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Biomedical subjects

A Urabe

Publications and source records attributed to A Urabe.

248 records · Page 14Linked to original sources
PubMed1979

The influence of steroid hormone metabolites on the in vitro development of erythroid colonies derived from human bone marrow.

Certain C19 and C21 steroid metabolites, when incubated with normal human bone marrow cells in culture, increased the number of erythroid colonies in the presence of erythropoietin. Among a number of pairs of C5 epimeric steroids tested, most 5beta (A:B cis) steroids stimulated the growth of both early erythroid progenitor cells (BFU-E) and late erythroid progenitor cells (CFU-E), whereas only a few 5alpha-(A:B trans) steroids stimulated the growth of CFU-E. No 5alpha-compounds of six pairs of steroids studied were found to stimulate BFU-E formation. This structure-activity relationship conforms with that previously observed in studies of steroid induction of ALA-synthase in avian embryo liver cells and hemoglobin synthesis in the cultured avian blastoderm. When human bone marrow cells were preincubated with the steroids for 2 d, followed by incubation with erythropoietin, only the 5 beta-compounds stimulated the growth of BFU-E. Similarly, when addition of steroids was delayed in relation to erythropoietin in the culture, only the 5 beta-derivative of a pair of C5 epimeric compounds displayed an enhancing effect on the growth of BFU-E. This effect required that the steroid addition be made no later than 48 h after initiation of the culture. These data demonstrate that certain natural steroid metabolites significantly stimulate erythropoiesis in normal human bone marrow cells in culture. They also indicate that 5 beta-compounds are more stimulatory than their 5 alpha-epimers, and they suggest that these 5 beta-steroids act preferentially on very primitive erythroid progenitor cells, probably on BFU-E.

Androstanes↗
PubMed1979

Uroporphyrinogen I synthase induction in normal human bone marrow cultures: an early and quantitative response of erythroid differentiation.

Uroporphyrinogen I (URO) synthase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] activity increased when cultures of normal human bone marrow cells were incubated with erythropoietin. The increase of URO synthase activity was a linear function of erythropoietin concentration in the culture medium and was proportional to the extent of heme synthesis as determined by 55Fe incorporation into heme. The onset of the increase in URO synthase activity, which occurred on day 4 of incubation with erythropoietin, preceded by 3 days the appearance of hemoglobin in colonies derived from erythroid progenitor cells. These results indicate that induction of URO synthase in normal human bone marrow cells incubated with erythropoietin is an early event and that URO synthase activity is a useful quantitative index of erythroid differentiation.

Adult↗
PubMed1979

Erythroid progenitors (BFU-e and CFU-e) in acute leukaemia.

Bone marrow erythroid progenitor cells were examined from 50 cases of acute leukaemia and from 20 normal subjects using an in vitro semisolid culture method. Numbers of both primitive erythroid progenitor cells (BFU-e) and later-stage erythroid progenitor cells (CFU-e) were remarkably depressed in patient with acute leukaemia in active phase. However, both BFU-e and CFU-e recovered to within normal range when the patients achieved remission. Peripheral blood BFU-e of children with acute lymphocytic leukaemia in remission were also examined and found to have values not significantly different from those of control subjects. There was no distinct correlation between the numbers of erythroid bursts or colonies and the duration of remission in patients with acute leukaemia in remission. The reduction of BFU-e and CFU-e in active acute leukaemia suggests the involvement of erythropoietic progenitors in the pathophysiology of this type of leukaemia.

Acute Disease↗
PubMed1977

Demonstration of granulopoietic factor(s) in the plasma of nude mice transplanted with a human lung cancer and in the tumor tissue.

A human lung cancer (OTUK-tumor) was transplanted serially to nude mice, which invariably developed a marked neutrophilia. In order to analyze this phenomenon, in vitro agar culture studies were carried out. A three- to fourfold increase of colony-forming units in culture was observed in the femurs of these nude mice. Moreover, the plasma of nude mice bearing this tumor, as well as the tumor extract, had a significantly higher colony-stimulating activity on mouse bone marrow cells than appropriate controls. This activity had the property to stimulate granulocyte and/or mixed cell type colonies rather than mononuclear cells. This activity was also demonstrated, in a dose-dependent way, on normal human bone marrow cells. These findings indicated that the OTUK-tumor produced human granulopoietic colony-stimulating activity, which may have stimulated granulopoiesis in vivo as well.

Animals↗
PubMed1976

Response of uraemic bone marrow cells to erythropoietin in vitro.

In vitro culture technique of bone marrow cells has been applied to study the cause of anemia in uraemic patients on maintenance haemodialysis. Incorporation of 59Fe into haem in bone marrow cells of the patients in the presence of erythropoietin, as well as the inhibitory effect of their plasma on the response of normal bone marrow cells to erythropoietin, was examined. Increase in haem synthesis rate by erythropoietin in the bone marrow cells of uraemic patients (n 14; 7.9 +/- 1.4) wasnot significantly different from that in normal bone marrow cells (n 9; 5.9 +/- 1.4,p greater than 0.05), thus indicating the presence of erythroid precursor cells with normal responsiveness to erythropoetin in uraemic patients. All the plasma from uraemic patients inhibited, in dose-dependent way, the response of normal bone marrow cells to erythropoietin. Levels of erythropoietin in the plasma samples of uraemic patients were much lower than those of the patients with iron deficiency anaemia with comparable Hb concentrations. On the basis of these results, the humoral inhibitory factor appears to play a significant role in the pathogenesis of renal anaemia, in addition to the low level of circulating erythropoietin.

Adolescent↗
PubMedDate not supplied

Interferons for the treatment of hematological malignancies.

Interferon (IFN) has diverse activities against the proliferation and function of various tumor cells. Recently, IFN-alpha has been widely used in the treatment of several hematological malignancies including chronic myelogenous leukemia (CML), multiple myeloma, and hairy cell leukemia. IFN-alpha is becoming a first-choice drug in the treatment of CML, because it has been reported to suppress or abolish the Ph1 chromosome in CML patients. IFN-alpha is used in combination with conventional chemotherapeutic regimens in the treatment of multiple myeloma. There are many ongoing trials that include IFN-alpha in their regimens to determine whether or not the prognosis of multiple myeloma can be improved. Although the precise mechanism of the action of IFN has not been fully explained, the clinical applications of IFN for various hematological malignancies are expanding.

Female↗
PubMedDate not supplied

Imipenem-cilastatin monotherapy in severe infections accompanying hematological malignancies.

Imipenem-cilastatin (imipenem 1 to 4 g/day) was administered to patients with severe infections accompanying granulocytopenia in hematological malignancies. Monotherapy with imipenem-cilastatin was effective in 62.1% of the patients, and also effective even they were severely neutropenic. When imipenem-cilastatin was administered as the first-choice therapy, the efficacy was much better, at 73.3%. Both Gram-positive and Gram-negative infections were curable by the monotherapy with imipenem-cilastatin.

Agranulocytosis↗
PubMedDate not supplied

Cyclosporin A inhibits DNA synthesis by epidermal Langerhans cells.

Cyclosporin A, a potent immunosuppressive drug currently used in organ transplant recipients, has been shown to exert in vitro a direct antiproliferative effect on a number of cell types present in the skin, including keratinocytes, fibroblasts, and endothelial cells. Although in vitro studies suggest that cyclosporin A may interfere with the functional capacities of epidermal Langerhans cells, there is no evidence that the treatment influences the distribution or number of Langerhans cells in vivo. We used a model of normal human skin graft to "nude" mice, which is free of the human systemic control mechanisms, for studies on the DNA synthesis of human Langerhans cells under the influence of cyclosporin A. The grafted animals were given daily subcutaneous (50 mg/kg) or intraperitoneal (5, 12.5, and 25 mg/kg) drug injections during three weeks, which resulted in mean blood levels comparable to those observed in treated patients with organ transplants or psoriasis, respectively. BrdU administered during the last week of the experiment was incorporated by all cells synthesizing DNA, including those passing through S-phase. Langerhans cells were detected on deparaffinized or frozen tissue sections of xenografts with anti-CD1a and anti-HLA DR monoclonal antibodies, and the number of BrdU-positive cells was determined by double labeling. Our results indicate that the Langerhans cell DNA synthesis is impaired by therapeutic levels of cyclosporin A.

Adult↗