bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON THE BIOLOGIC RELATIONSHIP OF ENDOTOXIN AND OTHER TOXIC PROTEINS
Authors: Condie Richard M. , Staab Edward V. , Good Robert A.
Published: June 2004

1. Agkistrodon piscivorus venom and E. coli endotoxin were shown to be immunologically distinct, and to differ in certain biologic properties: effects on immune response, body temperature, and circulating leukocyte count, and capacity to prepare for and provoke the local and generalized Shwartzman reaction.

2. Neither a single prior injection of venom nor the existence of hyperimmunity to lethal doses of venom protected rabbits against the local and generalized Shwartzman reaction.

3. Serial intravenous injections of sublethal doses of venom produced enhanced susceptibility to venom rather than refractoriness.

4. Preparation for both the local and generalized Shwartzman reaction with endotoxin appeared to enhance susceptibility of rabbits to challenge with venom.

5. Tolerance to bacterial pyrogens established by repeated injections of endotoxin is paralleled by increased resistance to snake venom given at least 1 week later, in mice and rabbits.

6. Zymosan failed to enhance susceptibility of rabbits to venom, but thorotrast increased the number of late deaths from venom.

7. Exposure of venom to ferrous sulfate interferes with its toxicity.
ANTIBODY FORMATION
Authors: Uhr Jonathan W. , Finkelstein Martin S. , Baumann Joyce B.
Published: June 2004

Injection of a small bacteriophage ϕX 174 into guinea pigs results in an accelerated elimination of phage detectable as early as 24 hours after injection. The immune nature of the accelerated elimination is indicated by its specificity, by the appearance of excess specific serum antibody after phage elimination, and by the prevention of accelerated elimination by 400 r whole body x-irradiation of guinea pigs prior to injection of phage. The early antibody response is considered to be a primary one since an analogous response occurs in newborn guinea pigs, antibody is not detectable in the sera of non-immunized animals, and the second challenge with ϕX stimulates a serum antibody response 100-fold greater than that after primary immunization. The early detection of immune elimination appears to be due, in part, to the small amounts of phage employed, since larger doses of phage delay the time of onset of detectable immune elimination. The early rise of serum antibody in the primary and secondary response appears exponential with a similar rate constant of antibody formation. The rate constant is also independent of dose. These findings have led to the suggestion that during this exponential phase, the relative rate of antibody formation at a cellular level may be constant for a given antigen.
STUDIES ON THE BINDING BETWEEN STREPTOCOCCAL M PROTEIN AND ANTIBODY
Authors: Grey Howard M.
Published: June 2004

A method for detecting type-specific antibody to type 12 ß-hemolytic streptococci is described. The method is based on the utilization of a partially purified I131 labeled streptococcal acid extract and the solubility of this extract in 40 per cent saturated ammonium sulfate as compared to the insolubility of antibody and antigen-antibody complexes at this salt concentration.

The salient features of this technique are:

(a) When absorbed sera were used, no non-type-specific reaction with antigen occurred.

(b) The sensitivity of the system allowed detection of type-specific antibody in hyperimmune antisera that had been diluted 1200-fold.

(c) The method does not rely on secondary manifestations of antigen-antibody interaction for the detection of antibody.

(d) As little as 0.03 µg of M12 protein was detected when soluble unlabeled M protein was used to inhibit the reaction between I131 M12 protein and anti-M12 antibody.

(e) The kinetics of the reaction between M protein and anti-M antibody can be studied, thereby making information available as to the quality as well as the quantity of antibody produced in this antigen-antibody system.
A STUDY OF IRON-INDUCED LIVER DAMAGE
Authors: Witzleben C. L. , Chaffey N. J.
Published: June 2004

The nature of short term iron-induced liver damage and its effect on the hepatic damage induced by other toxins have been studied by the use of histochemical techniques. The results suggest that a reduction of effective available sulfhydryl groups is a critical hepatotoxic property of storage iron. A reduction of glucose-6-phosphatase, consistently found in iron-loaded animals, demonstrates the sensitivity of the microsomes to the presence of storage iron. The mitochondria appear to be less sensitive, but may be affected under certain conditions. The results suggest that in order for simultaneously acting liver insults to result in additive damage, the mechanisms by which they act must have a critical and relatively specific relationship.
AGE AND SUSCEPTIBILITY OF MICE TO COXSACKIE A VIRUSES
Authors: Lerner A. Martin , Levin Howard S. , Finland Maxwell
Published: June 2004

Mice varying in age from 1 day to 8 months were inoculated intraperitoneally with Coxsackie A virus, type 9 and studies were made of the quantity of virus in striated muscle and myocardium, the presence of neutralizing antibody in the serum, and the pathological changes in the tissues.

The hind limbs of young (1- to 20-day-old) mice yielded high titers of virus and showed diffuse myositis, whereas only low yields of virus and focal myositis were obtained in older mice. In the 20-day-old mice the skeletal lesions were not accompanied by manifest symptoms and histologically showed evidence of regeneration progressing from the 3rd to the 11th day after inoculation. Older mice showed no symptoms and only focal myositis and low yields of virus were found in their hind limbs.

Coxsackie A9 virus replicated to relatively low titers in the hearts of young (1- to 40-day-old) mice without producing any demonstrable lesions whereas frank myocarditis with high yields of virus were demonstrated in mice infected at 8 months of age.

The data suggest that at least for the 2 strains used, the adult mouse should be considered susceptible to subclinical infection with Coxsackie A9 virus. Neither subclinical infection, nor antibody formation was demonstrable in young adult mice inoculated with a strain of Coxsackie A4 virus.
THE ENCEPHALOMYELITIC ACTIVITY OF MYELIN ISOLATED BY ULTRACENTRIFUGATION
Authors: Laatsch Robert H. , Kies Marian W. , Gordon Spencer , Alvord Ellsworth C.
Published: June 2004

A relatively simple preparation of guinea pig brain myelin, free of gross contamination by other cellular elements has been described. Electron microscopic evidence of the predominance of membranous (lamellar) forms was used as the criterion of purity of this fraction. The slight mitochondrial contamination of the myelin fraction was confirmed by its low succinic dehydrogenase activity. Quantitative bio-assay of the encephalitogenic activity of myelin showed it to have a higher specific activity than whole guinea pig brain. The low encephalomyelitic activity of the other subcellular constituents (nuclei and mitochondria) which were removed from myelin by ultracentrifugation in 30 per cent sucrose could be explained by a small amount of myelin contamination.

A basic protein of high specific encephalitogenic activity has been isolated from myelin by methods previously applied to whole brain. Although the protein is similar to nuclear histones, the following facts point to certain significant differences. Nuclei prepared by a different procedure from the one developed for the isolation of myelin were found to be non-encephalitogenic. Although basic protein could be extracted readily from these nuclei by dilute HCl, the same extraction procedure yielded little extractable protein from whole myelin. Myelin which had been defatted by cold chloroform-methanol yielded a basic protein which was highly encephalitogenic. The evidence presented thus supports the view that there exists in myelin a new basic protein responsible for the induction of experimental allergic encephalomyelitis, which is distinctly different from nuclear histones. The possible relationship of this protein to myelin structure and function has been discussed.
STUDIES ON THE TRANSPLANTED HEART
Authors: Chiba C. , Wolf P. L. , Gudbjarnason S. , Chrysohou A. , Ramos H. , Pearson B. , Bing R. J.
Published: June 2004

The metabolic changes in the homografted canine heart were studied in order to define the biochemical alterations accompanying homograft rejection. In several experiments, homograft rejection was accelerated by prior sensitization of the host animal.

The homografted heart released pyruvate and lactate as well as malic dehydrogenase and aldolase. Extraction of glucose by the graft usually remained positive. During the accelerated rejection, the release of pyruvate and lactate was more pronounced, and even glucose appeared in increased concentrations in coronary vein blood. In many experiments the respiratory quotient of the transplanted heart as well as its glucose-oxygen extraction ratio were elevated.

It seemed likely that the elevated respiratory quotients were the result of conversion of carbohydrates to fat, since the injection of thiamine hydrochloride resulted in further elevation of the respiratory quotient and in an increased myocardial pyruvate extraction. Apparently, thiamine corrected a metabolic block at the level of the cocarboxylase.

The metabolic block or blocks present in the transplanted heart are likely to be the result of diminution in intracellular enzymes and coenzymes resulting from increased cellular permeability. The redox potential across the transplanted heart was positive, indicating the absence of anoxia. The results illustrate that glycolysis proceeds in the transplanted heart in the presence of oxygen.

Histopathologic and histochemical studies show the earliest lesion to be an accumulation of lymphocytes around vessels at 3 hours. Swelling of vascular endothelium occurs. By 5 hours a polar perivascular cellular infiltrate of lymphocytes, plasma cells, macrophages, and histiocytes exists. Changes following at 19 hours show the appearance of Aschoff- and Anitschkow-like cells. Granulomatous myocarditis which was first perivascular became interstitial with lymphocytic and histiocytic invasion of the myocardium.

After 8 days acceleration of swelling of vascular endothelium and granulomatous lesions were observed and necrosis of the myocardium was prominent.

Endothelial hyperplasia occurred at 14 days. In the accelerated reaction these changes were intensified and necrosis began as early as 4 hours after grafting.

Histochemical changes of DPNH diaphorase, lactic, malic, and succinic dehydrogenase showed only significant diminution of malic dehydrogenase in the cardiac muscle which was concurrent with the increase of this enzyme in the serum.
DELAYED HYPERSENSITIVITY TO HAPTEN-PROTEIN CONJUGATES
Authors: Silverstein Arthur M. , Cell P. G. H.
Published: June 2004

The cross-reactions of conjugates carrying structurally related haptens have been studied in guinea pigs with delayed sensitivity to hapten-protein conjugates. The specificity of the delayed reaction has been found to be a function both of the nature and of the position of the substituent on the benzene ring; the cross-reactions shown in the delayed system, however, have been found to be appreciably more extensive than those reported for rabbit antibody systems employing identical haptens. This finding supports the earlier suggestion that the determinant in the delayed system is functionally larger than that required for reaction of antigen with conventional antibody.

Desensitization studies with cross-reacting antigens have indicated that the delayed hypersensitivity response is characterized by the production of a heterogeneous population of cells, all more or less closely adapted to the structure of the homologous hapten conjugate.
GROWTH CHARACTERISTICS OF MONKEY KIDNEY CELL STRAINS LLC-MK1, LLC-MK2, AND LLC-MK2(NCTC-3196) AND THEIR UTILITY IN VIRUS RESEARCH
Authors: Hull R. N. , Cherry W. R. , Tritch O. J.
Published: June 2004

The establishment of two strains of rhesus monkey kidney cells in continuous tissue culture, the development of a subline adapted to chemically defined medium, and the isolation of several clonal derivatives were described.

Growth characteristics, chromosome numbers, malignant potentiality, and freeze storage data are presented. The cells were studied for their sensitivity to a large number of viruses and were extensively compared with primary cultures of monkey kidney cells for sensitivity to poliovirus. The cell strains were not sensitive to all the viruses which could be grown in primary cultures of the same tissue but were susceptible to most of them. In some instances an advantage to the use of the cell strain for certain viruses was noted.
A LIPOGENIC TOXIN RELEASED THROUGH THE INTERACTION OF A NEW CYTOPATHIC AGENT (LIPOVIRUS) AND CULTURED HUMAN CELLS
Authors: Chang R. Shihman , Geyer Robert P. , Andrus Stephen B.
Published: June 2004

The release of a toxic product from cultured human cells infected by a new cytopathic agent (the lipovirus) was described. This toxin was dissociable from the infectious particles. It induced sudanophilia of human and mouse cells, an increase in the total fatty acid content, and a change in the major constituent fatty acids. Similar toxin was not demonstrated in cultures infected by the vaccinia herpes simplex, adeno 3, polyoma, polio 1 and 2, Coxsackie B1, parainfluenza A, and Rous sarcoma viruses. Preliminary characterization indicated that this toxin was resistant to tryptic digestion and could not be dialyzed or neutralized by human gamma globulin. It was inactivated at 58°C for 30 minutes, but stable at 37°, 4°, and –60°C. The significance of these findings is discussed.
THE CHARACTERIZATION OF STAPHYLOCOCCAL TOXINS
Authors: Kumar Surendra , Loken Keith I. , Kenyon Alan J. , Lindorfer Robert K.
Published: June 2004

The continuous flow paper electrophoretic methods used to isolate alpha hemolysin are presented.

The purity of the alpha hemolysin preparation is demonstrated by double agar diffusion, immunoelectrophoretic, and ultracentrifugation techniques.

Indirect evidence of purity is provided by the fact that rabbit immunized with purified alpha hemolysin produced detectable antibody only to alpha hemolysin.

Direct support is given to the "unitarian theory" by the demonstration that purified alpha hemolysin also possessed dermonecrotic, lethal, and leucocidal activities.

Further studies dependent on the availability of purified alpha hemolysin are outlined.
STUDIES OF THE GENERALIZED SHWARTZMAN REACTION PRODUCED BY DIET
Authors: McKay Donald G. , Wong Ting-Chao
Published: June 2004

The generalized Shwartzman reaction can be produced in pregnant rats by dietary means in the absence of injection of exogenous bacterial endotoxin. The experiment consists of a period of exposure to a diet low in tocopherol followed by exposure to a diet containing oxidized lipids during the gestation period. Pregnancy near term is an essential requirement for the development of the generalized Shwartzman reaction in these experiments. Fibrin thrombi were found in the renal glomeruli in 88.5 per cent, in the lungs in 94.2 per cent, in the liver in 11.4 per cent, in the spleen in 11.4 per cent, and in the adrenal in 40 per cent of animals that died spontaneously. There were pathologic alterations in the placenta which consisted of degeneration of the trophoblast, thrombosis of maternal blood channels in the giant cell trophoblast layer and in the labyrinth, congestion of the labyrinth, hemorrhage into the uterine cavity, placental separation, intra-uterine fetal death, decidual and uterine vein thrombosis, and placentitis in 10 per cent of the cases.

The mechanism by which the diet is instrumental in causing this reaction remains to be demonstrated.
THE FECAL FLORA OF VARIOUS STRAINS OF MICE. ITS BEARING ON THEIR SUSCEPTIBILITY TO ENDOTOXIN
Authors: Schaedler Russell W. , Dubos René J.
Published: June 2004

Adult mice from seven different colonies were studied with regard to (a) the numbers and types of bacteria that could be cultivated from their stools; (b) their resistance to the lethal effect of endotoxins prepared from three strains of Gram-negative bacilli.

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In six of the seven colonies, the stools yielded large numbers of various types of lactobacilli, enterococci, and Gram-negative bacilli. Most animals in these colonies died within 48 hours following injection of endotoxin.

The other mouse colony (NCS) has been maintained for the past three years at the Rockefeller Institute under exacting sanitary conditions; it is free of many types of common mouse pathogens. The stool flora of NCS mice yielded very large numbers of viable lactobacilli (109 per gm), representing at least three different morphological types. In contrast, it contained only few enterococci and Gram-negative bacilli (less than 106 per gm). Moreover, E. coli, Proteus sp., and Pseudomonas sp. could not be recovered from the stools under normal conditions. NCS mice proved resistant to the lethal effect of endotoxins.

These characteristics of the NCS colony prevailed whether the animals were housed continuously in individual cages on wire grids, or grouped continuously in large cages with wood shavings as litter. However, the composition of the bacterial flora could be rapidly and profoundly altered by a variety of unrelated disturbances such as sudden changes in environmental temperature, crowding in cages, handling of the animals, administration of antibacterial drugs, etc. The first effect of the change was a marked decrease in the numbers of lactobacilli and commonly an increase in the numbers of Gram-negative bacilli and enterococci. When tested 3 weeks after these disturbances some NCS animals were found to have become susceptible to the lethal effects of endotoxin.
THE EFFECT OF DIET ON THE FECAL BACTERIAL FLORA OF MICE AND ON THEIR RESISTANCE TO INFECTION
Authors: Dubos René J. , Schaedler Russell W.
Published: June 2004

A study was made of the effect of certain dietary regimens on the lactobacillus flora in the stools of mice and on their resistance to infection.

Semi-synthetic diets with purified casein or wheat gluten as sole source of protein, gave rise to much smaller numbers of viable lactobacilli in the stools than did other diets containing unidentified natural products—as present for example in mixtures of whole wheat and whole milk, or in certain commercial pellets. Furthermore, one of the lactobacillus types with rhizoid morphology disappeared completely from the stools of animals fed the semi-synthetic diet.

The change in the lactobacillus flora became apparent within a very few days after the animals had been shifted from the complex to the synthetic diet Moreover, this change was not completely reversible. Whereas the total numbers of lactobacilli increased when the animals were shifted back from the synthetic to the complex diets, the rhizoid lactobacilli which had disappeared completely from the stools reappeared only slowly or not at all.

In twelve consecutive experiments the three diets which gave rise to the large numbers of lactobacilli in the stools also conferred on the mice a much higher resistance to experimental infection with Staphylococcus aureus and Klebsiella pneumoniae, than did the semi-synthetic diets. However, direct evidence has not yet been obtained that the two kinds of phenomena were causally related.

Following administration of endotoxin there was a rapid and very large increase in the numbers of enterococci and coliform bacilli in mice fed the semi-synthetic casein diet, but not in those fed the pellets.

In two preliminary experiments carried out with another colony of mice, not pathogen-free, it was also found that the rhizoid type of lactobacilli disappeared from animals fed the semi-synthetic casein diet while enterococci and coliform bacilli progressively increased in numbers under the same conditions.

The dietary effects on the lactobacillus flora, and on resistance to experimental infection, were equally pronounced whether the mice were housed in individual cages on wire grids, or grouped in larger cages with wood shavings as litter. This was true even if the bedding was changed only once weekly and became therefore grossly soiled.
EFFECTS OF CHRONIC EXCESS SALT INGESTION
Authors: Dahl Lewis K. , Heine Martha , Tassinari Lorraine
Published: June 2004

Using the genetic technique of selective inbreeding, it has been possible to quickly develop two statistically separable populations from one unselected strain of Sprague-Dawley rats. One of these is very sensitive, the other very resistant, to the development of experimental hypertension from a high salt diet. It was suggested that similar genetic factors operate in man.
THE PLATING OF TUMOR COMPONENTS ON THE SUBCUTANEOUS EXPANSES OF YOUNG MICE
Authors: Henderson James S. , Rous Peyton
Published: June 2004

A procedure analogous to the plating of bacteria is described whereby some complex tumors have been taken apart and their components separately propagated. It was the outcome of finding that the forcible injection of Locke's solution followed by air can be used to split the subcutaneous connective tissue of sucklings and weanlings horizontally over the entire expanse of their backs or bellies, without inducing any complicating inflammation. Tumor fragments suspended in Locke's were widely scattered on the surfaces thus exposed. Most of them remained where they had lodged on the body wall, and rapidly becoming fixed in place, formed growths protected by the overlying cutaneous layer—which, throughout many weeks, remained unattached either to the wall or to them.

The procedure is more searching in its disclosure of tumor constituents than those currently employed, and it has the advantage that it preserves the neoplastic components that it reveals. It has been used thus far only to rescue for experimental purposes transplantable, benign, epidermal papillomas from the hidden carcinomas deriving from their cells, and to set free and maintain the neoplastic components of complex mammary tumors of milk factor type. Success was obtained with such of the latter as were chosen for separate propagation, though successive platings were sometimes required for their isolation. Incidentally the procedure revealed two components in the mammary growths which could not have been discerned by previous methods of search. Each formed tumors peculiar to itself.
VARIATION IN THE GROUP-SPECIFIC CARBOHYDRATE OF GROUP C HEMOLYTIC STREPTOCOCCI
Authors: Krause Richard M. , McCarty Maclyn
Published: June 2004

Certain strains of Group C hemolytic streptococci, termed Group C-intermediate, contain a group-specific carbohydrate antigen which gives a precipitin cross-reaction with A-variant antiserum. The carbohydrate antigens of these strains have a rhamnose:hexosamine ratio ranging from 2.4 to 2.6 whereas the ratio of typical Group C strains varies between 1.1 and 1.7. N-acetylgalactosamine, the major hexosamine in all of these strains is the principle determinant of Group C specificity. The high concentration of rhamnose in the C-intermediate carbohydrate suggests that a portion of the rhamnose oligosaccharide side chains are devoid of terminal N-acetylgalactosamine and thus react with Group A-variant antiserum. This view is supported by the fact that the induced variant enzyme, which destroys A-variant carbohydrate reactivity with the liberation of rhamnose oligosaccharides, has a similar action upon the Group C-intermediate carbohydrate. C-intermediate carbohydrate, after treatment with variant enzyme which removed approximately 25 per cent of the rhamnose, does not react with A-variant antisera.
SYNTHESIS OF VIRUS-SPECIFIC POLYMERS IN ADENOVIRUS-INFECTED CELLS: EFFECT OF 5-FLUORODEOXYURIDINE
Authors: Flanagan John F. , Ginsberg Harold S.
Published: June 2004

Biochemical synthesis in adenovirus-infected HeLa cells was studied utilizing 5-fluorodeoxyuridine (5-FUDR), a potent inhibitor of deoxyribonucleic acid production. Synthesis of saline-soluble DNA and infectious virus was completely suppressed by addition of the analogue to cells as late as 10 hours after infection. The inhibitory effect of this compound was totally reversed by addition of 10–6 M thymidine to the culture medium. Synthesis of DNA essential for virus production began 10 hours after infection and was completed by 16 hours after infection. These data support the hypothesis that the saline-soluble DNA is a precursor of infectious virus particles. Studies of antigen production indicated that formation of virus-specific proteins was directly dependent upon synthesis of DNA.
ROLE OF THE THYMUS IN IMMUNE REACTIONS IN RATS
Authors: Janković Branislav D. , Waksman Byron H. , Arnason Barry G.
Published: June 2004

Rats thymectomized at birth gained weight and otherwise developed normally, but were found to be very susceptible to intercurrent infections. Both Arthus reactivity and delayed hypersensitivity to BSA were markedly impaired in rats thymectomized during the first week of life and significantly impaired in rats thymectomized as late as 3 weeks after birth. The inhibition of Arthus reactivity in thymectomized rats was well correlated with their failure to develop significant titers of precipitating or hemagglutinating antibody. However, natural heteroagglutinin titers were not altered in these animals, and no abnormality of serum proteins, including γ-globulin could be detected by paper electrophoresis. The loss of immunologic activity could not be corrected by injecting homogenates of spleen or thymus before and during the sensitization period. Splenectomy at birth did not influence Arthus or delayed reactivity.
GLOMERULONEPHRITIS INDUCED IN SHEEP BY INJECTIONS OF HETEROLOGOUS GLOMERULAR BASEMENT MEMBRANE AND FREUND'S COMPLETE ADJUVANT
Authors: Steblay Raymond William
Published: June 2004

Sheep injected every 2 weeks with heterologous GBM and Freund's adjuvant by any one or combination of the following routes: intramuscular, subcutaneous, or intradermal, develop uniformly a fulminating, extracapillary glomerulonephritis, invariably fatal within 27 to 90 days after the first injection.

The chief histologic feature is marked fibroepithelial proliferation of Bowman's capsule with crescent formation. The appearance of the lesions resembles the acute, subacute, and chronic stages of human glomerulonephritis, and depends on when the animal was sacrificed.

Freund's adjuvant or heterologous GBM alone does not produce such a nephritis. The combination of placental tissue and Freund's adjuvant under the present experimental conditions was also unable to produce a nephritis.

The clinical course, increase in nitrogen retention, evolution of renal lesions, and death, all describe a fulminating disease. The disease most characteristically resembles fatal, fulminating human subacute glomerulonephritis.

The changes in serum proteins, decrease in serum albumin, and increase in serum globulin, occurred approximately the same in both the GBM-treated and the control adjuvant group. Similar changes have been reported from hyperimmunization alone, and so it is not clear how much these changes are due to immunization and how much is due to the nephritic process. The changes in serum cholesterol were not considered statistically significant.

Circulating serum antibodies which localized (by fluorescent antibody technique in vitro) on basement membrane structures of the heterologous donor kidney antigen or which produced nephritis in the heterologous donor species (rat and dog) were found in serum of sheep sick or dying of nephritis. The passive transfer of nephritis by serum antibodies marks the first successful instance of transfer of nephritis by serum antibody to a heterologous species from an animal which had developed nephritis itself. The serum antibodies involved in the transfer of disease to the donor species appear to be unrelated to the mediators of nephritis in the sheep and may represent only the previously known heteronephrotoxic antibodies. By various biologic criteria the sheep nephritis presumably occurs by an autoimmune mechanism. However, it is not known whether the sheep nephritis is mediated by sensitized cells and/or antibodies.

The latent period was estimated to end about 16 to 71 days after the first injection. Azotemia was estimated to begin about 17 to 78 days after the first injection. Proteinuria and azotemia began approximately 23 and 13 days before death. The rapid progression to a fatal termination defined the fulminating character of this disease.
GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO
Authors: Thorbecke G. J. , Asofsky R. M. , Hochwald G. M. , Siskind G. W.
Published: June 2004

Antibody formation in vitro by red and white pulp of the spleen and by bone marrow tissue was studied at various days after an intravenous booster injection of soluble antigens such as ovalbumin and bovine gamma globulin (BGG). When the booster injection of antigen was given early (10 days) after an intravenous primary injection, high antibody formation could be demonstrated in the spleen primarily 2 to 3 days after the injection, but much less afterwards. When the booster injection was given later (1 month) after the primary, the antibody production by the spleen lasted longer and higher serum titers were obtained. The bone marrow formed antibody in both cases but, particularly with the short interval between injections, its response was delayed as compared to the spleen. It was also shown that during antibody formation the production of gamma globulin in vitro was enhanced. Histologically the antibody production was always correlated to immature plasma cell proliferation, located at the border of red and white pulp and in the red pulp of the spleen.

When endotoxin had been injected at the time of a primary BGG injection, and a second antigen injection was given 5 to 10 days later, a booster response could be elicited which was sometimes limited to the white pulp on day 1, and on day 2 was divided between "red" and "white" pulp. The response induced at day 10, at the peak of secondary nodule proliferation, lasted very long and was accompanied by an enormous plasma cellular proliferation in and around the periarteriolar lymphoid areas of the spleen. The possible importance of the secondary nodules of the white pulp in the preparation for a secondary response is discussed.
THE ROLE OF ANTIBODY, DELAYED HYPERSENSITIVITY, AND INTERFERON PRODUCTION IN RECOVERY OF GUINEA PIGS FROM PRIMARY INFECTION WITH VACCINIA VIRUS
Authors: Friedman Robert M. , Baron Samuel , Buckler Charles E. , Steinmuller Robert I.
Published: June 2004

In guinea pigs, methotrexate and x-radiation have been employed to block the development of delayed hypersensitivity and of antibody to vaccinia virus during experimental infection.

Animals whose specific responses were blocked by x-radiation and methotrexate recovered from vaccinia virus infection as rapidly as non-treated control animals suggesting that these responses were not essential in recovery of the infected animals.

A virus-inhibiting substance with the properties of interferon was present in skin of untreated and methotrexate- and x-radiation-treated animals infected with vaccinia virus.
PATHOGENESIS OF EXPERIMENTAL SHOCK
Authors: Janoff Aaron , Weissmann Gerald , Zweifach Benjamin W. , Thomas Lewis
Published: June 2004

Fatal shock was produced in animals by drum trauma, temporary occlusion of the superior mesenteric artery, and bacterial endotoxin. Measurements were made of release of beta glucuronidase and cathepsins from the large granule fractions of livers, and of levels of circulating beta glucuronidase and acid phosphatase in these animals. Experiments were also carried out with animals rendered tolerant by previous exposure to sublethal amounts of trauma or by pretreatment with cortisone.

The results show that release of beta glucuronidase and cathepsins from the large granule fraction of liver was increased during traumatic and endotoxin shock in the rat. Similarly, circulating levels of acid phosphatase and beta glucuronidase were increased during traumatic shock in rats and rabbits, and during endotoxin shock in rats. The data also indicate that tolerance to traumatic injury, induced by prior conditioning, prevented the increase in levels of circulating acid phosphatase normally observed after stress, and may have been associated with an increased stability of hepatic lysosomal particles. In addition, cortisone, which appears to "stabilize" hepatic lysosomes in vivo, also reduced the increase in plasma acid phosphatase brought about by endotoxin and trauma.

From the foregoing observations, it is suggested that: (a) Disruption of lysosomes and release of their contained enzymes in free, active form may occur in liver and intestine of shocked animals. (b) The activation of lysosomal hydrolases within cells and their release into the circulation may play an important role in exacerbating tissue injury and accelerating the development of irreversibility during shock. (c) The increased stability of lysosomes of tolerant and of cortisone-treated animals may constitute an important component of the resistance of these animals to shock.
RELEASE OF GENETIC TRANSFORMING AGENT FROM PNEUMOCOCCAL CULTURES DURING GROWTH AND DISINTEGRATION
Authors: Ottolenghi Elena , Hotchkiss Rollin D.
Published: June 2004

Genetic transformations of pneumococcus mediated by streptomycin-induced lysates were studied to gain some insight into the nature of freshly released transforming principle, and the influence of the physiologic state of the donor population on the transformation process. It was found that streptomycin could make the DNA of sensitive cells available for transformation of other cells.

Living cultures of pneumococcus growing exponentially in ordinary media were also found to discharge significant quantities of genetically active DNA. Such cultures, not treated with any drug, showed no evidence of concomitant cell disintegration or death.

Both single markers and small linkage groups could be transferred in transformations mediated by drug-induced lysates and by filtrates of living cultures. The quantity of DNA liberated is small (less than 0.1 µg per ml), but these transformations are at least as efficient as transformations mediated by purified DNA, when compared on the basis of total DNA available. Up to 1 per cent of the cells in an average recipient culture can be transformed by a small quantity of culture fluid.

Both in drug-treated and in untreated cultures the amount of transforming activity increased and then decreased during growth of the culture. Although the source of transforming DNA in growing cultures could not be established, the decline in the transforming activity of aging drug-treated or untreated cultures was attributed to the presence of deoxyribonuclease. The release of this nuclease by pneumococcal cultures midway in exponential growth is sufficient to result in a mild degradation of the low concentration of freshly released transforming agent present.

Maximal release of active transforming agent by a living culture coincided in time with the development of maximal receptivity to exogenous DNA by that culture. As a result, recombinants could be recovered from appropriately genetically marked strains growing in each other's presence.

In view of these results, it seems possible that DNA-mediated transformations might provide, or might have provided, a mechanism of genetic recombination in nature for some bacterial species in which sexual mechanisms may not be available.
FACTORS RELATING TO THE VIRULENCE OF STAPHYLOCOCCI
Authors: Koenig M. Glenn , Melly Marian Ann , Rogers David E.
Published: June 2004

Four clumping factor-negative strains of Staphylococcus aureus were found to closely resemble the diffuse colonial variant of the Smith strain. All produced fatal intraperitoneal infections in mice, all grew in diffuse, streaming colonies in plasma or serum soft agar, and all behaved like encapsulated microorganisms in in vitro opsonic systems.

These staphylococci were resistant to phagocytosis in the peritoneal cavities of normal mice. When mice were immunized with heat-killed vaccines prepared from the Smith diffuse variant these strains were rapidly ingested by peritoneal leukocytes and the animals survived. This observation suggests that these strains share the same or a similar phagocytosis-retarding antigen.

While most pathogenic staphylococci isolated from human material do not behave like these unusual mouse-virulent strains, indirect evidence is cited to support the suggestion that other staphylococci may acquire similar phagocytosis-resisting characteristics during in vivo multiplication. Studies to support or refute this thesis are in progress.
EFFECTS OF BACTERIAL ENDOTOXIN ON RABBIT PLATELETS
Authors: Horowitz Herbert I. , Des Prez Roger M. , Hook Edward W.
Published: June 2004

Incubation of rabbit platelet-rich plasma with bacterial endotoxin results in activation of platelet factor 3, a precursor of blood thromboplastin. This platelet-endotoxin interaction is dose- and temperature-dependent, and is similar to the effects of antigen-antibody union in the presence of platelets. Injection of endotoxin intravenously is associated with a transient increase in platelet factor 3. Since platelet factor 3 can be demonstrated in platelet-poor plasma as well as platelet-rich plasma after endotoxin injection, it seems likely that an actual transfer of factor 3 from platelets to plasma occurs and that this activity is then rapidly inactivated or cleared from the blood stream.
SUPPRESSION OF ALLERGIC UVEITIS BY 6-MERCAPTOPURINE
Authors: Wirostko E. , Halbert S. P.
Published: June 2004

Experimental uveitis in rabbits was induced by single intraocular antigen injection. Treatment with 6-MP for 14 days suppressed the allergic inflammation and antibody response. A good correlation was demonstrated between the degree of uveitis and the antibody titer.
THE PROPAGATION OF THE VIRUS OF EPIZOOTIC HEMORRHAGIC DISEASE OF DEER IN NEWBORN MICE AND HELA CELLS
Authors: Mettler Norma E. , MacNamara Lester G. , Shope Richard E.
Published: June 2004

The New Jersey strain of EHD virus has been propagated in newborn Swiss mice by the intracerebral route and is regularly lethal beyond the first serial mouse passage. A complement-fixing antigen prepared from the brains of infected mice reacts positively with the sera of deer recovered from infection with either the New Jersey or South Dakota strain of virus, but not with the serum of normal deer. The mouse-passaged virus induced an inapparent infection in an experimental deer.

The virus can also be grown serially in HeLa cell culture and induces a characteristic cytopathic effect. It is neutralizable in such cultures to high titer by the sera of deer recovered from EHD (New Jersey strain) and to lower titer by the serum of a deer recovered from EHD (South Dakota strain). Normal deer serum does not neutralize the virus in tissue culture. The HeLa cell-passaged virus induced typical lethal EHD in an experimental deer and virus could be recovered from most of the tissues of this animal in HeLa cell culture. An unexplained prozone of inhibition of cytopathogenicity at low dilutions was observed in cultures of some of the organs.

The fact that EHD virus exhibited a limited sensitivity to sodium desoxycholate suggests that it may belong in the arbor virus group.
HISTOPATHOLOGICAL AND HISTOCHEMICAL ALTERATIONS IN THE EARLY STAGES OF CORNEAL GRAFT REJECTION
Authors: Polack Frank M.
Published: June 2004

Rejection of corneal grafts was produced in rabbits after skin from the corneal donor was grafted subcutaneously. Clinical observations showed that the graft sickness started at the periphery of the graft after blood vessels from the host cornea reached the scar. Histologic studies demonstrated that the scar tissue was first invaded by vessels and infiltrated by lymphocytes, monocytes, and plasma cells. This infiltrate reached the endothelium through the gap in Descemet's membrane. The early histological picture of the graft sickness was characterized by endothelial destruction and infiltration at its junction with the scar. Keratocytes changed in shape and apparently became active fibroblasts.

Decreased amounts of ground substance in the early stages of rejection, as indicated by appearance of haziness in the graft, were indicated in sections by a decrease in metachromatic staining. Diminished uptake of radioactive sulfate also occurred in the early stages of the graft sickness; which was followed by an elevated uptake of sulfate as the graft became opaque and filled with active fibroblasts.
A CARRIER STATE OF MUMPS VIRUS IN HUMAN CONJUNCTIVA CELLS
Authors: Walker Duard L. , Hinze Harry C.
Published: June 2004

Mumps virus in a carrier culture of human conJunctiva cells (C-M cultures) persisted through 5½ months of cultivation in a medium containing sufficient specific antiserum to keep the fluid free of infectious virus. Cells from the C-M cultures were cloned under antiserum with an efficiency equal to control, uninfected cultures (40 to 100 per cent). Of 269 C-M cell clones examined, the cells of 262 contained antigen. Eight infected clones were grown into cultures sufficiently large to demonstrate that they released infectious virus and adsorbed erythrocytes in a manner similar to the original C-M cultures. Two uninfected clones were as susceptible to the effects of a cytopathogenic line of mumps virus as were uninfected control cells.

In healthy, growing cultures of C-M cells 0.1 to 1.0 per cent of cells adsorbed erythrocytes to their surfaces, suggesting that these cells were releasing virus. Reduction of serum content of the medium to less than 3 per cent, depletion of the medium, or crowding of cultures resulted in hemadsorption by 50 to 90 per cent of cells and an increase of virus in the medium. In growing cultures hemadsorbing cells did not appear damaged. It was observed that cells could simultaneously exhibit hemadsorption and mitosis.
CINEMICROPHOTOGRAPHIC OBSERVATIONS ON GRANULE LYSIS IN POLYMORPHONUCLEAR LEUCOCYTES DURING PHAGOCYTOSIS
Authors: Hirsch James G.
Published: June 2004

Phagocytosis of yeast cell walls and of Bacillus megaterium by human, rabbit, and chicken polymorphonuclear leucocytes has been observed by phase contrast microscopy and recorded on motion picture film. In suitably thin preparations intracellular events could be visualized well.

Lysis of cytoplasmic granules began early in the course of the ingestion process, rupture occurring only in granules adjacent to the microorganism being engulfed. Formation of a visible vacuole about the ingested particle frequently followed degranulation.

Chicken polymorphonuclear leucocytes, with their large phase-dense granules, were particularly suitable subjects for observations on detailed morphologic aspects of granule lysis. Rupture took place rapidly (0.1 second or less); in place of the granule there appeared a clear zone, often with a small phase-dense round structure in its center. Also accompanying granule lysis was an increase in phase density of the adjacent surface of the microorganism. Over the course of the following few seconds the darkening on the organism faded, the dense small body disappeared from view, and the clear zone contracted towards the engulfed particle.

The observations are discussed in relation to the hypothesis that fusion takes place between the granule membrane and the invaginated cell membrane overlying the ingested particle, with discharge of granule contents directly into the phagocytic vacuole.
ALTERATION OF RESISTANCE OF THE RAT TO TUBERCULOSIS WHEN MAINTAINED ON AN ATHEROGENIC DIET
Authors: Costello Richard L. , Hedgecock Loyd W. , Hamilton Tom R.
Published: June 2004

Albino rats maintained for 50 to 60 days on rations containing cholesterol, sodium cholate, and thiouracil were found to be highly susceptible to the lethal effects of infection with Mycobacterium tuberculosis. Maximum loss of resistance occurred only when all three components were present in a single ration. A lesser degree of susceptibility resulted from the deletion of one or more of the factors from the diet. Animals maintained on control rations never died of the infection.

Histopathological studies of stained sections of tissues of infected animals revealed that the reaction of the host to the bacillus was more extensive and less well contained in animals fed the complete atherogenic ration than in the controls.
ISOLATION AND PROPERTIES OF A GROUP ANTIGEN OF STAPHYLOCOCCUS ALBUS
Authors: Morse Stephen I.
Published: June 2004

An antigen composed of glycerophosphate and glucose has been isolated from the cell walls of a strain of Staphylococcus albus. The antigen reacted with homologous and heterologous S. albus antisera. Similar material was isolated from the cell walls of three other S. albus strains. The antigen did not react with S. aureus antiserum nor with normal human or rabbit serum.

The antigen appeared to have a backbone structure of glycerophosphate with appended monoglucoside units. The antigenic determinant was shown to be glucose in alpha linkage.
THE FATE OF BACTERIA WITHIN PHAGOCYTIC CELLS
Authors: Cohn Zanvil A.
Published: June 2004

The influence of immune serum, PMN leucocytes, and macrophages from immunized animals and metabolic inhibitors on the intraphagocytic degradation of isotopically labeled bacteria has been evaluated.

Immune serum specifically delayed the degradation of a variety of P32- and C14-labeled organisms within both types of phagocytic cells. The active principle in immune serum was found to be a globulin which could be removed by adsorption with the homologous organism. The inhibiting action of immune serum was thought to be related to its combination with the bacterial surface and the subsequent temporary protection of the bacteria from leucocyte enzymes.

PMN leucocytes and macrophages obtained from immune hosts did not differ from normal cells in their ability to degrade homologous, labeled bacteria. Immune serum had the same inhibiting influence in the presence of "immune" cells as with cells from non-immunized hosts.

Iodoacetate, arsenite, and cyanide at concentrations which inhibited the glycolysis and respiration of both PMN leucocytes and macrophages had no influence on the rate of degradation of isotopically labeled bacteria engulfed by these cells. This implied that following the initial phagocytic events, the degradation of bacteria within leucocytes is not dependent upon the major pathways of energy metabolism.
STUDIES ON ARTIFICIAL ANTIGENS
Authors: Kantor Fred S. , Ojeda Antonio , Benacerraf Baruj
Published: June 2004

Dinitrophenyl conjugates of poly-L-lysine, varying in percentage conjugation and molecular weight have been found to induce skin reactivity and precipitating antibodies in guinea pigs. At best, 40 per cent of immunized animals developed delayed and immediate responses to DNP-polylysine, which is believed to reflect constitutional differences among the animals assayed. Only those animals capable of responding to DNP-polylysine, responded to an immunologically distinct poly-α-amino acid consisting of glutamyl and lysyl residues ("copolymer glu-lys"). The percentage of animals responding to the DNP-polylysine antigen decreased as the degree of DNP conjugation increased.