Search PubMed⌕ Search

Biomedical subjects

J L Turk

Publications and source records attributed to J L Turk.

At least 55 records · Page 3Linked to original sources
PubMed1991

Mononuclear cell trafficking and plasma protein extravasation into the CNS during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice.

Cellular traffic and plasma protein extravasation across the blood-brain and blood-spinal cord barrier (BBB) have been studied during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice, using a simultaneous double radioisotope method. There was a general correlation between the clinical course of disease and BBB breakdown, including a resealing of the barrier during remission, although breakdown appeared slightly to precede clinical presentation. The brain was markedly less affected than the spinal cord and was only minimally involved in the relapse phase of disease.

Animals↗
PubMed1991

An immunoelectron microscopical study of the expression of class II major histocompatibility complex during chronic relapsing experimental allergic encephalomyelitis in Biozzi AB/H mice.

Immunoelectron microscopical techniques have been used to study class II major histocompatibility complex (MHC) expression by cells in the spinal cords of Biozzi AB/H mice with chronic relapsing experimental allergic encephalomyelitis. Throughout the course of disease both astrocytes and endothelia failed to express significant levels of class II MHC antigens. The major central nervous system resident cell types found to express class II MHC antigens were the perivascular microglia, with infiltrating macrophages and some lymphocytes being strongly positive.

Animals↗
PubMed1991

Inhibition of chronic relapsing experimental allergic encephalomyelitis in the mouse by the alkyl-lysophospholipid ET-18-OCH3.

The effect of the anti-tumour agent alkyl-lysophospholipid (ALP) ET-18-OCH3 on the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the mouse was investigated. Experimental allergic encephalomyelitis developed in the majority (greater than 96%) of mice immunized with autologous spinal cord homogenate in Freund's complete adjuvant. Alkyl-lysophospholipid, in doses of 25 mg/kg/day or 50 mg/kg/day, inhibited the onset of clinical signs of acute phase CREAE when orally administered starting on the day of disease induction. Similarly if treatment with 50 mg/kg/day was delayed until day 9 post-inoculation the incidence of disease and severity of clinical signs were also significantly reduced (P less than 0.02) as compared with vehicle fed animals. However, when treatment began on day 12, just prior to the onset of clinical disease, although the incidence of disease was not significantly altered the severity of disease was significantly (P less than 0.002) reduced compared with vehicle treated animals. These data suggest that although the major effect of ALP is on the inhibition of the generation of the autoimmune response there appeared to be some therapeutic benefit at a later stage of acute disease. Therefore, this study was extended to the treatment of post-acute phase remission animals. It was found that the oral administration of 50 mg/kg/day marginally reduced and that 75 mg/kg/day significantly (P less than 0.05) reduced the incidence of relapsing disease compared with vehicle treated controls. This suggests that ET-18-OCH3 may have some potential in the treatment of ongoing autoimmune disease of the central nervous system.

Animals↗
PubMed1991

Suppression of demyelination by mitoxantrone.

The mode of action of the immunosuppressant mitoxantrone was examined in murine models of demyelinating disease. The drug has been shown to block antigen induced proliferative activity and to inhibit myelin degradation by leucocytes from paralysed mice. Mitoxantrone blocked myelin breakdown by macrophages although phagocytosis was not affected. Further evidence was obtained to indicate that mitoxantrone acts therapeutically in reducing, or at high dose, preventing signs of EAE developing in mice immunized with spinal cord homogenate and Freund's complete adjuvant. Mitoxantrone also significantly inhibited the incidence of relapse when treatment was initiated during the post-acute remission period.

Animals↗
PubMed1991

Effect of anticancer drugs on the release of interleukin-3 in vitro.

In this study several anticancer drugs were tested for their effect on the release of interleukin-3 (IL-3) from concanavalin A (Con A) stimulated mouse splenocytes in vitro. When Adriamycin or vincristine were added to the cultures at non-cytotoxic concentrations, the release of IL-3 was inhibited. However, bleomycin, FK156, FK565 and 4-OOH-cyclophosphamide (the in vitro active analogue of the anticancer and immunosuppressive drug cyclophosphamide) did not alter the release of IL-3 under the same conditions. It was confirmed that cyclosporin A inhibited the release of IL-3 in the same experimental system.

Animals↗
PubMed1991

Observations on the Kveim reaction using an animal model of granulomatous bowel disease.

Striking differences were observed between the visceral and cutaneous responses after tests with validated Kveim and normal spleen suspensions in a guinea pig model of granulomatous bowel disease. Five of six animals sensitised with BCG showed positive responses at the ileal Kveim test site whereas all six had negative cutaneous Kveim tests. Conversely, two of six animals sensitised with irradiated Mycobacterium leprae showed positive cutaneous Kveim tests and only one a positive response in the ascending colon. All six showed negative responses at the ileal Kveim test site. No positive visceral or cutaneous responses were observed in either group of animals after tests with normal spleen suspension. These findings are discussed in relation to the positive Kveim responses previously reported among patients with Crohn's disease, tuberculoid and lepromatous leprosy, and among seemingly healthy BCG vaccinated subjects. The findings provide further evidence in support of a possible mycobacterial aetiology for sarcoidosis and Crohn's disease.

Animals↗
PubMed1991

Selective impairment of T lymphocyte activation following contact sensitization with oxazolone.

We have previously reported that topical exposure of mice to oxazolone results in the appearance of regulatory mechanisms which markedly depress lymph node cell (LNC) proliferative responses to subsequent challenge with the same chemical. In the present study, we have sought to identify the cellular targets for such immunoregulation. Autoradiographic analyses revealed that although pre-exposure to oxazolone caused a substantial reduction of paracortical hyperplasia following challenge, the frequency of proliferating cells in lymphoid follicles was slightly increased. That B lymphocyte responses are unaffected by oxazolone-induced immunoregulation was confirmed by investigation of anti-hapten antibody formation by draining LNC. Challenge with oxazolone resulted in an accelerated antibody response in mice previously exposed to the same chemical. These data reveal that the active immunoregulation induced following sensitization with oxazolone is selective for T lymphocytes. Evidence is presented that CD4+ and CD8+ T lymphocytes possess equivalent sensitivity to these mechanisms.

Administration, Topical↗
PubMed1991

Expression of vascular addressins and ICAM-1 by endothelial cells in the spinal cord during chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse.

The expression of adhesion molecules on central nervous system (CNS) endothelia was examined during chronic relapsing experimental allergic encephalomyelitis (CREAE) in the Biozzi AB/H mouse. Active disease episodes (acute and relapse) were associated with the up-regulation of MALA-2, the murine homologue of intercellular adhesion molecule-1 (ICAM-1), on CNS endothelia and the infiltration of ICAM-1-positive mononuclear cells. In addition, the high endothelial venule (HEV)-associated MECA-325 antigen was evident in perivascular lesions, particularly in relapsing disease. The peripheral lymph node HEV-associated vascular addressin defined by MECA-79 antibody was not detectable in the CNS during CREAE. However, the mucosal HEV addressin was evident in lesions, which ultrastructurally was found to be expressed on the surface of endothelial cells by immunoelectron microscopy. The expression of adhesion molecules, such as ICAM-1, may provide a means by which both the initial neuroantigen-specific and the subsequent antigen-non specific cells extravasate into the CNS. Such infiltration may induce the expression of the vascular addressins which may then provide a means of site-selective cellular recruitment leading to disease progression.

Animals↗
PubMed1991

Antigen-specific and non-specific depression of proliferative responses induced during contact sensitivity in mice.

Exposure of the flank of mice to either oxazolone or trinitrochlorobenzene (TNCB) 5 days prior to the application of oxazolone on the ear resulted in a reduced capacity of oxazolone-induced draining lymph node cells to express IL-2 receptors, produce IL-2, protein, RNA and DNA. However, histological examination of the draining lymph node suggest that antigen-specific and antigen-non-specific influences differ with respect to the frequency of pyroninophilic cells. Pre-exposure to oxazolone suppressed the number of oxazolone-induced pyroninophilic T cell blasts, whereas draining lymph nodes from TNCB-pretreated mice contained significantly more pyroninophilic cells than from oxazolone-pretreated mice. However, the majority of these cells were incorporating little or no thymidine. Thus exposure to certain contact sensitizers induces at least two systemic control mechanisms which serve to regulate subsequent lymphoproliferative responses. These mechanisms appear to exert their influences at different stages of in-vivo T cell activation.

Animals↗
PubMed1990

Effect of anticancer drugs on the release of tumour necrosis factor in vitro.

The anticancer drugs Adriamycin, bleomycin, vincristine, 4-hydroperoxycyclophosphamide, FK156 and FK565 and the immunosuppressive drug cyclosporin-A were tested for their effect on lipopolysaccharide-induced tumour necrosis factor-alpha (TNF) release from rat peritoneal exudate cells in vitro. FK565 resulted in a marked enhancement of TNF release when added to cultures at doses of 1 microgram/ml and 10 micrograms/ml. However, FK156, Adriamycin, bleomycin, 4-hydroperoxycyclophosphamide, vincristine and cyclosporin A did not affect the release of TNF under the same conditions. Puromycin inhibited the release of TNF in the same system at non-cytotoxic doses of 1 microgram/ml and 10 micrograms/ml.

Animals↗
PubMed1990

Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice.

Experimental allergic encephalomyelitis (EAE) was induced in Biozzi AB/H (antibody high) mice by sensitization with spinal cord homogenate in adjuvant. Biozzi AB/H mice were highly susceptible to EAE induction and followed a chronic relapsing pattern of disease. Disease episodes were characterized by mononuclear infiltration of the central nervous system, with demyelination being particularly evident in relapse. The cellular infiltrates, which were associated with immunoglobulin deposition, consisted of macrophages and primarily CD4-positive T lymphocytes. However, similarly treated Biozzi AB/L (antibody low) mice were markedly less susceptible to EAE induction than AB/H mice. Thus, Biozzi mice should prove valuable for the study of chronic relapsing EAE.

Animals↗
PubMed1990

Endothelial cell expression of the intercellular adhesion molecule-1 (ICAM-1) in the central nervous system of guinea pigs during acute and chronic relapsing experimental allergic encephalomyelitis.

This study investigated the expression of intercellular adhesion molecule-1 (ICAM-1; CD54) by cells of the central nervous system (CNS) during acute experimental allergic encephalomyelitis (EAE) and chronic relapsing EAE (CREAE). In the CNS of normal guinea pigs, only a few endothelial cells expressed detectable levels of ICAM-1, whereas during the active phases of the disease ICAM-1 was present on cells of the perivascular infiltrate and the endothelia of both lesion- and non-lesion-associated blood vessels. In addition, cultured cerebrovascular endothelia maintained in 'standard' culture medium did not express ICAM-1, but they could be induced to express this antigen on incubation in a lymphocyte-conditioned medium. These findings suggest that the induction of ICAM-1 on CNS endothelia may be important in antigen presentation or in promoting lymphocyte extravasation across the blood-brain barrier in inflammatory disorders of the CNS.

Animals↗
PubMed1990

Effect of the immune modulating agents cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on an animal model of granulomatous bowel disease.

This study was undertaken to determine the effect of cyclophosphamide, methotrexate, hydrocortisone, and cyclosporin A on a model of granulomatous infiltration in the terminal ileum and draining lymph nodes of the guinea pig. Treatment groups of six animals were used and compared to untreated groups of 12. Epithelioid cell granulomas and primary macrophage granulomas were induced by the inoculation of BCG (Pasteur) and irradiated Mycobacterium leprae respectively into the terminal ileum of the guinea pig. The response to purified protein derivative of tuberculin was reduced in both groups of animals receiving any of these agents. Cyclophosphamide and methotrexate treated animals inoculated with BCG or M leprae showed a significant reduction of granulomatous infiltration at the inoculation site (p less than 0.05 and p less than 0.001 respectively). BCG inoculated animals treated with either hydrocortisone or cyclosporin A showed no reduction in granulomatous infiltration at either the inoculation site or the draining lymph nodes. By contrast M leprae inoculated animals receiving either of these agents showed a significant reduction of granulomatous infiltration at both the inoculation site (p less than 0.001) and in the primary draining lymph node (p less than 0.001). Ziehl Neelsen staining showed an increased proportion of animals with detectable acid fast bacilli (AFB) at the inoculation site in the groups receiving hydrocortisone (50%) and methotrexate (67%) compared to untreated controls (8%). No AFB were observed in any of the animals inoculated with M leprae. In conclusion, this model may be helpful in elucidating the mechanism of T lymphocyte response in Crohn's disease and the variable clinical response seen with the use of immunosuppressive agents in this condition.

Adjuvants, Immunologic↗
PubMed1990

Antigen-restricted antigenic competition induced by 2,4-dinitrochlorobenzene: association with depression of lymphocyte proliferation.

2,4,6-Trinitrochlorobenzene (picryl chloride) and 2,4-dinitrochlorobenzene (DNCB) fail to cross-sensitize with respect to contact sensitivity in mice. Nevertheless, topical exposure of mice to DNCB and other skin-sensitizing dinitrobenzene derivatives was found to result in a significant impairment of draining lymph node cell proliferative responses induced following epicutaneous challenge with picryl chloride 5 days later. The inhibition of picryl chloride induced proliferation was associated with an impairment of contact sensitization to this chemical. The effect of DNCB on subsequent responses to picryl chloride was transient and no longer detectable 15 days following exposure. The inhibition of proliferation and contact sensitization caused by DNCB was largely restricted to picryl chloride. Thus, DNCB failed to influence the development of contact allergy to the unrelated chemical 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) and exerted a far less pronounced effect on oxazolone-induced proliferative responses. These data, therefore, describe an antigen-restricted form of antigenic competition which is associated with a depression of the primary lymphocyte proliferative response.

Animals↗
PubMed1990

Denatured muscle grafts for nerve repair. An experimental model of nerve damage in leprosy.

About 20% of patients with leprosy develop localised granulomatous lesions in peripheral nerves. We report experiments in guinea-pigs in which freeze-thawed autogenous muscle grafts were used for the treatment of such mycobacterial granulomas. Granulomas were induced in guinea-pig tibial nerves and the animals were left for 7 to 100 days in order to assess maximal damage. The local area of nerve damage was then excised and the gap filled with denatured muscle grafts. Clinical assessment after periods up to 150 days showed good sensory and motor recovery which correlated well with the histological findings. The muscle graft technique may be of value for the treatment of chronic nerve lesions in selected cases of leprosy.

Animals↗
PubMed1990

Effect of presensitization with BCG and Mycobacterium leprae on granuloma formation to M. leprae.

Granulomas which develop in draining lymph nodes, following the intradermal injection of cobalt-irradiated Mycobacterium leprae into the ear of the guinea pig 2 and 5 weeks earlier, were studied in animals which had been presensitized with BCG vaccine or M. leprae and compared with granulomas that developed in previously unsensitized guinea pigs. Presensitization with mycobacteria accelerated the development of the granulomas. Granulomas in previously unsensitized guinea pigs were found ultrastructurally to contain phagocytosing macrophages similar to those in lepromatous leprosy, and M. leprae presensitization did not alter the type of granuloma found. Those in BCG-presensitized guinea pigs contained secretory epithelioid cells with rough endoplasmic reticulum similar to those found in borderline tuberculoid leprosy or reversal reactions. The significance of these findings in relation to the current use of vaccines in leprosy is discussed.

Animals↗