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Biomedical subjects

M Arita

Publications and source records attributed to M Arita.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effect of bepridil on intracellular calcium concentration and contraction in cultured rat ventricular myocytes.

We studied the effects of a new antiarrhythmic and antianginal agent, bepridil, on the intracellular calcium transient and contraction of cultured neonatal rat ventricular cells, and compared the effects with those caused by an authentic Ca2+ -entry blocker, D600 (methoxyverapamil). The Ca2+ transient was measured by using dual-wavelength microfluorometry of fura-2. The contraction was measured as a shortening of cell aggregates with the use of a video image-analyzing system. Both bepridil (1-30 microM) and D600 (1-30 microM) decreased the peak systolic amplitude of the Ca2+ transient in a concentration- and frequency-dependent manner. Bepridil, but not D600, significantly shortened the half-decay time of the Ca2+ transient and prolonged the time course of the contraction. D600 decreased the contraction in parallel with the decrease in the peak Ca2+ transient, whereas bepridil exerted no significant effect on the contraction. Bepridil (10 microM) induced a leftward shift (to lower amplitude of peak systolic Ca2+ transient) of the relation between the magnitude of contraction and the peak systolic Ca2+ transient, which was obtained by changing external Ca2+ concentration. In contrast, D600 (10 microM) did not affect the relation. The results suggest that the negative inotropic effect of bepridil (caused by its Ca2+ channel-blocking effect) is offset by its simultaneous increase in the sensitivity of contractile protein(s) to intracellular Ca2+, which may be a unique characteristic of this antiarrhythmic agent in a clinical setting.

Animals↗
PubMed1999

[Vibrio vulnificus infection: clinical and bacteriological analysis of four cases].

Vibrio vulnificus (V. vulnificus) infection has recently been drawing attention as a high mortality disease especially in a patient with the preexisting chronic liver disease. The illness caused by V. vulnificus is divided into three groups such as primary septicemia, wound infection and gastrointestinal illness. Primary septicemia, which is the most common in Japan, is defined as a systemic illness presenting fever or hypotension with recovery of V. vulnificus from blood or tissue without the apparent primary focus of infection. We diagnosed four cases as infectious diseases of V. vulnificus by isolating it from each clinical material in Kurashiki Central Hospital from 1984 through 1997. We investigated clinical manifestations of the four cases including season of the onset, presence of drinking habit, underlying diseases, consumption of raw seafood, symptoms, presence of disseminated intravascular coagulation (DIC) or shock, laboratory data, administered antibiotics and the outcomes of the treatment. And for each strain, we also performed in vitro drug susceptibility tests. The age of the patients ranged from 49 to 61 years old (mean 56), and all of the patients were male. Each of them had a chronic liver disease as an underlying disease. Two of them had a history of raw seafood consumption prior to the onset of the illness. Skin manifestations appeared in two of the four patients. All the patients complicated septic shock and DIC. V. vulnificus was isolated from the venous blood cultures of them. Three of the four were given a diagnosis of primary septicemia and one was made a diagnosis of acute cholecystitis which has never been reported previously. Three of the four patients died and only the rest was alive as a result of antimicrobial therapy. In the sensitivity tests, the four strains were revealed to be very sensitive to the antimicrobials such as minocycline, cephalosporins of the third generation and carbapenems. Once patients with a chronic liver disease are infected with V. vulnificus, their prognosis is poor. Every effort should be made to advise not to have uncooked seafood. Physicians should be informed about the characteristics of the disease caused by this bacteria and treat any suspicious case promptly and appropriately.

Bacteriological Techniques↗
PubMed1999

[Multicenter screening of Chlamydia pneumoniae pneumonia by ELISA method].

We prospectively investigated the etiology of community-acquired pneumonia among adult patients admitted to three general hospitals over one year. Antibody titers to Chlamydia pneumoniae were also measured by ELISA method to investigate the incidence and clinical pictures of C. pneumoniae pneumonia in Japan. Two hundred and fourteen patients were enrolled in the study. Seventeen patients (7.9%) satisfied the criteria for diagnosis of acute infection due to C. pneumoniae by ELISA method. C. pneumoniae was the 3rd leading causative agent following Streptococcus pneumoniae (21.5%) and Haemophilus influenzae (8.4%). Preexisting antibodies were detected in 62.1% of the patients. Most of the patients with C. pneumoniae pneumonia were aged, and had comorbidities of respiratory system. Superinfection with bacterial pneumonia was recognized in some patients. Though there are several problems, ELISA method is thought to be useful to diagnose C. pneumoniae pneumonia, and is suitable for screening tests.

Aged↗
PubMed1999

Interaction of poliovirus with its receptor affords a high level of infectivity to the virion in poliovirus infections mediated by the Fc receptor.

Poliovirus infects susceptible cells through the poliovirus receptor (PVR), which functions to bind virus and to change its conformation. These two activities are thought to be necessary for efficient poliovirus infection. How binding and conformation conversion activities contribute to the establishment of poliovirus infection was investigated. Mouse L cells expressing mouse high-affinity Fcgamma receptor molecules were established and used to study poliovirus infection mediated by mouse antipoliovirus monoclonal antibodies (MAbs) (immunoglobulin G2a [IgG2a] subtypes) or PVR-IgG2a, a chimeric molecule consisting of the extracellular moiety of PVR and the hinge and Fc portion of mouse IgG2a. The antibodies and PVR-IgG2a showed the same degree of affinity for poliovirus, but the infectivities mediated by these molecules were different. Among the molecules tested, PVR-IgG2a mediated the infection most efficiently, showing 50- to 100-fold-higher efficiency than that attained with the different MAbs. A conformational change of poliovirus was induced only by PVR-IgG2a. These results strongly suggested that some specific interaction(s) between poliovirus and the PVR is required for high-level infectivity of poliovirus in this system.

Animals↗
PubMed1999

Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence.

In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5' nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.

5' Untranslated Regions↗
PubMed1999

Monospecific anti-GD1b IgG is required to induce rabbit ataxic neuropathy.

Of 22 rabbits sensitized with GD1b, 12 developed experimental sensory ataxic neuropathy. The affected rabbits had a higher level of serum IgG monospecific to GD1b than the unaffected ones. The GD1b-positive neuronal cytoplasms of rabbit dorsal root ganglia had larger diameters than the negative ones. IgG antibody monospecific to GD1b may preferentially bind to large primary sensory neurons, causing sensory ataxic neuropathy.

Animals↗
PubMed1999

[Comparison of the therapeutic effects and acid suppression of H2-receptor antagonist and proton pump inhibitor in patients with gastric body ulcer--a prospective controlled trial].

We studied, the rate and the affecting factor of ulcer healing of patients with gastric body ulcer treated by H2-receptor antagonist (H2-RA) and proton pump inhibitor (PPI). Gastric acidity was also examined using 24 hr pH monitoring. No difference was observed between the affecting factor of ulcer healing and healing rate (94.7% and 94.9%) among the patients treated by H2-RA or PPI. The average time below pH3 during treatment with H2-RA or PPI were 17.4 +/- 4.3 hr and 23.0 +/- 1.5 hr, respectively. Acid suppression was superior in PPI treated group than in H2-RA group. From these findings, we concluded that H2-RA had sufficient therapeutic efficacy in treating gastric body ulcer.

Anti-Ulcer Agents↗
PubMed1999

Bepridil blunts the shortening of action potential duration caused by metabolic inhibition via blockade of ATP-sensitive K(+) channels and Na(+)-activated K(+) channels.

The effects of bepridil, a potent antiarrhythmic drug, on the activity of ATP-sensitive K(+) (K(ATP)) channels and Na(+)-activated K(+) (K(Na)) channels were examined in isolated patches from guinea pig ventricular myocytes. In inside-out membrane patches, K(ATP) channel currents were recorded with 140 mM [K(+)](i) and 140 mM [K(+)](o) solutions, and K(Na) channel currents were recorded by increasing [Na(+)](i) to 100 mM with 40 mM [K(+)](i), respectively. Bepridil (1-100 microM) inhibited the K(ATP) channel current in a concentration-dependent manner. The IC(50) value of bepridil was estimated to be 10.5 microM for outward K(ATP) channel currents (holding potential, +60 mV) and 6.6 microM for inward K(ATP) channel currents (holding potential, -60 mV). Bepridil (0.1-30 microM) also inhibited K(Na) channel currents measured at the holding potential of -60 mV, in a concentration-dependent manner with an IC(50) value of 2.2 microM. In coronary-perfused guinea pig right ventricular preparations, the metabolic inhibition (MI) achieved with the application of 0.1 microM carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone shortened the action potential duration (APD) in a time-dependent manner. When bepridil (10 microM) was applied 5 min after the introduction of MI, the APD shortening was significantly blunted. The concomitant application of a K(ATP) channel antagonist (glibenclamide, 1 microM) and a K(Na) channel antagonist (R56865, 10 microM) could mimic the effect of bepridil and attenuated the shortening otherwise produced by MI. These results suggest that bepridil inhibits both K(ATP) channels and K(Na) channels and blunts the shortening of APD during MI. These effects of bepridil may partly account for the alleged antiarrhythmic action of this drug during ischemia.

Action Potentials↗
PubMed1999

Finding Precursor Compounds in Secondary Metabolism.

A precursor is a compound which is transformed to a class of functional molecules within short steps. It is an important process in the production of natural drugs to decide whether a given compound is a precursor or not. We present two strategies to select precursor compounds in the secondary metabolism of terpenoids: one is to find the packing of basic molecules in the given cyclic structure, and the other is to find the synthetic map of the given set of compounds. Both strategies play important roles in reproducing tracer experiments on a computer.

Journal Article↗
PubMed1999

Integrating Application Programs for Bioinformatics Using a Web Browser.

We have constructed a general framework for integrating application programs with control through a local Web browser. This method is based on a simple inter-process message function from an external process to application programs. Commands to a target program are prepared in a script file, which is parsed by a message dispatcher program. When it is used as a helper application to a Web browser, these messages will be sent from the browser by clicking a hyper-link in a Web document. Our framework also supports pluggable extension-modules for application programs by means of dynamic linking. A prototype system is implemented on our molecular structure-viewer program, MOSBY. It successfully featured a function to load an extension-module required for the docking study of molecular fragments from a Web page. Our simple framework facilitates the concise configuration of Web softwares without complicated knowledge on network computation and security issues. It is also applicable for a wide range of network computations processing private data using a Web browser.

Journal Article↗
PubMed1998

Localization of alpha-tocopherol transfer protein in rat brain.

Vitamin E (alpha-tocopherol) is a fat-soluble antioxidant that is transported by plasma lipoproteins in the body. Alpha-tocopherol transfer protein (alpha-TTP), which was identified as a product of the causative gene for familial isolated vitamin E (FIVE) deficiency, is a cytosolic liver protein which plays an important role in the efficient circulation of plasma vitamin E in the body. In the present study, we detected the message for alpha-TTP at low levels in some rat tissues including brain, spleen, lung and kidney. In the brain, the alpha-TTP transcript was detected predominantly in the cerebellar cortex, as revealed by in situ hybridization histochemistry. In the cerebellar cortex, clusters of the hybridization signal were aligned with the Purkinje cell layer, although the signal was not detected in the Purkinje cells, but in the small cells around the Purkinje cells. This distribution pattern strongly suggests that the message for alpha-TTP is expressed in the Bergmann glial cells. Combined with the previous observation that there was severe Purkinje cell loss in patients with FIVE deficiency, the present data suggest that vitamin E is supplied to the Purkinje cells from the surrounding Bergmann glial cells with the help of alpha-TTP.

Animals↗
PubMed1998

Binding of alpha-tocopherylquinone, an oxidized form of alpha-tocopherol, to glutathione-S-transferase in the liver cytosol.

Alpha-tocopherol (vitamin E) is an important fat-soluble antioxidant in biological systems and, as a result of scavenging reactive oxygen, it is converted to alpha-tocopherylquinone. Alpha-tocopherol binds to alpha-tocopherol transfer protein (alphaTTP) in the liver cytosol, whereas alpha-tocopherylquinone does not. We found that alpha-tocopherylquinone binds to a liver protein with a molecular mass of about 40 kDa that is distinct from alphaTTP. This alpha-tocopherylquinone binding protein was purified further by multiple-step column chromatography. Sodium dodecylsulfate-polyacrylamide gel electrophoresis of the final preparation yielded a single band with an apparent molecular mass of 25 kDa, which microsequencing revealed was identical to glutathione-S-transferase (GST). The GST activity was inhibited in the presence of alpha-tocopherylquinone, as it is by other non-substrate ligands for GST, confirming that GST and alpha-tocopherylquinone interact directly. Alpha-tocopherylquinone binds to GST and may be transported to the site of metabolism or excreted in the bile as other non-substrate ligands for GST.

Amino Acid Sequence↗
PubMed1998

Increased QT dispersion in patients with vasospastic angina.

BACKGROUND: The risk factors for ventricular arrhythmias in patients with coronary vasospasm have not been identified. We evaluated QT dispersion in patients with vasospastic angina and its relation to susceptibility to ventricular arrhythmias during myocardial ischemia and reperfusion. METHODS AND RESULTS: We assessed the corrected QT (QTc) dispersion before induction of coronary artery spasm by intracoronary injection of acetylcholine (baseline) and 30 minutes after administration of isosorbide dinitrate in 50 patients with vasospastic angina and 50 patients with atypical chest pain. The baseline QTc dispersion was significantly greater in patients with vasospastic angina than in patients with atypical chest pain (mean+/-SD: 69+/-24 versus 44+/-19 ms, 95% confidence interval of mean difference [CI]: 16 to 33 ms; P<0.001). QTc dispersion decreased significantly, to 48+/-15 ms (CI: 15 to 26 ms; P<0.001 versus baseline), after administration of isosorbide dinitrate in patients with vasospastic angina but did not change significantly in patients with atypical chest pain (mean+/-SD: 41+/-17 ms, CI: -3 to 9 ms). During the provocation test, 24 of 50 patients with vasospastic angina experienced ventricular arrhythmias. The baseline QTc dispersion was significantly greater in patients with than without ventricular arrhythmias (mean+/-SD: 77+/-23 versus 61+/-19 ms, CI: 4 to 26 ms; P<0.05). CONCLUSIONS: Patients with vasospastic angina exhibited an increased baseline QTc dispersion compared with patients with atypical chest pain, which suggests that inhomogeneity of repolarization and susceptibility to ventricular arrhythmias are increased in patients with vasospastic angina, even when asymptomatic. The association between increased QTc dispersion and ventricular arrhythmias during the provocation test suggests that measurement of QT dispersion may help predict which patients with vasospastic angina are at high risk for ventricular arrhythmias during ischemia.

Acetylcholine↗
PubMed1998

Four conductance levels of cloned cardiac L-type Ca2+ channel alpha1 and alpha1/beta subunits.

Formation of single channel subconductance is one of the unique characteristics of the L-type Ca2+ channel. Although alpha1 subunit exhibits a primary function of the channel, it remains uncertain whether alpha1 subunit alone is able to produce subconductance. We tested this by studying single channel currents of cloned cardiac alpha1 subunit expressed in Chinese hamster fibroblast cells, with/without coexpression of cardiac beta subunit. The alpha1 subunit exhibited four distinct levels of conductance (22.7, 14.3, 6.2 and 3.2 pS). Coexpression of beta subunit significantly increased the number of openings in all four levels of conductance without changing the conductance values.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Class I antiarrhythmic drugs alter the severity of myocardial stunning by modulating ATP-sensitive K+ channels in guinea pig ventricular muscles.

The effects of various class I antiarrhythmic drugs and glibenclamide were examined on the recovery of contraction during reperfusion, in relation to the action potential duration (APD) seen during ischemia. Action potential and contractile tension were recorded from isolated guinea pig right ventricular muscles perfused with oxygenated Tyrode solution via the coronary artery. Ten minutes of no-flow ischemia shortened the APD at 90% of repolarization level (APD90) to 58% of control (pre-ischemic values). The APD90 was completely restored after 60 min of reperfusion. The developed tension was abolished during ischemia and recovered to 87% of control after 60 min of reperfusion. In the presence of Vaughan Williams class Ia drug cibenzoline (5 microM) or an ATP-sensitive potassium (K(ATP)) channel blocker glibenclamide (10 microM), the shortening of the APD90 during ischemia was significantly attenuated. However, the recovery of developed tension was significantly inhibited. Class Ic drug pilsicainide (10 microM) did not affect the ischemia-induced shortening of the APD90 or the recovery of developed tension after reperfusion. In the presence of class Ib drug mexiletine (10 microM), the shortening of the APD90 during ischemia was significantly facilitated. The recovery of developed tension in the presence of mexiletine tended to be improved, although the difference was not statistically significant. The developed tension measured after the 60 min reperfusion period following 20 min of no-flow ischemia was markedly depressed, indicating the presence of myocardial stunning. Mexiletine and pilsicainide significantly improved the recovery of developed tension and diminished the stunning. We conclude that cibenzoline and glibenclamide, which block cardiac K(ATP) channels inhibit contractile recovery after reperfusion by attenuating the shortening of APD during ischemia. In contrast, mexiletine, which activates K(ATP) channels (in addition to blockade of Na+ channels) improves contractile recovery by facilitating the shortening of APD during ischemia.

Animals↗