bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON EASTERN EQUINE ENCEPHALOMYELITIS
Authors: King Lester S.
Published: June 2004

The behavior of a fixed strain of Eastern equine encephalomyelitis virus was studied in guinea pigs after intraocular inoculation. Such inoculation concerns the central and not the peripheral nervous system.

The susceptibility to intraocular injection lies midway between the highly virulent intracerebral and the quite avirulent peripheral routes. The virus must act for 10 to 13 hours in order to induce a fatal infection. Removal of the inoculated eyeball before this interval almost always prevents fatality although it may allow immunity to develop. The virus, at suitable intervals after injection into the eye, may be recovered from successive and appropriate optic centers before it is demonstrable in non-optic portions. Approximately 24 hours are required for the virus to reach a significant concentration in the contralateral geniculate body, 36 hours in the contralateral visual cortex. Significant amounts of virus may be present in the optic chiasm and tract prior to involvement of the higher centers.

Virus placed in contact with the retina produces an insignificant, essentially non-specific reaction comparable to that produced at the site of direct intracerebral inoculation. In the retina there is no ganglion cell necrosis unless there is a complicating intraocular infection. In the cerebral visual centers the first reaction is inflammatory and interstitial, and may appear in the lateral geniculate body as early as 24 hours after injection. Neuronal necrosis is not the primary action of the virus on the nervous system in these experiments. The distribution of lesions in the brain is in excellent agreement with the method of direct testing for virus content, and is far more accurate than the latter.

The virus in its primary distribution through the nervous system follows the nerve pathways of the optic system. This occurs within the central nervous system, where presumably there is first an involvement of the nerve cell body and then a spread along the cell process or axone.
BLOOD PLASMA PROTEIN PRODUCTION AS INFLUENCED BY AMINO ACIDS
Authors: Madden S. C. , Noehren W. A. , Waraich G. S. , Whipple G. H.
Published: June 2004

When blood plasma proteins are depleted by bleeding with return of the washed red blood cells (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a uniform plasma protein production on a basal low protein diet. These dogs are clinically normal. By the introduction of variables into their standardized existence insight into the formation of plasma proteins can be obtained.

The liver basal diet maintains health in such hypoproteinemic dogs during periods as long as a year. 17 to 27 per cent of its protein content (entirely liver protein) is presumably converted into plasma protein.

Gelatin alone added to the liver basal diet causes very little if any extra plasma protein production.

The addition to gelatin of cystine, or tyrosine, or tryptophane, or of both tyrosine and tryptophane has little or no effect on its potency for plasma protein production.

When gelatin is supplemented by cystine and either tryptophane or tyrosine, 25 to 40 per cent of the protein content of the combination is converted into plasma protein—an efficiency equaling that of any protein hitherto tested.

Preliminary experiments indicate that methionine cannot substitute for cystine nor can phenylalanine substitute for tyrosine in the efficient combination of gelatin plus cystine plus tyrosine.

Laked red blood cells given by vein afford little or no material for plasma protein formation.

When the reserve stores of plasma protein building material are exhausted the dog can form little if any plasma protein during protein-free diet periods.
ELECTROPHORESIS OF ANTERIOR PITUITARY PROTEINS
Authors: Shipley Reginald A. , Stern Kurt G. , White Abraham
Published: June 2004

The moving boundary method of electrophoresis has been applied to a study of pituitary extracts and purified protein fractions derived from these extracts. The technique employed was that developed by Tiselius and involved the optical observation of the protein boundaries by Toepler's schlieren method. The present experiments were designed primarily to determine the number of proteins present, the degree of homogeneity of the various fractions, and the electrophoretic mobility of the individual components under standard conditions.

The preparations studied included crude gland extracts obtained with dilute alkali, glycerol, and saline; purified pituitary fractions prepared by isoelectric and precipitation procedures; and freshly prepared and aged solutions of crystalline prolactin.

The bulk of the crude gland extracts is composed of physiologically inert proteins, the gradual removal of which in the course of the chemical purification procedures could be controlled by electrophoretic analysis. Freshly prepared solutions of crystalline prolactin exhibit a high degree of electrochemical homogeneity. Upon storage, however, a second component, presumably denatured prolactin, is formed.
OSMOTIC PRESSURE STUDY OF PROTEIN FRACTIONS IN NORMAL AND IN NEPHROTIC SUBJECTS
Authors: Bourdillon Jaques
Published: June 2004

In serum of patients with nephrosis both albumin and globulin showed by osmotic pressure nearly double the molecular weights of normal albumin and globulin.

In the urines of such patients, on the other hand, both proteins showed molecular weights lower even than in normal serum.

The colloidal osmotic pressures were measured by the author's method at such dilutions that the van't Hoff law relating pressures to molecular concentrations could be directly applied. For the albumin and globulin of normal serum the molecular weights found were 72,000 and 164,000 respectively, in agreement with the weights obtained by other methods.
SEROLOGICAL STUDIES OF SWINE INFLUENZA VIRUSES
Authors: Shope Richard E.
Published: June 2004

1. Cross-neutralization tests with sera from swine recovered from infection with swine influenza indicated the serological identity of 7 strains of swine influenza virus obtained from different sources.

2. Cross-neutralization tests with sera from rabbits, immunized to swine influenza virus, exposed serological differences among the same 7 swine influenza virus strains. Two strains appeared to be serologically similar and were characterized by the ability to produce effective homologous virus-neutralizing sera which were, however, poor or ineffective against the heterologous virus strains. Two other strains were also serologically similar but produced antibodies effective not only against themselves, but against all heterologous strains as well. The remaining 3 strains were intermediate in their ability to produce heterologous virus-neutralizing antibodies.

3. The human influenza viruses included, especially strains WS and Oakham, were most effectively differentiated serologically from the swine influenza viruses by rabbit antisera.

4. The suggestion is advanced that swine antisera express the antigenic composition of the swine influenza viruses, while rabbit antisera reflect either their antigenic arrangement or the arrangement of the components responsible for their mouse pathogenicity. On this interpretation the 7 strains of swine influenza virus studied would be considered to have similar antigenic compositions but differing antigenic structures.

5. The serological differences among strains of the swine influenza virus, detectible by rabbit antisera, are probably of no practical significance so far as the natural disease, swine influenza, is concerned.
FAMILIAL MAMMARY TUMORS IN THE RABBIT
Authors: Greene Harry S. N.
Published: June 2004

The clinical and pathological course of 25 mammary tumors in rabbits has been described. The antecedent breast history and morphology of the growths allowed a natural classification into two distinct types, one of which was distinguished by a preexisting cystic mastitis and a papillary structure, while the other originated in clinically normal mammary tissue and was characterized by an adenomatous structure. The two types of neoplasia occurred almost exclusively in two family groups and heredity played a fundamental rôle both in the occurrence of the tumors and in the determination of tumor type. Endocrine changes, comparable with those found in animals after long continued administration of estrogenic substances, occurred in tumor-bearing rabbits and it was inferred that the spontaneous growths represented a natural counterpart of the experimental induction of neoplasia with estrone.
NEUTRALIZATION OF EPIDEMIC INFLUENZA VIRUS
Authors: Horsfall Frank L.
Published: June 2004

A linear relationship exists between the logarithm of the quantity of epidemic influenza virus neutralized and the logarithm of the quantity of antiserum which is capable of achieving this result. This relationship is the same for the serum of a ferret convalescent from experimental influenza as for the serum of a rabbit immunized with the virus. By means of the linear relationship between virus and antiserum it is possible to determine a fixed, rather than a relative, value for the neutralizing capacity of a serum.
THE IMMUNOLOGICAL RELATIONSHIP OF THE CAPSULAR POLYSACCHARIDE OF TYPE XIV PNEUMOCOCCUS TO THE BLOOD GROUP A SPECIFIC SUBSTANCE
Authors: Beeson Paul B. , Goebel Walther F.
Published: June 2004

1. The agglutination of human erythrocytes and the precipitation of the blood group A substance by Type XIV antipneumococcus horse serum are properties of the specific anticarbohydrate immune bodies in the serum.

2. Absorption of Type XIV antipneumococcus horse serum with the homologous bacterial polysaccharide removes the agglutinins for human erythrocytes as well as the precipitins for the group A substance.

3. Absorption of Type XIV antipneumococcus horse serum with the group A substance markedly diminishes the ability of the serum to agglutinate erythrocytes of all groups.

4. Absorption of Type XIV antipneumococcus horse serum with human erythrocytes causes a marked diminution in the precipitation with group A substance.

5. The chemical and immunological relationship between the specific substances of blood group A and the Type XIV Pneumococcus is discussed.
THE MANNER OF GROWTH OF FROG CARCINOMA, STUDIED BY DIRECT MICROSCOPIC EXAMINATION OF LIVING INTRAOCULAR TRANSPLANTS
Authors: Lucké Balduin , Schlumberger H.
Published: June 2004

The adenocarcinoma which commonly occurs in the kidney of leopard frogs has been transplanted into the anterior chamber of the eye where its growth characteristics have been studied by direct observation with the slit-lamp microscope. Such observations have been amplified by photographs taken at intervals to furnish permanent and objective records of the mode of development and progress of the growths, from earliest to advanced stages.

The fifteen tumors which fumished the transplants were typical large invasive adenocarcinomas having the usual irregular and apparently anarchic arrangement of their component tubules and acini. However, the transplanted tumors developed according to definite and well defined structural patterns, their type depending on the immediate physical environment. Three such morphogenetic patterns were observed.

Unimpeded outgrowths into the aqueous tumor characteristically assumed a tubulo-papillary arrangement; the earliest formation consisted of solid, purely epithelial cylinders, many of which at later stages acquired a lumen and thus became tubular; generally only the coarser projections developed vascular stalks. Further growth was made by repeated branching, and lateral outpouching of the tubules. Where the tumor grew in contact with firm, even surfaces, such as lens or cornea, differentiation was lost and broad membranes formed which gradually spread over the surfaces; secondarily, new cylindrical or tubular processes arose from such indifferent cellular carpets. Where the tumor made contact with loose tissue such as iris, it invaded this organ, and, supported by the stroma, assumed an acinar pattern quite like that of the original adenocarcinoma of the kidney. All three types of growth were sometimes found coexisting in different portions of the anterior chamber.

The rate of growth of transplanted tumors was followed by photographic records taken periodically. A fairly constant mode of progress was noted: after a variable period of lag and a period of gradual outgrowth, there followed rather abruptly a short period of rapid growth, after which growth increments gradually became smaller. Variations in growth rate due to season and to temperature were evident, but further experiments are required to evaluate the part played by these factors.

Attempts to transplant normal kidney in the anterior chamber were unsuccessful.

The manner of growth in the vitreus was found to be similar to that in the anterior chamber.

The factors that determine the manner of tumor growth are as yet imperfectly understood. Evidence is however accumulating to the effect that neoplastic growth is not as anarchic as is suggested by histologic sections of some tumors (26). The present experiments support the view that cancers are much more responsive to the laws governing growth and organization than is generally supposed.
SEROLOGICAL STUDIES ON SUGAR
Authors: Neill James M. , Hehre Edward J. , Sugg John Y. , Jaffe Evelyn
Published: June 2004

Solutions of all of the C. P. sucrose reagents of American manufacture that were tested gave reactions with Type II antipneumococcus serum. The capacity of that antiserum to react with sucrose solutions was removed by absorption with the homologous pneumococci or with Leuconostoc mesenteroides.

The serological reactivity was due not to sucrose itself but to accompanying substances that could be removed by precipitation with a proper concentration of alcohol or by treatment with activated carbon. Although Type II antipneumococcus serum was used to detect its presence the reactive material found in the sucrose can be considered to be only related and not identical with antigens of Type II pneumococci.
INHIBITION OF TRANSPLANTABLE MOUSE TUMOR GROWTH BY TISSUE EXTRACTS AND THEIR PROTEIN FRACTIONS
Authors: MacFadyen D. A. , Sturm Ernest , Murphy James B.
Published: June 2004

1. Mammary tissue of pregnant rabbits is found to contain an agent which inhibits the growth of Bashford Adenocarcinoma 63 in mice but this material is without effect on the Crocker Sarcoma 180.

2. Of the tissues so far studied the mammary gland of rabbits has yielded the most active product.

3. From the results it is probable that pregnancy enhances the production of the agent but this cannot be considered as established beyond doubt.

4. The factor is found, with diminished activity, only in the protein fraction obtained from the aqueous extract by full saturation with ammonium sulfate.
BLOOD PLASMA PROTEINS AS INFLUENCED BY INTRAVENOUS INJECTION OF GUM ACACIA
Authors: Yuile Charles L. , Knutti Ralph E.
Published: June 2004

By repeated weekly intravenous injections of gum acacia solution in dogs over periods of 4 to 5 months, it has been possible to maintain plasma protein concentration and total circulating protein at very low levels.

If sufficient numbers of such injections are given and then discontinued, plasma protein concentration will remain below the normal limits for several more months. Acacia remains in the blood during this time.

Reduction of fibrinogen concentration in such animals is out of proportion to and more marked than the changes in plasma protein concentration. This would indicate interference with liver function.

Plasma volume when determined at 7 day intervals during injection periods at first diminishes, then rises 20 to 25 per cent above basal levels. The total blood volume does not show such marked changes because of a decrease in red cell volume.

Globulins are reduced to a greater extent than albumin after a single injection of gum acacia, although both albumin and the globulins diminish. This cannot be accounted for by a decrease in fibrinogen alone. After 14 to 16 weekly injections, both albumin and globulins are more profoundly reduced.

During injection periods in such animals, it has not been possible to control quantitatively the dietary intake, a complication which has made it difficult to ascertain the effect of various protein diets upon the protein-acacia balance. The changes described, however, have taken place regardless of various types of animal protein diets.

Following periods of injection, in spite of very low plasma protein concentration and high acacia concentration in the blood, most of the dogs eat well and therefore they can be used during this period for controlled dietary experiments which may be of value in investigating the mechanism of the production and function of the plasma proteins.
PERMEABILITY OF THE HUMAN PLACENTA TO ANTIBODIES
Authors: Wiener Alexander S. , Silverman I. Jerome
Published: June 2004

The ratio of the titers of various antibodies, namely, hemagglutinins and syphilitic reagin, in the maternal blood to that of the corresponding antibody in the cord blood was found to be relatively constant, falling somewhere between 8 and 16. This figure may be considered the "index of permeability" of human placenta to antibodies, or the coefficient of distribution of antibodies between maternal and cord blood. The possible application of these findings to the study of the placental permeability to sensitizing antibodies (or reagins) is discussed.
CARDIAC LESIONS RESEMBLING ASCHOFF BODIES IN RABBITS
Authors: Loewe Leo , Lenke Sidney Edward
Published: June 2004

Cardiac lesions, resembling those of human rheumatic fever, have been observed in rabbits during the course of a seemingly spontaneous epizootic.
THE HYDROLYSIS OF HYALURONIC ACID BY BACTERIAL ENZYMES
Authors: Meyer Karl , Hobby Gladys L. , Chaffee Eleanor , Dawson Martin H.
Published: June 2004

An improved method is described for preparing the enzyme which hydrolyzes the polysaccharide acid contained in vitreous humor, umbilical cord, synovial fluid, and the mucoid phase of group A hemolytic streptococci.

Preparations have been obtained from pneumococci, group A hemolytic streptococci, Clostridium welchii, and from splenic tissue, which display the same specific activity.

Evidence is presented to show that the hydrolytic enzyme is not the same as that responsible for the lysis of pneumococci.

In pneumococci and hemolytic streptococci the major portion of the enzyme is bound to the cell structure. The enzyme from Clostridium welchii is associated with other carbohydrate-splitting enzymes in the culture medium and not with the bacterial cells.

It is suggested that the disappearance of the mucoid capsule of group A hemolytic streptococci is due to enzymatic hydrolysis of the acid polysaccharide.

The relation between enzyme activity and the virulence and invasiveness of group A hemolytic streptococci is briefly considered.
SYMPTOMATIC HERPES, A SEQUELA OF ARTIFICIALLY INDUCED FEVER
Authors: Warren Stafford L. , Carpenter Charles M. , Boak Ruth A.
Published: June 2004

1. Symptomatic herpes occurred in 190 (46.2 per cent) of 411 patients treated with fever induced by physical methods.

2. Herpes recurred in only 7, or 5.3 per cent, of 131 patients given subsequent fever treatments, suggesting that some immunity develops with the first attack.

3. An acute encephalitis-like syndrome of short duration and without sequelae developed in a group of patients with severe herpes following fever therapy.

4. A filter-passing virus, recovered from herpetic vesicles on patients treated with artificially induced fever, produced a fatal encephalitis in rabbits when inoculated intracerebrally and by corneal scarification. Intranuclear inclusion bodies were observed in corneal epithelial cells and in motor ganglion cells of the brain similar to those observed in rabbits injected with known strains of herpes virus.

5. Four strains of virus that had been recovered from herpetic vesicles appearing on patients subsequent to artificially induced fever were shown by cross-protection tests on rabbits to be immunologically related to the Frank strain of herpes virus.
ANTI-EGG ALBUMIN ANTIBODY IN THE HORSE
Authors: Pappenheimer Alwin M.
Published: June 2004

The reaction between three times recrystallized egg albumin and its antibody in the horse has been studied. The reaction exhibits a behavior typical of the Ramon diphtheria flocculation reaction.
A DISTINCTIVE SUBSTANCE ASSOCIATED WITH THE BROWN-PEARCE RABBIT CARCINOMA
Authors: Kidd John G.
Published: June 2004

A substance is regularly present in saline extracts of the Brown-Pearce rabbit carcinoma growth which is capable of fixing complement specifically in mixture with the sera of certain rabbits bearing the tumor or in which this has recently retrogressed, as the foregoing experiments have shown. The substance was not demonstrable in extracts of the normal tissues, virus papillomas, or uterine cancers of rabbits, nor in extracts of rabbit tissues infected with certain viruses (vaccine virus, Virus III, fibroma virus). The sera of normal rabbits, of those immune to a variety of infectious diseases, including syphilis, vaccinia, fibromatosis, and Virus III, and of others with uterine cancers or virus-induced papillomas, failed to fix complement specifically in mixture with extracts containing the antigen of the Brown-Pearce tumor.

The significance of the findings will be discussed in the succeeding paper, after consideration has been given to some of the properties of the serologically active material derived from the Brown-Pearce tumor.
ON CROSS REACTIONS OF EGG ALBUMIN SERA
Authors: Landsteiner K. , van der Scheer J.
Published: June 2004

Experiments are presented on the cross reactions of hen egg albumin immune sera with egg albumins of other species by means of exhaustion with heterologous proteins and by inhibition tests. From the results it can be concluded that the sera contain multiple, qualitatively distinct antibodies. For this, two not mutually exclusive explanations come into consideration: the presence in proteins of a number of different, perhaps similar, complex determinants, and the fact, established by previous results, that one antigenic grouping can call forth the formation of diverse antibodies.

It is inferred that cross reactions between proteins of kindred species are ascribable, in general, to similarity in determinant structures, and not to the distribution of identical determinant groups among the related proteins.
ANTIBODY FORMATION IN A TUBERCULOUS LESION AT THE SITE OF INOCULATION
Authors: Westwater John O.
Published: June 2004

Complement fixing antibody in animals injected with heat killed tubercle bacilli in oil appears earlier in the lesion at the site of injection than in the blood serum.

Complement fixing antibody in an extract prepared by suspending one part by weight of tissue from the local site in five parts of saline is in general in higher concentration than in the blood, for a period of approximately 3 weeks following injection. After this time the serum may show the higher titre.

The titre of antibody at the site of injection tends to increase with the quantity of heat killed bacilli injected into the skin, up to a definable maximum.

No evidence was found to support the opinion that local accumulation of antibody was caused by fixation of antibody contained in the serum and produced elsewhere in the body, for extracts of lesions produced by the injection of paraffin oil, old tuberculin, and cod liver oil showed no demonstrable antibody, or at most a very low titre, even when the serum titre was high. After reinjection of heat killed tubercle bacilli in oil into rabbits with antibody in the serum, antibody did not appear in the local lesion any earlier than in normal animals similarly injected.

These observations give evidence that antibody is formed in the skin at the site of injection of tubercle bacilli.
INFECTIVITY AND IMMUNITY RESULTING FROM THE INJECTION OF POLIOMYELITIS VIRUS BY THE INTRACUTANEOUS ROUTE
Authors: Stimpert Fred D. , Kessel John F.
Published: June 2004

The infectivity of poliomyelitis virus by the intracutaneous route occurs in certain strains but is not a constant character. The inconsistency of skin infectivity tests indicates that there is some property yet unknown which influences this characteristic.

Strains of poliomyelitis virus vary in the degree of immunity produced in experimental monkeys injected with active virus by the intracutaneous route and subsequently tested for resistance by intranasal injections. The variation has no relation to the virulence of the strain. Further investigation on the intranasal route of injection should be carried on so that this method may be used with greater assurance in immunity tests, and also in other procedures of poliomyelitis experimentation.
THE BEHAVIOR OF POX VIRUSES IN THE RESPIRATORY TRACT
Authors: Nelson John B.
Published: June 2004

Recovery from the transient pulmonary reaction which accompanies the nasal instillation of variola virus in mice was followed by a measurable protection against the homologous virus and also against vaccinia.

Variola virus which regularly survived in the lung of normally susceptible mice through the 5th day was noticeably reduced in titer on the 3rd day in the lung of recovered animals, and usually eliminated by the 5th day.

Vaccinia virus produced a less severe systemic reaction in recovered mice and its titer in the lung was significantly reduced on the 5th day.

The residence of both viruses in the lung of recovered mice was attended by pathological changes, visible macroscopically.
THE UTILIZATION OF IRON AND THE RAPIDITY OF HEMOGLOBIN FORMATION IN ANEMIA DUE TO BLOOD LOSS
Authors: Hahn P. F. , Ross J. F. , Bale W. F. , Whipple G. H.
Published: June 2004

The formation of hemoglobin in the anemic dog takes place at a very rapid rate. Radio-iron is detectable in the circulating red cells 4 hours after feeding. The absorbed labelled iron is entirely converted into hemoglobin within 4 to 7 days under standard anemic conditions.

When red cell production has been accelerated by iron feeding or diet factors or when the dose of iron is very small, the dog can turn out as hemoglobin almost all the absorbed radio-iron in 2 to 3 days.

In general, absorption of radio-iron as shown by utilization to form hemoglobin in anemic dogs is more efficient in small doses in single feeding experiments. As the iron intake is increased the percentage absorption rapidly falls.
ELECTROPHORESIS OF THE COMPLEMENT-FIXING ANTIGEN OF HUMAN INFLUENZA VIRUS
Authors: Bourdillon Jaques , Lennette Edwin H.
Published: June 2004

1. An electrophoretic study has been made of normal mouse serum, influenza mouse serum, and influenza mouse lung suspension. The mobilities of the protein fractions present have been determined at various pH's by the optical method.

2. The pH-mobility curve of the soluble (complement-fixing) antigen present in the lung suspension has been determined analytically by sampling and application of the complement fixation test. The results show that the complement-fixing antigen has a mobility definitely smaller than that of serum albumin and close to that of a globulin, with an isoelectric point close to pH 5.
THE OCCURRENCE OF MALARIA ANTIBODIES IN HUMAN SERUM FOLLOWING INDUCED INFECTION WITH PLASMODIUM KNOWLESI
Authors: Coggeshall L. T.
Published: June 2004

Evidence has been presented which indicates that antibodies appear in the serum of individuals following an induced malaria infection with Plasmodium knowlesi.
STUDIES ON ANTIBACTERIAL IMMUNITY INDUCED BY ARTIFICIAL ANTIGENS
Authors: Goebel Walther F.
Published: June 2004

1. Azoproteins containing structurally isomeric aldobionic acids evoke in rabbits antibodies which are both serologically and immunologically specific.

2. Antigens containing the azobenzyl glycosides of the synthetic gentio-biuronic and glucuronic acids evoke in rabbits antibodies which confer passive immunity on mice against infection with multiple lethal doses of virulent Type II pneumococci.
ENCEPHALOMYELITIS OF MICE
Authors: Theiler Max , Gard Sven
Published: June 2004

1. In the feces of approximately two-thirds of normal mice 6 weeks of age an agent in all respects similar to the virus of mouse encephalomyelitis can be recovered.

2. In isolated mice, fed on sterile food and water, excretion of virus has been shown to persist up to 53 days after isolation.

3. In normal mice known to be virus carriers virus has been demonstrated in the gastro-intestinal tract but not in the central nervous system, thoracic or abdominal viscera, or any organs of the head.

4. The source of the virus excreted in the feces has been shown to be located in all probability in the intestinal wall.

5. Evidence is presented that the virus can invade the animal organism, as virus has been demonstrated in the mesenteric lymph glands.
A TRANSMISSIBLE AGENT (THEILER'S VIRUS) IN THE INTESTINES OF NORMAL MICE
Authors: Olitsky Peter K.
Published: June 2004

Every experiment with the contents of one, or with those pooled from two to five of the normal stock of Rockefeller Institute strain of albino mice, 1 to 2 months of age, revealed the presence of a virus which, after intracerebral inoculation into normal mice, induced characteristic paralytic encephalomyelitis, indistinguishable from Theilerapos;s disease. No difference was seen in this effect of intestinal contents deriving from animals paralyzed during the course of spontaneous encephalomyelitis and from normal mice. The influence of age on carriage of virus, as well as on the persistence of the carrier state, is discussed.

The present, as well as previous work has shown that the virus found in normal (or paralyzed) mice is similar to that of Theiler's disease in all of its properties thus far investigated; among the strains of the latter now at hand it can be classified with those having a low degree of invasiveness after peripheral inoculation.

The virus has thus far been recovered from intestinal contents, intestinal walls, and mesenteric glands but not from the central nervous system of normal mice; from these sites, as well as from the central nervous system, in paralyzed mice. In order of concentration of virus, the contents have more, the walls less, and the glands least.
INFECTIOUS MYXOMATOSIS OF RABBITS
Authors: Smadel Joseph E. , Ward S. M. , Rivers Thomas M.
Published: June 2004

A second soluble antigen, separable from the virus, occurs in extracts of infected skin and in the serum of rabbits acutely ill with infectious myxomatosis. Like the first antigen (A), the second (B) is heat labile and has certain characteristics of a globulin. The two antigens precipitate in different concentrations of ammonium sulfate and can be separated by this method. Neither of the antigens after being heated at 56°C. precipitates in the presence of specific antibody but each is capable of inhibiting the activity of its antibody.
THE RENAL CLEARANCE OF HEMOGLOBIN IN THE DOG
Authors: Monke J. Victor , Yuile Charles L.
Published: June 2004

Simultaneous hemoglobin and creatinine renal clearance studies have been presented which indicate that hemoglobin is eliminated by the kidney at a rate which is 3 per cent of the creatinine clearance, above a plasma hemoglobin concentration of approximately 250 mg. per 100 cc. In dogs whose average glomerular filtration rate is 66 cc. per minute, about 2 cc. of plasma are cleared of hemoglobin per minute.

A definite renal threshold exists for hemoglobin at a plasma concentration of about 100 mg. per 100 cc., below which hemoglobinuria does not occur.

The uniformity of the process indicates that hemoglobinuria is not the result of a transient glomerular injury induced by the hemoglobin.

It is tentatively suggested that the experimental results obtained may be interpreted in terms of the following concept. The glomerulus permits the filtration of hemoglobin in amounts directly dependent upon plasma concentration. However, only 3 per cent of all the pores of the membrane are electrostatically large enough to permit the passage of an undissociated hemoglobin molecule. Of that hemoglobin which passes down the tubule, a relatively constant though small amount is recovered by the tubules by a process not unlike that of phagocytosis found elsewhere in the body. An average value for this "athrocytic" capacity in a medium-sized dog is 2 mg. of hemoglobin per minute. This pattern of renal hemoglobin excretion is in agreement with the principles of the modern theory of kidney function.
IDENTITY OF "INHIBITOR" AND ANTIBODY IN EXTRACTS OF VIRUS-INDUCED RABBIT PAPILLOMAS
Authors: Friedewald William F.
Published: June 2004

The "inhibitor" demonstrable in extracts of the virus-induced rabbit papillomas is identical with the antiviral antibody found in the blood of hosts bearing the growths. The conditions in these latter are frequently favorable to its extravasation in considerable amount into them. Its significance and its influence upon the recovery of virus from the papillomas are discussed.
THE INHIBITION OF THE BACTERIOSTATIC ACTION OF SULFONAMIDE DRUGS BY SUBSTANCES OF ANIMAL AND BACTERIAL ORIGIN
Authors: MacLeod Colin M.
Published: June 2004

Sulfonamide inhibitor has been demonstrated in extracts of fresh normal muscle, pancreas, and spleen of certain animals. When autolysis of tissues takes place the amount of inhibitor is greatly increased.

Fresh liver from beef, rabbit, and guinea pig is free of active inhibitor, although inhibitor is demonstrable in autolysates of this tissue. Fresh rabbit kidney is likewise free of active inhibitor. Following acid hydrolysis extracts of fresh rabbit liver and kidney cause sulfonamide inhibition.

Normal human urine contains little or no active inhibitor. However, upon acid hydrolysis, inhibitor is uniformly present.

Sulfonamide inhibitor is present in some, but not all, sterile serous effusions occurring during certain diseases. Inhibitor was found uniformly in pus. None was found in blood serum.

In certain species of bacteria the inhibitor is found in the cells only and is not demonstrable in the culture medium, whereas in other species, the inhibitor is found in the culture supernatant, and the cells themselves are relatively free.

The development of sulfapyridine fastness in a strain of Pneumococcus Type I is accompanied by a greatly increased production of sulfonamide inhibitor.
THE EFFECT OF TEMPERATURE ON THE GROWTH OF FROG CARCINOMA
Authors: Lucké Balduin , Schlumberger H.
Published: June 2004

From the results of these experiments we can now attempt to answer the questions proposed in the introduction.

Just as in normal tissues, it has been found that growth and development of a malignant neoplasm are influenced by temperature both quantitatively and qualitatively. The most striking effect was the acceleration in the rate of growth of the tumor at higher temperature, and retardation at lower. The ultimate size attained within periods averaging 3 months was regularly much greater at higher temperature.

Also, the character of growth was quite different. At high temperature, there was more efficient vascularization, and the tumors formed long, branching, tubular outgrowths and cysts; at low temperature the outgrowths were short and stubby and cysts were rare.

These differences were accentuated by repeatedly passing the tumor from one generation to another. In particular, in such serial passages, there was a remarkable tendency for the tumor to develop greatly dilated tubules and large cysts, which later, however, became solid as the result of ingrowth from the wall.

The experiments demonstrate that the carcinoma in the frog can exist over a wide range of temperature. Even a temperature as low as 4°, as in the hibernation experiment, produces no injury to the tumor. This result is consistent with the common occurrence of large, healthy, spontaneous tumors in frogs which have recently hibernated in their natural state.
STUDIES ON THE SENSITIZATION OF ANIMALS WITH SIMPLE CHEMICAL COMPOUNDS
Authors: Landsteiner K. , Di Somma A. A.
Published: June 2004

Sensitization of guinea pigs to picric acid was obtained by application of oil solutions to the skin, preferably on inflamed sites or by treatment with a compound of picric acid with n-butyl-p-aminobenzoate. The lesions obtained in sensitive animals on superficial administration bore resemblance to human eczema.

It seems probable that picric acid sensitization is an instance where a substance does not sensitize directly but after conversion into a more reactive compound, a principle which should be of wider application to instances where the original substance does not readily form conjugates.
THE PROLONGED COEXISTENCE OF VACCINIA VIRUS IN HIGH TITRE AND LIVING CELLS IN ROLLER TUBE CULTURES OF CHICK EMBRYONIC TISSUES
Authors: Feller A. E. , Enders John F. , Weller T. H.
Published: June 2004

1. The virus of vaccinia in so called roller tube cultures of mixed embryonic chick tissue rapidly increases to maximal titre.

2. Under these conditions the quantity of virus in the tissue remains at or near the maximum for at least 9 weeks and considerable amounts are present in the fluids removed each day.

3. The same results are obtained when only fragments of embryonic chick heart are employed.

4. Many, though not necessarily all, of the cells in infected cultures remain alive and retain the capacity to proliferate. The presence of these living cells is essential for the persistence of the virus.

5. No apparent differences in the rate or amount of growth of cells in infected as contrasted with non-infected cultures can be discerned in the gross.

6. It is suggested, but not proved, that virus is continually being produced rather than simply preserved throughout the period.
A SOLUBLE ANTIGEN OF LYMPHOCYTIC CHORIOMENINGITIS
Authors: Smadel J. E. , Wall M. J.
Published: June 2004

Anti-soluble substance antibodies and neutralizing substances, which develop following infection with the virus of lymphocytic choriomeningitis, appear to be separate entities. The times of appearance and regression of the two antibodies are different in both man and the guinea pig; the antisoluble substance antibodies appear earlier and remain a shorter time. Moreover, mice develop them but no demonstrable neutralizing substances.

Injection of formalin-treated, virus-free extracts containing considerable amounts of soluble antigen fails to elicit anti-soluble substance antibodies and to induce immunity in normal guinea pigs; administration of such preparations to immune pigs, however, is followed by a marked increase in the titer of anti-soluble substance antibodies in their serum. On the other hand, suspensions of formolized washed virus are effective in normal guinea pigs in stimulating both anti-soluble substance antibodies and protective substances, and in inducing immunity to infection.
NUTRITIONAL CYTOPENIA IN MONKEYS RECEIVING THE GOLDBERGER DIET
Authors: Day Paul L. , Langston William C. , Darby William J. , Wahlin Joel G. , Mims Virginia
Published: June 2004

Experiments are reported upon young rhesus monkeys which were given a diet essentially the same as the Goldberger black tongue-producing diet, supplemented in various ways. Those receiving the unsupplemented diet developed the syndrome characterized by leucopenia, anemia, gingivitis, diarrhea, and death, which has been previously described in monkeys receiving our diet of refined foodstuffs.

An animal receiving the Goldberger diet supplemented with ascorbic acid and liver extract exhibited normal growth and development and has maintained a normal blood picture for approximately 2 years.

Likewise, the feeding of a crude liver extract to an animal with profound anemia and leucopenia was followed by a dramatic reticulocyte response and ultimate recovery. However, the ash of liver extract failed to maintain a normal blood picture or to prolong life.

Supplementing the diet with ascorbic acid, thiamin chloride, nicotinic acid (or amide), and riboflavin failed to prevent the leucopenia, gingivitis, diarrhea, and death. The combination of nicotinic acid and riboflavin, however, appeared to have a definite erythropoietic effect.

Shigella paradysenteriae was isolated from the stools of several of the animals which received the deficient diet. Further studies are needed to clarify the relationship between the deficiency, the infection, and the blood picture.

Three of the animals exhibited edema of the face.

It is evident that the Goldberger diet, even when supplemented with nicotinic acid, riboflavin, thiamin, and ascorbic acid, is inadequate for maintenance of health in the young monkey. The nature of the deficiency manifestations would indicate that the diet is deficient in the substance or substances which we have previously termed vitamin M.
THE COMPARATIVE SUSCEPTIBILITY OF FETAL AND POSTNATAL GUINEA PIGS TO THE VIRUS OF EPIDEMIC INFLUENZA
Authors: Dettwiler Herman A. , Hudson N. Paul , Woolpert Oram C.
Published: June 2004

Experiments were carried out to determine the relative susceptibility of guinea pigs at different ages to the virus of epidemic influenza.

From a correlation of these studies on the mature fetus, the newborn, and the adult animal, with previously reported findings on the immature fetus, we draw two conclusions: first, that there is a gradually increasing resistance to infection with this virus during intrauterine development, with but little change thereafter; and second, that at the time of birth there is a sudden loss of infectibility by routes other than the intranasal.

These results illustrate then the benefits which may accrue if one projects into the period of antenatal life studies dealing with the age factor in relation to susceptibility to infection. It is implied that data collected from observations of the postnatal animal alone are of necessity incomplete and may be misleading.
QUANTITATIVE ASPECTS OF HOMOLOGOUS AND HETEROLOGOUS ACTIVE IMMUNITY TO STRAINS OF THE VIRUS OF EPIDEMIC INFLUENZA
Authors: Eaton Monroe D. , Pearson Harold E.
Published: June 2004

When mice are immunized by one intraperitoneal inoculation with active or inactive influenza virus (strain PR8, W.S., and Melbourne) the quantity required for protection against heterologous strains is about 10 times the homologous minimal immunizing dose. Three injections increase the immunity to all strains, but the ratio between the homologous and heterologous minimal immunizing dose is not altered.

Swine influenza virus given intraperitoneally fails to immunize against human strains unless the quantity injected is 1,000 times the minimal amount required for homologous immunity.

Intranasal immunization of mice with 1/100 M.L.D. of attenuated ferret passage strains PR8 and Philadelphia, or the tissue culture strain of swine influenza, gives a solid resistance to infection with heterologous strains. When smaller amounts of virus are given intranasally, strain specificity becomes more apparent, and with minimal doses the immunity may be effective only against the homologous and closely related strains.
THE ISOLATION OF THE BLOOD GROUP SPECIFIC B SUBSTANCE
Authors: Witebsky Ernest , Klendshoj Niels C.
Published: June 2004

The isolation of group specific B substance from human stomach juice is described. The substance is carbohydrate-like in nature and is as potent as the carbohydrate-like substance group A isolated from commercial pepsin and peptone respectively.
THE ANTIGENIC POTENCY OF EPIDEMIC INFLUENZA VIRUS FOLLOWING INACTIVATION BY ULTRAVIOLET RADIATION
Authors: Salk Jonas E. , Lavin G. I. , Francis Thomas
Published: June 2004

A study of the antigenic potency of influenza virus inactivated by ultraviolet radiation has been made. Virus so inactivated is still capable of functioning as an immunizing agent when given to mice by the intraperitoneal route.

In high concentrations inactivated virus appears to be nearly as effective as active virus but when quantitative comparisons of the immunity induced by different dilutions are made, it is seen that a hundredfold loss in immunizing capacity occurs during inactivation.

Virus in suspensions prepared from the lungs of infected mice is inactivated more rapidly than virus in tissue culture medium.

A standard for the comparison of vaccines of epidemic influenza virus is proposed.
QUANTITATIVE EXPERIMENTS WITH ANTIBODIES TO A SPECIFIC PRECIPITATE. I
Authors: Treffers Henry P. , Heidelberger Michael
Published: June 2004

1. Rabbits were injected with the washed specific precipitate from Type II antipneumococcus horse serum. Antibody in the resulting antiserum was determined by the quantitative agglutinin method using various specific precipitates as antigens.

2. Suspensions of Types I and II antipneumococcus horse specific precipitates, as well as the specific precipitates derived from Type VIII Pn (anti-C portion), and H. influenzae horse antisera were found to remove the same amount of antibody from the immune rabbit serum.

3. Purified antibody solutions prepared by dissociation methods from Types I and II antipneumococcus horse sera were found to remove the same quantity of antibody as did the homologous specific precipitates.

4. Specific precipitates from anti-crystalline egg albumin and anti-diphtheria horse sera were found to remove only a fraction of the antibody. The reasons for this are discussed.

5. A specific precipitate prepared from pepsin-digested Type I anti-pneumococcus horse serum removed all of the antibody to the homologous antigen from the rabbit anti-precipitate serum, but followed a different quantitative course.

6. From the quantitative course of these reactions and from experiments with specific precipitates from anti-Pn rabbit and pig sera it is concluded that the only antigenic specificity demonstrable for the antibodies investigated was that due to their common origin, and that the groupings responsible for their antibody function constitute either a small part of the total protein molecule or else are non-antigenic.
STRUCTURAL AND FUNCTIONAL TRANSFORMATIONS IN THE TUBULAR EPITHELIUM OF THE DOG'S KIDNEY IN CHRONIC BRIGHT'S DISEASE AND THEIR RELATION TO MECHANISMS OF RENAL COMPENSATION AND FAILURE
Authors: Oliver Jean , Bloom Frank , MacDowell Muriel
Published: June 2004

1. The wall of the proximal convolution in chronic canine nephritis is composed of various types of epithelial cells which can be recognized as definite structural types from their cytological characteristics.

2. The function of these cell types, as tested by their reaction to the administration of trypan blue, varies with their structural constitution.

3. As a result of the varied cellular content of its wall the abnormal proximal convolution handles trypan blue by mechanisms which differ both quantitatively and qualitatively from those of the normal convolution.

4. A distinguishing characteristic of the decompensated kidney in chronic canine nephritis is the inability of its epithelium to concentrate trypan blue within its cells and to prevent diffusion of the dye from the lumen into the tubule wall.

5. It follows: (a) (from conclusion 3), that it cannot be assumed that the renal mechanisms concerned with other substances are not unaltered and that comparisons of blood and urine concentrations (clearances) have similar significance in the normal and nephritic kidney; (b) (from conclusion 4), that tubular dysfunction may play a part in the ultimate failure of the compensating kidney in all forms of chronic Bright's disease where the tubule walls are similarly affected.