Activating mutations for the met tyrosine kinase receptor in human cancer

Recently, mutations in the Met tyrosine kinase receptor have been identified in both hereditary and sporadic forms of papillary renal carcinoma. We have introduced the corresponding mutations into the met cDNA and examined the effect of each mutation in biochemical and biological assays. We find that the Met mutants exhibit increased levels of tyrosine phosphorylation and enhanced kinase activity toward an exogenous substrate when compared with wild-type Met. Moreover, NIH 3T3 cells expressing mutant Met molecules form foci in vitro and are tumorigenic in nude mice. Enzymatic and biological differences were evident among the various mutants examined, and the somatic mutations were generally more active than those of germ-line origin. A strong correlation between the enzymatic and biological activity of the mutants was observed, indicating that tumorigenesis by Met is quantitatively related to its level of activation. These results demonstrate that the Met mutants originally identified in human papillary renal carcinoma are oncogenic and thus are likely to play a determinant role in this disease, and these results raise the possibility that activating Met mutations also may contribute to other human malignancies.     

Thermosiphon circulation in solar water heaters incorporating evacuated tubular collectors and a novel water-in-glass manifold

A study is reported of thermosiphon circulation in solar water heaters incorporating glass tubular evacuated collectors and a water-in-glass manifold of extremely simple design. The manifold is characterised by the absence of partitioning of the inner volumes of the absorber tubes into inlet/outlet channels and buoyancy effects are utilised to convey heat to a header pipe at the open end of the tubes. Solar energy input to the tubes has been simulated by electric heating. The thermosiphon system design is unusual in that there are no risers within the collector tubes, thus, the pressure head responsible for thermosiphon flow originates entirely from relatively short pipe runs between manifold and storage tank. Thermosiphon flow has been measured for a number of system designs and a wide range of operating conditions. The relative impedances of the system components has been evaluated allowing optimization of the system design. An investigation of the effect of withdrawal of hot water from the storage tank, with associated injection of cold water to the bottom of the tank, has illustrated that the self-regulating nature of the thermosiphoning system results in a large proportion of heat stored in the wate filled collector tubes being effieciently transferred to the storage tank, providing some water is drawn off intermittently.     

Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and testicular steroidogenesis in male hypercholesterolemic patients

STUDY OBJECTIVE: To determine if there are significant differences in birth outcomes and survival for infants delivered by certified nurse midwives compared with those delivered by physicians, and whether these differences, if they exist, remain after controlling for sociodemographic and medical risk factors. DESIGN: Logistic regression models were used to examine differences between certified nurse midwife and physician delivered births in infant, neonatal, and postneonatal mortality, and risk of low birthweight after controlling for a variety of social and medical risk factors. Ordinary least squares regression models were used to examine differences in mean birthweight after controlling for the same risk factors. STUDY SETTING: United States. PATIENTS: The study included all singleton, vaginal births at 35-43 weeks gestation delivered either by physicians or certified nurse midwives in the United States in 1991. MAIN RESULTS: After controlling for social and medical risk factors, the risk of experiencing an infant death was 19% lower for certified nurse midwife attended than for physician attended births, the risk of neonatal mortality was 33% lower, and the risk of delivering a low birthweight infant 31% lower. Mean birthweight was 37 grams heavier for the certified nurse midwife attended than for physician attended births. CONCLUSIONS: National data support the findings of previous local studies that certified nurse midwives have excellent birth outcomes. These findings are discussed in light of differences between certified nurse midwives and physicians in prenatal care and labour and delivery care practices. Certified nurse midwives provide a safe and viable alternative to maternity care in the United States, particularly for low to moderate risk women.     

Optic neuropathy in familial dysautonomia

Optic atrophy, which is indicative of a CNS disorder, is a rarely described manifestation of familial dysautonomia (Riley-Day syndrome). As these patients are now living longer, the prevalence of optic neuropathy also may be increasing. We present a man with familial dysautonomia and visual loss resulting from optic atrophy and visual field defect suggestive of chiasmal pathology.