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Biomedical subjects

Y Ono

Publications and source records attributed to Y Ono.

At least 181 records · Page 10Linked to original sources
PubMed2000

Rho kinase inhibitor HA-1077 prevents Rho-mediated myosin phosphatase inhibition in smooth muscle cells.

In smooth muscle, a Rho-regulated system of myosin phosphatase exists; however, it has yet to be established whether Rho kinase, one of the downstream effectors of Rho, mediates the regulation of myosin phosphatase activity in vivo. In the present study, we demonstrate in permeabilized vascular smooth muscle cells (SMCs) that the vasodilator 1-(5-isoquinolinesulfonyl)-homopiperazine (HA-1077), which we show to be a potent inhibitor of Rho kinase, dose dependently inhibits Rho-mediated enhancement of Ca(2+)-induced 20-kDa myosin light chain (MLC(20)) phosphorylation due to abrogating Rho-mediated inhibition of MLC(20) dephosphorylation. By an immune complex phosphatase assay, we found that guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) stimulation of permeabilized SMCs caused a decrease in myosin phosphatase activity with an increase in the extent of phosphorylation of the 130-kDa myosin-binding regulatory subunit (MBS) of myosin phosphatase in a Rho-dependent manner. HA-1077 abolished both of the Rho-mediated events. Moreover, we observed that the pleckstrin homology/cystein-rich domain protein of Rho kinase, a dominant negative inhibitor of Rho kinase, inhibited GTPgammaS-induced phosphorylation of MBS. These results provide direct in vivo evidence that Rho kinase mediates inhibition of myosin phosphatase activity with resultant enhancement of MLC(20) phosphorylation in smooth muscle and reveal the usefulness of HA-1077 as a Rho kinase inhibitor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Bacillus Calmette-Guérin perfusion therapy for the treatment of transitional cell carcinoma in situ of the upper urinary tract.

OBJECTIVES: The aim of this study is to evaluate the efficacy and safety of intrarenal bacillus Calmette-Guérin (BCG) instillation as a treatment for transitional cell carcinoma in situ (CIS) of the upper urinary tract. METHODS: Diagnostic criteria of upper urinary tract CIS were (1) positive urinary cytology, (2) negative multiple random biopsy of the bladder and prostatic urethra, (3) negative radiographic findings in the upper urinary tract and (4) two serial positive cytologies in selective ipsilateral urine sampling from the pyeloureteral system. Eleven patients diagnosed as having upper urinary tract CIS were enrolled in this study. Thus, 11 renal units were treated with BCG instillation. After placing a 6-french Double-J stent, BCG (80 mg) in 40 ml saline was instilled into the bladder weekly, 6 times in total as one course. RESULTS: At the end of one course, 9 cases showed negative urinary cytology. Among these 9 cases, 2 showed recurrence in the upper urinary tract after 4 months and 8 months of disease-free interval, respectively. These 2 cases have received an additional course of BCG instillation, but the urinary cytology did not normalize. Mean recurrence-free time was 19.6 months. Of the other 7 cases who responded to the first course of instillation, 6 cases were alive with no evidence of the disease. The remaining patient died of rectal cancer with no evidence of transitional cell carcinoma (TCC). Of the 2 cases who showed positive urinary cytology even after the first course, 1 underwent nephroureterectomy. The other case was diagnosed as having malignant lymphoma 3 months after the end of this instillation therapy, and he died of malignant lymphoma. As side effects, 8 cases (72.7%) showed bladder irritability, and 4 presented fever higher than 38 degrees C. However, no patient needed antitubercular treatment. CONCLUSION: As for the short-term response, BCG instillation for the treatment of upper urinary tract CIS is considered to be effective and safe. Longer follow-up and further experience with this treatment are required.

Adjuvants, Immunologic↗
PubMed2000

Spinal atypical teratoid/rhabdoid tumor in an infant.

Atypical teratoid/rhabdoid tumor of the central nervous system in infancy and childhood was established as an entity based on histological, immunohistochemical, and cytogenetic studies. We report the case of a 7-month-old girl who presented with progressive paraplegia and hypesthesia of her legs. Imaging studies revealed a spinal cord mass occupying the entire spinal canal below the T(7) level. Through a T(12)-L(3) laminectomy, the intramedullary tumor was partially debulked. Histologically, the tumor specimen had rhabdoid cells, and immunostaining showed vimentin and cytokeratin positivity. No abnormality of chromosome 22q was detected with the fluorescence in situ hybridization method.

Biomarkers, Tumor↗
PubMed2000

In vitro biological activities of a series of 2 beta-substituted analogues of 1 alpha,25-dihydroxyvitamin D3.

Biological activities of a series of 2beta-substituted analogues of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] were evaluated in vitro in terms of their binding affinity with regard to calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP). Additionally, reporter gene luciferase activities using either a rat 25-hydroxyvitamin D3-24-hydroxylase gene promoter, including two vitamin D-responsive elements (VDREs), in transfected rat osteoblast-like ROS17/2.8 cells, or a human VDR-GAL4 modified two-hybrid system in transfected human epitheloid carcinoma, cervix HeLa cells were examined. Binding affinity for VDR, transactivation potency on the target gene and VDR-mediated gene regulation of the hydroxyalkyl and hydroxyalkoxy 2beta-substituted analogues were almost comparable to those of 1alpha,25(OH)2D3, while the alkyl and alkenyl analogues were much less active than 1alpha,25(OH)2D3. This study investigated the biological evaluation of a series of 2beta-substituted analogues at the molecular level, with regard to the structural differences of alkyl, alkenyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, hydroxy and chloro substituents at the 2beta-position of 1alpha,25(OH)2D3.

Animals↗
PubMed2000

Difference spatial distribution function analysis of aqueous solutions. II. Hydration structures of dimethyl ether, 180 degrees ethyl methyl ether and 0 degree ethyl methyl ether solutions.

Monte Carlo simulations are systematically presented to demonstrate the influence of the hydrophobic group's steric bulk on hydration structure. We have simulated a dimethyl ether (DME), two conformations for ethyl methyl ether (0 degree EME and 180 degrees EME), and 0 degree ethanol solutions. Spatial distribution function (SDF), goo(x,y,z) and difference SDF (DSDF), delta goo(x,y,z), obtained from MC simulation in an infinitely dilute aqueous solution of ether show the three-dimensional probability of an atom-atom pair distribution between solute and solvent atoms. Based on the results of SDF in an infinitely dilute aqueous solution of ether, the distribution of hydration water molecules can be divided into hydrogen acceptor (HA) and hydrophobic hydration (HH), regions, and the spatial orientation of the hydrogen-bonded water in the HA region is found to form a triple-layer structure, as it does in alcohol solutions. From the results of an analysis of the DSDF delta goo(x,y,z) between the SDFs of EME and DME, it is apparent that the distribution changes of hydration water molecules in ether solutions are essentially similar to those in the alcohol solutions. Further, we show that the hydration water molecules are distributed mainly in the stable area in the binding energy's (BE) contour maps for each region.

Algorithms↗
PubMed2000

Difference spatial distribution function analysis of aqueous solutions. IV. Hydration structure changes of ethylene glycol solutions throughout conformational change process from gGg' to tGg' conformers.

Monte Carlo (MC) simulations were carried out for an infinitely dilute aqueous solution of two stable conformers (gGg' and tGg') and of three conformations between gGg' and tGg' conformers of ethylene glycol (EG) at 298K. Based on the spatial distribution function (SDF) goo(x,y,z), obtained from the MC simulation in the above conformations in liquid water, the high distribution of hydration water molecules could be divided into hydrogen acceptor (HA), hydrogen donor (HD), MIX (overlapped distribution of HA and HD), and hydrophobic hydration (HH) regions. The spatial orientations of hydrogen-bonded water molecules were found to be of a linear type with a triple-layer structure in the HA region and HA part (in the MIX region), and double-layer structures in the HD region and HD part (in the MIX region). In addition, it was apparent that the spatial orientations of these water molecules were of the linear type throughout the conformational change process from gGg' to tGg' conformers in liquid water. From the difference SDF (DSDF), deltagoo(x,y, z), between the SDFs of two conformations, we concluded that the distribution of hydration water molecules in the HA and HD parts of the MIX region are governed by the competition of internal hydrogen bonds between the hydrogen atom and two lone-pair electrons on the oxygen atom of an EG molecule.

Algorithms↗
PubMed2000

Difference spatial distribution function analysis of aqueous solutions. III. Hydration structures of alcohol and ether solutions having straight chain and branched alkyl groups.

Spatial distribution functions (SDFs), gOO(x,y,z) and gOH(x,y,z), obtained from Monte Carlo simulations at 298 K were applied to characterize the anisotropic structure of infinitely dilute aqueous solutions of alcohols and ethers having straight chain and branched alkyl groups. In spite of the different size and shape of the hydrophobic groups, the spatial orientation of the hydrogen-bonded water molecules was found to be of linear type with a triple layer structure in the hydrogen acceptor (HA) region and a double layer structure in the hydrogen donor (HD) region. The volumes and the coordination number (CN) in the HA region were essentially identical for all alcohol and ether solutions, but the volumes for the isopropyl alcohol (IPA) and isopropyl methyl ether (IPE) solutions were greater than those for the other solutions. In the hydrophobic hydration (HH) region, these values increased with increasing size and shape of hydrophobic groups, except in the case of IPA and IPE solutions. These results indicated that the hydration structures around the isopropyl group in alcohol and ether solutions differed from those in other solutions. From the results of the difference SDF (DSDF), AgOO(x,y,z), between SDFs gOO(x,y,z) for the two states, it was apparent that the distribution of hydration water molecules in the HA region for ether solution was characterized by the increase of the distribution in the direction of lone pair electrons on the oxygen atom of the solute molecule with increasing hydrophobicity.

Alcohols↗
PubMed2000

[Prophylactic efficacy of a basidiomycetes preparation AHCC against lethal opportunistic infections in mice].

The prophylactic effects of a Basidiomycetes preparation, AHCC, against experimental opportunistic infections were investigated in leukopenic mice. In cyclophosphamide-induced leukopenic mice, oral or intraperitoneal administration of the AHCC at doses of 1000 or 50 mg/kg/day, respectively, for 4 consecutive days prior to Candida albicans infection significantly prolonged the survival periods of the infected mice, and decreased the viable counts of C. albicans cells recovered from their kidneys. Similarly, the oral treatment with AHCC protected mice from lethal infection with Pseudomonas aeruginosa and intraperitoneal one also protected mice from infection with methicillin-resistant Staphylococcus aureus (MRSA). These results suggest a potential usefulness of the AHCC as a prophylactic agent for the management of patients with opportunistic infections.

Animals↗
PubMed2000

Transcatheter occlusion of patent ductus arteriosus using a 0.052-inch coil--immediate results.

Coil occlusion of a patent ductus arteriosus (PDA) was attempted with a 0.052-inch Gianturco coil. The patients' ages and body weights at occlusion ranged from 5.8 to 19.7 (12.3+/-5.0, mean+/-SD) years and 18.9-99.1 (44.8+/-23.7) kg, respectively. Three types of 0.052-inch Gianturco coils with loop diameters (mm) and coil lengths (cm) of 6x8 (diameter x length), 8x8, or 8x10 were used. The delivery system was prepared as reported by Hays et al with slight modification. The minimal diameter and the Qp/Qs of the PDA ranged from 2.3 to 4.7 (3.4+/-0.7) mm, and 1.1-1.8 (1.5+/-0.3), respectively. There were 7 cases with type A PDA and 3 with type B, and coils were successfully deployed in all. Complete occlusion in the catheter laboratory was achieved in 4 cases. A minor leak disappeared within 24 h in 3 cases and at 3 months follow-up in 1 case. A tiny leak without a heart murmur persisted in 2 cases at 3 months' follow-up. No procedure-related complications occurred. This technique has significant advantages over previously reported techniques using a 0.038-inch coil for type B, or A PDA with a minimal diameter of 3-4 mm or more.

Adolescent↗
PubMed2000

Role and relation of p70 S6 and extracellular signal-regulated kinases in the phenotypic changes of hypertrophy of cardiac myocytes.

Cardiac hypertrophy is characterized by increased cardiomyocyte protein synthesis, increased cell volume, and a shift in cardiac-specific gene expression to fetal isoforms. Using neonatal rat cardiomyocytes stimulated with fetal calf serum (FCS) as a model for cardiac hypertrophy, the present study investigated the role of 2 signal transduction pathways, extracellular signal-regulated kinase (ERK) and p70S6 kinase (p70S6K), in the attendant phenotype changes. FCS evoked both ERK and p70S6K activity, peaking at 20-40min, and simultaneously increased cardiac myocyte protein synthesis (evaluated by [3H]leucine incorporation and total cellular protein content), cell size (evaluated by morphometry and fluorescence-activated cell sorter analysis) and expression of a fetal isoform of the muscle specific gene skeletal alpha-actin (SKA). Rapamycin, a specific inhibitor of the mammalian target of rapamycin (mTOR), which is an upstream signaling of p70S6K, completely inhibited FCS-induced cell size increases and protein synthesis, but had no effect on SKA mRNA expression. PD98059, which inhibited ERK activity, attenuated cardiac-specific gene expression in a dose-dependent manner, but had no influence on protein synthesis or cell size. These results indicate divergent roles for the ERK and p70S6K pathways in the phenotypic changes associated with cardiac hypertrophy.

Actins↗
PubMed2000

Calcium antagonist inhibits glomerular cell apoptosis and injuries of L-NAME exacerbated nephrosclerosis in SHR.

Increased apoptosis of glomerular cells, with progression of glomerulosclerosis, overactivity of the renin-angiotensin system and elevation of glomerular pressure, follows chronic nitric oxide synthase (NOS) inhibition in spontaneously hypertensive rats (SHR). To gain insight into the regulation of glomerular cell apoptosis in severe nephrosclerosis, we investigated apoptosis, the expression of proliferative cell nuclear antigen (PCNA) in glomeruli, and glomerular morphometric changes in 20-week-old SHR, SHR treated with NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 80 mg/l in drinking water), and SHR treated with L-NAME and the calcium antagonist, efonidipine (20 mg/kg per day), for 3 weeks. Apoptosis in non-sclerotic glomeruli was quantified by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. The increase in systolic blood pressure and the severe proteinuria with severe nephrosclerosis induced by chronic NOS inhibition were completely prevented by efonidipine. Furthermore, the glomerular area and capillary tuft area were markedly increased in rats treated with efonidipine compared with both control rats (+30 and +42%, respectively, p<0.01) and rats treated with L-NAME (+35 and +56%, respectively, p<0.01)-treated rats. This calcium antagonist also significantly inhibited the both increases of the glomerular cell apoptosis index (-72%) and the PCNA index (+44%), therefore the alteration between apoptosis and proliferation slightly increased the number of glomerular cells (subcapsular, +22%, p<0.01; juxtamedullary, +2%, not significant). Thus, the calcium antagonist efonidipine seems to play an important role in the regulation of apoptosis and proliferation of glomerular cells and may be effective in preventing nephrosclerosis exacerbated by NOS inhibition.

Animals↗
PubMed2000

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

OBJECTIVE: To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. SUBJECTS AND METHODS: The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. RESULTS: The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). CONCLUSION: Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Asthma↗
PubMed2000

Genetic structure of the five-factor model of personality in a Japanese twin population.

Dimensional approaches have been used to describe the fundamental dimensions that underlie the entire domain of normal and pathological personality. We tested the five factor model of personality structure in a sample of Japanese twins, to clarify the contributions of genetic and environment. The revised NEO personality inventory (NEO-PI-R) was administered to 251 twin pairs, ranging in age from 15 to 27 years of age. The NEO-PI-R is a 240-item questionnaire which was developed to assess the dimensions of personality. Univariate genetic analysis showed that the AE model in which phenotypic covariances are explained only by additive genetic (A) and nonshared environment (E) is still a plausible model, and that the relative proportion of genetic influence was comparable to that reported by Loehlin (1992). Multivariate genetic analysis of the Japanese data suggested/revealed that the five factors are genetically dependent on each other and one common genetic factor mediates their interdependence. Previous studies have assumed that they are phenotypically independent and robust. Although there are sampling biases in the present study, it is noteworthy that the results for all five factors depicted by the NEO-PI-R were comparable to those reported by Western researchers, and the genetic structure of the five-factor model is complex.

Adolescent↗
PubMed2000

Ganglioglioma in a patient with Turcot syndrome. Case report.

A 33-year-old woman with Turcot syndrome harbored a brain tumor and colon cancer and had a familial history of this syndrome. On histological examination, the brain tumor was found to have large and diffusely scattered ganglion cells within a diffuse background of astrocytic cells in a fibrillary matrix. The tumor was diagnosed as a ganglioglioma. No germline mutation in the adenomatous polyposis coli gene was detected using a protein truncation assay. These findings indicate that this patient had brain tumor-polyposis syndrome Type 1 of Turcot syndrome. This is the first report of a ganglioglioma related to Turcot syndrome.

Adenomatous Polyposis Coli↗
PubMed2000

Alteration of the CDKN2/p16 gene is not required for HPV-positive uterine cervical cancer cell lines.

To determine whether alterations of the CDKN2/p16 might be involved in HPV-positive cervical cancers, we examined for alterations of this gene and function of the protein p16 to interact with CDK4 in 5 cervical cancer cell lines. No alteration of this gene was detected. Proteins for p16 and CDK4 were normally expressed and function of p16 to interact with CDK4 was not abrogated in these cell lines. These cell lines were human papillomavirus (HPV)-positive and carried wild-type p53. These findings suggest that phosphorylation of pRb by CDK4 is not critical in the carcinogenesis or in the establishment of HPV-positive cervical cancer cell lines, since HPV E6 or E7 viral-transforming proteins inactivate p53 and pRb tumor suppressor protein function, resulting in deregulated progression of the cell cycle.

Cyclin-Dependent Kinase 4↗
PubMed2000

Altered expression and function of beta1 integrins in a highly metastatic human lung adenocarcinoma cell line.

In order to investigate the relationship between beta1 integrins and the metastatic ability of cancer cells, we established a novel and highly metastatic cell line designated PC9-f9 from a poorly metastatic human lung adenocarcinoma cell line (PC9) in nude mice. PC9-f9 cells showed higher invasive activity in the Matrigel invasion assay than PC9 cells. Additionally, in cell adhesion assays, PC9-f9 cells adhered to laminin more strongly than PC9 cells and, unlike PC9 cells, adhered to collagen type IV and fibronectin. FACS analysis showed expression of the integrins alpha2beta1, alpha3beta1 and alpha6beta1 on both of the cell lines but alpha4beta1 and alpha5beta1 were neo-expressed on PC9-f9 cells. In cell adhesion inhibition assays, alpha3beta1 was the major laminin receptor for PC9 cells but not for PC9-f9 cells. Alternatively, PC9-f9 cells adhered to collagen type IV via alpha2beta1 and adhered to fibronectin mainly via alpha5beta1 but also moderately via alpha4beta1. The pretreatment of PC9-f9 cells with anti-beta1 monoclonal antibodies suppressed lung metastases by more than 50%. These data suggest that the altered expression and function of beta1 integrins allow PC9-f9 cells to become more adhesive and invasive, and lead to increased metastatic potential.

Adenocarcinoma↗