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Biomedical subjects

T Takeo

Publications and source records attributed to T Takeo.

6 recordsLinked to original sources

Tea catechins decrease micellar solubility and intestinal absorption of cholesterol in rats.

A(-)-epicatechin (EC) and (-)-epigallocatechin (EGC) mixture and a mixture of their gallates (ECG and EGCG, respectively) markedly lowered lymphatic cholesterol absorption in rats with a cannulated thoracic duct. A mixture of ECG and EGCG was more effective in reducing cholesterol absorption than the EC and EGC mixture. These catechins also tended to decrease lymphatic absorption of triacylglycerols, although not so pronounced as in cholesterol absorption. An in vitro study on micellar solubility of cholesterol showed that these catechin mixtures precipitated cholesterol solubilized in mixed bile salt micelles in a dose-dependent manner. A mixture of ECG and EGCG more effectively precipitated micellar cholesterol than a mixture of EC and EGC. When purified EC, EGC, ECG and EGCG were used, EGCG was more effective in precipitating micellar cholesterol than ECG. The effect of EC and EGC was comparable and weaker than their gallate esters. The bile acid concentration in the micelles was not affected by these catechins. A positive correlation was observed between the amount of coprecipitated EGCG and cholesterol. These results clearly show that tea catechins, in particular their gallate esters, effectively reduce cholesterol absorption from the intestine by reducing solubility of cholesterol in mixed micelles. The observation accounts for the hypocholesterolemic effect of tea catechins.

Animals

Intersite variation of estrogen receptors in human breast cancers and response to endocrine therapy. Which section of a large tumor is the best for estrogen receptor assay?

Estrogen receptor (ER) assays were performed by sucrose gradient centrifugation method at multiple sites in large breast cancers. Intersite variation of ER in a tumor was observed in 24 out of 35 cases. 16 tumors with relatively low ER levels showed different ER status with multiple assays. The results suggest that an assay performed on a small random part of a large tumor may not yield the true ER status. ER value at the largest cross-section was almost the same as the average ER values in each tumor. In addition, 21 cases were examined in relation to ER values at multiple sites in the large tumors and response to endocrine therapy. As the ER value at the largest cross-section was highly correlated with the therapeutic response to endocrine therapy of breast cancer, it would represent true ER status and level. The results suggest that the ER assay at the largest cross-section of a large tumor is an appropriate method to predict response to endocrine therapy.

Breast Neoplasms

Differential regulation of estrogen-dependent sexual development of rat brain by growth factors.

Intraventricular infusion of antiserum to nerve growth factor (ANGF), but not that to insulin, epidermal growth factor nor normal rabbit serum, resisted estrogen-induced behavioral defeminization in the female rat neonates. A significant number of the ANGF-treated rats showed lordosis as adults despite neonatal estrogen, but positive feedback of estrogen on serum luteinizing hormone was absent. Sexual phenotype in behavioral and gonadotropic functions may be under differential development regulation.

Animals

Interruption of the lordosis reflex of female rats by ventral midbrain stimulation.

The lordosis reflex, dorsiflexion of the vertebral column, is an estrogen-dependent, essential element of female sexual behavior in rodents. Unilateral electrical stimulation of the midbrain ventral tegmental area through a chronically implanted electrode in freely moving, estrogen-primed ovariectomized female rats caused a rapid and strong suppression of the lordosis reflex in response to either male mounts or manual cutaneous stimuli. The interruption occurred in a graded manner to increased stimulus intensity, with a threshold at 30 microA. The optimal frequency was at 75-125 Hz. After the termination of electrical stimulation, lordosis performance returned promptly to the pre-stimulation level. No aversive response accompanied the blockade of lordosis. Electrical stimulation specifically blocked lordosis, without disrupting the proceptive components of female sexual behavior. In 10 animals tested, concomitant injection of dopamine receptor blocker pimozide tended to offset the effects of electrical stimulation in 2 cases. Interruption of the lordosis reflex might be mediated by projections from the ventral tegmental area, which activate a descending pathway inhibitory to the lordosis reflex arc at or below the lower brain stem.

Afferent Pathways

Intensive individualized induction therapy with behenoyl cytarabine, daunorubicin and 6-mercaptopurine followed by intensive consolidation including intermediate-dose continuous cytarabine, mitoxantron, etoposide and vinca alkaloids in acute myeloid leukemia in adults.

Forty-one consecutive adult patients with acute myeloid leukemia (AML) were treated with an intensive individualized induction therapy of behenoyl cytarabine, daunorubicin, and 6-mercaptopurine, 29 patients (71%) achieved complete remission (CR). Patients then received three courses of intensive consolidation therapy, including intermediate-dose continuous cytarabine (400 mg/m2, for 5 days) and non-cross resistant drugs such as mitoxantron, etoposide and vincristine. During the course of the consolidation therapy, three patients died of infections and one died of myocardial infarction. Four patients underwent allogeneic bone marrow transplantation. The patients then received six courses of moderately intensive maintenance therapy for 1 year. The predicted 5-year continuing CR and disease-free survival rates of the CR patients were 62% (95% confidence limit, 41% to 83%) and 53% (33% to 73%), respectively. Although the number of patients in this study is small, the present study indicated that it may be possible to cure a fairly large proportion of AML patients by chemotherapy alone, if intensive induction therapy is followed by intensive consolidation therapy.

Acute Disease