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Yasuhiro Ogawa

Publications and source records attributed to Yasuhiro Ogawa.

At least 19 recordsLinked to original sources
PubMed2006

l-Caldesmon regulates proliferation and migration of vascular smooth muscle cells and inhibits neointimal formation after angioplasty.

OBJECTIVE: Light-type caldesmon (l-CaD) is a potent cytostatic and antiangiogenic protein that regulates cell growth and survival via modulation of the cell shape and cytoskeleton. The aim of this study is to explore the potential value of l-CaD for use as a cytostatic agent to inhibit neointimal formation after angioplasty by suppressing vascular smooth muscle cell (VSMC) growth and migration. METHODS AND RESULTS: We tested the cytostatic function of l-CaD in cultured VSMCs using assays for apoptosis, cell proliferation, and migration, and evaluated the expression pattern of relevant signaling proteins (focal adhesion kinase [FAK] and mitogen-activated protein kinases) in VSMCs. Transfection of adenoviral vector encoding l-CaD (Ad-l-CaD) resulted in progressive loss of actin stress fibers and cell retraction. Enzyme-linked immunosorbent assay demonstrated that Ad-l-CaD transfection increased the apoptosis rate by 75% and reduced BrdU uptake by 49%. Furthermore, transfection of Ad-l-CaD inhibited migration of VSMCs induced by platelet-derived growth factor-BB (PDGF) by 36% (P<0.05). Immunoblotting analysis revealed that l-CaD overexpression reduced PDGF-induced phosphorylation of both FAK and extracellular signal regulated-kinase (ERK). In balloon-injured rat carotid arteries, Ad-l-CaD transfection inhibited neointimal formation by 37% (P<0.05) without delaying re-endothelialization at 14 days. CONCLUSIONS: Overexpression of l-CaD suppressed cell growth and survival in VSMCs and inhibited neointimal formation after experimental angioplasty, partly by regulating the cytoskeletal tension-FAK-ERK axis.

Angioplasty↗
PubMed2006

Spectrins and ankyrinB constitute a specialized paranodal cytoskeleton.

Paranodal junctions of myelinated nerve fibers are important for saltatory conduction and function as paracellular and membrane protein diffusion barriers flanking nodes of Ranvier. The formation of these specialized axoglial contacts depends on the presence of three cell adhesion molecules: neurofascin 155 on the glial membrane and a complex of Caspr and contactin on the axon. We isolated axonal and glial membranes highly enriched in these paranodal proteins and then used mass spectrometry to identify additional proteins associated with the paranodal axoglial junction. This strategy led to the identification of three novel components of the paranodal cytoskeleton: ankyrinB, alphaII spectrin, and betaII spectrin. Biochemical and immunohistochemical analyses revealed that these proteins associate with protein 4.1B in a macromolecular complex that is concentrated at central and peripheral paranodal junctions in the adult and during early myelination. Furthermore, we show that the paranodal localization of ankyrinB is disrupted in Caspr-null mice with aberrant paranodal junctions, demonstrating that paranodal neuron-glia interactions regulate the organization of the underlying cytoskeleton. In contrast, genetic disruption of the juxtaparanodal protein Caspr2 or the nodal cytoskeletal protein betaIV spectrin did not alter the paranodal cytoskeleton. Our results demonstrate that the paranodal junction contains specialized cytoskeletal components that may be important to stabilize axon-glia interactions and contribute to the membrane protein diffusion barrier found at paranodes.

Animals↗
PubMed2006

Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells.

Motoneurons and oligodendrocytes in the embryonic spinal cord are produced from a restricted domain of the ventral ventricular zone, termed the pMN domain. The pMN domain is the site of expression of two basic helix-loop-helix transcription factors, Olig1 and Olig2, which are essential for motoneuron and oligodendrocyte development. Previous lineage-tracing experiments using Olig1-Cre and Olig2-GFP mice suggested that motoneurons and oligodendrocytes, but not astrocytes, are produced from the pMN domain. However, important questions remain, including the fate of neuroepithelial cells in the pMN domain, and specifically whether motoneurons and oligodendrocytes are the only types of cells produced in the pMN domain. We performed lineage-tracing experiments using a tamoxifen-inducible Cre-recombinase inserted into the Olig2 locus. We demonstrated that motoneurons and oligodendrocyte progenitors are derived from the Olig2+ progenitors in the pMN domain, and also found that a subset of astrocytes at the ventral surface of the spinal cord and ependymal cells at the ventricular surface are also produced from the pMN domain. These findings demonstrate that motoneurons and oligodendrocytes are not the only cell types originating from this domain.

Animals↗
PubMed2006

Klotho gene polymorphism may be a genetic risk factor for atherosclerotic coronary artery disease but not for vasospastic angina in Japanese.

BACKGROUND: The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes, including atherosclerosis. We tested the hypothesis that the G-395A polymorphism of the klotho gene is associated with increased risk for 2 types of ischemic heart disease in Japanese. METHODS: The study population consisted of 197 patients with coronary heart disease (CAD) who had >75% luminal diameter narrowing, 77 patients with vasospastic angina (VSA) without significant fixed coronary artery disease, and 331 healthy control subjects. RESULTS: The frequency of the A allele carriers of the klotho gene was significantly higher in the CAD group than in the control group (29.9% vs. 19.0%). The unadjusted odds ratio for CAD in the A allele carriers compared with the control group was 1.82 (p=0.004) and a traditional risk-adjusted logistic regression model revealed that the A allele was an independent predictor of CAD (odds ratio, 1.76; p=0.03). In contrast, the frequency of the A allele carriers was not significantly different in the VSA group (23.4%; adjusted odds ratio, 1.18. CONCLUSIONS: The -395A polymorphism of the human klotho gene may be a genetic risk factor for IHD and not for VSA.

Adult↗
PubMed2006

Preoperative assessment of vascular anatomy of inferior mesenteric artery by volume-rendered 3D-CT for laparoscopic lymph node dissection with left colic artery preservation in lower sigmoid and rectal cancer.

AIM: To determine the distance between the branching point of the left colic artery (LCA) and the inferior mesenteric artery (IMA) by computed tomography (CT) scanning, for preoperative evaluation before laparoscopic colorectal operation. METHODS: From February 2004 to May 2005, 100 patients (63 men, 37 women) underwent angiography performed with a 16-scanner multi-detector row CT unit (Toshiba, Aquilion 16). All images were analyzed on a workstation (AZE Ltd, Virtual Place Advance 300). The distance from the root of the IMA to the bifurcation of the LCA was measured by curved multi-planar reconstruction on a workstation. RESULTS: The IMA could be visualized in all the cases, but the LCA was missing in two patients. The mean distance from the root of the IMA to the root of the LCA was 42.0 mm (range, 23.2-75.0 mm). There were no differences in gender, arterial branching types, body weight, height, and body mass index. CONCLUSION: Volume-rendered 3D-CT is helpful to assess the vascular branching anatomy for laparoscopic surgery.

Adult↗
PubMed2006

Impact of plasma aldosterone levels for prediction of in-stent restenosis.

Aldosterone promotes vascular smooth muscle cell proliferation and endothelial dysfunction, suggesting the contribution to in-stent restenosis (ISR). This study evaluated any relation between plasma aldosterone levels and ISR 6 months after successful coronary stenting. We enrolled 156 consecutive patients with stable angina who underwent coronary bare metal stenting. Plasma aldosterone levels and other serum markers known to influence cardiovascular events were measured in all patients at baseline. Patients with restenosis were found to have significantly higher plasma aldosterone levels than their counterparts without restenosis (162 +/- 60 vs 122 +/- 60 pg/ml, p = 0.007). On logistic regression analysis, even after adjusting for clinical, angiographic, and other confounding variables, plasma aldosterone level per 10 pg/ml (odds ratio 1.34, 95% confidence interval 1.10 to 1.63, p = 0.006) proved to be the independent predictor of ISR. The area under the receiver-operating characteristic curve for plasma aldosterone level was 0.75, and the optimal cut-off value identified by receiver-operating characteristic analysis was 141.9 pg/ml, which had a predictive accuracy of 69%. In conclusion, the present findings indicate that plasma aldosterone levels at baseline are independent predictors of ISR and may constitute a potential therapeutic target.

Aged↗
PubMed2006

A self-contained polymeric 2-DE chip system for rapid and easy analysis.

We developed a polymeric 2-DE chip system. The chip consisted of an IEF region, an SDS-PAGE region, a valveless connection port, and a sample introduction port. A "junction structure" as a valveless connection port, which allowed separating and connecting the first- and second-dimensional gels, was fabricated between their regions. A "solution inlet" as a sample introduction port was fabricated to perform the liquid and sample introductions without solution leakage. Simultaneous sample monitoring was performed using the on-chip detection system. The performances of the system were demonstrated using commercially available proteins as a standard specimen and tissue-extracted proteins as the real samples. All procedures were employed without any movement of relocation part. This new 2-D separation system realized improved labor-intensive operations and a reduced experimental time.

Animals↗
PubMed2006

Umbilical metastasis from breast cancer related with tumor marker elevation.

We describe a 53-year-old woman with tumor marker abnormality caused by an umbilical metastasis from breast cancer. She had undergone breast conservation therapy (BCT) for breast cancer (T2N1M0) 9 years previously. Umbilical metastasis was detected 9 months after tumor marker elevation was first noted. After resection of the umbilical metastasis, tumor marker level decreased immediately and normalized. The patient is alive without other metastasis.

Abdominal Neoplasms↗
PubMed2006

Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Studies have reported an association between receipt of statin therapy and a reduction in complications after elective percutaneous coronary intervention (PCI). However, there are limited data on the effects of chronic statin therapy before the occurrence of an acute myocardial infarction (AMI). OBJECTIVE: This study investigated whether administration of chronic statin therapy before AMI was associated with a reduction in reperfusion injury in AMI patients undergoing PCI. METHODS: This was a retrospective study of consecutive patients with a first AMI who underwent successful reperfusion therapy with PCI within 24 hours after the onset of AMI between April 1998 and October 2003. Patients were stratified according to whether they had or had not been receiving chronic statin therapy for > or = 1 month before the onset of AMI. The following end points were compared after PCI: electrocardiographic resolution of ST segment elevation, defined as a reduction of > or = 50% from the initial value; achievement of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow; corrected TIMI frame count (cTFC); maximum serum creatine kinase (CK) level; and the type and frequency of ventricular arrhythmias. RESULTS: The study enrolled 386 patients, 40 of whom had been receiving statin therapy before the onset of AMI. The clinical characteristics of the 2 groups were similar at baseline, with the exceptions of a significantly higher rate of hyperlipidemia in the statin group compared with the nonstatin group (P < 0.001), significantly greater chronic use of aspirin therapy (P < 0.001), and significantly greater chronic use of antihypertensive medications (beta-blockers: P = 0.004; angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers: P = 0.007; calcium channel blockers: P = 0.006). Electrocardiographic ST segment resolution after PCI was observed in 87.5% and 69.9% of the statin and nonstatin groups, respectively (hazard ratio [HR]: 3.01; 95% CI, 1.15-7.90; P = 0.025). Achievement of TIMI grade 3 flow after PCI was seen in 95.0% of the statin group and 83.5% of the nonstatin group (HR: 3.75; 95% CI, 0.88-16.0; P = NS). Patients treated with a statin had a significantly lower mean (SD) maximum CK level compared with the nonstatin group (2300 [1449] vs 3538 [3170] IU/mL, respectively; P = 0.015) and a lower cTFC after PCI (18.8 [4.0] vs 24.2 [14.2]; P = 0.017). The difference in reperfusion arrhythmias between groups was not statistically significant. After adjustment for baseline covariates, pretreatment with a statin was found to be an independent predictor of ST segment resolution after PCI (HR: 2.95; 95% CI, 1.08-8.09; P = 0.035) and prevention of impaired coronary flow (HR: 3.00; 95% CI, 1.63-5.55; P < 0.001). CONCLUSION: In this study, receipt of chronic statin therapy before the onset of AMI was associated with improvement in epicardial perfusion and a reduction in myocardial necrosis after PCI.

Adrenergic beta-Antagonists↗
PubMed2006

Sentinel node biopsy in breast cancer patients treated with neoadjuvant chemotherapy.

A sentinel node biopsy (SNB) has been proved to be an accurate method to estimate the axillary lymph node status as a replacement for axillary lymph node dissection (AxLND) in patients with early breast cancer who have not been treated with neoadjuvant chemotherapy (NAC). We examined the feasibility and accuracy of performing SNB after NAC. Seventy breast cancer patients treated with NAC were enrolled in the current study during the period between March 2001 and June 2005. NAC performed preoperatively consisted of three to four times of CAF chemotherapy. Moreover, intra-arterial (subclavian artery and internal mammary artery) infusion of epirubicin and 5-fluorouracil was performed in addition to systemic CAF chemotherapy once to three times in patients with large breast tumors or bulky axillary lymph node metastases. The sentinel nodes were successfully identified in 63 out of 70 patients (identification rate: 90%). The mean number of sentinel nodes removed per patient was 1.5 (range 1-6). Of the 43 patients in whom AxLND was performed after the sentinel nodes were identified, 19 (44.2%) had positive sentinel nodes. In 8 of those 19 patients, the sentinel node was the only cancer positive lymph node. Among the 24 patients who had negative sentinel nodes it was found that one patient had a confirmed false negative result, thus yielding a false negative rate of 5%, and a sensitivity of 95%. There was no false negative patient who had a clinically negative lymph node status (N0) before NAC (17 patients), whereas the false negative rate was 6.3% in the subgroup of patients with a clinically positive lymph node status (N1, N2) before NAC (26 patients). As a result, SNB after NAC is thus considered to be able to effectively predict the axillary lymph node status in patients with a clinically negative lymph node status before NAC.

Adult↗
PubMed2005

An epoch-making application of discharge plasma phenomenon to gene-transfer.

We discovered an epoch-making gene transfer method utilizing discharge plasma. Although an electroporation method is commonly used in present gene transfer experiments, it cannot transfer genes into primary cells sufficiently. The atmospheric pressure discharge plasma employed in this study was originally used for surface treatment of non-biological materials. We hypothesized that it could provide a suitable effect on the surface of target cells and applied it to gene transfer into various types of cells. The plasma technology succeeded in the efficient transfer of green fluorescence protein (GFP) plasmid into post-mitotic neuronal cells obtained from cerebral cortices of rats, into which an electroporation with conventional equipment cannot transfer genes sufficiently, as the cells were attached. After the transfection of rat pheochromocytoma PC12 cells with the GFP gene by plasma treatment, the cells retained their function, that is, nerve growth factor-induced differentiation. Furthermore, gene transfer with the plasma technology was also applicable to other types of cell lines such as HeLa cells and Chinese hamster lung (CHL) cells as adherent cell lines, and Jurkat cells as a suspended cell line, and another type of primary cell, human umbilical vein endothelial cells (HUVEC). In conclusion, the plasma method is an epoch-making gene transfer technology which efficiently transfers genes into primary cells into which electroporation cannot transfer genes. Moreover, the method is able to universally transfer genes into various types of cells as the function of the cells was maintained.

Animals↗
PubMed2005

A novel transfection method for mammalian cells using gas plasma.

Introduction of foreign genes into target cells is a crucial step for achievement of gene therapy. We have recently developed a novel transfection system for eukaryotic cells, namely the electric pulse-activated gas plasma generator. To measure the transfection efficiency and mortality by flow-cytometry, we employed enhanced green fluorescent protein and propidium iodide staining, respectively. One day after the 1-3s plasma exposures with DNA concentration at 0.5 microg/microl, favorable transfection efficiencies (17.8-21.6%) and mortalities (0.65-2.86%) were obtained for HeLa-S3, HT-1080 and MCF-7 cells. The recipient cells became transiently permeable for plasmid DNA during the plasma exposure, suggesting that plasma-mediated transfection may involve similar mechanisms that accounts for electroporation. The relatively low mortality rates are encouraging in our attempt to apply this system to the various cell lines including the primary cell cultures.

Cell Line, Tumor↗
PubMed2005

In vivo imaging of hepatic fatty acid metabolism in patients with nonalcoholic steatohepatitis using semiquantative (123)I-BMIPP liver scan.

Recent progress of studies in NASH displays multi-disciplinary characters of the pathogeneses. Despite these advances, the strategic use of imaging modalities such as CT, US, and MRI, remains a relatively low priority in clinical situations, because these can only visualize the presence of fatty infiltration to the hepatic parenchyma, impossible to figure out the dynamic function of NASH liver. Morphological alteration such as CT value, MR signal intensity and echo-grade do not distinguish NASH from simple fatty liver. In this presentation, from a radiologic viewpoint, we show the feasibility of in vivo fatty acid imaging with (123)I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP). BMIPP is an (123)I labeled fatty acid analog for imaging damaged myocardium, using conventional nuclear imaging equipment. Under normal conditions, the energy source for myocardial utilization is dependent on the beta-oxidation of fatty acids. For energy production in ischemic myocardium, the drastic switch from reduced beta-oxidation of fatty acids to glucose metabolism is well known. BMIPP can detect the area of reduced fatty acids metabolism on myocardial imaging and the data can be converted into semiquantitative analysis. Therefore, we speculate that the use of BMIPP to in vivo hepatic imaging in NASH could highlight a lot of matters of NASH. Details of this presentation include: (1) Hepatic imaging with BMIPP; (2) Clearance of BMIPP from NASH liver; (3) semiquantitative analysis of hepatic BMIPP clearance and clinical features of NASH; (4) Profiles of NASH categorized by BMIPP imaging and (5) Preliminary data of BMIPP clearance in patients with Tamoxifen-induced NASH. The core of our stance in this presentation is searching for valuable advice on clinical use of BMIPP in patients with NASH from specialists in the field of HEPATOLOGY.

Journal Article↗
PubMed2005

CYP17 polymorphism and tamoxifen-induced hepatic steatosis.

Hepatic steatosis is a frequent complication, which sometimes develops nonalcoholic steatohepatitis (NASH), in breast cancer patients treated with tamoxifen, a potent antagonist of estrogen. Recently we reported the impairment of fatty acid beta-oxidation and the enhancing fatty infiltration to hepatocytes in aromatase deficiency (ArKO) mice as the estrogen deficiency models. This experimental observation let us speculate strong link between estrogen and hepatic steatosis. In this study, we investigated whether a polymorphism in the cytochrome P450c17alpha gene (CYP17), which is associated with circulating estrogen levels, influences the development of tamoxifen-induced hepatic steatosis. This consecutive study included 180 breast cancer patients undergoing tamoxifen treatment. Genomic DNA extracted from the peripheral blood of each patient was analyzed by restriction fragment length polymorphism (defined as the A1 and A2 alleles). The extent of hepatic steatosis was assessed by computed tomography (CT) as the liver/spleen (L/S) ratio. While receiving adjuvant tamoxifen, 57 of 180 patients developed hepatic steatosis (L/S ratio <0.9) without obvious changes in body mass index (BMI). We observed a significant association between the A2/A2 genotype and the development of hepatic steatosis compared with the A1/A1 genotype [odds ratio (OR), 3.60; 95% confidence interval (C.I.)=1.42-9.10]. The A1/A2 genotype was at an intermediately increased risk of hepatic steatosis (OR, 2.24; 95% C.I.=0.99-5.08). The presence of the A2 allele possibly increased the progression of hepatic steatosis with a gene dosage effect (P=0.06). Our results suggest that functional polymorphism in CYP17 may be involved in determining susceptibility of tamoxifen-induced hepatic steatosis.

Journal Article↗
PubMed2005

Gliogenic radial glial cells show heterogeneity in the developing mouse spinal cord.

The central nervous system of the mammalian embryo is organized according to the expression of region-specific transcription factors along the anteroposterior and/or the dorsoventral axis. For example, the dorsal ventricular zone (VZ) of the embryonic spinal cord expresses Pax3 and Pax7, the ventral VZ expresses Pax6, and the more ventral VZ expresses Nkx2.2. Properties of neuronal precursors located in the VZ are determined by the characteristic expression patterns of these transcription factors, leading to the generation of distinct classes of neurons. Recent studies demonstrated that radial glial cells produce neurons in addition to glia during central nervous system development. Thus, neuronal precursor diversity may be dependent upon the diversity of radial glial cells. To investigate this hypothesis, we analyzed the expression of radial glial cell markers and transcription factors in the mouse embryonic spinal cord. We show that radial glial cells indeed express domain-specific transcription factor. Moreover, they varied in expression of the astrocyte-specific glutamate transporter. The region where the astrocyte-specific glutamate transporter is strongly expressed in the ventral radial glial cells is closely related to the Pax6-expressing domain, and the weakly expressing region corresponding to the Nkx2.2-expressing domain. Furthermore, dorsal radial fibers expressed ephrin-B1. Thus, different types of radial glial cells exist in different domains defined by the transcription factor expression at E12.5. We also show that this diversity continues to the gliogenic stage of radial glial cells. This raises the idea that astrocytes generated from different domains along the dorsoventral axis in the mouse spinal cord have distinct characteristics.

Animals↗
PubMed2005

Selective COX-2 inhibitor regulates the MAP kinase signaling pathway in human osteoarthritic chondrocytes after induction of nitric oxide.

The purpose of this study was to examine the effect of cyclooxygenase-2 (COX-2) inhibitors on the mitogen-activated protein (MAP) kinase signaling pathway and synthesis of glucosaminoglycan after nitric oxide (NO) induction in articular human chondrocytes. After NO induction, the cells were divided into three groups that were treated with either ethanol (control); a selective COX-2 inhibitor (Celecoxib), or no additive, and evaluated. There were no differences in the effect of the selective COX-2 inhibitor on mitochondrial membrane potential or Annexin V levels. However, Celecoxib significantly decreased prostaglandin E2 (PGE2) production. Celecoxib also decreased the phosphorylation state of p38 and p44/42 of MAP kinase. The ratio of chondroitin-6 sulfate (C6S)/C4S was increased in response to the exposure to Celecoxib. Celecoxib did not affect apoptosis, but decreased the activation of MAP kinase in osteoarthritic chondrocytes after NO induction. NO-induced OA chondrocytes were associated with the p38 and the p44/42 MAPK signaling pathways, in a pathway that is distinct from PGE2-mediated apoptosis.

Annexin A5↗
PubMed2005

CYP17 polymorphism as a risk factor of tamoxifen-induced hepatic steatosis in breast cancer patients.

Oral administration of tamoxifen, an endocrine therapy for breast cancer, often induces hepatic steatosis (THS, tamoxifen-induced hepatic steatosis) as a complication, which can progress to non-alcoholic steatohepatitis (NASH). The development of this complication is strongly associated with three clinical risk factors; specifically, insulin resistance, central obesity, and hypertriglyceridemia, however a genetic predisposition to THS has yet to be investigated. The aim of this study is to determine whether genetic polymorphism of the P450c17alpha enzyme coded for by the CYP17 gene, responsible for regulating serum estrogen, has an association with THS. After obtaining informed consent from 180 eligible breast cancer patients treated with tamoxifen, DNA was collected and analyzed by restriction fragment length polymorphism assay and classified into alleles defined as A1 and A2. The absence or presence and extent of THS was evaluated by calculating the liver/spleen (L/S) ratio based on Hounsfield units with a CT scanner. Administration of tamoxifen led to THS (L/S ratio <0.9) in 57 (31.7%) of 180 patients while the remaining 123 (68.3%) patients did not develop THS. A significant difference in the distribution of CYP17 genotypes was observed between patients who developed THS and those who did not (P=0.021). A significantly higher frequency of the A2 allele was seen in the THS group (odds ratio, 1.90; 95% confidence interval, 1.21-2.99). Our study provides the first evidence that CYP17 polymorphism participates in the development of THS, and sheds light on the genetic causes of this side effect and genetic differences between tamoxifen-treated individuals.

Adult↗