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Biomedical subjects

H Ogata

Publications and source records attributed to H Ogata.

At least 91 records · Page 5Linked to original sources

A female carrier of Duchenne muscular dystrophy complicated with cardiomyopathy.

A 45-year-old female carrier of Duchenne muscular dystrophy (DMD) complicated with cardiomyopathy is described. She had no symptoms of muscle weakness or heart failure. Her chest X-ray film revealed marked cardiomegaly. Echocardiogram showed marked enlargement and severe hypokinesis of the left ventricle. In myocardial scintigraphic images, perfusion defects of the myocardium were revealed. Dystrophin immunostaining of myocardial biopsy specimens showed a mosaic pattern of dystrophin-negative and -positive fibers. Cardiomyopathy is sometimes the only clinical symptom in female carriers of DMD. They are thought to be in a high risk group for developing heart failure.

Cardiomyopathy, Dilated↗

[Effect of epilepsy surgery based on magnetic resonance imaging (MRI) classification].

We prospectively analyzed the effect of surgical procedures in epilepsy patients, except for those with mesial temporal lobe epilepsy. Twenty patients with a mean age of 26 years (range 3 to 58 years, 10 male and 10 female) underwent the surgical procedures. These patients were divided into 3 groups according to MRI findings, as follows; group A (localized type): localized lesions such as angiomas or benign tumors, group B (widespread type): widespread lesions such as regional encephalitis or stroke, visible on anatomical neuroimaging, and group C (cryptic type): no lesion visible on anatomical neuroimaging. Following surgery, 11 (85%) of the 13 patients in group A were seizure-free, one showed worthwhile improvement, and one, whose lesion was not removed totally, was unchanged. In group B, two patients (50%) were seizure-free and 2 (50%) showed worthwhile improvement. All the patients in group C showed worthwhile improvement. Lesionectomy, cortical excision, multiple subpial transection (MST) or a combination of these procedures were effective in groups A and B. Patients in group C had a chance to obtain worthwhile improvement by corpus callosotomy or cortical excision. Intracranial EEG recording provides useful information for epilepsy surgery in intractable cases.

Adolescent↗

Population pharmacokinetics and pharmacodynamics of TS-943 for selective nonpeptide platelet glycoprotein IIb/IIIa receptor antagonist in normal healthy subjects.

The pharmacokinetics and pharmacodynamics of TS-943 were evaluated with use of NONMEM in 36 healthy male subjects after constant infusion of five different single-dose regimens. Population analysis showed the plasma concentration-time profiles of TS-943 to be best-fit characterized by a two-compartment open model with constant infusion and first-order elimination. The pharmacodynamic model that best fitted the platelet aggregation was a sigmoid Emax model. The final estimates for baseline effect, 50% inhibitory concentration (IC50), and the Hill coefficient were 79.4%, 23.4 ng/mL and 1.63, respectively. The maximum effect (Emax) was fixed at 80% (submaximal aggregation response). In addition, correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The model estimates that the TS-943 plasma concentration necessary to double template bleeding time is approximately 63 ng/mL (ie, 2.7-fold greater than the IC50). The population approaches for pharmacokinetic-pharmacodynamic investigation can be useful for the analysis of concentration-effect relationships and concentration-adverse event relationships for a platelet glycoprotein IIb/IIIa receptor antagonist.

Adult↗

Smoking: a factor promoting onset and progression of diabetic nephropathy.

Although smoking was identified two decades ago as a factor promoting the onset and progression of nephropathy in Type 1 and then in Type 2 diabetes, its role has been largely neglected. More recently, it has been shown that smoking adversely affects renal haemodynamics and protein excretion even in subjects without renal disease. In addition, it impairs the prognosis for renal function in patients with non-diabetic renal disease. Recent studies have suggested the involvement of sympathetic activation, increased endothelin production, and impaired endothelial cell-dependent vasodilatation in the genesis of smoking-induced renal function impairement. Cessation of smoking apparently slows progression to renal failure, but the decision to stop smoking is difficult because of the high addictive potential of the habit. The challenge remains for diabetologists and nephrologists to motivate patients to stop smoking.

Diabetic Nephropathies↗

[Detection of rifampin-resistant Mycobacterium tuberculosis by line probe assay (LiPA)].

A recently described reverse hybridization-based line probe assay is used for the rapid detection of the mutations in the rpoB genes of rifampin-resistant Mycobacterium tuberculosis and for the identification of the M. tuberculosis complex. A multicenter study that included 5 laboratories was performed to evaluate the line probe assay in comparison with the in vitro susceptibility test. A total of 406 mycobacteria isolates which were composed of 103 rifampin-resistant and 230 rifampin-susceptible M. tuberculosis isolates, and 73 mycobacteria other than tubercle bacilli (MOTT), were subjected to this study. All 333 M. tuberculosis isolates were discriminated correctly from MOTT bacilli by a line probe assay. Concordance rates with sequencing results for five wild-type probes (S probes) and four specific mutations (R probes) for detecting the mutations in the rpoB genes were both 100%. The overall concordance rate with the in vitro susceptibility testing results was 98.5% (328 of 333 isolates). These results indicate that a line probe assay kit may be useful for the rapid diagnosis of rifampin-resistant tuberculosis.

Antibiotics, Antitubercular↗

[Limits of nucleic acid amplification tests for diagnosis of smear negative pulmonary tuberculosis].

STUDY OBJECTIVES: To assess the usefulness of commercial kits of nucleic acid amplification test (NAAT) for diagnosis of smear negative (SN) pulmonary tuberculosis. DESIGN AND PATIENTS: Retrospective study of patients who were diagnosed as, or suspected of pulmonary tuberculosis during 3 years from January 1996 to December 1998 in Fukujuji Hospital which has 100 beds for tuberculosis patients. MEASUREMENTS AND RESULTS: 145 smear-negative culture-positive pulmonary tuberculosis patients are entered to our analysis. The DNA-based amplification test kit (Amplicor Mycobacterium Tuberculosis Test (AMPL), Roche Diagnostic Systems, Basel, Switzerland) detected 39.2% (20/51, 95% confidence interval (CI): 25.8-52.6%) of smear-negative culture-positive (SNCP) pulmonary tuberculosis cases. The RNA-based amplification test kit (Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (AMTDT), Gen-Probe Inc., San Diego, Calif., USA) detected 40.5% (15/37, 95% CI: 24.7-56.3%) of SNCP pulmonary tuberculosis cases. For both NAATs (AMPL and AMTDT), between two groups with and without the NAAT at diagnosis of SNCP pulmonary tuberculosis, there was statistical difference in culture-positive rate (proportion of positivity in sputum culture tests at diagnosis), but no statistical difference in maximum number of colony of Mycobacterium tuberculosis (MTB). When stratified for the culture-positive rate, adjusted sensitivity for SNCP patients was 44.2% (AMPL) and 40.4% (AMTDT) respectively. On the other hand, among 245 patients with sputum AMPL positive results during the 3 years, 8 were smear-negative culture-negative (SNCN), only one out of these 8 cases was judged as true active tuberculosis without treatment. Among 89 patients with sputum AMTDT positive results, 7 were SNCN, and 3 out of them were judged as true active tuberculosis without treatment. CONCLUSION: Usefulness of commercial NAAT kits (AMPL and AMTDT) to diagnosis SN pulmonary tuberculosis is limited in the point of sensitivity.

DNA, Bacterial↗

Innate recognition of lipopolysaccharide by Toll-like receptor 4/MD-2 and RP105/MD-1.

The Toll family of receptors has been implicated in innate recognition and subsequent activation of defense programs against pathogens such as bacteria and fungi. TLR4, for example, signals the presence of lipopolysaccharide (LPS), a membrane constituent of Gram-negative bacteria. LPS signaling via TLR4 is greatly enhanced by a molecule referred to as MD-2, which is associated with the extracellular domain of TLR4. The TLR4/MD-2 complex, therefore, recognizes LPS. RP105, another member of the Toll family, has a striking similarity to TLR4 in that it is associated with an MD-2-like molecule MD-1. B-cells lacking RP105 are severely impaired in LPS-induced proliferation and antibody production. Studies employing transfectants showed that RP105/MD-1, like MD-2, enhances the LPS signaling via TLR4. RP105/MD-1 thus constitutes an LPS-signaling complex on B-cells. These results suggest that a variety of cell surface molecules regulate LPS recognition/signaling by TLR4.

Animals↗

Interferon-inducible gene family 1-8U expression in colitis-associated colon cancer and severely inflamed mucosa in ulcerative colitis.

Persistent severe inflammation in colonic mucosa is thought to cause the development of colon cancer in patients with ulcerative colitis (UC). However, predisposing genetic abnormalities have not been identified in this sequence. Using differential display PCR, we isolated cDNA fragments corresponding to mRNAs that were differentially expressed in colitis-associated cancer tissues and mucosa with mild inflammation in the colon of five UC patients. This molecular screening approach identified 60 cDNA fragments, and we sequenced 34 fragments. One cDNA fragment, which is identical to IFN-inducible gene family 1-8U, was strongly expressed in all five UC-associated cancers. 1-8U was also expressed in sporadic colon cancer tissues and colon cancer cell lines, but not in normal mucosa. This gene was strongly expressed in severely inflamed colonic mucosa of UC without colitis-associated colon cancer, although 1-8U expression was not related to the extent and duration of the disease. However, 1-8U was expressed in the colonic mucosa of all patients with chronic, continuously severe inflammation. These results indicated that IFN-inducible gene family 1-8U expression in inflamed colonic mucosa might be used as a preferential marker of colitis-associated colon cancer in UC.

Adenocarcinoma↗

MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4.

Toll-like receptor 4 (TLR4) is a mammalian homologue of Drosophila Toll, a leucine-rich repeat molecule that can trigger innate responses against pathogens. The TLR4 gene has recently been shown to be mutated in C3H/HeJ and C57BL/10ScCr mice, both of which are low responders to lipopolysaccharide (LPS). TLR4 may be a long-sought receptor for LPS. However, transfection of TLR4 does not confer LPS responsiveness on a recipient cell line, suggesting a requirement for an additional molecule. Here, we report that a novel molecule, MD-2, is requisite for LPS signaling of TLR4. MD-2 is physically associated with TLR4 on the cell surface and confers responsiveness to LPS. MD-2 is thus a link between TLR4 and LPS signaling. Identification of this new receptor complex has potential implications for understanding host defense, as well as pathophysiologic, mechanisms.

Animals↗

Subjective evaluations and objective measurements of the ischial-ramal containment prosthesis.

We examined 12 transfemoral amputees, 6 using the IRC socket and 6 the QL socket, to confirm whether the ischial-ramal containment (IRC) socket is truly superior to the quadrilateral (QL) socket. In subjective evaluation, the IRC group was significantly better in the total score and in items of comfort, that is, to sit on a chair and lumbar lordosis at heel off (Mann-Whitney test, P < 0.05), better but not significant in the items of comfortable to wear, comfortable to go up and down stairs, and truncal sway during stance phase. By computed tomography, the femur of the IRC group was kept in a position significantly more medial than that of the QL group (Mann-Whitney test, P < 0.05); but no significant difference in gluteal medial muscle atrophy ratios between the two groups was found (Mann-Whitney test, P > 0.05). By X-ray, the stump of the IRC group was maintained significantly more adducted during one foot standing on the prosthesis (Mann-Whitney test, P < 0.05), but the lateral force ratio during mid-stance of the IRC group was smaller, but not significantly, than that of the QL group. Physiological cost index (PCI), an indirect simple method for evaluating oxygen consumption of gait, had no significant difference between the two groups (Mann-Whitney test, P > 0.05), and a multiple regression analysis revealed that the stump length ratio and lateral force ratio during mid-stance were significant explanatory variables for predicting PCI (adjusted R square: 0.87, F-value: 11.85, P < 0.05). The results of this study have revealed that the advantage of the IRC socket is a tender feeling of the stump, but that the metabolic efficiency is not superior to the QL socket at the most comfortable speed.

Adult↗

Isokinetic strength of elbow extensor muscles correlates with race time in wheelchair half marathon racers.

It has been reported that grasping power and isometric muscle strength of elbow extensors in fine wheelchair racers were greater than the poor racers in the wheelchair full marathon. The purpose of the present study was to investigate the relationship between muscle strength of elbow extensors and flexors and the race time in wheelchair half marathon race. Four wheelchair half marathon racers who completed the half marathon division of the 16th Oita International Wheelchair Marathon (OIWM) in 1996 participated in the present study. The day before the race, all subjects reported to the training room and the isokinetic muscle strength of elbow extensor and flexor muscle groups was measured at angular speeds of 60 degrees, 120 degrees and 240 degrees/sec using the isokinetic dynamometer. There was a significant correlation between race time and isokinetic muscle strength of the elbow extensors at 60 degrees, 120 degrees and 240 degrees/sec, but not flexor muscles. Our findings suggest that increased muscle strength of elbow extensors may improve the race time in wheelchair half marathon race.

Adult↗

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical diagrams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway information is also represented by the ortholog group tables summarizing orthologous and paralogous gene groups among different organisms. KEGG maintains the GENES database for the gene catalogs of all organisms with complete genomes and selected organisms with partial genomes, which are continuously re-annotated, as well as the LIGAND database for chemical compounds and enzymes. Each gene catalog is associated with the graphical genome map for chromosomal locations that is represented by Java applet. In addition to the data collection efforts, KEGG develops and provides various computational tools, such as for reconstructing biochemical pathways from the complete genome sequence and for predicting gene regulatory networks from the gene expression profiles. The KEGG databases are daily updated and made freely available (http://www.genome.ad.jp/kegg/).

Animals↗

AAindex: Amino Acid Index Database.

AAindex is a database of numerical indices representing various physicochemical and biochemical properties of amino acids and pairs of amino acids. It consists of two sections: AAindex1 for the amino acid index of 20 numerical values and AAindex2 for the amino acid mutation matrix of 210 numerical values. Each entry of either AAindex1 or AAindex2 consists of the definition, the reference information, a list of related entries in terms of the correlation coefficient, and the actual data. The database may be accessed through the DBGET/LinkDB system at GenomeNet (http://www.genome.ad. jp/dbget/) or may be downloaded by anonymous FTP (ftp://ftp.genome. ad.jp/db/genomenet/aaindex/).

Amino Acids↗

Identification of squamous cell carcinoma antigen-2 in tumor tissue by two-dimensional electrophoresis.

The aim of this study was to identify two homologous serine proteinase inhibitor (serpin) molecules, squamous cell carcinoma (SCC) antigen-1 and -2, by two-dimensional electrophoresis (2-DE), combined with immunoblotting, and examine their expression in tumor tissue. The recombinant SCC (rSCC) antigen-1 showed four spots with p/ 6.5, 6.4, 6.3 and 6.0, whereas rSCC antigen-2 showed a more acidic spot with p/5.95. SCC antigen in tumor tissue appeared in three new acidic spots (p/5.7-5.5, M(r) 44 500), numbered 5, 6 and 7, besides the previously reported four spots numbered 1 to 4. These new acidic spots of SCC antigen apparently increased in SCC tissue. Treatment of tissue extract by carboxymethyl (CM)-papain agarose matrix extinguished spots 1 to 4 encoded on the SCCA1 gene, but not 5 to 7 on the SCCA2 gene. Overexpression of the SCCA2 gene may play an important role in the malignant behavior of tumor cells.

Antigens, Neoplasm↗

HGF activates signal transduction from EPO receptor on human cord blood CD34+/CD45+ cells.

Hepatocyte growth factor (HGF) is a multifunctional cytokine with early hematopoiesis-stimulatory activity. Here, we focus on its erythropoiesis-stimulatory effect on highly purified human hematopoietic progenitor cells (CD34+/CD45+ cells) derived from the cord blood. In immunoblot analyses, c-met protein (a receptor of HGF) was detected in the CD34+/CD45+ cells, although the expression levels were different among samples. The c-met expression was facilitated by incubation of the cells with stem cell factor (SCF) or interleukin 3 (IL-3), even if the expression level had been low. IL-6, G-CSF, or erythropoietin (EPO) did not show such a stimulatory effect on the c-met expression of the cells. When HGF was added to the CD34+/CD45+ cells in the presence of SCF, the numbers of CD36+/CD11b- cells (very early erythroid lineage cells) and BFU-E increased. EPO-dependent tyrosine phosphorylation of Stat 5 also increased, but the EPO receptor (EPO-R) expression remained unchanged in the CD34+/CD45+ cells treated with SCF + HGF. Our present study suggests that stimulation of the HGF/c-met signal is concomitant with induction of c-met protein by SCF. The subsequent enhancement of signal transduction via the activation of Stat 5 from the EPO-R plays a crucial role in the commitment of hematopoietic stem cells into erythroid lineage cells.

Antigens, CD34↗

Correlations between in vitro affinity of antipsychotics to various central neurotransmitter receptors and clinical incidence of their adverse drug reactions.

OBJECTIVE: This study was performed to determine whether in vitro affinities of currently available antipsychotics toward dopamine or other neuronal receptor systems are associated with their in vivo incidence of central and peripheral adverse drug reactions (ADRs). METHODS: For 17 antipsychotic drugs available in Japan, the clinical incidences of 7 different types of drug-induced ADRs (i.e., akathisia, dyskinesia, tremor, rigidity, drowsiness, hypotension and dry mouth) were obtained from both post-marketing ADR databases and the investigational clinical trials of eight pharmaceutical companies. Affinity constants (K(i)) of the respective drugs toward dopamine D(1) and D(2) receptors, alpha(1)-adrenoceptors, histamine H(1) receptors, serotonin 5-HT(2) receptors and muscarinic cholinoceptors, determined using rat brain synaptosomes, were obtained from the literature. Relationships between in vitro receptor-binding properties and in vivo incidences of the respective types of antipsychotic-related ADRs were analyzed using Spearman's rank correlation. RESULTS: Significant (P < 0.05) correlations were observed between the K(i) values for dopamine D(2) receptor and the clinical incidences of akathisia and dyskinesia (r(s) = -0.68 and -0. 66, respectively). Significant (P < 0.05) correlations were also observed between the K(i) values for alpha(1)-adrenoceptor and histamine H(1) receptor and the incidence of drowsiness (r(s)=-0.65 and -0.55, respectively), and between the K(i) values for three receptor systems (i.e., dopamine D(1) receptor, alpha(1)-adrenoceptor and histamine H(1) receptor) and the incidence of dry mouth (r(s) = -0.50, -0.81 and -0.62, respectively). CONCLUSION: Preclinical receptor-binding data of antipsychotic drugs toward central dopamine and other ancillary neurotransmitter systems may be useful for predicting not only in vivo antipsychotic potency but also clinical incidence of akathisia and dyskinesia for this class of agents. Newly developed antipsychotic drugs with more potent and selective antagonistic activity against the dopamine D(2) receptor may not necessarily be associated with a lower incidence of extrapyramidal ADRs.

Adverse Drug Reaction Reporting Systems↗

Static exercise-induced increase in blood pressure in individuals with cervical spinal cord injury.

OBJECTIVE: To compare the pressor response to static exercise in subjects with cervical spinal cord injury (SCI) at the C6 to C8 level with that in able-bodied control subjects. In these SCI subjects, the descending supraspinal sympathetic neurons and afferent pathways from the contracting muscles to peripheral vessels via the medullary cardiovascular center are damaged. DESIGN: Mean arterial blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, renin activity, vasopressin, aldosterone, and human atrial natriuretic peptide were measured during a 2-minute period of sustained contraction of elbow flexor group muscle in 7 SCI subjects and 7 age-matched able-bodied control subjects. RESULTS: Static exercise resulted in a significant increase in mean blood pressure (p<.05) in both SCI subjects (pre-exercise. 74.7+/-2.2 mm Hg; static exercise, 81.9+/-4.1 mm Hg) and control subjects (pre-exercise, 101.0+/-4.2 mm Hg; static exercise, 117.0+/-4.9 mm Hg). In SCI subjects, there was no change in heart rate during exercise, whereas in control subjects heart rate increased during exercise (p<.05) (pre-exercise, 8.7+/-3.8 beats/min: static exercise, 76.0+/-3.1 beats/min). There were no significant changes in the hormone levels in the SCI subjects throughout the experiment. CONCLUSION: The significant increase in mean blood pressure observed in the present study indicates the presence of peripheral control from muscle receptors and evoked pressor response during static exercise in SCI subjects.

Adult↗

Wheelchair marathon racing causes striated muscle distress in individuals with spinal cord injury.

OBJECTIVE: To assess the effects of wheelchair marathon racing in individuals with spinal cord injury (SCI) on circulating muscle enzymes and myoglobin. SUBJECTS: Thirty-one men with SCI, including 25 wheelchair marathon athletes and 6 sedentary men. DESIGN: Serum myoglobin (Mb), creatine kinase (CK) activity, and lactate dehydrogenase (LDH) were measured in participants of the 1995 Oita International Wheelchair Marathon Race (42.195 km). Blood samples were obtained 24 hours before, immediately after, 24 hours after, and 7 days after the race. RESULTS: Marathon racing resulted in significant increases in serum Mb, total CK activity, and LDH (p<.01) after the race. The peak Mb and LDH levels occurred immediately after the race; total CK activity peaked 24 hours after the race. Evaluation of cardiac muscle enzymes showed no significant changes in two CK isoenzymes (CK-MM and CK-MB). CONCLUSIONS: Propulsion of the wheelchair in a marathon race induced muscle stress in athletes with SCI. Completion of the marathon race did not cause cardiac muscle damage, however. Elevated muscle enzyme levels likely resulted from muscle distress rather than from dehydration.

Adult↗