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Biomedical subjects

S Handa

Publications and source records attributed to S Handa.

At least 235 records · Page 13Linked to original sources

[Serial changes in hemostatic molecular markers after urokinase therapy of acute myocardial infarction].

We have examined the changes in fibrinolysis after urokinase administration for 6 patients with acute myocardial infarction. Patients were treated with urokinase with doses between 960,000 and 1,440,000 units, and fibrinolytic activities were determined by using newly developed molecular markers: alpha 2-plasmin inhibitor (alpha 2-PI), plasminogen, alpha 2-PI plasmin complex (PIC) and FDP D dimer. We also used classical hemostatic tests such as prothrombin time (PT) and plasma fibrinogen level. These tests were measured with 1 to 2 hour intervals, during the first 6 hours of therapy, daily during the next 3 days, and subsequently on day 7 and 14. The initial intravenous administration of urokinase with a dose of 460,000 units produced a significant decrease in alpha 2-PI level, but induced only minimal changes in the level of fibrinogen, FDP-E, and FDP D-dimer, suggesting that enhancement of fibrinolytic activity was less pronounced under such therapy. This might be due to the ability of residual amounts of alpha 2-PI to sufficiently inhibit plasmin generation in the circulating blood. However, a subsequent injection of 960,000 units of urokinase into the coronary artery induced a profound reduction in the alpha 2-PI to an unmeasurable level, and resulted in a marked enhancement of fibrinolytic activity. The elevation of FDP-E and FDP D-dimer was accompanied with this decrease in alpha 2-PI and persisted for more than 6 hours after urokinase injection. Prolongation of PT due to decrease in fibrinogen level was also observed over 6 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Importance of collateral circulation to preserve the exercise capacity in patients with coronary artery disease].

We studied the effects of coronary collaterals on exercise capacity in relation with the coronary flow reserve. Thirty-one patients with single vessel disease of the left anterior descending artery (LAD) were selected using coronary angiography. Thirteen of them had angiographical collaterals. A Doppler coronary catheter was positioned in the proximal portion of the LAD, and the resting and peak coronary flow velocity was measured using an intracoronary injection of 6 ml of contrast material. Peak to resting velocity ratio was calculated as an index of the coronary flow reserve. Multi-stage treadmill exercise ECG test was performed, and the end point of the exercise was 0.1 mV depression of ST segment. The exercise capacity was expressed as the ratio of maximal to resting double product. In patients without collaterals, peak to resting coronary flow velocity ratio was correlated with double product ratio (r = 0.94, p less than 0.01). But in patients with collaterals, double product ratios were higher than those in patients without collaterals. We conclude that coronary collaterals preserve exercise capacity in spite of the low coronary flow reserve in the recipient coronary artery.

Aged↗

[Recurrent ischemia after acute myocardial infarction: clinical profile and significance of electrocardiographic ST changes during the attacks].

This study investigated the clinical characteristics of acute myocardial infarction (AMI) complicated by recurrent ischemia, especially relating to the electrocardiographic ST changes during the attacks. Fifty-six patients with AMI were complicated by recurrent ischemia (ischemia group), and 238 were not (non-ischemia group). The ischemia group was preceded by prior episodes of angina or myocardial infarction in 88%, as compared with 65% in the non-ischemia group (p less than 0.05). There were non Q wave infarction in 45% of the ischemia group, and 24% of the non-ischemia group (p less than 0.05). The overall in-hospital mortality rate was similar in the ischemia group (13%) and in the non-ischemia group (17%), although the causes were predominantly pump failure in the former and cardiac rupture in the latter. ST segment elevation occurred in 29 patients and ST depression occurred in 26 patients of the ischemia group during the attacks. Multivessel coronary arterial lesions were more frequently present in the latter subgroup than the former (38% vs 79%, p less than 0.05). The in-hospital cardiac deaths were also more frequently noted in the latter subgroup. Recurrent ischemia after AMI with concomitant electrocardiographic ST depression is a high risk subgroup, and, therefore, aggressive revascularization procedures may be indicated in such cases if suitable.

Coronary Vessels↗

[A case of myocardial infarction in a young man with systemic lupus erythematosus].

Apparently the incidence of coronary artery disease in systemic lupus erythematosus (SLE) has been increasing. However, most of the cases had been treated with corticosteroids, and had atherosclerotic lesions in the coronary arterial tree. A 21-year-old man with latent and untreated SLE had an attack of acute myocardial infarction. Coronary arteriography showed eccentric stenotic lesion at the proximal segment of the right coronary artery. One week later, in the 2nd coronary arteriography, this stenotic lesion was not able to be recognized. We supposed that the coronary artery occlusion was due to thrombus formation, and was not related to atherosclerosis, arteritis and embolus. He had no coronary risk factors. Laboratory data showed lymphocytopenia, proteinuria, positive antinuclear antibody, and positive LE cell, and the case was diagnosed as SLE. Subsequent investigations showed the presence of antibodies to cardiolipin. It was suggested that anticardiolipin antibody and other thrombogenic factors were the causes of the coronary occlusive thrombosis in this patient with SLE.

Adult↗

Structural studies of gangliosides by fast atom bombardment ionization, low-energy collision-activated dissociation, and tandem mass spectrometry.

Negative ion fast atom bombardment, low-energy collision-activated dissociation, and tandem mass spectrometry techniques were applied for the structural elucidation of gangliosides. The mass spectra were simplified by selecting a single molecular ion or fragment ion in the analysis of mixtures, and interference by background signals from the liquid matrix could be avoided. Introduction of collision-activated dissociation produced abundant fragment ions convenient for structural analysis. In the daughter scan mode, ions were produced by cleavage of the glycosidic bonds, and not by cleavage at the sugar ring. These ions all contain ceramide moieties, except the sialic acid fragment ion. In the parent scan mode, product ions resulting from cleavage at the sugar ring were detected beside the ions resulting from cleavage at the glycosidic bonds, and ions of oligosaccharide fragments were also detected. In parent scan mode spectra of gangliosides based on the sialic acid ion, all ions contained a sialic acid residue, and the observed ions were similar to those obtained in the high-energy collision-activated dissociation daughter scan mode. These results indicate the usefulness of low-energy collision-activated dissociation tandem mass spectrometry in the daughter and parent scan modes for the analysis of ganglioside structure, in combination with fast atom bombardment mass spectrometry and high-energy collision-activated dissociation mass spectrometry.

Carbohydrate Conformation↗

Had-1, a uridine 5'-diphosphogalactose transport-defective mutant of mouse mammary tumor cell FM3A: composition of glycolipids, cell growth inhibition by lactosylceramide, and loss of tumorigenicity.

Glycolipid compositions of mouse mammary tumor cell FM3A and its Newcastle disease virus-resistant mutant cell, Had-1, which was also characterized as a defective mutant of UDP-galactose transport to Golgi apparatus, have been studied. The major neutral glycolipid in FM3A was Gal beta 1-4Glc beta 1-1Cer (LacCer) (95%) and the rest was Glc beta 1-1Cer. The concentration of neutral glycolipids in Had-1 was only about one-fifth of that in FM3A. GlcB1-1Cer in Had-1 accounted for 79% of neutral glycolipids and the rest was LacCer, the content of which was decreased to 4% of that in FM3A. Ganglioside patterns of the two cell lines were similar, although gangliosides with N-glycolylneuraminic acid were increased in Had-1 cells compared with that in FM3A cells. The presence of NeuAc alpha 2-3-Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer, NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-2Cer, GM3, and GD3 was demonstrated by thin-layer chromatography immunostaining. 125I-Labeled Newcastle disease virus bound only poorly to gangliosides extracted from either FM3A or Had-1 cells on a high performance thin-layer chromatography plate. The effects of glycolipids on the growth of the two cell lines were also studied. Had-1 cells were more sensitive to glycolipids added exogenously than FM3A cells. Addition of GM3 had a stimulative effect on cell growth of Had-1. LacCer, Gal beta 1-3GalNAc beta 1-4Gal beta 1-4Glc beta 4-1Cer, and Glc beta 1-1Cer inhibited the growth of Had-1 cells. LacCer was the most potent inhibitor. LacCer immobilized on the culture plate also inhibited the growth of Had-1 cells. The inhibitory effect was recovered completely overcome by transferring the cells to LacCer-free medium. Had-1 cells were not tumorigenic in C3H/He mice, and furthermore the tumorigenic activity of FM3A cells was suppressed by the prior administration of Had-1 cells.

Animals↗

Diastolic pressure-volume relationship during handgrip exercise in patients with coronary artery disease.

There is some controversy regarding the mechanisms of an upward shift in the left ventricular diastolic pressure-volume curve during ischemia. The effects of handgrip exercise on the pressure-volume curve were examined in 21 patients with coronary artery disease and in 6 control subjects. Pressure-volume curves were constructed from digitized left ventricular pressure and volume derived from biplane left ventriculogram. Diastolic pressure-volume curve shifted upward in 12 patients with coronary artery disease during handgrip exercise (Group 1), but not in the other 9 patients who were similarly afflicted (Group 2). The upward shift did not occur in any control subject. No difference was observed in rate-pressure product gain during exercise. In Group 1, left ventricular end-diastolic pressure increased (p less than 0.01) and ejection fraction was reduced (p less than 0.01), although it did not change in Group 2. In Group 1, the time constant was prolonged (p less than 0.01) with no change in the coefficient for elastic modulus. In Group 2, these parameters remained unchanged. Group 1 was accompanied by more extensive asynergy than Group 2. Thus, isometric handgrip exercise resulted in an upward shift in the diastolic pressure-volume curve in patients with coronary artery disease. Incomplete relaxation and/or the viscoelastic properties of the left ventricle associated with ischemia could be responsible for this phenomenon.

Adult↗

The effect of beta-adrenergic blockade in dilated cardiomyopathy--a questionnaire study in Japan.

The effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 +/- 20.4 mg, mean +/- SD), propranolol (four patients, 26.3 +/- 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P less than 0.01). The mean cardiothoracic ratio decreased from 55.6% to 52.1% (P less than 0.01). The mean ejection fraction of the left ventricle measured by echocardiogram increased from 30.4% to 36.9% (P less than 0.01). Exercise tolerance in the treadmill test improved significantly. There was no change in blood pressure, nor were there arrhythmias seen on Holter electrocardiograms. In two patients, congestive heart failure deteriorated after administration of beta-blockers. It is concluded that beta-adrenergic blockade has a beneficial effect in most of the patients with dilated cardiomyopathy.

Adolescent↗

Uptake and metabolism of radiolabelled GM1-ganglioside in skin fibroblasts from controls and patients with GM1-gangliosidosis.

The uptake and metabolism of [3-3H-sphingosine]GM1-ganglioside was measured in cultured skin fibroblasts from controls and patients with infantile, juvenile and adult GM1-gangliosidosis. When dissolved in medium with phosphatidylserine, GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A linear increase in GM1-ganglioside endocytosis was shown with phosphatidylserine concentrations of up to 40 micrograms/ml. A pulse-chase study revealed that [3H]GM1-ganglioside was metabolized to GM2-ganglioside, GM3-ganglioside, ceramide dihexoside, ceramide monohexoside, ceramide and sphingosine. Sphingosine was recycled to sphingomyelin. In a 20-h pulse study, cell lines from patients with GM1-gangliosidosis of infantile, juvenile and adult types hydrolysed 2-5%, 20-44% and 54-58% of the total endocytosed GM1-ganglioside respectively. These values were lower than in control cells (64.17 +/- 5.43% (n = 10]. The hydrolysis rates of exogenous [3H]GM1-ganglioside in cultured fibroblasts from patients with various types of GM1-gangliosidosis closely reflected the clinical severity.

Cells, Cultured↗

Acidic glycosphingolipids of human amnion.

Six major acidic glycosphingolipids were isolated from human amnion using DEAE Sephadex A-25 and silica beads column chromatography. The structures of these glycosphingolipids were determined by methylation analysis, TLC immunostaining and/or negative ion FAB-MS, and were concluded to be II3 alpha NeuAcLacCer(GM3), IV3 alpha NeuAcnLc4-Cer (sialyl[alpha 2-3]paragloboside), IV6 alpha NeuAcnLc4Cer (sialyl[alpha 2-6]paragloboside), IV3 alpha NeuAcIII4 alpha FucLc4Cer (sialyl Lea), VI3 alpha NeuAcnLc6Cer (i-ganglioside) and II3 alpha (NeuAc alpha 2----8NeuAc)LacCer (GD3). In addition, several minor glycosphingolipids were detected with specific monoclonal antibodies, including glycolipids with NeuAc alpha 2-3Gal beta 1-4GlcNAc-beta 1- or NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1- determinant. Our results show that the glycosphingolipids of human amnion are characterized by having mainly type II chain analogues and onco-fetal antigens.

Amnion↗

Subepicardial microischemia formation induced by epicardial application of endothelin-1.

The effects of endothelin-1 (ET-1), applied topically on the epicardium, on the coronary microcirculation of the beating canine heart were investigated in situ. ET-1 (1, 10, 100, and 1,000 pmol) induced a dose-dependent elevation of the ST segment in the epicardial ECG (n = 5). After application of ET-1 (100 pmol), the beating hearts were rapidly cross-sectioned and freeze-clamped in 120 ms using a specially developed device (n = 6). By NADH fluorescence photography of the cross-sectioned frozen sample, an increased fluorescent area in the subepicardium was clearly observable. The fluorescent dye injected from the left atrium was negative in the NADH fluorescent area. It can be concluded that ET-1, when administered extravascularly, induces severe vasoconstriction and myocardial ischemia in the microcirculation of the beating canine heart.

Administration, Topical↗

Lichen planus in childhood: a report of 17 patients.

Lichen planus is a dermatosis of unknown origin with a very limited frequency in children. Over a period of one and a half years we observed 17 cases of childhood lichen planus. The classic form of the disease as seen in adults was the most common in these children; unlike adults, however, mucosal and nail involvement was uncommon. The natural history of the disease was similar to that in adults.

Age Factors↗

A case of malignant lymphoma simulating acute myocardial infarction.

A patient with malignant lymphoma suddenly collapsed, and ST segment elevation with complete atrioventricular block was observed on his electrocardiogram during an episode resembling acute myocardial infarction. Cardiac cineangiography revealed posterobasal asynergy of the left ventricle with no significant obstruction in the coronary arterial tree. Autopsy revealed diffuse invasion of the myocardium by lymphoma cells. Left ventricular wall motion was preserved even in the area of massive invasion; there was no true necrosis. Myocardial biopsy may be indicated in patients in whom there is a discrepancy between coronary pathoanatomy and wall motion abnormalities.

Diagnosis, Differential↗

Medical treatment or surgical intervention? A cooperative retrospective study on infective endocarditis--timing of operation.

Two hundred and five patients treated for infective endocarditis over the last 10 years were reviewed. There were 185 cases of native valve endocarditis (NVE) and 20 of prosthetic valve endocarditis (PVE). In the NVE group there were 175 clinically active patients and 10 non-active patients. The mortalities among 108 non-surgical and 57 surgical patients were 15.7% and 14.0%, respectively. Leading causes of deaths in the former were cardiac failure, embolism and cerebral hemorrhage. Patients with embolism showed significantly higher mortality. Culture negative endocarditis resulted in almost the same incidence of hospital death and urgent operation as staphylococcal endocarditis, and a higher incidence than streptococcal endocarditis. In 9 of 33 patients operated at our hospital, surgery was performed on an urgent basis and one NYHA class IV patient died. Indications for operation were intractable cardiac failure, uncontrollable infection and angina. In the PVE group, 3 of 4 patients operated in the active stage died of severe cardiac failure generated preoperatively. The only survivor was a patient operated early under stable hemodynamics. These results suggest that culture negative endocarditis should be observed as closely as staphylococcal endocarditis and early operation should be considered for patients with progressive cardiac failure, embolism and uncontrollable infection.

Anti-Bacterial Agents↗

Structure and sequence analysis of the human activin beta A subunit gene.

The cloned genomic DNA containing the human activin beta A subunit gene were analyzed by restriction endonuclease mapping, Southern blotting and DNA sequencing. The activin gene is composed of two exons interrupted by the 9-kb intron. The TATA, CCAAT and CT-stretch sequences were found in the 5'-flanking region of the gene. An intronic sequence contained SV40 enhancer core element in the vicinity of the exon 1. In the 3'-flanking region, we identified eight consensus polyadenylation sequences, five ATTTA motifs, CA element consisting of (CA)14, AP-1 binding site and two SV40 enhancer core elements. A dot matrix analysis revealed the high degree of conservation between the human and rat sequences within the 3'-flanking region, suggesting a possible functional significance.

Activins↗

[Coronary flow reserve and stenosis as the determinant of exercise capacity in patients with stable effort angina].

The coronary flow reserve was evaluated in 33 patients with stable effort angina and single vessel disease of the left anterior descending artery. We used a catheter-tip Doppler flow probe with injection of contrast media to the vessel in order to induce so-called reactive hyperemia. The reactive change was used as an index of the flow reserve of the coronary artery. In 15 patients out of 33, PTCA was performed and the change in the coronary flow reserve was evaluated. There was a good correlation between the coronary flow reserve and the exercise capacity in the treadmill ECG exercise test. As theoretically expected, the exercise capacity was determined by the coronary flow reserve. There was a poor correlation between the degree of stenosis shown in coronary arteriography and the coronary flow reserve. The degree of stenosis did not relate with the exercise capacity. The coronary flow reserve was increased with the procedure of PTCA. Though the patho-anatomic findings in coronary angiography give us important information to evaluate patients with ischemic heart disease, we concluded that these findings were still insufficient to allow us to estimate the flow reserve in the coronary artery. The exercise capacity did not relate well with the degree of stenosis.

Adult↗

Regulation of human renin and angiotensinogen genes.

We have constructed pUCSV0cat with low background of chloramphenicol acetyltransferase (CAT) activity and pUCSV3cat (positive control), both containing a SV40 polyadenylation signal 5' to the CAT-coding gene and to the SV40 promoter, respectively. Using this modified pUCSV0cat, we found that human embryonic 293 cells have the ability to activate the promoter of the human renin gene. In addition, we identified the cis-acting sequences responsible for cell-specific expression of the human angiotensinogen gene in its 5'-flanking region.

Angiotensinogen↗