PubMed Health⌕ Search

Biomedical subjects

Takashi Yokota

Publications and source records attributed to Takashi Yokota.

At least 19 recordsLinked to original sources
PubMed2006

Beta-catenin up-regulates Nanog expression through interaction with Oct-3/4 in embryonic stem cells.

It is well known that mouse embryonic stem (ES) cells can be maintained by the presence of leukemia inhibitory factor (LIF). Recent studies have revealed that Wnt also exhibits activity similar to LIF. The molecular mechanism behind the maintenance of ES cells by these factors, however, is not fully understood. In this study, we found that LIF enhances level of nuclear beta-catenin, a component of the Wnt signaling pathway. Expression of an activated mutant of beta-catenin led to the long-term proliferation of ES cells, even in the absence of LIF. Furthermore, it was found that beta-catenin up-regulates Nanog in an Oct-3/4-dependent manner and that beta-catenin physically associates with Oct-3/4. These results suggest that up-regulating Nanog through interaction with Oct-3/4 involves beta-catenin in the LIF- and Wnt-mediated maintenance of ES cell self-renewal.

Animals↗
PubMed2006

GABPalpha regulates Oct-3/4 expression in mouse embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts, and transcription factors Oct-3/4, Nanog, Sox2, and STAT3, are essential for their self-renewal. In this study, we searched for molecules downstream of STAT3 in ES cells. Using DNA chip analysis, we obtained GA-repeat binding protein (GABP) alpha. Expression of GABPalpha was restricted to undifferentiated ES cells and controlled by STAT3. We found that the expression level of Oct-3/4 is reduced by knockdown of GABPalpha. On the other hand, GABPalpha-overexpressing ES cells maintained the expression level of Oct-3/4 even in the absence of LIF. Moreover, the induction of Oct-3/4 repressors Cdx-2, Coup-tf1, and GCNF was stimulated by GABPalpha knockdown. These data suggest that GABPalpha upregulates the expression of Oct-3/4 via downregulation of Oct-3/4 repressors.

Animals↗
PubMed2006

Overexpression of glutathione peroxidase attenuates myocardial remodeling and preserves diastolic function in diabetic heart.

Oxidative stress plays an important role in the structural and functional abnormalities of diabetic heart. Glutathione peroxidase (GSHPx) is a critical antioxidant enzyme that removes H(2)O(2) in both the cytosol and mitochondia. We hypothesized that the overexpression of GSHPx gene could attenuate left ventricular (LV) remodeling in diabetes mellitus (DM). We induced DM by injection of streptozotocin (160 mg/kg ip) in male GSHPx transgenic mice (TG+DM) and nontransgenic wildtype littermates (WT+DM). GSHPx activity was higher in the hearts of TG mice compared with WT mice, with no significant changes in other antioxidant enzymes. LV thiobarbituric acid-reactive substances measured in TG+DM at 8 wk were significantly lower than those in WT+DM (58 +/- 3 vs. 71 +/- 5 nmol/g, P < 0.05). Heart rate and aortic blood pressure were comparable between groups. Systolic function was preserved normal in WT+DM and TG+DM mice. In contrast, diastolic function was impaired in WT+DM and was improved in TG+DM as assessed by the deceleration time of peak velocity of transmitral diastolic flow and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 13.5 +/- 1.2 vs. 8.9 +/- 0.7 ms, P < 0.01). The TG+DM values were comparable with those of WT+Control (tau; 7.8 +/- 0.2 ms). Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis, and apoptosis. Overexpression of GSHPx gene ameliorated LV remodeling and diastolic dysfunction in DM. Therapies designed to interfere with oxidative stress might be beneficial to prevent cardiac abnormalities in DM.

Animals↗
PubMed2006

Lower prevalence of circulating natural killer T cells in patients with angina: a potential novel marker for coronary artery disease.

OBJECTIVE: Atherosclerosis is an inflammatory disease. Natural killer T cells are a unique lymphocyte subset that can recognize lipid antigens presented by CD1d and secrete copious amounts of pro-atherogenic cytokines such as interferon-gamma. We have previously shown that natural killer T cells accelerate atherosclerosis in mice and macrophages incubated with oxidized low-density lipoproteins induce natural killer T cells to produce interferon-gamma. Thus, whether the prevalence of natural killer T cells in peripheral blood is altered in patients with angina pectoris and its correlation with coronary risk factors was determined. METHOD: Cell profiling was performed using flow cytometry in patients with stable angina, unstable angina (Braunwald IIIB), and healthy controls. Natural killer T cells in peripheral blood were identified by the expression of natural killer T specific invariant T cell receptor alpha-chain (Valpha24) and T cell receptor beta-chain (Vbeta11). RESULTS: Prevalence of natural killer T (Valpha24-Vbeta11 double positive) cells was significantly decreased in patients with unstable angina and stable angina compared with that in controls. No significant differences were observed in the prevalence between unstable and stable angina. Reduction of natural killer T cells was independently associated with the presence of angina. CONCLUSIONS: Lower prevalence of circulating natural killer T cells is related to the presence of coronary artery disease. As T cell receptor down-regulation or apoptosis after natural killer T cell activation and subsequent interferon-gamma release may contribute to atherogenesis, natural killer T cells can become a novel therapeutic target for the prevention and treatment of atherosclerotic vascular diseases.

Angina Pectoris↗
PubMed2005

Identification of histological markers for malignant glioma by genome-wide expression analysis: dynein, alpha-PIX and sorcin.

Glioblastoma multiforme (GBM), the most malignant class of glial neoplasm (grade IV in WHO criteria), carries the worst clinical prognosis among primary brain tumors in adults. To identify a set of genes involved in the tumorigenesis of GBM, we evaluated expression profiles of GBM tissues from 11 patients using a cDNA microarray representing 25,344 human genes. By comparing the profiles with those of normal brain tissue, we identified a number of differentially expressed genes: 54 with increased expression and 45 with reduced expression in GBMs. Semi-quantitative RT-PCR experiments with 6 of those genes confirmed higher expression of DNCH2, ARHGEF6, NPM1 and SRI and lower expression of NRGN and TM4SF2 in GBM tumors. Immunohistochemical staining for 3 of the respective gene products, dynein (product of DNCH2), alpha-PIX (product of ARHGEF6), and sorcin (product of SRI) indicated that this technique might be useful for histological grading of glial tumors. To establish criteria for this diagnostic approach, we scored glial tumor tissues of different histological grades according to the staining results; the scores were significantly higher in anaplastic astrocytomas and GBMs than in diffuse astrocytomas or normal brain tissues. These findings indicated that levels of these three proteins might serve as histological markers for malignant glioma classification.

Biomarkers, Tumor↗
PubMed2005

Identification of Zfp-57 as a downstream molecule of STAT3 and Oct-3/4 in embryonic stem cells.

Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass of blastocysts. Transcription factor STAT3 is essential for the self-renewal of ES cells. In this study, we searched for downstream molecules of STAT3 in ES cells. Using DNA chip analysis, we obtained zinc finger protein (Zfp)-57. The expression of Zfp-57 was restricted to undifferentiated ES cells and activation of STAT3 led to expression of Zfp-57. We also found that forced expression of a dominant-negative mutant of STAT3 or repression of Oct-3/4 expression led to down-regulation of Zfp-57. Targeted disruption of Zfp-57 resulted in no gross phenotypical defects, including expression of undifferentiated-state-specific genes. These data suggest that Zfp-57 is a downstream molecule of STAT3 and Oct-3/4 in ES cells, although dispensable for their self-renewal.

Animals↗
PubMed2005

A case of interstitial cystitis accompanying Sjögren's syndrome.

A 51-year-old woman with interstitial cystitis was referred for screening of autoimmune disease. She was positive for results of Schirmer and Saxon tests and for ss/A and ss/B antibodies. Autoantibodies to type 3 muscarinic acetylcholine receptor were detected in the patient's serum by Western blotting. We diagnosed her as having interstitial cystitis accompanying Sjögren's syndrome. To enable early treatment, interstitial cystitis should be considered when patients with Sjögren's syndrome complain of urinary symptoms.

Journal Article↗
PubMed2005

Congenital atrial standstill associated with coinheritance of a novel SCN5A mutation and connexin 40 polymorphisms.

BACKGROUND: Congenital atrial standstill has been linked to SCN5A. Incomplete penetrance observed in atrial standstill has been attributed in part to the digenic inheritance of polymorphisms in the atrial-specific gap junction connexin 40 (Cx40) in conjunction with an SCN5A mutation. OBJECTIVES: The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation identified in a family with atrial standstill. METHODS: Family members of an apparently sporadic case of atrial standstill underwent genetic screening of SCN5A and atrial-specific genes including Cx40. Biophysical properties of the wild-type (WT) and mutant SCN5A channels in a heterologous expression system were studied using the whole-cell patch clamp technique. RESULTS: The novel SCN5A mutation L212P was identified in the proband (age 11 years) and his father. The father was in normal sinus rhythm. The proband had no P waves on surface ECG, and his right atrium could not be captured by pacing. The recombinant L212P Na channel showed a large hyperpolarizing shift in both the voltage dependence of activation (WT: -48.1 +/- 0.9 mV; L212P: -63.5 +/- 1.5 mV; P < .001) and inactivation (WT: -86.6 +/- 0.9 mV; L212P: -95.6 +/- 0.8 mV; P < .001) and delayed recovery from inactivation. Further screenings for genetic variations that might mitigate L212P dysfunction revealed that the proband, but not his father, carries Cx40 polymorphisms inherited from his asymptomatic mother. CONCLUSION: These results suggest that genetic defects in SCN5A most likely underlie atrial standstill. Coinheritance of Cx40 polymorphisms is a possible genetic factor that modifies the clinical manifestation of this inherited arrhythmia.

Alleles↗
PubMed2005

Mural thrombus in an ectatic right coronary artery caused acute myocardial infarction at downstream coronary artery.

A 72-year-old woman was admitted to our institution because of sudden chest pain. Emergency coronary angiography revealed thrombotic occlusion of the distal right coronary artery. A large cylindrical thrombus was retrieved from her distal right coronary artery using a thrombus aspiration catheter. IVUS showed minimal atherosclerosis and moderate ectatic change at the proximal right coronary artery. A reconstructed IVUS image also showed that a mural thrombus with abrupt ending was still retained at the ectatic segment. Based on this evidence, coronary ectasia was thought to be the primary cause for the thrombus formation and acute myocardial infarction in this case.

Aged↗
PubMed2005

Emergency operation for phlegmonous gastritis.

Phlegmonous gastritis is a rare inflammatory lesion in which bacterial infection occurs in the gastric wall. A case of phlegmonous gastritis producing an intramural filling defect in the stomach is presented. Endoscopy showed edematous and reddened gastric mucosa with a mass lesion in the gastric body and antrum. An abdominal CT scan showed diffuse and irregular thickening of the gastric wall. At emergency operation, a total gastrectomy with splenectomy was performed. The most important differential diagnosis is carcinoma, especially scirrhous-type gastric cancer. Radiographic findings of phlegmonous gastritis resemble those of scirrhous gastric cancer. More frequent recognition of this disease, early diagnosis and prompt institution of treatment is essential.

Aged↗
PubMed2005

Pyogenic liver abscesses secondary to carcinoma of the sigmoid colon: a case report and clinical features of 20 cases in Japan.

We report a case of liver abscesses associated with sigmoid colon cancer in an 81-year-old woman. The patient was referred to our hospital because of a tumorous lesion of the sigmoid colon. Five days before the scheduled operation, she presented abdominal pain, fever and chill. Imaging scans revealed multiple liver abscesses in both lobes, which were successfully treated with intravenously administered antibiotics. Two weeks later, the patient underwent laparoscopic-assisted sigmoidectomy. Nineteen cases of liver abscess associated with colonic cancer have been reported during the past ten years in Japan, and we report the clinical features of these cases in this paper. An aggressive search for the underlying cause of pyogenic liver abscess should be an integral part of the definitive treatment of this disease.

Aged, 80 and over↗
PubMed2005

Functional analysis of the effect of forced activation of STAT3 on M1 mouse leukemia cells.

M1 mouse myeloid leukemia cells exhibit growth arrest and differentiation to monocytes/macrophages in response to leukemia inhibitory factor (LIF) stimulation. Although recent studies have demonstrated that STAT3 plays a central role in this process, it is unknown whether STAT3 activation alone is sufficient. To address this issue, we have established M1/STAT3ER cells, where STAT3 is selectively activated by 4-hydroxytamoxifen (4HT). 4HT stimulation did not have any effect on growth and morphology of M1/ STAT3ER cells, and did not induce the down-regulation of mRNA of c-myc and c-myb, which is necessary for M1 cell differentiation. On the other hand, mRNA of jun-B, IRF1 and p19 was increased by 4HT. DNA precipitation assay indicated that both stimulation of LIF and 4HT similarly activated STAT3ER. Introduction of a constitutive active MAP kinase kinase (MEK1) into M1/STAT3ER cells did not induce differentiation either. Together, our present data suggest that signaling other than the activation of STAT3 and MEK1 may be necessary for M1 cell-growth arrest and differentiation, while a set of early genes of LIF are induced by only STAT3 activation.

Animals↗
PubMed2004

Involvement of Ras in extraembryonic endoderm differentiation of embryonic stem cells.

Embryonic stem (ES) cells, derived from the inner cell mass of blastocyst can differentiate into multiple cell lineages. In this study, we examined the possible involvement of Ras in ES cell differentiation. We found that Ras was activated upon formation of embryoid bodies (EBs), an initial step in ES cell differentiation. When expressed during EB differentiation, a dominant-negative mutant of Ras suppressed induction of marker genes for extraembryonic endoderm differentiation, including GATA-4, GATA-6, alpha-fetoprotein, and hepatocyte nuclear factor 3beta, while an activated mutant promoted their induction. Expression of a Ras mutant that selectively activates the Raf/MEK/Erk pathway also enhanced induction of extraembryonic endoderm markers, and treatment with a MEK inhibitor resulted in their decreased expression. In addition, Ras stimulated downregulation of Nanog, a suppressor of endoderm differentiation in ES cells. These data suggest that Ras activation during EB differentiation plays a crucial role in initiation of extraembryonic endoderm differentiation.

Animals↗