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Biomedical subjects

P G Kerr

Publications and source records attributed to P G Kerr.

50 records · Page 3Linked to original sources
PubMed1991

Deoxyspergualin inhibits cytotoxic T lymphocytes but not NK or LAK cells.

Deoxyspergualin (DOSP) is a new immunosuppressive agent which probably inhibits various functions of monocytes, B cells and T cells. We examined the effects of deoxyspergualin on cellular cytotoxicity, including cytotoxic T lymphocyte (CTL) mediated killer, natural killer (NK) cell and lymphokine activated killer (LAK) cell killing. Deoxyspergualin inhibited cellular cytotoxicity generated by 7 days allo-antigenic challenge; it also inhibited cell killing if added on day 6 of this 7 day culture period. The drug did not significantly inhibit NK or LAK cell killing. The inhibitory effects of deoxyspergualin, however, were dependent on the serum used in the culture medium. Normal human serum (NHS) was associated with less inhibition than fetal calf serum (FCS). Finally, interleukin 2 (IL-2) was able to prevent the inhibitory effects of deoxyspergualin on antigen-specific cytotoxicity.

CD8 Antigens↗
PubMed1991

The evolution of the interstitial infiltrate in rejecting rat renal allografts: with particular reference to the production of gamma-interferon.

This study aimed to examine the evolution of the leucocytic infiltrate in rat renal allografts in the first 5 days of rejection. Immunohistology was used to assess the absolute numbers of infiltrating leucocytes in the rejecting allografts. The total infiltrate approximately doubled daily from day 1 through to day 4 (370 +/- 15 total leucocytes/mm2 of tissue on day 1 vs 5055 +/- 135 on day 4, p less than 0.05 for all days) and increased only a minor degree on day 5 (5485 +/- 535 leucocytes/mm2, p = n.s.). CD4 positive cells predominated until day 3, after which time CD8 positive cells greatly outnumbered CD4 positive cells (CD4:CD8 ratio day 3 1.83 vs day 5 0.53, p less than 0.05). Gamma-interferon was positive in T cells on day 2 (73% of all T cells) and was slightly positive on day 3 (5% of all T cells) but was negative on days 4 and 5. Activation markers such as IL-2Rs increased markedly from day 3. These findings favour a pivotal role for CD4 positive cells in the early phase of rejection and suggest that the early release of lymphokines by these cells is associated with the recruitment of CD8 positive cells to the allograft and the activation of those leucocytes present.

Animals↗
PubMed1989

The effects of OKT3 therapy on infiltrating lymphocytes in rejecting renal allografts.

OKT3 antibody therapy is effective in the treatment of renal allograft rejection. However its exact mode of action is unknown. Following OKT3 administration, peripheral blood lymphocytes fail to express the CD3 antigen, although other membrane antigens are relatively preserved. In this way the lymphocytes are unable to respond to foreign antigens. It is not known whether this modulation of CD3 on lymphocytes occurs within the rejecting allograft. Ten patients who received OKT3 therapy for steroid-resistant renal allograft rejection were studied. The aim of the study was to examine whether OKT3 antibody therapy altered the degree or the relative composition of the inflammatory infiltrate and to assess whether OKT3 treatment resulted in modulation of CD3 on intragraft lymphocytes. The study involved immunoperoxidase examination of biopsy material and flow cytometric analysis of peripheral blood lymphocytes obtained before and during treatment with OKT3 antibody. The results show that the total number of infiltrating leukocytes decreased after 5 days of treatment (3215 +/- 700 cells/l. 0 mm2 of tissue before vs. 1730 +/- 635 at day 5; P less than 0.001). The relative proportions of macrophages, total lymphocytes, CD4 +ve and CD8 +ve cells did not alter during therapy. Despite marked modulation of peripheral blood lymphocytes (CD3/CD2 ratio 0.89 +/- 0.13 before vs. 0.10 +/- 0.11 during treatment, P less than 0.001), there was no evidence of modulation of intragraft lymphocytes (CD3/CD2 ratio 0.98 +/- 0.14 before vs. 0.90 +/- 0.21 during treatment, P = NS). Although OKT3 antibody therapy is effective clinically at improving renal allograft rejection, this study demonstrates that it does not appear to cause modulation of the CD3 antigen on intragraft lymphocytes.

Adult↗
PubMed1989

Phenotypic definition of primed T cells in human renal allografts. Use of the CD45R marker.

Immunohistological studies indicate that T cells and macrophages are the major components of human kidney allograft infiltrates. Recent work has demonstrated a division of T lymphocytes into 2 subpopulations with distinct functions on the basis of their expression of the CD45R antigen (CD45R+ "naive" and CD45R- "memory" T cells). This study analyzes CD45R expression on circulating T cells and T cells infiltrating renal allografts in patients undergoing rejection and/or cyclosporine nephrotoxicity. The percentage of circulating T cells that expressed CD45R in patients with rejecting (63 +/- 4) or stable grafts (66 +/- 3) was not different from values obtained for normal donors (62 +/- 3). In contrast, the percentage of T cells expressing CD45R infiltrating rejecting grafts was 21 +/- 2 and was not affected by the stage of rejection; in patients with CsA toxicity the value was 22 +/- 6. The reduced proportion of T cells that expressed CD45R in the allograft may reflect a change in status from the naive state due to alloantigenic stimulation (which can be demonstrated in vitro) and/or a propensity of memory T cells to enter or be retained in an allograft.

Antigens, CD↗
PubMed1989

The effects of deoxyspergualin on lymphocytes and monocytes in vivo and in vitro.

It has been suggested that deoxyspergualin, a new immunosuppressant, may be immunosuppressive via a purely antimonocyte action. As this appears to be unlikely, this study examines the effect of deoxyspergualin on lymphocyte and monocyte function in vivo and in vitro. It is demonstrated that deoxyspergualin inhibits human lymphocyte proliferation in response to mitogens and allogeneic stimulation. Furthermore, it is demonstrated that this inhibition occurs no matter whether the monocytes or lymphocytes are treated with the drug. The drug appears to have a more significant effect on the lymphocyte component; rhIL-2 appears partly to overcome the deoxyspergualin-induced inhibition of lymphocyte proliferation in response to allogeneic stimulation. In a rat renal transplant model, deoxyspergualin-treated animals demonstrated a moderate interstitial infiltrate in their transplant kidneys that comprised approximately 50% each of macrophages and lymphocytes. There was significantly less activation (e.g. IL-2R expression) in the treated kidney infiltrates compared to rejected controls. Thus deoxyspergualin is an agent with immunosuppressive effects on both lymphocytes and monocytes and would appear to have more marked effects on lymphocytes.

Cyclosporins↗
PubMed1989

Bilateral pelviureteric junction obstruction causing renal failure in two elderly patients.

Two elderly patients presented with renal failure due to pelviureteric junction (PUJ) obstruction. After dialysis, obstruction was relieved by percutaneous nephrostomy and the diagnosis was established radiologically. Differential renal function was assessed by direct measurement or isotope scanning. Surgical correction resulted in both patients remaining free of dialysis at follow-up 2 years later. PUJ obstruction is an uncommon cause of renal failure, particularly in the elderly, but is potentially correctable.

Acute Kidney Injury↗
PubMed1989

Assessment of the symptomatic benefit of cool dialysate.

Symptoms were evaluated in 13 haemodialysis patients at dialysate temperatures between 37 and 35 degrees C. After a control period at 37 degrees C (stage 1) dialysate flow rate was increased from 300 ml/min in half the patients but no change in temperature was made (stage 2). In stage 3 dialysate temperature was reduced to 36.5 degrees C and in stage 4 to 35 degrees C. Blood pressure and temperature were measured pre- and post dialysis and patient completed a questionnaire indicating if they experienced any of nine specified symptoms: itch, restless legs, nausea, vomiting, headache, cramp, lethargy, hypotension and change in temperature. Trial stages were compared with chi 2 analysis using Yates correction. Symptoms per dialysis fell from 1.11 to 0.71 between stage 1 and 2 (p less than 0.0005). This was considered to be a trial effect. There was no further significant improvement in symptoms overall as the temperature was reduced to 35 degrees C. However, if complaints of coldness are excluded, there was a progressive reduction in symptoms from stage 1 to stage 4. Dialysate flow rate did not affect symptom reporting. There was no effect on body core temperature or blood pressure due to cool dialysate. Our results suggest there may be some benefit in lowering the dialysate temperature but this is small in relation to the placebo effect. Caution must be used in assessing similar studies using small numbers of dialyses.

Blood Pressure↗
PubMed1986

Hemodynamic and plasma renin responses to treatment of a renal arteriovenous malformation.

We report a case of a right renal arteriovenous malformation with high output cardiac failure and hypertension which was cured by nephrectomy. Hemodynamic findings pre- and post-operatively are presented. Plasma renin activity (PRA), both from peripheral venous and renal vein samples, was assessed. The fall in PRA associated with nephrectomy lends support to the suggestion that the renin-angiotensin system plays a role in the hypertension in these patients.

Adult↗