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Biomedical subjects

R Movva

Publications and source records attributed to R Movva.

5 recordsLinked to original sources

Comparison of once daily doses of lansoprazole (15, 30, and 60 mg) and placebo in patients with gastric ulcer.

OBJECTIVES: A multicenter, double-blind study was conducted in 268 patients to compare the safety and efficacy of 15, 30, and 60 mg of lansoprazole and placebo in the treatment of gastric ulcer. METHODS: The study included an 8-wk treatment period to assess healing and a 6-month posttreatment period to evaluate ulcer recurrence. Endoscopies were performed, GI symptoms and antacid use were assessed, and safety evaluations were conducted, including serum gastrin and biopsies of the lesions and the greater curvature of the stomach. RESULTS: At week 4, healing rates were significantly higher with lansoprazole 15 and 30 mg (64.6 and 58.1%, respectively) compared with placebo (37.5%). By week 8, healing rates were 76.7% with placebo, 92.2% with 15 mg of lansoprazole, 96.8% with 30 mg, and 93.2% with 60 mg of lansoprazole (p < 0.05). The drug was well tolerated, with no significant differences from placebo in the incidence of adverse events. Fasting serum gastrin increased in all lansoprazole groups, reaching a plateau by week 2 and returning to baseline levels by month 1 posttreatment. No significant increase in Grimelius-positive cells or inflammation was evident. All but two patients had normal gastric morphology evaluated by Solcia classification. CONCLUSIONS: Lansoprazole, 15, 30, and 60 mg, administered once daily before eating, healed gastric ulcers to an approximately equal degree, and all were significantly better than placebo.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Intracellular transport of GPI-anchored proteins by yeast.

We have investigated the effects of an inhibitor of ceramide biosynthesis on the glycosylphosphatidylinositol (GPI)-anchoring and intracellular transport of the yeast Gas1 protein. No effect on anchor attachment was demonstrable, but a selective delay in transport from the endoplasmic reticulum to the Golgi complex was observed. The compound also blocked remodeling of GPI-anchors from their base-sensitive to base-resistant forms. A recessive mutation was found that caused resistance to the drug, restored transport of Gas1p, but did not restore ceramide biosynthesis in the presence of the inhibitor. Our results suggest that intracellular transport of GPI-anchored proteins is stimulated by new ceramide synthesis. The role of ceramide may be direct or may be through its use in the remodeling of GPI-anchored proteins other than Gas1p. The need for ceramide can be overcome in the mutant strain.

Ceramides↗

Cyclosporins. Structure-activity relationships.

Cyclosporin A (Sandimmun) achieves immunosuppressive activity by complex formation with cyclophilin and subsequent binding of the binary complex to and inhibiting protein phosphatase 2B (calcineurin). Complexes of nonimmunosuppressive cyclophilin binding cyclosporin analogues do not inhibit protein phosphatase 2B, suggesting a crucial role for this enzyme in T cell activation. Binding of cyclosporin A to cyclophilins A, B, and C, respectively, results in complexes of significantly different inhibitory potency. The cyclosporin molecule thus has two functional domains, one mediating cyclophilin binding and a second one endowing affinity of the complex to calcineurin, thereby inhibiting its enzyme activity. Structure-activity studies and x-ray crystallography of cyclosporin-cyclophilin complexes indicate a crucial role of leucine side chains in positions 4 and 6 of the cyclosporin macrocycle for the calcineurin interaction.

Amino Acid Sequence↗

Increased expression in Escherichia coli of a synthetic gene encoding human somatomedin C after gene duplication and fusion.

A synthetic gene coding for human somatomedin C (SMC) was inserted into an Escherichia coli plasmid vector that contains the bacteriophage lambda pL promoter. Intracellular accumulation of the gene product after induction of the promoter was found to be low. A 200-fold greater yield was obtained with a similar plasmid containing two translationally fused copies of the SMC gene. A series of such tandem genes truncated at their 3' ends were generated with nuclease Bal 31. These gave intermediate expression levels that correlated with the expected sizes of their gene products. Comparison of RNAs extracted from cells containing either the monomer or tandem SMC gene constructions showed that there was no significant difference in expression at the transcriptional level. Pulse-chase experiments demonstrated that the tandem SMC protein was far more stable than the monomer SMC product.

Amino Acid Sequence↗