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Takashi Watanabe

Publications and source records attributed to Takashi Watanabe.

At least 91 records · Page 5Linked to original sources
PubMed2004

A non-enzymatic derived arachidonyl peroxide, 8-iso-prostaglandin F2 alpha, in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage participates in the pathogenesis of delayed cerebral vasospasm.

We performed serial measurements of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a non-enzymatic derived arachidonyl peroxide, in the cerebrospinal fluid (CSF) of 34 patients with subarachnoid hemorrhage (SAH). Patients were treated with open or endovascular surgery within 48 h of onset. Delayed cerebral vasospasm was verified by the presence of a low-density area on CT scan indicating focal cerebral infarction occurring after symptomatic delayed vasospasm. Concentrations of 8-iso-PGF2alpha in the CSF of 15 patients exhibiting delayed cerebral vasospasm were compared with those of 19 patients who did not exhibit vasospasm. The concentrations of 8-iso-PGF2alpha in the CSF of patients showing vasospasm were 42.4+/-37.1 pg/ml (mean+/-S.D., n=12) on Days 0-2, 66.4+/-41.0 pg/ml (n=14) on Days 3-5, 118.5+/-89.9 pg/ml (n=15) on Days 6-8, 86.2+/-70.2 pg/ml (n=11) on Days 9-11, 48.8+/-31.8 pg/ml (n=10) on Days 12-14, 27.8+/-20.1 pg/ml (n=7) after Day 20, while the concentrations in patients not showing vasospasm were 24.8+/-12.0 pg/ml (n=18) on Days 0-2, 25.7+/-15.2 pg/ml (n=19) on Days 3-5, 47.5+/-52.3 pg/ml (n=18) on Days 6-8, 56.7+/-72.0 pg/ml (n=13) on Days 9-11, 34.2+/-53.1 pg/ml (n=15) on Days 12-14, 20.1+/-18.2 pg/ml (n=10) after Day 20. CSF concentrations of 8-iso-PGF2alpha on Days 3-5 and Days 6-8 were significantly higher in patients showing vasospasm as compared to patients not showing vasospasm. CSF levels of 8-iso-PGF2alpha in patients showing vasospasm gradually increased in the days after onset of SAH and peaked on Days 6-8. Levels returned to normal after Day 20. These values on Days 3-5, Days 6-8, and Days 9-11 were significantly higher than the value after Day 20. Considering these data and the biological activities of 8-iso-PGF2alpha, such as development of inflammation, membrane perturbation and vasoconstriction, we conclude that 8-iso-PGF2alpha may play a role in delayed cerebral vasospasm after SAH.

Adult↗
PubMed2004

Stereoselective synthesis of atropisomeric korupensamines A and B utilizing planar chiral arene chromium complex.

Naphthyl tetrahydroisoquinoline alkaloids, atropisomeric korupensamines A and B and ent-korupensamine B, were synthesized by syn-selective cross-coupling of a planar chiral arene chromium complex with naphthylboronic acid and subsequent axial isomerization or tricarbonylchromium migration to the inverted arene face as a key step. Palladium(0)-catalyzed cross-coupling of planar chiral arene chromium complex 12 with naphthylboronic acid 9 gave syn-biaryl coupling product 13. syn-Biaryl chromium complex 13 was heated in 1:1 mixture of di-n-butyl ether and 1,2-dichloroethane to give a face-inverted anti-biaryl chromium complex 14 without axial isomerization. Korupensamine A was synthesized from the syn-biaryl chromium complex 13 via o-formyl syn-biaryl chromium complex 10, and ent-korupensamine B was prepared from the face-inverted anti-biaryl chromium complex 14. On the other hand, difluoro-substituted syn-biaryl chromium complex 40 with a formyl group afforded anti-biaryl chromium complex 41 containing a rotated central bond by heating in xylene. The chromium-complexed fluorine atom was easily substituted with an isopropoxy group by nucleophilic substitution. Use of these reactions allowed (+)-2-bromo-3,5-difluorobenzaldehyde chromium complex (37) as a single chiral source to be converted to atropisomeric korupensamines A and B, respectively.

Chromium Compounds↗
PubMed2004

Functions of pancreatic beta cells and adipocytes in bombesin receptor subtype-3-deficient mice.

We previously reported that mice lacking bombesin receptor subtype-3 (BRS-3) exhibit mild late-onset obesity and glucose intolerance [Nature 390 (1997) 160]. To examine the mechanism by which glucose intolerance is developed in these mice, we studied insulin release and proinsulin biosynthesis in isolated pancreatic islets and glucose uptake and facilitative glucose transporter (GLUT)-4 translocation in adipose tissues. Although islet insulin contents and the size and number of islets of Langerhans in BRS-3-deficient mice decreased, there was no difference in glucose-stimulated insulin release and proinsulin biosynthesis between BRS-3-deficient and wild-type control mice. In contrast, adipose tissues exhibited a marked difference: the uptake of [(14)C]2-deoxy-D-glucose by adipocytes isolated from BRS-3-deficient mice was not stimulated by 10(-7)M insulin addition, and membrane fractionation analysis showed that GLUT4 was barely detected in the fraction of plasma membrane in BRS-3-deficient mice in the presence of 10(-7)M insulin. Quantitative reverse transcription-PCR (RT-PCR) showed that mRNA levels of GLUT4, insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2, syntaxin 4, SNAP23, and VAMP-2 in adipose tissues of BRS-3-deficient mice were unchanged compared with those in wild-type control mice. We concluded that impaired glucose metabolism observed in BRS-3-deficient mice was mainly caused by impaired GLUT4 translocation in adipocytes.

Adipocytes↗
PubMed2004

Changes in activity of plasma thrombin activatable fibrinolysis inhibitor in pregnancy.

The thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described inhibitor of fibrinolysis. Changes in the concentration of plasma TAFI molecules that are present and functional after activation by thrombin-thrombomodulin complex (TAFI activity) during pregnancy have not previously been studied, and we therefore conducted a present prospective study. Plasma TAFI activity was assayed in 15 healthy non-pregnant women and 176 healthy pregnant women at various stages of gestation. TAFI activity was higher in pregnant than in non-pregnant women. TAFI activity seemed to increase progressively until around 20 weeks of gestation, then maintained a moderately elevated level until delivery, and promptly decreased after delivery.

Adult↗
PubMed2004

Coordinate downregulation of a novel imprinted transcript ITUP1 with PEG3 in glioma cell lines.

The human paternally expressed gene 3 (PEG3) on chromosome 19q13.4 is one of the candidate tumor suppressor genes for glioma. We have previously reported that the epigenetic silencing of PEG3 expression in glioma cell lines is dependent on aberrant DNA methylation of an exonic CpG island. Here, we have identified three expressed sequence tags (ESTs), H80201, H78825 and AW197312, that exhibit paternal allele-specific expression, using human monochromosomal hybrids containing the paternal or maternal origin of PEG3 locus. The EST H80201 was shown to be expressed only from the paternal allele in normal human lymphoblasts by utilizing a single nucleotide polymorphism (SNP). Monoallelic expression of EST H80201 was also detected in non-tumor adult human brain tissues of gliomas. These ESTs were located directly adjacent to PEG3 in a head-to-head orientation. We have named this new transcript, imprinted transcript 1, which is located upstream but oppositely oriented to PEG3 (ITUP1). The ITUP1 showed a similar expression profile with PEG3 in glioma cell lines. Bisulfite genomic sequencing and reverse transcription (RT)-PCR analysis indicated that hypermethylation of the promoter region correlated with the absence of these transcripts. This suggests that ITUP1 and PEG3 are coordinately regulated, and that downregulation of the both genes may be important in the development of glioma.

Alleles↗
PubMed2004

Functional mapping of neural pathways in rodent brain in vivo using manganese-enhanced three-dimensional magnetic resonance imaging.

This work presents three-dimensional MRI studies of rodent brain in vivo after focal and systemic administration of MnCl2. Particular emphasis is paid to the morphology and dynamics of Mn2+-induced MRI signal enhancements, and the physiological mechanisms underlying cerebral Mn2+ uptake and distribution. It turns out that intravitreal and intrahippocampal injections of MnCl2 emerge as useful tools for a delineation of major axonal connections in the intact central nervous system. Subcutaneous administrations may be exploited to highlight regions involved in fundamental brain functions such as the olfactory bulb, inferior colliculus, cerebellum and hippocampal formation. Specific insights into the processes supporting cerebral Mn2+ accumulation may be obtained by intraventricular MnCl2 injection as well as by pharmacologic modulation of, for example, hippocampal function. Taken together, Mn2+-enhanced MRI opens new ways for mapping functioning pathways in animal brain in vivo with applications ranging from assessments of transgenic animals to follow-up studies of animal models of human brain disorders.

Animals↗
PubMed2004

Endoscopic treatment or surgery for undifferentiated early gastric cancer?

BACKGROUND: Although almost all (96%) the surgical cases of undifferentiated intramucosal early gastric cancer (EGC) have been found not to have lymph node metastasis (LNM), local treatment by endoscopic mucosal resection (EMR) is not accepted as an alternative treatment to surgery for this type of EGC. If a subgroup of patients with undifferentiated EGC with negligible risk of LNM can be defined, unnecessary surgery can be avoided. This study was conducted to determine this subgroup among undifferentiated EGC patients in whom the risk of LNM can be highly ruled out in an attempt to identify candidates who can be treated by EMR. METHODS: Data from 175 patients surgically resected for undifferentiated EGC were retrospectively collected, and clinicopathological factors were multivariately analyzed to identify predictive factors for LNM. RESULTS: Multivariate logistic regression analysis identified two independent risk factors for LNM, namely, a large tumor (>/=20 mm, P = 0.011) and presence of lymphatic involvement (P = 0.0005). Using these two risk factors as the predictive factors, LNM was observed in 5.8% of patients who had neither of the two predictive factors, whereas 23.1% or 13.1% of patients with one or two predictive factors had LNM, respectively. In contrast, the LNM rate was calculated to be 60% in patients who had both factors. Lymph node metastasis was not found in any of 6 patients with small intramucosal lesions (<10 mm) without lymphatic involvement. CONCLUSIONS: An intramucosal undifferentiated EGC that is smaller than 10 mm without lymphatic involvement can safely be treated by EMR alone, given the negligible possibility of LNM. When histological examination of endoscopically resected specimens shows lymphatic involvement or unexpectedly larger tumor size than that determined at pre-EMR endoscopic diagnosis, an additional surgical procedure should be considered.

Adenocarcinoma↗
PubMed2004

Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.

Rho family GTPases, particularly Rac1 and Cdc42, are key regulators of cell polarization and directional migration. Adenomatous polyposis coli (APC) is also thought to play a pivotal role in polarized cell migration. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts directly with APC. IQGAP1 and APC localize interdependently to the leading edge in migrating Vero cells, and activated Rac1/Cdc42 form a ternary complex with IQGAP1 and APC. Depletion of either IQGAP1 or APC inhibits actin meshwork formation and polarized migration. Depletion of IQGAP1 or APC also disrupts localization of CLIP-170, a microtubule-stabilizing protein that interacts with IQGAP1. Taken together, these results suggest a model in which activation of Rac1 and Cdc42 in response to migration signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170, form a complex that links the actin cytoskeleton and microtubule dynamics during cell polarization and directional migration.

Actins↗
PubMed2004

In vivo 3D MRI staining of the mouse hippocampal system using intracerebral injection of MnCl2.

The morphology and function of the hippocampal system of C57BL/6J mice (n = 8) was studied in vivo using T1-weighted 3D magnetic resonance imaging (MRI) (117 microm isotropic resolution) after bilateral injection of MnCl(2) (0.25 microl, 5 or 200 mM) into the posterior hippocampal formation. The neuronal uptake of the T1-shortening Mn(2+) ions resulted in a pronounced MRI signal enhancement within the CA3 subfield and dentate gyrus with milder increases in CA1 and subiculum. This finding is in line with differences in the excitability of hippocampal neurons previously reported using electrophysiologic recordings. The subsequent axonal transport of Mn(2+) highlighted the principal extrinsic projections from the posterior hippocampal formation via the fimbria and the precommissural fornix to the dorsal part of the lateral septal nucleus. A strong MRI signal enhancement was also observed in the ventral hippocampal commissure. A time-course analysis revealed unsaturated conditions of Mn(2+) accumulation at about 2 h after injection and optimal contrast-to-noise ratios at about 6 h after injection. The present results using Mn(2+)-enhanced 3D MRI open new ways for studying the role of the hippocampal system in specific aspects of learning and memory in normal and mutant mice.

Animals↗
PubMed2004

Incorporation of arachidonic and linoleic acid hydroperoxides into cultured human umbilical vein endothelial cells.

The current study assessed the differential incorporation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE), arachidonic acid (AA), 12-hydroxyeicosatetraenoic acid (12-HETE) and the linoleic acid (LA) oxidation products, 13-hydroxyoctadecadienoic acid (13-HODE) and 13-hydroperoxyoctadecadienoic acid (13-HPODE), into human umbilical vein endothelial cells (HUVEC). Approximately 80-90% of AA (10(-8)-10(-5)M) and 80% of LA (10(-8)-10(-5)M) were incorporated into HUVEC within 12h, while less than 50% of the hydroxy metabolites (12-HETE, 12-HPETE, 13-HODE, 13-HPODE) were incorporated into HUVEC over 48h. Further, treatment of HUVEC with either 12-HPETE or 13-HPODE (concentrations of 10(-5)M) had no effect on cell number at a 48h time point when compared with control. These results demonstrate that exogeneous hydroxy metabolites are incorporated into HUVEC to a lesser degree than were endogenous fatty acids. Further, we speculate that 12-HPETE and 13-HPODE are rapidly metabolized to substances without significant cytotoxic effects.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2004

Attenuation of vascularity by preoperative radiosurgery facilitates total removal of a hypervascular hemangioblastoma at the cerebello-pontine angle: case report.

BACKGROUND: The surgical removal of solid, large, and deep-seated hemangioblastomas remains challenging because it is difficult to control bleeding during the procedure. We used preoperative radiosurgery in a solid, highly vascular hemangioblastoma at the left cerebello-pontine angle and present our angiographic, operative, and histologic findings. CASE DESCRIPTION: A 37-year-old paraplegic woman with multiple hemangioblastomas was re-admitted to our clinic with cerebellar ataxia 6 years after resection of a tumor at the fourth ventricle. A vertebral artery angiogram revealed that the 3.5 cm diameter hemangioblastoma at the left cerebello-pontine angle was highly vascular and fed by the left anterior inferior cerebellar artery and posterior inferior cerebellar artery. Nine months before surgical removal it was treated with stereotactic radiosurgery (gamma knife, margin dose 28 Gy) to inhibit tumor progression and to reduce its vascularity. The tumor was totally removed via the left lateral suboccipital approach; bleeding was well controlled and there were no complications. Pathologic examination of the content of the excised tumor revealed coagulation necrosis with hyaline degeneration of the tumor vessels, resulting in a marked decrease in its vascularity. CONCLUSION: Preoperative radiosurgery led to a marked reduction in the vascularity of this hypervascular hemangioblastoma and was useful for controlling bleeding from the tumor during resection. We succeeded to remove the vascular-rich hemangioblastma after the intentional preoperative radiosurgery. The pathologic changes induced by radiotherapy were confirmed by operative finding.

Adult↗
PubMed2004

Successful off-pump coronary artery bypass for Behcet's disease.

A 66-year-old woman with a 30-year history of Behcet's disease was referred for coronary surgery because of restenosed stent and crescendo angina. We succeeded in operating on her by off-pump coronary bypass with bilateral internal mammary arteries, which were anastomosed to the left anterior descending artery and diagonal artery. The grafts were patent postoperatively and she became free from angina. Coronary surgery for Behcet's disease is extremely rare and this experience prompted us to report this case.

Aged↗
PubMed2004

Predictive factors for lymph node metastasis of differentiated submucosally invasive gastric cancer.

BACKGROUND: For early gastric cancer, submucosal invasion may be unrecognized until histopathologic examination of the specimen obtained by EMR. Gastrectomy with lymphadenectomy is the standard treatment for such submucosal cancers. However, approximately 80% of submucosal cancers do not have lymph node metastasis. Unnecessary surgery could be avoided if a subgroup of patients with submucosal cancer with negligible risk of lymph node metastasis can be defined. This study was conducted to define such a subgroup. METHODS: Data from 104 patients surgically treated for differentiated submucosal cancers were retrospectively collected. A multivariate analysis of clinicopathologic factors was performed to identify predictive factors for lymph node metastasis. RESULTS: Three independent risk factors, namely, female gender (p=0.0174), deep invasion (> or =500 microm) into the submucosal layer (p=0.001), and presence of lymphatic involvement (p < 0.0001) were associated with lymph node metastasis. Lymph node metastasis was not observed in any patient who had limited submucosal invasion and absence of lymphatic involvement. The rate of lymph node metastasis was calculated to be 80% in patients who had both deep submucosal invasion and lymphatic involvement. CONCLUSIONS: If endoscopic resection specimens exhibit no deep penetration (<500 microm) into the submucosal layer and lymphatic involvement is absent, EMR may be sufficient treatment for submucosal well-differentiated early gastric cancers. A long-term follow-up study of patients with such lesions treated by EMR alone is required.

Adolescent↗
PubMed2004

Therapy of human pancreatic carcinoma based on suppression of HMGA1 protein synthesis in preclinical models.

Pancreatic carcinoma is one of the most aggressive tumors, and, being refractory to conventional therapies, is an excellent target for new therapeutic approaches. Based on our previous finding of high HMGA1 expression in pancreatic cancer cells compared to normal pancreatic tissue, we evaluated whether suppression of HMGA1 protein expression could be a treatment option for patients affected by pancreatic cancer. Here we report that HMGA1 proteins are overexpressed in pancreatic carcinoma cell lines, and their downregulation through an adenovirus carrying the HMGA1 gene in an antisense orientation (Ad Yas-GFP) results in the death of three human pancreatic carcinoma cell lines (PANC1, Hs766T and PSN1). Pretreatment of PANC1 and PSN1 cells with Ad Yas-GFP suppressed and reduced, respectively, their ability to form xenograft tumors in nude mice. To further verify the role of HMGA1 in pancreatic tumorigenesis, we used a HMGA1 antisense phosphorothioate oligodeoxynucleotide (ODN); its addition induced a decrease in HMGA1 protein levels and a significant reduction of the proliferation rate of PANC1-, Hs766T- and PSN1-treated cells. Therefore, suppression of HMGA1 protein synthesis by an HMGA1 antisense approach seems to be a feasible treatment strategy in pancreatic carcinomas.

Adenoviridae↗
PubMed2004

Noncontact method for sleep stage estimation.

This paper describes a novel method to estimate sleep stage through noninvasive and unrestrained means. The Rechtschaffen and Kales (R-K) method is a standard to estimate sleep stage. However, it involves restraining the examinee and, thus, induces psychological stress. Furthermore, it requires specialists with a high degree of technical expertise and the use of an expensive polygraph. The sleep estimation method presented here is based on the noninvasive and unrestrained pneumatic biomeasurement method presented by the authors. Sleep stage transition in overnight sleep and the relationship between sleep stage and biosignals measured using the pneumatic method was analyzed and from the results, a mathematical model of sleep was created. Based on this model, a sleep stage estimator, including a sleep stage classifier and observer, was designed. The sleep state transition equation was the basis for the design of this observer, while the observed relationships were the basis for designing a classifier. Agreement of the estimated sleep stages with those obtained using the R-K method for the non-REM stage was 82.6%, for the REM stage was 38.3 % and for Wake was 70.5 %, including disagreement. However, the new method might ultimately result in better estimation of sleep stage due to the fact that it does not physically restrain the patient and does not induce psychological stress.

Adult↗
PubMed2004

Crosstalk between elicitor-induced cell death and cell cycle regulation in tobacco BY-2 cells.

The molecular links between cell cycle control and the regulation of programmed cell death are largely unknown in plants. Here we studied the relationship between the cell cycle and elicitor-induced cell death using synchronized tobacco BY-2 cells. Flow cytometry and fluorescence microscopy of nuclear DNA, and RNA gel-blot analyses of cell cycle-related genes revealed that the proteinaceous elicitor cryptogein induced cell cycle arrest at the G1 or G2 phase before the induction of cell death. Furthermore, the patterns of cell death induction and defence-related genes were different in different phases of the cell cycle. Constitutive treatment with cryptogein induced cell cycle arrest and cell death at the G1 or G2 phase. With transient treatment for 2 h, cell cycle arrest and cell death were only induced by treatment with the elicitor during the S or G1 phase. By contrast, the elicitor-induced production of reactive oxygen species was observed during all phases of the cell cycle. These results indicate that although recognition of the elicitor signal is cell cycle-independent, the induction of cell cycle arrest and cell death depends on the phase of the cell cycle.

Aphidicolin↗
PubMed2004

The risk of birth defects in dichorionic twins conceived by assisted reproductive technology.

The purpose of this study was to examine whether dichorionic twins conceived by assisted reproductive technology (ART; intracytoplasmic sperm injection [ICSI], in vitro fertilization [IVF], gamete-intrafallopian tube transfer [GIFT]) have a higher risk of birth defects compared to dichorionic twins conceived naturally. We reviewed the medical records of 406 mothers with dichorionic twin pregnancies, who received continuous antenatal care from < or = 20 weeks of gestation and gave birth to infants after > or = 24 weeks of gestation in our institute. Birth defects were diagnosed at the time of hospital discharge according to the International Classification of Diseases, 10th Revision. Occurrence of birth defects was compared between twins conceived by ART and those conceived naturally using logistic regression analysis. Overall, 51 of 812 infants (51/812 = 6.2%) had birth defects. The incidence of birth defects in ART-conceived twins was significantly higher than that of naturally conceived twins with an odds ratio of 6.9 (95% confidence interval [CI] 2.1, 22.5), 3.7 (95% CI 1.2, 12.0), and 4.3 (95% CI 1.4, 14.3) for ICSI, IVF, and GIFT, respectively. The higher frequency of birth defects in ART-conceived twins was still significant after adjusting for higher maternal age in the ART group, with an adjusted odds ratio of 6.7 (95% CI 2.1, 21.9), 3.6 (95% CI 1.1, 11.5), and 3.7 (95% CI 1.2-11.8) for ICSI, IVF, and GIFT, respectively. Dichorionic twins conceived by ART, compared to dichorionic twins conceived naturally, had a much higher risk for birth defects diagnosed at hospital discharge.

Congenital Abnormalities↗