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Biomedical subjects

B M Hall

Publications and source records attributed to B M Hall.

At least 109 records · Page 6Linked to original sources
PubMed1984

Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response.

Whether the expression of DR antigens is altered in cadaver renal transplants was examined by the use of monoclonal antibodies to the non-polymorphic region of the DR molecule and an indirect immunoperoxidase stain. Expression of DR antigens increased considerably on renal tubular cells in all 25 biopsy specimens which showed severe cellular rejection, but in only 4 of 14 biopsy specimens with no or minimum evidence of rejection. 2 of these 4 specimens were from patients recently treated for severe rejection and the other 2 subsequently lost their grafts from chronic rejection. DR antigens were also expressed on the cell surface of isolated tubular cells aspirated from transplanted kidneys with acute cellular rejection but not on tubular cells in normal kidneys or aspirates from kidneys without rejection. Biopsy specimens with increased DR expression in tubules usually had an interstitial T cell infiltrate. Expression of DR antigens on tubular cells was not related to HLA-DR incompatibility between donor and host, or to the type of immunosuppressive therapy given. The expression of DR antigens on renal tubular cells may be induced by the infiltrating activated T cells or be a consequence of tubular regeneration following rejection or ischaemic damage. The increased expression of DR antigens on renal tubular cells during rejection makes these cells potential targets for delayed type hypersensitivity responses, which are only effective against DR antigen bearing cells.

Adult↗
PubMed1984

Identification of the cellular subpopulations infiltrating rejecting cadaver renal allografts. Preponderance of the T4 subset of T cells.

In the rejection response against renal allografts, the relative importance of helper/inducer T cells mediating a delayed-type hypersensitivity response and of T cells with direct cytotoxicity has not been defined. These subpopulations were identified with commercially available monoclonal antibodies and an indirect immunoperoxidase technique in 31 renal biopsies from patients undergoing acute rejection episodes and in 9 rejected nephrectomy specimens. T lymphocytes were the predominant cell population in all biopsies and in 8 of 9 nephrectomies. The T4 helper/inducer subset was equal to, or greater than, the T8 cytotoxic/suppressor subset in 28 of the 31 biopsies and in the 8 nephrectomy specimens that had histological evidence of cellular rejection. T4 lymphocytes were found predominantly in large areas of cellular infiltrate. T8 lymphocytes had a more diffuse interstitial distribution and were a minority of the cells in the large areas of cellular infiltration. These results show that helper/inducer T lymphocytes are often more frequent than cytotoxic/suppressor cells in acute renal allograft rejection in humans and they suggest that helper/inducer T cells may play an important role in the mediation of graft destruction.

Antibodies, Monoclonal↗
PubMed1984

Suppressor T cells in rats with prolonged cardiac allograft survival after treatment with cyclosporine.

DA rats treated with cyclosporine for 2 weeks after being grafted with an RT1-incompatible PVG heart graft did not reject the graft and developed a state of specific unresponsiveness to graft antigens. The cellular mechanisms maintaining this state of unresponsiveness were studied by testing the capacity of lymphocytes from these animals to effect or inhibit graft rejection in irradiated grafted hosts. Whole lymph node and spleen cell populations, and the T cell subpopulation separated from the latter, failed to restore the rejection of PVG hearts in irradiated DA recipients but restored third-party Wistar-Furth (W/F) rejection. Both whole spleen cells and the splenic T cell subpopulation had the capacity to suppress the ability of normal DA lymphocytes to cause graft rejection. Suppression was not dependent upon a state of chimerism in grafted cyclosporine -treated animals, and was not associated with any measurable alterations in the proportion of cytotoxic/suppressor T cells in lymphoid tissues. These studies show that the state of specific unresponsiveness that follows the treatment of heart grafted rats with cyclosporine is dependent, in part, upon active suppression that is induced or mediated by T lymphocytes. Many features of the immune reactivity of cyclosporine -treated grafted rats support the hypothesis that the mechanism of specific suppression in these animals is akin to that of enhancement, rather than to that of transplantation tolerance induced in neonatal rats.

Animals↗
PubMed1984

Ovarian function after renal transplantation: comparison of cyclosporin A with azathioprine and prednisone combination regimens.

Ovarian function was assessed in 24 women after renal transplantation who were treated either with cyclosporin A (10 patients) or with a combination of azathioprine and prednisone (14 patients) as immunosuppressive therapy. The different regimens were not associated with any differences in clinical or endocrine indices of ovarian function (LH, FSH, prolactin, testosterone, oestradiol, dehydroepiandrosterone sulphate). Excessive hair growth was common in both treatment groups. Levels of testosterone and dehydroepiandrosterone were higher in cyclosporin-treated women but this was due to prednisone-induced suppression of adrenal androgen output in the azathioprine- and prednisone-treated women. Excessive hair growth was present in postmenopausal women on both treatments suggesting that hypertrichosis is a consequence of renal transplantation and is not a specific side-effect of cyclosporin A therapy.

Adult↗
PubMed1984

Renal biopsy morphology in renal transplantation. A comparative study of the light-microscopic appearances of biopsies from patients treated with cyclosporin A or azathioprine prednisone and antilymphocyte globulin.

Nephrotoxicity is a major side effect of cyclosporin A (CSA) when used in renal transplantation, and the distinction between nephrotoxicity and rejection is important in patient management. One hundred twenty-five renal biopsies were examined from 56 patients entered into a controlled clinical trial aimed at comparing the efficacy of CSA therapy alone to a combination of prednisone, azathioprine, and antilymphocyte globulin (AZA). In order to define the histopathology of rejection and nephrotoxicity, all the biopsies were evaluated in a semiquantitative manner by an observer unaware of the clinical state of the patient. Comparison of the morphological appearances of 32 biopsies from patients on CSA, and 22 biopsies from AZA-treated patients performed during clinically apparent rejection episodes showed that the histological patterns of rejection were the same in both treatment groups. Comparison of the morphological features of 34 biopsies from patients receiving CSA and 13 from patients receiving AZA, performed during prolonged periods of post-transplant renal failure, who eventually recovered on continuation of original therapy, showed that there were no morphological features specific to the CSA-treated group. Five patients on CSA had oliguria which was prolonged by CSA nephrotoxicity. Thirteen biopsies from all five patients showed a diffuse interstitial fibrosis that was peculiar to this group of patients.

Antilymphocyte Serum↗
PubMed1984

Stimulation of renin release from rat renal cortical slices by cyclosporin A.

Cyclosporin A is known to produce increases in plasma and kidney renin in vivo. In this study, Cyclosporin A was shown to stimulate renin release in vitro in rat renal cortical slices. At the optimal concentration of 8 x 10(-6) M Cyclosporin A, renin release was stimulated by up to 43% during a 2 hr incubation at 37 degrees. This observation strengthens the hypothesis that the intra renal renin-angiotensin system may participate in the mechanism of Cyclosporin A nephrotoxicity.

Animals↗
PubMed1984

Lymphocyte subsets in Heymann nephritis.

Altered ratios of T lymphocyte subsets have recently been reported in some forms of glomerulonephritis, including membranous glomerulonephritis. Heymann nephritis is a model of membranous glomerulonephritis that can be induced in susceptible strains of rat by a single subcutaneous injection of renal tubular antigen in Freund's complete adjuvant. Monoclonal antibodies were used to identify cytotoxic/suppressor and helper/inducer T cells in the blood, spleen, peripheral lymph nodes, and, where relevant, the lymph node draining the antigen injection site in susceptible and nonsusceptible rat strains before and after immunization with renal tubular antigen. A marked interstrain variation in the proportions of T lymphocyte subsets was found, but this did not segregate strains that are susceptible to Heymann nephritis induction from those that are resistant. Neither the development of Heymann nephritis in susceptible strains or immunization of resistant strains with renal tubular antigen was associated with any specific alteration in the T lymphocyte subpopulations.

Animals↗
PubMed1984

Cyclosporin A and renal prostaglandin biosynthesis.

The effect of cyclosporin A (CyA) treatment of rats on prostaglandin synthesis in the renal cortex was studied. Renal cortical slices were prepared from control and CyA-treated rats and the release of prostaglandins into the medium during incubation at 37 degrees was measured. Rats killed 4 hours after receiving 100 mg/kg CyA orally showed no changes in renal slice release of PGE2, PGF2 alpha, 6-keto-PGF1 alpha or thromboxane B2. The slice release of 6-keto-PGF1 alpha was tested after 5 days of CyA treatment and again there was no difference from control rats. The effect of CyA added to slice incubations in vitro was examined: CyA had no effect on PGE2 or 6-keto-PGF1 alpha release in the presence or absence of angiotensin II. Under all of these experimental conditions there was evidence of CyA-induced stimulation of the renin-angiotensin system. Indomethacin treatment did not inhibit CyA-mediated accumulation of renin in the renal cortex. The results suggest that renal prostaglandins do not play a role in CyA-stimulated renin storage or release, or in CyA nephrotoxicity.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Testicular function after renal transplantation: comparison of Cyclosporin A with azathioprine and prednisone combination regimes.

Testicular function was assessed in 24 men after renal transplantation who were on either Cyclosporin A (CSA) (8 men) or a combination of azathioprine and prednisone (AZP) (16 men) as immunosuppressive therapy. The different regimes were not associated with any differences in clinical or hormonal (LH, FSH, prolactin, testosterone, estradiol) indices of testicular function although adrenal androgen (dehydroepiandrosterone sulphate) was suppressed in prednisone-treated men. Overall, however, poor graft function was associated with abnormal testicular function. Renal allograft function rather than immunosuppressive regime was the major determinant of gonadal function.

Adult↗
PubMed1983

The cellular basis of allograft rejection in vivo. III. Restoration of first-set rejection of heart grafts by T helper cells in irradiated rats.

An adoptive transfer model was used to examine the subpopulations of lymphocytes required to effect first-set rejection of directly vascularized heart allografts. PVG heart grafts are not rejected in irradiated DA hosts for at least 50 days. The adoptive transfer of 5 X 10(7) syngeneic lymph node cells (LNC) restores rejection to 14.4 +/- 2.4 days (mean +/- SD). Subpopulations of LNC, were separated by an indirect "panning" technique using the mouse antirat monoclonal antibodies W3/13, MRC OX8, or W3/25 to deplete the unwanted subsets of cells. Each subpopulation was tested, in a number equivalent to the number present in 5 X 10(7) normal LNC, for its ability to cause the rejection of heart grafts. Whole T cells (W3/13+) or helper/inducer T cells (W3/25+) restored graft rejection to 16.4 +/- 3.8 d and 16.0 +/- 2.4 days, respectively. Neither cytotoxic/suppressor T cells (MRC OX8+) nor B cells (Ig+) restored rejection. Indirect immunoperoxidase stains of the grafts showed that although W3/25+ cells predominated in the rejected tissue, MRC OX8+ cells were also present even in grafts from rats restored with inocula that contained less than 1% MRC OX8+ cells. Examination of lymphoid tissues suggested that the MRC OX8+ cells might be of host origin. By the time the grafts were rejected in irradiated hosts, significant thymic regeneration had occurred and there were large numbers of MRC OX8+ cells present in the thymus, as well as some in lymph nodes and spleen.

Animals↗
PubMed1983

High risk hypertensive pregnancies: maternal and foetal outcome.

Two hundred and thirty-six pregnant women were referred for assessment and management of hypertension and/or renal disease. A Unit consisting of a physician, an obstetrician and a perinatologist jointly assessed each patient and advised on management. All patients were hospitalized and at bed rest. Drug therapy was clonidine hydrochloride or methyl dopa and in some patients a vasodilator was added. The decision to deliver was dictated by foetal maturity and wellbeing, in conjunction with maternal condition. There was no maternal mortality and the overall perinatal survival was 97%. The outcome of these pregnancies compares favourably with studies previously reported and reflect a successful approach to management of high risk hypertensive pregnancies.

Adult↗
PubMed1982

Immunology of renal transplantation rejection.

Recent studies into the mechanisms of graft rejection have highlighted the complexity of this response. Although current immunosuppressive treatments are crude, laboratory observations on the mechanisms of graft rejection have already led to various techniques which may assist in the early diagnosis of rejection, in the prognosis of a rejection episode, and in the development of more specific therapy to prevent and treat rejection. Already, the monitoring of T-cell subsets in blood and graft infiltrates is of considerable help. These observations may lead to the advent of more specific and subtle immunosuppressive therapy, such as the use of monoclonal antibodies directed against T-cell subsets. In the long term, the induction of states of specific unresponsiveness to the graft holds great promise, as do the development of techniques to assess adequacy of immunosuppression and to detect the presence of specific unresponsiveness.

Animals↗