Biomedical subjects

S Miyazaki

Publications and source records attributed to S Miyazaki.

At least 19 recordsLinked to original sources

PubMed1992

Antibody to the inositol trisphosphate receptor blocks thimerosal-enhanced Ca(2+)-induced Ca2+ release and Ca2+ oscillations in hamster eggs.

The sulfhydryl reagent thimerosal enhanced the sensitivity of hamster eggs to injected inositol 1,4,5-trisphosphate (InsP3) or Ca2+ to generate regenerative Ca2+ release from intracellular pools. A monoclonal antibody (mAb) to the InsP3 receptor blocked both the InsP3-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR). The mAb also blocked Ca2+ oscillations induced by thimerosal. The results indicate that thimerosal enhances IICR sensitized by cytosolic Ca2+, but not CICR from InsP3-insensitive pools, and causes repetitive Ca2+ releases from InsP3-sensitive pools.

Animals↗

PubMed1992

Enduring suppression of hippocampal long-term potentiation following traumatic brain injury in rat.

This study investigated changes in synaptic responses (population spike and population EPSP) of CA1 pyramidal cells of the rat hippocampus to stimulation of the Schaffer collateral/commissural pathways 2-3 h after traumatic brain injury (TBI). TBI was induced by a fluid percussion pulse delivered to the parietal epidural space resulting in loss of righting responses for 4.90-8.98 min. Prior to tetanic stimulation, changes observed after the injury included: (1) decreases in population spikes threshold but not EPSP thresholds; (2) decreases in maximal amplitude of population spikes as well as EPSPs. TBI also suppressed long-term potentiation (LTP), as evidenced by reductions in post-tetanic increases in population spikes as well as EPSPs. Since LTP may reflect processes involved in memory formation, the observed suppression of LTP may be an electrophysiological correlate of enduring memory deficits previously demonstrated in the same injury model.

Animals↗

PubMed1992

Block of Ca2+ wave and Ca2+ oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs.

The concentration of cytoplasmic free calcium (Ca2+) increases in various stimulated cells in a wave (Ca2+ wave) and in periodic transients (Ca2+ oscillations). These phenomena are explained by inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR) from separate intracellular stores, but decisive evidence is lacking. A monoclonal antibody to the IP3 receptor inhibited both IICR and CICR upon injection of IP3 and Ca2+ into hamster eggs, respectively. The antibody completely blocked sperm-induced Ca2+ waves and Ca2+ oscillations. The results indicate that Ca2+ release in fertilized hamster eggs is mediated solely by the IP3 receptor, and Ca(2+)-sensitized IICR, but not CICR, generates Ca2+ waves and Ca2+ oscillations.

Animals↗

PubMed1992

Molecular basis for Glanzmann's thrombasthenia (GT) in a compound heterozygote with glycoprotein IIb gene: a proposal for the classification of GT based on the biosynthetic pathway of glycoprotein IIb-IIIa complex.

The genetic basis for Glanzmann's thrombasthenia (GT) was elucidated on a compound heterozygote with glycoprotein (GP)IIb gene: an opal mutation at the end of exon 17 (CGA----TGA) results in only a trace amount of GPIIb mRNA, and a splicing mutation at the acceptor site of exon 26 (CAG----GAG) causes an in-frame, exon skipping process from exon 25 to 27. This aberrant transcript encodes a single-chain polypeptide characterized by a 42-amino acid deletion, which includes the proteolytic cleavage site(s) and a unique, proline-rich region at the location corresponding to the carboxyl-terminal of the normal GPIIb alpha-chain. These characteristics are shared by a previously reported defective GPIIb molecule, which is neither assembled with GPIIIa nor transported to the cellular surface. Despite its normal transcription level, expression of the present defective GPIIb molecule was significantly decreased (approximately 6% of the control level). Because the precursor GPIIb molecule is assembled with GPIIIa in the endoplasmic reticulum (ER) and its processing, as well as stability, is dependent on the GPIIIa subunit, the defective GPIIb molecule may be rapidly degraded by the intrinsic quality control system of the ER due to its inability to form a stable heterodimer complex as a consequence of its misfolded structure. Although we did not confirm that the GPIIIa genes of this individual were normal, GPIIIa may be secondarily decreased (approximately 11% of control), because a large part of it could not be complexed, making it vulnerable to proteolysis. To elucidate the molecular basis for GT, we propose here a classification of GT based on the biosynthetic pathway of the GPIIb-IIIa complex.

Base Sequence↗

PubMed1992

Evidence that metalloendoproteases are involved in gamete fusion of Ciona intestinalis, ascidia.

The use of specific inhibitors and substrates of metalloendoproteases provides evidence that in many systems these enzymes are involved in membrane fusion events. In this study, we investigated whether metalloendoproteases are involved in Ciona sperm-egg fusion. In vitro fertilization assays with the metal chelator 1,10-phenanthroline, specific metalloendoprotease substrates, and the vital stain Hoechst 33342 suggested that a Zn(2+)-dependent metalloendoprotease(s) takes part in Ciona sperm-egg fusion. Furthermore, electrophysiological recordings showed that insemination carried out in the presence of either 1,10-phenanthroline or the substrate CBZ-Gly-Phe-NH2 fails to induce fertilization potential or any other change in membrane potential. These results support the hypothesis that in Ciona intestinalis, a metalloendoprotease(s) is functional in gamete fusion.

Animals↗

PubMed1992

Tissue distribution of monomeric glutathione peroxidase in broiler chicks.

It is known that there are two kinds of enzymes which show glutathione peroxidase activity, 'classical' glutathione peroxidase and glutathione S-transferase. Recently, a third enzyme was found, monomeric glutathione peroxidase, in broiler chick liver cytosolic fraction. To gain an insight into the possible physiological role of the monomeric glutathione peroxidase, the distribution of this enzyme in other broiler tissues was studied. The monomeric glutathione peroxidase was found in all tissues examined and in erythrocytes. The percentage of the total glutathione peroxidase activity accounted for by the monomeric enzyme ranged from 4 per cent in erythrocytes to 28 per cent in liver. Livers from three avian and two mammalian species contained the monomeric glutathione peroxidase. The contribution of the monomeric enzyme to total glutathione peroxidase activity with cumene hydroperoxide was high in poultry livers, while only trace monomeric glutathione peroxidase activity was found in mammalian livers. Chick monomeric glutathione peroxidase showed high activity toward phospholipid hydroperoxide. Thus, monomeric glutathione peroxidase might be an important enzyme in reducing membrane lipid hydroperoxides in birds.

Animals↗

PubMed1992

Expression of p53 in human esophageal carcinoma: an immunohistochemical study with correlation to proliferating cell nuclear antigen expression.

Immunolocalization of the nuclear protein p53 tumor suppressor gene product is considered to be one of the best methods of detecting a mutated form of p53. We have studied p53 immunohistochemically by using monoclonal antibody pAb1801 in 15 cases of esophageal squamous cell carcinoma. Immunoreactive p53 was observed in the nuclei of tumor cells in 4% paraformaldehyde-fixed, frozen sections (12 of 15) and paraffin-embedded sections (11 of 15), but not in routinely processed (10% formalin-fixed) specimens. p53 expression was closely correlated with the malignant phenotype, including dysplasia. p53 was not observed in histologically normal mucosa, except in three cases in which scattered immunoreactivity was observed in parabasal and basal cells. Immunostaining of ki67 and proliferating cellular nuclear antigen on adjacent tissue sections revealed that p53 expression was strongly correlated with ki67 and proliferating cellular nuclear antigen in carcinoma and dysplastic cells, but not in normal mucosa, suggesting involvement of the mutated form of p53 in the cell cycle of malignant cells. Immunohistochemical patterns of p53 were not related significantly to clinicopathologic parameters in the cases examined. Therefore, p53 expression was strongly associated with the proliferation of carcinoma cells but not with that of normal cells in esophageal carcinoma.

Aged↗

PubMed1992

The proliferative cell fraction in cytology specimens. A study of human esophageal carcinoma.

Immunostaining of cell cycle-related antigens, especially Ki-67, DNA polymerase alpha, and proliferating cell nuclear antigen, has become an important method to assess the proliferative activity of tumors. These three nuclear antigens were studied by immunohistochemical analysis of cytologic smears. These smears were obtained by scraping the cut surface of 10 cases of esophageal squamous cell carcinoma and were fixed and prepared by different methods. The results were compared with those of tissue sections to apply the immunocytochemical findings of these antigens to cytology specimens. Smears that were placed on Denhardt- or Neoprene-coated slides and subsequently fixed in 4% paraformaldehyde and methanol exhibited the best cell adherence to the slides, had minimal loss of antigenicity, and had good preservation of cell morphologic features for all three antigens examined. The percentage of positive tumor cells in the cytology smear was generally in good agreement with that in the tissue section. For these three antigens, proliferating cell nuclear antigen demonstrated a much higher percentage of positive cells than either Ki-67 or DNA polymerase alpha, in both the smears and the tissue sections. In summary, Ki-67, DNA polymerase alpha, and proliferating cell nuclear antigen can be immunolocalized successfully in cytology smears and may become another parameter to assess the proliferative activity of tumors in the field of diagnostic pathology.

Antigens, Neoplasm↗

PubMed1992

The in-vitro activity of RP 59500 against gram-positive cocci.

RP 59500 was more potent than erythromycin, josamycin, amoxycillin and ciprofloxacin, and as potent as vancomycin, against staphylococci and enterococci. Against streptococci, the activity of RP 59500 was very similar to that of amoxycillin, but was superior to that of erythromycin, josamycin, vancomycin or ciprofloxacin. Compared with the other antimicrobial agents tested, RP 59500 was the most active against erythromycin-resistant Gram-positive cocci.

Amoxicillin↗

PubMed1992

Treatment of Langerhans cell histiocytosis in children with etoposide.

Ten children with Langerhans cell histiocytosis (LCH) were treated with etoposide. For five patients, this was the initial diagnosis. The other five had failed to respond to previous therapies. Etoposide (100 mg/m2) was given intravenously twice a week for 4 weeks, followed by maintenance therapy every 2 to 4 weeks for 2 years. All 10 patients responded to etoposide, and 6 of them (60%) have been in complete remission for 3 to 36 months without any side effects. One patient relapsed with diabetes insipidus, one with a soft tissue mass, and two others developed multiple bone lesions. Chemotherapy with etoposide appears to be effective and safe for the treatment of children with systemic LCH.

Adolescent↗

PubMed1992

Separate isolation of Clostridium difficile spores and vegetative cells from the feces of newborn infants.

A modified taurocholate-cefoxitin-cycloserine-fructose agar medium, pH 5.5, on which vegetative cells alone could grow, was newly devised for separate isolation of Clostridium difficile vegetative cells and spores from feces. The ratio of C. difficile-positive feces from healthy newborn infants younger than 10 days of the age was 30.8%, and 93.3% of feces from healthy infants older than 20 days were positive for C. difficile. C. difficile spores alone were detected in twenty-one samples (75%) of C. difficile-positive Twenty-eight specimens. Only 10.7% (3/28) C. difficile vegetative cells alone were detected. C. difficile spores alone were detected in one of nine healthy adults. These collective results offer potential explanations for high frequent isolations of C. difficile from newborn infants without occurrence of pseudomembranous colitis.

Bottle Feeding↗

PubMed1992

The other mediator for adherence of Haemophilus influenzae organisms without involvement of fimbriae.

The number of the nontypeable Haemophilus influenzae (HiN) organisms that adhered to the primary mouse fetal lung cells was significantly more than type b Haemophilus influenzae (Hib) organisms. The average number of HiN organisms adherent to host cells was 2,291/100 host cells (range, 1,654-3,182), but that of Hib was markedly reduced to 147/100 host cells (range, 102-238). In this case, P value was less than 0.05 by using a paired Student t-test. The sonicated extract from HiN TMS11 organisms inhibited adherence of H. influenzae TMS11 organisms to monolayer at 76.3% and it inhibited adherence of Hib TMS24 organisms at 92.3%. This result indicates that a mediator existing on the surface of HiN organisms may be the same as that on type b organisms. The number of detected organisms in broncho and lung tissues 3 days after intranasal infection with HiN strains was significantly greater than that in infection with Hib strains. Therefore, in vitro adhesive capacity of H. influenzae organisms was correlative to infectivity by intranasal injection.

Animals↗

PubMed1992

T cell activation and T cell receptor variable region gene usage in measles.

T cell activation and T cell receptor variable (V) regions were studied with monoclonal antibodies in peripheral blood lymphocytes from 22 patients with measles. Increased (greater than 5%) activated T cells (HLA-DR+ CD3+ cells) were noted in 14 of the 22 patients. Elevations of V beta 5+ and V beta 8+ T cells were observed in two and four patients, respectively, and appeared to be associated with T cell activation. The duration of fever was significantly prolonged in those with increased (greater than 10%) activated T cells (p less than 0.01). These results suggest that T cell activation and the preferential expansion of V beta 8+ and V beta 5+ T cells are associated with the pathogenic process of measles.

Adolescent↗

PubMed1992

The pH dependent uptake of enoxacin by rat intestinal brush-border membrane vesicles.

The mechanism of the intestinal transport of enoxacin, an orally active fluoroquinolone antibiotic, has been investigated using brush-border membrane vesicles isolated from rat small intestine. The initial rate and time-course of enoxacin uptake were considerably dependent upon the medium pH (pH 5.5 greater than pH 7.5) and upon the percent ionization of the carboxyl group (pKa 6.2, anionic charge), namely, the degree of uptake of cationic form was higher than that of the zwitterionic form. There was evidence of transport into the intravesicular space as shown by the effect of extravesicular medium osmolarity on enoxacin uptake at steady state (30 min). This transport across the brush-border membrane was stimulated by the valinomycin-induced K(+)-diffusion potential (interior negative) and an outward H(+)-diffusion potential. Furthermore, changing the pH of the medium from 5.5 to 7.5 significantly decreased the effect of valinomycin-induced K(+)-diffusion potential on the enoxacin uptake. These results suggest that the uptake behaviour of the cationic form of enoxacin plays an important role in the intestinal absorption process of enoxacin.

Animals↗

PubMed1992

[A case of tracho-bronchial aspergillosis complicated with acute myeloblastic leukemia].

A 59-year-old male was admitted to our hospital in Jan. 1991 with complaints of general malaise and palpitation. Laboratory findings on admission showed anemia, thrombocytopenia and leukopenia consisted of 2.0% myeloblasts with Auerbodies. The bone marrow study showed granuloid hyperplasia with 45.5% myeloblasts. The diagnosis of acute myeloblastic leukemia (M1) was made. After BHAC-AMP therapy, he obtained complete remission. However, he complained of fever and cough, and his chest X ray film showed a focal infiltrative shadow in the right upper lung field. Antibiotics for bacteria and fungus were administered and the abnormal shadow improved in a week. However, as he had hemosputum, the bronchoscopic examination was performed, and multiple ulcers covered by yellow-white tissue were revealed on the wall of the trachea and bilateral main bronchi. Biopsy specimens obtained by transbronchial biopsy showed bronchial aspergillosis. Though intravenous infusion and inhalation of amphotericin B were effective for aspergillosis, he had a relapse of the leukemia and died in autumn, 1991.

Aspergillosis↗

PubMed1992

[Changes in serotypes of clinical isolates of Pseudomonas aeruginosa by anti-pseudomonal drugs].

Forty-two isolates of P. aeruginosa from various infections were each incubated in Mueller-Hinton broth including piperacillin, cefsulodin, ceftazidime, imipenem, gentamicin or norfloxacin (1MIC-4MIC) at 35 degrees C for 18 hours, and serotyped using monoclonal antibodies. Serotypes of 4 (9.5%)-8 (19.0%) of the 42 isolates each changed to different groups after incubation. No relationship was found between serotypes of the formed variants and anti-pseudomonal drugs used. When P. aeruginosa TA-2 was exposed to cefsulodin at different concentrations (1MIC and 2MIC) under the above conditions, the distinct variants different in serotypes were formed according to the drug concentrations. Furthermore, P. aeruginosa TA-2 and TA-13 were incubated in Mueller-Hinton broth including cefsulodin (1/2 or 2MIC) and gentamicin (1/2MIC), respectively, and the growth curves of parent and variant cells were determined. In the experiments, the variants appeared 6 hours after onset of the incubation and grew with the parents. The present results may explain our findings previously reported; coexistence of colonies different in serotype of P. aeruginosa isolated from some individual patients. The results indicate the possibility that alteration in bacterial surfaces in association with changes in serotypes might occur in vivo in these patients infected with P. aeruginosa and treated with anti-pseudomonal drugs.

Anti-Bacterial Agents↗

PubMed1992

[The study of pathogenic mechanisms of chronic Pseudomonas aeruginosa lung infections by mucoid strains].

Chronic Pseudomonas aeruginosa lung infection with mucoid strains is the predominant cause of death in cystic fibrosis (CF) or diffuse panbronchiolitis (DPB). This infection is characterized by a chronic course without spread of the bacteria to the blood when compared with other infections due to the non-mucoid strains. However, the mechanism of P. aeruginosa lung infection with the mucoid strains remains obscure. Intra-tracheal and systemic infection in mice, susceptibility to the bactericidal activity of fresh human and mouse serum, and adherent activity to mouse fetal lung cell were examined for mucoid and non-mucoid strains of P. aeruginosa. After intra-tracheal infection, the mucoid strains were distributed to other organs anormously but not the non-mucoid stains, and the bacterial number of the mucoid strains in the blood were significantly lower than that of the non-mucoid strains. On the other hand, when these strains were inoculated into the tail vein of mouse, the mucoid strain was eliminated more rapidly from blood as compared with the non-mucoid strain. The mucoid strains showed reduced bacteremic virulence when compared with non-mucoid strains with a 50% lethal dose (LD50) of 1.5 x 10(7) CFU/mouse as the mean value in a systemic infection. In contrast to the non-mucoid strains, the mucoid strains were sensitive to human fresh serum but were resistant to mouse fresh serum. The mucoid strains adhered to the monolayer of the mouse fetal lung cell 7-fold better than did non-mucoid strains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

In vitro and in vivo antibacterial activities of a new quinolone, OPC-17116.

The in vitro and in vivo antibacterial activities of OPC-17116 were compared with those of ofloxacin, enoxacin, ciprofloxacin, and tosufloxacin. The MICs of OPC-17116 for 90% of the strains tested were 0.125 to 8 micrograms/ml against gram-positive bacteria such as members of the genera Staphylococcus, Streptococcus, and Enterococcus: less than or equal to 0.063 to 16 micrograms/ml against members of the family Enterobacteriaceae; and less than or equal to 0.063 to 16 micrograms/ml against glucose-nonfermentative bacilli such as Pseudomonas aeruginosa. The activity of OPC-17116 against gram-positive organisms was comparable to that of tosufloxacin and higher than those of other reference drugs. The in vitro activity of OPC-17116 against gram-negative bacteria was similar to those of the reference drugs. In experimental systemic infections in mice with various organisms, the efficacy of OPC-17116 was similar to that of tosufloxacin and greater than those of ofloxacin, enoxacin, and ciprofloxacin. In a pyelonephritic model in mice with P. aeruginosa KU-1, OPC-17116 was as active as ciprofloxacin and more active than ofloxacin, enoxacin, and tosufloxacin. In respiratory tract infections in mice with Staphylococcus aureus Smith, Streptococcus pneumoniae TMS 3, and Klebsiella pneumoniae 3K25, the efficacy of OPC-17116 was generally greater than that of tosufloxacin. The peak level of OPC-17116 in the lungs of mice was 10 times higher than that in serum and was significantly greater than levels in lung achieved with an equivalent dose of the other quinolones. The therapeutic efficacy of OPC-17116 may depend not only on its in vitro activity but also on its high concentration in tissue.

Administration, Oral↗