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Biomedical subjects

K Toriyama

Publications and source records attributed to K Toriyama.

At least 73 records · Page 4Linked to original sources

[Kaposi's sarcoma].

Kaposi's sarcoma (KS) (Kaposi, 1872) is classified into at least three forms: 1) the classic form; in elderly men of southern European, Jewish, and Italian origin, 2) the endemic form; among native populations in equatorial Africa and 3) the epidemic form; as a complication of AIDS. As one additional form could be posttransplantation KS in organ transplant recipients. Histologically, KS is composed of two characteristic features; a proliferation of angiomatous lesion and of spindle-shaped cells. The pathological entity of the disease is still controversial. As a cause of the disease, human cytomegalovirus (HCMV) has been the subject based on epidemiologic, serologic, geopathologic and histopathologic observations. About half of KS cases with AIDS has shown evidence of HCMV infection as cytomegalic viral inclusions of the cells. In contrast, about 30% of AIDS cases without KS showed histological HCMV infection. A connection between HCMV and KS was suggested by the detection of herpes-type virus particles in several KS tissue culture lines and in a tumor specimen. DNA and RNA homologous with HCMV sequences have been detected in tumor tissue of both endemic and epidemic KS by electrophoretic methods. HCMV sequences was detected in extracted DNA of 30% of classic KS, using Southern blot technique. In situ hybridization technique using specific DNA probes for HCMV has been developed to reveal endogenous nucleic acid sequences in fixed tissue sections. However, some reports showed that by the in situ technique only a small number of KS cells in the AIDS cases and no case of the classic KS were positive for HCMV within KS lesions. HCMV infections are ubiquitous. There is a very high seropositivity of HCMV in African inhabitants as well as in Africans with endemic KS. A strong association between HCMV and KS was not known. As for HIV itself in AIDS with KS, previous studies have showed the presence of chromosomal abnormalities of KS cells, but not revealed the presence of HIV DNA sequences in KS. Vascular tumors were produced by NIH/3T3 cells transfected with KS DNA of AIDS. An oncogene isolated by transfection of KS DNA encodes a growth factor; FGF. Isolation of rearranged human transforming gene following transfection of KS DNA was performed. DNA having transforming genetic elements which have been repetitively transmitted into phenotypically normal NIH/3T3 cells through cycles of transfection was isolated from tissues of KS with AIDS.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

Prostaglandin E2 evokes intracellular calcium rise in mouse osteoblastic cell line, MC3T3E-1.

The effect of prostaglandin (PG) E2 on the intracellular free calcium concentration ([Ca2+]i) in mouse osteoblastic clone, MC3T3E-1 cells, was investigated with the fluorescent probe fura-2. In the growing phase of MC3T3E-1, PGE2 evoked a transient rise of [Ca2+]i in a dose-dependent manner in the range from 0.28 microM to 5.6 microM of PGE2. The elevation of [Ca2+]i induced by PGE2 was not affected by the presence of EGTA. Moreover, PGE2 (5.6 microM) evoked an acute accumulation of intracellular inositol-1,4,5-trisphosphate (InsP3). The absolute content of InsP3 increased from 5.8 pmole/10(6) cells to 19.2 pmole/10(6) cells within 30 sec after the PGE2 treatment. The degree of [Ca2+]i elevation induced by PGE2 was dependent on the day after subculturing. At day 3, the response to PGE2 was the most pronounced during the 8-day experimental periods. These data suggest that PGE2 evoked a [Ca2+]i rise via a phospholipase C-InsP3 pathway in osteoblasts, particularly in the growing phase.

Animals↗

[Screening for antagonistic agents to the lethal toxicity of neocarzinostatin. II. Effects of various drugs in inhibiting the toxicity of neocarzinostatin in vivo].

In clinical chemotherapy with neocarzinostatin (NCS) against cancers, side effects such as leukopenia, anorexia, vomiting and nausea were mainly observed when parenteral administration was used. To prevent these adverse side effects without changing the anticancer activity of the drug, we attempted to apply the two-route-infusion chemotherapy using NCS and antidotes for the NCS treatment devised by Baba. This report presents the results of our study on effects of some antidotes on the acute toxicity of NCS in mice and also on the antitumor activity of NCS against Sarcoma-180 in mice (ICR-JCL strain) when used with tiopronin. The results are summarized as follows. 1. LD50 values of NCS administered via intravenous route increased 2.3- to 3.2-fold when 150, 300, 500 or 1,000 mg/kg of tiopronin was administered subcutaneously together with NCS, 1.3- to 1.4-fold when 50 or 100 mg/kg of sodium thioglycolate was used. When antidotes were given prior to the administration of NCS, 1.8- to 5.4-fold increase in LD50 values of NCS resulted with 300, 500 or 1,000 mg/kg of tiopronin administered 1 hour prior to NCS, 2.3-fold increase resulted with 2,000 mg/kg reduced glutathione, 1.2-fold increase with 100 mg/kg of sodium thioglycolate and 1.9-fold increase with 1,000 mg/kg of L-cysteine monohydrochloride monohydrate. Furthermore, 4.8- to 13.1-fold increase in LD50 of NCS occurred when 150, 300, 500 or 1,000 mg/kg of tiopronin was administered 15 minutes prior to NCS. When these antidotes were administered 1 hour after the administration of NCS, however, no changes in the LD50 value occurred. 2. The LD50 value of NCS given intraperitoneally increased 1.6- to 5.8-fold when 150, 300, 500 or 1,000 mg/kg of tiopronin was administered intravenously at the same time as NCS, 1.4- to 1.6-fold when tiopronin was given 1 hour prior to NCS, intraperitoneally and 1.3- to 1.7-fold when it was given 1 hour after NCS. 3. It was recognized that the acute toxicity of NCS was the most effectively reduced by tiopronin, but only slightly by glutathione, sodium thioglycolate or L-cysteine monohydrochloride monohydrate. The action of tiopronin was the most effective when it was given subcutaneously 15 minutes prior to NCS administered intravenously. 4. The combination chemotherapy on Sarcoma-180 in mice using NCS intraperitoneally and tiopronin intravenously was markedly effective when these agents were given simultaneously.

Amino Acids, Sulfur↗

Ultrastructural study of lymphocytic interaction with hepatocytes and endothelial cells in acute non-A, non-B hepatitis.

In the liver biopsy specimens of all six patients with acute non-A, non-B hepatitis, the lymphocytic interaction with hepatocytes and sinusoidal endothelial cells was observed by electron microscopic study. Lymphocytes were in a close contact with damaged hepatocytes and interrupted endothelial cells, and the microvilli on the surface of these damaged hepatocytes were degenerated and lost. These findings pointed out the possibility that the lymphocyte may play one of the important roles in hepatocytic damage and endothelial cell damage in acute non-A, non-B hepatitis.

Acute Disease↗

[Usefulness of esophageal prosthesis in inoperable esophageal cancer].

Radiotherapy of inoperable esophageal cancer provided palliation for dysphagia in only 40% of the patients treated over the past 5 years at our hospital. The remaining patients were unable to eat a regular diet even after radiotherapy and to provide them with nourishment, a gastrostomy and/or IVH were required. We feel that the release of the patient from a medical environment will lead to a better quality of remaining life. From our experience with a prosthesis tube for palliation of a malignant esophageal stricture, 4 patients showed excellent results with this way of improving their oral intake.

Adult↗

[Antineoplastic effects and mechanism of action of IFN-alpha on brain tumors with use of fluorescent isothiocyanate-labelled IFN].

The antineoplastic effects and mechanism of IFN-alpha with a newly designed fluorescent isothiocyanate-labelled IFN-alpha were studied on three established glioma-cell lines and cultured cells of clinical brain tumors. Viability, cell cycle and cells showing positive reaction with fluorescent isothiocyanate-labelled IFN were analyzed by flow cytometry. U373MG glioma cells in contact with 10(4) IU/ml of IFN for 24 hours had a dose dependency, decreased viability, S-phase block in the cell cycle and high rate of positive reaction with fluorescent isothiocyanate-labelled IFN. Two surgical cases, except for one case, showed similar results and other cell lines or meningiomas were not affected by IFN. As the antineoplastic effects of IFN-alpha correlated with the rate of occurrence of positive cells with fluorescent isothiocyanate-labelled IFN, sensitive tumor cells may have a respective specific receptor for IFN-alpha, and, therefore, fluorescent isothiocyanate-labelled IFN-alpha might be of clinical value with regard to the problem of the receptor as well as sensitivity test.

Adenoma↗

Determination of malotilate and its metabolites in plasma and urine.

A method for the determination of malotilate (I), the corresponding monocarboxylic acid (II) and its decarboxylated product (III) in plasma is described. Plasma was extracted with chloroform spiked with internal standard. The residue, dissolved in methanol, was chromatographed on a reversed-phase column with a mobile phase of 60% acetonitrile and 1% acetic acid in water. The sensitivity limit for I, II and III was 50, 25 and 100 ng/ml of plasma, respectively. Compound I in the same plasma extract was also analysed by gas chromatography--electron-impact mass spectrometry. The base peaks m/z 160 for I and m/z 162 for internal standard (IV) were monitored; the sensitivity limit for I was 2.5 ng/ml of plasma. The determination of the metabolites of I, II and its conjugate (V), and isopropyl-hydrogen malonate (VI) in urine by high-performance liquid chromatography is also described. The limit of quantification for VI was 2.0 micrograms/ml, and the overall coefficient of variation of VI was 4.7%. The limit of quantification for II in urine was 0.5 micrograms/ml and that for V was 1.0 micrograms/ml as total II (II + V). The overall precision of the method was satisfactory. The method was used to determine plasma and urine concentrations in four dogs orally dosed with 100, 200 or 400 mg of malotilate.

Animals↗

[Screening for the antagonizing agents against lethal toxicity of neocarzinostatin. I. Inhibitory effects of various drugs on the toxicity of neocarzinostatin in vitro and in vivo].

Neocarzinostatin (NCS) used for the chemotherapy of leukemia and cancers such as stomach, pancreas and bladder, has been pointed out to have the side effects mainly causing leukopenia. In order to prevent these side effects of NCS by systemic administration, we have attempted to inject NCS directly into the tumor tissues and to inactivate NCS leaked from the tissues by the treatment of antidotes for NCS. The present report deals with the influence of some antidotes on the toxicity of NCS in vitro and in vivo. The results demonstrated that; Four SH-compounds, such as thiopronin, glutathione (reduced form), sodium thioglycolate and L-cysteine monohydrochloride monohydrate were effective to inactivate antibacterial activity of NCS against M. luteus ATCC 9341 in vitro. It was recognized that acute toxicity of NCS was reduced by pretreatment of these SH-compounds and its action was dose related. The LD50 values of NCS intravenous administration in mice increased 5.8- to 24-fold when 150, 300, 500 and 1,000 mg/kg of thiopronin were administered intravenously 2 minutes prior to NCS. And 2.3- to 4.2-fold by 500 and 1,000 mg/kg of glutathione (reduced form), 1.6- to 4.2-fold by 50, 100 and 200 mg/kg of sodium thioglycolate, 1.9- to 4.2-fold by 100, 200 and 400 mg/kg of L-cysteine monohydrochloride monohydrate respectively. On the other hand, pretreatment of NCS didn't affect the acute toxicity of thiopronin.

Animals↗

[Clinical evaluation of neocarzinostatin in digestive system cancer. 1. Administration of neocarzinostatin in advanced and recurrent carcinoma of the stomach].

This study was designed to evaluate the most effective administration method of NCS for advanced carcinoma of the stomach, mainly nonresectable and/or recurrent cases which were collected by our cooperative study group. Nine hundred seventy six cases were available for clinical evaluation. Rate of the efficacy of NCS alone and combined with 5-FU was higher (P less than 0.1) in the cases administrated intravenously by drip infusion than in those by one shot injection method, and adverse effects were fewer in the former than in the latter cases. The rate of efficacy of NCS was higher in cases treated with 4,000 mu/day alone intermittently 2-3 times for a week than in those with 2,000 mu/day alone every day. The rate of clinical effect was higher in the cases treated with 4,000 mu of NCS combined with 50 mg of 5-FU intermittently than in those with 2,000 mu of NCS combined with 250 mg of 5-FU every day, especially 20.6% of the former cases given more than 50,000 mu of NCS were interpreted as clinically effective by Karnofsky's criteria of I-A over.

Antibiotics, Antineoplastic↗

[Clinical evaluation of neocarzinostatin in digestive system cancer. 2. Clinical studies on the administration of neocarzinostatin in advanced and recurrent carcinoma of the pancreas].

The present study was designed to evaluate the efficacy of chemotherapy by NCS for advanced and/or recurrent carcinoma of the pancreas, mainly nonresectable cases in which exploratory laparotomy or construction of biliary fistula were performed. Three hundred fifty seven cases were available for the study. Of the 357 cases, 116 were treated with NCS alone 5-FU. In the former, the efficacy rate was higher in cases with 2,000 mu/body of NCS every day than in those with 4,000 mu/body of NCS intermittently 2-3 times for a week. 19.6% of the cases treated with more than 40,000 mu of NCS alone in total were interpreted as effective clinically by Karnofsky's criteria of I-A over. In the latter, the efficacy rate was higher in cases with 2,000 mu/body of NCS combined with 250 mg of 5-FU every day than in those with 4,000 mu of NCS combined with 500 mg of 5-FU intermittently, 22.5% of the cases given more than 40,000 mu of NCS in total were interpreted as effective clinically by Karnofsky's criteria of I-A over. The major adverse effects of NCS such as anorexia, vomiting and nausea were observed in 20% of total cases respectively, leucopenia in 10% and fever in 15% of them.

Antibiotics, Antineoplastic↗