, in this case that which
appeared in the Brochemische Zeitschrift (Hamburger Festschrift,
Band xi, p. 238), the only complete report published by me.
The short notice by which Drs. Loevenhart and Hooker judged
our work was nothing but a preliminary report, and contained, as
such reports occasionally do, some inaccuracies which I have
taken the privilege to correct in the article published in the Bvo-
chem. Zeitschr., l. c. (“ Die Wirkung der Total Extirpation Samt-
licher Speicheldriisen auf die Sekretorische Funktion des Magens
beim Hunde”). Even in this article the printer has allowed some
wrong figures to slip into the headings of tables C, D and F, pp.
257, 258 and 259, for which I am in no way responsible, but which
do not injure the main argument, especially as the editors of the
Biochem. Zeitschr. politely corrected them in a subsequent Be-
richtigung.
In Dr. Loevenhart’s experiment on April 8, submaxillary
extract was injected into dog No. 2 at about 3.10 to 3.15 P. M.,
the gastric juice of twenty minutes later showed a free HCl of
0.20 (titration with z/20 NaOH) but the proteolytic power with
addition of acid is declared to be “‘ good.” Butat 3.30 the stomach
of the same dog was catheterized and specimen A obtained after
the dog was allowed to smell meat for ten minutes. This speci-
men A was the most active that Loevenhart obtained. It came 35
38 SCIENTIFIC PROCEEDINGS (31).
minutes after the submaxillary extract was injected. Question is:
Would not this active juice have been secreted even without
the efforts to cause a psychic secretion, for the salivary extract in
my experience has a latent period in which it produces no very
marked secretion? After that period it may come; that is, a pro-
nounced secretion may come, even thirty minutes after injection
of salivary extract and even if there has been no chance for psychic
secretion. Pawlow, /. c., p. 70, states that in all cases the latent
period after the vagus stimulation of gastric secretion may be from
I5 minutes to one hour, and even more.
Hitherto we have known the term “ /atent period of secretion”
only in connection with the stimulation of a nerve going to gland
or muscle. We are not so familiar with the use of the term
“latent period” in connection with the chemical stimulation of a
gland. A moment’s reflection will bring the thought nearer to
us that even after nerve stimulation, pure and simple, chemical
events must transpire in the gland cells which require a certain
time for their elaboration. Now, if the stimulation is purely
chemical, and not through a nerve, the same or similar chemical
events must precede the actual outpouring of secretion. We are
still ignorant of the processes that occur during the “‘ latent period,”
but recent work indicates that they are partially electrical and
partially of a chemical nature. We must also consider that the
immediate effect of a chemical stimulation, like the immediate
effect of a nerve stimulation, may be inhibited.
There are so many side influences of a physical, nervous and
chemical nature which control the phenomenon of the “latent
period”’ that its exact nature and what transpires during it, is still
a matter of speculation.
It may, at first sight, seem paradoxical that the latent period of
secretion after sham feeding in dogs is stated by Pawlow to be only
5 to IO-I5 minutes, and the latent period after vagus stimulation
I5 minutes to one hour —for in both instances the stimulation is
transmitted by one and the same nerve to the identical synapses
in the gland cells. Pawlow explains this, p. 71, /. c., by his belief
that in artificial stimulation of the vagus, the stomach receives the
excitatory as well as inhibitive impulses, and the latter check
secretion.
EFFECTS OF EXTIRPATION OF THE SALIVARY GLANDS. 39
How can we conceive of inhibitive processes to explain a long
latent period of secretion, when chemical substances (for example,
salivary gland extracts) are injected intravenously? By an anal-
ogous experimental reasoning, we have learned (Pawlow, /. c.)
that it is impossible to imitate the influence and action which the
vagus exerts during normal life while digestion is going on, for
our laboratory methods are far too coarse and the complexity of
fibers in this magnificent highway of nerve tracks too intricate
for us to single out individually functioning secretory fibers.
We are not much better off when we attempt to imitate the
chemistry of the internal secretion of glands, for only in a single
instance has a hormon been isolated in a state that reveals its exact
chemic structure.
The chemic messengers are bodies of definite chemic structure
which are released with unerring exactness from their producing
organs ; but when we manufacture an organ extract, it is, of course,
possible that we may seize the hormon (if I may still use the term) ;
but unavoidably we must extract the entire tissue of the organ and
as a result obtain extracts, which contain materials that stimulate,
but also materials that may inhibit secretion. This occasional
inhibitive effect of salivary gland extract on gastric secretion has
brought to mind two ideas: either that Iam not dealing with a
hormon or stimulator at all, or that there may be two kinds of
chemic correlation, one that stimulates and the other that inhibits.
The conception which sees an antagonistic, as well as a syner-
gistic, correlation brought about by chemic messengers is at least
as rational, when applied to the physiologic correlation of organs
by means of chemic substances communicated to them by means
of the circulation, as when applied to the correlation of organs by
means of nerve elements. This relation of organs by means of
reciprocal (antagonistic or synergistic) action of nerves is not new
to physiologists, and has been brought home to us in a most im-
pressive manner by Meltzer, not to mention Ch. S. Sherrington,
New York, 1907. All of this is still hypothesis ; but this hy-
pothesis has been given color (1) by the seemingly paradoxical
effects of (2) such a pure substance as adrenalin, which does not
always cause constriction of vessels (only when they are severed
from the nerve centers) but sometimes may cause dilatation, when
in normal animals a certain vascular area is intact in connection
40 SCIENTIFIC PROCEEDINGS (31).
with its nerve centers,’ and of (4) gland extracts, which sometimes
raise blood pressure and often lower it (sometimes after a slight
previous rise), and (2) by the contradictory effects of some salivary
gland extracts on gastric secretion. All of this doubt will con-
tinue so long as we are compelled to deal with a complex mixture
of various substances in gland extracts and not with one pure sub-
stance of known composition.
To this consideration belongs, also, the antagonistic phenomena
reported by Lilienfeld, Morowitz and Delezenne as occurring in
blood coagulation (positive and negative phase of coagulation).
This is explained by Lilienfeld and also by Delezenne by the
isolation from blood plates and leucocytes of two substances, one
of which they term “ /euconuclein”’ which favors coagulation, and
the other, ‘ /zston,” which retards coagulation. Before the isola-
tion of these two substances the phenomenon of the positive and
negative phase during blood coagulation appeared paradoxical, and
the idea of a latent period of coagulation might have come to
many an experimentor. Just so with the latent period after chem-
ical stimulation of the glands; it may be due to inhibitive sub-
stances in the gland extracts used, and it is possible that this delay
in bringing about the effect after chemical stimulation of the gas-
tric glands, may disappear with a clearer knowledge of the chem-
istry of the gland extracts, and a more accurate method of pre-
paring them.
Besides the latent period of secretion, we must consider the
neutralization of the first acid secreted by the mucus present in
the stomach. Pawlow(‘“ Arbeit. d. Verdauungsdriisen,” /. c., p. 39)
calls attention to what he emphasizes as “Factum,”’ namely,
“ Even with a normal stomach and with a pure gastric juice 25 per
cent. of its acidity can be lost through neutralization by mucus.”
How much more must this neutralization take place in a stomach
that, as Loevenhart states, gave “much dark mucus.’ The very
efforts of catheterization increases the mucus formation, and after
the submaxillary gland extract was injected, if it had any stimu-
lating effect at all (I am not prepared to state whether it had or
not) this much is sure, the mucus had to be neutralized before
1 This latter effect of adrenalin is not a purely chemical effect but a mixed effect of
nerve and chemical phenomena, One and the same chemically pure substance cannot
be claimed to contain both stimulating and inhibitive substances.
EFFECTS OF ExTIRPATION OF THE SALIVARY GLANDs. 41
there could be free HCl. The extract was injected at 3.20 on
April 10; at 3.25 P. M. the gastric juice was drawn by cathe-
terization (8.8 c.c., specimen C). No free HCl was in it, but six
minutes after the injection of salivary extract the dog was shown
meat, and ten minutes after that there was a fourth catheterization
(the fourth in 30 minutes). This 5.3 c.c. was active juice and
Loevenhart and Hooker attribute it to psychic secretion.
Considering the latent period of secretion and the time for neu-
tralization by mucus, it is reasonable to inquire whether or not the
injection of extract had a feeble but delayed influence, although
Loevenhart and Hooker used only submaxillary extract and not
that of all four pairs of glands, and did not prepare it in the man-
ner I did.
Concerning the inflammation (gastritis) in the stomachs of their
dogs, I can very readily appreciate the difficulty, for I had been
thwarted and misled by diseased canine stomachs for almost a
year before we gradually learned to recognize, avoid and treat
them.
Evidences like these, naturally suggest that such experiments
cannot be successfully carried out in a few months. I was not
aware of Dr. Loevenhart’s criticism, until November 14, 1908.
That there are salivary extracts that have no peptogenic effects
whatever, and others that are variable, I have already stated in my
article in the Brochemische Zettschr., Vol. xi, p. 251 (“ Verschieden-
heiten in d. peptogenen Kraft d. Speicheldriisen Extrakten’’).
Then again, the complexity of the mechanism of gastric secre-
tion in dogs is such (Liochem. Zettschr., l. c., p. 253) that the ini-
tial depression caused by extirpation of the salivary glands prob-
ably may be gradually replaced by special efforts of the remaining
sources of stimulation to the gastric glandular apparatus.
This problem is far too deep and complicated to have years of
laborious experimentation set aside by a casual testing of two sick
dogs, as to whether a saline extract of the inactive submaxillary
gland alone can cause a secretion of gastric juice in animals not
deprived of their salivary glands.
That there may be defects in my work I am willing to accept
as a possibility, because a general knowledge of the history of
physiology reveals the status that the first results of similar ex-
42 SCIENTIFIC PROCEEDINGS (31).
perimental work are only in most exceptional instances without
defects or errors.
Such a defect in the connexus of cause and effect has recently
been brought to my knowledge and, today, makes it debatable
whether the name “hormon”’ is correctly applied by myself to
the stimulating quality of one gland extract upon the secretion
of another set of glands. The definition and conception of the
hormon allows a rather wide application, it is true, but it seems
to me it ought to be restricted to substances whose chemical
structure is at least approximately known and that have one pre-
dominant characteristic or specific effect on other glands, in which
effect they cannot be replaced by extracts from other organs or
tissues. This is not the case with the salivary extracts, for, as we
can learn (Biochem. Zeitschr., Vol. xi, p. 253), extracts of the
pyloric mucosa and of the spleen (Luciani) act in a similar manner
in stimulating gastric secretion.
Concerning the pepsinogenous effect of the spleen on the gas-
tric secretion, I refer to the work of Tarulliand Pascucci, executed
in Luciani’s laboratory and described in the latter’s splendid
work, ‘‘ Physiologie des Menschen,” translated into German by Bag-
lioni and Winterstein, Vol. ii, pp. 151 and 152. Onpage 153 it will
be seen that the extract must be made from an active spleen, as
Luciani says ‘‘a spleen that is hyperemic and swollen,’ which
means, taken from a dog during the height of the digestive period.
Extracts of spleen taken during the period of functional rest had
no pepsinogenous effect ; but the meaning of Luciani and his pupils
above mentioned is unmistakable. A chemical substance is formed
in the spleen during its activity which, when brought into the circu-
lation, is absorbed by the gastric glands and is capable of aug-
menting the quantity of the secreted pepsin. Additional emphasis
is given in these experiments to the fact that the extract should
only be made from a functionally active gland.
Whatever may be the final outcome of investigations concern-
ing the chemical nature of the hormones, Bayliss and Starling
consider that they were originally accidental by-products of the
activity peculiar and proper to the organ which has produced them.
Thereafter the next step in the development of a correlation is the
acquisition of a sensitiveness or a responsiveness to the hormones
EFFECTS OF EXTIRPATION OF THE SALIVARY GLANDS. 43
in any remote organ (‘Die Chemische Koordination der Funk-
tionen des Korpers,” Ergebnisse der Physiologie, Jahrgang v, p.
670). The only word to which I could take exception in this
explanation of Bayliss and Starling is the word “ accidental ”’
(“ Zufallige’”’ Nebenprodukte). I should like to enlarge this con-
ception when applying it to the digestive tract, and state that
the various segments of the digestive tube are correlated and co-
ordinated by a sensitiveness not only to accidental products, but to
the regular by-products which are known to accompany the
formation of the specific products of the organs of digestion.
An infirmity in the experimental logic, suggestive of a meta-
bolic by-product produced in the salivary glands during activity
which might be regarded as a chemical messenger to the secretory
apparatus of the stomach, might be found in the occasional failure
to produce total loss of gastric secretion after the salivary glands
are removed. In other words, we should expect to find invariable
“ Ausfalls-Erscheinungen,’ phenomena of lapse or total deficiency
of gastric secretion. That these do not occur after the salivary
glands are extirpated with that regularity that is necessary to
justify the use of the term “ hormon,”’ is at least partially explained
by the existence of several other sources wherefrom the secretory
apparatus of the stomach may receive its stimulations ; these other
sources have been sufficiently considered in the preceding and in
the Biochenusche Zeitschrift, Vol. xi, p. 253.
I do not wish to be understood as asserting that an extract of the
inactive submaxillary gland alone can have an effect in raising the
amount and proteolytic activity of gastric juice, but only, that, if it
possibly could exert such an effect, not sufficient time was allowed
after the injection in Dr. Loevenhart’s experiments to adequately
test this point of inquiry.
If there is anything of importance that has revealed itself to
us since the publication in the Biochemische Zeitschrift, Vol. xi,
p. 238, it has come through experimental study of the occasional
long latent period after injection of some salivary extracts and not
after others. This has suggested the existence of chemic sub-
stances which inhibit or check gastric secretion. These substances,
if they exist as definite chemical bodies, must be more abundant in
resting, than in functionally active, salivary glands.
44 SCIENTIFIC PROCEEDINGS (31).
There is nothing contradictory in the idea that one and the
same gland cell in one segment of the digestive tract may contain
two kinds of chemical messengers for the succeeding segment of
the digestive apparatus. One kind stimulates secretion in the fol-
lowing segment and a second kind inhibits or arrests it.
Starling (‘‘ Recent Advances in the Physiology of Digestion,”
p. 90) speaks only of hormones (from oppda, to excite, arouse or
stimulate). But on reflection it must be evident that for the nor-
mal regulation of life processes, it may, under certain conditions, be
equally important that any process of secretion or vascular tonus
should be capable of inhibition by chemical messengers. Two
such diagonally opposed chemical substances which are con-
cerned in coagulation have been isolated from lymphocytes by Lil-
ienfeld and Delezenne, one of which /euconuclein favors coagual-
tion and a second /zston which inhibits it. The leuconuclein
corresponds to the hormones but the Aisfon is an inhibitor. For
such chemic bodies — physiologic arresters like Azston —I would
suggest the name oliones from the Greek zwivwy, to inhibit, to
prevent, arrest or check.
16 (354)
A critical study of the conditions under which zymase and its
associated co-enzyme bring about alcoholic fermentation.
By GEORGE H. A. CLOWES.
[From the Agricultural Chemical Laboratory of Professor Buchner
in Berlin, and the New York State Laboratory, Buffalo. |
Zymase, the enzyme of yeast discovered in 1896 has since been
proved by Harden and Young to consist of two parts, (1) zymase
proper, an enzyme-like body possessed of high molecular com-
plexity, non-diffusible and thermo-labile, and (2) a readily dif-
fusible, thermo-stabile, relatively simple, chemical complex, which,
for lack of a better term, has been designated as the co-enzyme of
zymase.
Harden and Young separated the bodies in question by dif-
fusion, but owing to the paucity of their materials and the destruc-
tive effect exerted by secondary causes during the lengthy process
ALCOHOLIC FERMENTATION. 45
involved, it was found impossible to obtain any clear insight into
the conditions of physico-chemical equilibrium obtained in this
reaction. Buchner’s dauerhefe, that is to say, a preparation of
pressed yeast precipitated by an excess of acetone or alcohol
ether, can be prepared in large quantities and exhibits a high
degree of resistance to the action of destructive enzymes. We
therefore directed our attention to the preparation of dauerhefe
containing as large a zymase content and as small a co-enzyme
content as possible, our object being to study the effect exerted
by a preparation of this nature upon fermentable sugars, when
used in conjunction with varying proportions of a boiled yeast
extract containing co-enzyme. It was found possible to produce
a preparation of acetone dawerhefe which in itself alone possessed
no fermentative activity whatsoever, but which when used in con-
junction with a suitable quantity of boiled yeast extract, exhibited
an unusually active fermentation, 2 grams mixed with 6 grams of
sugar and 20 c.c. of extract producing from I to 2 grams of CO,
in the course of 8 to 10 days.
Having thus demonstrated that it is possible to obtain a stable
preparation containing relatively large quantities of zymase, and
also to prepare a relatively stable boiled extract of yeast contain-
ing co-enzyme, a series of experiments was commenced, the object
of which was to determine the effect of varying proportions of
co-enzyme used in conjunction with a constant amount of zymase,
and vice versa. In several series of experiments in which a con-
stant amount of zymase (2 grams dauerhefe), was used in con-
junction with 6 grams of sugar and from 1 to 50 units of co-
enzyme, it was found that the velocities of reaction and the
fermentation end results were directly proportional to the number
of units of co-enzyme employed up to an optimum concentration,
after which a fall in the value of both these quantities was to be
observed. The same phenomenon exhibited itself when varying
proportions of dauerhefe were employed with a constant amount
of co-enzyme, other conditions being constant.
The velocity of reaction %, is calculated from the formula
A I
ED aaa is
46 SCIENTIFIC PROCEEDINGS (31).
where A represents the relative molecular concentration of the
sugar and A — X the concentration at any given time 7. The
progress of the reaction is readily followed by estimating the loss
in weight of fermentation tubes due to the evolution of CO,. In
all cases in which no disturbing influence has been allowed to
exert an effect, this velocity of reaction is found to be constant for
a period of three or four days immediately following the establish-
ment of active fermentation. Provided all experiments are carried
out at a constant temperature and that other conditions are main-
tained on a uniform basis, the value of K is found to be directly
proportional to the product of the concentrations of the zymase
and its co-enzyme, according to the formula
VEN VEE,
kK 40)
where K and XK; represent velocities of reaction and 7 and Z, con-
centrations of zymase and C and C, concentrations of co-enzyme
in comparative series. The accuracy of this formula over a com-
paratively wide range was demonstrated by means of tables, in
which the observed and calculated values of K were compared for
a series of tubes in which zymase (dauerhefe) and co-enzyme
(boiled yeast extract) were employed in varying proportions.
Herzog, from experiments carried out previous to the discovery
of the heat-resistance component, came to the conclusion that the
fermentation process was to be represented by the formula
K Gne
m7 (a):
1
where C and C, represent comparative concentrations of zymase
and x has any value from 1 to 2. Such a formula would obvi-
ously only hold in those cases in which the ratios between zymase
and co-enzyme are maintained on a constant basis. The formula
which we have developed above gives results closely agreeing
with theoretical conclusions in all cases in which sources of experi-
mental error, such as the action of outside enzymes, are eliminated.
LIFE-SAVING ACTION OF ESERIN. 47
17 (355)
Presentation of a dog ten months after double nephrectomy
and replantation of one kidney.
By ALEXIS CARREL.
[From the Rockefeller Institute for Medical Research. |
The animal presented to the Society underwent the extirpation
and replantation of the left kidney and the extirpation of the right
kidney ten months ago. He is to-day in excellent health.
The result shows that the perfusion of the kidney with Locke’s
solution, the interruption of the renal circulation for fifty minutes
and the disconnection of the renal nerves with the central nervous
system do not produce any lesion of the kidney incompatible with
its functions.
18 (356)
A demonstration of the life-saving action of eserin in poi-
soning by magnesium.
By DON R. JOSEPH and S. J. MELTZER.
[From the Department of Phystology and Pharmacology of the
Rockefeller Institute for Medical Research. |
At the May meeting of this Society, one of us (J.) reported
that by the use of magnesium, certain toxic effects of physostig-
min can be completely overcome. In our present communication
we wish to bring out the fact that the antagonism between physo-
stigmin and magnesium is mutual, at least to a certain extent. We
wish to show an experiment which demonstrates that physostigmin
can overcome certain toxic effects of magnesium and thus save the
life of a poisoned animal.
Both these rabbits (A and B) received at about the same time
I.2 gram of magnesium sulphate per kilo of body weight. The
jnjections were given intramuscularly in the lumbar region. Rabbit
B received in addition one milligram of eserin, also intramuscularly.
Rabbit A is already dead. Rabbit B is still alive ; although anes-
thetic and limp, it breathes regularly and apparently is in no
danger of death.’
1 By the end of the meeting, rabbit B had recovered completely.
48 SCIENTIFIC PROCEEDINGS (31).
19 (357)
The mechanical destruction of pepsin.
By A. 0. SHAKLEE and S. J. MELTZER.
[From the Rockefeller Institute for Medical Research.]
At various times since 1884, one of us (M.) has studied the
effects of shaking upon living cells, such as red blood corpuscles,
bacteria, and arbacia eggs. Those experiments led to the general
conclusion that shaking, by virtue of the mechanical factor, exerts
a profound influence upon living organisms. In the present series
of experiments we intend to investigate the changes which shaking
may produce in the action of ferments. We began with the study
of pepsin, the determination of which is greatly facilitated by several
recently described reactions.
Solutions of pepsin, partly filling long bottles, were shaken at
room temperature and at a temperature of 33° C. for periods of
different lengths, by means of shaking machines. Our results
which we state here very briefly are unmistakable. Shaking under
these conditions destroys pepsin. Even short periods greatly
diminish its strength. If shaken long enough it is completely
destroyed. The temperature has a marked influence upon the
rate of destruction. Higher temperatures hasten the destruction.
That the effect is not due to oxidation was proved by substi-
tuting for the air in the bottles, hydrogen, carbon dioxide or
oxygen. There was no appreciable difference in the results.
It was also shown experimentally that the destruction was not
brought about by any rise of temperature caused by the shaking.
Maximum thermometers were fixed in the bottles perpendicular
to their long axes, that is, perpendicular to the direction of shak-
ing: in no case did the thermometer inside register as much as a
degree higher than the thermometer outside.
We have also found that the degree of shaking which occurs
in the animal body is sufficient to reduce the activity of pepsin.
This was determined by introducing a small bottle containing a
solution of pepsin into a dog’s stomach through an esophageal
fistula and permitting it to remain there for 24 hours or longer.
The pepsin strength was diminished as much as 40 per cent. com-
ACQUIRED RESISTANCE OF RED BLoop CELLs. 49
pared with that of the pepsin in a similar bottle kept in the ther-
mostat at a temperature of 39° C.
The reported results were demonstrated by the reactions for
pepsin of Jacoby and Solms, of Fuld, and of Gross.
20 (358)
A demonstration of the effects of CO, upon the
frog’s pupil.
By JOHN AUER.
[From the Department of Physiology and Pharmacology of the
Rockefeller Institute for Medical Research. |
Frogs placed in an atmosphere of CO, gas show within thirty
seconds, before any symptoms of excitement, a good constriction
of the pupil. This constriction becomes almost maximal within
five minutes ; there is no dilatation.
The same effect is exerted by CO, gas upon excised frog’s
bulbi.
When the frog’s iris, in the excised bulbus or in the living
animal, is under the influence of CO, gas, the powerful mydriatic
effect of adrenalin is strongly reduced.
Since CO, produces this myotic action upon excised bulbi, its
effect must be exerted, largely at least, upon the sphincter pupille,
that is, its action is peripheral. These experiments, however, do
not exclude a possible central action.
This myotic effect of asphyxia in frogs is interesting, as asphyxia
in mammals produces chiefly dilatation.
21 (359)
On the specific acquired resistance of red blood cells.
By RICHARD WEIL.
[From the Loomis Laboratory, Department of Experimental Pathol-
ogy, Cornell University Medical School, New York City. |
It is a well known fact that the serum plays a preponderating
role in the immune reactions of animals. On the other hand, it
has been amply shown that the immune characters of the serum
50 SCIENTIFIC PROCEEDINGS (31).
may be in no proportion to the immunity of the organism as a
whole. There must therefore be an additional factor, hypotheti-
cally designated by Behring as cytogenetic immunity. Of this
type of immunity there is the following experimental evidence.
In 1898, Kossel stated that if an animal were injected with eel
serum, its washed red cells manifested resistance to the hemolytic
action of the latter in vitro; a fact confirmed by Camus and Gley,
and by Tshistovitch. In 1908, it was shown by Morawitz and
Pratt that in animals injected with phenylhydrazin, the red cells
became resistant to all hemolytic agents. This they showed to
be not an immune reaction, but the direct result of the chemical
action of the drug on the red cells.
It was the object of the present series of experiments to deter-
mine whether it was possible to induce a specific resistance of the
red cells to poisons injected into the animal. Dogs and rabbits
were used. Among the hemolysins injected were : eel serum, and
dog serum ; saponin, and digitalin ; staphylolysin, tetanolysin, and
prodigiosus toxin; and phenylhydrazin. Eel serum, saponin,
and phenylhydrazin were selected for routine experimentation.
All of these were found to induce a severe grade of anemia. The
animals were bled at intervals, and the resistance of the corpuscles,
after repeated washings in salt solution, tested against a variety of
destructive agents. Eel serum was found to induce occasionally
a marked change inthe red cells ; saponin did so almost invariably,
in case the animal survived the treatment ; phenylhydrazin did so
without exception. Inthe early stage of treatment, the resistance
of the red cells to all hemolytic agents, including the injected
hemolysin, was diminished. In the later stages, it was increased in
a characteristic manner. The red cells of animals injected with
phenylhydrazin showeda marked increase of resistance to all types
of hemolysins. Animals injected with eel serum and with sapo-
nin came to possess a type of erythrocytes which were very resist-
ant to the specific injected hemolysin, but were almost invariably
more easily destroyed than normal control cells by all other hemo-
lytic agencies, including anisotonic salt solutions (demonstration).
In those animals injected with eel serum, which failed to develop a
specific resistance of the red cells, the serum showed marked anti-
hemolytic powers. It is evident, therefore, that the erythrocytes
have developed a specific immunity.
Butyric REACTION FOR SYPHILIS. 51
The cause of this resistance has been made the subject of
further study. After testing the saponin and eel serum on a
variety of red cells, the supernatant fluid was pipetted off, and
tested on normal red cells. It was found that the fluid which had
been in contact with resistant cells was least hemolytic, and vice
versa. It is conceivable that the resistant erythrocytes may either
absorb a disproportionate quantity of the hemolysin, or may con-
tain a neutralizing substance.
It has been customary in human pathology to judge of the
resistance of red cells according to their vulnerability in anisotonic
solutions of salt. The above described experiments indicate that
specific resistance to a circulating toxin may be associated with
marked loss of resistance to anisotonic solutions of salts. The
red cells in advanced cases of cancer have been shown (Lang and
others) to possess a greatly increased degree of resistance to aniso-
tonic solutions. The demonstration of a hemolysin in the circu-
lating blood of cancerous cases, and of an increased resistance
thereto on the part of the red cells, has made it possible to prove
that the resistance is specific to this hemolysin, and only accidental
and occasional for the anisotonic solutions.
22 (360)
The butyric reaction for syphilis in man and in the monkey.
By HIDEYO NOGUCHI.
[From the Rockefeller Institute for Medical Research. |
In a preliminary communication’ I stated elsewhere that an
increase in certain protein constituents of the blood serum and of
the cerebro-spinal fluid of patients suffering from active or latent
syphilis or parasyphilitic affections is a constant occurrence. I
wish to describe here briefly the technique of employing butyric
acid for the detection of this increase of protein.
Cerebro-spinal fluid. — One or two parts? of spinal fluid* are
mixed with five parts‘ of 10 per cent. butyric acid solution ° and are
lNoguchi: Jour. of Exp. Med., 1909, xi, p. 84.
20.1 or 0.2 c.c. are sufficient and convenient.
3 Must not contain blood.
40.5 c.c. for the quantities above specified.
5 Best in 0.9 per cent. salt solution.
52 SCIENTIFIC PROCEEDINGS (31).
heated over a flame to a brief boiling. One part’ of normal solu-
tion of NaOH is then added quickly to the heated mixture and
the whole is boiled once more for a few seconds. The presence
of an increased content of protein in a spinal fluid is indicated by
the appearance of a granular or flocculent precipitate which grad-
ually settles under a clear supernatant liquid. The intensity of
the reaction varies greatly according to the amount of the protein
which a given specimen contains, but the granular appearance of
the precipitate means a positive reaction for syphilis or parasyphi-
litic affections.
With normal or non-specific specimens there will be a slight
opalescence or sometimes a marked turbidity which, however,
does not settle out in several hours or even in 24 hours.
Blood serum. One part® of clear serum is mixed with nine
parts® of half saturated solution of ammonium sulphate. Upon
complete precipitation, the mixture is centrifugalized and the
compact deposit (globulin fractions) is separated from the super-
natant fluid by decantation. The deposit is then redissolved in
ten parts‘ of 0.9 per cent. salt solution, in which it easily dissolves.
The globulin solution thus obtained is ready for the acidification
with butyric acid. This is done by mixing one part of the solu-
tion with an equal part of Io per cent. butyric acid solution. It
is my custom to take 0.5 c.c. of each solution for mixing. On
standing, prompt and dense turbidity begins to appear in the tubes
containing the fractions of the serum of syphilitic or certain non-
syphilitic patients, while those from normal serum remain quite
clear after several hours, or show only slight opalescence with-
out precipitation.
A few words may be added here as to the results of investiga-
tions made with the above methods. About 250 specimens of
cerebro-spinal fluid, mostly of parasyphilitics, and about 300 speci-
mens of the blood of syphilitic and parasyphilitic patients, together
with many control specimens derived from patients with non-
syphilitic diseases and normal persons, have been studied.
1 Namely, 0.1 c.c. in this case.
2 Usually 0.5 c.c. is sufficient and convenient.
3 Namely, 4.5 c.c. in this instance.
45 c.c. in this instance.
Butyric REACTION FOR SYPHILIS. 53
Spinal fluid derived from parasyphilitic cases gives a typical
reaction, becoming granular in a few minutes and sedimenting in
from 10to 15 minutes. Cerebro-spinal fluid from cases of congeni-
tal, tertiary or secondary syphilis gives quite constantly a positive
reaction, but the intensity is usually less and two hours may be
required before the characteristic granular appearance becomes
manifest. Cerebro-spinal fluid from cases of cerebral or spinal
syphilis gives invariably a positive reaction. Negative reaction
was obtained with the spinal fluid from cases of acute anterior
poliomyelitis, epilepsy, alcoholic psychosis, dementia precox, senile
dementia, spastic paraplegia, lobar pneumonia and typhoid fever.
On the other hand, an abundant flocculent precipitate was usually
formed with the spinal fluid from cases of tubercular menin-
gitis, influenza meningitis, or epidemic cerebro-spinal meningitis.*
Cerebro-spinal fluid collected from two cases of hydrocephalus
also gave abundant precipitation. In all of these acute inflamma-
tory cases, except one of hydrocephalus, the Wassermann reaction
was, however, negative. A number of post-mortem spinal fluids
were examined with such results that it seems desirable to use the
method as a routine diagnosis for syphilis or parasyphilitic affec-
tions at autopsy. In the spinal fluid of two monkeys with active
experimental syphilitic lesion at the site of inoculation, which per-
sisted about 6 months, the reaction was positive.
Referring to the results of examinations of the blood serum,
it appears that the reaction is non-specific for syphilis, because a
similar reaction can be obtained in certain cases of tuberculosis,
carcinoma and Hodgkin’s disease.
In view of the constancy with which an abnormally high globu-
lin content attends the florid stage of syphilis and appears to be
present in an early primary stage, and is present in the late second-
ary and tertiary stages of imperfectly treated cases, one is thus en-
abled to follow the course of an anti-syphilitic treatment. Moreover
the butyric acid test is a more delicate indicator than the Wasser-
mann reaction, for the latter is very frequently negative in this latter
class of cases. Under conditions of adequate treatment, the globu-
lin fraction of the blood serum is not increased. A negative re-
4 These acute inflammatory conditions are quickly and perfectly excluded by clini-
cal and usual microscopical methods of diagnosis.
54 SCIENTIFIC PROCEEDINGS (31).
action with the butyric acid test indicates either the absence of
syphilitic infection or a successful cure of the disease. There is
no necessary relation between the Wassermann test and the quan-
tity of globulins in the luetic serum.
23 (361)
The quantitative separation of leucin from valin.
By D. D. VAN SLYKE and P. A. LEVENE.
[From the Rockefeller Institute for Medical Research. ]
Of the known amino-acids determined in semi-quantitative esti-
mations of final proteolytic products, leucin and its relatives, iso-
leucin and valin, have proven unusually difficult to prepare pure in
even approximately quantitative amounts. The separation of these
substances, because of their close physical and chemical similarity,
has offered almost insurmountable difficulties to previous investi-
gators. The acids form isomorphous mixtures which are absolutely
inseparable by crystallization ; and their esters have so nearly the
same boiling points that they cannot be fractionated by distillation.
Because of these difficulties, most investigators have not attempted
to separate the mixture, but have reported the entire mass as leucin.
Fischer’ states that all the figures reported from his laboratory for
leucin in protein hydrolyses refer to this mixture. Ehrlich? has
recently reported a method for separating the three substances, but
it involves a long process, large losses, and the racemization of the
isoleucin and valin.
We have been able to separate the leucin isomers readily from
valin in quantitative amounts. The method, which is very simple,
rests on the fact that if a molecular lead acetate solution is added
to an ammoniacal solution of the leucin-valin mixture, the leucins
are precipitated as analytically pure Pb(C,H,,O,N),. If too great
an excess of lead acetate is added, a portion of the valin may also
be precipitated. Consequently, the mixture is first analyzed, an
estimate of the proportion of leucin calculated from the carbon
content, and 20 per cent. excess of the theoretical amount of lead
1 Fischer: Unters. iiber Aminos., Polypeptide, und Proteine, p. 67.
2 Ehrlich: Bioch. Zeitschr., 8,'399, 1908.
SEPARATION OF LEUCIN FROM VALIN. 55
acetate used for precipitation. The valin is obtained analytically
pure by freeing the filtrate from lead with H,S, evaporating to dry-
ness, and washing with absolute alcohol. A slight amount of valin
dissolves, but is regained by evaporating the washings.
The following is a typical separation, the material being a por-
tion obtained by tryptic digestion of casein and fractional distilla-
tion of the amino-acid esters. 12.546 g. of the mixture was used.
Analysis showed 52.79 per cent. C, 9.55 per cent. H. The
mixture was suspended in 80 c.c. of boiling water. The flask was
removed from the flame and 20 c.c. of concentrated aqueous
ammonia added. The flask was loosely stoppered, and shaken
gently until the acids were dissolved. The leucin was then pre-
cipitated with 25 c.c. of M/1 lead acetate. The cooled solution
was filtered, and the precipitate washed with 50 c.c. of dilute
ammonia. 8.955 g. of lead salt, equivalent to 5.025 g. of leucin,
and 7.322 g. of valin were obtained analytically pure, making
12.347 g. from the original 12.546 g. Analytic data:
Lead salt: (1) 44.25 per cent. Pb; (2) 44.36 per cent. Pb.
Calculated for Pb(C,H,,O,N),, 44.29 per cent. Pb.
Valin: 51.44 per cent. C; 9.42 per cent. H. Calculated for
CATO, NG 5 t-24uper cent. € ; 9.47. per cent. Fi.
The specific rotation of the valin was [a]”pD-+ 26.51°.
The pure active substance has the rotation + 28.8°. The product
was partially racemized, the usual result of long tryptic digestion.
The lead-leucin salt contains a mixture of leucin and isoleucin.
Levene and Jacobs’ have shown that these isomers can be readily
separated in the absence of valin. The complete separation of the
two leucins from valin, therefore, renders the systematic separation
of all three comparatively easy of accomplishment. This is of im-
portance, not only for protein analysis, but also for the preparation
of pure active valin and isoleucin, a task which has hitherto been
extremely difficult.
The work will be reported in full in the Biochemische Zeitschrift.
1 Levene and Jacobs: Bioch. Zettschr., 9, 231, 1908.
56 SCIENTIFIC PROCEEDINGS (31).
24 (362)
Further studies on the constitution of inosinic acid.
By W. A. JACOBS and P. A. LEVENE.
[from the Rockefeller Institute for Medical Research. |
In a former article’ on the constitution of the inosinic acid ob-
tained from beef extract, we have demonstrated that by acid hydro-
lysis there is formed an intermediate product, a pentose phosphoric
acid, which we isolated as a well crystallized barium salt. From
the fact that this body showed strong reducing properties, it is
evident that the aldehyde group is free, and the phosphoric acid is
bound, ester-like, on one of the hydroxyl groups of the pentose.
As the inosinic acid itself does not reduce Fehling’s solution, it is
at once obvious that the hypoxanthin contained in its molecule
must be bound as in a glucoside on the aldehyde group. We also
mentioned that upon alkaline hydrolysis we were able to isolate a
small quantity of a silver compound of a purin-pentose complex
which gave all the qualitative tests for such a body.
Meanwhile it came to our notice that Haiser and Wenzel? had
obtained a compound of hypoxanthin and a pentose from karnin to.
which they gave the name zzostn. We have succeeded, by heating
the barium salt of inosinic acid in water solution in a sealed tube
at 125°—130°, in obtaining a mixture from which we have isolated
a substance which in all respects corresponds with Haiser and
Wenzel’s inosin.
From this substance we obtained a levorotatory pentosazone.
Furfurol distillation yielded the phloroglucid required by a pentose.
1 Levene and Jacobs: Berichte d. deut. chem. Gesell. , 41, 2703 (1908).
2 Haiser and Wenzel: Monatshefte fiir Chemie, 29, 157 (1908).
PERMEABILITY OF THE CELL PLAsMA MEMBRANE. 57
25 (363)
The significance of changes in the permeability of the plasma
membrane of the living cell in the processes of
stimulation and contraction.
By RALPH §. LILLIE.
[From the Physiological Laboratory, Zoélogical Department, Unt-
versity of Pennsylvania. |
The general facts indicating that stimulation is dependent on
a temporary increase in the permeability of the surface layer or
plasma membrane of the irritable element are as follows :
A. The nature of the motile process in such plants as Mimosa,
Dionea and the Cynarez, where the movement depends on a sud-
den loss of turgor. Such a change indicates either (1) a sudden
decrease in the concentration of the osmotically active substances
within the cell due to chemical action, or (2) a sudden loss of
impermeability relatively to the osmotically active substances.
The latter explanation is almost certainly the correct one.
B. The identity of the electrical change accompanying stimu-
lation in motile plant cells with that observed in irritable animal
tissues (Burdon-Sanderson), indicating a fundamental similarity in
the conditions of stimulation in the two classes of organisms.
C. The fact that the post-mortem increase in permeability is
accompanied by contraction in muscle cells; the same is, of
course, true of motile plant organs where the movement depends
on loss of turgor.
D. The nature of the electrical change accompanying stimu-
lation. If the irritable element represents a concentration-cell in
which a semi-permeable membrane (the plasma membrane) greatly
diminishes the velocity of the anion, while leaving that of the
cation practically unaltered (Ostwald-Bernstein membrane theory),
any marked increase in permeability relatively to the anion must
result in a fall of the potential difference between exterior and
interior of the irritable element. Such an electrical change actu-
ally occurs on death or injury of the element ; also momentarily
during stimulation. A demonstrable increase in permeability
occurs at death; inferentially, therefore, the same change occurs
during stimulation.
58 SCIENTIFIC PROCEEDINGS (31).
E. The fact that an irritable tissue loses irritability for a variable
usually brief) period after stimulation (refractory period), — indi-
cating that at that time the property of semi-permeability, on which
electrical stimulation depends (Nernst), —is temporarily lost.
The special observations presented in this paper are as follows:
1. Arenicola larve are stimulated intensely by pure isotonic
solutions of various salts (NaCl, KCl, NH,Cl, LiCl, SrCl,, BaCl,),
contracting to half their length for several seconds when first in-
troduced into the solution. At the same time a yellow pigment
contained in the cells of the organism diffuses freely to the exterior
and colors the solution.
2. Solutions which do not produce this strong initial contrac-
tion do not cause such loss of pigment. Isotonic CaCl, and MgCl,
(especially the latter) are instances. In these solutions the muscles
lose the power of contraction and the organism becomes stiff and
motionless (though still propelled by the cilia which remain
active). Addition of small quantities of CaCl, to a NaCl solution
prevents the strong initial contraction and loss of pigment
(antitoxic action).
3. MgCl, and similarly acting solutions appear to decrease the
permeability of the tissues, and so prevent the ionic transfer on
which stimulation depends. The general action of anzsthetics
consists in decreasing the normal permeability ; stimulating agencies,
on the other hand, have the reverse effect.
4. Strong solutions of fat-solvents (chloroform, ether, benzol,
(etc.) produce a contraction of the muscles accompanied by loss of
pigment, even in 7/2 MgCl,. This effect is to be referred to an
alteration of the lipoid substances in the plasma membrane. Such
alteration, if slight, decreases permeability (anzsthetic action in low
concentrations) ; if extreme, it produces the reverse effect, with re-
sulting stimulation.
5. The hypothesis is presented that the chemical effect of the
above changes in permeability depends essentially on their influence
in varying the rate at which carbon dioxid leaves the cell. The
velocity of the oxidative energy-yielding processes whose end-
product is CO, is thus varied with the rate of removal of this latter
substance from the system ; this velocity is accordingly increased
during the increased permeability of stimulation, and is decreased
LysINns, PRECIPITINS, AGGLUTININS., OPSONINS. 59
during anesthesia or inhibition, This view is supported by a con-
sideration of the electrical changes accompanying inhibition and
stimulation, respectively (‘ positive’’ and “ negative variations’’).
26 (364)
On the relative concentration of lysins, precipitins, agglutinins,
opsonins and related substances in the different body
fluids of normal and immune animals.
By F. ©. BECHT and J.R. GREER. (By invitation.)
[from the Hull Physiological Laboratory of the University of
Chicago. |
The present work was suggested by some of our previous
work with Prof. Carlson on the physiology of lymph. It was
suggested that it would be of profit to establish the differences
between serum and the other body fluids in their content of anti-
bodies of various kinds in normal and immune animals, with the
hope that it would have some bearing upon the problem of lymph
formation, and also upon the origin of these antibodies. Thus far
the hemolysins, hemagglutinins, bacterial agglutinins, bacterial
opsonins, hemopsonins, and precipitins have been studied in the
serum, neck lymph, thoracic lymph, pericardial fluid, cerebrospinal
fluid, and aqueous humor. The bacterio-lysins are also under
consideration.
The results with normal dogs have been the following : Hemo-
lysins are found in the serum, thoracic lymph, and neck lymph in
the normal animal. Serum and thoracic lymph contain them in
almost equal quantities, with a slight balance in favor of the serum.
The hemolytic power of the neck lymph is much lower than that
of the serum, and is almost entirely wanting in the lymph which
is secured without massage. In two of seven cases there was a
small amount of hemolysis in the pericardial fluid, in the remain-
ing cases there was no laking when the fluid was free from ery-
throcytes. There is no hemolysis in the cerebrospinal fluid, ex-
cept in one case where there was a trace of free hemoglobin. There
was no hemolysis in the aqueous humor. The hemagglutinins
run parallel with the hemolysins except that they act in higher
dilutions than the latter.
60 SCIENTIFIC PROCEEDINGS (31).
Bacterial agglutinins are found in the serum, thoracic lymph,
and neck lymph. The two lymphs were of equal strength, and
the serum was approximately ten times as strong. Pericardial
fluid, cerebro-spinal and aqueous humor were entirely lacking in
these anti-bodies. No precipitins for rabbit serum are found in
any of the body fluids of the normal dog.
The hemolytic power of the serum and thoracic lymph of dogs
immune to typhoid is slightly higher than that of the same fluids
of the normal animal. No increase has been noted in the other
fluids examined. The hemagglutinating power is increased in the
serum, neck lymph, thoracic lymph, and pericardial fluid, particu-
larly in the latter. The bacterial agglutinating power of the serum,
neck lymph, and thoracic lymph is much increased. The pericardial
fluid and aqueous humor are inactive or at most show only a trace.
The cerebro-spinal fluid has not yet been tested.
In dogs rendered immune to rabbit blood we have not yet
noted any very marked increase in hemolysins over those of the
normal animal. There was a marked increase of the hemaggluti-
nins in the serum, neck lymph and thoracic lymph, and in one
case in the pericardial fluid and aqueous humor. Immunization to
rabbit blood has no effect on the bacterial agglutinins. The injec-
tion of defibrinated rabbit blood did not produce precipitins for
rabbit serum in any of the body fluids of the animal. The work
on bacterial opsonins and hemopsonins in both normal and immune
animals has been entirely unsatisfactory.
The work is being continued and extended to cats and rabbits.
Later, lymph will be collected from various organs and extracts
from various tissues made with the hope of finding the source of
these antibodies. Parallel experiments are being made on the
number and kind of leucocytes in the various body fluids.
Drerary CONDITIONS ON PHYSIOLOGICAL RESISTANCE. OI
27 (305)
Studies of the influence of various dietary conditions on phys-
iological resistance. I. The influence of different pro-
portions of protein in the food on resistance to
the toxicity of ricin and on recupera-
tion from hemorrhage.'
By NELLIS B. FOSTER.
[fromthe Laboratory of Biological Chemistry of Columbia Univer-
sity, at the College of Physicians and Surgeons. |
It was planned to compare, in these experiments, the behavior
of two sets of dogs under variously induced pathological conditions.
The experiments were conducted on two pairs of dogs, each pair
being kept under identical conditions, so far as they could be con-
trolled, except with respect to the food. One animal of each pair
was given /zbeval amounts of protein in the daily diet, the other
received barely sufficient protein to provide for the necessary nitrog-
enous metabolism, the remaining ingredients of the food for each
animal being uniformly equal to the daily amounts ordinarily given
per kilo, in this laboratory, to perfectly healthy dogs. No attempt
was made to maintain equal caloric values in the diets. In each
experiment the animal was fed on a diet of hashed lean meat,
cracker meal and lard, the meat being gradually increased or dimin-
ished to a high or low plane, according to the plan in each case
and before the particular pathological condition was induced.
It was a part of the plan of the work to keep the animal in
each instance on a high or low plane of protein nutrition for a con-
siderable period before the pathological phase was brought into the
experiment. Such a course is not only desirable but essential,
for if, as has been claimed, a diet rich in protein exercises a dele-
1 This study was begun during the summer of 1905, at Dr. Gies’ suggestion and
thas been carried forward from time to time under his direction and with the aid of a
grant from the Rockefeller Institute. I am also indebted to Dr. Flexner for impor-
tant suggestions.
The work has been frequently interrupted by researches in other directions and
has been beset by unusual experimental difficulties. Although planned to be the first
of a series of investigations, in point of publication it is the second from this laboratory
on the general subject stated above. See Dissertation by Welker, Columbia University,
1908. It is Dr. Gies’ intention to continue investigation along these lines,
62 SCIENTIFIC PROCEEDINGS (31).
terious influence on the animal organism, that effect is not ordi-
narily an immediate one, but rather the slow perversion of organic
function induced by chronic misuse. Again, if benefit results from
a special diet under any condition, time may be required to make
that benefit clearly distinguishable. The dogs used in these ex-
periments were under daily observation for periods of at least two
months and in several cases for four months before inauguration
of the pathological phase.
In testing the physiological resistance of the dogs in these
experiments, use was made of two methods: (1) hypodermic in-
jection of the toxin, ricin; and (2) the withdrawal of definite
amounts of blood from one of the large arteries. Ricin was
selected because it produces some symptoms which are analogous
to those of acute infections, namely, fever, cardio-vascular embar-
rassment and marked prostration. As in the case of infections,
ricin also causes noticeable stimulation of metabolism, as is shown
by the increased elimination of nitrogen and sulfur after its injec-
tion. The disadvantages in its use are that immunity quickly
arises and that the material is so very toxic that no latitude is per-
mitted for minor individual peculiarities in animals. By experi-
ment I milligram per kilo was found to be the maximum non-
lethal dose for the commercial sample used.
EXPERIMENTS WITH RICIN.
Six dogs were subjected to inoculation with ricin. Of these,
three were on a high plane of protein nutrition, the daily amount
of food containing uniformly in each case 1.4 to 2.0 grams of N
per kilo of body weight. After inoculation with ricin (1 mg. per
kilo), all of these three specially well-fed animals died. A fourth
dog was on a medium plane of protein nutrition, 1.1 gram. of N
per kilo, and this dog survived the inoculation. Of the two remain-
ing animals of this group, both on a low plane of protein nutri-
tion, one died and one survived. The dog which survived received
the protein equivalent of 0.35 gram of N per kilo of body weight
during the experimental period and the one that died, 0.37 gram
of N per kilo.
In order to test the effect of exercise, the former of these two
dogs, after the completion of the above mentioned experiment, was
DiETARY CONDITIONS ON PHYSIOLOGICAL RESISTANCE. 63
allowed to run at large in the laboratory for six months (July 17,
1906, to Jan. 10, 1907), no effort being made to collect excretions
for analyses. During this time the protein content of the diet was
gradually dropped to an equivalent of 0.27 gram of N per kilo.
The animal was painfully thin but appeared to be in excellent
health. She was lively during the warm months of summer and
autumn, but with the advent of colder weather she became less
and less active and lost weight, although the laboratory was
adequately heated. It finally became evident that the diet must
be changed. The portion of meat in the diet was gradually in-
creased, but a diarrhea supervened, which proved fatal.
HEMORRHAGE EXPERIMENTS.
Although hemorrhage is one of the crudest factors for the
determination of physiological resistance, it has, nevertheless, the
advantage of being a real test, inasmuch as the production of new
blood is an exemplary reparative process. Hemorrhage, unlike
the injection of ricin, can also be gauged, to some degree at least,
to meet the individual resistance of the animal, as I have found in
these experiments. The procedure was uniform throughout this
part of the work. At the first hemorrhage from each animal, the
endeavor was made to take blood equivalent to 4 per cent. of the
body weight. After an interval of four days this procedure was
repeated; and again eight days after the initial hemorrhage,
making three hemorrhages at successive intervals of four days.
All operations were conducted under ether narcosis.
Six dogs were experimented on in this manner, three upon high,
three upon low, planes of protein nutrition, and four survived. Of
the two which died, one had been on a low plane of protein nurition
(0.4 gram of N per kilo) and one ona high nitrogen plane (1.4 gram
per kilo). Control animals on more extreme dietary conditions,
withstood the effects of greater hemorrhages. Therefore, it is
evident, I think, that these two deaths must be assigned to reasons
outside the realm of this research. In the case of the dog on the
high plane of protein nutrition, the cause is not far to seek; the
dog was a collie, apparently pretty well bred, and it is a matter of
common knowledge that these dogs have very low resistance.
The dog that died on a low plane of protein nutrition was a fox
terrier mongrel.
64 SCIENTIFIC PROCEEDINGS (31).
I. Outlines of the Experiments.
Nature of the experiment.
Dog No. N of food per kilo, Ricin. Hemorrhage.* o Raetle
Brame; 1 mg. per | Per’cent. of body weight.
kilo of body
weight. I 2 3
I 0.35 ae one aes ... | Very sick:
Survived.
II 1.10 a Survived,
III 0.37 — Died.
IV 1.5 + Died.
Vv 3.37 —for I mo. + Over fed :
0.51+—for 20 ds. Died.
VI 0.40 4- a0 ae a07 Died.
VII 0.44 pe Ba8 2.5 eos Died.
VIIl B57) a 4.0 | 4.3 3.1 | Survived.
IX 1.4 ee 3.8 2.3 0.6 | Died.
- 0.35 ee 4.2 4.0 4.0 | Survived.
0.81 6 4 3.7. | Survived.
XII ay Pops 0.23 ie a5 2.9 | Survived.
* The numerals above the figures for percentage indicate the number of the hemor-
rhage in the series applied to the dog in question.
+ The food was dropped to this equivalent at once after two days of fasting follow-
ing pronounced gastro-intestinal disturbances.
Il. General Summary.
Survived, 2
High plane of protein nutrition — 6 dogs
Died,
Totals (I — XII) 5 ist
urvive
Low “cc “e “ 5 dogs
Died,
High plane of protein nutrition — 3 dogs
Died,
Ricin experiments
Survived, 1
Low uC Ke Ke 2 dogs
Died, I
Survived, 2
High plane of protein nutrition — 3 dogs
|
Loe
|
Died, I
Hemorrhage experiments
Survived, 2
Low e 66 as 3 dogs
Died, I
In order to reduce individual idosyncrasy to its lowest terms
the last experiment of the series was conducted on two dogs from
DieTARY CONDITIONS ON PHYSIOLOGICAL RESISTANCE. 65
the same litter. These animals were half-breed Scotch terriers,
about two years old, that had lived together under the same con-
ditions until they were brought to the laboratory. One was grad-
ually accustomed to a diet containing only 0.2 gram of N per kilo,
the other to food containing 0.8 gram of N per kilo. As a matter
of further interest the opsonic index of these dogs was several
times estimated, using Staphylococcus aureus that had been ren-
dered pathogenic to dogs. This index was, and remained, the
same for both animals. The final hemorrhages were survived by
both animals and, so far as one might estimate, about equally well.
The accompanying tables present an outline of the experi-
ments and show details not mentioned above.
yin oUt ih
a AGC
Lt ia
nay
thee :
wi
lbs i i ‘ ip i
be , fi
Tine MARU LSMON Pye i PY, te ra
Thirty second meeting.
New York University and Bellevue Hospital Medical College.
February 17, 1909. President Lee in the chatr.
28 (366)
A method for the direct observation of normal peristalsis
in the stomach and intestines.
By YANDELL HENDERSON.
[Zrom the Physiological Laboratory of the Yale Medical School. |
When the abdomen is opened peristalsis ceases. Because of
this fact all previous investigators have found difficulty in making
observations directly upon the motility of the stomach and intes-
tines. The peristalsis which has been seen differs considerably
from that which the radiographs of Cannon have shown to be the
normal movements.
Failure of peristalsis, as Meltzer especially has pointed out, is
one of the characteristic and important phenomena of surgical
shock. I have advanced the hypothesis’ that the cause of shock
is acapnia. By applying this theory to the problem of maintain-
ing normal peristalsis after laparotomy, the following simple and
effective method was devised. After the administration of a
moderate dose of morphin, the animals (dogs of about 10 kilos)
were anesthetized with chloroform. So far as possible the hyper-
pnoea of the initial stage of anesthesia was avoided. The ab-
domen was laid open the entire length of the mid line. The omen-
tum was cut out, and the viscera moved sufficiently to bring into
view the upper colon, lower ileum, and the greater curvature of the
stomach from the pre-antral groove to the pylorus. A sheet of
transparent celluloid was inserted under the body wall and over
the viscera; and the air in the space back of this window was
washed out with a stream of carbon dioxide gas. To the trachea
was attached a tube 15 mm. in diameter and 2 meters in length.
Blood gas analyses showed that the blood-gases were thus main-
1Y, Henderson: American Journal of Physiology, 1908, xxi, 126.
(67)
68 SCIENTIFIC PROCEEDING (32).
tained normal, — not asphyxial in respect either to the oxygen or
carbon dioxide contents. When the stomach was distended with
air, and the large intestine and lower ileum with bread mush,
movements in these three parts of the alimentary canal were seen
identical with those shown by the radiographs of Cannon. In the
stomach a deep constriction developed at the pre-antral groove
every 15 seconds and moved toward the pylorus where it disap-
peared as its successor was developing. In the colon there was
active anti-peristalsis. In the ileum vigorous rhythmic segmenta-
tion was seen.
In other experiments I have found that animals under ordinary
operative conditions develop, and remain in, a state of acapnia.
This lowered carbon dioxide content of the blood and tissues, by
inducing loss of tonus, is the cause of the failure of peristalsis after
laparotomy. The essential point in the above described method
is the prevention of acapnia.
29 (367)
Studies on the effects of carbon mon-oxide poisoning.
By A. I. RINGER. (By invitation.)
[From the Physiological Laboratory of the New York University and
Bellevue Hospital Medical College. |
If an animal be allowed to breathe an atmosphere containing
carbon mon-oxide, it will soon present a series of circulatory,
respiratory, cerebral and metabolic disturbances, which, if carried
too far, will result in death. These disturbances are believed to
be brought about by the reduction of the oxygen-carrying capacity
of the blood, due to the formation of the relatively stable carbon
mon-oxide-hemoglobin, thus producing a state of progressive as-
phyxiation of the tissues. The severity of these disturbances de-
pends entirely upon the degree of asphyxiation; and, with the
exception of some individual peculiarities in a few of the twenty-
one dogs that I have experimented upon under anesthesia, all pre-
sented the same symptoms at the same stage of asphyxiation.
In nine experiments the following subjects were studied in
their relationship to the degree of saturation of the hemoglobin
with carbon mon-oxide: (1) the pulse, (2) the blood pressure,
EFFECTS OF CARBON MON-OXIDE POISONING. 69
(3) the number of respirations per minute, (4) the volume of air
respired per minute; in twelve experiments: (1) the physical
symptoms, (2) the point of onset of coma, (3) the point of death.
As soon as the animal begins to breathe the carbon mon-oxide
there is an immediate acceleration of the pulse, which steadily
gains in frequency until 45-50 per cent. of the hemoglobin is
saturated with carbon mon-oxide. Then the pulse rate is at its
maximum. After that it declines gradually until a point is reached
between 71-74 per cent. of carbon mon-oxide saturation, when
the pulse rate falls abruptly and the heart ceases to beat.
The blood pressure in about half the cases was found to go
gradually downward in spite of the markedly increased rate in the
heart beat. In the rest of the cases there was a preliminary rise
in pressure of about 10-15 mm. of Hg, which reached its maxi-
mum when 45-50 per cent. was saturated with carbon mon-oxide.
This was followed by a gradual decline, until when about 67 per
cent. of the hemoglobin was saturated, there was an abrupt fall in
blood pressure.
The number of respirations per minute, taking two character-
istic examples, was found to increase from a normal of 19 and 22
to 32 and 45, respectively, when about 50 per cent. of the hemo-
globin was saturated with carbon mon-oxide. In other cases there
was no increase in the rate of respiration at all, but there was a
marked increase in the depth of each inspiration. The volume of
air respired per minute, however, increased in all cases as soon as
the animal began to breathe the carbon mon-oxide. It presented
a curve with an ascending and descending limb. The maximum
ventilation of the lungs took place when about 45 per cent. of the
hemoglobin was combined with carbon mon-oxide. After that it
declined gradually. At about 65 per cent. saturation, however,
breathing became irregular, sometimes of the Cheyne-Stokes
variety. Respiration always stopped about one to three minutes
before the heart ceased beating.
When about 40 per cent. of the dog’s hemoglobin is deprived
of its oxygen carrying capacity, the animal begins to get weak.
It cannot stand on its legs. It isin a state of general indifference.
It does not partake of any food or drink, though it may be hungry.
It is seized with vomiting and occasionally has convulsive spells.
70 SCIENTIFIC PROCEEDINGS (32).
It responds to a call very slowly, and sometimes falls into a sleep,
from which it is aroused with difficulty. Actual coma sets in at a
point immediately following the decline in the pulse rate, or when
about 50 per cent. of the hemoglobin is saturated with carbon
mon-oxide. This has been found to be constant in all cases.
Death also takes place in all dogs at about the same point of
saturation. Nota single one reached the 75 per cent. mark. All
died between 71 and 74 per cent. of saturation of the hemoglobin
with carbon mon-oxide. Neither size, weight nor strength seemed
to influence the point of death.
From the foregoing it is seen that the symptoms of carbon
mon-oxide poisoning may be conveniently divided into three
stages: First or Compensatory Stage, which lasts up to 50 per
cent. saturation; second or Stage of Depression which lasts up to
about 70 per cent. saturation; third or Stage of Collapse.
SYMPTOMS OF THE FIRST OR COMPENSATORY STAGE.
Gradual increase in pulse rate.
High blood pressure.
Spasmodic attacks of vomiting.
Slight dyspnoea at first — more marked at the end.
Muscular weakness.
Drowsiness, indifference and deep sleep from which dog can be
aroused.
Om pw YS &
SYMPTOMS OF THE SECOND OR STAGE OF DEPRESSION.
1. Ushered in by clonic convulsion and muscular rigidity which
lasts for a few minutes.
2. Deep narcosis from which animal cannot be aroused.
3. Pulse declines gradually in rate, tension and volume.
4. Respiration either rapid and shallow, or slow and deep; it is
more or less regular.
5. Absolute loss of sensation.
SYMPTOMS OF THE THIRD OR STAGE OF COLLAPSE.
Pulse slow, irregular and of low tension.
Respiration irregular.
Loss of tone of sphincters.
Conjunctival reflex lost.
Death due to respiratory paralysis.
wm Bw NN
EFFECTS OF CARBON MON-OXIDE POISONING, 71
| Typical experiment of first series.— February 19,1908. Dog’s weight 9.7 Kg.
Ether anesthesia.
Time. Respiration,
2.15 P. M 22
Zeree 18 I per cent. CO respired
2535m «fi 24
2.50 ‘<6 36
3-058 ff 40
Cpe, 45
S235) ae 41
3:45) 5 40
B50) 6 36
Spey fe 32
BS Sin is 8 irregular
4.05 6c Io “c
4.08 Death
& fe)
o a 2D
Ep A i
am Volume of air Sa
Palen Al oiedpe |. deg
7 & minute. $ 2
BA 5S
(23) 0 Fs
140 90 1,750
148 go 1,925
164 92 2,000 20
180 96 2,125
204 | 104 2,250 47
194 94 2,250
166 | 88 2,100 54
120 72 1,925
82 62 1,650 66
56 40 1,175
68 | eae 75° 73
Typical experiment of second series.— March 2, 1908. Dog’s weight 6.6 Kg.
Dog placed in air-tight cage through which the gas mixture was driven by means
of .bellows, operated by a water pressure engine. The ventilation of the cage was
5,000 c.c. of air per minute.
Time, Respiration. Pulse. General condition.
10.30 A. M. | 16 104 | Dog in good condition.
TOss5e ° 0.4 per cent. CO respired
TROON ES 16 104 | Dog comfortable and quite active.
11.45 6c 16 116 “c “6 73 66 “ec
12.00 “ec 18 124 “cc “c “ec 6c ce
TiZesOn Lee Mo eX: 140 | Lies quietly; slightly drowsy.
T2rAGe aes 21 170 | Drowsiness marked.
rifers) UG 18 182 | Slight convulsion and vomiting.
20m iS 16 208 | Responds to sensory stimulus after
long latent period.
Hegiey 1 16 192 | Convulsions of clonic type.
Pain 0 17 196 | Slightly comatose; when called he
only opens his eyes.
2:05, <6 16 180 | Coma quite deep.
Xo) WG — 166 | All muscles and sphincters relaxed.
ZAG te — — | Taken out of cage. Blood sample
shows 52 per cent. of the Hb
saturated with CO. Dog placed
in warm place near radiator.
Braineemss Respiration slow and deep, 10-12
per minute.
4.00 Ԥ Dog began to move about.
A250 at Able to stand up and walk but falls
frequently, due to lack of coérdi-
nation.
alOnn se Walked about fairly well, but very
slowly.
Next morning
Dog perfectly well.
72 SCIENTIFIC PROCEEDINGS (32).
Experiments have also shown that a dog with as much as 69
per cent. of hemoglobin tied up with carbon mon-oxide which
corresponds to the end of the second stage, can be resuscitated if
proper treatment be instituted promptly.
30 (308)
Intestinal excretion during diarrhea.
By GEORGE B. WALLACE and HUGO SALOMON.
[From the Laboratory of the Von Noorden Clinic, Vienna.)
Analyses were made of the faeces of a number of patients with
diarrheas of different origin. During one period of observation
the patients were on the Schmidt-Strassburger diet, during a sec-
ond period the diet consisted of 250 grm. sugar daily. In those
cases where there was present an ulcerative process in the intes-
tine — tuberculosis, carcinoma—the amount of nitrogen in the
feces was markedly increased — being from 1.7 to 4. grm. daily
on the sugar diet. In cases of severe catarrhal inflammation it
was not over 1.5 grm.; in light catarrh it was within normal lim-
its. The fat and carbohydrate elimination showed no such strik-
ing differences although it was highest where an ulcerative condi-
tion was present. Of the inorganic constituents the alkali excre-
tion was fairly parallel to that of nitrogen. The other inorganic
constituents were increased by the ulcerative processes but in
some instances were increased equally where ulcerations were
absent.
The most striking result of the analyses is the high nitrogen
excretion which occurs in ulcerative processes in the intestine.
31 (369)
The vascularity of the kidney as influenced by sensory
‘ impulses.
By R. BURTON-OPITZ and DANIEL R. LUCAS.
[From the Physiological Laboratory, Columbia University. ]
Quantitative determinations of the blood-flow through the left
kidney were made with the aid of the stromuhr of Burton-Opitz.
On stimulation of the central end of the sciatic nerve, a slight de-
INFLUENCE OF TEMPERATURE ON HEMOLYSIS. 73
crease in the vascularity of this organ was observed. This decrease
apparently followed a tonic contraction of the blood vessels and
not a true constriction as is produced, for example, by stimulation
of the corresponding splanchnicus major. It seemed to be merely
a tonic reaction of the kidney against the high systemic blood
pressure which follows stimulation of the sciatic.
Similarly, the application of cold compresses across the back
in the region of the kidneys, reduced the blood-flow through this
organ, while hot compresses increased the flow. As the tempera-
ture of the organ itself, or of the tissues in its immediate vicinity,
was not changed by the compress, these variations in the vascu-
larity of the kidney must have been produced reflexly.
Stimulation of the distal ends of the vagi, below the point
where the cardiac branches are given off, did not change the blood
flow. The vagus, therefore, appears to carry no efferent vaso-
motor impulses to the kidney.
32 (370)
The influence of temperature on hemolysis in hypotonic
solutions.
By PAUL A. LEWIS.
[From the Antitorzin Laboratory of the Massachusetts State Board
of Flealth. |
Hemolysis in hypotonic solutions is progressively increased as
the temperature is decreased from thirty seven degrees centigrade
to five degrees centigrade. In order to bring out this fact, that
modification of Hamburger’s method for testing the resistance of
erythrocytes, which was introduced by Theobald Smith, was used.
The solutions were brought to the required temperature and then
the corpuscles were added. The differences are present both at
the points of beginning and complete hemolysis, but are only well
marked at the intermediate points. This accounts for results
obtained by Hamburger (1887 and 1903) who held that tempera-
ture within these limits was without influence.
The effect of temperature is the same whether sodium chloride
or cane-sugar is used to give tonicity to the fluid. The corpuscles
74 SCIENTIFIC PROCEEDINGS (32).
of the horse, rabbit, guinea-pig, calf, and sheep are equally affected.
The differences become well marked after a few minutes’ exposure
to the different temperatures, and thereafter bringing them to one
temperature fails to equalize the hemolysis even after many hours.
The effect, then, is on the corpuscle rather than on the surround-
ing fluid and is exerted chiefly in the first moments of exposure.
Temperatures above 37° C. act variously according to the
particular species whose blood is used. Horse corpuscles give
distinctly more hemolysis at 42° C. than at 37° C. Thecor-
puscles of the guinea-pig and the calf give still less hemolysis at
43° C. than at 37 °oG:
33 (371)
A carcinoma of the rat (Flexner-Jobling) considered from
the standpoint of immunity.
By F. P. GAY.
[From the Laboratory of the Cancer Commission of Harvard
University. |
Experiments have been in progress for the last year and a half
with the Flexner-Jobling rat tumor for the purpose of gaining some
insight as to the normal and artifically produced conditions of
resistance to this tumor.
The tumor as originally described by Flexner and Jobling was
a sarcoma and later became carcinomatous in structure. It has
shown no marked variations in histological structure during the
eight generations which we have cultivated it. White rats from
different dealers varied considerably in their susceptibility to in-
oculation with this tumor. Animals from the most susceptible
source gave 100 per cent. of ‘“‘takes’’ whereas the next most sus-
ceptible strain gave only 50 per cent. Following inoculation into
the region of the axilla metastases occur regularly in the lungs
but rarely in the adjacent lymph-nodes. The time of occurrence
of metastases would seem to be relatively constant in the most
susceptible rats. Metastases occur later and at more irregular
intervals in less susceptible animals.
The tumor may be transplanted from the metastases and such
“‘metastatic’’ tumors would seem after several generations to have
INFLUENCE OF TEMPERATURE UPON PEPSIN. 75
become somewhat more “virulent” in that such tumors grow
more rapidly and produce more extensive metastases of a more
epithelial type.
Animals that have failed to take the first inoculation of tumor
are very seldom susceptible to a second or third implantation.
The blood serum of such refractory animals gives no reaction of
fixation with cancer extract, and when injected simultaneously
with cancer in susceptible rats leads to no prevention of the growth
of the tumor. The refractory blood, however, when injected pre-
viously to or at the same time with the tumor in naturally insus-
ceptible rats gives a larger percentage of ‘takes’”’ than in control
animals.
If a tumor is removed during the “ premetastatic’’ period a
secondimplanted tumor seldom grows. Subsequent to this period
a second implanted tumor does grow.
When a primary growing tumor is left and a second implanted
during the premetastatic period, not only does the second tumor
fail to grow but the first tumor entirely disappears in many in-
stances. In cases in which the resorption of original tumor was.
incomplete, from lack of sufficient time the primary tumor showed
regressive changes in the nature of cell degeneration or a marked
increase of connective tissue stroma.
A reaction of fixation was found with the blood of a few ani-.
mals with tumor during the premetastatic period but never during:
metastatic period. The premetastatic period then would seem to
be characterized by an active defence on the part of the animal
body and during this period reimplantation of tumor increases this
resistance to such an extent that the original tumor is destroyed.
When this period is passed metastases occur and a second im-
planted tumor grows.
34 (372)
Influence of temperature upon pepsin.
By A. 0. SHAKLEE.
[From the Laboratory of the Department of Physiology and Phar-
macology of the Rockefeller Institute for Medical Research. ]
While studying the destruction of pepsin by shaking pepsin
solutions it was thought essential to make some study of the spon-
76 SCIENTIFIC PROCEEDINGS (32).
taneous deterioration that was seen to take place in solutions stand-
ing at corresponding temperatures, and also at body temperature.
One per cent. solutions of a commercial pepsin in hydrochloric
acid (0.1 per cent., 0.25 per cent. and 0.5 per cent.) were kept in
glass bottles at approximately the following temperatures: 5° C.,
20° C., 33° C., 37° C. From time to time samples were tested
by Fuld’s method, modified somewhat to decrease the error. The
following results were obtained for solutions in 0.25 per cent. hy-
drochloric acid at 37° C.:
Duration of heating DEE
be 7 . Te
in days. t(1—4)
0.5 days. 19.5 per cent. -48
0784 31 Ls 53
Os 35 . 54
ae SOS far 54
2.0 ‘ 53 oe -56
GO 73 - 54
hey, 80 oe 50
230 es 86 Ot 51
These results seem to indicate that the destruction of pepsin
under the conditions described takes place in accordance with the
law of the bimolecular reaction, and the formula which seems to
apply is:
X
"Cie ola
where X represents the destruction, in hundredths of the original
in time 4, and A represents a constant.
35 (373)
Synthesis of uric acid.
By NELLIS B. FOSTER and JAMES C. GREENWAY.
[from the Laboratory of Biological Chemistry of Columbia Univer-
sity, at the College of Physicians and Surgeons, and the
Wards of the New York Hospital. |
The possibility of a synthesis of uric acid from lactic acid and
urea has been considered by a number of investigators, but when
these substances are taken by way of the stomach, all researches
alike have failed to disclose any evidence of uric acid synthesis in
SERUM DIAGNOSIS OF SYPHILIS. Tix
mammals. The object of this study was first, to repeat the earlier
experiments of Minkowski; second, to find out if slight changes
of method would perhaps serve to show a synthesis of uric acid ;
and third, to consider the problem experimentally in relation to a
man suffering from chronic gout. In gout it is possible that an
abnormal synthesis of uric acid occurs, and also, since the uri-
colytic powers of the gouty organism are less active than normal,
a synthesis masked in a normal person might be evident in a per-
son suffering from gout.
The results of the experiments may be briefly summarized as
follows : when lactic acid is administered to a normal man who has
been fed on apurin free diet, there is no resulting increase of uric acid
in the urine, even when the amounts of lactic acid are very large
—. é., 20 grams ina dose. Ina dog ona purin free diet (milk,
eggs, and rice), following the hypodermic injection of lactic acid,
and of lactic acid and urea, there was in both instances a slight
increase in the percentage of total nitrogen excreted as uric acid.
The absolute amounts were also slightly increased as were those
of allantoin. These figures are difficult to interpret and we are
not prepared to assert without further investigation that there is a
synthesis of uric acid in the manner described.
In a case of chronic gout the effects of the lactic acid and urea
were entirely obscured by the irregularity of nitrogen excretion ;
periods of nitrogen retention and excretion making it impossible
to estimate the effects of the treatment.
36 (374)
Some critical considerations on the serum diagnosis of syphilis.
By HIDEYO NOGUCHI.
[From the Rockefeller Institute for Medical Research. |
In its application to the detection of syphilis antibody the
Bordet-Gengou phenomenon of complement fixation has received
but little consideration in its quantitative aspect. As will pres-
ently be pointed out it is only by respecting the quantitative rela-
tions of all reagents concerned that the test becomes reliable and
delicate. Even with an adequate quantity of antigen, blood cell
suspension and the patient’s serum the detection of the antibody
78 SCIENTIFIC PROCEEDINGS (32).
by means of complement fixation may or may not be successful
according to whether or not appropriate amounts of hemolytic
amboceptor and complement are employed. A large excess of
either one of these two reagents can prevent the test from reveal-
ing the presence of the antibody. While it is easy for a serologist
to see why complement should be used in definite and uniform
quantity, not every worker seems to be conscious of the disturbing
effects which are exerted by an excess of the amboceptor. In
view of the overlooking of certain principles of hemolysis by most
of the investigators of the present time a brief consideration of
this particular subject seems to be advisable. For the sake of con-
venience I take the example of the antisheep hemolytic amboceptor
for illustrating the influence of an excessive amount of the ambo-
ceptor upon the phenomenon of complement fixation. The effects
exerted by the excessive sensitization is two-fold. The first effect
is to augment gradually the activity of guinea-pig’s complement
by increasing doses of the amboceptor, until a maximum is
reached. Thus in the presence of one unit of amboceptor 0.1
c.c. of the complement is usually required to produce complete
hemolysis. By using four, eight and twenty units of the ambo-
ceptor the same effect is obtainable with 3, } and }, of the 0.1 c.c.
of complement respectively. For this reason it is impossible to
demonstrate a partial fixation of complement by using more than
several units of the amboceptor, and when several units are em-
ployed the test suffers in delicacy. The second effect is still more
disturbing than the first. It depends upon partial dissociation of
the complement from its combination with the antigen and anti-
body compound. A quantity of syphilis antibody just sufficient
to fix 0.1 c.c. of the complement against two units of the ambo-
ceptor is no longer efficacious to hold back the complement from
partial liberation against the influence brought on by more than
four units of the amboceptor. The fixation of the complement by
two and three units of syphilis antibody respectively is also quite
ineffective to prevent hemolysis when ten and twenty units of the
amboceptor are added. Under these conditions the test fails to
indicate the presence of any syphilis antibody although it is really
present. When eight units of syphilis antibody are employed the
fixation of complement becomes so firm that twenty units of the
amboceptor can no longer bring about its liberation.
Serum DIAGNosIS OF SYPHILIS. 79
From the foregoing it becomes at once evident that any system
of the complement fixation test in which definite and appropriate
amounts of these two vitally important reagents are not employed
is not delicate and accurate enough to be a reliable diagnostic
measure.
Referring to the method of Wassermann I may state that it
has all the disadvantages arising from the presence of unknown,
but often considerably large amounts of natural antisheep ambo-
ceptor contained in human serum. Wassermann was quite una-
ware that the natural antisheep amboceptor is capable of being
reactivated by guinea-pig’s complement, and hence he recommended
the use of two units of immune antisheep amboceptor of the rabbit
with the view of obtaining complete hemolysis. The reactivability
of the natural amboceptor by this complement has been dis-
covered since by Bauer who, in turn, proposed to utilize the
natural amboceptor and dismiss the use of the immune ambo-
ceptor. By systematic examination of more than 100 speci-
mens of human sera in regard to the content of natural antisheep
amboceptor I found that it varies from almost none to as many as
twenty units in 0.1 c.c., the quantity usually employed for each
tube in the fixation test. Thus the method of Wassermann is
destined to give unreliable and inaccurate reactions. Bauer’s modi-
fication is just as inaccurate as the original as it relies upon
unknown amounts of the natural amboceptor alone.
The method which I have recently perfected is also a comple-
ment fixation test and differs from the Wassermann method in
employing an antihuman hemolytic system instead of an antisheep
hemolytic system. Thus the human blood corpuscles are to be
hemolysed by means of an antihuman amboceptor prepared in the
rabbit and the complement of the guinea-pig. I use two units of
the amboceptor for each tube. In this new system the danger of
introducing any uncalculated amount of the hemolytic amboceptor
is absolutely excluded. As the fixation test is carried out with
definite and uniform amounts both of the complement and the
amboceptor, the results obtained with different specimens and at
different occasions are all comparable with one another. The
sharpness of the reaction enables one also to follow the fluctuation
of the antibody content even to a fraction of one unit.
80 SCIENTIFIC PROCEEDINGS (32).
Just as I had finished my experiments Tschernogubow
published an article in which he stated that he successfully
employed an antihuman amboceptor in combination with human
complement. As he made no statement as to the source and
strength of his antihuman amboceptor no judgment can be made
on his method. It is rather striking to observe that the amount
of the amboceptor he employed was 0.25 c.c. for each tube, in
contrast to 0.002 in my method. It may not be entirely out of
place to mention here some essential reasons why I use guinea-
pig’s serum as complement.
According to my observations the amount of complement in
human serum varies considerably in different individuals. In the
majority of specimens 0.1 to 0.03 c.c. of the fresh serum contain
about enough complement to produce complete hemolysis with
ten units of the amboceptor, while the same quantities do not cause
any marked hemolysis when two units of the amboceptor are
employed. Thus ten units of the amboceptor are to be used as a
necessary amount for utilizing human serum as complement.
Now in regard to the quantity of each specimen of human serum
to be used for complement it is essential to determine the exact
strength by a preliminary titration, because if we use some excess of
complement the test turns out completely negative. It appears
probable that human complement, like that of the rabbit, is not
very sensitive to the fixing action of the antigen-antibody of
syphilis. In this respect guinea-pig’s complement is excellent
The method which Tschernogubow recommended is to collect a
few drops of a patient’s blood in saline solution and use the sus-
pension both for the complement and corpuscles at the same time.
But, this does not permit one to make any estimation of the
complement content of the blood. Moreover, there is no direct
way of ascertaining whether any inhibition which may be observed
with a given specimen is due to the anticomplementary property
of antigen alone or to the combined action of the antigen and
syphilis antibody, because the complement and antibody exist in
the same serum side by side, if this latter is present at all. Again
the relying upon human complement makes impossible the testing
of any specimen of blood which has been allowed to stand for
several days, as the activity of complement rapidly diminishes and
NiTrRoGENouS METABOLISM IN CHRONIC NEPHRITIS. 8I
finally disappears under these conditions. His method is not
applicable to cerebrospinal fluid.
In contrast to the use of human complement the use of guinea-
pig’s serum does not possess one of the disadvantages enumerated.
The quantity of complement is always uniform and definite. The
human complement does not affect the reaction, because the
amount present is too trifling to be of any influence. It is possible
moreover to employ for the tests an old specimen of blood, dried
or moist, by my method, since guinea-pig’s complement is used.
Unlike Tschernogubow’s the present method enables one to repeat
the test in case of need.
Before leaving the subject I would like to point out certain
advantages from the technical standpoint of the method which I
recommend. The quantity of patient’s serum’ required for the
test is only two capillary drops (one for each of the two tubes)
and no preliminary inactivation at 56° C. is necessary. The hemo-
lytic indicator is readily prepared from the patient or a normal
person by mixing the blood with physiological salt solution in the
ratio of one drop of the blood to 4 c.c. of the saline solution, I c.c.
of such suspension being used for each tube. The antigen, com-
plement and amboceptor can be used either in liquid or in dried
form. This latter, as prepared on filter paper slips, can be pre-
served permanently under ordinary conditions at room temperature
and be employed in place of the corresponding liquid reagents.
In this simple form the test should have a wide application to the
sero-diagnosis of syphilis and as a measure and control of the
efficient treatment of the disease.
37 (375)
On nitrogenous metabolism in chronic nephritis.
By D. MANSON, L. KRISTELLER and P. A. LEVENE.
[from the Chenucal Laboratory of the Montefiore Hospital,
New York. |
The present work represents the results of observations on the
character of the nitrogenous metabolism in a patient who was
'Tn case of cerebrospinal fluid use 0.2 c.c, for each tube.
82 SCIENTIFIC PROCEEDINGS (32).
placed on a diet containing a sufficient supply of calories and a
limited proportion of protein, so that his kidneys could readily re-
move the end products of catabolism. That the capacity of the
kidneys were not overtaxed may be concluded from the fact that
the patient remained practically in nitrogenous equilibrium for four
months. On this patient it was attempted to establish whether
or not the abnormal, as v. Noorden termed it “‘bizarre”’ nitrogen
elimination observed in course of nephritis is conditioned exclu-
sively by faults of elimination.
CONCLUSIONS.
1. The elimination-capacity of the kidneys of the patient was
established by placing the patient on a diet containing a low pro-
portion of protein and a sufficient supply of calories. To this
standard diet varying quantities of urea were added, and the rate
of the nitrogen output was measured. The output of nitrogen on
the standard diet was generally about 5.5 grm. and the addition of
1.5 to 5.0 grm. of nitrogen in form of urea caused a rise in the
output never exceeding 6.25 grm. Thus it was concluded that
an intake of nitrogen below 7.0 grm. was the most suitable for
the condition of our patient.
2. Comparing the rate of elimination of nitrogen after the
administration of glycin, alanin, asparagin, with that after adminis-
tration of urea, one notes a slower rate after the administration of
the first two acids, and an equal rate after administration of aspar-
agin (probably owing to the presence of an acid amid group in the
molecule).
3. After administration of excessive protein in addition to the
standard diet, one notes a much lower rate of nitrogen elimination
than one should expect to find in a normal man, on the basis of
the work of Falta.
4. Of the total nitrogen removed by our patient in excess over
that on the standard diet, 80 per cent. was in form of urea,
while in normal man, as calculated from the tables of Folin,
the proportion of urea varies between 90 and 100 per cent.; in
a normal dog the proportion is always 100 per cent.
5. On the basis of these observations it was concluded that in
our patient the rate of conversion of protein into simple nitroge-
nous substances and into urea is below the normal.
FERTILIZING AND CYTOLYTIC EFFECT OF Soap. 83
6. The patient remained for four months in a condition of
nitrogenous equilibrium, and otherwise in good health, on a diet
containing about 6.5 grm. of nitrogen and 3,000 calories, which
were ultimately reduced to 2,500 calories to prevent a constant
gain in weight.
38 (376)
The formation of gluconic acid by the olive-tubercle organism
and the function of oxidation in some microorganisms.
By CARL L. ALSBERG.
[From the Office of Poisonous Plant Investigation, Bureau of Plant
Industry, U. S. Department of Agriculture. |
The olive-tubercle organism, Bacterium savastanot, recently de-
scribed by Erwin F. Smith,' when grown in the presence of
glucose and an excess of calcium carbonate, converts the
greater part of the glucose into calcium gluconate. The amount
of energy liberated thereby is exceedingly great in comparison to
the weight of the organisms. This is to be explained by the fact
that the energy requirements of microorganisms are very much
greater than those of higher forms, partly because of the dispro-
portion between the body surface and the body volume of micro-
organisms, and partly because microorganisms exist in a medium
which is an excellent conductor of heat.
39 (377)
On the fertilizing and cytolytic effect of soap.
By JACQUES LOEB.
[rom the Phystological Laboratory of the University of California. |
It has been shown by experiments on the eggs of sea-urchins,
starfish, and annelids that the artificial membrane formation is the
act which causes the unfertilized egg to develop. The agencies
which cause the artificial membrane formation, as a rule, injure
the egg. For the eggs of the starfish and certain other annelids
1Erwin F. Smith: Recent Studies of the Olive-Tubercle Organism. U.S. De-
partment of Agriculture, Bureau of Plant Industry, Bulletin No. 131, Part IV, Wash-
ington, 1908.
84 SCIENTIFIC PROCEEDINGS (32).
this injury is rather slight, and these eggs are able to develop into
larve without any further treatment. In the egg of the Califor-
nian sea-urchin this secondary, injurious effect connected with the
artificial membrane formation is more severe and demands a further
treatment of the egg. This consists in preventing the eggs from
developing for about from two to three hours after the membrane
formation, by depriving them of oxygen or by preventing oxida-
tions in the egg through the addition of a trace of potassium cyan-
ide. During this time the egg is able to recuperate from the in-
jurious effects of the membrane formation and is able to develop
perfectly normally into a pluteus if transferred into normal sea-
water. In my first experiments with this method, four years ago.
not more than ten per cent. of the eggs could be caused to develop
in this way. I have recently found that by a slight improvement
of the method all the eggs can be caused to develop into larve,
The segmentation is as a rule as normal as if the eggs were fer-
tilized by sperm. A second method of overcoming the injurious
effect caused by the artificial membrane formation consists in put-
ting the eggs for from 10 to 40 minutes into hypertonic sea-water.
This method also causes all the eggs to develop.
These experiments showed that the process of membrane for-
mation is the real cause which starts the development of the unferti-
lized egg ; and the question therefore arose what the nature of
this process is. My recent experiments have shown that the
agencies which cause hemolysis also cause the membrane for-
mation and the development of the unfertilized egg. I have thus
been able to show that saponin, solanin, digitalin, bile salts, fatty
acids, alkalis, hydrocarbons, ether and alcohols and the blood
serum of not too closely related forms cause the membrane forma-
tion of the unfertilized egg and its subsequent development.
There remained only one cytolytic substance which seemed to
form an exception, namely, soap, but experiments which I have
recently carried out have shown that it is possible to cause the
membrane formation and subsequent development of the egg with
sodium oleate.
If the unfertilized eggs of the sea-urchin are put into a mixture
of 50 c.c. N/2 sodium chloride + 0.2 c.c. N/1to sodium oleate,
the eggs form no membrane, nor do they undergo cytolysis ; but
DEPRESSION OF THE FREEZING PoINT OF WATER. 85
if they are transferred into sea-water they form membranes and a
smaller percentage of them undergoes cytolysis. If the eggs re-
main a short time only in the soap solution, they all form mem-
branes, but few cytolyze after being transferred into sea-water ; if
they remain for a longer time, they all form membranes but cyto-
lysis follows very soon after the membrane formation.
The question arises, why do the eggs form their membrane
only after they are transferred into sea-water? This is due to the
alkaline reaction of the sea-water. If we make the sea-water
faintly acid by the addition of hydrochloric acid no egg forms a
membrane or undergoes cytolysis after being transferred into sea-
water, and if we make the solution of sodium oleate in sodium
chloride slightly alkaline by the addition of sodium hydroxide the
eggs form membranes while they are in the soap solution.
If we allow the soap solution to act only long enough to cause
the membrane formation, but not long enough to cause cytolysis,
the eggs can be caused to develop larve. We may from all these
experiments draw the inference that the development of the resting
egg is caused by a superficial or mild cytolysis, and that the
spermatozoon must carry a cytolytic substance into the egg,
possibly a trace of higher fatty acid.
40 (378)
On the depression of the freezing point of water due to
dissolved caseinates.
By T. BRAILSFORD ROBERTSON and THEODORE C. BURNETT.
[From the Rudolph Spreckels Physiological Laboratory of the
University of California. |
The question whether or not proteins possess, in solution, a
definite osmotic pressure has been the subject of much controversy.
The original investigations of Graham! appeared to indicate that
colloids in general exert a high osmotic pressure. Subsequent
investigators, however, attribute these results to an admixture of
crystalloids and the investigations of Sebanejew,? Tamman,?®
1Graham: Phil. Trans. Roy. Soc., 1861, cli, 183.
2Sebanejew: Berichte d. deut. chem, Gesell., 1890, xxiii, 87; 1891, xxiv, 558;
xxvi, 385. Sebanejew and Alexandrow: Journ. of the Russian Phys.-chem. Soc.,
1891, p. 7; quoted after Maly’s Jahresber. f. Tierchem., 1891, xxi, 11.
’Tamman: Ze?t. f. physikal. Chem., 1896, xxi, 180.
86 SCIENTIFIC PROCEEDINGS (32).
Dreser,’ Koeppe’ and others indicate that when they are carefully
freed from associated inorganic substances the cryoscopic depres-
sion due to dissolved proteins is negligible, while Reid? finds that
proteins purified by repeated recrystallization, resolution and re-
crystallization frequently possess, in solution,‘ no measurable
osmotic pressure ; and he concludes that provided every precaution
be taken to exclude impurities (among which he includes inorganic
constituents) from the protein solution it will be invariably found
to possess no osmotic pressure whatever and that the osmotic
pressures observed in solutions incompletely purified are due, not
to protein, but to the associated impurities.
It appears to us that many of the above-quoted observations
and conclusions are vitiated by the fundamentally erroneous con-
ception that the inorganic constituents which are found associated
with proteins are invariably present as impurities and not in a state
of chemical combination. The manner in which this assumption
vitiates conclusions regarding the molecular weight (estimated from
the depression of the freezing-point or directly from the osmotic
pressure) of proteins will be clear from the following considera-
tions: Bases and acids have been demonstrated to form definite
salts of a constant composition with casein, serum globulin and pro-
tamin, and there can be no doubt whatever that similar compounds
are formed with other proteins. In solutions of casein and of
serum globulin it can be shown that as the neutral point is ap-
proached the alkali-binding power becomes less and from a variety
of data it can be shown that this phenomenon is due to a polymeri-
zation of the protein molecule according to equations of the type:
HXOH + HXOH = HXXOH + H,0* so that at or in the neigh-
borhood of the neutral point molecular aggregates are formed of such
dimensions that, in the cases of the proteins mentioned, the solu-
tion assumes the character of a suspension and the protein is pre-
cipitated ; addition of acid or alkali shifts the equilibrium in the
direction of the lower complexes and the protein goes into solution
again in the form of a salt. Similar phenomena may be safely as-
1Dreser: Arch. f. exper. Path. und Pharm., 1892, xxix, 314.
2Koeppe: Arch. f. d. ges. Physiol., 1896, \xii, 571.
3Reid: Journ. of Phystol., 1904, xxxi, 438.
*T. Brailsford Robertson : Journ. of Physical Chem., 1908, xii, 473.
DEPRESSION OF THE FREEZING POINT OF WATER. 87
sumed to occur in other protein solutions, although the polymeri-
zation of the protein, which occurs when the uncombined protein is
set free, may not result in actual precipitation. The elaborate
precautions which have been taken by many observers to free the
protein under investigation from accompanying inorganic sub-
stances, have, therefore, defeated their own ends by converting the
protein into molecular aggregates so enormous as to possess a
necessarily immeasurably small osmotic pressure.
Since it appears probable, therefore, that the dissolved sa/¢s of
proteins may exert a measurable osmotic pressure in solution, and
hence, cause an appreciable lowering of the freezing-point of water
in which they are dissolved, we have undertaken a series of deter-
minations of the lowering of the freezing-point of water, which is
brought about by dissolved (neutral) caseinates.
The solutions are made up as follows: Alkali of a given con-
centration is shaken up with excess of casein until no more casein
will dissolve and the solution is then filtered through rapid-filter-
ing paper. The resulting solution is a solution of the “neutral
caseinate’”’ of the base and is neutral to litmus.’ The cryoscopic
depression is estimated in the usual way. The following are the
results which have so far been obtained :
Experimental error of determination + 0.0025°.
Base. 7c oricentea ionic! pase A Indicating a concentration of
NH,OH m[50 0.045 m4
ae m | 33-3 -055 m [33-6
KOH m [50 +0325 m [57
a ¥ 0375 m | 49-3
“ m [33-3 .0425 m | 43-7
Ue fs :0475 m [38.9
(i m [20 05 m [37
at es -075 m [24.6
GK mis 5) m [18.5
LiOH m/59-5 .03 m [61.6
“ m [39.6 -045 m/ 41
“ m [23.8 .O7 m [26.4
OG m/17.8 .08 m [20.3
Since these solutions are neutral and no inorganic substance is
introduced save the base employed to dissolve the casein it is evi-
dent that the compounds of bases with casein cause, in solution in
!T, Brailsford Robertson: Journ, of Biol, Chem., 1907, ii, 336.
88 SCIENTIFIC PROCEEDINGS (32).
water, a definite cryoscopic depression. In harmony with deduc-
tions from titration- and conductivity-data’ the results are such as
indicate that casein behaves towards bases, essentially as a mono-
basic acid possessing a molecular weight, in solutions neutral to
litmus, of approximately 2,000.
41 (379)
The daily excretion of bacteria in the feces of healthy men.
By W. J. MACNEAL, LENORE L. LATZER and
JOSEPHINE E. KERR.
[From the Laboratory of Physiological Chemistry, Department of
Animal Husbandry, University of Illinois, Urbana, 11.)
During the past year we have examined at intervals of about
two weeks the fecal bacteria of each individual ina group of twelve
men who were the subjects of a prolonged metabolism experiment.
These men were fed a mixed diet, in quantity according to their
choice at the beginning of the experiment. Altogether we have
examined bacteriologically 266 stools.
The quantity of bacteria in each of these stools was estimated by
two different methods of microscopic counting and in about half of
them the quantity of bacterial dry substance was also estimated by
the gravimetric method of Strasburger.
In the individual examinations the largest number of bacteria
observed was 816 x 10° bacterial cells per gram fresh feces,
2,642 x 10° bacterial cells per gram dry feces. The smallest
number of bacteria counted was 124 x 10° per gram fresh feces,
983 x 10° per gram dry feces. By the gravimetric method the
largest quantity of bacterial dry substance observed was 42.53 per
cent. of the fecal dry substance or 13.2 per cent. of the moist
feces. The smallest quantity of bacterial dry substance observed
was 14.03 per cent. of the fecal dry substance or 2.6 per cent. of the
moist feces. Theaverage of all examinations was 375 x 10° bac-
terial cells per gram fresh feces; 1,587 x 10° bacterial cells per
gram dry feces; bacterial dry substance in fecal dry substance,
1T. Brailsford Robertson: Journ. of Physical Chem., 1908, xii, 479, etc.
DaiLty EXxcRETION OF BACTERIA IN THE FECES. 89
26.89 per cent.; bacterial dry substance in moist feces, 7.0 per
cent. The average daily quantity of fecal dry substance and of
fecal nitrogen was calculated from the analysis of eight-day period
collections, and the average daily bacteria and bacterial nitrogen
calculated upon these quantities, regarding the bacterial content of
the dry substance of the single stool, upon which the bacteria were
determined, as representative of the feces for that period. Calcu-
lated in this way the greatest values found were 58 x 10” bacterial
cells per day by count, and 9.15 grams bacterial dry substance,
containing 1.006 grams nitrogen, per day by the gravimetric
method. The smallest values were 14 x 10” bacterial cells and
1.87 grams bacterial dry substance, containing 0.194 gram nitro-
gen per day. The average of all examinations was 32 x 10”
bacterial cells, and 5.34 grams bacterial dry substance, containing
0.585 grams of nitrogen, per day.
There was considerable individual variation among the different
subjects of the group. For example, the average of all examina-
tions of Subject H was 40 x 10” bacterial cells and 7.26 grams
dry bacterial substance, containing 0.819 gram nitrogen, per day.
The average of all examinations of Subject B was 26 x 10” bac-
terial cells and 3.56 grams bacterial dry substance, containing 0.393
grams nitrogen, per day.
The nitrogen contained in the bacteria varied from 66.8 per
cent. to 23.3 per cent. of the total fecal nitrogen, the average of
all examinations being 46.3 per cent. Individual variation in this
respect was also considerable. In Subject I the average of all
examinations showed 57.4 per cent. of the total fecal nitrogen
contained in the bacteria; in Subject K this quantity was 32.1
per cent. These two subjects were the ones who showed the two
extremes (66.8 per cent. and 23.3 per cent., above) for the single
examinations.
A detailed account of these experiments will be published in a
short time in The Journal of Infectious Diseases.
go SCIENTIFIC PROCEEDINGS (32).
42 (380)
Further studies on the constitution of inosinic acid.
By WALTER A. JACOBS and P. A. LEVENE.
[From the Rockefeller Institute for Medical Research. |
In a former paper’ we have already communicated that the
inosin which we obtained from inosinic acid was identical with that
obtained from karnin by Haiser and Wenzel.?, We have now suc-
ceeded in isolating from inosin the pentose in a crystalline state.
The properties of this sugar are as follows: Melting point 87° C.
Its rotation in aqueous solution is (2), = — 19°.4. The osazone
melts at 163°-164° C. and shows a rotation when 0.2 gram are
dissolved in Io c.c. of a mixture of four parts pyridine to six parts
of alcohol of (2),= —0°.92. The benzylphenylhydrazone melts
at 128° C. and in absolute alcoholic solution rotates (d) >= —26°.46.
We therefore conclude that this sugar is neither xylose nor
arabinose as stated by Neuberg and Brahm®* and Bauer ‘ respec-
tively. We hope, by further study, to establish its exact nature.
43 (381)
The effect of heat on the anaphylactic properties of proteins.
By JOHN F. ANDERSON and M. J. ROSENAU.
[From the Hygienic Laboratory, P. H. and M. H. S.,
Washington, D. C.]
We have demonstrated that horse serum, egg-white and milk
when dried, then heated and redissolved, possess unaltered powers
of sensitizing and poisoning guinea-pigs in the sense of hypersus-
ceptibility.
The above named substances, when thoroughly dried, were
heated to 130° C. for two hours, 150° C. for ten minutes, or 170°
C. for ten minutes. We have previously shown that both the sen-
sitizing and toxic properties of liquid horse serum are gradually in-
1 Proc. Soc. Exp. MED. AND BIOL., 1909, vi, 56. Ber. d. deutschen chem. Gesell.,
1909, xlii, 335.
2 Monatshefte fiir Chemie, 1909, xxix, 157.
3 Ber. d. deutschen chem. Gesell., 1908, xli, 3376.
* Beitraze zur chem. Physiol. und Path., 1908, x, 345.
Skin REACTION IN CARCINOMA. gI
fluenced by heat and are practically destroyed at about 100° C.
The difference probably depends upon coagulation of the protein
and consequent failure of absorption.
Dried sensitive guinea-pig blood serum, containing anaphylac-
tin, withstands at least 100° C. for ten minutes.
44 (382)
A skin reaction in carcinoma from the subcutaneous injection
of human red blood cells.
By CHARLES A. ELSBERG.
[From the Mount Sinai Hospital. ]
Numerous investigators have shown that if the blood serum of
a patient suffering from carcinoma be mixed with normal human
red blood cells hemolysis occurs. The reaction takes place in
from 50 per cent. to 80 per cent. of patients with malignant disease.
It occurs with considerable frequency in tuberculosis, and more
rarely in other diseases.
It occurred to the writer, that, by the injection of red blood cells
under the skin of the carcinoma patient, it might be possible to
produce a local reaction at the site of the injection. Logically, a
local hemolysis should take place. Theoretically, such a reaction
might prove to be a delicate one ; it might give more positive and
definite results than the test-tube method. In the technique which
is used for the test-tube method the presence and degree of hemo-
lysis is indicated by the amount of laking of the red cells — that
is, by the amount of hemoglobin which has been set free. The tube
reaction gives no evidence of other substances than the hemoglo-
bin which have been liberated. A small amount of hemolysin in
the serum which is being tested might not be capable of detection.
If normal human blood cells are injected under the skin of a
patient whose serum is hemolytic, fresh quantities of hemolysin
would be continually carried to the cells, and therefore even a
small amount of hemolysin might cause hemolysis of the cells.
Every organic substance which was set free would enter the tissues
and might there have its effect.
Accordingly, after some experimentation, normal blood was in-
92 SCIENTIFIC PROCEEDINGS (32).
jected under the skin of patients suffering from carcinoma or other
disease. In patients with malignant disease, a decided local
reaction was observed. The technique employed was a very
simple one. Under aseptic precautions, blood was aspirated
from the median basilic vein of a normal individual (preferably
a child), every possible precaution being taken that the indi-
vidual was healthy and free from hereditary or acquired disease.
The blood was defibrinated, and the cells washed four times in
normal saline solution, care being taken that the washings and
centrifuging was thoroughly done. A 20 per cent. emulsion of
the red cells in normal saline solution was made and kept in the
ice-box for 24-48 hours before it was used. Five minims of this
24-48 hour old suspension of washed red blood cells were sub-
cutaneously injected into the anterior surface of the forearm of the
patient. In the patients in whom a “‘ reaction’ was obtained, the
following changes were noted in the skin at the site of the injection.
Six to eighteen hours after the injection, the affected area was
slightly raised and slightly tender, it had a more or less well defined
margin, it measured from two to four centimeters and it was of a
somewhat dusky red color. The changes in the skin reached their
maximum within one or two hours, and the red area then began
to fade, rapidly or slowly. Eight to twenty four hours after the
injection, the skin lesion had either entirely disappeared, or more
often, a brownish, bluish or lemon-yellow discoloration remained,
which persisted for a number of days.
In the patients who did not show this reaction, there was either
nothing to be seen at the site of the injection excepting the needle
puncture, or a brownish discoloration of the skin, or a bluish dis-
coloration, as is often seen after a hypodermic injection.
My investigations of this cutaneous lesion are very incomplete,
I have given thirty four injections to twenty patients with known
carcinoma, and every one of the cases had a positive reaction.
In most of the patients several injections were given of different
blood cells. With succeeding injections, the reaction was either
less marked or failed to appear. Of four patients with known
sarcoma, three gave a positive reaction. Injections were given to
over one hundred normal individuals or to those suffering from
diseases other than sarcoma or carcinoma. These included a
SKIN REACTION IN CARCINOMA. 93
variety of diseases, such as nephritis, tuberculosis of lungs,
bladder, kidneys (7 cases), leukemia, syphilis (2 cases), benign
tumors, acute and chronic inflammatory affections, etc. In all
but three cases, the reaction was negative. One patient with a
septic endocarditis gave a suspicious, but not a positive reaction,
Two other injections made in this patient were negative. This
case was among the earliest of our series, and therefore must be
accepted with caution. A patient who had been operated on for
a large rapidly growing lymphangioma of the suprapubic region
and had several large angiomata of the thigh with a large post-
operative hematoma of the scrotum, gave a marked positive
reaction. A patient with gastric symptoms, absence of hydro-
chloric acid and presence of lactic acid, with a loss of thirty
pounds in weight, gave a positive reaction. The operation failed
to show any carcinoma. I obtained no reaction in several patients
in whom malignant disease was suspected but in whom no
malignant disease was found at operation or at autopsy, and have
obtained positive reactions in several patients in whom carcinoma
was not suspected, but in whom carcinomatous disease was found
at operation. Jaundice seemed to have no influence upon the
appearance of the reaction.
In order to gain a more definite idea of the causation of the
skin changes, normal defibrinated blood was laked with distilled
water, and, after the tubes had been centrifuged, the supernatant
fluid was injected into a number of patients. For purposes of con-
trol, hypodermic injections of sterile distilled water were given.
All of the patients, whether suffering from malignant disease or
not, who received hypodermic injections of laked blood, presented
a skin lesion similar to that which was observed in carcinoma
patients after the injection of washed red blood cells. This seemed
to show that in the patients with carcinoma the reaction from the
blood cell injection was due to a local hemolysis. In the normal
individual or one suffering from some other disease, on the other
hand, there was no hemolysis and therefore no reaction. When,
however, the hemolyzable substances extracted from the red cells
by laking were injected, the characteristic local lesion was ob-
served. I have not yet been able to obtain pure human hemo-
globin for injection purposes.
94 SCIENTIFIC PROCEEDINGS (32).
A fuller account of the technique employed and a more exact
description of the cutaneous lesions observed, of the possible value
of red blood cell mixtures, z. ¢., of suspensions of the mixed red
blood cells of several individuals, of the possible value of some
animal red blood cells for injection purposes, of the significance
of the persistence or disappearance of the reaction after an opera-
tion, and many other aspects of the subject will be discussed in a
future communication. The number of injections thus far given
is far too small to allow of positive conclusions as to the reliability
of this method for diagnostic purposes. The results obtained thus
far have been striking. The purpose of this preliminary report is
to call attention to the fact that it is possible to cause a local
hemolysis in the living body by the subcutaneous injection of
washed normal human red blood cells, and that in patients with
malignant disease, especially carcinoma, a characteristic and easily
recognizable local skin lesion is caused by this injection.
Thirty third meeting.
Cornell University Medical College, New York City.
April 21,1909. President Lee in the chair.
45 (383)
The vascularity of the spleen as influenced by single nerves
of the plexus lienalis.
By R. BURTON OPITZ.
[From the Physiological Laboratory of Columbia University. |
The blood supply of the spleen was determined by means of
a stromuhr inserted into the splenic vein. The average for a dog
of 18.0 kilos body weight, with a spleen weighing 100 grm.,
amounted to 0.97 c.c. per second, the velocity of the blood stream
to 42.0 mm. per second, the venous pressure to 10.0 mm. Hg.
Vaso-constrictory influences were obtained on stimulation
of either splanchnicus major, or of the plexus lienalis. Single
nerves of the plexus, designated as «, 8, 7 and 0 also showed
strong vaso-constrictory powers. Thus, it was possible to trans-
fer from 30 to 50 c.c. of blood from the spleen into the systemic
circuit by moderate stimulation of either one of the nerves just
mentioned. The removal of so large a quantity of blood from
this organ by the constriction following the stimulation, resulted
in a rise in general blood pressure.
On the venous side the vaso-constrictions made themselves
felt by :
1. A quick sharp rise in the venous return and venous pressure.
2. A gradual decrease in the blood-flow and pressure.
3. A slow adjustment toward normal values.
(95)
96 SCIENTIFIC PROCEEDINGS (33).
46 (384)
An experimental study of the influence of kidney extracts and
of the serum of animals with renal lesions upon
the blood pressure.
By RICHARD M. PEARCE, M.D.
[from the Carnegie Laboratory of the University and Bellevue
Hospital Medical College, New York City.]
I. Extracts of the rabbit’s kidney injected into the rabbit cause
a slight increase in blood pressure which is barely more than that
due to the mechanical effect of the injection.
2. Extracts of the dog’s kidney injected into the dog cause a
decided fall in pressure ; an equal fall may be caused by the dog’s
urine. A series of control experiments indicates that the fall caused
by the kidney extract may be due to the urinary salts which it
contains.
3. Extracts of cat’s kidney cause a risein pressure ; as the cat’s
urine causes a fall, this rise in pressure indicates the possibility of
a kidney extract containing a pressor substance which cannot be
influenced by the depressor substance of the urine.
4. Rabbit’s kidney which in the rabbit produces a slight rise
when injected into the dog causes a drop comparable to that caused
by the dog’s kidney itself. Similarly the dog’s kidney, which in-
jected into the dog causes a drop, produces in the rabbit a rise
analogous to that produced by rabbit’s kidney. It is evident there-
fore that these pressor and depressor substances of the kidneys in
question do not have a constant effect on all animals as do the
extracts of the adrenal gland.
5. Extracts of kidneys which are the seat of various forms of
nephritis cause the same effect as extracts of normal kidneys.
6. The serum of dogs with considerable reduction of kidney
substance causes a slight fall in pressure ; the serum of dogs with
spontaneous nephritis gives divergent results, as does also the
serum of rabbits with various forms of acute nephritis. The serum
of dogs with chromate nephritis causes a slight rise, while that of
dogs with uranium nephritis produces a sharp and decided fall in
pressure. Although there is no uniformity in these results, their
OBSERVATIONS ON EFFECT OF ASPHYXIA AND CURARE. 97
general character, and especially the experience with uranium and
chromate sera of the dog, suggests that pressure-disturbing sub-
stances are present in the serum as the result of the kidney lesion.
The very slight evidence of the constant presence of a pressor
substance, however, offers little support to the theory that such a
substance is furnished by the diseased kidney or is due to dis-
turbances of metabolism caused by disease of the kidney.
47 (385)
Further observations on the effect of asphyxia and curare on
the reducing power of the blood after section of the
hepatic nerves in dogs.
By J. J. R. MACLEOD.
[From the Laboratory of Physiology, Western Reserve University,
Cleveland. |
In a previous communication on this subject (Macleod, American
Jour. of Phys., 1909, X XIII, 278) tt was concluded that section of
the hepatic nerves does not prevent the establishment of hypergly-
cemia as a result of asphyxia and curare poisoning (Table III,
p. 293, Zoc. cit.). The conclusion was based on the results of three
experiments in which asphyxia was practiced, and in two of which
marked hyperglycemia was observed ; and on one in which curare
was injected. Subsequent experiments of the same nature have
yielded results which do not corroborate the above conclusion for
asphyxiated animals, but do so for those which are curarized.
The following table gives the results of these experiments:
No. and nature Per cent. of reducing substance in blood.
of experiments.
Before. After.
102 asphyxia 0.104 ig i aa.
104 asphyxia {eae 0.262 (60 min.),
105 asphyxia Reais 0.176 (45 mm, ).
107 asphyxia 0.113 Neate ae Bae
0.304 (30 min. ).
108 curare 0.265 2383 (45 min. ).
0.354 (75 min. ).
109 curare 0.178 0.334 (40 min. ).
110 curare 0.146 eee es a
98 SCIENTIFIC PROCEEDINGS (33).
48 (386)
Toxin-antitoxin mixtures as immunizing agents.
By WILLIAM H. PARK and EUGENE FAMULENER.
[From the Research Laboratory of the Department of Health, New
York City. |
Ehrlich early suggested that injections of partially neutralized
diphtheria toxin produced active immunity. This was demon-
strated by Wernicke, Dreyer and Madsen, Morgenroth, ourselves
and others. Smith in a recent article suggested the use of such
mixtures in the immunization of children. The possibility of such
a practical application has suggested to us some experiments with
especial reference to the safety and effectiveness of the injections.
The proportion of toxin to antitoxin in the mixture required to
produce immunization. —In May, 1903, one of us reported some
experiments in which one set of horses were injected with mixtures
containing toxin .66 of L+ dose for each unit of antitoxin and
another with .66 of L+ for each 4 units of antitoxin. Three large
injections produced in the first series an average of 150 units, in
the second an average of 3 units in each c.c. of serum.
Smith injected three guinea pigs with 1 unit plus 1 L+ dose,
2 units plus 1.3 L+ dose, and 2 units plus 1 L+ dose respec-
tively. The litters born from the first and second animals showed
marked immunity at theend of eight months. The litter from the
third animal showed slight immunity at three months and none at
six months.
These experiments indicate that while even a proportion of 6
units of antitoxin to 1 L+ of toxin produces slight immunity, the
toxin must be in proportion of more than 1 L+ dose to 2 units to
give marked and lasting effects.
This brings us to the question of the safety of such mixtures.
The work of Morgenroth suggests that mixtures which are toxic
for one species are toxic for all. There is a difference, however,
among animals as to the amount of natural immunity and perhaps
therefore as to the development of serious symptoms or death from
a given quantity of toxin-antitoxin mixture. Even if all guinea
pigs lived, therefore, there would be a slight uncertainty in infants.
ANTIPERISTALSIS IN RELATION TO TUBERCLE BACILLI. 99
In a series of tests we found that the least proportion of diph-
theria toxin which was necessary to give lasting immunity was not
quite harmless in guinea pigs. Thus of four guinea pigs receiving
a mixture of 1 unit plus } L+ the two larger remained perma-
nently well, while the two smaller finally died of paralysis. Four
guinea pigs receiving one half the quantity of the same mixture all
remained alive. Two other series receiving still larger quantities
of the same mixture acted as the first lot. Some of these guinea
pigs received six months later two fatal doses of toxin without
serious poisoning.
It is interesting to note that three of these animals received
repeated injections of toxin in increasing amounts, until finally
6,000 fatal doses were given in one injection. The blood of the
animals at this time contained from 25 to 30 antitoxin units per
cubic centimeter. It is possible that the toxin used in these experi-
ments which was produced by Culture No. 8 may have more tend-
ency to promote late paralysis than that from other cultures such
as used by Smith.
49 (387)
Antiperistalsis in its relation to tubercle bacilli and other bac-
teria in the alimentary tract.
By ALFRED F. HESS.
[trom the Research Laboratory of the Department of Health, New
York City. |
Fifteen years ago Griitzner showed that charcoal, starch and
similar substances when introduced in normal salt solution into
the rectum, ascended in the intestinal tract and after from four to
six hours could be demonstrated in the stomach. His work was
confirmed by some and refuted by others. This problem has of
late assumed a new aspect inasmuch as some workers have
claimed that when bacteria are introduced in the same way, within
a short time they ascend by means of the antiperistaltic action of
the alimentary tract to the stomach, cesophagus and thence into
the respiratory tract. The most recent report of this phenomenon
comes from the Kaiserliche Gesundheitsant, which concludes that
this antiperistaltic movement must be considered, not only in exper-
100 SCIENTIFIC PROCEEDINGS (33).
imental studies on tuberculosis, but also in the prophylaxis against
infectious diseases ; more especially in the disinfection in cases of
cholera and typhoid fever, where the sputum may in this way be
contaminated.
The experimental facts claimed are: When Bacillus prodigiosus,
tubercle bacilli or other bacteria are suspended in from 10 to 20
c.c. of salt solution and are injected by rectum into an adult rabbit,
they may be recovered by culture or animal inoculation an hour
later from the small intestine, stomach, cesophagus, trachea, lungs
and other organs. These results are interpreted as proving con-
clusively that these bacteria, after traversing the gastro-intestinal
tract, have entered the trachea and lungs, and thence have been
transported throughout the body.
The technique previously employed was, in brief, to keep the
animal securely fastened following the injection, so that he could
not lick himself, to kill him after a variable period, and then under
the strictest asepsis to make numerous cultures from the contents
of the alimentary tract, from the macerated organs, and from the
heart’s blood.
It appeared that the foregoing facts could, for the most part,
be conceded, and nevertheless be open to quite a different interpre-
tation. With this question in view I undertook the following
series of experiments.
The technique which I made use of differs in two respects from
that used by others: (a) Large amounts of blood obtained for
examination were drawn from the ear vein or jugular vein, previous
to pithing the animal; (4) care was taken to avoid contact with
blood in the cultures made from the hollow viscera. In addition
it was found necessary to introduce other experiments.
The following is a summary of my results :
Of four experiments in which the animals were killed within
three hours of the rectal injection, in three bacteria were not pres-
ent above the ileo-czcal valve ; in one they were obtained in the
small intestine after seventy minutes ; in no instance could they be
cultivated from the stomach or cesophagus.
Furthermore of four other experiments where twenty-four
hours was allowed to elapse before killing the animal, in one the
tubercle bacillus was demonstrated by means of inoculation to be
ANTIPERISTALSIS IN RELATION TO TUBERCLE BACILLI. IOI
present in the stomach. In the three others the injected bacteria
were not found in the alimentary tract.
In the various experiments bacilli were recovered from the
lungs, liver and kidneys, urine and mesenteric glands.
In three of four experiments Bacillus prodigiosus was cultivated
from the blood within three hours of the rectal injection, and once
twenty-four hours later. In two instances, where attempt was
made tubercle bacilli were found in the blood twenty-four hours
after they had been introduced into the rectum. Forty-five and
fifty milligrams of a bovine culture had been injected, and 2 or 3
c.c. of blood was inoculated into each of six guinea pigs in both
instances. In none of these experiments was the organism found
in every blood culture, and in many of them the heart’s blood
tested proved to be sterile.
The result of these blood cultures suggested the injection of
the bacilli directly into the circulation with an injury as to their
subsequent distribution in the body. This work is still unfinished,
but it may be of interest to note in this connection that one hour
after injecting one forty-eight hour agar culture of Bacillus pro-
digiosus, this organism was found in the small intestine, and that
three hours following the injection of 130 mg. of tubercle bacilli
they were demonstrated in the stomach and small intestine. That
these tubercle bacilli did not enter the alimentary tract by way of
the lungs was shown by two experiments in which the pylorus
was ligated previous to the intravenous inoculation and the bac-
teria were found in the small intestine. In these instances the
bacteria either passed into the lumen of the stomach or intestine
from without, or entered by means of the bile passages. Further
experiments are being carried out to determine this question.
After it was shown that the bacteria entered the blood follow-
ing introduction into the rectum, it seemed necessary to inquire
whether they were excreted by the salivary glands and could
possibly in this way enter the upper part of the alimentary tract.
To this end three experiments were carried out on dogs. Rectal
injections of Bacillus prodigiosus were given in the manner de-
scribed and two or three hours later the secretion from the parotid
gland was obtained by means of a capillary tube inserted in the
opening of Stenson’s duct. In most instances this is easy to carry
102 SCIENTIFIC PROCEEDINGS (33).
out and five to ten cubic centimeters of saliva can thus be obtained
after giving the dog 1/100 gr. of pilocarpine subcutaneously.
None of the cultures made from the saliva showed Bacillus pro-
digiosus ; however, I do not believe that this route is absolutely
excluded.
One clinical test was made. A “typhoid-carrier’’ who is
known to have had typhoid bacilli in her stools for some years,
at times almost in pure culture, but at present in the ratio of about
ten per cent. of the total number of faecal bacteria, was submitted
to an examination. If the bacteria ascend from the intestine then
typhoid bacilli should be found in her stomach. This patient was
starved for eight hours; at the end of the period her mouth was
washed with sterile salt solution, and the washings tested for
typhoid bacillii Her stomach, which was found to be empty
after this period, was accordingly washed out and the washings,
which were of neutral reaction, likewise plated on Conradi-Dri-
galski media. Neither of these fluids was found to contain
typhoid bacilli, nor indeed colon bacilli.
From these experiments I conclude that bacteria injected by
way of the rectum into rabbits are not carried in a viable state
above the small intestine, and that they do not enter the respira-
tory tract by this route. In fact their presence in the small in-
testine may at times be due not to antiperistalsis, but to excretion
from the blood or the bile. Furthermore; where experiment has
showed them to be present in the lungs, the trachea and the
cesophagus, they have entered these organs by way of the blood
stream.
3 50 (388)
The action of soaps on the pneumococcus.
By SIMON FLEXNER and RICHARD V. LAMAR.
[From the Rockefeller Institute for Medical Research, New Vork.]
The object of the study to be reported briefly is the ascertain-
ing of the manner in which the pneumococcus is disposed of in the
body of infected animals that recover. The animal experiments
were made on full grown rats. A strain of pneumococcus fatal to
them in 1/10,000 of a cubic centimeter of a twenty-four hour
bouillon culture wasemployed. Strong solutions (1 to 5 per cent.)
INFLUENCE OF SHAKING UPON TRYPSIN AND RENNIN. 103
of soap (sodium oleate) precipitate the diplococci in an adherent
mass which afterwards undergoes complete solution in water or
salt solution. Solutions of soap of a strength of 1 to 10,000 do
not produce visible changes in the bacterial suspensions but reduce
slightly the number of viable cocci. Solutions of I to 15,000 or
I to 20,000 do not affect the viability in cultures but reduce some-
what the virulence. At the same time the diplococci appear some-
what swollen but not otherwise altered.
Untreated diplococci begin to multiply at once in the peritoneal
cavity of rats. The treated diplococci at first almost entirely dis-
appear from the cavity and begin to multiply after eight or more
hours and cause death at a later period than the controls. There
is a greater emigration of leucocytes in the case of the treated
cocci than in that of the controls. There is little or no phago-
cytosis. Normal goat serum does not affect the process appre-
ciably ; but immune goat serum prevents multiplication of the
treated cocci and brings about recovery of the rats but, under the
conditions of the experiment, not of the control rats injected with
untreated cocci. Phagocytosis does not play a direct part in the
recovery.
The experiments can be repeated zz vitro with approximately
similar results. The soap-treated cocci are subject to serum lysis,
while the untreated are not, and the lysis is not assisted but rather
hindered by the presence of living leucocytes. The study is being
continued.
51 (389)
The influence of shaking upon trypsin and rennin and a com-
parison of this influence with that upon pepsin.
By A. 0. SHAKLEE and 8. J. MELTZER.
[From the Department of Physiology and Pharmacology of the
Rockefeller Institute for Medical Research, New York. |
At the December meeting of this Society we mentioned our
studies of the effects of shaking upon ferments and reported that
pepsin can be practically destroyed by shaking. Our studies were
extended to other digestive ferments and we wish now to report
very briefly that shaking proves to be very injurious also to trypsin
104 SCIENTIFIC PROCEEDINGS (33).
and to rennin. Trypsin was tested by the casein method of Gross
and the rennin was determined by the method of Blum and Fuld
with slight modifications which will not be discussed here. Both
ferments were shaken at room temperature, and at 33°C.; also the
influence upon the results of different rates of shaking and of
changes in other conditions were investigated. We shall, however,
state here only that the destructive effect of shaking upon trypsin
and rennin is, as for pepsin, distinctly increased by increasing the
rate of shaking and by increasing the temperature at which the
shaking is carried on. There is a pronounced difference in the
resistance to shaking between pepsin and trypsin under the condi-
tions thus far studied, the latter being more readily affected. The
destructibility of rennin runs practically parallel with that of pepsin.
52 (390)
The influence of sodium and calcium upon direct and indirect
muscle irritability and their mutual antagonistic actions.
By DON R. JOSEPH and §S. J, MELTZER.
[from the Department of Physiology and Pharmacology of the
Rockefeller Institute for Medical Research, New York. |
By the researches of Kithne, Biedermann, Ringer, Loeb, and
many others, it is established that solutions of sodium chloride
cause rhythmical movements of the muscles of the frog, and that
the addition of a small quantity of calcium will stop them. By
the researches of Locke, Carslaw, Cushing, Poljakoff and Overton,
it is further established that solutions of sodium chloride abolish
indirect irritability, and that the addition of a small dose of calcium
restores it. There has been very little work done on the primary
effect of calcium upon the direct and indirect irritability of the
skeletal muscles of the frog and there are practically no researches
on the action of sodium upon the primary effects of calcium.
In our experiments, sodium and calcium chlorides were em-
ployed in M/1o solutions and were introduced by infusion through
the abdominal aorta according to the method described by
Cushing.’ The graphic records were obtained from the gastro-
1Cushing: American Jour. of Physiol., 1902, vi, 77.
EFFECTS OF MAGNESIUM UPON MEDULLA. 105
cnemius and the sciatic plexus was stimulated at about one minute
intervals by two consecutive shocks (make and break) from an
induction current.
In agreement with the above mentioned statements, we found
that sodium chloride reduces indirect (curare-like action) and
reduces moderately also direct (Poljakoff) irritability. Both are
promptly restored by the addition of a small dose of calcium. As
a new fact we may mention that the irritability is more readily
abolished in cooled frogs.
Although calcium restores indirect irritability when abolished
by sodium, it ado/ishes indirect irritability when injected primarily.
The dose necessary is considerably smaller than that of sodium for
the same effect. Again, the indirect irritability thus abolished by
primary infusion of calcium can be restored by sodium of which,
however, a larger dose is required than of calcium in a secondary
injection for a similar purpose.
Calcium also reduces or abolishes direct irritability, which again
can be restored by sodium. The loss of indirect and direct irrita-
bility by calcium is not exactly parallel. Cooling seems to favor
the effects also of calcium.
In these experiments neither sodium nor calcium exclusively
increased or decreased the irritability. Both depressed in primary
infusion and were mutually antagonistic in secondary infusions.
53 (301)
The effects of local applications of chloride and sulphate of
magnesium upon the centers in the medulla compared
with those of sodium chloride.
By J. AUER and 8. J. MELTZER.
[ From the Department of Physiology and Pharmacology of the Rocke-
Seller Institute for Medical Research. |
The three salts were applied in molecular solutions to the
exposed medulla oblongata of rabbits. Both salts of magnesium
abolished sooner or later all the functions depending upon the
centers located in the medulla, the average time until a complete
effect took place being fifteen minutes. Respiration stopped and
106 SCIENTIFIC PROCEEDINGS (33).
blood-pressure came down to forty or thirty millimeters of mercury
and sometimes even lower. Strong stimulations of the sciatic
nerve had now no effect upon blood-pressure. After curarin and
strychnin were given stimulation of the sciatic caused some rise
(spinal centers). Electric stimulation of the superior laryngeal
nerves or mechanical stimulation of the pharynx caused no de-
glutition. Injection of fluid into the cesophagus caused no con-
traction of that organ (no secondary peristalsis). Intravenous in-
jection or local application of calcium did not restore these func-
tions. In a few cases spontaneous respiration returned after a few
hours of continuous artificial respiration.
Sodium chloride had no depressing effect; on the contrary,
there was a moderate stimulating effect upon the respiration and
blood-pressure. There was a strikingly stimulating effect upon the
center of deglutition ; for eight or ten minutes the animal had to
swallow every ten or fifteen seconds.
54 (392)
Respiration by continuous intrapulmonary pressure without
the aid of muscular action.
By J. AUER and 8. J. MELTZER.
[From the Department of Physiology and Pharmacology of the
Rockefeller Institute for Medical Research. |
Investigations of the nature of the mechanism which keeps
up the respiration in the underpressure and overpressure methods
of Sauerbruch and of Brauer led to the discovery that the respi-
ration can be kept up for hours by a continuous stream of air
equal to fifteen or twenty millimeters of mercury without the aid
of any muscular action. The only requirement is that the air
stream must reach at least the bifurcation. If the air is intro-
duced simply through a tracheal cannula, as in the Brauer method,
and curare is given, the animal dies in a few minutes. Our object
was attained in three ways. In one method a slit was made in
the trachea and a glass tube, filling out about two thirds of the
trachea was introduced to the tracheal bifurcation or even a short
distance into the right bronchus. Air entered through this tube
and returned through the slit in the trachea and through the
THE PRopUCTION OF KIDNEY INSUFFICIENCY. 107
mouth and nose. In the second method a short tracheal cannula
was tightly ligated into the upper part of the trachea and a nar-
row tube was introduced through a small slit in the lower part of
the trachea into the right bronchus. The air entered through the
tracheal cannula and had to reach the lower end of the glass tube
before it could make its exit. Finally in a third method a long
O’Dwyer tube bent at right angles was introduced into the larynx,
the pharynx and mouth were packed with gauze, and a long soft
rubber catheter was introduced through the O’Dwyer tube deep
into the trachea so that its lower end reached the bifurcation. By
means of a T-tube the air entered through the O’ Dwyer tube into
the trachea and had no other escape than through the side open-
ings at the lower end of the catheter (the air passed through an
ether bottle; the animals also received morphin). By any of
these methods the animals (dogs and rabbits) continued to live
for a long time after their muscular action was completely elimi-
nated by curare. The thorax was wide open in most of the ex-
periments and the widely distended lungs showed only the vibra-
tions due to the heart beats. In many cases the lungs lost their
pink color. Opening the ether bottle for a second or two per-
mitted a momentary collapse of the lungs and in an instant they
again looked pink.
Besides the principle which is demonstrated by this new ob-
servation and the possibility of its practical application, it offers a
very convenient method for the study of the heart movements
without any interference from the respiratory movements.
55 (393)
Note on the production of kidney insufficiency by reduction of
the arterial circulation of the kidney.
By ALEXIS CARREL.
[From the Laboratories of the Rockefeller Institute for Medical
Research, New York. |
In order to obtain an insufficiency of the renal functions, I
attempted to find a method simpler and more practical than the
reduction of renal substance used by Tuffier, Bradford, Pearce and
others. This new method consists of reducing the renal circula-
108 SCIENTIFIC PROCEEDINGS (33).
tion by ligature or stenosis of the branches of the renal artery.
The operation is harmless and very simple. The results obtained
by Dr. Janeway show that it is efficient.
56 (394)
A modification of the Riva-Rocci method of determining blood-
pressure for use on the dog.
By THEODORE C. JANEWAY.
[From the Rockefeller Institute for Medical Research. |
Previous studies of the blood-pressure changes in living animals,
by repeated direct measurements from the femoral or carotid,
while accurate from the standpoint of the blood-pressure at the
moment of observation, have been of very limited value. When
used as a means of following the changes occurring over long
periods of time, as in the study of experimental kidney insuffi-
ciency, it is questionable whether a single pre-operative reading,
with several post-operative ones, afford in themselves any basis
for the conclusions drawn. The figures given by Volkmann for
the blood-pressure of different animal species show readings from
the dog of 104, 123, 143, 157, 166 and 172 mm., a variation so
wide that, in the light of our knowledge of the fluctuations of
blood-pressure in man, it suggests strongly the fallacy of any con-
clusions drawn from a comparison of two or three measurements
at long intervals.
To obtain some more definite idea of the changes occurring
from day to day in experimental animals, I have endeavored to
apply to the dog the commonly employed clinical methods. After
various attempts, the most satisfactory method was found to be a
modified Riva-Rocci cuff applied to the lower foreleg, the pulse
being palpated in the artery at the bend of the ankle or in the
plantar aspect of the paw. A rubber bag 7.5 x 15 cm., with a
slightly larger outer leather cuff, will fit almost any dog, the fore-
leg being not less than 8 cm. in length, and from II to £4 cm. in
circumference in a large number of laboratory dogs examined.
For small dogs a cuff 5 x 11 cm. is adequate. Measurements are
greatly facilitated by using a pressure bottle connected with the
cuff and the manometer through valves operated by foot pedals,
BLOOD-PRESSURE CHANGES. 109
leaving both hands free, in place of the usual rubber bulb or
Politzer bag as the source of pressure.
The greatest difficulty is the satisfactory palpation of the small
pulse in the foot. In certain dogs it is impossible, and animals
must be selected that possess a reasonably large and superficial
artery. It is impossible to appreciate the return of the pulse after
obliteration, but with practice, if the animal can be kept quiet, the
obliteration of the pulse can be appreciated within perhaps 10 or
I5 mm. limits of error, always on the side of under-estimation.
When the foot is cold, it should be wrapped in warm cloths to
dilate the vessels, before taking readings.
A number of experiments, in which I have followed the pres-
sure changes during an operation coincidently with a direct carotid
tracing, show that one can follow fairly rapid and marked fluctua-
tions of blood-pressure in this way, with reasonable certainty. The
results have no absolute, but, I am convinced, a real relative value.
For the solution of such problems as the one studied by Passler
and Heineke, and which Carrel and I are engaged in, I believe
that frequent approximate blood-pressure observations are of more
significance than a few isolated, though accurate, measurements.
57 (395)
Note on the blood-pressure changes following reduction of the
renal arterial circulation.
By THEODORE C. JANEWAY.
[From the Rockefeller Institute for Medical Research. |
Of the various workers who have studied the effects of reduc-
tion of kidney substance, only Passler and Heineke record system-
atic blood-pressure observations. They were able to make direct
measurements in the femoral on five dogs before and after operation,
and reported a rise in pressure in all, the smallest increase being
I5 mm., the greatest 29 mm., and the average 21.5 mm. These
figures are based on the comparison of single readings before
operation with one or more after operation, and are open to the
objections I have previously urged. Because of the small number
of reported observations in this field, I hope to be pardoned for
presenting my still very incomplete studies at this time, in order
110 SCIENTIFIC PROCEEDINGS (33).
that I may demonstrate one of the animals now living with
reduced kidney substance and hypertension.
I have made blood-pressure readings, by the rough method
previously described, on twenty-three dogs, over a period of fifteen
months. Asa guide to normal readings in the dog I have figures
from twelve dogs that were in good health, several of these being
finally checked by direct carotid tracings. In these twelve dogs
the average pressure, calculated from a number of readings on
each, lay between g1 and 119 mm., the highest individual reading
being 130 mm., and the lowest 85 mm. A number of observa-
tions made before operation on the ten nephrectomized dogs
showed an average blood-pressure between g0 and 117 mm.;
highest reading was 135 mm., lowest 80 mm. These readings
average lower than those obtained in man, but the method as
applied to the dogs is more comparable to the results of Gartner
in man, since the artery used is more peripheral, and the pressure
within it more subject to fluctuations due to variations in local vaso-
motor tone. As I have already said, however, the errors are all
on the side of too low readings; therefore, with a sufficient number
of pre-operative readings to give a fair average, the finding of a
marked rise in blood-pressure subsequently cannot be attributed
to errors inherent in the method.
The dogs studied were operated on by Dr. Carrel as already
described, with the exception of one after the method used by
Bradford, Passler,and Pearce. Four died from too extreme reduc-
tion of the arterial blood supply of inanition, and one of an abscess
unrelated to the operation. All showed a slight rise in pressure
in the first three to seven days, with subsequent fall, except one
dog that died of extensive resection in four days. The most strik-
ing of the fatal cases showed the following :
Blood-pressure, mm. Hg.
Dog 19. Maximum. Minimum, Average.
Before operation, 1'5/ dayS.....--cscscseseetsoeseees 110 100 106
Afterioperation;i2 (dayS.c.c-ssssersnentacensscese=> 135 120 127
Terminalipertods 14/days is cmeccrsssese-ee-e- 2-2) LLO 70 83
Five dogs are still living, one having been operated on 105
days ago, the others ashorter time. This dog, No. 12, shows the
following clear result:
ACUTE INSUFFICIENCY OF RIGHT HEART. ae
Blood-pressure, mm. Hg.
Maximum, Minimum. Average.
Before operation, 45 days .......sscsssesovsscevceoseers 110 80 fofe)
After as Hirst periods) AS dAaySis.ccccecsaccess 120 100 III
Gt Ks second period, 26 days............. 140 IIo 121
“ 6 third period, 31 days ............6 150 110 125
ae cs Whole perntOdiswcc.ssscctieses+eeorrses 120
He has gained from 12,770 grm. to 16,250 grm. and his urine has
been free from albumin for three weeks, but is increased in quan-
tity. A still more marked hypertension has been obtained in Dog
20, as the following table shows :
Blood-pressure, mm. Hg.
Maximum. Minimum, Average.
Betorevoperationy:-23/GAYSiccsessesoessecseses esses 135 95 117
After GG IS BO ceaphosonecobosonooosgeceet 175 130 150
This dog is excitable and single readings are liable to vary
somewhat on this account, but the comparison of the averages,
based on eleven observations before and twenty-one after operation,
or of either the highest or lowest readings, all show a true hyper-
tension asa result of the reduction of functioning kidney substancs
by this method. This dog has a persistent albuminuria, with casts
and red blood cells, and a daily urine quantity of about 500 c.c.
The three remaining dogs have not been under observation long
enough, or have not had sufficient reduction of circulation, to give
definite results as yet.
58 (396)
The effect of experimental acute insufficiency of the right
heart upon the volume of the organs.
By H. C. THACHER, M.D.
[From the Laboratory of the Medical Clinic in Titbingen.|
If a small balloon be introduced into the right auricle or ven-
tricle, its inflation interferes with the action of the right heart and
renders the heart insufficient to perform its normal work. The
effect of this upon the systemic circulation should be nearly simi-
lar to that caused by acute cardiac insufficiency in general. The
changes in the volumes of the brain, liver, spleen, kidney, and
extremity resulting from such cardiac obstructions were registered
by oncometry in rabbits, cats and dogs.
The carotid blood-pressure, which was always registered as an
I12 SCIENTIFIC PROCEEDINGS (33).
index of the degree of circulatory disturbance produced, falls
abruptly to a lower level when the balloon is inflated. It then
remains fairly constant until a final collapse occurs just before
exitus.
The liver and brain increase at once in volume as the result of
an acute passive dilatation caused mechanically by the increased
venous pressure. In the other organs and extremity a moderate
similar passive dilatation can be demonstrated if, but only if, they
have been put ina state of active contraction before the cardiac
obstruction is made. Thus when previously contracted directly,
by the intravenous injection of adrenalin, or reflexly, by sensory
irritation, their volume-curve rises during the period of cardiac
insufficiency. But unless thus previously contracted, the kidney,
spleen, intestine, and extremity decrease promptly in volume when
the heart is obstructed. This decrease overshadows the relatively
slight effects of the increased venous pressure, so that the presence
of the latter is only manifest in a short “additional fall” of the
volume-curve which occurs just at the moment when the obstruc-
tion is removed. This ‘additional fall” is synchronous with the
drop in the venous pressure, and occurs before the organs begin
to return to their normal size.
The decrease in volume of these organs, on the other hand,
does not correspond to the fall of arterial blood-pressure, but may
continue for as much as five minutes after the latter has reached
its lowest point. It is due rather to an active contraction of the
arteries and capillaries tending to compensate for the blood lost
from the circulation by stagnation in the veins, liver, and brain.
The foregoing work was conducted in the laboratory of the
Medical Clinic in Tubingen. I desire here to express my grati-
tude to Professor Romberg and his first assistant, Dr. Schlayer.
Thirty fourth meeting.
The Rockefeller Institute for Medical Research. May 26, 1909.
President Lee in the chair.
59 (397)
The comparative toxicity of sodium chloride and of
staining solutions upon the embryo of Fundulus.
By ELIZABETH COOKE and LEO LOEB.
[from the Laboratory of Experimental Pathology of the University
of Pennsylvania; and from the Marine Biological
Laboratory, Woods Fiole. |
What substances enter cells and upon what conditions the
entrance of various substances into cells and the permeability of
organized animal membranes generally depends, is as yet only very
imperfectly understood. The following experiments may not be
without interest in this connection.
In studying the toxicity of stains upon star-fish eggs, we find
thionin, Bismarck brown, methylene blue and neutral red all to be
very poisonous, if the solutions are exposed to light. Among
these, neutral red is perhaps less poisonous than the other stains.
Solutions of eosin are very much less toxic than the other sub-
stances. Thionin, Bismarck brown, methylene blue and neutral
red easily penetrate into ova and stain them in a characteristic
way. LEosin does not stain living cells, but only enters in combi-
nation with the dead protoplasm.
Very different is the degree of toxicity of these stains towards
the eggs of /undulus. Here, Bismarck brown, thionin, methylene
blue and eosin are devoid or almost devoid of toxic action, whilst
neutral red alone possesses any marked degree of toxicity, if the
solution acts in the light. And the latter stain is likewise the only
one able to enter the healthy ova of Funxdulus and to stain certain
parts of the embryo. We are therefore justified in the conclusion
that in the case of stains the toxicity of these substances towards
(113)
114 SCIENTIFIC PROCEEDINGS (34).
ova is dependent upon and is an indicator of their combination
with the protoplasm of certain cells of the embryo.
Now, it is not without interest to state that the toxicity of
neutral red varies according to the stage of development at which
the eggs are exposed to the influence of the staining solutions.
Ova immersed in a solution of neutral red and exposed to the light,
inside of sixteen hours after fertilization are most severely affected ;
ova exposed approximately twenty to thirty hours after fertilization
are somewhat more resistant, and ova which are exposed to the
light as late as two to four days after fertilization are affected only
to a very slight degree.
Correspondingly, we find that the older the embryo becomes,
the less is it liable to be stained with neutral red and in embryos
five days old we usually find almost the whole embryo unstained
with the exception of the newly developed liver which appears in
an orange-yellow color.
We may therefore conclude that the embryos of Fundulus
and their cells become less and less permeable for neutral red as
the development advances and that its toxicity decreases cor-
respondingly.
A curve of toxicity almost parallel to that of neutral red we find
in the case of isotonic sodium chloride solutions. During the first
sixteen hours isotonic solutions of sodium chloride are extremely
toxic to the embryo of /undulus ; from twenty to thirty hours there
is noticeable a certain decrease in toxicity ; while embryos two to
four days old develop in 5/8 N. sodium chloride solutions almost
as well as in sea water. We see, therefore, that the similarity of
the curves is very great and inasmuch as in the case of the neutral
red the variations in toxicity seem to depend upon variations in
the staining ability of this substance and therefore probably upon
the permeability of certain membranes or of the protoplasm of cer-
tain cells to the stain, we may assume as the most plausible ex-
planation that in the case of sodium chloride the variations in
toxicity also depend upon the permeability of certain organized
structures to the latter substance, and that therefore the conditions
of permeability in the embryo of /indulus depend upon the same
conditions in the case of the lipoid soluble neutral red and in the.
case of lipoid insoluble inorganic salts, a conclusion which is at.
INFLUENCE OF CALCIUM CHLORIDE UPON URINE. 115
variance with the views of Overton and Hoeber, but agrees with
the observations made by Jacques Loeb, Robertson and by the
botanist, Ruhland. We are well aware of the number of variable
factors which are to be taken into account in the interpretation of
these phenomena which may perhaps later necessitate a somewhat
more complicated explanation; but we believe that comparative
studies in the toxicity of stains and of various other substances will
prove to be of value in the elucidation of the problems of cell per-
meability and of the cause of toxicity.
60 (398)
The influence of calcium chloride and of adrenalin upon the
secretion of urine and upon absorption from the
peritoneal cavity.
By MOYER §S. FLEISHER and LEO LOEB.
From the Laboratory of Experimental Pathology of the Universit
Jf 14 Sy, LV
of Pennsylvania. |
I. Intraveneous injection of calcium chloride diminishes the
secretion of urine. Porges and Pribram ascribed this effect to the
lowering of blood pressure which follows the intravenous injection
of this substance. Our experiments, we believe, show such an
interpretation to be erroneous for the following reason :
If we add adrenalin to sodium chloride solutions the blood
pressure rises during the intravenous injection of this fluid and we
also find a noticeable increase in diuresis under the influence of
adrenalin. If we now add calcium chloride to the adrenalin-
sodium chloride mixture the blood pressure remains likewise very
high during the intravenous injection and the ultimate fall due to
the influence of calcium chloride is delayed for a considerable time,
but notwithstanding the high blood pressure produced by adrena-
lin which is in itself a substance favorable to diuresis, the addition
of calcium chloride again causes a marked decrease in diuresis.
The effect of calcium chloride in diminishing the secretion of urine
can therefore not be ascribed to its action on the blood pressure,
but to some other condition, most probably to its direct influence
upon the epithelial cells of the kidney, an interpretation originally
given by John B. MacCallum.
116 SCIENTIFIC PROCEEDINGS (34).
II. As Exner and Meltzer and Auer found, the intravaneous
(Meltzer and Auer) and intraperitoneal (Exner) injection of adrena-
lin delays the absorption of fluoresceine and other substances from
the tissues, from the peritoneal cavity and from the blood vessels.
On the other hand, we found that adrenalin has a distinctly accel-
erating effect upon absorption of isotonic sodium chloride solutions
from the peritoneal cavity, if adrenalin is injected repeatedly intra-
peritoneally during a period of two and a half hours. This accel-
erating effect is absent in nephrectomized animals; it is, however,
noticeable in rabbits injected twenty hours previously with uranium
nitrate and is still indicated in animals injected with uranium nitrate
three days before testing the absorptive power.
Adrenalin also causes an increase in the secretion of urine and
the improved absorption might therefore perhaps be ascribed to
the increased elimination of fluid through the kidneys. Such an
interpretation seems to be strengthened, if we consider that in
nephrectomized animals this effect of adrenalin is absent. On the
other hand, in individual experiments, parallelism between the ab-
sorption from the peritoneal cavity and the degree of diuresis fre-
quently is absent. In experiments concerning the effect of coffeine
upon the absorption from the peritoneal cavity we found that after
injection of coffeine the absorption from the peritoneum may be
very slight notwithstanding a very strong diuresis. We also notice
that during the first period of the action of uranium nitrate the in-
creased diuresis is not accompanied by a corresponding increase in
absorption.
Notwithstanding these possible objections, at the present we
cannot yet exclude the possibility that the improvement in absorp-
tion from the peritoneal cavity under the influence of adrenalin is
due to the diuretic action of this substance. The difference in
absorption from the peritoneal cavity which we notice in experi-
ments with animals after nephrectomy on the one hand and after
administration of uranium nitrate on the other hand, is of interest
and may perhaps bea causative factor in the edema which develops
in animals injected with uranium nitrate.
Furthermore these experiments suggest that adrenalin may
improve the absorption of water, but at the same time retard the
absorption of sodium chloride from the peritoneal cavity. We
have begun experiments, in order to decide this question.
STUDIES ON THE LiFE CYCLE oF PARAMECIUM. Ly
61 (399)
Observations on uricolysis, with particular reference to the
“uric acid infarcts” of the newborn.
By H. GIDEON WELLS and HARRY J. CORPER.
[From the Pathological Laboratory of the University of Chicago. |
Mendel and Mitchell demonstrated that in the embryo pig the
enzymes concerned with purin metabolism appear at different
stages of development, the uricolytic power not appearing until
after birth and being feeble during the first months of extra-uterine
life. If the same late development of uricolytic power were present
in the human fetus it would explain the occurrence of deposits of
urates in the kidneys of newborn infants. Schittenhelm and Schmidt
alone have studied uricolysis by infantile and fetal tissues, and
have claimed to get active uricolysis. This result is questionable,
because later work by Kunzel and Schittenhelm indicate absence
of uricolysis by adult tissues. We have found no evidence what-
ever of uricolytic activity on the part of fetal tissues at any stage
of development, nor of adult tissues. The latter observation is in
harmony with the negative results obtained by Wiechowski in ex-
periments 27 vitro and 7 vivo, and indicates that the human body
has little if any power to destroy uric acid. The statements in the
older literature that allantoin is found in the urine of pregnant
women has been disputed by Wiechowski, and our failure to
demonstrate uricolysis by human placenta as well as other fetal or
adult human tissues points in the same direction.
Additional observations are the demonstration of active urico-
lysis by the liver of the guinea pig, absence of uricolysis by spleen,
bone marrow and probably the leucocytes of the dog, and the
apparent absence of inhibitory power of dog serum upon uricolysis
by dog liver.
62 (400)
Studies on the life cycle of Paramecium.
By LORANDE LOSS WOODRUFF.
[From the Sheffield Biological Laboratory of Yale University. |
A year ago I reported to this society the results obtained up
to that time on the life cycle of Paramecium when subjected to a
118 SCIENTIFIC PROCEEDINGS (34).
varied environment. I wish now to bring the results up to date
(May 26, 1909).
A culture of Paramecium aurelia (caudatum) was started on
May 1, 1907, with a “ wild”’ individual isolated from a laboratory
aquarium, and during the twenty-five months which have elapsed
since that time it has been under daily observation. Infusions of
hay and grass together with any material that may be found in the
normal habitat of Paramecium have been employed as a culture
medium. The possibility of contamination by cysts or “wild”
Paramecia has been eliminated by boiling the infusion. Daily iso-
lation of an individual from each of the various lines of the culture
has enabled an accurate record of the division rate to be kept and
has precluded the possibility of endogamous conjugation.
So far the culture has attained the 1,185th generation. The
average rate of division for the entire period is over one and a half
divisions per day. The average rate has not fallen during any
ten-day periods as low as one division in two days, while during
several ten-day periods it has averaged over two and a half divisions
per day. Marked physiological depression has not been indicated
by the rate of division and consequently special stimuli have not
been employed to ‘‘ rejuvenate” the organisms.
The results thus far obtained certainly show that the life cycle
of Paramecium when subjected to a varied environment may be of
very great duration, and, I believe, strongly suggest that the life
history may be of unlimited duration.
63 (401)
Immunity to various species of trypanosomes induced in
mice by the cure of experimental infections.
By B. T. TERRY.
[From the Rockefeller Institute for Medical Research. |
When properly treated a temporary immunity was secured
against the organisms of surra of India, surra of Mauritius, caderas,
dourine and nagana. The immunity was specific in the sense that
it was active against the species cured but not against any other.
The immunity varied with the virus, the medicament, the time at
which the immunity tests were begun, the number of the tests, the
ImmuNITY TO VARIOUS SPECIES OF TRYPANOSOMES. eae)
intervals between them and the natural variations in the mice
employed.
Against the parasites of surra of India, surra of Mauritius,
caderas, nagana, and a toluidin blue resistant strain of nagana, an
immunity was produced which was strong enough to prevent one
or more subsequent inoculations of virus from infecting. The im-
munity to dourine was less strong.
In producing immunity to surra of India a single injection of
dichlorbenzidine plus amidonaphtol disulphonic acid, 1, 8, 3, 6,
or “Cl,” was more efficient than one of acetylatoxyl or arseno-
phenylglycin.
Even when the medicaments apparently prevented infection an
immunity was produced. It is interesting that two injections of a
mixture of “Cl” and acetylatoxyl has completely protected a
normal mouse against an inoculation with surra of India given six
days after the second treatment. The mixture protected about
twice as long as either of its two constituents used alone had done.
The immunity reaction distinguished with sharpness organisms
supposed to have had a common origin, namely, surra of India and
surra of Mauritius. Occasionally, however, these two species im-
munized against each other. With equal clearness the reaction
distinguished between organisms known to have had a common
origin, ¢. g., the toluidin blue resistant strain and the parafuchsin
resistant strain. When mice were immunized to the toluidin blue
trypanosomes, an inoculation with the same virus failed completely,
while the tests with the parafuchsin resistant strain and with all
others, infected and killed.
By means of the immunity reaction it was apparently possible
to separate in purity organisms that had been mixed zx vitro. By
inoculating a mixture of surra of India and surra of Mauritius into
mice immune to surra of India an infection with surra of Mauritius
was obtained. The surra of India was separated by inoculating
the mixture into mice immune to surra of Mauritius. Ina similar
way caderas and surra of India were separated.
When mice infected with a mixture of two species of trypano-
somes were cured, an immunity to both was produced.
In securing prolonged specific immunity, frequent injections of
the virus at close intervals were of value. A mouse cured of
120 SCIENTIFIC PROCEEDINGS (34).
caderas by a single injection of trypanred acquired an immunity
that lasted 50 days. Another mouse cured of surra of Mauritius
by acetylatoxyl and “Cl” hadastrongimmunity. In the 46 days
that followed treatment it received eleven inoculations of virulent
surra of Mauritius trypanosomes but did not become infected.
When next tested for its immunity (311th day), it was apparently
hypersensitive to infection. It was killed in 8 days by a greatly
attenuated surra of Mauritius strain. The attenuation was appar-
ently due to long continued passage through guinea pigs. One of
the two controls inoculated with this virus died on the twentieth
day. The other carried the trypanosomes for I11 days, recov-
ered spontaneously, and is still alive (184th day).
64 (402)
The leucin fraction of proteins. II.
By DONALD D. VAN SLYKE and P. A. LEVENE.
[From the Rockefeller Institute for Medical Research, New York. |
In a previous communication’ we have described a method for
quantitatively separating leucin and isoleucin from valin, the leucin
isomers being precipitated as normal lead salts. It has since been
found that from the specific rotation of the mixture of leucin and
isoleucin, as obtained analytically pure from the lead salts, the
percentage of each can be accurately calculated. The rotation
of d-leucin in 20 per cent. hydrochloric acid is + 36.8°, of
l-leucin + 15.6°. Consequently the proportions are calculated
by the formule :
R—15.6
per cent. d-isoleucin = ReGen 2)
Zee
6.8—R
per cent. d-leucin = sa iS 5 )
(R representing specific rotation in 20 per cent. hydrochloric acid).
The specific rotations of the isomers are unaffected by the boiling
acid used for hydrolysis, but are affected by boiling with alkalies.
Consequently the method is not applicable to products of alkaline
hydrolysis, which however is seldom used.
.) These Proceedings, 1909, vi, 54.
“ CALVIN,” VAHLEN’S ACTIVE PRINCIPLES OF ERGOT. 121
Analysis of the leucin fractions of casein and edestin gave the
following results, those obtained by Abderhalden being given for
comparison. The figures represent yield in grams from 100 grams
of protein.
Casein. Edestin.
V-S. and L. Abderhalden, V-S.andL. Abderhalden.
Leuci 8
eee 7 = 10.5 8.1 20.9
Isoleucin, 1.51
Valin, 6.69 1.0 5.6 0.45
Total ‘‘leucin fraction,” 16.04 11.5 ne Ey) 21.35
Our figures are based on analytically pure products. It is evident
that Abderhalden missed from 80 to go per cent. of the valin which
was undoubtedly calculated in with the leucin, as the two are not
separable by the methods previously available. Still other prod-
ucts in the necessarily crude mixture may account for the high
yield from edestin.
65 (403)
«“ Clavin,” Vahlen’s active principle of ergot.
By DONALD D. VAN SLYKE.
[From the Rockefeller Institute for Medical Research, New York. ]
In a recent paper Vahlen’ describes the isolation of the two
constituents of clavin, a crystalline substance isolated by him from
ergot. By means of their copper salts two substances, leucin and
“clavin base’”’ of the formula C,H,,O,N, were separated from the
clavin. From analysis of clavin it appeared to consist of leucin
and clavin base in molecular proportions, and was regarded as a
salt-like combination, similar to that in which some alkaloid bases
are found, the leucin acting as acid, the clavin base as base.
Vahlen regards clavin as the active principle of ergot in stimulat-
ing contraction of the uterus, and the clavin base as the active
constituent of clavin.
From the description of clavin, it appeared similar in both
physical and chemical properties to the mixture of leucin and valin
obtained from proteins. A sample of Vahlen’s clavin was obtained
from Merck and submitted to the process devised for determination
of leucin, isoleucin, and valin in the presence of one another.” The
1 Arch. f. exper. Path. u. Pharm., 1909, |x, 42.
? Levene and Van Slyke: These Proceedings, 1909, vi, 54.
122 SCIENTIFIC PROCEEDINGS (34).
clavin, which when purified free from ash had the properties de-
scribed by Vahlen, consisted entirely of these three amino acids,
the latter being isolated analytically pure: 2.02 grams of clavin
gave 0.79 gram of leucin, 0.45 gram isoleucin, 0.75 gram valin.
We have not yet determined whether any of these amino acids has
the pharmacological effect assigned to clavin.
66 (404)
Some effects of sodium benzoate.
By DANIEL R. LUCAS. (By invitation.)
[trom the Laboratory of Biological Chemistry of Columbia Uni-
versity, at the College of Physicians and Surgeons. |
This research was suggested to me by different experiences
with sodium benzoate when taken by mouth in the following ways :
A. Pure (1) as crystalline salt, or (2) in aqueous solution. B.
In neutral or alkaline solutions, or in mixtures rich in fat, carbo-
hydrate or protein, ¢. g., milk. C. With vegetable or fruit acids (1)
hoi, as in tomato soup, or (2) cold, as in canned plums, oranges,
lemons, etc. D. In beverages containing high percentages of
organic acids, ¢. g., cider, lemonade, grape juice, wine, etc. E.
In mixtures containing inorganic acids, e. g., artificial gastric juice.
Brunton has studied the effects of benzoic acid on enzymes and
bacteria. The strong inhibiting effect of this substance on their ac-
tivity is in striking contrast to the slight effect of sodium benzoate.
Doepner has shown that fairly large quantities of sodium benzoate
(2 per cent.) did not prevent the development of Proteus vulgaris
and, in strengths equal to 0.5 per cent., only slightly retarded the
development of B. enteritidis, B. fluorescens and B. coli. Fleck
found that benzoic acid in concentrations equal to 0.6-0.7 per cent.
caused marked inhibition of yeast fermentation and that the inhib-
iting action was markedly decreased by the amount of protein
present. Lehman observed that meat extract putrefies in the pres-
ence of I to 2 per cent. of sodium benzoate, but less benzoic acid
acts more strongly antiputrefactive when the reaction of the medium
is markedly acid. The action of sodium benzoate under markedly
acid conditions is the same as the actionof benzoic acid. Under such
conditions the action of the benzoate diminishes with decrease of
SoME EFFECTS OF SODIUM BENZOATE. 123
acidity. Chassevant and Garnier found that 1.4 gram of benzoic
acid per kilo was fatal to guinea pigs in five to seven hours ; larger
doses (2 grams per kilo) did not necessarily kill sooner.
The results of my own work may be briefly summarized as
follows :
Effects on microorganisms. —Sodium benzoate, in concentrations
of about I per cent., preserves fruits and vegetables which are
strongly acid. Crystals of free benzoic acid often appear in such
mixtures. Sodium benzoate (1 per cent.) added to weakly acid
fruits and vegetables does not preserve them well. Sodium ben-
zoate (I per cent.) added to fruits and vegetables, the acidity of
which has been neutralized, does not preserve them. Pure apple
juice, containing 0.1 per cent. of sodium benzoate, developed
mould after ten days; commercial benzoated cider under the same
conditions, without the further addition of benzoate, did not de-
velop mould or otherwise undergo degeneration.
Effects on taste. — Acid fruit juices containing I per cent. of so-
dium benzoate, have a biting taste, an effect due to the liberated
benzoic acid. Milk or alkaline vegetables treated with sodium
benzoate (1 per cent.) do not taste of benzoic acid at any time
during the first twenty-four hours after the treatment. After
twenty-four hours, however, acid decomposition begins in milk in
spite of the presence of 1 per cent. of sodium benzoate, when the
mixture tastes distinctly of benzoic acid. Sips of 1 c.c. of orange
juice, to which 1 per cent. of sodium benzoate has been added, cause
burning in the posterior part of the mouth, the throat, the esoph-
agus and stomach, with gastric discomfort, belching, uneasi-
ness of the bowels and excessive passage of gas by rectum.
Experiments on men with cider. Pure cider. —Pure apple
juice tastes sweet, bland; produces no stinging sensation in the
throat; and is ordinarily enjoyed and well borne in volumes
equal to 1,000 to 2,500 c.c. (ingested during a period of two or
three hours). It is diuretic in action and, in amounts varying
from 1,000 to 2,000 c.c., causes laxation of the bowels. This
effect frequently depends on the rapidity with which it is ingested ;
it does not ordinarily cause laxation even when taken in large
amounts, if ingested little by little. The average amount of pure
apple juice consumed during an evening by adult males who
124 SCIENTIFIC PROCEEDINGS (34).
had free access to it was about 1,200 c.c. (twenty subjects).
When from 1,000 to 2,500 c.c. of pure apple juice are con-
sumed neither headache, nausea, albuminuria nor sub-normal
temperature is produced. The specific gravity of the urine is
greatly decreased when a liter of pure unfermented cider is con-
sumed but the volume is markedly increased within forty-five
minutes after its ingestion. The forty gallons of pure apple juice
consumed by the human subjects of my investigation contained
considerable apple pulp and 2.716 grams of free acid (calculated
as acetic acid) per 1,000 c.c.
Benzoated cider. — Twenty four subjects were observed in the
first experiment. Twelve received pure apple juice; twelve
received samples of the same apple juice containing 0.1 per cent.
of sodium benzoate. As none of the subjects knew that they were
to receive at that time anything but pure apple juice, unfavorable
psychological influences were eliminated from the experiments.
Each subject received three question blanks to be filled out by
himself daily as long as any symptoms lasted, which, I am assured,
was done faithfully in every instance.
In comparison with those who received pure cider, the men who
drank the benzoated apple juice exhibited the following special
symptoms: Burning taste, fulness in the head, headache, nervous-
ness, nausea, vomiting, itching of the skin, unusual perspiration, ir-
regularity of bowels (constipation usually) decreased flow of urine,
increased specific gravity of the urine, and albuminuria. | Excessive
amounts of hippuric acid were eliminated, especially during the first
few hours, after ingestion of the benzoated apple juice.
Apple juice to which a small amount of sodium benzoate is
added becomes sweeter to the taste, but astringent, stinging, and
irritating to mucous membranes. The presence of 0.5 per cent.
of sodium benzoate renders cider quite unpalatable, but the pres-
ence of 0.1 per cent. may be overlooked by subjects not acquainted
with the taste of pure apple juice.
Ifthe apple pulp is previously filtered from the juice the effects of
added benzoate become much more evident. A liter of such
filtered cider, containing 0.2 to 0.3 per cent. of sodium benzoate,
caused albuminuria within three hours almost without exception
in the largest and soundest picked subjects. However, I myself
Some EFFects OF SopiuM BENZOATE. 125
was able to ingest 1,000 c.c. of apple juice containing 0.5 per cent.
of sodium benzoate, without any albuminuria arising. The amount
of hippuric acid in the urine was very large for the first few hours.
The secretion of urine was very much reduced for twelve hours,
while I suffered from some of the other symptoms above men-
tioned, although as a subject in a former investigation I ingested
as much as 6 grams per day, for three successive days, in milk on
a full stomach, without the slightest discomfort.
Small doses of sodium benzoate given with acid substances
to patients with albuminuria aggravated this condition and caused
alarming symptoms, classical of nephritis—for six days there-
after in one subject.
Experiments on dogs. First experiment. — One dog weigh-
ing 3.5 kilos fasted for twenty four hours and was then given
I gm. of sodium benzoate, decomposed with the theoretical
amount of hydrochloric acid to form sodium chloride and free
benzoic acid, with no excess of hydrochloric acid. In thirty
minutes the animal showed evidences of muscular weakness and
nausea, lay quietly and breathed in a laborious manner. This
continued for six hours. On the next day, twenty four hours
after the previous dose, the animal was given 4 gm. of sodium
benzoate with a sufficient amount of hydrochloric acid to de-
compose it into benzoic acid, plus 120 c.c. of 0.2 per cent. citric
acid. The animal became very weak in one hour, respirations
were reduced to nine per minute, and were very labored. Tonic
and clonic convulsions began one hour and fifteen minutes after
the dose was given. The animal, after several hard convulsions,
died two hours and twenty minutes after administration.
The autopsy showed congestion of various organs. There was
very pronounced congestion of the kidneys, stomach and intestines,
with ulceration in places. The liver and lungs also showed evi-
dences of infarcts.
Second experiment. — Two dogs had been fed on dog biscuits
and water for several weeks, and then fasted for thirty six hours.
Animal No. 1.— The first animal was a male, weighing 3.5
kilos. He was given a mixture of 3.5 gm. of sodium benzoate,
50 c.c. of water, 0.65 c.c. of concentrated hydrochloric acid (sp.
gr. 1.19) and 100 c.c. of citric acid (0.2 per cent.). The animal
126 SCIENTIFIC PROCEEDINGS (34).
became quite uneasy after receiving the dose. At the end of an
hour he showed great muscular weakness and tremor.
Animal No. 2.— The weight of the second animal was 4.25
kilos. It was given a mixture of 100 c.c. of 0.2 per cent. citric
acid, 50 c.c. of water and 0.85 c.c. of concentrated hydrochloric
acid (sp. gr. 1.19). This animal was entirely unaffected.
The same experiments were repeated on the same animals the
next day; the results were practically identical. The animal (1)
that received the free acid-benzoic acid mixture, however, was
more prostrated than on the previous day and showed general stiff-
ness of the muscles. At the end of six hours it was chloroformed
and autopsied, when it was found that the stomach contained
“ coffee ground”’ material. There were ecchymotic areas and some
places appeared to be ulcerated slightly. The intestines showed
marked congestion here and there and appeared to be slightly
ulcerated in places throughout. The grumous material in the
stomach and intestines gave a strong guaiac test and was undoubt-
edly modified blood. The liver and lungs showed considerable
congestion with some evidences of infarcts. The kidneys were
cyanotic, the cortex very much congested, while the medulla was
pale and anemic.
Further investigation is contemplated, especially on the influ-
ence of nephrectomy on the toxicity of benzoic acid.
I am indebted to many members of the Purdue University
Alumni Association of New York City for volunteering as subjects
in this investigation and thus making it possible for me to carry
out experiments ona large number of individuals. The Secretary,
Mr. Leslie Hustable, Mr. Ray C. Ewry, Mr. R. W. Parks, Mr. F.
M. Waltz and Mr. H. Worsham of that organization have given
me special assistance in various ways. I am also indebted to Drs.
A. E. Olpp and Matthew Steel, and Messrs. Herzfeld and Bisch
for cooperation, and to Drs. Foster, Mosenthal and Rosenbloom
for criticism and suggestions. Professor Gies has given me all the
facilities of his laboratory for the conduct of this research, as well
as valuable criticism and suggestions.
IMPROVEMENT OF THE FoLIn METHOD. rey,
67 (405)
An improvement of the Folin method for the determination of
urinary ammonia nitrogen.
By MATTHEW STEEL. (By invitation.)
[From the Laboratory of Biological Chemistry of Columbia Univer-
sity, at the College of Physicians and Surgeons. |
In the fall of 1907, during the progress of a metabolism re-
search on “the influence of magnesium sulphate on metabolism,” *
anomalous results were obtained in our quantitative determinations
of urinary ammonia, whenever the magnesium salt was injected
either subcutaneously or intravenously into the animal.” These
anomalous results were found to be due to the facts that the magne-
sium was eliminated into the urines in question in relatively large
quantities, as ammonio-magnesium phosphate and that the re-
sultant deposits of crystalline triple phosphate were not thoroughly
decomposed by sodium carbonate, as used in the Folin method,
whereby ammonia, in variable amounts, remained in its solid form as
triple phosphate in the urines under investigation. We, therefore,
sought another method that would liberate all the ammonia from
ammonio-magnesium phosphate without producing ammonia from
such compounds as urea in the urine. None, however, was found
that fulfilled both conditions. Consequently, we were obliged
either to devise a new method, or else modify the Folin process,
so as to make it liberate the ammonia from triple phosphate. We
chose the latter course.
Our attempt was to find some alkali which would liberate all
the ammonia from ammonio-magnesium phosphate and whichat the
same time would not convert into ammonia any of the amino or
imino radicals in the various organic compounds in the urine.
Varying quantities of milk of lime, baryta water, and sodium
hydroxide were added separately to weighed amounts of triple
phosphate. These mixtures were aérated as usual. The results
obtained made it evident that neither milk of lime nor baryta water,
1Steel: These Proceedings, 1908, v, 132; /ournal of Biological Chemistry, 1908,
v, 85.
?Steel and Gies: These Proceedings, 1908, v, 134; Journal of Biological Chem-
istry, 1908, v, 71.
128 SCIENTIFIC PROCEEDINGS (34).
even in large amounts, was capable of liberating all the ammonia
from triple phosphate, whereas sodium hydroxide, in comparatively
small amounts, discharged the ammonia completely. The first
condition was, therefore, solved. It now remained for us to ascer-
tain whether sodium hydroxide would produce ammonia from such
amino compounds as urea.
After many preliminary trials, in some strictly comparative tests
on normal urines, I found that from 0.5 gramto 1 gram of sodium
hydroxide, plus about 16 grams of sodium chloride, gave results
that were in perfect accord with those of the Folin method. Over
fifty comparisons were made.
In oder to ascertain positively whether the modified method
would produce ammonia from non-ammoniacal radicals, weighed
samples of urea, uric acid, glycocoll, taurin, leucin, tyrosin and
hippuric acid were added separately and also collectively to 25 c.c.
portions of urine and the results compared with the figures for the
ammonia obtained from equal volumes of the original urine. In
no case was any increase obtained. The tests were repeated, but
20 c.c. of a standard solution of ammonium chloride were substi-
tuted for the 25 c.c. of the urine. In these cases, also, no increase
of ammonia output was obtained.
As a final test of the efficiency of the modified method the
ammonia content was determined in a normal urine by both the
Folin method and the modified method. Then to equal volumes
of the original urine 0.5 gram samples of triple phosphate were
added, and the ammonia contents again determined by both
methods. The ammonia was also determined in separate portions
of the triple phosphate.
The results of these directly comparative tests showed that,
with the modified method, the ammonia obtained from the urines to
which the triple phosphate had been added exactly equaled the total
amount of ammonia obtained from the corresponding urine and
the triple phosphate separately whereas, wth the Folin method, only
from 70 to 80 per cent. of the total amount of this ammonia was
recovered.
OBSERVATIONS ON METABOLISM. 129
68 (406)
The depressor substance of dog’s urine; its disappearance in
experimental acute nephritis.
By RICHARD M. PEARCE.
[From the Carnegie Laboratory of the New York University and
Bellevue Hospital Medical College. |
The urine of a normal dog when injected intravenously into
another dog in doses of three cubic centimeters causes an immedi-
ate fall in blood pressure varying from 25 to 96 mm. of Hg. This
effect, constant for normal urine, is not always obtained when the
urine from a chromate or uranium nephritis of the third to fifth day
is used. It is still obtained, however, in arsenic and cantharidin
nephritis of the same periods. This difference suggests that in the
tubular lesions of chromate and uranium nephritis, which are
characterized by extensive epithelial destruction, some substance
normally eliminated is retained while in the glomerular nephritis
caused by arsenic and cantharidin poisoning this retention does
not occur. The elimination of the depressor substance would ap-
pear therefore to be a function of the tubular epithelium.
In animals with experimental nephritis of the tubular type the
disappearance of the depressor substance from the urine is fre-
quently associated with a lowering of the blood pressure which
would appear to indicate that the retained depressor substance has a
definite effect on the general blood pressure. This observation is
not based however on blood pressure determinations on the same
animal before and after the development of nephritis but by con-
trasting the pressure in animals with tubular nephritis with that of
normal animals and those with glomerular nephritis.
The nature of the depressor substance has not been determined.
69 (407)
Observations on the metabolism of a subject of diabetes.
By PHILIP A. SHAFFER.
[from the Laboratory of Pathological Chemistry, Department of
Experimental Pathology, Cornell Medical College. |
The subject of the observations was a patient in the service of
Dr. Warren Coleman in Bellevue Hospital. Different known
130 SCIENTIFIC PROCEEDINGS (34).
diets were used and the urine was analyzed over a period of more
than three months. A portion of the results of the last part of
the period is given in the accompanying table. The unusual fea-
tures of these results will be briefly discussed.
Between twenty and eighty grams of tofa/ B-oxybutyric acid
(the acetone and diacetic acid being calculated as f-oxybutyric
acid) were excreted each day for at least eighty days without any
signs of impending coma. For more than two months with this
severe acidosis the subject showed practically complete carbo-
hydrate intolerance. As shown in the table the diet was then
changed to 255 grams of oatmeal. On this diet the acidosis and
the glycosuria decreased very much, the former ultimately disap-
pearing. This comparatively sudden transition from a condition of
severe to one of mild diabetes is very striking and appears to con-
firm the good results obtained by von Noorden and others with his
so-called ‘oat cure.”
The dependence of /-oxybutyric acid production upon the
amount of fat in the food was very clearly shown throughout the
observations. The amount of total $-oxybutyric acid excreted
varied in general with the amount of fat eaten, which is not usually
the case. Note the effect of the addition of butter to the oatmeal
diet. The amount of food-fat appears to have determined, in this
instance, the amount of fat burned.
An increase in the amount of fat in the food which caused an
increased acidosis appeared to result also in a damage to the
carbohydrate tolerance ; with the increase of acidosis there was a
very marked decrease in the amount of sugar burned. This phe-
nomenon is just the reverse of that so often observed, z. ¢., the
decrease of acidosis with an increased burning of sugar, and again
emphasizes the close inter-dependence between the metabolism of
carbohydrate and fat.
The observations were terminated by the death of the patient.
The immediate cause of death was not definitely established but
was probably due to the phthisis which complicated the diabetes.
There was no sign of coma and in view of the absence of acidosis
and of the great improvement in carbohydrate tolerance we can
scarcely believe that the diabetes was immediately responsible.
The blood obtained at autopsy contained only traces of S-oxybutyric
acid, the whole blood containing about 0.3 gram. There was no
OBSERVATIONS ON METABOLISM. 131
suppression of urine, over 500 c.c. being passed in the last five
hours.
The urine of the last two days is of interest; there was no
acetone and no increase in glycosuria, but a very great increase in
ammonia and in total nitrogen indicating a marked ante-mortem
increase in protein katabolism.
Sugar was determined by titration with Fehling’s or Pavy’s
solutions; and f-oxybutyric acid and its derivatives by the writer’s
method.
Foep. Urine.
| SS
Total
NH. Fat. N. NH,—N. Sugar. fB-oxybutyric
acid,
Average for 5 days...... 256 164 19.0 4.6 328 19.0
Average for 2 days...... 180 187 19.0 293 24.7
165 18
255 gm. oatmeal.......... ps Le = 32 Es
fol 1.5 94 1.6
s¢ ut 5.8 I.I 72 0.9
<s 60 5.1 D2 85 5.1
Same, -++ 50 gm.. ........ i 6 Oe z3 ae, EEs3
Ot 6.0 2.65 119g 10.3
ot se 5.5 2.0 108 4.9
Ge ae 4.6 1.8 64 1.4
Same, washed butter....J «« “ 5.6 0.9 48 0.7
ut 53 6.2 0.8 34 0.6
KC 60 5.6 5 0.0
Same, regular butter..... : i oo 4 ae
Ot OG 5.9 0. 36 17 0.0
es uC 6.7 0.83 8 0.0
Toast, butter, canesugar, { 170 59 13.4 1.75 16 0.0
GEFEGh nonnonnoecehoceoansed less less 32.2 3-32 8 0.0
Died at 1 P. M. next day.
132 SCIENTIFIC PROCEEDINGS (34).
70 (408)
On the decomposition of caffeine in the liver.’
By W. 0. EMERY and WILLIAM SALANT.
[From the Laboratory for Synthetic Products and Pharmacological
Laboratory of the Bureau of Chemistry, U. S. Dept. of
Agriculture, Washington, D. C.]
The earlier workers on the metabolism of caffeine and theo-
bromine maintained that these substances may undergo partial or
complete transformation in the body with the loss of one or more
of the methyl groups. Investigations carried out recently seemed
to indicate that this was due to specific enzymes. Schittenhelm,
Brugsch and Pincussohn’ claimed to have found an enzyme in
the lungs of the horse capable of splitting off the methyl groups
of caffeine. Kotake* came to similar conclusions as a result of
studies on the decomposition of caffeine in beef livers. He added
varying amounts of caffeine to aqueous extracts of the liver which
he allowed to digest under antiseptic precautions at body tempera-
ture in the thermostat for four days. Liver extracts without caf-
feine, similarly treated, were used as controls. At the end of each
period the purin bodies were precipitated and total nitrogen deter-
mined. He found in every case much larger amounts of total
nitrogen in the extract containing caffeine than in the control, from
which he concluded that the increase of purin substances was due
to the reduction of caffeine to non-methyllated purins.
The work of Fuijitani* has shown that caffeine stimulates
peptic digestion zz vitro. The possibility of a stimulating action
of caffeine on intra-cellular enzymes is therefore not to be excluded,
and might explain the results of Kotake. Moreover, in Kotake’s
experiments no separation of the alkaloid was attempted.
We therefore carried out a series of experiments in which the
caffeine as well as the purin nitrogen was determined. Finely
minced fresh beef livers were allowed to stand twenty four hours
in the presence of 5 c.c. toluol and were filtered through paper.
1 Published by permission of the secretary.
2 Cent. f. d. ges. Physiol, u. Path, des Stoffewechs, 1908, 1x, 290.
8 Arch. internat. d. pharm. et de ther., 1905, xiv, 21.
4 Zeit. f. physiol. Chem., 1908, lix, 378.
On THE DECOMPOSITION OF CAFFEINE IN THE LIVER. 133
Half a gram of caffeine was added to a portion of the extract thus
obtained, and kept in the thermostat at body temperature for from
two to ten days. An equal quantity of the extract without adding
caffeine, similarly treated, was used as a control. As indicated in
the accompanying table, practically the entire amounts of caffeine
were regained. The total quantities of nitrogen found in the pre-
cipitated purins were approximately equal save in two experiments
in which the amounts of total nitrogen were from 13 to Ig per
cent. greater when caffeine was added than in the controls.
Digestion of liver extracts with and without caffeine in the
presence of hydrogen peroxide likewise failed to indicate the pres-
ence of a specific enzyme capable of splitting off the methyl group
in caffeine.
EXPERIMENTS.
Sart | Pemgames| Uizggse | digction a | QUEERS | Nirogen.s| CESS
. 250 Two. 0.5 0.0699 0.4935
250 Two. — 0.0704 —
I * 250 Four. 0.5 0.0660 0.4921
i 250 Four. — 0.0581 —
250 Eight. 0.5 0.0531 0.4915,
3 250 Eight. — 0.0522 —
300 Five. 0.5 0.0511 | 0.4918
Il X 300 Five. — 0.0499 | —
5 A 300 Ten. 0.5 0.0604 0.4799
300 Ten. — 0.0496 —
250 Four and 0.5 0.0345 | 0.4897
Ill i one half.
; 250 Four and -— 0.0370 —
one half.
500+ Four and 0.5 0.0416 | 0.495r
Iv < 5c.cm.H,O,| one half.
: 500+ Four and — 0.0441 “=
5 c.cm, H,O, one half.
300 Four. 0.5 0.0478 0.4931
V. I 300 Four. 0.5 0.0432 0.4952
300 Four. -- 0.0444 —
1 Total nitrogen was determined by E. C. Trescott.
134 SCIENTIFIC PROCEEDINGS (34).
71 (409)
The comparative toxicity of ethyl and amyl alcohol and
their effect on blood pressure.'
By WILLIAM SALANT.
[From the Pharmacological Laboratory, Bureau of Chemistry, VU. S.
Dept. of Agriculture. |
The experiments were carried out on frogs, rabbits, cats and
dogs. The alcohols were administered in various concentrations
and were given by mouth, injected subcutaneously, or into the
peritoneal cavity. The toxicity of amyl alcohol was in all cases
much greater than that of ethyl alcohol. The difference in the
toxicity of ethyl and amyl alcohol was even more marked in suba-
cute intoxication. The experiments on frogs showed that the
minimum fatal toxic dose of amyl alcohol is from one eighth to one
seventh that of ethyl alcohol, while the toxic dose of amy] alcohol
for the rabbit is only about one fourth to one half that of ethyl
alcohol.
The effect of ethyl and amyl alcohol on blood pressure.— The
experiments were carried out with 2 per cent. solutions on
healthy dogs 8 to 10 kilos in weight, and on cats. Morphine-
ether narcosis was employed for the dogs, and ether alone for cats.
Injections were made from a burette into the femoral vein. The
fall of blood pressure after amyl alcohol was introduced, was con-
siderably greater than that after the introduction of the same quantity
of ethyl alcohol. In some experiments, the injection of 15 c.c. of
2 per cent. amyl alcohol in thirty two seconds caused a fall of blood
pressure of 80 millimeters of mercury, while the same amount of
ethyl alcohol injected in four seconds was followed by a fall of
blood pressure, amounting only to 20 millimeters of mercury. In
other experiments in which from 25 to 50 c.c. of 2 per cent. ethyl
alcohol caused little noticeable change or only a slight fall of blood
pressure, after the injection of the same quantities of amyl alcohol,
the maximum fall of blood pressure amounted to 40 and 95 milli-
meters of mercury. The recovery was also much slower in all
cases after amyl alcohol and was much more gradual than the fall of
blood pressure. Experiments with from 3 to II c.c. of 2 per cent.
1 Published by permission of the secretary.
PENTOSURIA. 135
amyl alcohol carried out on cats has likewise shown a depressing
action on blood pressure, while 25 c.c. of ethyl alcohol failed to
show an appreciable change. Very small quantities of amyl alco-
hol (3 c.c. of a 2 per cent. solution) failed to reduce blood pressure
in dogs ; with larger quantities of it (10 c.c.) the fall of blood pres-
sure was 8 millimeters of mercury, when injected in one hundred
seconds. The same amount, however, when injected in seven sec-
onds lowered the blood pressure 50 millimeters of mercury. After
section of both vagi in dogs, the action of amyl alcohol was not
constant ; in two experiments the fall was greater, in one it was
less, than with the vagi intact. The action of ethyl alcohol under
these conditions likewise varied. In one experiment, amyl alco-
hol, 15 c.c. of a 2 per cent. solution, was injected after the intro-
duction of atropine sulphate, both vagi being cut ; the fall of blood
pressure was not as great as before the injection of atropine with
vagi cut, but the recovery of blood pressure to the same height as
it was before the introduction of atropine occurred in from two to
five minutes as against 35 seconds during the control period.
In this connection, it might be mentioned that some observa-
tions on the effect of caffeine on the depressing action of alcohol,
amyl and ethyl, have been made. In both instances, there was a
marked retardation of recovery of blood pressure. After the in-
jection of 25 to 50 c.c. of 2 per cent. solutions of caffeine, the
recovery was delayed, fifteen or twenty minutes.
72 (410)
Pentosuria.
By L. B. STOOKEY.
[From the Physiological Laboratory of the Unwersity of Southern
California. |
During the past two years one hundred urines which reduced
Fehling’s solution slightly were examined for identification of the
reducing substance. In fifteen cases pentose was found to be
present. Identification was made by (1) phenyl pentosazone
crystals, (2) phloroglucin reaction, (3) absorption spectrum. The
nature of the pentose was not determined. In all cases several
specimens were examined under dietetic precautions in order to
exclude alimentary pentosuria. In these fifteen cases no carbo-
136 SCIENTIFIC PROCEEDINGS (34).
hydrate other than pentose could be detected. The pentose con-
tent ranged between 0.1 and o.5 per cent. In all of these fifteen
urines containing pentose acetone was found in appreciable quantity.
Acetone was detected by treating the distillate with sodium nitro-
prusside and ammonia.
Five of these fifteen cases showed a positive tuberculin reaction
(subcutaneous injection of the bacillen emulsion), three gave a
history of chronic alcoholism but claimed to have been abstaining
for a considerable time, three were suffering from some obscure
intestinal disturbances, and in regard to the remaining four cases
little can be said at the present writing.
The points of interest to me are (1) apparent frequency of pen-
tosuria, (2) positive tuberculin reaction in one third of my cases of
pentosuria, (3) presence of acetone in every pentose-containing
urine examined,
RECAPIMURATION OF THE NAMES OF
(iP eAULHORS AND OF THE TITLES
OF THE “COMMUNICATIONS.
VOLUME VI
Alsberg, Carl L.
3'76. The formation of gluconic acid by the olive-tubercle
organism and the function of oxidation in some microorganisms.
Anderson, John F. [with M. J. Rosenau. |
381. The effect of heat on the anaphylactic properties of
proteins,
Auer, John
358. A demonstration of the effects of carbon dioxide upon
the frog’s pupil.
391. [With 8. J. Meltzer.] The effects of local applica-
tions of chloride and sulphate of magnesium upon the centers
in the medulla compared with those of sodium chloride.
392. [With S. J. Meltzer.] Respiration by continuous
intrapulmonary pressure without the aid of muscular action.
Banzhaf, Edwin J.
344. The further separation of antitoxin from its associated
proteins in horse serum.
Becht, F. C. [with J.R. Green.] (By invitation.)
364. On the relative concentration of lysins, precipitins,
agglutinins, opsonins and related substances in the different
body fluids of normal and immune animals.
Burnett, Theodore C. [with T. Brailsford Robertson. |
378. On the depression of the freezing point of water due
to dissolved caseinates.
Burton-Opitz, R.
369. [With Daniel R. Lucas.] The vascularity of the
kidney as influenced by sensory impulses.
383. The vascularity of the speen as influenced by single
nerves of the plexus lienalis.
(137)
138 SCIENTIFIC PROCEEDINGS (30-34).
Carrel, Alexis
355. Presentation of a dog ten months after double ne-
phrectomy and replantation of one kidney.
393. Note on the production of kidney insufficiency by
reduction of the arterial circulation of the kidney.
Clowes, G. H. A.
354. A critical study of the conditions under which zymase
and its associated co-enzyme bring about alcoholic fermentation.
Cooke, Elizabeth [with Leo Loeb. |
397. The comparative toxicity of sodium chloride and FS
staining solutions upon the embryo of Fundulus.
Corper, Harry J. [with H. Gideon Wells. ]
399. Observations on uricolysis, with particular reference
to the “uric acid infarcts” of the newborn.
Crile, George W.
340. Further observations on the clinical aspects of
hemolysis.
Elsberg, Charles A.
382. A skin reaction in carcinoma from the subcutaneous
injection of human red blood cells.
Emery, W. 0. [with William Salant. |
408. On the decomposition of caffeine in the liver.
Famulener, Eugene [with William H. Park. ]
386. Toxin-antitoxin mixtures as immunizing agents.
Fleisher, Moyer 8. [with Leo Loeb. |
398. The influence of calcium chloride and of adrenalin
upon the secretion of urine and upon absorption from the peri-
toneal cavity.
Flexner, Simon [with Richard V. Lamar. |
388. The action of soaps on the pneumococcus.
Foster, Nellis B.
365. Studies of the influence of various dietary conditions
on physiological resistance. 1. The influence of different pro-
portions of protein in the food on resistance to the toxicity of
ricin and on recuperation from hemorrhage.
373. [With James C.Greenway.] Synthesis of uric acid.
Gay, Frederick P.
371. A carcinoma of the rat [Flexner-Jobling] considered
from the standpoint of immunity.
NaMEs OF AUTHORS. 139
Gies, William J.
352. New apparatus designed especially to facilitate the
preservation of food for use in metabolism experiments. A
demonstration.
Greenway, James C. [with Nellis B. Foster. |
373. Synthesis of uric acid.
Greer, J. R. [with F. C. Becht.] (By invitation.)
364. On the relative concentration of lysins, precipitins,
agglutinins, opsonins and related substances in the different
body fluids of normal and immune animals.
Hanzlik, Paul J. [with P. B. Hawk. |
348. The uric acid excretion of normal men.
Hawk, P. B. [with Paul J. Hanzlik. |
348. The uric acid excretion of normal men.
Hemmeter, John C. (By invitation.)
353- Reply to recent criticism of Dr. Hemmeter’s experi-
mental study of effects of extirpation of the salivary glands on
the gastric secretion.
Henderson, Yandell.
366. A method for the direct observation of normal peris-
talsis in the stomach and intestines.
Hess, Alfred F. (By invitation.)
387. Antiperistalsis in its relation to tubercle bacilli and
other bacteria in the alimentary tract.
Jacobs, W. A.
362. [With P. A. Levene.] Further studies on the con-
stitution of inosinic acid.
380. [With P. A. Levene.] Further studies on the con-
stitution of inosinic acid.
Janeway, Theodore C.
394. A modification of the Riva Rocci method of deter-
mining blood-pressure for use on the dog.
395. Note on the blood-pressure changes following reduc-
tion of the renal arterial circulation.
Jobling, J. W.
345. Multiple tumors in mice.
Joseph, Don R.
356. [With S. J. Meltzer.] A demonstration of the life-
saving action of eserin in poisoning by magnesium.
140 SCIENTIFIC PROCEEDINGS (30-34).
390. [With 8. J. Meltzer.] The influence of sodium and
calcium upon direct and indirect muscle irritability and their
mutual antagonistic actions.
Kerr, Josephine E. [with W. J. MacNeal and Lenore L. Latzer. |
379. The daily excretion of bacteria in the feces of healthy
men.
Kristeller, L. [with D. Manson and P. A. Levene.]
375. On nitrogenous metabolism in chronic nephritis.
Lamar, Richard V. [with Simon Flexner. |
388. The action of soaps on the pneumococcus.
Latzer, Lenore L. [with W. J. MacNeal and Josephine E. Kerr. ]
379. The daily excretion of bacteria in the feces of healthy
men.
Levene, P. A.
346. [With D. D. Van Slyke.] On plastein.
361. [With D. D. Van Slyke.] The quantitative separa-
tion of leucin from valin.
362. [With W. A. Jacobs.] Further studies on the con-
stitution of inosinic acid.
375. [With L. Kristeller.]} On nitrogenous metabolism
in chronic nephritis.
380. [With Walter A. Jacobs.] Further studies on the
constitution of inosinic acids.
402. [With D. D. Van Slyke.] The leucin fraction of
proteins. II.
Levin Isaac
343. A clamp for direct transfusion of blood. A demon-
stration.
Lewis, Paul A.
370. The influence of temperature on hemolysis in hypo-
tonic solutions.
Lillie, Ralph 8.
363. The significance of changes in the permeability of the
plasma-membrane of the living cell in the processes of stimu-
lation and contraction.
Loeb, Jacques
377. On the fertilizing and cytolytic eftect of soap.
Names OF AUTHORS. I4I
Loeb, Leo
397. The comparative toxicity of sodium chloride and of
staining solutions upon the embryo of Fundulus.
398. [With Moyer S. Fleisher.] The influence of cal-
cium chloride and of adrenalin upon the secretion of urine and
upon absorption from the peritoneal cavity.
Lucas, Daniel R. [with R. Burton-Opitz. |
369. The vascularity of the kidney as influenced by sen-
sory impulses.
404. Some effects of sodium benzoate.
Lusk, Graham [with A. I. Ringer. |
341. The behavior of alanin in metabolism.
MacLeod, J. J. R.
385. Further observations on the effect of asphyxia and
curare on the reducing power of the blood after section of the
hepatic nerves in dogs.
MacNeal, W. J. [with Lenore L. Latzer and Josephine E. Kerr. |
379. The daily excretion of bacteria in the feces of healthy
men.
Manson, D. [with L. Kristeller and P. A. Levene. ]
375. On nitrogenous metabolism in chronic nephritis.
Meltzer, 8. J.
356. [With Don R. Joseph.] A demonstration of the
life-saving action of eserin in poisoning by magnesium.
357. [With A. O. Shaklee.] The mechanical destruction
of pepsin.
389. [With A. 0. Shaklee.] The influence of shaking
upon trypsin and rennin and a comparison of this influence with
that upon pepsin.
390. [With Don R. Joseph.] The influence of sodium
and calcium upon direct and indirect muscle irritability and
their mutual antagonistic actions.
391. [With J. Auer.] The effects of local applications
of chloride and sulphate of magnesium upon the centers in the
medulla compared with those of sodium chloride.
392. [With J. Auer.] Respiration by continuous intra-
pulmonary pressure without the aid of muscular action.
142 SCIENTIFIC PROCEEDINGS (30-34).
Noguchi, Hideyo
360. The butyric acid reaction for syphilis in man and in
the monkey.
3774. Some critical considerations on the serum diagnosis
of syphilis.
Novy, F. G.
351. Successful canine infection with cultures of Lezsh-
manta infantum (Ch, Nicolle).
Ott, Isaac [with John C. Scott.]
34'7. The action of bile and some of its constituents upon
intestinal peristalsis and the circulation.
Park, William H. [with Eugene Famulener. |
386. Toxin-antitoxin mixtures as immunizing agents.
Pearce, Richard M. ‘
384. An experimental study of the influence of kidney ex-
tracts and of the serum of animals with renal lesions upon the
blood pressure.
406. The depressor substance of dog’s urine ; its disap-
pearance in experimental acute nephritis.
Peskind, 8. (By invitation.)
394. Hemolysis in the sera of carcinoma and syphilis.
Ringer, A. I.
341. [With Graham Lusk.] The behavior of alanin in
metabolism.
367. (By invitation.) Studies on the effects of carbon mon-
oxide poisoning.
Robertson, T. Brailsford [with Theodore C. Burnett. ]
3'78. On the depression of the freezing point of water due
to dissolved caseinates.
Rosenau, M. J. [with John F. Anderson. |
381. The effect of heat on the anaphylactic properties of
proteins.
Salant, William
408. [With W. 0. Emery.] On the decomposition of
caffeine in the liver.
409. The comparative toxicity of ethyl and amyl alcohol
and their effect on blood pressure.
Salomon, Hugh [with George B. Wallace. |
368. Intestinal excretion during diarrhea.
NAMES OF AUTHORS. 143
Schultz, W. H. (By invitation.)
350. The effect of instilling adrenalin chloride into the
mammalian eye.
Scott, John C. [with Isaac Ott. ]
347. The action of bile and some of its constituents upon
intestinal peristalsis and the circulation.
Shaffer, Philip A.
407. Observations on the metabolism of a subject of
diabetes.
Shaklee, A. O.
357. [With 8S. J. Meltzer.] The mechanical destruction
of pepsin.
372. Influence of temperature upon pepsin.
398. [With 8. J. Meltzer.] The influence of shaking
upon trypsin and rennin and a comparison of this influence
with that upon pepsin.
Steel, Matthew.
405. An improvement of the Folin method for the deter-
mination of urinary ammonia nitrogen.
Stookey, L. B.
410. Pentosuria.
Terry, B. T.
401. Immunity to various species of trypanosomes induced
in mice by the cure of experimental infections.
Thacher, H.C. (By invitation.)
396. The effect of experimental acute insufficiency of the
right heart upon the volume of the organs.
Van Slyke, D. D.
346. [With P. A. Levene.] On plastein.
361. [With P. A. Levene.] The quantitative separation.
of leucin from valin.
402. [With P. A. Levene.] The leucin fraction ot
proteins. II.
403. ‘‘ Clavin,”’ Vahlen’s active principle of ergot.
Wallace, George B. [with Hugh Salomon. |
368. Intestinal excretion during diarrhea.
Weil, Richard
359. On the specific acquired relations of red blood cells.
144 SCIENTIFIC PROCEEDINGS (30-34).
Weinberger, William. (By invitation.)
342. An important source of error in Heller's test for
urinary protein.
Wells, H. Gideon
339. Studies on the chemistry of anaphylaxis.
399. [With Harry J. Corper.] Observations on urico-
lysis, with particular reference to the ‘uric acid infarcts’”’ of
the newborn.
Woodruff, Lorande Loss
400. Further studies on the life cycle of Paramecium.
PxesCUriyvEe PROCEEDINGS:
Thirtieth meeting.
College of Physicians and Surgeons, Columbia University, Oc-
tober 21,1908. President Lee in the chair.
Members present: Alsberg, Atkinson, Auer, Banzhaf, Burton-
Opitz, Crile, Dakin, Ewing, Famulener, Flexner, Gies, Harris,
Jobling, Joseph, Kast, Lee, Levene, Levin, Lusk, Mandel (A. R.),
Meltzer, Meyer, Morgan, Noguchi, Opie, Park, Pearce, Shaffer,
Terry, Van Slyke, Weil, Wells, Wolf.
Members elected: C. C. Guthrie, E. P. Lyon, Mazyck P.
Ravenel.
Thirty first meeting.
The Rockefeller Institute for Medical Research, December 16,
1908. President Lee in the chair.
Members present: Atkinson, Auer, Beebe, Burton-Opitz, Cal-
kins, Carrel, Clowes, Elsberg, Emerson, Ewing, Famulener, Foster,
Gies, Halsted, Hatcher, Jacobs, Janeway, Joseph, Kast, Lee, Le-
vene, Levin, Lewis, Lusk, Meltzer, Meyer, Morgan, Noguchi, Opie,
Pearce, Sherman, Terrey, Torrey, Van Slyke, Wadsworth, Weil,
Wood.
Members elected: Albert C. Crawford, W. H. Schultz, Thomas
A. Storey.
Thirty second meeting.
New York University and Bellevue Hospital Medical College,
February 17, 1909. President Lee in the chair.
Members present: Alsberg, Atkinson, Auer, Banzhaf, Beebe,
Berg, Burton-Opitz, Ewing, Famulener, Foster, Gay, Gies, Hen-
derson, Jacobs, Joseph, Kast, Lee, Levene, Levin, Lewis, Lusk,
Mandel, Meltzer, Meyer, Murlin, Noguchi, Opie, Pearce, Storey,
Terry, Wallace, Weil.
Members elected: John F. Anderson, T. G. Brodie, L. J. Cole,
Martin H. Fischer, Richard V. Lamar, Max Morse, Hans Zinsser.
(145)
1 46 EXECUTIVE PROCEEDINGS (30-34).
Officers elected: President, Frederic S. Lee; Vice-President,
William J. Gies ; Secretary, Eugene L. Opie; Treasurer, Graham
Lusk.
Thirty third meeting.
Cornell University Medical College, April 21, 1909. President
Lee in the chair.
Members present: Atkinson, Auer, Burton-Opitz, Elser, Ewing,
Flexner, Famulener, Gies, Janeway, Joseph, Kast, Lamar, Lee,
Lewis, Lusk, Mandel (J. A.), Meltzer, Meyer, Morse, Noguchi,
Norris, Oertel, Park, Pearce, Shaffer, Storey, Terry, Wallace,
Wolf.
Members elected: William W. Hale, Andrew Hunter, H. S.
Jennings, Peyton Rous, E. E. Southard, Charles R. Stockard, John
L. Todd.
Thirty fourth meeting.
The Rockefeller Institute for Medical Research, May 26, 1909.
President Lee in the chair.
Members present: Auer, Beebe, Ewing, Famulener, Flexner,
Gies, Hatcher, Joseph, Lee, Lewis, Loeb (Leo), Morse, Meyer
(Gustave), Pearce, Shaffer, Sherman, Terry, Van Slyke, Wallace,
Weil, Wolf.
Members elected: J. W. Draper Maury, C. W. Edmunds,
Adolph Meyer.
REGISTER OF NAMES AND ADDRESSES
Ore tie MEMBERS OF THE SOCIETY
BOR, EXPERIMENTAL. BIOLOGY
AND? MEDICINE:
ABBOTT ALEXANDER) Geijzcccecsccicieees sites ccleaner University of Pennsylvania.
ABEL we OHINM isme ce cessh sidsosbites siecevsleiasenesisninsnaeacies Johns Hopkins University.
LAD AMI aon GEORGE Sy usenssesseoeseeeescecnvacccecncees McGill University, Montreal.
PAT IEESRI ASUA Chast ccmeaen a cosiswseseiseceere cs New York Polyclinic Medical School.
ALSBERG, CARL L...... U. S. Department of Agriculture, Washington, D.C.
ANDERSON, JOHN F......... U.S. Public Health and Marine-Hospital Service,
Hygienic Laboratory, Washington, D. C.
SEKINSOND AMES) Bre sisescisecmcsvecsilisc. Department of Health, New York City.
PANTER Gt] ON cesisesisisiasidesesiesieseiececiass Rockefeller Institute for Medical Research.
IDANZHAR MS EEDWIIN, Ilacreeceecsmenet nese Department of Health, New York City.
BARDEEN? CHARIEES IR, tsissiecssai-csclseacidesessissaceases University of Wisconsin,
IBBMBE RR OLEAG artes soetstecstericisastectccs seer Cornell University Medical College.
BENEDICT, FRANCIS G...Nutrition Laboratory, Carnegie Institution, Boston.
IBENSU ENGuIN OB ERUG IRS» seociels oetesasisensacteene icles ce eerereieris's se University of Chicago.
BERG, WILLIAM N.....U. S. Department of Agriculture, Washington, D. C.
BRINCKERHOFF, WALTER R......... U. S. Public Health and Marine-Hospital
Service, Honolulu.
BRODLD alia: Gu nerhcecach cine nee acecisiacitc cles geiilaniidadanaa eects University of Toronto.
IBSROOUSG;, TEUARIE OW ascadsnconocbdastdosondooddoadsobnbocboauoahtoD New York University.
IBUNDING 1 © MEY qeccesiacictesiecemeneebidaccis saa salefataiciaccidenctes University of Virginia.
BURTON OBUUZMINUSSEIGT sts saincreriscesiereiniecisiestesidsceietiate neteste oe Columbia University.
BUXTON WBS GEM sec cci ssisisllslossioiicieoaaieaieiteseises Cornell University Medical College.
CAT IGINGT GARI ON: a .5. sacs cise csesioeaseseseeseesenvesese Columbia University.
CANNON ALTERS (Di pisesisccijnosme ein secisectiece ssl asislesewessece Harvard University.
GARITESON pe Alea astss sete ste viesre tieislelv slain olan oistajsiteinsisisbe siseieatcreets University of Chicago.
GARRET ALEXIS S: sec cececsecsaenens Rockefeller Institute for Medical Research.
CAIMGEND ENS Reber scianinre wcistcletiacioeisiscinis eainieoisile deolisseuiere simseeeea vera Yale University.
(SO WIES Hh Crap lete ANS Seca ici siciele dais sete oideteleloteivetciaesieigmiie sein decir University of Buffalo.
COLEM MEE eee eissmaacicidedacleissas uae ceesdevessssecstenancd ssasscecsenscass Yale University.
COVEMRUBUSHS. cecacseccastcaneactest shel caateseceseeecae Johns Hopkins University.
CONKLIN, pEEDIWIIN§ Ge feccacrs cite sticniaeuielserewicteTisiattslelelopletsorleinns os Princeton University.
COUNCIEMAN WILE DIAM Le cua netccnacssccesactcsinesaceresciee Harvard University.
CRAMPTON, C. WARD.............. Department of Education, New York City.
GRAMPTON A EIEN Vili seneeeich rc ciescsciemessislcivcsesso sereineaelote Columbia University.
148 SocrETy FOR EXPERIMENTAL BIOLOGY AND MEDICINE.
CRAWFORD, ALBERT C...........- Bureau of Animal Industry, U. S. Dept. of
Agriculture.
GRILLE, GEORGE IWeoy-s rerense aoe tene Western Reserve University, Cleveland.
CUNNINGHAM, "RICHARD (Hs7_.05,/0sese sore oe ecceieer eran Columbia University.
CUSHING; HARVEY, "Wiss 21.. oscars setenrsseeereeoeeeeesees Johns Hopkins University.
CUSHNY,, ARTHUR Rio. 56.52 -cos2ssesaaenesneee ee ree University College, London.
DAKING Hs oer eeee eee 819 Madison Avenue, New York City,
DAVENPORT, CHARLES B............ Carnegie Institution's Station for Experi-
mental Evolution, Cold Spring Harbor, Long Island, N. Y
DONALDSON) seis, - 220 co capers Wistar Institute of Anatomy, Philadelphia.
DDO NEAM, CED WABI) (hanes aeasererssasas a eeee ene seen en eeeneee New York University.
DUV AT, CHARLES? WhaJca.ceescoactonsessosaen sapere sas seeaee neers Tulane University.
EDMUNDS, KC, Wiccosssoecewesuesssriseeeoess-ee ts ceeaaeceaes University of Michigan.
EDSALL, DAVID) Losec: sons sede seceee sas -ne-se eee University of Pennsylvania.
ELSBERG, ©CHARDES Aric snc se-saeeeeeeee see ss cones a eee Mount Sinai Hospital.
EELSER, WA&LLIAM J). 2.252-24-902-0 pe eee Cornell University Medical College.
TEMERSON; FLAVENS:....c.cascceesnneeseeerosssesascterceeeeee Columbia University.
ERLANGER, JOSEPH 0225-25000 seseecs soo cee oe seeeeaes eee University of Wisconsin.
EWING, JAMES <...2:5scessss25>sose-eene-o oe Cornell University Medical College.
PAMULENER, Th2 Woo ncocsc osscnccesserce Department of Health, New York City.
FIELD, (CYRUS |W ioe ee. 5-aonasnlere cscs soccer University of Louisville.
FISHER: MARTIN GEeoree- ccc see cee ereee tenons Oakland College of Medicine.
ELEXNER, | SIMON) .cc-scemeetecesnaed Rockefeller Institute for Medical Research.
FLOURNOY, THOMAS! +. .52.c05cs-<sesceee oases Bellevue Hospital, New York City.
FOLIN, (OTTOs5 .o5chs-escscntaceesteep exer eek aeeed eee ee eee Harvard University.
FORD, WILLIAM W .22sccc000c: 22-025 teeccon es caeereee Johns Hopkins University.
FOSTER, NELLIS (Bii.25c:22iis-cece psassneed-coeeseeoeaeaeee Columbia University.
GAGER;\C. STUARTS wise. 00s0-500ccersneedss snewasseesaesn aes University of Missouri.
GAY; CE REDERIOR [Pit Seseresco-ceeacsess soci eee scene Harvard University.
GIBSON; ROBERT (B27. sscan cxnomsveseessoeenttese tere se eee University of Missouri.
GIES, WILLIAM 9 oo aoe cnn on sasn nice seep eee neseb eee ome eee Columbia University.
GLASER; OTTOUG, 5.0 soccp oan. ca scene ae none ee neeeeoe University of Michigan.
AGODA Hy CeCe nce son ene sane sees aaa Washington University, St. Louis.
HALE, Wi Wissecescccees U. S. Public Health and Marine-Hospital Service,
Hygienic Laboratory, Washington, D. C.
HALSTED;, WALLIAMS) 2.22 22200sscncsss<sesses cate snes Johns Hopkins University,
FARRIS, ISAACUE 3. 2222c0n< sacs tase sacceescsee 449 E. 57th St., New York City.
ELARRISON:| ROSS AG. 0.05 eccnce deseeeee eee nea hee eae Yale University.
HATCHER, ROBERT, ‘A..!<...22.sccssecscssee Gociell University Medical College.
RIATAL SHINKISHI@s¢.c.c-ca-e-eee oe Wistar Institute of Anatomy, Philadelphia.
HAWK, ‘PHILIPJB.. ccccesudeccssmes uke co eeseceecaes ooveecseseses University of Illinois.
HEKTOEN;, LUDWIG...222 5.-<e20020000se0s0edee-seeeeeseererese University of Chicago.
Rott oF MEMBERSHIP. 149
ELEN ERS O Nem VAIN IDS TeTi entre cSetcicaisisicieisicaisiorsieiesa die sicifosesle wisiesivieieiets’es Yale University.
FIBRE RE GHRISTVANCAN tcc. ch ales suajeiapessisevecesce coeesieesesiis Columbia University.
IBS. 1AENTEU® 1 eo gondastoopecncosnb badonececese oe SE ACE EEE nOcaCeD Columbia University.
LOWE UE Mm VV BILL CAM EAE Sic. ecicciseeeceisieccoscaaceieice sonme Johns Hopkins University.
FE HUME ERs © ANNTER Gretertertarsatssteissaidajeiste tine aio cd weiss Sale siewiessacne University of Michigan.
FUUN TS INEDD Sissi scislscees.c U. S. Public Health and Marine-Hospital Service,
Hygienic Laboratory, Washington. D. C.
ELUNMERT PAN DREW acnecniecececcedarcesacecioanen Cornell University, Ithaca, N. Y.
JACKS ONE LOLMES| Gi cris. onaaassecencctounenneasoeeckacnesn Albany Medical School.
WACORS WAT TDERVAC crs .ceneseesens Rockefeller Institute for Medical Research,
VANEWAN) DITEODORE ©... (5. fs.acsadsagscde-ematssdescdesedcns Columbia University.
SJTENINUIN GS palling Styereine cnr a tee ietctemnemre ancncech ena Johns Hopkins University.
OBIING MJAMES Wise ceerccscasensce cence Michael Reese Hospital, Chicago, Ill.
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JORDAN ED WINGO hens jeneitccaacemeaceecsceseneaiie daskeenscees University of Chicago.
JOSEPH ED ONO Rss ccccneccsccseacceis Rockefeller Institute for Medical Research.
IAS IE UID WAG ile acacleseciericacecieiicone sees New York Postgraduate Medical School.
KASTLE, JOSEPH H......... U. S. Public Health and Marine-Hospital Service,
Hygienic Laboratory, Washington, D. C.
GL ODZ OS ARG atest sisessieic Galea vceesimaeniauaicinarcese McGill University, Montreal.
IROCH VV AISD MUA beer, caneeteenccccsseoec nen scneswecbews donor University of Chicago.
NEANUARE SINIGEVAIRD Vise ertactece seccis Rockefeller Institute for Medical Research.
TERED IRM CH Sater sec tiacecantes alec eluaismcteiaiac teem aicmiswrenlew sete: Columbia University.
IGE VIENES ae Atchacsteascsimscciscd sles s Rockefeller Institute for Medical Research.
ETA WINGS IGIAVA Cette caaelsisieeciiciascaisc del stasis isle elena ca sectea tee ec eer Columbia University.
PEE WISH AUTRCAN SS arehjacrecaeeiaicitwases Rockefeller Institute for Medical Research.
SETAE LO RUAN IKON farses sieieriere mae steele TODD ap OAE SO RTCCIOC EOD University of Chicago.
VENTE INEM ISAIER HES eae setters tnisecetcnace cc ioe eneece ne ieee University of Pennsylvania.
TOE By PACOUES Er nsicesasan clic ciceseuniiewseie eas teseormis scat University of California.
MOEB IGE Ons cdstecetecmacsaswacwrsscdacuesassiosieceddaeaiss University of Pennsylvania.
LOEVENHARDT, ARTHUR (9% cicaccsesccccceswieniecossosvees soe University of Wisconsin,
LOMBARD; WARREN! Ps, onecisstescnteeasoeccecmeessisiseweler University of Michigan.
TEUSKS i GRAEDAM sercciciaaesssiesinsoeryauenebeacincanese sass eeten se New York University.
EMO Newt Eoaytbent Parsictecren cies etviesio ces sacle cecite ciaccise dele ae oe abistecicoe ores St. Louis University.
INVAC AIS IEUME RAS BS 5 ins oh selec otic nsiemam tice dae acaimneabsrenteesee University of Toronto.
MAC CATT UM Wiss Gureacsscinaies seemateiciucaesaecnasaster Johns Hopkins University.
INUACIDOWENes IDS Mbeceepanectacsandecone Carnegie Institution, Washington, D. C.
NA CEE OD ale in Rascrecs cece coacenenere Western Reserve University, Cleveland.
IEA GINIEAUE SEWNZASRID)| If crs creternarcciereisiewie eis es seein sis oie aeostetuatertecic sels University of Illinois.
INANE SEURUAINIGEEING Dos ar tcige aioticisiiatcteitn ss's pecing Sasol date eter Johns Hopkins University,
INANID) Estee URI ELC Rat Ne anasto na aeieaerresiatieg ciae'snve nase on vereniecele New York University.
NEANID Ea) OHINTA dteagslscitinat cae seciiee asses oe ee soe seaeadesciser sas New York University.
150 Society FOR EXPERIMENTAL BroLocy AND MEDICINE.
MatHews, Avner (Py i cces.:icecs a cstkapece perenne University of Chicago.
Maury, J. W. DeAPER > fo... o..ce ees case eee eee ee Columbia University.
MAYER, ALFRED.....--:2:25-223 Marine Laboratory of the Carnegie Institution,
Tortugas, Fla.
MEETZER, |S. ss ecnaieee tec coseeeset Rockefeller Institute for Medical Research.
MENDEL, LAFAYETTE 'B.....50. ccs-conc-aracsepanceee eee Yale University.
Mervin, ANOEPH::22-.-see0e Pathological Institute, Wards Island, New York.
Mrver, Gustave Mi 2 oo .ocecocsscccnanc- neeeeeoe ee eee Columbia University.
MORGAN, THOMAS T= 22.--. = .dsnpase- eke aeaee a eee eee Columbia University.
MORSE, MAX 5 2205 o.ccc. Secece center ee City College of New York.
MURLEIN, JOHN R. 2.0 .<ccccc0cecnceascarasseseccasnsenenss cadens EW VOR Pi Reaeanae
MuRpHy, JOHN B.......... Northwestern University Medical School, Chicago,
NoGucal, Himrvo. 2s ees Rockefeller Institute for Medical Research.
NORRES, CHAREES)- 20. omncsccorse~-scete een Bellevue Hospital, New York City.
Novy, FREDERICK G. 2220 ooo. 0 sasnstosetas on tasnsinesaass University of Michigan.
OERTEL, Horst........Sage Institute of Pathology, City Hospital, New York.
OPHUES, \WHELIAM. 3. 2.. cacarccesos ee Cooper Medical College, San Francisco.
Ovi, (HUGENE Ei. 7..3-5-0-0eseeees Rockefeller Institute for Medical Research.
OsBORNE, THOMAS B...........Connecticut Agricultural Experiment Station,
New Haven, Conn.
OST, ISAAC. 5S eee eee Medico-Chirurgical College, Philadelphia.
PAPPENHEIMER, ALVIN M...... .....--2--- Bellevue Hospital, New York City.
PA, WORE TUAW Tos oo ae ata si epee eee New York University.
Pare Erm (GEORGE Hs203.-. css ee ee Harvard University.
PEARce. RicHARD Mot 3535 ene ee ee New York University.
PRAGE, PRANZ.. 2 <oces = oad eee eee ene eee Harvard University.
PORTER, WiisiaMe 1 03225.0. 255 5so-e eee eee Harvard University.
PRATT, JOSEP E Bii22 25 2cccsaoectendneseneneeeh eene een eee Harvard University.
RAVENEE, \MAZVCEAE SE ston seucrs enone meee University of Wisconsin.
REICHERT, EDWARD TV ieicc-c2snc-no seca eee University of Pennsylvania.
RICHARDS, ALFRED N...Northwestern University Medical School, Chicago.
RICKETTS, (HOWARD "Tocco ceoeeere cee eens ees emene rene University of Chicago.
ROBERTSON; T= BRAISFORD 15. oon - nc -de nc cece nneneecees University of California.
ROSENAU, MILTON J..........-..-- U. S. Public Health and Marine-Hospital.
Service, Hygienic Laboratory, Washington, D. C.
ROUS, (PEWTON fee see eeee wena Rockefeller Institute for Medical Research.
SALANT, WILLIAM.....U. S. Department of Agriculture, Washington, D. C.
SCEESEZ: “WaT oon eee eee U. S. Public Health and Marine-Hospital
Service, Hygienic Laboratory, Washington, D. C.
SCHWWZER. Hayrz:) >< 2 ee eno eee St. Francis Hospital, New York City.
SHAPPER,- Pair Aq. .- ccesnenae-e-sarn ae -Cornell University Medical College.
Rott oF MEMBERSHIP. I51
HIERN MIANT mEDEONIR Va Gar cenisnticiiais aisiersitclaairale avielsinicieitinocieieis/sinie'sie Columbia University.
STOVE O Ness: © HOARY ESS SEG or rata sats ais Siesevwiejarn ova a blaiesiareioiaie seine sia'ere Baltimore Medical College.
SS VANCED pee GELIE, ORUANIG Dore eres reseratatota vislovedatcisieicraisiets sigs seiela’s. io/eiouans siss'ewieiars Harvard University.
SOLLMANNE oe HORATED eects ener se cieicteeisiis Western Reserve University, Cleveland.
SS OUI VANE DD org EGS cre clei recicic(esiovcinieiic rs cis eis ches wisleletioveltaie’simoveieetelelesie's Harvard University.
SMEWARIH GEORGE: Nii iescreccivatjecces Western Reserve University, Cleveland.
SMDIBES GEER C Yia Grol sieeeloielsieisteisisiioles actesisel Massachusetts Institute of Technology.
SP OGIWARID 8: CEUAGS Ns rissa anjois siaiais duleisloleieisaterepe sia woreelereten’s Cornell Medical School.
STOOKEY, LyMAn B. ......... University of Southern California, Los Angeles.
STOREY web OMAGH Avsiocsistetaissarinicsicic <stsiestelesiaisersiaseisstes/siisia s City College of New York.
STRONG S WIGHARID la peneeiaeee eee. U. S. Public Health and Marine-Hospital
Service, Manila.
SESE | LGD WAL eeratte sejctertcialetetec/atetsisielostelslsiesiele sete e sicins University of Pennsylvania.
SMMINEMR'S 1) OU GIZA Somciecisticemaasiesraacisnicesissesieicienisciiceh ters New York Hospital.
FIBA AIL ORS ALON Z Ol Es: sire sieejass scale « sats oinfose'e a's a'einis aieaie s eieis(ois ete University of California.
MEAGUE OSCAR 2 .ces.: U. S. Department of the Interior, Bureau of Science,
Manila.
MIRESROR pba dew snrstovassretsinietecuies ceistheners Rockefeller Institute for Medical Research.
“WG IDYD}, OEOSIEAS Secceodasoucenconesonenereecaceear nec McGill University, Montreal.
SORRY OLING © ceoeeneniecritesaecircieaaesses dare Cornell University Medical College.
WIG VCA ZI E ee Er oe Rise nseist aniosatctensiletaeaite stasis wlic asec a eine secioisieisenissiecss Harvard University.
DOIN D ERUIIET, SEORIANIKG Erg octets secenerto sais inielesteete onic sinc/ oars vatelieleotosiewisye Yale University.
VAN SLYKE, DONALD D............ Rockefeller Institute for Medical Research.
WAU GHAN AVITCTORUG. ¥. irate a caievsiecssiess roca tees tecactes University of Michigan.
AVADSWORME WAU GUSTUSI DB aicunesscaacecstnssedeaceeaneesiee Columbia University.
WIAMEACE | GEORGEUB ain «cis aissst ovale seeieeacncranccunencnetee New York University.
WARDEN, PAU RIE DS iaeian-lsisseiclsvnenisoencevoee eceeose ese University of Michigan.
WET PIRICHARD ss corsasise cscs saeascciovencs Cornell University Medical College.
VAT Cisse VNIDTOTE VA Mia El torrets oteci'eiscisitsiseisicise socseinnaei ation’ Johns Hopkins University.
WNP Gee GND O Nitvact ciractecricianeensine sere nsemensatae tenes University of Chicago.
WIDE TAM S EUORIBER Te Ua srrajarrccyeteisten ae ale ataielrete ete cates dateiee University of Buffalo.
WALES © Nea SIS MDUINGD I Seissietecalciccciasioe wcciste en taciuewticis amish macane Columbia University.
WVOLBA CHA Sev BURT ieaetcceac viadeiciusnsaceenaceeeemandeeeeee Albany Medical School.
WOT CHARTERS) Gale nes-ncactetesesenenesn Cornell University Medical College.
NVOOD REIRIAN CIS Geeta 95 crpresiajscut siesta tuleciaciont aetr sions niontses Columbia University.
NVGODRURE SILORAINDENUOSS sneshesaacceoctonc ere sec ceraete secon as Yale University.
ATES Ure NAOEIID Fen saceisiss ctinaiceeacivicnisnoatan cast estieneaiieine sooneee University of Japan.
WiERIGESMINOBERT avn caayecs sates selog ana sascetaaines ate eeneen Harvard University.
UNSER LU ANS erenicariinaadadssieetenus escaiirece veiecdertece seuss Columbia University.
Total number of members at the close of the academic year, 1908-09: 185.
OFFICERS:
1903-IQIO.
1903-'04 1904~’05 1905-06 1906-’07
President Meltzer Meltzer Wilson Flexner
Vice-President Park Ewing Dunham Dunham
Librarian Lusk Lusk Lusk
Treasurer Calkins Calkins Calkins Calkins
Secretary Gies Gies Gies Gies
1 Council — The Past Presidents and the Officers.
(152)
1907-08
Flexner
Morgan
Calkins
Gies
1908-’09 1909~-"10
Lee
Morgan
Lusk
Gies
Lee
Gies
Lusk
Opie
CexcolrPiED LIST OF MEMBERS OF THE
SOCIE EY POR) EXPERIMENTAL
BIOLOGY ANDY MEDICINE.
Resident (Greater New York).
Bellevue Hospital. Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University.—Russell Burton-Opitz, Gary N. Calkins, Henry E,
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Theodore C. Janeway,
Frederic S. Lee, Isaac Levin, J. W. Draper Maury, Thomas H. Morgan,
Henry C. Sherman, Augustus B. Wadsworth, Edmund B. Wilson, Francis
C. Wood, Hans Zinsser.
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, Chas.
R. Stockard, John C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinai Hospital,—Charles A. Elsberg.
New York City College.—Max Morse, Thomas A. Storey.
New York City Departments. Education.—C. Ward Crampton.
Flealth.—James P. Atkinson, Edwin J. Banzhaf, L. W. Famulener.
New York Hospital.—Douglas Symmers.
New York Polyclinic Medical School.—\saac Adler.
Wew York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Pathological Institute, Wards Island.—Adolph Meyer.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, Don R. Joseph, Richard V. Lamar,
P. A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave M. Meyer, Hideyo
Noguchi, Eugene L. Opie, Peyton Rous, B. T. Terry, Donald D. Van Slyke.
Sage Institute of Pathology, City Hospital. — Horst Oertel.
St. Francis Hospital.—Fritz Schwyzer.
819 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—Isaac F. Harris.
Non-Resident.
Albany Medical College.—Holmes C. Jackson.
Baltimore Medical College. —Charles E. Simon.
Carnegie Institution of Washington.—Francis G. Benedict (WVutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
(153)
154 SocIETY FOR EXPERIMENTAL BioLocy AND MEDICINE.
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fla.).
Connecticut Agricultural Experiment Station (New Haven).—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils.
Massachusetts Institute of Technology.—Percy G. Stiles.
Medico-Chirurgical College (Philadelphia).—Isaac Ott.
Michael Reese Hospital (Chicago).—James W. Jobling.
Northwestern University Medical School (Chicago).—J. B. Murphy,
Alfred N. Richards.
Oakland College of Medicine.—Martin H. Fischer.
U. S. Departments. Agriculture (Washington, D. C.).—Carl L. Als-
berg, William N. Berg, Albert C. Crawford, William Salant; Interior
(Philippine Islands, Bureau of Science, Manila).—Richard P. Strong, Oscar
Teague. TZyreasury(Public Health and Marine-Hospital Service).—Walter
R. Brinckerhoff, Honolulu, Hawaii; John F. Anderson, Wm. H. Hale,
Reid Hunt, Joseph H. Kastle, M. J. Rosenau and W. H. Schultz, Wash-
ington, D.C.
Universitics. Buffalo.—G. H. A. Clowes, Herbert U. Williams. Cai-
fornia.—Jacques Loeb, T. Brailsford Robertson, AlonzoE. Taylor. Chicago.
—R. R. Bensley, A. J. Carlson, Ludvig Hektoen, Edwin O. Jordan, Walde-
mar Koch, Frank R. Lillie, Albert P. Mathews, H. T. Ricketts, H. Gideon
Wells. Corne//.—Andrew Hunter. Harvard.— Walter B. Cannon, W. T.
Councilman, Otto Folin, Frederick P. Gay, G. H. Parker, Franz Pfaff, W.
T. Porter, Joseph H. Pratt, Theobald Smith, E. E. Southard, E. E. Tyzzer,
Robert M. Yerkes. ///inozs.—-Philip B. Hawk, Ward J. MacNeal. Japan.
—Naohidé Yatsu. /ohnus Hopkins.—John J. Abel, Rufus I. Cole, Har-
vey W. Cushing, W. W. Ford, W. S. Halsted, William H. Howell,
H. S. Jennings, Walter Jones, W. G. MacCallum, F. P. Mall, William H.
Welch. Louisville. —Cyrus W. Field. McGz/i (Montreal).—J. George
Adami, Oskar Klotz, John L. Todd, S. Burt Wolbach. Jichigan.—C. W.
Edmunds, Otto C. Glaser, Carl G. Huber, Warren P. Lombard, Frederick G.
Novy, Victor C. Vaughan, Aldred S. Warthin. JMssourt.—C. Stuart Gager,
Robert B. Gibson. Pennsylvania.—Alexander C. Abbott, David L. Edsall,
Ralph S. Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet. Princeton.—
Edwin G. Conklin. Southern California (Los Angeles).—Lyman B. Stookey.
St. Louis.—E. P. Lyon. Zoronto.—T.G. Brodie, A.B. Macallum. Tulane.—
Charles W. Duval. Wésconsin.—Charles R. Bardeen, C. H. Bunting, Joseph
Erlanger, Arthur S. Loevenhart, Mazyck P. Ravenel. Washington (St.
Louis).—C. C. Guthrie. Western Reserve (Cleveland).—George W. Crile,
J. J. R. Macleod, Torald Sollmann, G. N. Stewart. YVa/e.—R. H. Chitten-
den, L. J. Cole, Ross G. Harrison, Yandell Henderson, Lafayette B. Mendel,
Frank P. Underhill, Lorande Loss Woodruff.
University College (London).—Arthur R. Cushny.
Wistar Institute of Anatomy (Philadelphia).—H. H. Donaldson, Shin.
kishi Hatai.
INDEX
OF THE
SCIENTIFIC PROCEEDINGS.
By BERTHA
I. BARKER.
[THE NUMERALS IN THIS INDEX CORRESPOND WITH THE NUMERALS IN
PARENTHESIS ABOVE THE TITLES OF THE ABSTRACTS.
PAGES
ARE NOT INDICATED. |
Adrenalin chloride, effect upon mam-
malian eye of, 350.
Adrenalin, influence upon
and absorption, 398.
Agglutinins, concentration of, 364.
Alanin in metabolism, 341.
Alcohol, toxicity of ethyl and of amyl, |
409.
Alcoholic fermentation, zymase and,
354.
Alimentary tract, effect of antiperistal-
sis on bacteria in, 387.
Amy] alcohol, toxicity of, 409.
Anaphylactic properties of proteins,
381.
Anaphylaxis, chemistry of, 339.
Antiperistalsis in relation to bacteria,
387.
Antitoxin, separation from associated
proteins of, 344,
Arterial circulation of kidney, reduc-
tion of, 393.
Asphyxia, effect on the reducing power
of the blood of, 385.
secretion
Bacteria, excretion in feces of, 379;
in alimentary tract, 387.
Benzoate, sodium, 404.
Bile, action on peristalsis and circula-
tion of, 347.
Blood cells, acquired resistance of red,
359; injection in carcinoma of red,
382.
Blood, clamp for transfusion of, 343 ;
effect of ethyl and amyl alcohol on,
409 ; reducing power of, 385.
Blood pressure, changes after reduction
of renal arterial circulation of, 395 ;
effect of kidney extracts, and of
serum of animals with renal lesions
on, 384; Riva-Rocci method of de-
termining, 394.
Butyric acid reaction for syphilis, 360.
Caffeine in the liver, decomposition of,
408.
Calcium chloride, influence upon secre-
tion and absorption of, 398.
Calcium, influence upon muscle irri-
tability of, 390.
Carbon dioxide, effects on frog’s pupil
of, 358.
Carbon-monoxide poisoning, effects of,
367.
Carcinoma, a skin reaction in, 382;
hemolysins with, 349 ; of rat, 371.
Caseinates, depression of freezing point
of water with, 378.
Cell, permeability of plasma-mem-
brane of, 363.
Circulation, action of bile on, 347.
“Clavin,”’ 403.
Co-enzyme of zymase, 354.
Curare, effect on reducing power of the
blood of, 385.
Cytolytic effect of soap, 384.
(155)
156
SCIENTIFIC PROCEEDINGS (30-34).
[THE NUMERALS CORRESPOND WITH THOSE ABOVE THE ABSTRACTS, |
Depressor substance of dog’s urine, 406.
Diabetes, metabolism in, 407.
Diarrhea, intestinal excretion during,
368.
Dietary conditions, 365.
Ergot, Vahlen’s active principle of,
403.
Eserin, in magnesium poisoning, 356.
Ethyl alcohol, toxicity of, 409.
Excretion, intestinal, 368; of bacteria
in feces, 379 ; of uric acid, 348.
Eye, effect of adrenalin chloride upon,
350.
Feces, excretion of bacteria in, 379
Fertilizing effect of soap, 377.
Folin’s method for urinary ammonia,
405.
Food, preservation for metabolism ex-
periments of, 352.
Freezing point of water, depression of,
378.
Fundulus, embryo of, 397.
Gastric secretion, 353.
Gluconic acid, formation by olive-tuber-
cle organism of, 376.
Heart, volume of organs with insuffi-
ciency of right, 396.
Heat, effect on anaphylactic proper-
ties of proteins of, 381.
Heller’s test for urinary protein, 342.
Hemolysins in sera with carcinoma and
syphilis, 349.
Hemolysis, clinical aspects, of, 340;
in hypotonic solutions, 370.
Hemorrhage, recuperation from, 365.
Hepatic nerves, section of, 385.
Hypotonic solutions, hemolysisin, 370.
Immunity to trypanosomes, 401; with
carcinoma of rat, 371.
Immunizing agents, toxin-antitoxin
mixtures as, 386.
Infection with Leishmania infantum in
dog, 351.
Infections with trypanosomes in mice,
4ol.
Inosinic acid, constitution of, 362, 380.
Insufficiency of right heart, 396.
Intestinal excretion, 368.
Intestines, observation of normal per-
istalsis of, 366.
Intrapulmonary pressure, effect on res-
piration of continuous, 392.
Kidney, replantation of, 355; vascu-
larity of, 369.
Kidney extracts, influence on blood
pressure of, 384.
Kidney insufficiency by reduction of
arterial circulation, 393.
Leishmania infantum, 351.
Leucin fraction of protein, 402 ; sep-
aration from valin of, 361.
Life cycle of paramecium, 400.
Liver, decomposition of caffeine in,
408.
Lysins, concentration of, 364.
Magnesium chloride and sulphate, effect
on medulla of, 391.
Magnesium poisoning, eserin in, 356.
Medulla, effects of magnesium upon,
391.
Metabolism, behavior of alanin in,
341; in chronic nephritis, 375 ; in
diabetes, 407.
Metabolism experiments, apparatus for,
352.
Method, Folin’s, 405 ; for observation
of peristalsis, 366; of determining
blood pressure, 394; Riva-Rocci,
394.
Microérganisms, oxidation in, 376.
INDEx.
157
[THE NUMERALS CORRESPOND WITH THOSE ABOVE THE ABSTRACTS. |
Muscle, irritability of, 390.
Nephrectomy, double, 355.
Nephritis, metabolism in chronic, 375 ;
the disappearance of depressor sub-
stance from urine in experimental
acute, 406.
Newborn, ‘‘uric acid
399:
Nitrogen of urinary ammonia, 405.
Nitrogenous metabolism in chronic ne-
phritis, 375.
infarcts’’ of,
Olive-tubercle organism, 376.
Opsonins, concentration of, 364
Organs, volume of, 396.
Oxidation in some microdrganisms,
376.
Paramecium, life cycle of, 400.
Pentosuria, 410.
Pepsin, influence of temperature on,
372; mechanical destruction of,
357; shaking of, 389.
Peristalsis, action of bile on, 347 ; ob-
servation of normal, 366.
Peritoneal cavity, absorption from, 398.
Plasma-membrane of living cell, per-
meability of, 363.
Plastein, 346.
Plexus lienalis, influence on vascularity
of spleen of, 383.
Pneumococcus, action of soaps on, 388.
Precipitins, concentration of, 364.
Protein, influence on resistance to
toxicity of ricinand on recuperation
from hemorrhage of, 365 ; urinary,
342.
Proteins, anaphylactic properties of,
381; leucin fraction of, 402 ; sepa-
ration of antitoxin from, 344.
Pupil, effect of carbon dioxide on, 358.
Renal arterial circulation, reduction of,
395-
Rennin, shaking of, 389.
Resistance to toxicity of ricin, 365 ;
specific acquired, 359.
Respiration by continuous intrapulmo-
nary pressure, 392.
Ricin, toxicity of, 365.
Riva-Rocci method for
blood-pressure, 394.
determining
Salivary glands, effects of extirpation
of, 353-
Secretion, gastric, 353.
Sensory impulses, influence on kidney
of, 369.
Serum, antitoxin in, 344; diagnosis of
syphilis, 374 ; of animals with renal
lesions, 384.
Shaking of trypsin and rennin, 389.
Skin reaction in carcinoma, 383.
Soap, fertilizing and cytolytic effect
of, 377.
Soaps, action on pneumococcus of,
388.
Sodium benzoate, 404.
Sodium chloride, effect upon medulla
of, 391 ; toxicity of, 397.
Sodium, influence upon muscle irrita-
bility of, 390.
Spleen, vascularity of, 383.
Staining solutions, toxicity of, 397.
Stomach, observation of normal peri-
stalsis of, 366.
Synthesis of uric acid, 373.
Syphilis, butyric acid reaction for,
360; hemolysins with, 349 ; serum
diagnosis of, 374.
Temperature, influence on hemolysis
of, 370; influence on pepsin of, 372.
Toxicity of ethyl and amyl alcohol,
409; of sodium chloride and of
staining solution, 397.
Toxin-antitoxin mixtures, 386.
Transfusion of blood, clamp for, 343.
Trypanosomes, immunity to, 401.
158
SCIENTIFIC PROCEEDINGS (30-34).
[THE NUMERALS CORRESPOND WITH THOSE ABOVE THE ABSTRACTS. |
Trypsin, shaking of, 389.
Tubercle bacilli in relation to antiperi-
stalsis, 387.
Tumors in mice, 345.
Uric acid, excretion of, 348 ; synthesis
of, 373-
‘“‘Uric acid infarcts’? of the newborn,
399:
Unicolysis, 399.
Urinary protein,
342.
Heller’s test for,
Urine, depressor substance of, 406;
influence of calcium chloride and
adrenalin upon the secretion of,
398.
Vahlen’s active principle of ergot, 403.
Valin, separation from leucin, 361.
Vascularity of kidney, 369 ; of spleen,
383.
Zymase and alcoholic fermentation,
354.
ux tN
=
ry ‘ he air ware
Bada | ‘a Er ese be
PROCEEDINGS
t
yy
SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE
THIRTIETH MEETING
COLLEGE OF PHYSICIANS AND SURGEONS
COLUMBIA UNIVERSITY
NEW YORK CITY
OCTOBER 21, 1908
VoL_LuME VI
No. 1
NEW YORK...
DECEMBER I, 1908
CONTENTS,
H. GipEON WELLS: Studies on the chemistry of anaphylaxis. 1 (339).
GEORGE W. CRILE: Further observations on the clinical aspects of hemoly-
sis. 2 (340).
A. I, RINGER and GRAHAM Lusk: The behavior of alanin in metabolism.
3 (341).
WILLIAM WEINBERGER (By invitation): An important source of error in
Heller's test for urinary protein. 4 (342).
Isaac Levin: A clamp for direct transfusion of blood. A demonstration,
5 (343).
EpwIn J. BANzHAF : The further separation of antitoxin from its associated
proteins in horse serum. 6 (344).
J. W. JoBLinG: Multiple tumors in mice. 7 (345).
D. D. VAN SLYKE and P. A. LEveNE: On plastein. 8 (346).
Isaac Ort and JouN C. Scotr: The action of bile and some of its constit-
uents upon intestinal peristalsis and the circulation. g ($47).
PAUL J. HANZLIK and P. B. Hawk: The uric acid excretion of normal men
10 (348).
S. PESKIND (By invitation): Hemolysins in the sera of carcinoma and
syphilis. 11 (349).
W. H. ScuHuLrtz (By invitation): The effect of instilling adrenalin chloride
into the mammalian eye. 12 (350).
F. G. Novy: Successful canine infection with cultures of Zezshmania in-
Jantum (Ch. Nicolle), 13 (351).
WILLIAM J. Giles: New apparatus designed especially to facilitate the pres-
ervation of food for use in metabolism experiments. A demonstration.
14 (352).
The proceedings of the Society for Experimental Biology and Medicine are pub-
lished as soon as possible after each meeting. Regular meetings of the Society are held
in New York on the third Wednesdays of October, December, February, April and
May. A volume of the proceedings consists of the numbers issued during an
academic year.
The price per volume, sent postage prepaid, is one dollar. The price of copies
of the proceedings of any meeting is twenty cents each, postage prepaid. Subscriptions
are payable in advance.
Address communications to any of the following members of the Council of the
Society :
Past PRESIDENTS—S. J. Meltzer, Rockefeller Institute for Medical Research ;
Edmund B. Wilson, Columbia University; Simon Flexner, Rockefeller Institute for
Medical Research.
PRESIDENT — Frederic S. Lee, Columbia University.
VicE-PRESIDENT —Thomas H. Morgan, Columbia University.
TREASURER — Graham Lusk, New York University.
SECRETARY — William J. Gies, Columbia University.
MANAGING EpIToR—The Secretary, College of Physicians and Surgeons,
437 W. Soth St., New York City.
PROCEEDINGS
SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE
THIRTY FIRST MEETING
ROCKEFELLER INSTITUTE FOR MEDICAL
RESEARCH
NEW YORK CITY
DECEMBER 16, 1908
VoLUME VI
Nei2
NEW YORK
JANUARY I5, 1909
CONTENTS.
Joun C. HEMMETER (By invitation): Reply to recent criticism of Dr. Hem-
meter’s experimental study of effects of extirpation of the salivary glands
on the gastric secretion. 15 (353).
G. H. A. CLowes: A critical study of the conditions under which zymase
and its associated co-enzyme bring about alcoholic fermentation. 16
(354).
ALEXIS CARREL: Presentation of a dog ten months after double nephrec-
tomy and replantation of one kidney. 17 (355).
Don R. JosePpH and S, J. MELTZER: A demonstration of the life-saving
action of eserin in poisoning by magnesium. 18 (356).
A. O. SHAKLEE and S. J. MELTZER: The mechanical destruction of pepsin.
19 (357).
Joun Aver: A demonstration of the effects of CO, upon the frog’s pupil.
20 (358).
RICHARD WEIL: On the specific acquired resistance of red blood cells. 21
(359). :
HipEyo NoGucu1: The butyric acid reaction for syphilis in man and in the
monkey. 22 (360).
D. D. VANStyke and P. A. LEVENE: The quantitative separation of leucin
from valin. 23 (361).
W. A. Jacogs and P. A. LEVENE: Further studies on the constitution of
inosinic acid. 24 (362).
RALPH S. LILLIE: The significance of changes in the permeability of the
plasma membrane of the living cell in the processes of stimulation and
contraction. 25 (363).
F, C. BecuT and J. R. GREER (By invitation): On the relative concentra-
tion of lysins, precipitins, agglutinins, opsonins and related substances
in the different body fluids of normal and immune animals. 26 (364).
NELLIs B. Foster: Studies of the influence of various dietary conditions
on physiological resistance. I. The influence of different proportions of
protein in the food on resistance to the toxicity of ricin and on recupera-
tion from hemorrhage. 27 (365).
The proceedings of the Society for Experimental Biology and Medicine are pub-
lished as soon as possible after each meeting. Regular meetings of the Society are held
in New York on the third Wednesdays of October, December, February, April and
May. A volume of the proceedings consists of the numbers issued during an
academic year.
The price per volume, sent postage prepaid, is one dollar. The price of copies
of the proceedings of any meeting is twenty cents’ each, postage prepaid. Subscriptions
are payable in advance.
Address communications to any of the following members of the Council of the
Society :
Past PRESIDENTS— S. J. Meltzer, Rockefeller Institute for Medical Research ;
Edmund B. Wilson, Columbia University; Simon Flexner, Rockefeller Institute for
Medical Research.
PRESIDENT — Frederic S. Lee, Columbia University.
Vice-PRESIDENT—Thomas H. Morgan, Columbia University.
TREASURER — Graham Lusk, New York University.
SECRETARY — William J. Gies, Columbia University.
MANAGING EpIToR—The Secretary, College of Physicians and Surgeons,
437 W. 59th St., New York City.
CLASSIFIED LIST OF MEMBERS OF THE SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE.
Resident (Greater New York).
Bellevue Hospital.—Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University.—Russell Burton-Opitz, Gary N. Calkins, Henry E.
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Frederic S. Lee, Isaac
Levin, Thomas H. Morgan, Henry C. Sherman, Augustus B. Wadsworth,
Edmund B. Wilson, Francis C. Wood.
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, John
C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinai Hospital.—Charles A. Elsberg.
New York City College.—Thomas A, Storey.
New York City Departments. Education,—C. Ward Crampton.
Health.—James P. Atkinson, Edwin J. Banzhaf, L. W. Famulener.
New York Hospital.—Douglas Symmers.
New York Polyclinic Medical School.—\saac Adler.
New York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, James W. Jobling, Don R. Joseph, P.
A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave M. Meyer, Hideyo
Noguchi, Eugene L. Opie, B. T. Terry, Donald D. Van Slyke.
Sage Institute of Pathology, City Hospital.—Theodore C. Janeway,
Horst Oertel.
St. Francis Hospital.—Fritz Schwyzer.
$19 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—Isaac F. Harris.
Non-Resident.
Albany Medical College.—Holmes C. Jackson, S. Burt Wolbach.
Baltimore Medical College.—Charles E. Simon.
Carnegie Institution of Washington.—¥rancis G. Benedict (/Vutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fla.).
Connecticut Agricultural Experiment Station (New Haven).—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils.
Massachusetts Institute of Technology.—Percy G. Stiles.
Medico-Chirurgical College (Philadelphia).—\saac Ott.
Northwestern University Medical School (Chicago).—J. B. Murphy,
Alfred N. Richards.
U. S. Departments. Agriculture (Washington, D. C.).—Carl L. Als-
berg, William N. Berg, Albert C. Crawford, William Salant; Juterior
(Philippine Islands, Bureau of Science, Manila).—Richard P. Strong, Oscar
Teague. TZyeasury(Public Health and Marine-Hospital Service).—Walter
R. Brinckerhoff, Honolulu, Hawaii; Reid Hunt, Joseph H. Kastle, M. J.
Rosenau and W. H. Schultz, Washington, D. C.
Universitics. Buffalo.—G. H. A. Clowes, Herbert U. Williams. Cadz-
JSornia.—Jacques Loeb, T. Brailsford Robertson, Alonzo E. Taylor. Chicago.
—R. R. Bensley, A. J. Carlson, Ludvig Hektoen, Edwin O. Jordan, Walde-
mar Koch, Frank R. Lillie, Albert P. Mathews, H. T. Ricketts, H. Gideon
Wells. Harvard.— Walter B. Cannon, W. T. Councilman, Otto Folin,
Frederick P. Gay, G. H. Parker, Franz Pfaff, W. T. Porter, Joseph H. Pratt,
Theobald Smith, E. E. Tyzzer, Robert M. Yerkes. J//inozs.—Philip B.
Hawk, Ward J. MacNeal. /afan.—Naohidé Yatsu. Johns Hopkins. —
John J. Abel, Rufus I. Cole, Harvey W. Cushing, W. W. Ford, W. S.
Halsted, William H. Howell, Walter Jones, W. G. MacCallum, F. P. Mall,
William H. Welch. *Zaugsvi//e.—Cyrus W. Field. McGill (Montreal).—
J. George Adami, Charles W. Duval, Oskar Klotz. Michigan.—Otto C.
Glaser, Carl G. Huber, Warren P. Lombard, Frederick G. Novy, Victor
C, Vaughan, Aldred S. Warthin. J@ssouri.—C. Stuart Gager, Robert B.
Gibson. Penansylvania.—Alexander C. Abbott, David L. Edsall, Ralph S.
Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet. Princeton.—Edwin
G. Conklin. Southern California (Los Angeles).—Lyman B. Stookey. S/.
Louis.—E. P. Lyon. TZoronto.—A.B.Macallum. Wsconsin.—Charles R.
Bardeen, C. H. Bunting, Joseph Erlanger, Arthur S. Loevenhart, Mazyck
P. Ravenel. Washington (St. Louis).—C. C. Guthrie. Western Reserve
(Cleveland).—George W. Crile, J. J. R. Macleod, Torald Sollmann, G. N.
Stewart. YVale.—R. H. Chittenden, Ross G. Harrison, Yandeil Henderson,
Lafayette B. Mendel, Frank P. Underhill, Lorande Loss Woodruff.
University College (London).—Arthur R. Cushny.
Wistar Institute of Anatomy (Philadelphia).—H. H. Donaldson, Shin-
kishi Hatai.
Members present at the thirty first meeting:
Atkinson, Auer, Beebe, Burton-Opitz, Calkins, Carrel, Clowes, Elsberg,
Emerson, Ewing, Famulener, Foster, Gies, Halsted, Hatcher, Jacobs, Jane-
way, Joseph, Kast, Lee, Levene, Levin, Lewis, Lusk, Meltzer, Meyer, Mor-
gan, Noguchi, Opie, Pearce, Sherman, Terry, Torrey, Van Slyke, Wads-
worth, Weil, Wood.
Members elected at the thirty first meeting:
Albert C. Crawford, W. H. Schultz, Thomas A. Storey.
Dates of the next two regular meetings:
February 17, 1909 (sixth annual business meeting). April 21, 1999.
CLASSIFIED LIST OF MEMBERS OF THE SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE.
Resident (Greater New York).
Bellevue Hospital.—Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University.—Russell Burton-Opitz, Gary N. Calkins, Henry E.
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Frederic S. Lee, Isaac
Levin, Thomas H. Morgan, Henry C. Sherman, Augustus 2. Wadsworth,
Edmund B. Wilson, Francis C. Wood.
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, John
C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinai Hospital.—Charles A. Elsberg.
New York Department of Education.—C. Ward Crampton.
New York Department of Health.—James P. Atkinson, Edwin J. Banz-
haf, L. W. Famulener.
New York Hospital.—Douglas Symmers.
New York Polyclinic Medical School.—\saac Adler.
New York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, James W. Jobling, Don R. Joseph, P.
A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave M. Meyer, Hideyo
Noguchi, Eugene L. Opie, B. T. Terry, Donald D. Van Slyke.
Sage Institute of Pathology, City Hospital.—Theodore C. Janeway,
Horst Oertel.
St. Francis Hospital.—Fritz Schwyzer.
819 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—I\saac F. Harris.
Non-Resident.
Albany Medical College.—Holmes C. Jackson, S. Burt Wolbach.
Baltimore Medical College. —Charles E. Simon.
Carnegie Institution of Washington.—Francis G. Benedict (/Vutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fila.).
Connecticut Agricultural Experiment Station (New Haven).—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils.
Harvard University.—Walter B. Cannon, W. T. Councilman, Otto
Folin, Frederick P. Gay, G. H. Parker, Franz Pfaff, W. T. Porter, Joseph
H. Pratt, Theobald Smith, E. E. Tyzzer, Robert M. Yerkes.
G.
McGill Day Aan, as Gaotee “Adami,
Oskar Klotz.
Medico-Chirurgical College (Philadelphia),—Isaac Ott.
Northwestern University Medical School (Chicago). —J. B. Murphy,
Alfred N. Richards.
Princeton University.—Edwin G. Conklin.
U. S. Departments: Agriculture (Washington, D. C.).—Carl L. Alsberg, et
William N. Berg, William Salant. Jnterior, Bureau of Science (Manila).—
Oscar Teague; Public Health and Marine-Hospital Service.—Walter R.
Brinckerhoff (Honolulu), Reid Hunt (Washington), J. H. Kastle (Washing-
ton), M. J. Rosenau (Washington), Richard P. Strong (Manila).
University College (London).-—Arthur R. Cushny.
University of Buffalo.—G. H. A. Clowes, Herbert U. Williams.
University of California.—Jacques Loeh, T. Brailsford Robertson, Alonzo
E. Taylor.
University of Chicago.—R. R. Bensley, A. J. Carlson, Ludvig Hektoen,
Edwin O. Jordan, Waldemar Koch, Frank R. Lillie, Albert P. Mathews,
H. T. Ricketts, H. Gideon Wells.
University of Iilinois.—Philip B. Hawk, Ward J. MacNeal.
University of Japan.—Naohidé Yatsu.
University of Louisville.—Cyrus W. Field.
University of Michigan.—Otto C. Glaser, Carl G. Huber, Warren P.
Lombard, Frederick G. Novy, Victor C. Vaughan, Aldred S. Warthin.
University of Missourt.—C. Stuart Gager, Robert B. Gibson.
University of Pennsylvania.—Alexander C. Abbott, David L. Edsall,
Ralph S. Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet.
University of Southern California (Los Angeles).—Lyman B. Stookey.
University of St. Louts.—E. P. Lyon.
Untuersity of Torvonto.—A. B. Macallum.
University of Wisconsin.—Charles R. Bardeen, C. H. Bunting, Joseph
Erlanger, Arthur S. Loevenhart, Mazyck P. Ravenel.
Washington University (St. Louis),—C. C. Guthrie.
Western Reserve Ce (Cleveland).—George W. Crile, J. J. R.
Macleod, Torald Sollmann, G. N. Stewart.
Wistar Institute of poapads (Philadelphia).—H. H. Donaldson, Shin-
kishi Hatai.
Vale University. —R. H. Chittenden, Ross G. Harrison, Yandell Hen-
derson, Lafayette B. Mendel, Frank P. Underhill, L. L. Woodruff.
Members present at the thirtieth meeting:
Alsberg, Atkinson, Auer, Banzhaf, Burton-Opitz, Crile, Dakin, Ewing,
Famulener, Flexner, Gies, Harris, Jobling, Joseph, Kast, Lee, Levene,
Levin, Lusk, Mandel (A. R.), Meltzer, Meyer, Morgan, Noguchi, Opie,
Park, Pearce, Shaffer, Terry, Van Slyke, Weil, Wells, Wolf.
Members elected at the thirtieth meeting:
C. C. Guthrie, B/E) layon, Mazyck P. Ravenel.
Dates of the next two regular meetings:
December 16, 1908. February 17, 1909.
PROCEEDINGS
OF THE
SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE
THIRTY SECOND MEETING
NEW YORK UNIVERSITY AND BELLEVUE
HOSPITAL MEDICAL COLLEGE
NEW YORK CITY
FEBRUARY 17, 1909
VoLUME VI
No. 3
NEW YORK
MarRcH 15, 1909
CONTENTS.
YANDELL HENDERSON: A method for the direct observation of normal peris-
talsis in the stomach and intestines. 28 (366).
A. I, RINGER (By invitation): Studies on the effects of carbon mon-oxide
poisoning. 29 (367).
GEORGE B. WALLAcE and Huco SALomon: Intestinal excretion during
diarrhea. 30 (368).
R. Burton-Opitz and Danrex R. Lucas: The vascularity of the kidney as
influenced by sensory impulses. 31 (369).
Pau A. Lewis: The influence of temperature on hemolysis in hypotonic
solutions. 32 (370).
FREDERICK P. Gay: A carcinoma of the rat (Flexner-Jobling) considered
from the standpoint of immunity. 33 (371).
A. O. SHAKLEE: Influence of temperature upon pepsin. 34 (372).
manne be FosTer and JAMES C. GREENWAY: Synthesis of uric acid. 35
(373).
HIDEYO NoGucut: Some critical considerations on the serum diagnosis of
syphilis. 36 (374).
D. Manson, L. KRISTELLER and P. A. LEVENE: On nitrogenous metabo-
lism in chronic nephritis. 37 (375).
CARL L, ALSBERG: The formation of gluconic acid by the olive-tubercle
organism and the function of oxidation in some microérganisms. 38
(376).
Jacques Logs: On the fertilizing and cytolytic effect of soap. 39 (377).
T. BRAILSFORD ROBERTSON and THEODORE C. BURNETT: On the depres-
sion of the freezing point of water due to dissolved caseinates. 40 (378).
W. J. MACNEAL, LENORE L, LATZER and JOSEPHINE E. KERR: The daily
excretion of bacteria in the feces of healthy men. 41 (379).
WALTER A. Jacoss and P. A. LEVENE: Further studies on the constitution
of inosinic acid. 42 (380).
Joun F. ANDERSON and M. J. RosENAU: The effect of heat on the anaphy-
lactic properties of proteins. 43 (381).
CHARLES A, ELSBERG: A skin reaction in carcinoma from the subcutaneous
injection of human red blood cells. 44 (382).
The proceedings of the Society for Experimental Biology and Medicine are pub-
lished as soon as possible after each meeting. Regular meetings of the Society are held
in New York on the third Wednesdays of October, December, February, April and
May. A volume of the proceedings consists of the numbers issued during an
academic.year.
The price per volume, sent postage prepaid, is one dollar. The price of copies
of the proceedings of any meeting is twenty cents each, postage prepaid. Subscriptions
are payable in advance.
Address communications to any of the following members of the Council of the
Society :
Pie PRESIDENTS— S. J. Meltzer, Rockefeller Institute for Medical Research ;
Edmund B. Wilson, Columbia University; Simon Flexner, Rockefeller Institute for
Medical Research.
PRESIDENT — Frederic S. Lee, Columbia University.
VicE-PRESIDENT — William J. Gies, Columbia University.
SECRETARY — Eugene L. Opie, Rockefeller Institute for Medical Research.
TREASURER — Graham Lusk, New York University.
MANAGING EpiIToR—The Secretary, Rockefeller Institute for Medical Re-
search, 66th St. and Ave. A, New York City.
-—— SociErY Fo
EXPERIMENTAL BIOLOGY AND MEDICINE
-
}
THIRTY THIRD MEETING —
_ CORNELL UNIVERSITY MEDICAL COLLEGE
4
\
pd
oN MS YORK! CLEY |
2 APRIL 21, 1909
ges ‘Vi |
Pe OR). NEN YORK
cee ay
CONTENTS.
R. Burton-Opitz: The vascularity of the spleen as influenced by single
nerves of the plexus lienalis. 45 (383).
RICHARD M. PEARCE: An experimental study of the influence of kidney
extracts and of the serum of animals with renal lesions upon the blood
pressure. 46 (384).
J. J. R. Mac.teop: Further observations on the effect of asphyxia and
curare on the reducing power of the blood after section of the hepatic
nerves in dogs. 47 (385).
WrtiiAM H. PARK and EUGENE FAMULENER: Toxin-antitoxin mixtures as
immunizing agents. 48 (386).
ALFRED F. Hess: Antiperistalsis in its relation to tubercle bacilli and other
bacteria in the alimentary tract. 49 (387).
SIMON FLEXNER and RICHARD V. LAMAR: The action of soaps on the
pneumococcus. 50 (388).
A. O. SHAKLEE and S. J. MELTZER: The influence of shaking upon trypsin
and rennin and a comparison of this influence with that upon pepsin.
51 (389).
Don R. JosEPH and S. J. MELTZER: The influence of sodium and calcium
upon direct and indirect muscle irritability and their mutual antagonistic
actions. 52 (390).
J. AUER and S. J. MELTZER: The effects of local applications of chloride
and sulphate of magnesium upon the centers in the medulla compared
with those of sodium chloride. 53 (391).
J. AvER and S. J. MELTzeER: Respiration by continuous intrapulmonary
pressure without the aid of muscular action. 54 (392).
ALEXIS CARREL: Note on the production of kidney insufficiency by reduc-
tion of the arterial circulation of the kidney. 55 (393).
THEODORE C. JANEWAY: A modification of the Riva-Rocci method of de-
termining blood-pressure for use on the dog. 56 (394),
THEODORE C. JANEWAY: Note on the blood-pressure changes following re-
duction of the renal arterial circulation. 57 (395).
H.C. THACHER: The effect of experimental acute insufficiency of the right
heart upon the volume of the organs. 58 (396).
The proceedings of the Society for Experimental Biology and Medicine are pub-
lished as soon as possible after each meeting. Regular meetings of the Society are held
in New York on the third Wednesdays of October, December, February, April and
May. A volume of the proceedings consists of the numbers issued during an
academic year.
The price per volume, sent postage prepaid, is one dollar. The price of copies
of the proceedings of any meeting is twenty cents each, postage prepaid. Subscriptions
are payable in advance.
Address communications to any of the following members of the Council of the
Society :
Past PRESIDENTS—S. J. Meltzer, Rockefeller Institute for Medical Research ;
Edmund B. Wilson, Columbia University; Simon Flexner, Rockefeller Institute for
Medical Research.
PRESIDENT — Frederic S. Lee, Columbia University.
VicE-PRESIDENT — William J. Gies, Columbia University.
SECRETARY — Eugene L. Opie, Rockefeller Institute for Medical Research.
TREASURER — Graham Lusk, New York University.
MANAGING EpiITorR—The Secretary, Rockefeller Institute for Medical Re-
search, 66th St. and Ave. A, New York City.
Uf
PROCEEDINGS
OF THE
SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE
THIRTY FOURTH MEETING
THE ROCKEFELLER INSTITUTE FOR MEDICAL
RESEARCH
NEW YORK CITY
MAY 26, 1909
VoLuME VI
No. 5
NEW YORK
1909
CONTENTS.
ELIZABETH CooKE and Leo LogB: The comparative toxicity of sodium
nan and of staining solutions upon the embryo of Fundulus. 59
(397).
MOYER S. FLEISHER and Leo Logs: The influence of calcium chloride and
of adrenalin upon the secretion of urine and upon absorption from the
peritoneal cavity. 60 (398).
H. GIDEON WELLS and Harry J. Corper: Observations on uricolysis»
with particular reference to the ‘‘uric acid infarcts’’ of the newborn;
61 (399).
LORANDE Loss WoopruFF : Further studies on the life cycle of Paramecium.
62 (400).
B. T. Terry: Immunity to various species of trypanosomes induced in
mice by the cure of experimental infections. 63 (401).
DONALD D. VAN StykE and P. A. LEVENE: The leucin fraction of proteins.
II. 64 (402).
Donatp D. VAN SLYKE: ‘‘Clavin,’’ Vahlen’s active principle of ergot. 65
(403).
DANIEL R. Lucas : Some effects of sodium benzoate. 66 (404).
MATTHEW STEEL: An improvement of the Folin method for the determina-
tion of urinary ammonia nitrogen. 67 (405).
RICHARD M. PEARCE: The depressor substance of dog’s urine; its disap-
pearance in experimental acute nephritis. 68 (406).
PHILIP A. SHAFFER: Observations on the metabolism of a subject of dia-
betes. 69 (407).
W. O. EMERY and WILLIAM SALANT: On the decomposition of caffeine in
the liver. 70 (408).
WILLIAM SALANT: The comparative toxicity of ethyl and amyl alcohol, and
their effect on blood pressure. 71 (409).
L. B. Stookey ; Pentosuria. 72 (410).
The proceedings of the Society for Experimental Biology and Medicine are pub-
lished as soon as possible after each meeting. Regular meetings of the Society are held
in New York on the third Wednesdays of October, December, February, April and
May. A volume of the proceedings consists of the numbers issued during an
academic year.
The price per volume, sent postage prepaid, is one dollar. The price of copies
of the proceedings of any meeting is twenty cents each, postage prepaid. Subscriptions
are payable in advance.
Address communications to any of the following members of the Council of the
Society :
PAST PRESIDENTS— S. J. Meltzer, Rockefeller Institute for Medical Research ;
Edmund B. Wilson, Columbia University; Simon Flexner, Rockefeller Institute for
Medical Research.
PRESIDENT — Frederic S. Lee, Columbia University.
VicE-PRESIDENT — William J. Gies, Columbia University.
SECRETARY — Eugene I.. Opie, Rockefeller Institute for Medical Research.
TREASURER — Graham Lusk, New York University.
MANAGING EpirorR—The Secretary, Rockefeller Institute for Medical Re-
search, 66th St. and Ave. A, New York City.
CLASSIFIED LIST OF MEMBERS OF THE SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE.
Resident (Greater New York). -
Bellevue Hospital.—Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University. —Russell Burton-Opitz, Gary N. Calkins, Henry E.
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Theodore C. Janeway,
Frederic S. Lee, Isaac Levin, J. W. Draper Maury, Thomas H. Morgan,
Henry C. Sherman, Augustus PB. Wadsworth, Edmund B. Wilson, Francis
C. Wood, Hans Zinsser.
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, Chas.
R. Stockard, John C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinai Hospital.—Charles A. Elsberg.
New York City College.—Max Morse, Thomas A. Storey.
New York City Departments. Education.—C. Ward Crampton.
Hlealth.—James P. Atkinson, Edwin J. Banzhaf, L. W. Famulener.
New York Hospital.—Douglas Symmers.
New York Polyclinic Medical School.—Isaac Adler.
New York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Pathological Institute, Wards Island.—Adolph Meyer.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, Don R. Joseph, Richard V. Lamar,
P. A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave M. Meyer, Hideyo
Noguchi, Eugene L. Opie, Peyton Rous, B. T. Terry, Donald D. Van Slyke.
Sage Institute of Pathology, City Hospital. — Horst Oertel,
St. Francis Hospital. —Fritz Schwyzer.
819 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—Isaac F. Harris.
Non-Resident.
Albany Medical College. —Holmes C. Jackson.
Baltimore Medical College.—Charles E. Simon.
Carnegie Institution of Washington.—Francis G. Benedict (/Vutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fla.).
Connecticut Agricultural Experiment Station (New Haven).—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils.
Massachusetts Institute of Technology.—Percy G. Stiles.
Medico-Chirurgical College (Philadelphia).—Isaac Ott.
Michael Reese Hospital (Chicago).—James W. Jobling.
Northwestern University Medical School (Chicago).—J. B. Murphy,
Alfred N. Richards.
Oakland College of Medicine.—Martin H. Fischer.
U. S. Departments. Agriculture (Washington, D. C.).—Carl L. Als-
berg, William N. Berg, Albert C. Crawford, William Salant; Jnterior
(Philippine Islands, Bureau of Science, Manila).—Richard P. Strong, Oscar
Teague. Zyeasury(Public Health and Marine-Hospital Service).—Walter
R. Brinckerhoff, Honolulu, Hawaii; John F. Anderson, Wm. H. Hale,
Reid Hunt, Joseph H. Kastle, M. J. Rosenau and W. H. Schultz, Wash-
ington, D. C.
Universities. Buffalo.—G.H. A. Clowes, Herbert U. Williams. Ca/-
fornia.—Jacques Loeb, T. Brailsford Robertson, Alonzo E. Taylor. Chicago.
—R. R. Bensley, A. J. Carlson, Ludvig Hektoen, Edwin O. Jordan, Walde-
mar Koch, Frank R. Lillie, Albert P. Mathews, H. T. Ricketts, H. Gideon
Wells. Corne//.—Andrew-Hunter. Harvard.— Walter B. Cannon, W. T.
Councilman, Otto Folin, Frederick P. Gay, G. H. Parker, Franz Pfaff, W.
T. Porter, Joseph H. Pratt, Theobald Smith, E. E. Southard, E. E. Tyzzer,
Robert M. Yerkes. //nois.—Philip B. Hawk, Ward J. MacNeal. /afan.
—Naohidé Yatsu. Johns Hopkins.—John J. Abel, Rufus I. Cole, Har-
vey W. Cushing, W. W. Ford, W. S. Halsted, William H. Howell,
H. S. Jennings, Walter Jones, W. G. MacCallum, F. P. Mall, William H.
Welch. Louzsville.—Cyrus W. Field. McGill (Montreal).—J. George
Adami, Oskar Klotz, John L. Todd, S. Burt Wolbach. Michigan.—C. W.
Edmunds, Otto C. Glaser, Carl G. Huber, Warren P. Lombard, Frederick G.
Novy, Victor C. Vaughan, Aldred S. Warthin. Jssourvz.—C. Stuart Gager,
Robert B. Gibson. Pennsylvania.—Alexander C. Abbott, David L. Edsall,
Ralph S. Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet. Princeton.—
Edwin G. Conklin. . Southern California (Los Angeles).—Lyman B. Stookey.
St. Louis. —E. P. Lyon. Toronto.—T.G. Brodie, A.B. Macallum. Zz/ane.—
Charles W. Duval. .Wisconsin.—Charles R. Bardeen, C. H. Bunting, Joseph
Erlanger, Arthur.S. Loevenhart, Mazyck P. Ravenel. Washington (St.
Louis).—C. C, Guthrie. Western Reserve (Cleveland).—George W. Crile,
J. J. R. Macleod, Torald Sollmann, G. N. Stewart. Va/e.—R. H. Chitten-
den, L. J. Cole, Ross G. Harrison, Yandell Henderson, Lafayette B. Mendel,
Frank P. Underhill, Lorande Loss Woodruff.
University College (London).—Arthur R. Cushny.
Wistar Institute of Anatomy (Philadelphia).—H. H. Donaldson, Shin-
kishi Hatai.
Members present at the thirty fourth meeting:
Auer, Beebe, Ewing, Famulener, Flexner, Gies, Hatcher, Joseph, Lee,
Lewis, Loeb (Leo), Morse, Meyer (Gustave), Pearce, Shaffer, Sherman,
Terry, Van Slyke, Wallace, Weil, Wolf.
Members elected at the thirty fourth meeting:
C. W. Edmunds, J. W. Draper Maury, Adolph Meyer.
Dates of the next two regular meetings:
October 20, 1909. December 15, 1909.
.
“Ry
CLASSIFIED LIST OF MEMBERS OF THE SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE.
Resident (Greater New York).
Bellevue Hospital.—Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University.—Russell Burton-Opitz, Gary N. Calkins, Henry E.
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Frederic S. Lee, Isaac
Levin, Thomas H. Morgan, Henry C. Sherman, Augustus B. Wadsworth,
Edmund B. Wilson, Francis C. Wood, Hans Zinsser.
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, Chas.
R. Stockard, John C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinat Hospital.—Charles A. Elsberg.
New York City College.—Max Morse, Thomas A. Storey.
New York City Departments. Education.—C. Ward Crampton.
flealth.—James P. Atkinson, Edwin J. Banzhaf, L. W. Famulener.
New York FHospital.—Douglas Symmers.
WVew York Polyclinic Medical School.—\saac Adler.
New York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, James W. Jobling, Don R. Joseph,
Richard V. Lamar, P. A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave
M. Meyer, Hideyo Noguchi, Eugene L. Opie, Peyton Rous, B. T. Terry,
Donald D. Van Slyke.
Sage Institute of Pathology, City Hospital.—Theodore C. Janeway,
Horst Oertel,
St. Francis Hospital.—Fritz Schwyzer.
$19 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—Isaac F. Harris.
Non-Resident.
Albany Medical College.—Holmes C. Jackson, S. Burt Wolbach.
Baltimore Medical College.—Charles E. Simon.
Carnegie Institution of Washington.—Francis G. Benedict (WVutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fla.).
Connecticut Agricultural Experiment Station (New Haven).—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils.
Massachusetts Institute of Technology.—Percy G. Stiles.
Medico-Chirurgical College (Philadelphia).—Isaac Ott.
Northwestern University Medical School (Chicago).—J. B. Murphy,
Alfred N. Richards.
Oakland College.of Medicine.—Martin H. Fischer.
U. S. Departments. Agriculture (Washington, D. C.),—Carl L. Als-
berg, William N. Berg, Albert C. Crawford, William Salant; Jnlerior
(Philippine Islands, Bureau of Science, Manila).—Richard P. Strong, Oscar
Teague. Treasury(Public Health and Marine-Hospital Service).—Walter
R. Brinckerhoff, Honolulu, Hawaii; John F. Anderson, Wm. H. Hale,
Reid Hunt, Joseph H. Kastle, M. J. Rosenau and W. H. Schultz, Wash-
ington, D.C.
Universitics. Buffalo.—G. H. A. Clowes, Herbert U. Williams. Calz-
fornia.—Jacques'Loeb, T. Brailsford Robertson, Alonzo E. Taylor. Chicago.
—R. R. Bensley, A. J. Carlson, Ludvig Hektoen, Edwin O. Jordan, Walde-
mar Koch, Frank R. Lillie, Albert P. Mathews, H. T. Ricketts, H. Gideon
Wells. Corned/7.— Andrew Hunter. Aarvard.— Walter B. Cannon, W. T.
Councilman, Otto Folin, Frederick P. Gay,'G. H. Parker, Franz Pfaff, W.
T. Porter, Joseph H. Pratt, Theobald Smith, E. E. Southard, E. E. Tyzzer,
Robert M. Yerkes. J//inois.—Philip B. Hawk, Ward J. MacNeal. /apan.
—Naohidé Yatsu. Johns Hopkins.—John J. Abel, Rufus I. Cole, Har-
vey W. Cushing, W. W. Ford, W. S. Halsted, William H. Howell,
H. S. Jennings, Walter Jones, W. G. MacCallum, F. P. Mall, William H.
Welch. Loudisville.—Cyrus W. Field. McGil/ (Montreal).—J. George
Adami, Charles W. Duval, Oskar Klotz, John L. Todd. Michigan.—Otto C.
Glaser, Carl G. Huber, Warren P. Lombard, Frederick G. Novy, Victor
C. Vaughan, Aldred S. Warthin. J/ssourvi.—C. Stuart Gager, Robert B.
Gibson. FPennsylvania.—Alexander C. Abbott, David L. Edsall, Ralph S.
Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet. Princeton.—Edwin
G. Conklin. Southern California (Los Angeles).—Lyman B. Stookey. S¢.
Louts.—E. P. Lyon. Toronto.—T. G. Brodie, A. B. Macallum. Wscon-
siw.—Charles R. Bardeen, C. H. Bunting, Joseph Erlanger, Arthur S.
Loevenhart, Mazyck P. Ravenel. Washington (St. Louis).—C. C. Guthrie.
Western Reserve (Cleveland).—George W. Crile, J. J. R. Macleod, Torald
Sollmann, G. N. Stewart. Yal/e.—R.H. Chittenden, L. J. Cole, Ross G.
Harrison, Yandell Henderson, Lafayette B. Mendel, Frank P. Underhill,
Lorande Loss Woodruff.
University College (London).—Arthur R. Cushny.
Wistar Institute of Anatomy (Philadelphia).—H. H. Donaldson, Shin-
kishi Hatai.
Members present at the thirty third meeting:
Atkinson, Auer, Burton-Opitz, Elser, Ewing, Flexner, Famulener, Gies,
Janeway, Joseph, Kast, Lee, Lamar, Lewis, Lusk, Mandel (J. A.), Melt-
zer, Meyer, Morse, Noguchi, Norris, Oertel, Park, Pearce, Shaffer, Storey,
Terry, Wallace, Wolf.
Members elected at the thirty third meeting:
John L. Todd, Peyton Rous, H. S. Jennings, Andrew Hunter, Chas. R.
Stockard, E. E. Southard, Wm. W. Hale.
Dates of the next two regular meetings:
May 26, Ig09. October 20, 1909.
CLASSIFIED LIST OF MEMBERS OF THE SOCIETY FOR
EXPERIMENTAL BIOLOGY AND MEDICINE,
Resident (Greater New York).
Belleoue Hospital.—Thomas Flournoy, Charles Norris, Alwin M. Pap-
penheimer.
Columbia University.—Russell Burton-Opitz, Gary N. Calkins, Henry E.
Crampton, Richard H. Cunningham, Haven Emerson, Nellis B. Foster,
William J. Gies, Christian A. Herter, Philip H. Hiss, Frederic S. Lee, Isaac
Levin, Thomas H. Morgan, Henry C. Sherman, Augustus B. Wadsworth,
‘Edmund B. Wilson, Francis C. Wood, Hans Zinsser,
Cornell University Medical College.—S. P. Beebe, B. H. Buxton, Wil-
liam J. Elser, James Ewing, Robert A. Hatcher, Philip A. Shaffer, John
C. Torrey, Richard Weil, C. G. L. Wolf.
Mt. Sinai Hospital.—Charles A. Elsberg.
New York City College.—Max Morse, Thomas A. Storey.
New York City Departments. Education.—C. Ward: Crampton.
ffealth.—James P. Atkinson, Edwin J. Banzhaf, L. W, Famulener.
New York Hospital.—Douglas Symmers.
New York Polyclinic Medical School.—Isaac Adler.
New York Post-Graduate Medical School.—Ludwig Kast.
New York University.—Harlow Brooks, Edward K. Dunham, Graham
Lusk, Arthur R. Mandel, John A. Mandel, John R. Murlin, William H.
Park, Richard M. Pearce, George B. Wallace.
Rockefeller Institute for Medical Research.—John Auer, Alexis Carrel,
Simon Flexner, Walter A. Jacobs, James W. Jobling, Don R. Joseph,
Richard V. Lamar, P. A. Levene, Paul A. Lewis, S. J. Meltzer, Gustave
M. Meyer, Hideyo Noguchi, Eugene L. Opie, B. T. Terry, Donald D. Van
Slyke.
Sage Institute of Pathology, City Hospital.—Theodore C. Janeway,
Horst Oertel,
St. Francis Hospital.—F¥ritz Schwyzer.
4
819 Madison Avenue.—H. D. Dakin.
449 E. 57th Street.—Isaac F. Harris.
Non-Resident.
Albany Medical College.—Holmes C. Jackson, S. Burt Wolbach.
Baltimore Medical College.—Charles E. Simon.
Carnegie Institution of Washington.—Francis G. Benedict (Vutrition
Laboratory, Boston), Charles B. Davenport (Station for Experimental Evolu-
tion, Cold Spring Harbor, N. Y.), D. T. MacDougal (Washington), Alfred
G. Mayer (Marine Laboratory, Tortugas, Fla.).
Connecticut Agricultural Experiment Station (New Haven),—Thomas
B. Osborne.
Cooper Medical College (San Francisco).—William Ophiils,
Massachusetts Institute of Technology.—Percy G. Stiles.
Medico-Chirurgical College (Philadelphia).—\saac Ott.
Northwestern University Medical School (Chicago).—J. B. Murphy,
Alfred N. Richards.
Oakland College of Medicine.—Martin H. Fischer.
U. S. Departments. Agriculture (Washington, D. C.),—Carl L. Als-
berg, William N. Berg, Albert C. Crawford, William Salant; J#terior
(Philippine Islands, Bureau of Science, Manila).—Richard P. Strong, Oscar
Teague. Zveasury(Public Health and Marine-Hospital Service).—Walter
R. Brinckerhoff, Honolulu, Hawaii ; John F. Anderson, Reid Hunt, Joseph
H. Kastle, M. J. Rosenau and W. H. Schultz, Washington, D. C.
Universities. Buffalo.—G.H. A. Clowes, Herbert U. Williams. Cad-
fornia.—Jacques Loeb, T. Brailsford Robertson, Alonzo E. Taylor. Chicago.
—R. R. Bensley, A. J. Carlson, Ludvig Hektoen, Edwin O. Jordan, Walde-
mar Koch, Frank R. Lillie, Albert P. Mathews, H. T. Ricketts, H. Gideon
Wells. Harvard.— Walter B. Cannon, W. T. Councilman, Otto Folin,
Frederick P. Gay, G. H. Parker, Franz Pfaff, W. T. Porter, Joseph H. Pratt,
Theobald Smith, E. E. Tyzzer, Robert M. Yerkes. J//nozs.—Philip B.
Hawk, Ward J. MacNeal. /afan.—Naohidé Yatsu. Johns Hopkins. —
John J. Abel, Rufus I. Cole, Harvey W. Cushing, W. W. Ford, W. S.
Halsted, William H. Howell, Walter Jones, W. G. MacCallum, Fi P. Mall,
William H. Welch. Lowuisville.—Cyrus W. Field. McGil/ (Montreal).—
J. George Adami, Charles W. Duval, Oskar Klotz. Michigan.—Otto C.
Glaser, Carl G. Huber, Warren P. Lombard, Frederick G. Novy, Victor
C. Vaughan, Aldred S. Warthin. J/ssouri.—C. Stuart Gager, Robert B.
Gibson, Pennsylvania.—Alexander C. Abbott, David L. Edsall, Ralph S.
Lillie, Leo Loeb, Edward T. Reichert, J. Edwin Sweet. Princeton.—Edwin
G. Conklin. Southern California (Los Angeles).—Lyman B. Stookey. S¢.
Louis. —E. P. Lyon. Toronto.—T. G. Brodie, A.B. Macallum. Wiscon-
sin.—Charles R. Bardeen, C. H. Bunting, Joseph Erlanger, Arthur S.
Loevenhart, Mazyck P. Ravenel. Washington (St. Louis).—C. C. Guthrie.
Western Reserve (Cleveland).—George W. Crile, J. J. R. Macleod, Torald
Sollmann, G. N. Stewart. Yale.—R.H. Chittenden, L. J. Cole, Ross G.
Harrison, Yandell Henderson, Lafayette B. Mendel, Frank P. Underhill,
Lorande Loss Woodruff.
University College (London).—Arthur R. Cushny.
Wistar Institute of Anatomy (Philadelphia).—H. H. Donaldson, Shin-
kishi Hatai.
Members present at the thirty second meeting:
Alsberg, Atkinson, Auer, Banzhaf, Beebe, Berg, Burton-Opitz, Ewing,
Famulener, Foster, Gay, Gies, Henderson, Jacobs, Joseph, Kast, Lee,
Levene, Levin, Lewis, Lusk, Mandel, Meltzer, Meyer, Murlin, Noguchi,
Opie, Pearce, Storey, Terry, Wallace, Weil.
Members elected at the thirty second meeting:
John F. Anderson, T. G. Brodie, L. J. Cole, Martin H. Fischer, Richard
V. Lamar, Max Morse, Hans Zinsser.
Officers elected at the thirty second meeting :
President, Frederic S. Lee; Vice President, William J. Gies; Secretary,
Eugene L. Opie; Zveasurer, Graham Lusk.
Dates of the next two regular meetings:
April 21, 1909. May 19, 1909.
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