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Biomedical subjects

K Tsutsui

Publications and source records attributed to K Tsutsui.

At least 199 records · Page 11Linked to original sources
PubMed1986

Radiosensitizing effect of misonidazole in combination with an inhibitor of glutathione synthesis in murine tumors.

The radiosensitizing effects of misonidazole (MISO) in combination with D,L-buthionine-S, R-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, were studied in NFSa tumors of C3H/He mice. The radiation response of tumors was assayed by the tumor growth delay time. The GSH contents in tissues were assayed by high performance liquid chromatography (HPLC). GSH content in the tumors decreased to the minimum level (45% of the control), and then gradually recovered to 75% of the control, respectively, 12 and 24 hr after the intraperitoneal injection of 5 mmole/kg BSO. On the other hand, the maximum non-protein sulfhydryl (NPSH) depletion (29% of the control) in the liver of tumor bearing mice was achieved 6 hr after the administration of the same dose of BSO, but fully recovered 24 hr later. When 5 mmole/kg BSO was injected repeatedly 4 times at an interval of 6 hr, GSH content in the tumors decreased to 19% of the control 24 hr after the first injection of BSO. The radiosensitizing effect of 0.5 mmole/kg MISO was markedly increased by this BSO treatment. The enhancement ratio (ER) of this combined treatment was 1.93. On the other hand, ERs of 1.44 and 1.16 were obtained for MISO (0.5 mmole/kg) and for 4 injections of BSO (5 mmole/kg) in combination with radiation, respectively. Although a considerable increase in the radiosensitizing efficiency of MISO in vivo by the treatment with BSO was found without any notable side effects of the combination, more studies on toxicities are needed to get a definite conclusion on the clinical applicability of the combination.

Animals↗
PubMed1986

Combined effect of buthionine sulfoximine and cyclophosphamide upon murine tumours and bone marrow.

Two and four treatments of 5 mmol kg-1 of buthionine sulfoximine (BSO) at an interval of 12 h depleted the glutathione (GSH) content in NFSa tumours of C3H/He mice, respectively, to 24.0 and 1.78 percent of the untreated controls. BSO pre-treatments every 12 h enhanced the cytotoxicity of cyclophosphamide (CYC) towards artificial lung micrometastases of NFSa tumours giving enhancement ratios (ERs) ranging from 1.75 to 1.83 and from 2.41 to 2.73, for two and four BSO pretreatments respectively. Large ERs were obtained at low CYC doses (high cell survival). Four BSO pre-treatments at an interval of 12 h did not increase the cytotoxicity of CYC to bone marrow stem cells. Our results suggest a clinical applicability of the combination of BSO and CYC.

Animals↗
PubMed1986

Effect of vasopressin antagonist on water excretion in inferior vena cava constriction.

Elevated levels of plasma arginine vasopressin (AVP) have been suggested to impair water excretion in congestive heart failure. In the present study, to determine a role for AVP in the impaired water excretion in rats with the inferior vena cava constriction (IVC), two AVP antagonists were used in the IVC rats at the proximal portion of the hepatic vein under the diaphragm and in sham-operated (control) rats. After surgery, 48 hrs were allowed before the experiments were started. A mean cardiac index of 260.0 +/- 12.3 ml/min/kg in the IVC rats was significantly lower than that in the control rats, 323.6 +/- 13.2 ml/min/kg (P less than 0.01). The rats were given an antidiuretic antagonist, [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid), 2-(O-ethyl)-D-tyrosine, 4-valine] AVP (30 micrograms/kg) or the antagonist vehicle, i.p., and 20 min later they were administered 30 ml/kg of water orally. Minimal urinary osmolality (Uosm) in the IVC rats receiving the vehicle was significantly greater than the control rats (292.7 +/- 53.1 vs. 97.8 +/- 10.6 mOsm/kg H2O, P less than 0.01). The administration of the antidiuretic antagonist in the IVC rats decreased minimal Uosm to 90.0 +/- 3.6 mOsm/kg H2O. This value was significantly lower than the vehicle rats (P less than 0.01), and was a comparable level to minimal Uosm of 82.1 +/- 3.7 mOsm/kg H2O in the control rats receiving the antidiuretic antagonist. The IVC rats excreted 51.4 +/- 5.9% of the water load in three hr, a value significantly less than that excreted by the control rats, 95.1 +/- 6.0% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Variation in the hypoxic fraction among mouse tumors of different types, sizes, and sites.

Radiobiologically hypoxic fractions of 4 experimental tumors (RIF1, B16, EMT6/KU, SCCVII) of various sizes implanted subcutaneously (sc) or intradermally (id) were compared under identical conditions by using the paired survival curve assay method. The two survival curves for tumors in air-breathing and asphyxiated mice were almost parallel for EMT6/KU and SCCVII tumors, but not for RIF1 and B16 tumors. Therefore, hypoxic fractions were estimated by fitting the best parallel lines to the two sets of survival data. The values for 10 mm-diameter sc tumors in the hind legs of syngeneic mice were 4.7% for RIF1, 4.5% for B16, 14% for EMT6/KU, and 8.5% for SCCVII. The variation of the values is quite small in spite of the variety of biological characteristics of these tumors. Histological examination revealed that EMT6/KU and B16 tumors contained large necrotic areas, while SCCVII and RIF1 had small areas of necrosis. Thus, the hypoxic fraction and the proportion of necrosis in the histological specimens were not clearly correlated. The values for 6 mm and 16 mm sc EMT6/KU tumors were 5.9 and 22%, respectively, while that for 6 mm id tumors was 16%. The values for 5 mm and 18 mm sc SCCVII tumors were 0.86 and 8.4%, respectively. These results indicated that: (1) id EMT6/KU tumors had a higher hypoxic fraction than sc ones of the same size; (2) the hypoxic fraction increased with increase in tumor size in EMT6/KU tumors, while it reached a plateau at a certain size in SCVII tumors.

Animals↗
PubMed1985

Silver staining for selective detection of histones in polyacrylamide gels.

A simple silver-staining technique was developed for selective visualization of histones in polyacrylamide gels. The specificity of the stain was confirmed using a variety of protein mixtures and isolated histones. The staining procedure requires a relatively short time to perform (2.5-3 h), and the sensitivity to lysine-rich histones is comparable to that of the conventional Coomassie blue stain (about 0.1 microgram per band). A possible mechanism for the selective staining was deduced from a comparison with the widely used ultrasensitive silver staining.

Chemical Phenomena↗
PubMed1985

Developmental changes in the binding of follicle-stimulating hormone (FSH) to testicular preparations of mice and the effects of hypophysectomy and administration of FSH on the binding.

Changes with age in testicular FSH binding and the effects of hypophysectomy and administration of FSH on FSH binding were studied in mice. The binding per unit testicular weight reached a peak at 10-20 days of age and it rapidly decreased during 20-37 days. The total binding per two testes increased from 4 days of age, reaching a peak at 31 days, and decreased thereafter when the testis still continued growing. Scatchard plot analyses of the binding showed that the equilibrium constant of dissociation (Kd) was about 3 X 10(-10) M regardless of age, and the changes in FSH binding were due to changes in the number of binding sites. Hypophysectomy at 90 days of age induced a significant decrease in the testicular weight, but the concentration of FSH binding sites markedly increased 16 days after the operation. In hypophysectomized mice the total number of FSH binding sites was increased 1.8-fold as compared with intact mice. In contrast, hypophysectomy induced a decrease in the total number of LH-binding sites. Injections of 100 micrograms NIH-FSH-P-2 for 10 days to hypophysectomized mice significantly decreased the concentration and the total number of FSH binding sites as compared with those in saline-injected hypophysectomized mice. These results suggest that FSH reduces its own receptors in the testis of mice.

Animals↗
PubMed1985

Difference in the homology of two nuclear nonhistone protein fractions as compared by polyacrylamide gel electrophoresis.

The extent of homology between two protein fractions was compared by simple electrophoretic analysis. Nuclear proteins of several rodent cells of different origins were fractionated into acid-soluble and acid-insoluble fractions. The two protein fractions were subjected to polyacrylamide gel electrophoresis in separate gel systems, and protein bands with identical mobilities were sought either in all possible combinational pairs of cell types or in all cell types. The paired and overall homology indices calculated from these data and chi-square testing of the results indicated that acid-soluble nuclear nonhistone proteins are more homologous than acid-insoluble nuclear proteins. Several factors which might have affected the results were discussed.

Animals↗
PubMed1984

Mechanism of silver staining of histones: evidence for involvement of clustered lysine residues.

Pretreatment of histones with formaldehyde markedly enhances the formation of metalic silver from ammoniacal silver ion. The rate of silver reduction was determined with different histones by spectrophotometric measurement of colloidal silver stabilized in solution, and the apparent reactivity thus determined was found to be in the decreasing order of H1 greater than H2B greater than H2A greater than H3 greater than H4. Involvement of lysine residues was suggested since this order coincides with that of lysine content of these histones. However, the exceptionally high reactivity of histone H1 can be explained only when greater contribution of clustered lysine residues is assumed. Amino group modification and tryptic digestion studies of H1 corroborated this assumption.

Animals↗
PubMed1984

Cross-linking of proteins to DNA in newly synthesized chromatin by diisopropylfluorophosphate, a serine protease inhibitor.

When nascent DNA of SV40 pulse labeled with [alpha-32p]dCTP in a permeable cell system was treated in situ with diisopropylfluorophosphate (DFP), a significant fraction of radioactivity was found to be covalently complexed with proteins. The adduct formation was demonstrated by density separation in CsCl, selective precipitation of the complexed DNA with SDS-KC1, and visualization of cross-linked proteins after SDS-PAGE. No cross-linking occurred with mature SV40 chromatin labeled in vivo and extracted from nuclei of infected cells. The DFP-induced DNA-protein cross-linking reaction appears to involve the protein's sulfhydryl groups since pretreatment with some sulfhydryl reagents completely inhibited the reaction.

Animals↗
PubMed1984

Partial purification of Simian virus 40 large T antigen by immunoaffinity chromatography and its detection by enzyme-linked immunosorbent assay.

Simian virus 40 (SV40) large T antigen was partially purified from small amounts of SV40-infected and SV40-transformed cells by immunoaffinity chromatography with high recovery. T antigen, in both crude and partially purified states, was detected rapidly by a sensitive and quantitative enzyme-linked immunosorbent assay (ELISA). Stability of the partially purified T antigen was found to increase by addition of 0.01% bovine serum albumin (BSA).

Animals↗
PubMed1984

Development of "granulosa" cell tumors from intrasplenic testicular transplants in castrated ACI rats.

A day-old testis was transplanted into the spleen of one-month-old castrated ACI male rats. For the first six months, diffuse hyperplasia of the interstitial cells was conspicuous with progressive deletion of spermatogenic cells in the seminiferous tubules. Then multiple foci of hyperplastic nodules started to appear, mainly near the tunica albuginea, in all castrated rats, but never in noncastrated rats. These nodular tissues gradually fused together (so-called Leydig cell tumors) and at about 12 months, other distinct tumor foci, morphologically indistinguishable from ovarian granulosa cell tumors, developed in and replaced the nodular tissues. The specific binding of follicle stimulating hormone to the "granulosa" cell tumor tissues was demonstrated. The hypothesis is presented that Sertoli cells were involved in the hyperplastic nodules and ultimately gave rise to the "granulosa" cell tumors.

Animals↗
PubMed1984

[Changes in meal patterns and endogenous chemical determinants related to food intake following intra-ventricle III infusion of mazindol].

To clarify suppressive effects of mazindol on food intake in rats, changes in body weight, meal patterns as well as 24-hr food intake, and endogenous chemical substances were investigated following the intra-ventricle III infusion of 0.03 mumole mazindol. Experiments were carried out under the condition of a 12: 12 light-dark cycle (light: 0800-2000 hr). Mazindol decreased food intake as well as body weight after a 12 hr starvation. Reduced food consumption was observed during 12 hr following the injection. Weight reduction, however, lasted over all 3-tested days. When food was available ad. lib., mazindol decreased meal size during the 4 hr after injection and prolonged postprandial intermeal interval during the 4 hr period starting 2 hr after the injection. The infusion of mazindol also produced relative hyperglycemia and decreased free fatty acids, which was not accompanied with hyperinsulinemia. These findings, together with other reports, indicates that mazindol, unlike amphetamine and fenfluramine, possesses inhibitory actions on the hypothalamic feeding center.

Animals↗