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Biomedical subjects

H Shimura

Publications and source records attributed to H Shimura.

At least 127 records · Page 7Linked to original sources
PubMed1990

Rapid detection and size determination of PuO2 particles using a charged-particle imaging video monitor system.

A charged-particle imaging video monitor system was constructed and applied to video imaging of the position profile of PuO2 particles on filter paper. The imaging video monitor system consists of a detector head, a silicon intensifier target (SIT) camera, a video frame memory, and a personal computer. The system can display the distribution image of PuO2 particles becoming gradually clearer on a video monitor. The integrated image that is transferred to the computer is analyzed quantitatively for the radioactivity of each PuO2 particle deposited on the filter paper. The system can not only rapidly distinguish PuO2 particle contamination from Rn daughter products, but can also determine the size distribution of the PuO2 particles.

Particle Size↗
PubMed1990

Cloning of malignantly transformed rat thyroid (FRTL) cells with thyrotropin receptors and their growth inhibition by 3',5'-cyclic adenosine monophosphate.

Differentiated rat thyroid cells, designated FRTL, are totally dependent on TSH for their growth. We continuously cultured FRTL cells in the absence of TSH and found that another type of cell appeared in the culture. The new cells were large, flattened and epithelial-like, and none of them exhibited thyroglobulin immunoreactivity. Since they grew independently of TSH, we further cloned these mutated cells by the limited dilution method in the absence of TSH. cAMP production in the cloned cells (FRTL-Tc) was stimulated dose-dependently by TSH. The TSH concentration that produced a maximal level of cAMP in FRTL-Tc cells was 1 order of magnitude higher than in FRTL cells. A [125I]TSH binding study confirmed that the FRTL-Tc cells had TSH receptors with the same binding capacity but a higher Kd than those of FRTL cells. A [125I]cyanopindolol binding study revealed that the FRTL-Tc cells had acquired beta 2-adrenergic receptors and that isoproterenol or epinephrine could stimulate cAMP production in the cells. TSH or beta-adrenergic agonists inhibited the growth of these cells, as did (Bu)2cAMP. When FRTL-Tc cells were transplanted into the sc tissue in Fisher rats, they grew as a tumor in all of the animals (n = 10). Metastasis of the tumors to the lung and liver occurred. These results indicate that FRTL-Tc cells are malignantly transformed cells with TSH receptors derived from thyroid epithelial cells and also suggest that the role of cAMP in the proliferation of the transformed cells might be different from that in normal cells.

Adenylyl Cyclases↗
PubMed1990

Transformation by v-H-ras does not restore proliferation of a set of temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts.

Three temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts (3Y1tsD123, 3Y1tsG125, and 3Y1tsH203, each belonging to distinct complementation groups) were transformed with plasmid DNA carrying Harvey murine sarcoma virus cDNA. The criteria for transformation were increase in saturation cell density, capability to clone in soft agar, and alteration in the cellular morphology. At 39.8 degrees C (restrictive temperature of the parental cell lines), all the transformed sublines of each mutant ceased to proliferate and were arrested reversibly in the G1 phase of the cell cycle like the parental lines. At both 39.8 degrees C and 33.8 degrees C (permissive temperature for the parental lines), all the untransformed parental lines synthesized p21ras at low rate. At 33.8 degrees C, all the transformed sublines synthesized p21ras at much higher rate and expressed the morphological phenotype characteristic to v-H-ras-induced transformation. At 39.8 degrees C, the rate of p21ras synthesis was not changed in the transformed sublines of 3Y1tsD123 and 3Y1tsG125, and the morphology of transformed phenotype also remained intact. In the transformed subline of 3Y1tsH203, the rate of p21ras synthesis was lowered at 39.8 degrees C to that seen in the untransformed parental line, and the transformed phenotype in morphology disappeared. In all of the transformed sublines, the amount of v-H-ras mRNA markedly expressed at both 33.8 degrees C and 39.8 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Hepatoprotective compounds from Canarium album and Euphorbia nematocypha.

Successive purification of the extract from Canarium album and Euphorbia nematocypha, guided by antihepatotoxic activity in primary cultured rat hepatocytes, led to the isolation of brevifolin (1), hyperin (2), ellagic acid (3) and 3,3'-di-O-methylellagic acid (4) as hepatoprotective compounds. Compounds 1,3 and 4 also reduced carbon tetrachloride (CCl4)-induced liver damage in mice. The hepatoprotective activities of 1, 2, 3 and 4 in vitro and in vivo are apparently due to their antioxidative effects, which were exhibited by further studies using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and CCl4-induced lipid peroxidation systems.

Animals↗
PubMed1990

Characterization of alpha 1-adrenergic receptor subtypes linked to iodide efflux in rat FRTL cells.

We have characterized alpha 1-adrenergic receptor subtypes in functional rat thyroid cells, FRTL, with relation to iodide efflux, and have also examined the effect of TSH on alpha 1 receptor subtypes. FRTL cells grown in a medium containing 5 mU TSH/ml (6H cells) had five times the number of alpha 1 receptors of those maintained in TSH-free medium (5H cells) (11.2 fmol/10(6) cells compared with 2.0 fmol/10(6) cells). Pretreatment with chlorethylclonidine (CEC; 10 mumols/l), which inactivates only alpha 1b receptors, caused 98.8% and 97.0% decreases in the density of specific [3H]prazosin-binding sites in 5H and 6H cells respectively. LIGAND computer program analysis of the displacement curves for 2-(2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4 benzodioxane (WB4101) showed that FRTL cells contained mostly low-affinity WB4101 sites. Using the phenoxybenzamine inactivation method, we found a linear relationship between alpha 1 receptor density and the cytosolic free Ca2+ concentration response in FRTL cells. Pre-exposure of intact FRTL cells to CEC caused a 98.7% decrease in noradrenaline-stimulated maximal increase in cytosolic free Ca2+. Also, CEC and 3,4,5-trimethoxy-benzoic acid 8-(diethylamino) octyl ester (TMB-8), but not nicardipine, inhibited noradrenaline-stimulated iodine efflux. The results suggest that FRTL cells contain mostly the alpha 1b-adrenergic receptor subtype; that the alpha 1b receptors mediate cytosolic free Ca2+ and iodide efflux responses, and that TSH enhances these responses by increasing the alpha 1b receptor density without affecting the post-receptor mechanism.

Animals↗
PubMed1990

Thyrotrophin increases the alpha 1b-adrenergic receptors in rat thyroid gland in vivo.

Using chlorethylclonidine (CEC), an alpha 1b-adrenergic receptor-selective antagonist, we characterized alpha 1-adrenoceptor subtypes in rat thyroid gland, and investigated the effect of methimazole (MMI)-induced high TSH levels on alpha 1 receptor subtypes and noradrenaline-induced iodide organification. The density of thyroid alpha 1-adrenergic receptors was increased about sixfold in rats treated with MMI for 3 weeks compared with controls. Pretreatment of thyroid membrane preparations with CEC (10 mumol/l) caused an 83% decrease in specific 2-[beta-(hydroxy-3-[125I]iodophenyl) ethylaminomethyl]tetralone binding sites in MMI-treated rats, but only a 43% decrease in control rats. The density of CEC-insensitive alpha 1 receptors (alpha 1a) was similar in MMI-treated and control rats, so MMI was shown to increase CEC-sensitive alpha 1 receptors (alpha 1b). Noradrenaline-stimulated iodide organification was threefold greater in MMI-treated rats than in control rats when values were expressed as a per cent increase over basal levels. Pretreatment of thyroid lobes with 10 mumol CEC/l for 30 min caused a 66% decrease in maximal noradrenaline-induced iodide organification in MMI-treated rats, but a significantly lower decrease (49%) in control rats. These results suggest that the rat thyroid gland contains both alpha 1a and alpha 1b receptors, both of which mediate noradrenaline-induced iodide organification, and also that TSH enhances noradrenaline-induced iodide organification by increasing alpha 1b receptor density.

Adrenergic alpha-Antagonists↗
PubMed1990

[Study of tissue drug concentration of fluorinated pyrimidine anticancer drugs--comparison of 5'DFUR and UFT].

In order to verify the tumor-selective toxicity of fluorinated pyrimidine anticancer drugs, we conducted an investigation of the clinical pharmacology of two of these drugs, 5'DFUR and UFT. 5'DFUR was administered to 8 patients and UFT to 8 other patients in respective dosages of 800-1,000 mg/day and 400-600 mg/day an average of 6 days before the patients underwent surgery for cancer of the large bowel, and the concentrations of these drugs in tissue were then measured. No 5'DFUR whatsoever was detected in serum, the lymphnodes, normal large bowel tissue, or cancerous large bowel tissue after administration of this drug. Moreover, levels of the active substance, 5-FU, after administration of 5'-DFUR were low in serum, the lymphnodes, normal large bowel tissue (0.033 +/- 0.024 microgram/g), and cancerous large bowel tissue (0.034 +/- 0.020 microgram/g), and no difference was observed between normal and cancerous large intestine tissue. On the other hand, tegafur was detected in all of the tissues following the administration UFT, and the concentration of 5-FU was significantly high, particularly in cancerous large bowel tissue (0.108 +/- 0.057 microgram/g) compared to normal sites (0.044 +/- 0.048 microgram/g) (p less than 0.05). The above results indicate that UFT is a promising drug for use in chemotherapy for cancer of the large bowel.

Antineoplastic Agents↗
PubMed1989

Mechanism of selective killing by dilinoleoylglycerol of cells transformed by the E1A gene of adenovirus type 12.

Rat 3Y1 fibroblasts transformed by the E1A gene of adenovirus type 12 (E1A-3Y1 cells) are highly sensitive to the cell-killing effect of 1,3-dilinoleoylglycerol (DLG) administered in a culture medium, whereas the parental 3Y1 cells are less sensitive (H. Shimura et al., Cancer Res., 48: 578-583, 1988). The selective cytotoxicity of DLG to E1A-3Y1 cells was markedly reduced by the simultaneous administration of nonspecific antioxidants such as vitamin E, butylated hydroxytoluene, and ascorbic acid. Specific scavengers for oxygen radicals had no effect. Lipoxygenase inhibitors (nordihydroguaiaretic acid, esculetin, and baicalein) reduced the DLG-mediated selective cytotoxicity, whereas cyclooxygenase inhibitors (acetylsalicylic acid and indomethacin) showed no effect. The intracellular and extracellular contents of the products from lipid peroxidation as measured by the thiobarbituric acid test were significantly greater in E1A-3Y1 cells than in the parental 3Y1 cells. In comparison with DLG, linoleic acid and monolinoleoylglycerol were equally toxic to E1A-3Y1 and parental 3Y1, and trilinoleoylglycerol was weakly toxic to both types of cells. Scanning electron microscopy revealed that numerous holes about 0.2 micron in diameter were scattered all over the surface of the E1A-3Y1 cells after treating the cultures with DLG. These results suggest that; (a) the DLG-mediated cytotoxicity to the E1A-transformed cells is attributable to lipid peroxidation; (b) the structural property of DLG is essential to the E1A specificity of cytotoxicity; and finally (c) the destruction of the cell membrane is the basis of cytotoxicity of DLG.

Adenovirus Early Proteins↗
PubMed1989

The uptake of anticancer drugs by tumor tissues and lymph node and the effectiveness of postoperative adjuvant chemotherapy on survival time.

Forty-one patients with advanced gastric cancer underwent gastrectomy and the correlation between tissue uptake of the adjuvant drug and the prognosis were studied. The patients were preoperatively administered Tegafur (Futraful, Taiho Pharmaceutical Co. Ltd, Japan) and samples of tissue were obtained intraoperatively. 5-FU levels in the tumor and lymph nodes were measured by gas chromato-massfragmentography (GCMF). The patients in whom the 5-FU uptake by the tissues was measured and who were given over 60 g of Tegafur as postoperative adjuvant chemotherapy, were divided into two groups; namely, one group in whom the 5-FU uptake by the tumor tissue and lymph nodes was over 0.05 microgram/g and the other in whom the uptake was lower than 0.05 microgram/g. There were no significant differences in the background factors of either group. Each survival rate was calculated by the Kaplan-Meier method, and the generalized Wilcoxon method was used for statistical analysis. There was no statistically significant correlation between the 5-FU uptake by the tumor and the prognosis, however the 5-year survival rate in the group whose 5-FU uptake of the lymph nodes was over 0.05 microgram/g was statistically significant (p = 0.018).

Combined Modality Therapy↗
PubMed1989

The high sensitivity of cells transformed by E1A gene of adenovirus type 12 to diacylglycerol-mediated cell killing.

Viability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was markedly impaired by the administration of dilinoleoylglycerol (DLG) to the culture medium. To identify the gene(s) of Ad12 responsible for the high sensitivity to DLG, we established several transformed sublines of 3Y1 induced by the viral E1A gene or by the mutants of Ad12 which have mutations in the E1A region. All of the transformed sublines of 3Y1 expressing either the 12S or the 13S message from the E1A region were highly sensitive to the cytotoxicity of DLG. We propose that the high sensitivity of Ad12-transformed cells to the DLG mediated cytotoxicity is attributable to the common function of E1A-12S and E1A-13S mRNA products.

Adenoviridae↗
PubMed1989

Enhancement of the activity of thyroid-stimulating antibodies by anti-human IgG antibodies in vitro.

In an attempt to determine whether or not anti-human IgG antibodies could influence the activity of thyroid-stimulating antibodies (TSAb), we investigated the effects of anti-human Fc antibody (anti-Fc antibody) and IgG from rheumatoid arthritis patients (RA-IgG) on TSAb activity using FRTL-5 cells. It was found that these anti-human IgG antibodies enhanced the TSAb activity in vitro. FRTL-5 cells were first incubated with Graves' disease IgG for 30 min at 37 degrees C, then washed and incubated in Hanks' balanced salt solution with anti-human IgG antibodies for 60 min at 4 degrees C, and then for a further 120 min at 37 degrees C. The level of cAMP accumulated in the medium was determined by RIA. Anti-Fc antibody significantly augmented the cAMP formation stimulated by 16 out of 24 Graves' IgGs, whereas anti-F(ab')2 antibody did not potentiate cAMP accumulation. Three of five RA-IgGs, which are usually defined as specific antibodies for the Fc fragment of human IgG, mimicked these stimulatory effects. Protein A also potentiated the cAMP formation stimulated by Graves' IgGs. Furthermore, there was a significant correlation between the TSAb titres of these Graves' IgGs and the potentiating effects of anti-Fc antibody (r = 0.495, P less than 0.05, n = 21). These results suggest that the interaction of TSH receptor antibody with anti-human IgG antibodies might modulate thyroid function in Graves' disease.

Antibodies, Anti-Idiotypic↗
PubMed1989

Induction of DNA synthesis by cholera toxin in the temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts at a restrictive temperature.

Four temperature-sensitive mutants of rat 3Y1 fibroblasts representing separate complementation groups (3Y1tsD123, 3Y1tsF121, 3Y1tsG125 and 3Y1tsH203) are arrested at a restrictive temperature of 39.8 degrees C mainly with a G1-phase DNA content (temperature arrest). Cholera toxin (CT) (3 micrograms ml-1) induced DNA synthesis at 39.8 degrees C in the temperature-arrested cultures of two mutants (3Y1tsD123 and 3Y1tsG125). This effect of CT was not mimicked by other agents known to elevate the cellular level of cyclic AMP, such as dibutyryl-cyclic AMP, prostaglandin E1 and forskolin, suggesting that the elevation of cellular cyclic AMP level per se is not responsible for the induction of DNA synthesis by CT. Addition of the B subunit of CT to the temperature-arrested cultures of 3Y1tsD123 and 3Y1tsG125 did not induce DNA synthesis at 39.8 degrees C, indicating that the binding of CT to the cell surface alone is insufficient for the induction. The CT-treated cell membrane fraction prepared from temperature-arrested 3Y1tsG125 cells had similar activity for [32P]ADP-ribosylation of the 45 X 10(3) Mr protein to that prepared from cells proliferating at a permissive temperature of 33.8 degrees C. All these results suggest that 3Y1tsG125 cells utilize a CT-responsive signal transduction pathway, different from adenylate cyclase cascade, for preparation for entry into S phase in the temperature-arrested 3Y1tsG125.(ABSTRACT TRUNCATED AT 250 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Distributions of tegafur in tissues of gastric adenocarcinoma patients: tissue uptakes and concentrations in plasma after oral and rectal administrations.

Fifty-one gastric adenocarcinoma patients were divided into two groups, according to the route of administration of the anticancer drug. One group was given FT-207 (tegafur, an enteric coated granule) orally and the other group, FT-207 in the form of a suppository. Blood and tissue concentrations of the drug were examined after a three-day administration of 750 mg at 09.00 and 21.00 hours. There were no significant differences between the two groups with respect to the concentrations of FT-207 and its metabolite 5-FU in the tissues. Levels of 5-FU in the excised tumor averaged 0.256 and 0.160 micrograms/g, in oral and rectal administrations, respectively, and levels in normal lymph nodes averaged 0.174 and 0.179 micrograms/g, respectively. The difference in 5-FU levels between normal and tumor tissues was statistically significant (P less than 0.05).

Adenocarcinoma↗
PubMed1988

Active production and membrane anchoring of carcinoembryonic antigen observed in normal colon mucosa.

Normal colon mucosa was found to produce carcinoembryonic antigen (CEA) quite actively as cancerous tissues do when maintained in an organ culture, although the fresh normal mucosae contained a very small quantity of CEA unlike cancerous tissues. This is consistent with an active expression of CEA mRNA in normal mucosa comparable to that in cancerous tissues actively producing CEA, and suggests that the normal cell product was rapidly released into the lumen of digestive tract and turned into normal fecal antigens (NFAs) previously found in feces. 3H-Labeled precursors of glycophospholipid such as ethanolamine and stearic acid were incorporated into CEA produced by both normal and cancerous tissues, suggesting that CEA in normal mucosa is anchored to the cell membrane through a glycophospholipid as in cancerous tissues.

Blotting, Northern↗
PubMed1988

Selective cytotoxicity of phospholipids and diacylglycerols to rat 3Y1 fibroblasts transformed by adenovirus type 12 or its E1A gene.

The colony-forming ability of rat 3Y1 fibroblasts transformed by adenovirus type 12 (Ad12) was drastically reduced when the cells were cultivated for 18 h in medium augmented with 300 micrograms/ml of liposomes composed of either phosphatidylcholine (PC) or phosphatidylinositol. In contrast, those of untransformed 3Y1 cells and simian virus 40-transformed and polyomavirus-transformed 3Y1 cells were not. The cytotoxicity of PC liposomes was also observed in 3Y1 cells transformed by plasmid DNA containing Ad12-E1A gene but not in those transformed by adenovirus type 2, Rous avian sarcoma virus, or plasmid DNA carrying v-Ha-ras oncogene. The extensive killing of Ad12-transformed and E1A-transformed 3Y1 cells occurred in liposomes of dioleoyl-PC and of dilinoleoyl PC but not those of dipalmitoyl PC, distearoyl-PC, or diarachidonyl PC, suggesting that the acyl groups of phospholipids play an important role in cytotoxicity. Dilinoleoylglycerol, 60 micrograms/ml, was also cytotoxic selectively to Ad12-transformed and E1A-transformed 3Y1 cells, although the toxicity of lysophosphatidylcholine or linoleic acid was not specific to these transformants. These results suggest that cell transformation by Ad12 is characterized by a high sensitivity to exogenously administered phospholipids and diacylglycerol that contain oleoyl or linoleoyl acyl groups and that the sensitivity is attributable to the expression of E1A gene of Ad12.

Adenovirus Early Proteins↗