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Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 217 records · Page 12Linked to original sources

Establishment of cutaneous Leishmania enriettii infection in hamsters.

A model of a self-healing type of cutaneous leishmaniasis was established in hamsters using the guinea pig parasite Leishmania enriettii. L. enriettii was passaged several times in hamsters without losing its infectivity for guinea pigs or for hamsters. The course of the infection in hamsters resembled that of guinea pigs, with the exception that the lesion at the site of parasite inoculation did not ulcerate and no metastatic lesions developed spontaneously. Moreover, unlike guinea pigs, infected or recovered hamsters were skin test unresponsive to various preparations of L. enriettii antigens. However, histological examination of draining lymph nodes showed features of a cell-mediated immune response, and in vitro inhibition of macrophage migration was demonstrable using peritoneal exudate cells from recovered animals and specific leishmanial antigen. Antibody was demonstrable by indirect immunofluorescence starting 1 week after infection. Recovered animals were immune to reinfection; however, the passive transfer of peritoneal exudate cells or serum from recovered animals did not confer protection against L. enriettii infection in normal animals.

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Influence of rodent malaria on the course of Leishmania enriettii infection of hamsters.

Plasmodium yoelii infection was established in hamsters, and the effect of this type of malaria on concurrent Leishmania enriettii infection was examined. It was found that the course of the L. enriettii infection was affected by P. yoelii and that this effect depended on the relative timing of the two infections. A chronic malarial infection with Plasmodium berghei was also established in hamsters, and this was found to affect the course of a concurrent L. enriettii infection in a similar manner to P. yoelii. These results are discussed in relation to current knowledge of the immunosuppressive effects of plasmodia.

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Central and peripheral action of suppressor cells in contact sensitivity in the guinea-pig.

Suppressor cells were demonstrated in the spleen of guinea-pigs made specifically unresponsive to dinitrofluorobenzene (DNFB) with dinitrobenzene sulphonic acid (DNBSO3). Transfusion of these cells at the same time as sensitization with DNFB, produced a significant reduction in the immunoblasts proliferating in the draining lymph node 4 days later. Transfusion on the day of skin testing produced no greater suppression of skin reactivity than cells taken from animals made hypo-reactive to DNFB by contact with dinitrothiocyanate benzene (DNTB). It is concluded that there are at least two sites that suppressor cells can act. In the case of total unresponsiveness induced by DNBSO3, action is both central and in the periphery. In the case of hyporeactivity induced by DNTB, in which there is no defect in proliferation of T cells in response to antigen, the action of these cells is confined to the periphery. results of spleen weight studies suggest that suppressor cells homing in the spleen respond by proliferation to epicutaneously applied DNFB.

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Binding of heterologous anti-brain antibodies to mouse B cells.

Antibodies produced in rabbits against mouse brain are able to react with the majority of lymph node and spleen murine lymphocytes, as demonstrated by indirect immunofluorescence. Cells stained by a suitably absorbed rabbit anti-mouse brain serum showed various degrees of fluorescence, from bright fluorescent rings to a few speckles per cell; lymphocytes from the spleen of deprived mice (B mice) predominantly stained in small caps. Double labelling experiments in which B cells were identified by their 'easily detectable' surface immunoglobulin revealed that a great proportion of these cells had two overlapping caps, a large one formed by the anti-immunoglobulin serum and a small one formed by the anti-brain serum. Up to 10 per cent of these spleen B cells, however, appeared as strongly fluorescent as T cells, with the suitably absorbed heterologous anti-brain serum. No anti-immunoglobulin activity was detected in this serum. It is therefore suggested that some B cells may bear on their surfaces a theta or theta-related antigen similar to that on T cells.

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Detection of immune complexes in mice infected with Mycobacterium lepraemurium.

A specific binding test was used to detect immune complexes containing antigens of Mycobacterium lepraemurium in the serum and tissues of infected mice. Complexes were precipitated by antiserum against immunoglogulin, free antigen removed by washing and the presence of bound antigen demonstrated by measurement of uptake of radioactively labelled specific antibody by the precipitate. Tests were done both with 125I-labelled FAB prepared from an immune from rabbit antiserum against M. Lepraemurium and with 125I-labelled IgG precipitate. Out of seventy-nine serum samples taken monthly up to the 5th month after infection, only there were positive (one at 2 months and two at 3 months). Kidneys taken from infected mice were also examined for immune complexes. Although deposits of IgM and sometimes of IgG were observed by immunoflourescence in glomeruli of normal mice, deposits of IgG were more frequent later on in infected mice. Nevertheless, binding tests done on acid eluates were positive in only one out of fifty-three infected mice.

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Modification of cutaneous leishmaniasis in the guinea-pig by cyclophosphamide.

Pretreatment of guinea-pigs with cyclophosphamide (Cy) (300 mg/kg) 3 days before cutaneous infection with Leishmania enriettii caused an increased intensity of the lesion at the site of infection and an increase in the incidence of widespread metastases. Decreased levels of circulating antibody were found from the first to fourth week after infection. Decreased delayed type hypersensitivity could only be detected beyond 4 weeks. Peritoneal macrophages obtained form guinea-pigs 3 days after Cy pretreatment showed increase rather than decreased ability to phagocytose L. enriettii. Phagocytosis of L. enriettii by peritoneal macrophages obtained from guinea-pigs pretreated with Cy 24 days previously was normal. It is suggested that more attention should be taken of antibody levels during the early phase of infection and that control of infection could be due to a synergism between antibody and cell-mediated immunity. Upset in the balance by suppression of either function might lead to the development of widespread metastatic lesions.

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Comparison of allergic aspermatogenesis with that induced by vasectomy. I. In vivo studies in the guinea-pig.

Groups of male and female guinea-pigs were immunized with homologous epdidymal sperm in Freund's complete adjuvant (FCA) and skin tested at weekly intervals with a heat-treated extract of the sperm or with PPD. In females, the skin response to both antigens was similar to that to any standard protein antigen. In males, the response to sperm extract varied with the induced auto-immune orchitis, reaching a maximum immediately after testis lesion was most severe and as recovery was beginning (shown histologically): the response to PPD was decreased at 1 week after immunization, but subsequently was similar to that in females. Skin tests on guinea-pigs 8 months after bilateral vasectomy (when both ends of vasa were ligated), showed no evidence of delayed hypersensitivity to sperm, although there was marked histological evidence of reduced spermatognesis, due to back pressure atrophy.

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Comparison of the effect of various antisera and cobra venom factor on inflammatory reactions in guinea-pig skin. I. Non-specific inflammation due to the intradermal injection of turpentine.

Guinea-pigs were treated with agents which lowered the serum complement levels and the effect on the inflammatory reaction to intradermal turpentine was studied. A comparison was made between two antisera to beta1C/beta1A globulin which had been prepared in different ways. One was made using C3 fixed to zymosan particles as the antigen, and the other using chemically extracted beta 1C/beta1A globulin. The antisera to beta1C/beta1A globulin (zymosan) was found to have the greater anti-inflammatory activity. The effect of each on the parameters of complement studied, and on the circulating platelet count, was much the same. An antiserum to serum factors fixed to zymosan during C3 activication was prepared free of anti-beta1C/beta1A globulin antibodies. This was found to have some of the anti-inflammatory activity of the anti-beta1C/beta1A globulin (zymosan), as well as lowering total complement levels. Anti-gamma globulin andheterologous immune complexes also lowered serum complement levels and were antiinflammatory. However, all the above agents were also found to reduce the number of circulating platelets. This was in contrast to CVF which reduced complement levels by 90 per cent. but had no effect on platelet numbers. CVF also reduced the inflammatory response but was no more effective than the other agents. In view of these findings a role for the participation of the complement system, possibly involving the alternate pathway of activation of C3, is discussed as well as the participation of platelets in the reaction.

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Comparison of the effect of various antisera and cobra venom factor on inflammatory reactions in guinea-pig skin. II. The Arthus reaction and the local Shwartzman reaction.

The ability of antisera to guinea-pig C3 to inhibit the Arthus and local Shwartzman reactions was studied. They were found to reduce the non-haemorrhagic component of the active and reversed passive Arthus reactions and to delay the appearance of the haemorrhage in the active Arthus reaction. Cobra venom factor, however, had no effect on the non-haemorrhagic components of these reactions and only delayed the appearance of the haemorrhage of the active Arthus reaction. There appeared to be a correlation between the serum complement level and the time taken for the haemorrhage to appear, and between the circulating platelet count and the extent of the non-haemorrhagic, oedematous component of the reaction. The haemorrhagic component of the local Shwartzman reaction was not affected by decomplementation with cobra venom factor. The ability of the antisera to inhibit the haemorrhage of the Shwartzman reaction was not dependent on lowering the serum complement titre. However, the haemorrhage was inhibited if the circulating platelet count was also reduced to very low numbers. Antiserum to zymosan alone had the same effect as anti-beta1C/beta1A globulin (zymosan) in blocking the reaction, although it did not alter the complement levels or the platelet counts. The possibility of an immunological cross-reactivity between zymosan and endotoxin in this action is discussed.

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The fine structure of the reticulum cells in lymph-nodes from cyclophosphamide-treated thymectomised mice.

In mice depleted of lymphocytes by thymectomy and cyclophosphamide treatment the popliteal lymph nodes showed macrophages, fibroblasts, endothelial cells and a heterogeneous group of cells here described as reticulum cells. Some of these both within and outside the germinal centres had fine long processes, i.e., were dendritic, and some had deep cytoplasmic invagination. Interdigitating cells were not a feature of the nodes and there was little evidence of migration of cells through post-capillary venules.

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Chronic malarial infection in Balb/C mice. Effect on the immune response to sheep erythrocytes and histological changes in the liver and spleen.

Chronic malarial infection was established in Balb/c mice by following Plasmodium berghei yoelii with P.b. berghei infection. It was found that the IgG plaque-forming cell response to sheep erythrocytes was depressed for at least six months. A preliminary investigation of the histological changes in the spleen and liver is described. The possibility that chronically infected mice could serve as a model for the tropical splenomegaly syndrome is discussed.

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