Production of platelet-activating factor by endothelial cells.
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Biomedical subjects
Publications and source records attributed to R Taylor.
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From a study population of 208 consecutive first cadaver renal transplant recipients a proportional hazard model was used to simultaneously quantify the role in graft failure of matching for specific HLA antigens and constitutional factors (age, sex, duration of dialysis (Dt), and pre- (PTr) and peri-(PerTr) operative transfusions) that influence nonspecific immune response. A comparison was also made of graft survival in patients treated by the two principal methods of dialysis, hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The advisability of including nonimmunological failures in studies of graft survival was also considered. The analysis indicated that factors influencing a patient's innate nonspecific immune response (e.g., Dt and PTr) are important determinants of graft survival and should be taken into account when considering matching for specific HLA-B or DR antigens prior to transplantation. While there was no overall effect of dialysis type on graft survival, the influence of other risk factors depended on the method of dialysis. Failure to identify and exclude graft loss for nonimmunological reasons can give rise to misleading conclusions in analysis of immunoregulatory factors in organ transplantation.
To determine whether the decline in glucose tolerance with age is related to changes in peripheral tissue insulin sensitivity, 11 healthy older (65-85 years) and 12 healthy younger (20-38 years) subjects, matched for physical activity and body mass index, were studied. The glucose-insulin infusion technique, in which glucose and insulin are infused at constant rates over 150 min, was used to assess peripheral tissue insulin sensitivity. The metabolic clearance rate (MCR) of glucose, which reflects peripheral tissue insulin sensitivity, is derived from the resulting steady-state blood glucose. Fasting blood glucose was similar in the two groups, but mean blood glucose 2 h after an oral glucose load was higher in the older group. MCR of glucose expressed per kilogram lean body mass was almost identical in both groups (13.3 +/- 1.3 vs. 13.5 +/- 1.3 ml/kg lean body mass/min, respectively). Evidence of decreased glucose tolerance with normal peripheral tissue insulin sensitivity suggests that changes in other factors may be more important than previously recognised.
Forty-five patients with metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) and cimetidine. Patients received coumarin, 100 mg orally daily; cimetidine administration, 300 mg orally four times daily, was initiated on day 15 of therapy, and treatment with both drugs was continued until progression of disease. Three patients are too early to evaluate (on study less than or equal to 2 months with no change in tumor status). Objective responses (greater than or equal to 50% reduction in measurable disease) occurred in 14 of 42 evaluable patients (33.3%) (the 95% confidence interval based on this rate is +/- 14.3%), with three complete responses and 11 partial responses (PR). Complete responses lasted 9.5, 4+, and 9.5+ months. The median duration of response for the PR group was 5 months (range, 4 to 21+ months). Twelve patients experienced stabilization of disease ranging from 4 to 16.5+ months. No response was seen in 16 patients. There was no symptomatic, hematologic, or chemical (organ dysfunction) toxicity among the 45 patients treated. Coumarin and cimetidine appear to be safe and active agents in the treatment of metastatic renal carcinoma. Further studies are required to determine the optimal dose and scheduling of these agents.
To test whether acute alcohol withdrawal has an effect on pulmonary function, we studied 33 smoking alcoholics admitted for a four-week period of rehabilitation during which they consumed no alcohol. Flow-volume curves, lung volumes by body plethysmography, and single breath diffusing capacity for carbon monoxide were measured on admission, at two weeks, and at four weeks. We found no significant change in pulmonary function between the results on admission and after four weeks of abstinence from alcohol. We conclude that short-term cessation of alcohol did not significantly influence pulmonary function in our subjects.
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Glucose tolerance and the prevalence of impaired glucose tolerance (IGT) and diabetes in the Polynesian populations of Rarotonga and Niue were studied in 1980. Both Rarotongans and Niueans have been considerably influenced by sociocultural modernization and (in the case of Rarotonga) tourism. In both populations, the prevalence of abnormal glucose tolerance exceeded 10% in men and 15% in women. There was an association between glucose tolerance and age and obesity in both sexes, but not between glucose tolerance and physical activity. Glucose tolerance did not differ between Rarotongans and Niueans after allowing for differences in age and obesity. Comparisons between normal subjects, those with impaired glucose tolerance (IGT) and diabetic subjects with respect to factors that are traditionally associated with glucose intolerance provided some support for IGT as a truly intermediate diagnostic category of glucose tolerance.
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The syndrome known as tropical diabetes seems to be distinct from the two main types common in developed countries. Major pancreatic exocrine disease may or may not be present, and within these two groups there are clinical and biochemical variants. For these conditions the term malnutrition-related diabetes has been proposed. Although malnutrition is a plausible unifying factor, there is a good case for retaining the term tropical diabetes until there is more information on clinical and biochemical features and on aetiology.
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Recent evidence suggests that, during endocytosis, receptors for many polypeptide ligands are spared degradation and are recycled to the plasma membrane for re-utilization. The univalent ionophore monensin was shown to inhibit membrane recycling. We therefore examined its effects on insulin interactions with isolated rat hepatocytes to characterize further receptor endocytosis and recycling in these cells. At 10 degrees C, in the absence of endocytosis, no change in insulin binding was observed. However, at 37 degrees C a concentration-dependent decrease in 125I-insulin binding was seen in the presence of insulin; this reached a maximum of 60% at 1 nM-insulin. Competitive binding studies showed this to be due to a 50-60% decrease in cell-surface insulin-receptor concentration, although the total cellular receptor concentration remained unchanged, suggesting that monensin causes the intracellular sequestration of receptors. Time-course studies of the processing of 2.5 nM-insulin showed that monensin produced a 50-60% decrease in surface binding, accompanied by a similar decrease in internalization and total inhibition of insulin degradation. When hepatocytes with 125I-insulin prebound to their surface receptors at 10 degrees C were warmed to 37 degrees C, monensin had no effect on internalization, but caused marked impairment of intracellular insulin degradation. It is concluded that monensin inhibits receptor recycling and cellular insulin degradation.
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The mechanisms of insulin insensitivity in diabetes are poorly understood. We have therefore assessed the relationship between glucose disposal during a euglycaemic clamp, muscle glycogen formation, and the activities of insulin regulated enzymes within skeletal muscle in five Type 1 (insulin-dependent) diabetic patients, both on conventional injection therapy (HbA1 11.0 +/- 1.0 (SD) %) and after 6 weeks continuous subcutaneous insulin infusion (HbA1 7.6 +/- 1.4%, p less than 0.01). On both regimens, overnight euglycaemia before the clamp was maintained with an intravenous insulin infusion. The increase in clamp glucose requirements (insulin 0.1 U X kg-1 X h-1) between injection therapy and continuous subcutaneous insulin infusion was significant (6.2 +/- 0.9 (SE) to 7.0 +/- 0.9 mg X kg-1 X min-1, p less than 0.05), but small compared to differences between subjects. Glucose requirement remained lower than in control subjects (10.4 +/- 0.7 mg X kg-1 X min-1, p less than 0.05). The increase in muscle glycogen with the clamp was slightly higher on continuous subcutaneous insulin infusion (9.5 +/- 2.5 mg/g protein) than on injection therapy (8.5 +/- 2.4 mg/g, p less than 0.05), but less than in control subjects (17.9 +/- 2.1 mg/g, p less than 0.05). The expressed activity of glycogen synthase and pyruvate dehydrogenase increased significantly between fasting and the end of the clamps in the patients (p less than 0.001 and less than 0.005), but was not significantly different between the two treatment regimens. Expressed glycogen synthase activity at the end of the clamp was lower on both treatments than in control subjects (p less than 0.05). Both enzyme activities were, however, highly correlated with glucose requirement between patients, (r = 0.89-0.94, p less than 0.05-0.02), and glycogen synthase was similarly correlated in the control subjects (r = 0.84, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In order to investigate the cellular mechanisms of the insulin resistance displayed by subjects with chronic renal failure, adipocyte insulin receptor status and in vitro insulin sensitivity were studied. Adipocytes from uremic subjects displayed normal maximum specific insulin binding (2.55 +/- 0.23 v 2.57 +/- 0.09% per 10 cm2 cell membrane, although half-maximum binding was observed at 91 +/- 8 (uremic) and 139 +/- 11 (control) pmol/L (P less than 0.005). In six subjects restudied after three months of continuous ambulatory peritoneal dialysis, maximum specific insulin binding fell as a consequence of changes in both receptor affinity and number (2.87 +/- 0.20 v 2.05 +/- 0.17% per 10 cm2 cell membrane, P less than 0.01). Basal and maximal rates of lipogenesis were similar in the uremic and control groups, and half-maximal stimulation occurred at 13.5 +/- 4.4 and 21.4 +/- 3.0 pmol/L, respectively (NS). During continuous ambulatory peritoneal dialysis, adipocyte insulin sensitivity did not change significantly as assessed by stimulation of lipogenesis or glucose uptake (half-maximal stimulation at 12.0 +/- 4.0 v 26.4 +/- 11.0 and 23.1 +/- 7.1 v 29.0 +/- 7.5 pmol/L, before and during dialysis, respectively). These data suggest either that adipose tissue and muscle display differential insulin sensitivities in chronic renal failure or that other factors such as circulating inhibitors of insulin action are not detected by in vitro assays.
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Glucose turnover and recycling from glucose derived 3-carbon intermediates were examined in overnight fasted patients with compensated hepatic cirrhosis and in age- and weight-matched normal control subjects. Fasting blood concentrations of glucose, lactate and glycerol were similar in both groups but blood pyruvate (60 +/- 10 vs. 80 +/- mumol/l, P less than 0.05), blood alanine (0.23 +/- 0.02 vs 0.34 +/- 0.02 mmol/l, P less than 0.01) were decreased and serum insulin increased (19 [13-24]v 7 [4-11] mU/l, P less than 0.01) in cirrhotic subjects. Absolute glucose turnover, assessed by analysis of decay of [3H]-3-glucose specific activity was decreased in cirrhotic patients (8.1 +/- 0.6 v 12.1 +/- 0.7 mol/kg-1 min-1). Glucose "recycling", assessed by the difference between absolute glucose turnover and that given by [14C]-1-glucose data, was normal in cirrhotic patients suggesting that Cori cycle (glucose-lactate-glucose) activity was normal. These data support previous findings of decreased peripheral glucose utilisation and insulin resistance in cirrhotic patients.
Tuberculoproteins A and C obtained from culture filtrate of Mycobacterium tuberculosis by alcohol fractionation were utilized in an enzyme-linked immunosorbent assay to measure the amount of reactive IgG in the sera from advanced and moderately advanced tuberculosis patients, leprosy patients and normal individuals. The A-protein detected significant levels of IgG in the sera from both advanced and moderately-advanced tuberculosis patients and patients with leprosy as compared to the normal group. Employing the C-protein, only sera from the advanced tuberculosis patients group gave significantly positive results when compared with the normal control group. The data show that the A-protein is more potent than the C-protein and has a potential serodiagnostic value.