This study demonstrates that P1 and P2 are critical potentials in a circuit of verapamil-sensitive ILVT and suggests the presence of a macroreentry circuit involving the normal Purkinje system and the abnormal Purkinje tissue with decremental property and verapamil-sensitivity.

Cardiac event rates were significantly lower in the Japanese than in the USA and European populations. However, large myocardial perfusion defects and decreased cardiac function, as well as diabetes mellitus, could be predictors of high event rates and, thus, beneficial for risk stratification of Japanese patients with ischemic heart diseases.

The (pro)renin receptor ((P)RR), which is a recently discovered molecule of the renin-angiotensin system, plays an important role in the development of cardiovascular diseases. However, the molecular properties and the subcellular distribution of (P)RR remain controversial. In this study, (P)RR-Venus in Chinese hamster ovary (CHO) cells ((P)RR-Venus-CHO) or endogenous (P)RR in human vascular smooth muscle cells (VSMC) were constitutively cleaved without any stimulation, and secretion of the aminoterminal fragment (NTF-(P)RR) into the media was determined using western blot analysis. Immunofluorescent analysis showed robust expression of (P)RR in the endoplasmic reticulum (ER) or the Golgi but not in the plasma membrane. Moreover, we identified ADAM19, which is expressed in the Golgi, as one of cleaving proteases of (P)RR. Transfected ADAM19 evoked the shedding of (P)RR, whereas transfected dominant negative ADAM19 suppressed it. Although (P)RR contains a furin cleavage site, neither the furin-deficient LoVo cells nor furin inhibitor-treated VSMC lost NTF-(P)RR in the media. The secreted NTF-(P)RR induced the renin activity of prorenin in the extracellular space. We describe that (P)RR is mainly localized in the subcellular organelles, such as the ER and Golgi, and (P)RR is cleaved by ADAM19 in the Golgi resulting in two fragments, NTF-(P)RR and CTF-(P)RR. These results may suggest that (P)RR is predominantly secreted into the extracellular space. Hypertension Research (2011) 34, 599-605; doi:10.1038/hr.2010.284; published online 27 January 2011Keywords: ADAM19; ectodomain shedding; (pro)renin receptor; renin-angiotensin system INTRODUCTION The (pro)renin receptor ((P)RR) is a recently discovered molecule of the renin-angiotensin system (RAS), which plays pivotal roles in the regulation of the cardiovascular system under normal and pathological conditions. (P)RR binds both renin and prorenin, which is the precursor form of renin. 1 Although the binding of renin to (P)RR may increase its catalytic activity, the binding affinity between (P)RR and renin is lower than that of (P)RR and prorenin. These results indicate that it may be necessary to focus on the interaction between (P)RR and prorenin. Prorenin does not display protease activity in the plasma because the enzymatic cleft is covered by the prosegment. 2 However, the binding of prorenin to (P)RR evokes the renin activity without removal of its prosegment. This nonproteolytic activation of prorenin contributes to the activation of the local RAS. In addition to the enzymatic activity, renin/prorenin has been shown to provide other (P)RR-mediated effects. 3 The binding of renin/prorenin to (P)RR induces the activation of intracellular signaling, including the p38 MAP kinase-HSP27 cascade, the PI3K pathway and the ERK 1/2 pathway; these effects occur independently of angiotensin II, which is a final product of RAS. 2,4,5 Although this evidence strongly supports (P)RR localization in the plasma membrane, the subcellular localization of (P)RR remains unknown. (P)R...

Probucol administered beginning 4 weeks before PTCA appears to reduce restenosis rates.

Norovirus is one of the most common causes of nonbacterial gastroenteritis in humans. A total of 603 fecal specimens collected from sporadic pediatric cases of acute gastroenteritis in Japan from 2004 to 2005 were tested for the presence of norovirus by RT-PCR. It was found that 51 (8.5%) specimens were positive for norovirus. The norovirus genotypes detected in this study were GII/1, GII/2, GII/3, GII/4, GII/6, and GII/7. Of these, GII/3 was the most predominant (52.9%), followed by GII/4 (37.2%) and others. It was noticed that four distinct types of recombinant noroviruses were co-circulating and the variant norovirus GIIb suddenly emerged to be the leading strain in Japan for the first time. A novel norovirus nomenclature was proposed, in which worldwide noroviruses were classified into seven distinct genogroups (I-VII). Norovirus GI and GII consisted of 16 genotypes with 32 subgenotypes and 23 genotypes with 34 subgenotypes, respectively. Of note, human and porcine noroviruses had a close genetic relationship within GII. Interestingly, multiple short amino acid motifs located at N terminus, S domain, P1 domain, P2 domain, and C terminus of capsid gene correctly defined the phylogenetic norovirus genogroups, genotypes, and subgenotypes. Another interesting feature of the study was the identification of eight hitherto unreported recombinant noroviruses. It was noteworthy that three different types (intergenogroup, intergenotype, and intersubgenotype) of recombination in noroviruses were also found. This is the first report to demonstrate the existence of intergenogroup and intersubgenotype recombinations in noroviruses and highlights a possible route of zoonoses in humans because porcine, bovine and murine noroviruses belong to genogroups II, III, and V, respectively.

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A total of 402 fecal specimens collected during July 2003-June 2004 from infants and children with acute gastroenteritis, encompassing five localities (Maizuru, Tokyo, Sapporo, Saga, and Osaka) of Japan, were tested for the presence of norovirus by RT-PCR. It was found that 58 (14.4%) fecal specimens were positive for norovirus. Norovirus infection was detected throughout the year with the highest prevalence in December. Norovirus GII was the most predominant genogroup (98.3%; 57 of 58). The genotypes detected in this study were GI/4, GII/2, GII/3, GII/4, and GII/6. Of these, NoV GII/3 (known as the Arg320 virus cluster) was the most predominant genotype (43.9%), followed by NoV GII/4 (the Lordsdale virus cluster; 35.1%) and others. Two norovirus strains clustered with a "new variant designated GIIb" and a "new variant of GII/4" were found circulating in Japan for the first time. It was interesting to note that NoV GIIb and NoV GII/3 appeared to be the recombinant strains and the recombination site was demonstrated at the overlap of ORF1 and ORF2. The majority (96%) of the dominant norovirus strains were identified as the recombination of GII/3 capsid and GII/12 polymerase. The recombination in the NoV GIIb capsid gene at the breakpoint located at P1 domain was also identified. Obviously, NoV GIIb isolate in Japan had double recombination. This is the first report demonstrating the existence of different "new variants" co-circulating in Japanese infants and children with acute gastroenteritis.

Purpose: Quantitative gated single-photon emission computed tomography (SPECT) is known to have high accuracy and precision for measurement of the principal cardiac functional parameters. We hypothesised that normal values for EF and LV volumes may differ among nationalities, and that optimal threshold values specific to the study population are required. Results: EF for women and men was 74% ± 9 % and 63% ± 7% (p<0.0001). EDV, ESV and SV were significantly smaller in women than in men. Based on multiple regressions for linear models, the primary and secondary predictors of EF, EDVI, ESVI were gender and age. By stepwise multiple regression analysis, the statistically significant third predictor for EDV, ESV, SV and SVI was body weight. No colinearity was found between age and body weight. Important factors for the studied Japanese population included a high incidence of small hearts in women and the relatively advanced age of the population (the mean age ±SD was 64.1±10.0 years for women and 60.9±11.7 years for men).Conclusion: EF and volumes by gated SPECT with QGS were significantly affected by gender and ages, with body weight as the third predictor for volumes. Moreover, the normal limits were so specific for the population studied that standards appropriate for the study 3/27 should be utilized.