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Biomedical subjects

K Minato

Publications and source records attributed to K Minato.

At least 55 records · Page 3Linked to original sources
PubMed1994

[Effects of antiandrogen TZP-4238 on the prostatic androgen receptor and prostatic androgen in rat].

TZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and dogs. The effects of TZP-4238 on the androgen receptor and androgen content were examined in comparison with other antiandrogens in rats. The prostate DHT levels decreased markedly within 4-8 hr after a single oral administration of TZP-4238 8mg/kg. The prostatic testosterone concentrations fell below the detection limit (5pg/g of tissue) at 4-12 hr after the initiation of treatment. The plasma testosterone level also fell to 60% of the control level after 4-8 hr and then returned to the normal range. Eight percent of DHT present in normal prostatic tissue was located in the nuclear fraction. TZP-4238 reduced the concentration of DHT in nuclei to 50% of the normal level. The concentration of the plasma drug which induced a 50% decrease in the prostatic DHT, the IC50, was about 10ng/ml, while the IC50 value for plasma testosterone was 30-50ng/ml. After oral administration of 15-OH TZP-4238, the main metabolite, the level of plasma testosterone was significantly elevated above the control level. The androgen receptor level was markedly reduced at 24 hr following castration and returned to the normal range within 5 hr of a single injection of testosterone. TZP-4238 reduced the nuclear androgen receptor level to 60% at 24 hr after a single oral dose and then, the receptor content returned to its original level. Both 15-OH TZP-4238 and cyproterone acetate also reduced the androgen receptor and DHT contents to 50%. A series of in vivo studies demonstrated that TZP-4238 inhibited the uptake of testosterone and the decrease of DHT and testosterone, and decreased the nuclear androgen receptor in the rat prostate.

Androgen Antagonists↗
PubMed1993

[Biliary metabolites of levonorgestrel in rats].

The metabolism of levonorgestrel (LNG) in the bile following oral administration of the drug was examined in female rat. 1) Within 48 h after administration of 14C-labelled LNG (LNG-14C), 67-82% of the radioactivity was excreted into the bile. 2) Almost all the metabolites in the bile were conjugated with glucuronic acid or sulfuric acid and only a small amount of the unchanged compound was found. 3) After treatment of these metabolites in the bile with beta-glucuronidase and arylsulfatase, more than ten aglycones were detected on TLC. Three main aglycones, M1, M2 and M3, were isolated. They accounted for 68.0, 0.8 and 11.5% of the radioactivity excreted into the bile, respectively. 4) The structures of M1 and M2 were assumed to be 13-ethyl-18,19-dinor-5 alpha,17 beta-pregn-20-yne-3 alpha,17- diol and 13-ethyl-18,19-dinor-5 beta,17 beta-pregn-20-yne-3 alpha,17-diol, respectively, by NMR and LC/MS analyses, and confirmed by direct comparison with respective authentic samples. M3 was assigned to be 13-ethyl-18,19-dinor-5 alpha,17 beta-pregn-20-yne-3 alpha,16 beta,17-triol by NMR, LC/MS and GC/MS analyses and acetonide derivation. 5) Isolation of the glucuronide metabolite, M4, from the bile, was achieved by column chromatography using Amberlite XAD-2 and Sephadex LH-20. Hydrolysis of this compound with beta-glucuronidase released M1 and glucuronic acid. After M4 was converted to an acetylated-methyl ester derivative, the definite structural assignment of M4 was established to be M1-3-O-yl glucuronic acid by NMR analysis. The NOE effect and the value of the corresponding coupling constant of the anomeric proton showed that the glucoside moiety was in the beta configuration. These findings suggested that LNG was predominantly converted to 5 alpha-reduced metabolites and that the 5 beta-metabolite accounted for less than 1% of the total metabolites in female rats. These metabolites were excreted as glucuronides into the bile.

Administration, Oral↗
PubMed1993

Differences in clinicopathological characteristics and major prognostic factors between B-lymphoma and peripheral T-lymphoma excluding adult T-cell leukemia/lymphoma.

A total of 541 consecutive patients treated between 1975 and 1985, 449 with B-lymphoma and 92 with peripheral T-lymphoma, excluding adult T-cell leukemia/lymphoma (ATL), termed peripheral non-ATL T-lymphoma, were analysed. Clinicopathological features that were predominantly associated with B-lymphoma were low and intermediate grades (defined by the Working Formulation), diffuse large cell type, stage II disease, bulky disease, favourable extranodal sites that are defined as a group of primary tumors such as the eye, Waldeyer's ring, thyroid, and stomach, while other features predominantly associated with peripheral non-ATL T-lymphoma were high grade pathology, diffuse mixed-cell and immunoblastic type, systemic "B" symptoms, poor performance status (PS), generalized lymphadenopathy, involvement of organs such as liver, skin, and nose, leucocytosis, and a high levels of serum alkaline phosphatase. The survival curve for B-lymphoma was better (P < 0.01) than that for peripheral non-ATL T-lymphoma. Multivariate analysis revealed that the major prognostic factors were pathology, stage, and primary site for B-lymphoma, while stage, PS, and total protein levels were important for peripheral non-ATL T-lymphoma. These results indicate that B- and peripheral non-ATL T-lymphomas appear to have different biological characteristics.

Adult↗
PubMed1993

[A case of long-term survival in a patient with small cell lung carcinoma with syndrome of inappropriate secretion of anti-diuretic hormone].

A 73-year-old man was admitted on April 1984 because of an abnormal shadow on chest X-ray. He was diagnosed as having small cell lung carcinoma (oat cell type) with inappropriate secretion of antidiuretic hormone (SIADH). Initial chemotherapy with cyclophosphamide, ACNU, vincristine, adriamycin, cis-platinum and etoposide was administered. The mass subsequently disappeared, and the serum sodium level normalized. About 2 years later, the patient developed a relapse of the primary lesion with hyponatremia. The same regimen as the initial chemotherapy was initiated and a complete response was again obtained. Similar episodes were repeated four times, and he died in April 1991. This patient survived for about seven years after the initial treatment without maintenance chemotherapy.

Aged↗
PubMed1992

Adult T-cell leukemia/lymphoma (ATL)--clinical, histopathological, immunological and immunohistochemical characteristics.

Twenty-one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium-sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA-DR. That is, the predominant neoplastic cell phenotype was the helper T-cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA-DR+, and CD29- and CD45RO- in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA-DR+, and CD45RA- in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs--the skin, peripheral blood and lymph nodes--of the same patient.

Adult↗
PubMed1992

Quantitative assessment of digitized portal images: effect of sampling frequency on observer performance.

To investigate spatial resolution requirements for digitized portal images in radiation therapy, observer performance tests were performed. One hundred twenty portal images were digitized with sampling frequencies of 0.700, 0.350, and 0.175 mm for observation. Receiver operating characteristic analysis was used to determine the acceptable sampling frequency for clinical portal images. The detectability of setup errors was significantly better on the original images than on the digitized images with sampling frequencies of 0.700 mm (P = .005) and 0.350 (P = .046). Some clinical disadvantages might accrue with the use of a sampling frequency of 0.350 mm or larger.

Humans↗
PubMed1992

Differences in cellular proteins between high and low metastatic potential sublines from the methylcholanthrene-induced rat fibrosarcoma cell line.

The purpose of the present study was to determine with two-dimensional electrophoresis whether two sublines (high and low metastatic potential to lymph nodes) of rat fibrosarcoma induced by methylcholanthrene have differences in cellular proteins. The high metastatic potential subline had a specific protein in the protein map of the whole cell lysate. Its isoelectric point was 6.4 and the molecular weight was 18,000. This specific protein appeared in maps of the precipitate of 1,000 g centrifugation and in the supernatant from treatment with 0.5% Nonidet P-40 (NP-40). But this specific protein was not stained by five lectins, concanavalin A, wheat germ agglutinin, Ulex europeus agglutinin-1, Dolichis biflorus agglutinin, and Ricinus communis agglutinin. Apparently, this high metastatic potential subline has a specific protein in the plasma membrane which has no glycochain.

Animals↗
PubMed1992

Difference of physiological responses to swimming and running.

The purpose of this research is to investigate the range of response to the treadmill running and swimming. Cardiovascular changes and substrates changes in blood were examined before and after healthy male subjects (swimming group (SG) has swimming habits and running group (RG) has practiced basketball or baseball or running more than four days a week) swam and ran for 10 to 15 minutes voluntarily. Average heart rate was recovered more quickly in case of running than swimming in the RG, but in the SG there was no difference. Diastolic blood pressure recovered to the rest condition faster in the SG than RG. In case that subjects have done familiar exercise, free fatty acids increased a little more after 10 minutes than in case of unfamiliar exercise. These results suggest that response of habitual exercise showed lesser change of diastolic blood pressure and more increase of free fatty acids. There might be a difference in physiological responses between usual sports and other kinds, so that we had to be careful when we apply different styles of activity to use training.

Adult↗
PubMed1992

[Inhibitory effect of amlexanox on asthmatic attacks in an aspirin sensitive asthmatic].

The anti-allergic action of amlexanox is reported to be associated with inhibition of the release of LTC4, LTD4 and histamine, and with antagonistic activity on leukotrienes. The patient was a 18-year-old female who had suffered from bronchial asthma since the age of fifteen. We diagnosed the case as aspirin sensitive asthma because of development of a severe asthmatic attack with syncope after oral administration of an analgesic for treatment of a common cold at the age of seventeen. She also had sensitivity to toothpaste. Three-minute aerosol inhalation challenge with 0.1, 1 and 10% solution of sulpyrine was performed as a stepwise increment at 20 minutes intervals. This inhalation test was positive and it evoked simultaneous increases of LTC4, LTD4 and histamine in the peripheral blood. Since the commencement of oral administration of 150 mg per day of amlexanox, the patient has had no attacks for about 8 months. In the second inhalation test, premedication with amlexanox elevated the threshold of sulpyrine and inhibited the release of LTC4, LTD4 and histamine. We report that amlexanox was of use to control asthmatic attacks in this aspirin-sensitive asthmatic patient.

Adolescent↗
PubMed1991

Multilineage antigen expression and possible autocrine secretion of an interleukin 1 by Ph1-positive leukemic cell line KOPM-28.

A newly established Ph1-positive cell line, KOPM-28 was analyzed for immunological phenotype and the release of biological substance. The surface marker analysis revealed myelomonocytoid antigens, erythroid antigens and megakaryocyte-platelet antigens. Also, the cells could be induced for hemoglobin synthesis by the addition of hemin. The conditioned medium of this cell line showed the presence of interleukin 1 (IL-1) activity but not interleukin 2. Exogenous IL-1 and the conditioned medium stimulated the DNA synthesis of the cells themselves. Consequently, the yield substance works on the growth of original cells as an autocrine fashion, and might act on other normal cells as a paracrine factor.

Antigens, Neoplasm↗
PubMed1991

Prognostic factors for pleural lymphoma patients.

Prognostic factors in 47 patients with pleural lymphocytic lymphoma developing in chronic tuberculous pyothorax were evaluated using Cox's proportional hazards model. There were 41 men and six women, aged 44-80 (median 61) years. Approximately 70% of the patients had localized disease in Stages I and II, and 30% advanced disease in Stages III and IV. Histologically, 27 patients had the diffuse large, immunoblastic type and 12 had others. In the other seven patients, histological subtyping of the lymphocytic lymphoma was impossible because of degenerative or necrotic changes in the histologic specimens. A diagnosis of lymphocytic lymphoma of B-cell type was made in one case using combined cytologic and surface maker findings on a cell suspension. In addition, immunologic and immunohistochemical studies revealed another 40 cases to be proven B-cell lymphomas. Poor performance status and elevated levels of BUN and GPT were significantly associated with shortened survival in a Cox's proportional hazards model. A poor performance status and high levels of serum BUN and GPT suggested a marked deterioration in a patient's condition. When compared with previous literature describing prognostic factors in patients with B-cell lymphomas and with lymphocytic lymphomas with unfavorable histologies or associated with long-standing inflammations, the only common prognostic factors was performance status. The significance of primary site in predicting survival from lymphocytic lymphoma is discussed.

Adult↗
PubMed1991

[A case of spindle cell (squamous) carcinoma (WHO) of the lung].

A 76-year-old man with spindle cell (squamous) carcinoma of the lung developed fatal respiratory failure after limited thoracic irradiation at a total dose of 18 Gy. He developed severe pulmonary toxicity, which presented as dry cough, dyspnea, and pulmonary infiltrates extending beyond the radiation field. Microscopically, a transitional form of squamous to spindle-shaped cells was observed in the primary tumor, located at right S8. Immunohistochemical examination showed positive staining of spindle cells for keratin, vimentin, and EMA, but not for desmin. These results indicate that the spindle cells had characteristics of squamous epithelial cells, and differed from carcinosarcoma. Distant metastatic lesions were composed of only the spindle cell component.

Aged↗
PubMed1991

[Acquired coagulopathy caused by administration of parenteral broad-spectrum antibiotics].

Between October 1988 and May 1989, four cancer patients treated by broad-spectrum antibiotics developed a hemorrhagic diathesis induced by vitamin k (VK) deficiency. Activated partial thromboplastin time (APTT), prothrombin time (PT), factor II (FII) and protein induced by vitamin k absence of antagonist-II (PIVKA-II) were measured after administration of antibiotics and VK in all 4 patients. All these patients had been receiving intravenous hyperalimentation (IVH) and antibiotics for various infections. But all or them developed hemorrhagic diathesis within five days after the initiation of broad-spectrum cephem antibiotics (LMOX or CMNX). The abnormalities were 1) marked decrease of F II (6-18%), 2) prolongation of APTT (58.4-200 seconds), 3) prolongation of PT (7-21%), 4) marked increase of PIVKA-II (17-80 less than AU/ml). After being treated by intravenous administration of VK, hemorrhagic diathesis and abnormalities of coagulation tests except for PIVKA-II were corrected quickly in three evaluated patients. The measurement of PIVKA-II seemed to be useful to diagnose the hemorrhagic diathesis caused by VK deficiency in the patients during administration of antibiotics.

Aged↗
PubMed1991

The development of a treatment model for lymph node metastasis in nude mice transplanted with rat fibrosarcoma clone A.

We have tried to establish a model for lymph node metastasis in nude mice transplanted with clone A of methylcholanthrene-induced rat fibrosarcoma. Tumor cells transplanted either subcutaneously or intrafootpad metastasized exclusively to the lymph nodes in nude mice treated with antiasialo GM1 antiserum. In the experiments of intrafootpad transplantation, all the mice died of disseminated lymph node metastasis if the leg was not resected, or was resected more than 3 weeks after the transplantation of clone A. Some mice whose legs were amputated 1 or 2 weeks after transplantation could be cured by amputation alone. The maximum effective dose of in vitro active drug could improve the survival in mice, and 3/5, 4/5, and 3/5 mice treated with MMC, ACNU and CDDP respectively were cured even if their legs were amputated 3 weeks after transplantation. This tumor-bearing animal system was considered to provide a valuable experimental model for lymph node metastasis.

Amputation, Surgical↗
PubMed1990

Establishment of a camptothecin analogue (CPT-11)-resistant cell line of human non-small cell lung cancer: characterization and mechanism of resistance.

Camptothecin-11 (CPT-11) is a new derivative of camptothecin, a plant alkaloid antitumor agent, and a good candidate for clinical trials because of higher antitumor activity, less toxicity, and high aqueous solubility. CPT-11 is known to be altered into an active form, SN-38, by esterase in in vivo. CPT-11-resistant cells (PC-7/CPT) established from a human non-small cell lung cancer cell (PC-7) by stepwise, continuous treatment with CPT-11 exhibit about a 10-fold increase in resistance to the drug. CPT-11-resistant cells show a moderate cross-resistance to camptothecin (x8.6) and SN-38 (x8.6), and weak cross-resistance to Adriamycin (x2.2) and 5-fluorouracil (x2.4). The comparative studies between the parent (PC-7) and resistant (PC-7/CPT) cell lines with respect to their growth characterization shows a longer cell doubling time (45.8 versus 35.5 h), a lower cloning efficiency (3.2 versus 7.1%), and a lower population of S-phase cells (26.4 versus 36.0%) in the CPT-11-resistant cells. This observation may partly explain the resistance to CPT-11, a drug whose activity is cell cycle specific. Accumulation of CPT-11 is nearly the same in both cell lines. However, the intracellular concentration of SN-38 formed in the parent cells was 2-fold greater than in the CPT-11-resistant cells. This alteration may affect to some extent to the resistance. As assayed by relaxation of supercoiled plasmid DNA, the total activity of DNA topoisomerase I from the CPT-11-resistant cells was shown to be reduced to one-fourth its level in sensitive cells. The reduced activity was caused by a reduction of amount of DNA topoisomerase I. Furthermore, the enzyme from the resistant cells was shown to be 5-fold more resistant to CPT-11 than the enzyme from the parent cells. Thus, decreased total activity of topoisomerase I may play an important role in cellular resistance to CPT-11, and it appears that this decreased activity is due to a resistant form of topoisomerase I in CPT-11 resistant cells.

Antineoplastic Agents, Phytogenic↗
PubMed1990

Characterization of an etoposide-resistant human small-cell lung cancer cell line.

We established an etoposide (VP-16)-resistant human small-cell lung cancer cell line (H69/VP) by stepwise exposure to VP-16. The resistance of H69/VP to VP-16 was 9.4-fold that of the parent cell line (H69/P). H69/VP showed cross-resistance to Adriamycin (ADM), (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino) carbonyloxy]-1H-pyrano[3',4':6,7]indolizino [1,2-b]quinoline-3,14(4H,12H)-dionehydrochloride trihydrate (CPT-11), teniposide (VM-26), vindesine (VDS) and vincristine (VCR). The amount of DNA topoisomerase II (topo.II) was nearly the same in H69/P and H69/VP cells. The catalytic activity of topo.II in H69/VP cells was lower than that in the H69/P line. Accumulation of [3H]-VP-16 in H69/VP was 6.1-7.5 times lower than that in H69/P. According to Northern blot analysis, the mdr-1 mRNA level in H69/VP was markedly higher than that in H69/P. These findings suggest that H69/VP has a typical multidrug resistance (MDR) phenotype and that alteration of the drug accumulation mediated by P-glycoprotein may play an important role in resistance to VP-16. Reduced topo.II activity may also be associated with VP-16 resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Clinical effects of cepharanthin (Ceph.) on leukopenia by chemotherapy in lung cancer patients.

In order to examine the clinical efficacy of cepharanthin (Ceph.) for preventing leukopenia caused by chemotherapy in lung cancer patients, a randomized trial was carried out. Subjects were 45 patients with non-small cell lung cancer (NSCLC) receiving initial treatment with cisplatin (CDDP) +adriamycin (ADM) +mitomycin C (MMC). Ceph. was given at a dose of 1 mg/kg to the administration group (Ceph. group) and changes in the peripheral leukocyte count were examined in both the Ceph. and non-Ceph. groups. The Ceph. group showed a reduction in the number of cases with a count nadir less than 3,000/microliters (p less than 0.05), a shortening of the time that leukocyte counts stayed under 2,000/microliters, corresponding to the time in which granulocyte counts were less than 500/microliters (p less than 0.05), and also a reduction of the time for leukocyte counts to recover from nadir to 2,000 or 3,000/microliters (p less than 0.05) measured from the commencement of chemotherapy. These results suggest that administration of Ceph. has an antileukopenic effect in anticancer treatment, and makes it possible to reduce the period of risk for infection, allowing effective regimens to be administered repeatedly in shorter intervals.

Adult↗