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Biomedical subjects

A Kuramoto

Publications and source records attributed to A Kuramoto.

At least 127 records · Page 7Linked to original sources
PubMed1990

Reduced DNA topoisomerase II in VP-16 resistant mouse breast cancer cell line.

VP-16 resistant cells, FvprB350 (50B-3), were isolated from mouse breast cancer cell line FM3A. 50B-3 cells showed 84-fold higher resistance than their parent cells. Reduced drug uptake was not found in resistant cells. Quantitative analysis of drug-stimulated DNA cleavage activity using 3'32P end-labeled pBR322 restriction fragments showed that VP-16 stimulated DNA-topoisomerase II cleavable complex forming activity in crude nuclear extract from 50B-3 cells was approximately one-fifth as compared with that of FM3A wild-type cells. Dot-blot analysis of RNA extracted from the two cell lines showed that mRNA levels of topoisomerase II in 50B-3 cells drastically decreased and catalytic activity was also 1/2-1/3 as compared with that of parent cells. 50B-3 cells showed cross resistance to VM-26, m-AMSA, adriamycin. These findings suggest that reduced topoisomerase II activity (cellular levels) and cleavable complex forming activity may be significant factors in the marked drug resistance.

Animals↗
PubMed1990

Fibroblast colony-forming cells with high sensitivity to serum mitogen(s) exist in bone marrow of patients with chronic myelocytic leukemia.

Marrow fibroblast colony formation was studied in patients with myeloproliferative disorders, using human serum or platelet-derived growth factor plus plasma-derived serum as growth-stimulating factors. Colony numbers negatively correlated with the patient's age, but were not different from those of controls. However, both maximum and average cell numbers per colony were significantly increased in patients with chronic myelocytic leukemia (CML) as compared to controls. These results suggest that fibroblast colony-forming cells with high sensitivity to human serum mitogen(s) exist in a CML bone marrow. These may possibly be involved in one of the mechanism concerned with promoting fibrosis in this disease.

Adult↗
PubMed1990

An early phase II study of CPT-11: a new derivative of camptothecin, for the treatment of leukemia and lymphoma.

An early phase II study of a new camptothecin analog and an inhibitor of topoisomerase I, CPT-11, was conducted in 62 patients with refractory leukemia and lymphoma by four different treatment schedules in a multiinstitutional cooperative study. CPT-11 therapy resulted in four complete remissions (CRs) and three partial remissions (PRs) in 29 assessable non-Hodgkin's lymphoma (NHL) patients, one PR in three Hodgkin's disease (HD), one CR and one PR in 11 acute lymphoblastic leukemia (ALL), and one PR in 15 acute myelogenous leukemia (AML) patients. Single infusion of 200 mg/m2 every 3 to 4 weeks produced no response in both leukemia and lymphoma patients. Sixty-minute infusions of 40 mg/m2/d for 5 days every 3 to 4 weeks or for 3 days weekly produced four CRs (17%) and four PRs (17%) in 24 patients with malignant lymphoma. Sixty-minute infusions of 20 mg/m2 twice a day for 7 days every 3 to 4 weeks resulted in one CR and two PRs in 12 patients with acute leukemia. No response was seen in an acute leukemia patient by another treatment schedule. CPT-11 was effective in two (15%) of 13 primarily refractory leukemia and lymphoma cases, in two of four relapsed cases, and in seven (17%) of 41 relapsed and refractory cases. Major side effects were leukopenia (91%) and gastrointestinal (GI) (76%). CPT-11 was shown to be effective against refractory leukemia and lymphoma, and thus deserves further clinical study; the novel antitumor activity mode of this drug predicts no cross-resistance to presently available antitumor drugs.

Adolescent↗
PubMed1990

Different expression of CD36 antigen molecule on the surface of megakaryocyte lineage leukemias and megakaryocyte leukemia cell lines MEG-01 and HEL.

Peripheral blood leukemic cells from four patients with peroxidase negative acute leukemia, which expressed neither myeloid nor lymphoid cell surface antigens, were analyzed by using monoclonal antibodies (MoAb) capable of recognizing megakaryocyte-platelet-related antigens. Leukemic cells from one case reacted with 5F1 MoAb, whereas cells from all the tested cases reacted with OKM5 MoAb, which belongs to the same CD group as 5F1 (CD36). Also, culture cells from megakaryoblastic leukemia cell line, MEG-01, and human erythroleukemia cell line, HEL, showed a different pattern of expression for the CD36 antigen molecule detected by 5F1 and OKM5 MoAb, individually. Furthermore, we have demonstrated that the epitopes recognized by 5F1 and OKM5 MoAb appear on the same CD36 molecule on the surface of HEL cells by means of the two-color analysis using FACS-IV. On the basis of our experiments, we conclude that, CD36 molecule, a receptor for TSP, is synthesized and expressed in at least two ways, inside the cells and on the surface of megakaryocyte lineage leukemias and megakaryocytic leukemia cell lines MEG-01 and HEL. This is strongly suggestive that thrombospondin (TSP)-mediated adhesion represents an alternative pathway for cytoadherence, and that CD36 expression on various kinds of cells may lack some essential modifications or components necessary for the TSP receptor activity.

Antibodies, Monoclonal↗
PubMed1990

Immunophenotype, histopathology and clinical stage: their predictive value in the prognosis of non-Hodgkin's lymphomas.

The relationship between immunophenotype, histopathology and clinical stage in influencing prognosis was evaluated in 99 cases of non-Hodgkin's lymphoma (NHL). All cases were histopathologically classified according to the system of the international conference on working formulation (WF), immunologically analysed by flow cytometry with a panel of monoclonal antibodies and clinically staged by the Ann Arbor scheme. Eighty eight percent of T- and 87.7% of B-phenotype NHLs respectively received combination chemotherapies with or without radiotherapy. Early stages I and II showed higher response rates (86% for T- and B-NHL) compared to the advanced ones III and IV (58% for T-NHL and 65% for the B-NHLs), p less than 0.05. Higher overall survival rates were observed in low and intermediate grade NHLs, p less than 0.05. The early stages further showed relatively higher survival rates in T- than in B-phenotype of intermediate grade NHL. Low grade NHL had the highest survival rates in both early and advanced stages, whereas the survival rate was the lowest in high grade NHL irrespective of the clinical stages. Immunophenotype, pathological grade and clinical stage jointly displayed varied predictive values in the prognosis of NHL. Since the present prognostic models are based on histological and staging criteria only, the results suggest that, phenotype should be included in the classification systems or prognostic models for the NHLs, thus facilitating the establishment of effective lineage specific therapies.

Adolescent↗
PubMed1989

Localization of chemotactic activity and 64 kD protein phosphorylation for human polymorphonuclear leukocytes in N-terminus of the chemotactic protein LUCT/IL-8.

A synthetic peptide, AVLPRSAKEL (LU10), the N-terminal amino acid sequence of chemotactic protein (LUCT/IL-8), showed chemotactic activity to polymorphonuclear leukocytes (PMN) with an ED50 of 5 nM for comparable to that of LUCT. Native LUCT and LU10 specifically induced the phosphorylation of 64 kD protein of PMN, and serine residue in the 64 kD protein was major phosphorylated amino acid. Furthermore, native LUCT enhanced the release of myeloperoxidase and beta-glucuronidase from PMN in the presence of cytochalasin B and FMLP, but LU10 did not. These results strongly suggest that the active site for both chemotactic stimulation and 64 kD protein phosphorylation is localized on the sequence of N-terminal 10 amino acids of LUCT.

Amino Acid Sequence↗
PubMed1989

Purification and partial primary sequence of a chemotactic protein for polymorphonuclear leukocytes derived from human lung giant cell carcinoma LU65C cells.

A chemotactic protein for polymorphonuclear leukocytes (lung carcinoma-derived chemotaxin [LUCT]) was purified from culture fluid of the human lung giant cell carcinoma LU65C cells to electrophoretically homogeneous form through five sequential purification steps: DEAE-Sepharose, CM-Sepharose, HPLC on carboxyl-methylated-polyvinylalcohol resin, hydrophobic, and reversed-phase. The molecular mass was determined as approximately 10 kD by SDS-PAGE and isoelectric point was 10.7. The chemotactic activity (ED50 0.75 x 10(-9) M) was sevenfold more potent than that of FMLP (5 X 10(-9) M) and comparable with that of C5a (10(-9) M). NH2-terminal amino acid sequence and amino acid composition of LUCT strongly suggest that it may be closely related to the putative protein encoded by the cDNA clone (3-10C) and almost identical with a part of sequence of the chemotactic factor derived from stimulated human leukocytes in the 6th to 32nd, but not the NH2-terminal 5 amino acids. These results indicate that the carcinoma cells produce LUCT without any added stimulant and suggest that the previously isolated chemotactic monokines may correspond to des(1-5) of LUCT in the NH2-terminal region.

Amino Acid Sequence↗
PubMed1989

Abnormal Ca2+ homeostasis in platelets of patients with myeloproliferative disorders: low levels of Ca2+ influx and efflux across the plasma membrane and increased Ca2+ accumulation into the dense tubular system.

Ca2+ influx and efflux in unstimulated platelets and Ca2+ uptake by simultaneously isolated two membrane fractions of platelets from patients with myeloproliferative disorders (MPD) have been investigated. In MPD, Ca2+ influx and efflux across the plasma membrane in unstimulated platelets were in equilibrium at significantly lower levels than in normals. Ca2+ uptake by external membrane fraction isolated from MPD platelets was lower, whereas, uptake by internal membrane fraction enriched with dense tubular system (DTS) from MPD platelets was significantly higher than that from normal platelets. This corresponded with the membrane associated Ca2+-activated ATPase activity. These abnormalities of calcium ion movement in plasma membrane and dense tubular system illustrates one of the mechanisms of qualitative abnormalities of MPD platelets.

Adenosine Triphosphatases↗
PubMed1989

Altered cytokine activities are related to the suppression of synthesis of normal immunoglobulin in multiple myeloma.

The content of peripheral blood B cells (B1+) was reduced in patients of multiple myeloma (MM) and not in those with benign monoclonal gammopathy (BMG) compared to normal donors (P less than 0.01). This observation correlated with the suppression of synthesis of normal immunoglobulin (Ig) in MM. Thus, cytokine activities regulating the proliferation of normal mature B cells, such as B cell stimulatory factor 1 (BSF-1)/interleukin 4 (IL-4), B cell growth inhibitory factor (BIF) and IL-2 in peripheral blood T cells, and IL-1 in peripheral blood adherent cells, were investigated in patients with BMG (n = 7) and MM (n = 28). All patients of MM having a marked suppression of synthesis of all other normal Ig, had significantly lower levels of BSF-1 activity and inversely higher levels of BIF activity than those of normal donors. However, patients with BMG having no suppression of synthesis of normal Ig had BSF-1 and BIF activities similar to normal donors. There was no significant difference in IL-1 and IL-2 activities between both normal donors and BMG versus MM patients. These data show that in MM altered cytokine activities correlate with suppression of synthesis of normal Ig.

B-Lymphocytes↗
PubMed1989

BSF-2/IL-6 does not augment Ig secretion but stimulates proliferation in myeloma cells.

Human myeloma cells were highly purified from bone marrow aspirates of 21 patients with advanced immunoglobulin G (IgG)-type multiple myeloma. B-cell stimulatory factor 2 (BSF-2)/interleukin-6 (IL-6) was originally characterized as a cytokine that can enhance immunoglobulin secretion from activated normal B cells and increase the expression of secretory-type Ig mRNA in these B cells, but that does not augment proliferation of activated B cells. However, recombinant IL-6 (rIL-6) could not enhance M-protein (IgG) secretion in freshly isolated myeloma cells in vitro but could augment proliferation of myeloma cells, although myeloma cells constitutively expressed IL-6 receptors. Furthermore, expression of secretory-type IgG (gamma-chain) mRNA in myeloma cells was not changed in the presence of IL-6. These results show that IL-6 is not an enhancing factor in Ig secretion from myeloma cells, and thus signal transduction through IL-6 in myeloma cells may be altered as opposed to activated B cells.

Adjuvants, Immunologic↗
PubMed1989

Analysis of peroxidase negative acute leukemias by monoclonal antibodies: III. Acute lymphoblastic leukemia.

Peripheral-blood leukemic cells from 45 patients with peroxidase negative acute lymphoblastic leukemia (ALL), which did not express either myeloid or megakaryocyte-platelet-related cell surface antigens, were analyzed by using monoclonal antibodies capable of recognizing T- or B-cell-associated and/or T- or B-cell-restricted antigens. Numerous subclasses of ALL, including B-cell lineage leukemias and T-cell lineage leukemias, were identified phenotypically and immunophenotypically in an effort to more accurately characterize the heterogeneous ALLs, their states of differentiation, and their relationships to normal B- and T-lymphoid cells. Among the cases studied, only seven (15.6%) were found to have stem cell (undifferentiated) leukemia (Ia+, CD24+, CD9+, CD34+). It is concluded that the use of monoclonal antibodies for the characterization of heterogeneous ALLs improves the specificity of leukemia classification, which may contribute to the selection of more effective forms of therapy for the types of leukemia identified.

Antibodies, Monoclonal↗
PubMed1989

Transforming growth factor-beta regulates growth as well as collagen and fibronectin synthesis of human marrow fibroblasts.

Three growth factors present in platelets, namely platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-beta) and epidermal growth factor (EGF), have been implicated in the pathogenesis of bone marrow fibrosis frequently associated with myeloproliferative disorders. In this study, regulation of the proliferation, as well as collagen and fibronectin synthesis from marrow fibroblasts by TGF-beta was investigated. TGF-beta alone at high plating density stimulated the proliferation of cells at low concentrations, but rather showed inhibition at high concentrations in both MPD patients and control subjects. In the presence of PDGF, which has been confirmed to be a main growth factor for marrow fibroblasts, low concentration of TGF-beta inhibited the proliferation at low cell density, but there was no inhibition at high cell density. The synthesis of both type I and type III procollagen was enhanced by high concentrations of TGF-beta in both MPD patients and control subjects, while PDGF or EGF showed no effect. The fibronectin synthesis was also enhanced by TGF-beta, but not by PDGF or EGF. These results suggest that growth and stromal protein synthesis of fibroblasts causing marrow fibrosis are regulated by TGF-beta as well as PDGF and EGF, when these factors are released or leaked from platelets or megakaryocytes into marrow environment in MPD patients.

Adult↗