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Biomedical subjects

A Urabe

Publications and source records attributed to A Urabe.

At least 145 records · Page 8Linked to original sources
PubMed1989

Effects of recombinant human erythropoietin on hematopoietic progenitors of chronic hemodialysis patients in vitro and in vivo.

Erythroid progenitors were assayed in 20 chronic hemodialysis patients before and after administration of recombinant human erythropoietin (rhEpo) using a methylcellulose culture method. Hemoglobin concentrations, hematocrit values and the proportion of marrow erythroblasts increased significantly during rhEpo treatment. The numbers of erythroid progenitors (CFU-e and BFU-e) in the patients' marrow also increased following rhEpo administration. Our data suggest that rhEpo is an effective drug for treating anemia caused by chronic renal failure and the administration of rhEpo results in an increase in the numbers of erythroid progenitors.

Adult↗
PubMed1989

Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor: a preliminary report.

PURPOSE: The expansion of an abnormal hemopoietic stem cell line is responsible for the myelodysplastic syndromes, which are characterized by pancytopenias, often resulting in lethal infections. Cloned granulocyte colony-stimulating factor (G-CSF) was recently shown to enhance the growth and differentiation of normal granulocyte progenitor cells in vitro. The aim of our study was to examine the effects of recombinant human G-CSF in patients with myelodysplastic syndromes. PATIENTS AND METHODS: Four patients with myelodysplastic syndromes and one patient with smoldering acute myelogenous leukemia following the occurrence of a myelodysplastic syndrome received recombinant human G-CSF by intravenous infusion for six days. Patients received different dosage levels (50 to 1,600 micrograms/m2). RESULTS: A response was seen in all patients, with an increase in both immature myeloid cells in the bone marrow and mature granulocytes in the peripheral blood. The dose levels that could stimulate granulocytopoiesis differed among patients. CONCLUSION: These results suggest that, at least in some cases of myelodysplastic syndromes, granulocytopenia can be improved by G-CSF, although it still remains to be determined whether the increase in the number of granulocytes is due to the differentiation and maturation of the myelodysplastic clone or restoration of a residual normal clone.

Adult↗
PubMed1989

Nature of so-called "metaplasia of the apocrine epithelium". Macrophages attack apocrine epithelium". Macrophages attack apocrine epithelium.

Immunohistochemical and electron-microscopic studies were performed on the lesion termed "metaplasia of the apocrine epithelium." which was seen in association with an apocrine adenocarcinoma. The cells of this so-called "metaplasia" lacked cytokeratin, which was present in the apocrine epithelium. Surprisingly, the lesion ultrastructurally consisted mainly of terminally differentiated macrophages, the cytoplasms of which were filled with numerous phagosomes and lipid droplets. The cells lacked a desmosomal connection at their borders and some had Langerhans granule-like structures in the cytoplasm. The luminal wall was often infiltrated with macrophages and lymphocytes, and, in some portions, was replaced by macrophages with a large cytoplasm filled with numerous phagosomes. The immunohistochemical and ultrastructural findings indicate that the lesion is not composed of cells of the apocrine epithelial origin, but of macrophages that have ingested apocrine epithelium.

Aged↗
PubMed1989

Cyclosporin A inhibits directly in vivo keratinocyte proliferation of living human skin.

A direct in vivo antiproliferative effect of cyclosporin A (CsA) on human epidermal keratinocytes (EK) grafted onto nude mice was evaluated. Using pulse-labeling of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analogue incorporated into the nuclei of DNA-synthesizing (S-phase) cells, the antiproliferative effect of CsA was revealed as a decrease in the number of BrdU-positive human EK grafted onto nude mice receiving a daily subcutaneous injection of 50 mg/kg of CsA. The blood level of CsA in the treated mice, evaluated by a radioimmunologic assay, was 679 +/- 501 ng/ml (n = 3). Using an antibody to leukocyte common antigen, it was shown that no human lymphocytes were present in the grafted skin. Therefore, this antiproliferative effect of CsA on human EK seems to be due to a direct effect on EK rather than to lymphocyte regulation.

Animals↗
PubMed1989

Malignant hidroacanthoma simplex.

A case of malignant hidroacanthoma simplex is described. Histological examination revealed that the malignant cells had arisen from a tumor cell nest of benign hidroacanthoma simplex and invaded the dermis. Two years and 7 months after the excision of the original thigh lesion, a groin lymph node metastasis was discovered. The metastatic tumor cells in the lymph node were histologically similar to the carcinoma cells in the original thigh lesion and had enzymatic and ultrastructural features resembling eccrine sweat duct.

Aged↗
PubMed1989

Binding properties and proliferative effects of human recombinant granulocyte-macrophage colony-stimulating factor in primary leukemia and lymphoma.

Binding of radiolabeled human granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied with blast cells from eight patients with acute myeloblastic leukemia (AML), and neoplastic lymphoid cells from one patient with acute lymphoblastic leukemia (ALL), two patients with chronic lymphocytic leukemia (CLL) and one patient with undiagnosed B cell neoplasia. In all AML cases studied, Scatchard graphs of the direct binding data were curvilinear, and were best fitted by curves derived from a two-binding-site model; one site with high affinity (Kd1 = 12-71 pM; 174-602 sites/cell) and the other with low affinity (Kd2 = 0.5-2.7 nM; 1137-6020 sites/cell). A cross-linking study on blast cells from one AML patient demonstrated specific bands which were similar to those reported for peripheral blood neutrophils. Furthermore, blast colony assays for the same preparations showed remarkable proliferative response to GM-CSF in the concentration range from 0.3 nM to 7.0 nM (ED50 greater than 0.7 nM). This concentration range is approximately one order of magnitude higher than that which is effective for colony formation from normal bone marrow progenitors (ED50 in equilibrium 0.1 nM). No significant correlation could be observed between the responsiveness of blast progenitors to GM-CSF, and the numbers or affinities of GM-CSF binding sites demonstrated on blast cells. In studies with neoplastic lymphoid cells from four patients, 125I-GM-CSF also specifically bound in two cases, while response to GM-CSF was not observed in these cases. These results indicate that the expression of GM-CSF receptor is not restricted to the GM-CSF-responsive AML blast cells, but can be observed in other AML blast cells and even in neoplastic lymphoid cells.

Binding Sites↗
PubMed1989

Treatment of pure red cell aplasia that is resistant to conventional immunosuppressive therapy with intermittent administration of methotrexate.

Two patients with pure red cell aplasia were treated with intermittent administration of methotrexate. One who was refractory to conventional immunosuppressive therapy showed a favorable response to methotrexate within 2 weeks of treatment and entered complete remission. The other also showed an increase in reticulocytes within 3 weeks of methotrexate treatment. Although continuous administration of methotrexate was abandoned in the second case because of its hepatotoxicity, our results suggest that methotrexate may be effective in patients with pure red cell aplasia refractory to conventional immunosuppressive therapy.

Drug Resistance↗
PubMed1989

Binding of iodinated erythropoietin to rat bone marrow cells under normal and anemic conditions.

Specific binding sites for erythropoietin (Epo) were shown in normal and anemic rat bone marrow cells using [125I]labeled human recombinant Epo. When rats were treated once or several times with phenylhydrazine or malotilate, or by phlebotomy, the serum Epo level determined by RIA began to increase rapidly. Thereafter, both the number of erythroid colony-forming unit (CFU-E)-derived colonies and the Epo binding capacity of bone marrow cells increased almost simultaneously in response to induced anemic states, suggesting that the amount of Epo binding in bone marrow cells may reflect in vivo erythropoiesis. Scatchard analysis of the binding data from normal rats revealed the presence of a single class of binding sites (Kd = 0.18 +/- 0.04 nM, 38 +/- 5 sites/cell). In anemic states, the apparent average receptor number per cell increased (52-62 sites/cell) without changing in binding affinity toward Epo. Furthermore, [125I]Epo was cross-linked to the cell surface molecule of approximately 165 kd in nonreducing conditions and 75 kd in reducing conditions. Autoradiographic analysis indicated that Epo receptors were distributed on immature erythroid cells. Proerythroblasts were the most heavily labeled, whereas orthochromatic erythroblasts and cells of myeloid and lymphoid lineages were not labeled. Calculations based on Scatchard and autoradiographic analysis showed that proerythroblasts have 390 receptor sites per cell, twice as many as basophilic or polychromatophilic erythroblasts have. These results are consistent with the stage-specific action of Epo in physiological differentiation of erythroid cells.

Anemia↗
PubMed1989

Identification and analysis of human erythropoietin receptors on a factor-dependent cell line, TF-1.

We have recently established a novel cell line, TF-1, from bone marrow cells of a patient with erythroleukemia, that showed an absolute growth dependency on each of three hematopoietic growth factors: erythropoietin (EPO) granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin 3 (IL-3). EPO stimulated the proliferation of TF-1 cells even at the physiologic concentration (0.03 U/mL). We performed binding experiments on TF-1 cells using radioiodinated EPO. The binding of radioiodinated EPO to TF-1 was specific, time- and temperature-dependent, and saturable. Scatchard analysis of the saturation binding data suggested the existence of a single class of binding sites (kd = 0.40 nmol/L; number of binding sites = 1,630 per cell). TF-1 cells were usually maintained in RPMI 1640 containing 10% fetal bovine serum and 5 ng/mL GM-CSF. The kd and the number of the EPO receptors were not changed by incubating the cells with IL-3, although culturing the cells in the presence of EPO resulted in down-modulation of EPO receptors. The chemical cross-linking study demonstrated that two molecules with apparent molecular weights of 105 kilodalton (Kd) and 90 Kd were the binding components of EPO. Present data suggest that human EPO receptors are very similar to the previously reported murine EPO receptors.

Cell Division↗
PubMed1989

Tunicamycin modulates binding of 125I-erythropoietin to Friend erythroleukemia cells.

The effects of tunicamycin and neuraminidase treatment on the specific binding of 125I-erythropoietin to a murine erythroleukemia cell clone, B8, were investigated. Neuraminidase treatment of B8 cells did not affect the specific binding of erythropoietin, but tunicamycin treatment caused a 2.5 to 4-fold increase in the amount of 125I-erythropoietin binding. Scatchard analysis of the binding data showed that the increase in the amount of binding resulted from increased affinity of the receptor. These results suggest that N-linked sugars of the erythropoietin receptor protein are involved in the interaction of erythropoietin with the cell-surface receptors on B8 cells.

Animals↗
PubMed1989

Cyclosporin A does not modify Langerhans' cell number and distribution in normal human skin.

We used the model of human skin graft on nude mouse to investigate a possible influence of systemically administered cyclosporin A (CsA) on epidermal Langerhans' cells (LC). This experimental model has the advantage of being independent of the systemic humoral and cellular influences of a human host. No change in the human LC distribution or number could be observed after 3 weeks of CsA therapy as revealed by anti-CD1 and anti-HLA-DR immunohistochemical stainings and the cell counting, despite the evidence of the drug effect on the keratinocyte proliferation. However, our findings do not rule out the possibility that CsA influences the LC functional capacities responsible for the local cell-mediated immunity responses.

Animals↗
PubMed1989

In vitro immunoglobulin production in mitogen-stimulated cultures of peripheral blood and bone marrow cells from young and old adults, and cases of benign monoclonal gammopathy.

Peripheral blood samples collected from normal individuals and patients with benign monoclonal gammopathy (BMG) were separated and assayed for their T-cell subpopulations, PHA blast formation as well as immunoglobulin (Ig) synthesis in vitro. Bone marrow cells of most the cases were also assayed for Ig synthesis. Age-related changes of T-cell subsets and PHA blast formation revealed a marked leveling off after the 8th decade. Comparing the age-related increase in Ig synthesis in peripheral blood lymphocytes, PWM-induced Ig synthesis of bone marrow cells was only slightly increased. The distribution of values for T-cell subsets, PHA blast formation and Ig synthesis in the BMG cases more closely resembled that in the aged than that in the age-matched controls. Immunoregulatory functions seem to be affected in BMG.

Adult↗
PubMed1989

Aplastic anemia. Immunosuppressive therapy in a multi center trial in Japan.

We evaluated the biologic characteristics and effectiveness of immunosuppressive agents in patients with a severe form of aplastic anemia in a multicenter study. Treatment with a bolus of methylprednisolone (mPSL) was associated with a good response and a partial response in 19.4% and 1.4% of the patients, respectively. In contrast, two kinds of antilymphocyte globulin (ALG) were effective for 9.4% and 15.6% of the severe form of aplastic anemia, and two kinds of antithymocytoglobulin (ATG) were effective in 30.8% and 37.2% of the patients, although the difference between ALG and ATG was not statistically significant. We recommend that patients diagnosed as having severe aplastic anemia should be referred as soon as possible for treatment with immunosuppressive agents or bone marrow transplantation, the latter depending on disease severity, age, and potential availability of an HLA-identical sibling donor.

Adolescent↗
PubMed1988

Induction of the receptor for erythropoietin in murine erythroleukemia cells after dimethyl sulfoxide treatment.

Biologically active 125I-labeled human recombinant erythropoietin (EPO) was used to demonstrate specific receptors for this erythroid-specific hemopoietic growth factor on the cell surface of murine erythroleukemia cell clone B8. The binding of radioiodinated EPO to these cells was time and temperature dependent, specific, saturable, and reversible. During erythroid differentiation by dimethyl sulfoxide, B8 cells displayed a rapid and marked increase in the amount of specific 125I-EPO binding before the appearance of hemoglobin-containing cells. Scatchard analysis of the saturation binding data revealed that B8 cells had a single class and low number (350 to 650) of EPO receptors per cell with an apparent Kd of 1.2 to 1.4 nM. In addition, the number of EPO receptors on B8 cells was increased twice by induction with DMSO for 1 day, but the binding affinity of EPO toward its receptors did not change significantly. Affinity cross-linking experiments with disuccinimidyl suberate demonstrated two radiolabeled components with apparent molecular weights of 145,000 and 130,000 under both reducing and nonreducing conditions. Labeling of the two components was inhibited by incubation of cells with unlabeled EPO. These results suggest that some murine erythroleukemia cells potentially express EPO receptors as a differentiation marker of erythroid lineage, which contain two polypeptides with molecular weights of 109,000 and 94,000.

Affinity Labels↗