Biomedical subjects
J Hamburger
Publications and source records attributed to J Hamburger.
Effect of thioglycollate on macrophage lysosomal enzymes.
Mice peritoneal macrophages obtained after i.p. injection of a medium containing thioglycollate (Institut Pasteur, Paris) have increased levels of beta glucuronidase and acid phosphatase, when compared with macrophages obtained without previous thioglycollate injection. The maximum increase is observed between 7 and 10 days after injection and reaches up to 3 to 4 times the normal activity. When using separately the various components of the medium, the same phenomenon may be observed but never to the same degree. The injection of thioglycollate also produces: a) an increase in total number of peritoneal cells, and b) an increase in the percentage of macrophages among these cells. Kinetic studies suggest that thioglycollate injection first induces an increase in the number of peritoneal macrophages and subsequently macrophage modifications resulting in lysosomal enzyme increase.
Plasmodium berghei. III. The partial separation of a putative species-specific antigen from a soluble extract.
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Kinetics of immunological responses, resistance to reinfection, and pathological reactions to infection with Trichinella spiralis.
Changes in immune responses, resistance to reinfection, and pathological reactions were studied serially in mice that had been infected for four to 40 weeks with 150 larvae of Trichinella spiralis. Immediate footpad hypersensitivity reactions to antigens of Trichinella were present throughout the period of observation. Delayed hypersensitivity reactions 48 hr after injection of antigen were first seen in mice infected for 14 weeks and gradually increased in size thereafter. Intestinal adult worm burdens were determined one week after challenge with 5000 larvae. There was resistance to reinfection and accelerated expulsion of worms in animals challenged three weeks after the primary infection; this resistance waned at seven and 13 weeks but reappeared in mice infected for 20 weeks or longer. Counts of larvae in muscle were determined four weeks after challenge with 5000 larvae. Marked resistance was present four weeks after the primary infection and was maintained for the duration of the study.
[Recent studies on graft immunology].
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Some implications of transplantation research for biology and medicine.
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Plasmodium berghei: I. Immunochemical properties of fractions of a soluble extract.
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Plasmodium berghei: II. Immunobiological properties of fractions of a soluble extract.
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Plasmodium berghei: use of free blood stage parasites to demonstrate protective humoral activity in the serum of recovered rats.
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Studies on mouse macrophage arming factor and its molecular weight.
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Presence of antigen-antibody complexes in antiallogeneic and antixenogeneic sera.
Antilymphocyte sera (ALS), either allogeneic (for example, Lewis anti-August rat serum) or xenogeneic (the classic ALS), may retain the antigen used for the immunization of the animal producing the serum in the form of antigen-antibody complexes, at least when the animal is bled within the first 2 weeks following the last immunizing injection. Evidence for this has been obtained in vivo and in vitro. In vivo experiments showed that injection of Lewis anti-August serum to a normal Lewis rat can induce a delayed active immunization against the August strain. In vitro studies proved the presence of August antigens in the anti-August sera, by precipitation of the antigen-antibody complexes with 6 M urea, removal of the antibody by filtration, and demonstration that the filtrate specifically inhibits complement-dependent cytotoxicity of anti-August antibodies. The interpretation of a number of previous works on so-called passive enhancement of grafts or on various effects of ALS may have to be reconsidered on the basis of these findings.
T and B cell population changes in young and in adult rats infected with Plasmodium berghei.
Malaria infection in young rats is characterized by high parasitemia, severe anemia, and death. Parasitemia is lower in older rats, and the rats usually survive. This study was designed to investigate the immunological basis of this difference. T cell numbers in the thymuses and spleens of young (4 weeks old) and in adult (18 weeks old) infected and control rats were determined by killing with anti-theta serum and complement. The number of complement receptor lymphocytes (B cells) in spleens was determined after these cells had formed rosettes with sensitized, complement-coated sheep erythrocytes. Infection in young rats was characterized by progressive and severe thymic involution and by decreasing numbers of T and B cells in the spleen. In 18-week-old rats, T cell numbers in the spleen were slightly below those of controls early in infection but exceeded normal values by day 15. Progressive thymic involution was not a feature of infection in adult rats. The number of complement receptor lymphocytes in the spleens of adult rats decreased dramatically early in infection but were nearly normal by day 15. Severity of malarial infection in young rats is related to the inability of their lymphocytes to respond to Plasmodium berghei antigens early in infection in a way that leads to immunity.
Schistoma mansoni soluble egg antigens: determination of the stage and species specificity of their serologic reactivity by radioimmunoassay.
Three highly purified Schistosoma mansoni egg antigens reactivity with sera from mice with chronic schistosomiasis mansoni (major serologic antigens-MSA1, MSA2, and MSA3) were utilized in radioimmunoassays for determining their stage and species specificity. Inhibition studies revealed that MSA1 was completely stage specific, since its binding to S. mansoni chronic infection serum (CIS) could not be inhibited either with cercarial or adult worm antigen. MAS2 and MSA3 were specific with regard to adult worm antigen but their binding to CIS was slightly inhibited by cercarial antigen. Immature eggs in comparison with mature eggs contained only negligible amounts of MSA1 whereas MSA2 and MSA3 were present in large quantities. Fluid from eggs hatched in spring water (hatch fluid-HF) contained considerable amounts of MSA1 as well as MSA2 and MSA3. With regard to species specificity, MSA1 essentially did not cross-react with crude soluble egg antigen (SEA) from Schistosoma japonicum and Schistosoma haematobium whereas MSA2 and MSA3 showed partial cross-reactivity. Antibody dilution studies with sera from animals and humans infected with heterologous schistosome species (i.e., S. japonicum and S. haematobium) indirectly confirmed the high degree of species specificity of MSA1. The degree of serologic specificity of MSA1 as demonstrated in this study parallels that of the sensitizing activity of S. mansoni eggs and SEA for granuloma formation, as demonstrated in previous investigations. This study, therefore, indicates that MSA1 may be a major immunopathologically active egg antigen. In addition, the high degree of species specificity of MSA1 suggests its use in the serodiagnosis of schistosomiasis mansoni.
Plasmodium berghei: characteristics of a selected population of small free blood stage parasites.
The characteristics of a selected population of small blood stage parasites obtained by differential centrifugation of a population of P. berghei parasites freed by continuous flow sonication are described. About 10% of these free parasites are merozoites, many others are transitional forms having some merozoite characteristics. The parasite preparations are infectious and sufficiently resistant to incubation at 37 degrees C to be useful experimentally. Disc gel electrophoresis analysis indicates that these small parasites differ in composition from an unselected intraerythrocytic P. berghei population.
Mechanisms of allograft rejection.
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Interaction between protective antibodies and malaria parasites (Plasmodium berghei): involvement of low avidity antibodies.
Free Plasmodium parasites were incubated with a standardized amount of immune serum in a small volume of fluid or a larger one. When these parasites were tested for infectivity in and in vivo test system the parasites incubated in the larger volume of fluid were more infective. Other aliquots of free P. berghei parasites were incubated with a standaridzed amount of immune serum and then reincubated with or without dilution of the suspending fluid. Those parasites reincubated after dilution were more infective than reincubated without dilution. These results were interpreted as indicating that the malaria parasite-protective antibody interaction is readily reversible probably due to the low avidity of the protective antibodies.
Schistosoma mansoni soluble egg antigens. I. Identification and purification of three major antigens, and the employment of radioimmunoassay for their further characterization.
A cell-mediated immunologic granulomatous response to Schistosoma mansoni eggs is now generally accepted as being responsible for the hepatosplenic disease of chronic schistosomiasis. Previous investigations have demonstrated that a soluble extract of S. mansoni eggs (SEA) both induces and elicits granulomatous hypersensitivity and other forms of cell-mediated immunologic reactivity. Mice with chronic light S. amnsoni infections show spontaneous suppression of granulomatous hypersensitivity in the presence of high levels of anti-SEA antibodies. Immunodiffusion analysis using antiserum obtained from these mice and SEA resulted in the identification of three major serologic antigens which have been designated MSA1, MSA2, and MSA2. Initial studies with Sephadex G-200 gel filtration and polyacrylamide gel electrophoresis indicated that the three antigens were markedly different in m.w. and at least two of the three were glycoproteins. The antigens were then extracted from crude SEA by adsorption to a concanavalin A Sepharose affininity column. The eluted antigens were separated from each other by ion exchange chromatography on DEAE cellulose. On polyacrylamide gel electrophoresis (PAGE) MSA1 and MSA2 were homogenous; MSA3 was estimated to be 70% pure. The purified antigens were radiolabeled and were passed through Sephadex G-200 or Bio-Gel A 1.5 columns to determine their m.w. These studies have shown that MSA1 and MSA2 are glycoproteins of m.w. 137,000 and 465,000 daltons, respectively; the m.w. of MSA3 is in the range of 50,000 to 70,000 daltons. PAGE of the purified antigens revealed the following R.F.s: MSA1=0.34, MSA2=0.20, and MSA3=0.48. MSA1 and MSA2 were employed in radioimmunoassays using the ammonium sulfate method of Farr. On the basis of immunodiffusion analysis and radioimmunoassay, MSA1 exhibits a degree of stage and species specificity consistent with the granulomatous response to S. mansoni eggs. The potential specificity of the MSA1 radioimmunoassay and its great sensitivity suggest a role in the immunodiagnosis of schistosomiasis.
Nature of macrophage modifications induced by the macrophage activating factor(s) (MAF): effect of enzymes and temperature.
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