bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF IN VITRO CULTIVATION ON THE PATHOGENICITY OF VENEZUELAN EQUINE ENCEPHALOMYELITIS VIRUS
Authors: Koprowski Hilary , Lennette Edwin H.
Published: June 2004

Continued in vitro cultivation in a Maitland type medium resulted in a marked modification of the extraneural pathogenicity of the Venezuelan equine encephalomyelitis virus.

The ability of the virus to induce lethal infections after peripheral inoculation was almost completely lost for mice 42 or more days of age, was somewhat reduced for mice 28 days of age, but was still retained for mice 21 or less days of age. The virulence of the virus by the cerebral route remained essentially unaffected for mice of any of the experimental age groups.

Prolonged cultivation also resulted in almost complete attenuation of the virus for rabbits and guinea pigs by the intraperitoneal route.
STUDIES ON THE FLEXNER GROUP OF DYSENTERY BACILLI
Authors: Perlman Ely , Goebel Walther F.
Published: June 2004

A quantitative study of the serological cross-reactions of the somatic antigens of Types I, III, and I-III Shigella paradysenteriae has been made.

From the results obtained it has been concluded that the somatic antigens of Shigella paradysenteriae (Flexner) Types I, III, and I-III are single chemical substances. The specificity and serological cross-reactions exhibited by these antigens are dependent upon similarities in their chemical constitutions.
FURTHER STUDIES ON EFFECTS OF TISSUE EXTRACTS ON STAPHYLOCOCCUS AUREUS
Authors: Nutini Leo G. , Lynch Sister Eva Maria
Published: June 2004

1. The ability of alcoholic-precipitated extracts of beef tissue—brain, spleen, heart, and kidney—to stimulate the growth of Staphylococcus aureus, in vitro, and to convert the yellow S form to a white R variant with altered biochemical characteristics conforming to those of an avirulent organism, has been confirmed.

2. The avirulence of the white R variant has been established by tests in vivo on mice.

3. Staphylococcus aureus infections induced subcutaneously, intraperitoneally, and intravenously in mice responded favorably to brain extract following subcutaneous or oral administration. The mortality was 2 per cent in 444 experimental animals and 81 per cent in 448 control animals.

4. The extracts appeared equally efficient when used therapeutically (mortality 2 per cent of 162 experimental animals and 90 per cent in the control series) or prophylactically (mortality 2 per cent of 282 experimental animals and 76 per cent in 286 control mice). Extracts of brain and spleen were more effective than those of either heart or kidney.

5. Studies concerning the mechanism of action of the tissue extracts indicate that they prevented the formation of toxin by Staphylococcus aureus, and had but little effect on toxin actions.

6. Toxicity tests revealed that the brain and spleen extracts were relatively non-toxic, dosages equivalent to 2 per cent of the body weight being well tolerated. Kidney and heart extracts were much more toxic, producing mortality in dosages as low as 0.3 per cent of the body weight.
NUTRITION OF THE HOST AND NATURAL RESISTANCE TO INFECTION
Authors: Schneider Howard A.
Published: June 2004

The property of a diet of whole wheat and whole dried milk to promote a higher survival rate among a stock of heterogenetic, outbred W-Swiss mice subjected to S. enteritidis infection, over that promoted by a "synthetic" diet, has been shown to be a function of the infecting bacterial population.

Broth cultures so prepared as presumably to yield S. enteritidis organisms of uniform character have consistently failed to reveal an effect of diet on natural resistance, even though the parent bacterial populations revealed a dietary effect.

The dietary difference effect on natural resistance could not be demonstrated with an avirulent culture of S. typhimurium, or with a freshly prepared virulent culture of S. typhimurium presumably uniform in character.

The dietary effect on natural resistance was demonstrated by employing a 1:1 mixture of avirulent and virulent cultures of S. typhimurium.
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA
Authors: Wood W. Barry , McLeod Charlotte , Irons Edwin N.
Published: June 2004

The phagocytosis which occurs in the lungs of rats receiving sulfonamide is due neither to an opsonizing action of the sulfonamides nor to type-specific antibody. The evidence presented indicates that the destruction of the pneumococci is brought about by a phagocytic mechanism independent of both opsonization and capsular injury.
IMMUNITY IN EXPERIMENTALLY INDUCED INFECTIOUS HEPATITIS
Authors: Havens W. Paul
Published: June 2004

1. 9 human volunteers, convalescent from infectious hepatitis experimentally induced by a strain of virus employed in this laboratory, were resistant when reinoculated with the same strain of virus, 6 to 9 months later.

2. 8 out of 12 previously healthy control subjects developed infectious hepatitis with jaundice following administration of this same material.

3. The demonstration of homologous immunity produced by this strain of virus is in agreement with the demonstration by others of homologous immunity produced by another strain of infectious hepatitis virus.
THE PROPERTIES OF T ANTIGENS EXTRACTED FROM GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Lancefield Rebecca C. , Dole Vincent P.
Published: June 2004

1. T antigens of group A hemolytic streptococci have been obtained in soluble form by digestion of the bacterial cells with pepsin or trypsin. Large quantities of this antigen were readily extracted from type 1 strains, whereas only small amounts could be obtained from strains of other types.

2. The T antigen, prepared in this way from a type 1 strain, was partially purified by chemical precipitation and further enzymatic digestion. An active fraction, apparently protein in nature, was separated electrophoretically at pH 7.00. The separated material, pooled and analyzed at the same pH, gave only a single peak. The isoelectric point of this substance was about pH 4.50. An elementary analysis was obtained. Although the T antigen was resistant to digestion with proteolytic enzymes and ribonuclease, it was readily inactivated by heat, especially in acid media and in strong salt solutions. The serological activity of this purified T substance was lost after exposure to ultraviolet radiation.

3. Analysis by means of the ultracentrifuge showed that the material was polydisperse and therefore probably impure.

4. The soluble form of the T substance was active in the precipitin reaction, in the fixation of complement, in inhibition of T agglutination, and as an antigen when injected into rabbits. The antibodies produced did not protect mice against infection with virulent strains of hemolytic streptococci containing the same T antigen.

5. The immunological specificity of T antigen in soluble form is the same as that of the T antigen in the intact streptococcus from which it was derived
THE EFFECTS OF VENOUS OBSTRUCTION UPON INTERSTITIAL PRESSURE IN ANIMAL AND HUMAN SKIN
Authors: McMaster Philip D.
Published: June 2004

The changes of intracutaneous pressure in the limbs of mice and human beings have been followed during and after periods of venous obstruction with almost unhindered arterial flow. During the first 30 minutes of obstruction the interstitial pressure in the tense skin of the lower legs of mice, a pressure which is slightly higher than that in the loose skin of the ears, backs, and thighs (21), rose from 2.6 to 4.6 cm. of water to about 32 cm., thereafter remaining constant. It would appear that the escape of fluid from the capillaries is checked at this pressure. In the skin of the arm and leg of man the interstitial pressure rose from 2.5–3.7 cm. of water to 15.0–23.0, within 15 to 27 minutes after venous obstruction had been produced, mounting no higher during the period of observation. When venous obstruction had existed for about 20 minutes or more the subjects sometimes experienced sensations of relief from congestion as if some tissue adjustment or the opening of some venous by-pass in the marrow had occurred, preventing a further rise of pressure. However this may be, the pressures still appeared to be great enough to prevent further escape of fluid from the capillaries, at least for the time being.
THE ACTIVATING EFFECT OF MAGNESIUM AND OTHER CATIONS ON THE HEMOLYTIC FUNCTION OF COMPLEMENT
Authors: Mayer Manfred M. , Osler Abraham G. , Bier Otto G. , Heidelberger Michael
Published: June 2004

1. The evidence presented indicates that Mg++, or other cation such as Ca++, Ni++, or Co++, is essential for the hemolytic action of C'. Ca++, Ni++, and Co++ are less effective than Mg++. The hemolytic system usually does not contain sufficient Mg++ for optimal hemolytic activity so that a marked enhancement can be obtained by addition of extra Mg++.

2. The enhancing action of tissue fluids can be ascribed to their contribution of Mg++.

3. Substances which bind Mg++ and Ca++ are anticomplementary when added to the usual hemolytic system which contains only a small quantity of Mg++. This type of anticomplementary effect can be overcome by addition of extra Mg++.

4. Ca++ may also be essential to the lytic process but its action is much less pronounced than that of Mg++.
STUDIES ON MALARIAL PARASITES
Authors: Geiman Quentin M. , Anfinsen Christian B. , McKee Ralph W. , Ormsbee Richard A. , Ball Eric G.
Published: June 2004

1. Methods of recovering adequate amounts of Plasmodium knowlesi from the monkey (Macaca, mulatta) for biochemical studies and in vitro cultivation are described.

Concentrates of red blood cells parasitized with P. knowlesi can be obtained by differential sedimentation of parasitized blood because of physical and chemical changes produced by the parasites in the host cell and the plasma of the blood.

2. Two different techniques, the rocker-dilution and the rocker-perfusion methods, are described for the cultivation of malarial parasites. Details of the apparatus, assembly, and sterilization are given, as well as methods of counting and evaluating parasites.

3. In a series of 235 control experiments for 20 to 24 hours using three types of apparatus, the average rate of multiplication was 3.9. Each technique has specific value for studying the various aspects of metabolism, nutrition, and the action of antimalarial drugs.
DISSOCIATION OF HEMAGGLUTINATING AND ANTIBODY-MEASURING CAPACITIES OF INFLUENZA VIRUS
Authors: Francis Thomas
Published: June 2004

Preparations of Type B influenza virus, propagated in the embryonated egg and obtained in the form of allantoic fluid, were found after heating at 56°C. for 30 minutes to retain the capacity to agglutinate erythrocytes but no longer measured specific antibody when used as antigen in titrations of serum antibody.

The dissociation of the two activities suggests the presence in such virus preparations of a complex virus antigen comprising, (1) a heat-stable component which agglutinates erythrocytes and reacts primarily with specific antibody; (2) a heat-labile component reacting with a factor of normal serum which ordinarily tends to inhibit the hemagglutinating activity of influenza virus.

The relation of the reagents to other known serological activities of influenza virus is being studied.
ALLERGIC ENCEPHALOMYELITIS IN MONKEYS IN RESPONSE TO INJECTION OF NORMAL MONKEY NERVOUS TISSUE
Authors: Morgan Isabel M.
Published: June 2004

By subcutaneous injection of central nervous tissue emulsified with adjuvants according to Freund's technique it has been possible to induce in the majority of monkeys an acute disseminated encephalomyelitis which is interpreted as an isoimmunization to CNS tissue. Positive reactions occurred only in response to CNS tissue containing white matter; i.e., cerebral white matter, spinal cord (whether normal or poliomyelitis-infected), and cortical "gray" matter (with an estimated 10 per cent contamination with white matter). No reaction occurred when peripheral nerve or kidney suspension or saline alone was injected with adjuvants. The perivascular and extravascular infiltration induced was confined to the CNS.
THE EFFECT OF dl-METHIONINE, l-CYSTINE, AND dl-ISOLEUCINE ON THE UTILIZATION OF PARENTERALLY ADMINISTERED DOG HEMOGLOBIN
Authors: Miller Leon L. , Alling Eric L.
Published: June 2004

1. Further observations on the utilization of parenterally administered dog hemoglobin show that oral supplements of dl-methionine and l-cystine improve the efficiency of utilization of hemoglobin N, while a fed supplement of dl-isoleucine alone is without effect.

2. When N-isoleucine is added to a fed supplement of methionine or methionine and cystine, the utilization of parenterally given hemoglobin N is even better than with the sulfur-containing amino acids alone.

3. A suggested approach to the problem of designing the quantitatively "ideal" amino acid mixture lies in the definition of what may be called total organism-amino acid patterns of rat, dog, man, etc. These may vary considerably not only at different developmental stages in a given species, but also certainly from one species to another.

4. Further attempts to detect globin in the peripheral circulation have pointed to the need for a highly specific procedure such as that an immunologic method may offer.

5. Reduced hemin in dog plasma migrates with α1-globulin and albumin in veronal buffer at pH 8.5 and the colored zones give strong hemochromogen absorption bands.
STUDIES ON SPREADING FACTORS
Authors: Hechter Oscar
Published: June 2004

The spreading response induced by intradermal administration of hyaluronidase is influenced not only by enzyme concentration, but also by the volume and pressure of the injection. These pressure-volume factors influence the rate of spreading and determine the final area of spreading. When a constant volume is injected, the rate of spreading to the area determined by the volume of injection is a function of the enzyme concentration. These and other findings have led to the conclusion that hyaluronidase is an effective spreading agent only when the slow diffusion of enzyme in skin is accelerated by a localized increase of interstitial pressure and volume. These considerations of hyaluronidase action in skin have been utilized to explain the shape of the dosage-response curve of hyaluronidase spreading activity, and the differences in the spreading reactions between crude snake venoms and purified hyaluronidase. The significance of the findings as related to the rôle of hyaluronidase in bacterial invasiveness, and in the assay of S. F. are briefly discussed.
DESOXYCORTICOSTERONE ACETATE
Authors: Knowlton Abbie I. , Loeb Emily N. , Stoerk Herbert C. , Seegal Beatrice C.
Published: June 2004

1. Desoxycorticosterone acetate (DCA) and NaCl, in the dosage employed in normal rats, caused renal and cardiac hypertrophy, characteristic changes in the renal tubular epithelium, atrophic changes in the subcapsular zone of the adrenal cortex, and serum electrolyte changes characterized by a rise in sodium and fall in potassium.

2. In rats rendered nephritic with a rabbit anti-rat-kidney serum, the same regimen caused similar changes. In addition, DCA given concurrently with NaCl greatly intensified the nephritic process and gave rise to striking arterial hypertension.

3. A diet, virtually sodium-free, administered to normal and nephritic rats receiving daily injections of DCA abolished or reduced to a minimum the effects of this steroid; i.e., a liberal ingestion of NaCl was essential for the potentiation of the action of DCA.

4. The addition of KCl to the drinking water of rats receiving DCA and NaCl tended to correct the depression of the level of potassium in the serum, but had no effect upon the hypertension in nephritic animals nor upon the anatomical lesions.

5. The mechanism by which the sodium ion potentiates the activity of DCA has not been established.
ANTIBODY FORMATION IN MEN FOLLOWING INJECTION OF FOUR TYPE-SPECIFIC POLYSACCHARIDES OF PNEUMOCOCCUS
Authors: Heidelberger Michael , MacLeod Colin M. , Hodges Richard G. , Bernhard William G. , di Lapi Marie M.
Published: June 2004

1. Random selections of the sera of trainees injected 2 months previously with the specific polysaccharides of Types I, II, V, and VII pneumococci contained quantities of antibody to Types I, II, and VII sufficient to account for the favorable results of the immunization procedure.

2. As in earlier studies, the levels of the antibody for the C polysaccharide remained relatively constant before and after the injections.

3. The serum from the preliminary bleedings often contained antibody to the Type VII polysaccharide. This remained relatively constant in a control group injected with saline.
THE SIGNIFICANCE OF LESIONS IN PERIPHERAL GANGLIA IN CHIMPANZEE AND IN HUMAN POLIOMYELITIS
Authors: Bodian David , Howe Howard A.
Published: June 2004

1. The peripheral ganglia of eighteen inoculated chimpanzees and thirteen uninoculated controls, and of eighteen fatal human poliomyelitis cases, were studied for histopathological evidence of the route of transmission of virus from the alimentary tract to the CNS.

2. Lesions thought to be characteristic of poliomyelitis in inoculated chimpanzees could not be sharply differentiated from lesions of unknown origin in uninoculated control animals. Moreover, although the inoculated animals as a group, in comparison with the control animals, had a greater number of infiltrative lesions in sympathetic as well as in sensory ganglia, it was not possible to make satisfactory correlations between the distribution of these lesions and the routes of inoculation.

3. In sharp contrast with chimpanzees, the celiac and stellate ganglia of the human poliomyelitis cases were free of any but insignificant infiltrative lesions. Lesions in human trigeminal and spinal sensory ganglia included neuronal damage as well as focal and perivascular inflitrative lesions, as is well known. In most ganglia, as in monkey and chimpanzee sensory ganglia, these were correlated in intensify with the degree of severity of lesions in the region of the CNS receiving their axons. This suggested that lesions in sensory ganglia probably resulted from spread of virus centrifugally from the CNS, in accord with considerable experimental evidence.

4. Two principal difficulties in the interpretation of histopathological findings in peripheral ganglia were revealed by this study. The first is that the specificity of lesions in sympathetic ganglia has not been established beyond doubt as being due to poliomyelitis. The second is that the presence of characteristic lesions in sensory ganglia does not, and cannot, reveal whether the virus reached the ganglia from the periphery or from the central nervous system, except in very early preparalytic stages or in exceptional cases of early arrest of virus spread and of lesion production.
AN INACTIVE PRECURSOR OF STREPTOCOCCAL PROTEINASE
Authors: Elliott Stuart D. , Dole Vincent P.
Published: June 2004

1. Streptococcal proteinase is derived from an inactive precursor found in culture filtrates of proteinase-producing streptococci.

2. The precursor can be converted into the proteinase by low concentrations of trypsin but not by chymotrypsin.

3. In cultures grown in suitable media the conversion of precursor to proteinase is effected autocatalytically. This reaction occurs under reducing conditions and is initiated by active proteinase present in low concentrations with the precursor.

4. The autocatalytic reaction is suppressed or retarded by conditions which decrease the activity of the proteinase, e.g. by growing cultures at 22°C. instead of at 37°C. or by growing them under markedly aerobic conditions. It is also retarded in the presence of casein.
THE EFFECT OF ULTRAVIOLET IRRADIATION ON VARIOUS PROPERTIES OF INFLUENZA VIRUSES
Authors: Henle Werner , Henle Gertrude
Published: June 2004

The effect of ultraviolet irradiation on various properties of the influenza viruses Types A and B has been analyzed. The studies involved propagation and interference in the allantoic sac of the chick embryo, inhibition of embryonic development, toxicity for white mice, hemagglutination including the adsorption-elution mechanism, immunizing capacity for mice and, finally, complement fixation activities in the presence of antibodies to the 600S antigen (human convalescent and postvaccination sera) and the 30S antigen (convalescent sera only). It has been shown that the various activities of the influenza viruses were affected by irradiation at different rates, indicating that they are based, at least in part, on different constituents of the virus particle. On account of these differences in the susceptibility of the various properties to ultraviolet light it was possible (a) to differentiate between the interference phenomenon as observed in the allantoic sac, and the development of non-agglutinability in red cells by either homologous or heterologous fresh virus, and (b) to separate individual steps involved in the mechanism of infection of susceptible host cells. The implications of these findings are discussed.
STUDIES ON GLYCOGEN NEPHROSIS IN ALLOXAN-TREATED DIABETIC RATS
Authors: Curtis G. W. , Robbins S. L. , Glickman I.
Published: June 2004

Two hundred and seven albino rats were injected subcutaneously with alloxan in doses varying from 140 to 200 mg. per cent per kilo of body weight. Fifty-nine animals which developed hyperglycemia (blood sugar levels above 150 mg. per cent) were observed for periods from 5 days to 32 weeks.

Postmortem examination of the kidneys of these diabetic animals revealed glycogen deposition in the loops of Henle and convoluted tubules in 26 rats or 44 per cent. Glycogen could not be demonstrated in the glomeruli. Within the time limits of this experiment (32 weeks) no intercapillary glomerulosclerosis was observed.

The following facts were revealed regarding glycogen nephrosis in alloxan diabetes:

(a) Its appearance in the kidneys of the diabetic rats depended solely upon the terminal blood sugar levels of these animals. A value of 350 mg. per cent was the critical level, above which glycogen nephrosis was almost invariably demonstrable. With terminal levels below 300 mg. per cent no glycogen nephrosis was found.

(b) No relationship existed between the postmortem finding of glycogen nephrosis and the initial blood sugar level, or the maximum height of the hyperglycemia attained by individual rats.

(c) The results suggest that glycogen nephrosis is a reversible lesion.
A STUDY OF THE COMPETITION OF LECITHIN AND ANTITOXIN FOR CL. WELCHII LECITHINASE
Authors: Zamecnik Paul C. , Lipmann Fritz
Published: June 2004

Lecithin has been found to interfere with the combining reaction of Cl. welchii alpha toxin (lecithinase) and its antitoxin. If the lecithinase is first brought into contact with lecithin, and the antitoxin is then added, the antitoxin fails to stop the enzymatic reaction, but gradually decelerates it. If the lecithinase is brought into contact with both lecithin and antitoxin at the same instant, it appears to combine in part with each, and the enzymatic process takes place at a reduced rate, which gradually declines further. If the lecithinase is first brought into contact with antitoxin, before the lecithin is added, the enzymatic reaction is completely inhibited.

This ability of lecithin to inhibit the antitoxin-toxin combination cannot be explained adequately as a non-specific coating of the toxin-enzyme by the lecithin. It is rather suggested that lecithin and antitoxin compete specifically for combination with the same regions on the enzyme molecule.

Lecithin has similarly been found to interfere with the combination of Crotalus terrificus venom and its antiserum.

The above findings provide a partial explanation for the lack of effectiveness of antitoxin when given late in the course of Cl. welchii infection.
EPIDEMIC DIARRHEAL DISEASE OF SUCKLING MICE
Authors: Cheever F. Sargent , Mueller J. Howard
Published: June 2004

1. The disease was almost certainly infectious.

2. Its eradication offered much greater practical difficulties than are presented by certain other infections of mice.

3. A definite tendency toward greater susceptibility in first litters as contrasted with subsequent ones was noted.

4. Advantage could be taken of this increasing resistance to keep the infected colony in efficient production, but accidental loss of the stock prevented the continuation of the plan for a time sufficient to exclude possible failure due to seasonal variation.

5. Multiple etiologies may well have existed even within this circumscribed outbreak.

6. Experimental investigation of the condition offers extraordinary difficulties but its thorough understanding promises to bring new light to basic problems of disease.
THE METABOLISM OF AMINO ACIDS AND CASEIN DIGEST IN PHLORHIZINIZED DOGS
Authors: Hawkins W. B. , McKee F. W. , Hawley G. M. B. , Kummer A. J.
Published: June 2004

When solutions of sugar-forming amino acids are given parenterally or orally to phlorhizinized dogs, extra sugar and nitrogen are excreted in the urine.

The route of administration does not influence the way in which the amino acids are metabolized. 89 percent of the expected sugar was recovered when the acids were fed and 81 per cent when the acids were administered parenterally.

Casein digests are metabolized like the amino acids with extra sugar and nitrogen excreted in the urine.

When casein digest is given orally there is an average conversion into sugar of 53 per cent, as compared with 56 per cent intravenously.

Solutions of amino acids or casein digests are readily available sources to the body of nitrogen and carbohydrate.
ELECTROPHORETIC STUDY OF ANTIVIRAL SERA
Authors: Koprowski Hilary , Richmond Gilbert , Moore Dan H.
Published: June 2004

1. Sera of animals immunized against Japanese B encephalitis, Venezuelan equine encephalomyelitis, and Western equine encephalomyelitis viruses were fractionated by electrophoresis.

2. Electrophoretic patterns of rabbit sera before and after immunization against Japanese B virus showed no consistent change traceable to antibody formation.

3. To determine the antibody content, the electrophoretic fractions of the respective sera were mixed in varying dilutions with infected mouse brain suspensions, and the neutralizing titers of the fractions were compared.

4. In all instances serum fractions containing γ-globulin were protective, whereas in no case did serum albumin show any virus-neutralizing activity. The Japanese B encephalitis antibody appeared to be associated entirely with the γ-globulin. The Venezuelan and Western equine encephalomyelitis antibodies were associated with the ß- and γ-globulins and probably possessed an average electrophoretic mobility between that of ß- and γ-globulins.

5. Normal rabbit serum similarly separated electrophoretically showed no neutralizing properties.

6. Chickens, whose electrophoretic serum pattern is markedly different from that of rabbits, were also immunized against the Japanese B encephalitis virus. Their antisera were electrophoretically fractionated and similarly subjected to neutralization tests. The specific neutralizing capacity of chicken serum was considerably lower than that of rabbit serum and no neutralizing activity was found in the fractions containing the faster moving components. The antibody appeared to be associated with component 4 which had a mobility of approximately 2.3 x 10–5 cm.2/volt/sec.
A STUDY OF THE INHIBITION OF STREPTOCOCCAL PROTEINASE BY SERA OF NORMAL AND IMMUNE ANIMALS AND OF PATIENTS INFECTED WITH GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Todd Edgar W.
Published: June 2004

Antiproteinase sera were prepared by immunizing horses with filtrates from a selected strain of group A streptococcus. This strain, which produced high titred proteinase but no erythrogenic toxin, was selected from forty-two strains of group A streptococci which produced varying amounts of proteinase. A few strains belonging to groups B, C, and G were also tested; they were all proteinase-negative. Methods are described for titrating streptococcal proteinase in crude culture filtrates and for measuring the antiproteinase activity of serum.

The antiproteinase titres of sera from immunized horses ranged from 125 units to 1,000 units per cc. in contrast to the low titres of normal horse sera, only 5 per cent of which had titres as high as 10 to 30 units per cc.

The available evidence suggests that the antiproteinase activity of immune sera is dependent on the action of specific antibody for streptococcal proteinase. Patients infected with group A streptococci do not develop high anti-proteinase titres. There appears to be no correlation between the occurrence of rheumatic fever and the antiproteinase titre of the patient's serum.
MODE OF ACTION OF STREPTOMYCIN ON TYPE b HEMOPHILUS INFLUENZAE
Authors: Alexander Hattie E. , Leidy Grace
Published: June 2004

In all of ten strains of H. influenzae examined prior to exposure to streptomycin a very small fraction of the bacteria formed colonies in the presence of 1,000 units of streptomycin per cc. These variant organisms possess the characteristics of bacterial mutants.

1. Different independent cultures of the same strain on different occasions, and even cultures seeded in a single test with the same inoculum, show marked variation in prevalence of resistant variants in populations of comparable size. This variation is just as great in genetically homogeneous culture sources as in heterogeneous sources. Evidence is presented for the continuous random occurrence of these resistant organisms.

2. The rate of occurrence of the resistant members is not significantly different for the ten strains studied; it varies from 2.6 x 10–11 to 7.0 x 10–11 per bacterium per bacterial generation. The results of five different tests on the same strain show comparable variation, 2.9 x 10–11 to 5.3 x 10–11. This low rate contributes evidence consistent with the mutation hypothesis.

3. Variants exhibiting resistance to 1,000 units of streptomycin per cc. transmit this trait unchanged in degree through many generations. The results obtained after twelve or more subcultures in streptomycin-free media suggest that in a portion of the colonies resistant to streptomycin an additional trait, differing from those exhibited by the parent culture, is associated; the nutritional requirements of these cultures are different.
MULTIPLICATION AND SPREAD OF THE VIRUS OF ST. LOUIS ENCEPHALITIS IN MICE WITH SPECIAL EMPHASIS ON ITS FATE IN THE ALIMENTARY TRACT
Authors: Peck John L. , Sabin Albert B.
Published: June 2004

1. Beginning at 24 hours after intravenous injection of about 10 million intracerebral LD50 of virus there was evidence of simultaneous, progressive multiplication in the brain and intestinal tract.

2. When the virus was introduced directly into the brain or the nasal cavities and mouth, none was found in the intestinal tract until there was general centrifugal spread from the central nervous system during the last stages of the infection at 96 or 120 hours after inoculation when the virus in the entire brain had reached a concentration of about 3 billion LD50.

3. Centrifugal spread began when the virus in the brain reached a concentration of about 400 million LD50 and virus appeared in the pharynx, tongue, and adrenals before it was demonstrable in the intestinal tract, blood, or viscera such as the spleen, liver, and kidneys.

4. Despite the high concentrations of virus which developed in the intestinal tract following intravenous inoculation, it was not demonstrable in the stools, differing in this respect from Theiler's virus in mice and poliomyelitis virus in human beings and monkeys.

5. No antiviral agent was found in the stools, but the urine of normal mice having a pH of 5.6, inactivated large amounts of St. Louis encephalitis virus.

6. There was no evidence of multiplication in the nasal mucosa of mice which succumbed with encephalitis following nasal instillation of the virus, the course of events being comparable in this respect to the behavior of the M.V. poliomyelitis virus in rhesus monkeys.

7. At the terminal stage of infection the virus content per milligram of tissue was as great in the leg muscles as in the sciatic nerves. Since this was also true for the urinary bladder, heart, lungs, and tongue among other tissues, and since the amount in the blood was too negligible to account for it, it would appear that the virus either accumulated in these tissues by diffusion from the nerve fibers, along which it was spreading from the central nervous system, or that it multiplied in some constituent other than the nerve fibers.
THE RELATION TO THE COURSE OF AVIAN MALARIA OF BIOTIN AND A FAT-SOLUBLE MATERIAL HAVING THE BIOLOGICAL ACTIVITIES OF BIOTIN
Authors: Trager William
Published: June 2004

Biotin deficiency produced by a synthetic biotin-deficient diet was as effective in decreasing the resistance of chickens to infection with Plasmodium lophurae as biotin deficiency produced by a diet high in egg white.

In moderately biotin-deficient ducks Plasmodium cathemerium at first multiplied more slowly than in adequately fed controls. The parasitemia in the deficient animals later overtook that in the controls and attained higher peak parasite numbers. The multiplication of P. cathemerium was notably inhibited in ducks inoculated when they were approaching death from biotin deficiency.

The total and differential leucocyte count of biotin-deficient chickens did not differ significantly from that of adequately fed controls.

During infection of chickens with P. lophurae and ducks with either P. lophurae or P. cathemerium significant changes occur in the concentration in the plasma of free biotin and of a material which on hydrolysis yields a fat-soluble substance (FSF) having the biological activities of biotin but differing chemically from it. In ducks which survived infections with P. cathemerium or P. lophurae the biotin concentration rose very early in the course of the infection, before there was any anemia. It fell slightly, rose to a peak at about the time of the peak parasite number, and then returned to normal. The concentration of bound FSF, which was determined in terms of its biotin activity, increased at first, then decreased, then rose and continued at a high level throughout the period of decline in parasitemia. In most of the animals which died of either infection the free biotin, instead of returning to normal, rose to very high values Just before death, while the bound FSF, instead of remaining at a high value, fell to very low values, reaching zero in several animals. Greater resistance seemed to be associated with a greater excess of bound FSF over free biotin. In animals about to die the free biotin exceeded the bound FSF.

The biotin content of the liver of ducks and chickens fed an adequate diet and killed just after having undergone an infection with either P. lophurae or P. cathemerium was much less than that of control uninfected animals.

When P. lophurae was cultured in vitro in suspensions of duck erythrocytes a very wide range in biotin concentration in the culture fluid did not affect its rate of multiplication. Plasma protein fractions relatively rich in FSF at a concentration of 0.75 per cent inhibited multiplication, while comparable concentrations of plasma fractions poor in FSF did not.

The results obtained fit the assumption that the substance in plasma which yields FSF is directly concerned in resistance to avian malaria.
THE MECHANISM OF AERIAL DISINFECTION BY GLYCOLS AND OTHER CHEMICAL AGENTS
Authors: Puck Theodore T.
Published: June 2004

Theoretical analysis of the mechanism of action of chemical aerial disinfectants reveals that the rapid killing action which is obtained cannot be accounted for by a collision process between germicidal aerosol particles and the air-borne bacteria. However, a mechanism involving condensation of germicide molecules in the vapor state on to the bacteria-containing droplets results in a theoretical velocity of the correct order of magnitude.

Experimental tests of this theory show that pure germicide vapors free of aerosol droplets are almost instantly lethal to air-borne bacteria. Conversely, pure germicidal aerosols in the absence of vapor, had no effect on air-borne bacteria within 20 minutes or more. Therefore, it may be concluded on both theoretical and experimental grounds that rapid air sterilization requires the existence of the germicide in the vapor state.
THE TRANSMISSION OF THE VIRUS OF LYMPHOCYTIC CHORIOMENINGITIS BY TRICHINELLA SPIRALIS
Authors: Syverton J. T. , McCoy O. R. , Koomen J.
Published: June 2004

In experiments in which guinea pigs were infected concurrently with the virus of lymphocytic choriomeningitis and the parasitic nematode, Trichinella spiralis, proof was obtained that trichinella larvae, after maturation in the muscles, had acquired the virus and were capable of transmitting it to new susceptible hosts. Transmission resulted both when living larvae were fed to normal guinea pigs and when triturated dead larvae were injected subcutaneously.

Control experiments and other tests made plain that transmission of the virus was not due to mere adherence of it to the outer surface of the larvae but that these actually harbored it.

The significance of these experiments in relation to natural transmission of the virus of lymphocytic choriomeningitis remains to be determined.
MORPHOLOGICAL AND OTHER CHARACTERISTICS OF THE AGENT OF FELINE PNEUMONITIS GROWN IN THE ALLANTOIC CAVITY OF THE CHICK EMBRYO
Authors: Hamre Dorothy , Rake Helen , Rake Geoffrey
Published: June 2004

The agent of feline pneumonitis has been grown in the allantoic cavity for 50 serial passages. During this time the amount of agent in allantoic fluid increased about 100-fold. The titer of the agent in the allantoic fluid of the individual embryo reached a peak on the 5th day and then declined. Large inocula were required in order to obtain maximal titers. The toxic factor was present in suspensions of chorioallantoic membranes in allantoic fluid from heavily infected eggs, and could be neutralized by the specific antitoxin produced in rabbits by injection of toxin in yolk sac suspensions.

Electron micrographs of the agent of feline pneumonitis grown in the allantoic cavity show that the elementary body is composed of a dense centrally located substance surrounded by a thinner material, part or all of which is the limiting membrane. Separation of these two portions of the body may be due partially or entirely to distortion during drying. The wrinkled surface of the elementary bodies is evidence that such distortion does occur. The average diameter of gold-shadowed bodies is 525 mµ.
STUDIES ON SPREADING FACTORS
Authors: Hechter Oscar , Scully Ella L.
Published: June 2004

The reaction between normal serum and hyaluronidase has been studied in vitro and under in vivo conditions in skin. Using in vitro conditions of incubation, serum exhibits antihyaluronidase activity as measured by assay of hyaluronidase spreading activity in skin. This confirms the work of others, who have previously described the serum inhibitory factor using other tests of hyaluronidase activity. When, however, hyaluronidase and setum are allowed to incubate in skin under in vivo conditions, no inhibitory influence of serum upon hyaluronidase spreading activity is evident. This latter finding has been taken to indicate that the environmental conditions in skin are unfavorable for the inhibitory reaction of serum upon hyaluronidase. The disparity between the in vivo and in vitro effectiveness of serum, and the significance of the serum factor as a defense mechanism against invasive processes, have been briefly discussed.
CYTOCHONDRIA OF NORMAL CELLS, OF TUMOR CELLS, AND OF CELLS WITH VARIOUS INJURIES
Authors: Opie Eugene L.
Published: June 2004

Bodies that may be designated cytochondria occupy the greater part of the cytoplasm of the normal and tumor cells that have been studied. They are characterized (a) by their behavior as discrete particles with surface properties that cause osmotic changes in the presence of water; (b) by reactions to stains which show that they have a rim surrounding a clearer (lipoid) center; (c) by their varying, relation to the basophile substance (ribonucleic acid) of the cytoplasm.

Mitochondria which have characteristic reactions to stains promptly lose their distinctive reactions in the presence of solvents or as the result of pathological changes, becoming apparently indistinguishable from other cytochondria.

Changes that occur in cytochondria give insight into the pathogenesis of a variety of pathological lesions. Hydropic swelling of cytochondria caused by chloroform, butter yellow, and other agents, representing one variety of parenchymatous degeneration or cloudy swelling, results in changes similar to those following the immersion of fresh tissues in water.

When parenchymatous cells undergo fatty degeneration as the result of injury fat accumulates within cytochondria.
THE NATURE OF NON-SPECIFIC INHIBITION OF VIRUS HEMAGGLUTINATION
Authors: Friedewald William F. , Miller Edward S. , Whatley L. Ross
Published: June 2004

A study of the component in serum and tissue extracts responsible for non-specific inhibition of hemagglutination with mumps virus and the PR8 and Lee strains of influenza virus has yielded the following results:

1. The inhibitory factor was found in high titer in human serum and in saline extracts of various organs procured at autopsy (lung, liver,kidney, spleen). The inhibition titers of extracts of these organs were usually higher than the serum titers, whereas the titers of muscle extracts were invariably lower.

2. Similar results were obtained with serum and tissue extracts from normal rabbits and guinea pigs.

3. The serum inhibition titers were not affected by heating to 75°C. for 30 minutes, whereas the titers of the tissue extracts were usually reduced by heating at 65°C. or 75°C. for 30 minutes.

4. Saline extracts of human and chicken red blood cells also contained an inhibitory substance in high titer, and these cells showed marked agglutination with influenza and mumps viruses. Rabbit red cells, on the other band, underwent little or no agglutination with these viruses and extracts of these cells failed to cause inhibition. Sheep red cells varied in their capacity to agglutinate and also in their yield of the inhibitory substance.

5. When the virus receptor substance was removed from chicken red cells by adsorption and elution with influenza virus, extracts of the cells no longer yielded the inhibitory factor.

6. The inhibitory substance did not neutralize influenza virus in mice and it failed to fix complement when mixed with influenza or mumps viruses.

7. Evidence was obtained that some virus was released from the inhibitory substance after incubation for 6 hours at 22°C. or 37°C.

The implications of these findings are discussed.
ON THE ORIGIN OF HEPARIN
Authors: Oliver Jean , Bloom Frank , Mangieri Carmen
Published: June 2004

1. The spontaneous mast cell tumor of the dog contains heparin.

2. The cytoplasmic particulate content of the tumor mast cells varies with their anaplasia. This conclusion is based on the following findings: (a) in the immature cell of the more malignant tumor the particulate matter appeared in the living cells by phase microscopy to be composed of greyish illdefined particles or as a fine, weakly metachromatic granulation in the fixed and stained preparation; (b) in the mature cells of a relatively benign mast cell tumor, both in the living cell and in stained preparations, the particulate matter occurred in the form of discrete, dense, and strongly metachromatic granules, resembling those of the normal mast cell.

3. The heparin content was large (fifty times that of dog liver) in the growth with mature cells and only moderate (1.7 times) in that with immature cells.

4. Since there may be a great amount of greyish particulate matter (or fine stained granules) in a tumor of relatively low heparin content, it is suggested that this material represents an early or precursor phase in the development of heparin.

5. This possibility and the fact that the blood stream may be invaded by mature tumor mast cells of large heparin content without evident disturbance in the coagulability of the blood suggest the value of a comprehensive biochemical study of the heparin of mast cell tumors.
THE MORPHOLOGY AND BEHAVIOR OF NEOPLASTIC MAST CELLS CULTIVATED IN VITRO
Authors: Paff George H. , Bloom Frank , Reilly Christopher
Published: June 2004

Fragments from two mast cell tumors of the dog have been cultured in vitro. Studies on the living and on fixed and stained preparations revealed the following:

Only mast cells grew out from the original tumor fragments though these contained other types of cells. They grew in some of the roller tube cultures in a sheet resembling an epithelium but in hanging drop cultures they lay separate and were irregularly spindle or star-shaped with long protoplasmic processes.

The cytoplasmic granules of the proliferating mast cells varied in size, number, and tinctorial properties. In most of the cells they stained metachromatically, in occasional cells some of the granules only could be stained, and in a few none could be stained.
AMINO ACID COMPOSITION OF HIGHLY PURIFIED VIRAL PARTICLES OF INFLUENZA A AND B
Authors: Knight C. A.
Published: June 2004

Microbiological assays for amino acids were made on hydrolysates of four to five highly purified preparations each of influenza A virus (PR8 strain) and influenza B virus (Lee strain). The results of the assays indicated that these strains of influenza virus contain approximately the same amounts of alanine, aspartic acid, glycine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, and valine. However, significant differences were found in the values for arginine, glutamic acid, lysine, tryptophane, and tyrosine. It is believed that these differences may provide, at least in part, a chemical explanation for some of the differing properties of the PR8 and Lee strains of influenza viruses.
THE SUPERINFECTION OF THE RABBIT PAPILLOMA (SHOPE) BY EXTRANEOUS VIRUSES
Authors: Syverton Jerome T. , Berry George Packer
Published: June 2004

1. The potentialities that viruses have for the superinfection of virus tumors have not been recognized nor has the fact that a single cell can harbor more than one virus.

2. Rabbit papillomas, induced by the papilloma virus (Shope), were superinfected by B virus, myxoma virus, vaccinia virus, and probably, virus III. Similar attempts at superinfection by herpes virus were without success. The criteria for parasitization included the histopathological finding of specific inclusion bodies, the recovery of each virus by suitable animal passage, and the immunological identification of each virus.

3. Papillomas and probably the individual cells thereof were readily infected simultaneously by two viruses when the combination of B virus and myxoma virus was used.

4. Cells of the Shope papilloma have a selective affinity for certain extraneous viruses introduced at a site distant from the tumor growths. It was found that exceptionally few cells in the basal layers of the epidermis escaped when myxoma virus was used as the superinfecting agent.

5. The cells of an epidermoid carcinoma which terminated the rabbit papilloma-to-carcinoma sequence were readily infected by B virus with resultant multiple intranuclear inclusion bodies in single cells.

6. Attempts to establish a prolonged superinfection of cells of the Shope papilloma by virus III were unsuccessful. This rabbit tumor differs therein from the Brown-Pearce tumor, an epithelioma of rabbits, in its susceptibility to infection with virus III.
MULTIPLE VIRUS INFECTION OF SINGLE HOST CELLS
Authors: Syverton Jerome T. , Berry George Packer
Published: June 2004

Evidence is presented to show that two or more viruses can simultaneously manifest their characteristic activities within individual epithelial cells of the normal rabbit's cornea. This evidence, together with that previously presented (1, 5, 6), makes plain that multiple virus infection of a single host cell can take place in corneal cells, in the cells of chick embryos, and in those of rabbit tumors, both benign (Shope's papilloma) and malignant.

Certain implications of the findings are discussed.