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Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Extensive full-thickness defects of both the upper and the lower eyelids continue to be a challenge for reconstructive surgeons. Ectropion of the lower eyelid and an unnatural canthal shape are pitfalls to be avoided in total eyelid reconstruction. We here present a case in which an extensive full-thickness defect of the upper and lower eyelids after tumor resection was successfully reconstructed by means of periosteal flap canthoplasty from the infraorbital margin. A 73-year-old woman had in situ melanoma on her left eyelids. The lids were almost completely removed as a result of tumor resection. The conjunctival defect was covered with oral mucosa. And the tarsal layer was reconstructed with auricular cartilage. A periosteal flap pedicled at the origin of the lateral canthal tendon was harvested from the infraorbital margin. The flap was fixed with sutures on the cartilage graft for the lower eyelid. The cartilage graft for the upper eyelid was sutured laterally on the basal portion of the periosteal flap as the lateral canthus. The skin defect of the upper eyelid was covered with a bipedicled orbicularis oculi flap and skin graft. The lower eyelid was reconstructed with a combination of an angular artery transposition flap and a cheek rotation flap. Thirteen months after the surgery, the reconstructed eyelids had good function without ectropion. And the reconstructed canthus had a natural sharp shape. Total eyelid reconstruction using periosteal flap canthoplasty combined with auricular cartilage and oral mucosa grafts is useful for extensive full-thickness defects of the upper and lower eyelids. Level of evidence: Level V, therapeutic study.

Introduction: Those who are considered to be low risk in short term such as 10 year risk actually have high risk of cardiovascular disease for the remaining lifespan at younger age. Absolute risk of Lifetime risk (LTR) is more useful and understandable for lay audience compared with short term risk or relative risk. CKD (Chronic Kidney Disease) is global burden of cardiovascular disease (CVD) and hypertension is damaging complication of CKD for CVD. To date, there have been no reports of LTR with the outcome of CVD death based on CKD in Asian population. Hypothesis: We sought to estimate LTR of CVD death stratified by the status of CKD and hypertension. Methods: We used data from EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) which is designed to pool data from nationwide and regional cohort studies in Japan. Modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death at each index age starting from 40 years according to CKD stratified by Hypertension. Participants were classified into four groups, which were those without CKD and hypertension (CKD-/HT-), those with CKD but without hypertension (CKD+/HT-), those without CKD but with hypertension (CKD-/HT+), and those with both CKD and hypertension (CKD+/HT+). Results: A total of 44,582 participants from 8 cohorts was included in the analysis. Mean follow-up period was 14.9 years with 662,488 person years and total CVD death was 1,035 in men and 1,160 in women. The LTRs at the index age of 40 years increased in groups with CKD and/or HT as follows: 12.6% (95% confidence interval: 9.4 - 14.5%) in CKD-/HT- group, 20.6% (11.4 - 25.9%) in CKD+/HT- group, 23.2% (19.9 - 25.2%) in CKD-/HT+ group, and 27.9% (21.7 - 32.9%) in CKD+/HT+ group for men; 11.3%(8.9 - 13.2%), 17.4%(13.2 - 20.4%) , 17.8%(15.3 - 19.8%) , and 22.7%(19.5 - 25.2%) for women. Conclusions: We observed that complication of CKD and hypertension are collectively responsible for lifetime risk due to CVD death. Management of blood pressure from an early age is important to reduce CVD mortality in CKD patients.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): H20–Junkankitou [Seishuu]–Ippan–013; H23–Junkankitou [Seishuu]–Ippan–005; H26-Junkankitou [Seisaku]-Ippan-001; H29–Junkankitou–Ippan–003 and 20FA1002 OnBehalf EPOCH-JAPAN Introduction Absolute risk of Lifetime risk (LTR) is useful estimate for risk communication compared with short term risk or relative risk especially for young people. Proteinuria is leading cause of end-stage kidney disease (ESKD) and independent risk factor for cardiovascular disease (CVD). Although nonproteinuric renal disease is global burden of ESKD, it has been poorly focused. To date, there have been no reports of impact of proteinuria and low eGFR on LTR with the outcome of CVD death in Asian population. Purpose We aimed to estimate LTR of CVD death stratified by the status of proteinuria and low eGFR. Methods We used modified Kaplan-Meier approach to estimate the remaining lifetime risk of cardiovascular death based on EPOCH-JAPAN(Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) database. LTR was estimated at each index age starting from 40 years for those with proteinuria and without proteinuria stratified by low eGFR, which is defined as eGFR Results A total of 47,292 participants from 9 cohorts was included in the analysis. Mean follow-up period was 14.6 years with 690,463 person years and total CVD death was 1,075 in men and 1,193 in women. The LTRs at the index age of 40 years were as follows: 17.7% (95% confidence interval: 15.4 – 19.0%) in Proteinuria (-)/Low eGFR (-) group, 26.2% (20.2 – 31.1%) in Proteinuria (-)/low eGFR (+) group, 24.5% (15.1 – 29.3%) in Proteinuria (+) group for men; 15.3%(13.7 – 16.5%), 29.9%(14.7 – 46.8%) , 28.3%(19.4 – 34.7%) for women. Conclusions We observed that those without proteinuria with low eGFR have equivalently high LTR with those with proteinuria. These results indicate that even in the absence of proteinuria, low eGFR has high impact on LTR. Lifestyle modification from young age is necessary to prevent from renal dysfunction.

Although various production methods for 3D vascularised tissues have been developed, constructing capillary-like structures branching from perfusable large channels remains difficult. This study describes a method to fabricate tube-shaped 3D liver-like tissue (tubular liver tissue) with large channels and capillary-like structures using a perfusion device. The perfusion device functions as an interface between the tissue and an external pump, as it has connectors equipped with anchors that hold the tissue in response to its shrinkage, which is accompanied by the self-organisation of capillary-like structures. Histological analysis revealed that perfusion via the large channel induced capillary formation around the channel and maintained proper tissue functions. Accompanied by structural examinations, global gene expression analysis supported this finding; specifically, genes involved in angiogenesis were enriched in the perfused condition. Furthermore, we confirmed the penetrability of the capillary-like structures by infusing India ink, as well as substance exchange by measuring the amounts of secreted albumin. These lines of evidence indicate that our method can be used to construct 3D tissues, which is useful for fields of in vitro tissue regeneration for drug development and regenerative medicine.

International audience; Meiotic recombination starts with the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to PRDM9-binding sites. The molecular steps occurring from PRDM9 binding to DSB formation are unknown. Using proteomic approaches to find PRDM9 partners, we identified HELLS, a member of the SNF2-like family of chromatin remodelers. Upon functional analyses during mouse male meiosis, we demonstrated that HELLS is required for PRDM9 binding and DSB activity at PRDM9 sites. However, HELLS is not required for DSB activity at PRDM9-independent sites. HELLS is also essential for 5-hydroxymethylcytosine (5hmC) enrichment at PRDM9 sites. Analyses of 5hmC in mice deficient for SPO11, which catalyzes DSB formation, and in PRDM9 methyltransferase deficient mice reveal that 5hmC is triggered at DSB-prone sites upon PRDM9 binding and histone modification, but independent of DSB activity. These findings highlight the complex regulation of the chromatin and epigenetic environments at PRDM9-specified hotspots.

Meiotic recombination is essential for faithful segregation of homologous chromosomes during gametogenesis. The progression of recombination is associated with dynamic changes in meiotic chromatin structures. However, whether Sycp2, a key structural component of meiotic chromatin, is required for the initiation of meiotic recombination is still unclear in vertebrates. Here, we describe that Sycp2 is required for assembly of the synaptonemal complex and early meiotic events in zebrafish spermatocytes. Our genetic screening by N-ethyl-N-nitrosourea mutagenesis revealed that ietsugu (its), a mutant zebrafish line with an aberrant splice site in the sycp2 gene, showed a defect during meiotic prophase I. The its mutation appeared to be a hypomorphic mutation compared to sycp2 knockout mutations generated by TALEN mutagenesis. Taking advantage of these sycp2 hypomorphic and knockout mutant lines, we demonstrated that Sycp2 is required for the assembly of the synaptonemal complex that is initiated in the vicinity of telomeres in wild-type zebrafish spermatocytes. Accordingly, homologous pairing, the foci of the meiotic recombinases Dmc1/Rad51 and RPA, and γH2AX signals were largely diminished in sycp2 knockout spermatocytes. Taken together, our data indicate that Sycp2 plays a critical role in not only the assembly of the synaptonemal complex, but also early meiotic recombination and homologous pairing, in vertebrates., Author summary Meiosis is an essential type of cell division whose purpose is to produce gametes, such as eggs and sperm, for sexually reproducing eukaryotes. Most cells in the human body are diploid cells containing two homologous copies of each chromosome. Meiosis halves the genetic contents of diploid cells and produces haploid gametes with a single copy of each homologous chromosome pair. The faithful transmission of chromosomes is one of the main tasks in meiosis, since extra or missing chromosomes are common causes of genetic disorders, birth defects and infertility. Prior to proper segregation, homologs must pair up and be physically connected. This is achieved by homologous recombination initiated by programmed DNA double-strand breaks. Since it can be deleterious to cells, this initiation step is highly regulated by factors that are not fully understood. In this study, we found that Sycp2, a structural component of meiotic chromatin in metazoans, is essential for the initiation of homologous recombination, meiotic chromatin organization, and homologous pairing in zebrafish. These findings support recent biochemical studies that Sycp2 and Sycp3 serve as a vertebrate counterpart of S. cerevisiae Red1.

Background: Daprodustat (GSK1278863) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for treatment of anemia associated with chronic kidney disease (CKD). The effect of daprodustat in Japanese CKD patients with anemia has not been previously investigated. Methods: We evaluated the relationship between daprodustat dose and hemoglobin response in Japanese patients on hemodialysis (HD) with anemia in a 4-week, phase II, double-blind, placebo-controlled study. After interrupting their erythropoiesis-stimulating agent for between 2 and 8 weeks, subjects with hemoglobin 8.5-10.5 g/dL were randomized to placebo or daprodustat 4, 6, 8, or 10 mg orally once daily. Hemoglobin, erythropoietin (EPO), and vascular endothelial growth factor (VEGF) levels during therapy were evaluated. Results: Eighty-six of 97 randomized subjects completed the study. Mean baseline hemoglobin ranged from 9.68 to 9.92 g/dL across groups. After 4-week administration, mean hemoglobin changes were -0.28, -0.01, 0.54, and 0.97 g/dL in the 4, 6, 8, and 10 mg groups, respectively, as compared to -1.41 g/dL for placebo. Dose-dependent increase in plasma EPO concentration were observed up to 8 mg, with the 10 mg dose responses being similar to 8 mg. Plasma VEGF concentrations were minimally changed, even though 5 subjects treated with 6-10 mg reached EPO >500 mIU/mL. Conclusion: Daprodustat 4-10 mg once-daily produced dose-dependent increase in hemoglobin relative to placebo in Japanese HD subjects. The doses evaluated in the study have moderately increased endogenous EPO without changes in circulating VEGF levels.

The acidic phospholipid cardiolipin (CL) is localized on polar and septal membranes and plays an important physiological role in Bacillus subtilis cells. ClsA, the enzyme responsible for CL synthesis, is also localized on septal membranes. We found that GFP fusion proteins of the enzyme with NH2-terminal and internal deletions retained septal localization. However, derivatives with deletions starting from the COOH-terminus (Leu482) ceased to localize to the septum once the deletion passed the Ile residue at 448, indicating that the sequence responsible for septal localization is confined within a short distance from the COOH-terminus. Two sequences, Ile436-Leu450 and Leu466-Leu478, are predicted to individually form an amphipathic α-helix. This configuration is known as a membrane targeting sequence (MTS) and we therefore refer to them as MTS2 and MTS1, respectively. Either one has the ability to affect septal localization, and each of these sequences by itself localizes to the septum. Membrane association of the constructs of this enzyme containing the MTSs was verified by subcellular fractionation of the cells. CL synthesis, in contrast, was abolished after deleting just the last residue, Leu482, in the COOH-terminal four amino acid residue sequence, Ser-Pro-Ile-Leu, which is highly conserved among bacterial CL synthases.

Garlic (Allium sativum L.) has been used worldwide as a food and for medicinal purposes since early times. Garlic cultivars exhibit considerable morphological diversity despite the fact that they are mostly sterile and are grown only by vegetative propagation of cloves. Considerable recombination occurs in garlic genomes, including the genes involved in secondary metabolites. We examined the genomic DNAs (gDNAs) from garlic, encoding alliinase, a key enzyme involved in organosulfur metabolism in Allium plants. The 1.7-kb gDNA fragments, covering three exons (2, 3, and 4) and all four introns, were amplified from total DNAs prepared from garlic samples produced in Asia and Europe, leading to 73 sequences in total: Japan (JPN), China (CHN), India (IND), Spain (ESP), and France (FRA). The exon sequences were highly conserved among all the sequences, probably reflecting the fully functional alliinase associated with the flavor quality. Distinct intraspecific variations were detected for all four intron sequences, leading to the haplotype classifications. A close relationship between JPN and CHN was observed for all four introns, whereas IND showed a more divergent distribution. ESP and FRA afforded clearly different variants compared with those from Asian sequences. The present study provides information that could be useful in the development of an additional molecular marker for garlic authentication and quality control.

During meiosis, a programmed induction of DNA double-strand breaks (DSBs) leads to the exchange of genetic material between homologous chromosomes. These exchanges increase genome diversity and are essential for proper chromosome segregation at the first meiotic division. Recent findings have highlighted an unexpected molecular control of the distribution of meiotic DSBs in mammals by a rapidly evolving gene, PR domain-containing 9 (PRDM9), and genome-wide analyses have facilitated the characterization of meiotic DSB sites at unprecedented resolution. In addition, the identification of new players in DSB repair processes has allowed the delineation of recombination pathways that have two major outcomes, crossovers and non-crossovers, which have distinct mechanistic roles and consequences for genome evolution.

Fiz1 and Hipk2 contribute to lymphomagenesis via activation of IL-7 signaling pathway. IL-7R, FLT3, and CD43 are surface antigens expressed during the transition from pro-B to pre-B cells in BM. To understand interactions between their signaling pathways, we analyzed spontaneous mouse B-LBLs with dual MLV integration into Stat5a and Fiz1 or Stat5a and Hipk2. MLV integration resulted in up-regulation of these genes in lymphoma cells compared with normal pro-B cells from the BM. In lymphomas with both integrations into Stat5a and Fiz1, increases in phosphorylated STAT5A and expression of c-Myc, a target gene of STAT5A, were observed following stimulation of the FLT3. Clones with the dual integrations grew faster in IL-7 and FLT3L-supplemented medium than clones with Stat5a integration alone. On the other hand, in lymphomas with integrations into Stat5a and Hipk2, increases in phosphorylated STAT5A and expression of c-Myc were observed following cross-linking of CD43. In conclusion, FLT3 and CD43 signaling pathways involve STAT5A via Fiz1 and Hipk2 in B-LBLs. Identification of the dual MLV integration sites in B-LBLs, therefore, will provide an excellent tool for identification of the signaling pathways in B-LBLs.

Background The importance of statins in cardiovascular prevention has been demonstrated in various patient subsets. This study aimed to evaluate the effects of statins on long-term outcomes of Japanese patients undergoing their first coronary revascularization. Methods and Results A total of 9,225 patients undergoing their first coronary revascularizations during 2000-2002 were divided into 2 groups according to the use of statins at discharge; patients with acute myocardial infarction were not included. Statins was administered to only 28.5% (n=2,630) of the patients. The median follow-up period was 3.5 years. Patients on statin therapy showed lower all-cause (5.2% vs 10.0%; p

ZFP521 was previously identified as a putative gene involved in induction of B-cell lymphomagenesis. However, the contribution of ZFP521 to lymphomagenesis has not been confirmed. In this study, we sought to elucidate the role of ZFP521 in B-cell lymphomagenesis. To this end, we used a retroviral insertion method to show that ZFP521 was a target of mutagenesis in pre-B-lymphoblastic lymphoma cells. The pre-B-cell receptor (pre-BCR) signaling molecules BLNK, BTK and BANK1 were positively regulated by the ZFP521 gene, leading to enhancement of the pre-BCR signaling pathway. In addition, c-myc and c-jun were upregulated following activation of ZFP521. Stimulation of pre-BCR signaling using anti-Vpreb antibodies caused aberrant upregulation of c-myc and c-jun and of Ccnd3, which encodes cyclin D3, thereby inducing the growth of pre-B cells. Stimulation with Vpreb affected the growth of pre-B cells, and addition of interleukin (IL)-7 receptor exerted competitive effects on pre-B-cell growth. Knockdown of BTK and BANK1, targets of ZFP521, suppressed the effects of Vpreb stimulation on cell growth. Furthermore, in human lymphoblastic lymphoma, analogous to pre-B-cell lymphoma in mice, the expression of ZNF521, the homolog of ZFP521 in humans, was upregulated. In conclusion, our data showed that the ZFP521 gene comprehensively induced pre-B-cell lymphomagenesis by modulating the pre-B-cell receptor signaling pathway.

Background: The purpose of this study was to assess the left ventricular (LV) diastolic function in elderly patients with aortic stenosis (AS). Methods: The subjects included 11 consecutive elderly patients with AS (AS group), and 17 elderly patients with hypertensive LV hypertrophy (HT group), all were more than 70 years of age. Echocardiographic and Doppler examinations were performed, and the data was analyzed to determine the LV end-diastolic dimension (LVDd), the LV mass index (LVMI), fractional fiber shortening (FS), the aortic valve resistance (AVR), peak aortic flow velocity (peak V), and the maximal early diastolic transmitral flow velocity (E). The flow propagation velocity (FPV) was measured during early LV filling phase using a color M-mode Doppler method. Then, (i) FPV/E were compared between the two groups; and (ii) correlations between FPV/E and LVMI, LVDd, AVR, and FS/peak V were assessed in the AS group. Results: FPV/E was significantly lower in the AS group than in the HT group (P < 0.01). There were significant negative correlations between FPV/E and LVMI (r =−0.728, P

Ethanol jet phenomena were observed with local contact microwave heating. The ethanol jet heights (velocities) and the shapes were measured by the high speed video camera (Redlake Motionmeter, 1000 fps. black & white CCD. 292pix×110pix, 0.2mm special resolution) and the effects of the exit diameter on the velocity were considered. The microwave output power was from 20W to 60 W. The microwave generator was MATSUSHITA TO-465 A with N-type connector. The coaxial cable was FUJIKURA 3.5 D QEFV (5.6 mm of outer diameter). The exit diameter was from 1 mm to 6 mm. The test section was covered by alumimum plates of 2 mm thickness and the microwave shader (Nisshinbo Engineering MP 135 R-20). The fuel chamber was brass. The jet shapes had many variations as fir tree type, umbrella type, mushroom type, and so on. As the results, the jet velocity was increased with the microwave output power and showed a maximum at an exit diameter in this research.

A 66-year-old man had a progressive increase in the pacing threshold over a one-year period, resulting from chronic myocarditis. Following steroid therapy, the pacing threshold decreased and became stabilized, and was accompanied by a decrease in the serum creatine kinase, cardiac myosin light chains and pro-collagen III peptide values, but cardiac function did not improve. Endocardial biopsy showed that there was no progression in the fibrosis. The pacing failure improved, but the cardiac function did not. It was believed that the steroid therapy suppressed the progression of the inflammation and fibrosis caused by the chronic myocarditis.

A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented with chronic ulcers on both feet while undergoing treatment with etanercept. Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor (TNF) agents are known to induce vasculitis, vasculitis can also be caused by active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF therapy must be evaluated carefully.

The relationship between the location and size of an infarction and QT dispersion was investigated in 84 Japanese patients with chronic myocardial infarction (54 with anteroseptal infarction and 30 with inferior infarction). The control group consisted of 23 subjects without ischemic heart disease (13 normal subjects and 10 hypertensive patients). Corrected QT dispersion (maximum corrected QT interval minus minimum corrected QT interval: QTc dispersion), was significantly larger in the anterior infarction group than in the control group (69.9+/-21.5 msec vs 53.0+/-17.6 msec), while the inferior infarction group showed no significant difference from control subjects. QTc dispersion was significantly greater in the patients with large anterior infarcts than in those with small anterior infarcts (80.5+/-20.5 msec vs 61.9+/-18.8 msec). In patients with chronic myocardial infarction, QT dispersion is influenced by the infarct location and size. Accordingly, interpretation of QT dispersion data should take these factors into consideration.

Objective -We assessed the reflection pressure wave using noninvasive measurement of wave intensity (WI) in patients with cardiomyopathy. Methods and results - Subjects included 8 patients with hypertrophic cardiomyopathy (HCM group) and 10 patients with dilated cardiomyopathy (DCM group).Twelve healthy subjects were used as a control group. By using a combined Doppler and echo-tracking system, changes in vascular diameter (dD) and blood flow velocity (dV) were recorded simultaneously at the common carotid artery and dD x dV was measured as WI. In the components of WI, the positive component of early systolic phase (FE) and the negative component following FE (B) were significantly reduced in the DCM group. There was a significant positive correlation between FE and B in all 3 groups. The appearance time of B was significantly shorter in the HCM group and significantly longer in the DCM group compared with the control group. Conclusions - It was suggested that the value of the reflection pressure wave was influenced by the left ventricular contractility, and that the effect of the reflection pressure wave appeared earlier in patients with HCM and later in patients with DCM compared with the control subjects.

The basal part of the interventricular septum (IVS) is known to show different hypertrophic features from those observed in the other parts of the left ventricular wall. These are considered to reflect physiological changes that occur with normal aging. However, these changes have not been carefully evaluated, and their clinical significance has not been defined. We assessed these changes echocardiographically. The subjects were patients at least 70 years of age in whom localized hypertrophy in the basal part of the IVS was seen during the whole cardiac cycle on echocardiography. The prevalence was 6.3% among 96 consecutively studied patients. All 6 patients had a history of hypertension. Echocardiographic findings were as follows: 1) the left atrium was mildly or moderately dilated, 2) there was no evidence of either dilatation or narrowing of the left ventricular cavity, 3) the left ventricular wall motion appeared normal and indices of systolic function were within normal limits in all subjects except one who had a history of myocardial infarction, 4) the angle formed by the aorta and the IVS averaged 106.7 degrees (range: 95 to 120 degrees), 5) Doppler examination showed increases in the ratio of the peak flow velocity during atrial systole to the peak flow velocity early in diastole, and 6) prolongation of the deceleration time of the flow velocity early in diastole. The last of these findings suggested left ventricular diastolic dysfunction, but peak flow velocity at the left ventricular outflow tract was normal. There was no evidence of stenosis of the left ventricular outflow tract. Localized hypertrophy in the basal part of the IVS in elderly patients could be a type of cardiac hypertrophy caused by hypertension. On echocardiography, the basal part of the IVS seemed to protrude toward the left ventricular cavity, but there was no evidence of stenosis in the left ventricular outflow tract.

若年層に好発し, 特徴的な組織像を示すとされている, まれな良性卵巣腫瘍である硬化性間質性腫瘍の1例を経験したので, その細胞像と免疫組織学的特徴を報告する. 症例は33歳の女性で不妊症にて他院受診後, 卵巣腫瘍の疑いにて当院に紹介となった. 内診で子宮後方に鵞卵大腫瘤が触知された. 超音波検査, CTにて充実性腫瘍が認められ, 右卵巣摘出術が施行された. 手術時の捺印細胞診では, 異型性に乏しい小型の2種類の細胞が散見された. 一方は豊富な細胞質に円形核を有する細胞で, 他方は紡錘核を持つ比較的裸核状の細胞であった. 背景はきれいで, 壊死細胞などの悪性を示唆する所見もなく, 良性と診断された. 組織学的にこの充実性卵巣腫瘍は, 浮腫状の部分と細胞豊富な部分から構成されていた. 後者では細胞像に一致して, 豊富な細胞質に円形核を持つ細胞と, 紡錘状細胞質に紡錘核を持つ細胞との2種類が認められた. 酵素抗体間接法による免疫染色で, 2種類の細胞とも, 非上皮性マーカーのvimentin, desminに対し陽性所見がみられた. 硬化性間質性腫瘍に関する今回のわれわれの報告では捺印細胞像と組織像とを比較検討できたものの, 今後症例を集積してさらに検討する必要があると思われる.

Among the congenital anomalies of the coronary arteries, a left circumflex artery (LCX) defect is extremely rare. A 49-year-old man who developed an acute anterior infarction underwent coronary angiography, which revealed complete occlusion of the left main trunk, but the territory usually supplied by the LCX had been perfused by the superdominant right coronary artery. Treatment of the left main trunk by percutaneous coronary intervention produced a favorable result. Accurate evaluation of the principal vessels and the extent of compensatory perfusion is important when diagnosing ischemic heart disease accompanied by anomalous coronary arteries and for choosing the best treatment modality. (Circ J 2004; 68: 91 - 93)

Murine leukemia retrovirus (MLV) vectors are highly effective tools for introducing a foreign gene into a target host genome. However, it remains unclear how integrated retroviral promoter activity is influenced by the upstream or downstream sequences and how the host cell phenotype is influenced by the integrated promoter activity. Herein, we analyzed a set of pre–B lymphoma clones in which the MLV genome was integrated into the signal transducer and activator of transcription factor 5a (Stat5a) gene. Among the clones, the lymphoma clones with a provirus integrating into the middle position of the palindromic target sequences showed significantly higher transcription of the Stat5a gene; and p300 and other transcriptional factors formed complexes, with binding to the proviral-host junctional DNA segment. By using a luciferase assay, the upstream and downstream sequences of the provirus contributed to the up-regulation of proviral promoter activity. In concomitance with the higher Stat5a transcription, the immunoglobulin gene recombination was arrested. Antiapoptotic activity was significantly higher, with an increase in Bcl-xL, one of the targets of STAT5A, when IL-7 was supplied. Thus, a minute difference between MLV integration sites can lead to large differences in the host phenotype through the formation of transcription factor complexes on the proviral-host junctional DNA segment, suggesting that caution is necessary in monitoring integration sites when working with MLV vectors.

The present study evaluated the association between preoperative hemoglobin A1c (HbA1c) levels and cardiovascular outcomes in patients with type 2 diabetes mellitus (DM) treated with hypoglycemic agents and undergoing coronary revascularization. We conducted a multicenter registry of Japanese patients undergoing first elective coronary revascularization. The present study included 3,571 patients whose HbA1c value at the index hospitalization was available. Of the 3,571 patients, 2,067 did not have DM and 1,504 had type 2 DM. Of the patients with type 2 DM, 202 had a HbA1c level of6% (very low HbA1c group [VLG]), 426 had a HbA1c level ofor =6% but7% (low HbA1c group), 405 had a HbA1c level of '7% but8% (intermediate HbA1c group), and 471 had a HbA1c level ofor =8% (high HbA1c group). The patients with type 2 DM treated with diet only were not included in the present study. The VLG had the lowest rate of freedom from major adverse cardiovascular events (MACE), a composite of cardiovascular death, myocardial infarction, and stroke. On multivariate analyses, the low HbA1c group had the lowest hazard ratio for MACE relative to those without DM (hazard ratio 1.13, 95% confidence interval 0.80 to 1.55). The VLG, intermediate HbA1c group, and high HbA1c group were significantly associated with an increased risk of MACE. On multivariate analyses of patients with DM using the low HbA1c group as a reference, a high HbA1c group level was significantly associated with an increased risk of MACE. The VLG and intermediate HbA1c group tended to be associated with an increased risk of MACE (VLG, hazard ratio 1.54, 95% confidence interval 0.98 to 2.40; intermediate HbA1c group, hazard ratio 1.44, 95% confidence interval 0.98 to 2.13). In conclusion, patients with type 2 DM treated with hypoglycemic agents and undergoing first elective coronary revascularization had significantly worse cardiovascular outcomes than patients without DM, except for patients with DM and a HbA1c of 6% to 7%. In the patients with DM, those with a HbA1c of 6% to 7% tended to have the lowest risk of MACE.

The importance of statins in cardiovascular prevention has been demonstrated in various patient subsets. This study aimed to evaluate the effects of statins on long-term outcomes of Japanese patients undergoing their first coronary revascularization.A total of 9,225 patients undergoing their first coronary revascularizations during 2000--2002 were divided into 2 groups according to the use of statins at discharge; patients with acute myocardial infarction were not included. Statins was administered to only 28.5% (n=2,630) of the patients. The median follow-up period was 3.5 years. Patients on statin therapy showed lower all-cause (5.2% vs 10.0%; p0.0001) and cardiovascular (3.2% vs 6.2%; p0.0001) mortality than those without statins (n=6,595) by Kaplan-Meier analysis and log-rank test. After adjustment by multivariate analysis according to 29 variables, statin therapy remained as an independent predictor of reduced all-cause (relative risk ratio (RR) 0.71, 95% confidence interval (CI) 0.59-0.86, p=0.0005) and cardiovascular (RR 0.72, 95% CI 0.56-0.91, p=0.0067) mortality. The validity of RR of statin therapy in multivariate analysis was further confirmed by risk adjustment using propensity scores (all-cause mortality: propensity-adjusted RR 0.70, 95% CI 0.58-0.85, p=0.0003; cardiovascular mortality: propensity-adjusted RR 0.70, 95% CI 0.54-0.89, p=0.0038).Statin therapy started at hospital discharge was associated with increased chance of survival in Japanese patients undergoing their first coronary revascularization.

Background— Observational registries comparing coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI) have reported long-term survival results that are discordant with those of randomized trials. Methods and Results— We conducted a multicenter study in Japan enrolling consecutive patients undergoing first CABG or PCI between January 2000 and December 2002. Among 9877 patients enrolled, 5420 (PCI: 3712, CABG: 1708) had multivessel disease without left main involvement. Because age is an important determinant when choosing revascularization strategies, survival analysis was stratified by either age ≥75 or P =0.26). After adjustment for baseline characteristics, survival outcome tended to be better after CABG (hazard ratio for death after PCI versus CABG [HR], 95% confidence interval [CI]: 1.23 [0.99-1.53], P =0.06). Adjusted survival outcomes also tended to be better for CABG among elderly patients (HR [95%CI]: 1.37 [0.98-1.92] P =0.07), but not among nonelderly patients (HR [95% CI]: 1.09 [0.82-1.46], P =0.55). Unadjusted and adjusted survival outcome for CABG and PCI were not significantly different in any subgroups when elderly patients were excluded from analysis. Conclusions— In the CREDO-Kyoto registry, survival outcomes among patients

We describe a patient with acute myocardial infarction, which was thought to result from plaque rupture or thrombosis because of coronary artery spasm. The vasospasm was most likely induced by stimulation of the α-adrenergic receptors during alternating heat exposure during sauna bathing and rapid cooling during cold water bathing. This report emphasizes the dangers of rapid cooling after sauna bathing in patients with coronary risk factors.

Among the congenital anomalies of the coronary arteries, a left circumflex artery (LCX) defect is extremely rare. A 49-year-old man who developed an acute anterior infarction underwent coronary angiography, which revealed complete occlusion of the left main trunk, but the territory usually supplied by the LCX had been perfused by the superdominant right coronary artery. Treatment of the left main trunk by percutaneous coronary intervention produced a favorable result. Accurate evaluation of the principal vessels and the extent of compensatory perfusion is important when diagnosing ischemic heart disease accompanied by anomalous coronary arteries and for choosing the best treatment modality.

Using X-ray computed tomography (CT) and selective graft angiography, the authors studied the necessity of metallic markers in coronary artery bypass grafts on 45 patients (mean age 57.2 years) with 87 saphenous vein grafts. Eight patients had 17 markers. X-ray CT was performed after surgery using an apparatus with a 1-second scanning time. Noncontrast X-ray CT was performed on horizontal sections, at 5-mm intervals, from the lower margin of the aortic arch to the lower left ventricle. A contrast medium was then injected into the antecubital vein (3 ml/second, total 30 ml) in one cross-section at the level of bifurcation of the pulmonary artery. Aortography (60 degrees in the left anterior and oblique positions, 20 ml/second, total 40 ml) was performed concurrently. Selective graft angiography was taken in the same direction, using 4 cm right of the Judkins with reference to the aortographic image and position of five clips on the sternum. Aortography revealed 79 patent and 8 occluded grafts. Selective graft angiography was easily performed even in grafts without markers. A cross-section of the occluded graft could not be seen with X-ray CT. Grafts with markers were often masked by artifacts produced by markers on X-ray CT. The number of observed graft slices (marker-positive grafts) was only 1.2 +/- 1.1 slices, significantly (p0.01) lower than marker-negative grafts (4.1 +/- 3.1 slices). In particular, the number of marker-positive right coronary artery grafts was 0.4 +/- 0.9 slices. Four of five right coronary artery grafts were unobservable due to artifacts. In grafts without markers, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of X-ray CT to graft patency were 100%, 85.7%, 98.4%, 100%, and 98.6%, respectively. This study suggests that metallic markers may not be necessary for coronary artery bypass grafts.