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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 865 records · Page 48Linked to original sources

Photoinactivation of the thiamine transport system in Saccharomyces cerevisiae with 4-azido-2-nitrobenzoylthiamine.

A newly synthesized photoreactive thiamine derivative, 4-azido-2-nitrobenzoylthiamine was found to be a competitive inhibitor of the thiamine transport system in Saccharomyces cerevisiae, exhibiting an apparent Ki of 36 nM. When exposed to visible light, 4-azido-2-nitrobenzoylthiamine irreversibly inactivated the thiamine transport. 4-Azido-2-nitrobenzoylthiamine-dependent photoinactivation of thiamine transport was partially protected by thiamine, but not by the nitrene-trapping reagent p-aminobenzoate. On the other hand, the irradiation of the yeast cells in the presence of 4-azido-2-nitrobenzoylthiamine did not significantly lead to inactivation of the biotin transport system. The results suggest that 4-azido-2-nitrobenzoylthiamine is a specific irreversible inhibitor of the thiamine transport system in Saccharomyces cerevisiae.

Cell Membrane↗

Possible functional roles of carboxyl and histidine residues in a soluble thiamine-binding protein of Saccharomyces cerevisiae.

The reaction of a soluble thiamine-binding protein of Saccharomyces cerevisiae with water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, at pH 4.5, results in a remarkable loss of its binding activity with thiamine. Thiamine above 0.1 mM substantially protects the protein against this inactivation. In addition to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, the thiamine-binding protein is also inactivated by diethylpyrocarbonate. The inactivation is time-dependent and follows second-order kinetics. Restoration of the binding activity by incubation of inactivated protein with hydroxylamine was observed. thiamine and pyrithiamine are effective to prevent the inactivation. From these results it is strongly suggested that both the carboxyl and the histidine residues in the protein are involved in the binding site for thiamine. It is proposed that the binding involves interactions between charged groups on the protein with the quaternary nitrogen of the thiazolium moiety and with the basic ring nitrogen of the pyrimidine moiety in thiamine molecule.

Acid Phosphatase↗

Effect of ethinyl estradiol on development of mouse fetuses.

Pregnant ICR/JCL mice were given orally 0.02, 0.3, or 2.0 mg/kg body weight/day of ethinyl estradiol in olive oil or vehicle alone on day 11 through day 17 of pregnancy. Pregnant mice of another group received a single oral dose of ethinyl estradiol on day 8 or day 11 of pregnancy. A lethal effect on fetuses of both groups with single and continuous exposure to ethinyl estradiol was observed in a dose-response relationship. Growth suppression of fetuses was only found at term in a dose-response relationship following continuous exposure to ethinyl estradiol. Hypertrophic nipples were seen in 42% of surviving female fetuses prenatally exposed to 2.0 mg/kg of ethinyl estradiol singly on day 11 of gestation. There was not an increase in other congenital malformations in any of the treated groups. These findings indicate that administered ethinyl estradiol can affect the developing mouse embryo but the embryotoxic doses in the mouse are substantially greater than the usual therapeutic or contraceptive doses in the human.

Abnormalities, Drug-Induced↗

Representation of T cell functions in liver bearing hepatocellular carcinoma.

Thymus-derived cells (T cells) were stained by the immunofluorescent technique, and found to be predominate around the cancer cell nests, in the interstitium, and in the lumen of the sinusoid of the liver bearing hepatocellular carcinoma (hepatoma). The marked T cell predominance in the liver obtained at autopsy in 19 of 13 patients with hepatoma indicates that specific T cell-mediated immunity may be maintained even in the terminal stage of cancer in these patients.

Carcinoma, Hepatocellular↗

Improved modification of yeast uricase with polyethylene glycol, accompanied with nonimmunoreactivity towards anti-uricase serum and high enzymic activity.

The highly purified uricase from Candida utilis was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2), which was synthesized from monomethoxypolyethylene glycol (MW 5,000) and cyanuric chloride. Modification of approximately 36 out of the total 98 amino groups in the uricase molecule led to the complete loss of the binding ability towards antiuricase serum from rabbit with the retention of high enzymic activity (45% of native uricase). The modified uricale cleared more slowly from the plasma of mice compared with native uricase.

Animals↗

Studies on the mechanism of "exaggerated natriuresis" in essential hypertension.

Prompt and exaggerated natriuresis and diuresis were seen one to two hours after the starting of an infusion of 300 ml of 3% saline for one hour in patients with essential hypertension on a high sodium chloride intake. There were no significant differences in urinary volume and sodium excretion after the saline load in patients with normal and low plasma renin activity. The inhibition of angiotensin converting enzyme with SQ 14225 in patients with normal plasma renin activity did not produce additional natriuresis and diuresis after the saline load. Mean arterial blood pressure and/or changes in mean arterial blood pressure after the saline load showed a positive correlation with urinary volume and sodium excretion in each collection period in hypertensive subjects. Free water reabsorption in hypertensives was lower at high levels of osmolar clearance than that in control subjects. These results suggest that "exaggerated natriuresis" in essential hypertension is due to a decrease in tubular sodium reabsorption, which may be the result of intrarenal hemodynamic changes related to high blood pressure per se. The decreased medullary osmolar gradient is a possible contributing factor in the enhanced sodium and water excretion, while the renin-angiotensin-aldosterone system does not seem to play an important role.

Aldosterone↗

Development of ovarian tumors experimentally studied in mice by 60Co-ray irradiation.

Female C3H strain mice aged 5 to 6 weeks were exposed to a single dose of 400 Rad irradiation to their lower abdomens and the morphological changes of their ovaries were observed until 72 weeks after irradiation. The incidence of tumor development increased gradually from 34 weeks after irradiation till 72 weeks, when ovarian tumors were noted in more than 90% of the animals. Three types of ovarian tumors developed after a prolonged period, postirradiation: tubular adenoma, granulosa cell tumor and luteinizing tumor. Mixed tumor types account for 68% of the tissue examined. The tubular adenoma is believed to arise from the germinal epithelial inclusion cyst, the granulosa cell tumor and luteinizing cell tumor arise from the interstitial cells. In the case of the granulosa cell tumor, it is believed that tumor cells one capable of secreting estrogen, because vaginal smears demonstrated estrus and histological sections of endometrium demonstrated hypertrophy.

Adenoma↗

Ovarian tumors in children and adolescents less than 20 years age.

Reports are made of the analytical results of 76 cases with ovarian neoplasma under 20 years of age who had been treated at the Kurume University Hospital from January 1952. The incidence of ovarian tumors was 5.5% in all age groups, and the youngest patient was 5 years of age, the mean age being 15 years. Histologically, these tumors comprised 48 cases (63%) of germ cell origin, showing characteristically of ovarian tumors occurring in childhood and adolescence. The total 76 cases included 40 of malignant tumors, which were subdivided into 13 of embryonal carcinoma, 12 of solid teratoma, 9 of dysgerminoma, 5 of simple carcinoma, and 1 case of granulosa cell tumor. In all the cases the clinical stage was important factor for prognosis, and the prognosis of embryonal carcinoma was poorest, with only 4 cases of survival out of 13 cases. But the prognosis of dysgerminoma was comparatively good, with 8 cases of survival out of 9 cases. It is worthy of note that this tumor was highly radiosensitive, since 3 out of 4 cases at stage III and stage IV had been surviving for over 5 years.

Adolescent↗

Chemotherapy of malignant ovarian tumors; therapeutic results of ifosfamide.

Here are reported the therapeutic results of ifosfamide on primary ovarian malignancies in 30 cases which were treated at Kurume University Hospital from September 1978 to December 1980. These cases were advanced or recurrent ones, and histologically, they consisted of serous cystadenocarcinoma in 22 cases, mucinous cystadenocarcinoma in 2, unclassified adenocarcinoma in 1, and malignant teratoma in 5. In the ifosfamide therapy, 2 grams or 40 mg/kg per day were given intravenously for 5 consecutive days, and as observing the blood state and the general condition, it was repeated every 3 weeks. The drug was given from 1 to 7 courses, and the average was 3.3 courses. The effect was evaluated by Koyama-Saito's criteria and Karnofsky's criteria; the response rate was 48% in the adenocarcinoma group and 20% in the malignant teratoma by the former criteria, while the rate was 64% and 20%, respectively, by the latter one. As main side effects, there were seen hemorrhagic cystitis, nausea and vomiting, and the myelotoxicity was low.

Adenocarcinoma↗

Inhibition of thiamine transport in baker's yeast by methylene blue.

Methylene blue was found to inhibit thiamine transport competitively (Ki = 0.63 microM) in baker's yeast. The dye was also effective in abolishing the growth inhibition of Saccharomyces cerevisiae by pyrithiamine which is known to be taken up by a common transport system for thiamine in yeast cells. A possible mechanism for the inhibition by methylene blue of the thiamine transport system in baker's yeast is discussed.

Biological Transport↗

Active transport of dimethialium in Saccharomyces cerevisiae.

Dimethialium, a derivative of thiamine which has a methyl group in place of hydroxyethyl group at the t-position of the thiazole moiety, was found to be accumulated in nonproliferating cells of Saccharomyces cerevisiae by the same transport mechanism for thiamine. The results strongly support the supposition that thiamine as well as dimethialium can be transported and accumulated without obligatory phosphorylation in yeast cells, since dimethialium is not phosphorylated by yeast thiamine pyrophosphokinase.

Biological Transport, Active↗