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Biomedical subjects

A Urabe

Publications and source records attributed to A Urabe.

At least 163 records · Page 9Linked to original sources
PubMed1988

Expression of the functional erythropoietin receptors on interleukin 3-dependent murine cell lines.

Two distinct hemopoietic growth factors, interleukin 3 (IL-3) and erythropoietin (EPO), support the growth and development of erythroid cells in a sequential manner in vitro. Stimulation of multipotential stem cells by IL-3 appears to develop committed erythroid progenitor cells that respond to EPO. When several murine IL-3-dependent cell lines were assayed for their ability to respond to EPO, the growth and survival of the three cell lines showing the profiles of either myeloid or mast cell lineage (IC-2, DA-1, FDC-P2) were stimulated by EPO in a dose-dependent fashion. To determine whether the biologic effects were mediated through the specific receptors for EPO, we performed binding experiments on these cells with radioiodinated EPO. All of these cells displayed significant levels of specific binding for EPO. Among a family of hemopoietic growth factors, only unlabeled EPO was able to compete for the binding of radioiodinated EPO to the cells. Analysis of the binding data revealed the existence of a single case of binding sites in extremely low abundance. IC-2 cells were used to study the effects of IL-3 on the regulation of expression of EPO receptors. It was demonstrated that a decrease in IL-3 concentration in the culture medium increased the responsiveness to EPO and the amount in specific binding of EPO as well. These results suggest that some IL-3-dependent cell lines have functional EPO receptors and their expression may be modulated by IL-3.

Animals↗
PubMed1988

Effect of recombinant human erythropoietin on the anemia of chronic renal failure.

Phase I and Phase II studies of recombinant human erythropoietin (rhEpo) were conducted in normal volunteers and in anemic patients with chronic renal failure on maintenance hemodialysis. Three hundred U/person of rhEpo was administered intravenously to healthy normal volunteers in the Phase I study, resulting in no subjective or objective changes. In the Phase II study, 66 patients with chronic renal failure on maintenance hemodialysis with less than 20% hematocrit values were treated with rhEpo in doses of 50 U/kg to 200 U/kg two or three times a week. Hematocrit values increased significantly during the 12 weeks, and the patients' conditions improved. Patients previously requiring blood transfusions became transfusion-independent during our study. There were no obvious side effects, thus indicating the safety and efficacy of rhEpo in the anemia of chronic renal failure.

Adult↗
PubMed1988

Serum erythropoietin titers in the aged.

Erythropoietin (Epo) titers in the aged (from 70 to 89 years) were determined by a radioimmunoassay. Epo levels in normal elderly subjects were not different from levels in the young volunteers. The serum Epo levels in elderly patients with anemia were inversely related to hemoglobin levels; their regression coefficient was not worse than that found in young patients. It is suggested that the reactivity of Epo production to anemia in the aged may not be worse than that reactivity in the young.

Aged↗
PubMed1988

Effects of type beta transforming growth factors on haematopoietic progenitor cells.

The effects of type beta transforming growth factors (TGF-beta s) on normal human and murine haematopoietic progenitor cells were examined using bone marrow colony assays. In erythroid colony assays, TGF-beta 1 inhibited human CFU-E derived colony formation, BFU-E derived burst formation, and murine BFU-E derived burst formation in a dose dependent manner between 0.1 and 5.0 ng/ml. However, murine CFU-E derived colony formation was unaffected even at a concentration of 5.0 ng/ml TGF-beta 1. In myeloid colony assays, different sensitivity of progenitor cells to the inhibitory effects of TGF-beta s was observed between both species. TGF-beta 1 inhibited murine granulocyte-macrophage colony (GM-colony) formation and granulocyte colony (G-colony) formation in a dose dependent manner between 0.1 and 5.0 ng/ml, but had no remarkable effects on human GM-colony and G-colony formation. TGF-beta 2 also had similar inhibitory effects on haematopoietic progenitor cells, while its inhibitory effect was less potent than that of TGF-beta 1. Thus our data suggest that TGF-beta may be involved in negative regulation of haematopoiesis and that its inhibitory action may be restricted in lineage and/or species specific manner.

Animals↗
PubMed1988

Synergistic effect of dolichyl phosphate and human recombinant granulocyte colony-stimulating factor on recovery from neutropenia in mice treated with anti-cancer drugs.

Severe hematopoietic injury in mice was induced by using either 5-fluorouracil, adriamycin, mitomycin C, or vinblastine. Daily subcutaneous administration of purified human recombinant granulocyte colony-stimulating factor (rG-CSF; 0.3-10.0 micrograms/day) markedly accelerated recovery from the drug-induced granulocytopenia in a dose-dependent manner, as reported previously. On the other hand, daily intraperitoneal administration of dolichyl phosphate (Dol-P) also enhanced granulopoiesis to accelerate recovery from granulocytopenia, although the effect of Dol-P was relatively moderate as compared with that of rG-CSF. A synergistic recovery of granulopoiesis was observed when Dol-P was administered together with rG-CSF to the mice treated with anti-cancer drugs. Joint use of Dol-P (1 mg/day) and rG-CSF (0.3 micrograms/day) was as effective as a higher dose of rG-CSF (3 micrograms/day). Joint use of Dol-P (1 mg/day) and rG-CSF (3 micrograms/day) was sometimes more effective.

Agranulocytosis↗
PubMed1988

[Diagnosis of leukemia and lymphoma].

Leukemia and lymphomas were traditionally diagnosed by cytology and histology, but recently analyses of cell surface markers, gene rearrangement and so on have been used to make accurate the diagnosis. The differential diagnosis and some aspects of early diagnosis of hematological malignancies were interpreted in this paper.

Acute Disease↗
PubMed1988

Clinical effect of recombinant human erythropoietin on anemia associated with chronic renal failure. A multi-institutional study in Japan.

Clinical effect and safety of recombinant human erythropoietin (r-HuEPO) were evaluated in 66 hemodialysis patients with intractable anemia. Initially, 50U/kg dry weight (DW) of r-HuEPO was administered intravenously at the end of every hemodialysis procedure for 4 weeks, then the dosage was increased to 100 and 200U/kg DW for poor responders. The patients' hematocrits rose from 19.8 +/- 2.3% (pretreatment) to 30.2 +/- 4.9% after 12 weeks. From 206 U of blood transfusion requirement in the 3-month period before the study, only 34 U were needed after treatment. Serum iron and ferritin levels fell significantly during the study, and iron storage was considered to be one of the decisive factors in the response to r-HuEPO. Blood pressure rose in the course of r-HuEPO administration, but uncontrollable hypertension was rarely observed. There was no significant adverse effect of r-HuEPO except for this mild hypertension. These results indicate that r-HuEPO is an excellent therapeutic aid for the anemia associated with chronic renal failure.

Adult↗
PubMed1988

[Gamma interferon therapy of cancer patients].

A phase I and a phase II study of recombinant gamma-interferon (S 6810) were conducted on a cooperative basis involving 11 and 57 institutions, respectively. In the phase I study, a total of 40 courses were administered to 31 patients. High fever exceeding 38 degrees C with chills was observed in approximately 80%. Other toxicities were fatigue (50%), gastrointestinal symptoms (30-40%), changes in hepatic enzymes, and hematological toxicities (20-30%). Dose-limiting factors were judged to be hypotension, leucopenia and CNS toxicity. Since the optimal dose for the phase II study was considered to be 5 X 10(6) U/m2 by daily chronic schedule, a further study was conducted using this dose. Response rates were as follows: 14.3% (renal cell cancer), 11.8% (multiple myeloma) 40.0% (chronic lymphocytic leukemia), 16.7% (non-Hodgkin lymphoma), and 67% (mycosis fungoides). Complete response was obtained in one case each of renal cell cancer, malignant lymphoma and mycosis fungoides. Moreover, intermittent high-dose gamma-interferon against renal cell cancer induced a response rate of 21.4%, significantly higher than the 8.6% obtained by continuous administration. Local injection against cutaneous malignancies resulted in a 55.3% response rate. Anti-viral effect against herpes zoster infection was also preliminarily evaluated. Among 4 cases, 3 responded subjectively well to local injection of gamma-interferon, which is a hopeful result, although a randomized trial is still needed.

Carcinoma, Renal Cell↗