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Biomedical subjects

Y Kitamura

Publications and source records attributed to Y Kitamura.

At least 613 records · Page 34Linked to original sources
PubMed1988

[Results of combination chemotherapy in advanced urothelial cancer].

Between April 1982 and March 1988, 28 patients with advanced urothelial cancer were treated with combination chemotherapy incorporating cisplatin at our hospital and the response was evaluated. Fourteen of them were managed by the CAP chemotherapy (cyclophosphamide 300-500 mg/m2 day 1, doxorubicin 30-50 mg/m2 day 1, cisplatin 40-90 mg/m2 day 2), 7 by the FAP chemotherapy (fluorouracil 300 mg/m2 day 1-5, doxorubicin 30 mg/m2 day 1, cisplatin 15 mg/m2 day 1-5) and 7 by the MEP chemotherapy (etoposide 100 mg/m2 day 1-3, cisplatin 20 mg/m2 day 1-5, methotrexate 300 mg/body day 6). Four patients (28.6%) responded to the CAP regimen; a complete response was gained in one patient who had pulmonary metastasis of excised ureteral cancer and a partial response in 3 patients with intravesical and nodal (N3, N4) cancer. A partial response was noted in 3 patients (42.9%) in the FAP group. They had intravesical lesions and two of them had regional node metastasis (N3). A higher response rate (85.7%) was obtained by the MEP regimen; a complete response in 2, who had intravesical and nodal (N2, N4) cancer, and a partial response in 4 patients, 1 had intravesical cancer, 1 had nodal (N2) and intravesical cancer and 2 had nodal or lung metastasis of excised renal pelvic cancer. Toxicity included mild to severe vomiting, alopecia, myelosuppression and mild renal or liver dysfunction. High dose metoclopramide provided a high degree of protection against cisplatin induced emesis. The results with the MEP regimen are promising for the advanced, metastatic urothelial cancer.

Adult↗
PubMed1988

The cause of anemia in mutant mice of Sl/Slt genotype: hypoplasia in bone marrow and restricted hyperplasia in spleen.

The cause of the severe anemia in Sl/Sld mice is attributed to (1) hypoproduction of erythrocytes due to a defect in the erythropoietic microenvironment and (2) bleeding from stomach ulcers. Sl/Slt mice also showed a moderate anemia, but bleeding from stomach ulcers was excluded as a cause of the anemia, because no significant amount of radioactivity was excreted in feces after the injection of 59Fe-labeled erythrocytes. The activity of erythropoiesis in the bone marrow and spleen was compared between Sl/Slt and congenic +/+ mice using three different criteria: the number of erythroblasts, 59Fe incorporation, and the number of erythropoietic precursor cells. All three parameters in the femur were lower, and those in the spleen were higher in Sl/Slt mice than in +/+ mice, suggesting that the low erythropoietic potential in the bone marrow of Sl/Slt mice is partially compensated by the spleen. In fact, splenectomy aggravated the anemia of Sl/Slt mice. The enhanced erythropoiesis in Sl/Slt spleens may explain our previous finding that numbers and sizes of spleen colonies were normal when bone marrow cells were injected into irradiated Sl/Slt mice. Sl/Slt mice may be a useful model for studying biological characteristics of the hematopoietic microenvironment.

Anemia↗
PubMed1988

Changes in numbers and types of mast cell colony-forming cells in the peritoneal cavity of mice after injection of distilled water: evidence that mast cells suppress differentiation of bone marrow-derived precursors.

Two different types of cells in the peritoneal cavity of mice produce mast cell colonies in methylcellulose. "Large" mast cell colonies are produced by bone marrow-derived precursors resembling lymphoid cells by light microscopy (L-CFU-Mast), whereas "medium" and "small" mast cell colonies are produced by morphologically identifiable mast cells (M-CFU-Mast and S-CFU-Mast, respectively). In the present study we eradicated peritoneal mast cells by intraperitoneal (IP) injection of distilled water. The regeneration process was investigated to clarify the relationship between L-CFU-Mast, M-CFU-Mast, and S-CFU-Mast. After injection of distilled water, M-CFU-Mast and S-CFU-Mast disappeared, but L-CFU-Mast increased, and then M-CFU-Mast and S-CFU-Mast appeared, suggesting the presence of a hierarchic relationship. When purified peritoneal mast cells were injected two days after the water injection, the L-CFU-Mast did not increase. In the peritoneal cavity of WBB6F1-+/+ mice that had been lethally irradiated and rescued by bone marrow cells of C57BL/6-bgJ/bgJ (beige, Chédiak-Higashi syndrome) mice, L-CFU-Mast were of bgJ/bgJ type, but M-CFU-Mast and S-CFU-Mast were of +/+ type. The injection of distilled water to the radiation chimeras resulted in the development of bgJ/bgJ-type M-CFU-Mast and then S-CFU-Mast. The presence of mast cells appeared to suppress the recruitment of L-CFU-Mast from the bloodstream and to inhibit the differentiation of L-CFU-Mast to M-CFU-Mast.

Animals↗
PubMed1988

Macroscopic intestinal colonies of mice as a tool for studying differentiation of multipotential intestinal stem cells.

Macroscopic nodules composed of regenerating intestinal epithelium were developed within an area of the murine jejunum ulcerated by X-irradiation (1700 rads). The authors investigated whether such intestinal nodules were clonal and whether this method was useful as a tool for studying differentiation of intestinal stem cells. For examination of the clonality, intestinal nodules were produced in the jejunum of (C57BL/6 X DS)F1-Pgk-1b/Pgk-1a mice that carried X-chromosome inactivation mosaicism for the phosphoglycerate kinase gene. All intestinal nodules contained only 1 type of phosphoglycerate kinase, suggesting the monoclonal origin of nodules. Histochemical and electron microscopic studies showed the presence of absorptive epithelial, goblet, and entero-endocrine cells in most intestinal nodules, suggesting the multipotentiality of the nodule-forming stem cells. Moreover, villi developed on the top of some intestinal nodules, implicating the potential of the multipotential stem cell to construct the highly organized structure. The result indicates that the intestinal nodule method is useful for investigating differentiation potentials of multipotential intestinal stem cells.

Animals↗
PubMed1988

Failure of W/Wv mouse-derived cultured mast cells to enter S phase upon contact with NIH/3T3 fibroblasts.

Although W/Wv mutant mice are profoundly deficient in tissue mast cells, these mice do have cells with similar features of mast cells that develop from their bone marrow cells as efficiently as those from congenic +/+ mice in pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM). With cultured mast cells (CMCs), we analyzed the mechanism of mast-cell deficiency in tissues of W/Wv mice. CMCs were established from bone marrow cells of W/Wv and congenic +/+ mice with PWM-SCM, and then co-cultured with various mouse fibroblast cell lines without PWM-SCM. All the examined mouse embryo-derived fibroblast cell lines maintained CMCs derived from +/+ mice, but not CMCs from W/Wv mice, for greater than 2 weeks. Mast cells in S phase were observed only in CMCs derived from +/+ mice under these conditions. The poor survival of W/Wv CMCs as compared with +/+ CMCs was not owing to a differential death rate but to the inability of W/Wv CMCs to continue active proliferation on fibroblasts without PWM-SCM. By synchronizing CMCs at the G1 phase of the cell cycle, the defect in W/Wv CMCs was further characterized as a failure to transit G1 and enter the S phase upon contact with fibroblasts. This finding indicates the indispensable function of the W gene product(s) for this response.

Animals↗
PubMed1988

Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells.

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of [35S] sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate [35S] proteoglycans. When "MMC-like" cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these "second generation PMC" formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.

Animals↗
PubMed1987

Stopped-flow investigation of the reaction between vitamin E radical and vitamin C in solution.

Kinetic study of the reaction between vitamin E radical and vitamin C has been performed. The rates of reaction of vitamin C (ascorbic acid 1, 6-0-stearyl ascorbic acid 2, and 2,6-O-dipalmitoyl ascorbic acid 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl) in benzene-ethanol (2:1, v/v) solution have been determined spectrophotometrically, using stopped-flow technique. The second-order rate constants obtained are 549 +/- 30 M-1s-1 for 1, 626 +/- 53 M-1s-1 for 2, and 4.84 +/- 1.41 M-1s-1 for 3 at 25.0 degrees C. The result shows that the ascorbic acid ester 2 having a long-alkyl-chain at 6-position is 1.14 times as reactive as the ascorbic acid 1, whereas the ascorbic acid ester 3 substituted at 2-position is only 0.01 times as reactive as the ascorbic acid 1.

Ascorbic Acid↗
PubMed1987

Phenotypic changes of bone marrow-derived mast cells after intraperitoneal transfer into W/Wv mice that are genetically deficient in mast cells.

The ability of mouse IL-3-dependent, bone marrow culture-derived mast cells (BMMC) to generate serosal mast cells (SMC) in vivo after adoptive transfer to mast cell-deficient mice has been defined by chemical and immunochemical criteria. BMMC differentiated and grown from WBB6F1-+/+ mouse progenitor cells in medium containing PWM/splenocyte-conditioned medium synthesized a approximately 350,000 Mr protease-resistant proteoglycan bearing approximately 55,000 Mr glycosaminoglycans, as defined by gel filtration of each. Approximately 85% of the glycosaminoglycans bound to the cell-associated BMMC proteoglycans were chondroitin sulfates based upon their susceptibility to chondroitinase ABC digestion; HPLC of the chondroitinase ABC-generated unsaturated disaccharides revealed these glycosaminoglycans to be chondroitin sulfate E. As determined by heparinase and nitrous acid degradations, approximately 10% of the glycosaminoglycans bound to BMMC proteoglycans were heparin. In contrast, mast cells recovered from the peritoneal cavity of congenitally mast cell-deficient WBB6F1-W/Wv mice 15 wk after intraperitoneal injection of BMMC synthesized approximately 650,000 Mr protease-resistant proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 105,000 Mr. Thus, after adoptive transfer, the SMC of the previously mast cell-deficient mice were like those recovered from the normal WBB6F1-+/+ mice that were shown to synthesize approximately 600,000 Mr proteoglycans that contained approximately 80% heparin glycosaminoglycans of approximately 115,000 Mr. As assessed by indirect immunofluorescence staining and flow cytometry using the B1.1 rat mAb (an antibody that recognizes an epitope located on the neutral glycosphingolipid globopentaosylceramide), approximately 5% of BMMC bound the antibody detectably, whereas approximately 72% of the SMC that were harvested from mast cell-deficient mice 15 wk after adoptive transfer of BMMC were B1.1-positive; approximately 82% of SMC from WBB6F1-+/+ mice bound the antibody. These biochemical and immunochemical data are consistent with the results of previous adoptive transfer studies that characterized mast cells primarily on the basis of morphologic and histochemical criteria. Thus, IL-3-dependent BMMC developed in vitro, cells that resemble mucosal mast cells, can give rise in vivo to SMC that express phenotypic characteristics of connective tissue mast cells.

Animals↗
PubMed1987

Effects of pertussis toxin on the alpha 2-adrenoceptor-inhibitory GTP-binding protein-adenylate cyclase system in rat brain: pharmacological and neurochemical studies.

Behavioral excitement and the increase in locomotion were observed in male adult rats four days after an intraventricular injection of 5 micrograms pertussis toxin (IAP). Clonidine (100 micrograms/kg s.c.)-induced locomotor hypoactivity was not observed in animals pretreated with 1 and 5 micrograms IAP. IAP caused a significant (P less than 0.05) decrease in the KD value of [3H]clonidine binding and enhanced GTP (1 microM)-induced decrease in the binding to cortical membranes from rat brain. In addition, the inhibition of adenylate cyclase induced by alpha 2-receptor stimulation (100 microM adrenaline plus 100 microM propranolol) was completely suppressed in the cerebral cortical membranes by IAP pretreatment. It is suggested that the system consisting of alpha 2-receptor, the inhibitory GTP-binding protein (Ni) and adenylate cyclase inhibits some animal behaviors and cyclic AMP formation. Moreover, IAP seems to inactivate Ni, subsequently producing behavioral excitement and it inhibits clonidine-induced sedation.

Adenylate Cyclase Toxin↗
PubMed1987

Changing processes from bone marrow-derived cultured mast cells to connective tissue-type mast cells in the peritoneal cavity of mast cell-deficient w/wv mice: association of proliferation arrest and differentiation.

Connective tissue-type mast cells (CTMC) and mast cells grown in vitro exhibit many differences in morphology, biochemistry, and function. When cultured mast cells of WBB6F1-+/+ mouse origin were injected into the peritoneal cavity of genetically mast cell-deficient WBB6F1-W/Wv mice, however, the cultured mast cells acquired characteristics similar to CTMC. In this study, we analyzed the changing process. When the density of the cultured mast cells was measured by Percoll density gradient centrifugation, the proportion of dense mast cells increased after injection into the peritoneal cavity. Because the increase in proportion of dense mast cells paralleled the increase in proportion of heparin-containing mast cells, both parameters may be used as an index for differentiation activity of cultured mast cells into CTMC. When proliferation activity of mast cells was estimated by the incorporation of bromodeoxyuridine, the proliferation activity decreased after the i.p. transfer. Moreover, when cultured mast cells were recovered 10 wk after the i.p. transfer, the mast cells almost lost proliferation activity in the same culture condition that had been used for establishment of cultured mast cells from the bone marrow of WBB6F1-+/+ mice. These results demonstrate that the proliferation arrest and the acquisition of CTMC-like characters are associated after i.p. transfer of cultured mast cells.

Animals↗
PubMed1987

Interleukin 4 as an essential factor for in vitro clonal growth of murine connective tissue-type mast cells.

We investigated the biological activity of IL-4 to murine connective tissue-type mast cells (CTMC). When purified peritoneal mast cells, typical CTMC, were incubated with pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM) in methylcellulose, about one-fifth of mast cells showed clonal growth. Recombinant IL-4 alone did not stimulate the clonal growth, and purified IL-3 alone induced development of a small number of tiny clusters. In contrast, addition of IL-4 to IL-3 increased the number of clusters by a factor of 10. The number and size of clusters induced by the combination of IL-3 and IL-4 were comparable to those of mast cell clusters induced by PWM-SCM. The present results indicate that IL-4 is an essential factor for in vitro clonal growth of CTMC.

Animals↗
PubMed1987

Growth-stimulating effect of pharmacological doses of estrogen on androgen-dependent Shionogi carcinoma 115 in vivo but not in cell culture.

Shionogi carcinoma 115 (SC115) had been accepted for 20 years as an androgen-dependent mouse mammary tumor, the growth of which is stimulated only by androgen. However, we very recently found that the growth of SC115 tumors in vivo is stimulated not only by physiological doses of androgen but also by pharmacological doses of estrogen through the estrogen receptor system. In the present study, the growth-stimulative effect of estrogen on an androgen-dependent cloned cell line (SC-3) derived from SC115 cells, which showed androgen- and estrogen-dependent growth in vivo, was examined in vitro. In serum-supplemented medium (Eagle's minimum essential medium containing 2% steroid-free fetal calf serum), testosterone or 5 alpha-dihydrotestosterone (10(-9)-10(-6) M) significantly stimulated the growth of SC-3 cells (3.2-fold increase in cell number at day 10 in culture containing 10(-8) M androgens) and changed the shape of SC-3 cells from epithelial to spindle (fibroblast-like), whereas 17 beta-estradiol (10(-12)-10(-6) M) even in high concentrations had no such effects on SC-3 cells. Contrary to the effect of 17 beta-estradiol in vivo, 17 beta-estradiol as well as cyproterone acetate (10(-8)-10(-6) M) inhibited the growth-stimulative effect of testosterone (10(-8) M) on SC-3 cells in a dose-dependent manner in the serum-supplemented medium. The anti-androgen and 17 beta-estradiol also showed comparable competitive effects on [3H]testosterone binding to androgen receptor in SC-3 cells. In serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.2% bovine serum albumin], testosterone [10(-8) M] also markedly stimulated the growth of spindle-shaped SC-3 cells, and epidermal growth factor (1 ng/ml) enhanced the growth-stimulative effect of testosterone, whereas 17 beta-estradiol (10(-8)-10(-6) M) in the absence or presence of epidermal growth factor had no growth-stimulative effect on SC-3 cells. We conclude that the growth of SC115 cells is stimulated by either physiological doses of androgen or pharmacological doses of estrogen in vivo but only by androgen in cell culture.

Androgens↗
PubMed1987

Retroviral expression of the human IL-2 gene in a murine T cell line results in cell growth autonomy and tumorigenicity.

In mature T lymphocytes (T cells) the regulated expression of the genes for interleukin-2 (IL-2) and its receptor (IL-2R) constitutes an essential part in controlling the cell growth. Evidence has been provided which suggests the involvement of an aberrant function of the IL-2 system in developing T cell neoplasms, particularly the adult T cell leukemia/lymphoma (ATL). As an approach to examine the extent of the IL-2 system contribution to T cell neoplasms, we created the experimental conditions wherein both IL-2 and IL-2R are expressed constitutively in a murine T cell line. We made use of a retroviral vector to infect an IL-2-dependent CTLL-2 line and lead to the expression of human IL-2. Here, we show that the virus-infected cells not only proliferate in vitro in the absence of exogenously supplied IL-2 under certain conditions, but also develop tumors (lymphomas) in nude and syngeneic mice.

Animals↗