Characteristics of Highly Polymorphic Segmental Copy-Number Variations Observed in Japanese by BAC-Array-CGH

Segmental copy-number variations (CNVs) may contribute to genetic variation in humans. Reports of the existence and characteristics of CNVs in a large Japanese cohort are quite limited. We report the data from a large Japanese population. We conducted population screening for 213 unrelated Japanese individuals using comparative genomic hybridization based on a bacterial artificial chromosome microarray (BAC-aCGH). We summarize the data by focusing on highly polymorphic CNVs in ≥5.0% of the individual, since they may be informative for demonstrating the relationships between genotypes and their phenotypes. We found a total of 680 CNVs at 16 different BAC-regions in the genome. The majority of the polymorphic CNVs presented on BAC-clones that overlapped with regions of segmental duplication, and the majority of the polymorphic CNVs observed in this population had been previously reported in other publications. Some of the CNVs contained genes which might be related to phenotypic heterogeneity among individuals

Dimethyl sulfoxide-respiring bacteria in Suribati Ike, a hypersaline lake, in Antarctica and the marine environment

Dimethyl sulfoxide (DMSO) occurs worldwide, especially in marine environments as well as in lakes and rainwater. DMSO respiration by bacteria is assumed to play an important role in the sulfur cycle in Antarctica and on earth. We first studied whether DMSO-respiring bacteria existed in Antarctica. Eight strains were isolated that grew by DMSO respiration under anaerobic conditions from water of the halocline in a meromictic lake, Suribati Ike, near Syowa Station in Antarctica. All of them were related to known species belonging to the genus Marinobacter based on 16S rRNA gene sequences. Using a clone library analysis of 16S rRNA gene sequences, 38 of total 48 clones from water of the halocline were identified as Marinobacter. Studies on the various anaerobic respiration capabilities by bacteria in the halocline water found only DMSO respiration. Studies on bacteria with anaerobic respiration abilities in seawater from the Pacific Ocean and Seto Inland Sea, showed that either DMSO-respiring or nitrate-respiring bacteria were present and that all of isolates capable of DMSO respiration were closely related to Vibrio species

Clinical application of the Personal Dialysis Capacity (PDC) test: Serial analysis of peritoneal function in CAPD patients

Clinical application of the Personal Dialysis Capacity (PDC) test: Serial analysis of peritoneal function in CAPD patients.BackgroundPeritoneal damage has been reported since the beginning of CAPD therapy.MethodsTo clarify the change of peritoneal function in CAPD patients, we used the Personal Dialysis Capacity (PDC) test in 22 patients with 49 serial studies and 14 patients with single studies. The data were expressed at the condition of 2.5% (2.27g/dl of glucose), four times at 2,000 ml/day.ResultsIn the mass analysis, the urea generation rate, creatinine generation rate, PNA/PCR, and water removal via the peritoneum (PD) were kept at the same level for almost eight years, and then gradually decreased. Urine volume and residual renal creatinine clearance (CCr) became zero at six years. On the other hand, PD CCr increased gradually with the time course of CAPD, and therefore the total CCr remained at the level of 6.0ml/min even after six years. Weekly urea KT/V decreased gradually from almost 2.800 to 2.000. The protein loss remained approximately 7.0g/day for the initial five years, then became 6.0g/day, except in five patients who showed levels above 10.0g/day on the first test of PDC. Weekly urea KT/V was correlated with residual renal CCr (P < 0.005), and significantly correlated with total CCr (weekly urea KT/V = -0.2798 + 0.3720 × total CCr; r = 0.915, P < 0.001). In the serial analysis, when the first and the last tests were compared, the urea generation rate increased significantly (mean ± sd, 2.800 ± 3.204 vs. 3.882 ± 3.382; P < 0.0001); however, water removal via PD (1364 ± 887 vs. 813 ± 609; P = 0.021), total ultrafiltration (1762 ± 841 vs. 1124 ± 843; P = 0.042), and weekly urea KT/V (2.285 ± 0.486 vs. 2.112 ± 0.512; P = 0.026) decreased significantly. The delta water removal via PD/duration became negative (-10.03 ± 6.59 ml/week) in all 7 patients after more than four years, however, it was positive (+14.40 ± 7.84 ml/week) in 6 of 10 patients after less than one year.ConclusionThese results suggest that water removal via PD increases within one year, then decreases after four years. The PDC test is useful to evaluate the change of peritoneal function in mass and serial analyses

High Excess Risk of Heart Disease Mortality among Hiroshima Atomic Bomb Male Survivors Exposed Near the Hypocenter

Heart disease (HD) mortality is the second leading cause of death in Japan. The HD mortality risk among Atomic bomb survivors is slightly positive but shows a statistically significant dose-response relationship with initial radiation dose, as reported by the Radiation Effects Research Foundation. In that report, dosimetry was based on initial radiation only, with the effect of indirect radiation dose not taken into consideration. The atomic bomb radiation, however, consisted of both initial and residual radiation. We reevaluated the dose-response relationship for HD mortality using exposure distance (ground distance between the location where exposed and the hypocenter) as a surrogate indicator of radiation dose. At Hiroshima University, a cohort study has been conducted with Hiroshima Atomic Bomb Survivors (ABS) since 1970. We selected 29605 subjects from the ABS who were exposed at 3.5 km or less from the hypocenter and alive on January 1, 1970. These subjects, referred to as “Hiroshima hibakusha” in this paper, were followed until December 31, 2010. We stratified the cohort data with respect to sex and age at the time of bombing (ATB) into 10-year age groups. For each stratum, by applying an extended Cox regression model with time-dependent covariates, we analyzed the risk of HD mortality using either initial radiation dose or exposure distance as an explanatory variable. The results indicate a high excess risk in males and older age ATB females who were exposed near the hypocenter. This difference may be explained by the effect of female sex hormone on the circulatory system among young age ATB females. Some unknown risk factor related to exposure distance was also implicated in the elevated risk of HD among the Hiroshima hibakusha, especially in males. This necessitates further study.This research was supported in part by Grants-in-Aid for Scientific Research (A) 24249039 (2012–2014), and the Joint Usage/Research Center (RIRBM), Hiroshima University

Adsorption of Urinary Proteins on the Conventionally Used Urine Collection Tubes: Possible Effects on Urinary Proteome Analysis and Prevention of the Adsorption by Polymer Coating

One possible factor determining recovery of trace amount of protein biomarker candidates during proteome analyses could be adsorption on urine tubes. This issue, however, has not been well addressed so far. Recently, a new technical device of surface coating by poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (poly(MPC-co-BMA)) has been developed mainly to prevent the adsorption of plasma proteins. We assessed whether conventionally used urine tubes adsorb trace amount of urinary proteins and, if any, whether the surface coating by poly(MPC-co-BMA) can minimize the adsorption. Proteinuric urine samples were kept in poly(MPC-co-BMA)-coated and noncoated urine tubes for 15 min and possibly adsorbed proteins and/or peptides onto urine tubes were analyzed by SDS-PAGE, 2-DE, and the MALDI-TOF MS. It was found that a number of proteins and/or peptides adsorb on the conventionally used urine tubes and that surface coating by poly(MPC-co-BMA) can minimize the adsorption without any significant effects on routine urinalysis test results. Although it remains to be clarified to what extent the protein adsorption can modify the results of urinary proteome analyses, one has to consider this possible adsorption of urinary proteins when searching for trace amounts of protein biomarkers in urine

High Initial-dose Dependency of Cerebrovascular Disease Mortality among Female Survivors of the Hiroshima Atomic Bomb Exposed in Teens : A Cohort Study, 1970-2010

Several studies have been conducted on cerebrovascular disease mortality in Atomic bomb survivors. Previous studies have investigated the relationship between mortality and initial radiation dose after adjusting for the effects of sex and age at the time of the bombing (ATB), and detected a weak (but statistically significant) dose-response relationship was detected. The objective of the present study was to examine whether the sex- and age ATB-specific cerebrovascular disease mortality among Hiroshima atomic bomb survivors can be explained by the initial radiation dose. At Hiroshima University, a cohort study has been conducted with Hiroshima Atomic Bomb Survivors (ABS) since 1970. We selected 30,378 subjects from the ABS who were exposed at 3.5 km or less from the hypocenter and still alive on January 1, 1970. These subjects were followed up until December 31, 2010. The cohort data were stratified with respect to sex and age ATB into 10-year age groups. For each stratum, using Cox regression, we performed survival analyses of the risk of cerebrovascular mortality using the initial radiation dose and the exposure distance (the ground distance between the exposure location and the hypocenter) as explanatory variables. The results indicated that the risks to females exposed at 10 to 19 years old were highly dependent on the initial radiation dose (hazard ratio: 1.51, p < 0.001), while the risks to males were not. There might exist some radiation exposure effects limited to women who were in their teens at the time of exposure. However, the background mechanisms remain unclear, necessitating further study.This study was supported in part by Grants-in-Aid for Scientific Research (A) 24249039, Young Scientists (B) 23790694, and 23700337 from the Japanese Ministry of Education, Culture, Sports, Science and Technology

Cast: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and munc13-1

The cytomatrix at the active zone (CAZ) has been implicated in defining the site of Ca2+-dependent exocytosis of neurotransmitter. We have identified here a novel CAZ protein of ∼120 kD from rat brain and named it CAST (CAZ-associated structural protein). CAST had no transmembrane segment, but had four coiled-coil domains and a putative COOH-terminal consensus motif for binding to PDZ domains. CAST was localized at the CAZ of conventional synapses of mouse brain. CAST bound directly RIM1 and indirectly Munc13-1, presumably through RIM1, forming a ternary complex. RIM1 and Munc13-1 are CAZ proteins implicated in Ca2+-dependent exocytosis of neurotansmitters. Bassoon, another CAZ protein, was also associated with this ternary complex. These results suggest that a network of protein–protein interactions among the CAZ proteins exists at the CAZ. At the early stages of synapse formation, CAST was expressed and partly colocalized with bassoon in the axon shaft and the growth cone. The vesicles immunoisolated by antibassoon antibody–coupled beads contained not only bassoon but also CAST and RIM1. These results suggest that these CAZ proteins are at least partly transported on the same vesicles during synapse formation

Advance Requests of In-patients and Their Families regarding Medical Intervention Practices at the End of Life

Much emphasis is being placed nowadays on Advance Care Planning（ACP）. Under this circumstance, we report on the “advance-request form” prepared by our hospital, along with some relevant considerations. ［Intended Persons and Method］A total of ５３９ newly admitted patients and their families were asked to sign and submit the “advance-request form,” indicating their preferences on the following three kinds of end-of-life interventional practices:（ １）cardiac massage,（２）endotracheal intubation and mechanical ventilation, and（３）use of vasopressors. ［Results］Completed questionnaires were returned by ２１５ male and ３２４ female patients（average age :８２．３ years）. Of the responders, ７２（１４％）indicated their desire for all the three of the aforementioned interventions（［１］,［２］, and［３］）,６５（１２％）indicated their desire for only（１）, ４５（８%）indicated their desire for only（１）and（３）, １４（３%）indicated their desire for only（３）, while the remaining３４１（６３%）requested that none of these to be implemented. Of all the patients, ８７（１６％）patients were able to make their own decisions. ［Conclusion］About ３０％ or more patients and their families indicated their desire for some kind of life-sustaining treatment at the end of life. We believe that ACP only prioritizes a patient’s right to self-determination and that the practice of ACP should not lead to withholding of life-sustaining treatment