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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
PubMed2001

Effects of antihypertensive agents on blood pressure during exercise.

The relationship between blood pressure (BP) and cardiovascular morbidity has been appreciated for many years. Casual BP may not be representative of the pressure at other times. It is recognized that BP during exercise may be a more accurate predictor than casual BP. There is, however, little information about the effects of antihypertensive drugs on the BP during exercise. This study was designed to investigate the effects of various antihypertensive agents on BP during exercise. Sixty-four patients (age, 49+/-10 years) with untreated essential hypertension (WHO I, II) were studied during a supine ergometric exercise regimen. A graded exercise test was started at a workload of 50 W, and the load was increased by 25 W every 3 min. The hemodynamic responses to exercise were evaluated by changes in systolic and diastolic BP (SBP, DBP) and heart rate (HR). Plasma norepinephrine (NE) levels were measured at rest and during submaximal exercise, and before and after 4 weeks of treatment with metoprolol (METO), doxazosin (DOXA), trichlormethiazide (TCTZ), nifedipine (NIFE), amlodipine (AMLO) and temocapril (TEMO) between left ventricular mass index (LVMI) and BP values at rest, during exercise, and during the recovery period after exercise were assessed by multiple regression analysis. The stepwise selection (forward conditional) method showed that LVMI was significantly associated with SBP during submaximal exercise and during the recovery period. All antihypertensive treatments decreased SBP and DBP (p<0.01) at rest. METO, AMLO and TEMO significantly lowered SBP (p<0.05) during exercise, whereas DOXA, TCTZ and NIFE induced no change in SBP. The exercise-induced increase of plasma NE was further enhanced by METO and NIFE but not by AMLO, DOXA, or TCTZ, and it was significantly suppressed by TEMO (p<0.01). These results suggest that BP during exercise is more highly associated with the progression of left ventricular hypertrophy (LVH) than is casual BP. Because antihypertensive agents differ in their effects on exercise hemodynamics, we recommend that hemodynamic factors during exercise be considered when selecting the optimal antihypertensive medication for highly active patients.

Adult↗
PubMed2001

[Pulmonary hypertension in patients with congenital and acquired heart diseases].

Pathophysiology of pulmonary hypertension in patients with congenital and acquired heart diseases are described. The broken down of the pulmonary hypertension is left ventricular dysfunction and/or left atrial overloading, and high blood flow in pulmonary circuit with intra-cardiac or intra-vascular shunt. There are pulmonary venous, reactive, and arterial hypertension, related with the mechanism. The worsening of pulmonary venous hypertension induces acute hemodynamic pulmonary edema. The high blood flow in the pulmonary circulation due to large shunt develops Eisenmenger syndrome related with aging.

Heart Defects, Congenital↗
PubMed2000

Enhanced shear-induced von Willebrand factor binding to platelets in acute myocardial infarction.

Recent investigations have suggested that von Willebrand factor (vWF) plays a crucial role in platelet thrombosis under flow conditions. The effects of plasma obtained from 15 patients with acute myocardial infarction and 10 patients with the chest pain syndrome as controls, on shear-induced vWF binding to platelets and subsequent platelet activation, as evidenced by microparticle release, were investigated by quantitative flow cytometry. Platelet-rich plasma was obtained from a 38-year-old healthy male volunteer with blood type O. Stored plasma from either the acute myocardial infarction or control patients was then added to the freshly prepared platelet-rich plasma in equal volumes. The mixtures were then exposed to specific shear rates in an optically modified cone-plate viscometer. The number of vWF molecules bound to the platelet surface and the number of microparticles released from the platelets were then measured by quantitative flow cytometry using an FITC-conjugated anti-vWF monoclonal antibody. The shear-induced increase in vWF binding to the platelet surface was enhanced in the presence of plasma from patients with acute myocardial infarction (acute myocardial infarction plasma). The shear-induced release of microparticles from platelets was enhanced from 889+/-134 in the presence of control plasma to 1045+/-222 in the presence of the acute myocardial infarction plasma (p<0.05). Acute myocardial infarction plasma also reduced the shear rate threshold required to induce measurable shear-induced vWF binding from 10800 s(-1) to 9000 s(-1). We conclude that the plasma of acute myocardial infarction patients contains factors that enhance shear-induced vWF binding and vWF-mediated platelet activation, which may contribute to thrombotic re-occlusions of the coronary arteries in patients who have received reperfusion treatments.

Aged↗
PubMed2000

Detection of antibody to sialyl-i, a possible antigen in patients with Meniere's disease.

An autoimmune hypothesis for the etiology of Meniere's disease has been proposed. In this study, we focused on gangliosides as potential antigens for autoantibodies in Meniere's disease patients. In an attempt to investigate ganglioside antigens which respond to the serum of patients with Meniere's disease, we analyzed gangliosides of human acoustic neurinomas, and used them as antigens to broadly explore gangliosides that react to serum. All the acoustic neurinoma samples used in the present study showed a similar ganglioside profile on TLC (thin-layer chromatography). For the microscale ganglioside analysis, a newly developed TLC blotting/secondary ion mass spectrometry (SIMS) system together with TLC immunostaining method was employed. Most of the ganglioside bands could be analyzed, and they were identified as GM3, GM2, SPG, GM1a, GD3, S-i (sialyl-i ganglioside) and GD1a. GD1a was the predominant ganglioside and many neolactoseries gangliosides were recognized by immunological analysis. Next, the immune reactivity of serum samples, from patients with Meniere's disease, with the acoustic neurinoma gangliosides was studied by TLC immunostaining. The result showed that five of 11 patients with Meniere's disease and one of eight normal subjects reacted with a specific band, which was identified as S-i by the TLC blotting/SIMS system. The findings of the present study indicate that S-i ganglioside is an autoantigen and possibly involved in the pathogenesis of Meniere's disease.

Autoantibodies↗
PubMed2000

Platelet aggregation induced by ADP or epinephrine is enhanced in habitual smokers.

A novel system has been developed to evaluate biochemically induced platelet aggregation by means of a particle-counting technique that uses laser light scattering. Using this system, we compared the differences in platelet aggregability between 90 smoking healthy males after 10 hours of smoking abstinence and 141 age-matched nonsmoking healthy males. Smokers had more small spontaneous platelet aggregates and more medium and large aggregates induced by 1 or 5 microM of epinephrine than nonsmokers. No large aggregates with 5-microM epinephrine-induced platelet aggregation were seen in 10% of smokers and 24% of nonsmokers; these subjects showed no small aggregates in spontaneous aggregation at all. Smokers had significantly more small, medium, and large aggregates induced by 1 microM of adenosine diphosphate (ADP) than nonsmokers. Smokers showed a positive correlation between age and 1-microM epinephrine-induced large platelet aggregates, percent reduction of optical density, and 1-microM ADP-induced medium and large aggregates. Smokers also showed a positive correlation between fibrinogen concentration in plasma and small spontaneous aggregates. On the other hand, nonsmokers showed a significant positive correlation between age and small spontaneous aggregates, and a positive correlation between fibrinogen and 1- or 5-microM epinephrine-induced large aggregates, and between 1 microM ADP-induced large aggregates and percent reduction of optical density. These results confirmed that platelet aggregability is enhanced in smokers, and we speculate that long-term smoking might enhance the sensitivity of platelets to epinephrine or ADP.

Adenosine Diphosphate↗
PubMed2000

Induction of apoptosis by novel synthesized acylamides of human lymphocytes.

To investigate a pathway to apoptosis which may involve ceramides and to elucidate the minimum structure which leads to apoptosis, we synthesized several novel acylamides. Although the four synthesized compounds were different in structure from C2-ceramide, they caused Jurkat cells to undergo apoptosis. The most effective of them was N-myristoyl-D-alaninol (D-MA), as shown by DNA fragmentation (detected with propidium iodide) and a decrease in the mitochondrial transmembrane potential (DeltaPsi(m)) (detected with rhodamine 123). Nevertheless, peripheral blood leukocytes exhibited no change after D-MA exposure, like after C2-ceramide or anti-Fas antibody treatment. The DNA fragmentation and DeltaPsi(m) caused by D-MA were blocked by a caspase-3 specific inhibitor as in the case of anti-Fas antibody stimulation. Quantification of ceramides by metabolic labeling with [(14)C]palmitic acid and HPTLC showed no increases in the ceramide levels on stimulation with D-MA, C2-ceramide or anti-Fas antibodies. Furthermore, D-MA had an apoptosis-inducing effect on an anti-Fas-resistant subline of Jurkat cells. These data suggest that D-MA may cause apoptosis of Jurkat cells without distinct ceramide formation and that this apoptotic pathway is very comparable, i.e. not identical, to that induced by anti-Fas antibodies.

Alanine↗
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↗