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Biomedical subjects

I Hayakawa

Publications and source records attributed to I Hayakawa.

At least 19 recordsLinked to original sources
PubMed1995

Mechanisms of 4-quinolone resistance in quinolone-resistant and methicillin-resistant Staphylococcus aureus isolates from Japan and China.

Ninety-two and 33 methicillin-resistant Staphylococcus aureus (MRSA) strains were isolated in Japan and China respectively. They were categorised as ofloxacin-susceptible (MIC < 12.5 mg/L), moderately (MIC 12.5-25 mg/L) or highly (MIC > or = 50 mg/L) ofloxacin-resistant. 4-Quinolone concentrations required to inhibit purified DNA gyrase from the moderately and highly quinolone-resistant MRSA were at least 20 times higher than those required to inhibit the equivalent enzyme from quinolone-susceptible strains. Reconstitution assays demonstrated that the 4-quinolone-resistant MRSA had a mutation in subunit A of DNA gyrase. A portion of the gyrA gene from amino acids codons 40-115 was sequenced. Four moderately resistant and seven highly resistant MRSA contained a Ser-->Leu substitution at amino acid 84; one moderately and one highly resistant MRSA and one moderately resistant methicillin-susceptible S. aureus (MSSA) strain contained a Glu-->Lys substitution at amino acid 88. Eight MRSA, including one quinolone-susceptible strain and one MSSA contained a silent mutation at amino acid 86. Uptake of ofloxacin in moderately resistant strains was almost the same in the presence or absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), whereas in highly resistant strains, uptake increased when CCCP was added. Restriction fragment length analysis of the norA gene with the restriction endonuclease SfcI showed a mutation of nucleotide position 1085 in all MRSA strains tested except for one highly quinolone-resistant strain. Thus the mechanisms of 4-quinolone-resistance in these MRSA isolates involved alterations in both DNA gyrase and antimicrobial uptake and efflux.

Anti-Infective Agents↗
PubMed1995

Contribution of the C-8 substituent of DU-6859a, a new potent fluoroquinolone, to its activity against DNA gyrase mutants of Pseudomonas aeruginosa.

Inhibitory effects of five quinolones against DNA gyrases purified from four quinolone-resistant clinical isolates of Pseudomonas aeruginosa and the quinolone-susceptible strain PAO1 were examined. All of the quinolone-resistant strains tested were found to be DNA gyrase mutants. The 50% inhibitory concentrations (IC50s) of the quinolones for these DNA gyrases roughly correlated with their MICs. Interestingly, gyrase inhibition by DU-6859a was found to be significantly less affected by these mutations that inhibition by other currently available quinolones. To assess the enhanced activity shown by DU-6859a, the effects of quinolones with altered substituents at the N-1, C-7, and C-8 positions of the quinolone ring of DU-6859a were tested. Measurement of MICs for four DNA gyrase mutants and IC50s for their purified DNA gyrases showed that removal of the C-8 chlorine of DU-6859a significantly increased MICs and IC50s for DNA gyrase mutants. However, no deleterious effects were observed when either the fluorine on the cyclopropyl substituent at the N-1 position or the cyclopropyl ring at the C-7 substituent was removed. Moreover, removal of the C-8 chlorine also increased the MIC for 19 of 20 quinolone-resistant clinical isolates. Our results led to the conclusion that DU-6859a is much more active against quinolone-resistant clinical isolates of P. aeruginosa than other currently available quinolones, probably because of its strong inhibitory effects against mutant quinolone-resistant DNA gyrases, and that the C-8 chlorine is necessary for these potent effects.

Anti-Infective Agents↗
PubMed1994

Possible intermolecular interaction between quinolones and biphenylacetic acid inhibits gamma-aminobutyric acid receptor sites.

The combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, is known to specifically induce functional blockade of the gamma-aminobutyric acid (GABA) receptors. The mechanisms of these drug interactions were further examined. Scatchard analysis of [3H]muscimol binding to rat brain plasma membranes in the presence of enoxacin and BPAA revealed that a significant decrease in the number of muscimol binding sites was produced without affecting the affinity of binding to the receptors. In the presence of norfloxacin, BPAA inhibited muscimol binding the most potently of the six BPAA-related compounds tested. Fenbufen and 9,10-dihydro-gamma-oxo-2-phenanthrenebutyric acid also inhibited the binding, and 4-biphenylcarboxylic acid and methyl 4-biphenylacetate inhibited it slightly, but 3-benzoylpropionic acid exhibited no competitive inhibition. Accordingly, hybrid molecules of norfloxacin and BPAA were synthesized for stereochemical analysis of these drug interactions. A hybrid with a -CONH(CH2)3- chain between norfloxacin and BPAA (flexible structure) inhibited muscimol binding, and intracisternal injection of this hybrid caused clonic convulsions in mice more potently than the combination of norfloxacin and BPAA did. In contrast, a hybrid linked by -CONH- (stretched structure) showed almost no such inhibitory effect. 1H NMR analysis indicated the presence of intramolecular attraction at the quinoline ring of the hybrid exhibiting the antagonistic activity. These results suggest the possibility that quinolones and BPAA interact with the GABA receptor at nearby sites and that the binding affinity of quinolones to the GABA receptors is largely enhanced by the intermolecular interaction with BPAA.

Animals↗
PubMed1992

Antimicrobial activity of DU-6859, a new potent fluoroquinolone, against clinical isolates.

DU-6859, (-)-7-[(7S)-amino-5-azaspiro(2,4)heptan-5-yl]-8-chloro-6- fluoro-1-[(1R,2R)-cis-2-fluoro-1-cyclopropyl]-1,4-dihydro-4-oxoquinol one-3- carboxylic acid, is a new fluoroquinolone with antibacterial activity which is significantly better than those of currently available quinolones. The MICs for 90% of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis clinical isolates (MIC90s) were 0.1, 3.13, 0.1, and 0.39 microgram/ml, respectively. MIC50s of DU-6859 against quinolone-resistant, methicillin-resistant S. aureus were 8-, 32-, 64-, and 128-fold lower than those of tosufloxacin and sparfloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin, respectively. DU-6859 inhibited the growth of all strains of Streptococcus pneumoniae and Streptococcus pyogenes at 0.1 and 0.2 microgram/ml, respectively, and was more active against enterococci than the other quinolones tested. Although the activity of DU-6859 against Pseudomonas aeruginosa was roughly comparable to that of ciprofloxacin at the MIC50 level, it was fourfold more active than ciprofloxacin at the MIC90 level. DU-6859 was also more active against other glucose-nonfermenting bacteria, Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, than the other drugs tested. Strains of Bacteroides fragilis and Peptostreptococcus spp. were susceptible to DU-6859; MIC90s were 0.39 and 0.2 microgram/ml, respectively. DU-6859 generally showed activities twofold or greater than those of ciprofloxacin and the other drugs against almost all members of the family Enterobacteriaceae. The action of DU-6859 against the clinical isolates was bactericidal at concentrations near the MICs. DU-6859 activity was not affected by different media, pH, inoculum size, or human serum but was decreased in human urine.

Anti-Infective Agents↗
PubMed1992

Radiotherapy for pediatric brain stem glioma: radiation dose, response, and survival.

An analysis of 39 patients under 20 years of age with brain stem glioma treated with radiotherapy between 1977 and 1991 was undertaken. Twenty-eight (71.2%) of the patients responded well to initial radiotherapy, and 11 (28.8%) responded poorly. Median survival for the total patient population was 10 months. Response rates and median survivals were influenced by radiation dose: 45.5% and 9 months at doses less than 4499 cGy (n = 11), 83.3% and 13 months at doses between 4500 and 5499 cGy (n = 12), 66.7% and 11.5 months at doses between 5500 and 6499 cGy (n = 9), and 100% and 10 months at doses more than 6500 cGy (n = 7). Multivariate analysis revealed the response to initial radiotherapy was the only predictor of survival with radiation doses up to 6499 cGy. Four of the patients who responded well demonstrated radiological and/or histological calcification within or around the tumor at the time of clinical deterioration. Radiation injury was confirmed in two autopsy cases. The possibility that intratumoral radiation injury causes clinical deterioration is suggested.

Adolescent↗
PubMed1991

Significance of the methyl group on the oxazine ring of ofloxacin derivatives in the inhibition of bacterial and mammalian type II topoisomerases.

A study was made of the correlation between the in vitro inhibitory effects of several quinolones, including four ofloxacin derivatives, on bacterial DNA gyrase from Escherichia coli KL-16 and on topoisomerase II from fetal calf thymus. No correlation was observed between the inhibitions of DNA gyrase activity and topoisomerase II activity. On the other hand, the inhibitory effects of these quinolones against topoisomerase II were closely correlated with their inhibition of cell growth. Furthermore, among the oxazine derivatives tested, the derivative with a methyl group at position 3 in an S configuration showed the highest activity against DNA gyrase and derivatives without a methyl group on the oxazine ring were more potent against topoisomerase II than those with a methyl group. Among these derivatives, DR-3355, the S isomer of ofloxacin, showed the highest activity against DNA gyrase and low activity against topoisomerase II. These results indicate that the methyl group on the oxazine ring plays an important role in the inhibitory activities of ofloxacin derivatives for these enzymes.

Animals↗
PubMed1991

Inhibition by quinolones of DNA gyrase from Staphylococcus aureus.

In order to clarify the mechanism of action of quinolones against Staphylococcus aureus, the subunit A and B proteins of DNA gyrase were separately purified from a crude extract of S. aureus FDA 209-P. The reconstituted enzyme exhibited ATP-dependent DNA supercoiling activity. The inhibitory effects of quinolones on the supercoiling activity of the purified enzyme were measured by the quantitative electrophoresis method (17), using plasmid DNA, pBR322 or pUB110, as substrates and expressed as the 50% inhibitory concentrations (IC50s). The IC50s of ofloxacin, DR-3355 (l-ofloxacin), ciprofloxacin, tosufloxacin, sparfloxacin, and DS-4524, a new quinolone derivative, for pBR322 were 63.0, 37.8, 30.5, 46.0, 28.5, and 3.2 micrograms/ml, respectively. These values were closely correlated with antibacterial activity (MIC), with correlation coefficients of 0.953 for pBR322 and 0.938 for pUB110. These results indicate that, in S. aureus, as in gram-negative bacteria, DNA gyrase is likely to be a major target enzyme of quinolones.

4-Quinolones↗
PubMed1990

Human macrophage scavenger receptors: primary structure, expression, and localization in atherosclerotic lesions.

Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), alpha-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis.

Amino Acid Sequence↗
PubMed1989

Rerupture of intracranial aneurysms during angiography.

We analyzed 70 patients (64 from the literature and 6 of our own cases) who had suffered from rerupture of their aneurysms during angiography. When these cases are compared with those who had suffered rupture of their aneurysms only once and a rerupture, which did not coincide with angiography, they were clinically distinguished by a higher Hunt-Hess grade, a higher rate of IC aneurysms, less operability, far miserable outcome and concentration of aneurysmal rerupture within three hours after the initial subarachnoid haemorrhage. It is suggested waiting at least 3 hours after SAH before performing angiography and to use digital subtraction angiography in order to prevent aneurysmal rerupture during angiography.

Adult↗
PubMed1989

Nephritogenic glycoprotein. XIII. Isolation and its immunochemical characterization of the antigenic substance of membranous glomerulonephritis induced by a single injection of crude nephritogenoside in homologous animals.

Studies on the immunochemical characterization were made on the antigenic substance of membranous glomerulonephritis (MG) that is induced, in homologous animals, by a single footpad injection of rat crude nephritogenoside (CNG). In rats injected with rat CNG, typical MG with immunofluorescent granular pattern (immune complex type nephritis) was produced 3-4 months after the injection. Since CNG nephritis is a model which induces MG only in homologous animals, the development of MG in this model should be explained by antigen-autoantibody immune complex mechanism. Thus, the features of the antigenic substance contained in CNG was immunochemically investigated, utilizing the serum (autoantibody) of rats with MG as well as rabbit antiserum to rat tubular brush border antigen (FXIA) (heteroantibody). As a result, two different fractions (fr. 31 and fr. 36) were separated from the antigenic substance contained in CNG: that is, fr. 31 reacts only with rabbit antiserum to rat tubular brush border antigen (FXIA) (heteroantibody) but does not react with the serum (autoantibody) of rats with MG. Fr. 36 does not react with rabbit antiserum to FXIA (heteroantibody) and reacts only with the serum (autoantibody) of rats with MG (which was induced by a single footpad injection of CNG or soluble FXIA). These results suggest immunologically that fr. 36 is the main antigen responsible for the development of MG which is induced in homologous animals by a single footpad injection of CNG.

Animals↗
PubMed1989

[Development of a light curing denture base resin].

We developed the light cured direct relining material and used it clinically. In this study, a partial change in its components was made to improve both its strength and manipulability with the aim of using it as a denture base material. The physical properties of the new material, bonding to resin teeth, fit, as well as procedure were discussed. As for physical properties, the bending strength of the new material was increased by improving its organic filler, it becoming comparable to that of heat curing resin. The water absorption of the new material was the lowest of compared materials. The bonding strength of this material to resin teeth was increased by treatment with a light cured bonding agent and the fit of the new material to a test model was comparable to that of heat curing resin. Thus, the new material seems to be quite clinically effective as a denture base resin.

Composite Resins↗
PubMed1989

Role of dipeptidyl peptidase IV (gp 108) in passive Heymann nephritis. Use of dipeptidyl peptidase IV-deficient rats.

Injection of antibodies to renal tubular membrane (Fx1A) into Lewis rats induces granular deposits of IgG in glomeruli and proteinuria (passive Heymann nephritis, PHN), and similar lesions are also induced by antibody to one of the antigens in Fx1A, dipeptidyl peptidase IV (DPP IV, gp 108). In this study, the role of DPP IV in PHN was investigated using DPP IV-deficient F344 rats. The amount of DPP IV found in F344 rat kidneys was less than 0.05% of that present in Wistar rats, and injection of anti-DPP IV antibody into F344 rats did not induce proteinuria. Injection of anti-F344 Fx1A rabbit antibodies that contain no detectable anti-DPP IV antibody into Lewis or F344 rats induced PHN, characterized by granular deposits of rabbit IgG in glomeruli and massive proteinuria, although the appearance of proteinuria was delayed in comparison with that occurring in response to injection of anti-Wistar Fx1A antibodies. These results indicate that DPP IV may contribute to, but is not essential for, the induction of PHN.

Animals↗
PubMed1989

[Craniopharyngioma with malignant transformation--a report of two cases].

Two cases of a craniopharyngioma with malignant transformation are reported. Case 1 involved a 3-year-old male who had received a partial resection and radiotherapy for a suprasellar tumor. Histologically, a biopsy specimen showed craniopharyngioma. Eight years later, the child died of an intracerebral and nasopharyngeal invasion of the recurrent tumor. Case 2 involved a 9-year-old male who initially had been diagnosed as having a craniopharyngioma in the suprasellar region. Five years after the first operation, he died from growth of the tumor in spite of radiotherapy and a partial resection. The pathological examinations of these two cases showed an apparent transition of the craniopharyngioma into a squamous cell carcinoma.

Ameloblastoma↗
PubMed1987

Inhibition of DNA gyrase by optically active ofloxacin.

Inhibition of DNA gyrase activity by optically active ofloxacins was studied and compared with the inhibition of norfloxacin and ciprofloxacin. The (-)-isomer of ofloxacin inhibited the supercoiling activity of gyrase from Micrococcus luteus more effectively than did the (+)-isomer. The 50% inhibitory concentrations of (-)-, (+/-)-, and (+)-ofloxacin; norfloxacin; and ciprofloxacin for gyrase from Escherichia coli were 0.78, 0.98, 7.24, 0.78, and 1.15 microgram/ml, respectively. These values correlated well with the antibacterial activity of each compound against intact bacterial cells.

Anti-Bacterial Agents↗
PubMed1987

Heymann nephritis in rats induced by human renal tubular antigens: characterization of antigen and antibody specificities.

An injection of human renal tubular fraction, Fx1A, with Freund's complete adjuvant in rats induces Heymann nephritis (HN) with clinical and morphological features similar to rat Fx1A-induced HN. The present study was undertaken to characterize antibody specificities and the corresponding antigen involved in human Fx1A-induced HN. In sera of rats immunized with human Fx1A, not only anti-human Fx1A antibody but also antirat Fx1A antibody was detected by enzyme immunoassay. Eluted antibody from the glomeruli also showed both activities. In an inhibition study of enzyme immunoassay, binding of the eluted antibody to human Fx1A was inhibited by both human and rat Fx1A and also by partially purified gp330, but not by purified gp108. Furthermore, binding of the eluted antibody to rat Fx1A was inhibited by both rat and human Fx1A. On immunoblot, the eluted antibody mainly reacted with a 440 kD glycoprotein of human Fx1A which showed the same mobility as rat gp330. The antibody also reacted with a band of gp330 of rat Fx1A. These results indicate that the 440 kD glycoprotein in humans is a counterpart of rat gp330 and that the eluted antibody has dual specificities to both human 440 kD glycoprotein and rat gp330, suggesting that the cross-reactive antibody is responsible for human Fx1A-induced HN.

Animals↗
PubMed1987

Identification of gp108, a pathogenic antigen of passive Heymann nephritis, as dipeptidyl peptidase IV.

Our previous paper showed that the glycoprotein of Mr 108,000 (gp108) is one of the major components of rat renal tubular brush border antigens and that an injection of anti-gp108 antiserum in rats induces passive Heymann nephritis with acute and severe proteinuria. In this study, gp108 was identified as a monomer of dipeptidyl peptidase IV (DPP IV). The anti-gp108 antibody was shown to immunoprecipitate DPP IV from Triton-extract of renal tubular membrane fractions. DPP IV was co-purified with gp108 from the Triton-extract by columns of DEAE-cellulose and Bio-gel A-1.5 m. The ratio of DPP IV activity and gp108 content was nearly constant throughout the purification steps. The final purified gp108 showed a high specific activity of DPP IV, comparable to that reported for purified rat DPP IV. These results indicate that gp108 is a monomer of DPP IV.

Animals↗