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Biomedical subjects

S Harada

Publications and source records attributed to S Harada.

At least 631 records · Page 35Linked to original sources

[Safety evaluation of micronomicin VI. Subacute toxicity in rabbits after drip intravenous infusion].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Subacute toxicity studies of MCR in rabbits were carried out by drip intravenous infusion (d.i.v.) comparing with intramuscular injection (i.m.) for 30 days (doses; d.i.v. = 4, 25, 63 mg/kg, i.m. = 63 mg/kg). The results of the studies are as follows: Animals did not die at any dose. Renal disorders occurred mainly at the dose level of 63 mg/kg; they were almost similar to those observed when administered by i.m., and the grade of disorders in d.i.v. was the same as in i.m. The maximum safety dose was 4 mg/kg.

Aminoglycosides↗

[Clinical experience with cefoperazone in respiratory tract infections and studies on its penetration into pleural effusion].

Patients with bronchopulmonary infections were treated with cefoperazone (CPZ), and the serum and pleural effusion concentrations were determined after 2g CPZ drip infusion. The following results were obtained: Eight of 10 patients treated with CPZ responded with a significant clinical improvement. Side effects were found in 4 cases; eruption in 1 case, fever and granulocytopenia in 1 case, elevation of GPT in 1 case, and thrombocytopenia in 1 case. But these side effects disappeared immediately after cessation of CPZ treatment. Intravenous drip infusion of 2 g CPZ yielded a peak serum concentration of 112.0 --210.0 micrograms/ml immediately after the end of drip infusion, and a peak pleural effusion concentration of 8.8--43.0 micrograms/ml at 2--6 hours after the end of drip infusion. The ratio of peak pleural effusion concentration to peak serum concentration was 4.4--26.9%.

Adolescent↗

Case of sarcoidosis with uncommon tumorous mass formation in bulbar conjunctiva.

A case of sarcoidosis with ocular involvement, including uncommon tumorous mass formation on the bulbar conjunctiva, was reported. The patient was a 62-year-old woman who had been suffering from chronic bronchiolitis for several years. The conjuctival masses, yellowish brown in color with localized injection and follicles, were found in both eyes. In addition to the conjunctival masses, the common manifestations of sarcoidosis were observed in the eyes, showing nodules on the iris and trabeculum, discrete fluffy "snowball" opacities in the vitreous, and perivascular nodules on the retinal vessels. Microscopically, the biopsy specimen obtained from he conjunctival masses was composed of epithelioid tubercles with Langhans type and foreign body type giant cells. Ziehl-Neelsen stain revealed no tuberculous bacilli. Transbronchial lung biopsy also revealed epithelioid tubercles. Both ocular and pulmonary lesions were observed to respond well to treatment with corticosteroid hormone. We emphasized that patients with interstitial pneumonitis or pulmonary fibrosis should be examined ophthalmologically, and recommended conjunctival biopsy in patients with suspected sarcoidosis.

Biopsy↗

Cell-mediated immunity to Epstein-Barr virus (EBV) and natural killer (NK)-cell activity in the X-linked lymphoproliferative syndrome.

The activity of T-cell-mediated immunity to Epstein-Barr virus (EBV) was assessed by an assay of regression of the outgrowth of EBV-infected autologous B cells. Regression and natural killer (NK)-cell activities were compared for patients and their mothers from five families with X-linked lymphoproliferative syndrome (XLP) and three control groups. Seven of the 10 patients with XLP exhibited weak T-cell activity against autologous EBV-infected lymphoblastoid cell lines (LCL) comparable to EBV-seronegative controls. In contrast, 8 of 10 obligate carrier females of XLP had unusually strong activity, which was comparable to anti-early-antigen (EA) positive controls. The results of the regression assays correlated with their EBV serology: mothers showed high titers, and their affected sons showed low-titer EBV-specific antibody responses. Defective NK-cell activity was found only in the patients with XLP. NK and regression activities did not correlate. Our findings explain, in part, the vulnerability to EBV of males with XLP and why their mothers are protected from life-threatening phenotypes of XLP.

Antibodies, Viral↗

Negative inotropic effects of tiapamil (Ro11-1781) and verapamil in rabbit myocardium.

The effects of tiapamil (Ro11-1781) and verapamil on contractility were studied at 1 Hz in isolated rabbit left atrium and right ventricular papillary muscle. The ED50 of tiapamil for the depression of contractility was 33 and 18 times higher than that of verapamil in the former and latter tissue, respectively. In the presence of 100 microM of tiapamil or 10 microM verapamil, the positive staircase phenomenon in papillary muscle was reversed to a negative one. Also, the depression of contractility tended to be less in the first and second responses after a longer interruption of driving stimuli. Both drugs antagonized the inotropic effects of Ca2+ competitively and the pA2 for tiapamil was less than that for verapamil by 1.01. The potency ratios of tiapamil to verapamil for the contractility in this study correspond roughly with those found in clinical use.

Animals↗

Epstein-Barr virus-induced diseases in boys with the X-linked lymphoproliferative syndrome (XLP): update on studies of the registry.

Analyses of 100 subjects with the X-linked lymphoproliferative syndrome (XLP) in 25 kindreds revealed four major interrelated phenotypes: infectious mononucleosis, malignant B-cell lymphoma, aplastic anemia, and hypogammaglobulinemia. Eighty-one of the patients died. Two male subjects were asymptomatic but showed immunodeficiency to Epstein-Barr virus (EBV). Seventy-five subjects had the infectious mononucleosis phenotype and concurrently, 17 subjects of this group had aplastic anemia. All subjects with aplastic anemia died within a week. Aplastic anemia did not accompany hypogammaglobulinemia or malignant lymphoma phenotypes. Hypogammaglobulinemia had been detected before infectious mononucleosis in three subjects, after infectious mononucleosis in five subjects, and was not associated with infectious mononucleosis in 11 boys with hypogammaglobulinemia. In nine subjects infectious mononucleosis appeared to have evolved into malignant lymphoma; however, the majority of patients with malignant lymphoma showed no obvious antecedent infectious mononucleosis. One subject had infectious mononucleosis following recurrent malignant lymphoma. Twenty-six of 35 lymphomas were in the terminal ileum. Results of immunologic and virologic studies of 15 survivors revealed combined variable immunodeficiency and deficient antibody responses to EBV-specific antigens. Mothers of boys with XLP exhibited abnormally elevated titers of antibodies of EBV. Subjects of both sexes with phenotypes of XLP should be investigated for immunodeficiency to EBV. Persons with inherited or acquired immunodeficiency may be vulnerable to life-threatening EBV-induced diseases.

Agammaglobulinemia↗

C-19393 E5, a new carbapenem antibiotic. Fermentation, isolation and structure.

A new carbapenem antibiotic, C-19393 E5, was isolated from the culture filtrate of Streptomyces griseus subsp. cryophilus C-19393 as a minor component. The chemical structure of the antibiotic was determined by comparing its spectral data with those of the known 5,6-cis carbapenem antibiotics and confirmed by partial synthesis from epithienamycin B as shown in Fig. 1. The antibiotic has a broad antimicrobial spectrum and shows strong inhibitory activity against beta-lactamases.

Anti-Bacterial Agents↗

Beta-lactamase inhibitory activities and synergistic effects of 5,6-cis-carbapenem antibiotics.

Twelve 5,6-cis-carbapenem antibiotics were examined for their beta-lactamase inhibitory activities, their types of inhibitions, and their synergistic activities with other beta-lactam antibiotics. All the carbapenems inhibited eight types of beta-lactamases including cephalosporinases which were insensitive to clavulanic acid and sulbactam. The sulfonyloxy ethyl carbapenems were the most active inhibitors; they inhibited all beta-lactamases in a progressive fashion, whereas some of the hydroxyl compounds exerted non-progressive inhibition against several beta-lactamases such as those of Escherichia coli TN713 and Proteus vulgaris GN4413. Several carbapenems were inactivated by the beta-lactamases of Citrobacter freundii GN1706, P. vulgaris GN4413, E. coli TN713, and Klebsiella pneumoniae TN1698. Most of the carbapenems potentiated the antibacterial activities of ampicillin and cefotiam against beta-lactamase-producing bacteria.

Anti-Bacterial Agents↗

Immune deficiency in the X-linked lymphoproliferative syndrome. I. Epstein-Barr virus-specific defects.

Eleven males with XLP were evaluated for EBV-specific antibodies during periods of 2 to 7 yr. Variable responses to EBV-specific antigens were found. All 11 patients had subnormal anti-EBNA titers, which probably reflected a T cell deficiency. The patients showed four different patterns in their anti-VCA response: 1) two boys who had experienced malignant lymphoma mounted no antibodies at all; 2) two patients showed intermittent anti-VCA titers; 3) four males had persistently elevated anti-VCA titers; and 4) three patients showed normal anti-VCA titers. ADCC against EBV-infected cells was abnormally low in six patients and was elevated in two patients given gamma-globulin. ADCC titers did not correlate with anti-VCA titers. However, most patients with XLP failed to effect regression of autologous EBV-infected lymphoblastoid cell lines, indicating a deficiency in long-lived T cell-mediated immunity to EBV.

Antigens, Viral↗

[Clinical studies on cefmetazole in respiratory infections].

Cefmetazole (CMZ) was used for the treatment of respiratory infections in 10 cases; six cases of bronchopneumonia, 2 cases of acute exacerbation of chronic pulmonary emphysema or bronchitis disease, 1 case of acute exacerbation of chronic respiratory failure and 1 case of lung abscess. CMZ was administered by intravenous drip infusion at a daily dose of 2 to 4 g for 5 to 24 days. Intramuscular injection of gentamicin was combined in 2 cases. Clinical results were as follows; excellent in 6 cases, good in 2 cases, fair in 1 case and poor in 1 case. As to the side effects of the drug, allergic reaction with fever and eosinophilia was observed in 1 case. This side effect disappeared immediately after cessation of CMZ. In view of the above, CMZ may be considered to be a clinically useful antibiotic against respiratory infections.

Adult↗

Mechanism of alcohol sensitivity and disulfiram-ethanol reaction.

Human aldehyde dehydrogenase (ALDH) consists of two main isozymes with low and high Km for aldehyde. ALDH isozymes in hair sheats were tested from 40 Japanese using isoelectric focusing and blood acetaldehyde determination with gas chromatography. About 43% of Japanese, who lacked the low Km enzyme (ALDH I) showed an elevated acetaldehyde concentration due to their inability to metabolize acetaldehyde quickly and effectively. Studies regarding the inhibitory reaction of disulfiram and its metabolites have been performed. Among the metabolites, diethylamine inhibited the low Km enzyme strongly. It is presumed that vasomotor symptoms and high acetaldehyde concentration in blood after alcohol intake in patients who are treated with disulfiram might be mainly due to a decrease in activity of the low Km enzyme caused by diethylamine which is produced in vivo as one of the metabolites from disulfiram, rather than to an inhibitory reaction of disulfiram only. Thus, alcohol sensitivity in Mongoloids and disulfiram-ethanol reaction may have a common mechanism.

Acetaldehyde↗