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Usui D.,Shizuoka Institute of Epilepsy and Neurological Disorders | Shimada S.,Tokyo Womens Medical University | Shimojima K.,Tokyo Womens Medical University | Sugawara M.,Tokyo Womens Medical University | And 6 more authors.
American Journal of Medical Genetics, Part A | Year: 2013

Duplications of the 2q33 region are rare; to date, only 13 patients have been reported to have this chromosomal abnormality. The reported duplications are of varying size, and the patients shared developmental delay and minor dysmorphic findings. In this study, we identified a duplication of 2q32.1-q33.3 in a patient with psychomotor developmental delay, epilepsy, and autistic behavior. The duplicated region of this patient was reciprocal to the 2q32-q33 deletion syndrome. Chromosomal microarray testing confirmed the 19.5Mb of duplication that includes over 100 genes, some of which could have functional relevance to the neurological features of this patient. The SATB homeobox 2 gene (SATB2)-the primary gene responsible for the 2q32-q33 deletion syndrome-may be one of them, because of its expression in the cortical projection neurons of the developing brain. The duplication of the potassium channel tetramerisation domain-containing 18 gene (KCTD18) and the ADAM metallopeptidase domain 23 gene (ADAM23) may also contribute to the phenotype. FISH analysis confirmed a tandem configuration of the duplicated segments. This result is in agreement with our previous study, in which we observed that duplicated segments as interstitial duplications are generally inserted in the tandem configuration. © 2012 Wiley Periodicals, Inc.

Hayase S.,U.S. National Institutes of Health | Hayase S.,Fukushima Medical University | Sasaki Y.,U.S. National Institutes of Health | Sasaki Y.,Kuwana East Medical Center | And 16 more authors.
Thyroid | Year: 2015

Background: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Method: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Results: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. Conclusion: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer. © 2015 Mary Ann Liebert, Inc.

Fukumoto Y.,Tohoku University | Yamada N.,Mie University | Matsubara H.,National Hospital Organization Okayama Medical Center | Mizoguchi M.,Kurume University | And 15 more authors.
Circulation Journal | Year: 2013

Background: We have previously demonstrated that long-term inhibition of Rho-kinase ameliorates pulmonary arterial hypertension (PAH) in animal models. In the present study, we examined the clinical effects of mid-term oral treatment with an extended release formulation of AT-877 (fasudil hydrochloride), a specific Rho-kinase inhibitor (AT-877ER) on PAH. Methods and Results: 23 PAH patients were treated with either placebo (10/2 females/males, 51±16 years, idio-pathic PAH (IPAH) in 6, PAH associated with connective tissue disease (CTD-PAH) in 3, PAH with congenital heart disease (CHD-PAH) in 2, and portal PAH in 1) or AT-877ER (6/5 females/males, 47±14 years, IPAH in 2, CTD-PAH in 5, and CHD-PAH in 4); 3 patients were excluded. We performed a 6-min walk test and right heart catheterization in the remaining 20 patients, before and 3 months after the treatment (placebo n=11, AT-877ER n=9). Although there were no significant differences between the 2 groups for the 6-min walk distance, pulmonary hemodynamics tended to be improved in the AT-877ER group, especially the prevalence of improved cardiac index from baseline, which was significantly higher in the AT-877ER than in the placebo group. In the AT-877ER group, serum levels of hy-droxyfasudil, an active metabolite of AT-877ER tended to correlate with improvements in the cardiac index and mean pulmonary artery pressure. Conclusions: Mid-term treatment with oral AT-877ER showed additional improvement in pulmonary hemodynam-ics in patients with PAH.

Kojima M.,Komono Kosei Hospital | Okubo S.,Kuwana East Medical Center | Mizubayashi R.,Yokkaichi Diabetes Clinic | Isaka N.,Murase Hospital | And 13 more authors.
Nephrology Dialysis Transplantation | Year: 2013

Background. A thiazide diuretic used in combination with benazepril is superior to amlodipine plus benazepril in reducing albuminuria in hypertensive patients with diabetes. However, calcium channel blockers have diverse characteristics. Thus, we investigated whether combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. Methods. Hypertensive patients with type 2 diabetes and albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age 67.0 ± 7.6 years) were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n = 71) or olmesartan plus trichlormethiazide (1 mg/day; n = 72) for an additional 6 months. The primary end point was urinary excretion of albumin at 6 months after randomization. Results. At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively, and was reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7 (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline values]. Blood pressure did not differ between the two groups throughout the study period. Conclusions. Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan. © The Author 2013.

Okano H.,Suzuka General Hospital | Takahashi M.,Jichi Medical University | Isono Y.,Suzuka General Hospital | Tanaka H.,Suzuka General Hospital | And 10 more authors.
Hepatology Research | Year: 2014

Aim: To characterize hepatitis E in Mie prefecture and to investigate whether raw pig liver sold as food in Mie is contaminated with hepatitis E virus (HEV) strains similar to those recovered from patients. Methods: Seventeen patients with sporadic acute hepatitis E treated from 2004 to 2012 were studied. A total of 243 packages of raw pig liver from regional grocery stores were tested for the presence of HEV RNA. The partial genomic sequences of human and swine HEV isolates were determined and subjected to the phylogenetic analyses. Results: The HEV isolates recovered from the 17 patients segregated into genotype 3 (n=15) and genotype 4 (n=2), and 15 genotype 3 isolates further segregated into 3e (n=11) and 3b (n=4). Pig liver specimens from 12 (4.9%) of the 243 packages had detectable HEV RNA. All 12 swine HEV isolates were grouped into genotype 3 (3a or 3b). Although no 3e strains were isolated from pig liver specimens, two 3b swine strains were 99.5-100% identical to two HEV strains recovered from hepatitis patients, within 412-nt partial sequences. Conclusion: The 3e HEV was prevalent among hepatitis E patients. HEV RNA was detected in approximately 5% of pig liver sold as food. The presence of identical HEV strains between hepatitis patients and pig liver indicated that pigs play an important role as reservoirs for HEV in humans in Mie. Further studies are needed to clarify the source of 3e HEV in the animal and environmental reservoirs. © 2013 The Japan Society of Hepatology.

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