Comparison of the effects of several potassium-channel openers on rat bladder and rat portal vein in vitro.

1. The ability of several K-channel openers to inhibit KCl-induced contractions of rat bladder detrusor and spontaneous mechanical activity in rat portal vein was examined. 2. Lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 dose-dependently relaxed rat detrusor, precontracted with 20 mM KCl. With the exception of pinacidil, concentrations of these agents below 30 microM did not inhibit 80 mM KCl-included contractions. Pinacidil (10 microM) produced a small, but significant (P < 0.05) relaxation of 80 mM KCl-induced mechanical activity. Minoxidil sulphate and BRL 38226 produced some relaxation of 20 mM but not 80 mM KCl-induced contractions. 3. Glibenclamide (0.3-3 microM) antagonized the relaxant effects of lemakalim, pinacidil, Ro 31-6930, RP 49356, P1060 and S 0121 in a competitive manner (pA2 values 6.3-6.6). The effects of minoxidil sulphate and BRL 38226 were fully antagonized by 3 microM glibenclamide. 4. Lemakalim, pinacidil, S 0121, BRL 38226 and minoxidil sulphate were each approximately 8 times more potent as inhibitors of the spontaneous contractions of rat portal vein than KCl-induced contractions of the rat detrusor. Minoxidil sulphate was approximately 30 times more potent in the rat portal vein than in the bladder. This may indicate that either minoxidil sulphate is acting at different recognition sites in these two tissues, or that this compound has an additional mechanism of action in the portal vein. 5. With the exception of minoxidil sulphate, all the compounds tested stimulated 86Rb efflux and 42K efflux from preloaded rat detrusor strips.(ABSTRACT TRUNCATED AT 250 WORDS)     

Allelic frequency of a p53 polymorphism in human lung cancer.

p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies.     

Host factors in lung cancer risk: a review of interdisciplinary studies.

Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk.     

Factor VIII complex in uraemia and effects of haemodialysis

Levels of the factor VIII complex were found to be raised in patients with chronic renal failure and further raised by regular dialysis. Increased fibrinogen concentrations were also found. These results suggest the existence of a prothrombotic state in uraemia that is exacerbated by haemodialysis. Ristocetin-induced platelet agglutination, however, was depressed in uraemia and worsened by dialysis. This defect may be transferred to normal platelets from dialysed uraemic plasma, suggesting the existence of an inhibitor of the interaction between factor VIII and platelet glycoprotein. These results may help to explain the anomaly of a prolonged bleeding time together with accelerated atherogenesis that is found in patients with uraemia receiving dialysis.     

Physical Activity of Asthmatic and Nonasthmatic Children

Questionnaires examining behaviors and attitudes related to physical activity and asthma were administered to 408 urban schoolchildren aged 11-13 years. Asthmatics (16% of the sample) were more frequently active and were more anxious prior to exercise than nonasthmatics, but did not differ significantly from nonasthmatics in enjoyment of exercise or in physical self-concept. The motives for performing exercise or sport were similar in the two groups, although the asthmatics perceived less pressure to be active from parents or school than the nonasthmatics. It is concluded that asthmatic children have favorable behaviors and attitudes in relation to exercise and sport.     

Increased incidence of thyroid disease among men with hypergonadotropic hypogonadism

An association between hypothyroidism and hypogonadism has been described in the syndrome of autoimmune polyglandular failure and in Klinefelter's syndrome. The incidence of thyroid disease among males with hypogonadism was evaluated. Patients were divided into those with hypergonadotropic hypogonadism (Group I; N = 19) and those with isolated hypogonadotropic hypogonadism (Group II; N = 17), according to their serum concentrations of follicle-stimulating hormone, luteinizing hormone, and testosterone. Nine cases of thyroid diseases were encountered in Group I; these included benign and malignant thyroid tumors, hypothyroidism due to Hashimoto's thyroiditis, and hypothyroidism due to amiodarone therapy. Only one case of thyroid disease (hypothyroidism due to Hashimoto's thyroiditis) was found in Group II (p <0.01). Patients of Group I were also significantly older than patients of Group II (51 ± 4 versus 37 ± 4 years; p <0.01); and patients with thyroid diseases were also older than those without thyroid disorders (60 ± 6 versus 43 ± 6 years, p <0.1). It is concluded that older subjects with hypogonadism and long-term elevation of levels of serum gonadotropins should undergo careful evaluation of thyroid gland morphology and function.