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Biomedical subjects

M Iwata

Publications and source records attributed to M Iwata.

At least 343 records · Page 19Linked to original sources
PubMed1994

Human leukocyte antigen-class II-positive human corneal epithelial cells activate allogeneic T cells.

PURPOSE: To achieve a better understanding of the mechanism of corneal immune diseases, including corneal allograft rejection, the authors examined the potential of human corneal epithelial (HCE) cells to activate allogeneic T lymphocytes. METHODS: The mixed lymphocyte-HCE cell reaction (MLCER) was performed as follows: HCE cells from primary cultures, with or without treatment with interferon-gamma (IFN-gamma), were treated with mitomycin C and then mixed with peripheral blood lymphocytes (PBL) from normal volunteers. Triplicate cultures were incubated for 7 days. Interleukin-1-alpha (IL-1-alpha) was added to some cultures to examine its effect on MLCER: The lymphocyte responses were measured by 3H-thymidine uptake for the last 18 hours of incubation in MLCER: RESULTS: IFN-gamma-treated, HLA-class-II-bearing HCE cells stimulated allogenic lymphocytes, whereas IFN-gamma nontreated, class-II-negative HCE cells did not. The stimulation by IFN-gamma-treated HCE cells was blocked by anti-HLA class II monoclonal antibody. In addition, exogenous IL-1-alpha reduced the lymphocyte response in MLCER: This effort was inhibited by indomethacin. CONCLUSIONS: This study demonstrates that HLA-class-II-bearing HCE cells can activate allogeneic PBL by a major histocompatibility complex class II-dependent mechanism. In addition, HCE cells may regulate immune reactions, probably through prostaglandin production caused by IL-1.

Antigen-Presenting Cells↗
PubMed1994

[The correlation between the MICs deduced from Showa disk method and the MICs determined by micro-dilution method].

Disc diffusion technique is useful to routine drug susceptibility testing for bacteria in clinical laboratories because of the advantages on simplicity and cost. Kirby-Bauer (KB) method recommended by NCCLS is using widely as a standard method of disk diffusion test, and simply categorize microorganisms as being susceptible, moderately susceptible, intermediate or resistant to different antimicrobial agents by the use of break point. In the determination of breakpoints, the relationship between MICs and clinical results and pharmacokinetics parameters (Cmax, T1/2 and AUC) are significantly considered. However, there are variance of pharmacokinetics among a race, moreover, breakpoint is not yet established in Japan. In report to doctor from clinical laboratory, the MIC might be better than that by breakpoint since there are such problems of breakpoint. Showa disk was developed as mono-disk method being able to deduce MIC from the linear regression between MIC and zone diameter. Therefore, it is thought that Showa disk is one of valuable methods for the routine drug susceptibility testing for bacteria in Japan. There is one problem, which is that MIC deduced by Showa disk is based on the relationship with agar dilution method although the determination method of MIC is going to turn into micro-dilution method, so we compared the MICs deduced from zone diameter of Showa disk method with the MICs determined by broth micro-dilution method by using a challenge set of 110 gram-positive and gram-negative bacteria for 7 antimicrobial agents. The total agreement of MIC within 1-log2 dilution difference was 77% and the correlation coefficient was 0.929. As results, a good relationship was obtained except the results of tetracycline and ofloxacin for beta-lactamase non-producing H. influenzae, and ceftizoxime for E. coli, and K. pneumoniae.

Anti-Bacterial Agents↗
PubMed1994

[A case of so-called benign metastasizing leiomyoma].

A 44-year-old female was admitted to our hospital for the purpose of undergoing hysterectomy for removal of multiple uterine tumors. A chest X-ray film obtained on admission revealed a solitary nodule in the right lung field. The resected specimen containing the uterine tumors revealed well differentiated leiomyoma with no nuclear atypia or mitotic figures. The resected specimen from the pulmonary tumor revealed histologic findings similar to those of the uterine myomas, being devoid of any signs of mitosis. Similar cases have been reported as so-called benign metastasizing leiomyoma, and are generally regarded as low grade malignancy or leiomyomatosis. However, we consider this case to have had a primary pulmonary leiomyoma associated with uterine myoma since the pulmonary lesion was solitary and no mitotic figures were detectable. As the concept of metastasizing leiomyoma is confusing, the accumulation of additional case reports is necessary.

Adult↗
PubMed1994

[A case of allergic bronchopulmonary fungosis caused by several kinds of fungi].

A 36-year-old man, who had been treated for bronchial asthma since 10 years of age was admitted to Haibara General Hospital because of asthma attack and abnormal chest X-ray shadows. Chest roentgenogram on admission revealed patchy and consolidation shadows in both lung fields. Blood eosinophilia (15%, 1,155/mm3) and elevation of total IgE (7,800 IU/ml) were demonstrated by laboratory examination. Bronchography showed central bronchial ectasia in right B2, B3, B6 and left B1+2, B3 and B6. Investigations of allergy demonstrated elevated specific IgE levels, positive immediate and late skin reactions, positive "dual" asthmatic responses and positive precipitating antibodies for Aspergillus fumigatus, Penicillium luteum and Cladosporium cladosporioides. Aspergillus fumigatus, Penicillium spp. and Cladosporium spp. were cultured from his sputa. From these clinical symptoms and findings of tests of allergy, all three kinds of fungi, Aspergillus fumigatus, Penicillium and Cladosporium, were considered as causative antigens in this case of allergic bronchopulmonary fungosis.

Adult↗
PubMed1993

Okadaic acid inhibits glucocorticoid-induced apoptosis in T cell hybridomas at its late stage.

Glucocorticoids induce apoptosis in murine T cell hybridomas. It was inhibited by okadaic acid and calyculin A, potent inhibitors of protein phosphatase 1 and 2A, but not by 1-norokadaone, a structural analog of okadaic acid without phosphatase inhibitory activity. The inhibitory effect of okadaic acid was significant even when it was added 9 h after the start of the culture. Okadaic acid did not prevent either the translocation of glucocorticoid receptor from the cytoplasm to the nucleus or the induction of luciferase activity in the T cell hybridoma transfected with a plasmid containing the luciferase gene under the control of glucocorticoid response elements. These results indicate that protein dephosphorylation is an essential step for glucocorticoid-induced apoptosis in T cell hybridomas, and that the step is at the late stage of the apoptotic process.

Animals↗
PubMed1993

Early mobilization of Ca2+ is not required for glucocorticoid-induced apoptosis in thymocytes.

Contradictory results have been reported on the question of the role of Ca2+ in glucocorticoid-induced apoptosis in thymocytes. To resolve this problem, we investigated the effect of dexamethasone, a synthetic glucocorticoid, on intracellular Ca2+ concentration ([Ca2+]i), by microscopic fluorometry that enables us to monitor real-time [Ca2+]i of cells loaded with fura-2, a fluorescent Ca2+ indicator, on a single cell basis. The results indicated that dexamethasone does not induce an increase in [Ca2+]i above control level both in murine and rat thymocytes at least for 1 h after the start of the culture. We also investigated whether the depletion of extracellular Ca2+ with EGTA or buffering intracellular Ca2+ with quin-2/AM inhibited glucocorticoid-induced apoptosis as reported on rat thymocytes. Dexamethasone-induced apoptosis in both murine and rat thymocytes, however, was not inhibited by EGTA. High concentrations (25 microM and over) of quin-2/AM inhibited DNA fragmentation, but failed to inhibit cytolysis. Calmodulin inhibitors, trifluoperazine and calmidazolium, also inhibited DNA fragmentation as reported, although they markedly enhanced cytolysis. Therefore, glucocorticoid-induced death is not inhibited by quin-2/AM or calmodulin inhibitors. Furthermore, we have previously found that a proper combination of the calcium ionophore, ionomycin, and the protein kinase activator, PMA, inhibits corticosterone-induced apoptosis. These results suggest that an early increase in [Ca2+]i is neither induced by glucocorticoids nor responsible for glucocorticoid-induced apoptosis in thymocytes.

Aminoquinolines↗
PubMed1993

A brain extracellular matrix proteoglycan forms aggregates with hyaluronan.

Unlike many tissues, the adult central nervous system extracellular matrix (ECM) has few known components. Previously, we characterized a large chondroitin sulfate proteoglycan, pgT1, from adult rat brain which has the properties of a general brain ECM component and is immunologically distinct from aggrecan and versican (Iwata, M., and Carlson, S.S. (1993) J. Neurosci. 13, 195-207). In this study we demonstrate that pgT1 binds hyaluronan with relatively high affinity. The pgT1 preparation isolated from rat brain aggregates in non-denaturing conditions. This aggregation is abolished by incubation of pgT1 with Streptomyces hyaluronidase. Examination of these aggregates by electron microscope reveals a structure in which an average of 18 subunits arise laterally from opposite sides of an elongated 350-nm filament. These pgT1 aggregates resemble the proteoglycan aggregates in cartilage which are composed of aggrecan and hyaluronan. Using affinity coelectrophoresis, we measure a dissociation constant (Kd) of 0.9 +/- 0.2 nM for the interaction of pgT1 and hyaluronan. These new findings, combined with the general distribution of pgT1 in brain, suggest that pgT1/hyaluronan aggregates are an extended general structure of the brain extracellular matrix network.

Animals↗
PubMed1993

MR imaging findings of tremors associated with lesions in cerebellar outflow tracts: report of two cases.

Two cases with severe tremors were studied by means of electromyograms using surface electrodes and also by magnetic resonance (MR) imaging. The first case was associated with multiple sclerosis and demonstrated a severe postural cerebellar tremor and an alternate activation of antagonist muscles in the right arm. The second case, with hemorrhage in the brainstem, demonstrated a severe tremor at rest and mixed synchronous and alternating activation of antagonist muscles in the left forearm. MR imaging studies localized lesions possibly responsible for these tremors. In the first case a lesion was located in the superior cerebellar peduncle just under the decussation, and in the second case a lesion was found between the red nucleus and the thalamus, with possible involvement of both the cerebellothalamic and nigrostriatal pathways. The first case accords with the theory that a lesion located in the dentate nucleus and its projection can cause severe postural cerebellar tremor. The lesion demonstrated in the second case may be responsible for "cerebellar tremor at rest" or "static (resting) cerebellar tremor."

Adult↗
PubMed1993

Divergence of gene expression in neurohypophysial hormone precursors among salmonids.

Salmonid fish have pairs of genes for various hypothalamic and pituitary hormones including neurohypophysial hormones, vasotocin, and isotocin, probably because they are tetraploid. The problem here is whether two genes for the same hormone are expressed equally or differently. We therefore examined expression patterns of vasotocin and isotocin genes in four salmonid species using Northern blot analysis with chum salmon cDNAs as hybridization probes. The presence of two vasotocin and also two isotocin genes was confirmed by Southern blot analysis in rainbow trout and sockeye salmon which were not examined previously. Prior to Northern blot analysis, isotocin-I cDNA of sockeye salmon was determined and compared to those of chum salmon and masu salmon, since molecular probes are so specific that cross-species hybridization often leads misinterpretation in a quantitative study. The nucleotide sequence of sockeye salmon isotocin-I cDNA showed sufficiently high homology (> 96.0%) to those of chum salmon and masu salmon for cross-species hybridization among salmonids. Northern blot analysis showed that both isotocin-I and isotocin-II genes were well expressed in all species examined. Expression of isotocin-I gene tended to be relatively higher than that of isotocin-II gene in all species. However, expression pattern of vasotocin-I and vasotocin-II genes did not coincide among species. Expression of vasotocin-II genes was very weak or scarce in masu salmon and rainbow trout, while that in sockeye salmon was stronger than vasotocin-I gene expression. The present result may reflect complicated molecular evolution of salmonid vasotocin genes probably both in regulatory and coding regions.

Amino Acid Sequence↗
PubMed1993

Modification of metabolism and neurotoxicity of hexane by co-exposure of toluene.

The effects of co-exposure of hexane and toluene were investigated in field surveys and animal experiments. One field survey suggested that increase of hexane content in adhesives might have caused an outbreak of polyneuropathy in a vinyl sandal manufacture in Japan. The animal experiments proved that co-exposure of hexane and toluene decrease hexane neurotoxicity and urinary excretion of hexane metabolites in rats. The results also suggested that toluene might inhibit metabolism of hexane. Another recent field survey indicated that the ratio of urinary 2,5-hexanedione to hexane exposure in the workers co-exposed to hexane and toluene decreased in parallel with in more crease of toluene concentration. The results indicated that urinary excretion of 2,5-hexanedione could be depressed by co-exposure of toluene even in the workers exposed to relatively low concentrations. These above-mentioned results suggest that co-exposure of hexane and toluene could inhibit hexane metabolism and decrease hexane neurotoxicity in both experimental animals and workers. Although metabolism of hexane could be easily modified by toluene or other solvents and might not be a good indicator for hexane exposure in mixed exposure, urinary 2,5-hexanedione might be a good indicator for neurotoxicity of hexane even in mixed exposure.

Adhesives↗
PubMed1993

Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small-cell lung cancer.

Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.

Adult↗
PubMed1993

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Adult↗
PubMed1993

Dissolution, stability, and morphological properties of conventional and multiphase poly(DL-lactic-co-glycolic acid) microspheres containing water-soluble compounds.

Multiphase microspheres of poly(DL-lactic-co-glycolic acid) (PLGA) containing water-soluble compounds were prepared by a multiple-emulsion solvent evaporation technique. These compounds were dissolved in the aqueous phase of a W/O emulsion with soybean oil as the oil phase. This emulsion was dispersed throughout the matrix of the microsphere. The morphological properties of the multiphase microspheres during in vitro dissolution studies were compared to those of conventional microspheres prepared from the same polymer. Drug release from the multiphase microspheres was characterized by an initial uniform release for the first 20 days followed by a more rapid phase of drug release. Chlorpheniramine maleate (CPM) and brilliant blue (BB) were the soluble model compounds investigated. The release rates of these agents from the multiphase microspheres were independent of the drug content in the microspheres. The release profiles from the conventional microspheres showed a lag time of 10 and 16 days for the CPM and BB, respectively. The dissolution rate of the model soluble compounds from the conventional microspheres increased as the loading in the microspheres increased. No differences in the degradation rate of the PLGA from the multiphase and the conventional microspheres were seen during the dissolution studies.

Acetonitriles↗
PubMed1993

Semantic process in kana word reading: activation studies with positron emission tomography.

Regional cerebral blood flow was measured by positron emission tomography to study changes during Japanese kana word or kana non-word reading tasks. The main cortical activation was observed bilaterally in the lateral and medial occipital gyri, and the left posterior inferior temporal area in both kana word and kana non-word tasks. In addition, the kana word task activated the right posterior inferior temporal area. Comparison of the mean regional cerebral blood flow increases revealed that the kana word task activated the left posterior inferior temporal area more than the kana non-word task, suggesting the role of the semantic process as well as the morphological one in this area.

Adolescent↗
PubMed1993

The SV2 protein of synaptic vesicles is a keratan sulfate proteoglycan.

We have determined that synaptic vesicles contain a vesicle-specific keratan sulfate integral membrane proteoglycan. This is a major proteoglycan in electric organ synaptic vesicles. It exists in two forms on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, i.e., the L form, which migrates like a protein with an M(r) of 100,000, and the H form, with a lower mobility that migrates with an M(r) of approximately 250,000. Both forms contain SV2, an epitope located on the cytoplasmic side of the vesicle membrane. In addition to electric organ, we have analyzed the SV2 proteoglycan in vesicle fractions from two other sources, electric fish brain and rat brain. Both the H and L forms of SV2 are present in these vesicles and all are keratan sulfate proteoglycans. Unlike previously studied synaptic vesicle proteins, this proteoglycan contains a marker specific for a single group of neurons. This marker is an antigenically unique keratan sulfate side chain that is specific for the cells innervating the electric organ; it is not found on the synaptic vesicle keratan sulfate proteoglycan in other neurons of the electric fish brain.

Animals↗