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Biomedical subjects

G Proud

Publications and source records attributed to G Proud.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1985

Functional analysis of T and B cells from blood and thyroid tissue in Hashimoto's disease.

B lymphocytes from Hashimoto blood and thyroid tissue have been cultured with autologous T cells from thyroid/blood to assess their ability to synthesise IgG and thyroid autoantibody. Thyroid B cells were able to synthesize microsomal antibody spontaneously in the absence of T cells or pokeweed mitogen (PWM) and this synthesis was increased in the presence of thyroid T cells without PWM or with blood T cells with PWM. In contrast, blood B cells did not secrete thyroid autoantibody spontaneously but could be induced to do so by thyroid T cells spontaneously or by blood T cells with PWM. Despite these differences, lymphocytes from blood and thyroid tissue secreted microsomal or thyroglobulin antibodies in culture which were similar in terms of the IgG subclass distribution. It would appear, therefore, that although the state of activation of B and T cells is different in blood and thyroid tissue, the precursors of thyroid autoantibody secreting cells are the same.

Autoantibodies↗
PubMed1985

Renovascular hypertension: ten years' experience in a regional centre.

In a unit serving a population of three million, 60 hypertensive patients with renovascular disease were identified over a 10-year period. The presence of renovascular disease was usually suggested by intravenous urography (IVU), although this was falsely negative in 21 per cent of cases; isotope renography (IR) was normal in a similar proportion of patients (25 per cent). Eight patients were treated medically and 52 underwent surgical procedures; nephrectomy in 32, autotransplantation in 10, by pass graft in six and percutaneous transluminal angioplasty in four. Twenty-three per cent of patients were cured, 37 per cent improved and 40 per cent unchanged one year after surgery, but the response could not be accurately predicted. Clinical features were of some value in that those patients most likely to benefit from surgery were younger, had less severe hypertension of shorter duration, smoked less, had less severe retinopathy and less cardiomegaly. There was also a trend for those with better renal function and less electrocardiographic evidence of left ventricular hypertrophy to benefit from surgery. The IVU and IR did not predict response to surgery but arteriographic appearances of fibromuscular dysplasia indicated there should be a favourable response. The renal vein renin ratio, basal or stimulated, was of no prognostic value since approximately two-thirds of patients with ratios above or below the threshold value had some benefit from surgery. We conclude that the surgical treatment of renovascular hypertension is worthwhile but the number of patients suitable for surgery is small. Clinical features and the results of simple investigations provided the best guide to surgical outcome in our patients.

Adult↗
PubMed1984

Surgical aspects of continuous ambulatory peritoneal dialysis--3 years experience.

Since January 1979, 122 patients (mean age 38.5 years, range 5-72 years) with chronic renal failure have been treated with continuous ambulatory peritoneal dialysis (CAPD). Peritoneal access was achieved by inserting silicone rubber Tenckhoff peritoneal dialysis catheters (Quinton, Seattle, Washington) by an open (76 per cent) or closed technique. Actuarial analysis showed a patient survival of 98 and 94 per cent and a success rate of 88 and 64 per cent at 1 and 2 years, respectively. Currently, 74 patients are using CAPD and 8 have been treated for 30-36 months. Thirty-five patients (29 per cent) required two or more peritoneal catheters and 69 per cent of these patients are still on CAPD. Catheter-related peritonitis was the most frequent complication (233 separate episodes in 94 patients) and necessitated catheter removal in 16 per cent of episodes, although 37 per cent of patients from whom catheters were removed because of peritonitis later resumed CAPD. Extravasation of dialysate from the peritoneal cavity (31 episodes) and catheter obstruction (31 episodes) required surgical replacement of catheters in 8 and 23 cases, respectively. Twenty patients (16 per cent) developed 24 abdominal hernias, only one of which caused failure of CAPD. Infective and mechanical complications of CAPD frequently require surgical intervention but only occasionally result in failure of the technique, and even multiple catheter replacements are compatible with successful long term CAPD.

Abdomen↗
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

Intravenous methylprednisolone at the time of renal transplantation.

Ninety-five consecutive transplants performed prior to the introduction of methylprednisolone bolus at transplantation were compared to 136 consecutive transplants performed after the policy change. No difference was found in the incidence of reversible or irreversible rejection in the two groups. The treated group were exposed to a higher total dose of steroid than the non-treated group. Routine bolus methylprednisolone therapy at transplantation is not recommended.

Adult↗
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↗
PubMed1982

Peritonitis in continuous ambulatory peritoneal dialysis. Laboratory and clinical studies.

During a three year period, 1979-81, 82 patients were treated by continuous ambulatory peritoneal dialysis (CAPD). The incidence of peritonitis was reduced significantly during the three years from one episode per 20 patient-weeks to one episode every 37 patient-weeks. 83% of the 136 episodes of peritonitis were treated successfully by antibiotic therapy alone. 62% of the total episodes were managed successfully with intraperitoneal cefuroxime. in 13 (16%) patients, CAPD failed because of peritonitis. Hospital admission for peritonitis has been reduced to a mean of 4.3 days per patient per year of CAPD. Fron January to September, 1982, Clostridium-difficile colitis developed in 13 patients. This complication was associated with considerable mortality and morbidity and has prompted a change in antibiotic policy. Patients with peritonitis are now given intraperitoneal netilmicin and intravenous vancomycin. Peritonitis remains the main complication of CAPD, but can be minimised by development of adequate facilities for performing CAPD.

Adolescent↗
PubMed1982

Superiority of B locus matching over other HLA matching in renal graft survival.

Graft survival after 348 consecutive first cadaver-donor renal transplants was significantly improved by HLA matching when recipients who had received pretransplant blood transfusions were matched with their kidney donor for two HLA-B locus antigens. No other type of HLA matching significantly improved graft survival in transfused recipients nor did any type of HLA matching in non-transfused recipients. Matching for one HLA-DR antigen had no benefit in transfused recipients. Only two patients received kidneys matched for both DR antigens and only two of those in whom DR matching had been performed had not been transfused. These results indicate that pretransplant blood transfusion and selection of graft recipients predominantly on the basis of HLA-B matching has significantly reduced the renal graft rejection rate in Newcastle upon Tyne over two years. Thus, HLA-B antigen matching should be adopted as the main criterion for kidney sharing between transplant centres.

Adult↗
PubMed1981

Renal transplantation in patients on continuous ambulatory peritoneal dialysis.

Over a two year period 15 patients on CAPD and 65 patients predominantly treated by haemodialysis received first grafts. There was no difference in graft survival in these two groups. In the continuous ambulatory peritoneal dialysis (CAPD) patients there were no post operative episodes of peritonitis, apart from one patient who had peritonitis at the time of transplantation. No technical difficulties were encountered at the time of grafting. CAPD is not a contraindication to transplantation.

Adolescent↗