Biomedical subjects

Y Miyata

Publications and source records attributed to Y Miyata.

At least 163 records · Page 9Linked to original sources

PubMed1996

[Coronary artery bypass grafting for ischemic heart disease associated with acromegaly: a case report].

Coronary artery bypass grafting (CABG) for ischemic heart disease associated with acromegaly has never been reported in Japan, though coronary artery sclerosis is known as complicating factor in acromegaly. A 44-year-old man with ischemic heart disease was admitted to our hospital and emergency percutaneous transluminal coronary recanalization was performed. After admission, he was diagnosed as acromegaly from endocrinological studies and operated on CABG. The peri- and post-operative course was uneventful in spite of our fear for complications due to acromegalic heart muscle disease.

Acromegaly↗

PubMed1996

[Clinical study of serum antibodies specific to Chlamydia trachomatis in patients with chronic nonbacterial prostatitis and prostatodynia].

The etiological role of Chlamydia trachomatis in chronic nonbacterial prostatitis is controversial. To assess whether C. trachomatis relates to chronic nonbacterial prostatitis, we investigated the serum levels of immunoglobulin G (IgG) and IgA antibodies specific for C. trachomatis in 41 patients with chronic nonbacterial prostatitis and 47 patients with prostatodynia. The positive rates of the IgG antibody were 29% and 28% in patients with chronic nonbacterial prostatitis and prostatodynia, respectively. There was little difference in the positive rates of the IgG and IgA antibodies for C. trachomatis, between patients with chronic nonbacterial prostatitis and prostatodynia. Also, there was no significant difference in the positive rate of the IgG antibody between 51 patients complaining of urinary symptoms and 25 complaining of referred pain. However, a high positive rate of the IgG antibody (80%) was observed in patients with hematospermia. Our findings suggest that C. trachomatis could not be etiologically responsible for chronic nonbacterial prostatitis, but that it may be related to hematospermia.

Adult↗

PubMed1995

Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system, II: Neuropeptides and amino acids.

In a previous study, we have found acetylcholine and/or L-DOPA in 10 colonial clones from one cell line of Drosophila larval central nervous system (CNS). In this study, to characterize clonal neuronal phenotypes further, we have examined three neuropeptides and 19 amino acids using HPLC system. Substance P and proctolin were found in seven and eight out of ten clones, respectively. On the other hand, somatostatin was expressed in all ten clones. GABA and taurine were not detected in any clones. Glutamate, which is an excitatory transmitter in Drosophila, was found in all the clones, although its content was different seven times among them. Glycine, which is not known as a transmitter in Drosophila, was found to be unevenly expressed among them. Therefore, the conspicuous expression of peptides or amino acids in some clones suggests that the substances have a special role in Drosophila CNS.

Amino Acids↗

PubMed1995

Interaction between casein kinase II and the 90-kDa stress protein, HSP90.

Purified casein kinase II (CKII) aggregates and loses activity under physiological salt conditions and within the range of physiological temperatures. In accord with our previous report [Miyata, Y., & Yahara, I. (1992) J. Biol. Chem. 267, 7042-7047], we report here that HSP90 protects CKII from the aggregation and inactivation by forming soluble CKII-HSP90 complexes. Surface plasmon resonance (SPR) measurements revealed that CKII binds to immobilized HSP90 within minutes. The KD of the binding is approximately 10(-7) M. ATP does not influence the interaction. The membrane-overlay method revealed that HSP90 binds to the catalytic CKII alpha subunit. Heparin, which binds to CKII alpha, inhibited the binding of CKII to HSP90-Sepharose. In addition, HSP90 competed with DNA for binding to CKII. Finally, SPR experiments showed that a peptide corresponding to the heparin and DNA binding site of CKII alpha binds to immobilized HSP90. These results indicate that HSP90, DNA, and heparin compete with each other for binding to a common site of CKII alpha. If the binding of CKII to DNA is biologically significant, it could be possibly regulated also by HSP90.

Amino Acid Sequence↗

PubMed1995

Autophosphorylation of grp94 (endoplasmin).

The 94-kDa glucose-regulated protein (endoplasmin, grp94) is an abundant member of the 90-kDa molecular chaperone family in the endoplasmic reticulum. We have found earlier that the 50% homologous 90-kDa heat shock protein, hsp90, has ATP-binding site(s) and autophosphorylating activity (Csermely, P., and Kahn, C. R. (1991) J. Biol. Chem. 266, 4943-4950). In the present paper we demonstrate that highly purified grp94 is also able to autophosphorylate itself on serine and threonine residues. grp94 can be freed from the co-purifying casein kinase II by concanavalin A affinity chromatography, and its phosphorylation is unaffected by activators and inhibitors of numerous protein kinases known to associate with the homologous hsp90. The autophosphorylation persists in immunoprecipitates and in SDS-polyacrylamide gel-purified and renatured grp94. Autophosphorylation displays a monomolecular kinetics, is activated by micromolar calcium concentrations, has an extreme heat stability, and can utilize both ATP and GTP with relatively high km values of 243 +/- 14 microM and 116 +/- 23 microM, respectively. Sequence analysis of grp94 shows the presence of two ATP-binding sites. The major product of limited proteolysis of grp94 by chymotrypsin or papain is an N-terminal 85-kDa fragment that can bind to ATP-agarose but does not show autophosphorylation. Our data suggest that grp94 has an enzymatic function analogous in many respects to the similar activity of hsp70, hsp90, and grp78 (BiP). Autophosphorylation may participate in/regulate the complex formation of these proteins, so it may be involved in their chaperone function.

Adenosine Triphosphate↗

PubMed1995

A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38.

The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10-hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT-11 administration. The model was developed with a training set consisting of pharmacokinetic studies in 36 patients who received a 90-min i.v. infusion of CPT-11 at a dose of 100 mg/m2. A multiple regression analysis of CPT-11 or SN-38 concentrations observed at each time point in the training set was used to predict the AUC of CPT-11 or SN-38. The final sampling models using only two time points were: AUCCPT-11 = 3.7891*C2.5 + 14.0479*C13.5 + 1.5463 AUCSN-38 = 0.5319*C2.5 + 19.1468*C13.5 + 72.7349 where C2.5 and C13.5 are the plasma concentration of CPT-11 (micrograms/ml) or SN-38 (ng/ml) at 2.5 and 13.5 h after the initiation of CPT-11 infusion, respectively. The models were validated prospectively on a separate test data set of 12 patients receiving the same dose of CPT-11 investigated in a previous study. Validation of the final LSM on the test data set gave values of root mean square error (RMSE) of 12.72% and 5.97% for the AUC of CPT-11 and that of SN-38, respectively. The model can be used to monitor the AUCs of both CPT-11 and SN-38 for the early prediction of toxicities and to establish a pharmacokinetically based dose modification strategy for safe administration of CPT-11.

Adult↗

PubMed1995

Porphyromonas gingivalis fimbria-stimulated bone resorption in vitro is inhibited by a tyrosine kinase inhibitor.

Our previous study (Y. Kawata, S. Hanazawa, S. Amano, Y. Murakami, T. Matsumoto, K. Nishida, and S. Kitano, Infect. Immun. 62:3012-3016, 1994) showed that Porphyromonas gingivalis fimbriae stimulate bone resorption in vitro. Since it has recently been demonstrated that tyrosine kinase encoded by the c-src gene plays an important role in osteoclastic bone resorption, in the present study we examined the effect of a tyrosine kinase inhibitor on the fimbria-stimulated bone resorption. Genistein, a potent inhibitor of tyrosine kinase, markedly inhibited bone resorption stimulated by the fimbriae. Genistein also inhibited induction of several tyrosine-phosphorylated proteins in the fimbria-treated calvarial bone cells from mouse embryos.

Animals↗

PubMed1995

Expression and phosphorylation of BiP/GRP78, a molecular chaperone in the endoplasmic reticulum, during the differentiation of a mouse myeloblastic cell line.

To determine the functional significance of endoplasmic reticulum chaperones in hematopoietic cells, we analyzed the expression and post-translational modification of BiP/GRP78 and GRP94 as well as the cytoplasmic chaperones HSP70 and HSC70 during the differentiation of a mouse myeloid leukemia cell line, M1. The amounts of BiP/GRP78 and GRP94 increased several-fold when M1 cells were induced to differentiate into macrophage-like cells by treatment with interleukin-6 (IL-6). Synthesis began to increase at 4 hr after IL-6 treatment. The phosphorylated form of BiP/GRP78 increased during the later stages of differentiation. These data suggested that the chaperone activity of BiP/GRP78 and GRP94 may be needed for differentiated macrophage-like cells or for the differentiation event itself, and that functionally different BiP/GRP78 accumulate during the differentiation of M1 cells.

Animals↗

PubMed1995

A novel hexahydrodibenzofuran derivative with potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells from Lindera umbellata bark.

A novel cinnamoyl-hexahydrodibenzofuran derivative (1) was isolated from the bark of Lindera umbellata. The structure was determined by extensive spectroscopic analysis to be (5aR*,6R*,9R*,9aS*)-4-cinnamoyl-3,6-dihydroxy-1-methoxy-6-me thyl- 9-(1-methylethyl)-5a,6,7,8,9,9a-hexahydrodibenzofuran. Compound 1 showed potent inhibitory activity on melanin biosynthesis of cultured B-16 melanoma cells without causing any cytotoxicity in the cultured cells or skin irritation in guinea pig.

Animals↗

PubMed1995

[Recent advances in chemotherapy for advanced gastric cancer: from the standpoint of survival advantages].

Recently, there have been many reports indicating higher response rates in combination chemotherapies for advanced gastric cancer. Since 1990, several randomized controlled trials (RCT) have been reported, which showed evidences of survival impacts in such cases. Patients treated with chemotherapy obtained significant survival advantages over those with best supportive care in three RCTs. The RCT from EORTC also resulted in more significant survival prolongation in FAMTX than in FAM, and FAMTX should be a reference arm for new regimens. Some RCTs are now under way to establish a standard therapy for advanced gastric cancer. From the analysis of long-term results of Japanese studies, 3% of entry cases survived longer than 5 years with no evidence of disease by chemotherapy. Chemotherapy for gastric cancer should be evaluated with survival advantages or rate of long-term survivors in future studies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Concurrent chemotherapy and radiation therapy for locally advanced carcinoma of the esophagus.

A pilot study was undertaken to clarify the efficacy of concurrent chemoradiotherapy against locally advanced esophageal carcinoma. The 20 patients in this study had previously untreated esophageal carcinoma with evidence of T4 disease and/or distant node metastases. Chemotherapy consisted of protracted infusion of 5-fluorouracil at a dose of 400 mg/m2/day on days 1-5 and 8-12, combined with a 2-h infusion of cisplatinum at 40 mg/m2 on days 1 and 8. Radiation treatment for the mediastinum was administered 5 days per week for 3 wk at 2 Gy/day, along with chemotherapy. These schedules were repeated twice to give a total radiation dose of 60 Gy. For patients who responded, two additional courses of chemotherapy were administered. Five of the 20 patients had UICC stage III disease and 15 had stage IV. Seventeen (85%) of the 20 patients exhibited an objective response, including 6 (30%) complete responses. Local control was excellent with 10 (50%) complete responses. Toxic effects were severe. Major toxicities were leukocytopenia of grade 3 or more in 45% of the patients and esophagitis, including four perforations. There were two treatment-related deaths. The median survival time was 9 mo (range: 2 to 34+). Concurrent chemotherapy and radiotherapy was effective even for locally advanced esophageal carcinoma, but was associated with significant toxicity.

Aged↗

PubMed1995

Clinical pharmacokinetics and pharmacodynamics of paclitaxel: a 3-hour infusion versus a 24-hour infusion.

The present study was conducted to compare the pharmacokinetics and pharmacodynamics (PD) of paclitaxel between Phase I trials of 3- and 24-h infusions and to determine the most informative pharmacokinetic parameter to describe the PD. Twenty-seven patients were treated in a Phase I study of paclitaxel by a 3-h infusion at one of six doses: 105, 135, 180, 210, 240, and 270 mg/m2. Pharmacokinetic data were obtained from all patients. Paclitaxel concentrations were measured in the plasma and urine using HPLC. The pharmacokinetics and PD were compared with those of a Phase I trial of paclitaxel by a 24-h schedule previously performed. The maximum tolerated dose of paclitaxel by a 3-h infusion was determined to be 240 mg/m2. The major toxicities were granulocytopenia, neuromuscular toxicities, and hypotension. Apparent differences in pharmacodynamic relationships for the change in granulocytes with dose, peak concentration, and areas under the concentration versus time curve were observed between the 3- and 24-h schedules. However, the relationship between the duration of plasma concentration above 0.05 microM and the change in granulocytes could be fitted to the same sigmoid maximum effect model in either schedule (P < 0.01). There were no clear relationships between peripheral neuropathy or hypotension and any pharmacokinetic parameters. The pharmacokinetics and PD of paclitaxel were schedule dependent. The duration of plasma concentration above 0.05 microM could be a common pharmacokinetic parameter predicting granulocytopenia for both schedules.

Agranulocytosis↗

PubMed1994

Chemical analysis of neurotransmitter candidates in clonal cell lines from Drosophila central nervous system. I. ACh and L-dopa.

To characterize neuronal phenotypes, aminergic neurotransmitters, i.e. acetylcholine (ACh), catecholamine (CA)s and other biogenic amines (serotonin, octopamine), were surveyed in 10 colonial clones from one cell line of Drosophila larval CNS using HPLC-ECD system. ACh, which is a neurotransmitter in Drosophila, was found in 7 out of 10 clones. CAs, their metabolites, and other amines were not detected in any clones. However, all the 10 clones expressed L-dopa, a precursor of CAs. Consequently, seven clones expressed ACh and L-dopa. L-dopa as a novel neurotransmitter candidate was discussed.

Acetylcholine↗

PubMed1994

Phorbol myristate acetate stimulates osteoclast formation in 1 alpha,25-dihydroxyvitamin D3-primed mouse embryonic calvarial cells by a prostaglandin-dependent mechanism.

Our previous study provided a novel assay system utilizing devitalized bone slices for study of the differentiation of osteoclast progenitors into preosteoclasts and mature osteoclasts among calvarial cells of mouse embryos. Using this assay system, we examined the effect of phorbol myristate acetate (PMA) on osteoclast formation as assessed by the appearance of tartrate-resistant acid phosphatase (TRAP)-positive cells and bone resorption lacunae. PMA alone was directly unable to induce the appearance of TRAP-positive cells and bone resorption lacunae of calvarial bone cells of mouse embryos. However, PMA markedly stimulated increases in the number of TRAP-positive cells and area of the resorption lacunae of the calvarial cells when the bone cells were primed by 1 alpha,25-(OH)2D3. This stimulatory effect of PMA was dose dependent. H-7, having relatively high affinity for protein kinase C, strongly inhibited in a dose-dependent fashion the stimulatory effect of PMA on the bone resorption of the hormone-primed calvarial cells. We also examined the involvement of prostaglandin in this stimulatory effect of PMA. Indomethacin, a cyclooxygenase inhibitor, markedly abolished the stimulatory effect of PMA on the bone resorption of the calvarial cells. PMA stimulated prostaglandin E2 (PGE2) production by the calvarial cells primed with 1 alpha,25-(OH)2D3 in a dose-dependent fashion. However, the PMA stimulation of the PGE2 production was significantly inhibited by H-7 and also by indomethacin. Furthermore, we observed that the addition of PGE2 to the calvarial cells primed with 1 alpha,25-(OH)2D3 for 1 or 3 days resulted in an increased number of TRAP-positive cells and increased bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Glutamic acid potentiates hepatocyte response to mitogens in primary culture.

Adult rat hepatocytes in primary culture responded to epidermal growth factor (EGF) by increased DNA synthesis. When hepatocytes were cultured in Leibovitz L-15 medium, their response to EGF was low compared with that in Williams' medium E or Koga's medium L. Furthermore, female rat hepatocytes showed almost no response to the mitogenic action of EGF compared with male rat hepatocytes in L-15 medium. Addition of glutamic acid (1-20 mM) to EGF-containing L-15 medium not only enhanced DNA synthesis > tenfold in both male and female hepatocytes, but eliminated the sex differences in DNA synthesis. Aspartic acid, glutamine, or ornithine at 20 mM did not replace the glutamic acid effect on DNA synthesis. Proline also enhanced EGF-induced DNA synthesis, although it was less effective than glutamic acid. Therefore, this effect may be specific to a high concentration of glutamic acid. Glutamic acid by itself did not stimulate DNA synthesis at any concentrations tested. In the presence of glutamic acid, EGF showed a dose-dependent (0.5-20 ng/ml) stimulation of DNA synthesis with a maximal effect at 10 ng/ml. Almost the same effect was obtained with transforming growth factor alpha (0.5-20 ng/ml). Glutamic acid also induced an expansion of the mitogenic action of angiotensin II. Since glutamic acid did not affect [125I]EGF binding to hepatocytes or its processing, the effect may occur internal to the receptor. These results suggest that glutamic acid modulates the sensitivity of the hepatocyte response to mitogens.

Amino Acids↗

PubMed1994

Therapeutic response and potential pitfalls in phase I clinical trials of anticancer agents conducted in Japan.

The published reports of phase I clinical trials of anticancer agents conducted in Japan from 1981 to 1991 were reviewed. A total of 56 clinical studies that evaluated 38 different agents were reviewed. An average of five agents were studied each year. A total of 2200 patients had been recruited into the 56 clinical trials conducted during this period. A total of 91 patients (4.1%) responded to the treatment, with 23 showing a complete response (1.1%) and 48, a partial response (2.2%). In all, 62% of the responses were observed when patients were treated with doses ranging from 76% to 125% of the recommended doses for phase II studies. The response rates obtained for hematological malignancies were higher than those reported for other malignancies. The past status of phase I clinical trials in Japan can be summarized as follows. (1) A median of seven institutes participated in a single trial. The number of institutes participating correlated with the number of patients enrolled. However, too many institutes participated in a single phase I clinical trial in some studies. (2) The median duration of study for the clinical trials was 14 months. The duration of study was too long in some studies, considering the small number of patients enrolled. In conclusion, the methodology of phase I clinical trials of anticancer agents conducted in Japan should be improved in an efficient and scientific manner, especially for the testing of imported agents.

Antineoplastic Agents↗

PubMed1994

Newly established cell lines from Drosophila larval CNS express neural specific characteristics.

From the central nervous system of Drosophila melanogaster 3rd instar larvae, eight continuous cell lines have been established (named ML-DmBG1 to 8). Using ML-DmBG2, single colony isolation was carried out and six colonial clones were obtained. All reacted to the antibody to horseradish peroxidase, which is a neuronal marker in insects. Acetylcholine, a known neurotransmitter in Drosophila, was detected in three of the colonial clones by high performance liquid chromatography. Therefore, it is concluded that the established colonial clones are neural cells originating in the larval central nervous system. Among them, some variation was observed with respect to morphology, acetylcholine content, and reactivity to anti-HRP. The variation may reflect the heterogeneity of cells composing the central nervous system.

Acetylcholine↗

PubMed1994

Inhibition of 15-hydroxy prostaglandin dehydrogenase activity in rabbit gastric antral mucosa by 13-hydroperoxyoctadecadienoic acid.

The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE), a hydroperoxy adduct of linoleic acid (LA), on the activities of prostaglandin (PG) synthesizing and catabolizing enzymes in rabbit gastric antral mucosa was examined. 13-HPODE had no effect on the synthesis of PGE2, PGF2 alpha and PGD2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa at concentrations ranging from 5-20 microM. On the other hand, at 1-10 microM, it inhibited the activity of 15-hydroxy PG dehydrogenase (PGDH), which catalyzes the initial step of catabolism of PGs, in a dose-dependent manner. The concentration required for 50% inhibition was approximately 1 microM. Experiments utilizing LA, 13-hydroperoxyoctadecadienoic acid and Fe2+ indicated the requirement of the hydroperoxy moiety for the inhibitory effect of 13-HPODE on the PGDH activity. These results suggest that 13-HPODE has the potential to increase the levels of biologically active PGs in gastric mucosa by preventing their inactivation and may have functional effects within the stomach.

Animals↗