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61.
Hamada K Sasaki T Koni PA Natsui M Kishimoto H Sasaki J Yajima N Horie Y Hasegawa G Naito M Miyazaki J Suda T Itoh H Nakao K Mak TW Nakano T Suzuki A 《Genes & development》2005,19(17):2054-2065
PTEN is an important tumor suppressor gene. Hereditary mutation of PTEN causes tumor-susceptibility diseases such as Cowden disease. We used the Cre-loxP system to generate an endothelial cell-specific mutation of Pten (Tie2CrePten) in mice. Tie2CrePten(flox/+) mice displayed enhanced tumorigenesis due to an increase in angiogenesis driven by vascular growth factors. This effect was partially dependent on the PI3K subunits p85alpha and p110gamma. In vitro, Tie2CrePten(flox/+) endothelial cells showed enhanced proliferation/migration. Tie2CrePten(flox/flox) mice died before embryonic day 11.5 (E11.5) due to bleeding and cardiac failure caused by impaired recruitment of pericytes and vascular smooth muscle cells to blood vessels, and of cardiomyocytes to the endocardium. These phenotypes depend strongly on p110gamma rather than on p85alpha and were associated with decreased expression of Ang-1, VCAM-1, connexin 40, and ephrinB2 but increased expression of Ang-2, VEGF-A, VEGFR1, and VEGFR2. Pten is thus indispensable for normal cardiovascular morphogenesis and post-natal angiogenesis, including tumor angiogenesis. 相似文献
62.
Yukitoshi Izumi Kazuhiro Tokuda Kazuko A. O’Dell Charles F. Zorumski Toshio Narahashi 《Neuroscience letters》2007
Oseltamivir (Tamiflu) is now being stockpiled by several governments as a first line treatment for an anticipated outbreak of avian influenza caused by H5N1. However, abnormal behaviors and death associated with the use of Tamiflu have developed into a major issue in Japan where Tamiflu is often prescribed for seasonal influenza. Thus, it is critical to determine neuropsychiatric effects of oseltamivir and to establish methods for safe administration. Using juvenile rats and rat hippocampal slices, we investigated whether oseltamivir has adverse effects on the central nervous system. Systemic injection of oseltamivir (50 mg/kg i.p.) produced no change in behavior within 2 h. However, prior injection of oseltamivir significantly altered the duration of loss of lightning reflex following ethanol injection (3.3 g/kg, i.p.). Ethanol injection in the presence of oseltamivir also resulted in enhanced hypothermia. In the CA1 region of hippocampal slices, oseltamivir (100 μM) induced paired-pulse facilitation in population spikes without changes in excitatory postsynaptic potentials. Similarly, 3 μM oseltamivir carboxylate, the active metabolite of oseltamivir, facilitated neuronal firing, though the facilitation did not involve GABAergic disinhibition. Moreover, oseltamivir carboxylate produced further facilitation following administration of 60 mM ethanol. These findings indicate that oseltamivir has effects on the central nervous system, especially when combined with other agents. 相似文献
63.
Shigefumi Yukihiro Shigeru Okada Kazuhiro Takeuchi Hajime Inoue 《Pathology international》1995,45(1):19-25
The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency. 相似文献
64.
Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease 总被引:5,自引:0,他引:5
Nakamuta M Kohjima M Morizono S Kotoh K Yoshimoto T Miyagi I Enjoji M 《International journal of molecular medicine》2005,16(4):631-635
Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased; however, the mechanisms involved in the pathogenesis of NAFLD have not been thoroughly investigated in humans. In this study, we evaluated the expression of fatty acid metabolism-related genes in NAFLD. Real-time RT-PCR was performed using liver biopsy samples from 12 NAFLD patients. The target genes studied were: acetyl-CoA carboxylase (ACC) 1, ACC2, and fatty acid synthase (FAS) for the evaluation of de novo fatty acid synthesis; carnitine palmitoyltransferase 1a (CPT1a), long-chain acyl-CoA dehydrogenase (LCAD), and long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase alpha (HADHalpha) for beta-oxidation in the mitochondria; peroxisome proliferator-activated receptor- (PPAR-) alpha and cytochrome P450 2E1 (CYP2E1) for oxidation in peroxisomes and microsomes (endoplasmic reticulum) respectively; and diacylglycerol O-acyltransferase 1 (DGAT1), PPAR-gamma, and hormone sensitive lipase (HSL) for triglyceride synthesis and catalysis. In NAFLD, expression of ACC1 and ACC2, but not FAS was increased, indicating that de novo fatty acid synthesis is enhanced in NAFLD. In contrast, expression of CTP1a, a rate-limiting enzyme, was remarkably decreased, indicating that beta-oxidation in the mitochondria was decreased, although the expression of LCAD and HADHalpha was increased. Expression of PPAR-alpha was increased, whereas that of CYP2E1 was reduced. The expression of DGAT1, PPAR-gamma, and HSL was enhanced. These data suggest that in NAFLD, increased de novo synthesis and decreased beta-oxidation in the mitochondria lead to accumulation of fatty acids in hepatocytes, although the extent of oxidation in peroxisomes and microsomes remains unclear. 相似文献
65.
Shigesaburo Miyakoshi Eiji Kusumi Tomoko Matsumura Akiko Hori Naoko Murashige Tamae Hamaki Koichiro Yuji Naoyuki Uchida Kazuhiro Masuoka Atsushi Wake Yoshinobu Kanda Masahiro Kami Yuji Tanaka Shuichi Taniguchi 《Biology of blood and marrow transplantation》2007,13(7):771-777
Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI. 相似文献
66.
Uehara S Tamura M Nata M Ji G Yaegashi N Okamura K Yajima A 《Journal of human genetics》2000,45(3):119-126
67.
PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis 总被引:20,自引:2,他引:20
Kobayashi Kazuhiro; Mlzuno Kunihiko; Hida Akiko; Komakl Rie; Tomita Keiko; Matsushita Ikumi; Namlki Mikio; Iwamoto Teruaki; Tamura Shohzoh; Minowada Shlgeru; Nakahori Yutaka 《Human molecular genetics》1994,3(11):1965-1967
We analyzed DNA from 63 Japanese men with either azoospermiaor severe oligospermia whose Y chromosomes were cytogeneticallynormal. A total of 16 loci were examined: 15 loci on the longarm between DYS7E and DYZ1, and the YRRM1 locus, a candidategene for the azoospermic factor, AZF. One patient with a perlcentricinversion of the Y chromosome was also included. We detectedmicro-deletions in ten individuals. The YRRM1 gene was Involvedin only three of them. The remaining seven patients showed deletionbetween DYS7C and DYS239 in common, indicating the presenceof at least one additional gene, deletion of which causes azoospermia. 相似文献
68.
Comparative studies on the induction of micronucleated erythrocytesby three recombinant human erythropoietins (rhEPOs) such asepoetin 相似文献
69.
Kazuhiro Tsukamoto Nobutaka Ohta Yasumasa Shirai M. Emi 《Journal of human genetics》1998,43(4):278-279
Tumor necrosis factor alpha (TNFα) in activated monocytes exerts cytotoxic activity and has a variety of other biological
effects. We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the gene located at 6p21.3.
High heterozygosity (0.80) makes this polymorphism a useful marker in the genetic study of disorders affecting immunological
response and cell differentiation.
Received: June 2, 1998 / Accepted: June 24, 1998 相似文献
70.
Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer 总被引:5,自引:0,他引:5
Ito R Oue N Yoshida K Kunimitsu K Nakayama H Nakachi K Yasui W 《Virchows Archiv : an international journal of pathology》2005,447(4):717-722
Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our
serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas.
CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric
carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics
and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal
metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression
was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive
CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases
that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression
of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis. 相似文献