Search PubMed⌕ Search

Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 217 records · Page 12Linked to original sources
PubMed1989

Liquid chromatographic-atmospheric pressure ionization mass spectrometric analysis of toremifene metabolites in human urine.

A liquid chromatographic-atmospheric pressure ionization mass spectrometric method has been developed for the analysis of toremifene metabolites in human urine after oral administration. This ionization source is a useful device for studying metabolites of toremifene because the total effluent from high-performance liquid chromatography is fed through an interface with a direct heating nebulizer and vaporizer at atmospheric pressure. To obtain good sensitivity the use of the right mobile phase is very important: ammonium acetate in methanol in the case of toremifene and its metabolites. Four unconjugated and three glucuronide-conjugated metabolites were detected in human urine. The majority of these were new and distinguishable from known metabolites.

Antineoplastic Agents↗
PubMed1989

Rapid homogeneous enzyme immunoassay of plasma protein C.

A homogeneous EIA (H-EIA) technique for plasma protein C antigen using horseradish peroxidase (HRP) was developed. This technique, which avoids the bound/free separation and washing procedures and shortens the assay time to 30 min, has several advantages over the conventional EIA technique. The measurement was valid for 1.0% to 200% of the plasma protein C level and had intraassay coefficients of variation of 2.3-11.0%. The results of this assay correlated well with those of conventional sandwich EIA (x) with a regression equation of y = 0.782x + 6.637, r = 0.911 (n = 59). This method, which may also be applicable to automatic assay systems, is considered to be suited for clinical laboratory use.

Antigens↗
PubMed1989

Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases.

Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2 alpha and 12.8 min t1/2 beta), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2 beta s of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration X time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics.

Administration, Oral↗
PubMed1989

Antihypertensive compounds with potent protein kinases inhibitory activity.

A new indorocarbazole antibiotic SF2370 has been found in the culture broth of Actinomadura sp.; it has also been found to have the activities of antihypertension and diuresis. Derivatives of SF2370, NA0344, NA0345 and NA0346, when injected (0.1-1 mg/kg i.v.) significantly lowered the blood pressure of anesthetized normotensive rats and showed a long lasting antihypertensive action. In the case of p.o. administration to conscious restrained SHRs, measurement of blood pressure by the plethysmographic method indicated that 10 mg/kg of the compounds was enough to lower the blood pressure; the antihypertensive activities were found to remain more than 12 hrs after oral administration. By studying of the mode of antihypertensive action, these compounds dose dependently relaxed the isolated aortic preparation contracted by norepinephrine. In addition, it was found that protein kinase C activity of mice brain was inhibited by the compounds; the IC50 values were in the range of 0.062-0.20 microM. Moreover, a superprecipitation of actomyosin from smooth muscle of chicken gizzard was inhibited by the compounds, having an IC50 values of 0.31-0.72 microM.

Animals↗
PubMed1989

Intercalating agents with covalent bond forming capability. A novel type of potential anticancer agents. 2. Derivatives of chrysophanol and emodin.

Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells. Representative compounds were spectrophotometrically studied for their capacity to interact with natural and denatured DNA. In general, those anthraquinones bearing an amino function interact with DNA. 1,8-Dimethoxyanthraquinones are incapable of intercalating into DNA. 1- or 8-Monohydroxymono-methoxyanthraquinones, however, interact with DNA to some extent. No straightforward correlation is apparent between the DNA-affinity data of the compounds studied spectrophotometrically and their cytotoxic effects. Cytotoxic potencies of these compounds on cell growth inhibition during a 72-h period are inversely correlated to their potencies when inhibiting [3H]TdR incorporation into DNA during the initial 30 min of exposure. Surprisingly, some compounds that showed more cytotoxicity did not inhibit initial TdR incorporation (0-30 min), while some others that strongly inhibited TdR incorporation initially did not exhibit cytotoxicity in 72 h. The results suggest that the cytotoxicity produced by these compounds is time dependent and is not a direct result of initial inhibition of DNA replication.

Animals↗
PubMed1989

Impaired susceptibility of human trophoblast to MHC nonrestricted killer cells: implication in the maternal-fetal relationship.

Mammalian pregnancy has frequently been termed "Nature's allograft," and there is developing evidence that the placental trophoblast cells in their key position at the maternal fetal interface are responsible for escape mechanisms to the maternal immune system. In this paper, we show impaired susceptibility of human trophoblastic tumor cells to major histocompatibility complex (MHC) nonrestricted cytotoxicity systems such as natural killer (NK) cells and lymphokine-activated killer (LAK) cells. LAK cells were induced by the culture of peripheral blood mononuclear lymphocytes (PBL) in recombinant interleukin-2 (rIL-2). Among 21 cultured cell lines derived from various tissues and organs tested, five choriocarcinoma-derived cell lines gave decreased levels of LAK lysis. Cold-target inhibition study and trinitrophenyl (TNP) modification experiment clearly indicated that the impaired sensitivity of trophoblast cells to LAK lysis is due to the decrease of a common target molecule recognized by LAK effector cells. It is suggested that the impaired susceptibilty of trophoblast to MHC nonrestricted killer cells should be functional for the survival of the semiallogeneic fetus.

Cytotoxicity, Immunologic↗
PubMed1989

[Brain metastasis of ovarian cancer treated by chemotherapy including cis-platin: a case report].

A 57-year-old woman was admitted to our department with headache and dizziness. About 8 months ago, she suffered from ovarian cancer disseminated in pleura and peritoneum, and was treated successfully with CAP therapy only (Cis-platin, Adriamycin and Cyclophosphamide). Intracerebellar metastasis of ovarian cancer was suspected on CT scan, and CAP therapy was employed again. She was relieved from all symptoms a week after starting the therapy. Follow up CT scan showed complete remission of the lesion. She was well for about 3 months, but was admitted again because of consciousness disturbance and headache with multiple brain metastasis. PVB therapy (Cis-platin, Vinblastine and Pepleomycin) was employed this time, and complete remission was seen again. But regrowth of intraabdominal mass lesion appeared, and she died from multiple organ failure 5 months after PVB therapy. Autopsy was not permitted, but CT scan 3 days before death revealed no intracranial lesion. Distant metastasis of ovarian cancer may become more prevalent with the development of combination chemotherapy, but no case of brain metastasis has been reported to have been treated with chemotherapy only. The authors suggest the possibility of successful treatment of such a lesion with chemotherapy including Cis-platin.

Adenocarcinoma↗
PubMed1989

[Low sensitivity of choriocarcinoma cell lines to tumor necrosis factor (TNF)-alpha].

Sensitivity of cultured choriocarcinoma cell lines to tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma was examined and compared with that of other cultured tumor cell lines. Tumor cells were cultured with 1,000 mu/ml of TNF-alpha and/or 100 mu/ml of IFN-gamma for 24hr. Antitumor effects of the lymphokines were measured by 3H-thymidine uptake and tetrazolium salt (MTT) colorimetric assay. The results revealed that TNF-alpha and/or IFN-gamma had little anti-tumor effect on the choriocarcinoma cell lines tested, while they had cytostatic and cytotoxic effects on other cultured tumor cell lines including Panc-1 (pancreatic carcinoma cell line), Lovo (colon carcinoma cell line) and Ishikawa (uterine endometrial carcinoma cell line). We also examined the effect of TNF-alpha and IFN-gamma on the expression of major histocompatibility complex (MHC) class I antigens in these tumor cell lines by means of cellular binding radioimmunoassay. No enhancing effect was observed on choriocarcinoma cell lines after the treatment with TNF-alpha and/or IFN-gamma. These results suggested the existence of a unique property of choriocarcinoma cells which results in the resistance to host immune attacks.

Choriocarcinoma↗
PubMed1989

[Low susceptibility of choriocarcinoma cell lines to lymphokine activated killer (LAK) cells].

We investigated the anti-tumor effect of lymphokine activated killer (LAK) cells on various carcinoma cell lines as it may play an important role in the immunotherapy of gynecologic cancers. Peripheral blood lymphocytes (PBL) were cultured in 10 U/ml of recombinant interleukin-2 (rIL-2). The cytotoxic action of LAK and natural killer (NK) on carcinoma cell lines was measured by a standard 4-hr 51Cr-releasing assay. Daudi and RPMI 1788, NK resistant B cell lines were lysed by rIL-2 activated PBL although they were not killed by human fresh PBL. LAK cells thus induced were markedly cytotoxic to sixteen carcinoma cell lines. However, five choriocarcinoma cell lines were resistant to LAK action because specific action was less than 30% at effector/target ratio of 20. The cold target competitive inhibition experiments showed that the choriocarcinoma cell line GCH-1 induced much lower inhibition than Daudi cells. These results indicate that the low susceptibility of the choriocarcinoma cell lines to LAK cells could be due to the lack of the effector molecules recognized by killer cells.

Cell Line↗
PubMed1988

A proposed mild type of acute retinal necrosis syndrome.

Six patients had peripheral to midperipheral pale yellow retinal exudates typical of acute retinal necrosis syndrome but which extended gradually to the posterior pole and remained isolated without becoming confluent. These exudates resulted in localized retinochoroidal degeneration without retinal detachment, in contrast to acute retinal necrosis syndrome. Antibody titers in aqueous humor were increased to varicella-zoster virus in some of the patients examined. The findings led us to hypothesize that this mild, self-limiting course is one of the natural developments of acute retinal necrosis syndrome, although somewhat modified by corticosteroid or acyclovir therapy, and that acute retinal necrosis syndrome consists of varying degrees of severity from mild to fulminant types.

Acute Disease↗
PubMed1988

DNA polymorphism in the human Thy-1 gene.

Thy-1 is a membrane glycoprotein expressed predominantly in brain tissue and occasionally in lymphoid tissue. The human Thy-1 gene is located on chromosome 11q22.3. Although two allelic forms of Thy-1 exist in mice (Thy-1.1 and Thy-1.2), no allelic forms have been described for the human Thy-1 gene. We describe a polymorphic MspI site within the human Thy-1 gene that distinguishes two alleles, 8 and 9, which are represented in a northern European population at frequencies of 0.7 and 0.3, respectively. Thy-1, therefore, provides a potentially useful marker to identify linkages with human disease genes located near 11q22.

Alleles↗