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Background Nocturnal hypertension assessed by a home blood pressure monitoring (HBPM) device is associated with an increased risk of cardiovascular events. However, it is still difficult to assess nighttime blood pressure (BP) frequently. The purpose of this cross-sectional study was to identify significant correlates of nocturnal hypertension assessed by an HBPM device in patients with hypertension who are treated with antihypertensive drugs. Methods We measured nighttime BP, morning BP, and evening BP by an HBPM device for 7 consecutive days in 365 medicated patients with hypertension. Results Of the 365 subjects, 138 (37.8%) had nocturnal hypertension defined as a mean nighttime systolic BP of ≥ 120 mm Hg. Receiver operating characteristic curve analyses showed that the diagnostic accuracy of morning systolic BP for subjects with nocturnal hypertension was significantly superior to that of evening systolic BP (P = 0.04) and that of office systolic BP (P Conclusions Morning systolic BP of ≥ 125 mm Hg, a history of cerebrovascular disease, and bedtime dosing were significant correlates of nocturnal hypertension in medicated patients with hypertension, and may help detect this risky BP condition. Clinical trials registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000019173).

Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion ( Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

A recent study revealed that recurrence of myocarditis occurs in a significant proportion of patients, but multiple recurrences of myocarditis have rarely been reported. The pathophysiology and best treatments for multiple recurrences of myocarditis remain unclear. A 60-year-old man presented to our emergency department with fever and chest pain. Physical examination, imaging, and laboratory findings were consistent with fulminant myocarditis. Paired titers confirmed adenovirus infection. The patient was treated with intra-aortic balloon pump and percutaneous cardiopulmonary support for 7 days and was discharged with near-normal electrocardiographic and echocardiographic findings on day 26. Over the subsequent 3 years, the patient experienced six episodes of recurrence of myocarditis with a progressive decrease in his ability to perform activities of daily living. At the time of his sixth recurrence, he died of ventricular fibrillation. Autopsy revealed mild enlargement of the left ventricle, extensive inflammatory cell infiltration, and mild interstitial fibrosis, suggesting left ventricle remodeling because of repetitive myocarditis. We have presented a case of multiple recurrences of myocarditis. This is the largest number of recurrences in a single patient reported to date. Further studies are needed to elucidate the underlying pathogenesis and best treatment of this condition.

Bacteria can adhere to cardiac endothelium damaged by regurgitation or a shunt jet; however, healthy cardiac endothelium is supposedly resistant to bacterial adhesion. A 22-year-old man presented to our emergency department with fever. Physical examination revealed no obvious cardiac murmur, but there was evidence of splinter hemorrhages and Janeway lesions. Transthoracic echocardiography did not reveal vegetative lesions, but a 15 × 7-mm vegetation was identified on the surface of the left ventricular muscle just below the anterolateral commissure of the mitral valve without regurgitation or a shunt jet by means of transesophageal echocardiography. Surgery was performed on the seventh day, but the patient's postoperative course was unstable. Some complications occurred because the vegetation existed in a unique location. Although the patient continued to have an uncontrollable infection over the subsequent course, he was discharged on the 94(th) hospital day. We present a case of a vegetation in a unique location without exposure to regurgitation or a shunt jet. This case indicates that vegetative lesions may develop even in the absence of regurgitation and shunt jets. In case of infective endocarditis where a vegetation exists in a unique location, comprehensive testing or strategy are required to treat this condition.

The Japanese marten (Martes melampus) invades houses through holes and causes excrement problems. These holes should be covered to prevent the marten's intrusion into houses. However, there is no information about what size of hole they can squeeze through. Therefore, we investigated the sizes of the holes that they could pass through using three reared individuals in summer and winter. We put a bait in an experimental box with a replaceable front panel, which had a square or round hole. The minimum passable sizes were recorded in summer. For a square hole the minimum size was 5.0 cm for each side, and for a round hole the minimum sized hole had a diameter of 5.5 cm. It is necessary to cover holes of these sizes or more to prevent their house invasion. The body weight and the hole shape had no significant effect on the minimum passable area. On the other hand, the season had a significant effect on the minimum passable areas. The shoulder seems to be the limiting factor for whether the martens can pass through the holes. Therefore, the seasonal change in the body size around the shoulder may affect the minimum passable area of holes.

Purpose: We sought to evaluate the visual measurements of coronary artery calcium (CAC) in chest CT without ECG gating, and to compare their predictive abilities for obstructive coronary artery disease (CAD). Methods: We analyzed 163 subjects who underwent both coronary and chest CT examinations at 6 centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and then classified into none (0), mild (1–99), moderate (100–400), and severe (>400) grades. Chest CT images were reconstructed with standard 5.0 mm axial slices. CAC in chest CT scans was measured using two methods: Weston score (sum of the assigned score of each vessel, range: 0–12) and number of slices showing CAC (Ca-slice#). Results: We found excellent inter-observer agreement in the estimates of the Weston score and Ca-slice# (R² = 0.913 and 0.955, respectively). When each of the two scores was divided into four levels, good agreement with the 4-grade Agatston score was observed (kappa value = 0.604 and 0.794, respectively). Of the 155 patients remaining after excluding non-diagnostic studies, obstructed CAD, defined as the presence of ≥70% stenosis on CT angiography, was found in 43 (27%). Receiver-operator characteristic curves of 4-grade hierarchies of Agatston score, Weston score, and Ca-slice# provided similar diagnostic powers to detect obstructed CAD (0.722, 0.706, and 0.718, respectively).Conclusion: The visual assessments of CAC detected by ECG non-gated chest CT scans were in good agreement with the ECG-gated Agatston score and also provided equivalent power to detect obstructive CAD. This study was registered at UMIN-CTR (identifier: UMIN000039178; registered date; Jan 16, 2020)

For achieving flame-retardant AZX912 magnesium alloy with superior mechanical properties, cast ingots were solution-treated at different temperatures of 420–525 °C prior to extrusion at 280 °C. With increasing solution treatment temperature, brittle Al2Ca intermetallic compound changed from a network-like morphology to a spheroidized shape, with an increase in hardness and became unbroken during extrusion. As the solution treatment temperature increased, cracking of Al2Ca particles during tensile deformation tended to be restricted due to hardening and spheroidizing behaviors, and tensile elongation of extruded alloys significantly enhanced from 11.2 to 19.2%. High mechanical strength was maintained with an improvement in ductility when increasing the solution treatment temperature up to 510 °C. The extruded alloy solution-treated at 510 °C exhibited a superior balance between mechanical strength and ductility, with a high ultimate tensile strength of 367 MPa and a good elongation of 16.8%.

Background Both genetic and environmental factors contribute to type 2 diabetes development. We used consomic mice established from an animal type 2 diabetes model to identify susceptibility genes that contribute to type 2 diabetes development under specific environments. We previously established consomic strains (C3H-Chr 11NSY and C3H-Chr 14NSY) that possess diabetogenic Chr 11 or 14 of the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of spontaneous type 2 diabetes, in the genetic background of C3H mice. To search genes contribute to type 2 diabetes under specific environment, we first investigated whether sucrose administration deteriorates type 2 diabetes-related traits in the consomic strains. We dissected loci on Chr 11 by establishing congenic strains possessing different segments of NSY-derived Chr 11 under sucrose administration. Results In C3H-Chr 11NSY mice, sucrose administration for 10 weeks deteriorated hyperglycemia, insulin resistance, and impaired insulin secretion, which is comparable to NSY mice with sucrose. In C3H-Chr 14NSY mice, sucrose administration induced glucose intolerance, but not insulin resistance and impaired insulin secretion. To dissect the gene(s) existing on Chr 11 for sucrose-induced type 2 diabetes, we constructed four novel congenic strains (R1, R2, R3, and R4) with different segments of NSY-derived Chr 11 in C3H mice. R2 mice showed marked glucose intolerance and impaired insulin secretion comparable to C3H-Chr 11NSY mice. R3 and R4 mice also showed impaired insulin secretion. R4 mice showed significant decreases in white adipose tissue, which is in the opposite direction from parental C3H-Chr 11NSY and NSY mice. None of the four congenic strains showed insulin resistance. Conclusions Genes on mouse Chr 11 could explain glucose intolerance, impaired insulin secretion, insulin resistance in NSY mice under sucrose administration. Congenic mapping with high sucrose environment localized susceptibility genes for type 2 diabetes associated with impaired insulin secretion in the middle segment (26.0–63.4 Mb) of Chr 11. Gene(s) that decrease white adipose tissue were mapped to the distal segment of Chr 11. The identification of diabetogenic gene on Chr 11 in the future study will facilitate precision medicine in type 2 diabetes by controlling specific environments in targeted subjects with susceptible genotypes.

Introduction. Streptozotocin- (STZ-) induced diabetes is under polygenic control, and the genetic loci for STZ susceptibility are mapped to chromosome (Chr) 11 in Nagoya-Shibata-Yasuda (NSY) mice. In addition to Chr11, other genes on different chromosomes may contribute to STZ susceptibility in NSY mice. The aim of this study was to determine whether NSY-Chr14 contributes to STZ susceptibility and contains the STZ-susceptible region. Materials and Methods. A consomic C3H-14NSY strain (R0: homozygous for NSY-derived whole Chr14 on the control C3H background), two congenic strains (R1: the region retained proximal and middle segments of NSY-Chr14 and R2: the region retained a proximal segment of NSY-Chr14), and parental NSY and C3H mice were intraperitoneally injected with a single injection of STZ at a dose of 175 mg/kg body weight at 12 weeks of age. Blood glucose levels and body weights were measured at days 0, 1, 2, 4, 5, 7, 8, and 14 after STZ injection. At day 14 after STZ injection, pancreata were dissected and fixed. Results. After STZ injection, blood glucose levels were significantly higher in R0 mice than in C3H mice. However, blood glucose levels in R0 mice were not as severely affected as those in NSY mice. In R1 and R2 mice, blood glucose levels were similar to those in C3H mice and were significantly lower than those in R0 mice. Body weights were decreased in NSY and R0 mice; however, this change was not observed in R1, R2, and C3H mice. Although islet tissues in all strains exhibited degeneration and cellular infiltration, histological changes in NSY and R0 mice were more severe than those in R1, R2, and C3H mice. Conclusions. These data demonstrated that NSY-Chr14 was a STZ-susceptible chromosome and that STZ susceptibility was mapped to the distal segment of NSY-Chr14.

Mechanisms of acute myocardial infarction caused by traumatic coronary artery injury have been reported. However, late-onset coronary artery stenosis associated with trauma is less well known. We experienced a case in which acute myocardial infarction of the right coronary artery occurred at the time of blunt chest trauma (BCT) caused by a traffic accident and an increase in coronary artery stenosis in the left anterior descending artery (LAD) branch about 1 year later. A comparison of a volume-rendering image created from enhanced-contrast computed tomography at the time of trauma and coronary angiography revealed that the trauma site and the stenotic lesion in the LAD were in very close proximity, suggesting to us that traumatic coronary artery injury without flow limitation may have developed into high-grade stenosis in the LAD 1 year later. In this case we were able to demonstrate a causal relationship between BCT and delayed coronary artery stenosis. After BCT, it is necessary to be aware of the possibility of delayed coronary artery stenosis even if coronary injury is absent in the acute phase.

Tensile properties, formability and thermal conductivity of Mg-3Zn-0.5Ca-0.5Al-xMn (x: 0.1–1.5 in wt%) sheet alloys with different Mn contents were investigated. Benefitting from dense Al-Mn nanoscale spherical precipitates, yield strength was significantly enhanced by 39 MPa with increasing the Mn content from 0.1 wt% to 1 wt%. In the meanwhile, excellent formability was maintained with Erichsen values larger than 8 mm. Further increasing the Mn content to 1.5 wt% did not contribute to strengthening due to the formation of coarse β-Mn particles. In spite of larger additive amount, thermal conductivity improved for the 1 wt% Mn added alloy compared to the 0.1 wt% Mn added alloy due to the increased amount of Al-Mn nanoscale spherical precipitates, which reduced a content of Al solute atoms. High strength (average yield strength: 180 MPa), high formability (Erichsen value: 8.5 mm) and high thermal conductivity (133 W/(m K)) were simultaneously achieved in the 1 wt% Mn added alloy.

Key Clinical Message The present case demonstrated a rare situation alternating between a repetitive atrial tachycardia (AT) and ventricular tachycardia (VT). A unique induction mechanism was noted in which the VT was induced after Wenckebach AV node conduction block following the repetitive rapid AT.

The microstructure and mechanical properties of flame-resistant AZX912 magnesium alloy extruded at different temperatures in the range of 250–400 °C were investigated. With decreasing extrusion temperature from 400 °C to 250 °C, the grain size of dynamically recrystallized grains significantly decreased from 13.6 to 1.8 µm, and the amount of fine Mg17Al12 precipitates, with sizes of 50–200 nm, increased due to dynamic precipitation. The extrusion texture, with the basal plane and 10 1 ¯ 0 > direction, mostly parallel to the extrusion direction, was remarkably strengthened as the extrusion temperature increased. This may be attributed to the enhanced activity of the prismatic slip. Nanoscale Mg17Al12 precipitates significantly enhanced the mechanical strength, but deteriorated the ductility. The bar extruded at 250 °C exhibited the highest mechanical strength, which was due to the combined effect of the remarkably refined grain structure and the large amount of nanoscale Mg17Al12 precipitates. The extrusion at 400 °C resulted in the lowest tensile elongation, which was attributed to both grain coarsening and basal texture strengthening. The bar extruded at 300 °C exhibited a good balance between mechanical strength and tensile ductility.

A hallmark of CD4+ T cell activation and immunological synapse (IS) formation is the migration of the microtubule organization center and associated organelles toward the APCs. In this study, we found that when murine CD4+ T cells were treated with a microtubule-destabilizing agent (vinblastine) after the formation of IS, the microtubule organization center dispersed and all of the major cellular organelles moved away from the IS. Cytokines were no longer directed toward the synapse but were randomly secreted in quantities similar to those seen in synaptic secretion. However, if the actin cytoskeleton was disrupted at the same time with cytochalasin D, the organelles did not shift away from the IS. These findings suggest that there is a complex interplay between the microtubules and actin cytoskeleton, where microtubules are important for directing particular cytokines into the synapse, but they are not involved in the amount of cytokines that are produced for at least 1 h after IS formation. In addition, we found that they play a critical role in mobilizing organelles to reorient toward the synapse during T cell activation and in stabilizing organelles against the force that is generated through actin polymerization so that they move toward the APCs. These findings show that there is a complex interplay between these major cytoskeletal components during synapse formation and maintenance.

In order to investigate the relationships between microstructure and mechanical properties of extruded Mg–9mass%Al–1mass%Zn–2mass%Ca (AZX912) alloy, the AZX912 alloy ingots with and without solution treatment (ST) were extruded at a low temperature of 523 K, and some extrusions were subsequently annealed at 473–573 K. The as-extruded bar exhibited dynamically recrystallized fine grains, and the amount of fine Mg17Al12 precipitates in grains. Grain coarsening occurred with an increased grain size from ~2 to ~8 μm after annealing. Solution treatment seems to affect grain coarsening during extrusion. All extruded bars exhibited basal texture, and the extruded bar annealed at 573 K exhibited slightly lower texture intensity than the others. The extruded bar exhibited high mechanical strength of 377 MPa and medium elongation of 6.6%, when solution treatment before extrusion and final annealing were not applied. The high mechanical strength was likely attributed to the small grain size, large work hardening and a great amount of fine Mg17Al12 precipitates in the extrusions.

Background and purpose We assessed the causes of death and efficacy of permanent inferior vena cava (IVC) filters for preventing new pulmonary embolisms (PE) in Japanese deep vein thrombosis (DVT) patients with or without PE. Methods and subjects We studied the clinical outcomes during the follow-up period of 1 day to 9 years (median: 18 months; mean: 28 months) in 66 of 72 consecutive patients (44 with acute PE, 27 with intrapelvic DVT, and 1 with floating femoral vein thrombosis). Fifty of 66 patients received anticoagulant therapy after the filter placement. Results Five patients died within 1 month (median 9 days) after the filter placement: three from recurrence of PE, one from cancer, and one from sepsis. Two of the three patients with recurrence of PE had preexisting intracardiac thrombi in the right atrium or main pulmonary artery before filter implantation. Ten patients died from the underlying disease (cancer: 7; brain hemorrhage: 1; amyotrophic lateral sclerosis: 1; pneumonia: 1) over 1 month after the filter placement (median follow-up period: 21 months). No new symptomatic PE recurrence was observed over 1 month after the filter placement. The 61 patients with long-term follow-up had no deterioration of DVT, and all the 31 patients who underwent multi-slice computed tomography showed no PE recurrence or filter thrombus occlusion, fracture, or migration. Conclusions Underlying diseases and preexisting intracardiac thrombi may be the determining factors for the prognosis of DVT patients. Permanent IVC filters with anticoagulant therapy may be effective for preventing death from new PE in Japanese DVT patients.

Background The clinical relevance of examining human atrial natriuretic peptide (HANP) or left atrial appendage (LAA) wall-motion velocity during sinus rhythm in paroxysmal atrial fibrillation (AF) patients has not been clearly elucidated. Methods The subjects were 38 patients with paroxysmal AF who underwent transesophageal and transthoracic echocardiography during sinus rhythm. The presence of spontaneous echocontrast (SEC) was examined with transesophageal echocardiography and LAA wall-motion velocity (LAAWV) was measured with transthoracic tissue Doppler echocardiography. Plasma HANP was measured within 3 hours after echocardiography. Results Human atrial natriuretic peptide ranged from 12 to 106 pg/mL with an average of 43 ± 24 pg/mL and had a significant correlation with LAAWV (r = −0.57) or LAA flow velocity (r = −0.41). HANP was significantly higher in patients with SEC than in patients without SEC (64 ± 29 vs. 34 ± 15 pg/mL, P = 0.008) and LAAWV was significantly lower in patients with SEC than in patients without SEC (13 ± 5 vs. 20 ± 5 cm/sec, P = 0.002). HANP >44 pg/mL had a sensitivity of 73% and specificity of 89% for diagnosing SEC. SEC was more frequently observed (73%) in patients with HANP >44 pg/mL and/or LAAWV

A 68-year-old woman exhibited an increasingly protruding mass on the left heart border on chest X-ray. Transthoracic echocardiography revealed an echo-free mass in the anterior pericardial space. Transesophageal echocardiography revealed blood flow from the proximal left anterior descending coronary into a large coronary artery aneurysm measuring 61 mm × 51 mm in diameter and a quadricuspid aortic valve with a small cusp between the left and right coronary cusps. Coronary angiography demonstrated the presence of a coronary aneurysm connected to the proximal left coronary anterior descending artery. A giant coronary artery aneurysm and pulmonary artery fistulas extending from the left and right coronary arteries were confirmed by surgeons and successfully treated with surgery.

Both genetic factors and diabetogenic environmental factors, such as a high-sucrose diet (HSD), are involved in the development of type 2 diabetes. In this study, the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of type 2 diabetes and C3H mice used as controls, were fed a HSD, a high-fat diet (HFD) or a regular diet (RD) from weaning. In C3H mice, HFD significantly increased body weight gain, but maintained glucose tolerance. In contrast, in NSY mice, HSD resulted in increased body weight gain and liver steatosis and increased glucose intolerance to a greater extent than HFD. Furthermore, we performed DNA microarray analysis to detect differences in hepatic gene expression levels in both strains under HSD. We then performed RT-PCR analysis on selected genes to evaluate basal expression level under RD and changes under HSD conditions. HSD-fed NSY, but not C3H mice, exhibited increased hepatic expression levels of Pparg2, an isoform of Pparg as well as G0s2, a target of Pparg, which are known to be adipocyte-specific genes. Compared to RD-fed C3H mice, hepatic expression levels of Kat2b (transcriptional regulation), Hsd3b5 (steroid hormone metabolism) and Cyp7b1 (bile acid metabolism) were initially lower in RD-fed NSY mice, and were further decreased in HSD-fed NSY mice. Expression of Metallothionein (Mt1) and Metallothionein 2 (Mt2) was significantly lower in NSY mice compared to C3H mice, irrespective of dietary condition. These data suggest that elucidation of this heterogeneity in response to HSD might contribute to further understanding of the gene-environment interactions leading to diabetes in humans.

The quantitative trait locus (QTL) mapping in segregating crosses of NSY (Nagoya-Shibata-Yasuda) mice, an animal model of type 2 diabetes, with nondiabetic strain C3H/He mice has identified diabetogenic QTLs on multiple chromosomes. The QTL on chromosome 11 (Chr11) (Nidd1n) showing the largest effect on hyperglycemia was confirmed by our previous studies with homozygous consomic mice, C3H-11NSY, in which the NSY-derived whole Chr11 was introgressed onto control C3H background genes. C3H-11NSYmice also showed a streptozotocin (STZ) sensitivity. In the present study, we constructed heterozygous C3H-11NSYmice and the phenotypes were analyzed in detail in comparison with those of homozygous C3H-11NSYand C3H mice. Heterozygous C3H-11NSYmice had significantly higher blood glucose levels and STZ sensitivity than those in C3H mice. Hyperglycemia and STZ sensitivity in heterozygous C3H-11NSYmice, however, were not as severe as in homozygous C3H-11NSYmice. The body weight and fat pad weight in heterozygous C3H-11NSYmice were similar to those in C3H and homozygous C3H-11NSYmice. These data indicated that the introgression of Chr11 of the diabetes-susceptible NSY strain onto diabetes-resistant C3H caused marked changes in the glucose tolerance and STZ susceptibility even in a heterozygous state, and suggested that the mode of inheritance of a gene or genes on Chr11 for hyperglycemia and STZ sensitivity is additive.

One very striking feature of T-cell recognition is the formation of an immunological synapse between a T cell and a cell that it is recognizing. Formation of this complex structure correlates with cytotoxicity in the case of killer (largely CD8 + ) T-cell activity, or robust cytokine release and proliferation in the case of the much longer lived synapses formed by helper (CD4 + ) T cells. Here we have used electron microscopy and 3D tomography to characterize the synapses of antigen-specific CD4 + T cells recognizing B cells and dendritic cells at different time points. We show that there are at least four distinct stages in synapse formation, proceeding over several hours, including an initial stage involving invasive T-cell pseudopodia that penetrate deeply into the antigen-presenting cell, almost to the nuclear envelope. This must involve considerable force and may serve to widen the search for potential ligands on the surface of the cell being recognized. We also show that centrioles and the Golgi complex are always located immediately beneath the synapse and that centrioles are significantly shifted toward the late contact zone with either B lymphocytes or bone marrow-derived dendritic cells such as antigen-presenting cells, and that there are dynamic, stage-dependent changes in the organization of microtubules beneath the synapse. These data reinforce and extend previous data on cytotoxic T cells that one of the principal functions of the immunological synapse is to facilitate cytokine secretion into the synaptic cleft, as well as provide important insights into the overall dynamics of this phenomenon.

Diabetes mellitus (DM) is one of the major non-genetic risk factors for Alzheimer disease (AD). However, the mechanism by which DM increases the risk of AD has not been elucidated. Here, we summarize recent findings to address this question. Whereas neuropathological studies in humans suggest that DM does not increase Aβ accumulation in the brain (a major hallmark of AD), earlier works in animal models show that Aβ does accumulate. Therefore, alternate mechanisms might exist. Recent studies using the human brain indicate that insulin signaling is impaired in the AD brain. In neurons, this insulin signaling plays a key role in modulating synaptic function and neuronal senescence besides regulating tau phosphorylation, another hallmark of AD. On the other hand, in cerebrovessels, DM causes vascular remodeling, which involves increased RAGE (receptor for advanced glycation endproducts) expression, and AD is associated with cerebrovascular amyloid angiopathy (CAA). Our recent study involving AD mice with DM has revealed that a vicious circle underlies the interaction between AD and DM. Interestingly, in our mouse model, AD increased RAGE expression, and DM worsened CAA. The contribution of vascular factors such as RAGE expression and CAA to the impairment of insulin signaling will be discussed. This impaired insulin signaling might be a possible link between AD and DM. Moreover, insulin signaling is also involved in the mechanism of aging, decreasing with an increase in age. An identification of the mechanism whereby DM modifies the pathological condition of AD through the modulation of insulin signaling is required to develop potential therapeutics for AD not only with but also without DM.

Aims To investigate the clinical outcomes of paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) in patients on dialysis. Methods and results Between May 2004 and December 2008, 95 patients on dialysis with 124 lesions were treated with PES alone, and were compared to 184 patients on dialysis with 244 lesions treated with SES alone, retrospectively. One-year major adverse cardiac event (MACE) including stent thrombosis, target lesion revascularisation (TLR), myocardial infarction (MI) and cardiac death were compared. Baseline characteristics were similar except for previous CABG (p = 0.02) and reference vessel diameter (p = 0.04). During hospitalisation, all cause death was more frequently observed in the PES group (p = 0.004). In-hospital MACE was not significantly different (p = 0.8). The incidence of 1-year MACE in the PES group was lower than that in the SES group (14.7%, 28.3%, p = 0.04), mainly due to the reduction of TLR (11.6%, 25.0%, p = 0.03). Rates of stent thrombosis (0%, 2.7%, p = 0.1), MI (1.1%, 3.8%, p = 0.2), and cardiac death (3.2%, 4.4%, p = 0.6) were not significantly different. Conclusions PES appears to be more efficient in reducing angiographic and clinical restenosis in dialysis patients compared with SES.

SummaryStenosis of the left main coronary artery (LMCA) due to extrinsic compression, producing symptoms of myocardial ischemia, is called left main compression syndrome. We report on a 43-year-old male with acute coronary syndrome who developed left main compression syndrome while waiting for a lung transplantation secondary to interstitial pneumonia, but underwent successful LMCA stenting as emergent treatment. Coronary angiography 3 months after the operation showed good stent patency in the LMCA, and the clinical course was favorable.

Diabetogenic loci for type 2 diabetes have been mapped to mouse chromosome (Chr) 11 and 14 in the Nagoya-Shibata-Yasuda (NSY) mouse, an animal model of type 2 diabetes. We aimed to obtain direct evidence of these genes on each chromosome and to clarify their function and interaction in conferring susceptibility to type 2 diabetes.We established three consomic strains homozygous for diabetogenic NSY-Chr11, NSY-Chr14 or both on the control C3H background (C3H-11(NSY), C3H-14(NSY) and C3H-11(NSY)14(NSY), respectively), and monitored diabetes-related phenotypes longitudinally. The glucokinase gene was sequenced as a positional candidate gene on Chr11.C3H-11(NSY) mice showed hyperglycaemia associated with impaired insulin secretion and age-dependent insulin resistance without obesity. C3H-14(NSY) mice exhibited hyperglycaemia mainly due to insulin resistance, with a slight increase in percentage body fat. C3H-11(NSY)14(NSY) double consomic mice showed marked hyperglycaemia and obesity, which was not observed in single consomic strains. Sequences of the glucokinase gene were allelically variant between NSY and C3H mice.These data provide direct evidence that Chr11 and Chr14 harbour major susceptibility genes for type 2 diabetes. These two chromosomes interact to cause more severe hyperglycaemia and obesity, which was not observed with the presence of either single chromosome, indicating different modes of gene-gene interaction depending on the phenotype. Marked changes in the phenotypes retained in the consomic strains will facilitate fine mapping and the identification of the responsible genes and their interaction with each other, other genes and environmental factors.

Background It is unknown whether adenosine triphosphate disodium (ATP) administration during primary percutaneous coronary intervention (PCI) is useful in anterior acute myocardial infarction (AMI). Methods The study was a prospective, non-randomized, open-label trial. Primary PCI was successfully performed in 204 consecutive patients with first anterior AMI. ATP at a mean dose of 117 μg/kg/min for 45 min on an average was infused intravenously during PCI in 100 patients (Group 1). In the other 104 patients, normal saline was administered (Group 2). ST-segment resolution (STR) was estimated 90 min after recanalization. The no-reflow ratio was measured 2 weeks later, using intravenous myocardial contrast echocardiography. Left ventricular ejection fraction (LVEF), LV regional wall motion (LVRWM), and LV end-diastolic volume index (LVEDVI) were measured 6 months later. Results Baseline patient characteristics of the two groups were similar, including TIMI risk scores. Significant STR (≧50% resolution compared to baseline) (66% versus 50%; Group 1 versus Group 2, p =0.02), no-reflow ratio (24% versus 34%, indicated by mean values, p =0.02), LVEF (61% versus 55%, p =0.0007), LVRWM (−1.56 versus −2.05, using the SD/chord, p =0.0001), and LVEDVI (60 ml/m 2 versus 71 ml/m 2 , p =0.0007) were significantly better in Group 1, and the no-reflow ratio, LVEF, LVRWM and LVEDVI were significantly better in ATP-administered patients, regardless of antecedent angina or advanced age. ATP Administration was consistently identified as a significant determinant for STR, no-reflow ratio, LVEF, LVRWM, and LVEDVI. Conclusions Intravenous ATP administration during reperfusion is an independent determinant of STR and the no-reflow ratio, and LVEF, LVRWM, and LVEDVI at 6 months after primary PCI.

Summary Background and purpose Administration of adenosine attenuates myocardial stunning after reperfusion in a canine experimental ischemic model. However, it is unknown whether administration of adenosine triphosphate disodium (ATP) during reperfusion can attenuate myocardial stunning after coronary recanalization in patients with acute myocardial infarction (MI). Therefore, we sought to elucidate the effects of ATP administration on serial changes of left ventricular systolic function before and after coronary recanalization. Methods In 27 patients with first ST-elevation acute anterior MI, in whom primary percutaneous coronary intervention (PCI) was completed within 10 h after symptom onset, ATP at a mean rate of 103 μg/kg/min (n = 16) or normal saline (n = 11) was intravenously administered for 1 h during reperfusion. Left ventricular regional wall motion within the initially severely ischemic region was serially analyzed using the standard wall motion score index (WMSI) by transthoracic echocardiography. Results Means of WMSIs were similar shortly before primary PCI in both groups (2.79 in ATP group and 2.69 in controls). They changed to 2.56 and 2.22 shortly after PCI, 2.49 and 2.39 on day 2, 2.34 and 2.30 on day 3, 2.19 and 2.25 on day 10, and 1.85 and 2.02, 6 months later, respectively. Transient improved regional wall motion within the initially severely ischemic region was observed shortly after PCI in controls (10.3% of observed segments); however, it was significantly suppressed in the ATP group (2.55%). The percent recovery of WMSI on day 10, which was defined as WMSI on day 10 normalized by improvement of WMSI for 6 months, was 63.8% in ATP group and 65.7% in controls, implying ATP administration could not reduce myocardial stunning by day 10 after primary PCI. Conclusions The high-dose administration of ATP during primary PCI prevented transient improved wall motion shortly after coronary recanalization rather than preventing left ventricular stunning. These results suggest that ATP can prevent reperfusion injury during primary PCI.

Many mammal species can cause crop damage simultaneously at one location; therefore, we designed and tested three fence types that targeted medium and large mammals. Ten mammal species were targeted (Japanese hare, raccoon dog, red fox, Japanese marten, masked palm civet, Eurasian badger, Asiatic black bear, wild boar, sika deer, and Japanese macaque). All three fences were electric and an expanded metal lath carried the current. To prevent invasions through lower gaps, the gap between the expanded metal lath and the ground surface was closed using a corrugated polyvinyl chloride sheet as an insulating material. After the fences were constructed, infrared-triggered cameras were set up both inside and outside the fences. All three fences prevented invasion by the targeted species. Overall, these fences had high practical value for nine of the targeted species; the exception was the Asiatic black bear, which was observed only once.

Using a generalized linear mixed model approach, we determined the most important risk factors affecting the probability of damage by sika deer in a forest plantation in Japan. Candidate risk factors included tree species, stand age, peripheral dwarf bamboo community, topographical factors, snow depth, and human disturbance factors. Based on this model, we developed a risk map of forest damage. The model indicated that the most important risk factor was stand age, followed by tree species and maximum snow depth. Our predictive model has practical use due to its high classification accuracy (83.9%). To decrease damage from sika deer, an afforestation plan that incorporates these factors should be implemented. Because it is based on common, forest GIS data that have recently been compiled by several local governments in Japan, our modeling method of deer damage can easily be adapted to other areas.

This study examined the role of left atrial (LA) appendage wall velocity (LAAWV) measurement in addition to LA size for the noninvasive assessment of thrombogenesis in patients with atrial fibrillation (AF) and normal plasma D-dimer levels.In 58 non-valvular AF patients, LAAWV and the LA volume index (LAVI) were determined by transthoracic echocardiography. LA appendage flow velocity and severity of spontaneous echo contrast (SEC) were determined by transesophageal echocardiography.LAAWV was strongly correlated with LA appendage flow velocity (r = 0.82), and LAVI was weakly correlated with LA appendage flow velocity (r = -0.37). As SEC severity increased, LAAWV decreased (p0.001) and LAVI increased (p0.001). Among 52 patients with normal D-dimer levels, LAAWV10 cm/s had 71 % sensitivity and 94 % specificity for diagnosing severe SEC. Severe SEC was not found in 18/32 large LAVI patients (34 mL/m(2)), but 17 of the 18 patients (94 %) had LAAWV10 cm/s. Severe SEC was found in 3/20 patients with normal LAVI, but all of them showed LAAWV10 cm/s.The noninvasive measurement of transthoracic LAAWV in addition to LA volume is clinically relevant for quantitatively assessing thrombogenesis in AF patients with normal D-dimer levels.

We assessed sexual variation in food quality and gut macrostructure in adult male and pregnant female sika deer, Cervus nippon (Temminck, 1838), in Japan during winter. These variations might have important implications relative to sexual differences in habitat use, forage acquisition, and digestive strategy. According to the sexual dimorphism-body size hypothesis the larger males would feed on poorer forage and have heavier stomach contents and heavier intestine contents and longer intestines than smaller females. However, the food quality in rumen contents of males was higher than, or at least similar with, that of pregnant females. In correspondence to food quality, the relative weights of stomach contents and intestines with contents, the relative lengths of intestines to the lengths of body and total intestines in pregnant females were similar to adult males. The relative weights of omasum and abomasum tissues in pregnant females were greater than in males. Our findings suggest sexual differences in feeding strategy in sika deer in Japan during winter. To meet greater nutritional demands of high metabolic rate and gestation, pregnant females seemed to maintain a greater volume of digesta in guts and had more stomach tissues than expected by the sexual dimorphism-body size hypothesis to compensate for poorer forage quality.

We carried out this study to clarify the relationships between the seasonal changes of bark stripping and food quality, and between bark-stripping intensity and bark nutrition with age of veitch fir (Abies veitchii) by sika deer (Cervus nippon) in the northern Mount Fuji district, from June 2000 to July 2003. We found that sika deer gnawed and ate all of the bark stripped, and a seasonal change in bark stripping occurred from December to May or June with a peak in March–April. The stripping period largely overlapped with the periods of low food availability and poor food nutrition (indicated by fecal chemical component index) of sika deer, from January to April. Both bark nutritional quality and bark-stripping intensity related to stand age and tree size of veitch fir negatively. Consequently, bark-stripping intensity related to bark nutritional quality positively. February is the worst forage period in terms of both quantity (due to deep snow) and quality (indicated by fecal chemical components). There was a time lag of 1 to 2 months in the peak of bark stripping in March–April when compared with the poor forage period in February. This time lag may suggest that sika deer need more nutritious and easily digested food from March due to increased nutrient demands that result from depleted body condition in both sexes, gestation of pregnant females, and the recovery of active metabolism.

Sexual size dimorphism was found in many Apodemus species, and males were dominant in many cases (review, Montgomery 1989). However, it was not found in wild populations of A. speciosus (Imaizumi 1962; Miyao and Mori 1967). Imaizumi (1962) did not find any sexual difference in external morphology (head and body length, ear length, and hind foot length) in the Izu, Miura, and Izuoshima populations. Imaizumi (1962) determined the age class of each sample by checking molar wear, and showed that males and females belonging to the same age class were not different in these external traits. However, Oh and Mori (1998) showed sexual difference in growth of body weight and external morphology of A. speciosus under captivity. There was no sexual difference at birth for all characters, but significant differences were found at nearly 40 days of age in body weight, head and body length, and tail length. Thus, there is inconsistency in sexual dimorphism between wild and captive A. speciosus. It is therefore, necessary to clarify the sexual dimorphism in wild populations of A. speciosus.

We report a case of a 56-year-old man with a cardiac tumor, which grew and spread rapidly in the right heart. Using transthoracic echocardiography (TTE) in the substernal window, a transvenous biopsy of the tumor was performed safely. The tissue diagnosis revealed a diffuse large B cell lymphoma. After undergoing chemotherapy, the tumor was completely cured and the patient continues to be in good health. A biopsy using TTE in the substernal window may be a useful method to diagnose right-sided extensive tumors.

Browsing by sika deer (Cervus nippon Temminck) on hinoki cypress (Chamaecyparis obtusa (Sieb. et Zucc.) Endl.) was monitored for approximately 3 years on 300 trees at three sites on Mount Takahara, central Japan. We investigated the seasonal change in browsing on hinoki cypress in relation to the availability of other food plants (dominated by Sasa nipponica Makino et Shibata) and preferred food plants (deciduous broad leaves). Browsing occurred mostly from November to April, while no browsing damage occurred from June to October. Browsing was observed in November, even when the amount of other food plants did not decrease. Therefore, the cause of browsing cannot be fully explained by a decreased availability of other food plants. Comparison of fecal composition and food availability showed that deer had a preference for deciduous broad leaves. The availability of these preferred plants decreased in November and increased in May. Chemical analysis of the hinoki cypress and deciduous broad leaves (crude protein and neutral detergent fiber) showed that the quality of deciduous broad leaves decreased in November, and as a result the quality of hinoki became higher than that of the deciduous broad leaves. Browsing on hinoki cypress occurred when the availability of deciduous broad leaves decreased, and vice versa. These results suggest that the availability of preferred food plants influences browsing on hinoki cypress by sika deer.

Bark stripping of hinoki cypress (Chamaecyparis obtusa (Sieb. et Zucc.) Endl.) by sika deer (Cervus nippon Temminck) was monitored for 4 years on approximately 300 trees at three sites on Mt Takahara, central Japan. We investigated the effects of snow cover and food availability on seasonal and yearly changes in bark stripping. Bark stripping occurred during snowy periods (January and February) when less food was available because of the snow cover. The most serious bark stripping was observed in 1996 when the snow was the deepest and food resources were the poorest among the 4 years of the study. In contrast, bark stripping did not occur in 1999 when the snow was thin and, consequently, more food was available. These results suggest that snow cover and food avail-ability influence the occurrence and intensity of bark stripping both seasonally and annually.

Linkage analysis and congenic mapping have localized 18 loci (Idd1-18) that contribute to the development of autoimmune type 1 diabetes in the nonobese diabetic (NOD) mouse. By using a congenic NOD strain which possesses recombinant MHC from a closely related CTS strain, a susceptible region (Idd16) was mapped to the segment adjacent to, but distinct from class II A and E genes (Idd1). The tumor necrosis factor alpha gene (Tnf), which is located within the Idd16 region, has been suspected to be a candidate gene for type 1 diabetes in the NOD mouse. Although the protein-coding region in Tnf has been sequenced in the NOD mouse and its related strains, the complete upstream region (approximately 1400 bp, including the 5'-untranslated region) has not yet been studied. To study the possible contribution of the transcriptional regulation of Tnf to susceptibility to type 1 diabetes, we determined the complete nucleotide sequences of the NOD strain and its related strain, CTS, in comparison with the non-diabetic control strain, C57BL/6. The nucleotide sequence of the 5'-upstream region in the NOD mouse was identical to that in the C57BL/6 mouse, but different from that in the CTS mouse. In particular, a C to A substitution at position 3408 in the CTS mouse creates a new GATA family binding site, which may be responsible for the lower incidence of type 1 diabetes in the NOD. CTS-H-2 congenic strain despite the presence of the same class II MHC.

The aim of this study was to clarify whether atherosclerotic plaque morphology, as defined by quantitative analysis with intravascular ultrasound (IVUS) images, was related to the immunohistochemical findings. Twenty-five coronary lesions in 25 patients who had ultrasound guidance during directional coronary atherectomy (DCA) were enrolled. The lesions retrieved by DCA were analyzed and divided into 3 groups (lesions infiltrated with both macrophages and lymphocytes: group IML; lesions infiltrated with macrophages but not lymphocytes: group IM; and non-infiltrated lesions: group NI). The mean plaque echo level divided by the mean adventitia echo level (MPEL/MAEL) and the heterogeneity of the distribution of plaque echo levels (HDPEL) were calculated. The proportion of patients with acute coronary syndromes was significantly different among the groups: IML (n=14), IM (n=5), and NI (71%, 0% and 17%, respectively; p

Type 1 diabetes is characterized by T-cell-mediated autoimmune destruction of pancreatic β-cells. Currently, approximately 50 type 1 diabetes susceptibility genes or chromosomal regions have been identified. However, the functions of type 1 diabetes susceptibility genes in T cells are elusive. In this study, we evaluated the correlation between type 1 diabetes susceptibility genes and T-cell signaling. The expression levels of 22 candidate type 1 diabetes susceptibility genes in T cells from nonobese diabetic (NOD), control C57BL/6 (B6), and NOD-control F1 hybrid mice were analyzed in response to 2 key immunoregulatory cytokines: interleukin-2 (IL-2) and transforming growth factor β (TGF-β). Exogenous gene expression studies were also performed in EL4 and Jurkat E6.1 T-cell lines. Significant differences in the expression of Clec16a, Dlk1, Il2, Ptpn22, Rnls, and Zac1 (also known as Plagl1) were observed in T cells derived from the 3 strains of mice, and TGF-β differentially influenced the expression of Ctla4, Foxp3, Il2, Ptpn22, Sh2b3, and Zac1. We found that TGF-β induced Zac1 expression in both primary T cells and EL4 cells and that exogenous expression of Zac1 and ZAC1 in T-cell lines altered the expression of Il2 and DLK1, respectively. The results of our study indicate the possibility that additional genetic pathways underlying type 1 diabetes susceptibility, including those involving Clec16a, Dlk1, Rnls, Sh2b3, and Zac1 under IL-2 and TGF-β signaling in T cells, may be shared between human and NOD mice.