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Carbon fiber-reinforced plastics (CFRP) are leading functional materials with superior strength and low mass density compared to metal. Our previous factory site analyses found that CFRP processing generates fibrous debris and fine micro/nano-sized particles of various shapes. The present interventional study was conducted at a factory located in Japan and evaluated debris consisting of various-sized particles generated during the industrial processing of CFRP, such as cutting, grinding, and turning of CFRP pipes, using real-time particle monitoring devices of the following: PM4 Digital Dust Monitor (DDM), handled Optical Particle Counter (OPC), Condensation Particle Counter (CPC), and Scanning Mobility Particle Sizer (SMPS). In addition, personal exposure of workers was evaluated using a novel wearable PM2.5-compatible device (P-sensor). First, we confirmed the presence of micro/nano particles in the dust generated during industrial processing of CFRP. Finer CFRP-generated particles were detected by the nanoparticle-compatible devices; CPC and SMPS, but not by OPC or DDM. The dynamic detection pattern of the P-sensor resembled that recorded by the nanoparticle-compatible devices. The novel wearable P-sensor can be used to measure finer particles generated by CFRP processing in occupational settings. Second, the exposure assessment was conducted twice and the levels of the micro/nano particles in the second survey were significantly (less than half) lower than that in the first survey. By avoiding immediate power-off of the exhaust system after operations, the scattering of particles was effectively reduced. Our results indicate that effective use of local exhaust ventilation system improves the workplace environment for particle exposure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first confirmed in Japan on January 15, 2020. The Fukuoka Institute of Health and Environmental Sciences conducted testing using polymerase chain reaction (PCR) for SARS-CoV-2 from January 31 to March 4, 2020. Samples (n = 119) were collected from 81 patients suspected of having SARS-CoV-2 infection, presenting with fever, cough, fatigue, pneumonia, and other symptoms; all the samples tested during that period were negative. To identify the pathogens responsible for these symptoms, we conducted multiplex PCR. Respiratory viruses, human metapneumovirus (hMPV) was detected in 10 patients (12%), human rhinovirus (HRV) in 3 patients (4%), and influenza B virus in 1 patient (1%). In addition, the patients who had the viruses were significantly older than those who did not. Infections with hMPV and HRV have been associated with a risk of severe illness and death among older adults. Therefore, differentiating SARS-CoV-2 from other respiratory viruses, such as hMPV and HRV, is necessary to prevent and control the spread of infection, especially in older adults.

The present study aimed to clarify the process of peer support formation and the promotion of recovery in people using psychiatric day care. From January to March 2014, semi-structured interviews were conducted with 18 participants with mental illness living in the community in Japan. The qualitative data were analyzed using a modified grounded theory approach. The results described a two-stage process: (1) awareness of peers with similar disability and distress and (2) formation and utilization of peer support. These results suggest that adjusting the environment and engaging in activities assisting others are useful for facilitating peer support and promoting the recovery of users in psychiatric day care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Objective: The goal of this retrospective study was to clarify the clinical implications of immunohistochemically detected protein expression for genes that are frequently mutated in pancreatic neuroendocrine tumors (PNETs)., Background: The clinical management of PNETs is hindered by their heterogenous biological behavior. Whole-exome sequencing recently showed that 5 genes (DAXX/ATRX, MEN1, TSC2, and PTEN) are frequently mutated in PNETs. However, the clinical implications of the associated alterations in protein expression remain unclear., Methods: We collected Grade 1 and 2 (World Health Organization 2017 Classification) primary PNETs samples from 100 patients who underwent surgical resection. ATRX, DAXX, MEN1, TSC2, and PTEN expression were determined immunohistochemically to clarify their relationships with prognosis and clinicopathological findings., Results: Kaplan-Meier analysis indicated that loss of TSC2 (n = 58) or PTEN (n = 37) was associated with significantly shorter overall survival, and that loss of TSC2 or ATRX (n = 41) was associated with significantly shorter recurrence-free survival. Additionally, loss of ATRX or TSC2 was significantly associated with nodal metastasis. In a multivariate analysis, combined loss of TSC2 and ATRX (n = 31) was an independent prognostic factor for shorter recurrence-free survival (hazard ratio 10.1, 95% confidence interval 2.1-66.9, P = 0.003) in G2 PNETs., Conclusions: Loss of ATRX, TSC2, and PTEN expression might be useful as a method of clarifying the behavior and clinical outcomes of Grade 1 and 2 PNETs in routine clinical practice. Combined loss of TSC2 and ATRX had an especially strong, independent association with shorter recurrence-free survival in patients with G2 PNETs. Loss of pairs in ATRX, TSC2, or PTEN would be useful for selecting the candidate for postoperative adjuvant therapy., Competing Interests: The authors have no financial conflicts of interest related to this work. The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Inappropriate treatment of growth plate injury may cause complications such as malunion or early arrest of the growth plate. Identification of intra-articular lesions is mandatory in patients with a growth plate injury of the distal tibia. Arthroscopic assessment is useful in identifying intra-articular injury. We report three cases of intra-articular growth plate injury of the distal tibia that were treated via internal fixation with arthroscopic assessment in our hospital., Materials and Methods: All three cases were performed pre- and postoperative arthroscopic assessment and open reduction and internal fixation with a cannulated cancellous screw (CCS; Meira, Japan). All patients were then examined for postoperative complications, functional recovery, at the end of the final follow-up consultation., Results: Intraoperatively, a small cartilage injury was found in the non-fracture area in two cases; the remaining case had a reversed cartilage fragment at the talus, which was arthroscopically removed., Conclusions: Arthroscopic assessment followed by internal fixation is a useful minimally invasive method for the identification of intra-articular lesions such as osteochondral injury or free bodies.

Objective: In 2010, we established the Miyazaki Comprehensive Hearing Care Network (MCHCN) for early identification and intervention in children with congenital and late-onset/acquired hearing loss with the cooperation of related administrative bodies in Miyazaki prefecture. The central roles of the MCHCN program are played by the Hearing Care Center (HCC) at the University of Miyazaki Hospital established in 2010 to facilitate audiological diagnoses, hearing aid interventions, and educational efforts, as well as linkage with the Department of Otolaryngology for surgical interventions. Herein, we aimed to present the main outcomes of the MCHCN program organized by the HCC at the University of Miyazaki Hospital., Methods: The MCHCN consists of two different networks, the Newborn Hearing Screening Network (NHSN) and the Pediatric Hearing Care Network (PHCN). All children suspected of having hearing loss by Newborn Hearing Screening (NHS) are referred to the HCC via the NHSN. In addition, children suspected of late-onset/acquired hearing loss by municipality-led health checkups, pediatricians, public health nurses, and childcare workers are referred to the HCC via the PHCN. Children who were born in Miyazaki prefecture between January 2010 and December 2017 and referred to the HCC for detailed hearing examination were included in this study., Results: Within the study period, 89,390 infants were born in Miyazaki prefecture, and 84,737 (94.9%) of them underwent NHS. A total of 698 infants and 182 children with suspected hearing loss were referred to the HCC via the NHSN and PHCN, respectively. Of the 880 referrals, 169 were diagnosed with hearing loss, which included 80 children with bilateral hearing loss and 89 children with unilateral hearing loss. Of the 80 children with bilateral hearing loss, 76 began wearing hearing aids and 15 had cochlear implants in the follow-up period. In children with bilateral conductive hearing loss, 4 children with bilateral middle ear anomalies underwent ossiculoplasty, following which two of these children no longer required hearing aids. Imaging assessments performed on 71 of the 89 children with unilateral hearing loss revealed that 20 of the 30 (66%) children who underwent CT exhibited ossicular anomalies and 28 out of the 48 (58%) children who underwent MRI were found to have ipsilateral cochlear nerve hypoplasia. Among the 169 children with hearing loss, no follow-up loss was observed during the period of this study., Conclusion: The MCHCN that was organized at the initiative of the HCC at the University of Miyazaki Hospital has enabled the provision of comprehensive and continuous support, ranging from diagnosis to intervention, not only for children with suspected hearing loss referred based on their NHS results but also for those who pass the screening. Via this system, children with late-onset/acquired hearing loss can be identified early and can receive medical interventions tailored to the cause of their hearing loss while simultaneously avoiding a loss to follow-up., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Sensitivity to detect breast cancer (BC) is not high in a dense breast due to masking in mammography. To evaluate the breast density, a volumetric measurement system has been recently developed that measures the percent fibroglandular tissue volume (percent FGV, hereafter termed as "FG%") to the breast volume (BV). This study was designed to investigate whether evaluation using FG% can accurately predict the masking risk by comparing with the current standard method of subjective visual estimation (SVE)., Methods: Using pre-biopsy mammograms of 114 cases histopathologically diagnosed with BC in our facility, SVE based on BI-RADS (5th edition) and volumetric measurements of FG% were conducted. Performance to predict the masking risk was evaluated using the area under the receiver operating characteristic curve (AUC). Relationship between these parameters and the masking risk was evaluated by the adjusted multivariate linear regression analysis., Results: The AUC of SVE values was 0.742 (95% CI 0.641-0.822), while that of FG% was as significantly low as 0.560 (95% CI 0.427-0.685) (P = 0.0014). The SVE values correlated with the detection of BC in mammography (P = 0.0035), but there was no significant relationship with FG% (P = 0.74). The median BV and FGV were 313 cm 3 (IQR 191-440) and 63 cm 3 (IQR 44-102), respectively. The FGV was comparable to the data for Caucasian women reported in previous studies, but the BV was one-half of the previous data., Conclusion: The current volumetric measurement system to evaluate FG% to BV was found to be insufficient in the performance to predict the masking risk in Japanese women with relatively small-sized breasts.

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci ( P <5 × 10 -8 ) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci- TMEM18 , TM4SF4 , MXD3-LMAN2 , PSORS1C1-PSORS1C2 , and HNF4A -are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578 , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout., Competing Interests: The authors declare no competing interests.

Coxsackievirus (CV)-A6 has been the primary causative agent of hand, foot, and mouth disease (HFMD) in Japan since 2011. In Fukuoka, CV-A6-associated HFMD caused epidemics in 2013, 2015, and 2017. This paper reports the genetic characteristics of the CV-A6 entire viral protein 1 (VP1) derived from patients with HFMD in Fukuoka between 2013 and 2017. CV-A6 was detected in 105 of 280 clinical specimens, and the entire VP1 sequences could be analyzed for 90 of the 105 specimens. Phylogenetic analysis revealed that the CV-A6 strains were classified into clade A and subgrouped into subclade A3 or subclade A4. Each subclade strain carried amino acid substitutions in the presumed DE and GH loops of the VP1, and no amino acid substitutions were identified as deleterious to the protein function. No significant difference was found in the clinical symptoms between the genetic subclades using statistical analyses. In conclusion, this study clarified the genetic diversity of CV-A6 in Fukuoka from 2013 to 2017. The emergence of the CV-A6 strains was classified into derived new subclades based on phylogenetic analysis of the VP1 gene that may cause CV-A6-associated HFMD epidemics approximately every 2 years., (© 2018 Wiley Periodicals, Inc.)

Background: Development of cardiovascular disease (CVD), including coronary artery disease, arrhythmia, and ischemic stroke, depends on environmental and genetic factors. To investigate the epigenetic basis of myocardial infarction (MI), we performed an epigenome-wide association study for this condition in elderly Japanese subjects. A total of 192 case subjects with MI and 192 control subjects were recruited from hospital attendees and the general population, respectively. Genome-wide DNA methylation (DNAm) profiles for DNA isolated from whole blood were obtained by analysis with an Infinium HumanMethylation450 BeadChip. The relation of DNAm sites found to be significantly associated with MI to nearby single nucleotide polymorphisms (SNPs) previously shown to be associated with CVD was assessed in the control group., Findings: Three DNAm sites (cg06642177, cg07786668, cg17218495) showed genome-wide significant associations with MI ( p  = 4.33 × 10 -8 , 3.96 × 10 -10 , and 3.77 × 10 -8 , respectively). Two of these sites (cg07786668, cg17218495) still showed such associations after adjustment for classical risk factors of MI ( p  = 1.04 × 10 -7 and 6.60 × 10 -8 , respectively). The DNAm sites cg07786668 and cg17218495 are located in ZFHX3 (zinc finger homeobox 3) and SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4) genes, respectively. SNPs in ZFHX3 or SMARCA4 that were previously found to be associated with CVD were not significantly associated with these DNAm sites in our control subjects., Conclusions: We identified two DNAm sites-cg07786668 in ZFHX3 and cg17218495 in SMARCA4 - that are independently and significantly associated with MI. Our results suggest that the development of MI might be influenced by changes in DNAm at these sites via a pathway that differs from that affected by CVD-associated SNPs in these genes. The Kita-Nagoya Genomic Epidemiology (KING) study, which was the source of control samples in the present study, was registered in ClinicalTrials.gov (NCT00262691) on 6 December 2005.

Background: The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested., Methods and Results: We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37-6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16-21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87-16.77; p = 0.076)., Conclusions: The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

Background and Aim: Western studies have suggested two distinct etiologies of esophagogastric junction (EGJ) cancer: Helicobacter pylori-associated atrophic gastritis and non-atrophic gastric mucosa resembling esophageal adenocarcinoma. The present study investigated whether endoscopic gastric mucosal atrophy can distinguish between these two types of EGJ adenocarcinoma., Methods: Data were collected from patients with Siewert type II, T1 EGJ adenocarcinoma who underwent endoscopic or surgical resection at eight Japanese institutions in 2010-2015. Clinicopathological characteristics of EGJ cancers with and without endoscopic gastric mucosal atrophy were compared. EGJ was defined as the lower end of the palisade vein and/or the top of the gastric folds., Results: Of the 229 patients identified, 161 had endoscopic gastric mucosal atrophy and 68 did not. The latter group was younger (64 vs 70 years, P = 0.000); had a higher proportion of patients negative for H. pylori (90% vs 47%, P < 0.0001); and had higher rates of gastroesophageal reflux disease symptoms (43% vs 12%, P = 0.017), mucosal breaks (25% vs 15%, P = 0.009), Barrett's esophagus (BE, 78% vs 42%, P < 0.0001), and tumors above the EGJ (81% vs 19%, P < 0.0001) and on the upper-right side (74% vs 38%, P < 0.0001) than the former group. Multivariate analysis showed that H. pylori positivity (odds ratio [OR] = 13.0, P < 0.001), long-segment BE (OR = 0.025, P = 0.033), and longitudinal (OR = 8.6, P = 0.001) and circumferential (OR = 4.7, P = 0.006) tumor locations were independently associated with gastric mucosal atrophy., Conclusion: Two distinct types of EGJ cancer were identified, with and without endoscopic gastric mucosal atrophy. These types were associated with different tumor locations., (© 2017 The Authors. Digestive Endoscopy © 2017 Japan Gastroenterological Endoscopy Society.)

An increasing number of Shiga toxin 2f-producing Escherichia coli (STEC2f) infections in humans are being reported in Europe, and pigeons have been suggested as a reservoir for the pathogen. In Japan, there is very little information regarding carriage of STEC2f by pigeons, prompting the need for further investigation. We collected 549 samples of pigeon droppings from 14 locations in Kyushu, Japan, to isolate STEC2f and to investigate characteristics of the isolates. Shiga toxin stx 2f gene fragments were detected by PCR in 16 (2.9%) of the 549 dropping samples across four of the 14 locations. We obtained 23 STEC2f-isolates from seven of the original samples and from three pigeon dropping samples collected in an additional sampling experiment (from a total of seven locations across both sampling periods). Genotypic and phenotypic characteristics were then examined for selected isolates from each of 10 samples with pulsed-field gel electrophoresis profiles. Eight of the stx 2f gene fragments sequenced in this study were homologous to others that were identified in Europe. Some isolates also contained virulence-related genes, including lpfA O26, irp 2, and fyuA, and all of the 10 selected isolates maintained the eae, astA, and cdt genes. Moreover, five of the 10 selected isolates contained sfpA, a gene that is restricted to Shiga toxin-producing E. coli O165:H2 and sorbitol-fermenting Shiga toxin-producing E. coli O157:NM. We document serotypes O152:HNM, O128:HNM, and O145:H34 as STEC2f, which agrees with previous studies on pigeons and humans. Interestingly, O119:H21 was newly described as STEC2f. O145:H34, with sequence type 722, was described in a German study in humans and was also isolated in the current study. These results revealed that Japanese zoonotic STEC2f strains harboring several virulence-related factors may be of the same clonal complexes as some European strains. These findings provide useful information for public health-related disease management strategies in Japan.

Background: Myocardial infarction (MI) is a leading cause of death worldwide. Given that a family history is an independent risk factor for coronary artery disease, genetic variants are thought to contribute directly to the development of this condition. The identification of susceptibility genes for coronary artery disease or MI may thus help to identify high-risk individuals and offer the opportunity for disease prevention., Methods and Results: We designed a 5-step protocol, consisting of a genome-wide linkage study followed by association analysis, to identify novel genetic variants that confer susceptibility to coronary artery disease or MI. A genome-wide affected sib-pair linkage study with 221 Japanese families with coronary artery disease yielded a statistically significant logarithm of the odds score of 3.44 for chromosome 2p13 and MI. Further association analysis implicated Alström syndrome 1 gene (ALMS1) as a candidate gene within the linkage region. Validation association analysis revealed that representative single-nucleotide polymorphisms of the ALMS1 promoter region were significantly associated with early-onset MI in both Japanese and Korean populations. Moreover, direct sequencing of the ALMS1 coding region identified a glutamic acid repeat polymorphism in exon 1, which was subsequently found to be associated with early-onset MI., Conclusions: The glutamic acid repeat polymorphism of ALMS1 identified in the present study may provide insight into the pathogenesis of early-onset MI.

Previous research has suggested that a singly presented facial stimulus having a direct gaze holds spatial attention. This study examined whether facial stimulus having a direct gaze can also capture spatial attention in a relative dot-probe paradigm (facial stimulus having a direct gaze was presented concurrently with that having an averted gaze). The results showed that participants oriented their spatial attention to a facial stimulus having a direct gaze rather than to that with an averted gaze. This attentional bias depended on gaze-perception mechanisms as observed in the lack of attentional bias to a direct gaze from unnatural-looking eyes (i.e., white pupil/iris and black sclera). These findings raise the possibility that the attentional effect implicated in the perception of a direct gaze is induced regardless of the stimulus context.

Aim: The present study examined whether the self-efficacy of interpersonal behavior influenced the interpersonal behavior of schizophrenia patients using psychiatric day-care services., Methods: Thirty-nine patients with schizophrenia were examined with the Interpersonal Relations subscale of the Life Assessment Scale for Mentally Ill, the Self-efficacy Scale of Interpersonal Behavior, the Brief Assessment of Cognition in Schizophrenia-Japanese version, and the Positive and Negative Syndrome Scale., Results: The Life Assessment Scale for Mentally Ill score was significantly correlated with the self-efficacy of interpersonal behavior, and was also significantly correlated with neurocognitive functions and negative symptoms. However, the Self-efficacy Scale of Interpersonal Behavior score was not correlated with neurocognitive functions and negative symptoms. To examine the causal correlations between the above social, psychological and clinical factors, multiple regression analysis was performed with the self-efficacy of interpersonal behavior, neurocognitive functions, and negative symptoms as the independent variables and interpersonal behavior as the dependent variable. The self-efficacy of interpersonal behavior was found to contribute to interpersonal behavior as well as neurocognitive functions., Conclusion: The self-efficacy of interpersonal behavior contributed to the interpersonal behavior as well as the neurocognitive functions in the case of schizophrenia patients in the community. This suggested that interventions targeting the self-efficacy of interpersonal behavior, as well as those targeting neurocognitive functions, were important to improve the interpersonal behavior of schizophrenia patients undergoing psychiatric rehabilitation in the community., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Enterohemorrhagic Escherichia coli serovar O157 (O157) strains with highly similar pulsed-field gel electrophoresis (PFGE) patterns were isolated in Japan during 2007 and 2008. Several genetic features related to O157 evolution were investigated to indicate whether homoplasy might have contributed to the highly similar PFGE patterns in these strains. The O157 strains were classified in lineage I/II, as defined by a lineage-specific polymorphism assay-6 with an atypical allele in Z5935 (code: 231111). Analysis of the insertion sites of stx(2) phage in these strains showed that the sites were "occupied" in yehV and "intact" in wrbA, indicating that the strains were derived from "Cluster 1" of "Subgroup C." When a specific single-nucleotide polymorphism in ECs2357 in clade 8 strains was investigated, all of the strains in the present study were confirmed to be clade 8 strains. These results indicated that the O157 strains in this study had common genetic features, suggesting that the highly similar PFGE patterns of these strains were not due to homoplasy. Because no common source of these strains could be identified in 2007 to 2008 in Japan, these strains may have emerged from a unique O157 clade 8 clone and then spread by dissemination in Japan.

Objective: We have performed a genome-wide association study (GWAS) to identify genetic variants that confer susceptibility to myocardial infarction (MI) in Japanese and Korean populations., Methods: A total of 17,447 Japanese or Korean individuals from four independent subject panels was examined. Japanese subject panels A, B, and C comprised 134 individuals with MI and 137 controls, 1431 individuals with MI and 3161 controls, and 643 individuals with MI and 1347 controls, respectively, whereas the Korean population comprised 1880 individuals with MI and 8714 controls. A GWAS for MI was performed in Japanese subject panel A with the use of the Affymetrix GeneChip Human Mapping 500K Array Set., Results: Seventy single nucleotide polymorphisms (SNPs) significantly (P<1.0×10(-7)) associated with MI by the GWAS were examined further in Japanese subject panel B, revealing two SNPs (rs6929846 of BTN2A1, rs2569512 of ILF3) to be significantly (P<0.0007) associated with MI. The rs6929846 SNP of BTN2A1, but not rs2569512 of ILF3, was also significantly associated with MI in Japanese subject panel C. However, the association of neither rs6929846 nor rs2569512 with MI was replicated in the Korean population., Conclusion: BTN2A1 may be a susceptibility gene for MI in Japanese individuals., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Adiponectin is an adipocyte-derived protein that is down-regulated in obesity-linked disorders. Variants of the adiponectin gene (ADIPOQ) have been shown to affect adiponectin level. We have now examined the relation of polymorphisms of ADIPOQ to adiponectin concentration and to metabolic disorders in the Kita-Nagoya Genomic Epidemiology study, a population-based study of elderly Japanese. The genomic region including ADIPOQ was genotyped for 30 single nucleotide polymorphisms in 500 subjects of a screening population with the use of a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Four polymorphisms were then selected for genotyping in an additional 2797 subjects. Serum adiponectin level was negatively associated with metabolic abnormalities after adjustment for age and sex. The minor alleles of the rs1656930, Ile164Thr, and rs9882205 polymorphisms were associated with a low serum adiponectin level. Whereas the minor alleles of rs1656930 and rs9882205 were common (minor allele frequency of 6.2 and 38.5%, respectively), that of Ile164Thr was rare (0.9%). The minor allele of rs1656930 was positively associated with systolic blood pressure and the prevalence of hypertension. The association of rs1656930 with adiponectin level was replicated in an independent population. A subject with the 164Thr/Thr genotype had an extremely low serum adiponectin level (0.6 μg/ml) and the phenotype of metabolic syndrome. Our results suggest that a common variant of ADIPOQ, the minor allele of rs1656930, is associated with hypoadiponectinemia and hypertension. Screening for a common genetic background underlying low adiponectin levels might provide important information for assessment and management of metabolic disorders., (© 2011 Macmillan Publishers Limited All rights reserved 1018-4813/11)

Purpose: We sought to evaluate the use of the Onco type DX Breast Cancer Assay for identifying candidates for adjuvant therapy in patients with estrogen receptor (ER)-positive, node-negative primary Stage I or IIA breast cancer., Methods: A retrospective case-control study was conducted on 40 patients who underwent surgery between 2000 and 2008. Cases (n = 10) were patients who had metastases after surgery. Controls (n = 30) were patients who did not develop metastases and were individually matched to their case with respect to age. All patients were analyzed with regard to age, tumor size, histological grade, HER2 status, and the values of Recurrence Score (RS), ER score and PgR score generated by Onco type DX. We also divided the patients into low, intermediate or high-risk groups according to individual RS values., Results: RS, risk category and histological grade were associated with metastases in patients with ER-positive, node-negative Stage I or IIA breast cancer. However, ER status, tumor size and PgR status were not associated with metastases. Histological grade was associated with RS value and the distribution pattern of risk category (P < 0.001 for each)., Conclusions: Both histological grade and risk-category classification were effective in identifying women at risk of developing distant metastases after initial therapy for ER-positive, node-negative Stage I or IIA breast cancer. These patients may benefit from the addition of adjuvant therapy at diagnosis.

Shiga toxin 2f-producing Escherichia coli (O115:HNM) with eae was isolated from a symptomatic patient in Fukuoka Prefecture, Japan. The patient was a 23-year-old male and his symptoms were diarrhea, abdominal pain, headaches and a fever (37.7 degrees C). He had eaten raw chicken meat, raw chicken eggs, cooked chicken meat and raw vegetables about 13 h prior to the onset of the symptoms. The patient's specimen was examined, and no diarrheagenic agents were detected except for Shiga toxin 2f-producing E. coli (STEC(2f)) with eae. This is the first report of the serotype O115:HNM possessing stx(2f). We discuss the necessity of routinely using stx(2f)-detecting PCR primers for detection of this enteric pathogen.

Background and Purpose: Although genetic epidemiologic studies have implicated several genetic variants as risk factors for ischemic or hemorrhagic stroke, the genetic determinants of these conditions remain largely unknown. We performed an association study to identify gene polymorphisms that confer susceptibility to atherothrombotic cerebral infarction, intracerebral hemorrhage, or subarachnoid hemorrhage., Methods: The study population comprised 3432 unrelated Japanese individuals: 1362 stroke patients (822 with atherothrombotic cerebral infarction, 333 with intracerebral hemorrhage, and 207 with subarachnoid hemorrhage) and 2070 controls. The genotypes for 50 polymorphisms of 38 candidate genes were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology., Results: An initial chi(2) test (false discovery rate <0.05) and subsequent multivariable logistic-regression analysis with adjustment for conventional risk factors (P<0.05) revealed that the -14C-->T polymorphism (rs1800977) of ABCA1, the A-->C (rs3027898) and C-->T (Ser532Leu, rs1059703) polymorphisms of IRAK1, and the G-->C (Cys2229Ser) polymorphism (rs619203) of ROS1 were significantly associated with atherothrombotic cerebral infarction; that the -428G-->A polymorphism (rs710968) of LIMK1 was significantly associated with intracerebral hemorrhage; and that the 13989A-->G (Ile118Val) polymorphism (NC&#95;000007.12) of CYP3A4 was significantly associated with subarachnoid hemorrhage., Conclusions: Genotypes for ABCA1, IRAK1, and ROS1 may prove useful for assessment of the genetic risk for atherothrombotic cerebral infarction, whereas those for LIMK1 and CYP3A4 may be similarly beneficial in assessment of the genetic risk for intracerebral hemorrhage and subarachnoid hemorrhage, respectively. Validation of these findings will require additional studies with independent subject panels.

Metabolic syndrome is a risk factor for cardiovascular disease. The aim of the present study was to identify genetic variants that confer susceptibility to atherothrombotic cerebral infarction among individuals with metabolic syndrome in order to allow prediction of genetic risk for this condition. The study population comprised 1284 unrelated Japanese individuals with metabolic syndrome, including 313 subjects with atherothrombotic cerebral infarction and 971 controls. The genotypes for 296 polymorphisms of 202 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The Chi-square test, multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of hypertension, hypercholesterolemia, and diabetes mellitus, as well as a stepwise forward selection procedure revealed that the 2445G-->A (Ala54Thr) polymorphism (rs1799883) of FABP2, the -108/3G-->4G polymorphism of IPF1 (S82168), the A-->G (Thr94Ala) polymorphism (rs2241883) of FABP1, the G-->A (Asp2213Asn) polymorphism (rs529038) of ROS1, the -11377C-->G polymorphism (rs266729) of ADIPOQ, the 162A-->C polymorphism (rs4769055) of ALOX5AP, the -786T-->C polymorphism (rs2070744) of NOS3, and the 3279C-->T polymorphism (rs7291467) of LGALS2 were associated (P<0.05) with the prevalence of atherothrombotic cerebral infarction. Among these polymorphisms, the 2445G-->A (Ala54Thr) polymorphism of FABP2 was most significantly associated with this condition. Our results suggest that FABP2, IPF1, FABP1, ROS1, ADIPOQ, ALOX5AP, NOS3, and LGALS2 are susceptibility loci for atherothrombotic cerebral infarction among Japanese individuals with metabolic syndrome. Genotypes for these polymorphisms, especially for the 2445G-->A (Ala54Thr) polymorphism of FABP2, may prove informative for the prediction of genetic risk for atherothrombotic cerebral infarction among such individuals.

The aim of the present study was to identify gene polymorphisms that confer susceptibility to obesity. A total of 5448 unrelated Japanese individuals from two independent populations were examined: subject panel A comprised 4252 individuals who visited participating hospitals; subject panel B comprised 1196 community-dwelling elderly individuals. The genotypes for 95 polymorphisms of 67 candidate genes were determined. The chi(2) test revealed that six polymorphisms were related (p<0.05) to the prevalence of obesity in subject panel A; after application of Bonferroni's correction, however, only the 2677G --> A/T polymorphism (rs2032582) of the ATP-binding cassette, subfamily B, member 1 gene (ABCB1) was significantly associated (p=0.0003) with obesity. Subsequent multivariable logistic regression analysis also revealed that the 2677G --> A/T polymorphism of ABCB1 was significantly associated with obesity. For validation of this association, the 2677G --> A/T polymorphism of ABCB1 was examined in subject panel B and again found to be significantly associated with obesity. Body mass index was significantly (p=0.01) greater for individuals with the variant T allele of this polymorphism than for those with the GG genotype in the combined subject panels A and B. Our results suggest that the ABCB1 genotype may prove informative for assessment of genetic risk for obesity in Japanese individuals.

Background: Although several environmental factors influence the development of myocardial infarction (MI), genetic factors have been shown to contribute to individual susceptibility to this condition., Objective: To identify gene polymorphisms that confer susceptibility to MI in order to allow assessment of genetic risk for this condition., Methods: 3433 unrelated Japanese people (1931 men, 1502 women) were entered into the study. These comprised 1328 subjects with MI (1036 men, 292 women) and 2105 controls (895 men, 1210 women). The genotypes for 40 polymorphisms of 31 candidate genes were determined with a method that combines PCR and sequence-specific oligonucleotide probes with suspension array technology., Results: The chi(2) test revealed that six polymorphisms were significantly (false discovery rate <0.05) related to the prevalence of MI. Further examination by multivariable logistic regression analysis with adjustment for age, sex, body mass index and the prevalence of hypertension, diabetes mellitus and hypercholesterolaemia, in addition to a stepwise forward selection procedure found that the A-->C (Gln1334His) polymorphism (rs3742207) of the collagen type IV alpha-1 gene (COL4A1) and the A-->G polymorphism (rs4804611) of the zinc finger protein 627 gene (ZNF627) were significantly (p<0.05) associated with the prevalence of MI. The variant C allele of COL4A1 was protective against MI, whereas the variant G allele of ZNF627 represented a risk factor for this condition., Conclusions: Determination of genotypes for COL4A1 and ZNF627 may prove informative for assessment of the genetic risk for MI.

Although various environmental factors, such as a high-salt diet, a smoking habit, excessive alcohol intake, and physical inactivity, influence the development of hypertension, genetic variation also contributes to an individual's susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to hypertension, and thereby contribute to the prediction of the genetic risk for this condition. The study population comprised 2752 unrelated Japanese individuals (1370 men, 1382 women), including 1276 subjects with hypertension (774 men, 502 women) and 1476 controls (596 men, 880 women). The genotypes for 50 polymorphisms of 35 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the Chi-square test and subsequent multivariable logistic regression analysis with adjustment for age, sex, body mass index, smoking status, and the prevalence of diabetes mellitus and hypercholesterolemia revealed that the -14C-->T polymorphism of ABCA1, the C-->G (Ser2229Cys) polymorphism of ROS1, the C-->T (Asn591Asn) polymorphism of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4, the C-->G and A-->C polymorphisms of ADIPOR1, and the -519A-->G polymorphism of MMP1 were significantly (P<0.05) associated with the prevalence of hypertension. Systolic and diastolic blood pressure differed significantly among genotypes for the -14C-->T polymorphism of ABCA1 and the C-->G (Ser2229Cys) polymorphism of ROS1, with the variant T and G alleles, respectively, being related to increased blood pressure. These results suggest that polymorphisms of ABCA1 and ROS1 are determinants of blood pressure and the development of hypertension in Japanese individuals. Determination of genotypes for ABCA1 and ROS1 may thus prove informative for the prediction of the genetic risk for hypertension.

Background: The aetiology of metabolic syndrome is complex, being determined by the interplay of both genetic and environmental factors. The aim of this study was to identify genetic polymorphisms that confer susceptibility to metabolic syndrome, to allow prediction of genetic risk for this condition., Methods: The study population comprised 2417 unrelated Japanese subjects (1522 with metabolic syndrome and 895 controls). The genotypes for 44 polymorphisms of 31 candidate genes related to lipid metabolism were determined using a combination of PCR and sequence-specific oligonucleotide probes with suspension array technology., Results: The chi(2) test and subsequent multivariate logistic regression analysis with adjustment for age, sex and smoking status found that the-3A-->G and 553G-->T (Gly185Cys) polymorphisms of APOA5, the 2052T-->C (Val653Val) and 1866C-->T (Asn591Asn) polymorphisms of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4 and the 1014T-->A polymorphism of C1QTNF5 were significantly (false discovery rate <0.05) associated with the prevalence of metabolic syndrome, with the variant alleles of APOA5 and C1QTNF5 representing risk factors for and those of LDLR and CYP3A4 being protective against this condition. Serum levels of triglycerides and high-density lipoprotein (HDL) cholesterol differed significantly (p<0.05) among APOA5 genotypes; the serum level of HDL cholesterol differed among LDLR genotypes; and the fasting plasma glucose level and body mass index differed between CYP3A4 and C1QTNF5 genotypes, respectively., Conclusions: APOA5, LDLR, CYP3A4 and C1QTNF5 are susceptibility loci for metabolic syndrome in Japanese people. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome.

Although several environmental factors, including a high-calorie diet and physical inactivity, influence the development of type 2 diabetes mellitus, genetic factors have been shown to contribute to individual susceptibility to this condition. The purpose of the present study was to identify gene polymorphisms that confer susceptibility or resistance to type 2 diabetes mellitus, and thereby to contribute to assessment of the genetic risk for this condition. The study population comprised 5259 unrelated Japanese individuals (2980 men, 2279 women), including 1640 subjects with type 2 diabetes mellitus (1071 men, 569 women) and 3619 controls (1909 men, 1710 women). The genotypes for 94 polymorphisms of 67 genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Evaluation of genotype distributions by the chi-square test revealed that the 13989-->G (Ile118Val) polymorphism of the cytochrome P450, subfamily IIIA, polypeptide 4 gene (CYP3A4) was significantly (false discovery rate, 0.000009) associated with the prevalence of type 2 diabetes mellitus. Multivariable logistic regression analysis with adjustment for age and sex also revealed that the 13989-->G (Ile118Val) polymorphism of CYP3A4 was significantly (P=0.00002) associated with the prevalence of type 2 diabetes mellitus, with the AG genotype being protective against this condition. Genotyping for CYP3A4 may thus prove informative for assessment of the genetic risk for type 2 diabetes mellitus.

Background: The purpose of this study was to identify risk factors for disease recurrence and unfavorable prognosis after surgical resection for stage I non-small cell lung cancer in patients with tumor diameters of < or =20 mm., Methods: One hundred sixty-three patients who had pathologic stage I non-small cell lung cancer with tumor diameters < or =20 mm and who had undergone a lobectomy with mediastinal lymph node dissection were retrospectively reviewed. The relationships between clinicopathologic factors and clinical outcomes, including recurrence and survival, were then examined. The clinicopathologic factors examined in this study were age, sex, smoking status, preoperative serum carcinoembryonic antigen level, pathologic tumor size, histologic subtype, histologic grade, and visceral pleural invasion., Results: Among the clinicopathologic factors that were examined, the histologic grade of the carcinoma status was significantly related to a high risk of recurrence when analyzed using univariate (p = 0.01) and multivariate analyses (p = 0.049). Regarding survival, patients with poorly differentiated carcinomas showed a significantly unfavorable overall survival (p < 0.001), disease-specific survival (p = 0.003), and disease-free survival (p = 0.002) compared with patients with well-/moderately differentiated carcinomas according to univariate analyses. A Cox proportional hazards model indicated that a poorly differentiated carcinoma status was the only independent factor for an unfavorable overall survival (p = 0.02), disease-specific survival (p = 0.046), and disease-free survival (p = 0.04)., Conclusions: Poor differentiation of tumor was the only risk factor for recurrence and an unfavorable prognosis for stage I non-small cell lung cancer patients with tumor diameters of < or =20 mm.

Objectives: The aim of the study was to identify gene polymorphisms that confer susceptibility to metabolic syndrome in order to allow reliable assessment of genetic risk for this condition., Methods and Results: The study population comprised 1788 unrelated Japanese individuals (1033 men, 755 women), including 1017 subjects with metabolic syndrome (634 men, 383 women) and 771 controls (399 men, 372 women). The genotypes for 158 polymorphisms of 133 candidate genes were determined with a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that the -1131T-->C polymorphism of the apolipoprotein A-V gene (APOA5) was significantly associated with the prevalence of metabolic syndrome, with the C allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that APOA5 genotype (CC+TC versus TT) significantly affected the prevalence of metabolic syndrome. The C allele of this polymorphism was associated with an increased serum concentration of triglycerides and a decreased concentration of HDL-cholesterol., Conclusions: Genotype for APOA5 may prove reliable for assessment of genetic risk for metabolic syndrome.

Acinic cell carcinoma of the breast is an uncommon neoplasm. Since the first case of this rare variant of breast carcinoma was reported in 1996, only 10 cases have been reported in the English-language literature. Reported herein is the first case of primary acinic cell carcinoma of the breast in a Japanese woman. To the naked eye, the tumor appeared well circumscribed and the cut surface was grayish-pink and hemorrhaging. Microscopically, the tumor was predominantly made up of a monotonous proliferation of cells with a finely granular cytoplasm, resembling acinic cells of the parotid gland. Some neoplastic cells had a clear cytoplasm. In spite of extensive sampling, no common histological patterns of breast carcinoma such as in situ and invasive ductal carcinoma were recognized in the present case, indicating that the present case was pure acinic cell carcinoma. In addition, the immunohistochemical profile of this tumor was identical to that of the acinic cell carcinoma of the salivary gland: estrogen receptor, progesterone receptor, HER2 and cytokeratin (CK)20 were negative and amylase and CK7 were positive. The patient has been well for 22 months since the wide local excision of the tumor and no signs of salivary neoplasm are evident to date.

The purpose of the present study was to identify gene polymorphisms for reliable assessment of genetic factors for type 2 diabetes mellitus. The study population comprised 4853 unrelated Japanese individuals (2688 men, 2165 women), including 1489 subjects with type 2 diabetes mellitus (969 men, 520 women) and 3364 controls (1719 men, 1645 women). The genotypes for 148 polymorphisms of 124 candidate genes were determined with a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Sixteen polymorphisms were related (p<0.05) to the prevalence of type 2 diabetes mellitus as determined by the chi-square test. Multivariable logistic regression analysis with adjustment for age, sex, and the prevalence of smoking revealed that, among these polymorphisms, the -603A --> G polymorphism of the gene for coagulation factor III (F3) was significantly (p<0.001) associated with the prevalence of type 2 diabetes mellitus, with the -603G allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that F3 genotype (GG versus AA + AG) significantly (p<0.001) and independently affected the prevalence of type 2 diabetes mellitus. Genotype for F3 may prove reliable for assessment of genetic factors for type 2 diabetes mellitus. Determination of the genotype for this gene may contribute to personalized prevention of this condition.

Vascular inflammation plays an important role in the development of myocardial infarction (MI). Lymphotoxin alpha (LTA) is a cytokine with multiple functions in regulation of the immune system and inflammatory reactions. The aim of this study was to examine whether polymorphisms of the LTA gene are associated with the risk of MI in Japanese men and women. A case-control association study was performed for the 252A-->G and 804C-->A polymorphisms of the LTA gene and the prevalence of MI. The study population comprised 3,689 unrelated Japanese individuals (2,486 men, 1,203 women), including 1891 patients with MI (1,493 men, 398 women) and 1798 control subjects (993 men, 805 women). Among the control subjects 257 individuals (108 men, 149 women) who had none of the conventional risk factors for coronary artery disease (CAD) were defined as low-risk controls. Genotypes for the two polymorphisms were determined with a fluorescence-based allele-specific DNA primer assay system. Among all study subjects the 252A-->G and 804C-->A polymorphisms exhibited linkage disequilibrium. No association of either polymorphism with MI was detected in men or in women in comparisons with total control or low-risk control subjects. However, each of the two polymorphisms was associated with the prevalence of type 2 diabetes mellitus both in men with MI and in those without MI in a recessive genetic model. No association was detected between the polymorphisms and other conventional risk factors for CAD. The LTA gene thus does not appear to be a susceptibility locus for MI in Japanese men or women, although it might affect susceptibility to type 2 diabetes in Japanese men.

Aims: The aim of the study was to identify genes that confer susceptibility to coronary artery spasm and clarify the interaction between genetic and environmental factors in this condition., Methods and Results: The study population comprised 2188 Japanese individuals, including 593 subjects with coronary artery spasm (453 men, 140 women) and 1595 controls (762 men, 833 women). The genotypes for 35 polymorphisms of 29 candidate genes were determined with an allele-specific DNA primer-probe assay. Multivariable logistic regression analysis adjusted for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolaemia, and hyperuricaemia revealed a significant association with coronary artery spasm of one polymorphism (242C-->T in the NADH/NADPH oxidase p22 phox gene) in men and two polymorphisms (-1171/5A-->6A in the stromelysin-1 gene and -634C-->G in the interleukin-6 gene) in women. A stepwise forward selection procedure revealed that smoking was the most important risk factor for coronary artery spasm and that the effects of these polymorphisms on this condition were statistically independent of smoking., Conclusion: The NADH/NADPH oxidase p22 phox gene is a susceptibility locus for coronary artery spasm in men, and the stromelysin-1 and interleukin-6 genes are susceptibility loci in women.

Background: Transforming growth factor-beta (TGF-beta) is an important regulator of vascular remodeling and is involved in the pathogenesis of atherosclerosis. A T-->C transition at nucleotide 29 of the TGF-beta1 gene results in a Leu-->Pro substitution at amino acid 10 of the signal peptide. We have now examined a possible association of TGF-beta1 genotype with myocardial infarction (MI) in a Japanese population., Methods and Results: TGF-beta1 genotype was determined in 315 Japanese patients (234 men and 81 women) with MI and 591 control subjects (289 men and 302 women). We found that age, body mass index, and incidence of habitual smoking, hypertension, diabetes mellitus, and hypercholesterolemia did not differ between the 2 groups for either men or women. Multivariable logistic regression analysis, however, demonstrated the frequency of the T allele to be significantly higher in male subjects with MI than in controls (TT + TC versus CC; P<0.0001, odds ratio 3.5, 95% CI 2.0 to 6.3). In contrast, the T allele was not associated with the prevalence of MI in women. In both male MI patients and controls, the serum concentration of TGF-beta1 was significantly higher in individuals with the CC genotype than in subjects with the TT or TC genotype., Conclusions: Findings suggest that the T allele at nucleotide 29 in the TGF-beta1 gene is a risk factor for genetic susceptibility to MI, at least in middle-aged Japanese men.

Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familial hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals, including 6 with HCM, was subjected to genetic and clinical assessment. Five exons of the cTnT gene were sequenced in all family members. A heterozygous or homozygous T(340)-->A (Phe(110)-->Ile) mutation in exon 9 of the cTnT gene was detected in 11 subjects. Morphological and functional evaluation of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderate cardiac hypertrophy. Cardiac hypertrophy and other clinical features in the 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM. Thus, the clinical features of HCM due to the Phe(110)-->Ile mutation in the cTnT gene appear to be modified by a gene dosage effect., (Copyright 2000 S. Karger AG, Basel)

We investigated the association between variations in the endothelial constitutive nitric oxide synthase (ecNOS) gene and the presence of myocardial infarction. The results indicate that the mutant allele (ecNOS'4a) is an independent risk factor for myocardial infarction in the Japanese population, especially in those lacking other conventional risk factors.

The renin-angiotensin system is important in cardiovascular remodeling. Although a variant of the angiotensinogen gene is associated with an increased generation of angiotensinogen, it is unclear how this genetic variant might influence the activity of the renin-angiotensin system and thereby contribute to the predisposition to coronary artery disease (CAD). The relation between genetic polymorphisms in the gene-encoding angiotensinogen and the risk of CAD in middle-aged Japanese men was investigated. Two polymorphisms in exon 2 of the angiotensinogen gene, M235T and T174M, were analyzed in 327 patients with CAD and 352 matched control subjects. The genotype distribution of both polymorphisms did not differ between patients with CAD and control subjects. No combination of genotypes of the two polymorphisms was associated with CAD. Results indicate that the M235T and T174M variants of the angiotensinogen gene are not associated with CAD in Japanese men.

The frequency of acute and chronic pancreatitis is 3.3 and 2.1%, respectively, in 107,754 adult autopsies in Japan. Acute pancreatitis is highly associated with liver diseases of various etiologies such as subacute hepatitis (16.1%), fulminant hepatitis (13.5%), biliary cirrhosis (10.5%), cholangiocarcinoma (8.6%) and postnecrotic cirrhosis (7.1%). Chronic pancreatitis is also closely related to various liver diseases. It is suggested that the portal venous stasis in liver diseases may predispose the patients to develop pancreatitis regardless of the etiology of liver diseases.