A single-nucleotide polymorphism tagging set for human drug metabolism and transport

Interindividual variability in drug response, ranging from no therapeutic benefit to life-threatening adverse reactions, is influenced by variation in genes that control the absorption, distribution, metabolism and excretion of drugs. We genotyped 904 single-nucleotide polymorphisms (SNPs) from 55 such genes in two population samples (European and Japanese) and identified a set of tagging SNPs that represents the common variation in these genes, both known and unknown. Extensive empirical evaluations, including a direct assessment of association with candidate functional SNPs in a new, larger population sample, validated the performance of these tagging SNPs and confirmed their utility for linkage-disequilibrium mapping in pharmacogenetics. The analyses also suggest that rare variation is not amenable to tagging strategies.     

Opsonic activity against zymosan of normal human serum of different blood types

Summary Serum opsonic activity against zymosan was found to be decreased more markedly in highly diluted O type serum than in the other 3 types, among which no difference was noted. Heat-killed bacteria were equally well opsonized with any type of serum. This peculiar activity of O type serum against zymosan was not affected by the removal of isohemagglutinins. No inhibitory activity was demonstrable in O type serum.This work was supported in part by a Grant-in-Aid from the Japan Medical Research Foundation and Grants-in-Aid (Project Nos. 157253 and 544050) from the Ministry of Education, Science and Culture of Japan.     

α-Adrenoceptor blocking action of hymenin,a novel marine alkaloid

Summary In the rabbit isolated aorta, hymenin (10^–6 M) a novel marine alkaloid, caused a parallel rightward shift of the dose-response curve for norepinephrine without affecting that for histamine or KCl, suggesting that hymenin is a competitive antagonist of -adrenoceptors in vascular smooth muscles.Acknowledgments. We thank Ms A. Kajiwara and Ms M. Hamashima of this institute for their technical assistance, and Prof. Y. Hirata of Meijo University for his encouragement.     

Real-time spectroscopy of transition states in bacteriorhodopsin during retinal isomerization.

Real-time investigations of the rearrangement of bonds during chemical transformations require femtosecond temporal resolution, so that the atomic vibrations within the reacting molecules can be observed. Following the development of lasers capable of emitting ultrashort laser flashes on this timescale, chemical reactions involving relatively simple molecules have been monitored in detail, revealing the transient existence of intermediate species as reactants are transformed into products. Here we report the direct observation of nuclear motion in a complex biological system, the retinal chromophore of bacteriorhodopsin (bR568), as it undergoes the trans-cis photoisomerization that is fundamental to the vision process. By using visible-light pulses of less than 5 femtosecond in duration, we are able to monitor changes in the vibrational spectra of the transition state and thus show that despite photoexcitation of the anti-bonding molecular orbital involved, isomerization does not occur instantly, but involves transient formation of a so-called 'tumbling state'. Our observations thus agree with growing experimental and ab initio evidence for a three-state photoisomerization model and firmly discount the initially suggested two-state model for this process.     

几种有机锑(Ⅲ)化合物与共轭极性化合物的反应

讨论了几种有机锑（Ⅲ）化合物与共轭极性化合物的反应性质．在防湿、防空气的条件下，锑原子上连有亲核原子N，S的Sb（NEt2）3，Sb（SEt）3与共轭极性化合物反应，反应机理被推测为1，4加成反应，而连有烃基的有机锑（Ⅲ）化合物SbPr3，SbPh3不与共轭极性化合物反应．丙烯酸胺与Sb（NEt2）3的反应随后处理方法不同，产物也不同，并且SbPr3，Sb（SPh）3能引发甲基丙烯酸甲酯（MMA）聚合．     

Comparative aspects of structure and action of molluscan neuropeptides.

A number of neuropeptides were isolated from the ganglia and muscles of molluscs, and their actions were examined. Diverse neuropeptides, in addition to several classical neurotransmitters, were suggested to be involved in the regulation of the anterior byssus retractor muscle of Mytilus. A wide structural variety of members of the Mytilus inhibitory peptide family was observed in each of the genera Mytilus, Achatina and Helix. Gly-Trp-NH2, the C-terminal dipeptide fragment of the neuropeptide AGPWamide, showed a more potent action than the parent peptide in all of the muscles examined. Peptides related to some molluscan neuropeptides were found to be distributed interphyletically. Some neuropeptides containing a D-amino acid residue were found in Achatina and Mytilus. These aspects of molluscan neuropeptides are thought not to be exceptional.