bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF THE INTESTINAL FLORA ON THE GROWTH RATE OF MICE, AND ON THEIR SUSCEPTIBILITY TO EXPERIMENTAL INFECTIONS
Authors: Dubos René J. , Schaedler Russell W.
Published: June 2004

Mice delivered by Caesarian section were used to develop a new mouse colony which has been maintained in an environment protected from contact with common mouse pathogens, but not in the germ-free state. These mice, designated as NCS, were compared with animals of the same sex and age coming from the parent colony maintained under ordinary conditions.

The NCS mice grew more rapidly than ordinary mice on complete diets; moreover, they continued to gain weight—although at a slower rate—when fed deficient diets which caused ordinary mice to stop growing, or to lose weight.

The NCS mice proved much more susceptible than ordinary mice to certain experimental bacterial infections. In contrast, they were much more resistant than ordinary mice to the lethal effect of large doses of endotoxins. However, they responded to injection of minute amounts of these endotoxins by a marked increase in susceptibility to staphylococcal infection.

Bacteriological studies revealed striking qualitative differences between the intestinal flora of NCS and ordinary mice. When NCS mice were contaminated—either by contact or by feeding—with a strain of Escherichia coli recovered from the intestine of ordinary mice, they acquired the characteristics of the latter animals with regard to weight gain on various diets, and to response to bacterial pathogens and endotoxins.

NCS mice have been found well suited to the study of several nutritional, bacteriological, and immunological problems and it appears that their production on a large scale will not present unsurmountable difficulties.
IMMUNOLOGIC PRODUCTION OF ANTIANGIOTENSIN
Authors: Deodhar Sharad D.
Published: June 2004

Angiotensin II was coupled with bovine γ-globulin (BGG) through the following series of reactions.

See PDF for Structure

By determinations of the aromatic amine and tyrosine contents of p-aminobenzoylangiotensin II, the number of p-aminobenzoyl residues introduced per molecule of angiotensin II was calculated.

Absorption spectra (between 250 and 500 mµ) of BGG complexes of p-aminobenzoylangiotensin II and six different para substituted aromatic amines were compared.

Specific activities (dog units/millimicromole) of the different intermediate products were determined. Presence of a terminal, free amino group does not appear to be an absolute requirement for the biological activity of angiotensin II, since substitution of a p-aminobenzoyl radical in this group yields a product with 40 to 50 per cent of the activity of the parent compound. Angiotensin I, on the other hand, is completely inactivated under identical circumstances. Possible implication of this finding has been discussed.
IMMUNOLOGIC CROSS-REACTIONS AMONG MAMMALIAN ACUTE PHASE PROTEINS
Authors: Gotschlich Emil , Stetson Chandler A.
Published: June 2004

Crystalline rabbit Cx-reactive protein has been compared immunologically with the analogous crystalline C-reactive protein of man.

Immunologic cross-reactivity has been demonstrated between the acute phase proteins of man, rabbit, and monkey.

Double-diffusion reactions in agar and passive cutaneous anaphylaxis reactions in vivo both indicate that these acute phase proteins are antigenically closely similar but not identical.

Guinea pigs with delayed hypersensitivity to C-reactive protein exhibit delayed skin reactions when tested with Cx-reactive protein and vice versa.
STUDIES ON THE Cx-REACTIVE PROTEIN
Authors: Wood Harrison F. , Anderle Sonia , Hammond Carolyn W. , Miller C. Phillip
Published: June 2004

Young adult rabbits (2 to 3 kg.) were subjected to a single total body exposure of x-radiation ranging from 50 to 1200 r and tested frequently for the presence of Cx-reactive protein in their blood.

It usually appeared in two phases separated by an interval of several days. The primary phase occurred 24 to 48 hours after irradiation in almost all (92 of 97) rabbits exposed to 500 r or more and in 4 of 16 exposed to 300 r or less. The secondary phase occurred during the 2nd week in many of the rabbits irradiated with 900 r or more and in a few irradiated with 700 r.

Autopsy cultures failed to demonstrate the presence of infection in rabbits which died or were sacrificed during the primary phase. Bacterial infection was demonstrated, however, in almost all (21 of 24) rabbits autopsied and cultured during the secondary phase.

After the disappearance of the primary phase in rabbits exposed to 700 or 900 r, the secondary phase could be elicited by initiating bacterial infection. Within 6 to 24 hours after intravenous inoculation of E. coli, Cx-reactive protein reappeared in the blood and persisted until death or termination of the experiment. Reappearance of the protein also followed the intravenous injection of killed E. coli but it disappeared again 1 to 2 days later.

The results indicate that the primary phase is elicited by radiation injury per se and the secondary phase by bacterial infection.
TYPE AND GROUP POLYSACCHARIDES OF GROUP D STREPTOCOCCI
Authors: Elliott S. D.
Published: June 2004

Polysaccharides extracted from cell walls of 4 serological types of Group D streptococci were serologically type-specific. Acid hydrolysates of all 4 contained hexosamine (glucosamine), rhamnose and glucose.

A polysaccharide extracted from 2 serological types by either alkaline treatment or mechanical disruption was serologically group-specific. Acid hydrolysates contained glucose and no other single component in comparable amount. The group-specific polysaccharide, which may be of a dextran-like nature, is probably situated wholly or in part at the surface of the streptococcus.
SPECIFIC AND NON-SPECIFIC IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS IN MICE
Authors: Louria Donald B.
Published: June 2004

The course of lethal cryptococcosis in mice was modified by immunization with the same strain or different strains of Cryptococcus neoformans. Protection was associated with a definite decrease in tissue fungus multiplication over the initial 7 days of infection. Such immunity was species-specific and did not protect against heterologous challenge with Staphylococcus aureus, Klebsiella pneumoniae, or Mycobacterium tuberculosis.

Similar modification of lethal cryptococcosis was produced by intraperitoneal inoculation of 100 to 200 µg. of Salmonella endotoxin 7 days prior to challenge. In non-specifically (endotoxin) immunized mice there was only a minimal reduction in tissue cryptococcus census during the 1st week of infection.

When small numbers of virulent cryptococci were injected intravenously into normal mice, tissue populations rose markedly in all organs studies during the first 7 days. A progressive fall in tissue fungus census was then observed in most mice during the next 6 months.

The increase in resistance to cryptococcal challenge following specific immunization, the non-specific protection conferred by injection of bacterial endotoxin and the ability to control and eventually reduce infections with small inocula may well be dependent in each case on the development of specific antibody.
FUNCTIONAL AND METABOLIC PROPERTIES OF POLYMORPHONUCLEAR LEUCOCYTES
Authors: Cohn Zanvil A. , Morse Stephen I.
Published: June 2004

The effects of a purified bacterial lipopolysaccharide endotoxin on homogenous populations of rabbit polymorphonuclear leucocytes have been studied in vitro under defined conditions. Employing a 500-fold range of concentration (0.1 to 50.0 µg./ml.), it was shown that endotoxin enhanced the rate at which staphylococci were killed by leucocytes. The mechanism underlying the increased killing was found to be a direct stimulation of the phagocytic activity of the leucocyte and not mediated by the release of bactericidins or opsonins from the treated cells. In the presence of 10 per cent serum all concentrations of endotoxin enhanced phagocytosis, whereas at lower serum concentrations, the higher doses of lipopolysaccharide inhibited the phagocytic activity of the cells.

Similar concentrations of endotoxin were capable of increasing the utilization of glucose and the production of lactic acid. Endotoxin treated leucocytes exhibited no change in oxygen consumption, and only a slight depression in glycogen synthesis.

It appeared that endotoxin could interact and alter the functional and metabolic properties of leucocytes in the absence of serum.

The demonstration of enhanced phagocytic activity of endotoxin-treated cells was dependent upon the particular opsonic requirements for the organism under study.
STUDIES ON SUSCEPTIBILITY TO INFECTION FOLLOWING IONIZING RADIATION
Authors: Miller C. Phillip , Hammond Carolyn W. , Anderle Sonia K.
Published: June 2004

Ten week old female CF-1 mice were subjected to a single total body exposure of x-radiation in one of the following doses: 300, 400, and 500 r. At intervals thereafter, susceptibility to bacterial infection was determined by intraperitoneal challenge with graded inocula of Pseudomonas aeruginosa. Mice exposed to 400 or 500 r were also challenged by intravenous inoculation.

The LD50 of the test microorganism in each challenge was estimated from the mortality data.

Exposure to 300 r caused little increase in susceptibility to this experimental infection. 400 r caused a moderate increase on the 3rd day post-irradiation with return to normal on the 17th. Leucocyte counts (geometric means) following this dose of radiation did not fall below 1200.

500 r caused a marked increase in susceptibility which lasted from the 3rd to 11th day, during which period the leucocyte counts were below 800. On the 20th day, susceptibility to infection was normal, although the geometric mean of leucocyte counts was only 2200.

Comparison of mortalities resulting from equivalent inocula introduced by the two routes (intravenous and intraperitoneal) showed no difference in unirradiated mice. However, among mice irradiated with 400 or 500 r, higher mortalities resulted from intravenous inoculation. The difference was found to be due to the establishment of a small focus of infection at the site of intravenous injection as a result of leakage of a minute fraction of inoculum into the perivenous tissues of the tail. Bacterial multiplication occurred in such foci in irradiated (leucopenic) mice, but not in unirradiated mice, nor at the site of intraperitoneal inoculation even in irradiated mice.
THE HISTOLOGICAL DISTRIBUTION OF BLOOD GROUP SUBSTANCES A AND B IN MAN
Authors: Szulman Aron E.
Published: June 2004

The mapping out of the histologic distribution of blood group antigens A and B in human tissues was performed by means of the fluorescent antibody technique. Human hyperimmune sera were conjugated with fluorescein isocyanate and applied to frozen sections of human material obtained at autopsy or after surgical removal. The material examined encompassed A, B, and AB subjects. In the latter the anti-A and the anti-B conjugate elicited the same picture. Group O tissues were used for controls and were uniformly negative. The secretor status of subjects was determined from the saliva or by the Lewis typing of erythrocytes.

The results fall into the following main divisions:

Endothelia of Vessels.—Widespread localization was demonstrated in the cell walls of endothelium of capillaries, veins, arteries, and of sinusoidal cells of spleen.

Stratified Epithelia.—These showed good outlining of cells of the Malpighian (and the granular, when present) layers. In transitional epithelia, cells of the basal and contiguous layers gave specific staining.

Mucus-Secreting Apparatus.—Positive staining was obtained in glands, goblet cells, and secreting surface epithelia. In non-secretors there was no identifiable antigen with the important exception of the deeper parts of gastric foveolae, deeper parts of crypts of Lieberkühn of bowel mucosa and Brunner's glands of the duodenum.

Various Organs of Secretion and Excretion.—The pancreas (exocrine portion) and the sweat glands were found to produce the antigen irrespectively of secretor status. Breast, prostate, and endometrial glands on the other hand apparently secrete the antigen in conformity with the subject's secretor:non-secretor make-up.

Thus the secretor:non-secretor status governs principally the antigens associated with mucous secretions and this in most but not all locations. The possible nature of this control is briefly discussed.
IMMUNOLOGICAL STUDIES OF HUMAN γ-GLOBULIN
Authors: Edelman G. M. , Heremans J. F. , Heremans M.-Th. , Kunkel H. G.
Published: June 2004

Two major antigenic fragments were obtained from various purified γ-globulin preparations after papain treatment. One, the F component, had a mobility faster than the original γ-globulin and the second, the S component, had a slower mobility. Similar F and S components were also obtained with certain homogeneous myeloma proteins which were closely related to γ-globulin immunologically. Additional minor antigenic components were detected with certain antisera. The technique of immunoelectrophoresis was particularly useful for bringing out the different antigenic constituents obtained after papain treatment.

The F and S components as well as a midfraction were isolated by chromatography on DEAE-cellulose. These were immunologically homogeneous and could be utilized to absorb F and S antibodies from various antisera. The relative amount of F and S antibodies varied in different antisera from individual rabbits immunized with whole γ-globulin.

Whole γ-globulin was separated by zone electrophoresis into a fast migrating and a more slowly migrating fraction. Each of these gave rise to F and S components after splitting with papain. The F components of the two γ-globulins were similar in mobility, while the S components showed marked mobility differences although antigenically they were very similar. The mobility differences of the parent γ-globulin appeared to be primarily related to the differences in the S component.

Certain antisera against pathological γ-globulins were found to give double lines with a wide variety of γ-globulin preparations in agar diffusion. These were shown to be related to the F and S antigenic determinants of γ-glubulin. This relationship was evident by a number of procedures utilizing both Ouchterlony plate techniques and immunoelectrophoresis. The question of whether these findings indicate heterogeneity of γ-globulin in relation to the F and S antigenic components, or whether different antigenic groups on one molecule can give rise to separate lines in certain instances, is discussed.
ESTRADIOL REDUCES INCORPORATION OF RADIOACTIVE SULFATE INTO CARTILAGE AND AORTAS OF RATS
Authors: Priest Robert E. , Koplitz R. Marlene , Benditt Earl P.
Published: June 2004

Estradiol in large amounts reduces the incorporation of radioactive sulfate into cartilage and aortas of rats.

This reduction becomes apparent within 3 days for cartilage and 3 weeks for aorta.

The effect is not mediated through suppression of testosterone secretion and the hypophysis is not necessary for the effect to be demonstrated.

The thoracic segment of aortas from normal rats incorporates more sulfate than does the abdominal segment and this difference is reduced following the administration of estradiol.
ANTIGEN-ANTIBODY REACTIONS IN ALLERGIC HUMAN TISSUES
Authors: Rappaport Ben Z.
Published: June 2004

Skin sensitizing human antibodies were conjugated with various fluorescent dyes without significant loss in their ability to combine with specific antigen in vitro.

A biopsy of the skin site challenged with egg albumin in a patient sensitive to this antigen could be stained specifically by the fluorescent reagins. The epithelial cells of the epidermis, sweat glands, hair follicles, and sebaceous glands in such a challenged site showed specific staining. In addition to the epithelial cells, the most intense staining was in macrophages and in pericapillary cells. The endothelium of the small blood vessels stained less intensely. Fibrous tissue bundles were specifically stained.

The immunologic staining with the conjugated reagins was similar to but more intense than that obtained with conjugated rabbit anti-egg albumin globulins.
BIOCHEMICAL STUDY OF CELLULAR ANTIGEN-ANTIBODY REACTION IN TISSUE CULTURE
Authors: Tokuda Akira , Hayashi Hideo , Matsuba Kinishiro
Published: June 2004

Decrease in the protease activity of the culture fluid observed at later stages of the antigen-antibody reaction is believed to be due to the release of an inhibitor by the cells. The inhibitor was submitted to partial purification: it is heat-stable, non-precipitated by trichloracetic acid and non-dialyzable. It inhibits certain cellular and tissue proteases and papain but is inactive against trypsin. It is suggested that the balance between protease and anti-protease released may determine the intensity, extent, and duration of certain sensitization phenomena.
GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO
Authors: Thorbecke G. J.
Published: June 2004

Gamma globulin formation in vitro by various tissues was studied using the incorporation of C14-L-lysine into a protein precipitable by a specific anti rabbit gamma globulin serum prepared in a sheep.

It was demonstrated that the rate of gamma globulin formation in similar numbers of spleen cells is much higher if taken from an immunized rabbit at the height of antibody formation than that in normal spleen cells. Besides spleen, other tissues shown to form gamma globulin in normal adult rabbits were: peripheral lymph nodes, bone marrow, lung, mesenteric lymph nodes, appendix, and thymus.

In tissues from newborn rabbits gamma globulin formation could not be demonstrated. Rabbits 1 week old already showed a beginning of significant gamma globulin formation in appendix tissue, followed approximately 3 weeks later by gamma globulin synthesis in spleen and thymus. Histological observations on these tissues were described and correlated with findings on gamma globulin formation.

In the discussion an attempt has been made to relate these observations on newborn and immature rabbits to those available in the literature on antibody formation in newborn animals.
NON-SPECIFIC RESISTANCE TO EXPERIMENTAL CHOLERA IN EMBRYONATED EGGS
Authors: Finkelstein Richard A. , Ransom John P.
Published: June 2004

It has been confirmed that 11- and 13-day-old chick embryos are susceptible to lethal infection with minute inocula of V. cholerae, while 15-day-old embryos are relatively resistant.

Twenty strains of E. coli were found to vary in their capacity to kill chick embryos, without relationship to their human enteropathogenicity. Prior infection of 13-day-old embryonated eggs with E. coli strains selected for low embryo virulence had a marked protective effect against superinfection with V. cholerae.

This effect was duplicated by pretreatment of embryos with killed E. coli cells or endotoxin preparations but not with a suspension of killed cells of a Gram-positive species. Preparatory E. coli infection induces a phase of vibriostasis in the 13-day-old egg which may be sufficient to tide the embryo over into the phase of relative insusceptibility associated with age. Younger embryos exhibit only a lag in death under similar conditions.

The chick embryo is presented as a potentially valuable tool for the study of combined infections and of the mechanisms of natural resistance.
AN EARLY EFFECT OF DIPHTHERIA TOXIN ON THE METABOLISM OF MAMMALIAN CELLS GROWING IN CULTURE
Authors: Kato Iwao , Pappenheimer A. M.
Published: June 2004

At concentrations of 0.1 Lf (0.25 µg.)/ml., or greater, diphtheria toxin produces an immediate decrease (40 ± 5 per cent) in the steady-state level of incorporation of inorganic phosphate into ATP by cultures of normal human kidney cells growing at 37°C. in the presence of glucose. The effect is readily reversible by specific antitoxin for a period of 30 minutes or more after adding toxin. Protein synthesis in these cells continues at a normal rate for 60 minutes after adding toxin and the toxin-treated cells are able to take up and concentrate potassium ions normally for at least 1 hour. Even high concentrations of toxin (5 Lf/ml. or more) fail to effect either protein synthesis or ATP formation by cultures of spleen cells from the mouse, an animal that is relatively resistant to the lethal action of the toxin. Of various inhibitors studied, antimycin A most closely resembles toxin in its action, both on protein synthesis and on ATP formation. Mouse cells are considerably more resistant to antimycin A than are human kidney cells.

Human kidney cells treated with saturating doses of toxin continue to form RNA at a normal rate for about 1 hour, after which the rates of both Pi32 incorporation and of 6-C14-orotic acid incorporation into RNA sharply decline and continue at about 40 to 50 per cent their initial rate. At 37°C., S35-methionine incorporation into cell protein ceases altogether 60 to 75 minutes after addition of a saturating dose of toxin.

The effect of saturating doses of toxin on S35-methionine incorporation into human kidney cell protein at different temperatures, has been studied.

It is concluded from the present studies that diphtheria toxin exerts a primary, reversible effect at the surface of susceptible cells where it inhibits cytochrome-linked phosphorylation concerned with transport of inorganic phosphate across the cell membrane.
THE EXPERIMENTAL DISEASE THAT FOLLOWS THE INJECTION OF HUMAN LEPROSY BACILLI INTO FOOT-PADS OF MICE
Authors: Shepard Charles C.
Published: June 2004

When leprosy bacilli from human patients are inoculated into the foot-pads of CFW mice, a microscopic granuloma containing acid-fast bacilli develops in a characteristic manner. This has been seen in 22 of 22 instances with leprosy bacilli from nasal washings, in 12 of 16 instances with leprosy bacilli from skin biopsies, and in none of 16 cases where the nasal washings were not observed to contain leprosy bacilli.

Quantitative studies revealed a relationship between the number of bacilli inoculated and the time required for the appearance of the lesions. The incubation period was usually 1 to 2 months when the dose was 105.5 to 106.0 bacilli and about 6 months when the dose was about 103 organisms.

After the development of the lesion, the number of bacilli harvested was usually in the range 104.5 to 106.0, regardless of the number inoculated. When the inoculum has contained 102.0 to 103.5 acid-fast bacilli, and harvests were reasonably prompt, there were regular increases of 50- to 1000-fold.

Passage to new groups of mice has been successful 11 of 12 times. Most of these were second passages. One strain has been maintained in 3 passages with a total increase in acid-fast bacilli of 4 x 104-fold. Another strain has been through 4 passages with a total increase of about 4 x 106-fold.

Cultures on bacteriological media favorable for the growth of most known mycobacterial species have not shown growth of mycobacteria.
A STUDY OF THE FINE STRUCTURE OF THE KIDNEY IN CASEIN-INDUCED AMYLOIDOSIS IN RABBITS
Authors: Cohen Alan S. , Calkins Evan
Published: June 2004

Renal amyloidosis, produced in rabbits by subcutaneous casein injections, was studied by light and electron microscopy.

The earliest change before amyloid was detected was the appearance of endothelial cell blebs and mild endothelial cell proliferation.

Amyloid was deposited between the basement membrane and the endothelial cell. The cytoplasm of the latter, when over amyloid, was devoid of fenestrations but otherwise had normal inclusions.

Basement membrane excrescences were observed both early and late in the development of the disease, while basement membrane thickening was common with advanced disease. The integrity of the lamina densa of the basement membrane appeared to be preserved through the amyloid deposit.

Epithelial cell foot process broadened and fused with advanced disease. The absence of the foot processes was particularly noticeable in areas adjacent to amyloid deposits.

Epithelial cell cytoplasm contained multiple vacuoles. The cytoplasmic strands connecting the foot processes to the body of the cell were significantly attenuated.

The substance of the amyloid consisted of fibrils that were oriented in parallel bundles in areas adjacent to the endothelial cell. The fibrils were <300 A wide and ranged in length up to 5000 A.
MAST CELL DEGRANULATION AND HISTAMINE RELEASE OBSERVED IN A NEW IN VITRO SYSTEM
Authors: Lagunoff David , Benditt Earl P.
Published: June 2004

A method is described by which mast cells harvested from the rat peritoneal cavity can be deposited on the surface of a Millipore filter without gross injury, permitting observation of morphological and chemical changes induced by a variety of agents.

These isolated peritoneal mast cells respond to 48/80 and to polymyxin B but not to dextran or ovomucoid with degranulation and histamine release. Thus four agents which in vivo appear to have similar activities have been found by means of in vitro analysis to operate by at least two different mechanisms.
CHANGES IN BLOOD COAGULATION DURING THE CLEARING OF LIPID EMULSIONS BY LIPOPROTEIN LIPASE
Authors: Hirsch Robert L. , Kellner Aaron , Ireland Rosemary
Published: June 2004

The clearing of lipid emulsions by postheparin plasma from rabbits or human beings was accompanied regularly by a sharp reduction in the recalcification time of the plasma. No change in blood coagulation took place when the activity of lipoprotein lipase, the clearing enzyme, was inhibited by means of heat or the action of a surface-active agent. In control studies, the recalcification time of postheparin plasma was not altered by the addition of glycerol, free fatty acids, or the products of hydrolysis of a lipid emulsion. Taken together, the findings indicated that a heat-labile factor was released during the course of clearing which was capable of inactivating reversibly the anti-coagulant properties of heparin.
ANTIGEN-ANTIBODY REACTIONS IN ALLERGIC HUMAN TISSUES
Authors: Rappaport Ben Z.
Published: June 2004

The skin of atopic patients contains specific reaginic antibodies in all epidermal cells, in unchallenged as well as antigen-challenged areas. The reagins are also present in the epithelial cells of sebaceous glands, sweat glands, hair follicles and also in macrophages and pericytes. Judged by staining characteristics, their immunologic reaction in tissues with antigen is identical with that of rabbit antibodies.

Comparison of tissues stained with conjugated reagins and conjugated anti-human globulin antibodies demonstrates the close relationship of reagins and globulins.

In antigen-challenged tissues the macrophages and pericytes become enlarged and stain more intensely with toluidine blue. No such changes in morphology or staining are present in histamine-tested or unchallenged atopic tissues.
ENTEROVIRAL RIBONUCLEIC ACID
Authors: Holland John J. , Hoyer Bill H. , McLaren Leroy C. , Syverton Jerome T.
Published: June 2004

A relatively sensitive and adequately reproducible assay of infectious enteroviral RNA was obtained by exposing calf serum-grown HeLa cells to RNA suspended in 2 M magnesium sulfate solution. Highly purified enteroviral preparations yielded RNA exhibiting more than 0.1 per cent of the infectivity of whole original virus and infectivity regressed linearly with dilution.

Radioisotope experiments with P32-labeled RNA and spectrophotometric studies demonstrated that Gierer-Schramm phenol extraction permits almost quantitative recovery of high molecular weight RNA from poliovirus. Intact chromatography-purified type 2 poliovirus in the analytical ultracentrifuge showed a sharp boundary and a sedimentation coefficient of S20, w = 147 ± 5S. Phenol-extracted poliovirus RNA exhibited a heterodisperse sedimentation pattern with a large proportion of homogeneous, rapidly sedimenting material having a coefficient of S20, w = 37 ± 2S.

Although the bulk of extracted poliovirus RNA as measured by radiophosphorus labeling was not taken up by cells, the infectious fraction of RNA was adsorbed rapidly by HeLa-cell or L strain mouse fibroblast monolayers, indicating a possible dissimilarity between the bulk of extracted virus RNA and a relatively small fraction responsible for infectivity.

Enhancement of poliovirus RNA infectivity for HeLa cells by high ionic-strength magnesium sulfate solution appeared due partly to an effect of hypertonicity on cells, and partly to an effect of high-concentration divalent cation on RNA itself, but not to enhancement of adsorption. Poliovirus RNA adsorbed by HeLa cells apparently was rapidly received within the cells since it became quickly insusceptible to ribonuclease.

Heterologous nucleic acids and degradation products to the level of oligoribonucleotides inhibited infectivity of poliovirus RNA for HeLa cells. This inhibitory activity appeared due to intermolecular complexing, since exposure of cells to heterologous RNA immediately before or after exposure to virus RNA failed to reduce infectivity.

Ultraviolet absorption spectra demonstrated that the RNA within intact poliovirus is more hypochromic (and thus more extensively hydrogen-bonded) than is the same RNA isolated by phenol extraction, and suspended in 0.02 M phosphate buffer.
ANAPHYLACTIC REACTIONS IN THE SKIN OF THE GUINEA PIG WITH HIGH AND LOW MOLECULAR WEIGHT ANTIBODIES AND GAMMA GLOBULINS
Authors: Ovary Zoltan , Fudenberg Hugh , Kunkel Henry G.
Published: June 2004

High molecular weight (19S) γ-globulin produces passive cutaneous anaphylaxis (PCA) reactions with its specific antiserum only when it is used as intravenous antigen. Reversed PCA reactions cannot be produced when the 19S protein is injected intradermally in contradistinction to the results with 7S γ-globulin.

Antibodies of the high molecular weight class, when injected intradermally, also failed to give PCA reactions following antigen injection. Heterophile antibodies from the sera of patients with infectious mononucleosis, demonstrated to be entirely of the 19S type, gave negative reactions, while 7S heterophile antibodies from guinea pig did give reactions following intravenous injection of sheep cells. Anti-B isoagglutinins of the 19S class failed to react, while those of the 7S class of similar titer gave clear reactions following the injection of B substance.

Evidence was obtained that 19S antibodies were capable of inhibiting the PCA reactions obtained with the 7S type, indicating that interaction with antigen occurred. The failure to elicit PCA reactions appeared to be due to an inability to fix to guinea pig tissues in a manner similar to that known for 7S antibodies and γ-globulin.
STUDIES ON IMMUNE CELLULAR INJURY
Authors: Ross Ann , Lepow Irwin H.
Published: June 2004

A model system for the investigation of immune cellular injury in primary isolates of a fixed-tissue cell of human origin has been described, using metabolism-inhibition and uptake of trypan blue as independent criteria of cytoxicity. Cytotoxic effects on human amnion cells were produced by the combination of specific rabbit antibody and factors in normal human serum which were indistinguishable from the components of hemolytic complement and calcium and magnesium ions. The data have been discussed in relation to the apparent multiplicity of serologic systems which can effect cellular injury. The nature of the cell and the source of antibody or normal serum constituents have been emphasized as factors which may influence the experimental selection of a given humoral mechanism.
FATE OF STAPHYLOCOCCI WITHIN HUMAN LEUKOCYTES
Authors: Melly Marian Ann , Thomison John B. , Rogers David E.
Published: June 2004

Direct observations by phase microscopy have demonstrated that small numbers of pathogenic staphylococci survive prolonged periods of time within living human polymorphonuclear leukocytes. Non-pathogenic microorganisms are rapidly destroyed in similar preparations.

Leukocytes in which staphylococci remained viable often appeared less vigorous after ingesting microorganisms, but intracellular survival could not be correlated with obvious leukocyte damage with any consistency.

Both pathogenic and non-pathogenic cocci were seen to divide within living granulocytes during the first few minutes after ingestion. Occasionally pathogenic staphylococci multiplied in dying cells after long periods of intracellular residence.

Phagocytosis of more than one pair of staphylococci by a single leukocyte appeared to act as a stimulus to bacterial destruction. Multiple ingestions of pathogenic staphylococci reduced the incidence of survival of the total microbiol population contained within the cell.
IN VIVO DETOXIFICATION OF ENDOTOXIN BY THE RETICULOENDOTHELIAL SYSTEM
Authors: Wiznitzer T. , Better N. , Rachlin W. , Atkins N. , Frank E. D. , Fine J.
Published: June 2004

Evidence is presented that

The normal RES extracts endotoxin from the circulation and inactivates it very rapidly.

When the RES has been damaged, whether by a blockading agent, such as thorotrast, or by a reversible degree of hemorrhagic shock, it cannot extract more than a small per cent of the amount of the endotoxin the normal system can extract.

Of that fraction of endotoxin which is extracted, very little is detoxified.

An organ like the kidney, which does not contain a significant amount of RE tissue, does not extract more than an insignificant percentage of the injected amount, and therefore does not detoxify endotoxin.

Since dephosphorylation is a process concurrent with detoxification, and does not occur in an organ which does not extract or inactivate a significant amount of injected endotoxin, it is probable that this process is an indirect index of detoxification.

Within the time limits of these experiments, plasma alone does not inactivate endotoxin.
STUDIES ON PRIMARY ATYPICAL PNEUMONIA
Authors: Liu Chien
Published: June 2004

A factor present in fresh normal human or guinea pig serum enhances the primary atypical pneumonia (PAP) antibody titers in serological reaction with its homologous virus as tested by indirect fluorescent antibody staining. This factor is not properdin. It has many properties similar to complement but may not be identical with complement. The addition of this enhancement factor to human sera convalescent from primary atypical pneumonia has made the serological test more sensitive without affecting its specificity.
STRUCTURE AND DEVELOPMENT OF VIRUSES AS OBSERVED IN THE ELECTRON MICROSCOPE
Authors: Morgan Councilman , Howe Calderon , Rose Harry M.
Published: June 2004

Stages in the development and release of Western equine encephalomyelitis virus are illustrated and described. It is suggested that precursor particles 22 mµ in diameter differentiate at template sites close to membranes bordering cytoplasmic vacuoles and that these particles either pass into the lumen of the vacuole, acquiring in the process a coat and peripheral membrane, or are dispersed in the cytoplasm and extruded through the cellular wall, emerging as viral particles on the surface. Although necrosis and dissolution of the cell with release of contents, including virus, may intervene at any stage of infection, ejection of virus from the vacuoles presumably can occur without rupture of the cell. The virus consists of a 30 mµ core separated by a zone of lesser density from a sharply defined peripheral membrane 45 to 48 mµ in diameter. Precursor particles, as well as viral particles, occasionally crystallize, the former in the cytoplasm, the latter in vacuoles and probably on the cellular surface.
THE SITE OF ACTION OF THE STAPHYLOCOCCUS ALPHA TOXIN
Authors: Thal Alan P. , Egner Willadene
Published: June 2004

The present study concerns the site of action of the staphylococcus alpha toxin. This powerful necrotizing agent produced by pathogenic strains of staphylococcus is very probably important in the pathogenesis of localized staphylococcus disease and in the shock-like picture sometimes associated with staphylococcus septicemia. Our previous studies had suggested that the toxin has a selective effect on vascular smooth muscle.

In investigating this problem further, the following observations were made.

1. The toxin produces an immediate hyperperistalsis and sustained increase in intraluminal tension progressing ultimately to atony and flaccid paralysis in the isolated smooth muscle preparation.

2. The addition of specific antitoxin prior to exposure to toxin prevents this reaction. However, when antitoxin is added after the toxin, no ameliorating effect is seen.

3. The toxin is rapidly and irreversibly bound to its substrate since washing the bowel segment 30 seconds after exposure to toxin fails to change the course of the reaction.

4. Vena caval segments exposed to toxin exhibit a similar initial rise in intraluminal tension followed by flaccid paralysis at which point they no longer respond to epinephrine stimulation.

5. When the toxin is infiltrated in the neighborhood of muscular blood vessels in the living rabbit selective necrosis of smooth muscle cells of the vessel walls is seen.

6. The selective effect on smooth muscle is emphasized by the failure of the toxin to affect the contractility of skeletal and cardiac muscle.

7. Perfusion of the isolated kidney and heart produces an increased resistance to flow after toxin is added to the perfusate.

8. Epithelial cells and fibroblasts in tissue culture exposed to high concentration of toxin for 2 hours are unaffected in their ability to recover and metabolise. This is in marked contrast to the effect on the smooth muscle preparation.

The probability that the toxic effect on smooth muscle cells explains some of the local and systemic effects of staphylococcus infection is discussed.
EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM
Authors: Berry L. Joe , Smythe Dorothy S.
Published: June 2004

There exists an inverse proportionality between number of heat-killed cells of Salmonella typhimurium injected intraperitoneally into mice and the quantity of urinary nitrogen the animals excrete during a 17 hour period following the subcutaneous administration of 2 units of ACTH. This relationship has been developed into an assay for bacterial endotoxin. Mice immunized against S. typhimurium require 10 to 20 times the number of cells needed by control animals to suppress urinary nitrogen excretion to the same extent. Intravenous saccharated iron oxide sensitizes animals so that fewer heat-killed salmonellae can be detected. Heat-killed cells of Staphylococcus aureus are without effect in the assay. Several lipopolysaccharides derived from Gram-negative bacteria are effective in preventing the rise of urinary nitrogen excreted in response to ACTH and the amount required, compared to the LD50, is in the same ratio for all of them. Citrated mouse serum partially inactivates the endotoxin during in vitro incubation for 1 hour at 37°C. while normal serum does not. Dichloroisoproterenol protects mice against the lethal effects of lipopolysaccharide and it lowers its effectiveness in the assay. The minimum amount of endotoxin reliably determined by the test is 0.25 µg. of an E. coli preparation that was given intravenously in mice in which the reticuloendothelial system had been "blocked" with saccharated iron oxide.
STUDIES ON THE PATHOGENESIS OF STAPHYLOCOCCAL INFECTION
Authors: Goshi Keiichi , Cluff Leighton E. , Johnson Joseph E.
Published: June 2004

Necrosis of rabbit skin produced by thermal injury was found to result in a striking increase in local infectivity of staphylococci that were coagulase-positive and hemolytic, but no local increase in the infectivity of non-pathogenic staphylococci. Infection produced in necrotic burns extended beyond the area of burn and was characterized by hemorrhage, edema, and necrosis of contiguous normal skin. Such infections, however, never resulted in bacteriemia or metastatic abscesses, and there was no effect of the necrotic burn upon the infectivity of staphylococci injected into normal skin of the burned animal. Recovery of rabbits from severe burn infections was associated with the development of high titers of serum antibody to the alpha hemolysin or dermonecrotoxin of the staphylococcus. Thirty to 100 days after the initial burn infection, it was found that rabbits could no longer be infected in a necrotic burn, although infection induced in normal skin of these resistant animals was no different from that in normal rabbits.

Immunity to infection by pathogenic staphylococci in necrotic burns could be induced by vaccination with potent alpha hemolysin toxoid, and this immunity was passively transferable with rabbit antiserum. No strain specificity was detected for this immunity in that immunization with toxoid prepared from bacteriophage type 52/42B/80/81 staphylococci protected animals against infection in a necrotic burn by other typable and non-typable staphylococci.

Histopathological study of infected necrotic burns in normal rabbits showed extensive necrosis, hemorrhage, edema, and many masses of bacteria but leucocytic infiltration was observed only at the margin of the infection. In contrast, the infected necrotic burns in animals immunized with alpha hemolysin toxoid showed few bacteria and marked leucocytic infiltration throughout the burn.

These experiments have, therefore, demonstrated a significant immunity to infection by pathogenic staphylococci in necrotic tissue but not in normal skin, associated with serum antibody to the alpha hemolysin or dermonecrotoxin of the bacteria. The implications of these findings are discussed.
LATENT VIRAL INFECTION OF CELLS IN TISSUE CULTURE
Authors: Bader John P. , Morgan Herbert R.
Published: June 2004

A study of the metabolic requirements for the growth of psittacosis virus in L cells has been extended to the water-soluble vitamins. In a system in which a balanced salt solution was used to deplete the cells of their vitamin constituents, only thiamine was essential for psittacosis virus production. Extended depletion of cells with media deficient in specific vitamins demonstrated that pantothenate, niacin (niacinamide), pyridoxine (pyridoxal), and choline, in addition to thiamine, were essential for maximal growth of psittacosis virus. No requirement for biotin, inositol, folic acid, or riboflavin was demonstrated, although the possibility of incomplete vitamin depletion of the cells has not been eliminated. In most cases in which a specific vitamin requirement was shown the decreased yield of virus was correlated with a delay in the cytopathic effects produced in the cell cultures by psittacosis virus.
THE EFFECT OF VARIED OXYGEN SUPPLY AND OF FOOD INTAKE ON WATER MOVEMENT IN SURVIVING LIVER TISSUE
Authors: Opie Eugene L
Published: June 2004

Water movement in liver slices has been measured in the presence of varied oxygen supply and during the progress of gastrointestinal digestion.

Maximum water intake occurs both with anoxia and with exposure to oxygen when animals have received no food during 20 to 24 hours. It diminishes almost immediately after the ingestion of food and is least after 8 to 10 hours when digestion is nearly complete. These changes coincide with the passage of amino acids from the gastrointestinal tract to the liver by way of the blood.

Movement of water into the liver cells is favorable to the entrance of dissolved substances and when it is greatest with approaching anoxia the movement promotes the diffusion of oxygen into the cells.
METABOLIC EFFECTS OF LATHYROGENIC AGENTS ON CARTILAGE IN VIVO AND IN VITRO
Authors: Karnovsky Morris J. , Karnovsky Manfred L.
Published: June 2004

The effects of lathyrogenic agents in vivo and in vitro are described, in respect to some biochemical indices of cartilage metabolism. Lathyrogenic agents in vivo inhibited the incorporation of radiosulfate into rat epiphyseal cartilage and the isolated chondroitin sulfate. No significant changes in hydroxyproline or hexosamine content of epiphyseal cartilage were found, but there was a marked increase in water content. The content of chondroitin sulfate, measured as uronic acid, was decreased. The importance of taking growth rate differences between control and experimental rats into account in assessing the effects of lathyrogenic agents in vivo is emphasized.

In an in vitro system, utilizing fresh calf costal cartilage slices, the presence of low concentrations of lathyrogenic agents markedly affected various metabolic events. The incorporation into cartilage slices of sulfate-S35, glucose-U-C14, and glycine-1-C14 was significantly depressed, as was the production of organic acids, including lactic acid. In general, these effects were more severe under anaerobic conditions. Glutamine restored the activities of the slices treated with lathyrogenic agents to control values obtained in the absence of either lathyrogen or glutamine.
TRANSMISSION OF SWINE INFLUENZA VIRUS BY LUNGWORM MIGRATION
Authors: Sen H. G. , Kelley G. W. , Underdahl N. R. , Young G. A.
Published: June 2004

Experimental evidence is presented which confirms the reports by Shope (1, 2) that swine lungworms can serve as an intermediate host in transmitting swine influenza virus to pigs. The virus is present in a masked non-infective form as he showed and a provocative stimulus is necessary to initiate infection. Multiple injections of Ascaris extract or the migration of Ascaris larvae furnished the needed provocation. The virus could be elicited in the spring and summer as well as fall and winter, from the pathogen-free, colostrum-deprived pigs.
THE SUSCEPTIBILITY OF MICE TO BACTERIAL ENDOTOXINS
Authors: Schaedler Russell W. , Dubos Rene J.
Published: June 2004

Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins.

When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins.

NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination.

Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 µg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 µg. or less), administered alone, caused a marked but transient loss of weight.

Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived.

These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli.