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Biomedical subjects

M Shibata

Publications and source records attributed to M Shibata.

At least 631 records · Page 35Linked to original sources

A streptothricin-like antibiotic mixture, A-269A (and A-269A').

A streptothricin-like antibiotic, A-269A (referred to as A-269A hereafter) was isolated from the culture broth of Streptomyces sp., strain No. A-269. In this paper, the characterization of the producer, and the production, isolation, physico-chemical properties and biological properties of A-269A are reported. The structure of the antibiotic was also examined by 1H NMR, 13C NMR and fast atom bombardment mass spectra studies. From the spectroscopic data, A-269A was assumed to be a mixture of antibiotic LL-BL 136 and an isomeric compound in which the carbamoyl group is substituted on C-12' hydroxyl instead of C-10 hydroxyl.

Aminoglycosides↗

On the structure-activity relationship of histamine H2-receptor antagonists based on the X-ray crystal structures and 1H-NMR spectra of amidine derivatives.

The conformation of six amidine compounds, which possess a common 3-[(4-thiazolyl)methylthio]propionylamidine framework but exhibit different activities as histamine H2-receptor antagonists, have been subjected to both single crystal X-ray structural and 1H-NMR analyses. The X-ray studies suggest a correlation between antagonist activity and the relative spatial orientation of the thiazolyl and amidine nitrogen atoms. This correlation is supported by a comparison of the conformations observed for the amidines with those of other H2-receptor antagonists and reveal that a folded conformation, specifically the NH...N intramolecular hydrogen-bonded configuration, is important for antagonist activity. The 1H-NMR measurements on the active amidine compounds show that the intramolecular NH...N bond is likely to be present in solution.

Amidines↗

IgG antibody level to mycobacterial glycoprotein in pulmonary tuberculosis by ELISA.

Sera from patients with active pulmonary tuberculosis and sera from appropriate control individuals were assayed for IgG, IgA and IgM antibodies against glycoprotein from tubercle bacilli by an enzyme-linked immunosorbent assay. The mean antibody levels in IgG and IgA were significantly higher in the tuberculosis patients than in the controls. By measuring IgG antibody, this assay may provide a diagnostic tool to distinguish patients with active pulmonary tuberculosis from patients with other pulmonary disease.

Enzyme-Linked Immunosorbent Assay↗

Computer modeling of the neurotoxin binding site of acetylcholine receptor spanning residues 185 through 196.

A model of the complex between the acetylcholine receptor and the snake neurotoxin, cobratoxin, was built by molecular model building and energy optimization techniques. The experimentally identified functionally important residues of cobratoxin and the dodecapeptide corresponding to the residues 185-196 of acetylcholine receptor alpha subunit were used to build the model. Both cis and trans conformers of cyclic L-cystine portion of the dodecapeptide were examined. Binding residues independently identified on cobratoxin are shown to interact with the dodecapeptide AChR model.

Amino Acid Sequence↗

Interaction scheme of the binding of acetylcholine receptor with cobratoxin and erabutoxin.

Snake toxins bind to the periphery of acetylcholine receptor which overlaps with the agonist site, thus inhibiting the ion channel opening mechanism. It has been proposed (Stroud and Finer-Moore, 1985) that the residues lying between Cys 130 and Cys 142 of the alpha-subunit of the acetylcholine receptor participate in the binding of toxins. A three-dimensional model of acetylcholine with cobratoxin and erabutoxin is built based on the interaction scheme proposed by Smart et al. (1984). The differences in the hydrogen bonding schemes between the two complexes are discussed. The results show the effect of the conservative substitution (Asp/Glu) at position 42 in the toxins on the binding interactions.

Animals↗

Aging and urinary bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of age on induction of carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6] in the urinary bladder epithelium was examined in 130 male and 130 female F344 rats. Rats of both sexes 6, 52, and 98 weeks old were given 0.025% BBN in their drinking water for 20 weeks. Then approximately half the rats were sacrificed, while the rest were maintained without further treatment for 10 weeks. Examination of the rats revealed an age-related increase in the induction of urinary bladder carcinoma, although the total intakes of BBN and urinary excretions of its proximate carcinogen were not age related. Rats treated with BBN at 98 weeks of age developed more squamous cell carcinomas and invasive carcinomas than the 2 younger groups. This study demonstrated an increased risk of urinary bladder carcinogenesis with age in animals.

Aging↗

Carcinogenicity of bucetin in (C57BL/6 X C3H)F1 mice.

The carcinogenicity of bucetin [(3-hydroxy-p-butyrophenetidide) CAS: 1083-57-4], an antipyretic analgesic drug, was examined in 300 (C57BL/6 X C3H)F1 mice. Groups of 50 mice of each sex were treated with 1.5 or 0.75% bucetin in their basal diet for 76 weeks and then fed a basal diet for 8 weeks. Control groups were given a basal diet for 84 weeks. In 10 of 46 (22%) male mice given the high dose of bucetin and in 6 of 45 (13%) given the low dose, renal cell tumors were induced. Dysplastic lesions of the proximal tubules were frequently seen in the males given bucetin in a dose-related fashion. Neither tumorous nor preneoplastic lesions developed in the kidneys of bucetin-treated female mice and control animals. Papilloma of the urinary bladder in 1 male mouse and papillary or nodular hyperplasia in 9 mice of both sexes were observed in groups given the high dose of bucetin.

Aminophenols↗

[Thirty-five cases of tuberculosis in childhood].

Thirty five children with tuberculosis admitted to the Hokkaido University Hospital from 1970 through 1984 wer reviewed. They were 7 cases of meningeal tuberculosis, 8 of military tuberculosis, 15 of primary tuberculosis and 5 of adult type pulmonary tuberculosis. Fifteen (43%) of the 35 cases were below 2 years, and over half of these younger cases were hematogenous spread such as meningeal and military types. Instead of hematogenic spread in these cases, erythrocyte sedimentation rate and CRP stayed in moderate values. Thirty one (91.2%) of the 34 cases having precise record had no history of BCG inoculation. Over half of the cases were infected from adults in the immediate household, and the sources of infection were found after the diagnosis of childhood tuberculosis in about half of these cases. Although incidence of the childhood tuberculosis are decreasing in recent years, childhood tuberculosis resulting hematogenous spread with poor prognosis in advanced state still exists, so it is important to remark the childhood tuberculosis at out patient clinics.

Adolescent↗

[Pharmacokinetic and clinical studies of cefuzonam in pediatrics].

Pharmacokinetic and clinical studies were conducted to evaluate cefuzonam (L-105, CZON), a new cephem type antibiotic, in the pediatric field. A total of 9 pediatric patients (2-14 years) was treated with intravenous injection of CZON: 4 cases with one shot of 20 mg/kg, 2 cases with one shot of 40 mg/kg and 3 cases with drip infusion over 1 hour of 40 mg/kg. CZON concentrations in serum and the excretion in urine were determined. Mean serum concentrations of CZON after one shot intravenous injection of 20 mg/kg were 49.0, 22.7, 9.03, 2.13, 0.37, and 0.09 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg one shot intravenous injections, mean serum concentrations were 117.5, 68.0, 26.2, 8.80, 0.63 and 0.19 micrograms/ml at 15, 30 minutes, 1, 2, 4 and 6 hours, respectively. With 40 mg/kg intravenous drip infusions over 1 hour, mean concentrations were 57.1, 78.8, 12.9, 1.12 and 0.23 micrograms/ml at 30 minutes, 1, 2, 4 and 6 hours, respectively. Mean half-lives were 0.69 hour for 20 mg/kg one shot injections, 0.44 hour for 40 mg/kg one shot injections, and 0.58 hour for 40 mg/kg 1 hour drip infusions. Urinary recovery rates in 6 hour after administration were 70.8% (mean) for the 20 mg/kg one shot injection, 44.1% (1 case) for the 40 mg/kg one shot injection, and 60.0% (mean) for the 40 mg/kg 1 hour drip infusion. CZON was administered in 26 cases of pediatric infections, and the clinical efficacy, antibacterial activity, and side effects were evaluated. Of the 26 cases 2 were excluded for the reason of not having bacterial infection, and the remaining 24 cases were assessed. Included in the 24 cases were 16 cases of acute pneumonia, 2 cases of acute purulent lymphadenitis, and 1 case each of acute bronchitis, acute purulent otitis media, acute apical periodontitis, staphylococcal scalded skin syndrome (SSSS), acute pyelonephritis, and acute enteritis. Clinical efficacy evaluation showed 19 excellent cases and 5 good cases, with an efficacy rate of 100%. Bacteriologically, Staphylococcus aureus 1 strain, Streptococcus pneumoniae 1 strain, beta-Streptococcus 1 strain, Haemophilus influenzae 10 strains, Haemophilus parainfluenzae 1 strain, Proteus mirabilis 1 strain, and Campylobacter jejuni 1 strain were determined or assumed as pathogens, but all of them were eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

Multistep modeling (MSM) of biomolecular structure application to the A-G mispair in the B-DNA environment.

A multistep modeling procedure has been evolved to study the structural changes introduced by lesions in DNA. We report here the change in the structure of regular B-DNA geometry due to the incorporation of Ganti-Aanti mispair in place of a regular G-C pair, preserving the helix continuity. The energetics of the structure so obtained is compared with the Ganti-Asyn configuration under similar constrained conditions. We present the methodology adopted and discuss the results.

Computer Graphics↗

Multistep modeling of protein structure: application to bungarotoxin.

Modelling of bungarotoxin in atomic details is presented in this article. The model-building procedure utilizes the low-resolution crystal coordinates of the c-alpha atoms of bungarotoxin, sequence homology within the neurotoxin family, as well as high-resolution x-ray diffraction data of cobratoxin and erabutoxin. Our model-building procedure involves: (a) principles of comparative modelling, (b) embedding procedures of distance geometry, and (c) use of molecular mechanics for optimizing packing. The model is not only consistent with the c-alpha coordinates of crystal structure, but also agrees with solution conformational features of the triple-stranded beta sheet as observed by NOE measurements.

Bungarotoxins↗

Promoting effect of sodium chloride in 2-stage urinary bladder carcinogenesis in rats initiated by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The promoting effect of sodium chloride (NaCl) in 2-stage urinary bladder carcinogenesis in F344 rats initiated by 2 doses of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was investigated. The incidences of PN hyperplasia were significantly higher in rats initiated with 0.01 or 0.05% BBN when they were given diet containing 10% NaCl for 32 weeks than when they were given control diet. The incidence of papilloma in rats given 0.05% BBN followed by diet containing 10% or 5% NaCl tended to be higher than that in control rats. The urine of rats given diet containing NaCl was larger in volume and had lower osmolality than that of controls. The total urinary sodium and chloride contents were also increased, whereas those of potassium and phosphorus were decreased. No calculus formation or crystalluria was observed. These data suggest that excess intake of sodium as NaCl has a weak promoting effect in 2-stage urinary bladder carcinogenesis.

Animals↗

Comparison of influences of stimulation of the Ammon's horn and subiculum to thermosensitive preoptic and septal neurons.

Thermosensitive preoptic and septal (PO/SP) neurons were studied for their responsiveness to electrical stimulation of the dorsal Ammon's horn (DAH) and the ventral subiculum (VSB) of the hippocampal formation in the rat. DAH stimulation affected only 14 (16%) of 90 PO/SP thermosensitive neurons whereas VSB stimulation affected 77 (86%) units. The results suggests that the DAH has no major role in thermoregulation in the rat.

Animals↗

Responses of preoptic thermosensitive neurons to poikilothermia-inducing peptides--bombesin and neurotensin.

Microelectrophoretic application of bombesin (BS) and neurotensin (NT) to thermosensitive and non-thermosensitive neurons in the preoptic and anterior hypothalamus (PO/AH) of anesthetized rats depressed the activity of 78 (54.2%) of 144 neurons and that of 66 (51.6%) of 128 neurons, respectively. The depressing effects of both peptides which were uniformly observed across warm-sensitive and cold-sensitive neurons in the PO/AH are consistent with their poikilothermic actions.

Animals↗

Step response analyses of the cardiovascular system and their application to the measurement of systemic and pulmonary vein compliances.

A theoretical analysis of the step response in the closed cardiovascular system induced by a sudden shift of the right cardiac output curve predicted that if the relations of the right heart output (COr) and the total systemic capillary flow (CFs) to the systemic venous pressure (Psv) are linear, then the time course of Psv change will become monoexponential with a time constant T given by T = Csv/(Gr + Gs), where Csv is the systemic vein compliance and Gr and Gs are the conductances of the transient COr-Psv and CFs-Psv relationships. A similar prediction was obtained for the time constant T of the pulmonary vein pressure (Ppv) response to the step change in the left cardiac output (COl) curve, pulmonary vein compliance (Cpv) and the conductances of the COl curve, and the pulmonary capillary flow (CFp) curve against Ppv. The actual Psv or Ppv changes following sudden alteration of the COr or COl curve by inflation and deflation of the balloon in the right or left atrium revealed monoexponential time courses. Semilogarithmic plots of the transient vein pressure changes yielded correlation coefficients of -0.995 +/- 0.006 (means +/- SD) in 11 curves for Psv and 0.977 +/- 0.017 in 16 curves for Ppv (P less than 0.01). The assumed linearity of dynamic COr and COl curves was confirmed by beat by beat COr-Psv and COl-Ppv relationships during the step responses, except for the first few beats immediately after the balloon maneuver. The linearity of the dynamic CFs curve was examined by measuring CFs with a double-step balloon maneuver so as to cause rapid equilibrium between COr and CFs at varied moments of the transient process. The correlation coefficient between CFs and Psv thus obtained was 0.98 +/- 0.04 (P less than 0.01). A similar linearity of the dynamic CFp-Ppv relationship was suggested from their steady-state curves. The values of Csv calculated from the experimental data were 1.70 +/- 0.12 ml/mmHg/kg body wt in 11 curves and those of Cpv were 0.13 +/- 0.03 ml/mmHg/kg in 15 curves. These results are mostly consistent with those previously reported.

Animals↗

In vitro growth and chemosensitivity studies of childhood cancers using clonogenic assay.

We evaluated the usefulness of the recently developed Human Tumor Clonogenic Assay (HTCA) for chemosensitivity studies in childhood cancers. A total of 20 childhood cancer specimens containing 8 neuroblastomas, 4 malignant lymphomas, three hepatoblastomas, two rhabdomyosarcomas, two germinomas and one adrenal carcinoma were assayed. Overall, 65 per cent (13/20) of tumor cell specimens showed adequate colony forming ability to yield the sensitivity of anticancer drugs. The pattern of in vitro sensitivity of a particular tumor to most anticancer drugs tested was not dissimilar to the clinical experiences of these agents. The overall in vitro response rate of childhood cancers to anticancer agents was 51 per cent. A retrospective analysis of this assay revealed a true positive rate of 57 per cent and a true negative rate of 100 per cent.

Antineoplastic Agents↗