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Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 109 records · Page 6Linked to original sources
PubMed1986

Accessory cell function of cells isolated from Mycobacterium leprae-induced granulomas.

The large cells from Mycobacterium leprae-induced granulomas in guinea pig lymph nodes were separated by Percoll discontinuous density gradient centrifugation and on a fluorescence-activated cell sorter (FACS) using cross-reacting monoclonal antibody to human MHC Class II antigens. Large Percoll-separated cells (83% Class II antigen positive and 52% macrophage-specific antigen positive) and FACS-separated cells are able to act as antigen-presenting cells for T-cell proliferation to PPD. In previous studies, macrophage antigen-positive cells consistently failed to act as accessory cells. This indicates that there is a population of accessory cells which are macrophage antigen negative and MHC Class II antigen positive present in these M. leprae-induced granulomas.

Animals↗
PubMed1986

Thiol-disulfide exchange by thrombospondin: evidence for a thiol and a disulfide bond protected by calcium.

Thrombospondin (Tsp), a protein secreted by activated platelets, forms disulfide-linked complexes with thrombin [K. J. Danishefsky, R. J. Alexander and T. C. Detwiler (1984) Biochemistry 23, 4984]. Thiols and disulfide bonds of Tsp were analyzed, and a search was made for other Tsp covalent complexes. Platelets in 1 mM EDTA were activated with ionophore A23187, and the secreted proteins were analyzed by gel electrophoresis in sodium dodecyl sulfate. One millimolar dithioerythritol (DTE) decreased the electrophoretic mobility of Tsp, indicating reduction of an intrachain disulfide bond; Ca2+ prevented this effect. Electrophoresis of single-chain Tsp prepared with 50 mM DTE in either EDTA or Ca2+ also revealed a Ca2+-stabilized intrachain disulfide bond. Ca2+ prevented the retention of Tsp on an activated thiol-Sepharose column, indicating protection of a thiol by Ca2+. Incubation at 37 degrees C for 60 min resulted in complexes with apparent mass much greater than 500 kDa. Formation of complexes was prevented by N-ethylmaleimide, by a temperature less than 25 degrees C, and by Ca2+ or Mg2+. From pH 6 to 9, complexes formed better at lower pH. Two-dimensional (nonreduced/reduced) electrophoresis revealed Tsp but no other constituents of the complexes. With 10 nM thrombin, complexes formed faster and included thrombin; Ca2+ only partially inhibited. The complex was very susceptible to dissociation by low concentrations (2.5 mM) of DTE. It is concluded that Tsp has a reactive thiol and an intrachain disulfide bond that are protected by Ca2+. When these groups are unprotected, there is intermolecular thiol-disulfide exchange.

Blood Platelets↗
PubMed1986

Immunocytochemical identification and quantitation of mononuclear cells in the meninges during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig.

To investigate the role of mononuclear cells in the meninges at all stages of chronic relapsing experimental allergic encephalomyelitis, juvenile guinea pigs were inoculated with isogeneic spinal cord in Freund's complete adjuvant (FCA) in parallel with animals inoculated with FCA alone as age-matched controls. Cytospins were prepared of the meningeal inflammatory cells obtained by washing the brains of these animals. These cytospins were stained by indirect immunoperoxidase, using a panel of monoclonal antibodies (Mabs) recognizing "activated" macrophages (M phi s), Ia antigen, total T cells and a putatively T-cell-suppressor subset, and an antiserum against immunoglobulins. The inflammatory response was quantitated and the proportions of the different cell types were determined. It was found that the total number of infiltrating cells correlated with the neurological symptoms of the disease. "Activated" M phi s increased significantly during the disease, in line with clinical signs. The expression of the Ia antigen, found on both lymphocytes and M phi s, also appeared to correlate with the disease. There was no increase in putative T-suppressor-cells during remission but there was a significant rise in the proportion of both cells staining with anti-immunoglobulins and plasma cells during relapse.

Animals↗
PubMed1986

Potentiation of release of interleukin-2 by bleomycin.

The antineoplastic drug bleomycin, which has not been shown to have immunosuppressive activity, was tested for its effect on concanavalin A-induced interleukin-2 production. When the drug was added to splenocytes of Lewis rats or Balb/c mice in the presence of concanavalin A, in optimal conditions for interleukin-2 production, no detectable effects were seen. However, using a suboptimal dose of concanavalin A, bleomycin increased interleukin-2 release significantly. This effect was achieved using less than 1 microgram/ml bleomycin. In addition, bleomycin was tested for its ability to alter interleukin-1 production by peritoneal exudate macrophages. The drug seems to increase the release of interleukin-1 from peritoneal exudate macrophages of Lewis rats without any lipopolysaccharide added or with a suboptimal concentration of lipopolysaccharide. It is suggested that bleomycin, and probably other cytotoxic drugs, may modulate the immune response through its effects on the release of immunostimulating cytokines such as interleukin-1 and -2.

Animals↗
PubMed1986

A study of the prostaglandin and thromboxane content of the central nervous tissues with the development of chronic relapsing allergic encephalomyelitis.

Levels of PGE, PGF2 alpha, 6-oxo-PGF1 alpha and thromboxane (TXB2) in spinal cords and cerebellums of guinea pigs at different stages of chronic relapsing allergic encephalomyelitis (CREAE) were compared with those in Freund's adjuvant-treated, age-matched controls. PGE and TXB2 levels were found to be increased in spinal cords during acute and relapse phases of the disease. The number of lesions in the spinal cord was similarly increased in acute and relapse stages. There was, however, no similar correlation between number of lesions and eicosanoid levels in the cerebellum with the clinical stages of the disease based on hind limb paralysis. In the acute phase and remission lesion numbers were low, and high levels, similar to those found in the spinal cord, were only found in the relapse phase. Eicosanoid levels were high in the acute phase and remission, and generally low in relapse. The spinal cord levels of eicosanoids in remission and relapse correlated well with previous data obtained from the CSF of patients with multiple sclerosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

The effect of cyclophosphamide in vivo on the expression of lymphocyte markers, detected by monoclonal antibodies, in the rat.

Surface markers on lymphocytes from the thymus, lymph node and spleen of the rat were examined in single cell suspensions using a panel of monoclonal antibodies. These were used particularly to investigate Pan T, TH (T-helper), TS/C (T-suppressor-cytotoxic) and Ia antigens. The expression of these markers in rats treated with a single dose of cyclophosphamide (100 mg/kg body weight) was followed for 3 weeks after treatment. Maximum changes were detected at 3 days and recovery took up to 3 weeks to near completion. Comparison was made with histological observations of the effect of CY on these organs. At 3 days, the thymus showed maximum weight loss and gross cortical depletion. This associated with significant drop in the expression of the TS/C marker on small and large lymphocytes. Regeneration of the cortex, beginning at 7 days, was associated with the presence of many large pyroninophilic cells. This was accompanied by an increase in the expression of the TS/C marker on both small and large lymphocytes. The mesenteric lymph node showed marked depletion of the B-cell areas at 3 days. There was also a significant drop in TS/C and Ia expression and a marked rise in Pan T and TH. TS/C expression recovered rapidly with a rebound at 7 days. However, the expression of Pan T and TH did not return to normal until 21 days. In the spleen there was a similar decrease in the lymphocytes populating the B-cell areas at 3 and 7 days with an increase in the expression of Pan T and TH, and a decrease in the expression of Ia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effect of cyclophosphamide on T-lymphocyte marker expression in T-cell areas of some lymphoid organs of the rat.

Surface markers on rat lymphocytes from thymus and T-cell areas of lymph node, spleen and Peyer's patches were examined in histological sections after one single dose of Cyclophosphamide (CY, 100 mg/kg body weight). A panel of monoclonal antibodies was used: W3/13, W3/25 and OX8 to investigate Pan T, TH and Ts/c marker expressions respectively. Ts/c marker expression showed a marked and significant reduction in both thymus and lymph node lymphocytes 3 days after CY treatment. This was followed by return to normal in the thymus and a significant rebound increase in the lymph node by day 7 after treatment. This Ts/c marker expression in both the spleen and Peyer's patches showed a significant increase on both day 3 and 7 after CY treatment. Mast cells were observed in large numbers in the thymus and lymph node but not in the spleen and Peyer's patches. TH marker expression was increased significantly in lymph nodes, spleen and Peyer's patches. No change was observed in Pan T marker expression in any of the tissues at any of the times examined.

Animals↗
PubMed1985

Accessory cell function of cells of the mononuclear phagocyte system isolated from mycobacterial granulomas.

Epithelioid cells from BCG-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas were examined for their ability to act as accessory cells for T-cell proliferation to mitogen (Con A) and antigen (PPD). The granuloma cells were separated on a FACS using monoclonal antibody specific to guinea pig macrophages. Epithelioid cells (which are Ia negative) were able to support proliferation to Con A but not to antigen. Cultures containing Ia positive granuloma macrophages from M. leprae sensitized animals did not show responsiveness to Con A or to PPD. Oil-induced peritoneal exudate macrophages from BCG or M. leprae immunized animals were able to act as accessory cells for both mitogen and antigen proliferation. The nonresponsiveness of cultures containing epithelioid cells stimulated with PPD or M. leprae granuloma macrophages stimulated with Con A was not due to suboptimal or supraoptimal accessory cell:lymphocyte ratios.

Animals↗
PubMed1985

The effect of hydrocortisone and cyclosporin A on bacillus Calmette-Guérin epitheloid cell granulomas.

The injection of bacillus Calmette-Guérin (BCG) intradermally into the ear of guinea pigs leads to the formation in the draining lymph node of granulomas containing epithelioid cells with rough endoplasmic reticulum (RER) and an absence of phagocytosed material. BCG granulomas in hydrocortisone- or cyclosporin A (CsA)-treated animals contain mononuclear phagocytes with no RER. In CsA-treated animals, these cells contain fragments of phagocytosed organisms. CsA was given at two doses, 25 mg/kg orally and 50 mg/kg ip. The higher dose completely suppressed the delayed hypersensitivity (DH) response to purified protein derivative (PPD) but the lower dose did not affect the level of the DH response, but had a profound effect on epithelioid cell formation. The role of lymphokines in the maturation of the monocyte/macrophage to epithelioid cells is discussed.

Animals↗
PubMed1985

Correlation between prostaglandin and thromboxane levels and clinical signs in cyclosporine A-treated guinea pigs with acute experimental allergic encephalomyelitis.

Prostaglandin E, prostaglandin F2 alpha and thromboxane B2 levels were measured in the spinal cord and cerebellum of guinea pigs with acute experimental allergic encephalomyelitis treated with Cyclosporine A in a schedule which delayed the onset of the disease and completely suppressed it in 40% of the animals. A correlation was found between the eicosanoid levels in the central nervous system and clinical signs of the disease. Where lesions were completely suppressed the levels of eicosanoids were normal. The number of lesions found correlated well with the clinical state of the animals.

Animals↗
PubMed1985

A comparison of the effects of hydrocortisone on peritoneal inflammatory exudates, the tuberculin reaction and contact sensitivity-to DNFB in the guinea pig.

Hydrocortisone acetate, injected subcutaneously in five doses in a depot producing vehicle, causes prolonged suppression of the ability of guinea pigs to produce a chronic inflammatory reaction in the peritoneal cavity and also of the tuberculin reaction. This suppression of the tuberculin reaction persists for at least 65 days after the last dose of hydrocortisone. Suppression of both peritoneal exudate and the tuberculin reaction was associated with a preferential depletion of macrophages at the reaction site. A similar regime had no effect on the ability of guinea pigs to manifest contact sensitivity reactions to 2,4-dinitrofluorobenzene although there was a similar drop in macrophages in the lesion. It appears that the effect of hydrocortisone on delayed hypersensitivity reactions is not directly related to the functional contribution of macrophages in the inflammatory reactions, and may be related to the site of the inflammatory reaction in the skin.

Animals↗
PubMed1985

Predictive value of assessment of lymph node weight and T-lymphocyte proliferation in contact sensitivity in acrylates.

An assessment of T-lymphocyte proliferation and lymph node weight is proposed as a predictive test for contact sensitizers of industrial origin. Data are presented showing increased T-lymphocyte proliferation following epicutaneous application of a variety of industrially important acrylate-like chemicals which appear to correlate well with their ability to sensitize in the guinea pig. These data were compared with those obtained after application of 2,4-dinitro-1-fluorobenzene (DNFB) a strong sensitizer, and 2,4-dinitrothiocyanatebenzene (DNTB) a nonsensitizer when given epicutaneously. It is suggested that this quantitative approach, in parallel with a simple one-dose immunization, may provide a better picture of sensitization potential than the longer multidose immunizations currently in use.

Acrylates↗
PubMed1985

Effect of depletion of epidermal dendritic cells on the induction of contact sensitivity in the guinea-pig.

Guinea pig skin was depleted of Langerhans cells (LC) as assessed by ATPase and Ia staining using several techniques. The LCs were depleted either by tape-stripping or exposure of the animals to UV-B or UV-C radiation. Guinea-pigs were sensitized to 2,4-dinitrochlorobenzene (DNCB) by application of the sensitizer to the epidermis depleted of LC. Minimally suppressed contact reactions were found in animals exposed to both wavelengths of radiation, but this was shown to be a systemic rather than a local effect. Tape-stripping did not alter the degree of contact sensitivity when guinea-pigs were sensitized with a large dose of DNCB. When a non-sensitizing dose of DNCB was applied to the ear depleted of LC by tape-stripping, contact sensitivity resulted. Although the depletion of LCs was 97% following UV-B, 93% with UV-C and 78% after tape-stripping, at no time were LCs completely absent from the epidermis.

Animals↗
PubMed1985

The mononuclear phagocyte system in granulomas.

A comparison is made between immunologically induced and non-immunologically induced granulomas in guinea-pigs injected with metals (zirconium and aluminum) or with mycobacteria (BCG vaccine and Mycobacterium leprae). Immunological granulomas were characterized by epithelioid cells and fibrosis, whereas non-immunological granulomas contained phagocytosing macrophages with little evidence of fibroblast activation. Epithelioid cells carry the same specific macrophage antigen as phagocytosing macrophages and this can be detected by the use of a specific monoclonal antibody. However, they differ from phagocytosing macrophages in that they are poorly phagocytic, not glass adherent and lack Ia antigen. They are however secretory cells with rough endoplasmic reticulum. A relation between the presence of these cells and increased collagen synthesis is indicated. A study of accessory cell function showed that the epithelioid cells of BCG granulomas were able to support mitogen-induced but not antigen-induced proliferation of T lymphocytes. The macrophages of M. leprae granulomas did not support either a mitogen- or antigen-induced proliferative response.

Animals↗
PubMed1985

Epicutaneous induction of tolerance with acrylates and related compounds.

Epicutaneous application of acrylates and related compounds 14 and 7 days before sensitization with either methyl acrylate or trimethylol propane triacrylate induced tolerance to the resultant contact reactions. This tolerance could not be correlated with either the degree of cross reactivity between these compounds or with their ability to react covalently with amino or sulphydryl groups of proteins. These results are discussed in relation to other epicutaneous tolerizers in the dinitrobenzene and poison ivy systems.

Acrylates↗
PubMed1985

Immune response to a thymus-independent antigen (DNP-Ficoll) in the guinea pig.

Guinea pigs immunized with DNP30-Ficoll produced IgM antibody only. No IgG1, IgG2, IgE antibodies or delayed hypersensitivity were detected in these animals. However, Arthus reactions, induced by the hapten coupled to a foreign carrier or the whole antigen, were found. The time course of the IgM response was limited and the response to reinjection of the antigen reduced. Cyclophosphamide (CY), given 3 days before primary immunization, prolonged the IgM response. Given on the day of immunization or 3 days after CY reduced this response. CY given on days +3 or +7 after primary immunization completely suppressed the response to antigen reinjected 42 days later. Arthus reactions were totally suppressed by CY given on the day of immunization, or 3 or 7 days later.

Animals↗