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Biomedical subjects

S Handa

Publications and source records attributed to S Handa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Attenuation of KATP channel-opener induced shortening of repolarization time by alpha 1-adrenoceptor antagonist during ischemia in canine heart.

The purpose of the study was to determine whether a new KATP channel opener, Y 26763 (Y), can influence the electrophysiological properties in the ischemic myocardium as well as to determine whether the blunting effect of the alpha 1-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of repolarization time can be related to the KATP channel activity. The anterior descending branch of the left coronary artery was ligated four times for 5 minutes, separated by 15 minutes of reperfusion (stages 1-4) to test the dose-dependent effect of drugs on repolarization. Dogs received either vehicle (n = 9), Y (0.4, 2.0, and 4.0 micrograms/kg at stages 2, 3, and 4, respectively, with 0.4 microgram/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at each of stages 2-4, n = 8), or a combination of these two drugs (BN + Y, the same dose of BN and Y in groups BN and Y, respectively, n = 9). Drugs were administered into the left atrium. The monophasic action potential (MAP) and regional electrograms were recorded. The MAP90 and the duration of the slow deflections (DSD) of the regional electrogram were used as markers of repolarization. The Vmax of the MAP and the rapid deflections (DRD) of the regional electrogram were used as markers of conduction. Y augmented an ischemia-induced shortening of MAP90 and DSD in proportion to an increase in the dose given and the plasma concentration (P < .05-.01), especially at the epicardial site. BN and BN + Y blunted the ischemia-related shortening of MAP90 and DSD, causing a reduction in repolarization time dispersion between the ischemic and normal zones. There were no significant changes in the Vmax or DRD in the ischemic zone between periods before and after an increase in each drug dose in the four groups. None of the seven dogs developed ventricular tachycardia (VT)/ventricular fibrillation (VF) in the Y group, whereas two of the eight dogs in the BN group, three of the nine dogs in the BN + Y group, and three of the nine dogs in the control group developed VT/VF. These results suggest that the alpha 1-adrenergic blocker bunazosin blunts the shortening effect of KATP channel activator on repolarization time, and that the KATP channel opener Y may be antiarrhythmic, although the repolarization time dispersion during myocardial ischemia is increased.

ATP-Binding Cassette Transporters↗
PubMed2000

Giant negative T waves in Guillain-Barré syndrome.

A Guillain-Barré syndrome patient showed giant negative T waves on electrocardiography at the height of the disease, with large left ventricular hypokinesis on echocardiography and extensive defects on 123I-meta-iodobenzylguanidine myocardial scintigraphy. Gamma-globulin improved the neurological symptoms, and the above abnormalities resolved. We speculate that cardiac sympathetic nerve endings were transiently damaged, with consequent myocardial injury, due to norepinephrine toxicity.

3-Iodobenzylguanidine↗
PubMed2000

Conventional cold excision combined with dermabrasion for rhinophyma.

A 65-year-old man, farmer by occupation, presented with redness and gradual enlargement of the nose. Examination revealed marked nodular enlargement of the nose and loss of normal nasal contours. Sebaceous material could be expressed from widened pores. The patient was diagnosed as rhinophyma of moderate degree. He was treated with cold knife excision combined with dermabrasion. A literature scan revealed that currently there is no evidence of superiority of much popular laser surgery over conventional cold knife surgery combined with dermabrasion for rhinophyma. Conventional surgery is time-tested, and it does not require expensive equipment or special training.

Aged↗
PubMed2000

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase.

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.

Analysis of Variance↗
PubMed2000

Evaluation of global and regional left ventricular function obtained by quantitative gated SPECT using 99mTc-tetrofosmin for left ventricular dysfunction.

OBJECTIVE: The quantitative gated SPECT (QGS) software is able to calculate LV volumes and visualize LV wall motion and perfusion throughout the cardiac cycle using an automatic edge detection algorithm of the left ventricle. We evaluated the reliability of global and regional LV function assessment derived from QGS by comparing it with the results from left ventriculo-cineangiography (LVG). PATIENTS: In 20 patients with left ventricular dysfunction who underwent ECG gated 99mTc-tetrofosmin SPECT, the end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (LVEF) were calculated. The QGS-assessed regional wall motion was determined using the cinematic display. RESULTS: QGS-derived EDV, ESV and LVEF correlated well with those by LVG (p<0.001 for each). There was a good correlation between wall motion score (WMS) derived from the QGS and the LVG (r=0.40, p<0.05). In some patients with extensive myocardial infarction, there was a discrepancy in the regional wall motion results between QGS and LVG. CONCLUSIONS: The ECG-gated SPECT using QGS is useful to evaluate global and regional LV functions in left ventricular dysfunction.

Adult↗
PubMed2000

Platelet surface P-selectin molecules increased after exposing platelet to a high shear flow.

BACKGROUND: P-selectin is known to play a crucial role in leucocyte recruitment at sites of vascular injury. Although platelet surface expression of P-selectin molecules are well known to occur after platelet stimulation by chemical agonists such as alpha-thrombin, it is still uncertain whether P-selectin expression occurs in the process of the more physiological platelet activation pathway mediated by interaction between von Willebrand factor (vWF) and platelet receptor proteins, including glycoprotein (GP) Ibalpha and GP IIb/IIIa, occurring under high shear rates generated by blood flow. METHODS: We have developed a method to detect P-selectin molecules expressed on platelet surface with flow-cytometer and monoclonal antibody, which can bind exclusively to P-selectin (WGA1), directly conjugated with fluorescein isothiocynate. This method allowed us to measure platelet surface P-selectin molecules semiquantitatively. RESULTS: We demonstrated that a significant increase in platelet surface P-selectin molecules occur after exposing platelets to a relatively high shear rate of 10,800 s(-1). We have also demonstrated that shear-induced surface expression of P-selectin as well as microparticle release from platelets depended at least on the interaction between von Willebrand factor and glycoprotein Ibalpha, a platelet surface receptor for the former. CONCLUSIONS: Shear-induced von Willebrand-mediated surface expression of P-selectin may play a role in leucocyte recruitment in platelet thrombi at vascular injury sites.

Antibodies, Monoclonal↗
PubMed2000

[Different inhibiting effects of abciximab and tirofiban on platelet thrombus formation on a collagen surface under flow conditions].

OBJECTIVES: Recently developed anti-GPIIb/IIIa agents effectively inhibit acute thrombotic occlusion of coronary arteries after interventional treatment, and have similar inhibiting effects on plasma ligand binding to GPIIb/IIIa. Clinical investigation has revealed that abciximab, the chimeric monoclonal antibody against GPIIb/IIIa, has superior in vivo antithrombotic effects to other agents. The inhibiting effects of abciximab and another anti-GPIIb/IIIa agent, tirofiban, were investigated on platelet thrombus formation on a collagen surface under flow conditions. METHODS: Blood was drawn from 6 normal volunteers and anticoagulated with a specific inhibitor of thrombin, argatroban, at a final concentration of 100 microM. Platelets were rendered fluorescent by addition of mepacrine to a final concentration of 10 microM. Mepacrine is concentrated in the dense granules of platelets and leukocytes, but does not accumulate in red blood cells, so platelet thrombi can be detected by fluorescence microscopy even in the presence of red blood cells. Horizontal glass slips covered with fibrillar type I collagen were assembled in a Hele-Shaw type flow chamber. RESULTS: Platelet thrombi were developed on the collagen surface even in the absence of platelet activating agents. Both abciximab and tirofiban inhibited the platelet thrombus formation. Single platelet adhesion on the collagen surface was inhibited only by abciximab and not by tirofiban. CONCLUSIONS: The superior in vivo antithrombotic effects of abciximab may be partially explained by its inhibiting effects on the platelet adhesion on exposed subendothelial matrix.

Abciximab↗
PubMed2000

Plasma concentration of von Willebrand factor in acute myocardial infarction.

Recent investigations have revealed the crucial role of von Willebrand factor (vWF) in platelet thrombus formation under flow conditions. The plasma concentrations of vWF were measured together with various hemodynamic and hemostatic parameters in 51 cases of acute myocardial infarction. In 10 randomly selected cases, the plasma concentrations and distribution of multimers vWF were serially determined after reperfusion therapy by percutaneous transluminal coronary angioplasty (PTCA). The vWF concentration at the onset of the acute myocardial infarction was significantly higher than in an age-matched control group (vWF AG: 18.7 +/- 1.2 microg/ml vs. 10.3 +/- 0.5 microg/ml, p = 8.43 x 10-(12), mean +/- SE). Simultaneous determination of hemodynamic and hemostatic parameters revealed that the only two parameters that were significantly correlated with the patients' plasma vWF concentrations were their pulmonary capillary wedge pressure (PCWP) and heart rate, suggesting a relationship between hemodynamic changes induced by the onset of myocardial infarction and the vWF plasma concentrations. Serial determinations revealed that the vWF concentrations had not changed 1 h after reperfusion therapy, but that they significantly increased by 24 to 72 h. The distribution of the larger multimers of vWF also increased in the acute and subacute phase. The vWF concentration and multimer distribution normalized 14 days after the onset of the myocardial infarction. Our findings suggest that the vWF concentration increased in acute myocardial infarction patients, possibly in association with the hemodynamic deterioration that occurs in acute myocardial infarction.

Adult↗
PubMed1999

Stereochemical course of biotin-independent malonate decarboxylase catalysis.

Malonate decarboxylases, which catalyze the conversion of malonate to acetate, can be classified into biotin-dependent and biotin-independent enzymes. In order to reveal the stereochemical course of the reactions catalyzed by the biotin-independent enzymes from Acinetobacter calcoaceticus and Pseudomonas fluorescens, a chiral substrate, malonate carrying (13)C in one carboxyl group and (3)H at one of the methylene positions, was prepared and used in the reactions catalyzed by these two enzymes. The decarboxylation of (R)-[1-(13)C(1), 2-(3)H]malonate in (2)H(2)O gave a pseudo-racemate of chiral acetate which was converted via acetyl-CoA into malate with malate synthase. From the relative proportions of the isotopomers of malate present, determined by (3)H NMR analysis, it was concluded that in the decarboxylation of malonate by these two biotin-independent enzymes COOH is replaced by H with retention of configuration. The same stereochemical outcome had been previously observed for the reaction catalyzed by the biotin-dependent malonate decarboxylase from Malonomonas rubra (J. Micklefield et al. J. Am. Chem. Soc. 117, 1153-1154, 1995).

Acinetobacter calcoaceticus↗
PubMed1999

Platelet spontaneous aggregation in platelet-rich plasma is increased in habitual smokers.

Cigarette smoking is a well-known risk factor for atherosclerotic disorders. Several authors have suggested that platelet aggregability is important in smoking-induced vascular injury. When platelet-rich plasma is stirred at 37 degrees C in the absence of chemical stimulants, small aggregates of platelets may be formed, but it was difficult to detect small aggregates by conventional aggregometer using optical density. Recent technological advances have made it possible to detect small aggregates by using a newly developed assay system that employs laser light scattering. In the present study, we attempted to measure platelet aggregation by this method, using laser light scattering in 54 nonsmoking healthy males and 51 healthy male habitual smokers who were age matched. In smokers, blood was obtained after 10 hours of smoking abstinence. No significant difference in platelet aggregation was induced by 1 microM or 5 microM of ADP between smokers and nonsmokers. In smokers, plasma fibrinogen levels and the number of small aggregates formed in the absence of chemical stimulants was significantly higher than in nonsmokers. Small aggregates formed in the absence of stimulants correlated positively with the concentrations of von Willebrand factor (vWF) antigen (r=0.2654, p<0.01) and of fibrinogen (r=0.2834, p<0.01). The formation of these small aggregates was inhibited by monoclonal antibody against GPIIb/IIIa blocking fibrinogen binding to GPIIb/IIIa but not inhibited at all by monoclonal antibody against GPIb blocking vWF binding to GPIb. From these results, enhanced platelet aggregability in smokers was confirmed, and it was suggested that GPIIb/IIIa is concerned in platelet spontaneous aggregation, although vWF may not directly influence on the platelet spontaneous aggregation. Since the mechanism of spontaneous aggregation and the effect of increased spontaneous aggregability on the progression of atherosclerosis remains unclear, further study was considered necessary.

Adult↗
PubMed1999

Enhanced shear-induced platelet aggregation in acute myocardial infarction.

BACKGROUND: Experiments under controlled flow conditions indicate that the binding of von Willebrand factor (vWF) to platelet glycoprotein (GP) Ibalpha and integrin alphaIIbbeta3 (GP IIb/IIIa complex) is crucial for aggregation at elevated shear rates. We have tested how the plasma of patients with acute myocardial infarction affects this process. METHODS AND RESULTS: Citrated plasma was obtained from 18 patients with acute myocardial infarction within 6 hours from the onset of symptoms and from 26 control subjects with chest pain syndrome without evidence of ischemia. Aggregation of normal platelets at high shear rates was significantly greater in the presence of patient than control plasma and was inhibited by both anti-GP Ibalpha and anti-alphaIIbbeta3 monoclonal antibodies. The observed values (mean+/-SD) were 47.6+/-17.8% versus 30.1+/-9.9% at 10 800 s-1 (P<0.01) and 32.9+/-14.1% versus 17.5+/-9.5% at 7200 s-1 (P<0.01), respectively, and were positively correlated with plasma vWF antigen levels and ristocetin cofactor activities. In contrast, at the lower shear rate of 1200 s-1, aggregation was similar in the presence of control or patient plasma and was not inhibited by the anti-GP Ibalpha antibody. Both vWF antigen and platelet aggregation decreased 2 weeks after the onset of myocardial infarction. CONCLUSIONS: Shear-induced platelet aggregation is enhanced in plasma in the presence of acute myocardial infarction, apparently as a result of increased vWF concentration. This may contribute to the onset of acute coronary artery thrombosis and early reocclusion after reperfusion treatment.

Adult↗
PubMed1999

Occurrence of monosialosyl pentahexaosylceramide GalNAc-GM1 as specific tumor-associated ganglioside of human head and neck squamous cell carcinomas.

In a recent study of the ganglioside profiles of human head and neck squamous cell carcinomas versus normal tissue, one unidentified GX ganglioside was found exclusively in tumor extracts, migrating between GM1 and GD3 by thin-layer chromatography. To determine the chemical structure of this ganglioside which accounted for 3-8% of the total gangliosides, the lipid samples were pooled and separated by high-pressure liquid chromatography to obtain individual ganglioside species purified to homogeneity. The tumor-associated GX ganglioside was analyzed by gas-liquid chromatography, mass spectrometry and immunostaining on thin-layer plates with mouse monoclonal antibodies after enzymatic cleavage. The data allowed the identification of GX ganglioside as GalNAc-GM1 that has been reported as a very minor brain ganglioside in humans. Thus, GalNAc-GM1 is a specific tumor-associated ganglioside in human head and neck squamous cell carcinomas that could be potentially valuable for clinicians.

Carcinoma, Squamous Cell↗
PubMed1999

GT1b in human metastatic brain tumors: GT1b as a brain metastasis-associated ganglioside.

We studied ganglioside expression in 12 human metastatic brain tumors metastasized from colon (4), renal (3), lung (2), esophagus (1), pancreas (1), and mammary (1) carcinomas. GM3 was the major common ganglioside expressed in brain metastatic tumor tissues, and GT1b was also present in all the metastatic brain tumor tissues. The latter was identified by TLC-immunostaining and characterized structurally by secondary ion mass spectrometry combined with 'Far-Eastern blot'. The immunohistochemical analysis of frozen tissue sections confirmed localization of GT1b in the tumor cell membrane or cytosol. GT1b was shown to be expressed both in the primary colon carcinoma and the metastasis of a single patient by immunohistochemical procedure. In systemic carcinomas without brain metastasis, GM3 was a common major component, but no GT1b was detected. These findings indicate that GT1b is a brain metastasis-associated ganglioside. We speculate that the presence of GT1b would be a useful marker for estimating metastatic potentials to the brain.

Adenocarcinoma↗
PubMed1999

On the mechanism of the failure of mitochondrial function in isolated guinea-pig myocytes subjected to a Ca2+ overload.

OBJECTIVE: The influence of agents that inhibit the movement of Ca2+ across the mitochondrial membrane or Ca2+ dependent changes to this membrane upon the response of isolated ventricular myocytes to a Ca2+ overload has been investigated. METHODS: The changes of intracellular Ca2+ and Mg2+ ([Ca2+]i, [Mg2+]i) (as reflected by cellular ATP), mitochondrial membrane potential (psi m) and NADH was measured upon the response of isolated ventricular myocytes to a Ca2+ overload. RESULTS: A slow depolarization of psi m during Ca2+ depletion and its prompt recovery on Ca2+ repletion were unaffected by ruthenium red, clonazepam, CGP-37157 which is a high potent inhibitor of the mitochondrial Na+/Ca2+ antiport or cyclosporin A but a large delayed sustained depolarization was inhibited. The slow small fall in [Mg2+]i on Ca2+ depletion and a rapid recovery on Ca2+ repletion were unaffected by ruthenium red, clonazepam, CGP-37157 or cyclosporin A. A delayed sustained larger rise in [Mg2+]i was inhibited. The marked sustained fall in NADH autofluorescence that occurs on Ca2+ overload was attenuated and transient in the presence of ruthenium red, CGP-37157 and cyclosporin A. CONCLUSION: These results are consistent with an increase in Ca2+ cycling across the mitochondrial membrane provoked by the combined Na+ and Ca2+ overload of cardiac myocytes, causing a depolarization sufficient to uncouple respiration and lead to the depletion of cellular ATP.

Adenosine Triphosphate↗
PubMed1999

Bonelike apatite coating on organic polymers: novel nucleation process using sodium silicate solution.

A bonelike apatite layer was formed on organic polymers when sodium silicate was used as a catalyst for the apatite nucleation, and modified simulated body fluid was used as a medium for the apatite growth. The apatite-forming ability was the highest when the SiO2 concentration and SiO2/Na2O mole ratio of the sodium silicate solution were above 2.0 M and 1.0-1.5, respectively. It is assumed that particular silicate oligomers with structures such as dimer, linear trimer and cyclic tetramer contribute to the apatite nucleation the most. The apatite layer was formed not only on limited surfaces but also on the whole surfaces of fine PET fibers constituting a fabric. This method is expected to enable the bonelike apatite coating on various kinds of materials with complex shapes.

Apatites↗