Characterization of three new apparently related high frequency antigens

1. To study the relative contributions of luminal nutrition, bile and pancreatic secretions and hormonal factors in intestinal adaptation, lactation hyperphagia was chosen as a model for increased luminal nutrition, either alone (intestinal transection control group) or in combination with (i) exclusion of bile and pancreatic secretions from the jejunum (by transposition of the jejunum above the Ampulla of Vater) or (ii) exclusion of bile, pancreatic secretions and exogenous luminal nutrition from the jejunum (proximal Thiry-Vella by-pass group). 2. The results confirm that in lactation there is mucosal hyperplasia with increases in villus height and crypt depth, and in small-bowel wet and defatted dry-tissue weights per unit length of intestine. 3. There are corresponding changes in absorptive function with increased glucose and water absorption per unit length of intestine. 4. These structural and functional adaptive changes are proportionately greater in ileum than in jejunum. 5. The exclusion of exogenous luminal nutrition, bile and pancreatic secretions from the jejunum did not diminish the degree of intestinal mucosal hyperplasia and functional adaptation seen in lactation. 6. Diversion to the ileum of greater than normal amounts of bile, pancreatic secretions and luminal nutrition did not further increase the degree of mucosal hyperplasia and enhanced absorption seen in the lactating intestinal transection control group. 7. Unlike other models of intestinal adaptation, the changes in small-bowel mucosal structure and function seen in lactation are probably due to hormonal factors.     

Muscle fiber composition and blood ammonia levels after intense exercise in humans

The relationship between fiber type composition and the increase in blood ammonia was examined following a maximal O2 consumption (VO2max) test. Muscle biopsies were taken from the middle portion of the vastus lateralis for determination of fiber type percentages. Two subject groups were selected on the basis of a high (HST) or low (LST) percentage of slow-twitch fibers and compared for blood ammonia and lactate levels after exercise at work loads of approximately 85 and 110% of VO2max. An inverse relationship was found between the percentage of slow-twitch fibers and the increase in blood ammonia. Blood ammonia increased after exercise at both 85 and 110% of VO2max. However, the increase was twofold greater for the LST group following the 110% work effort. The increases in blood ammonia and lactate were positively correlated for both groups following exercise. The results suggest that the proportion of slow-twitch fibers plays an important role in determining the magnitude of the increase in blood ammonia after intense exercise.     

Correction of increased prostacyclin synthesis in Bartter's syndrome by indomethacin treatment

The role of prostacyclin and thromboxane A2 in the pathogenesis of Bartter's syndrome was investigated by measurement of the urinary excretion of 6-keto-PGF1 alpha and thromboxane B2, respectively, in five patients. The prostaglandin metabolites were extracted from urine by a reproducible method and measured by specific radioimmunoassays. The patients with Bartter's syndrome excreted about four-times as much 6-keto-PGF1 alpha as the normal controls. In contrast, there was no significant difference in the urinary excretion of thromboxane B2 between the patients and the controls. In a second part of the study, three patients were treated with indomethacin (150 mg/day for four days), an inhibitor of prostaglandin synthesis. This regimen suppressed urinary excretion of 6-keto-PGF1 alpha by 43% and that of thromboxane B2 by 46%. It is suggested that the increase in prostacyclin production is responsible for both the hyperreninemia and and the other endocrine derangements as well as the hyporesponsiveness of blood pressure to intravenous infusion of vasopressors in patients with Bartter's syndrome.     

The effect of the cyclin-dependent kinase inhibitor olomoucine on cell cycle kinetics

The effect of the cyclin-dependent (CDK) inhibitors olomoucine and roscovitine on cell kinetics was studied. To this end, nonsmall cell lung cancer (NSCLC) cell line MR65 and neuroblastoma cell line CHP-212 were pulse labeled with bromodeoxyuridine (BrdUrd) and chased in culture medium, to which various concentrations of olomoucine or roscovitine were added. A dose-dependent inhibition of the G1/S-phase and G2/ M-/G1 transitions was observed. Furthermore, S-phase progression was also inhibited in a dose-dependent manner. Similarly, roscovitine, another CDK inhibitor with a 10-fold higher efficiency for both CDK1 and CDK2 as compared to olomoucine, showed the same effects at a 10-fold lower concentration. At the highest tested doses both olomoucine (200 microM) and roscovitine (40 microM) induced a complete cell cycle block in both cell lines, paralleled by the appearance of apoptotic figures. In these cultures a decrease in CDK1 protein level was found as shown by Western blotting. Bivariate CDK1/DNA analysis confirmed these observations and showed that a subpopulation of cells with characteristics of apoptosis became CDK1 negative. The presented data suggest that cyclins and CDKs are involved at an important nodal point shared by pathways regulating cellular proliferation and apoptosis.