Search PubMed⌕ Search

Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 757 records · Page 42Linked to original sources
PubMed1982

Antithrombotic activity and the mechanism of action of trapidil (Rocornal).

Antithrombotic activity and the mechanism of action of trapidil were investigated, as compared with those of aspirin and dipyridamole. Trapidil at oral doses of 30 and 100 mg/kg inhibited arterial thrombosis in rats, while aspirin and dipyridamole at doses up to 300 mg/kg showed only a mild activity. This action may be explained by the fact that trapidil at concentrations ranging from 139 microM to 251 microM exerted 50% inhibition of platelet aggregation induced by ADP, arachidonic acid, thrombin or thromboxane A2 mixture, inhibition of platelet release reaction induced by ADP, arachidonic acid or thrombin, disaggregatory effect on aggregated rabbit platelets by arachidonic acid and potentiating action on antiaggregatory action of prostacyclin in vitro. In vitro actions of trapidil were apparently different from those of aspirin and dipyridamole. Trapidil also showed inhibition of platelet phosphodiesterase activity and thromboxane synthetase activity. Trapidil was expected to be an effective antithrombotic agent. The antithrombotic action of trapidil may be mediated by the inhibition of platelet function which is characterized by the inhibition of both thromboxane synthetase and phosphodiesterase activities, and by the potentiation of the antiaggregatory action of prostacyclin.

Adenosine Triphosphate↗
PubMed1982

Increase in histidine decarboxylase activity in skin of genetically mast-cell-deficient W/Wv mice after application of phorbol 12-myristate 13-acetate: evidence for the presence of histamine-producing cells without basophilic granules.

Histidine decarboxylase (HisDCase, EC 4.1.1.22) activity in mouse skin increased by a factor of more than 10 after a single application of phorbol 12-myristate 13-acetate. The cell type that was responsible for the increase in HisDCase activity was examined by using (WB X C57BL/6)F1-W/Wv mice, which are genetically deficient in tissue mast cells. In contrast to a report that increase of ornithine decarboxylase (EC 4.1.1.17) activity occurs in the epidermis [O'Brien, T. G., Simisiman, R. C. & Boutwell, R. K. (1975) Cancer Res. 35, 2426-2433], the HisDCase activity was found to increase in the dermis. Although most of the histamine in the dermis was present in mast cells, the increase in HisDCase activity in the skin in W/Wv mice was comparable with that in congeneic +/+ mice. This increase of HisDCase activity in the skin of W/Wv mice was abolished by prior x-ray irradiation (800 rads; 1 rad = 0.01 gray) but was restored by subsequent bone marrow transplantation. Because mice, in general, are known to lack basophilic leukocytes, the present results suggest the existence of histamine-producing cells without basophilic granules that are derived from the bone marrow.

Animals↗
PubMed1982

Deciduoma formation in uterus of genetically mast cell-deficient W/Wv mice.

The role of mast cells in deciduoma formation in the uterus of mice was investigated by using genetically mast cell-deficient (WB x C57BL/6)F1-W/Wv (hereafter called WBB6F1-W/Wv) mice. Deciduoma formation occurred in castrated WBB6F1-W/Wv mice after estradiol-progesterone injection and traumatization in spite of their deficiency of mast cells. Injection of diphenhydramine, which blocks histamine receptors, inhibited deciduoma formation in WBB6F1-W/Wv mice as well as in congenic +/+ mice. THe uterus of WBB6F1-W/Wv mice contained about 10% of the amount of histamine found in the uterus of +/+ mice. These results suggest that mast cells are not essential for formation of deciduomata and that histamine originating from sources other than mast cells may be important in deciduoma formation.

Animals↗
PubMed1982

Survival of host mast cells after establishment of hematopoietic chimerism by graft-versus-host reaction in nonirradiated F1 hybrid mice.

Since the tissue mast cell has been shown to be progeny of the multipotential hematopoietic stem cell (CFU-S), and the CFU-S is a sensitive target of graft-versus-host (GVH) reaction, we examined whether or not the mast cell is also the target of GVH reaction. Giant granules of C57BL/6-bgJ/bgJ mice were used as a marker of donor cells. When 10(8) spleen cells of C57BL/6-bgJ/bgJ mice were injected into nonirradiated (C57BL/6 X CBA)F1 hybrid mice, erythrocytes and neutrophils became of donor type in about one-half of the recipient mice. In the bone marrow and spleen of the chimeric mice, the CFU-S was of donor type as well. In contrast, mast cells of host type remained in many tissues of the chimeras. Moreover, mast cell precursors with capabilities of proliferation and differentiation were preserved in the skin of chimeras. The present results suggest that the effect of systemic GVH reaction on mature mast cells and the mast cell precursor fixed in the skin is significantly less severe than that on the CFU-S itself.

Animals↗
PubMed1982

Presence of pluripotent haemopoietic precursors in vitro (CFU-mix) in haemopoietic tissues from mice of W/Wv genotype.

The presence or absence of haemopoietic precursors, which produce mixed colonies in vitro (CFU-mix) was examined in the bone marrow and spleen of (WB X C57BL/6) F1-W/Wv mice. Despite the failure of macroscopically evident colony-formation in the spleens of irradiated mice, haemopoietic cells of W/Wv mice did produce macroscopically-evident mixed colonies containing erythroid cells, macrophages, and often megakaryocytes, in culture medium. The size and constitution of mixed colonies derived from W/Wv mice were comparable to those of mixed colonies from congenic +/+ mice. The present results appear consistent with in vivo haemopoiesis in the W/Wv mice, which is obviously deficient, but sufficient for survival.

Anemia, Macrocytic↗
PubMed1982

Proliferative response of mouse seminal vesicle epithelium to androgen and estrogen, assayed by incorporation of [125I]iododeoxyuridine.

The proliferation and death of androgen- and estrogen-responsive cells in the seminal vesicles of mice were investigated. Since 5-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) was incorporated into seminal vesicle DNA, and since the steroid-induced change in [125I]IdUrd uptake by whole seminal vesicles paralleled the change in the mitotic index in epithelial cells, [125I]IdUrd uptake was used as an index in epithelial cells, [125I]IdUrd uptake was used as an index for the proliferation of epithelial cells. Injections of testosterone propionate (TP) in castrated mice induced a 50-fold increase in [125I]IdUrd uptake. When androgen-induced cell proliferation was labeled with [125I]IdUrd, the incorporated radioactivity was retained in mice given continuous TP injections but not in mice given continuous TP injections but not in mice given 17 beta-estradiol (E2) or vehicle. Although the injection of E2 into castrated mice induced a 10-fold increase in [125I]IdUrd uptake, E2 did not increase seminal vesicle weight, and when estrogen-induced cell proliferation was labeled with [125I]IdUrd, the incorporated radioactivity was not retained in mice given continuous E2 injections. The simultaneous injections of E2 and TP showed no significant additive effect on [125I]IdUrd uptake. The present results suggest that 1) androgen induces proliferation and differentiation of the seminal vesicle epithelium and maintains the differentiated cells; 2) estrogen induces epithelial cell proliferation without further differentiation or maintenance of the resulting cells. The seminal vesicle epithelial cells responsive to estrogen may be the same cells that are responsive to androgen.

Animals↗
PubMed1982

Proliferative pattern of seminal vesicle cells and the production of testosterone and 5 alpha-androgens from birth to adulthood in mice.

Proliferation of seminal vesicle cells and the concentration of testicular and serum androgens (testosterone and 5 alpha-androgens) from birth to adulthood were investigated in mice. The weight of the seminal vesicles increased significantly from day 0 to day 10 after birth (approximately 0.1-1 mg), remained nearly constant in the next 10 days, and increased again (1-50 mg) thereafter. As an index of cell proliferation, two distinct peaks of 5-[125I]iodo-2'-deoxyuridine ([125I]IdUrd) uptake by the whole seminal vesicles were found at days 8 and 30. Types of proliferating cells examined by autoradiography after injection of [3H]thymidine were partially testis-dependent fibromuscular and epithelial cells in the first peak and largely testis-dependent epithelial cells in the second peak. The [125I]IdUrd uptake values found around day 20 and after day 40 were similar to those in neonatally castrated mice. Concentrations of testicular and serum androgens were relatively high on days 8, 30, 35, 40, and 60 (0.2-0.7 ng/mg tissue and 1.3-2.2 ng/ml, respectively) but were very low on day 18 (0.02 ng/mg tissue and 0.4 ng/ml). These findings lead to the hypothesis that androgens secreted from neonatal and prepubertal mouse testes play a major role in the proliferation of seminal vesicle cells and that the quiescent interval of androgen secretion and action occurs around the 20th day after birth in mice.

Aging↗
PubMed1982

[Effects of protizinic acid on the prostaglandins system and the production of oxygen radicals].

Effects of protizinic acid (PRT) on prostaglandins (PG) and the production of oxygen radicals were compared with those of other non-steroidal anti-inflammatory agents. Oral administration of 30 mg/kg of PRT, indomethacin (IM), or ibuprofen (IB) significantly inhibited arachidonic acid-induced erythema in guinea pigs. Although 30 mg/kg of PRT significantly inhibited PGE2-induced erythema, IM and IB did not significantly inhibit it. PRT inhibited phospholipase A2 (PLA2) activity, and the IC50 value was 2.1 X 10-4 M. On the other hand, IM and IB exerted no effect on the PLA2 activity at 3 X 10-4 M. These results suggest that PRT possesses a broader pharmacological activity on the PG system than IM and IB. As for effects on the production of oxygen radicals, in order of relative inhibitory potency was PRT greater than metiazinic acid (MA) = IM greater than IB = phenylbutazone (PB) in the xanthine oxidase assay, PB great than IM greater than PRT greater than MA = IB in the rabbit neutrophil myeloperoxidase assay, and IM greater than PB greater than PRT greater than MA greater than IB in the guinea pig macrophage assay. In the rabbit neutrophil and aggregated IgG-bound micropore filter assay, the order was PRT greater than MA greater than PB greater than IM = IB. Thus, the inhibitory effects of PRT was verified in all experiments on the production of oxygen radicals in contrast to IB. In particular, it could be especially meaningful that PRT showed the most potent activity in the aggregated IgG-bound micropore filter assay which has been reported to be a good model for studying the pathogenesis of inflammatory diseases believed to be caused by immune complexes.

Animals↗
PubMed1982

Hormone receptors and Japanese breast cancer.

In Japan, the incidence of breast cancer is remarkably lower than in Western countries. We examined tumor estrogen (ER) and progesterone receptors (PgR) in 1060 Japanese breast cancer patients. In Japan, 58% and 36% of breast cancers revealed measurable amounts of cytosol ER and PgR, respectively. These rates are slightly lower than those reported in Western countries, which were found to be 60-80% and 40-60%, respectively, though the difference is mainly confined to postmenopausal non-overweight (less than 60 kg) patients. The objective remission rates to endocrine therapy were 48% for ER+ tumors, 10% for ER-tumors, 66% for ER+, PgR+ tumors, 30% for ER+, PgR- tumors and 10% for ER-, PgR- tumors. These response rates are similar to those in Western breast cancer patients. ER and/or PgR in the breast cancer cytosol are useful markers for predicting response to endocrine therapy. The present findings also indicate that ER- tumors are estrogen independent but ER+ tumors include both estrogen-dependent and -independent tumors and that some of ER+ but endocrine-resistant tumors have postreceptor defect. The presence of ER+ but endocrine-resistant tumors may be due in part to the loss of hormone-dependency of estrogen-dependent breast cancer during endocrine therapy. The transformation of hormone-dependent mouse tumor cells into independent tumor cells was demonstrated as one of the mechanisms involved in the loss of hormone-dependency.

Breast Neoplasms↗
PubMed1982

Different effects of dimethylbenz(alpha)anthracene and tetradecanoylphorbol acetate on differentiation of mast cells in the skin of mice.

The effects of the application of 7,12-dimethylbenz(alpha)anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the differentiation of tissue mast cells were investigated. Giant granules of beige (C57BL/6-bgJ/bgJ, Chédiak-Higashi syndrome) mice were used to distinguish different populations of mast cells. In the normal C57BL/6 mice that had been irradiated and injected with bone marrow cells of beige C57BL/6 mice (bgJ/bgJ leads to +/+ chimeras), mast cells in the skin remained normal in type and mast cell precursors in the bone marrow and peripheral blood were of the beige type. When DMBA was painted onto the skin of such bgJ/bgJ leads to +/+ chimeras, the number of beige mast cells increased, but the number of normal mast cells did not change. On the other hand, the number of both normal and beige mast cells increased when TPA was applied to the bgJ/bgJ leads to +/+ chimeras. Autoradiographic study showed that beige mast cells proliferated more than normal mast cells after DMBA applications, whereas the proliferations was comparable in both types of mast cells after TPA applications. The present results indicate that the effects of DMBA applications on differentiation of mast cells are different from those of TPA applications.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Evidence for involvement of mast cells in tumor suppression in mice.

Mast cell-deficient W/Wv mice had an increased tumor incidence after subcutaneous treatment with 3-methylcholanthrene, compared with that in normal congenic mice treated in the same way. This increased tumor incidence was suppressed to the normal level when the carcinogen was given after the mast cell deficiency had been overcome by transplantation of bone marrow cells from normal congenic mice. The W/Wv mice, however, were not defective in natural killer and T-cell-mediated cytotoxic activities. These results support the hypothesis that mast cells are involved in tumor suppression.

Animals↗
PubMed1982

Bile reflux: a possible cause of stomach ulcer in nontreated mutant mice of W/WV genotype.

The chronic antral ulcer developed spontaneously in (WB X C57BL/6)F1-W/WV mice. Natural history of the ulcer was investigated to make clear the mechanisms involved in the development of ulcer in this mutant mouse. Although no histopathologic abnormalities of the stomach were detected at the fifth day after birth, erosions developed at the tenth day and the severity of the ulcerative lesions advanced with age. Antral pH of the W/WV mice was higher than that of the congenic +/+ mice, and the content of gastrin in the glandular stomach of the former was lower than that of the latter. Therefore, hyperacidity cannot be the cause of the ulcer in the W/WV mice. Bilirubin was demonstrable in the stomach contents of the suckling W/WV mice. After subcutaneous injection of [35S]sulfobromophthalein, the 35S radio-activity in the stomach contents of the 10-day-old W/WV mice was about 40 times as great as that observed in the +/+ littermates. As the peak of the bile reflux occurred shortly before the development of obvious ulcer that penetrated beyond the muscularis mucosae, the bile reflux could be a cause rather than a result of the ulcer.

Animals↗
PubMed1982

Necessity of bile for and lack of inhibitory effect of retinoid on development of forestomach papillomas in nontreated mutant mice of the W/Wv genotype.

The pathogenesis of papillomas which developed spontaneously in the forestomach of WB X C57BL/6 F1-W/Wv mutant mice was investigated. The thickness of the forestomach epithelium was used as a quantitative index for development of papillomas. From the 15th day after birth, the forestomach epithelium of the W/Wv mice was significantly thicker than that of the congenic +/+ mice. Administration of aromatic retinoic acid analog (ethyl all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-3,7-dimethyl-2,4,6,8 -nonatetraenoate) did not suppress development of papillomas. Since papillomas did not appear in the stomach which was removed from the W/Wv embryos and grafted to the s.c. space produced in the back of the adult mice and since a considerable amount of bile reflux preceded development of papillomas, bile reflux may be a cause of papillomas in W/Wv mice.

Alleles↗
PubMed1982

Effect of splenectomy on establishment of hematopoietic chimerism in nonirradiated mice.

When spleen cells (1.5 x 10(8)) from beige C57BL/6 (bgJ/bgJ, Chediak-Higashi syndrome) mice were injected into nonirradiated (C57BL/6 x CBA)F1 hybrid mice, the hematopoietic stem cells of the hybrid host were eradicated by graft-versus-host (GVH) reaction, and peripheral neutrophils of the host changed from normal type to beige type with giant sudanophilic granules in 20 days after the cell injection. Effect of splenectomy on the establishment of such hematopoietic chimerism was investigated. The splenectomy carried out either before or after the cell injection reduced the proportion of mice in which more than 90% of peripheral neutrophils became of beige type. Since the mortality of mice which received splenectomy at various days prior to or after the cell injection paralleled the proportion of establishment of chimerism, the splenectomy does not seem to affect directly the establishment of chimerism but indirectly through the modification of the intensity of GVH reaction.

Animals↗