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Biomedical subjects

K Ohta

Publications and source records attributed to K Ohta.

At least 505 records · Page 28Linked to original sources
PubMed1993

Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells.

Endothelins (ET) produce endothelium-dependent vasodilation through nitric oxide (NO) synthesis. The present study was designed to elucidate the cellular mechanism by which ET induces synthesis and release of endothelium-derived NO by cultured bovine endothelial cells (EC). Binding studies revealed that bovine EC membrane had the binding sites of a novel agonist (BQ3020) for non-isopeptide-selective receptor subtype (ETB). Affinity labeling studies showed a major labeled band with the apparent molecular mass of 50 kD. Northern blot analysis demonstrated the expression of mRNA for ETB receptor. BQ3020 rapidly and dose dependently induced formation of inositol-1,4,5-triphosphate and increased intracellular Ca2+ concentrations in fura-2-loaded cells. Concomitantly, BQ3020 dose dependently stimulated production of both nitrate/nitrite (NOx) and cyclic GMP; a highly significant correlation existed between NOx and cGMP production. The stimulatory effect on NOx and cGMP production by ETB agonist was inhibited by NO synthase inhibitor monomethyl-L-arginine; this effect was reversed by coaddition of L-arginine, but not D-arginine. NOx and cGMP production stimulated by BQ3020 was inhibited by pretreatment with pertussis toxin. ETB agonist-induced NOx production was blocked by a calmodulin inhibitor and an intracellular Ca2+ chelator, but not by an extracellular Ca2+ chelator or a Ca2+ channel blocker. These data suggest that endothelins stimulate ETB receptor-mediated phosphoinositide breakdown via pertussis toxin-sensitive G-protein(s), which triggers release of intracellular Ca2+, thereby activating Ca2+/calmodulin-dependent NO synthase in EC.

Amino Acid Oxidoreductases↗
PubMed1993

Microtubule nucleating activity of centrosomes in cell-free extracts from Xenopus eggs: involvement of phosphorylation and accumulation of pericentriolar material.

We have studied the regulation of microtubule nucleating activity of the centrosome using cell-free extracts from Xenopus eggs. We found that the number of microtubules per centrosome increases dramatically with time during incubation of isolated centrosomes in interphasic egg extracts prepared 20-30 minutes after electric activation of cytostatic factor (CSF)-arrested eggs. The increase in microtubule nucleation was still conspicuous even when KCl-treated centrosomes (centrosomes stripped of their microtubule nucleating activity by 1 M KCl treatment) were incubated in interphasic extracts. Electron microscopy and immunostaining by anti-gamma-tubulin and 5051 human anti-centrosome antibodies revealed that pericentriolar material (PCM) was accumulated during the increase in microtubule nucleation from centrosomes in interphasic extracts, suggesting regulation of centrosomal activity by PCM accumulation. The ability of egg extracts to activate microtubule nucleation from centrosomes was also assumed to be regulated by phosphorylation, since addition of protein kinase inhibitors into interphasic extracts totally blocked the increase in microtubule nucleation from the KCl-treated centrosome. The ability of CSF-arrested mitotic extracts to increase microtubule nucleation from KCl-treated centrosomes was 3.5- to 5-fold higher than that of interphasic extracts, while PCM accumulation in mitotic extracts seemed to be similar to that in interphasic extracts. The increase in microtubule nucleation from KCl-treated centrosomes was strikingly enhanced by the addition of purified p34cdc2/cyclin B complex to interphasic extracts, but not by MAP kinase, which is activated downstream of p34cdc2/cyclin B. These results suggest two pathways activating centrosomal activity in egg extracts: accumulation of PCM and phosphorylation mediated by p34cdc2/cyclin B.

Alkaloids↗
PubMed1993

Interleukin-1 beta induces nitric oxide production by a mouse pituitary tumour cell line (AtT20/D16).

To elucidate whether anterior pituitary cells express the nitric oxide (NO) synthase gene, we studied the synthesis of NO and the expression of NO synthase (NOS) mRNA by a mouse pituitary tumour cell line (AtT20/D16). Interleukin-1 beta (IL-1 beta) stimulated production of NO2-/NO3-(NOx) in a time-dependent manner and both NOx and cyclic GMP formation were stimulated in a dose-dependent manner by IL-1 beta. IL-1 beta-induced NOx production and intracellular cyclic GMP formation were similarly blocked by an NO synthase inhibitor, NG-monomethyl-L-arginine (LNMMA), whose effect was reversed by L-arginine, but not by D-arginine. Dexamethasone inhibited IL-1 beta-induced NOx production in a dose-dependent manner. A calmodulin inhibitor (W-7) showed no effect on IL-1 beta-induced NOx production, whereas cycloheximide and the actinomycin D completely inhibited NOx production. Northern blot analysis using cDNA for mouse macrophage-inducible NOS as a probe revealed the expression of inducible NOS mRNA in the cells only after exposure to IL-1 beta. Although IL-1 beta stimulated ACTH release from tumour cells, LNMMA failed to affect ACTH release stimulated by IL-1 beta. These results demonstrate for the first time that a pituitary tumour cell line (AtT20/D16) possesses cytokine-inducible and Ca2+/calmodulin-independent NOS, although NO may not be involved in ACTH release.

Amino Acid Oxidoreductases↗
PubMed1993

[Pathogenesis of idiopathic pulmonary fibrosis--is hepatitis C virus involved?].

Hepatitis C virus (HCV) is a new virus discovered in 1989. Since HCV is known to cause fibrotic changes in the liver, we studied whether HCV is involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Firstly, we assessed anti-HCV antibodies by enzyme-linked immunosorbent assay (ELISA) in the sera obtained from 66 IPF patients (46 males and 20 females; mean age +/- SEM, 61.5 +/- 10.1). We observed a significantly high prevalence of anti-HCV antibodies in IPF compared with 9,464 age-matched controls (28.8% vs 3.66%, p < 0.05). To confirm the results, recombinant immunoblotting assay (RIBA) was conducted on the 19 ELISA-positive sera, and 8 sera (12.2%) were found to be definitely positive. Secondly, we searched for HCV in the blood of IPF patients by reverse transcription-polymerase chain reaction. As preliminary data, four out of 28 cases (14.3%), all of which were pathologically diagnosed as UIP, were positive for HCV. In conclusion, although further investigation is required, a high prevalence of anti-HCV antibodies and the existence of HCV itself in the blood may suggest the possibility that HCV infection plays an important role in the pathogenesis of IPF.

Aged↗
PubMed1993

Surgical strategy for papillary carcinoma of the thyroid in an iodine rich area: decision on the operation table.

In iodine rich areas the incidence of papillary carcinoma of the thyroid is extremely high but its prognosis is favorable. When papillary carcinoma is confined to one lobe, our standard surgical procedure has been total lobectomy with isthmusectomy rather than total thyroidectomy. Our followup study of 185 such patients reveals considerable difference in the outcome between the 85 patients with gross thyroid capsular invasion and the 100 patients without, regardless of the presence of cervical lymph node metastasis. In the latter group, the tumor could be completely resected in all patients; although 4 cases had recurrence and required reoperation, 3 patients are alive and well and one died of other disease. In contrast, 20 patients in the former group had incomplete resection of the tumor, 4 patients developed recurrence and needed to be reoperated and 7 patients eventually died of thyroid cancer. One hundred thirty three patients (71.9%) underwent modified neck dissection at the time of surgery to find lymph node metastasis in 37 of 59 cases (62.7%) without gross thyroid capsular invasion and 64 of 74 cases (86.5%) with such invasion. The difference is statistically significant (P < 0.05). From these results we conclude that for papillary thyroid cancer in iodine rich areas total lobectomy with isthmusectomy is the treatment of choice when gross thyroid capsular invasion is not recognized on the operation table. However, when gross thyroid capsular invasion is recognized, total or near total thyroidectomy has to be performed.

Adult↗
PubMed1993

[A case of marked eosinophilia in peripheral blood induced by rhGM-CSF].

A 53-year-old man underwent chemotherapy (CDDP, VDS, MMC) for treatment of lung cancer. He was given 125 micrograms/m2 of GM-CSF subcutaneously every day for 8 consecutive days, in order to prevent neutropenia. Three days after starting GM-CSF therapy, marked eosinophilia in peripheral blood was observed. The maximum eosinophil count was 89% of leukocytes. Nine days after stopping the treatment with GM-CSF, the number of eosinophils had normalized spontaneously. There were no clinical symptoms except for slight fever, up to 37.5 degrees C. Moreover, there was no relationship between the number of eosinophils and the serum levels of cytokines (IL-3, IL-5, GM-CSF), although we observed minimal but significant elevation of serum ECP level. This case indicates that GM-CSF may induce marked eosinophilia rather than widely stimulating granulocytes and monocytes.

Blood Proteins↗
PubMed1993

[Estimations of organ dose and health risk of the mass chest X-ray examinations in children].

In Japan, mass chest X-ray examinations are mandated by law for schoolchildren and students. Recently, questions of the justification of such X-ray examination have arisen. In this study the absorbed doses of each organ, and the health detriments from the mass chest X-ray examinations to schoolchildren and students were estimated. The doses of organs were measured by the TLDs (Mg2SiO4), slab phantom, and anthropomorphic phantom. The probability of fatal cancer, and the resultant reduction in life expectancy induced by mass chest X-ray examinations were calculated by the multiplicative risk projection model of the ICRP-1990. The absorbed doses of lung, thyroid glands, esophagus, stomach, breast, and red bone marrow in first-year elementary schoolchildren were 90, 30, 90, 60, 90, and 30 muGy, respectively, and the doses in ovaries and testes were almost nil. Each organ dose of first-year students of junior high school was about 1.5 times that for elementary schoolchildren. The total radiation-induced lifetime cancer risk of schoolchildren and students was from 0.3 x 10(-5) to 0.9 x 10(-5) per person by the multiplicative risk projection model of the ICRP-1990 and a factor of 2 for the DDREF (dose and dose rate effectiveness factor). The reduction in life expectancy by radiation induced fatal cancer was from 15 x 10(-5) years to 50 x 10(-5) years per person. The results of this study suggest that subjects of mass chest X-ray examinations should be carefully selected from the viewpoint of radiation protection.

Adolescent↗
PubMed1993

[Gene analysis of maple syrup urine disease (MSUD)].

Maple syrup urine disease (MSUD), an autosomal recessive hereditary metabolic disorder, is due to defective oxidative decarboxylation of the branched-chain alpha-ketoacids (BCKAs) derived from transamination of the three branched-chain amino acids, valine, leucine and isoleucine. The oxidative decarboxylation of three BCKAs is catalysed by the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex. BCKDH consists of three catalytic components: E1, E2 and E3. The E1 component is further composed of two subunits, E1 alpha and E1 beta. To clarify the mechanisms involved in MSUD, measurements of the enzyme activity in cultured cells, measurements of the generation time in cultured cells, complementation analysis and immunoblot analysis were performed. To further elucidate the molecular mechanisms of MSUD, we and others isolated and characterized cDNAs encoding BCKDH-E1 alpha, E1 beta, E2 and E3. The human genome structures of BCKDH -E1 alpha, E1 beta and E2 were also characterized. Gene mutations in E1 alpha, E1 beta and E2, respectively, were identified at the molecular level in three cases of classical MSUD. It became clear that the molecular mechanisms of MSUD involved not only the function of each subunit but also the protein-protein interactions between each subunit. In an attempt to further analyse the molecular basis of MSUD, we carried out complementation analyses by somatic cell hybridization, and identified the affected component of BCKDH complex in the MSUD patient. Furthermore, to rapidly screen for gene mutations, we used PCR-SSCP analysis. Seventeen patients with MSUD were examined using these methods. Defects of E1 alpha, E1 beta and E2 subunits were suspected in 8, 5, and 4 patients, respectively, by complementation analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1993

[Adult T cell leukemia/lymphoma effectively treated with chronic oral etoposide].

A 52-year-old man, who complained of tarry stool and systemic lymphadenopathy, was admitted to our hospital on July 2, 1992. Biopsy showed diffuse large cell lymphoma. Leukocytosis with atypical lymphocytes was not shown in the peripheral blood, but there was an elevated serum LDH level. The man was found to have both HTLV-I antibody and the monoclonal integration of proviral DNA in malignant lymph node cells obtained at biopsy. The diagnosis was lymphoma-type adult T-cell leukemia (ATLL). The chemotherapy regimens of MI-FP, CHOP and modified DHAP were used for the treatment, but were not effective. So, he was treated with etoposide 75 mg orally for 25 days (chronic oral etoposide therapy) and achieved partial remission. This chemotherapy induced myelosuppression with neutropenia, but there was no documented infection. Chronic oral etoposide therapy is an effective regimen for patients with relapse or refractory lymphoma.

Administration, Oral↗
PubMed1993

[Clinical evaluation of granisetron for nausea and vomiting induced by anticancer drugs--optimal dose-finding study].

The efficacy, safety and usefulness of oral granisetron for nausea and vomiting induced by the administration of anticancer drugs were compared among four doses using the subjects registered through telephone calls by the physicians-in-charge. The clinical efficacy of the drug was assessed as "remarkably effective" or "effective" in 50.0% (11/22) in the 0.5 mg group. 68.4% (13/19) in the 1 mg group, 81.0% (17/21) in the 2 mg group and 78.3% (18/23) in the 4 mg group. The antiemetic effect of the drug persisted for approximately 24 hours in the 2 mg and 4 mg groups. No adverse event or abnormal laboratory value fluctuation which might pose a clinical problem was observed. From these results, single administration of oral granisetron at a dose of 2 mg once a day was considered to be the optimal administration and dosage for nausea and vomiting induced by the administration of anticancer drugs.

Administration, Oral↗
PubMed1993

[Clinical evaluation of granisetron for nausea and vomiting induced by anticancer drugs--multi-centered placebo-controlled double-blind comparative study].

A placebo-controlled double-blind comparative trial was conducted to objectively assess the antiemetic effect on nausea and vomiting induced by anticancer drugs including cisplatin (CDDP) and safety of granisetron tablet (2 mg). In the present trial, single oral administration of the trial drug was performed one hour before the start of CDDP administration. 1) In clinical efficacy, the drug was assessed as "remarkably effective" or "effective" in 76.9% (30/39) in G group and 15.2% (7/46) in P group. The drug was assessed as "extremely useful" or "useful" in 84.6% (33/39) and 13.3% (6/45) in respective groups. These results indicated that G group was statistically significantly better than P group in these parameters. 2) In safety rating, the drug was assessed as "safe" in 100% (49/49) in G group and 95.9% (47/49) in P group, indicating equivalent levels between these groups. 3) The antiemetic effect of granisetron tablet was not dependent on patient's background factors including sex, P.S., the dose of CDDP and the number of anticancer drugs concomitantly used with CDDP. 4) The clinical effect of single oral administration of granisetron tablet (2 mg) persisted for approximately 24 hours. 5) In terms of the safety of the trial drug, there was no adverse event or abnormal laboratory fluctuation which might pose a clinical problem. From the above results, it was concluded that single oral administration of granisetron at a dose of 2 mg could suppress nausea and vomiting induced by the administration of anticancer drugs.

Administration, Oral↗
PubMed1993

Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis.

We developed a highly sensitive, convenient assay for measuring blocking-type anti-acetylcholine receptor antibodies, which inhibit the binding of 125I-labeled alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptor (AChR). This procedure detected inhibitory activities in sera from 76% of patients with myasthenia gravis. Results of an experiment done with synthetic peptide corresponding to the alpha-BuTx binding region in the alpha-subunit of Torpedo AChR suggested that this inhibition is due to nonspecific steric hindrance caused by the binding of antibodies to a region other than the alpha-BuTx site, rather than by direct binding to the latter site. The inhibitory activities of the blocking-type antibodies and the titers of non-blocking-type antibodies were correlated. Moreover, the blocking-type antibodies could dissociate 125I-labeled alpha-BuTx from 125I-labeled alpha-BuTx-human AChR complex, and their dissociation activities showed good correlation with the inhibitory activities.

Amino Acid Sequence↗
PubMed1993

[Phase I clinical study of TT-62. Research group of TT-62].

TT-62 is a new derivative of FdUMP, which is the active metabolite of 5-FU. A phase I clinical study of TT-62 was conducted by a cooperative study. The same patients received single and 2-week oral administration of TT-62. Starting from 60 mg/m2 (1n), the dose was escalated to 420 mg/m2 (7n). In the single administration, the maximum tolerated dose (MTD) could not be determined. In the 2-week administration, MTD was 420 mg/m2, and the dose limiting factor was gastro-intestinal disturbances such as anorexia, nausea, vomiting and diarrhea. Increases in GOT.GPT and a decrease in hemoglobin content were observed. After administration was stopped all side effects disappeared. TT-62 was detected mainly in the plasma, while trace amounts of 5-FU and FUdR were also detected. TT-62 was excreted mostly in the urine, as alpha-fluoro-beta-alanine (FBAL). The cumulative urinary excretion of FBAL was about 80% of the total dose, and the oral absorption of TT-62 was thus thought to be good.

Administration, Oral↗
PubMed1993

[Epidural opioids for post-operative pain control in pediatric patients with cerebral palsy].

The safety and efficacy of epidural opioids as postoperative analgesics for children with cerebral palsy were studied in 85 pediatric patients with cerebral palsy. The patients were 5 to 15 years of age and were undergoing elective orthopedic operations on the lower extremities. These patients were divided into four groups. All the patients received inhalational anesthesia combined with caudal anesthesia, while the patients in groups 2, 3, and 4 were given epidural morphine (40 micrograms.kg-1), buprenorphine (3 micrograms.kg-1), or butorphanol (30 micrograms.kg-1) at the end of operation, respectively. Number of patients who received analgesics more than 2 times within 24 hours after operation was larger in group 1 than in groups 2-4. Although groups 2-4 compared with group 1 were still sedated at 24 hours after the operation, there was no difference in degree of sedation among the groups 2-4. The epidural opioids did not increase the frequency of side effects such as nausea, vomiting etc. The authors conclude that epidural opioids achieve safe and useful postoperative pain control in children with cerebral palsy.

Adolescent↗