Search PubMed⌕ Search

Biomedical subjects

R L Jackson

Publications and source records attributed to R L Jackson.

287 records · Page 16Linked to original sources
PubMedDate not supplied

Substitution of Ser61----Gly61 in human apolipoprotein C-II does not alter its activation of lipoprotein lipase.

Lipoprotein lipase (LpL) activity is enhanced by apolipoprotein C-II (apoC-II), a 79 amino acid residue peptide. The minimal apoC-II sequence required for activation of LpL resides between residues 56-79. To determine the possible role of an acyl-apoC-II intermediate involving Ser61 in enzyme catalysis, a synthetic peptide of apoC-II containing residues 56-79 was synthesized and compared to the corresponding peptide with serine at position 61 being substituted with glycine. With two different LpL assay systems, both peptides enhanced enzyme activity. Since glycine does not contain a hydroxyl group, these results rule out the possibility that an acyl-apoC-II intermediate with Ser61 is required for enzyme activation.

Amino Acids↗
PubMedDate not supplied

Attenuation of atherosclerosis in a modified strain of hypercholesterolemic Watanabe rabbits with use of a probucol analogue (MDL 29,311) that does not lower serum cholesterol.

Probucol is a drug that lowers plasma cholesterol in both humans and animals. In low density lipoprotein (LDL) receptor-deficient Watanabe rabbits, probucol reduces the progression of atherosclerosis. This effect may be attributed to the antioxidant and/or the cholesterol-lowering properties of the drug. In the present report we studied the antiatherogenic effect of a probucol analogue (MDL 29,311) that possesses antioxidant activity but that does not lower cholesterol. Modified Watanabe rabbits (11-12 weeks of age) produced by crossing British Brown and Japanese Watanabe rabbits were fed normal chow (n = 8), chow containing 1% probucol (n = 9), or chow containing 0.1% (n = 9), 0.5% (n = 8), or 1% (n = 6) probucol analogue. After 70 days serum cholesterol levels and the percent area of sudanophilic lesions in the thoracic region of aortas were determined. Total serum cholesterol was significantly lowered (p less than 0.05) in the probucol group (560 +/- 54 mg/dl) compared with that of controls receiving no drug (731 +/- 67 mg/dl) but was not lowered in the analogue groups (722-802 mg/dl). The lesioned area (mean% +/- SEM) in the probucol group (16 +/- 3) was significantly lower (p less than 0.01) than in the controls (52 +/- 8). There were 43 +/- 7%, 33 +/- 8%, and 35 +/- 5% of lesions for the 0.1%, 0.5%, and 1% analogue groups, respectively. After combining the data for the 0.5% and 1% analogue groups, the value (34%) was lower than that of the controls and almost reached significance (p = 0.066). The mean serum drug concentration in the 1% probucol group was 58 +/- 4 micrograms/ml compared with 13 +/- 2, 44 +/- 8, and 74 +/- 8 micrograms/ml for the 0.1%, 0.5%, and 1% analogue groups, respectively. Thus, the decreased effectiveness of the probucol analogue in preventing atherosclerosis could not be explained by a lack of bioavailability. LDLs isolated from rabbits treated with the drug were resistant to Cu(2+)-induced lipid peroxidation, as determined by thiobarbituric acid-reactive substances. The resistance within the analogue groups was dependent on the number of antioxidant molecules per LDL particle. However, there was no significant difference in atherosclerotic lesions between these two groups, suggesting, although not definitively, that the maximal antiatherogenic effect had been reached. Our data suggest that the antioxidant activity of this class of compounds may play an important role in reducing atherosclerosis, but not in reducing cholesterol levels, and that hypocholesterolemic and possibly other activities of probucol might further enhance its antiatherogenic activity.

Animals↗
PubMedDate not supplied

Growth and maturation of children with insulin-dependent diabetes mellitus.

The purpose of this paper is to define criteria used for classifying patients into varying degrees of diabetic control and to verify that children with diabetes maintained in higher degrees of metabolic control do not have delayed growth and maturation. Growth records of 252 children with insulin-dependent diabetes who have been under continuous observation in our clinic at three- to five-month intervals for at least three years and up to 16 years have been individually reviewed and analyzed. All children received two daily injections of a mixture of two parts of an intermediate to one part of regular insulin and were instructed to eat structured meals of high-quality selected foods. An over-all rating for diabetic control based primarily on the frequency and degree of glycosuria was made for the time period between clinic visits. The over-all diabetic control rating and the size of the subgroups were "good"--20 per cent, "fair to good"--64 per cent, and "fair"--16 per cent. All children maintained in "good" and "fair to good" control (84 per cent), grew and matured at a normal rate regardless of the age at onset or duration of diabetes. All children in lower degrees of control coming under care for greater than 24 months after diagnosis had accelerated growth during the early months after attaining a higher degree of control.

Adolescent↗
PubMedDate not supplied

Changes in basement membrane thickening and pulse volume concomitant with improved glucose control and exercise in patients with insulin-dependent diabetes mellitus.

Ten patients with type I diabetes mellitus were enrolled in a program of exercise and carbohydrate "control" using self-monitored glucose determinations and self-adjusted insulin. Glucose control was improved for the group, although normoglycemia was not uniformly achieved. Pulse volume measurements performed at the onset and after 8-10 mo documented a drop in systolic arm blood pressure with increases in the ankle-arm index (P < 0.001). Quadriceps biopsy was successfully performed at the beginning and after 8-10 mo for analysis of basement membrane thickening (BMT) in seven patients. Six patients showed a decrease in basement thickening on rebiopsy (P = 0.02). One patient showed increased BMT. This was the only patient to maintain a mean hemoglobin A1c of greater than 10% for the duration of the study. These observations indicate that abnormalities of BMT and pulse volume recordings may be more labile measurements than previously thought and may be amenable to therapeutic intervention. The relationship of these variables to the severe micro- and macrovascular sequelae of diabetes mellitus remains to be established.

Adolescent↗
PubMedDate not supplied

Clinical pharmacologic studies with human insulin (recombinant DNA).

Normal fasting subjects were used to study the pharmacokinetics of human insulin (recombinant DNA). Purified pork insulin (PPI) was used as a control agent. There was no difference in serum concentrations between neutral regular human insulin and PPI after intravenous administration. When given subcutaneously, peak concentrations are occasionally higher for human insulin than for PPI. The bioavailability indices for the two insulins are essentially the same. NPH human insulin produced a slightly higher serum concentration after 4 h than did NPH PPI. Studies with 70/30 NPH-regular mixtures suggest that the affinity of protamine for human insulin is less than that for PPI. The serum insulin concentrations after lente human insulin and PPI were not different. These studies, and a review of the published clinical pharmacologic literature, indicate that when present the differences between human insulin and PPI are minimal.

Animals↗