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Biomedical subjects

S Handa

Publications and source records attributed to S Handa.

At least 37 records · Page 2Linked to original sources

Beta-1-selectivity is not essential to achieve therapeutic efficacy with beta-blockade therapy for idiopathic dilated cardiomyopathy.

This study investigated the therapeutic efficacy of two different beta-blockers, metoprolol (beta 1-selective) and nipradilol (nonselective) for the treatment of idiopathic dilated cardiomyopathy (DCM). The New York Heart Association functional class improved in the metoprolol group (n = 9) and the nipradilol group (n = 9), but not in the control group who received conventional therapy (n = 8). The left ventricular ejection fraction increased in both the beta-blocker groups (p < 0.01, p < 0.05). Lymphocyte beta-adrenoceptors were upregulated in the nipradilol group (p < 0.01). Cardiac events were less common in both the beta-blocker groups than in the control group (both p < 0.05). Thus, nipradilol improved symptoms and cardiac function with a favorable effect on sympathoneuronal activity as well as metoprolol in patients with DCM. Therefore, beta 1-selectivity is not essential to achieve therapeutic efficacy with beta-blockade therapy for DCM.

Adrenergic beta-Antagonists

Effect of the angiotensin-converting enzyme inhibitor alacepril on ventricular function and beta-adrenoceptor number in rabbits with aortic regurgitation.

This study was performed to determine the effects of the angiotensin-converting enzyme inhibitor alacepril on hemodynamic variables and beta-adrenoceptor number in rabbits with heart failure induced by aortic regurgitation. Aortic regurgitation was induced by perforation of the aortic valve in 12 rabbits. Sixty mg/kg of alacepril was administered by gastric tube for 7 days after manifestation of aortic regurgitation to 6 rabbits (group AR + A). The other 6 rabbits with aortic regurgitation were administered vehicle in the same fashion (group AR + C). Seven rabbits underwent sham operation (group S). One week after induction of aortic regurgitation left ventricular end-diastolic pressure was higher and cardiac output was lower in AR + C than in S. End-diastolic and end-systolic left ventricular diameter were larger and left ventricular weight was also higher in AR + C than in S. For each of these parameters, the opposite findings were obtained from a comparison of AR + A and S. Myocardial beta-adrenoceptor density and norepinephrine content were reduced in AR + C, but were restored in AR + A. These findings indicate that alacepril has beneficial effects on ventricular remodeling and function, and on sympatho-neuronal regulation in the volume-overloaded myocardium.

Angiotensin-Converting Enzyme Inhibitors

[Identical male twins showing progression from hypertrophic cardiomyopathy to dilated cardiomyopathy-like features].

Twenty-three-year-old identical male twins with hypertrophic cardiomyopathy which progressed into the dilated phase are reported. The younger brothers first presented at age 16 with an abnormal electrocardiogram. Hypertrophic nonobstructive cardiomyopathy with an asymmetric septal hypertrophy was diagnosed. He was treated with beta-blocker, but he stopped taking the drug as he had no symptoms at that time. He presented again at age 21 years with symptoms of apparent congestive heart failure. Echocardiography showed marked dilatation of the left ventricle with thin wall which was compatible with dilated cardiomyopathy. The elder brother presented with an initial echocardiogram showing systolic anterior movement of the mitral valve without asymmetric septal hypertrophy. He presented again with his brother aged 21 years when his echocardiogram showed slight dilatation of the left ventricle, although he did not complain of cardiac symptoms. These identical twins are the first reported cases of hypertrophic cardiomyopathy progressing to the deteriorated dilated phase.

Adult

[An autopsied case of primary pulmonary hypertension complicated by hepatopulmonary syndrome].

A 57-year-old man, who had received a transfusion five years before, was admitted to our hospital complaining of worsening dyspnea on exertion. Cardiac catheterization was performed, and pulmonary hypertension was diagnosed. Liver dysfunction was also documented. We administered diuretics and observed his clinical course. Gradually worsening hypoxemia and radioisotope accumulation in the kidney following a lung perfusion scintigram suggested the existence of an intrapulmonary shunt. The patient died seven years later due to exacerbation of heart failure secondary to pulmonary infection. Autopsy revealed remarkable hypertensive pulmonary arteriopathy as well as abnormal dilation of precapillary pulmonary arterioles. Esophageal varices suggested portal hypertension. Marked hypoxemia and intrapulmonary vascular dilation suggest the contribution of an hepatopulmonary syndrome.

Dilatation, Pathologic

[Pharmacokinetic, bacteriological and clinical studies of SY5555 in the pediatric field].

Pharmacokinetic, bacteriological and clinical studies on SY5555, a new oral penem, were carried out, and the following results were obtained. 1. MICs were determined for 6 drugs, SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefaclor (CCL), cefotiam (CTM), cefpodoxime (CPDX), cefdinir (CFDN) against 20 strains of bacteria isolated from patients who were subsequently treated with SY5555. MICs of SY5555 for Gram-positive cocci ranged from 0.05 to 0.10 microgram/ml against 10 strains of Staphylococcus aureus. The MIC was < or = 0.025 microgram/ml against one strain of Streptococcus pyogenes, and MICs were from < or = 0.025 to 0.39 microgram/ml against Streptococcus pneumoniae. These MIC values were equivalent or superior to those of the other 5 drugs. MICs of SY5555 for Gram-negative bacilli were 0.39 and 6.25 micrograms/ml against Haemophilus influenzae, and these values were equivalent to those of the other drugs, except CPDX. The MIC of SY5555 was 0.39 microgram/ml against 2 strains of Escherichia coli, and this value was equivalent or superior to those of CVA/AMPC and CCL, similar or inferior to those of CPDX and CFDN, and inferior to that of CTM. The MICs of several drugs were determined for 10 strains of Bordetella pertussis and 30 strains of Campylobacter jejuni isolated from patients before this clinical study. The MICs of SY5555 against the 10 strains of B. pertussis were compared with those of 7 drugs, CCL, CTM, CPDX, ampicillin (ABPC), piperacillin (PIPC), imipenem (IPM) and erythromycin (EM). The MIC of SY5555 was 0.78 microgram/ml against all of the strains. This value was superior to those of CCL, CTM and CPDX, similar or inferior to that of IPM and inferior to those of PIPC and EM. The MICs of SY5555 against the 30 strains of C. jejuni were compared with those of 7 drugs. CCL, CTM, CPDX, CFDN, ABPC, IPM and EM, and the MIC of SY5555 was < or = 0.025 microgram/ml or 0.05 microgram/ml and these values were equivalent or superior to those of the 7 reference drugs. 2. SY5555 dry syrup was administered orally at 30 min. after meals, to a total of 5 patients, at doses of 5.0 and 10.0 mg/kg to 2 patients each and at a dose of 15.0 mg/kg to one patient and the plasma concentrations were determined. Peak concentrations were detected 1 to 3 hours after administration in all patients and the peak concentrations were 0.93 and 1.21 micrograms/ml at the 5.0 mg/kg dose, 2.85 and 5.49 micrograms/ml at the 10.0 mg/kg dose and 5.79 micrograms/ml at the 15.0 mg/kg dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral

Structure of a novel phosphocholine-containing glycoglycerolipid from Mycoplasma fermentans.

Mycoplasma fermentans is thought to be a pathogen of rheumatoid arthritis or cofactor of AIDS. A novel phosphocholine-containing glycoglycerophospholipid named GGPL-I was isolated from a M. fermentans-infected human helper T-cell culture. It was revealed that GGPL-I is a lipid component of the M. fermentans and a major immunological determinant. The GGPL-I was purified by DEAE-Sephadex column chromatography and repeated Iatrobeads column chromatography. The purified glycophospholipid was subjected to structural characterization by thin-layer chromatography, Fourier-transform infrared spectrometry, liquid secondary ion mass spectrometry, and nuclear magnetic resonance spectroscopy. Its structure was determined to be as follows: 6'-O-phosphocholine-alpha-glucopyranosyl-(1'-3)-1,2-diacyl-sn-glycerol. This glycoglycerophospholipid is unique in containing phosphocholine, which is attached to C-6 of glucose. The stereospecific numbering (sn) of naturally occurring GGPL-I was determined through comparison with chemically synthesized compounds.

Carbohydrate Conformation

Effect on short-term prognosis and left ventricular function of angina pectoris prior to first Q-wave anterior wall acute myocardial infarction.

The prognostic significance of angina pectoris before the development of first Q-wave anterior wall acute myocardial infarction (AMI) was assessed in 153 patients. A total of 100 patients in this study had angina before Q-wave AMI, whereas 53 patients had no antecedent symptoms of angina. The presence of angina before AMI was associated with a lower incidence of complications including sustained ventricular tachycardia or fibrillation (7% vs 25%, p = 0.0022), pump failure (24% vs 47%, p = 0.0035), cardiac rupture (1% vs 17%, p = 0.0001), and a lower in-hospital mortality rate (11% vs 28%, p = 0.0067). The peak creatine phosphokinase activity was lower in patients with than without antecedent angina (1,727 +/- 1,238 vs 2,675 +/- 2,569 IU/liter, respectively, p = 0.023). There was no difference in the prevalence of multivessel coronary artery disease or the presence of collateral circulation between the 2 groups. Left ventriculography revealed a higher left ventricular ejection fraction (54 +/- 13% vs 46 +/- 11%, p = 0.034) and smaller left ventricular end-diastolic volumes (75 +/- 15 vs 86 +/- 18 ml/m2, p = 0.017) in patients with than without antecedent angina. These findings suggest that the presence of angina before AMI may be associated with a protective effect on left ventricular function during anterior wall AMI. Although the precise mechanisms underlying the beneficial effects are unknown, they may be related to the development of collateral channels or ischemic preconditioning.

Adult

A new method for detecting beta 1,4-galactosyltransferase activity in sera of cancer patients.

A new method for assaying the activity of the enzyme that catalyzes the formation of a cancer-associated glycolipid, paragloboside (nLc4Cer), from lactotriaosylceramide (Lc3Cer) and UDP-galactose has been developed that is based on a time-resolved fluoroimmunoassay (TRFIA) with a Europium (Eu)-chelate-labeled antibody. The substrate, Lc3Cer, immobilized on a microtiter plate, was incubated with UDP-galactose, MnCl2, Triton CF-54, and the enzyme. The content of the incubation product, nLc4Cer, was determined by the TRFIA with anti-nLc4Cer monoclonal antibody H-11 as the first antibody and Eu-labeled anti-mouse IgM antibody as the second one. The lower limit of detection of nLc4Cer was estimated to be 0.2 pmol. This method was used to detect the galactosyltransferase activity in sera from patients with colorectal cancer or benign colorectal adenomas and from healthy subjects of a reference sample group. The reference interval was 0-0.25 pmol/25 microliters serum/2 h. Activity was significantly greater in patients with colorectal cancer than in those with colorectal benign adenoma (P < 0.05) and the subjects of the reference sample group (P < 0.01).

Adenoma

Molecular mimicry between GQ1b ganglioside and lipopolysaccharides of Campylobacter jejuni isolated from patients with Fisher's syndrome.

We isolated Campylobacter jejuni from 2 patients with Fisher's syndrome subsequent to enteritis. Crude lipopolysaccharide fractions were extracted from the bacteria and separated by thin-layer chromatography. Monoclonal antibodies to GQ1b ganglioside (GMR13 and 7F5) reacted with both lipopolysaccharide fractions, indicating that the lipopolysaccharides bear the GQ1b epitope. This is the first report of molecular mimicry between neural tissue components and the antecedent infectious agents of Fisher's syndrome.

Antibodies, Monoclonal

Blotting of glycolipids and phospholipids from a high-performance thin-layer chromatogram to a polyvinylidene difluoride membrane.

A simple method of blotting glycosphingolipids from a high-performance thin-layer chromatography (HPTLC) plate to a polyvinylidene difluoride (PVDF) membrane is described. The developed HPTLC plate is dipped in a solvent mixture (isopropanol/0.2% CaCl2/methanol, 40/20/7 by volume) for blotting, after which first a PVDF membrane and then a glass microfiber filter is placed on the plate. The assemblage then is pressed for 30 s with heating. Most of the glycosphingolipids that are separated on the HPTLC plate can be blotted quantitatively and detected with the reagents used on the plate. Detection of the glycosphingolipids on the membrane was confirmed to be more sensitive than that on the HPTLC plate by both chemical visualization and immunological staining. The glycosphingolipids blotted on the membrane could be reextracted. Blotting of phospholipids can be done by the same method. The results suggest that this method can be used in the purification and characterization of glycosphingolipids and in the detection of proteins which recognize glycosphingolipids and phospholipids.

Animals

A simple and quantitative purification of glycosphingolipids and phospholipids by thin-layer chromatography blotting.

A new and simple method for purifying glycosphingolipids and phospholipids by using "TLC blotting" was established. Glycosphingolipids separated by two-dimensional thin-layer chromatography (TLC) were made visible with primuline reagent, and then bands were marked with a drawing colored pencil. The glycosphingolipids that separated on the HPTLC plate were transferred by TLC blotting to a polyvinylidene difluoride membrane together with the color marks. The marked areas were excised after which their glycosphingolipids were extracted and monitored by TLC. By this method, 20 glycosphingolipids showing homogeneous bands on a HPTLC plate were isolated from the neutral glycosphingolipid fraction of human meconium. Moreover, 10 kinds of acidic glycosphingolipids were purified as homogeneous bands from the bovine acidic glycosphingolipid fraction. The yields of glycosphingolipids (13 different ones) ranged from 68 to 92%, the mean value being 82.3%. The glycosphingolipids were confirmed to be purified as intact forms by mass spectrometric analysis and chromatographic mobilities on a HPTLC plate. The same procedure could also be used to purify phospholipids.

Animals

Abnormalities in sympathoneuronal regulation are localized to failing myocardium in rabbit heart.

OBJECTIVES: This study investigated the differences in sympathoneuronal regulation between acute left ventricular failure and chronic biventricular failure to determine whether an increase in plasma norepinephrine concentration plays a primary role in the genesis of the desensitization phenomenon in heart failure. BACKGROUND: It remains to be determined whether plasma norepinephrine plays a primary role in the pathogenesis of sympathetic desensitization in heart failure in vivo. METHODS: Acute left ventricular failure was induced by aortic regurgitation in seven rabbits. Chronic heart failure was induced by adriamycin treatment in another seven rabbits. RESULTS: Cardiac output was lower in rabbits with aortic regurgitation than in seven sham-operated rabbits. Left ventricular end-diastolic pressure was higher in rabbits with aortic regurgitation, but no significant difference in right ventricular end-diastolic pressure was observed. Beta-adrenoceptor density and norepinephrine concentration in the left ventricular myocardium were lower in rabbits with aortic regurgitation; no such differences were observed for the right ventricular myocardium. Cardiac output was lower in adriamycin-treated rabbits than in seven control rabbits. Both left and right ventricular end-diastolic pressures were higher in experimental rabbits than in control rabbits. Myocardial beta-adrenoceptor density and norepinephrine content were reduced in both ventricles. CONCLUSIONS: In chronic heart failure induced by adriamycin, sympathoneuronal activity was altered in both ventricles, whereas in acute left ventricular failure induced by aortic regurgitation, sympathoneuronal activity was affected only in the left ventricle despite a similar increase in plasma norepinephrine concentration in both animal models. Local abnormalities in sympathoneuronal regulation in failing myocardium therefore appear to be responsible for these phenomena.

Acute Disease