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Biomedical subjects

M Tsuchiya

Publications and source records attributed to M Tsuchiya.

At least 379 records · Page 21Linked to original sources

Alcohol-induced enhancement of intestinal gamma-glutamyl transpeptidase activity in rats and humans: a possible role in increased serum gamma-glutamyl transpeptidase activity in alcoholics.

It is a well-known phenomenon that serum gamma-glutamyltranspeptidase (gamma-GTP, EC 2.3.2.2.) activity is increased after chronic consumption of ethanol, and gamma-GTP has been, therefore, widely used as a sensitive marker for detection of alcoholism and its related liver disease. However, the precise mechanisms whereby the chronic ethanol consumption leads to an increase in serum gamma-GTP activity are not fully understood. In the present study, we investigated the relationship between the intestinal and serum gamma-GTP activities after chronic ethanol consumption both in rats and humans. Chronic ethanol feeding to rats resulted in a significant increase in serum gamma-GTP activity associated with a significant increment of the intestinal gamma-GTP activity. The histochemical staining of gamma-GTP in the mucosa of the small intestine of these animals demonstrated enhanced gamma-GTP activity at the microvilli of the brush border membrane, lamina propria of the mucosa, and endoplasmic reticulum of the intestinal epithelial cell. The augmented activity in the lamina propria was mainly localized at the submucosal lymphatics. Histology of the small intestine of human alcoholics was, more or less, similar to those observed in alcoholic rats. We further investigated the gamma-GTP activity in the mesenteric lymph using the animal model of lymphorrhea, and found that the gamma-GTP activity was increased by 83% when expressed per unit of lymph in the ethanol-fed rat, accompanied by a marked decrease of serum gamma-GTP activity, suggesting a close relationship between the serum and the intestinal gamma-GTP via the lymphatic channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Affinity of drugs for dopa-auto-oxidation melanin and tyrosinase-catalyzed dopa-melanin in vitro.

We examined spectrophotometrically the ability of drugs to bind with dopa-auto-oxidation melanin or tyrosinase-catalyzed dopa-melanin. Each drug, at 5 X 10(-5) M, was incubated at 37 degrees C for 8 h with 0.4 mg of synthetic melanins in 20 mM potassium phosphate buffer at pH 7.0 or in 20 mM acetate buffer at pH 4.8. Chloroquine, thioridazine, befunolol, pindolol, daunomycin and 5-fluorouracil bound to melanin at pH 7.0 and 4.8. Methotrexate bound to melanin at pH 4.8, but not at pH 7.0. Pilocarpine, epinephrine, acyclovir, vincristine and colchicine did not bind to dopa-auto-oxidation melanin or tyrosinase-catalyzed dopa-melanin.

Catechol Oxidase↗

Terpentecin, an inhibitor of DNA synthesis.

Terpentecin at a concentration of 0.78 microgram/ml decreased the number of viable cells of Escherichia coli NIHJ to less than one thousandth the starting number in an hour when added to an exponentially growing culture in a nutrient broth. During this time, the turbidity of the cell suspension kept increasing as fast as the control. Microscopic inspection of the cells exposed to terpentecin under these conditions revealed that the cells were elongated. Terpentecin at a concentration of 6.25 micrograms/ml inhibited incorporation of [14C]thymidine into the acid-insoluble material of cells of E. coli NIHJ by 70% in 30 minutes in contrast to little or no inhibition of the incorporation of [14C]uridine or [14C]leucine. Under similar conditions, terpentecin did not inhibit either membrane transport (uptake) of [14C]thymidine into the cells or the metabolic conversion of the precursor into various cellular acid-soluble components. Terpentecin at a higher concentration (70 micrograms/ml) inhibited by 40% in 30 minutes the incorporation of [methyl-3H]thymidine triphosphate into the DNA fraction of toluene-treated cells of E. coli JE6296 (pol A-). Terpentecin showed stronger antibacterial activities against Bacillus subtilis M45T (rec-) and E. coli BE1121 (rec A-) than against their corresponding wild type strains. However, terpentecin showed no mutagenicity by the Ames test with Salmonella typhimurium strains TA100, TA98, TA92, TA1538, TA1537 and TA1535, and with E. coli WP2 (uvr A). Terpentecin at a lower concentration (0.07 micrograms/ml) inhibited growth in vitro of mouse leukemia L1210 cells by 50%. With the mammalian cells again the incorporation of [14C]thymidine into the acid-insoluble cell material was inhibited more strongly than incorporation of [14C]uridine and [14C]leucine. There was no sign of mutagenicity by the micronucleus test using mice.

Animals↗

[Radiation therapy of intracranial germ cell tumors].

The results of radiation therapy in 31 patients with intracranial germ cell tumors have been analyzed. The five-year survival rates were 70.1% for germinomas and 38.1% for teratomas. Three patients with germinoma have since died of spinal seeding. The prophylactic irradiation of the spinal canal has been found effective in protecting spinal seeding, since no relapse of germinoma has been observed in cases that received entire neuraxis irradiation, whereas teratomas and marker (AFP, HCG) positive tumors did not respond favorably to radiation therapy, and the cause of death in these patients has been local failure. Long-term survivors over 3 years after radiation therapy have been determined as having a good quality of life.

Adolescent↗

T lymphocyte subpopulations and immunoglobulin-containing cells in the colonic mucosa of ulcerative colitis; a morphometric and immunohistochemical study.

T lymphocyte subpopulations and immunoglobulin containing cells in the colonic mucosa of 25 patients with ulcerative colitis have been studied using an indirect immunoperoxidase technique. In ulcerative colitis a marked increase in the population of Leu 3a positive cells (helper/inducer T cells) and IgG containing cells was observed in the mucosal lamina propria. In the intraepithelial spaces, a remarkable decrease in the population of Leu 2a positive cells (suppressor/cytotoxic T cells) and a marked increase in the number of Leu 3a positive cells were revealed. There was a very significant correlation between the population of IgG containing cells and the ratio of Leu 3a positive cells to Leu 2a positive cells in the lamina propria of patients with ulcerative colitis. These results suggest that an imbalance of mucosal immunoregulatory T cells and an increased production of IgG occurred in correlation with inflammatory activities of ulcerative colitis.

Adolescent↗

Microcirculatory disturbances in endotoxin-induced disseminated intravascular coagulation. The effects of heparin and gabexate mesilate on locomotive and metabolic changes of neutrophils.

Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent technique and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes sticking to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E coli, O-111B4, Difco, USA) was infused intravenously at a dose of 2 mg/kg/hr. After starting the infusion of endotoxin, the number of sticking cells were gradually increased on the venular endothelium followed by a transient neutropenia. In order to investigate the distribution of infused endotoxin in the microvasculature, FITC-labeled endotoxin (Sigma, USA) was used. After administration of FITC-endotoxin, multiple patches of fluorescence along the venular walls were observed, while no fluorescent conjugates were found at the sticking neutrophils and along the arteriolar walls. ChL activities of neutrophils were also dramatically elevated, which may reflect the enhanced ability to generate oxyradical species. To investigate the inhibitory effects of heparin sodium and gabexate mesilate which was a synthetic protease inhibitor on locomotive and metabolic changes of neutrophils induced by endotoxemia, both agents were administered prior to endotoxin infusion. Gabexate mesilate attenuated these changes, but heparin sodium did not show any improving effects. It was concluded that endotoxin primarily affects the venular endothelial cells, resulting in the activation of neutrophils. Gabexate mesilate was more likely to attenuate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC than heparin sodium.

Animals↗

[Clinical research of radiotherapy in brain metastasis].

One hundred and four patients with brain metastasis were received the conventional radiotherapy from 1980 to 1985 at 3 hospitals. Results were as follows. 1. Primary sites were lung (41 cases), breast (34) and others (29). 2. Tumor was 3.15 cm in mean size (0.6-8.2 cm) and 2.6 in number of average (1-15) 3. Radiation dose was 46.5 Gy in average (30-66 Gy) and almost of all cases were irradiated with whole brain field. 4. Over all response rate on CT findings was 65.4% (CR rate: 23.1%) and 63.4% for lung and 73.5% for breast cancer. 5. Survival rate were 25.5% in 1 year, 8.8% in 2 year, 5.4% in 3 year and 3.6% in 5 year. 6. The longer interval was between onset of brain metastasis and primary treatment, the longer survival after brain irradiation. 7. No significant differences of survival rate were seen in size and in number of brain metastasis and with on without improvement of neurological symptoms. 8. The better response was on CT, the better prognosis after radiotherapy. 9. Identification of treatment for brain metastasis according to patient's characteristics and tumor factors were important.

Adult↗

[Histopathological changes in the brain after radiotherapy of brain metastasis].

This is the histopathological analysis of 18 post-irradiated brains with metastases of breast cancers. There was no evidence of radiation necrosis, except for one with demyelinization and one with degeneration of nerve cells. There was no radiation damage in re-irradiated group. Whole brain irradiation of about 40 Gy may be safe, but that of 60 Gy or more may be not so safe. It may be more useful for preventing of radiation damage to take split-course-method or shrinking-technique at doses of 40 Gy or more. The combination of chemotherapy and radiation therapy seems to aggravate the course of radiation damage.

Adult↗

5-lipoxygenase inhibitor (AA-861) attenuates neutrophil-mediated oxidative stress on the venular endothelium in endotoxemia.

Neutrophil-mediated oxidative stress on the rat mesenteric microcirculation was studied in the experimental model of endotoxin-induced disseminated intravascular coagulation (DIC) by using an intravital fluorescent microscope equipped with a Silicon Intensifier Target Image Tube camera and luminol-dependent chemiluminescence (ChL) analysis. Leukocytes adhering to the venules were visualized by the injection of acridine orange, a fluorochrome tracer which shows high affinity to white cells. Endotoxin (E. coli, O-111 B4) was administered intravenously at a dose of 2 mg/kg/hour. After starting the infusion of endotoxin, the number of adherent cells gradually increased in the venular endothelium and was followed by a transient neutropenia. ChL activities from neutrophils were also significantly elevated, which may reflect the enhanced ability to generate oxygen-radicals. To elucidate the role of 5-lipoxygenase products in the locomotive and metabolic changes of neutrophils, the effects of AA-861, a specific inhibitor of 5-lipoxygenase was tested. In addition prednisolone and indomethacin were evaluated. AA-861 and prednisolone reduced neutropenia, leukocyte adhesion to the venular walls and ChL activities from neutrophils. It was concluded that 5-lipoxygenase may modulate neutrophil-mediated oxidative stress on microvasculature in endotoxin-induced DIC.

Acridine Orange↗

Real-time visualization of oxyradical burst from single neutrophil by using ultrasensitive video intensifier microscopy.

Dynamics of oxyradical burst from single human neutrophils stimulated by opsonized zymosan was visualized by using an ultrasensitive video intensifier microscopy in the presence of chemiluminescence probe. Luminol-dependent photonic burst activities were clearly corresponding to the distribution of zymosan-treated neutrophils. Heterogeneity of photon-bursting period and the maximum photonic intensity among reactive cells was demonstrated. This may reflect functional heterogeneity of the ability to release oxyradicals among neutrophils.

Free Radicals↗