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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.

In four probe sensing for measurement of voltage-current curve of superconducting layer-coated tapes, it has been reported that, when a large accidental defect is included in the region between the voltage probes, the critical current value estimated with the one micro-volt/cm criterion is low when the voltage probe spacing is small but it becomes higher when the spacing is larger. In the present work, a simulation study was carried out to reproduce the feature stated above and to describe the dependence of critical current value on the voltage probe spacing under the co-existence of a large crack and multiple small cracks. In simulation, the current shunting model at cracks and a Monte Carlo simulation method were applied to a model superconducting tape, which was composed of one local section with a large crack and multiple local sections with small cracks of different size from each other. The experimentally observed increase in critical current with increasing voltage probe spacing in the large defect included tape was reproduced well by the present simulation. Then, it was shown that the increase in critical current of the large crack-included region with increasing voltage probe spacing is caused by the increase in the ligament part-transported current and shunting current at the large crack due to the increase in critical voltage for determination of critical current. Furthermore, it was shown that the upper and lower bounds of the critical current of the region, in which a large crack and multiple small cracks exist, can be derived from the voltage-current curve of the section with a large crack, and the critical current of the region is given by the upper bound for a given size of the largest crack when the difference in size between the large crack and multiple small cracks is large.

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. Electronic supplementary material The online version of this article (10.1186/s12870-018-1621-x) contains supplementary material, which is available to authorized users.

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.

To accurately estimate the damage of soil-structure systems during earthquakes, reliable analytical methods and appropriate modeling of soils and structures are necessary. Herein seismic response analyses are performed on an embankment, a caisson-type composite breakwater, and a caisson-type quay wall to verify the applicability of the strain space multiple mechanism model, where both the total and updated Lagrangian (TL/UL) formulations are introduced based on the large deformation (finite strain) theory. Both infinitesimal and large deformation analyses are performed to examine the effect of geometrical nonlinearity. All of the computed results (e.g., deformation and excess pore pressure ratio) indicate that the TL and UL formulations are theoretically and numerically equivalent, validating the computer program for large deformation analysis. In addition, the large deformation analyses decrease the amount of deformations compared to the infinitesimal deformation analysis in these three cases. This tendency becomes more significant as the amplitude of the input ground motions increases. We also perform a centrifuge model test to investigate the large deformation mechanism of liquefiable sloping ground and compare the experimental results with numerical simulations. The comparison indicates that the large deformation analysis by the UL formulation reasonably simulates the experiment, whereas the infinitesimal deformation analysis overestimates the deformation.

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.

This study presents definitions of principal stress/strain range and mean stress/strain introduced by utilizing Itoh-Sakane criterion for multiaxial loading including non-proportional loading, and shows the method of calculating the non-proportional factor which expresses the severity of non-proportional loading under the multiaxial 3D loading. This paper also shows a method of visually presenting the stress/strain, the non-proportionality of loading and the damage evaluation.

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 FST = 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.

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). A total of 140 consecutive patients (81 men, mean age: 57 ± 18 years) with normal LAD (

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.

According to previous phylogeographic studies, high mountains at low latitudes are important areas for the study of the evolutionary history of arctic–alpine plants in surviving the Pleistocene climatic oscillations. To evaluate this hypothesis, we elucidated the genetic structure of the arctic–alpine plant, Loiseleuria procumbens, in the Japanese archipelago, which corresponds to one of the southernmost limits of its distribution, using 152 individuals from 17 populations that covered the entire distribution of the Japanese archipelago and Sakhalin, in addition to samples from Sweden. Based on 854 bp of chloroplast DNA, we detected eight haplotypes. Along with haplotype distribution, strong genetic differentiation between populations in central and northern Japan was elucidated by a neighbour-joining tree (100%) and spatial analysis of molecular variance (79%), which is consistent with other alpine plants in Japan, regardless of the species' range. In addition, the southernmost populations from northern Japan showed specific genetic structure, although the remaining areas of northern Japan and Sakhalin harboured an homogenous genetic structure. Our results suggest that the populations in central Japan persisted for a long time during the Pleistocene climatic oscillation and that genetic divergence occurred in situ, supporting our hypothesis in conjunction with a previous study of another arctic–alpine plant, Diapensia lapponica subsp. obovata. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 97, 403–412.

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.

Aim We aimed to elucidate how the current geographic distribution of alpine plants in the Japanese archipelago was shaped during Quaternary climatic oscillations, using Potentilla matsumurae as a case study. According to previous phylogeographic studies, post-glacial range fragmentation (vicariance scenario) and stepwise migration (dispersal scenario) are both possible. We thus aimed to assess which scenario is more probable for the distribution changes of alpine plants in the Japanese archipelago. Location The alpine zone in the Japanese archipelago. Methods Using amplified fragment length polymorphism we determined the genotype of 161 individuals of P. matsumurae from 22 populations. Relationships among individuals and populations were examined using principal coordinates analysis and a neighbour-joining (NJ) tree, respectively. To examine the genetic population structure, we performed analysis of molecular variance (amova) and structure analysis. Results Differentiation between central Honshu and northern Japan was not very strong based on the principal coordinates analysis among individuals, the NJ tree of populations (59% bootstrap support), or amova (12% of genetic variation). Moreover, structure analysis did not detect clear geographic differentiation across populations. Although the populations in central Honshu were structured geographically (Mantel test: r = 0.45, P

Previous phylogeographic studies of arctic-alpine plants have partly elucidated that alpine areas at the southernmost edges of their distribution have been one of the most important areas for the survival of populations through Quaternary climatic oscillations. To reveal the genetic structure of arctic-alpine plants near the southern edge of their range in East Asia, 159 samples of Diapensia lapponica subsp. obovata (Diapensiaceae) were collected from 22 populations in Japan. Based on 1,134 bp of chloroplast DNA (cpDNA), we determined 10 haplotypes. Neighbor-joining (NJ) analysis, including D. lapponica from Sweden and Schizocodon soldanelloides, revealed that all haplotypes in Japan were monophyletic. Genetic differentiation between populations of central Honshu and northern Japan was strongly supported by the NJ tree (100%), analysis of molecular variance (AMOVA, 68%), and Monmonier’s algorithm (>95%). The most ancestral haplotype rarely occurred in Japan, which implied that the extant genetic structure was not caused by genetic divergence during colonization. Thus, these results suggest that the arctic-alpine plant D. lapponica subsp. obovata survived climatic oscillations in central Honshu. This finding supports the hypothesis that high mountains in temperate regions were important for survival of arctic-alpine plants during Quaternary climatic oscillations.

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 values167 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 (P0.05), 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, P0.001, 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.

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.

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. (Circ J 2007; 71: 1360 - 1365)

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.

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.

A preliminary synthesis of the geographic distribution patterns of intraspecific cpDNA variations in Japanese alpine plants is presented by studying five species, namely, Pedicularis chamissonis, Primula cuneifolia, Loiseleuria procumbens, Cardamine nipponica, and Anemone narcissiflora. Nucleotide sequences of the noncoding regions of cpDNA recognized multiple cpDNA haplotypes in these species. Phylogenetic analyses of these haplotypes suggest two or three major cpDNA clades; each clade has a clearly disjunct distribution pattern in the northern parts of Japan, and in the central parts of Japan. The southernmost clades endemic to central Honshu in Japan were found in all the species (Central Honshu clade). We estimate that the major clades of Pedicularis chamissonis and Primula cuneifolia separated from a common ancestor before the last glacial period (>0.6 and 0.47 million years ago, respectively). We speculate that the common distribution patterns of the cpDNA clades observed in central Honshu were formed by dynamic climatic changes (e.g., glacial events in the Pleistocene) and that the alpine regions of central Honshu acted as refugia for alpine plants during warm interglacial periods.

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. (Circ J 2006; 70: 1128 - 1132)

Background Early defibrillation and cardiopulmonary bypass have been postulated to be a promising intervention against out-of-hospital cardiac arrest (OHCA); however, little is known about the long-term prognosis. The effects of early recovery of circulation (ROC) on neurological recovery and the long-term outcome in patients with OHCA were examined. Methods and Results Functional recovery and long-term (22.0±15.3 months) outcome were examined in 100 patients with definite diagnosis of OHCA. Spontaneous circulation recovered in 79% of the patients (using on-site counter shock in 20% of the patients). Cardiopulmonary bypass was performed in 38 of the OHCA patients. The total survival and favorable neurological recovery rates were 40% and 25%, respectively. The patients with favorable recovery obtained early ROC (28.2±16.0 min). Receiver-operating characteristic analysis showed that a period of less than 35 min for ROC was the optimal period for achieving a favorable recovery, with sensitivity of 68% and specificity of 73%. The patients with a prior history of heart failure or reduced left ventricular ejection fraction exhibited more frequent, exacerbated heart failure and ventricular arrhythmias. Conclusions Early ROC using on-site counter shock or cardiopulmonary bypass might result in better long-term outcome in patients with OHCA of cardiac origin. (Circ J 2005; 69: 1302 - 1307)

Interspecific hybridization is one of the major factors leading to phylogenetic incongruence among loci, but the knowledge is still limited about the potential of each locus to introgress between species. By directly sequencing three DNA regions: chloroplast DNAs (matK gene and trnL-F noncoding region), the nuclear ribosomal external transcribed spacer (ETS) region, and internal transcribed spacer (ITS) regions, we construct three phylogenetic trees of Asian species of Mitella (Saxifragaceae), a genus of perennials in which natural hybrids are commonly observed. Within this genus, there is a significant topological conflict between chloroplast and nuclear phylogenies and also between the ETS and the ITS, which can be attributed to frequent hybridization within the lineage. Chloroplast DNAs show the most extensive introgression pattern, ITS regions show a moderate pattern, and the ETS region shows no evidence of introgression. Nonuniform concerted evolution best explains the difference in the introgression patterns between the ETS region and ITS regions, as the sequence heterogeneity of the ITS region within an individual genome is estimated to be twice that of an ETS in this lineage. Significant gene conversion patterns between two hybridizing taxa were observed in contiguous arrays of cloned ETS-ITS sequences, further confirming that only ITS regions have introgressed bidirectionally. The relatively slow concerted evolution in the ITS regions probably allows the coexistence of multiple alleles within a genome, whereas the strong concerted evolution in the ETS region rapidly eliminates heterogeneous alleles derived from other species, resulting in species delimitations highly concordant with those based on morphology. This finding indicates that the use of multiple molecular tools has the potential to reveal detailed organismal evolution processes involving interspecific hybridization, as an individual locus varies greatly in its potential to introgress between species.

CpDNA variation in Japanese beech, Fagus crenata (Fagaceae), was studied in 45 populations distributed throughout the species' range. Two cpDNA regions were sequenced: the non-coding region between the trnL (UAA) 5′exon and trnF (GAA), and the trnK region (including matK). Thirteen distinct cpDNA haplotypes were recognized and each haplotype was found to be geographically structured. Two major clades (I and II+III) were revealed in phylogenetic analyses among the haplotypes using F. sylvatica as an outgroup. The haplotypes of Clade I were distributed mainly along the Japan Sea side of the Japanese Archipelago, while those of Clade II+III occurred chiefly along the Pacific Ocean side. Consequently, the distribution of the two major cpDNA clades suggests that there were two migration routes in the history of F. crenata; one along the Japan Sea and the other along the Pacific Ocean side of the Japanese Islands.

The Kamimura River, an upper tributary of the Yahagi River, flows through steep valleys in the mountainous Kamiyahagi area of Gifu Prefecture. The Tokai Gou flood of September 11-12, 2000 destroyed embankments along the river, and exposed sedimentary layers at Umi that are typical of a lacustrine depositional setting. This confirms the existence of a paleo-lake from which the name Umi originated. The lake was formed as the result of a huge landslide that dammed up the Kamimura River. To determine when the landslide occurred, radiocarbon (14C) ages of trees buried in lacustrine sediments were determined using accelerator mass spectrometry (AMS). The 14C ages are 300±25, 340±25, 345±25 and 380±25 BP for the outermost rings of tree trunks, which include bark, and a single age of 620±25 BP. Calibrated ages of (1637), (1520, 1590, 1624), (1517, 1597, 1619) and (1482) cal AD within a range of 1455-1643 cal AD are consistent with a landslide triggered by the Tensho Earthquake of January 18, 1586, which had an estimated magnitude of 8.2-8.3 and an epicenter in Ise Bay.

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.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 aged85 years (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,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.

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.

Summary • 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.

The activities of a water-soluble peptidoglycan fragment derived from Staphylococcus epidermidis (SEPS) were examined as to their role in proliferation of spleen mononuclear cells (SMNC) from various strains of mice, the production of cytokines in vitro, and the induction of an inflammatory reaction in vivo. The proliferation of SMNC from C3H/HeN, C57BL/6, AKR, DBA/2, and ddY mice in reaction to SEPS in vitro showed a peak on day 3 and was greater than that of SMNC from BALB/c mice. The cells of SMNC from C3H/HeN mice responsive to SEPS were indicated to be mainly macrophages. A time kinetics experiment showed a coincidence in the proliferation of SMNC in reaction to SEPS and the detection of colony-stimulating factor (CSF) activity. Interleukin 2 (IL-2) activity was not detected during the incubation periods. When SEPS was administered to mice, much stronger mRNA transcripts of granulocyte-macrophage (GM)-CSF were detected in the lungs of C3H/HeN mice than in BALB/c mice. On the other hand, the amounts of IL-1 and PGE2 produced by SMNC of BALB/c mice stimulated by SEPS were greater than those produced in C3H/HeN mice. SEPS was confirmed to induce arthritis in BALB/c mice, but not in C3H/HeN mice. Our findings suggest that the production of GM-CSF is involved in the in vitro proliferation of SMNC in reaction to SEPS and that along with IL-1 and PGE2 production, contributes to the inflammation by SEPS in vivo.

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.

We have recently reported that chronic and systemic administration of tumor necrosis factor alpha (TNF) inhibits development of autoimmune diabetes in NOD mice and BB rats, animal models of insulin-dependent diabetes mellitus (IDDM). During these experiments, we unexpectedly found that in vivo production of TNF stimulated by a single injection of lipopolysaccharide was enhanced approximately 10 times in the long-term diabetic BB rats (P less than 0.0001), whose mean duration of diabetes with more than 16.8 mM (300 mg/dl) of nonfasting blood glucose level was 26.2 +/- 2.1 days, as compared to that in the rats of nondiabetes and in the rats at the onset of diabetes, whose mean duration of diabetes was 1.4 +/- 0.6 days. The long-term diabetic, but not short-term-diabetic, rats were also associated with increased levels of serum fructosamine/albumin (P less than 0.01) and triglyceride (P less than 0.01) and with a decreased level of serum albumin (P less than 0.01). The in vivo TNF productivity in the diabetic rats, including the short-term- and long-term-diabetic rats, was correlated positively with the level of fructosamine/albumin (P less than 0.05) and negatively with the level of serum albumin (P less than 0.05), but not with levels of blood glucose. None of these correlations were observed in nondiabetic rats. The increased LPS-induced serum TNF activity in the long-term diabetic state was observed not only in BB rats but also in NOD mice and GK rats, a model of non-IDDM, irrespective of sexes and ages, indicating that the enhancement of in vivo TNF production was a result of long-term diabetes. These findings indicate that some factor(s) associated with the long-term-diabetic state may prime macrophages in vivo to produce TNF. Further study is needed to reveal a mechanism of the enhanced TNF production and its possible relevance to various abnormalities associated with the chronic hyperglycemic state.

Increasing evidence suggests that an intimate correlation may exist between the production of a cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF) and the ability to metastasize spontaneously in the lungs in murine transplantable tumors. In the present study, we further examined the cytokine production by tumor cells with the ability to metastasize in the liver. Four out of 8 test tumors, which produced metastasis in the lungs but not in the liver, exhibited the ability to produce GM-CSF activity in culture. Three other tumors produced metastasis in the liver but not in the lungs. These tumor cells exhibited no ability to produce GM-CSF, but two of them expressed an interleukin-6 (IL-6) mRNA and also produced IL-6 activity in the culture fluids. One of the two IL-6-producing tumors and the remaining liver metastatic tumor produced interleukin-1 (IL-1) as revealed by bioassay and neutralization test. In the tumor cells producing pulmonary metastasis, neither IL-6 gene expression nor IL-1 production could be detected. The last test tumor, which produced no metastasis either in the lungs or liver, produced neither GM-CSF, IL-1 nor IL-6. Furthermore, injection of antisera reactive to recombinant murine IL-6 caused a marked decrease of the number of liver metastases of an IL-6-producing tumor, but not lung metastases of a GM-CSF-producing tumor, which could be markedly inhibited by injection of anti-recombinant murine GM-CSF sera. These results suggest the possibility that there may be a correlation between the cytokines produced by tumor cells and their organ specificity in spontaneous metastasis, and also indicate that these tumor models may provide a useful tool for studies on the role of cytokines in tumor metastasis.