Reduced pain sensitivity of episodic pain syndrome model mice carrying a Nav1.9 mutation by ANP-230, a novel sodium channel blocker.

The sodium channel Nav1.9 is expressed in the sensory neurons of small diameter dorsal root ganglia that transmit pain signals, and gain-of-function Nav1.9 mutations have been associated with both painful and painless disorders.

Familial episodic limb pain in kindreds with novel Nav1.9 mutations.

We previously performed genetic analysis in six unrelated families with infantile limb pain episodes, characterized by cold-induced deterioration and mitigation in adolescence, and reported two new mutations p.R222H/S in SCN11A responsible for these episodes. As no term described this syndrome (familial episodic pain: FEP) in Japanese, we named it as"".

RNF213 Rare Variants in Slovakian and Czech Moyamoya Disease Patients.

RNF213/Mysterin has been identified as a susceptibility gene for moyamoya disease, a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The p.R4810K (rs112735431) variant is a founder polymorphism that is strongly associated with moyamoya disease in East Asia.

Identification of MMP1 as a novel risk factor for intracranial aneurysms in ADPKD using iPSC models.

Cardiovascular complications are the leading cause of death in autosomal dominant polycystic kidney disease (ADPKD), and intracranial aneurysm (ICA) causing subarachnoid hemorrhage is among the most serious complications. The diagnostic and therapeutic strategies for ICAs in ADPKD have not been fully established. We here generated induced pluripotent stem cells (iPSCs) from seven ADPKD patients, including four with ICAs.

Biological Monitoring of Human Exposure to Neonicotinoids Using Urine Samples, and Neonicotinoid Excretion Kinetics.

Background: Neonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.

Paradoxical increases in serum levels of highly chlorinated PCBs in aged women in clear contrast to robust decreases in dietary intakes from 1980 to 2003 in Japan.

Objective: Exposure to polychlorinated biphenyls (PCBs) is considered to have culminated between 1950 and 1970 in Japan, and exposure through diet, the major exposure route, has decreased significantly over the last 10 years. The primary goal of the present study was to investigate the long-term trends and congener profiles of serum and dietary levels of PCBs using historical samples.

Methods: Using banked samples collected in 1980, 1995, and 2003 surveys, we determined the daily intakes and serum concentrations of 13 PCB congeners (#74, #99, #118, #138, #146, #153, #156, #163, #164, #170, #180, #182, and #187) in women.

Association analyses confirming a susceptibility locus for intracranial aneurysm at chromosome 14q23.

Previous linkage analyses of intracranial aneurysm (IA) have proposed several genetic susceptibility loci; however, some loci remain contradictory. The objective of this study was to confirm these loci in a Japanese population using allelic and haplotype association analyses. We set high-density single nucleotide polymorphism markers in previously suggested IA loci and conducted an association analysis in 29 cases and 35 controls from a small community in Akita, Japan.

Birth of cloned miniature pigs derived from somatic cell nuclear transferred embryos activated by ultrasound treatment.

The present study was carried out to determine (1) the optimal duty cycle of ultrasound for activation of pig oocytes and cloned embryos derived from miniature pig fetal fibroblasts and (2) whether cloned embryos can develop to term following activation by ultrasound stimulation. When oocytes were exposed to ultrasound with 20% or 30% duty cycle, the blastocyst formation rates were significantly (P < 0.05) higher than that of oocytes exposed to ultrasound with 10% duty cycle.

Combination of linkage and association studies for brain arteriovenous malformation.

Background And Purpose: Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background.

Methods: A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program.

Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm.

Background And Purpose: In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci.

Dimorphic gene expression patterns of anorexigenic and orexigenic peptides in hypothalamus account male and female hyperphagia in Akita type 1 diabetic mice.

Progression of the diabetic trait is usually more rapid in males than females. The major aim of the present study is to explore sexual dimorphism in the hypothalamus in Akita mice. Akita male mice develop hyperphagia, reducing anorexigenic proopiomelanocortin (POMC), and increasing orexigenic neuropeptide Y (NPY) mRNA levels compared with wt males.

Proteomic analysis for protein carbonyl as an indicator of oxidative damage in senescence-accelerated mice.

The senescence-accelerated prone mouse strain 8 (SAMP8) exhibits a remarkable age-accelerated deterioration in learning and memory. In this study, we identified carbonyl modification, a marker of protein oxidation, in liver and brain of SAMP8 from peptide mass fingerprints using MALDI-TOF mass spectrometry in combination with LC-MS/MS analysis. Carbonyl modification of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in liver at 3 month and hippocampal cholinergic neurostimulating peptide precursor protein (HCNP-pp) in brain at 9 month were higher in SAMP8 compared with control SAMR1.

Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm: a preliminary study.

Background: Our previous studies have shown a significant linkage of intracranial aneurysms (IAs) to chromosome 17.

Methods And Results: Nine genes (TNFRSF13B, M-RIP, COPS3, RAI1, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108 genes that are located between D17S1857 and D17S1871 by excluding 99 genes that were pseudogenes, hypothetical genes, or well-characterized genes but not likely associated with IA. Direct sequencing of all coding and regulatory regions in 58 cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed.

Single nucleotide polymorphisms and haplotypes of protein C and protein S genes in the Thai population.

Protein C (PC) and protein S (PS) play key roles in an anticoagulant pathway in order to control the haemostatic system. We identified single nucleotide polymorphisms (SNPs) and/or haplotypes in the promotor and exons of the whole PC and PS genes and in the 3'-untranslated region of the PS gene in 55 Thai individuals. The PC gene revealed 10 haplotypes.

Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.

Background And Purpose: Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms (SNPs) with IA in these candidate genes.

A nonsense polymorphism (Y319X) of the solute carrier family 6 member 18 (SLC6A18) gene is not associated with hypertension and blood pressure in Japanese.

We investigated the possible association of solute carrier family 6 member 18 (SLC6A18) with hypertension and blood pressure in Japanese, since the homologous murine XT2 gene was recently reported to be associated with hypertension. The entire coding region of SLC6A18 was sequenced in 30 unrelated Japanese subjects. The deleterious effects of the observed nonsynonymous single nucleotide polymorphisms (SNPs) on the phenotype were predicted using bioinformatics software.

Assessment of human exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in Japan using archived samples from the early 1980s and mid-1990s.

Persistent organic pollutants have been linked to various adverse effects on human health. We conducted a retrospective exposure assessment for 11polychlorinated biphenyl (PCB) congeners and 4 polybrominated diphenyl ether (PBDE) congeners. We analyzed paired samples of blood and food duplicate portions collected in the 1980s (1980 survey, N=40) and the mid-1990s (1995 survey, N=40) from females (five participants from each of eight sites per survey) living throughout Japan, from Hokkaido to Okinawa.

Protein S and protein C gene mutations in Japanese deep vein thrombosis patients.

Objectives: Coagulation factor V Leiden has not been detected in Japanese patients suffering from thrombosis. Hitherto, the constitutional background of Japanese thrombotic patients has never been systematically examined. We have performed a systematic investigation to determine pathogenesis for deep vein thrombosis in a Japanese population.

Mechanism of site-specific DNA damage induced by ozone.

Ozone has been shown to induce lung tumors in mice. The reactivity of ozone with DNA in an aqueous solution was investigated by a DNA sequencing technique using 32P-labeled DNA fragments. Ozone induced cleavages in the deoxyribose-phosphate backbone of double-stranded DNA, which were reduced by hydroxyl radical scavengers, suggesting the participation of hydroxyl radicals in the cleavages.

Characterization of two novel mutations of the antithrombin gene observed in Japanese thrombophilic patients.

We investigated the molecular basis of reduced functional levels of antithrombin (AT) in two individuals suffering from thromboembolic events. In each case direct sequencing of amplified DNA revealed 13,260-13,262 del in one patient and 2511C>A in the other patient, predicting a heterozygous E381del and P16H, respectively. Both patients had no 20210A allele and factor V Leiden mutation.

Genome-wide scan for Japanese familial intracranial aneurysms: linkage to several chromosomal regions.

Background: Genetic factors have an important role in the pathogenesis of intracranial aneurysm (IA). The results of previous studies have suggested several loci.

Methods And Results: From 29 IA families with > or =3 individuals affected by IA, we used nonparametric (model-free) methods for linkage analyses, using GENEHUNTER and Merlin software.

Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder.

Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis.