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Biomedical subjects

B K Shenton

Publications and source records attributed to B K Shenton.

At least 109 records · Page 6Linked to original sources
PubMed1986

Aspirate cellularity as a rapid indicator of renal allograft rejection.

No rapid and unequivocal test exists to diagnose renal allograft rejection. Despite advances in immunosuppression over the last 20 years, rejection is still the major problem in clinical organ transplantation. Most transplant centres report a renal graft survival rate of about 60 per cent at 5 years and the majority of graft losses are due to rejection. An influx into the graft of various cell types has been implicated in the diagnosis of rejection but it takes up to 24 h to obtain such information histologically. We have carried out fine needle aspiration biopsy of the allografts and estimated the number of white cells in the aspirate using a fluorescence activated cell sorter. Studies were performed in 34 cases of normal allograft function, 8 of rejection, 8 of acute tubular necrosis and 8 of cyclosporin nephrotoxicity. There was a statistically significantly higher cell number in the group undergoing rejection (P less than 0.01; Wilcoxon unpaired test) when compared to each of the other three groups. We believe that this technique, which takes only a few minutes to perform, could yield much valuable information. It deserves further study.

Biopsy, Needle↗
PubMed1986

Effect of perioperative blood transfusion on recurrence of colorectal cancer.

The aim of the present study was to examine the outcome of 517 patients undergoing curative surgery for colonic and rectal cancer, and to compare the recurrence and mortality rates in transfused and non-transfused groups of patients. The two groups were evenly matched for age, sex, Dukes' stage and histological differentiation. There were significantly more rectal tumours in the transfused group (P less than 0.01), but the distribution of colonic lesions did not differ. Life table analysis revealed that the transfused patients had a 20 per cent greater probability of recurrence at 5 years (P less than 0.005) and there were 16 per cent more cancer related deaths (P less than 0.01). Even when all rectal cancers were excluded, a similar trend was seen for the colonic lesions: a 24 per cent greater probability of recurrence at 5 years (P less than 0.025) and 15 per cent more cancer related deaths (P less than 0.02). We conclude that blood transfusion may be associated with increased mortality and recurrence in patients undergoing curative surgery for colorectal cancer.

Aged↗
PubMed1985

The influence of surgical operations on components of the human immune system.

Surgical operations have been shown to cause a variety of immunological disturbances in man both in vivo and in vitro. With few exceptions the overall picture is one of a generalized state of immunodepression in the postoperative period. The implications of these observations are that host defences may be compromised by surgical procedures, thus providing a 'fertile soil' for bacterial invasion and tumour cell metastasis at the very time when risks from invading pathogens and viable tumour cells are maximal. We have studied the effects of surgical operations on the immune system in 35 patients with benign disease. Surgical procedures were classified as either minor (n = 15) or major (n = 20). A panel of monoclonal antibodies was used to identify peripheral blood lymphocyte subpopulations and analysis was performed using flow cytometry. Simultaneous estimations of plasma alpha-1 proteinase inhibitor (alpha-1-PI), alpha-2-macroglobulin (alpha-2-M), alpha-2-pregnancy-associated glycoprotein (alpha-2-PAG) and plasma suppressive activity (PSA) on stimulated allogeneic lymphocytes were performed before operation and on postoperative days 1, 3, 7, 17 and 21. Circulating numbers of all lymphocyte subpopulations fell significantly following surgery, except for B lymphocytes which did not change. The magnitude, and duration of the reduction in cell numbers and the subpopulation affected was significantly related to the degree of surgical trauma, and returned to pre-operative values by postoperative day 7. Changes in alpha-1-PI, alpha-2-M, alpha-2-PAG and PSA were also significantly related to the degree of surgical trauma, and these plasma changes persisted longer than the cellular disturbances. Surgical operations induce a reversible depression of cellular immunity which precedes plasma suppressive activity in its return to pre-operative levels. Immunostimulating agents such as interferon and the interleukins deserve evaluation as prophylactic agents pre-operatively.

Blood Proteins↗
PubMed1985

CAPD and renal transplantation.

Continuous ambulatory peritoneal dialysis (CAPD) is believed to improve the immune competence of end-stage renal failure patients and to increase the risk of graft rejection following subsequent renal transplantation. At this centre, 220 consecutive renal transplants have been studied in patients treated by either CAPD or haemodialysis (HD). Patient and graft survival was not significantly different for the two treatment groups over a five year follow-up. When only first cadaver recipients were considered (152 grafts) one-year graft survival (non-immunological failures excluded) was 77 per cent for CAPD and 79 per cent for HD patients (P greater than 0.05). Time on dialysis and number of pre-operative transfusions were significantly greater for the HD patients (P less than 0.05). A group of HD and CAPD patients were identified as being matched for age, sex, HLA, A, B, DR antigen matches, pre-operative transfusions and time-on dialysis. One-year graft survival of the CAPD patients was 82 per cent and for the HD patients 61 per cent. Studies of patient lymphocyte function and plasma suppressive activity in vitro revealed no differences between CAPD and HD treated patients. CAPD is not an immunological risk factor in renal transplantation and its continued use in the preparation of patients for transplantation is recommended.

Adolescent↗
PubMed1985

Inhibition of natural killing and antibody-dependent cell-mediated cytotoxicity by the plasma protease inhibitor alpha 2-macroglobulin (alpha 2M) and alpha 2M protease complexes.

Over the past few years increasing attention has been given to the relationship between the immune response and proteases. The aim of our present study was to examine the dose-response effect of purified alpha 2-macroglobulin (alpha 2M) with varying degrees of protease (trypsin) saturation on natural killing (NK) and antibody-dependent cell-mediated cytotoxicity (ADCC). The results demonstrated that alpha 2M with 50% trypsin saturation (fast alpha 2M) was more inhibitory in both assays than alpha 2M with no bound protease (slow alpha 2M).

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Immunosuppressive plasma factors in malignant disease.

Naturally occurring substances in plasma capable of suppressing immune responses have been described in health and in benign and malignant diseases. The present study attempted to identify the factors responsible for the immunosuppressive activity of plasma from healthy subjects (n = 5) and patients with benign (10) and malignant (12) diseases. Plasma samples were fractionated by gel filtration and the distribution of specific protein was determined. The suppressive activity of plasma and plasma fractions against autologous and allogenic lymphocytes was measured using a rapid in vitro electrophoretic test. Plasma suppressive activity (PSA) was low in normal subjects and well nourished patients with benign disease and was associated entirely with alpha-2-macroglobulin (a2M). PSA was significantly increased in patients with malignancy and was associated mainly with a2M although immune complexes, IgG and small molecular weight substances were also immunosuppressive. Plasma a2M concentrations were similar in all groups but the suppressive activity associated with a2M differed dramatically. The study demonstrates that PSA can be measured quantitatively and that a2M is an important immunoregulatory protein in cancer patients. On the basis of the results obtained a new hypothesis of tumour-mediated immune suppression is proposed.

Adult↗
PubMed1984

In situ subpopulations of lymphocytes in human colorectal carcinomas.

Subpopulations tumour-infiltrating lymphocytes were studied in 13 patients with colorectal carcinoma using cryostat immunohistochemistry. Murine monoclonal antibodies (MAB) to the surface phenotype of lymphocyte subpopulation were used in an indirect immunoperoxidase method to demonstrate T (MAB OKT3), T helper (MAB OKT4), T suppressor (MAB OKT8) and B lymphocytes (MAB B1). Langerhans cells were demonstrated using MAB OKT6. All cells reacting with each monoclonal antibody were more prevalent in the stroma of the tumour than within the sheets of malignant cells. In both these areas, OKT8-positive cells were significantly more numerous than OKT4-positive cells, as estimated quantitatively by point counting on a fixed grid. In uninvolved areas of normal mucosa, OKT4-positive lymphocytes were in the majority. OKT6-positive cells were present in large numbers within tumour cells and in close association with lymphoid aggregates. The presence of large numbers of OKT8-positive cells in situ in human colorectal carcinomas may be a cellular mechanism in favour of tumour growth. OKT6-positive cells in situ suggest that mechanisms for antigen processing and presentation are well represented in human colorectal carcinomas.

Antibodies, Monoclonal↗
PubMed1983

The role of protease in immunoregulation.

Whilst immunodepression is widely recognized in patients subject to trauma or chronic disease, the mechanism of this process is poorly understood. We found that most of the lymphocyte suppressive activity of plasma from severely ill patients was attributable to the protein alpha 2-macroglobulin (alpha 2 M) and low molecular weight peptide (less than 10000). The only major variation in alpha 2 M concentration was found in patients subject to trauma, when it was depressed at times of high plasma suppressive activity. In order to explain qualitative immunosuppressive differences in alpha 2 M we studied its functional role as the main route for binding and degrading proteolytic enzyme (protease). In normal plasma minor degrees of protease complex formation to alpha 2 M caused greatly increased suppressive activity due principally to alpha 2 M and the abnormal appearance of low molecular weight peptide (less than 10000). Study of protease inhibitor function in patients suffering from acute or chronic illness suggested that in these patients their plasma becomes immunosuppressive due to inadequate handling of protease, resulting in alpha 2 M-protease complexes or inhibitory peptides persisting in the circulation. Opportunities for background immunoregulation by altering protease metabolism are considered.

Acute Disease↗
PubMed1983

A possible mechanism of immunoregulation produced by alpha 2-macroglobulin.

Most of the plasma suppressive activity was associated with alpha 2M in both normal subjects and cancer patients. alpha 2M binding to physiological levels of proteases was associated with an increase in the ability to suppress lymphocyte reactivity in the TEEM test. alpha 2M binding to proteases released a peptide that was a component of the alpha 2M; this peptide suppressed lymphocyte reactivity to mitogenic, antigenic, and allogenic stimuli in the TEEM test and in the lymphocyte transformation assay. Physically and biologically similar peptides have been found in the plasma of cancer patients and patients with thermal burns, uremia, and acute pancreatitis.

Acute Disease↗
PubMed1983

A new mechanism of humoral immunodepression in chronic renal failure and its importance to dialysis and transplantation.

Whilst chronic renal failure (CRF) patients are known to have an impaired immune response the explanation is unclear. We investigated the immunosuppressive effect of plasma from CRF patients on an in vitro assay of normal lymphocyte function. One hundred and sixty regular dialysis patients had significantly greater plasma suppressive activity (PSA) than that of normal healthy subjects. PSA decreased after haemodialysis but increased after blood transfusion. Renal allograft recipients with low PSA were more likely to have accelerated rejection. Assay of the functional capacity of plasma for inhibiting protease (e.g. plasmin, thrombin, trypsin) suggest that high PSA is associated with the excess formation of protease-inhibitor complexes and liberation of immunoregulatory peptide (less than 10,000 daltons).

Adolescent↗