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Yuichiro Tanaka

Publications and source records attributed to Yuichiro Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2005

Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer.

PURPOSE: Cytochrome P450 1B1 (CYP1B1), a dioxin inducible member of the CYP supergene family, is overexpressed in various human malignancies including prostate cancer. We hypothesized that promoter/enhancer CpG methylation contributes to the regulation of CYP1B1 expression in human prostate tissue. EXPERIMENTAL DESIGN: Expression and induction of the CYP1B1 gene in clinical prostate tissues and prostate cancer cell lines were investigated. The methylation status of the CYP1B1 gene was analyzed in 175 prostate cancer and 96 benign prostatic hyperplasia samples using methylation-specific PCR (MSP) and bisulfite-modified DNA sequencing. MSP primers covered dioxin response elements (DRE) and Sp1 sites that are important for the expression of CYP1B1. RESULTS: Expressions of CYP1B1 mRNA and protein were increased in prostate cancer. The aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) heterodimer complex activates gene transcription by binding to the DREs of CYP1B1. In prostate cancer cells, CYP1B1 mRNA was induced by 2,3,7,8-tetrachlorodigenzo-p-dioxin (TCDD) and/or demethylation agent (5-aza-2-deoxycytidine). There was no change in the expressions of AhR and ARNT. Methylation of promoter/enhancer regions was significantly higher in benign prostatic hyperplasia compared with prostate cancer. MSP-positive patients had significantly lower risk for prostate cancer as compared with MSP-negative patients. There was no correlation between CYP1B1 methylation status and clinicopathologic features. CONCLUSIONS: CYP1B1 is overexpressed in prostate cancer and regulated by hypomethylation of its promoter/enhancer region. This is the first report about CYP1B1 regulation in human clinical prostate samples showing that hypomethylation of the CYP1B1 gene may play an important role in prostate cancer.

Aged↗
PubMed2005

CpG methylation at promoter site -140 inactivates TGFbeta2 receptor gene in prostate cancer.

BACKGROUND: The action of transforming growth factor beta (TGF-beta) is mediated through type 1 (TbetaRI) and type 2 (TbetaRII) receptors. Prostate cancer cells are often resistant to TGF-beta signaling due to loss of TbetaRII expression. The authors of the current study hypothesized that CpG methylation of the TbetaRII promoter at the Sp1 binding site -140 mediates this loss of TbetaRII expression in prostate cancer. METHODS: Sixty-seven prostate cancer (PC) samples, 8 benign prostatic hyperplasia (BPH) samples, and 4 prostate cancer cell lines (DUPro, LNCaP, ND-1 and PC-3) were analyzed for 1) TbetaRII mRNA expression by semiquantitative RT-PCR, 2) TbetaRII protein expression by immunohistochemistry, and 3) TGFbetaRII promoter methylation at CpG site -140 by methylation specific PCR and bisulfite DNA sequencing. Prostate cancer cell lines were treated with the demethylating agent 5aza2'deoxycytidine to determine if TbetaRII gene expression could be increased by blocking promoter methylation. RESULTS: mRNA and protein expression of TbetaRII was lower in the PC samples than in the BPH samples. CpG methylation at site -140 was higher in PC than in BPH (P < 0.01). Promoter methylation was inversely correlated with TbetaRII mRNA expression in the PC and BPH samples (P < 0.0001). PC3, ND1, and DUPro TbetaRII mRNA expression increased following treatment of cells with 5-aza-2'-deoxycytidine. CONCLUSION: CpG methylation of the TbetaRII promoter at CPG site -140 leads to functional loss of the TbetaRII gene in prostate cancer. Treatment with 5-aza-2' deoxycytidine can restore gene expression. The current study results report the first association between prostate cancer and loss of the TGF- beta signaling pathway by TbetaRII DNA promoter methylation.

Azacitidine↗
PubMed2005

A container for transporting small laboratory animals for magnetic resonance imaging.

We have constructed a simple container, consisting of a propylene tube, a High-Efficiency Particulate Aerosol (HEPA) filter and a rubber glove, for transporting small animals to magnetic resonance imaging (MRI) facilities that are located outside a pathogen-free environment. Results of pathogens analysis indicate that the container is able to prevent infection by several microorganisms. The quality of the MR images of mice and rats transported in, and imaged while in the container was satisfactory. This container can be useful for examinations that required the use of instruments located outside clean animal units, ensuring safety for both humans and animals.

Aerosols↗
PubMed2005

Postoperative vasospasm of unruptured paraclinoid carotid aneurysms: analysis of 30 cases.

This study was conducted to determine the incidence, severity, and causes of delayed vasospasm after clipping of unruptured paraclinoid aneurysms of the internal carotid artery (ICA). A retrospective analysis was made of 30 patients, who underwent clipping of unruptured paraclinoid aneurysms in our institution between 1991 and 1998. We compared angiograms before and after operation and classified them into two groups: vasospasm group and non-vasospasm group. Eleven variables were assessed as to their relationship to delayed vasospasm. There were 9 patients (30%) in the vasospasm group, of which 3 patients (10%) were clinically symptomatic. For all symptomatic patients, aggressive treatment, including triple-H therapy, was conducted with good outcome. The number of clips used (p<0.04) and temporary occlusion of the ICA (p<0.005) were statistically significant factors associated with the incidence of vasospasm. It is suggested that mechanical stimulation to the vascular wall of the ICA is responsible for causing spasm in addition to intraoperative bleeding around the dural ring.

Adult↗
PubMed2005

A saccular-like dissecting aneurysm of the anterior cerebral artery that developed 2 years after an ischemic event.

BACKGROUND: A rare case of a growing dissecting aneurysm, which was located at the horizontal (A1) segment of the anterior cerebral artery (ACA), is reported. CASE DESCRIPTION: A 53-year-old woman experienced left hemiparesis and alien hand syndrome. A computerized tomography scan showed an infarction in the right frontal lobe, and cerebral angiography revealed a false lumen and intimal flap at the A1 segment of the ACA. Magnetic resonance angiography demonstrated that the stenosis progressed 6 months later and improved 1 year later. Cerebral angiography showed a saccular-like aneurysm 2 years later. The surgery was planned for prevention of aneurysmal rupture. The aneurysm, which was cocoon shaped, was exposed surgically and was resected. Histological examination of the aneurysm showed arterial dissection. The postoperative course was uneventful without additional neurological deficits. CONCLUSION: This is the first case report of A1 dissecting aneurysm presenting with an ischemic event in the literature. The sequential change of the configuration was curious to develop aneurysmal dilatation in 2 years. Long-term follow-up is necessary even after disappearance of the arterial dissection.

Aortic Dissection↗
PubMed2005

Vascular endothelial growth factor restores erectile function through inhibition of apoptosis in diabetic rat penile crura.

PURPOSE: Vascular endothelial growth factor (VEGF) is known as a multifunctional protein with roles in angiogenesis stimulation and apoptosis inhibition. We hypothesized that intracavernous administration of VEGF would recover erectile dysfunction due to diabetes by protection from apoptosis in the penile cavernosum. MATERIALS AND METHODS: A total of 30, 6-month-old male Sprague-Dawley rats were divided into 2 large groups, namely 20 with diabetes and 10 healthy controls. The diabetic group received intraperitoneal injection of streptozotocin (STZ) to induce diabetes. Intracavernous injection of VEGF was administered to randomly selected STZ diabetic rats 6 weeks after STZ injections. Erectile functional studies were performed in 10 STZ and 10 STZ plus VEGF rats at 12 weeks. After completion of the functional study the penile crura were collected for molecular and immunohistochemical studies. RESULTS: Mean intracavernous pressure in the diabetic group was significantly lower than in controls and low pressure was significantly recovered by VEGF treatment. Gene expression of pro-apoptotic and anti-apoptotic factors were present in the control, diabetic and VEGF treated groups. However, anti-apoptotic protein expression was lacking in the diabetic group and it was recovered by VEGF treatment. The apoptotic index in the diabetic group was significantly higher than in controls and this index was significantly decreased in the VEGF treated group. CONCLUSIONS: The decrease in and recovery of intracavernous pressure correlated significantly with a variation in anti-apoptotic protein expression in the diabetic and VEGF treated groups. To our knowledge this is the first study to show that intracavernous injection of VEGF restores erectile dysfunction through the inhibition of apoptosis in diabetic rats.

Animals↗
PubMed2005

Surgical treatment for aneurysmal subarachnoid hemorrhage in the 8th and 9th decades of life.

OBJECTIVE: Industrialized countries are facing a rapid increase of their senior populations. Consequently, the number of elderly patients with aneurysmal subarachnoid hemorrhage is increasing. The purpose of this study was to assess the results of surgical repair for ruptured aneurysm in elderly patients. METHODS: We retrospectively investigated elderly patients (ages 70-89 yr) who were undergoing surgical treatment for ruptured aneurysm during the 15-year period 1988 to 2002 and compared patients in the 8th and 9th decades of life. Generally, patients were treated surgically within 72 hours after ictus. RESULTS: Of the total of 2835 patients, there were 509 patients (18.0% of total patients) in the 8th decade and 99 patients (3.5%) in the 9th decade of life. Because data were incomplete and patients who received ventricular drainage or ventriculoperitoneal shunt without aneurysmal repair were excluded, 449 and 89 patients in the 8th and 9th decades of life, respectively, were analyzed. No differences in sex, preoperative grade, preoperative computed tomographic findings, location of aneurysm, and aneurysm size were observed between the two decades. Preoperative grade and computed tomographic findings were predictors of favorable outcomes in the 8th and 9th decades. Patient age was a significant predictor of outcome in the 8th but not in the 9th decade. CONCLUSION: To the best of our knowledge, this study is the largest series of its kind to date. Advanced age alone does not exclude adequate surgical repair in patients with aneurysmal rupture in the 9th decade of life.

Aged↗
PubMed2004

Expression and methylation status of 14-3-3 sigma gene can characterize the different histological features of ovarian cancer.

We hypothesize that 14-3-3 sigma gene expression and its regulation by methylation can characterize histological types of primary human epithelial ovarian cancer. To test this hypothesis, ovarian cancer cell lines and 54 ovarian cancer tissue samples were analyzed for expression and methylation of 14-3-3 sigma gene using methylation specific PCR. The results of our experiments demonstrate that 14-3-3 sigma gene was methylated and inactivated in ES-2 ovarian cell line, which was derived from clear cell adenocarcinoma. Treatment of this cell line with demethylating agent 5-aza-2'-deoxycytidine restored the expression of 14-3-3 sigma gene. In human ovarian cancer tissues, the expression of 14-3-3 sigma protein was inactivated in most of the ovarian clear cell carcinoma tissues. Interestingly, 14-3-3 sigma protein expression was positive in significantly higher percentages of serous (89.5%), endometrioid (90%), and mucinous (81.8%) ovarian adenocarcinoma tissues. The ovarian clear cell carcinoma samples with inactivated 14-3-3 sigma protein were highly methylated, suggesting that inactivation of 14-3-3 sigma gene is through DNA methylation. Using direct DNA sequencing, 14-3-3 sigma gene methylation on all the 17 CpG sites was significantly higher in ovarian clear cell carcinoma as compared to other histological types of ovarian cancer (serous, endometrioid, and mucinous). This is the first report suggesting that 14-3-3 sigma gene expression and methylation status can characterize histological features of different types of ovarian cancer.

14-3-3 Proteins↗
PubMed2004

Polymorphisms of the CYP1B1 gene as risk factors for human renal cell cancer.

PURPOSE: CYP1B1 activates various environmental carcinogens in human tissues, including renal tissues. We hypothesize that certain polymorphisms of the CYP1B1 gene are risk factors for renal cell cancer. The rationale for this hypothesis is that chemical procarcinogenic compounds require metabolic activation by oxidative enzymes such as CYP1B1 to be transformed into potentially carcinogenic forms. To test this hypothesis, we investigated the genotypic distributions of six different loci on the CYP1B1 gene and their association with renal cell cancer. EXPERIMENTAL DESIGN: DNA from 211 cases of human renal cell cancer and 200 healthy controls was analyzed by sequence-specific PCR and direct DNA sequencing to determine the genotypic frequencies of six different polymorphic loci on the CYP1B1 gene. RESULTS: The results of this study demonstrate that the frequencies of genotype 119T/T and genotype 432G/G were significantly higher in renal cell cancer patients compared with healthy normal controls. The relative risks were calculated as 3.01 and 2.17 for genotypes 119T/T and 432G/G, respectively, in renal cell carcinoma patients. These genotypic distributions were also significantly different between male and female patients. The relative risks of genotype 119T/T were calculated as 3.95 in males and 1.92 in females, and the relative risks of genotype 432G/G were calculated as 2.81 in males and 1.35 in females. CONCLUSIONS: The present study demonstrates for the first time that the polymorphisms at codons 119 and 432 may be risk factors for renal cancer, especially in the male population.

Aryl Hydrocarbon Hydroxylases↗
PubMed2004

Endovascular therapy versus surgical clipping for basilar artery bifurcation aneurysm: retrospective analysis of 117 cases.

OBJECTIVE: The purpose of this study was to retrospectively evaluate and compare the feasibility, indication and limitations of two treatment options, clipping and coil embolization, for basilar artery (BA) bifurcation aneurysms. MATERIALS AND METHODS: During the last 13 years, 117 patients with 117 BA bifurcation aneurysms were treated exclusively with direct surgery until February 1997, and with either direct surgery or coil embolization therapy since March 1997. Of them, 76 (65%) aneurysms were treated with direct clipping and 41 (35%) were treated with Guglielmi detachable coils (GDCs) embolization. The 76 surgically clipped aneurysms were analyzed on the basis of the pre-operative angiograms as to whether coil embolization would be feasible or not if each case had been attempted. The 41 embolized aneurysms, on the other hand, were analyzed as to whether clipping surgery would be feasible or not if it had been attempted. RESULTS: In the total 117 aneurysms, complete coil obliteration was judged to be possible and simple in 61 (52%) aneurysms, possible with complex techniques (difficult) in 29 (25%) and impossible in 27 (23%). Whereas, complete obliteration with direct clipping was judged to be simple in 66 (57%) aneurysms, difficult in 38 (32%) and impossible in the remaining 13 (11%). Linear correlation as to the technical difficulty was found in 61 (52%) aneurysms, but 14 (12%) had marked discrepancy between the two methods. Of the 76 patients treated with clipping surgery, 17 (22%) were left with some post-operative neurological deficits, and in six out of the 17 aneurysms, embolization might have been simple. There were complications in two patients; one procedure-related and the other with late re-bleeding due to aneurysmal re-growth, in the embolization, group. CONCLUSIONS: Endovascular therapy is an effective alternative for treating BA bifurcation aneurysms, although a quarter of the cases cannot be obliterated completely. It is important to select a suitable treatment option in each case depending on the patient's condition and the angiographical features of each aneurysm as well as the characteristics of the two methods.

Adult↗
PubMed2004

Spatial learning transiently disturbed by intraventricular administration of ouabain.

The presence of sodium-potassium-adenosine triphosphatase (Na+,K+-ATPase) on the surface of arachnoid cells indicates that active transport of electrolytes and water occurs there. Previously, we accidentally found that intraventricular administration of TGF-beta1 impaired rat spatial learning. Levels of Na+,K+ -ATPase were decreased in arachnoid cells with fibrosis. To characterize the role of the Na+,K+ -ATPase, Wistar rats were intraventricularly administered a total of 200 microl of ouabain, at concentrations of 10(-5), 10(-4) and 10(-3) M, for one week with an osmotic pump, and were examined with a Morris water maze. Latency for reaching the platform did not significantly differ between ouabain-administered rats and controls. Spatial learning was impaired in a dose-dependent manner. Na+,K+ -ATPase activity of arachnoid cells ceased during ouabain administration, and recovered completely three weeks after the end of ouabain administration. The present results suggest that the Na+,K+ -ATPase on the surface of arachnoid cells contributes to maintenance of rat spatial learning.

Animals↗
PubMed2004

Ruptured distal middle cerebral artery aneurysm.

OBJECT: Ruptured distal middle cerebral artery (MCA) aneurysms are uncommon, and their clinical and radiological features are poorly understood. To clarify characteristics of these lesions, the authors undertook a retrospective analysis of nine patients with ruptured distal MCA aneurysms. METHODS: The medical records of patients who underwent surgical repair of ruptured intracranial aneurysms between 1988 and 2002 at Shinshu University Hospital and its affiliated hospitals were retrospectively evaluated. The authors found only nine patients with a ruptured distal MCA aneurysm, and their clinical, neuroimaging, and intraoperative findings were evaluated. CONCLUSIONS: This study of nine patients with distal MCA aneurysms is the largest series to date. Eight lesions were saccular aneurysms that were clipped and the remaining one was a mycotic aneurysm that was trapped. Eight of the nine patients suffered cerebral hematomas with subarachnoid hemorrhage. All patients had good outcomes after obliteration of their aneurysm, although their preoperative condition was not good.

Aged↗
PubMed2004

Functional role of the Na+/H+ exchanger in the regulation of cerebral arteriolar tone in rats.

OBJECT: In vascular smooth-muscle cells, the Na+/H+ exchanger (NHE) is involved in the regulation of [Na+]i, pHi through [H+], and cell volume. Recently, investigations have determined that this exchanger contributes to ischemia and reperfusion injury in coronary circulation. Nonetheless, there is limited information on this glycoprotein in cerebral circulation, especially microcirculation. Thus, the authors in the present study examined the role of NHE in the regulation of cerebral arteriolar tone and its related mechanisms in vitro. METHODS: The internal diameter of isolated pressurized intracerebral arterioles in rats was monitored with the aid of a microscope. To examine the basal activity of NHE two kinds of Na+/H+ exchange inhibitors (FR183998 and 5-[N,N-hexamethylene]amiloride) were administered in the arterioles. Furthermore the authors studied the effects of nitric oxide (NO) synthase inhibitor (NG methyl-L-arginine), Na+/K+ -adenosine triphosphatase (NKA) inhibitor (ouabain), and the Na+/Ca++ exchange inhibitor (SEA0400) on the vascular response induced by either of the Na+/H+ exchange inhibitors. Both of the Na+/H+ exchange inhibitors constricted the arteriole. Subsequent application of NO synthase inhibitor further decreased the diameter of the arterioles. The Na+/H+ exchange inhibitor-induced constriction was completely abolished in the presence of ouabain and SEA0400. CONCLUSIONS: The NHE is active in the basal condition and regulates cerebral arteriolar tone through NKA and the Na+/Ca++ exchanger. Endogenous NO is not related to the activity of NHE in basal conditions.

Amiloride↗
PubMed2004

[Treatment of craniopharyngiomas in children].

PURPOSE: The purpose of this article is to assess, in a 25-year retrospective study, the clinical outcome in children with craniopharyngioma. PATIENT AND METHODS: From 1978 to 2002, 12 children younger than 15-year-old underwent treatment with surgery and/or radiotherapy for craniopharyngioma. The clinical course and outcome were reviewed. RESULTS: The median age was 7.3 years (range, 3 to 12 years) at the time of initial surgical resection. With a mean follow-up period of 132 months (range, 29 to 255 months), 1 patient died of tumor progression due to malignant transformation at 205 months after the initial surgery and the overall outcome was good in 11 patients. Out of 12 patients 4 presented a recurrence of their tumor, 2 after an apparently gross total removal. Because of tumor recurrence, 2 received conventional radiation therapy and 3 received gamma knife radiosurgery. There was neither operative mortality nor major complication. All patients required hormonal replacement postoperatively. CONCLUSIONS: The goal in the treatment of craniopharyngiomas is to achieve total removal without morbidity. Our results compared favorably with the previous reports in the literature. MRI follow-up should be performed even in patients whose primary tumor is resected "completely". Suitable combination of open surgery, conventional radiotherapy and gamma knife radiosurgery may result in optimal functional outcome. Recovery from postoperative pituitary dysfunction can be occasionally expected.

Child↗
PubMed2003

Six polymorphisms on estrogen receptor 1 gene in Japanese, American and German populations.

OBJECTIVE: Estrogen receptor 1 ( ESR1) plays an important role in various estrogen-related diseases, the incidences of which are significantly lower in the Japanese population than in Western populations. We hypothesize that polymorphisms in exon 1 of the ESR1 gene are associated with a lower incidence of estrogen-related diseases in the Japanese population. METHODS: The genetic distributions of six different ESR1 gene polymorphisms were investigated among 200 Japanese, 200 Americans and 112 Germans using a novel sequence-specific polymerase chain reaction (SSP) technique and direct DNA sequencing. RESULTS: The frequencies of variant genotypes on codons 10 and 87 located on exon 1 were significantly lower in the Japanese population than other populations. The polymorphism on codon 87 was not detected in the Japanese population, although other populations showed the homozygous and heterozygous variant genotype on this codon. Other loci, intron 1, and codons 243 and 594 were not different among these populations. CONCLUSIONS: This is the first report to demonstrate the polymorphisms at codons 10 and 87 of ESR1 are significantly low for the Japanese population. Thus, inherited alterations in ESR1 polymorphisms may be associated with changes of estrogen effects and, thereby, may possibly explain inter-population differences in incidences of estrogen-mediated diseases.

Adult↗
PubMed2003

CYP1B1 gene polymorphisms have higher risk for endometrial cancer, and positive correlations with estrogen receptor alpha and estrogen receptor beta expressions.

The estradiol metabolites by CYP1B1 received particular attention because of their causative role in malignant transformation of endometrium. We hypothesize that polymorphisms of CYP1B1 gene can predict higher incidence of endometrial cancer. To test this hypothesis, the genetic distributions of six different CYP1B1 gene polymorphisms were investigated, by sequence-specific PCR and direct DNA sequencing, in 113 Japanese endometrial cancer patients and 202 healthy controls. We also investigated whether the expression of estrogen receptors (ERalpha and ERbeta), progesterone receptor, and androgen receptor genes are influenced by the CYP1B1 genotypes in endometrial cancer. The results of our study demonstrated that the distributions of CYP1B1 genotypes at codons 119 and 432 were significantly different between endometrial cancer patients and healthy normal controls. The relative risks of 119T/T and 432G/G in endometrial cancer were calculated as 3.32 and 2.49 compared with wild-types. The 119T/T showed significant correlation for positivities of ERalpha and ERbeta. The 432G/G also showed weak correlations for ERalpha positivity. Other loci, intron 1, codon 48, and codon 449 were not different between endometrial cancer patients and healthy normal control. This is the first report that demonstrates that the rare polymorphisms at codons 119 and 432 of CYP1B1 gene have higher risk for endometrial cancer, and positive correlations with ERalpha and ERbeta expressions in endometrial cancer.

Adult↗
PubMed2003

Estrogen receptor alpha polymorphisms and renal cell carcinoma--a possible risk.

Renal cell carcinoma is the most common form of kidney cancer. However, the genetic basis of renal cancer is not fully understood. Estrogens and their receptors (ERs) have been shown to play a role in various cancers and it is speculated that they can also affect the human kidney. One of the animal models utilized to study the effects of estrogens on renal cancer is the Syrian hamster. Exposing these hamsters to estrogens results in the development of kidney cancer and thus, the hormone-ER complex may be playing a role. The ER is expressed in reproductive as well as non-reproductive tissues and is implicated in the control of proliferation, differentiation, and development of many tissues. There are two types of ERs and they are the alpha and beta forms. Genetic polymorphisms of various factors have been shown to play a role in the alteration of their functions. The NH2-terminal region of the ERalpha protein influences its structure and function and thus, inherited variants of the ERalpha gene may alter tissue responsiveness to estrogens and possibly lead to renal carcinogenesis. Polymorphisms have been determined in the coding region of the human ERalpha gene and are located at the following codons: 10 T-->C, 85 G-->C, 87 G-->C, 243 C-->T, 325 C-->G, and 594 G-->A. There are also two polymorphisms that have been identified in intron 1 and give rise to a PvuII and XbaI restriction site. These polymorphisms of ERalpha have been shown to be associated with various cancers. Based on the evidence, it is hypothesized that polymorphisms of the ERalpha gene are associated with renal cell carcinoma.

Animals↗