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Biomedical subjects

H Kishida

Publications and source records attributed to H Kishida.

At least 73 records · Page 4Linked to original sources

Effect of Apafant on bronchial hyperresponsiveness and down-regulation of beta-adrenoceptors induced by endotoxin in guinea pigs.

Intraperitoneal injection of endotoxin resulted in bronchial hyperreactivity to histamine in guinea pigs. In addition, endotoxin (lipopolysaccharide, LPS) caused a decrease in the relaxation of the lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol (isoprenaline), and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Apafant (CAS 105219-56-5, WEB 2086) was effective in the prevention of endotoxin-induced changes, i.e., bronchial hyperreactivity to histamine, a decrease in the relaxation of lung parenchymal strips induced by isoproterenol and a reduction in the number of beta-adrenergic binding sites in the lung membrane preparation in guinea pigs. Ketotifen and ozagrel also prevented the bronchial hyperresponsiveness and endotoxin-induced deterioration of the beta-adrenergic system. No remarkable effect was observed with cromolyn sodium and salbutamol in the bronchial hyperreactivity to histamine induced by endotoxin in guinea pigs. Cromolyn sodium also caused no influence on the down-regulation of beta-adrenoceptors.

Adrenergic beta-Agonists↗

Effects of apafant on PAF-induced downregulation of beta-adrenoceptors in guinea pigs.

We examined the effects of platelet-activating factor (PAF) on beta-adrenoceptors and the functional response to isoproterenol in guinea pig parenchymal strips. PAF caused a reduction in the relaxation of guinea pig lung parenchymal strips induced by the beta-adrenoceptor agonist, isoproterenol. In addition, PAF decreased the density of beta-adrenoceptors in guinea pig lung without any change in the affinity. Apafant, a potent PAF antagonist, inhibited the above changes, indicating that it inhibited the downregulation of beta-adrenoceptors. These findings suggest that apafant may be effective in nonspecific airway hyperreactivity in asthma.

Adrenergic beta-Agonists↗

Nonlinear pattern analysis of ventricular premature beats by mutual information.

The frequency of ventricular premature beats (VPBs) has been related to the risk of mortality. However, little is known about the temporal pattern of occurrence of VPBs and its relationship to autonomic activity. Hence, we applied a general correlation measure, mutual information, to quantify how VPBs are generated over time. We also used mutual information to determine the correlation between VPB production and heart rate in order to evaluate effects of autonomic activity on VPB production. We examined twenty subjects with more than 3000 VPBs/day and simulated random time series of VPB occurrence. We found that mutual information values could be used to characterize quantitatively the temporal patterns of VPB generation. Our data suggest that VPB production is not random and VPBs generated with a higher value of mutual information may be more greatly affected by autonomic activity.

Adult↗

A long-range physical map of human chromosome 21q22.1 band from the YAC continuum.

The human Chromosome (Chr) 21q22.1 region contains several genes for cytokines and neurotransmitters and the gene for superoxide dismutase (mutant forms of which can cause familial amyotrophic lateral sclerosis). A region of approximately 5.8 Mb encompassing D21S82 and the glycinamide ribonucleotide transformylase (GART) loci was covered by overlapping YAC clones, which were contiguously ordered by clone walking with sequence-tagged site (STSs). A total of 76 markers, including 29 YAC end-specific STSs, were unambiguously ordered in this 5.8-Mb region, and the average interval between markers was 76 kb. Restriction maps of the YAC clones with rare-cutting enzymes were simultaneously prepared, and the restriction sites were aligned to obtain a consensus restriction map of the proximal region of the 21q22.1 band. The restriction map made from 44 overlapping YACs contains 54 physically assigned STSs. By integrating the consensus map of the adjacent 1.8-Mb region, we obtained a fine physical map spanning 6.5 Mb of human Chr 21q22.1. This map contains 24 precisely positioned end-specific STSs and 12 NotI-linking markers. More than 39 potential CpG islands were identified in this region and were found to be unevenly distributed. This physical map and the YACs should be useful as a reference map and as a resource for further structural analysis of the Giemsa-negative band (R-band) of Chr 21q22.1.

Base Sequence↗

Adenosine mediates the antiarrhythmic effect of ischemic preconditioning in isolated rat hearts.

Adenosine appears to mediate the preconditioning-induced reduction in infarct size in rabbits and dogs, but little is known about the role of adenosine in preconditioning-induced protection against ischemia-induced arrhythmias. We compared the effects of preconditioning induced by 2 cycles of 5 min of global ischemia and 2 cycles of 5 min of perfusion with either adenosine (100 mumol/L) or the adenosine A1-selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 100 nmol/L) in protecting against ischemia-induced arrhythmias in Langendorff-perfused rat hearts. Preconditioning reduced the incidence of ventricular tachycardia (VT) from 100 to 58% and the incidence of sustained VT or ventricular fibrillation (VF) from 92 to 33%. Perfusion with adenosine reduced the incidence of VT from 100 to 55%, the incidence of VF from 67 to 9% and the incidence of sustained VT or VF from 92 to 9%. CCPA reduced the incidence of sustained VT or VF from 92 to 25%. These interventions provided a true reduction in the severity of arrhythmias, rather than merely a delay in the onset. Our results suggest that the stimulation of A1 receptor by adenosine is involved in triggering ischemic preconditioning-induced protection against ischemia-induced arrhythmias in rats.

Adenosine↗

Significant characteristics of variant angina patients with associated syncope.

To determine whether syncope predisposes to sudden cardiac death, variant angina patients with syncope during cardiac attacks were compared with those without syncope. There were 240 consecutive patients (193 males and 47 females) diagnosed with variant angina pectoris. Thirty patients had a history of syncope during cardiac attacks while the remaining 210 had none. The incidence of cardiac events in the former group was 10.0% (3 of 30) and 10.5% in the latter. There were 3 cases of sudden cardiac death, all in the latter group. Significant clinical variables in the syncope patients included inferior ST-segment elevation and serious arrhythmias. We conclude that there is no relationship between syncope during variant angina and sudden cardiac death.

Adult↗

Prognostic indicators of major cardiac events in patients with asymptomatic coronary artery disease.

We investigated the role of myocardial ischemia in acute myocardial infarction and cardiac death in 253 patients with asymptomatic coronary disease (206 men, 47 women, mean age: 55 +/- 8 years). Patients were divided into two groups: those with angina pectoris with no history of myocardial infarction (AP group, 93 patients) and those with a history of myocardial infarction (MI group, 160 patients). We also examined the usefulness of exercise electrocardiographic and Holter electrocardiographic findings as prognostic indicators of cardiac events. After 24-hour Holter electrocardiograms were obtained in both groups, patients were assigned to subgroups with or without silent myocardial ischemia (SMI) based on the presence or absence of transient ST-segment depression. Prognostic indicators were evaluated by multiple regression analysis. Cardiac events occurred in 26 (10.3%) of 253 patients; in 6 patients these events were fatal. The incidence of cardiac events was significantly higher in the SMI group than in the non-SMI group (16.4% versus 5.6%, p < 0.05). SMI was identified as a significant prognostic indicator in the overall population (p = 0.0088), as were the number of diseased coronary arteries in the AP group (p = 0.0152), and SMI (p = 0.0022) in the MI group. There were 3 deaths related to cardiac events in each group. The mean time from onset of angina pectoris to death was 73 +/- 41 months compared with 33 +/- 43 months in the MI group. Our findings suggest that the severity of the coronary lesion and SMI were important predictors of major cardiac events, and that the mechanism of the onset of cardiac events was different in the AP and MI groups.

Adult↗

1.8-megabases fine physical map encompassing IFNAR and AML1 loci on human chromosome 21q22.1.

A long-range restriction map of the 1.8-megabases (mb) region encompassing the area between the interferon-alpha receptor and the acute myelogenous leukemia loci on human chromosome 21q22.1 was constructed after analysis of both the contiguous yeast artificial chromosome (YAC) clones and genomic DNA. Analysis of pulsed-field gel electrophoresis of lymphoblastoid DNA digested with three rare-cutting enzymes, Not I, Mlu I, and Nru I, revealed the positions of 17 markers on each restriction map. The 1.8-mb YAC contig that covers this region was obtained through YAC walking mediated by sequence-tagged sites (STSs), with 29 STSs including 12 newly generated YAC end-specific STSs. The consensus restriction map from 15 overlapping YACs and the positioning of the STS markers on each clone allowed 24 markers including 4 Not I-linking STSs to be ordered and mapped physically. Comparison of the maps revealed that the proximal region contains more unmethylated CpG islands than the distal region, which suggests that many expressed genes are in the proximal region. This fine consensus physical map will be informative and useful for construction of contigs of cosmid, P1, or BAC clones for further large-scale sequencing in this gene-rich region.

Base Sequence↗

Cosmid assembly and anchoring to human chromosome 21.

A human chromosome 21-specific cosmid library from the Lawrence Livermore National Laboratory has been analyzed by two complementary methods, fingerprinting and hybridization; 40% coverage of the entire chromosome 21 has been achieved. To prepare a contig pool, approximately 9300 cosmid clones randomly selected from the library were fingerprinted and automatically assembled into 467 overlapping sets by the fluorescence-tagged restriction fragment method. The average size of the overlapping sets was 9.5 cosmids with minimal tiling paths consisting of 5.4 cosmids with a 10-kb extension each. However, as many as 10% of overlaps within members were estimated to be false. For regional localization, we hybridized gridded arrays of cosmids with inter-Alu-PCR probes obtained from YAC clones and somatic cell hybrids and assigned 592 cosmids to 26 subregions of 21q. Of these, 371 clones were incorporated into 139 contigs, anchoring the total 1864 cosmids to the subregion. The remaining 221 clones were mapped as orphans. To correlate the cytogenetic, YAC, and cosmid maps on 21q, the translocation breakpoints of the chromosomes contained in the somatic cell hybrids were mapped with respect to the STS content of the YACs. From the gene cluster regions, 176 ribosomal and 25 alphoid clones were isolated by hybridization. Together, these sets of anchored contigs and cosmids will provide a valuable resource for construction of a high-resolution map and for isolation of genes of interest from chromosome 21.

Animals↗

Activation of inward current associated with M-potassium current inhibition in m1-muscarinic receptor-transformed NG108-15 cells by KST-5452, a novel cognition enhancer.

The electrophysiological effects of KST-5452 [3-(m-phenoxybenzylidene)-quinuclidine], an M1 muscarinic acetylcholine receptor (muscarinic AChR) binding compound, were studied in NG108-15 neuroblastoma x glioma hybrid cells transfected with m1 muscarinic AChR cDNA. Application of KST-5452 to m1-transformed NGPM1-27 cells elicited a sustained inward current associated with decreased conductance and reduced M-current relaxations at a holding potential of -20 mV. The KST-5452-induced responses were blocked by pirenzepine, suggesting that KST-5452 acts as a potent excitant via M1 muscarinic AChRs in brain neurons.

Acetylcholine↗