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Biomedical subjects

C A Stuart

Publications and source records attributed to C A Stuart.

93 records · Page 6Linked to original sources

Specific receptors and growth effects of insulin and insulin-like growth factors in a human cell line derived from mixed mesodermal tumor of the uterus.

OBJECTIVE: Mixed mesodermal tumors of the uterus are highly malignant. The purpose of our present study was to investigate possible roles of insulin and insulin-like growth factors I and II (IGF-I and IGF-II) in the growth and development of these tumors. METHODS: Specific binding and growth effects of insulin, IGF-I, and IGF-II were studied in SK-UT-1 cells, derived from a human mixed mesodermal tumor of the uterus. The receptors were further characterized by competitive binding and chemical cross-linking studies. RESULTS: Binding studies with 125I-insulin, 125I-IGF-I, and 125I-IGF-II revealed the presence of specific binding sites for these three growth factors. Specificity studies revealed that the binding sites for IGF-I and IGF-II are distinct. Binding of IGF-II was much higher than insulin and IGF-I binding. Scatchard analysis of the binding data revealed that the cell line has a higher number of IGF-II receptor (100,000 sites per cell) than insulin (1400 sites per cell) and IGF-1 (1200 sites per cell) receptors. The effect of these growth factors on cell growth was studied by monitoring the cell number and incorporation of [3H] thymidine into the DNA of the cells. Insulin-like growth factor-II was potent in stimulating the growth of these cells, but IGF-I did not have any effect. Insulin stimulated DNA synthesis only at pharmacologic concentrations. CONCLUSION: These results indicate that IGF-II is mitogenic to mixed mesodermal tumors of the uterus. Insulin-like growth factor II may be involved in the growth regulation of mixed mesodermal tumors of the uterus.

Binding, Competitive↗

Oral branched-chain amino acids decrease whole-body proteolysis.

BACKGROUND: This study reports the effects of ingesting branched-chain amino acids (leucine, valine, and isoleucine) on protein metabolism in four men. METHODS: To calculate leg protein synthesis and breakdown, we used a new model that utilized the infusion of L-[ring-13C6]phenylalanine and the sampling of the leg arterial-venous difference and muscle biopsies. In addition, protein-bound enrichments provided for the direct calculation of muscle fractional synthetic rate. Four control subjects ingested an equivalent amount of essential amino acids (threonine, methionine, and histidine) to discern the effects of branched-chain amino acid nitrogen vs the effects of essential amino acid nitrogen. Each drink also included 50 g of carbohydrate. RESULTS: Consumption of the branched-chain and the essential amino acid solutions produced significant threefold and fourfold elevations in their respective arterial concentrations. Protein synthesis and breakdown were unaffected by branched-chain amino acids, but they increased by 43% (p < .05) and 36% (p < .03), respectively, in the group consuming the essential amino acids. However, net leg balance of phenylalanine was unchanged by either drink. Direct measurement of protein synthesis by tracer incorporation into muscle protein (fractional synthetic rate) revealed no changes within or between drinks. Whole-body phenylalanine flux was significantly suppressed by each solution but to a greater extent by the branched-chain amino acids (15% and 20%, respectively) (p < .001). CONCLUSIONS: These results suggest that branched-chain amino acid ingestion suppresses whole-body proteolysis in tissues other than skeletal muscle in normal men.

Adult↗

Effect of adding a sulfonylurea in patients with non-insulin-dependent diabetes mellitus previously well controlled with insulin.

OBJECTIVE: To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment. METHODS: Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide). RESULTS: The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension. CONCLUSION: In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.

Clinical Trial↗