Phylogeography of the temperate grassland plant Tephroseris kirilowii (Asteraceae) inferred from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq) data.

A group of temperate grassland plant species termed the "Mansen elements" occurs in Japan and is widely distributed in the grasslands of continental East Asia. It has been hypothesized that these species are continental grassland relicts in Japan that stretch back to a colder age, but their migration history has not been elucidated. To assess the migration history of the Mansen elements, we performed phylogeographic analyses of Tephroseris kirilowii, a member of this group, using single-nucleotide polymorphisms (SNPs) obtained from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq). It was estimated that the Japanese populations of T. kirilowii were divided from those of continental East Asia at 25.2 thousand years ago (ka) with 95% highest probability density interval (HPD) of 15.3-40.0 ka and that Japanese clades first diverged at 20.2 ka with 95% HPD of 10.4-30.1 ka. As the climatically suitable range during the last glacial maximum (LGM) estimated using ecological niche modeling (ENM) was limited in Japan and there was a slight genetic differentiation among Japanese populations, a post-glacial expansion of T. kirilowii in the Japanese Archipelago was indicated.

Phylogeography of the East Asian grassland plant, Viola orientalis (Violaceae), inferred from plastid and nuclear restriction site-associated DNA sequencing data.

To elucidate the origin and migration history of the "Mansen elements," a group of temperate grassland plants mainly distributed in northeastern Asia, phylogeographic analyses based on chloroplast DNA markers and double-digest restriction site-associated DNA sequencing (ddRAD-seq) data were performed on Viola orientalis, one of the representative species of the group. Phylogenetic analyses using ddRAD-seq data revealed that the populations of V. orientalis were clustered into five clades, among which the continental clades made of populations from Russia and Korea diverged more than 100,000 years earlier than the Japanese clades. The Japanese clade likely diverged during the last glacial period, followed by a further post-glacial divergence into the Kyushu and the Honshu subclades. Our study demonstrated that V. orientalis originated in the continental area of northeastern Asia and, during the last glacial period, has spread southward through the Korean Peninsula across the Japanese Islands. This finding supports the previously proposed evolutionary hypothesis regarding the origin and migration routes of the Mansen elements.

Efficacy and safety of ustekinumab in East Asian patients with moderately to severely active ulcerative colitis: a subpopulation analysis of global phase 3 induction and maintenance studies (UNIFI).

BACKGROUND/AIMS: We aimed to evaluate the efficacy and safety of ustekinumab (UST) in the East-Asian population with moderate to severely active ulcerative colitis (UC). METHODS: This sub-analysis was conducted on data from East-Asian patients included in the UNIFI program (NCT02407236). UNIFI consisted of two double-blind, placebo-controlled trials: an 8-week induction study and a 44-week randomized withdrawal maintenance study. RESULTS: Of 133 East-Asian patients (Japanese: 107, Korean: 26) who underwent randomization, 131 completed induction study and 111 entered maintenance study. In the maintenance study, 78 patients were randomized. Patients who received UST 130 mg and UST 6 mg/kg showed numerically higher clinical remission at week 8 in the induction study (5/44 [11.4%] and 5/45 [11.1%], respectively) compared with those who received placebo (0/44, 0%). The proportion of patients achieved clinical remission at week 44 was numerically higher in the UST 90 mg q12w group (10/21, 47.6%), but similar in the UST 90 mg q8w group (5/26, 19.2%) compared to placebo (7/31, 22.6%). Serious adverse events were reported in 1 patient in UST 130 mg group, but no patient in UST 6 mg/kg group through week 8 in the induction study, and 1 patient in UST 90 mg q12w group and 5 patients in the UST 90 mg q8w group in the maintenance study. No deaths were reported in East-Asian patients throughout the study. CONCLUSIONS: UST induction and maintenance treatments were effective in East-Asian patients with moderate to severe UC; the efficacy and safety profiles were consistent with the overall population.

Phylogeography of Pulsatilla cernua (Ranunculaceae), a grassland species, in Japan.

The genetic diversity and structure of Pulsatilla cernua, a continental-grassland relict, were investigated using variations in chloroplast DNA (cpDNA) and microsatellites of nuclear DNA. In the analyses of three cpDNA regions, 17 haplotypes were found in 24 populations of P. cernua from Japan, Korea, and Russia. Although the route and time of migration between the continent of Asia and Japan could not be well resolved, the cpDNA haplotype network suggests the existence of several ancient lineages in Japan and a recent secondary migration from Japan to the continent. Microsatellite analyses did not indicate genetic structure among the Japanese populations, indicating the existence of gene flow across the distribution area until recently. These results indicate that the present fragmentation of P. cernua in Japan may reflect a rapid, recent reduction from a previously large, continuous distribution.

Transcriptome-wide mining, characterization, and development of microsatellite markers in Lychnis kiusiana (Caryophyllaceae).

BACKGROUND: Lychnis kiusiana Makino is an endangered perennial herb native to wetland areas in Korea and Japan. Despite its conservational and evolutionary significance, population genetic resources are lacking for this species. Next-generation sequencing has been accepted as a rapid and cost-effective solution for the identification of microsatellite markers in nonmodel plants. RESULTS: Using Illumina HiSeq 2000 sequencing technology, we assembled 67,498,600 reads into 91,900 contigs and identified 11,403 microsatellite repeat motifs in 9563 contigs. A total of 4510 microsatellite-containing transcripts had Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 124 pathways with significant scores. Many microsatellites in the L. kiusiana leaf transcriptome were linked to genes involved in the plant response to light intensity, salt stress, temperature stimulus, and nutrient and water deprivation. A total of 12,486 single-nucleotide polymorphisms (SNPs) were identified on transcripts harboring microsatellites. The analysis of nucleotide substitution rates for 2389 unigenes indicated that 39 genes were under strong positive selection. The primers of 6911 microsatellites were designed, and 40 of 50 selected primer pairs were consistently and successfully amplified from 51 individuals. Twenty-five of these were polymorphic, and the average number of alleles per SSR locus was 6.96, with a range from 2 to 15. The observed and expected heterozygosities ranged from 0.137 to 0.902 and 0.131 to 0.827, respectively, and locus-specific FIS estimates ranged from - 0.116 to 0.290. Eleven of the 25 primer pairs were successfully amplified in three additional species of Lychnis: 56% in L. wilfordii, 64% in L. cognata and 80% in L. fulgens. CONCLUSIONS: The transcriptomic SSR markers of Lychnis kiusiana provide a valuable resource for understanding the population genetics, evolutionary history, and effective conservation management of this species. Furthermore, the identified microsatellite loci linked to the annotated genes should be useful for developing functional markers of L. kiusiana. The developed markers represent a potentially valuable source of transcriptomic SSR markers for population genetic analyses with moderate levels of cross-taxon portability.

Clinical characteristics and outcomes in super-elderly patients (>85 years) with heart failure: single center observational study in Japan.

AIM: The number of elderly patients with heart failure is increasing in Japan owing to the increase in the aging population. In the field of emergency medicine, the treatment and management of elderly patients with heart failure are key issues. We aimed to clarify the clinical characteristics and outcomes of these patients. METHODS: We enrolled 72 consecutive patients (age, 76.5 ± 12.5 years) with heart failure who were admitted to our hospital between January 1 and December 31, 2010. The characteristics and outcomes of super-elderly patients aged >85 years (n = 21) were compared with those of patients aged ≤85 years (n = 51). RESULTS: The overall prevalence of chronic atrial fibrillation was high (43.1%). Underlying diseases, left ventricular function, renal function, in-hospital mortality, hospital stay period, and major complications were similar between the two groups. The super-elderly group had a significantly higher mortality rate and lower event-free survival rate after discharge (log-rank test, P = 0.0018 and P = 0.0032, respectively).The incidence of readmission for heart failure recurrence was 55.0% in the super-elderly group and 25.0% in the younger group. CONCLUSION: There were no significant differences in the background characteristics and in-hospital treatment between super-elderly heart failure patients and younger patients. High mortality and cardiovascular event rates after discharge were observed in the super-elderly group.

Delayed ventricular septal perforation caused by minimal branches occlusion during coronary artery stenting.

A 75-year-old woman was admitted to our hospital with stable effort angina pectoris. The coronary angiogram showed 90 % stenosis at the left anterior descending artery and stenting was successfully performed. Three months later, a newly audible systolic heart murmur was heard. Computed tomography revealed a ventricular septal perforation. Coronary angiogram immediately after stenting showed major septal branch was intact but two small septal branches were occluded. In the angiography after septal perforation occurred, these small septal branches remained occluded and stent restenosis was not observed. The ventricular septal perforation was presumed to be due to occlusions of minimal septal branches.

Pleistocene climatic oscillations and the speciation history of an alpine endemic and a widespread arctic-alpine plant.

Even in cases in which geographic isolation appears to have driven the speciation of regional endemics, range shifts during the Pleistocene climatic oscillations may also have influenced their evolutionary history. Elucidating speciation history can provide novel insights into evolutionary dynamics following climatic oscillations. We demonstrated a sister relationship between the Japanese alpine endemic Cardamine nipponica and the currently allopatric, widespread arctic-alpine Cardamine bellidifolia (Brassicaceae) based on internal transcribed spacer (ITS) sequences and 10 other nuclear genes. Speciation history was inferred using demographic parameters under the isolation with migration model. The estimated demographic parameters showed that the population size of C. nipponica was similar to that of C. bellidifolia and that gene flow occurred exclusively from C. nipponica to C. bellidifolia after speciation. The inferred speciation history, which included gene flow, suggests that geographic barriers between the peripheral C. nipponica and the widespread C. bellidifolia were reduced during the Pleistocene. The asymmetric introgression implies that genetic isolation may have been involved in the speciation of C. nipponica. Our results suggest that even currently allopatric species may not have diverged solely under geographic isolation, and that their evolutionary history may have been influenced by Pleistocene range dynamics.

Molecular evolution of cryptochrome genes and the evolutionary manner of photoreceptor genes in Cardamine nipponica (Brassicaceae).

Various photoreceptors in plants are used to monitor important environmental light signals and regulate plant development. Despite their functional importance, recent studies have demonstrated that red/far-red absorbing phytochromes or blue/UV-A absorbing cryptochromes are involved in local adaptation within a species' range. In the present study, to exemplify the intraspecific photoreceptor evolutionary pattern, the genetic structures of cryptochrome genes (CRY1 and CRY2) in Cardamine nipponica (Brassicaceae), of which PHYE, a gene coding one of the phytochromes, was found to be involved in local adaptation between central and northern Japanese populations. Although clear genetic differentiations between central and northern Japan were detected (CRY1: F (ST) = 0.63, CRY2: F (ST) = 0.53), overall nucleotide diversity was very low (CRY1: π (Total) = 0.0014, CRY2: π (Total) = 0.0013), and the polymorphism patterns were neutral (CRY1: Tajima's D = 0.084, P = 0.32, CRY2: D = -0.014, P = 0.39). Therefore, the involvement of cryptochromes in the adaptation to local environments is difficult to postulate. Consequently, this study along with our previous findings suggest that intraspecific photoreceptor gene polymorphisms in C. nipponica were mostly suppressed by purifying selection due to their functional importance as photoreceptors, while some of the photoreceptors may play substantial roles in adaptation to local environments.

Application of the isolation with migration model demonstrates the pleistocene origin of geographic differentiation in Cardamine nipponica (Brassicaceae), an endemic Japanese alpine plant.

The Pleistocene was characterized by a cyclic pattern of cold and warm climatic periods, or climatic oscillations, which caused fluctuations in the distributions of organisms. This resulted in drastic changes in demography, thereby accelerating the genetic divergence of populations. Phylogeographic studies have elucidated the history of populations during the Pleistocene. However, given the lack of model-based analysis of population histories, previous phylogeographic studies could not adequately evaluate the effect of these Pleistocene climatic oscillations on the genetic divergence and migration events between populations. Populations of Japanese alpine plants in central and northern Japan are highly differentiated, and a history of isolation between regions during the Pleistocene was inferred. Using sequences of 10 nuclear genes (ca. approximately 7,000 bp in total) from Cardamine nipponica (Brassicaceae), we applied an isolation with migration (IM) model to test the significance of the isolation history between central and northern Japan and to assess whether range shifts during the Pleistocene climatic oscillations were involved in the genetic differentiation between regions. The estimated divergence time indicates that the two regions were separated about 100,000-110,000 years ago. The exclusive occurrence of closely related haplotypes within each region (parsimony network) and the high level of genetic differentiation between the regions (mean F(ST) = 0.417) indicate that genetic divergence occurred following the isolation of the two regions. Therefore, the genetic differentiation between regions was shaped during the Pleistocene, especially during the last glacial and inter and postglacial periods. In addition, our multilocus analysis showed that populations in central and northern Japan were completely isolated after they split. Geographic separation and subsequent restricted migration events among mountains could explain this isolation history between regions. Furthermore, genetic drift in the reduced populations would remove evidence of occasional migration, emphasizing the isolation history. Therefore, our application of a demographic model demonstrated the Pleistocene origin of geographic differentiation statistically and provided a plausible migration history for C. nipponica.

Molecular evolution of phytochromes in Cardamine nipponica (Brassicaceae) suggests the involvement of PHYE in local adaptation.

Given that plants are sessile organisms, traits involved in adapting to local environments and/or in monitoring the surrounding environment, such as having photoreceptors, are significant targets of natural selection in plant evolution. To assess the intraspecific adaptive evolution of photoreceptors, we investigated sequence variations in four phytochrome genes (PHYA-C and PHYE) of Cardamine nipponica (Brassicaceae), an endemic Japanese alpine plant. The genealogies of haplotypes and genetic differentiations showed inconsistent patterns of evolution across phytochromes, suggesting that evolutionary forces were distinct in phytochromes of C. nipponica. An overall low level of nucleotide diversity in phytochrome genes suggests that the evolution of phytochromes is constrained by purifying selection within C. nipponica, which is consistent with previous findings on phytochromes. However, PHYE alone exhibited a non-neutral pattern of polymorphisms (Tajima's D = 1.91, P < 0.05) and an accumulation of nonsynonymous substitutions between central and northern Japan. In particular, the PHY domain, which plays an important role in stabilizing the active form (Pfr) of phytochromes, harbored a specific nonsynonymous fixation between regions. Thus, our finding indicates that local adaptation is involved in the evolution of PHYE in C. nipponica and is the first to suggest the involvement of PHYE in local adaptation.

Prognostic implications of left atrial dilation evaluated by echocardiographic volume in patients with normal left atrial antero-posterior dimensions.

BACKGROUND: The purpose of this study was to clarify the clinical characteristics and prognostic implications of left atrial (LA) dilation evaluated echocardiographic volume in patients with normal LA dimension (LAD). METHODS: A total of 140 consecutive patients (81 men, mean age: 57 ± 18 years) with normal LAD (<39 mm for women and <41 mm for men) who underwent conventional echocardiography and tissue Doppler imaging were enrolled. LA volume (LAV) ≥29 ml/m(2) was defined as abnormal LAV. Hospitalization for heart failure (HF) and cardiac death were defined as cardiac events. RESULTS: Eighty-seven (62%) of the patients had LA dilation, defined as a normal LAD but an abnormal LAV. Patients with LA dilation were significantly older and had a significantly higher left ventricular (LV) mass index (LVMI) and incidences of hypertension and HF than did patients with both normal LAD and normal LAV. Logistic regression analysis revealed that increased LVMI was an independent (p < 0.01) determinant of LA dilatation. During a follow-up period of 16 ± 10 months, ten patients had cardiac events. Patients with cardiac events had a higher incidence of LA dilation than those without cardiac events (100 vs. 59%, p < 0.05). A Kaplan-Meier survival curve showed that patients with LA dilation had a significantly lower survival rate than those with both normal LAD and normal LAV (log rank 6.1, p = 0.014). CONCLUSIONS: LV hypertrophy is an independent determinant of LA dilation in patients with normal LAD. Assessment of LA morphology using LAV can contribute to risk stratification in patients with normal LAD.

Consistent geographic structure among multiple nuclear sequences and cpDNA polymorphisms of Cardamine nipponica Franch. et Savat. (Brassicaceae).

Molecular phylogeography has inferred the history of differentiation between regions and/or among populations following the Pleistocene climatic oscillations, mostly based on the genetic structure of organelle DNA. However, such genetic structure only reflects the history of a single gene, and studies based on single-copy genes of nuclear DNA (nDNA) are required for phylogeography, although their efficiency remains unclear. To examine the utility of nDNA loci, the genetic structures of three genes from Cardamine nipponica, which is closely related to the model species Arabidopsis thaliana, were elucidated: the nDNA genes DET1, PHYA, PHYE, as well as chloroplast DNA (cpDNA). In 279 individuals collected from throughout the range of the species, strong genetic differentiation between northern and central Japan was found for all loci. This result suggested that populations in central Japan experienced a different history from those in northern Japan during the Pleistocene climatic oscillations. In addition, the evidence of refugia at the edges of the distribution, where the genetic structure was less influenced by colonization following range expansion, was shown for several loci. The specific genetic structure within the southernmost populations of northern Japan suggested that this region was also isolated during range expansion. Hence, the consistent history among loci and a more detailed history from several loci indicated that cpDNA can represent the history of vicariance and demonstrated the efficiency of single-copy nuclear genes in phylogeography.

Insulin resistance functionally limits endothelium-dependent coronary vasodilation in nondiabetic patients.

Insulin resistance (IR) is now considered to be a risk factor for coronary arterial atherosclerosis and is likely to be involved in a limited endothelium-dependent vasodilatory function in peripheral circulation. We investigated whether IR impairs endothelial vasodilator function in the noninfarcted coronary artery. In 14 nondiabetic patients (10 males, 66 +/- 6 years) who were selected from 214 patients underwent IR evaluation by glucose clamp, a Doppler flow wire was used to measure coronary flow changes (percent volume flow index, %VFI) during intracoronary administration of papaverin (10 mg) and stepwise administration of acetylcholine (Ach; 1, 3, 10 microg/ml per minute) into the non-infarcted left circumflex coronary artery. Insulin resistance was comparatively evaluated by an euglycemic hyperinsulinemic glucose clamp (M value, mg/m(2) per minute) or by a 75g-oral glucose tolerance test (120-min immunoreactive insulin; 120' IRI, pmol/l). Eight patients (57%) were defined as having IR on the basis of results obtained by both the glucose clamp method (M values <167 mg/m(2) per minute) and 120' IRI (>384 pmol/l). There was no difference between papaverin-induced %VFI increases in IR and non-IR subjects (328% +/- 43% vs. 361% +/- 87%). However, IR subjects showed significantly lower Ach-induced %VFI increases in a dose-dependent manner (P < 0.05), especially when low (1 microg/ml per minute) and moderate (3 microg/ml per minute) doses of Ach were used (165% +/- 18% or 248% +/- 29% in non-IR subjects vs. 130% +/- 20% or 183% +/- 41% in IR subjects, P < 0.001, respectively). Moreover, %VFI increase at a low dose of Ach infusion significantly correlated with M values or 120' IRI ([%VFI Ach 1 microg] = 85.9 + 0.35 [M values], r = 0.58, P = 0.038; [%VFI Ach 1 microg] = 176.8 - 0.47.[120' IRI], r = -0.57, P = 0.035). Insulin resistance limits endothelium-dependent coronary vasodilation in association with the severity of IR in non-diabetic patients.

Long-term outcome of first-generation metallic coronary stent implantation in patients with coronary artery disease: observational study over a decade.

BACKGROUND: In the era of drug-eluting stents, percutaneous coronary intervention (PCI) has been considered an established therapeutic modality for patients with coronary artery disease (CAD). However, little is known about the long-term prognosis. METHODS AND RESULTS: Using data obtained from a single-center registry for cases of first-generation bare metallic stent (BMS) implantation, a 10-year follow-up study in patients with CAD was performed. Data for 125 serial patients (aged 62+/-9 years, 104 males) in whom a BMS was successfully implanted was analyzed. Cardiac death (n=16 [12.8%]), including sudden cardiac death (n=9 [7.2%]), non-cardiac death (n=17 [13.6%]) and non-fatal acute myocardial infarction (n=16 [12.8%]) were documented. At 10 years, cumulative probabilities of target and non-target lesion revascularization were 20.5% and 41.5%, respectively, and only 39.2% of the patients were free from cardiac events (cardiac death/myocardial infarction/unplanned revascularization). Age and left ventricular ejection fraction (LVEF) were significant predictors of total death, and LVEF and the use of diuretics were predictors of cardiac events. CONCLUSIONS: Stabilization of the initial stented site was relatively good and the majority of cardiac events might have originated in non-target lesions. Prevention of systemic arteriosclerosis progression is important for patients with CAD, even after successful PCI.

Chloroplast DNA phylogeography of Pedicularis ser. Gloriosae (Orobanchaceae) in Japan.

Phylogeographic analyses using chloroplast DNA (cpDNA) variation were performed for Pedicularis ser. Gloriosae (Orobanchaceae). Eighty-one plants of 18 populations of 6 species (P. gloriosa, P. iwatensis, P. nipponica, P. ochiaiana, P. sceptrum-carolinum and P. grandiflora) were analyzed. Fifteen distinct haplotypes were identified based on six cpDNA regions: the intergenic spacer between the trnT and trnL 3'exon, trnL 3'exon-trnF, atpB-rbcL, accD-psaI, the rpl16 intron and the trnK region (including the matK gene). Via phylogenetic analyses of the haplotypes, two continental species, P. sceptrum-carolinum and P. grandiflora, were placed at the most ancestral position in the trees. The former species is widely distributed in the Eurasian continent, and the latter is distributed in Far East Asia. Two robust major cpDNA clades (clades I and II) were revealed in the Japanese archipelago, although the statistical values of monophyly of these clades were weak. Clade I included the haplotypes (A-1, A-2, B-1, B-2 and J) of three species (P. gloriosa, P. iwatensis and P. ochiaiana), and Clade II included seven haplotypes (C-D, E-1, E-2 and F-H) of P. nipponica. These results suggest that this series originated on the Eurasian continent and that subsequently populations at the eastern edge of the continent differentiated into the two Japanese lineages.

Assessment of left ventricular ejection fraction using long-axis systolic function is independent of image quality: a study of tissue Doppler imaging and m-mode echocardiography.

BACKGROUND: Quantitative assessment of left ventricular ejection fraction (LVEF) is technically difficult in patients with poor image quality (IQ). Mitral annulus velocity assessed by pulsed tissue Doppler imaging (TDI) and mitral annulus motion assessed by M-mode echocardiography has been shown to correlate with LVEF. Furthermore, mitral annulus sites are easy to identify even in patients with poor IQ. The purpose of this study was to determine whether these methods are useful for estimating LVEF in patients with poor IQ. METHODS: One hundred ten patients underwent TDI and M-mode echocardiography simultaneously. Mitral annulus velocity and mitral annulus motion were obtained from each of the four mitral annulus sites. Mean mitral annular peak systolic velocities (Sm) and mean mitral annular motions (MAM) were calculated by averaging at each site. IQ was defined according to a previous report. RESULTS: Both Sm and MAM were successfully measured in all patients. Mean Sm and mean MAM correlated with LVEF. These correlations were observed not only in patients with good IQ (p < 0.001, r = 0.61 for mean Sm; p < 0.001, r = 0.61 for mean MAM) or fair IQ (p < 0.001, r = 0.58 for mean Sm; p < 0.001, r = 0.68 for mean MAM) but also in patients with poor IQ (p < 0.05, r = 0.42 for mean Sm, p < 0.001, r = 0.61 for mean MAM). Using optimal cutoff values of mean Sm and mean MAM in each IQ group, sensitivity and specificity for identifying LVEF < 50% were comparable among three IQ groups. CONCLUSIONS: Assessment of long-axis systolic function by TDI and M-mode echocardiography enables estimation of LVEF even in patients with poor IQ.

Refugia of Potentilla matsumurae (Rosaceae) located at high mountains in the Japanese archipelago.

Molecular phylogeographic studies have revealed the genetic patterns and glacial-interglacial history of many plant and animal species. To infer the Quaternary history of alpine plants in the Japanese archipelago, which is poorly known, we investigated 203 individuals of Potentilla matsumurae and its varieties from 22 populations. We found 11 haplotypes based on approximately 1400 bp of two intergenetic spacers in chloroplast DNA (trnT-L and rpl20-rps20). The distribution of these haplotypes was geographically structured, which was supported by haplotype composition, principal component analysis, and unweighted pair group method with arithmetic mean (UPGMA), and N(ST) (0.71) was significantly greater than G(ST) (0.68). In addition to the positive correlation between genetic and geographic distance (Mantel test, r = 0.497, P < 0.001), an abrupt genetic change was detected between mountains in central Honshu and the Tohoku region. This genetic boundary was further supported by analysis of molecular variance (AMOVA), and high variation (54.0%) was explained by differences on either side of this boundary. Moreover, haplotypes in central Honshu were thought to have diverged, based on an outgroup comparison. These results suggest that mountains in central Honshu served as refugia during the Quaternary climatic oscillation, although the results could not reveal the history of most mountains in the Tohoku region and Hokkaido. Nevertheless, following floristic studies, our results indicate that alpine plants in Japan experienced a history different from that in Europe; i.e. they retreated into refugia during warm periods to avoid forest development, rather than glaciers.

Long-term outcome of implanted cardioverter defibrillators in survivors of out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Little is known about the long-term outcome of implantable cardioverter defibrillator (ICD) therapy in survivors of out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS: The frequency of lethal ventricular arrhythmias and whether ICD implantation can prevent recurrence of cardiac arrest were examined. Long-term (24.4+/-11.9 months) outcome was examined in 23 patients with OHCA who were treated with an ICD (OHCA group) and 35 patients without OHCA (non-OHCA group) who were treated with an ICD. Patients in both groups had same clinical backgrounds; however, those in the OHCA group showed a significantly lower incidence of induced ventricular arrhythmias (71%) than the non-OHCA group (96%). In the follow-up period, patients in the OHCA group had almost the same incidence of ICD discharge (30%) as patients in the non-OHCA group (40%). The rate of recurrence of ventricular fibrillation in the OHCA patients was 13%, and it was difficult to estimate the rate by induced ventricular arrhythmia. CONCLUSION: The results suggest that ICD implantation for survivors of OHCA with favorable neurological recovery might be effective for preventing recurrence of cardiac arrest.

Distribution of chloroplast DNA haplotypes in the contact zone of Fagus crenata in the southwest of Kanto District, Japan.

We have investigated cpDNA haplotype distribution in 24 populations of Fagus crenata in the southwest of Kanto District, Japan, and clarified the extent of intermixing of haplotypes in the contact zone by additional fine-scale analysis of two areas. Two cpDNA haplotypes belonging to different lineages were detected, and their distribution had geographical structure. Intermixed populations with the two haplotypes were limited to a narrow area. The geographical boundary between the haplotypes extended from Hakone to the west of the Kanto Mountains through the northern foot of Mt Fuji. No relationship was observed between the boundary location and the current topography of the southwest of Kanto District.