Search

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06–1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34–2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06–1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms. [ABSTRACT FROM AUTHOR]

Objective Recently, TMEM127 was shown to be a new pheochromocytoma susceptibility gene; this is consistent with its function as a tumour suppressor gene ( Journal of Clinical Endocrinology and Metabolism, 2009, 94, 2817). Most pheochromocytomas arise from the adrenal medulla, and in approximately half of the cases, the tumours are bilateral ( Journal of Clinical Endocrinology and Metabolism, 2009, 94, 2817; Journal of the American Medical Association, 2004, 292, 943; Human Mutation, 2010, 31, 41; Science, 2009, 325, 1139). The aim of the present study was to determine whether TMEM127 mutations are involved in the pathogenesis of pheochromocytomas/paragangliomas in Japanese subjects. Patients and Methods For this study, 74 unrelated patients with pheochromocytoma/paraganglioma who tested negative for mutations and deletions in RET, VHL, SDHB and SDHD were recruited through a multi-institutional collaborative effort in Japan. The TMEM127 gene sequence was determined in their germline DNA, and tumour DNA was analysed for the loss of heterozygosity. In addition, their TMEM127 gene sequences were compared with sequences from 114 normal healthy, ethnically matched controls. Results Among the 74 eligible patients, two unrelated patients (2·7%) with bilateral adrenal pheochromocytoma were found to have an identical germline TMEM127 mutation (c.116_119delTGTC, p.Ile41ArgfsX39) associated with 2q deletion loss of heterozygosity, which was also previously described in a Brazilian case ( Journal of the American Medical Association, 2004, 292, 943). We also determined that none of the 114 normal healthy controls had this deletion mutation. Conclusion This is the first report showing that TMEM127 mutation plays a pathological role in pheochromocytoma in an Asian population. Although our surveillance is limited, the prevalence and the phenotype of this gene mutation appear to be similar to those reported in previous studies. [ABSTRACT FROM AUTHOR]

Abstract: Anisakid nematodes are known to cause the zoonotic disease, anisakiasis, through the consumption of raw or undercooked fish. The parasites most frequently associated with the disease in humans are categorized as Anisakis type I, which comprise several species of the genus Anisakis. The larvae show primitive forms and lack the detailed morphological characteristics required for precise species identification. Thus, molecular characterization is necessary for determining the species of Anisakis type I larvae and acquiring important clinical and epidemiological information. In this study, we isolated Anisakis type I larvae from hairtail fish caught off the coasts of Taiwan and Japan. The ribosomal DNA (rDNA) internal transcribed spacer (ITS) region was sequenced, and restriction fragment length polymorphism (RFLP) analyses using HinfI and HhaI was carried out for species identification. Most larvae isolated from hairtail caught in Taiwan were Anisakis typica (84%), while those isolated from hairtail caught in Japan were almost exclusively identified either as Anisakis simplex sensu stricto (65%) or Anisakis pegreffii (33%). This is the first report of A. typica in fish obtained from Taiwan. Our results shed the light on the epidemiology of Anisakis type I larvae, which is a potential cause of human anisakiasis in Taiwan and Japan. [ABSTRACT FROM AUTHOR]

Abstract: Anisakis simplex complex presently comprises three sibling species, A. simplex sensu stricto, A. pegreffii and A. simplex C. A. simplex is a common parasite in fishes and cephalopods and capable of causing anisakiasis in humans. Therefore, identification of sibling species of A. simplex was important for human health. In this study, one hundred Anisakis type I larvae isolated from eighty five patients with anisakiasis in Hokkaido and Kyushu in Japan were analyzed by adapting the new molecular method that can identify the sibling species of A. simplex complex. Based on the restriction fragment length polymorphism (RFLP) pattern of ITS regions including 5.8 subunit rRNA gene, we identified two sibling species, A. simplex s. str. and A. pegreffii. However, the infection rate of A. simplex s. str. was significantly higher than that of A. pegreffii. Eighty four (98.8%) out of the eighty five patients were infected with A. simplex s. str. On the contrary, one patients (1.2%) in Kyushu infected with A. pegreffii. This study provided basic information about human infection with A. simplex complex. Furthermore, we suggested that A. simplex s. str. is the most important etiological agent in Japan. [Copyright &y& Elsevier]

The SDHA, SDHB, SDHC, and SDHD genes code for subunits of succinate dehydrogenase (SDH), which forms part of the mitochondrial respiratory chain. Germline mutations in the genes encoding SDHB and SDHD have been reported in familial paragangliomas/pheochromocytomas and in apparently sporadic pheochromocytomas. SDHB and SDHD mutations are widely distributed along the genes with no apparent hot spots. SDHB mutations are often detected in malignant and extra-adrenal pheochromocytomas. SDHD mutations are also detected frequently in head and neck paragangliomas. We sequenced the entire coding regions of the SDHB and SDHD genes in 17 pheochromocytomas. Weidentified novel heterozygous G to A point mutations at the first base of intron 3 of the SDHB gene in a malignant extra-adrenal abdominal pheochromocytoma patient, and at the first base of codon 111 of the SDHD gene in an adrenal pheochromocytoma patient. Further, we confirmed the SDHD mutation by DHPLC. The prevalence of SDHB and SDHD mutations in pheochromocytomas we examined was 12% (2/17). Thus, we identified two novel SDH mutations in Japanese pheochromocytomas. Further studies will investigate the oncogenic potential of these mutations. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Paragonimiasis is a particular foodborne parasitic disease that is endemic to southern Kyushu, including Kagoshima Prefecture, Japan. We previously detected Paragonimus westermani triploid larvae in meat samples obtained from wild boars and sika deer hunted in Akune City, Kagoshima Prefecture. These mammals act as paratenic hosts and their meat is a source of human paragonimiasis. Paratenic host mammals and humans become infected with the lung fluke, P. westermani, following consumption of second intermediate hosts, freshwater crab species, namely, Geothelphusa dehaani or Sawagani in Japanese, and Eriocheir japonica or Mokuzugani in Japanese. Therefore, this study aimed to investigate the current infection status of P. westermani in freshwater crabs in Akune City. We collected freshwater crabs from 15 locations and found that the prevalence of P. westermani metacercariae was 1.6% for Sawagani (15 of 941 examined) and 22.1% for Mokuzugani (21 of 95 examined). Based on the morphological characterization of metacercariae and molecular analyses of the internal transcribed spacer 2 region and mitochondrial 16S rRNA gene region using PCR-restriction fragment length polymorphism and sequencing, all metacercariae were identified as the triploid form of P. westermani. These results indicate that Sawagani and Mokuzugani serve as second intermediate hosts to maintain the life cycle of triploid P. westermani. Further, infection in crabs potentially leads to subsequent P. westermani infections in wild mammals, including wild boars and sika deer, both of which are considered important types of game meat in Japan.

Ascaris lumbricoides or roundworm is one of the key soil-transmitted helminths affecting humans. A small number of infections continue to occur in Japan, suggesting plant foodstuff contamination as the source of infection. To understand the current status of ascariasis incidence and to identify potential sources of infection, we extensively surveyed the available literature and collected data from testing facilities that examined clinical samples or foodstuffs. We observed that from 2002 onwards, there was a decrease in the number of ascariasis cases reported in scientific journals. Data from a clinical testing facility indicated that the number of detected cases declined remarkably from 2009. Foodstuff testing facilities reported that 11 of 10,223 plant foodstuff specimens were contaminated with anisakid nematodes but not with Ascaris. Imported kimchi was suspected as the most probable source of ascarid nematode infection, as one Ascaris egg-positive sample was detected among 60 kimchi samples in a testing facility. Therefore, the sources of Ascaris infection are still not fully known and need to be clarified to establish preventive countermeasures to safeguard Ascaris infections that continue to occur in Japan.

Chromogranin A (CHGA) is a major protein in the secretory granules of chromaffin cells. CHGA also gives rise to cardiovascular/metabolism regulatory peptides, such as catestatin (CST) and pancreastatin (PST). While CST is a potent inhibitor of catecholamine secretion, PST is a potent physiological inhibitor of glucose-induced insulin secretion. Recently, several SNPs were identified in the CST and PST domains of CHGA locus in different populations. Among the discovered SNPs, CST variant allele Ser-364 was associated with blood pressure alteration and PST variant allele Ser-297 was associated with significantly higher plasma glucose level. In this study, we examined whether these CST and PST variant alleles exist and influence cardiovascular and metabolic phenotypes in Japanese population. Our study comprised of 343 Japanese subjects aged 45-85 years (143 men and 200 women, mean age 66 ± 8 years). We determined the genotypes of CST and PST by PCR-direct sequencing method and carried out genotype-phenotype association analysis. In 343 participants, the minor allele frequency of CST variant Ser-364 was 6.10%. On the other hand, we did not detect the PST variant Ser-297 in this entire study population. The presence of Ser-364 allele was associated with increased in baPWV (an index of systemic arterial stiffness) that suggests an initiation and/or progression atherogenesis and hypertension. The Ser-364 allele was also associated with elevated systolic blood pressure and pulse pressure, consistent with increased baPWV. In conclusion, the CST Ser-364 allele may increase the risk for cardiovascular diseases in Japanese population.

Measuring the levels of the plasma free metanephrines (PFMs) represents a recently developed and promising test for the diagnosis of pheochromocytoma in the United States and Europe. As this test has not yet been evaluated in Japan, it is necessary to evaluate the diagnostic efficacy of measuring the levels of PFMs compared with the standard measurement of the urinary excretion of metanephrines (uMNs) whose reliability is well established to detect of pheochromocytoma. A total of 101 Japanese subjects clinically suspected of having pheochromocytoma in were included in this study. Subsequently, we prospectively measured the PFMs levels in all patients, compared with those of biochemical markers of the catecholamine secretion and metabolisms in the plasma and urine. All subjects with adrenal tumors underwent tumor excision. Data were available for 84 of the 101 patients, 47 of whom had histopathologically proven pheochromocytoma and 37 were finally diagnosed with non-pheochromocytoma. The results of comparisons in the accuracy of measurement for diagnosis of pheochromocytoma between PFMs and the urinary excretion of metanephrines (uMNs) were 0.980 VS 0.951 for AUC of receiver operatorating characteristic (ROC) curve, 0.957 VS 0.894 for sensitivity, and 0.973 VS 0.946 for specificity, respectively. Although the differences were small, the results of our study definitely demonstrated that measurement of PFMs was not inferior to standard urinary metanephrines (uMNs) measurement, which is established to be the most reliable biochemical method to detect pheochromocytoma. This study clearly shows measuring the PFMs levels to be a reliable and efficient method for diagnosing pheochromocytoma in Japanese patients, as demonstrated in previous reports.

Although Proteus mirabilis is a common human pathogen, bacteremia caused by the organism, especially strains producing extended-spectrum beta-lactamase (ESBL), has rarely been investigated. We examined 64 cases of P. mirabilis bacteremia identified in the Minami Ibaraki Area, Japan, between 2001 and 2010 and compared the characteristics of cases with ESBL-producing and ESBL-non-producing strains (13 and 51 cases, respectively). All ESBL-producing strains with the gene encoding the CTX-M-2-group were genetically nonidentical. Isolation of ESBL-producing strains was significantly associated with onset in a hospital (p = 0.030), receiving hemodialysis (p = 0.0050), and previous antibiotic use within 1 month (p = 0.036; especially penicillin and/or cephalosporin (p = 0.010) and fluoroquinolone (p = 0.0069)). Isolation was also associated with inappropriate antibiotic therapy on the 1st and 4th days (p = 0.011 and 0.032, respectively) but not with mortality on the 30th day. These findings indicate that, for P. mirabilis bacteremia, isolation of ESBL-producing strains causes delay of initiating appropriate antimicrobial therapy but may not be associated with mortality.

Feline cases of lung fluke infection were recently reported in the upper basin of the Oi River in Shizuoka Prefecture. The causative species of these cases were not identified, although a field survey conducted about 40 years ago in this area demonstrated the prevalence of Paragonimus miyazakii metacercariae in intermediate host crabs. To clarify the current status of lung fluke metacercarial infection in host crabs, we collected the Japanese freshwater crab or Sawagani, Geothelphusa dehaani, at 14 sampling sites in the Kawane area, which is located in the upper basin of the Oi River. Sawagani harboring Paragonimus metacercariae were collected at all sampling sites in this study with a total prevalence of 42% (281 of 677 crabs examined) and a range of 16% to 92%. The number of metacercariae per infected crab ranged from 1 to 19 with a mean of 2.2. Based on the morphological features of the metacercariae and adult worms recovered from rats that were experimentally infected with the metacercariae, the lung flukes examined were identified as P. miyazakii Kamo, Nishida, Hatsushika and Tomimura, 1961; ITS2 sequence data corroborate this conclusion. P. miyazakii is still widely prevalent in this area, implying that the recently reported feline paragonimiasis cases were likely caused by P. miyazakii infection.

For microbial ecological analysis, 14 strains of Methylobacterium aquaticum isolated from water samples were subjected to clustering analysis on the basis of ribotyping and RAPD-PCR tests. The ribopatterns after digestion with EcoRI obtained from 14 strains of M. aquaticum were used to divide the strains into two groups (Groups I and II) with a similarity of 55%. From the analysis of RAPD patterns using primer 208, the 14 strains were divided into 3 groups (A-C) based on a homology of 45% or greater, and from that using primer 272, there were 4 groups (A-D) based on a homology of 50% or greater. The chlorine resistance (99.9% CT values) of these isolates was also experimentally confirmed, and we attempted to define the connection between chlorine resistance and the geno-cluster. The average CT value of group I was 0.89 mg•min/l and the average of group II was 0.69 mg•min/l. No remarkable differences in the CT values for the groups were found.

Pseudomonas aeruginosa strains were isolated from 45 of 370 (12.2%) cockroaches captured in hospitals. By cockroach species, the bacterial strains were isolated from 39 of 181 (21.5%) Periplaneta fuliginosa and 6 of 183 (3.3%) Blattella germanica, showing a significant difference (p<0.01). Many P. aeruginosa-carrying cockroaches inhabited locker rooms (66.7%) and kitchens (17.8%). In terms of serotyping, many isolates were typed into groups A, G, and B. In drug sensitivity tests, strains showed the highest sensitivity to ciprofloxacin with an MIC90 of 0.25 microg/ml, followed by 2 microg/ml meropenem, and 4 microg/ml ceftazidime, gentamicin, and ofloxacin. In contrast, many strains were resistant to cefotaxime and minocycline, accounting for 86.7% of all resistant strains. However, there was no multidrug-resistant P. aeruginosa strain, and all strains were negative for the metallo-beta-lactamase gene (IMP-1 and VIM-2). These findings suggested that cockroach-derived P. aeruginosa may contaminate hospital environments, for which the control of disease-carrying insects in hospitals is important.

A multiplex PCR method was established for the rapid identification of Anisakis simplex sensu stricto, A. pegreffii, A. physeteris, Pseudoterranova decipiens, Contracaecum osculatum and Hysterothylacium aduncum. The sequence alignment of the internal transcribed spacer 1 region (ITS-1) between A. simplex s. str. and A. pegreffii showed a high degree of similarity, but only two C-T transitions were observed. To differentiate A. simplex s. str. from A. pegreffii, an intentional mismatch primer with an artificial mismatched base at the second base from the primer 3' end was constructed. This intentional mismatch primer, which produced a PCR band only from A. pegreffii DNA, was able to differentiate the two morphologically indistinguishable sibling species of A. simplex. Specific forward primers for other anisakid species were also designed based on the nucleotide sequences of the ITS region. The multiplex PCR using these primers yielded distinct PCR products for each of the anisakid nematodes. The multiplex PCR established in this study would be a useful tool for identifying anisakid nematodes rapidly and accurately.

Parasites morphologically consistent with Anisakis simplex sensu lato collected from the coast of Japan and Western North Pacific Ocean were examined by PCR-RFLP of the ITS region (ITS1, 5.8 subunit rRNA gene and ITS2) and mtDNA cox1. The RFLP patterns of rDNA generated by HinfI and HhaI showed that 100% of the larvae collected from Hokkaido and 94% of adults collected from Western North Pacific Ocean were identified as A. simplex sensu stricto. On the other hand, 97% of the larvae collected from Fukuoka prefecture were identified as A. pegreffii. A hybrid genotype was found in adults in Western North Pacific Ocean and larva in Fukuoka prefecture. These findings revealed that A. simplexs. str. is primarily distributed in the North Pacific Ocean and A. pegreffii is primarily distributed in the southern Sea of Japan. RFLP analysis of mtDNA cox1 showed different patterns between A. simplex s. str. and A. pegreffii after digestion with HinfI. This polymorphism obtained by RFLP analysis of mtDNA cox1 proved the usefulness as new genetic markers to distinguish two sibling species.

Plasma non-HDL cholesterol (HDL-C) concentration that is simply estimated from plasma total cholesterol and HDL-C concentrations, without the influence of plasma triglyceride concentration, has been included as a therapeutic target for hypertriglyceridemic patients in the most recent National Cholesterol Education Program (NCEP) recommendations. In the present study, we estimated plasma non-HDL-C concentration in Japanese subjects to clarify the correlation of plasma non-HDL-C to other plasma lipid concentrations, and to evaluate the NCEP recommendation. Plasma non-HDL-C concentration has a positive correlation with low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations. From our analysis, 140 mg/dl of plasma LDL-C concentration, which is the level for the diagnosis of hyper-LDL cholesterolemia, corresponds to 169 mg/dl of non HDL-C concentration. The relationship between plasma non-HDL-C and LDL-C concentrations in Japanese subjects is quite similar to that described in the NCEP guideline. Thus, we suggest that non-HDL-C is a useful risk marker in Japan, as recommended by the NCEP.