Search PubMed⌕ Search

Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 91 records · Page 5Linked to original sources

Nerve damage induced by mycobacterial granulomas in guinea pig sciatic nerves.

A possible model for nerve damage in leprosy has been developed in the sciatic nerve of the guinea pig. Intraneural injection of 10(7) BCG organisms into an unsensitized animal induces an epithelioid cell granuloma in 2 weeks similar to that found in tuberculoid leprosy patients. In contrast, intraneural injection of 10(9) cobalt-irradiated Mycobacterium leprae organisms induces a macrophage granuloma in 5 weeks, similar to that found in lepromatous leprosy patients. Histological, immunohistochemical, electron microscopical and electrophysiological studies have demonstrated that the lesions induced in the experimental animals show many of the features documented in studies of nerve damage in leprosy patients.

Animals↗

Study of DTH and resistance in Mycobacterium lepraemurium infection using a T-cell line isolated from mice infected with Mycobacterium bovis (BCG).

A T-cell line of mixed phenotype (60% L3T4+, 40% Lyt-2+) was isolated from mice infected with Mycobacterium bovis (BCG). This line responded to M. lepraemurium and BCG but not to M. leprae and produced TCGF spontaneously. It also produced factors which stimulated macrophages to secrete hydrogen peroxide and superoxide anion. In vivo studies showed that only L3T4+ cells were required to transfer DTH responses and that Lyt-2+ cells suppressed this response. Both L3T4+ and Lyt-2+ cells were required to inhibit M. lepraemurium multiplication in vivo.

Animals↗

Enhancement of interleukin-2 release in rats by treatment with bleomycin and adriamycin in vivo.

Spleen cells from rats previously injected with bleomycin (10 mg/kg) or Adriamycin (1 mg/kg) were able to release higher levels of interleukin-2 (IL-2) than cells from untreated animals. The difference in IL-2 release was detected after the cells were exposed to a suboptimal dose of concanavalin A (0.5 micrograms/ml) for 24 h. By cytofluorimetry, these drugs did not change the proportion of W3/25+ (helper) or OX-8+ (suppressor) T-cell subsets. In contrast, the immunosuppressive drug cyclophosphamide inhibited the IL-2 release from spleen cells under the same conditions. It is suggested that some anti-cancer antibiotics may be able to enhance the release of IL-2 while other cytotoxic drugs with more immunosuppressive potential could inhibit the release of this mediator.

Animals↗

Interleukin 1 and prostaglandin production by cells of the mononuclear phagocyte system isolated from mycobacterial granulomas.

A study has been made of the activity of interleukin 1 (IL-1) and prostaglandins (PGs) in the culture supernatants from unstimulated and lipopolysaccharide (LPS)-stimulated mycobacteria-induced granuloma cells. Both epithelioid cells from bacillus Calmette-Guerin (BCG)-induced granulomas and macrophages from Mycobacterium leprae-induced granulomas, separated on a fluorescence-activated cell sorter using monoclonal antibody specific to guinea pig macrophages, spontaneously secreted low levels of IL-1 (assayed by thymocyte comitogenic and fibroblast mitogenic activities) into culture supernatants. However, culture supernatants from LPS-stimulated epithelioid cells showed significantly higher IL-1 activity than those from unstimulated cells. In contrast, LPS stimulation of M. leprae granuloma macrophages failed to enhance IL-1 production. Nevertheless, IL-1 activity in the culture supernatants from stimulated mycobacterial granuloma cells of both types was much lower than that from LPS-stimulated peritoneal exudate macrophage culture supernatants. There was no detectable amount of prostaglandin E2 (PGE2) in the culture supernatants from both unstimulated and LPS-stimulated BCG- and M. leprae-induced granuloma cells in comparison to much higher levels of PGE2 produced by unstimulated (0.28-6.2 ng/ml) or LPS-stimulated (greater than 15 ng/ml) peritoneal exudate macrophages. However, BCG granuloma cells either secreted prostaglandin F2 alpha (PGF2 alpha) spontaneously or produced comparable levels of PGF2 alpha to those from peritoneal exudate macrophages on stimulation, while M. leprae granuloma macrophages produced much lower levels of PGF2 alpha.

Animals↗

Epithelioid cell granuloma induction in the guinea pig by haptenated Mycobacterium leprae.

Fluorescein isothiocyanate (FITC)-conjugated Mycobacterium leprae (FITC-M. leprae) was injected intradermally into the ears of guinea pigs and granuloma formation in the draining postauricular lymph nodes was studied. At 2 weeks, there was an increase in weights and infiltration of the draining lymph nodes in half of the animals injected with FITC-M. leprae. At 5 weeks, there was a significant increase in the weights and infiltration of these draining lymph nodes in the guinea pigs injected with haptenated M. leprae compared with those injected with unconjugated M. leprae. At 5 weeks, there was also a significant increase in delayed type hypersensitivity responses to 25 micrograms purified protein derivative. Histologically, epithelioid cell granulomas were seen in these lymph nodes as early as 2 weeks when FITC-M. leprae was used as the source of antigen. Enhancement in the immunogenicity of M. leprae by conjugation with FITC has been postulated.

Animals↗

The modulation of class II histocompatibility antigens and 'activated' macrophage determinant in the spinal cord during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig--relevance to the induction of remission?

Cryostat sections of spinal cord of guinea pigs with chronic relapsing experimental allergic encephalomyelitis (CREAE) were stained with monoclonal antibodies recognising a Strain 13-specific Ia epitope, a non-strain-specific Ia antigen and an 'activated' macrophage determinant. It was found that both Ia antigens and the 'activated' macrophage determinant, observed on infiltrating cells within both perivascular and meningeal compartments, appeared to be modulated during the course of CREAE. This correlated with the neurological symptoms of the disease. Blood vessels and 'glial' cells expressed both Ia determinants. 'Glial' cells also expressed the 'activated' macrophage antigen. These antigens were modulated with the course of the disease.

Animals↗

Identification and quantitation of the expression of T cell surface markers during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig.

As there were discrepancies in previous data on the T cell nature of cells infiltrating the meninges at all stages of chronic relapsing experimental allergic encephalomyelitis (CREAE), experiments have been performed using a further monoclonal antibody (Mab) recognizing total T cell populations and the classic E rosetting technique. Cytospins were prepared of the meningeal inflammatory cells obtained by washing the brains of these animals, and stained by indirect immunoperoxidase. It was found that the T cell, as defined by both E rosetting and staining with the Mab CT5, is the major cell type found in the meninges during the development of CREAE. However, the staining with the Mab CT7, which recognizes a functionally relevant antigen, showed that there is a discrepancy between the numbers of lymphocytes stained compared to the results with CT5 and E rosettes. Furthermore, the antigen recognized by CT7 appeared to be modulated during the disease. The possible functional relevance and its relation to clinical remission and relapse are discussed.

Animals↗

Effects of adriamycin, 4-hydroperoxycyclophosphamide and ASTA Z 7557 (INN mafosfamide) on the release of IL-2 and IL-1 in vitro.

Adriamycin (ADR), 4-hydroperoxycyclophosphamide (4-OOHCYP) and the new cyclophosphamide derivative AZ 7557 (AZ) were tested for their effects on the release of the Interleukins IL-2 and IL-1 from rat spleen cells and peritoneal exudate macrophages respectively. ADR was found to enhance IL-2 release and less effectively IL-1 release. 4-OOHCYP and AZ were found to inhibit IL-2 release but had no effect on IL-1 production. It is suggested that the modulation of IL-2 levels by these drugs is unlikely to be mediated by their effects on IL-1.

Animals↗

Changes in lymphocyte subsets after treatment with cyclophosphamide and during the development of contact sensitivity in the guinea pig.

Changes in lymphocyte subpopulations were investigated in guinea pig lymph nodes during the development of contact sensitivity to 2,4-dinitrofluorobenzene (DNFB) and following the injection of cyclophosphamide (CY; 300 mg/kg) using a panel of monoclonal antibodies against guinea pig lymphocyte surface markers. Application of a sensitizing dose of DNFB to the ear resulted in a significant increase in the number of cells recovered from the draining auricular and cervical lymph nodes, 4 and 6 days post sensitization. A significant increase in the number of cells in the contralateral cervical node was found at day 6 but not at day 4. At 4 days postsensitization the proportions of Ia positive lymphocytes were higher than those of immunoglobulin positive B cells in the draining auricular and cervical node and the contralateral cervical lymph nodes suggesting T-cell "activation". Four and six days after sensitization there were no significant changes in the proportions of Pan T and T suppressor/cytotoxic (Ts/c) positive lymphocytes in the draining auricular and cervical lymph nodes. Although contact sensitivity is "classically" a T-cell mediated phenomenon there was a significant increase in the proportion of B cells found in the draining auricular node 4 days after sensitization as compared to the "normal" auricular node. 1, 2, 3 and 7 days after injection of CY there was a significant depletion in the proportion of B-lymphocytes in the cervical lymph node. This effect was maximal between 2 and 3 days after CY and was paralleled by an increase in the proportion of Pan T positive cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dissociation between delayed-type hypersensitivity and resistance to pathogenic mycobacteria demonstrated by T-cell clones.

One Lyt-2+ clone and fourteen T-helper clones (Lyt-1+ L3T4+ Lyt-2-) were isolated from Mycobacterium lepraemurium-infected BALB/c and C57BL/6 mice. All the clones were tested for their ability to transfer delayed-type hypersensitivity adoptively, and six clones were tested for their ability to transfer resistance. It was found that four L3T4+ clones that transferred delayed-type hypersensitivity responses locally and one L3T4+ clone that did not had no effect on resistance. The Lyt-2+ clone transferred increased resistance locally (77% reduction in the numbers of organisms recovered from the infection site) but did not transfer delayed footpad responses.

Animals↗

Distribution of a guinea pig lymphocyte cell surface antigen of defined function, as detected by the mouse monoclonal antibody MSgp 1.

A mouse anti-guinea pig monoclonal antibody, designated MSgp 1, was derived from a fusion between NS-1 myeloma cells and splenocytes hyperimmunised with guinea pig thymocytes. The MSgp 1 determinant is expressed by a subset of small thymocytes and lymph node T cells which participate in mixed leukocyte reactions. The determinant is modulated by antigen in vivo, and MSgp 1 antibody will prevent MHC class II driven proliferation in vitro. In addition, MSgp 1 reacts with a minor population of lymph node B cells, but not with a chronic B cell leukaemic cell line. Resident peritoneal macrophages express the MSgp 1 determinant, whereas chronic oil-induced peritoneal macrophages do not. The role of MSgp 1 defining guinea pig helper T cells is discussed by comparisons with other documented T helper cell reagents.

Animals↗

An antigenic determinant common to lymphocytes and Langerhans cells of the guinea pig.

A mouse anti-guinea pig monoclonal antibody, designated MSgp 2, was derived by the fusion of NS-1 myeloma cells with mouse splenocytes hyperimmunized with guinea pig B cells. MSgp 2 reacts with an antigen present on the majority of lymphocytes. An unexpected finding was the expression of the MSgp 2 antigen on epidermal Langerhans cells, as defined by cell morphology, expression of MHC class II antigen and presence of Birbeck granules in positive cells. It is suggested that the tissue distribution of MSgp 2 antigen on lymphocytes of the lymph node could indicate a role for this determinant in cell migration.

Animals↗

Immunogenicity of acrylate chemicals as assessed by antibody induction.

The immunogenicities of two acrylate chemicals, trimethylolpropane triacrylate (TMPTA) and methyl acrylate (MeAc), and one related vinyl compound, 4-vinyl pyridine (4VP), were investigated by determining the in vivo induction of IgG antibodies in guinea pigs. The injection of the chemicals emulsified in Freund's complete adjuvant resulted in the induction of serum antibody responses against MeAc and 4VP but not TMPTA. However, antibody with anti-TMPTA activity was produced following immunization of guinea pigs with TMPTA conjugated to protein, which allowed comparisons to be made of the immunogenic structural features of the compounds.

Acrylates↗

Inhibition of release of interleukin-2 by vincristine and vinblastine.

The antineoplastic drugs Vincristine (VCR) and Vinblastine (VBL) were tested for their effects on Concanavalin A induced Interleukin-2 (IL-2) release by rat splenocytes. Both drugs were found to inhibit IL-2 release in vitro. This effect was noted at doses of 10 ng/ml and 100 ng/ml in case of VBL and at doses of 1 ng/ml, 10 ng/ml and 100 ng/ml with VCR. The in vivo effect of these drugs was studied by injection into rats three days before culture of splenocytes. This also resulted in inhibition of IL-2 release. The effect was manifested with VCR at doses of 0.1 mg/kg bw and 0.5 mg/kg bw and with VBL at 2 mg/kg bw. These drugs were also tested for their effect on Interleukin-1 (IL-1) release by lipopolysaccharide (LPS) stimulated rat peritoneal exudate cells (PEC's) in vitro. No modulation of the production of IL-1 was seen.

Animals↗

Induction of sensitization and tolerance in contact sensitivity with haptenated epidermal cells in the guinea-pig.

Haptenated murine Langerhans' cells (LCs) have been reported to induce contact sensitivity when injected via the subcutaneous, intraperitoneal and, in some instances, the intravenous route. Similar studies were undertaken to elucidate the role of the LC in the induction of contact sensitivity in the guinea-pig. The subcutaneous injection of dinitrophenylated epidermal cells induced hapten-specific contact sensitivity in a dose-dependent fashion. This contrasts with the tolerance that was induced by the intravenous or intraperitoneal injection of similarly haptenated cells. Contact sensitivity by haptenated epidermal cells could be induced in syngeneic and allogeneic recipients and did not require the transfer of viable cells. Using the monoclonal antibody MSgp2, which detects LCs, LC-enriched and LC-depleted populations were prepared by an 'indirect antibody' panning technique. It was found that a haptenated LC-depleted epidermal cell population (0.1% LC) induced the same degree of contact sensitivity or tolerance, depending on the route of immunization, as a haptenated 'freshly isolated' epidermal cell population (1% LC). Whereas, a purified population of haptenated LC (85-90%) induced no significant degree of contact sensitivity or tolerance. These results confirm our previous conclusions based the in vivo depletions of Langerhans' cells, and suggest that the epidermal Langerhans' cell is not essential for the induction of contact sensitivity in the guinea-pig. However, this does not exclude the possibility that the LC is involved in the elicitation of contact sensitivity in a sensitized animal.

Animals↗

Enhancement of the delayed-type hypersensitivity reaction by oxazaphosphorines.

Delayed hypersensitivity reactions include tuberculin type, Jones Mote type reactions and contact sensitivity. These reactions are increased in guinea pigs and other species by pretreating the animals with a single dose of up to 300 mg/kg cyclophosphamide (CY). CY also reverses immunological tolerance and other forms of immunological unresponsiveness, including antigenic competition. Regulation of these hypersensitivity responses may be controlled by CY-sensitive B- or T-suppressor cells, depending on the species and the model. CY does not appear to act by increasing IL-2 production in the same way as other anti-cancer agents.

Adjuvants, Immunologic↗