Search PubMed⌕ Search

Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 145 records · Page 8Linked to original sources
PubMed1983

The effect of a single dose of cyclophosphamide on the kinetics of antibody production in the guinea pig.

Cyclophosphamide (CY) 250 mg/kg was given before, at the same time or after immunization with dinitrophenylated bovine gammaglobulin (DNP47-BGG) in Freund's incomplete adjuvant (FIA). CY, given on day +3 or +7 strongly suppressed both IgG subclasses. CY, on the day of immunization, reduced the IgG2 but not IgG1 anti-DNP antibody synthesis. Carrier BGG, injected 42 days after initial immunization, caused a secondary anti-hapten IgG1 response. This was not altered by CY treatment. The secondary anti-BGG response in animals pretreated with CY was also not affected. However, IgG1 anti-BGG in the other groups given CY on day 0, +3 or +7 was delayed and reduced. IgG2 anti-BGG was suppressed in guinea-pigs treated with CY, 3 or 7 days after primary immunization. DNP-BGG-specific IgE serum antibodies, not detectable in CY untreated animals, were found in guinea pigs given CY on days 0, +3 or +7. It is suggested that the kinetics of the IgG1 and IgG2 primary immune response differ, as does the development of IgG1 and IgG2 specific immunological memory.

Animals↗
PubMed1983

A comparison of the conjugation of DNTB and other dinitrobenzenes with free protein radicals and their ability to sensitize or tolerize.

Of several dinitrobenzenes tested, 2,4-dinitrothiocyanatebenzene (DNTB) was found to be the only one that did not induce contact sensitivity when applied to the guinea pig ear epicutaneously, but when applied epicutaneously it induced tolerance to 2,4-dinitrofluorobenzene (DNFB). The manner in which DNFB, DNTB, and other dinitrobenzene compounds conjugated in vitro to soluble proteins, at physiologic pH, was examined. By measuring the free amino and sulfydryl radicals in the protein before and after conjugation, it was possible to determine to which groups the hapten was bound. It was found that although all the haptens bound to the free sulfydryl groups, DNTB was the only one that did not bind to amino groups. It is suggested that to be an epicutaenous tolerizer, as opposed to sensitizer, a hapten should bind to sulfydryl groups exclusively. It is hoped that a search for agents binding in a similar manner will reveal epicutaneous tolerizers for important industrial sensitizers.

Animals↗
PubMed1983

Contact sensitivity to acrylate compounds in guinea pigs.

As reports of contact dermatitis in humans due to acrylate compounds have increased considerably in recent years, it was decided to investigate the ability of these chemicals to evoke contact sensitivity skin reactions in guinea pigs. 21 different acrylate and methacrylate compounds were scanned for their ability to induce contact sensitivity, using 5 different sensitization protocols. Contact reactions of varying intensities were produced to all the mono-, di- and triacrylates tested. However, it was not possible to sensitize guinea pigs to any methacrylates. It would appear that guinea pigs cannot be contact sensitized to acrylate chemicals that are substituted on carbon 2.

Acrylates↗
PubMed1983

Analysis of cells of the mononuclear phagocyte series in experimental mycobacterial granulomas by monoclonal antibodies.

Two distinct types of granulomas were produced in the draining lymph nodes by immunizing guinea pigs with Mycobacterium bovis BCG or Mycobacterium leprae, as reported earlier (Narayanan et al., J. Pathol. 134:253-265, 1981). In the BCG-induced granuloma there is successful containment, killing, and degradation of the organisms with the presence of epithelioid cells and fibrosis. M. leprae, on the other hand, induces a granuloma where there is an absence of organization of the cells, failure to completely degrade the organisms, absence of epithelioid cells, and minimal fibrosis. By using a macrophage-specific monoclonal antibody and an anti-Ia monoclonal antibody and applying the immunoperoxidase, immunofluorescence, and fluorescence-activated cell sorter analysis techniques, the epithelioid cells of the BCG granuloma were found to have macrophage-specific antigen, but not detectable amounts of Ia antigen. This suggests that these cells have a close relationship to other cells of the mononuclear phagocyte series with which they share a common antigen. The absence of Ia antigen, on the other hand, suggests that epithelioid cells may not be involved in antigen presentation or other accessory cell functions where the presence of Ia antigen is crucial. The macrophages in the M. leprae-induced granuloma expressed both macrophage-specific and Ia antigens.

Animals↗
PubMed1983

Experimental model for dermal granulomatous hypersensitivity in Q fever.

Q fever has been associated with granulomatous changes in clinical biopsy material obtained from liver and bone marrow. Local reactions to skin testing have been described in previously sensitized humans, but histological studies of such reactions have not been reported. We note that delayed hypersensitivity reactions to whole-cell phase I Q fever vaccine in immunized guinea pigs have a time course of development of induration characteristic of granulomatous hypersensitivity. Histological examination of such skin reactions on day 9 after testing revealed epithelioid cell infiltration and the presence of large numbers of multinucleated giant cells. Prominent in the sections were fragments of disintegrating polymorphonuclear leukocytes having the appearance of leukocytoclasis. Electron microscopic studies confirmed the presence of epithelioid changes in cells of the mononuclear phagocyte series, as well as extensive collagen deposition. This animal system affords a readily reproducible model of dermal granulomatous hypersensitivity and an opportunity to analyze the immunological basis of this reaction.

Animals↗
PubMed1983

Role of the major histocompatibility complex in resistance and granuloma formation in response to Mycobacterium lepraemurium infection.

Resistance to a subcutaneous infection with a moderate dose of Mycobacterium lepraemurium was investigated in C57BL/6 mice and in three congenic strains with the BALB background (BALB/c, BALB/B, and BALB/K). Resistance after 10 weeks of infection was found not to be linked to the major histocompatibility complex. The ability to develop a delayed hypersensitivity response to an ultrasonicate of M. lepraemurium was associated with the background genes, and this ability had no influence on resistance to M. lepraemurium. Granuloma formation at the infection site in the early stages appeared to be linked to the H-2b haplotype. The types of cells involved in the granulomas were also investigated.

Animals↗
PubMed1983

Lysozyme and angiotensin converting enzyme levels in experimental mycobacterial granulomas.

A study has been made on mycobacterial-induced granulomas in guinea-pig lymph nodes. Lysozyme and angiotensin-converting enzyme (ACE) were measured in the auricular lymph nodes and serum of guinea-pigs which had received live BCG (Pasteur) or Cobalt (Co)-irradiated armadillo-derived Mycobacterium leprae intradermally into the ear or dinitrofluorobenzene (DNFB) painted epicutaneously upon the ears. In the lymph nodes with granulomas induced by either live BCG or killed M. leprae, the mean concentrations of lysozyme and ACE varied directly with the mean weight of the lymph nodes but the temporal pattern of weight change differed with the two agents. In M. leprae recipients at the time of peak lymph node weight, serum lysozyme and ACE values were significantly greater than those observed in controls; in animals receiving live BCG (Pasteur), serum lysozyme but not ACE values were elevated significantly at the time of peak lymph node weight. Four days following the epicutaneous application of DNFB, where there was no granuloma, there was a similar increase in the concentration of lysozyme and ACE in the lymph nodes. At the same time, there was also significant elevation in the serum lysozyme and ACE concentrations. Thus, in the granulomatous responses, the parallel tissue and serum changes in lysozyme and ACE concentrations were consistent with increased production and secretion of each enzyme by cells of the mononuclear phagocyte series. The increased lysozyme and ACE concentrations found in the lymph nodes of DNFB sensitised animals gives further evidence that such changes are not unique to granulomas. Finally, the intradermal administration of dead M. leprae in guinea pigs also produced increased lysozyme and ACE levels similar to that found in leprosy in man.

Animals↗
PubMed1983

Bleeding and cupping.

Bleeding and cupping have been used in medicine since ancient times in the treatment of fevers and local inflammatory disorders. Local bleeding, by 'wet cupping', was effected by a scarificator or by leeches. John Hunter recommended venesection in moderation but preferred leeches for local bleeding. Bleeding as an accepted therapeutic practice went out of vogue in the middle of the nineteenth century as a result of the introduction of modern scientific methods. Dry cupping and the use of leeches, as counter irritants, persisted until the middle of this century.

Bloodletting↗
PubMed1983

Chronic cell-mediated immune reactions to metals.

Cell mediated immune reactions may underly toxic reactions to certain metals, particularly Cr, Ni, Zr, Be, and Hg. Metal conjugated to a carrier protein forms the immunogen, but how the metal acts as a hapten is poorly understood. The possibility that the metal changes the antigenicity of the protein by changing its configuration is discussed and could explain cross reactions between Zr and Cr. Most reactions are contact sensitivity reaction, but granulomas may also develop to Be and Zr. These are epithelioid cell lesions associated with fibroblast proliferation and increased collagen synthesis. Sensitization of guinea pigs to Be and Hg is possible by epicutaneous contact. Cr, Ni, and Zr sensitivity need Freund's adjuvant and frequent intradermal injections. Three initial protocols have been compared and their efficacy for each metal assessed. Specific unresponsiveness for Cr and Ni can be induced by intratracheal installation prior to attempted sensitization. After sensitivity has developed, unresponsiveness to Cr can be induced by intravenous injection of the metal together with an epicutaneous application given within 24 hours. Flare up of old Cr reaction sites can also be induced by intravenous injection of the metal. The reaction lasts for 48 hours, is associated with increased vascular permeability and subepidermal infiltration with basophil leucocytes.

Animals↗
PubMed1982

Comparison of mycobacterial granulomas in guinea-pig lymph nodes.

A study was made of mycobacterial-induced granulomas in guinea-pig lymph nodes. Live BCG (Pasteur) induced a granuloma containing epithelioid cells while Cobalt irradiated Mycobacterium leprae induced a granuloma comprised of phagocytic macrophages. The granulomas were quantitated by measurement of lymph node weight and the areas of infiltration in histological sections. The time course of granuloma formation induced by Co-irradiated M. leprae was veary different from the time course of the granuloma formation induced by BCG. Collagen synthesis assessed by incorporation of 14C-proline into collagenase sensitive protein was greater in lymph nodes draining the site of injection of Co-irradiated BCG than those draining the site of injection of Co-irradiated M. leprae during the first 10 weeks. Collagen synthesis was delayed in the nodes from animals injected with live BCG for at least 10 weeks. Single cell suspensions of draining lymph nodes containing granulomas consisted of lymphocytes and large cells (epithelioid cells and macrophages). A high proportion of the large cells were found to be non-adherent in the live BCG-induced epithelioid cell granuloma. In contrast, M. leprae-induced granulomas contained a high percentage of adherent large cells. In both the granulomas, the majority of large cells were esterase positive and showed the presence of fibronectin. Most of the large cells in the granulomas did not carry receptors for the Fc component of IgG or the C3 component of complement and did not exhibit peroxidase activity.

Animals↗
PubMed1982

The origin, morphology, and function of epithelioid cells.

Epithelioid cells are cells of the mononuclear phagocyte system found in certain granulomas mainly associated with intense immunological activity. These cells show little phagocytic activity. In certain experimental granulomas such as those produced in guinea pigs sensitive to zirconium, and at sites of intense inflammatory reaction in man, they may contain varying amounts of rough endoplasmic reticulum ("secretory" epithelioid cells). In other situations such as tuberculoid leprosy and in some cases of sarcoidosis they may have the appearance of activated macrophages or take on a multivesicular appearance ("vesicular" epithelioid cells). It is suggested that "vesicular epithelioid cells could develop from "secretory" epithelioid cells by a process of degeneration. In studies comparing granulomas induced in lymph nodes draining the site of intradermal injection of mycobacteria, epithelioid cell granulomas were produced with BCG vaccine, whereas, the granulomas induced by Mycobacterium leprae contained undifferentiated macrophages that contained phagocytosed organisms. The BCG granulomas were in addition characterised by fibroblast infiltration, the presence of collagen and resolution by fibrosis. M. leprae granulomas showed little evidence of fibroblastic activity. Biochemical studies confirmed that BCG granulomas formed new collagen in vitro, whereas this did not take place with M. leprae granulomas. It is suggested that epithelioid cells could play an important role in fibrosis possibly by the secretion of a fibroblast activating factor.

Animals↗
PubMed1982

Effect of cyclophosphamide on immunological control mechanisms.

Cyclophosphamide (CY) given before immunization causes greatly increased delayed hypersensitivity skin reactions. Increased cell-mediated immunity is associated with depletion of B-lymphocytes from lymphoid tissue and a depression of those lymphocytes whose precursors turn over more rapidly. In the guinea pig, replacement studies showed that the depleted cells were not T-lymphocytes and had immunoglobulin adherent to their surface, a characteristic of B-lymphocytes. Delayed hypersensitivity reactions increased by CY include chemical contact sensitivity, the tuberculin reaction, delayed hypersensitivity to tularemia vaccine and the Jones-Mote reaction to soluble protein antigens. Pretreatment with CY can also increase the antibody response to some antigens, but depress the response to others. In addition, CY has been found to reverse immunological tolerance where this form of unresponsiveness is due to suppressor cells. CY can also enhance the immune response following depression by antigenic competition or desensitization. Other drugs with a similar, but lesser, effect include melphalan, azathioprine and methotrexate.

Animals↗
PubMed1982

H-2 linkage control of resistance to subcutaneous infection with Mycobacterium lepraemurium.

The H-2 linkage of the gene or genes controlling resistance to subcutaneous infection with 10(7) Mycobacterium lepraemurium organisms was investigated by using H-2 congenic strains on BALB and B10 backgrounds. Resistance was assessed by counting the organisms present at the infection site in the footpad and in the draining (right popliteal) lymph node 20 weeks after infection. When mice of BALB and B10 backgrounds with the same H-2 haplotype were compared, the BALB mice were always more susceptible. However, BALB/K (H-2k) mice were more susceptible than BALB/B (H-2b) mice, and BALB/B mice were more susceptible than BALB/c (H-2d) mice. There was no detectable difference in the resistance of B10.D2/n (H-2d) mice and B10 (H-2b) mice, but B10.BR (H-2k) mice were more susceptible than mice of the other two B10 strains. BALB/K was the only strain in which a high proportion of mice showed significant dissemination of organisms to the liver and spleen.

Animals↗
PubMed1982

Kinetics of the relation between suppressor and effector mechanisms in contact sensitivity in the guinea-pig.

Cyclophosphamide (300 mg/kg) given before or up to 2 days after sensitization, induces increased contact skin reactions at 8 days. Reactions were suppressed with cyclophosphamide (CY) given between 3 and 5 days after sensitization; reactivity returned on day 10. CY, given on days 6 to 8, only suppressed reactions when skin tests were made 4 days later. This temporary depression of contact sensitivity corresponds with the maximal reduction of peripheral blood lymphocytes. CY given 1-2 days after DNFB produced decreased T-cell proliferation in local lymph nodes 4 days after sensitization. CY given 3 days after DNFB produced maximal T-cell suppression on 5 day nodes. Massive increase in T-cell proliferation in 5 day nodes occurred when CY was given on the day of sensitization or the day before. Thus CY given around sensitization acts mainly on suppressor cells whereas given later, the action is principally on the effector functions.

Animals↗