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Biomedical subjects

U J Lewis

Publications and source records attributed to U J Lewis.

At least 55 records · Page 3Linked to original sources

Multiple forms of growth hormone: detection in medium from cultured pituitary adenoma explants.

Three pituitary adenomas obtained from patients wtih acromegaly were maintained in organ explant culture for a period of 12 days in a defined culture medium. Lyophilized culture medium from each was then examined by electrophoresis to determine which forms of growth hormone were secreted by the explants. All three explants secreted principally the major form of growth hormone. One adenoma however secreted unusually large amounts of two slowly migrating forms which were in low concentration in the GH-containing granules of normal pituitaries. On the other hand the adenoma produced a much lower amount of a 20,000-dalton variant than was seen in normal pituitary glands. The other two adenomas did not secrete the relatively large amounts of the slowly migrating forms although the quantity of the 20,000-dalton form was less than the amount seen in the normal pituitary. There was no evidence of proteolytic alteration of the growth hormone during the culturing process. In companion experiments with rat pituitary glands the growth hormone did not undergo proteolytic degradation in the gland left in situ for 96 h at 5 degrees C.

Adenoma↗

Hyperglycemic activity of the 20,000-dalton variant of human growth hormone.

The 20,000-dalton structural variant of human growth hormone was inactive as a hyperglycemic agent in dogs when injected 10 h prior to a glucose tolerance test. Limited digestion with subtilisin did not generate hyperglycemic activity. These results are in contrast to those obtained with human growth hormone where subtilisin treatment potentiated the weak hyperglycemic activity of the undigested hormone. The results suggest that the 15 amino acid sequence that is deleted from the variant is either directly responsible for hyperglycemic activity or that a modification in tertiary structure produced by the deletion prevents a necessary proteolytic processing.

Animals↗

Effect of calcium, insulin and growth hormone on membrane fluidity. A spin label study of rat adipocyte and human erythrocyte ghosts.

ESR spectra were recorded from rat epididymal adipocyte ghosts labeled with the 5-nitroxide stearic acid spin probe, I(12,3). Polarity-corrected and approximate order parameters, that are sensitive to the flexibility of the incorporated label, were used to evaluate the membrane lipid fluidity. Addition of CaCl2 a 37 degrees C decreased the fluidity, as indicated by positive increases in the order parameters. The ordering effect of Ca2+ was concentration-dependent, reached saturation at approx. 3--4 mM, and was completely reversed by excess EGTA. Previous studies indicated that low- and high-affinity sites on adipocyte plasma membranes are able to bind 45Ca2+, and our results suggest that Ca2+-induced alterations in the lipid fluidity involve cation binding to low-affinity sites. The cellular movements of Ca2+ and, in particular, the binding of Ca2+ to the plasma membrane may play important roles in insulin's action on fat cell function. The possibility that insulin directly alters the membrane fluidity was tested by adding hormone to freshly-prepared I(12,3)-labeled adipocyte ghosts. Insulin, at concentrations (10(-6) M) that enhance glucose uptake into intact adipocytes, did not affect the fluidity of ghosts suspended in buffers with or without Ca2+. The fluidities of I(12,3)-labeled rat adipocyte ghosts or human erythrocyte ghosts were also unaffected by various forms of human growth hormone.

Adipose Tissue↗

Comparative potency of subtilisin-cleaved and intact human growth hormone measured in growth hormone-deficient human subjects.

Eight GH-deficient subjects received both subtilisin-cleaved human GH (hGH-S) and intact hGH (hGH-I) during short term balance studies to compare the potency of these two forms of GH. Both forms caused nitrogen retention, calciuria, postassium retention, and elevation of blood glucose. The effects on plasma insulin concentrations were inconstant at the doses used. hGH-S was more potent than hGH-I, as measured by nitrogen and potassium retention, and the differences reached levels of statistical significance. hGH-S also caused greater calciuria and increases in fasting the postprandial blood glucose and in postprandial insulin in absolute terms, but these differences did not reach levels of statistical significance. In no instance was hGH-I significantly more potent than hGH-S. We conclude hGH-S, a two-chain form of hGH, caused significantly greater nitrogen and potassium retention in human subjects in short term balance studies than hGH-I.

Blood Glucose↗

Insulin secretion from pancreatic islets: effect of growth hormone and related proteins.

Insulin responses to clinical grade human growth hormone (hGH), intact hGH, naturally occurring diabetogenic substance (NDS), and subtilisin cleaved forms of hGH (S1 and S3) were studied using hypophysectomized rat pancreatic islets. While clinical grade hGH (200 microgram/ml) elicited a prompt and sustained release of insulin, purified intact hGH (200 microgram/ml) did not. Naturally occurring diabetogenic substance, isolated from clinical grade hGH preparations, stimulated insulin release at 200 ng/ml. Upon repeat stimulation with NDS, a significantly greater insulin release than with initial stimulation was observed. Although S3 (200 microgram/ml) elicited significant insulin release, S1 (200 microgram/ml) did not. Direct stimulation of insulin release with clinical grade hGH is not due to intact hGH but another proteins(s) such as NDS. Enzymic modification of intact hGH appears to enhance insulin stimulatory capacity.

Animals↗