bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF ANTIBACTERIAL DRUGS ON THE FECAL FLORA OF MICE
Authors: Dubos Rene , Schaedler Russell W. , Stephens Mallory
Published: June 2004

Oral administration of penicillin, terramycin, or chloramphenicol to NCS mice rapidly brought about profound changes in their fecal flora. The lactobacilli disappeared completely, whereas the numbers of enterococci and Gram-negative bacilli reached very high levels. In contrast, no effect on the fecal flora could be detected following administration of isoniazid in any amount.

The intensity and duration of the effects on the fecal flora were related to the type of drug and to the amount of it administered. Chloramphenicol produced disturbances which were less profound and of shorter duration than those produced by penicillin or terramycin.

The duration of the disturbances in the fecal flora produced by antibacterial drugs was markedly conditioned by the nutritional regimen. The fecal flora returned to its pretreatment state (large numbers of lactobacilli, few enterococci, and few Gram-negative bacilli) within less than 4 weeks after discontinuing the drug when the mice were fed a complex diet of ill defined composition (commercial pellets). Contrariwise, the fecal flora remained markedly different from that of control mice when the animals were fed semisynthetic diets containing as source of protein either 15 per cent casein or 15 per cent wheat gluten (both supplemented with cystine); or 15 per cent wheat gluten supplemented with lysine, threonine, and cystine.

The fecal flora of mice treated with penicillin contained large numbers of lactose-fermenting Gram-negative bacilli, not found in the untreated animals. These lactose fermenters persisted for several months after discontinuance of the drug in mice fed either the casein or gluten diets, but they disappeared rapidly from mice fed pellets.

Similar results, although less striking, were obtained with Swiss mice from colonies maintained under usual conditions, and therefore having a fecal flora more complex than that of NCS mice.
SUPPRESSION OF BLOOD GROUP AGGLUTINABILITY OF HUMAN ERYTHROCYTES BY CERTAIN BACTERIAL POLYSACCHARIDES
Authors: Ceppellini Ruggero , Landy Maurice
Published: June 2004

Erythrocytes coated with bacterial capsular polysaccharides, notably the Vi antigen, were no longer agglutinated by antibodies directed against the various antigens native to the red cell surface. These effects could not be attributed to prevention of antibody uptake even though in some systems the uptake of antibody was diminished. In fact, agglutination by Rh-incomplete antibody was brought back to the original titer only after the sensitized Vi-coated cells had been subjected to ten alternating exposures to globulin and antiglobulin. Hemagglutination by Newcastle, mumps, and influenza viruses was also suppressed. Erythrocytes coated with Vi polysaccharide assumed the distinctive physicochemical attributes of this acidic polymer which results in a stabilization of the erythrocyte suspension as manifested by increased electrophoretic mobility and a striking decrease in the rate of sedimentation. Among the possible models for explaining the nature of the Vi effect on immune agglutination, the data favor interference with lattice formation.
THE HISTOGENESIS OF BASEMENT MEMBRANES
Authors: Pierce G. B. , Midgley A. R. , Ram J. Sri
Published: June 2004

A parietal yolk sac carcinoma of the mouse that secretes large quantities of basement membrane-like material has been used to study the formation of basement membranes. Suitably characterized fluorescein-labeled antibodies against this material stained basement membranes of epithelial structures and vessels, as well as reticulin. When absorbed with reticulin and vascular basement membranes of the spleen until these structures no longer fluoresced, the antibody still stained the basement membrane-like material of the tumor, its normal embryonic counterpart (Reichert's membrane), and the basement membranes at the bases of epithelial cells.

The observation made previously that parietal yolk sac cells secreted, in the absence of connective tissue and reticulin, the basement membrane (Reichert's membrane) upon which they rested has been confirmed through the localization of ferritin-labeled antibody to the endoplasmic reticulin of the secreting cells.

Since a basement membrane proven to be an epithelial secretion is antigenically similar to basement membranes at the bases of all epithelial cells studied but antigenically different from connective tissue elements, it is postulated that the basement membranes at the bases of epithelial cells in general are an epithelial secretion, and are not a condensation of ground substance as is commonly believed.
ANTIGEN-ANTIBODY REACTION IN THE PATHOGENESIS OF BILATERAL RENAL CORTICAL NECROSIS
Authors: Lee Leung
Published: June 2004

In the presence of reticuloendothelial blockade, the intravenous injection of a protein antigen into specifically immunized rabbits or the infusion of soluble immune complexes into normal animals has been shown to result in the production of bilateral renal cortical necrosis. The similarity in the pathogenesis of this lesion and that seen in the classical generalized Shwartzman reaction produced by bacterial endotoxins is indicated by (a) the failure of both lesions to develop in animals pretreated with large doses of heparin, (b) by the finding of "heparin-precipitable fibrinogen" in the circulation, and (c) by the presence of massive fibrin deposits within the glomerular capillaries. These findings indicate that antigen-antibody reactions in vivo are capable of activating the blood coagulation system and that the mode of action of bacterial endotoxins may have an immunological basis.
ON THE RELATION OF INFLAMMATION TO THE CHEMICAL CONSTITUTION OF INJURIOUS AGENTS. ON THE PHARMACOLOGY OF INFLAMMATION
Authors: Opie Eugene L.
Published: June 2004

Changes characteristic of an inflammatory reaction caused by the injection of an injurious agent into the peritoneal cavity were measurable by the quantity of peritoneal fluid, by the number of leucocytes that entered the cavity, and by the abundance of exuded protein.

Inflammation increased in severity along with ion dissociation and increase of the valence of electrolytes. With chlorides, sulfates, and nitrates it increased in each instance with the valence of their basic ions. The reactions caused by sodium chloride, sodium sulfate, and sodium citrate increased with the valence of their acid ions.

Salts of heavy metals which fix and precipitate proteins caused more active inflammation than did other electrolytes.

Histamine and arginine caused active inflammatory reactions with similar characteristics.

The amino compounds, urea, citrulline, and creatinine, glycine, alanine, histidine, arginine, and histamine, produced inflammatory reaction in the order of severity with which, in foregoing experiments, they had caused necrosis when injected into the dermis.

The acids and alkalis that were tested caused active inflammation when their acidity approached pH 1 or their alkalinity pH 11 respectively, but with approximate neutrality the inflammatory reaction became scant. These changes were in accord with the extent of necrosis when acid or alkalis, in foregoing experiments, were injected into the dermis.

When histamine or arginine combines with hydrochloric acid to form histamine dihydrochloride or arginine monohydrochloride alkalinity is lost and inflammatory reactions caused by the hydrochlorides are relatively mild. The characteristic changes which accompany histamine and arginine do not occur. The combination of histamine with phosphoric acid to form histamine acid phosphate has similar relation to histamine.

Inflammatory reactions caused by monobasic, dibasic, and tribasic sodium phosphate increased in activity in accord with increasing alkalinity referable to the basic ions of these salts.

The activity of inflammatory reactions has been found to vary in accord with the chemical constitution of the injurious agents that have been tested.
THE DEVELOPMENT OF THE IMMUNE RESPONSE
Authors: Bellanti Joseph A. , Eitzman Donald V. , Robbins John B. , Smith Richard T.
Published: June 2004

By intensive stimulation with large amounts of Salmonella flagellar antigen, newborn rabbits were induced to form high titer flagellar agglutinins usually by the 7th to 10th day of life. Characterization of the agglutinins at various times during the first 30 days of life revealed that the earliest antibody which appeared was a gamma-1 macroglobulin, and that 7S gamma-2 globulins did not appear until the 4th or 5th week of life. In contrast, the adult animals produced macroglobulin antibodies for only 3 to 5 days before the lower molecular weight variety appeared. The infant macroglobulin appears to be similar in all respects to adult macroglobulin antibodies.

These data are interpreted to indicate that the newborn and adult rabbit differ in their response to this type of stimulus not in timing of macroglobulin antibody production, but chiefly in the prolonged interval, which precedes the development of the capacity for the 7S type response in the newborn animal.
STUDIES OF THE MECHANISM OF ACTION OF THE SHOPE RABBIT PAPILLOMA VIRUS
Authors: Rogers Stanfield , Moore Margaret
Published: June 2004

These studies make plain that the Shope papilloma virus induces the production of an arginase in rabbit squamous epithelium, and provide evidence that the information for the synthesis of the enzyme is derived from the virus rather than the rabbit. This form of induction is therefore different from that brought about by chemicals such as galactosides (36).

Striking differences were shown between the physiochemical properties of Shope virus-induced arginase and other arginases of domestic and Kansas cottontail rabbits.

The absence of a requirement for manganese suggests the mechanism of splitting off urea from arginine by papilloma arginase probably differs from that of previously described arginases.

These findings (particularly the experiments in which it was demonstrated that papilloma growth could be greatly reduced by giving animals supplemental arginine in the presence of small amounts of the arginase inhibitor, canavanine) provide evidence that suggests the following mechanism of action for the virus: viral DNA introduces into rabbit epithelium the information for the synthesis of an arginase for which the cells have no control mechanism. The arginase depletes cellular arginine and, in turn, the synthesis of arginine-rich nuclear histones (2), thereby freeing the nucleus for greater synthetic activity (4, 35), which results in more rapid growth of the papilloma cells.

Domestic rabbit papillomas induced with purified virus derived from wild rabbit papillomas were shown to contain an antigen which reacts immunologically like a wild rabbit antigen. It was distinct from the arginase, the protein coat of the virus, and the Vx-2 antigen. The presence of the wild rabbit antigen seems indicative of integration of the virus DNA in the host genome of the wild rabbit.

Other incidental findings include the description of a simple method, accurate to within 1 per cent, for determining the partial specific volume of a protein, and the description of a modification of the Richards and Schachman method (9) enabling the determination of the molecular weight and homogeneity of a protein with as little as 0.25 mg and with an accuracy of 2 per cent.
THE FATE OF INJECTED BENCE JONES PROTEIN
Authors: Meyer Franz , Putnam Frank W.
Published: June 2004

Bence Jones protein injected into rabbits was excreted rapidly into the urine. The excreted protein retained the physicochemical and immunochemical properties of the injected Bence Jones protein. In spite of the rapid excretion, a significant portion of the injected Bence Jones protein was found to be metabolized. After reinjection of radioactive Bence Jones protein into the donor patient, only a little radioactivity was recovered in the urinary protein. The implications of these results are discussed.
ANTIBODY FORMATION INITIATED IN VITRO
Authors: Fishman M. , Adler F. L.
Published: June 2004

The diffusion chamber technique permitted the demonstration of specific antibody formation in x-irradiated recipients of such chambers filled with normal lymph node cells and a cell-free homogenate of macrophages which had been incubated in intro with T2 bacteriophage.

The activity of the cell-free homogenate was retained in its RNA fraction isolated by means of the phenol method.

No antibody formation occurred if such RNA was treated with RNAase. On sucrose gradients (5 to 20 per cent), the active RNA was found to be present in the top third layer.

The question of the possible presence of antigen complexed to the RNA is discussed.
ELECTRON MICROSCOPIC STUDIES OF EXPERIMENTAL NEPHRITIS WITH FERRITIN-CONJUGATED ANTIBODY
Authors: Andres Giuseppe A. , Seegal Beatrice C. , Hsu Konrad C. , Rothenberg Mildred S. , Chapeau Madeleine L.
Published: June 2004

Acute, subacute, and chronic glomerulonephritis, similar in certain features to human glomerulonephritis, has been produced in rabbits by repeated injections of bovine serum albumin. The ratio of antigen to antibody was the factor determining the development and type of glomerulonephritis. This is in confirmation of the observations of Dixon, Feldman, and Vazquez.

With the aid of the ferritin antibody technique it was shown that antigen aggregates (probably antigen-antibody complexes) are present in the blood, cross the endothelium and the basement membrane, and accumulate as dense deposits between the basement membrane and the epithelial cytoplasm.

In the deposits electron-dense aggregates formed by antigen or by antigen-antibody complexes and material which might be other endogenous proteins may be identified.

In rabbits dead of anaphylactic shock following injection of bovine serum albumin, dense material was found within glomerular capillaries, presumably formed by the embolic deposition of antigen-antibody complexes, since the immunofluorescein and immunoferritin techniques demonstrated the presence of both BSA and rabbit globulin.
STUDIES ON THE MULTIPLICATION AND THE PROPERTIES OF THE LACTIC DEHYDROGENASE AGENT
Authors: Notkins Abner Louis , Shochat Stephen J.
Published: June 2004

The procedure used to determine the infective titer of the LDH agent, the reproducibility of this assay, and the relationship between virus dose and plasma enzyme activity were described. Multiplication of the LDH agent began within 6 hours after infection and reached 1010.8 ID50/ml of plasma within 24 hours. The titer rapidly decreased over the next 72 hours but viremia persisted for at least 16 months with titers as high as 105.2 ID50/ml. The appearance of the LDH agent in the circulation preceded the first noticeable rise in plasma LDH activity by close to 24 hours. After 10 months, when the plasma titer of the LDH agent had decreased nearly one millionfold, the plasma enzyme LDH had decreased by less than 50 per cent.

The LDH agent is inactivated by ether but withstands lyophilization, and freezing and thawing. It is stable at low temperatures. Ultracentrifugation at 105,000 G for 2 hours leaves less than 0.1 per cent of the LDH agent in the supernatant fluid and filtration through gradocol membranes suggesst that the upper size of the LDH agent is about 55 mµ.

Spread of the LDH agent from infected to uninfected mice kept in the same cage and transmission from mothers (infected prior to mating) to their offspring was relatively low.
THE ROLE OF THE CHEEK POUCH IN EFFECTING TRANSPLANTATION IMMUNITY IN THE HAMSTER
Authors: Shepro David , Kula Nora , Halkett James A. E.
Published: June 2004

The cheek pouch of the hamster is alymphatic.

Molecules, too large to penetrate the vascular endothelium, reach general circulation by slowly diffusing through the cheek pouch membrane to vessels found in the connective tissues in the neck and these vessels drain primarily into the superficial cervical node.

The tissues of the cheek pouch membrane limit the diffusion of large particles and it is this "barrier" which explains, in part, the "privilege" conferred by the cheek pouch.
PASSIVE TRANSFER OF CONTACT SENSITIVITY BY TRITIATED THYMIDINE-LABELED LYMPHOID CELLS
Authors: Najarian John S. , Feldman Joseph D.
Published: June 2004

Passive transfer of tritiated thymidine-labeled lymphoid cells sensitized to the simple chemical DNFB into homologous guinea pigs resulted in positive contact skin reactions 24 hours after skin testing with DNFB. Labeled sensitized cells were found to accumulate at these sites, whereas, labeled nonsensitized lymphoid cells did not appear non-specifically in contact skin reaction sites. The labeled cells were small and large lymphocytes and immature cells of the lymphoid series. The maximum reactions were obtained at 24 hours, with an average of 3.4 per cent of the infiltrating mononuclear cells showing a label. At 48 hours, the macro- and microscopic reactions were similar to the 24 hour reactions but diminished in intensity, and the number of labeled cells in the infiltrates had decreased to 1 per cent of the total infiltrating mononuclear cells. ¼ to ⅓ of the labeled cells were found within the epidermis in the test skin sites.

These data have indicated that contact sensitivity, like tuberculin sensitivity, required the sensitized cell to initiate the skin reaction and that the majority of the cellular infiltrate was the result of non-specific host response to injury.
FETAL RESPONSE TO ANTIGENIC STIMULUS
Authors: Silverstein Arthur M. , Uhr Jonathan W. , Kraner Keith L. , Lukes Robert J.
Published: June 2004

The fetal lamb in utero is able to form large amounts of specific antibody in response to antigenic stimulus as early as the 66th to 70th day of the 150 day gestation period. Among the several antigens employed, the fetal lamb responded earliest, and with the highest titers, to bacteriophage φX. Slightly less effective as an antigen was horse ferritin, while ovalbumin proved to be a weak antigen, especially in younger fetuses. Ineffective in stimulating an antibody response at any time during fetal or early neonatal life were diphtheria toxoid, Salmonella typhosa, and BCG. Thus, it may not be feasible to fix precisely the time of onset of immunologic responsiveness in a species, inasmuch as it appears to differ so greatly from one antigen to another.

The quantity of antibody found 10 days after φX immunization was not significantly different in fetuses injected at 60 to 120 days of gestation. The earliest anti-phage antibody produced by the lamb fetus is a macroglobulin sensitive to the action of 2-mercaptoethanol. Only in older fetuses with longer lasting stimuli were appreciable amounts of 7S γ-globulin antibodies formed.

The conformity of these observations to theories on the ontogenesis of the immune response is discussed.
EXPERIMENTAL LATHYRISM IN THE CHICK EMBRYO
Authors: Orloff Serge D. , Gross Jerome
Published: June 2004

1. C14-labeled ß-aminopropionitrile distributed throughout the egg contents within 10 minutes postinjection. By ion exchange chromatography and electrophoretic analysis three major components of the extractable dialyzable radioactive material could be demonstrated, representing at least 80 per cent of the total. The acidic and basic components were identified as ß-aminopropionitrile and cyanoacetic acid, while the fraction isoelectric at pH 5.3, consisting of two components, remained unidentified.

2. Less than 1 molecule of ßAPN per 100 molecules of protein was present in the highly purified extractable lathyritic bone collagen indicating that binding of the lathyrogen is not a factor in collagen extractability.

3. The proximity of ßAPN to collagen in bone is not essential to its extractability.

4. The effect of incubation temperature of the embryo on collagen extractability suggests the involvement of a metabolic process in this phenomenon.
CHEMICAL BASIS FOR AN IMMUNOLOGICAL SPECIFICITY OF A STRAIN OF STAPHYLOCOCCUS AUREUS
Authors: Juergens William G. , Sanderson Arnold R. , Strominger Jack L.
Published: June 2004

Antisera, prepared against formalin-killed cells of Staphylococcus aureus, strain Copenhagen, agglutinated the cell walls of this strain. The agglutination was inhibited by the teichoic acid from the cell wall of this strain, by any degradation product of this teichoic acid which contained the α-acetylglucosaminyl-ribitol unit, by α-phenyl-acetylglucosaminide, and by N-acetylglucosamine, but not by a large number of other haptens related to the cell wall. In quantitative experiments, however, only 40 to 50 per cent of antibody adsorption to cell wall could be inhibited by teichoic acid or by N-acetylglucosamine. The α-acetylglucosaminyl-ribitol unit in the teichoic acid is, therefore, an important immunological determinant in the cell wall of this strain, although other immunological specificities may also exist.

The cell walls were also agglutinated by heterologous antisera prepared against streptococcal Group A carbohydrate or against horse serum azophenyl-ß-acetylglucosaminide. The heterologous agglutination, however, was specific for the ß-acetylglucosaminyl-ribitol units in the teichoic acid.
EVIDENCE THAT THE L-ASPARAGINASE OF GUINEA PIG SERUM IS RESPONSIBLE FOR ITS ANTILYMPHOMA EFFECTS
Authors: Broome J. D.
Published: June 2004

Cells of the original line of lymphoma 6C3HED, which regularly prove susceptible to the effects of guinea pig serum in vivo, were cultured in Eagle's medium devoid of L-asparagine; after a latent period of 2 or more weeks, during which time the cell population declined markedly, some of the cells began to proliferate, and thereafter continued vigorous growth. On implantation into mice the proliferating cells were found, however, to have completely and permanently lost their susceptibility to the effects of guinea pig serum.

By contrast, when cultures of the original line of 6C3HED cells were prepared in Eagle's medium to which L-asparagine was added in a concentration of 20.0 mg/liter or more, they proliferated vigorously from the beginning; after long periods of growth in the enriched medium in vitro they remained susceptible to the effects of guinea pig serum upon test in vivo. Other amino acids, purines, and pyrimidines were unable to substitute for L-asparagine in this relation. Furthermore, a variant subline of 6C3HED cells which had become insensitive to guinea pig serum under in vivo conditions did not require L-asparagine for growth in tissue culture.

It seems plain from the findings as a whole, that in 6C3HED cells, L-asparagine dependence in vitro is associated with the in vivo character of guinea pig serum sensitivity, and conversely L-asparagine independent variants are insusceptible to the effects of guinea pig serum. The implications of the findings complement those of a companion paper in which direct evidence is provided that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects.
THE IN VIVO INTERACTION BETWEEN STAPHYLOCOCCUS BACTERIOPHAGE AND STAPHYLOCOCCUS AUREUS
Authors: Bartell P. F. , Thind I. S. , Orr T. , Blakemore W. S.
Published: June 2004

Staphylococcus bacteriophage 81 is capable of in vivo interaction with Staphylococcus aureus, Type 80/81. This is immediately made evident by increased levels of bacteriophage and concomitant survival of 81 per cent infected mice. The reaction is dependent upon the use of active, type-specific bacteriophage. The maximal protective effect is observed at a bacteriophage to bacteria ratio of 1:2 and decreased quantities of bacteriophage result in decreased protection. Time and sequence of administration are also determining factors. It is evident that bacteriophage administered intravenously is capable of interaction with the infecting bacterial cell at the site of infection. In vivo produced bacteriophage is apparently eliminated or otherwise rendered nondetectable fairly rapidly, occurring within a period of 5 to 10 days. However, it appears that host defense mechanisms are stimulated in the process and actively play a protective role against subsequent challenge inocula administered up to 3 weeks later.
SELECTIVE DESTRUCTION IN TESTIS INDUCED BY 7,12-DIMETHYLBENZ [a] ANTHRACENE
Authors: Ford Elizabeth , Huggins Charles
Published: June 2004

After a single feeding or intravenous injection of 7,12-dimethylbenz[a]anthracene, the testis of rat was severely and selectively damaged, whereas the ovary of sisters was spared from injury. After many weeks, complete recovery of the testis ensued. The destructive effect of 7,12-DMBA on testis was not shared by other powerful carcinogenic hydrocarbons; 3-methylcholanthrene; benzo[a]pyrene; 2-acetaminophenanthrene.

The primary sites of destruction inflicted by 7,12-DMBA on testis were spermatogonia and resting spermatocytes, the only cells in testis which synthesize deoxyribose nucleic acid. No other cells in the germinal epithelium are damaged by 7,12-DMBA. The severe atrophy of testis that ensues after some weeks is secondary to destruction of precursors in the seminiferous cell line. Moreover, interstitial cells of testis are not destroyed by the hydrocarbon.

Estimation of malic dehydrogenase is a simple and useful quantitative measure of damage and subsequent repair in testis. Following administration of 7,12-DMBA, the level of MDH had an inverse relationship to weight of the testis.
STUDIES ON THE TRANSMISSION AND THE EXCRETION OF THE LACTIC DEHYDROGENASE AGENT
Authors: Notkins Abner Louis , Scheele Christina
Published: June 2004

The lactic dehydrogenase agent (LDH agent) was found in the urine, feces, and saliva of mice within 24 hours after inoculation. The titer of virus in these materials appears to be directly related to the titer in the plasma. Infection by the oral route occurred only when a high concentration of virus was used.

Animals infected prior to mating rarely transmitted the LDH agent to their progeny. However, 91.2 per cent of the progeny of mothers infected during gestation and 51.5 per cent of the progeny of mothers infected within 48 hours after giving birth became infected with the LDH agent. Evidence is discussed which suggests that the transmission of the LDH agent from the infected mother to her offspring is related to the titer of the LDH agent in the maternal circulation.
THE PURIFICATION AND PARTIAL CHARACTERIZATION OF SEVERAL FORMS OF HOG RENIN SUBSTRATE
Authors: Skeggs Leonard T. , Lentz Kenneth E. , Hochstrasser Harry , Kahn Joseph R.
Published: June 2004

Hog renin substrate has been separated into three major (A, B, and C) and two minor forms (D and E) by DEAE cellulose chromatography. Two of the major forms (B and C) have been further fractionated into two additional types (1 and 2) by countercurrent distribution.

The purification of substrates A, C1, and C2 has been completed. Analysis shows that all three are glycoproteins with molecular weights of about 57,000, and have similar amino acid compositions. Differences exist in the sialic acid, glucosamine, and neutral hexose content, which may account for different physical properties.

All the forms of the substrates are attacked by renin at similar rates, and appear to yield the same angiotensin I.
EVIDENCE THAT THE L-ASPARAGINASE OF GUINEA PIG SERUM IS RESPONSIBLE FOR ITS ANTILYMPHOMA EFFECTS
Authors: Broome J. D.
Published: June 2004

A number of the properties of the L-asparaginase present in guinea pig serum have been examined and shown to be indistinguishable from those of the agent responsible for inhibiting cells of lymphoma 6C3HED in vivo.

The patterns of instability of the enzyme to changes in temperature and pH were found to parallel closely those of the antilymphoma agent. L-Asparaginase activity was essentially absent from the serum of newborn guinea pigs and this failed to inhibit 6C3HED cells. On separating guinea pig serum proteins by salt precipitation, electrophoresis, and chromatography on DEAE cellulose, antilymphoma activity was found only in fractions which contained L-asparaginase.
EPIDEMIOLOGY AND PATHOGENESIS OF STAPHYLOCOCCAL INFECTION
Authors: Simon Harold J.
Published: June 2004

An aerosol-induced staphylococcal infection of previously non-infected guinea pigs is described. Investigations concerning the dynamics of this infection indicate that:

1. An infection ("carrier state") could be established predictably in every animal exposed to the aerosol inoculum.

2. Infection was limited to the upper respiratory tract and occurred without apparent systemic dissemination.

3. Cross-infection between infected and non-infected animals did not occur.

4. The initially established infection persisted in detectable form for 6 days or less in the majority of exposed animals.

5. Tetracycline administration prior to and following aerosol infection with tetracycline-resistant strains significantly prolonged the duration of the carrier state.

6. When tetracycline-resistant strains were employed, the infection could be recalled predictably by means of tetracycline administration.

7. Infection initiated with a tetracycline-susceptible strain could not be recalled by tetracycline administration.

8. The mechanism(s) of action of tetracycline in recalling the attenuated infection is (are) unknown. It (they) may not be wholly attributable to ecological changes alone, at least as these are usually considered. The indigenous microflora diminished and changed as a result of tetracycline administration, and no growth-enhancing effect of the antimicrobial of the infection strains was detectable in vitro.

9. The experimental model described lends itself well to the study of attenuated staphylococcal infection in guinea pigs, and to more general studies of staphylococcal epidemiology and pathogenesis.
POTENTIATION OF THE LETHAL EFFECT OF ENDOTOXIN BY HETEROLOGOUS PLASMA
Authors: Beller Fritz K. , Debrovner Charles H. , Douglas Gordon Watkins
Published: June 2004

The intravenous injection of endotoxin in human plasma into rabbits produces a marked potentiation of lethal effect, when compared to the mortality associated with comparable doses of endotoxin in saline alone. A similar enhancement was noted with other heterologous plasma (guinea pig, rat) but not with homologous plasma. The potentiating factor is not in the albumin or gamma globulin fractions, is not concerned with fibrinogen, and is heat-labile. Tolerance of the recipient animal to endotoxin destroys the lethal effect. Within a period of 3 hours, endotoxin and human plasma may be administered separately, without regard to timing or sequence, without loss of the lethal effect. The enhancement of lethal effect is not avoided by pretreatment with heparin or cortisone. Preliminary experiments indicate that the loss of lethal effect found after incubation of endotoxin-plasma mixtures may be due to a separate inhibitor, but is not due to loss of the potentiating factor.
EXPERIMENTAL TRANSMISSION OF INFLUENZA VIRUS INFECTION IN MICE
Authors: Schulman Jerome L. , Kilbourne Edwin D.
Published: June 2004

Evidence has been presented that with the experimental model described, infected mice vary in their ability to transmit influenza virus infection. This variation is not explained by differences in titers of influenza virus in the nose, throat, trachea, or lungs of good transmitters. Older mice acquire transmitted influenza virus infection more readily than younger mice.

Seasonal variations in the incidence of transmitted influenza virus infection occur.
TRANSPLACENTAL TRANSMISSION OF HOMOTRANSPLANTATION ANTIBODIES
Authors: Halasz Nicholas A. , Orloff Marshall J.
Published: June 2004

Pregnant rabbits were sensitized to unrelated does by skin transplantation. The offspring of these sensitized animals rejected skin from the same donor in a markedly accelerated fashion. The transplacental passage of agents responsible for homograft rejection is therefore suggested. Since accelerated rejection rather than enhancement occurred, more than the usual humoral antibodies must have been thus transmitted. The presence of another antibody-like substance is postulated. This appears to be sessile in nature, usually fixed to lymphocytes, but transmissible without these cells under special circumstances, such as occur in micropore chambers or hemochorial placentae. These allow the prolonged dose contact of sensitized and non-sensitized lymphocytes, and thus may permit the transfer of this, usually sessile, but apparently non-fixed antibody.
ALLERGIC INFLAMMATION
Authors: Movat Henry Z. , Fernando Neil V. P. , Uriuhara Tsuneo , Weiser William J.
Published: June 2004

The fine structure of collagen fibrils at sites of antigen-antibody interaction is described.

Following injection of antigen (BSA or ferritin) into the center of the cornea of hyperimmune rabbits, an acidophilic ring of precipitate forms at the periphery of the cornea, where antigen and antibody interact in optimal proportions. The precipitate is soon removed by infiltrating polymorphs, but persists longer in leukopenic animals.

Electron microscopic examination of the cornea showed no alteration of the collagen fibrils in the area of antigen-antibody precipitation or in the remaining cornea. Contrary to many claims there was no swelling, fragmentation, or disintegration of the fibrils and they had a normal periodicity.

Polymorphs infiltrated the precipitates and phagocytosed the antigen-antibody complexes. There was some ultrastructural evidence that degradation of the complexes took place in the polymorphs.
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S.
Published: June 2004

Cortisone is known to protect mice against the lethal effects of endotoxin. It also elevates liver tryptophan pyrrolase (TP) activity, an enzyme that converts tryptophan into an intermediate which, in turn, is transformed in a series of reactions into nicotinamide, a component of the pyridine nucleotides. In the present report, results of experiments attempting to link the prophylactic action of cortisone in endointoxication to metabolism of tryptophan are described. It was shown first that both nicotinamide and diphosphopyridine nucleotide (DPN), compounds along the pathway initiated by TP, are each as effective as cortisone in protecting mice against lethality of different amounts of endotoxin. L-Tryptophan, which alone results in an increase in liver TP, fails to protect against endotoxin when it is given either 4 hours before or concurrently with the toxin while it potentiates the toxin when administered 4 hours later. Cortisone, nicotinamide, and DPN all fail to protect mice against lethality when given 4 hours after endotoxin but they do not potentiate it as does tryptophan.

Additional evidence linking tryptophan metabolism to endotoxin poisoning was derived from assays for TP. Activity of the enzyme in livers of mice 17 hours after injecting an LD50 of endotoxin is less than one-half the control value. It remains below normal for 48 hours. In adrenalectomized mice, TP activity is about the same as in mice 17 hours after endotoxin. Animals protected against lethality of endotoxin by cortisone have normal levels of TP but if the cortisone is given 4 hours after the toxin, TP activity is the same as in mice given endotoxin alone. Tryptophan is unable to maintain a normal level of TP when it is given concurrently with endotoxin. TP activity is not depressed when mice made tolerant to endotoxin are given an injection of endotoxin at the LD50 level for normal animals. Normal activity of the enzyme was always observed in livers of mice protected against endotoxin but not in those where protection failed.

The total amount of oxidized pyridine nucleotides (PN+) in livers of mice 17 hours after an LD60 of endotoxin is about two-thirds the normal level. Animals injected with either cortisone or nicotinamide at the same time as endotoxin maintain the PN+ level in liver.

Mice exposed to 5°C during the postinjection period can be protected with cortisone or nicotinamide against lethality of endotoxin but not with DPN. Changes in TP activity do not parallel those found in mice kept at 25°C. The toxic manifestations of endotoxin appear to be different, therefore, in animals stressed by cold.
EFFECTS OF CHRONIC EXCESS SALT INGESTION
Authors: Dahl Lewis K. , Heine Martha , Tassinari Lorraine
Published: June 2004

By selective inbreeding, two strains of rats were developed previously that differed markedly in their susceptibility to the development of experimental hypertension from excess salt ingestion (1, 2). The present report indicates that with animals derived from the same strains, similar differences in response were obtained in rats subjected to either combined desoxycorticosterone-NaCl (DOCA-salt) treatment or unilateral renal artery compression without extra dietary salt. Thus differences in genetic substrate appear to influence the development of experimental hypertension produced by these three techniques and possibly this may hold true for all "varieties" of experimental hypertension. If true, it might allow the development of a unifying hypothesis that could be relevant not only to experimental hypertension but perhaps to human hypertension as well.

The DOCA-salt regimen was more toxic to the animals than unilateral renal artery compression. Tentatively, this was ascribed to either, or both, the younger age or the higher NaCl intake of the animals in the former.
ASSOCIATION OF "NATURAL" ANTIBODIES TO GRAM-NEGATIVE BACTERIA WITH THE γ1-MACROGLOBULINS
Authors: Michael J. Gabriel , Rosen Fred S.
Published: June 2004

"Natural" antibodies to representative species of Enterobacteriaceae were found to be principally associated with the γ1-macroglobulin prepared from Cohn fraction III-I of pooled human plasma. The amount of antibodies present was estimated by measuring the bactericidal, hemagglutinating, mouse-protective, and opsonophagocytic activities of this fraction. Comparison with the antibody activity of γ2-globulin of Cohn fraction II showed that up to 100 times more antibody activity on a weight basis was present in the macroglobulin fraction. These findings suggest that differences between natural and immune antibody result from the physicochemical properties of 2 different classes of immune globulin.
INSULIN-INDUCED GLOMERULOSCLEROSIS IN THE RABBIT
Authors: Mohos Steven C. , Hennigar Gordon R. , Fogelman John A.
Published: June 2004

An attempt has been made to induce intercapillary glomerulosclerosis in rabbits by immunization with insulin incorporated in Freund's adjuvant and followed by repeated challenges with subcutaneously given insulin. It was observed that lesions resembling human diabetic glomerulosclerosis with occasional nodule-like formation could be produced and that the challenge insulin injections produced proteinuria. The presence of a delayed type of hypersensitivity seemed necessary for the lesions to occur as did the dissemination of the immunizing material to the kidneys. The experiment also disclosed that intravenously given DIS-tagged insulin localizes in a subtly different kind of glomerular lesion with different staining properties. The significance of these findings and the possible role of insulin treatment in the pathogenesis of human diabetic glomerulosclerosis is discussed.
PASSIVE TRANSFER OF TRANSPLANTATION IMMUNITY
Authors: Najarian J. S. , Feldman J. D.
Published: June 2004

Passive transfer of homograft immunity was successfully achieved by injection of the supernatant obtained from tissue-sensitized lymphoid cells disrupted by sonic vibration. The effective substance destroyed specific skin homografts within 6 days but did not reject non-specific skin grafts in this time. No evidence of transferred antigen or of transfer factor was found when the effective material was passed to irradiated recipients carrying test grafts. By a variety of physiochemical procedures the "soluble substance" behaved like a gamma globulin and was considered to be a transplantation antibody.
THE CROSS-REACTIVITY AND TRANSFER OF ANTIBODY IN TRANSPLANTATION IMMUNITY
Authors: Fujii Genshichiro , Nelson Robert A.
Published: June 2004

A close inomunochemical relationship of Forssman-type antigens in cells or in a methanol extract of guinea pig kidneys, lymph nodes, and platelets, of horse kidneys, and of sheep erythrocytes was demonstrated by complement-fixation, agglutination, and inhibition of hemolysis. The dissociation of antibody from several cross-reacting complexes and re-association with antigens of erythrocytes used for immunization was inferred from quantitative hemolytic assays. This preferential affinity of antibody for the antigen used for immunization is proposed as an immunochemical model for reactions which function in graft rejection phenomena wherein the donor and recipient tissues share cross-reacting antigens.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N. , Grossowicz Nathan
Published: June 2004

The production of oxygen-stable hemolysin in growing and resting Group A streptococci has been induced by RNA, by detergents, and by mammalian blood serum proteins, in the presence of glucose, Mg++, and cysteine. Of the serum proteins, albumin and α lipoprotein could act as inducers. In the case of both these serum proteins treatment with trypsin did not affect the capacity to induce hemolysin production, but removal of the bound lipids by alcohol-ether or chloroform-methanol destroyed this property.

In comparisons of the conditions of production and of activity between the hemolysin produced by RNA on one hand and albumin and detergents on the other, some data indicated similarities among the hemolysins, and others, differences. The similarities included similar degrees of temperature dependence for production and equal degrees of inhibition by serum ß lipoprotein. Differences found among these hemolysins included differences between, the rate of production of the RNA hemolysin from that of albumin or detergent hemolysin by both resting and growing streptococci, and the failure of utilization of glucosamine as an energy source for the production of albumin hemolysin, in contrast with that of RNA hemolysin. The fact that the data have in some cases indicated similarities and in other cases differences among the hemolysins raises the question of whether these are different molecular species, or a single hemolysin synthesized by the streptococci via different pathways of metabolism, or complexes of a single hemolytic moiety with various molecular carriers.
OXYGEN-STABLE HEMOLYSINS OF GROUP A STREPTOCOCCI
Authors: Ginsburg Isaac , Harris T. N.
Published: June 2004

The oxygen-stable streptococcal hemolysins, which can be induced by a number of diverse substances, have been studied. Differences among these hemolysins have been found in electrophoresis, chromatography, pH stability, and susceptibility to some organic solvents and to an enzyme, RNAase. These properties have in each case been found to characterize the inducing substances as well.

In a number of instances it has been found possible to incubate one inducer with the hemolysin induced by another of these agents and then, after appropriate fractionation, to find hemolytic activity in the fraction containing the fresh inducer. These observations suggest that the oxygen-stable streptococcal hemolysins are constituted as carrier-hemolysin complexes, the carriers being the set of molecular species effective as inducers, and the prosthetic group being transferred from one carrier to another under appropriate conditions.

After transfer of the hemolytic moiety from a hemolysin molecule which is susceptible to inactivation by a given agent or set of conditions to a carrier which is not itself significantly affected by this agent, the new, derived, hemolysin has been found not to be inactivated by the agent. The hemolysins of this group can thus be inactivated by enzymatic attack on the prosthetic group, or by hydrolysis or deformation of the postulated carrier molecule.
SEROLOGIC DEMONSTRATION OF DUAL SPECIFICITY OF RABBIT BIVALENT HYBRID ANTIBODY
Authors: Fudenberg H. H. , Drews Genevieve , Nisonoff A.
Published: June 2004

Hybrid, bivalent antibody molecules bearing specific combining sites for both ovalbumin and bovine gamma globulin were produced by reoxidation of a mixture of the 3.5S fragments of the two specifically purified antibodies. The dual specificity and the properties of the hybrid antibody were demonstrated by mixed agglutination and two stage agglutination experiments, and by test systems utilizing inhibition of agglutination or dispersal of agglutinates followed by antiglobulin reactions.
THE ROLE OF THE ALVEOLAR MACROPHAGE IN THE CLEARANCE OF BACTERIA FROM THE LUNG
Authors: Green Gareth M. , Kass Edward H.
Published: June 2004

Pulmonary clearance of bacteria was studied using histologic, bacteriologic, and radiotracer methods. When mice were exposed to an aerosol of P32-tagged Staphylococcus aureus or Proteus mirabilis, and the rate of disappearance of viable bacteria compared with the rate of their mechanical removal, it was found that bacterial viability declined 80 to 90 per cent in 4 hours, whereas radioactivity declined by only 14 to 20 per cent. The marked disparity in these rates indicated that mechanical removal comprised a relatively small fraction of the total clearing process. The in situ bactericidal action of the lung predominated over the mechanical removal process in achieving clearance of the inhaled bacteria. By immunofluorescent methods, the inhaled bacteria were found to be localized in the alveolar spaces and within alveolar macrophages. These observations suggest that the bactericidal action of the bronchopulmonary tree is due primarily to the phagocytic activity of the alveolar macrophages, and that the action of the mucociliary stream, in relation to bacterial particles, may be largely related to the transport from the lung of phagocytes containing material of bacterial origin.
THE FORMATION AND PROPERTIES OF POLIOVIRUS-NEUTRALIZING ANTIBODY
Authors: Svehag Sven-Eric , Mandel Benjamin
Published: June 2004

Transient 19S antibody formation was induced in rabbits by single or repeated stimuli with a small dose of poliovirus. Available evidence indicated that cessation of 19S synthesis was due to lack of continuous antigenic stimulation and not to loss of cells participating in antibody formation. "Immunological memory" in 19S antibody formation was demonstrable only within 2 to 3 days following discontinuation of synthesis but not thereafter.

Following stimulation with a high dose of polio-virus both 19S and 7S antibodies were formed. The kinetics of their formation differed in several respects: (a) 19S antibody preceded 7S antibody by ⩾1½ days; (b) 19S antibody rose to peak titers at a rapid exponential rate within 1 week, while 7S antibody increased at a slow decelerating rate for ⩽3 weeks; (c) 19S antibody formation was short-lasting while 7S antibody synthesis endured. A renewed formation of both antibodies occurred following restimulation with a high antigen dose. The secondary 19S and 7S antibody responses were similar to the respective primary responses, and the preexistence of 7S antibody synthesis did not detectably alter the secondary 19S response.

Both 19S and 7S antibodies were formed and the kinetics of their formation was similar (a) for infectious and non-infectious (UV-) poliovirus antigen; (b) for the serologically unrelated poliovirus and Coxsackie B-4 virus; (c) when poliovirus was administered by different routes; (d) when 1-day-old or adult rabbits were immunized; (e) in antibody responses to poliovirus in rabbit, guinea pig, and man.

Whole body x-irradiation 20 hours prior to antigenic stimulus (high dose) resulted in delayed but markedly prolonged 19S antibody formation and inhibition of 7S antibody synthesis.

Thus, the formation of 19S and 7S antibody differed in (a) antigen dose requirements for induction and maintained synthesis; (b) kinetics; (c) retention of memory; and (d) sensitivity to prior x-irradiation. These differences are best explained on the assumption that the two antibodies are produced by different cells.