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Biomedical subjects

R F Mahler

Publications and source records attributed to R F Mahler.

7 recordsLinked to original sources

Diabetes is associated with a high incidence of endothelial-binding antibodies which do not correlate with retinopathy, von Willebrand factor, angiotensin-converting enzyme or C-reactive protein.

Increasing evidence implicates endothelial cell dysfunction in the development of diabetic microvascular disease, but its precise nature is elusive. This study sought to extend previous observations on the association between diabetes and the endothelial cell-derived glycoprotein von Willebrand factor (vWF), in a study of 777 diabetic patients. Compared with a mean of 1.07 +/- 0.18 iu/ml in a non-diabetic population, vWF was found to be elevated to 1.59 +/- 0.14 iu/ml in the whole sample, but particularly in those with retinopathy or microalbuminuria. It was studied whether such an elevation is part of an acute phase response, or is accompanied by other indicators of endothelial cell dysfunction. Plasma samples were examined for vWF, and serum for angiotensin converting enzyme (ACE), C-Reactive protein (CRP), IgG and IgM endothelial cell-binding antibodies (anti-EC Ig). A strong positive association was found (p less than 0.005) between the extent of elevation of vWF and the presence of diabetic retinopathy. ACE and CRP were rarely raised, and their levels did not correlate with either diabetic retinopathy or vWF levels. However, 52% of the patients had circulating anti-EC IgG or IgM, although their presence did not correlate with retinopathy, or with vWF, ACE or CRP. Thus diabetic retinopathy and probably nephropathy is associated with a specific but generalised disturbance of vascular endothelial cell function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improvement in insulin secretion in diabetes after diazoxide.

Diazoxide 5 mg/kg/day was administered to four normal subjects for five days and, together with insulin, to ten diabetic subjects for seven days. In every case there was a substantial increase in the insulin response to combined stimulation of the pancreatic beta cells with 1 mg of glucagon and 2 g of tolbutamide given intravenously. Similar increases were not seen in four diabetics who received placebo with insulin. It is likely that the observed improvements reflected increased insulin stores which resulted from diazoxide inhibition of insulin release. These findings suggest that poor insulin responses in diabetics may be due, at least in part, to chronic overstimulation of the beta cells. Pharmacological agents such as diazoxide, which inhibit glucose-induced insulin release, may have a place in preserving and restoring insulin secretion in diabetes.

Administration, Oral

Effect of phenylalanine and its metabolites on the metabolism of leucocytes and lymphocytes.

1. The pathogenesis of the mental retardation in phenylketonuria remains obscure. Leucocytes have proved of value in the study of other inborn errors of metabolism. The lymphocyte is a suitable model cell for the study of mammalian metabolism, because of its ability to divide in vitro in response to various stimuli. 2. We have examined the effects of phenylalanine, phenylpyruvate, phenyl-lactate and phenylacetate on the human leucocyte and the resting and phytohaemagglutinin-stimulated rabbit lymphocyte. 3. Phenylpyruvate and phenyl-lactate reduced acetate incorporation into leucocyte lipid by 38% and 48% respectively. Only phenyl-lactate reduced acetate incorporation into the resting and stimulated lymphocyte, by 20% and 34% respectively. 4. Glucose incorporation into leucocyte lipid was unaffected by phenylalanine, phenylpyruvate and phenyl-lactate. Only phenyl-lactate inhibited (46%) the production of CO2 from glucose. 5. Phenylalanine and leucine incorporation into trichloroacetic acid-insoluble material of resting and stimulated lymphocytes was inhibited by phenyl-lactate (10-42%), phenylpyruvate (27-57%) and phenylacetate (19-39%). 6. Uridine incorporation into resting and stimulated cells was inhibited by phenyl-lactate (22-26%), phenylpyruvate (42-52%) and phenylacetate (20%). 7. Thymidine incorporation into resting lymphocytes was reduced by phenyl-lactate, phenylpyruvate, phenylacetate and phenylalanine by 12-26%. Incorporation into the stimulated cell was inhibited by phenylpyruvate and phenyl-lactate (90%) and phenylacetate (66%). 8. Phenylalanine inhibited lymphocyte pyruvate kinase and phenylpyruvate inhibited citrate synthetase. 9. These results are compared with published data relating to experimental hyperphenylalaninaemia and the effects of these metabolites on nervous tissue in vitro.

Acetates

Diabetic complications in a patient with coexisting anterior hypopituitarism.

We present a patient who developed insulin-requiring diabetes several years after the onset of symptoms of anterior hypopituitarism. It is likely that the hypopituitarism protected him against the development of diabetic retinopathy and glomerular basement membrane thickening but not against neuropathy and atheroma. The significance of this in relation to the growth-hormone-microangiopathy hypothesis is discussed.

Aged