bluuebunny/crossref_metadata_2025 huggingface dataset:
PLASMA FIBRINOLYSIS IN MAN: THE EFFECT OF CHYLOMICRONS DERIVED FROM DIFFERENT DIETARY FATS
Authors: Farquhar John W. , Merigan Thomas C. , Sokolow Maurice
Published: June 2004

The plasma fibrinolytic activity, measured in vitro, of 17 healthy normal young males was consistently and equally inhibited by prior ingestion of equal amounts of either a relatively saturated animal fat (butterfat) or a highly unsaturated vegetable fat (safflower oil).

This effect was further studied by the addition of purified chylomicrons derived from ingestion of either butterfat, safflower oil, or egg yolk to an in vitro system. The inhibitory effect was quantitatively similar in all experiments despite wide variations in composition of the fed fat and pronounced differences in fatty acid composition of the lipids of the chylomicrons.

It seems reasonable to suggest from our data that the proteins and the nonfatty acid portions of the chylomicron phospholipids may be important determinants of the inhibitory effect of chylomicrons on fibrinolysis.
THE RELATIONSHIP OF DELAYED HYPERSENSITIVITY AND CIRCULATING ANTIBODY TO EXPERIMENTAL ALLERGIC THYROIDITIS IN INBRED GUINEA PIGS
Authors: McMaster Philip R. B. , Lerner Edwin M. , Exum Eurmal D.
Published: June 2004

Strain 13 histocompatible guinea pigs developed allergic thyroiditis after immunization with thyroid extracts derived from the same strain or from other strains of guinea pigs. This thyroiditis appeared as early as 5 days after immunization, and by 7 weeks was uniformly present and generally severe. 7 weeks after immunization, the anti-thyroid antibody titer correlated with the presence and degree of thyroiditis. However, at certain other times after immunization, the titer did not correlate with the thyroiditis. By contrast, all animals with thyroiditis, which were skin-tested with thyroid extract, exhibited delayed hypersensitivity. Moreover, all those which failed to respond with delayed reactions, when skin-tested, had not developed thyroiditis. The present work correlates the presence of experimental allergic thyroiditis with delayed hypersensitivity.
PREPARATION AND EFFECTS OF AN ANTI-MAST CELL SERUM
Authors: Smith Douglas E. , Lewis Yevette S.
Published: June 2004

In an attempt to obtain an antiserum that would bring about widespread destruction of mast cells in the rat, rabbits were immunized with mast cells isolated from the peritoneal cavities of rats. Striking evidence of anti-mast cell activity was indicated in vivo by mast cell disruption and in vitro by positive interfacial precipitin tests of the serum from rabbits so treated. The time course of the production of anti-mast cell activity in the rabbit serum was established. Normal rabbit serum was without effect on mast cells in the several tests. The same was true for rabbit anti-rat liver serum except when it was applied directly to tissues containing mast cells. In the latter case mast cell disruption ensued, but it appeared different from that evoked by anti-mast cell serum.

Intraperitoneal injection of anti-mast cell serum was followed by destruction of all of the mast cells of the mesentery and of the majority of mast cells in the ear, scrotum, and abdominal skin. The time course of this destruction, of the phagocytosis of the mast cell debris, and of the repopulation of the tissues with new mast cells was established. Attending the disruption of mast cells the levels of tissue histamine dropped sharply but returned toward normal as new mast cells appeared. In the scrotum and abdominal skin 5-hydroxytryptamine did not fall below normal and was markedly above normal at the time when histamine and mast cell content were lowest. Reddening and swelling of the muzzle, ears, feet, and scrotum were present during the first few days after injection of the anti-mast cell serum. Intraperitoneal injection of normal rabbit serum was without any of the above effects. Similarly injected rabbit anti-rat liver serum had no effect on the mast cells or upon the levels of histamine and 5-hydroxytryptamine in the ear, scrotum, or abdominal skin. It caused no reddening and swelling of the muzzle, ears, feet, and scrotum. It was attended, however, by destruction of the mast cells and by a sharp fall in the histamine content of the mesentery. Gross changes in the tissue of the peritoneal cavity following anti-mast cell and anti-liver serum were described.

The possible significance of the several findings were discussed.
CONCERNING THE SURFACES OF CELLS OF STAPHYLOCOCCUS PYOGENES
Authors: Sall Theodore , Mudd Stuart , Taubler James
Published: June 2004

A strain of pathogenic Staphylococcus aureus, grown under special conditions, accumulates extracellular metabolites about the bacterial cells. This phenomenon may simulate, but is differentiable from, the capsulation of, for instance, the mucoid "Smith" strain. The special nutrient requirements, namely lactose, mannitol, vitamin, and gelatin containing medium, promote the production and accumulation about the cells of, in particular, soluble coagulase. A mutant of this parent strain, deficient in capacity to elaborate soluble coagulase and fibrinolysin, does not accumulate metabolites about its cells, even under the special growth conditions. To avoid confusing this phenomenon, which at least in vitro is essentially artifactitious, with true capsulation, we suggest the term pseudocapsulation.
THE LATHYROGENIC EFFECT OF ISONICOTINIC ACID HYDRAZIDE (INAH) ON THE CHICK EMBRYO AND ITS REVERSAL BY PYRIDOXAL
Authors: Levene C. I.
Published: June 2004

When applied to the chorio-allantoic membrane of the chick embryo, isoniazid was shown to produce an increase in the fragility of the embryo and in the amount of collagen which was extractable from the bones with cold 1 M sodium chloride. The administration of pyridoxal reversed these phenomena almost completely.

The effect of isoniazid differed from that of ß-aminopropionitrile in that the latter was of greater magnitude, and was not affected by pyridoxal; whereas ß-aminopropionitrile caused skeletal deformities, isoniazid even at 12 times the concentration produced no deformities.

The aldehyde group of pyridoxal was shown to be necessary for its interaction with isoniazid.
THE EFFECT OF BACTERIAL ENDOTOXINS ON THE WATER INTAKE AND BODY WEIGHT OF MICE
Authors: Dubos Rene J. , Schaedler Russell W.
Published: June 2004

Injection of endotoxin of Gram-negative bacilli into NCS mice caused an immediate reduction or interruption of water intake by these animals, with a resultant loss of body weight.

Endotoxins prepared by three different techniques from four different cultures of Gram-negative bacilli yielded products having approximately the same activity in inhibiting water intake. The minimum effective dose was 0.1 µg. or less. With all toxin preparations tested, the duration of the effect was directly related to the dose injected.

The heat-killed cells of Esch. coli proved approximately as effective as the endotoxins prepared from Gram-negative bacilli. In contrast, heat-killed cells of Mycobacterium tuberculosis (BCG) were much less active, and heat-killed cells of Staphylococcus aureus were essentially inactive.

Mice previously treated with endotoxin exhibited a marked degree of tolerance to the inhibition of water intake caused in normal animals by a subsequent treatment with the same material. Tolerance could also be induced by vaccination with heat-killed Gram-negative bacilli. Tolerance overlapped from one bacterial species to another but was more pronounced toward the endotoxin prepared from the bacterial culture with which the animal was vaccinated.

The duration of the inhibitory effect of endotoxin on water intake was much shorter with mice fed a complete diet than with mice fed a deficient diet (corn).

It took approximately the same dose of endotoxin (0.1 µg.) to inhibit water intake, reduce the influx of polymorphonuclear leucocytes, and enhance staphylococcal infection.
STRUCTURE AND DEVELOPMENT OF VIRUSES AS OBSERVED IN THE ELECTRON MICROSCOPE
Authors: Rifkind Richard A. , Godman Gabriel C. , Howe Calderon , Morgan Councilman , Rose Harry M.
Published: June 2004

Sequential stages in the development and release of ECHO 9 virus have been illustrated and described. It is suggested that viral particles differentiate and become oriented in columns upon a fine filamentous lattice at cytoplasmic template sites which are distinct from the endoplasmic reticulum. Subsequently, virus is dispersed in the peripheral cytoplasm and gains egress from the cell through rents in the plasma membrane. Complete cellular disruption with viral release may supervene. The virus consists of a 13 to 15 mµ dense core and a poorly defined outer membrane, 22 to 24 mµ in diameter. Incomplete forms, lacking the core, are observed in the cytoplasm but have not been seen in the extracellular space.
THE IMMUNE RESPONSE OF RABBITS TOLERANT TO BOVINE SERUM ALBUMIN TO THE INJECTION OF OTHER HETEROLOGOUS SERUM ALBUMINS
Authors: Weigle William O.
Published: June 2004

Immunological tolerance produced in rabbits by neonatal injections of BSA can be terminated by a series of injections of certain heterologous serum albumins which cross-react with BSA. Injections of albumins distantly related to BSA were more effective in terminating the tolerant state than injections of albumins closely related to BSA. It was concluded from results obtained with several heterologous albumins that immunological tolerance to BSA is directed to both the over-all antigenic or physical-chemical composition of the protein and the individual determinant groups present on the protein. Several possible mechanisms were given to explain the ability of cross-reacting albumins to terminate the tolerant state of BSA-tolerant rabbits.

A possible relationship between the termination of tolerance in BSA-tolerant rabbits injected with cross-reacting albumins and autoimmunily was discussed. It was also suggested that the relative ease with which tolerance could be established to heterologous serum proteins in comparison to bacterial antigens is the result of the close serological and physical-chemical relationship of the heterologous serum proteins to the serum proteins of the rabbit.

Rabbits injected with 500 mg of BSA during the first 5 days of life failed to form antibody capable of either eliciting an immune elimination of an injection of I* BSA given 3 to 4 months later or complexing with the circulating I* BSA.
IMMUNOCYTOLOGICAL EFFECTS OF VARIED INOCULA OF INFLUENZA VIRUS
Authors: Watson Barbara K.
Published: June 2004

Variation in the amount and quality of influenza virus injected into the amniotic sac of the chick embryo led to differences not only in the yield of virus but also in the immunofluorescent cytology of the infection.

The production of infectious virus was associated with a predominance of cells in which the virus antigens were first detected along the cell surface in contact with the amniotic fluid, later deeper in the cytoplasm, and finally, though to a lesser extent, in the nucleus.

When the virus yield was primarily non-infectious hemagglutinin the virus antigens appeared in reverse sequence; i.e., nucleus first, then adjacent cytoplasm, and ultimately throughout the entire cell.

Under conditions of "autointerference," the immunofluorescence seen in some of the cells failed to progress beyond the nuclear or early cytoplasmic stage, while many other cells remained unreactive throughout the experimental period.

With the largest dose used a pale intranuclear reaction was localized 1 hour after injection but the embryo died shortly thereafter.
EXPERIMENTAL GENETIC RECOMBINATION IN VIVO BETWEEN ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM
Authors: Schneider H. , Formal Samuel B. , Baron L. S.
Published: June 2004

Antibiotic-pretreated mice were fed orally an Hfr culture of streptomycin-resistant E. coli and 1 day later, a streptomycin-resistant F- S. typhimurium culture. Hybrids were recovered in relatively small numbers from the feces of these mice within 24 hours demonstrating that genetic recombination can occur within the intestinal tract of a mammalian host under experimental conditions. These hybrids multiplied rapidly and persisted throughout the course of the experiment. In addition, hybrids were recovered which had not been observed in single matings performed in vitro.
STUDY OF THE ADSORPTION ON AND DESORPTION FROM POLYSTYRENE-HUMAN SERUM ALBUMIN CONJUGATES OF RABBIT ANTI-HUMAN SERUM ALBUMIN ANTIBODIES HAVING DIFFERENT SPECIFICITIES
Authors: Webb Tom , Lapresle Claude
Published: June 2004

An insoluble specific adsorbent for anti-human serum albumin antibodies was prepared by coupling human serum albumin (H.S.A.) to polystyrene by azo bonds. Rabbit anti-H.S.A. immune serum was passed through a column of the adsorbent. It was shown that different volumes of the immune serum were required for the saturation of the different determinant groups of H.S.A. by their corresponding antibodies.

The elution of the anti-H.S.A. antibodies adsorbed on the column was achieved by passing successively through the column an acetate buffer pH 3.0 and a solution of 0.1 N HCl in 0.15 M NaCl. The antibodies were eluted in three different fractions, each of which was composed of γ-globulins only. These three fractions contained different proportions of antibodies of different specificities.
THE LOCATION AND NATURE OF ENTEROVIRUS RECEPTORS IN SUSCEPTIBLE CELLS
Authors: Holland John J. , McLaren Leroy C.
Published: June 2004

It is shown that enterovirus receptors are found mainly in the microsomal fraction of disrupted primate cells. Greater virus adsorption was exhibited by disrupted cells than by intact cells, indicating that enterovinis receptor may be present on intracellular membranes as well as on the surface of the cell. Polio-virus receptor is an integral part of, or is firmly attached to, the insoluble lipoproteins of the cell. All attempts to solubilize receptor have either destroyed virus-adsorbing activity, or have failed to separate it from sedimentable lipoproteins. The destruction of poliovirus receptor activity by proteolytic enzymes, surface active agents, organic solvents, concentrated urea solutions, phenol, formaldehyde, etc., all strongly indicate that this receptor function depends upon integrity of a protein portion of the membrane lipoproteins.
THE INFLUENCE OF INFLUENZA VIRUS INFECTION ON EXOGENOUS STAPHYLOCOCCAL AND ENDOGENOUS MURINE BACTERIAL INFECTION OF THE BRONCHOPULMONARY TISSUES OF MICE
Authors: Sellers Thomas F. , Schulman Jerome , Bouvier Claude , McCune Robert , Kilbourne Edwin D.
Published: June 2004

Mice infected with a non-mouse-adapted Asian strain of influenza A virus suffered an impaired capacity to destroy or remove staphylococci introduced by the respiratory route. This temporary inhibition of local defense mechanisms was of 7 to 10 days' duration.

The persistence of staphylococci in the lung following influenza did not appear to alter the nature of the pathologic reaction to influenza virus.

The presence of influenza virus infection in the respiratory tract of the mouse did not alter the fate of intravenous staphylococci in the lung or other organs.

In 40 to 50 per cent of mice with influenza, purulent bronchopneumonia and infection with Pasteurella and Hemophilus of murine origin were noted. A minority of control animals evidenced such infection.

The administration of antimicrobials to which the murine bacteria were susceptible prevented both the appearance of the endogenous infection with Pasteurella or Hemophilus and the purulent sequelae to influenza virus infection. The true picture of uncomplicated bronchopulmonary influenza virus infection was thus separated from the combined virus-bacteria effect otherwise encountered.
CHANGES PRODUCED IN MOUSE PLASMA PROTEINS BY ACUTE BACTERIAL INFECTIONS
Authors: Williams Curtis A. , Wemyss Courtney T.
Published: June 2004

The immunoelectrophoretic patterns of plasma proteins from mice are altered significantly by acute infections. Some proteins are dissociated into two or more components, some showed striking increase in plasma concentration, others are depleted, and certain ones appear which are undetectable in normal samples.

ß1-C dissociated into two electrophoretic components under a variety of conditions in addition to infections. Endotoxins and killed organisms in vivo, and specific precipitate absorption, heat and aging in vitro produced this change. Endotoxins injected into mice also induced a rise in haptoglobin though not as sharply or predictably as acute infection.

Preliminary results with samples from hospital patients with acute diseases are discussed. It was concluded that study of experimental diseases in laboratory animals by these techniques could provide a fruitful basis for the investigation of the plasma protein changes in similar human diseases.
THE INFLUENCE OF HYDROCORTISONE ON THE ACTION OF EXCESS VITAMIN A ON LIMB BONE RUDIMENTS IN CULTURE
Authors: Fell Honor B. , Thomas Lewis
Published: June 2004

The effect of hydrocortisone has been studied in organ cultures of the cartilaginous long bone rudiments from 7-day chick embryos and of the well ossified limb bones from late fetal mice. In the chick rudiments, which grow rapidly in culture, the growth rate was much reduced by hydrocortisone, less intercellular material was formed, and the hypertrophic cells of the shaft were much smaller than in the controls in normal medium. In the late fetal mouse bones, which grow very little in culture, hydrocortisone had no obvious effect on growth but arrested resorption of the cartilage. These effects resemble those described by others in the skeleton of animals treated with cortisone or hydrocortisone.

The influence of hydrocortisone on the response of the chick and mouse explants to excess vitamin A was investigated. In the presence of excess vitamin A, cartilage (chick, mouse) and bone (mouse) rapidly disintegrated, but when hydrocortisone also was added to the medium, this dissolution of the intercellular material was much retarded, though not suppressed.

The retardative action of hydrocortisone on the changes produced by excess vitamin A in skeletal tissue in culture, contrasts sharply with the strongly additive effect of the two agents on the skeleton in the intact animal (Selye, 1958). It is suggested that this discrepancy between the results obtained in vitro and in vivo is probably due to systemic factors that operate in the body but are eliminated in organ cultures.
THE ROLE OF OPSONINS IN THE CLEARANCE OF LIVING AND INERT PARTICLES BY CELLS OF THE RETICULOENDOTHELIAL SYSTEM
Authors: Jenkin Charles R. , Rowley Derrick
Published: June 2004

An investigation of the clearance of bacteria and colloids from the blood stream of mice has shown that both living and inert particles require serum factors (opsonins) in order that they may be phagocytosed by the macrophages of the reticuloendothelial system. It has been demonstrated that after the injection of a large dose of colloid there is a depletion of these serum opsonins which appears to account for the reduced rate of clearance of a second dose of colloid or living bacteria, since replacement of these factors leads to normal clearance. The significance of these results is discussed and it is suggested that in "blockaded" animals there is a depletion of serum opsonins rather than a saturation of phagocytic cells.
PYELITIS, AN IMPORTANT FACTOR IN THE PATHOGENESIS OF RETROGRADE PYELONEPHRITIS
Authors: Andersen Burton R. , Jackson George Gee
Published: June 2004

Pyelitis with acute and chronic pyelonephritis and also primary chronic pyelitis were easily initiated in female rats by a single non-traumatic retrograde infusion of bacteria into the urinary tract. The virulence of the bacterial species and the time of observation were related to the type and extent of lesions, but pyelitis regardless of the virulence appeared to be an important factor. The apex and fornix of the renal pelvic lumen were anatomic sites of persistent pyelitis which permitted local proliferation of bacteria for long periods. Cortical and medullary lesions were anatomically related to these areas of underlying pyelitis. Spread of infection followed a pattern of contiguity rather than ascending tubular infection. The experimental model has many of the features of chronic urinary infections in man and suggests that pyelitis is an important factor in the pathogenesis of chronic pyelonephritis initiated by retrograde infection.
COMPARATIVE STUDIES IN ROUS SARCOMA WITH VIRUS, TUMOR CELLS, AND CHICK EMBRYO CELLS TRANSFORMED IN VITRO BY VIRUS
Authors: Erichsen Stian , Eng Jan , Morgan Herbert R.
Published: June 2004

The chick embryo fibroblast infected by Rous sarcoma virus in vitro acquires the capacity to produce the acid mucopolysaccharides which are found in the tumors caused by this virus and which are also produced by tumor cells in vitro. The transformed cell acquires synthetic as well as morphologic, metabolic, and proliferative properties characteristic of Rous sarcoma tumor cells in vivo and in vitro and the transformed cell may be analogous to the tumor cell produced by virus infection in vivo.
INDICATIONS OF HEREDITARY, SPATIAL REARRANGEMENT OF ANTIGEN COMPLEXES, IN THE INFLUENZA VIRUS
Authors: Magill Thomas P.
Published: June 2004

During passage in mice which had been vaccinated with the homologous, and with closely related strains of influenza virus, the passage strain developed a lessened susceptibility to the deleterious effects of the "immune" environment, concommittant with which was a developed capacity to evoke antibodies which reacted with earlier strains of virus—a capacity which was inapparent in the parent strain. However, the parent strain exhibited a relatively broad range of surface reactivity which was not apparent in the derived strain.

The data are interpreted to mean that the hereditary change resulted from spatial rearrangement and quantitative redistribution of antigens in the virus particle (in which the surface is viewed as being distinct from the inner bulk), and are viewed as enhancing the idea that influenza virus variation (i.e., "mutation") may result from a rearrangement of existing hereditary elements.
THE ROLE OF HUMORAL ANTIBODIES IN REJECTION OF SKIN HOMOGRAFTS IN RABBITS
Authors: Kretschmer Roberto R. , Peréz-Tamayo Ruy
Published: June 2004

Gross and microscopic observations of skin homograft rejection carried out in cortisone-conditioned and non-conditioned rabbits seem to indicate that humoral antibodies play an important role in the phenomenon. Thus, local administration of isoimmune serum to animals bearing skin homografts resulted in a significantly earlier rejection of that particular test graft without modifying the course of a neighboring control-skin graft. This result appears to support the idea that homograft rejection is not only due to cellular antibodies but to a combination of both humoral and cellular immune responses, which should not be regarded as completely unrelated.
ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS IN MAN
Authors: Franklin Edward C. , Stanworth Denis R.
Published: June 2004

The antigenic properties of normal 19S γ-globulin, pathologic macroglobulins, ß2A-myeloma proteins, and Bence Jones proteins have been compared with 7S γ-globulin and the small 3.5S units derived from it by gel diffusion precipitin techniques.

These studies demonstrate that the determinant groups on the 7S γ-globulin molecule responsible for the cross-reaction with each of the other proteins are associated with the two fragments of 7S γ-globulin which have the antibody-combining sites.

The antigenic specificity of the 7S γ-globulin which distinguishes it from each of these proteins is associated primarily with the fragment that is richest in hexose and can not combine with antigen. However when compared with certain of the paraproteins additional antigenic specificity was also found to reside in the fragments with antibody-combining activity.

The finding of similar antigenic relationships in rabbit γ-globulins suggests that some of the biological properties associated only with the 7S γ-globulins and not with the other immune globulins may reside in the fragment which also carries the antigenic specificity of the protein.
THE BEHAVIOR OF THREE DIFFERENT KINDS OF ANTIBODIES IN TUBERCULOSIS: ANTIPROTEIN, ANTIPOLYSACCHARIDE, AND ANTIPHOSPHATIDE
Authors: Takahashi Yoshio , Mochizuki Koji , Nagayama Yoshitame
Published: June 2004

In human tuberculosis as in experimental tuberculosis, there exist in the serum of tuberculous patients three different kinds of antibodies completely distinct from each other, antipolysaccharide, antiprotein, and antiphosphatide. The two former antibodies are produced whenever tuberculous infection takes place or exists and they persist for a long period, even though tuberculous disease be arrested. On the contrary, the production of the antiphosphatide seems to be mainly conditioned by the outbreak of tuberculous disease following infection, because none of the tuberculin-positive healthy persons tested gave a positive phosphatide hemagglutination test. The antiphosphatide hemagglutination test furnishes useful information about the extent or the activity of tuberculous disease.

No correlation was noticed between the degree of tuberculin skin hypersensitivity and the amount of any of the three antibodies.

The usefulness of the phosphatide hemagglutination test in the diagnosis of tuberculosis is discussed.
BIOCHEMICAL BASIS FOR ALTERATIONS IN STRUCTURE AND FUNCTION OF HELA CELLS INFECTED WITH NEWCASTLE DISEASE VIRUS
Authors: Wheelock E. Frederick , Tamm Igor
Published: June 2004

The ability of NDV-infected HeLa cells to synthesize DNA, protein, and RNA was investigated by measuring the incorporation of tritiated precursors into these substances at intervals after infection of cells with a virus/cell multiplicity of 500:1. A significant decrease in incorporation of precursors into DNA and protein was first observed at 3¼ hours after infection. By 4½ hours, an 80 to 90 per cent decrease had occurred, and by 5¼ hours, incorporation of precursors into DNA and protein was almost completely inhibited. Incorporation of precursor into RNA decreased gradually following infection; by the 10th hour, a 40 per cent decrease had occurred.

These results, integrated with earlier observations on biological aspects of infection, suggest the following causal relationships among events in NDV-infected cells: (a) The cessation of virus production is probably caused by inhibition of protein or RNA synthesis, and is not due to inhibition of DNA synthesis or to interferon. (b) The production of infective virus does not per se interfere with the ability of an infected cell to divide, nor is inhibition of mitosis caused by either inhibition of DNA synthesis or development of marked degenerative changes in infected cells. Inhibition of mitosis may be the result of inhibition of protein or RNA synthesis, (c) Marked cell damage could have been caused by inhibition of protein, DNA, or RNA synthesis, (d) Interference by NDV with the multiplication of influenza virus was probably due to the inhibitory effects of NDV on cellular biosynthetic activities.
THE RELATIONSHIPS BETWEEN SERUM COMPLEMENT ACTIVITY AND THE DEVELOPMENT OF ALLERGIC LESIONS IN RABBITS
Authors: Rhyne Marie Britt , Germuth Frederick G.
Published: June 2004

Total serum hemolytic complement activity is consistently reduced in animals undergoing accelerated "serum sickness". The time of maximum reduction in complement titer invariably coincides with the time of complete antigen disappearance. This temporal relationship supports the belief that the reduction in complement titer is brought about by in vivo antigen-antibody combination.

The intravenous administration of a single daily large dose of BGG-precipitated complexes produces a marked but temporary reduction in total complement hemolytic activity. On the other hand, multiple injections of soluble BGG immune complexes prepared in antigen excess failed to even temporarily alter complement titers. Animals undergoing the development of accelerated "serum sickness" treated by either type immune complex showed a significantly reduced incidence of arterial lesions. Apparently, this inhibiting effect on the development of arterial lesions was independent of variations in total complement hemolytic activity.
ALTERATIONS IN THE OXIDATIVE METABOLISM OF RATS WITH INDUCED TOLERANCE: IN VITRO STUDY OF DIAPHRAGM
Authors: Rubin Arnold D. , Cascarano Joseph , Zweifach Benjamin W.
Published: June 2004

Oxidative metabolism of diaphragms from endotoxin- and trauma-tolerant rats was investigated, utilizing the reduction of tetrazolium salt. It was found that diaphragms from normal and stress-tolerant animals did not differ in "oxidative performance" (activity in the absence of the redox dye phenazine methosulfate). However, diaphragms from tolerant animals exhibited a highly significant enhancement in "oxidative potential" (activity in the presence of phenazine methosulfate). This change was apparently not precipitated by adjustments in circulatory dynamics, nor was it related to reticuloendothelial stimulation. The suggestion is made that the effects observed may develop through the secondary release of endogenous epinephrine.

Evidence is presented suggesting that the enhancement of "oxidative potential" exhibited by the parenchymal tissues of tolerant animals represents an adaptation in metabolism whereby pools of potentially oxidizable foodstuffs are stockpiled.
THE ROLE OF LIVER AND SPLEEN IN THE METABOLISM OF INTRAVENOUSLY INJECTED FAT IN RABBITS
Authors: Van Den Bosch J. , Evrard E. , Billiau A. , Joossens J. V. , De Somer P.
Published: June 2004

The uptake of intravenously injected coconut oil emulsion by the liver and spleen was investigated by gas-liquid chromatography in normal, triton-injected, and hypercholesterolemic rabbits. The lauric and myristic acids from this emulsion, almost absent in the tissues of normal animals, were used as marked acids.

In normal rabbits only the liver took up a quantitatively important fraction of the injected fat. The uptake by the spleen appears to be due to a different mechanism than that of the liver. In rabbits given triton the liver was incapable of taking up large quantities of fat, while the uptake in the spleen was undisturbed. 12 hours after injection the plasma, liver, and spleen of normal animals contained only 14 per cent of the dose. With animals given triton 71 per cent of the injected dose was recovered, most of it in the plasma.

Hypercholesterolemic rabbits cleared an injected fat emulsion and took fat into the liver at the same rate as the controls.

When triton is injected 6 hours after the administration of the emulsion, the fat taken up in the liver reappears in the plasma.
THE EFFECTS OF MAMMALIAN AND OTHER CATIONIC POLYPEPTIDES ON THE CYTOCHEMICAL CHARACTER OF BACTERIAL CELLS
Authors: Spitznagel John K.
Published: June 2004

Cationic polypeptides interact with bacterial cells of E. coli and B. anthracis. They confer upon the cells some of the characteristics of cationic particles. Since bacterial cells usually behave as anions, acidic dyes at high pH levels differentiate between cells which have and those which have not interacted with cationic polypeptides. Under the conditions of these experiments it appeared that cationic polypeptides tend to be sorbed in highest concentration in the surface layers of the cells. Electrovalent binding to anionic cell components and detergent action are probably among the mechanisms involved in the interaction between the polypeptides such as histones and bacterial cells.

The differential staining of bacterial cells which have interacted with cationic polypeptides is feasible and reasonably selective. It should be useful in determining whether bacterial cells interact with host cationic polypeptides in vitro.
STUDIES ON THE MECHANISM OF THE FORMATION OF THE PENICILLIN ANTIGEN
Authors: Levine Bernard B. , Ovary Zoltan
Published: June 2004

An excess of D-benzylpenicillenic acid (BPE) was reacted with human γ-globulin, human serum albumin, gelatin, and poly-L-lysine in aqueous solution buffered at pH 7.5–8.0. Under these conditions, BPE reacted predominantly with lysine ϵ-amino groups of the proteins to form the mixture of diastereomers of ϵ-N-(D-α-benzylpenicilloyl)-lysine groups (Di-BPO-Lys). BPE reacted also, but to a considerably smaller extent, with cystine disulfide linkages of human γ-globulin and human serum albumin to form D-benzylpenicillenic acid-cysteine mixed disulfide groups (BPE-SS-Cys). Conjugates containing large numbers of BPE or D-penicillamine mixed disulfide groups were prepared by reaction of BPE or D-penicillamine with thiolated human γ-globulin under mild oxidizing conditions.

Anti-penicillin antibodies were produced in rabbits by immunization with either potassium penicillin G (PG) or a preincubated mixture of PG with normal rabbit serum (PG-NRS) in complete Freund's adjuvant. Specific precipitation analyses in aqueous and gel media (Ouchterlony), PCA analyses, and specific inhibition of these reactions with haptens were carried out on the rabbit anti-PG and anti-(PG-NRS) sera, using the above conjugates as antigens. The anti-penicillin antibodies were found to be directed against the diastereomeric mixture of N-(D-α-benzylpenicilloyl) groups, predominantly the Di-BPO-Lys groups. By these techniques, no antibodies directed against the BPE-mixed disulfide or the D-penicillamine mixed disulfide groups were detected.

Three out of six patients with histories of allergic reactions to PG responded with wheal-and-erythema reactions to the N-(D-α-benzylpenicilloyl) (BPO) groups contained in BPE-human gamma globulin conjugate. Another such patient exhibited serum antibodies specific for the BPO group. One patient being treated with 25 gm per day of PG showed the presence of non-dialyzable antigenic BPO-conjugates in his serum.

These results demonstrate that the diastereomeric BPO groups (predominantly Di-BPO-Lys groups) are major antigenic determinant groups responsible for PG hypersensitivity in rabbits and human beings. The possible clinical usefulness of multivalent Di-BPO conjugates and univalent Di-BPO haptens is discussed.
STUDIES ON THROMBIN-INDUCED PLATELET AGGLUTINATION
Authors: Shermer Richard W. , Mason Reginald G. , Wagner Robert H. , Brinkhous Kenneth M.
Published: June 2004

A one-stage macroscopic test for platelet agglutination was used to study the effect of thrombin and thrombin-cation mixtures on washed platelets. Conclusions regarding platelet agglutination are as follows:

(a) Canine, bovine, or human thrombin alone does not cause agglutination of canine or human platelets.

(b) Thrombin with calcium or magnesium causes rapid platelet agglutination. Both calcium and magnesium are active at physiologic concentrations. Divalent manganese or cadmium ions can be substituted for calcium or magnesium.

(c) The agglutination reaction is affected but little by the species of origin of thrombin or platelets, or by variations in ionic strength or pH over a broad range.

(d) Temperature at which the reaction is carried out is critical; optimal temperature for the test is 28°C.

(e) Agglutination is inhibited by high ionic strength, by pH values outside the range 6.4–8.6, and by temperatures outside the range 25–28°C. High concentrations of calcium have a specific inhibitory effect.

(f) Platelet agglutination time is as sensitive an index of thrombin concentration as is the fibrinogen clotting time.

A comparison is made between divalent cations which influence platelet agglutination induced by thrombin, TAg', and TAg. A similar comparison is made of cations influencing the action of thrombin on the "substrates," fibrinogen, TAMe, and platelets.
STUDIES OF ACUTE PHASE PROTEIN
Authors: Kushner Irving , Kaplan Melvin H.
Published: June 2004

A method is presented for the immunohistochemical localization of Cx-reactive protein in rabbits, based on the use of a defined antiserum and rigorous fixation techniques requisite for this antigen. In animals in which inflammatory lesions and CxRP response were induced by intramuscular injection of typhoid vaccine, Cx-reactive protein was localized only in the area of local inflammation within muscle fibers showing morphologic evidence of necrotic change. Within such altered fibers, CxRP was observed in peripheral segments of myofiber or in subsarcolemmal sarcoplasm, in scattered deposits in sarcoplasm, and in vacuolar inclusions. No CxRP was found at any time in polymorphonuclear or mononuclear cells in the inflammatory lesion, nor in contralateral muscle, regional or distal lymph nodes, liver, spleen, thymus, heart, or kidney, except as traces in lumens of vessels or interstitium. CxRP was first detected in necrotic myofibers at the inflammatory site after a latent period of 8 to 10 hours following injection of the inflammatory stimulus and could be demonstrated in these sites for the 48 hours of the experiment. It could not be observed at the inflammatory site before appearance in the blood. Identical histologic localization in necrotic myofibers at the site of the local lesions was found following induction of granulocytopenia with nitrogen mustard. These findings are consistent with the hypothesis that CxRP is formed locally at the site of inflammation from tissue elements undergoing necrotic change. Alternatively, secondary deposition from the blood at the inflammatory site cannot be excluded, but is considered less likely in view of the failure to obtain evidence of a cellular localization of CxRP in other organs.
THE VACUOLATING VIRUS OF MONKEYS
Authors: Gaylord W. H. , Hsiung G.-D.
Published: June 2004

Cells infected with the vacuolating virus, SV40, respond by swelling to several times their normal volume. Within enlarged nuclei, virus-containing inclusions appear which are acidophilic and Feulgen-positive. The formation of nuclear inclusions is followed by the appearance of cytoplasmic vacuoles and then shrinkage of the cell. Inclusions were found to exhibit unique double staining when a light-green counterstain was used in the Feulgen reaction. The virus is of low electron density, round, and 300 A in diameter. It occurs in large numbers, singly and in short chains, and it appears to multiply at the expense of chromatin.
STUDIES ON THE INTERRELATIONSHIP BETWEEN THE BLOOD-BRAIN BARRIER AND ENTRY OF VIRUSES INTO THE CENTRAL NERVOUS SYSTEM
Authors: Sellers Margret I. , Lavender John F.
Published: June 2004

Inhalation of elevated concentrations of CO2 produces a significant increase in the susceptibility of mice to intravenously inoculated Type II poliovirus. The CO2 effect is directly proportional to the concentration; 2.5 minutes inhalation of a mixture of 30 per cent CO2-70 per cent O2 produces maximal effects, while lower concentrations of CO2 require correspondingly longer periods. The threshold level is 7 per cent; inhalation of lower concentrations, even for long periods of time, fails to enhance virus infectivity. Placing the animals in the CO2 atmosphere before injection of virus does not influence susceptibility; virus must be in the circulation at the time CO2 is inhaled if enhancement of infectivity is to be elicited. The effect is completely reversible, disappearing almost immediately upon withdrawal of the animals from the CO2 atmosphere. CO2 mediates an increase in the entry of virus into the CNS from the circulation but does not affect the spread of virus within the CNS; susceptibility of mice to intracerebrally inoculated poliovirus is not influenced by CO2 inhalation. The mechanism(s) of action of CO2 can be explained, in part, by the dilatation of cerebral blood vessels and increased rate of blood flow through the CNS produced by the CO2. However, other factors, which remain unidentified, contribute to the net effect of CO2.

The relationship between the mechanism of action of CO2 and the provoking effects of trauma and violent exercise in poliomyelitis is discussed. Also, a relationship between the CO2 tension of the blood and environmental temperatures on poliovirus susceptibility is proposed.
PHYSICAL PROPERTIES OF ANTIBODY TO BOVINE SERUM ALBUMIN AS DEMONSTRATED BY HEMAGGLUTINATION
Authors: Benedict Albert A. , Brown Ronald J. , Ayengar Rajalakshmi
Published: June 2004

Rabbit antibovine serum albumin antisera were fractionated by zone electrophoresis on starch, zone ultracentrifugation in sucrose density gradients, and diethylaminoethyl-cellulose chromatography, and were assayed by the passive HA technique. Antisera had at least two antibodies: one associated with a fraction characterized as a γ-2 globulin with a sedimentation rate of 7.3S and low anionic binding (fraction I), and one associated with a fraction characterized as a γ-1 globulin (or ß-globulin) with a sedimentation rate of 20.4S and high anionic binding (fraction IV). The HA titers of fractions I and IV of early sera were approximately equal. On prolonged antigenic stimulation fraction IV agglutinin decreased in concentration and the relative concentration of fraction I agglutinin increased. Chromatographic analysis of hyper-immune sera yielded 2 additional HA fractions with intermediate anionic binding. These results indicated that rabbits synthesize anti-BSA antibodies similar to rabbit anti-cellular antibodies.

Rabbit anti-BSA precipitin migrated mainly as a γ-2 globulin and the agglutinin migrated with γ- and ß-globulins. The evidence suggested that the HA method might measure antibody not measured by the quantitative precipitin technique.
ISOLATION AND PROPERTIES OF A SURFACE ANTIGEN OF STAPHYLOCOCCUS AUREUS
Authors: Morse Stephen I.
Published: June 2004

A technique is described for the isolation and purification of an antigen released into the culture medium by Staphylococcus aureus strain Smith.

The antigen was found to be homogeneous when examined by free electrophoresis and analytic ultracentrifugation. Immunologic homogeneity was established by immunoelectrophoresis and quantitative precipitin tests using high titer antiserum prepared against the homologous organism.

Chemical analysis showed that the antigen contained 70 per cent carbohydrate, of which approximately 30 to 35 per cent was believed to be glucosamine. The analytic data suggested that another amino sugar, probably carboxylated, was also present, but extreme lability of this compound to mild hydrolytic procedures has thus far precluded further identification. The remainder of the antigen was composed of alanine, glutamic acid, aspartic acid, lysine, glycine, serine, and threonine. No muramic acid was found.

The chemical and physical data indicate that the antigen described herein is a previously unrecognized component of Staphylococcus aureus.

The purified compound was capable of absorbing agglutinating antibody from antiserum prepared against S. aureus Smith, indicating that it was a surface component of this encapsulated staphylococcus. It is proposed that the antigen be known as the Smith surface antigen (SSA).

The injection of SSA into rabbits did not produce precipitating antibodies. However, SSA did precipitate at low concentrations (0.5 µg/ml) with antiserum prepared against S. aureus Smith and one other strain of S. aureus tested. Antiserum against two other aureus strains reacted only with high concentrations of SSA. SSA did not react with S. albus antiserum or with normal sera from several animal species. Experiments are in progress to define further the distribution of SSA.

Intradermal injection of small quantities of SSA into rabbits immunized with S. aureus Smith evoked a reaction of cutaneous hypersensitivity, which was maximal in 8 to 12 hours.

SSA appeared to be the substance responsible for the ability of S. aureus Smith to resist engulfment by phagocytes, since absorption of Smith antiserum with SSA effectively removed opsonizing antibodies.

SSA induced protection in mice against experimental staphylococcal disease. The subcutaneous injection of 0.1 µg resulted in protection against a subsequent intraperitoneal challenge with 50 to 100 LD50's of S. aureus Smith suspended in mucin. Increasing as well as decreasing the immunizing dose resulted in significantly less protection.
DESTRUCTION OF EPIDERMAL CELLS IN VITRO BY AUTOLOGOUS SERUM FROM NORMAL ANIMALS
Authors: Terasaki Paul I. , Chamberlain Charles C.
Published: June 2004

Sera and plasma from normal rats and rabbits were shown to be extremely toxic in vitro to autologous epidermal cells. On the other hand, mouse sera and newborn rat sera were innocuous to autologous epidermal cells. Viability of cells was assessed by the method of eosin dye exclusion upon 2 hour incubation at 37°C. Testicular cells were also killed by autologous sera, but polymorphonuclear leukocytes, lymphocytes, and lymph node cells were not affected.

Autotoxicity of sera could be destroyed by the depletion of complement components with an antigen-antibody precipitate, heat, zymosan, and NH3. Moreover, activity of sera could be absorbed out by epidermal cells, though not by lymph node cells or erythrocytes. Such absorption of toxicity was not individual-specific since homologous epidermal cells also absorbed toxicity, and in addition, were killed by fresh normal serum. Enzyme inhibitors such as soybean trypsin inhibitor and ϵ-amino-n-caproic acid did not affect the activity of fresh autologous serum.

It is suggested that a natural barrier exists between the basal cells of the epidermis and the plasma which prevents the autodestructive process under normal conditions. Any injury to this barrier may than lead to necrosis and death of the epidermis as seen in various pathological conditions.
STUDIES ON THE BIOLOGIC RELATIONSHIP OF ENDOTOXIN AND OTHER TOXIC PROTEINS
Authors: Staab Edward V. , Condie Richard M. , Good Robert A.
Published: June 2004

1. Injections of sublethal quantities of Agkistrodon piscivorus venom into endotoxin-treated rabbits produces a consistent early death.

2. The endotoxin-induced hypersusceptibility state (EIHS) to venom is produced by intravenous, intradermal, and intraperitoneal administration of endotoxin. The latency and duration of the EIHS vary with the route of administration.

3. EIHS is induced by as little as 1 gamma of endotoxin administered intravenously. Although the degree of susceptibility was no greater with a 100 gamma dose than with 1 gamma, 1 mg of endotoxin made the rabbits susceptible to smaller venom doses.

4. EIHS was demonstrated with intravenous, intradermal and intraperitoneal injection of Agkistrodon piscivorus venom. Endotoxin-pretreated animals were not as susceptible to venom given intramuscularly.

5. Normal rabbits are very resistant to venom given intradermally and intraperitoneally.

6. Enhanced susceptibility to intravenous endotoxin was demonstrated in animals pretreated with sublethal doses of moccasin venom. It differed from EIHS in its short duration and its outcome: a late, slowly progressive death.

7. EIHS was demonstrated with other venoms: Crotalus adamanteus and Vipera russellii, and in a modified form (resulting in late death) with Notechis scutatus. Endotoxin pretreatment had no effect on susceptibility to Naja flava, Bungarus candidus, or Crotalus durissus terrificus venoms.

8. Major hypotheses regarding the nature of endotoxin-induced alterations in non-specific resistance were considered in relation to EIHS to venom.
THE ROLE OF THE SYMPATHETIC NERVOUS SYSTEM IN THE GENERALIZED SHWARTZMAN REACTION
Authors: Palmerio C. , Ming S. C. , Frank E. , Fine J.
Published: June 2004

Unilateral denervation of the renal pedicle was performed in a series of rabbits. 5 to 21 days later two intravenous injections of E. coli endotoxin were given 18 hours apart. In seven rabbits the generalized Shwartzman reaction developed in the non-denervated kidney. Four of the seven denervated kidneys did not show the reaction, and in the remaining three only a mild reaction was present. From these and previous observations we conclude that an intact sympathetic nervous system as well as endotoxin from the intestine, are necessary for the production of the generalized Shwartzman reaction.