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Biomedical subjects

B M Hall

Publications and source records attributed to B M Hall.

At least 91 records · Page 5Linked to original sources
PubMed1986

Diagnosis of renal allograft rejection by analysis of fine-needle aspiration biopsy specimens with immunostains and simple cytology.

Fine-needle aspiration biopsy specimens of renal transplants were analysed by means of commercially available monoclonal antibodies and an immunoperoxidase stain. Three cellular features associated with acute cellular rejection were identified--heavy infiltrates of activated T cells or large mononuclear cells strongly expressing HLA-DR antigens, and HLA-DR expression by renal tubular cells. A combination of semiquantitative scores for these features correctly identified rejection in 32 of 34 cases, with no false positives in cases of cyclosporin nephrotoxicity or stable graft function.

Antibodies, Monoclonal↗
PubMed1986

Immunopathology of renal allograft rejection analyzed with monoclonal antibodies to mononuclear cell markers.

The composition of the mononuclear cell infiltrate in rejecting renal allografts was determined on 96 renal biopsies and 22 nephrectomy specimens by the use of monoclonal antibodies to mononuclear cell surface markers and an indirect immunoperoxidase staining technique. During rejection the composition of the infiltrate was heterogeneous, with T cells (T11), monocytes (OKM1) and HLA-DR expressing mononuclear cells the most frequent sub-populations. B cells (B1) and activated T cells, identified by OKT10, were always in the minority. The T cells infiltrate usually included the helper/inducer (T4) and cytotoxic (T8) subclasses, which suggests that both may contribute to the mediation of rejection. Whether T4 or T8 predominated in the graft did not relate to the ratio of T4:T8 in blood, the HLA A, B or DR incompatibilities of the graft, or the immunosuppressive used. The frequency of T11, T4, T8, HLA-DR positive cells and monocytes, but not B cells, increased with the severity of rejection and was similar in biopsies from patients immunosuppressed with Cyclosporine (CSA) to those given a combination of azathioprine, prednisone and antilymphocyte globulin (AZA). Severe rejection episodes which did not respond to treatment with corticosteroids were more often characterized by a predominance of T8 over T4 cells and T cells infiltrating the glomeruli. In grafts with evidence of cellular rejection, renal tubular cells were shown to have a marked increase in their expression of HLA-DR antigens compared to normal kidneys or grafts with minimal rejection. The expression of HLA-DR antigens on graft tubular cells correlated with the presence of T cells in the interstitium and the severity of rejection, except for moderate rejection in CSA treated biopsies, in which HLA-DR expression was lower than in AZA biopsies. These immunopathological studies have demonstrated that a variety of potential effector cells exist within the graft, and several features have been identified which may assist in assessing the prognosis of the rejection episode.

Antibodies, Monoclonal↗
PubMed1986

Expression of HLA antigens on renal tubular cells in culture. I. Evidence that mixed lymphocyte culture supernatants and gamma interferon increase both class I and class II HLA antigens.

The altered expression of HLA antigens on tissues during rejection is of potential importance to both the initiation and effector arms of the alloimmune response. Associated with rejection episodes, renal tubular cell expression of HLA DR (class II) antigens has been observed to be markedly increased. In this study an in vitro assay using cultured renal tubular cells from normal human kidneys was developed. Monoclonal antibodies to detect HLA DR and HLA A,B,C (class I) molecules were used to identify these antigens on cultured tubular cells either by indirect immunofluorescence stains and flow cytometric analysis or by immunoperoxidase stains with cytological analysis. With these techniques normal cultured cells had little membrane or cytoplasmic HLA DR but did have membrane HLA A,B,C. Culture of renal tubular cells with either supernatants from mixed lymphocyte cultures or purified gamma interferon induced expression of HLA DR, with maximum expression occurring between day 4 and day 6. Increased HLA A,B,C expression was also observed. This increased expression of HLA antigens was shown not to be dependent upon increased cell division of the cultured cells, and removal of gamma interferon from the cultures resulted in a decay in both HLA DR and A,B,C expression within days. HLA expression was inhibited by addition of protein synthesis inhibitor cycloheximide, but not by the addition of puromycin, mitomycin C, or actinomycin D--which suggested that tubular cells had transcribed m RNA for both HLA DR and A,B,C antigens. Expression of HLA antigens was not inhibited by cyclosporine, corticosteroids, or azathioprine. These studies demonstrate that the increased expression of HLA antigens seen in renal allografts at the time of rejection episodes can be explained by the release of lymphokines, especially gamma interferon, by infiltrating cells, and that reduced HLA DR expression of transplanted kidneys in patients treated with cyclosporine is not due to the drug directly inhibiting HLA expression by graft cells.

Antibodies, Monoclonal↗
PubMed1986

Renal tubular transport of cyclosporine A (CSA) and associated changes in renal function.

In an effort to understand the mechanisms of nephrotoxicity of cyclosporine A (CSA), this study has been undertaken to evaluate the CSA clearance by the kidney and its tubular transport, with simultaneous studies on the multiple renal functional parameters. New Zealand white rabbits weighing approximately 2.5 kg were used in the study. Rabbits were infused with 14C labelled inulin to determine GFR. Blood pressure was monitored throughout the study via ear artery cannula. The rabbits were catheterized by the bladder and remained conscious throughout the entire study. When an infusional steady state was achieved, three clearance periods of 15 minutes were undertaken, followed then by a bolus of 10 mg/kg CSA, followed by an infusion of 1 mg/kg. A further three clearance periods were undertaken, studying the clearance of CSA at the same time as the GFR. Additional studies were made of plasma renin activity, aldosterone, 6-keto-PGF1 alpha, urinary sodium excretion and urinary potassium excretion rate. CSA was determined in whole blood and urine by HPLC. The results indicate that CSA, as determined by HPLC, has a whole blood renal clearance of 0.029 +/- 0.011 ml/min/kg body weight. Glomerular filtration rate showed no difference in animals pretreated with an infusion of mannitol when comparing pre- and post-CSA administration. Without mannitol, there was a significant decrease in the GFR following administration of CSA. CSA administration was accompanied by a rise in plasma renin activity in animals treated with mannitol and without mannitol. The rate of 6-keto-PGF1 alpha excretion without pretreatment with mannitol showed a significant rise following CSA administration.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Influence of cyclosporine A (CSA) on intrarenal control of GFR.

In the acute clinical situation, CSA produces reversible renal impairment. Studies by Morris et al. [1982] and others indicate that this is rapidly reversible when the drug is ceased. A series of studies have been performed in rats with the aim of examining changes in GFR, together with changes in the intrarenal renin-angiotensin system and renal release of prostaglandins. Rats were treated for 3-7 days with CSA and at the end of the experiment kidneys were removed and renal cortical slices prepared. There was increased renin secretion from the CSA-treated rats, compared to controls, and the response was dose-dependent. There was an increase in renal cortical renin content paralleling the renin release. Determinations of plasma renin in these animals also indicated a rise in plasma renin activity associated with time. In animals not pretreated with CSA, the renal cortical slices incubated with CSA demonstrated a stimulation of renin release. A further group of rats pretreated with 100 mg/kg/day of CSA for 3-7 days showed no change in renal slice release of 6-keto-PGF1 alpha, thromboxane B2, PGE2 and PGF2 alpha. This data indicates that the renal renin-angiotensin system is activated by CSA and produces a dissociation of the linkage between renal slice prostaglandin release and the renin angiotensin system. This would indicate that CSA affects the intrarenal control of GFR. However, the exact site of the modulation remains to be determined.

Animals↗
PubMed1985

Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. Mediation of specific suppression by T helper/inducer cells.

DA rats grafted with major histocompatibility complex-incompatible PVG heart grafts and treated with cyclosporine (CY) for 10 d do not reject their grafts, and develop a state of specific unresponsiveness toward PVG allografts. Cells from these animals tested in an adoptive transfer assay were incapable of restoring PVG graft rejection, and capable of specifically inhibiting the capacity of adoptively transferred normal lymph node cells (LNC) to do so. They effected third party Wistar/Furth (W/F) graft rejection, however. Adoptive transfer assays with purified subpopulations of the lymphocytes that mediated this effect showed that W3/25+ T cells of the helper/inducer subclass, when injected alone, failed to restore rejection, and were also able, when injected with normal LNC or the W/25+ cells separated from them, to prevent these cells from effecting rejection. MRC OX8+ T cells of the cytotoxic/suppressor subclass, B cells, and serum from rats with long-surviving grafts all failed to inhibit the allograft responsiveness of normal LNC, and thus were not identified as mediators of the state of specific unresponsiveness. These results show that the specific unresponsiveness that develops in rats with long-surviving grafts, and which, in part at least, is responsible for prolonged graft survival, is due to an alteration in the alloreactivity of the helper/inducer subclass of T cells. These cells not only lack the capacity to initiate a rejection response against the alloantigens of the graft, but also have the ability to inhibit the capacity of normal W3/25+ cells to do so.

Animals↗
PubMed1985

Hypertension in pregnancy. A study of 142 women presenting before 32 weeks' gestation.

This study evaluates the outcome of 142 consecutive pregnancies in women in whom hypertension was diagnosed before 32 weeks' gestation and who were managed by a team comprising obstetricians, physicians and perinatologists. Arterial pressure was lowered to 140/90 mmHg or lower with clonidine hydrochloride or methyldopa therapy to which, in most cases, a vasodilator, hydralazine or diazoxide was added. The outcome of patients who were managed by the multidisciplinary team from the clinical onset of their disease was compared to the outcome of those who were transferred after the onset of hypertension from other centres. A greater perinatal mortality rate was found among the infants of patients with pre-eclampsia and patients with essential hypertension in pregnancy when the mothers were referred late for management. Reasons for the difference in pregnancy outcome are not clear. Possible explanations are discussed which emphasize the need for further study to establish optimal management of this common complication of pregnancy.

Antihypertensive Agents↗
PubMed1985

Treatment of renal transplantation rejection. Cyclosporin A versus conventional treatment with azathioprine, prednisone and antithymocyte immunoglobulin in primary cadaveric renal transplantation.

In a prospective randomized clinical trial to compare treatment with cyclosporin A to conventional treatment with azathioprine, prednisone and antithymocyte immunoglobulin in cadaveric renal transplantation, 34 patients were entered into both treatment groups and were examined regularly for seven to 43 months. Renal graft survival at one year was 72% among patients receiving cyclosporin A therapy and 75% among those receiving conventional therapy. Rejection was a frequent complication of both treatments; irreversible rejection occurred in six patients receiving treatment with cyclosporin A and in 10 patients receiving conventional therapy. The nephrotoxicity of cyclosporin A was its main side-effect. A similar proportion of kidneys in both groups (65% and 69%) were initially affected with post-transplant oliguria, but recovery of function took significantly longer in the group receiving cyclosporin A therapy (median, 29 days versus 11 days, P less than 0.001). The results of this pilot study suggest that cyclosporin A can be used safely in patients with post-transplantation oliguria, and indicate that long-term graft survival with cyclosporin A is comparable to that achieved with azathioprine, prednisone and antithymocyte immunoglobulin.

Adolescent↗
PubMed1985

Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell.

DA rats treated with hyperimmune anti-PVG serum and grafted with (DA X PVG)F1 heart grafts in which graft survival was prolonged for greater than 75 d were used to examine the cellular mechanisms that maintain the state of specific unresponsiveness found in these animals. The capacity of lymphocytes from these animals to effect or inhibit graft rejection on adoptive transfer to irradiated heart-grafted hosts was tested. Spleen cell populations and the T cell subpopulation separated from spleen cells in vitro failed to restore rejection of PVG heart grafts in irradiated DA recipients but restored third party Lew graft rejection. Whole spleen cells had the capacity to suppress the ability of normal DA LNC to cause graft rejection, but T cells from spleen only delayed the restoration of rejection. LNC and recirculating T cells from rats with enhanced grafts adoptively restored PVG rejection, however. These studies show that the state of specific unresponsiveness that follows the induction of passive enhancement is dependent in part upon active suppression, which is induced or mediated by T lymphocytes. The recirculating pool of lymphocytes in these animals is not depleted of specific alloreactive cells with the capacity to initiate and effect rejection. Thus, these animals' unresponsiveness is not like that found in transplantation tolerance induced in neonatal rats, but is, in part, due to a suppressor response that can inhibit normal alloreactive cells' capacity to initiate and effect rejection.

Animals↗
PubMed1985

Post-transplant acute renal failure in cadaver renal recipients treated with cyclosporine.

The outcome of patients with acute renal failure following cadaveric renal transplant has been evaluated in a prospective, controlled trial, comparing treatment with cyclosporine (CSA) to prednisone, azathioprine, and antilymphocyte globulin (AZA). There was a high incidence of acute post-transplant renal failure in both groups: 37 of 51 CSA and 31 of 45 AZA patients, due to the long exposure of kidneys to warm and cold ischemia. Onset of adequate renal function was delayed for three or more weeks in 27 (53%) CSA and only nine (20%) AZA patients, and the only predisposing factor found was donor hypotension. All nine AZA and 18 of the 27 CSA patients with prolonged oliguria subsequently had a spontaneous diuresis. Nine of the CSA patients were changed to azathioprine and prednisone because of suspected CSA toxicity, and eight of these kidneys began functioning within days, even though they had been oliguric for 21 to 83 days. Of these nine patients, five had adequate long-term function on AZA, three developed CMV infections that were fatal to two individuals, and two rejected their grafts. Plasma CSA levels fluctuated widely in all patients, but were not higher in any group, including those with prolonged oliguria. During the oliguric period, biopsy specimens proved rejection was more common in the nine patients who had their CSA stopped than in the other CSA patients, and seven of these nine developed a diffuse interstitial fibrosis that was thought to be a manifestation of CSA toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗