Search PubMed⌕ Search

Biomedical subjects

S Handa

Publications and source records attributed to S Handa.

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

Epitope mapping of rat neutralizing monoclonal antibody against human immunodeficiency virus type-1 by a phage peptide library: comparison with ELISA using synthetic peptides.

We generated a rat monoclonal antibody (mAb W#10) with the ability to neutralize human immunodeficiency virus type 1IIIB (HIV-1IIIB) infection. The epitope recognized by mAb W#10 was defined as R-I-Q-R-G-P-G by enzyme-linked immunosorbent assay (ELISA) with the use of synthetic peptides. The filamentous phage clones displaying random 15-amino-acid peptides on the amino terminus of the pIII coat protein reacting with mAb W#10 were identified with affinity and immunological selection procedures. Thirteen out of 16 selected phage clones contained the G-X-G-R-X-F sequence in the coat protein region representing significant homology to a part of conserved G-P-G-R-A-F sequence in the V3 loop of various HIV-1 strains. In addition, the phage clones included the G-X-G sequence in the sequence detected by synthetic peptides as the recognition site. The selected phage clones were stained by mAb W#10 specifically and were able to compete with mAb binding to cells expressing viral antigens.

Amino Acid Sequence↗
PubMed1999

Isolation and characterization of a novel Forssman active acidic glycosphingolipid with branched isoglobo-, ganglio-, and neolacto-series hybrid sugar chains.

Equine kidney and spleen contain a Forssman active glycosphingolipid, and the structure of this glycolipid has been reported to be that of a globopentaosylceramide (GalNAcalpha-1,3GalNAcbeta-1,3Galalpha-1, 4Galbeta-1,4Glcbeta-1,1'Ceramide). We found that equine kidney contains several other anti-Forssman antibody-reactive glycosphingolipids. One of these acidic Forssman active glycosphingolipids was isolated and characterized by means of NMR, mass spectrometry, permethylation studies, and TLC-immunostaining. This glycolipid contains three moles of galactose, one mole of glucose, three moles of N-acetylgalactosamine, one mole of N-acetylglucosamine, and one mole of N-acetylneuraminic acid, and is stained on TLC with anti-Forssman antibodies and anti-GM2 ganglioside antibodies. HOHAHA and ROESY experiments and permethylation studies showed this glycolipid oligosaccharide to be branched at the innermost galactose; one chain has an isoglobo structure with a terminal Forssman disaccharide and the other chain is branched through the linkage of N-acetylglucosaminebeta-1,6 to the inner galactose. The nonreducing end of the GM2 trisaccharide is linked to this glucosamine. The structure of the oligosaccharide of the glycolipid presented here is a novel type, having branched isoglobo-, ganglio-, and neolacto-series oligosaccharides. Mass spectrometric analyses indicated the ceramide moiety of the glycolipid to be composed predominantly of hydroxy fatty acids (C20:0, C22:0, C23:0, C24:0, and C25:0) and hydroxysphinganine. GalNAcalpha-1,3GalNAcbeta-1,3Galalpha-1,3[GalNAcbet a-1, 4(NeuAcalpha-2,3)Galbeta-1,4GlcNAcbeta-1,6]Galbeta+ ++-1,4Glcbeta-1, 1'Ceramide

Animals↗
PubMed1999

Electrophysiologic and blood-flow responses in the endocardium and epicardium to disopyramide and MS-551 during myocardial ischemia in the dog.

The aim of this study was to determine whether a quantitative relation exists between changes in regional myocardial blood flow (RMBF) and those in electrophysiologic determinants recorded via left ventricular endocardial and epicardial bipolar electrograms after administration of disopyramide (DP) and a class III antiarrhythmic drug, MS-551 (MS), during myocardial ischemia in the dog. Dogs were given DP (1 mg/kg, i.v., n = 14), MS (1 mg/kg, i.v., and 0.1 mg/kg/min, d.i.v., n = 13), or saline (n = 12). The effective refractory period (ERP) was determined by an S1-S2 extrastimulus method, and RMBF by a nonradioactive microsphere technique. The duration of regional electrograms (DRE) was measured as an indicator of conduction time in the myocardium. DP blunted ischemia-induced shortening of ERPs and lengthened DREs at the endocardial and epicardial sites, with a greater effect seen epicardially (p < 0.01 each). DP reduced RMBF, especially at the endocardial surfaces of the ischemic zone (p < 0.05). MS prolonged ERPs at the endocardial and epicardial sites in the ischemic and normal zones (p < 0.05-0.01), but there were no significant differences between the two sites. MS prolonged DREs (p < 0.05), but the magnitude of the prolongation of the DREs was similar to the values in the control group. MS had no effects on RMBF. DP treatment prolonged DREs at both sites in the ischemic zone more markedly than MS or saline treatment (p < 0.01 each). DP reduced RMBF at the endocardial site of the ischemic zone more markedly than MS or saline (p < 0.05 in each). Accordingly, MS prolonged ERPs, but did not increase disparities between endocardial and epicardial sites in the ischemic myocardium, whereas DP had a greater ERP-prolonging effect at the epicardial site than at the endocardial site. DP reduced endocardial RMBF more markedly than epicardial RMBF. These observations suggest that differences in ERPs between endocardial and epicardial ischemic myocardium caused by DP treatment are not due to the difference in RMBF reduction between the two tissue layers, and that DP and MS do not affect the same population of ion channel(s) when ERPs are prolonged.

Animals↗
PubMed1999

Vitiligo: clinical findings in 1436 patients.

We retrospectively analyzed the clinical and epidemiological profiles of patients with vitiligo attending the pigmentary dermatoses clinic. One thousand four hundred and thirty-six patients were seen between 1989 and 1993. Males constituted 54.5% of the group and females 45.5%. Mean age of the patients was 25 years, and average disease duration at the time of hospital visit was 3.7 years. Vitiligo vulgaris was the commonest form of the disease in 1002 (69.8%) patients followed by focal vitiligo in 214 (14.9%) and segmental vitiligo in 72 (5.0%). The sites of onset were the face, trunk, and legs in descending order of frequency. Less than 20% body area involvement was seen in 1356 (94.4%) of the patients. Leukotrichia was present in 165 (11.5%), and Koebner's phenomenon was observed in 72 (5.0%). Twenty nine (2.0%) patients had associated halo nevi. Of the various diseases associated with vitiligo, atopic/nummular eczema was seen in 20 (1.4%) patients, bronchial asthma in 10 (0.7%), diabetes mellitus in 8 (0.6%), thyroid disease in 7 (0.5%), and alopecia in 6 (0.4%). A family history of vitiligo was present in 165 (11.5%) patients.

Adolescent↗
PubMed1999

Synchrotron microangiography reveals configurational changes and to-and-fro flow in intramyocardial vessels.

In 8 dogs, in situ microangiography using synchrotron radiation visualized penetrating transmural arteries (PTAs) with a diameter of >60 micrometers and allowed quantitation of vessel diameters of >140 micrometers. Myocardial contraction reduced the vascular short-axial diameters to 87 +/- 17% (n = 62, P < 0.001, paired t-test) of the end-diastolic values and increased the longitudinal dimension to 129 +/- 5% (n = 45, P < 0.001). The diameter reduction in the subendocardial PTA segments was significantly more marked than that in the subepicardial PTA segments (60 +/- 12 vs. 88 +/- 12%, n=13, P < 0.001, paired t-test). Intracoronary administration of dobutamine (0.1 micrograms. kg-1. min-1) increased, and in contrast, partial clamping of the coronary artery (ischemia) decreased, the configurational changes. To-and-fro blood flow was clearly observed in PTAs with visual identification of capacitive backflow, resistive forward flow during ischemia on coronary arteriography, and even under baseline conditions in coronary venography. Thus this method advances our understanding of mechanical influences on the coronary circulation.

Animals↗
PubMed1999

Branching patterns of intramural coronary vessels determined by microangiography using synchrotron radiation.

The intramural coronary artery (IMCA) with a diameter of 50-500 micrometers is critical for blood supply to the inner layers of heart muscle. We introduced digital measurement to microangiography using monochromatic synchrotron radiation and quantified branching patterns of the IMCA, the epicardial coronary artery (EPCA), and the distal ileal artery (DIA). The pre- and postbranching diameters were measured (95-1,275 micrometers) in seven dogs. A typical arterial segment divided into two nearly equivalent branches, and a regression line of daughter-to-mother diameter plots was almost identical among the EPCA (y = 0.838x - 16.7 in micrometers), IMCA (y = 0.737x - 2.18), and DIA (y = 0.755x + 8.63). However, a considerable difference was present at a segment where a proximal IMCA branched off from an EPCA (y = 0.182x + 90.2). Moreover, a proximal IMCA diameter had no relationship to the branching order from an EPCA. The precision of this method was confirmed by the good correlation of diameter measurements between two independent observers (r = 0.999, y = 1.02x - 1.07). In conclusion, using digital microangiography we demonstrated that the self-similar branching pattern of coronary arteries was discrete at the connection between the IMCA and EPCA.

Angiography↗
PubMed1999

Intramyocardial vascular volume distribution studied by synchrotron radiation-excited X-ray fluorescence.

We evaluated the vascular volume distribution with fine resolution (0.1-1.3 mg myocardial tissue) in the sagittal plane of the left ventricle by using the microsphere filling method in 21 dogs. The coronary arterial volume density in the sagittal plane did not exhibit normal distribution and was characterized by variability among the outer-to-inner layers and within the layers (+2SD/-2SD > 80 times), and the median values in the layers ranged from 4.7 to 22. 9 nl/mg myocardial tissue. The fractal analysis of vascular volume revealed a self-similar nature with a fractal dimension (D value) similar to that of flow distribution (1.20 +/- 0.05 and 1.24 +/- 0. 09 for vascular volume and flow distribution, respectively) and had a more marked variability than the flow. The correlation of the regional vascular volume between adjacent regions decreased as the distance increased. However, the correlation coefficients in the endocardial-to-epicardial direction were significantly higher than those in the anterior-to-posterior direction (P < 0.05 by paired t-test). In conclusion, we determined intramyocardial vascular volume density in the sagittal plane, and the distribution revealed considerable variability, self-similarity, and asymmetry in the correlation among the adjacent regions. These observations could be related to the characteristics of the intramural coronary vascular network.

Animals↗
PubMed1999

Prediction of coronary artery lesions in unstable angina by iodine 123 beta-methyl iodophenyl pentadecanoic acid (BMIPP), a fatty acid analogue, single photon emission computed tomography at rest.

Iodine 123 beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP), a beta-methyl-branched fatty acid analogue, has been proven by experimental studies to reveal abnormalities in fatty-acid-related metabolism. This study was undertaken to validate the accuracy and limitations of 123I-BMIPP imaging at rest in detecting myocardial metabolic abnormalities and predicting coronary lesions in unstable angina (UA). One hundred UA patients without prior myocardial infarction were studied. 123I-BMIPP and thallium 201 chloride (201TlCl) imaging with single photon emission computed tomography (SPECT) and coronary and left ventricular cineangiography (LVC) were performed 1 week after the last episode of angina. There was reduced uptake of 123I-BMIPP imaging in 70 patients, reduced uptake of 201TlCl in 41, and abnormal LVC contraction in 49 patients. There were significant increases in severity scores of 123I-BMIPP imaging along with increases in the number of stenosed coronary arteries and the severity of stenosis in individual coronary arteries. There was a significant reduction in 123I-BMIPP severity scores 1 month after percutaneous transluminal coronary angioplasty (p < 0.01) and a significant correlation between the severity scores of 123I-BMIPP and LVC (r=0. 579, p<0.001). Overall rates of sensitivity and specificity in detecting significant coronary stenosis by 123I-BMIPP imaging were 74% and 86%, respectively, whereas rates of sensitivity and specificity in detecting significant coronary stenosis by 201TlCl were 31% and 91%, respectively. 123I-BMIPP sensitivity increases to 86% if only advanced coronary stenosis of >90% is included. In conclusion, 123I-BMIPP myocardial imaging is an effective method of predicting coronary artery lesions of UA patients without provocative test.

Adult↗
PubMed1999

Non-surgical reduction of septal myocardial mass in a patient with hypertrophic obstructive cardiomyopathy.

Non-surgical reduction of septal myocardial mass was performed with success in a 48-year-old male with hypertrophic obstructive cardiomyopathy. Angioplasty balloon inflated in the first septal branch of the left anterior descending artery dramatically reduced the pressure gradient across the outflow tract of the left ventricle. Following injections of absolute alcohol into the artery with the balloon kept inflated induced a small septal myocardial infarction. By hemodynamic evaluation, the peak pressure gradient of 108 mmHg before the procedure was decreased to 30 mmHg. Clinical improvement in New York Heart Association (NYHA) functional class was obtained. At 3-month follow-up, the patient was doing quite well; the gradient was only 10 mmHg at rest and 25 mmHg with Valsalva maneuver.

Angioplasty, Balloon↗
PubMed1999

[Percutaneous transluminal septal ablation with ethanol in hypertrophic obstructive cardiomyopathy: a case report].

A 48-year-old man with hypertrophic obstructive cardiomyopathy was treated by nonsurgical septal ablation. He had previously received medical treatment using atenolol and verapamil, but severe symptoms of chest discomfort, dyspnea, and shortness of breath had persisted for 2 years. Under coronary angiography control, the first major septal branch of the anterior descending coronary artery was catheterized with a 2.0 mm coaxial percutaneous transluminal coronary angioplasty balloon catheter. After inflation of the balloon, 1.5 ml of absolute alcohol was slowly injected into the septal artery to induce a small septal infarction. The left ventricular outflow pressure gradient was decreased from 108 before to 30 mmHg after the procedure as measured by Doppler echocardiography. His chest symptom improved from New York Heart Association class III to II and left ventricular outflow gradient was maintained at 0 mmHg (at rest) at 3 months after treatment. This is a new, less invasive treatment using catheterization instead of surgical myectomy. The indication, complication, and long-term effect of the treatment must be carefully evaluated, but this is expected to become a useful method.

Angioplasty, Balloon, Coronary↗
PubMed1998

Functional compensation of the low platelet count by increased individual platelet size in a patient with May-Hegglin anomaly presenting with acute myocardial infarction.

Platelets are known to play a crucial role in normal hemostasis as well as in thrombus formation at sites exposed to blood flow, as in coronary thrombosis. Thus, low platelet count is a strong negative risk factor for the occurrence of arterial thrombosis, such as occurs in acute myocardial infarction. We encountered a patient with May-Hegglin anomaly, presenting with acute myocardial infarction in his sixth decade, even though his platelet counts had always been less than 50 x 10(3)/microl. We investigated the characteristics of his platelets under the effect of shearing and found that shear-induced platelet aggregation and binding of soluble von Willebrand factor (vWF) to platelets could be induced, even when the patient's platelet count was less than 10 x 10(3)/microl, but that virtually no aggregation or vWF binding by normal platelets could be induced by shearing when platelet counts were less than 50 x 10(3)/microl. We conclude that the low platelet counts in a patient with May-Hegglin anomaly can be functionally compensated for by larger individual platelets, in view of the vWF-dependent platelet thrombus formation occurring under the effect of blood flow and that that is why most patients with May-Hegglin anomaly do not have a bleeding tendency, even though their platelet counts are very low.

Blood Platelets↗
PubMed1998

3-Amino-5-hydroxybenzoic acid synthase, the terminal enzyme in the formation of the precursor of mC7N units in rifamycin and related antibiotics.

The biosynthesis of ansamycin antibiotics, like rifamycin B, involves formation of 3-amino-5-hydroxybenzoic acid (AHBA) by a novel variant of the shikimate pathway. AHBA then serves as the starter unit for the assembly of a polyketide which eventually links back to the amino group of AHBA to form the macrolactam ring. The terminal enzyme of AHBA formation, which catalyzes the aromatization of 5-deoxy-5-amino-3-dehydroshikimic acid, has been purified to homogeneity from Amycolatopsis mediterranei, the encoding gene has been cloned, sequenced, and overexpressed in Escherichia coli. The recombinant enzyme, a (His)6 fusion protein, as well as the native one, are dimers containing one molecule of pyridoxal phosphate per subunit. Mechanistic studies showed that the enzyme-bound pyridoxal phosphate forms a Schiff's base with the amino group of 5-deoxy-5-amino-3-dehydroshikimic acid and catalyzes both an alpha, beta-dehydration and a stereospecific 1,4-enolization of the substrate. Inactivation of the gene encoding AHBA synthase in the A. mediterranei genome results in loss of rifamycin formation; production of the antibiotic is restored when the mutant is supplemented with AHBA.

Actinobacteria↗
PubMed1998

Antibodies to GT1a ganglioside in patients with Guillain-Barré syndrome.

Serum antibodies from 8 (13%) of 62 patients with the acute Guillain-Barré syndrome (GBS) and 1 of 3 patients with the Miller Fisher syndrome (MFS) recognized a minor ganglioside in bovine and human brain trisialoganglioside fractions. The ganglioside antigen migrated between GD1a and GD1b on thin-layer chromatograms. The structure of this ganglioside was established to be GT1a by thin-layer chromatography blotting and mass spectrometry. GT1a a ganglioside was also detected in human and bovine peripheral nerves by thin-layer chromatogram immunostaining. Serum from the GBS patients had IgM, IgG, or IgA antibodies against GT1a detectable by enzyme-linked immunosorbent assay (ELISA). Serum from the MFS patient also had elevated levels of IG against GT1a. None of the sera from 43 patients with other neurological diseases or from 24 healthy controls reacted with GT1a. Sera from 6 of 8 GBS patients with anti-Gt1a antibodies also reacted with GQ1b. There was no difference in the incidence of anti-GT1a immunoglobulins in acute GBS patients with or without oculomotor abnormalities. Levels of anti-GT1a antibodies correlated temporally wit clinical symptoms in GBS patients. Although the incidence of dysphagia was slightly higher in GBS patients with anti-GT1a antibodies than in those without, the number of patients studied may have been too small to detect an association between anti-GT1a antibodies and an a specific clinical variant of GBS. Our data demonstrate that a proportion of GBS patients have antibodies against GT1a ganglioside and suggest that these antibodies may play a role in the pathogenesis of neuropathy in GBS.

Adult↗