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C Nishimura

Publications and source records attributed to C Nishimura.

At least 55 records · Page 3Linked to original sources
PubMed1992

A receptor-binding peptide from human interleukin-6: isolation and a proton nuclear magnetic resonance study.

In order to locate the receptor-binding region of human interleukin-6 (IL-6), twelve peptide fragments were prepared by digestion of IL-6 with lysylendopeptidase. A significant activity of the receptor-binding was observed only for a peptide Ile88-Lys121, although the activity was estimated at 10(4)-fold less than that of intact IL-6. Solution structure of the peptide Ile88-Lys121 was analyzed by using two-dimensional nuclear magnetic resonance (NMR) spectroscopy. The results indicate the presence of alpha-helices in the regions Leu93-Phe106 and Glu110-Ser119. On the basis of the NMR data, we also prepared two peptides. Four-fold less binding activity than that of the peptide Ile88-Lys121 was observed for the peptide Ile88-Arg105, but no activity for the peptide Glu110-Lys121. These results suggest that the helical peptide Ile88-Arg105 composes a part of the receptor-binding region.

Amino Acid Sequence↗
PubMed1992

Role of leucine residues in the C-terminal region of human interleukin-6 in the biological activity.

Site-directed mutagenesis of two sets of three periodic leucine residues which appear at every seventh position in the C-terminal region of human interleukin-6 (IL-6) was performed. Both receptor-binding and immunoglobulin (Ig)-induction activities of a triple mutant Leu168,175,182-->Val were only 1% compared with those of wild-type IL-6. However, the mutant Leu152,159,166-->Val had 13% receptor-binding and 2% Ig-induction activities of those of wild-type IL-6. In order to obtain more direct information on the receptor-binding region, we prepared two synthetic peptides. A significant binding activity was observed for the peptide Leu168-Met185, but not for the peptide Leu152-Arg169. These results indicate that leucine residues in the C-terminal region, especially Leu168, Leu175, and Leu182, play an important role in the receptor-binding and Ig-induction activities.

Amino Acid Sequence↗
PubMed1992

Site-directed mutagenesis of His-42, His-188 and Lys-263 of human aldose reductase.

The role of His42, His188, and Lys263 residues in the catalytic action of human aldose reductase was investigated in association with various inhibitors of this enzyme by site-directed mutagenesis. While mutations at His42- greater than Gln, His42- greater than Tyr, His188- greater than Gln, and His188- greater than Tyr brought small change in the kinetic parameters, Lys263- greater than Glu mutation markedly increased the Km value for the substrate DL-glyceraldehyde by a factor of 60. Lys263- greater than Met substitution resulted in approximately 14 fold elevation of Km for the substrate. By contrast, mutation of Lys263- greater than Arg significantly decreased the Km for the substrate with concomitant reduction in kcat. Moderate increase in Km values for the cofactor NADPH was demonstrated for mutated enzymes. These results are indicative of the possible role of Lys263 in the substrate binding through electrostatic interaction. The inhibitor constants (Ki) for structurally diverse aldose reductase inhibitors against mutated enzymes demonstrated different degree of alteration, indicating binding sites of aldose reductase inhibitors on the enzyme molecule vary from one another, and some of the sites are more closely correlated with the physicochemical property of Lys263.

Aldehyde Reductase↗
PubMed1992

Duration of action of supplemental doses of vecuronium is related to the duration after the initial dose.

Vecuronium was administered in an initial dose of 0.1 approximately 0.3 mg.kg(-1) and in supplemental doses of 0.03 mg.kg(-1) or 0.05 mg.kg(-1) in 74 patients (ASA class 1 or 2) scheduled for abdominal surgery. The duration of the neuromuscular blockade provided by vecuronium after both the initial and supplemental doses was determined using the evoked integrated electromyographic device. A statistically significant positive correlation (correlation coefficient: 0.83 approximately 0.91) was found between the duration of action of the initial dose and that of the first to fourth supplemental doses. The regression lines of each of the first four supplemental doses to the initial dose were very similar to each other. These results suggest that, since the duration of action of supplemental doses of vecuronium was prolonged in patients showing a long duration of action of the initial dose, it would be wise to avoid blind adherence to a predetermined schedule for supplemental administration. Rather, anesthesiologists should take into account the patient's response to the initial dose and then decide the most appropriate timing for supplemental doses. Moreover, since vecuronium shows little cumulative effect even after 4 supplemental administrations in clinical-range doses, it can be concluded that vecuronium can be safely used in a wide dose range.

Journal Article↗
PubMed1992

In-vitro activity of new carbapenem antibiotics: comparative studies with meropenem, L-627 and imipenem against pathogenic Nocardia spp.

MICs of two new carbapenems, meropenem and L-627, and imipenem were determined against 98 strains of the Nocardia asteroides group (i.e. N. asteroides sensu stricto, Nocardia farcinica and Nocardia nova), 46 strains of Nocardia brasiliensis and 17 strains of Nocardia otitidiscaviarum. Meropenem and L-627 were less active against the N. asteroides group than imipenem. Among the three species of the N. asteroides group, N. nova was the most sensitive to all the carbapenems. Meropenem was more active than imipenem against both N. brasiliensis and N. otitidiscaviarum with MIC50 values of 28.3-53.3 mg/L. L-627 was less active than meropenem.

Carbapenems↗
PubMed1992

[Clinical studies on pediatric purulent meningitis--clinical symptoms and prognosis].

In 149 patients with purulent meningitis we encountered in the period of 20 years from 1970 to 1990, their clinical symptoms and prognosis were investigated. Death or sequela was noted in many of the patients having loss of consciousness, stiffness of the members and/or cyanosis as primary clinical symptoms, or having hypoalbuminemia (less than 2.5 g/dl) and/or thrombocytopenia as abnormal laboratory findings, or having excessive protein levels and/or excessively low sugar levels in cerebro-spinal fluid. Early initiation of adequate antibiotic therapy, as well as symptomatic treatment using transfusion, steroids and anticonvulsants, are important.

Female↗
PubMed1992

[Clinical studies on pediatric purulent meningitis--statistical analysis of etiology and therapy].

In a total of 149 children with purulent meningitis we encountered in our institute in the last 20 years, the causatives, the changes in therapeutic management and the prognosis were investigated. The causatives could be detected in 109 patients (73%): H. influenzae; 30 patients (20%), S. pneumoniae; 18 patients (12%), E. coli; 13 patients (9%), GBS; 7 patients (5%) and S. aureus; 6 patients (4%). These five causatives were detected in 49% of the total patients, or 67% of the patients in whom causatives could be detected. Of these five causatives, E. coli were detected the most frequently in the first half of 1970's, but, in recent years, the detection of GBS, S. pneumoniae and H. influenzae has been remarkably increasing. In spite of progress in antibiotics, the prognosis of the disease due to S. pneumoniae, GBS and S. aureus was poor. In the majority of the patients who died, the death came within five days after hospitalization due to loss of consciousness, convulsion etc. It is therefore necessary not only to initiate strong antibiotic treatment as soon as possible after early diagnosis, but also to take symptomatic measures such as steroidal treatment, treatment of shock etc.

Anti-Bacterial Agents↗
PubMed1992

Identification and characterization of aldose reductase in cultured rat mesangial cells.

Although the enhanced activity of the polyol pathway has been detected in diabetic glomeruli, the intraglomerular localization of this pathway has not yet been well defined. In this study, we attempted to identify aldose reductase, a key enzyme of the polyol pathway, in cultured rat mesangial cells and to characterize the properties of this enzyme using enzymological and immunological methods. When the aldose reductase (DL-glyceraldehyde-reducing) activity was analyzed in mesangial cell extract, the Lineweaver-Burk plot showed concave downward curvature, and the Michaelis constant was 0.83 mM DL-glyceraldehyde, and this activity was noncompetitively inhibited by an aldose reductase inhibitor, ICI-128,436. The enzyme activity was enhanced by the addition of sulfate ion and partially suppressed by barbital. The enzyme cross-reacted with the antisera against rat lens and testis aldose reductases on Ouchterlony plate, and migrated to the region of molecular weight of about 36,500 Da on Western blotting. The presence of aldose reductase mRNA was also confirmed by Northern analysis using cDNA for rat aldose reductase, 10Q. From these results, it was concluded that the aldose reductase may exist in rat glomerular mesangial cells and may play a role in the development of diabetic glomerulopathy, though the coexistence of aldehyde reductase(s) may not be fully ruled out.

Aldehyde Reductase↗
PubMed1992

Dynamical conformational change of DNA induced by synthetic polymers: direct observation by fluorescence microscopy.

Brownian motion and Higher-order structure of DNA molecules complexed with synthetic polymers: poly-L-arginine (pArg) and polyacrylamide (pAAm), were observed using fluorescence microscopy. Quantitative analyses of the conformation and motion of the complexes demonstrate that these two polymers influence the structure of DNA molecules in an opposite way. The electrostatic binding of pArg induces contraction of DNA, whereas the intercalative pseudo-grafting of pAAm extends DNA.

Acrylic Resins↗
PubMed1992

[The localization of aldose reductase mRNA in the rat lens].

The localization of aldose reductase (AR), which is thought to be involved in the pathogenesis of sugar and galactosemic cataracts, has been studied using various methods. The AR exists in the lens and its presence is considered to be important at the site of the cataractogenesis. In this study, the localization of AR messenger RNA (ARmRNA) in the lenses of 3-week old and fetal rats was studied by in situ hybridization using a complementary DNA to the rat AR gene. In the lens of 3-week-old rats, ARmRNA was present in the lens-epithelium and the equatorial superficial cortex. The distribution profile was similar to that of AR-immunoreactivities revealed by an immunocytochemical study. In the fetal lens, however ARmRNA was present in the epithelium and the equatorial region, while AR-immunoreactivity was observed mainly in the center of the lens.

Age Factors↗
PubMed1991

Structural analyses of a channel-forming fragment of colicin E1 incorporated into lipid vesicles. Fourier-transform infrared and tryptophan fluorescence studies.

Structural changes upon binding to the membrane of a COOH-terminal channel-forming thermolytic fragment of colicin E1 have been studied by means of a variety of spectroscopic techniques. Circular dichroism measurements show that the thermolytic fragment predominantly takes a helical structure in aqueous and detergent solutions. Fourier transform infrared spectroscopic measurements indicate that the content of the beta-structure is significantly increased when the thermolytic fragment is bound to vesicles. On the basis of the result of tryptophan fluorescence measurements, we have concluded that each of the three tryptophan residues of the thermolytic fragment exists in different environments, i.e. one is buried in the lipid bilayer, one exists on the cis side of the vesicles, and one exists near the surface of the lipid bilayer. The Fourier transform infrared and fluorescence data have been used along with the crystal structure of colicin A, which is highly homologous to colicin E1 in structure and function, to propose a model of the thermolytic fragment bound to the lipid vesicles.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of the recombinant human aldose reductase expressed in baculovirus system.

Large quantities of recombinant human aldose reductase were produced using Spodoptera frugiperda cells and properties of the enzyme were characterized. Direct purification of the recombinant aldose reductase by affinity column chromatography using Matrex gel orange A yielded a single 36 kDa band, similar in size to the purified human muscle aldose reductase, on a sodium dodecyl sulfate-polyacrylamide gel after silver staining. The isoelectric point of the recombinant enzyme was 5.85 which is identical to the human muscle aldose reductase. Following the treatment with an acylamino-acid releasing enzyme, the blocked NH2-terminal amino acid was identified to be acetylalanine. The successive NH2-terminal sequence and that of the COOH-terminal peptide concurred with the expected translated sequence. Kinetic analyses of the recombinant enzyme activity for various substrates and the cofactor, NADPH, demonstrated a good agreement with the previously reported kinetic data on the purified human aldose reductase. A high concentration of (NH4)2SO4 elicited a significant increase in both Km and Kcat for DL-glyceraldehyde as well as D-glucose. Although IC50 values for most of the aldose reductase inhibitors with recombinant enzyme were found to fall within the comparable range of those obtained with nonhuman mammalian enzymes, the IC50 value for epalrestat was more than 10-fold higher in the recombinant enzyme. These results indicate that the recombinant human aldose reductase expressed in the baculovirus system possesses structurally and enzymatically similar properties as those reported for the native human enzyme and should serve as a superior enzyme preparation to nonhuman mammalian enzymes for the screening of the efficacy and potency of newly developed aldose reductase inhibitors.

Aldehyde Reductase↗
PubMed1991

Site-specific mutagenesis of human interleukin-6 and its biological activity.

Amino acid substitutions of human interleukin-6 (IL-6) were performed. Single substitution Met162----Ala and double substitutions Leu159.166----Val resulted in a significant decrease of IL-6 activity in the production of immunoglobulin (Ig) from B-cells. Single substitution Leu166----Val or Leu159----Val gave a slight or no significant decrease in the Ig-induction activity, respectively. The receptor-binding activity of each IL-6 mutant was also examined. It was observed that the decrease of the receptor-binding activity was generally in parallel with that of the Ig-induction activity. We therefore suggest that hydrophobic side-chains existing in Met162, Leu159, and Leu166 are significantly involved in the receptor-binding of IL-6.

Animals↗
PubMed1991

Chemical modification and 1H-NMR studies on the receptor-binding region of human interleukin 6.

Oxidation of the Met residues of human interleukin 6 (IL-6) molecule has been performed. Reactivity of Met for the oxidation reaction was found to decrease in the order of Met50, Met118, Met185, Met162, and Met68. Chemical modifications involving oxidation and carboxypeptidase A digestion of IL-6 have led to the assignments of the methyl proton resonances of Met162 and Met185, respectively. The hydroxynitrobenzyl chromophore attached to Trp158 in the IL-6 molecule showed a different absorption spectrum when the labeled IL-6 was bound to the soluble IL-6 receptor. This result indicates that Trp158 is near the receptor-binding region in IL-6. On the basis of the 1H-NMR and chemical modification data, it has been concluded that Trp158 is in spatial proximity to Met162, His165 and Met185. The receptor-binding activity decreased with an increase in the number of oxidized Met residues. Of these five Met residues, Met162 was the residue in which the receptor-binding activity decreased in the most parallel degree with that of the oxidation reaction.

2-Hydroxy-5-nitrobenzyl Bromide↗
PubMed1991

Thy 1+ asialo GM1+ dendritic epidermal cells in skin defense mechanisms of vaccinia virus-infected mice.

To define different growths of vaccinia virus (VV) in the footpad, ear and tail skin of ddY and BALB c mice, we investigated the roles of Ia+ Langerhans cells (LC) and Ia- dendritic epidermal cells (DEC) in the skin defense mechanisms. With respect to LC obtained from the footpad, ear and tail skin of BALB/c mice, the level of lysosomal enzyme, phagocytic, antigen-presenting and antiviral activities were almost the same. Footpad DEC exhibited higher natural killer (NK)-like lysis activity against YAC-1 target cells than ear and tail DEC. The NK-like lysis activity of footpad DEC was also seen in athymic nude mice (BALB/c nu/nu) but not in NK cell-defective beige mice (C57BL/6 bg/bg). The footpad DEC activity was completely abolished by in vitro and in vivo treatment with anti-Thy 1.2 or anti-asialo GM1 antibody, and VV replicated in the footpad 10(3) fold more than in the untreated group, but not by treatment with anti-Iad antibody. When footpad Thy 1.2+ asialo GM1+ DEC were adoptively transferred to the tail skin of syngeneic mice, followed by intradermal challenge of the mice with VV, viral replication in the tail skin was markedly suppressed. These results indicated that the pathogenicity of VV in the skin is affected by Thy 1.2+ asialo GM1+ DEC rather than by Ia+ LC.

Animals↗
PubMed1991

[The prediction of the need for postoperative mechanical ventilation in patients with myasthenia gravis undergoing transsternal thymectomy].

During a sixteen-year period, 51 patients with myasthenia gravis underwent trans-sternal thymectomy including extended resection of the adipose tissue around thymus. Using the criteria of risk factors described by Leventhal and Kimura, a predictive score was assessed for our 51 patients. Leventhal's scoring system achieved an accuracy of 54.3%, a sensitivity of 20.0% and a specificity of 63.9%. And, Kimura's scoring system achieved an accuracy of 75.0%, a sensitivity of 81.8% and a specificity of 73.0%. From this study it was concluded that Kimura's scoring system is statistically more adaptive for Japanese than Leventhal's scoring system, and the Leventhal's accuracy may have increased by adding "bulbar symptoms" and "preoperative crisis" as other risk factors and by decreasing "points" for "duration of myasthenia" and "pyridoxamine dosage", and the "Kimura's " accuracy may have increased by decreasing "7 points" for preoperative crisis. Consequently, patients who received postoperative ventilation were compared with the group who did not, with respect to the 19 factors. Evidence is that Osserman's type, bulbar symptoms, preoperative crisis and preoperative % VC were influenced to require the postoperative ventilation, but sex, age, thymic histology, duration of myasthenia and pyridoxamine dosage were not any influenced to require the postoperative ventilation.

Adult↗