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T Motoji

Publications and source records attributed to T Motoji.

At least 73 records · Page 4Linked to original sources
PubMed1989

Expression and characterization of erythropoietin receptors on normal human bone marrow cells.

We studied the specific binding of 125I-labeled bioactive recombinant human erythropoietin (Epo) to human bone marrow mononuclear cells (BMNC) obtained from normal subjects. The 125I-labeled Epo bound specifically to the BMNC. Scatchard analysis of the data showed two classes of binding sites; one high affinity (Kd 0.07 nM) and the other low affinity (Kd 0.38 nM). The number of Epo binding sites per BMNC was 46 +/- 16 high-affinity receptors and 91 +/- 51 low-affinity receptors. The specific binding was displaced by unlabeled Epo, but not by other growth factors. Receptor internalization was observed significantly at 37 degrees C, but was prevented by the presence of 0.2% sodium azide. These findings indicate that human BMNC possess two classes of specific Epo receptors with characteristics of a hormone-receptor association.

Binding, Competitive↗
PubMed1989

Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures.

The effects of recombinant hemopoietic factors on the clonal growth of human megakaryocyte progenitors were explored using serum-free cultures of nonadherent and T-cell-depleted marrow cells. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner, the activity being lower than that of recombinant interleukin 3 (rIL-3). Recombinant IL-3 and rGM-CSF acted synergistically on megakaryocyte colony formation when rGM-CSF was added to cultures containing suboptimal concentrations of rIL-3. However, the number and size of colonies did not increase with rGM-CSF when cultures were plated with an optimal dose of rIL-3. Recombinant erythropoietin (rEpo) by itself did not stimulate the growth of megakaryocyte progenitors. Recombinant Epo did, however, produce a significant increase in the number and size of megakaryocyte colonies in the presence of rIL-3 or rGM-CSF. Other factors, including recombinant granulocyte colony-stimulating factor, recombinant interleukin 1 alpha, recombinant interleukin 4, and recombinant interleukin 6 showed no capacity to generate or enhance megakaryocyte colony formation when added to cultures alone or in combination with varying concentrations of rIL-3. These results show that rIL-3, rGM-CSF, and rEpo affect human megakaryocytopoiesis by themselves or by interacting with each other.

Blood Physiological Phenomena↗
PubMed1989

Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia.

The colony-promoting activities of recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) and recombinant granulocyte colony-stimulating factor (rG-CSF) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units [L-CFU]) from 21 patients with acute myeloblastic leukemia (AML) were examined using blast colony assay and compared to colony promotion stimulated by phytohemagglutinin-stimulated leukocyte-conditioned medium (PHA-LCM). Recombinant GM-CSF stimulated blast colonies in 13 out of 20 cases examined (1 case not done). The magnitude of stimulation by rGM-CSF varied significantly according to the type of AML, but in general was lower than that of PHA-LCM. Blast cells of type M1 did not form any colonies with rGM-CSF, although numerous colonies were produced with PHA-LCM. Type M4 blasts formed fairly large numbers of colonies, though slightly less than those stimulated by PHA-LCM. Blasts of type M2 and M5 formed colonies with the stimulation of rGM-CSF, but the numbers were considerably smaller than type M4 and those stimulated with PHA-LCM. Recombinant G-CSF stimulated blast colonies in only 5 out of 21 cases, 3 of them being type M2. The number of cases responding to rG-CSF was significantly smaller than that responding to rGM-CSF, and even in cases in which colonies were formed, the magnitude of stimulation was minimal. From these results it seems likely that blast cells of different types of AML require a different kind of CSF for their optimal growth; type M4 blasts responded to the stimulation of rGM-CSF well, but blasts of other types of AML responded poorly. Thus, except for type M4, CSF(s) other than rGM-CSF seems to be required for the sufficient growth of L-CFU. Recombinant G-CSF is not likely to play an essential role in the proliferation of leukemic blasts of most types. Previous exposure to rGM-CSF and rG-CSF did not alter the self-renewal capacity, cellular phenotype, and morphology of colony cells, indicating that the direction and degree of differentiation of L-CFU stimulated by rGM-CSF or rG-CSF were not different from those stimulated with PHA-LCM.

Colony-Stimulating Factors↗
PubMed1988

Clonal growth of human megakaryocyte progenitors in serum-free cultures: effect of recombinant human interleukin 3.

Human megakaryocyte colony formation was observed in serum-free agar cultures with a medium containing deionized bovine serum albumin, iron-saturated transferrin, 2-mercaptoethanol, and recombinant human interleukin 3 (IL-3). Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti-alkaline phosphatase technique, using monoclonal antibody against platelet glycoprotein IIb/IIIa. Colony numbers reached a peak at day 14, with a mean of 47 megakaryocyte colonies (range 23-104) per 2 x 10(5) bone marrow mononuclear cells. Recombinant human IL-3 stimulated the growth of megakaryocyte progenitors. Similar results were obtained using nonadherent, T-cell-depleted mononuclear cells. These findings suggest that IL-3 stimulates the growth of megakaryocyte progenitors directly without activation of accessory cells, or the requirement of factors present in the serum or plasma. This serum-free culture system may be useful for studying the effects of purified natural and recombinant biological regulators on human megakaryocyte progenitors.

Colony-Forming Units Assay↗
PubMed1987

Effect of recombinant interferons on colony formation of blast progenitors in acute myeloblastic leukemia.

The effect of recombinant interferons (rIFNs) on primary and secondary colony formation by blast progenitors (leukemic colony-forming units, L-CFU) from the peripheral blood of patients with acute myeloblastic leukemia (AML) was examined. rIFN-alpha, rIFN-beta, and rIFN-gamma inhibited L-CFU in a dose-dependent manner. When 3000 U/ml rIFN-alpha, -beta, and -gamma were added, L-CFU were suppressed to 20%, 12%, and 40% of the control cultures, respectively. The concentrations of rIFN-alpha, -beta, and -gamma required for 50% inhibition of colony formation were 63, 29, and 250 U/ml, respectively. The self-renewal capacity of L-CFU was inhibited by rIFNs in a dose-dependent manner, the degree of inhibition being the same for all three rIFNs. These rIFNs also inhibited normal granulocyte-macrophage progenitors to a similar degree as L-CFU. Taken together, these in vitro studies indicate that these rIFNs may be efficacious in the treatment of AML, though development of granulocytopenia may be observed as a complication of IFN therapy.

Antibodies, Monoclonal↗
PubMed1986

Cell surface markers of acute non-lymphocytic leukemias: leukemia type and its expression of C3 and Fc receptors.

Seventeen untreated human acute non-lymphocytic leukemias (ANLL) were classified into four groups according to the presence or the absence of complement receptor and Fc receptor for IgG and IgM: Group I having neither C3 nor Fc receptors, Group II having either C3 or Fc receptor and Group III having both C3 and Fc receptors. ANLL of Group II was further subdivided into two groups: Group IIa having only Fc receptor and Group IIb having only C3 receptor. The morphologic and cytochemical analysis of ANLL in these groups revealed that the most immature type with regard to their myeloid-monocyte lineage was Group IIb followed by Groups I, IIa and III. Two cases of Group IIb were regarded as M1 type by French-American-British (FAB) group classification and one of them had a Ph1-chromosome. The survival rate of patients in each group was investigated and Group IIb patients showed the tendency for the longest period of survival.

Acute Disease↗
PubMed1985

The effect of 5-azacytidine and its analogues on blast cell renewal in acute myeloblastic leukemia.

Blast cells from patients with acute myeloblastic leukemia were exposed to 5-azacytidine (5-aza) and its analogues 5-aza 2'-deoxycytidine (5-aza-dr) and 6-azacytidine (6-aza). Simple negative exponential survival curves were obtained for the three drugs, but the sensitivity varied; 5-aza-dr was most toxic, 6-aza was least toxic, and 5-aza was intermediate. Colonies surviving drug exposure were replated; 5-aza and 5-aza-dr were found to increase secondary plating efficiency, whereas 6-aza was inactive. The findings provide indirect evidence for a role for DNA methylation in the regulation of blast cell self-renewal.

Azacitidine↗
PubMed1985

Neoplastic angioendotheliosis with B lymphocyte markers on neoplastic cells: a case report.

Neoplastic angioendotheliosis (NAE) is a rare disease characterized by the occlusion of small vessels by apparently neoplastic medium-sized cells. The origin of these cells remains undetermined, mainly because the diagnosis in most of these cases has been made on autopsy. This report describes a case of NAE from whom a biopsy specimen was obtained and studied immunohistologically. The cells occluding small vessels of this patient bear B cell markers such as monoclonal immunoglobulin (mu, lambda), Leu14, B1, OKB2, and Dako-PanB, whereas they do not react with antibodies against delta- and kappa-chain of immunoglobulin (Ig), or antibodies against markers of T cells, myelomonocytic cells and endothelial cells. These results show clearly that the cells occluding the small vessels of this patient are neoplastic and of B cell lineage. This is the first case of NAE in whom the neoplastic cells in the blood vessels have been proved to be of lymphocytic lineage.

Antibodies, Monoclonal↗
PubMed1984

Hemopoietic stem cells: their roles in human leukemia and certain continuous cell lines.

Hemopoietic stem cells may give rise to progeny like themselves or undergo determination; this event is followed by a series of maturation divisions ending in proliferatively inert but functional cells. In normal hemopoiesis and acute leukemia stem cell renewal is not exact; proliferative capacity is lost gradually. As a consequence, clonal populations cannot be continued indefinitely. Postdeterministic differentiation normally leads to cellular diversity; following transformation this diversity is increased, with the production of blast cells together with one or more myelopoietic lineage. The blasts are heterogeneous both in their proliferative capacity and their phenotypes, as determined using immunologically defined markers. Both self-renewal and determination are considered to be irreversible in vivo. By contrast, in continuous myelopoietic cell lines self-renewal is sufficiently precise to confer immortality on the populations. Furthermore, both determination and renewal may in some instances be reversible. The differences between normal or leukemic hemopoiesis in vivo and continuous lines in culture limits the value of the latter for studies of normal blood formation or the clonal hemopathies.

Azacitidine↗
PubMed1983

Lysis of leukemia and lymphoma cells by autologous and allogeneic interferon-activated blood mononuclear cells.

Studies were undertaken to determine whether leukemia and lymphoma cells would be lysed by autologous and allogeneic interferon (IFN) activated peripheral blood mononuclear cells (PBMC). PBMC from healthy donors and from patients were cultured with and without 500 U of highly purified human fibroblast IFN/ml for 24 hr, and then their cytotoxic activity was assayed by a 5-hr 51Cr-release test. Of primary tumor cells isolated from patients, the cells of 5 of 15 patients with acute nonlymphocytic leukemia (ANLL), 5 of 9 patients with acute lymphocytic leukemia (ALL), 2 of 3 patients with chronic phase chronic myelogenous leukemia (CML), 2 of 3 patients with blastic phase CML, 1 patient with hairy cell leukemia, and 6 patients with diffuse non-Hodgkin's lymphoma were sensitive to IFN-activated PBMC of healthy donors, whereas the cells of 3 of the ANLL patients, 2 of the ALL patients, and 3 of the lymphoma patients were sensitive to unstimulated PBMC. Of the ANLL cells tested, myeloblasts, promyelocytes, and monoblasts were sensitive to either unstimulated or IFN-activated PBMC. Compared with the ANLL cells, the lymphoma cells were statistically significantly sensitive to activated effector cells (p less than 0.025). On the basis of the unlabeled target competition test and the recovery of cytotoxic cells within the fractions enriched in natural killer (NK) cells, NK cells appeared to mediate the above unstimulated and IFN-boosted cytotoxicity. In experiments using autologous effector-target cells from 11 patients, the addition of 500 U of IFN/ml enhanced the lytic activity of PBMC against autologous lymphoma cells in 1 patient, and higher concentrations of IFN, i.e., 2500 or 3500 U/ml, enhanced their cytotoxic activity against autologous leukemia or lymphoma cells in 4 of 8 patients. These data indicate that IFN-activated allogeneic PBMC are able to lyse both myeloid and lymphoid tumor cells, whereas higher concentrations of IFN are required to enhance lytic activity against autologous tumor cells.

Cytotoxicity, Immunologic↗
PubMed1982

Proliferative state and radiosensitivity of human myeloma stem cells.

Human myeloma stem cells were detected by their capacity to form colonies in culture. Cells separated from aspirated marrow were cultured for 10 days in semi-solid methylcellulose with medium conditioned by T lymphocytes stimulated by phytohaemagglutinin (PHA-TCM). The colonies formed consisted mostly of lymphoplasmacytoid cells or plasma cells, and the immunoglobulins in the patients' myeloma cells were demonstrated also in the cytoplasm of the colony cells. The number of colonies were proportional to the number of cells plated and to the concentration of PHA-TCM. When the proportion of proliferating colony-forming units of multiple myeloma (CFU-MM) was studied using the (3H)-dT-suicide technique, the high-specific-activity (3H)-dT killed 21-45% of the CFU-MM in 7 myeloma patients. According to a single dose of Co-y-irradiation, the mean doses for impairment of regeneration (Do) were 1.00 and 1.63 Gy in 2 cases, the extrapolation numbers being 1.6 and 2.0.

Aged↗