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Biomedical subjects

Y Murakami

Publications and source records attributed to Y Murakami.

At least 181 records · Page 10Linked to original sources

Dilated cardiomyopathy in Noonan's syndrome: a first autopsy case.

The first autopsy case of dilated cardiomyopathy associated with Noonan's syndrome is described. A 9-month-old girl with Noonan's syndrome died from cardiac failure. Autopsy showed biatrial and biventricular enlargement of the heart. The posterior half of the ventricular septum and right ventricular wall were remarkably thin. Other parts of the wall were nearly normal in thickness, but both ventricular cavities were dilated. Microscopically, the myocardium of both ventricles consisted of mainly abnormally thinned, elongated, and loosely arranged myocardial fibers lacking immunoreactivity to anti-dystrophin antibody. Myocardial disarray was not found except for where it normally existed. The abnormal changes of the myocardial fibers were considered to be primary. Common cardiomyopathy associated with Noonan's syndrome is a hypertrophic type. Various types of cardiovascular abnormality associated with Noonan's syndrome, including dilated cardiomyopathy, might be disclosed by further investigation and precise diagnosis of Noonan's syndrome.

Cardiomyopathy, Dilated↗

Novel process for enzymatic hydrolysis of proteins in an aqueous two-phase system for the production of peptide mixture.

A novel process for the production of peptide mixtures is proposed. Biologically active peptides were synthesized using a thermolysin-catalyzed hydrolysis of a corn protein (zein) in an aqueous two-phase system. The mixture of peptides which was selectively recovered from the dextran-rich bottom phase had a higher angiotensin-converting enzyme (ACE) inhibitory activity than native zein.

Angiotensin-Converting Enzyme Inhibitors↗

Detection of epidemics in their early stage through infectious disease surveillance.

BACKGROUND: Surveillance of infectious diseases is done in many countries. The aims of such surveillance include the detection of epidemics. In the present study, the possibility of detecting an epidemic in its early stage using a simple method was evaluated for 16 infectious diseases. METHODS: We used as an index the number of cases per week per sentinel medical institution in the area covered by a health centre in infectious disease surveillance in Japan in 1993-1997. Periods of epidemics in health centre areas were determined according to the reported indices. The simple method used for detecting the early stage of an epidemic is that if the index exceeds a critical value, then an epidemic will begin in the following 4 weeks. The sensitivity, specificity and positive predictive value for this epidemic warning were evaluated for given critical values. RESULTS: When the specificity of the epidemic warning was more than 95%, the sensitivity was more than 60% in ten diseases, and more than 80% in four diseases (influenza-like illness, rubella, hand-foot-and-mouth disease, and herpangina). The positive predictive value was between 15.6% and 31.4% in these ten diseases. CONCLUSION: The early stage of epidemics of some infectious diseases might be detectable using this simple method.

Communicable Diseases↗

Molecular and biochemical characterization of a novel hydroxycinnamoyl-CoA: anthocyanin 3-O-glucoside-6"-O-acyltransferase from Perilla frutescens.

We have isolated and characterized a cDNA, PfAT208, encoding hydroxycinnamoyl-CoA: anthocyanin 3-O-glucoside-6"-O-acyltransferase (3AT) from Perilla frutescens. The identity of the cDNA was established by determination of the reaction products with recombinant enzyme overexpressed in Escherichia coli. The deduced amino acid sequence has a few regions that are conserved in a CoA-dependent acyltransferase family. The recombinant enzyme produced in yeast could utilize cyanidin 3-glucoside and cyanidin 3,5-diglucoside, putative substrates in vivo, as well as other anthocyanins. The inhibitory effects of diethyl pyrocarbonate and N-ethylmaleimide on the recombinant 3AT activities suggest that histidine and cysteine residues are important for their catalytic function. These properties are in common with anthocyanin 5-O-glucoside-6"-O-acyltransferase (5AT). In Northern analysis, a transcript of PfAT208 was detected in the young leaves of perilla red forma. The properties of other cDNAs, gentian GAT106 and petunia PhAT48, isolated during the above cloning procedure are also described.

Acyl Coenzyme A↗

Impaired vasodilatation response to amrinone in the forearm of patients with congestive heart failure: role of endothelium-derived nitric oxide.

Recent in vitro experiments have shown that amrinone enhances the release of nitric oxide (NO) from the endothelium and induces NO mediated vasodilatation. This in vivo study examined whether amrinone causes vasodilatation mediated by endothelium-derived NO, and whether this effect is attenuated in patients with endothelial dysfunction. Eight patients with congestive heart failure and 10 age- and sex-matched healthy volunteers were studied. Forearm blood flow (FBF) was measured before and during infusion of drugs of acetylcholine, amrinone, and nitroglycerin in incremental doses. After the completion of these measurements, 100 micromol of N(G)-monomethyl-L-arginine (L-NMMA) was infused intraarterially. Thereafter, FBF measurement in response to incremental doses of amrinone was repeated. Infusion of incremental doses of amrinone caused a comparable increase in amrinone plasma concentration in both groups. Baseline FBF was 3.2+/-0.79 ml/min/100 ml in controls vs. 2.91+/-0.79 ml/min/100 ml in patients (p = 0.43). In both groups, FBF increased in response to acetylcholine, amrinone, and nitroglycerin. During infusion of the highest dose of nitroglycerin, FBF was not different between the two groups (p = 0.51); however, FBF during infusion of the highest doses of acetylcholine and amrinone was significantly less in patients than in controls: 9.75+/-2.69 vs. 24.87+/-8.65 ml/min/100 ml (p < 0.001) and 3.79+/-1.21 vs. 7.15+/-2.06 ml/min/100 ml (p < 0.001), respectively. L-NMMA significantly depressed the increase in FBF in response to amrinone in controls, but not in patients. In conclusion, the selective PDE III inhibitor, amrinone, has endothelium-derived NO-mediated vasodilating effects in addition to direct effects. This property may be impaired in patients with endothelial dysfunction.

Acetylcholine↗

Localization of major, high molecular weight proteins in Bacteroides forsythus.

Bacteroides forsythus produces species-specific major proteins with high molecular weights of 270 and 230-kDa (270K and 230K). A specific antibody raised against 270K was used for Western blot analysis and immunoelectron microscopy. Western blot analysis showed that the 270K and 230K proteins were immunologically similar. Immunogold labeling of ultrathin-sectioned bacterial cells and biochemical fractionation revealed that these proteins were localized at the outermost cell surface, not in the cytoplasm. These results suggest that major proteins ubiquitous to this species may form the S-layer.

Animals↗

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome.

We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

Aged↗

An epidemiological study of supernumerary primary teeth in Japanese children: a review of racial differences in the prevalence.

OBJECTIVE: To clarify the prevalence of supernumerary primary teeth in Japanese children, we evaluated this prevalence in a sample of 8122 children aged 3-6 years. Furthermore, we undertook a statistical comparison of the findings of the present study with those of previous investigations on the prevalence of supernumerary primary teeth in Japanese, Chinese and Caucasian children. SUBJECTS: The subjects used in the study consisted of 8122 children aged 3-6 years (4102 boys and 4020 girls). The children were examined in kindergartens. METHODS: The prevalence of supernumerary primary teeth was recorded by visual inspection. Statistical analysis was carried out using the chi 2 test. RESULTS: Four cases of supernumerary primary teeth were found among the children examined, and thus the prevalence was 0.05%. All of the supernumerary primary teeth were located in the maxillary lateral incisor area. CONCLUSIONS: The prevalence in a sample of 8122 Japanese children was 0.05% and that in a combined sample of 65,068 Japanese children was 0.06%.

Anodontia↗

Pharmacokinetics and safety of ascending single doses of DZ-2640, a new oral carbapenem antibiotic, administered to healthy Japanese subjects.

DZ-2640 is the ester-type oral carbapenem prodrug of an active parent compound, DU-6681. The pharmacokinetics and safety of DU-6681 were investigated in six studies after oral administration of a single dose of DZ-2640 to healthy male Japanese volunteers at doses of 25, 50, 100, 200, and 400 mg (as the equivalents of DU-6681) in the fasted state. The same volunteers received the drug at a dose of 100 mg in the fasted and fed states to examine the effect of food intake on the bioavailability of DZ-2640. The concentrations of DU-6681 in plasma and urine were determined by a validated high-performance liquid chromatography method and a bioassay. A good correlation between both methods was seen, indicating an absence of major active metabolites. The mean maximum concentrations of DU-6681 in plasma (C(max)) ranged from 0.263 microgram/ml (25-mg dose) to 2.489 microgram/ml (400-mg dose) and were reached within 1.5 h following drug administration. After reaching the C(max), plasma DU-6681 concentrations declined in a monophasic manner, with a half-life of 0.47 to 0.89 h. The area under the concentration-time curve (AUC) and C(max) increased almost linearly with the dose up to the 200-mg dose. The AUC and C(max) increased less than proportionally after administration of the 400-mg dose, suggesting a reduction in drug absorption. The plasma protein binding of DU-6681 was in the range of 23.3 to 25.6%. The cumulative urinary recoveries (0 to 24 h) were in the range of 31.9 to 44.9%. The AUC was slightly but statistically significantly reduced by food intake. However, the C(max), half-life, and recovery in urine were not affected by food intake. The renal clearance (402 to 510 ml/min) was much greater than the mean glomerular filtration rate (ca. 120 ml/min), which indicated active tubular secretion of the drug. A mild transient and moderate diarrhea was observed in two of six volunteers in the study with a single dose of 25 mg. Mild soft stools were observed in two of six volunteers who received a 400-mg dose of the drug.

Biological Assay↗

A novel TATA-binding protein-binding protein, ABT1, activates basal transcription and has a yeast homolog that is essential for growth.

Identification of a novel mouse nuclear protein termed activator of basal transcription 1 (mABT1) that associates with the TATA-binding protein (TBP) and enhances basal transcription activity of class II promoters is described. We also identify mABT1 homologous counterparts in Caenorhabditis elegans and Saccharomyces cerevisiae and show the homologous yeast gene to be essential for growth. The mABT1 associated with TBP in HeLa nuclear extracts and with purified mouse TBP in vitro. In addition, ectopically expressed mABT1 was coimmunoprecipitated with endogenous TBP in transfected cells. More importantly, mABT1 significantly enhanced transcription from an adenovirus major late promoter in a reconstituted cell-free system. We furthermore demonstrate that mABT1 consistently enhanced transcription from a reporter gene with a minimal core promoter as well as from reporter genes with various enhancer elements in a cotransfection assay. Taken together, these results suggest that mABT1 is a novel TBP-binding protein which can function as a basal transcription activator.

Amino Acid Sequence↗

Effects of aspirin-like drugs on nitric oxide synthesis in rat vascular smooth muscle cells.

The purpose of this study was to investigate the effects of aspirin-like drugs on nitric oxide (NO) synthesis in rat vascular smooth muscle cells (VSMCs). We measured the accumulation of nitrite, a stable oxidation product of NO, and the expression of inducible NO synthase (iNOS) mRNA and protein in rat cultured VSMCs. Sodium salicylate, aspirin, and indomethacin dose-dependently enhanced nitrite production by interleukin (IL)-1beta-stimulated VSMCs at therapeutic plasma concentration ranges. Increased nitrite production by aspirin-like drugs was accompanied by increased iNOS mRNA and protein accumulation in VSMCs. Addition of IL-1beta activated nuclear factor kappaB (NF-kappaB) in VSMCs, but sodium salicylate did not affect IL-1beta-induced NF-kappaB activation. The nonselective lipoxygenase (LO) inhibitor nordihydroguaiaretic acid inhibited sodium salicylate-induced nitrite production, whereas the selective 5-LO inhibitor caffeic acid did not influence production of nitrite. The 12-LO product 12-HETE dose-dependently enhanced nitrite production by IL-1beta-stimulated VSMCs, whereas the 15-LO product 15-HETE did not. Our study demonstrates that aspirin and the aspirin-like drugs, sodium salicylate and indomethacin, increase NO synthesis in IL-1beta-stimulated VSMCs by upregulation of iNOS transcription via a 12-LO pathway. These effects were independent of NF-kappaB activation. In addition to the direct inhibition of platelet function, aspirin-like drugs may contribute to the reduction of atherothrombotic risk in myocardial ischemia via enhancing NO production by VSMCs.

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

Peroxisome proliferator-activated receptor-gamma ligands inhibit nitric oxide synthesis in vascular smooth muscle cells.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a key player in glucose metabolism. If PPARgamma ligands modulate nitric oxide (NO) synthesis in the vascular tissue, they may affect the process of plaque formation and postangioplasty restenosis. We investigated the effects of PPARgamma ligands on NO synthesis in vascular smooth muscle cells. Incubation of cultures with interleukin-1beta (10 ng/mL) for 24 hours caused a significant increase in the production of nitrite, a stable metabolite of NO, in cultured rat vascular smooth muscle cells. The PPARgamma agonists troglitazone and 15-deoxy-triangle up(12,14)-prostaglandin J(2) (15d-PG J(2)) dose-dependently inhibited nitrite production by interleukin-1beta-stimulated vascular smooth muscle cells. Decreased interleukin-1beta-induced nitrite production by the PPARgamma agonists was accompanied by decreased inducible NO synthase mRNA and protein accumulation. Interleukin-1beta induced nuclear factor-kappaB activation in vascular smooth muscle cells, and both troglitazone and 15d-PG J(2) markedly suppressed this nuclear factor-kappaB activation. PPARgamma ligands inhibit NO synthesis in cytokine-stimulated vascular smooth muscle cells, suggesting that these agonists may act directly on the vascular smooth muscle and influence the process of atherosclerosis and restenosis.

Animals↗

Synthesis of decalin type chiral synthons based on enzymatic function.

Enzymatic monobenzoylation of (+/-)-2-hydroxy-decahydro-5,5,8a-trimethyl-1-naphthalenemethano l derivatives (1-4) using vinyl benzoate in organic solvent gave the optically active diols (1-4) and monobenzoates (16-19). The enantiomeric excess (ee) of the enzymatic reaction products were found to be in the range of 11% to 49%. On the other hand, enzymatic hydrolysis of the acetoxybenzylidene acetal (+/-)-25d, e was found to give more than 90% ee of (10aS)-25d, e in moderate yield. Finally, the 90% ee of (10aS)-25e was converted to the 90% ee of the desired (8aS)-1.

Enzymes↗

Nicotine-induced noradrenaline release from the isolated rat stomach by activation of L- and N-type calcium channels.

We examined the effect of nicotine on the release of endogenous noradrenaline (NA) from the isolated, vascularly perfused rat stomach. The stomach was perfused via the coeliac artery with Krebs-Ringer solution containing 10 microM pargyline at a constant flow rate of 4 ml per minute. Nicotine was once applied in the perfusion medium for 2 min. Nicotine (10(-6) - 10(-4) M) evoked NA release in a concentration-dependent manner. The nicotine (3 x 10(-5) M)-evoked NA release was abolished by hexamethonium and tetrodotoxin. Diltiazem and isradipine [blockers of L-type voltage-activated calcium channel (VACC)] and omega-conotoxin GVIA (a blocker of N-type VACC) also abolished this nicotine-evoked NA release. Previously we reported that N-type, but not L-type, VACCs are located on the gastric postganglionic sympathetic nerve terminals, since the NA release evoked by electrical stimulation of periarterial nerves around the left gastric artery (postganglionic sympathetic nerves) was abolished by omega-conotoxin GVIA, but not by diltiazem (Yokotani et al., Jpn. J. Pharmacol. 78, 75- 77, 1998). From these results, it was suggested that nicotine activates nicotinic acetylcholine receptors located on the sympathetic ganglia, thereby evoking NA release by activation of L-type VACC located on the gastric sympathetic ganglia and N-type VACC probably located on the sympathetic nerve terminals in the rat stomach.

Animals↗

Carotenoids in human blood plasma after ingesting paprika juice.

We investigated the presence of different carotenoids in male human subject after the ingestion of paprika juice, and identified capsanthin, capsanthone, cucurbitaxanthin A, 11-cis-capsanthin, lutein and zeaxanthin in the human plasma. These results suggest that capsanthone and 11-cis-capsanthin might be as important as capsanthin for human health.

Capsicum↗