PubMed Health⌕ Search

Biomedical subjects

J G Bowen

Publications and source records attributed to J G Bowen.

At least 19 recordsLinked to original sources
PubMed1998

Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T-lymphocytes.

Experiments were performed to investigate the immunological site of action of an immunomodulatory factor (IMF), isolated from the gastrointestinal nematode Heligmosomoides polygyrus. IMF inhibited antibody production in murine and human 'T-helper (Th-2) driven' immunoassays. The effects were mediated via T lymphocytes as T cell-depleted cultures failed to respond to IMF, a result confirmed by prepulsing discrete cell subsets with the immunomodulant. Although the molecular nature and mode of action of IMF has yet to be determined, it would appear to be a relatively small non-proteinaceous molecule. From this data, we suggest that H. polygyrus secretes a systemically-active IMF from the intestinal lumen, to down-regulate Th-2 cell development in order to promote its survival in a potentially immunologically hostile environment.

Adjuvants, Immunologic↗
PubMed1993

Identification of phospholipase D (PLD) activity in mouse peritoneal macrophages.

It is now believed that PLD may contribute to the sustained generation of diacylglycerol (DAG) within activated cells. DAG can be formed from phosphatidylcholine by the sequential actions of PLD and phosphatidic acid phosphohydrolase. Phorbal myristate acetate (PMA, 1 microM), A23187 (10 microM) or platelet-activating factor (PAF, 100 nM) caused significant enhancement of intracellular 14C-phosphatidic acid levels 2-5 min after the addition of stimulus, in cultures of peritoneal macrophages pre-labelled with 14C-palmitate. Bacterial lipopolysaccharide (LPS) (5 micrograms/ml) or zymosan (375 micrograms/ml) also stimulated the production of 14C-phosphatidic acid, but over a longer time course (15-60 min). In the presence of 1% ethanol each stimulus caused significant production of 4C-phosphatidylethanol at the expense of 14C-phosphatidic acid, thus confirming a contribution of PLD in these reactions. This is the first report of PLD activity in this cell type.

Animals↗
PubMed1992

Disease-modifying anti-rheumatic drugs: strategies for screening.

Rheumatoid arthritis, a disease of unknown aetiology, has a multifactorial pathogenesis which may result in irreversible connective tissue destruction and loss of joint function. The search for drugs which offer more than symptomatic relief is a long term, largely unachieved aim of many pharmaceutical companies. This review briefly outlines those features of the aetiopathogenesis which appear to offer targets for therapeutic intervention and the structured strategy and test systems that can be used to detect drugs which may be capable of halting disease progression.

Animals↗
PubMed1989

Murine chronic graft-versus-host disease as a model of systemic lupus erythematosus: effect of immunosuppressive drugs on disease development.

The effect of a number of drugs commonly used to treat the more severe exacerbations of the autoimmune disease systemic lupus erythematosus (SLE) in humans has been investigated in the murine chronic graft-versus-host (GVH) induced model of lupus. This was undertaken in order to determine the value of this model for the investigation of immunomodulant drugs, with particular regard to the reproducibility of disease induction and methods of monitoring disease progression. The drugs were azathioprine, cyclophosphamide, cyclosporin A and dexamethasone. All of these, except for azathioprine, reduced disease severity, assessed as the development of lupus nephritis. Anti-ssDNA autoantibodies were also reduced in titre in the dexamethasone-treated group. Overall, these findings, combined with the reproducible induction of disease seen in this model, support the use of chronic GVH disease as a model for SLE and show that the induced disease can be ameliorated by drugs effective in the treatment of SLE in humans.

Animals↗
PubMed1986

Decreased autologous mixed lymphocyte reaction in myasthenia gravis.

Myasthenia gravis is an autoimmune disease in which the autoantigen, the acetylcholine receptor at the neuromuscular junction, is well characterized. As with many other autoimmune diseases, however, the basic cause of immune malfunction is unknown. The autologous mixed lymphocyte reaction (AMLR) involves the proliferation of T lymphocytes when co-cultured with autologous non-T cells and may reflect in vivo mechanisms of immune control. We have measured the AMLR in 22 patients with myasthenia gravis and found the magnitudes of the peak responses to be significantly depressed compared to those of 41 normal healthy controls. Proliferative responses of T cells from myasthenic patients to the mitogens, Concanavalin A and Phytohaemagglutinin-P, were also found to be significantly depressed relative to controls. These abnormal immune cell responses can be, in part, interpreted in terms of defective suppressor cell functions in myasthenia gravis.

Acetylcholinesterase↗
PubMed1985

Comparison of a medium supplement--'Nu-Serum'--and foetal calf serum in RPMI 1640 used for the murine allogeneic mixed lymphocyte reaction.

A commercially available medium supplement, Nu-Serum, was compared with foetal calf serum for its ability to support the murine allogeneic mixed lymphocyte reaction. Nu-Serum supported proliferation whilst at the same time producing significantly lower counts in unstimulated cultures. There was considerably less batch-to-batch variation with Nu-Serum than with foetal calf serum, which obviated the need for pretesting in order to find a suitable batch.

Age Factors↗
PubMed1980

Radioiodination of rat hepatoma-specific antigens and retention of serological reactivity.

Papain-solubilized tumour-specific antigens from the aminoazo dye-induced rat hepatoma D23 were purified by a combination of lectin affinity and immunoadsorbent column chromatography. Isolated antigens were radio-iodinated using three procedures and analysed for their reaction with specific antibodies in syngeneic immune sera by double-antibody co-precipitation tests and by the rebinding of labelled antigens to specific and non-relevant antibodies immobilized on Sepharose-4B. Soluble hepatoma D23-specific antigens were labile to radiolabelling, and for optimal retention of serological reactivity it was necessary to protect the antigenic determinant by performing the chloramine T method of iodination with antigen bound to the immunoadsorbent followed by elution from the solid phase with 3M NaSCN. Immunoadsorption chromatography indicated that one consequence of radiolabelling hepatoma D23-specific antigen with 125I was a reduction in the affinity of the labelled antigen for its syngeneic specific antibody.

Animals↗
PubMed1979

Tumour antigens and alloantigens. II. Lack of association of rat hepatoma-D23-specific antigen with beta 2 microglobulin.

It has previously been shown that the tumour-specific antigen of the chemically-induced rat hepatoma D23 has determinants recognised by alloantisera raised against normal syngeneic liver and spleen. However, no reactions were observed with alloantisera raised against syngeneic erythrocytes suggesting that the alloantigeneic determinant responsible for this cross-reactivity is not a major serologically-defined histocompatibility antigen. This concept has been further examined using a defined turkey anti-rat beta 2 microglobulin antiserum. This antiserum failed to block the binding of syngeneic antihepatoma D23 sera to hepatoma D23 target cells as assessed using membrane immunofluorescence and complement-dependant 51Cr release tests. Furthermore, immune precipitates formed from soluble tumour extracts containing hepatoma D23 specific antigen with turkey anti-rat beta 2 microglobulin failed to generate a tumour-specific antibody response in syngeneic rats althouth a cross-reactive antiserum was produced following immunization of allogeneic rats with the immune precipitate.

Animals↗
PubMed1978

Transitional cell carcinoma: circulating tumor antigen correlated with presence/absence of tumor (leukocyte migration assay).

Sera from patients with TCC of the urinary bladder have been fractionated. We tested the fractions for activity in the leukocyte migration test, using peripheral blood leukocytes from TCC patients, other cancer patients, and healthy control donors as indicator cells. The results suggest that an antigen associated with TCC can be detected in the sera of patients bearing TCC but not in tumor-free individuals.

Antigens, Neoplasm↗
PubMed1976

Serum factor levels during the growth of rat hepatoma nodules in the lungs.

The levels of tumour-specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour-specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour-specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour-specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed.

Animals↗
PubMed1976

Isolation and characterization of tumour-specific antigen from the serum of rats bearing transplanted aminoazo dye-induced hepatomas.

Tumour-specific antigen has been purified from the serum of animals bearing large progressively growing transplants of an aminoazo dye-induced hepatoma (D23). Antigenic activity was detected by the capacity of serum fractions to neutralize reactivity of antibody in hepatoma immune serum for cell surface expressed antigen on viable hepatoma cells as assessed by using the indirect membrane immunofluorescence test. Serum from animals bearing large i.p. grafts of tumour was fractionated by gel filtration on Sephadex G-150 columns at pH 7.3 and pH 2.8 to yield a crude antigen fraction which was further purified by affinity chromatography by using syngeneic rat hepatoma D23 immune IgG insolubilized on Sepharose 4B. The purified antigen exhibited a pI of approximately 4.6 on analytical gel isoelectric focusing. Molecular weight determination on Sephadex G-200 at pH 7.3 in nondenaturing buffer indicated a primary molecular weight of 55,000 and a small amount of aggregated material (mol. wt. greater than 250,000).

Animals↗