We have previously reported on the analysis of germ-line mutations in Japanese von HippelLindau disease (VHL) patients and found mutations in 26 families. We have now extended these studies to include an additional 41 VHL families. Germ-line mutation of the VHL gene was screened by DNA-SSCP, direct sequencing, and Southern blot analysis. To summarize all of the data we have studied in this and our previous report, germ-line mutations have been detected in 55 of 77 (73%) (type 1: 41 / 62 (66%) and type 2: 14/15 (93%)) families. We found similarities in the nature of germ-line mutations including mutational incidence, location, and DNA substitution patterns between Japanese and Western VHL. These similarities may reflect the predominance of endogenous mutational processes. We also found several interesting characteristics in Japanese VHL. Twenty of 41 (49%) intragenic mutations were unique and not reported in the Western VHL. Four mutations (Arg113Stop, Gln132Stop, Leu158Val, and Cys162Tyr) previously characterized as type 1 mutations were identified in the type 2 (with pheochromocytoma) Japanese families. Genotype-phenotype correlation study suggested non-missense mutations predicted to result in the loss of VHL function were associated with the occurrence of renal cell carcinoma, as in sporadic tumors. Our data add to the diversity of VHL germ-line mutations and provide a better understanding of VHL disease in terms of both clinical management and molecular pathogenesis.
We study a new s-process path through an isomer of 186 Re to improve a 187 Re-187 Os nucleo-cosmochronometer. The nucleus 187 Re is produced by this new path of 185 Re(n,γ) 186 Re m (n,γ) 187 Re. We measure a ratio of neutron capture cross-sections for the 185 Re(n,γ) 186 Re m and 185 Re(n,γ) 186 Re gs reactions at thermal neutron energy because the ratio with the experimental uncertainty has not been reported. Using an activation method with reactor neutrons, we obtain the ratio of R th = 0.54 ± 0.11%. From this ratio we estimate the ratio of Maxwellian averaged cross sections in a typical s-process environment at kT = 30 keV with a help of the temperature dependence given in a statistical-model calculation because the energy dependence of the isomer/ground ratio is smaller than the absolute neutron capture cross-section. The ratio at kT =30 keV is estimated to be R st = 1.3 ± 0.8%. We calculate the s-process contribution from the new path in a steady-flow model. The additional abundance of 187 Re through this path is estimated to be N s = 0.56 ± 0.35% relative to the abundance of 186 Os. This additional increase of 187 Re does not make any remarkable change in the 187 Re-187 Os chronometer for an age estimate of a primitive meteorite, which has recently been found to be affected strongly by a single supernova r-process episode.
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