bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON THE SHOPE RABBIT PAPILLOMA VIRUS
Authors: Noyes Wilbur Fiske
Published: June 2004

A method has been devised to determine the location of infective Shope virus in the papillomas of cottontail rabbits. Frozen sections of the growths were burned selectively with a microcautery to destroy either the keratinized or proliferating layer and the sections were then applied directly to the sensitized epidermis of domestic rabbits. No papillomas appeared when the keratohyaline and keratinized areas had been eliminated leaving the proliferating cell layer, whereas papillomas arose when the proliferating cell areas were destroyed leaving the keratohyaline and keratinized layers. The results indicate that infective Shope papilloma virus is situated mainly, perhaps entirely, in the keratohyaline and keratinized areas of cottontail papillomas. This is in accord with the previous disclosure by the fluorescence technique that virus antigen in demonstrable quantity is present only in these situations.
DETERMINATION OF TYPE IN CAPSULATED TRANSFORMANTS OF PNEUMOCOCCUS BY THE GENOME OF NON-CAPSULATED DONOR AND RECIPIENT STRAINS
Authors: Jackson Stanley , MacLeod Colin M. , Krauss Marjorie R.
Published: June 2004

Capsulated transformants producing type II polysaccharide have been obtained by reactions between a number of R mutants of type II pneumococcus.

All the IIR strains except II-R36 yielded extracts which transformed 2 VIIIR strains to VIIIS. Two of the IIR strains were transformed to VIIIS by an extract of 1 VIIIR strain.

The most striking result was the production of both IIS and VIIIS transformants by the action of extracts of both VIIIR strains applied to cells of II-RB. This suggests that the determination of capsular type in pneumococcus does not depend on single allelomorphic genes; it seems more likely that a number of genes may be required to determine type specificity, and that some genes may be common to different types, possibly in connection with common biochemical pathways for some stages of polysaccharide synthesis.

This is further indicated by the finding that extracts of capsulated strains of each of the types I, II, III, VII, VIII, XIV, and XVIII are capable of giving IIS transformants with 1 or more of the IIR strains in addition to the expected donor-type transformants.

Strain II-R36 was transformed by extracts of all S types except type VII, but the only transformants found were of the donor type. It appears that II-R36 may have multiple genetic deficiencies for type II capsulation, possibly in the form of a deletion. This may be the case also with IIIS strains since only IIIS transformants were found when IIIS extract was applied to any of the IIR strains.
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Rowe Wallace P. , Hartley Janet W. , Law Lloyd W. , Huebner Robert J. ,   With the Technical Assistance of John D. Estes, William T. Lane, and Britton H. Smith
Published: June 2004

Eight mouse colonies were surveyed for prevalence of antibody to mouse polyoma virus. Frequency of HI antibody varied from 0 to 84 per cent in adult mice in different colonies. Antibody was infrequent in mice less than 3 months of age, and increased in frequency with age. There was no evidence that infection was specific for particular mouse strains. The highest frequency of infection was found in colonies in which breeding mice are housed in proximity to mice inoculated with polyoma virus or passage tumors, and within an infected colony, the incidence of infection was greatest in rooms housing mice inoculated with polyoma virus. Mice from a colony free of antibody became infected when held in room or cage contact with virus-inoculated mice, but at very low rates except in mothers of inoculated litters. These results were interpreted as indicating that artificial contamination of the environment is an important factor in determining the prevalence of infection in the colonies observed.

There was no correlation between polyoma infection and spontaneous leukemia in AK. mice.
STUDIES ON THE ADJUVANT ACTION OF BACTERIAL ENDOTOXINS ON ANTIBODY FORMATION
Authors: Ward Peter A. , Johnson Arthur G. , Abell Murray R.
Published: June 2004

Histologic changes occurring in the rabbit spleen during the primary response to intravenous injection of bovine gamma globulin alone and in combination with bacterial endotoxin have been described. The predominant morphologic changes associated with antibody formation in animals that received antigen alone were confined to the follicular areas of the spleen. Only minimal changes were seen in the red pulp. No new cellular types appeared following endotoxin stimulus. Rather, a profound augmentation of events observed following a single injection of bovine gamma globulin alone appears to account for the higher levels of antibody incited by this adjuvant. The cell type important in antibody formation under these conditions appeared to be a modified reticular cell. Plasma cells were not part of the cellular reaction. A hypothesis describing the primary antibody response is presented.
THE CYTOTOXIC ACTION OF IMMUNE GAMMA GLOBULIN AND COMPLEMENT ON KREBS ASCITES TUMOR CELLS
Authors: Green H. , Fleischer R. A. , Barrow P. , Goldberg B.
Published: June 2004

The in vitro exposure of Krebs ascites tumor cells to the action of rabbit immune gamma globulin alone does not result in any changes in the cell concentration of amino acids, ribonucleotides, RNA, DNA, or protein, nor in the rate of entry of potassium into the cell.

The exposure of the cells to antibody + complement results in the following changes within a few minutes:—

(a) Loss of about two-thirds of the free amino acids and ribonucleotides.

(b) Loss of about 90 per cent of the intracellular potassium.

(c) Loss of about three-quarters of the cell RNA to the medium, part appearing as TCA-soluble and the rest as TCA-insoluble products. There were no changes detectable in DNA.

(d) A small increase in total free amino acid of the cell suspension.

(e) Loss of from 30 to 60 per cent of the cell protein.

The loss of these substances is believed to occur through a cell membrane which is still intact, as judged by phase and electron microscopy, and still able to discriminate to a small degree against passage of larger molecules.
STUDIES ON TUBERCLE BACILLUS-MONOCYTE RELATIONSHIP
Authors: Fong Jacob , Chin Dennis , Akiyama Hajime J. , Elberg Sanford S.
Published: June 2004

Studies of the relationship of protective serum factor to cellular resistance and to tuberculin skin sensitivity have demonstrated that protective serum factor may exist independently of a high level of cellular resistance, and that both protective factor and cellular resistance may be demonstrable without a concomitant hypersensitivity of the delayed type.

The experiments with absorbed sera and the globulin fraction of immune serum indicated no specific association of protective serum factor with antibody globulin.

The protective factor in immune serum was found to be thermostable and non-dialyzable.

In vitro exposure of virulent tubercle bacilli to the immune serum from BCG-immunized animals failed to alter the bacterial capacity for destruction of monocytes and for intracellular proliferation.

In vitro cultivation of normal and immune monocytes in normal or immune serum was not effective in changing the native susceptibility or resistance of these cells.

Effective manifestation of resistance to virulent tubercle bacilli by immune monocytes was found to require the continuous presence of immune serum.

The intracellular passage of virulent tubercle bacilli in an immune system (immune monocytes cultivated in immune serum) resulted in a decreased bacterial potential for destruction of normal monocytes when these were cultivated in the presence of immune serum.
THE METABOLISM OF SILICON IN THE RAT AND ITS RELATION TO THE FORMATION OF ARTIFICIAL SILICEOUS CALCULI
Authors: Keeler Richard F. , Lovelace Stuart A.
Published: June 2004

The urinary excretion of silicon in the rat was found to be enhanced beyond normal levels by the administration of various chemical forms of silicon. The excretion was enhanced to a much greater degree by the administration of ethyl silicate than by magnesium trisilicate, sodium metasilicate, or water glass. The tolerance level of rats to sustained daily doses of ethyl silicate fed via stomach tube was approximately 15 to 30 mg. of silicon per rat per day. Urinary silicon excretion was found to be a straight line function of the concentration of ethyl silicate administered, via stomach tube, with approximately 18 per cent of the administered silicon appearing in the urine at all levels tested. Using sustained dietary additions of ethyl silicate as a means of enhancing urine silicon levels, artificial siliceous urinary calculi were consistently produced on zinc pellets implanted in the bladders of rats.
RENAL GLOMERULAR LESIONS INDUCED BY RABBIT ANTI-RAT COLLAGEN SERUM IN RATS PREPARED WITH ADJUVANT
Authors: Rothbard Sidney , Watson Robert F.
Published: June 2004

Renal glomerular lesions were induced by rabbit serum containing antibody to rat collagen injected intravenously into rats prepared with subcutaneously administered Freund adjuvant. Neither the anti-collagen serum nor the adjuvant alone induced the lesion. The lesions were characterized by diffuse glomerular injury with swelling, shredding, and fusion of the basement membranes, crescent formation, cellular proliferation, numerous multinuclear giant cells, and capillary hyaline thrombi.

Various rabbit antisera, including those against fish collagen or rat serum failed to induce the renal lesion when substituted for anti-rat collagen serum. Also, anti-rat collagen serum absorbed with its homologous antigen, native rat collagen, failed to induce the lesion. Although complete adjuvant, i.e. with mycobacteria, in which normal serum was incorporated enhanced the glomerular lesion which resulted from intravenous injection of anti-collagen serum, the incomplete adjuvant without serum was sufficient.

Comparison of the renal lesions induced by anti-collagen serum with nephrotoxic nephritis induced in rats by rabbit anti-kidney serum showed that they differ histologically. Also the antisera used to produce these two renal lesions differ immunologically.

Antibodies to normal rabbit serum developed in rats injected intravenously with rabbit anti-rat collagen serum after preparation with adjuvant, but not when adjuvant was omitted. The pathogenesis of the renal injury is discussed as a manifestation of an antigen-antibody reaction, with nephritis occurring only after the adjuvant-stimulated antibody to the rabbit globulin has been formed in the rat and has reacted with the rabbit anti-rat collagen already fixed by its homologous antigen in the kidney.
MACROGLOBULINEMIA
Authors: Korngold Leonhard , van Leeuwen Gerda
Published: June 2004

The monomers obtained by treating γ1-macroglobulins with mercaptoethanol have proved to be antigenically different from normal 7S 7γ-globulin.

The depolymerization of the macroglobulins resulted in the loss of several antigenic determinants, although the monomers still cross-reacted with antisera against macroglobulins.

Reaggregation of the monomers occasionally resulted in the reconstitution of some or all of the antigenic determinants that were lost during depolymerization.

Repeated freezing and thawing of pathological macroglobulins in iodoacetate resulted in their complete antigenic destruction.

Repeated freezing and thawing of one of the monomers in excess iodoacetate resulted in the degradation to a protein antigenically indistinguishable from Bence Jones protein. The other two monomers studied were stable under these conditions.
EXPERIMENTAL PULMONARY PNEUMOCYSTIS CARINII INFECTION IN RABBITS
Authors: Sheldon Walter H.
Published: June 2004

Moderate to marked interstitial pneumonitis with many Pneumocystis organisms was found in rabbits treated with cortisone and antibiotics and instilled intranasally with a suspension of lung tissue from either a patient or a rabbit with this infection. Organisms and pulmonary lesions of similar severity and frequency were present in controls treated in the same manner but instilled with either saline or a boiled suspension of normal human lung tissue. The administration of antibiotics and infected rabbit lung suspension only produced less marked lung changes with fewer organisms. Rare organisms and minute foci of pneumonitis were encountered in normal rabbits which had received neither hormone, antibiotics, nor inoculum.

The pulmonary lesions in the cortisone-treated rabbits resembled closely the findings in patients with the subclinical form of Pneumocystis pneumonitis. They did not reproduce the massive lesions of widespread Pneumocystis pneumonia in infants.

The findings indicate that latent pulmonary Pneumocystis infection was widespread in these rabbits but do not establish the transmission of the disease. The activation of latent infection was dependent on an impairment of host resistance which in these experiments was produced most effectively by the administration of cortisone. The differences between the experimental lesions and those of typical Pneumocystis pneumonia in infants suggest that in man an unknown defect of host defenses other than that induced by prolonged hormone administration accounts for the increased susceptibility to the infection. It is concluded that in the presence of widespread latent Pneumocystis infection the development of active disease is a manifestation of altered host resistance.
A QUANTITATIVE STUDY OF THE KINETICS OF BLOOD CLEARANCE OF P32-LABELLED ESCHERICHIA COLI AND STAPHYLOCOCCI BY THE RETICULO-ENDOTHELIAL SYSTEM
Authors: Benacerraf B. , Sebestyen Martha M. , Schlossman Stuart
Published: June 2004

1. The clearance of P32-labelled heat-killed E. coli and staphylococci from the blood follows an exponential function of the time, and the bacteria are phagocytized principally by the RES of the liver and spleen.

2. The rates of clearance of equivalent number of E. coli from the blood is rapid in rabbits and slow in mice and appears to be related to the level of antibodies in the serum of these animals.

3. Unlike E. coli, staphylococci are cleared rapidly and efficiently by the RES from the blood of mice which have a sufficient level of serum antibody against these bacteria.

4. The numbers of bacteria, phagocytized by the liver or the spleen respectively, depend upon the rate of clearance and the extent of opsonization of the bacteria. Rapidly cleared, well opsonized E. coli are removed almost exclusively by the liver, while less efficiently phagocytized bacteria are also cleared by the spleen in large numbers.

5. The rate of clearance of E. coli and the efficiency with which they are phagocyted by the RES in mice have been shown to be directly related to the level of antibody in the serum.

6. Treatment of mice with S. typhi or Serratia marcescens endotoxins increases the rate of clearance of E. coli from the blood and the level of antibody against E. coli in the serum. The enhanced clearance of E. coli can be transferred to normal mice by the serum of endotoxin-treated mice.
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Hartley Janet W. , Rowe Wallace P. , Chanock Robert M. , Andrews Basil E.
Published: June 2004

Treatment of guinea pig erythrocytes with types A and B influenza viruses rendered them inagglutinable by polyoma virus; also, the inhibitory effect of ovomucin on polyoma virus hemagglutination was destroyed by pretreatment of the ovomucin with various myxoviruses. These results indicate that polyoma virus and myxovirus erythrocyte receptor sites are identical. However, no destruction by polyoma virus of its own or of myxovirus receptors or inhibitors was detected.

No serologic relationship was detected between polyoma virus and members of the myxovirus group; differences in size and stability further indicate their distinctness.

No evidence was found of biologic or serologic relationship of polyoma virus with encephalomyocarditis virus or mouse encephalomyelitis virus.
THE EFFECT OF ANTIGENIC STIMULATION ON INCORPORATION OF PHOSPHATE AND METHIONINE INTO PROTEINS OF ISOLATED LYMPH NODE CELLS
Authors: Kern Milton , Eisen Herman N.
Published: June 2004

Isolated lymph node cells incorporate inorganic orthophosphate into a protein fraction. The phosphorylated product is a phosphoprotein. The rate of phosphate incorporation into phosphoprotein was determined in cells isolated from regional lymph nodes at varying times after antigen injection. The rate was unaltered on the 3rd day, but was enhanced on the 4th day after injection. Parallel results were obtained with L-methionine incorporation into the same gross protein fraction. Possible relationships between antibody formation and the observed enhancement in phosphate incorporation into phosphoprotein are discussed.
THE EFFECTS OF BACTERIAL ENDOTOXIN ON LIPIDE METABOLISM
Authors: LeQuire V. S. , Hutcherson J. D. , Hamilton R. L. , Gray M. E.
Published: June 2004

Single intravenous injections of Shear's polysaccharide in varying dosages invariably produced an elevation in the levels of the total serum lipides 24 hours after injection of endotoxin. The total serum cholesterol and lipide phosphorus were also affected, although they did not change with smaller doses of endotoxin and were rarely elevated to the same degree as were the total serum lipides.

The degree of elevation of the serum lipides was apparently related to the amount of endotoxin injected up to a certain point, beyond which there was no further increase.

There were two types of response to endotoxin by the serum lipides, a moderate increase and an uncontrolled increase. Higher dosages of endotoxin and fasting apparently increased the incidence of the latter response.

No direct correlation could be made between serum lipide responses and histologic evidence typical of the generalized Shwartzman reaction following this regimen of endotoxin injection. The Shwartzman reaction did occur with greater frequency and with lower dosages of endotoxin in fasted animals.

Animals given repeated injections of endotoxin showed an initial increase in serum lipides followed by a progressive decrease to normal levels as tolerance to the febrile action of endotoxin appeared. The febrile tolerance as well as the unresponsiveness of the serum lipides to endotoxin was abolished by thorium dioxide (thorotrast) in these animals. In similar experiments a "breakthrough" of lipide unresponsiveness to endotoxin was obtained by increasing the amount of endotoxin injected.

Some of the implications of these results for the metabolic alterations produced by bacterial endotoxins are discussed.
EFFECTS OF BACTERIAL ENDOTOXIN ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S.
Published: June 2004

Urinary nitrogen excretion over a 17 hour period without food and water was determined for mice poisoned with endotoxin and for control mice with and without the subcutaneous injection of 5 mg. cortisone acetate. Endotoxin did not alter the quantity of nitrogen excreted, compared with that of control mice, but in both groups of animals cortisone increased urinary nitrogen by the same amount.

A balance between the quantity of protein catabolized (as estimated by increased urinary nitrogen excretion) and the total carbohydrate stored as a result of cortisone administration was found in fasted and in fed mice but not in endotoxin-poisoned mice.

Endotoxin inhibited the motility of the gastrointestinal tract and blocked the absorption of food.

Injections of ACTH in normal mice increased protein degradation and carbohydrate synthesis. In endotoxin-poisoned animals, ACTH failed to alter urinary nitrogen excretion and carbohydrate reserves. ACTH increased susceptibility to endotoxin.

The number of heat-killed cells of S. typhimurium required to block the increase in urinary nitrogen caused by an injection of ACTH was found to be 108. A partial block was found with 5 x 107 cells but not with 105 cells.

Mice infected with S. typhimurium excreted less than the normal amount of urinary nitrogen in response to ACTH 6 to 23 hours postinfection while normal amounts of nitrogen were eliminated 54 to 71 hours postinfection. The number of viable cells in the mice during the earlier period was less than the number of dead cells required to alter the nitrogen output, while the reverse was true during the later period.
RATIOS OF VACCINIA VIRUS PARTICLES TO VIRUS INFECTIOUS UNITS
Authors: Overman John R. , Sharp D. Gordon
Published: June 2004

Total virus particle counts, infectivity titrations and the ratios between particles and infective units have been determined for vaccinia virus infected tissues. Growth curves of vaccinia in the chorioallantoic membrane are characterized by relatively low ratios from 1 to 4 days after inoculation and a marked rise in the ratio at more prolonged intervals. Ratio determinations of vaccinia virus passages in the egg, rabbit skin, and guinea pig skin have been made to study the phenomenon of adaptation in different hosts. The embryonated egg chorioallantoic membrane shows no variation in the ratio of particles to infectious units during passage and it is concluded that this host is completely susceptible to vaccinia. During adaptive passages on the skin of rabbits and guinea pigs relatively large amounts of non-infective virus appear as indicated by a rise in the particle-infectivity ratios. The extent of ratio increase appears related to the general resistance of the host to the virus. Finally, treatment of crude tissue extracts with sonic vibration is described as an aid in dispersing the virus particles for quantitative particle counts.
STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCI
Authors: Foley Marie Judith , Wood W. Barry
Published: June 2004

A quantitative study of the combined antiphagocytic effects of the M protein and the hyaluronic acid capsules of four strains of Group A streptococci revealed the following facts relating to their intraperitoneal virulence in mice and rats:

1. The most virulent strain, S23M (matt), produced both a large hyaluronic acid capsule and a full complement of M protein, the combined effects of which rendered the organism highly resistant to surface phagocytosis.

2. The slightly less virulent strain, T14/46 (matt virulent) was somewhat more susceptible to surface phagocytosis owing to the fact that its smaller capsule was less antiphagocytic than that of the S23M organism.

3. The glossy variant of the S23 strain (S23G), which ranked third in virulence, was still more susceptible to surface phagocytosis because of its lack of detectable M substance. Its large hyaluronic acid capsule, however, was capable of protecting it against phagocytosis on glass.

4. The least virulent strain, T14 (matt avirulent), was the most susceptible of all to phagocytosis. Though it possessed both M substance and capsule, which together prevented its phagocytosis on glass, each of them was shown to be quantitatively and functionally deficient as compared to Strain S23M.

The differences in phagocytability, which appear to be directly related to the pathogenicity of the organisms, could be adequately demonstrated in vitro only by phagocytic tests designed to measure surface phagocytosis in the absence of opsonins. This fact is in keeping with the observation, previously reported, that surface phagocytosis plays a critical role in the defense of the host, particularly during the earliest stages of experimental streptococcal infections. Its possible relation to suppuration during the later stages of infection is also discussed.
ELECTRON MICROSCOPIC OBSERVATIONS ON THE DEVELOPMENT OF HERPES SIMPLEX VIRUS
Authors: Morgan Councilman , Rose Harry M. , Holden Margaret , Jones Ellyn P.
Published: June 2004

Study of the J.M. strain of herpes simplex virus in human amnionic and HeLa cell tissue cultures revealed the presence of intranuclear crystals composed of viral particles with a single membrane enclosing a central body. Randomly dispersed virus with double coats was seen in the nuclear matrix and between multiple membranes at the nuclear periphery. The majority of intracytoplasmic viral particles were within walled vacuoles. It is suggested that this strain of virus differentiates and frequently crystallizes at template sites which are characterized by aggregates of granules near the nuclear margin; that particles, either singly or occasionally in small groups, become enclosed by a second peripheral membrane while still within the nucleus; that the virus can pass into the cytoplasm through reduplications of the nuclear membrane which are deposited behind the virus in such a manner as to prevent rupture of the nucleus; that most of the intracytoplasmic virus is contained within sacks formed by nuclear membranes; and that rupture of these sacks at the cell surface results in extrusion of virus without disruption of the cell. No evidence was obtained to support the hypothesis that virus develops in the cytoplasm. Examination of the H.R. and C.G. strains of herpes simplex virus in identical cell lines grown under similar conditions failed to show viral crystals, but reduplication of the nuclear membranes was evident. Study of the J.M. strain in cells of chicken embryo chorioallantoic membranes indicated that the basic mechanisms of viral development and release did not differ from those operating in HeLa and human amnionic cells.
GAMMA GLOBULIN PRODUCTION IN GERMFREE RATS AFTER BACTERIAL CONTAMINATION
Authors: Gustafsson Bengt E. , Laurell Carl-Bertil
Published: June 2004

The earlier observed pronounced hypogammaglobulinemia in germfree rats of different ages has been confirmed. Using an immunologic technique the concentration of immunologic gamma globulins were found to vary between 10 and 15 per cent of the values observed in ordinary rats. Upon contamination of germfree rats with the normal microbial flora a pronounced lag phase was noted before the gamma globulin level became normal. This lag phase was most pronounced in growing rats.

Newborn rats seem to start gamma globulin production more rapidly than older germfree rats. The response with regard to gamma globulin production on contamination of germfree rats with different types of bacterial cells through the natural routes is not identical.
ACUTE HEPATIC NECROSIS INDUCED BY BRUCELLA INFECTION IN HYPERTHYROID MICE
Authors: Bradley G. Mary , Spink Wesley W.
Published: June 2004

When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined.

Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed.
STUDIES OF L FORMS AND PROTOPLASTS OF GROUP A STREPTOCOCCI
Authors: Freimer Earl H. , Krause Richard M. , McCarty Maclyn
Published: June 2004

L forms of Group A streptococci have been isolated by the use of penicillin gradient agar plates. Osmotically fragile protoplasts of Group A streptococci have been obtained by the use of Group C phage-associated lysin which lyses Group A streptococci and their isolated cell walls. Membranes surrounding these enzymatically derived protoplasts have been isolated, and chemical and immunological studies indicate that they are free of cell wall carbohydrate and M protein. The streptococcal protoplasts reproduce as colonies which are morphologically indistinguishable from streptococcal L forms. Evidence is presented to show that these two streptococcal derivatives are serologically and physiologically related to each other as well as to the parent streptococcal strain from which they were isolated.
INFLUENCE OF HORMONES ON LIVER
Authors: Huggins Charles , Yao Fung-O
Published: June 2004

Modification of the endocrine milieu intérieur by administration or withdrawal of hormones considerably influenced the concentration in liver of lactic dehydrogenase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconic dehydrogenase. Hormones effective in this regard are thyroxine, estradiol-17ß, dihydrotestosterone, and 3α-hydroxysteroids in the androstane series. These hormonal effects are both organ-selective and, in liver, enzyme-selective.

Thyroxine and steroids are not equivalent in their influence on the 3 hepatic dehydrogenases. Thyroxine was preeminent in this regard among hormones investigated in the present experiments.

Each of the pyridine nucleotide-linked dehydrogenases in liver had an individually characteristic response to the administration of various hormones which was reflected in its hepatic level. The concentration in liver of lactic dehydrogenase was profoundly raised or lowered, respectively, by the administration of thyroxine or by thyroidectomy, and injection of steroids had small influence on its level.

The levels of glucose-6-phosphate dehydrogenase and of 6-phosphogluconic dehydrogenase were considerably influenced by injection of thyroxine, estradiol-17ß, or testosterone. Sex steroids did not increase the levels of these enzymes in hypophysectomized or thyroidectomized rats unless thyroxine was administered concurrently.

Under designated conditions, it was found that the concentration of 6-phosphogluconic dehydrogenase was increased by hormonal methods which did not elevate the concentration of glucose-6-phosphate dehydrogenase. But high levels of glucose-6-phosphate dehydrogenase were not achieved without a considerable elevation of 6-phosphogluconic dehydrogenase as well.
EFFECT OF DIETARY PROTEINS AND AMINO ACIDS ON THE SUSCEPTIBILITY OF MICE TO BACTERIAL INFECTIONS
Authors: Schaedler Russell W. , Dubos Rene J.
Published: June 2004

Young mice were maintained for periods of 1 to 6 weeks on experimental diets containing all known growth factors, but differing in their protein and amino acid contents. All diets were supplemented with L-cystine.

The effect of the nutritional regimen on infection was tested by inoculating the animals with either one of four pathogens (Mycobacterium tuberculosis var. bovis, Mycobacterium fortuitum, Staphylococcus aureus, Klebsiella pneumoniae type C), and by observing the survival time. The infective dose was administered by either one of three routes: intravenous, intraperitoneal, or air-borne (aerosol).

In some experiments, the animals were maintained in groups of five throughout the tests. In other experiments they were housed in individual cages. This difference in housing did not affect the results in a detectable manner.

Mice fed diets containing 5 or 8 per cent casein as sole source of amino acid (except for cystine supplementation) proved more susceptible to the experimental diseases than did mice fed diets containing 15 or 20 per cent of the same protein.

Susceptibility to infection developed when wheat gluten, or soybean α-protein, was substituted for casein—even in high concentrations (15 or 20 per cent).

In one experiment, mice were fed a diet containing as sole source of amino acids a mixture of soybean and rice flour, so designed as to provide a protein concentration of 15 per cent, with an amino acid pattern similar to that of casein. These animals gained weight at the same rate as those fed a diet containing 15 per cent casein and they exhibited a satisfactory level of resistance to bacterial infection.

The infection-enhancing effect of low casein concentration (5 and 8 per cent) could be corrected by supplementing the diet with the proper mixture of amino acids. This could be done using either synthetic or natural amino acids. In contrast, susceptibility to infection developed when low casein diets were supplemented with unbalanced mixtures of amino acids.

The infection-enhancing effect of gluten diets could not be corrected by supplementing the latter with lysine even though this supplementation markedly improved weight gains in uninfected animals.

It appears in conclusion that the relative proportion of the various amino acids in the diet is as important a factor as their total amount in conditioning resistance to bacterial infections. This effect of nutrition on resistance can be detected irrespective of the route of infection: intravenous, intraperitoneal, or air-borne. Moreover, the effect has been observed with two strains of mice differing markedly in their natural resistance to bacterial infection.
STUDIES ON THE PATHOGENESIS OF ACUTE INFLAMMATION
Authors: Allison Fred , Lancaster Margie G.
Published: June 2004

The relation of intravascular fibrin to the leucocytic sticking reaction in ear chambers of rabbits injured by heat was investigated in two ways. First, attempts were made to destroy the thin layer of fibrin believed to coat the surfaces of cells involved in the sticking reaction. Second, white cell sticking was studied after fibrinogen had been removed from the blood stream. The results of these experiments were as follows:—

1. Activation of fibrinolysin in vivo by streptokinase did not impair sticking of white blood cells.

2. Administration of streptokinase parenterally did not lower fibrinogen blood levels appreciably even when the amount used was large.

3. Thromboplastin infusions alone reduced circulating fibrinogen to low levels but leucocytic sticking was not prevented. Furthermore, frequent death of animals due to pulmonary embolism made such experiments prohibitive.

4. Addition of streptokinase to thromboplastin infusions protected against embolic deaths but did not influence sticking even though the fibrinogen levels achieved were quite low.

5. Finally, when thrombin was added to infusions of thromboplastin and streptokinase, no circulating fibrinogen could be detected. Under such circumstances leucocytic sticking following heat injury occurred without reduction.

These findings were interpreted as evidence against a primary role of the blood clotting mechanism in causing the sticking of white blood cells to injured endothelium. Alternative explanations were discussed.
STUDIES ON IMMUNE HEMOLYSIS: PREPARATION OF A STABLE AND HIGHLY REACTIVE COMPLEX OF SENSITIZED ERYTHROCYTES AND THE FIRST COMPONENT OF COMPLEMENT (EAC'1); INACTIVATION OF CELL-FIXED C'1 BY SOME COMPLEMENT REAGENTS
Authors: Klein Paul G.
Published: June 2004

The interaction of sensitized sheep crythrocytes (EA) with guinea pig complement inactivated by treatment with hydrazine or ether has been studied. In both cases EA is converted into EAC'1. The hemolytic reactivity of this complex with respect to a complement reagent that contains C'4, C'2, and C'3 (R1) decays rapidly in the presence of hydrazine-treated complement (R4) or decomplemented guinea pig serum, but not in the presence of ether-treated guinea pig serum or of saline. The rate of decay of EAC'1 is dependent on the temperature, the reaction volume, and the amount of the inactivating reagent. The capacity of R4 and of decomplemented serum to inactivate EAC'1 can be markedly reduced by treatment with ether. The essential conditions for obtaining an optimally reactive EAC'1 consist in exposing EA to ether-treated guinea pig serum in the cold. This procedure yields a highly reactive EAC'1, even when the cells are sensitized with suboptimal amounts of amboceptor.
STUDIES ON THE ANTIGENIC PROPERTIES OF COMPLEMENT
Authors: Klein Paul G. , Burkholder Peter M.
Published: June 2004

Evidence is presented to show that guinea pig complement fixed on sensitized sheep red cells acts as a specific agglutinogen. Agglutinating antibodies that react with cell-fixed complement can be produced by immunizing rabbits with a complex of stromata-amboceptor-complement or with guinea pig serum globulin. These agglutinins can be removed by precipitation with guinea pig serum. They are, therefore, distinct from immunoconglutinins.
STUDIES IN THE PATHOGENESIS OF EXPERIMENTAL DYSENTERY INTOXICATION
Authors: Penner Abraham , Bernheim Alice Ida
Published: June 2004

The introduction of Shiga toxin into the ventricular system of the brain with major location in the third ventricle resulted in a response similar to that following the administration of the toxin either intravenously or by cross-circulation. The intravenous administration at the dosage level employed would have elicited no response. These observations lend support to the hypothesis that Shiga toxin activates some mechanisms in the central nervous system which are capable of producing visceral lesions. These mechanisms are those which control the vasomotor components of homeostasis. This hypothesis permits an explanation of the proximo-distal and intramural features of the lesion.
RELATION OF A ß1-GLYCOPROTEIN OF HUMAN SERUM TO THE COMPLEMENT SYSTEM
Authors: Müller-Eberhard H. J. , Nilsson U.
Published: June 2004

The protein of human serum, tentatively designated ß1C-globulin, was shown to possess serological activity and to be related to the complement system. Another serum protein (ß1A-globulin) was identified as the inactivated form of ß1C-globulin.

Incubation of fresh serum with various immune precipitates or with soluble γ-globulin aggregates at 37°C. resulted in the removal of ß1C-globulin. Treatment of fresh serum with zymosan at 17 and 37°C. had a similar effect. In both instances ß1C-globulin was removed from serum, apparently by conversion to ß1A-globulin. However, isolated ß1C-globulin did not react with immune precipitates or zymosan, nor did ß1C-globulin of serum previously heated at 56°C.

Highly purified ß1C-globulin was tested for complement component activity by means of the usual reagents. All of the preparations examined were found to reconstitute the hemolytic activity of guinea pig R3. However, they failed to reconstitute R3 obtained from human serum. Isolated ß1A-globulin was found to be inactive in all systems.

When isolated ß1C-globulin in either phosphate or in borate buffer was stored at 37°C., the activity detected by means of guinea pig R3 declined within 6 days to 20 to 30 per cent of its original value. As the activity decreased, ß1C-globulin was gradually converted to ß1A-globulin.

Addition of ß1C-globulin to a limited complement system (human C') caused an increase of both initial velocity and final degree of hemolysis.

Although ß1C-globulin did not cause lysis of EAC'1, 4, 2, it fully prevented the otherwise rapid decay of EAC'1, 4, 2 at 37°C., and so presumably interacted with this complex.
GENETIC STUDY OF HUMAN CELLS IN VITRO
Authors: Chang R. Shihman
Published: June 2004

The isolation of carbohydrate variants from cultures of HeLa and conjunctival cells was described. Factors inherent in the cell culture system, such as parent populations and dialyzed serums, have been shown to influence the outcome of variant isolations. Established stable variants incorporated significantly more pentoses or lactate into various cell fractions than the parent cultures. Besides their abilities to propagate continuously in the selecting environments, the variants multiplied slower, were more susceptible to sub-zero preservation and the cytotoxic effect of D-2-deoxyglucose, showed lower cloning efficiencies and were less susceptible to the deleterious effect of glucose oxidase.

The ribose variants also differed from the parent cultures in morphological appearance such as formation of multinucleated cells and ring-shaped colonies. They converted more ribose into other component sugars of mucopolysaccharides than the parent cultures. Preliminary analyses of the mucopolysaccharides extracted from the ribose variants and parent cultures showed large difference in their carbohydrate (Molisch-positive materials) and DNA ratios. Evidence suggests that a sequence of interrelated events from genetic selection to primitive morphogenesis has been established.
IMMUNOLOGICAL STUDIES ON A C POLYSACCHARIDE COMPLEX OF GROUP A STREPTOCOCCI HAVING A DIRECT TOXIC EFFECT ON CONNECTIVE TISSUE
Authors: Schwab John H. , Cromartie William J.
Published: June 2004

A macromolecular complex of C polysaccharide and peptide derived from Group A streptococcal cells produces a multinodular, remittent, and intermittent lesion of dermal connective tissue following a single intradermal injection. This lesion is greatly modified, both in the gross and microscopically, in rabbits hyperimmunized with a Group A streptococcal vaccine.

The immune serum, absorbed to yield only antibodies against C polysaccharide as indicated by agar diffusion techniques, will precipitate and neutralize the toxic material. This neutralization and in vitro precipitation can be inhibited with formamide-isolated C polysaccharide hapten and with N-acetylglucosamine, the primary directive group of this antigen. This clearly demonstrates that antibodies against the group-specific C polysaccharide are responsible for resistance to this toxic material.

The immunological and other properties of the toxic C polysaccharide complex, the fact that it is a product of Group A streptococci, the gross and microscopic features of the experimental lesion produced with this substance, and the observations on the chronic course of the experimental lesion, indicate that this toxic material should be investigated as a possible factor in the pathogenesis of the non-suppurative sequelae associated with Group A streptococci.
STUDIES OF PHAGOCYTOSIS OF GROUP A STREPTOCOCCI BY POLYMORPHONUCLEAR LEUCOCYTES IN VITRO
Authors: Hirsch James G. , Church Alice B.
Published: June 2004

Studies have been made on phagocytosis and killing of Group A streptococci during mixing with suspensions of leucocytes in vitro. Under appropriate test conditions an anti-phagocytic effect can be demonstrated for the streptococcal hyaluronic acid capsule as well as for its M protein.

The results obtained suggest an explanation for the suitability of human, but not rabbit, blood for opsonophagocytic tests designed to measure type-specific streptococcal antibodies. Human sera contain a factor which counteracts the anti-phagocytic effects of streptococcal hyaluronic acid capsules, and hence human blood serves well for detection of antibodies which combine with the only other phagocytosis-resisting component of this microorganism, namely M protein. In contrast, rabbit sera contain none of this factor, and addition of antibody to M protein to phagocytic test systems employing rabbit serum does not necessarily render the streptococci susceptible to engulfment by white cells, since the hyaluronic acid capsule may continue to interfere with phagocytosis.

The nature of the human serum factor which opsonizes encapsulated streptococci is unknown. It does not appear to be an antibody or an enzyme capable of depolymerizing hyaluronic acid.
ON THE ROLE OF RIBONUCLEIC ACID IN ANIMAL VIRUS SYNTHESIS
Authors: Tamm Igor , Nemes Marjorie M. , Osterhout Suydam
Published: June 2004

Adenosine, but not guanosine, was capable of blocking the inhibitory effect of 5,6-dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) on influenza virus multiplication in the chorioallantoic membrane in vitro. At virus inhibitory concentrations DRB caused marked inhibition in uptake of adenosine-8-C14 into RNA of uninfected host cells, but it had little effect on uptake of C14-L-alanine into host cell proteins or on cellular oxygen consumption. The activity of DRB in inhibiting multiplication of the DNA-containing adenovirus was similar to its inhibitory activity on multiplication of the RNA-containing influenza virus. These and earlier results are discussed from the point of view of the important role of RNA in the reproduction of DNA-containing viruses.
STUDIES ON FRACTIONS OF METHANOL EXTRACTS OF TUBERCLE BACILLI
Authors: Williams Curtis A.
Published: June 2004

Fractions of methanol extract which had been previously demonstrated to increase the resistance of mice to experimental tuberculosis have been subjected to an examination of their toxic and allergenic properties.

The criteria for toxicity were: (a) production of inflammatory skin reactions in guinea pigs; (b) induction of weight loss in mice by intraperitoneal injection; and (c) depression of resistance to staphylococcus infections in mice.

Allergenicity of a preparation was investigated by (a) its ability to evoke a hypersensitive skin response in guinea pigs previously sensitized with whole tubercle bacilli; and (b) its capacity to induce hypersensitivity to one or more of its components when injected under appropriate conditions into guinea pigs.

Fraction F I, a preparation precipitated from methanol extract by slow concentration at 45°C., was found to possess some toxicity and some allergenicity by all of the criteria employed.

Subfraction F I-P, precipitated from aqueous suspensions of F I by 33 per cent ethanol and 0.5 per cent NaCl, was apparently the F I component responsible for these activities. The saline-ethanol-soluble subfraction, F I-S, was neither toxic nor allergenic by the tests performed.

These findings were considered of particular interest inasmuch as F I-S, despite its small yield, had been shown earlier to be the most active single substance used as vaccine to increase resistance to experimental tuberculosis in mice.
GENETIC STUDIES OF INFLUENZA VIRUSES
Authors: Kilbourne Edwin D. , Murphy James S.
Published: June 2004

The passage of newly isolated, filamentous Asian (A2) influenza viruses in the presence of non-infective PR8 (A) virus results in the rapid emergence of virus of Asian (A2) antigenicity but PRS-like growth capacity and spherical morphology.

Evidence is presented that this effect results from genetic interaction of the infective Asian and non-infective PR8 viruses rather than from spontaneous change of the Asian strain.

It is concluded that influenza viral morphology, growth rate and growth capacity are associated genetic traits which distinguish unadapted from adapted strains, and which are transferable by recombination.

A pragmatic consequence of these experiments is the fact that conditions have been defined for the rapid adaptation of early passage influenza virus isolates to the chick embryo allantoic sac. Such adaptation is attended by an increase in viral yield which has obvious implications for vaccine production during future epidemics with new antigenic types.