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Biomedical subjects

A Kuramoto

Publications and source records attributed to A Kuramoto.

At least 55 records · Page 3Linked to original sources
PubMed1994

Gene regulation by the 5'-untranslated region of the platelet-derived growth factor A-chain.

Platelet-derived growth factor (PDGF) A-chain gene contains a long 5'-untranslated region (5'-UTR) of 850 bp. We evaluated the role of the 5'-UTR by chloramphenicol acetyltransferase (CAT) assay. CAT activity appeared when the fragment +99 bp downstream from the initiation site (+1) was present but disappeared in the fragment to +184 bp. It appeared again at +338 bp but disappeared again to +609 bp. The fragment from +99 to +184 inhibited CAT activity by a post-transcriptional mechanism, as RNA of CAT was observed but CAT activity was not.

Base Sequence↗
PubMed1994

Expression of the thrombospondin receptor (CD36) on the cell surface in megakaryoblastic and promegakaryocytic leukemias: increment of the receptor by megakaryocyte differentiation in vitro.

In this report we describe four cases of acute megakaryocytic leukemia demonstrated by the presence of megakaryocyte-platelet-related cell-surface antigens. These were detected utilizing flow cytometry and monoclonal antibodies in addition to both platelet peroxidase activity, which was shown by ultrastractural cytochemistry, and emergence of differentiation antigens, while culturing these leukemic cells. The blasts of one patient possessed both platelet GpIb and GpIIb/IIIa cell-surface antigens detected by AN51(CD42b), J15, P2, and HPL2(CD41), respectively, whereas the remaining three patients almost completely lacked GpIb cell-surface antigen. Hence the former were diagnosed as immature(pro)megakaryocytic leukemia and the latter as acute megakaryoblastic leukemia from the viewpoint of immunophenotypic analysis. While we cultured these leukemic cells in conditioned medium prepared from phytohemagglutinin-stimulated leukocytes and interleukin 3, expression of CD36(OKM5) antigen (thrombospondin receptor) increased gradually according to the differentiation and maturation of these cells. Finally, all leukemic cells differentiated to mature megakaryocytes. The function of CD36 on these cells remains to be elucidated.

Antigens, CD↗
PubMed1994

Abnormal factor VIII Hiroshima: defect in crucial proteolytic cleavage by thrombin at Arg1689 detected by a novel ELISA.

We have established an ELISA for detecting thrombin cleavage of the FVIII light chain at Arg1689. The method used a coating alloantibody which recognized amino acid residues 2248-2312 in the C2 domain, together with a second monoclonal antibody, NMC-VIII/10, which recognized residues 1675-1684 in the amino-terminal region of the light chain. FVIII antigen (FVIII:Ag) was measured after treatment of plasma with various concentrations of thrombin. The FVIII:Ag of normal plasma was reduced in a dose-dependent manner by the thrombin, falling to 28% in the presence of 100 U/ml enzyme. The concentration of thrombin that achieved 50% reduction (IC50) was approximately 1.0 U/ml. The plasma of four haemophilia A positive (A+) and two haemophilia A reduced (AR) patients were analysed. The IC50 of all patients was more than 1.0 U/ml, indicating that thrombin cleavage of the FVIII light chain was defective. One haemophilia A+ plasma did not respond to thrombin in this ELISA system. The patient (TI) was a haemophiliac with FVIII coagulant activity of 0.04 U/ml and FVIII:Ag of 1.78 U/ml. In addition, immunoblotting of the purified FVIII from TI showed that thrombin cleavage of the 80 kilodalton (kD) light chain was impaired. The patient's DNA was amplified using the polymerase chain reaction with a set of synthetic oligonucleotide primers spanning amino acid residues 1646-1714. Sequence analysis of the amplified DNA fragments revealed a cytosine to thymine transition, converting an arginine 1689 to cysteine. This abnormal FVIII was designated as FVIII Hiroshima. Our ELISA system is a simple and useful method of evaluating the proteolytic cleavage by thrombin at Arg1689.

Arginine↗
PubMed1994

Platelet-derived growth factor expression in accelerated and blastic phase of chronic myelogenous leukaemia with myelofibrosis.

Myelofibrosis is sometimes associated with accelerated and blastic phase of chronic myelogenous leukaemia (CML). In order to investigate the role of platelet derived growth factor (PDGF) in this pathogenesis, expression and production of PDGF was studied in the blast cells from 11 patients. Five patients had myelofibrosis with myeloid blasts, while six patients did not show fibrosis, including three with myeloid blasts and three with lymphoid blasts. PDGF-A chain transcript was expressed in most of the patients. On the other hand, PDGF-B chain transcript was detected in all of the five patients with myeloid blasts and with fibrosis, in one of the three patients with myeloid blasts and without fibrosis, and in none of the three lymphoid crisis patients without fibrosis. In the patients with myeloid blasts and with fibrosis, PDGF protein, PDGF-AB and/or PDGF-BB, was found to be secreted from blast cells. In addition, the PDGF activity in the culture of myeloid blasts from two patients with fibrosis was also growth stimulatory for human marrow fibroblasts. These results suggest that expression and secretion of PDGF-AB or PDGF-BB in blast cells play an important role in the pathogenesis of marrow fibrosis associated with accelerated and blastic phase of CML.

Adult↗
PubMed1994

Hodgkin's disease associated with chronic myeloid leukemia. Determination of bcr-abl rearrangement in paraffin-embedded tumors using the polymerase chain reaction.

A patient showing lymph node enlargement and tumors in the neck and axilla in the course of Philadelphia (Ph1) chromosome-positive chronic myeloid leukemia (CML) was seen. There were no hematological findings suggestive of crisis. RNA was isolated from formalin-fixed and paraffin-embedded tissue specimens for the polymerase chain reaction of bcr-abl. CML-type products were detected in the peripheral blood, but no bcr-abl products were found in the lymph nodes. These findings indicate a very rare case in which Hodgkin's disease developed during the course of CML.

Base Sequence↗
PubMed1994

The potential for bidirectional promoter activity of the human PDGF-A chain gene.

Platelet-derived growth factor (PDGF) is a heterodimeric glycoprotein consisting of A and B chains. A functional promoter had been identified in the 5' flanking region of the human PDGF-A chain gene. We found that the PDGF-A chain promoter region possesses the potential for bidirectional activity. This bidirectional promoter activity is influenced by the 5'-untranslated region (5'-UTR) and serum concentration. The 5'-UTR may regulate expression of the PDGF-A chain by transcription in the opposite direction.

Chloramphenicol O-Acetyltransferase↗
PubMed1994

Identification of 5' regulatory elements of the PDGF-A chain gene, and interaction with single-stranded DNA binding protein.

The expression of platelet-derived growth factor (PDGF) is controlled in a very complicated manner. To clarify the mechanism of regulation of the PDGF-A chain gene, deletion analysis of the 5'-flanking region was performed. We identified a positive regulatory element 25 base pairs (bp) upstream of TATAA, a negative element 135 bp upstream, a positive element 223 bp upstream and a negative element further upstream. These regulatory sites of the PDGF-A chain gene may be involved in tissue specificity, developmental regulation, and transformation. In addition, our analysis suggested the presence of a strand non-specific single-stranded DNA binding nuclear protein in the positive regulatory element 25 bp upstream of TATAA.

Base Sequence↗
PubMed1994

Expression of platelet membrane glycoprotein V in human megakaryocytes and megakaryocytic cell lines: a study using a novel monoclonal antibody against GPV.

Glycoprotein V (GPV) is a platelet membrane protein with a molecular weight of 82 kD, and one of the leucine rich glycoproteins (LRG). By reverse transcription-polymerase chain reaction (RT-PCR), GPV cDNA was amplified from mRNA of platelets and megakaryocytic cell lines. However, since there are few reports indicating whether GPV protein is expressed in megakaryocytes as a lineage and maturation specific protein, we studied the GPV expression at the protein level by using a novel monoclonal antibody (1D9) recognizing GPV. Flow cytometric and immunohistochemical analysis indicated that GPV was detected on the surface and in the cytoplasm of only the megakaryocytes in bone marrow aspirates. In a megakaryocytic cell line UT-7, GPV antigen increased after treatment with phorbol-12-myristate-13-acetate (PMA). These data indicate that only megakaryocytes specifically express the GPV protein among hematopoietic cells and that the expression of GPV increases with differentiation of the megakaryocyte as GPIb-IX complex.

Antibodies, Monoclonal↗
PubMed1994

Estimation of chronic phase duration in Ph-positive chronic myelocytic leukemia treated with busulfan: statistical analysis on Japanese patients.

Chronic phase duration was analyzed in 148 Japanese patients with Ph-positive chronic myelocytic leukemia (CML) treated only with busulfan, and multivariate proportional hazard models were constructed to infer the prognosis of a given patient, and to evaluate the prognostic importance of the clinical findings. To make an accurate estimation of an individual patient's prognosis, we introduced a piecewise linear model for describing a hazard function in each prognostic variable. Of the 11 prognostic variables initially analyzed, the absolute count of peripheral basophils was revealed as the most important prognostic factor. A high basophil count was clearly a factor in cases with poor prognosis. The statistical model selection based on the criteria of model approximation finally suggested a model with three covariates; absolute count of peripheral basophils, platelet count, and presence or absence of additional chromosome abnormalities superimposed on the translocation of 9;22. By analyses based on the above model, we estimated that the median of the chronic phase duration for the patients with poor and good prognosis was 12 and 75 months, respectively. The piecewise linear model was well suited for an accurate estimation of an individual patient's prognosis. Thus, the model constructed here would become a reliable control to evaluate investigational approaches, such as hydroxyurea, interferons, and/or bone marrow transplantation.

Adolescent↗
PubMed1994

A patient with anaplastic large cell lymphoma (Ki-1 lymphoma) showing clonal integration of HTLV-1 proviral DNA.

We encountered a patient with anaplastic large cell lymphoma (Ki-1 lymphoma) that originated in the stomach and showed histiocytic lymphoma-like morphology. CD43 antigen was positive, and rearrangement of TCR-beta gene was observed. The lymphoma was the T-cell type. Though no atypical lymphocytes or histological images specific to adult T-cell leukemia were observed, clonal integration of HTLV-1 proviral DNA was noted. Viruses such as HTLV-1 appear to be involved in the development of some anaplastic large cell lymphomas.

Adult↗
PubMed1994

Cancer incidence in atomic bomb survivors. Part III. Leukemia, lymphoma and multiple myeloma, 1950-1987.

This paper presents an analysis of data on the incidence of leukemia, lymphoma and myeloma in the Life Span Study cohort of atomic bomb survivors during the period from late 1950 through the end of 1987 (93,696 survivors accounting for 2,778,000 person-years). These analyses add 9 additional years of follow-up for leukemia and 12 for myeloma to that in the last comprehensive reports on these diseases. This is the first analysis of the lymphoma incidence data in the cohort. Using both the Leukemia Registry and the Hiroshima and Nagasaki tumor registries, a total of 290 leukemia, 229 lymphoma and 73 myeloma cases were identified. The primary analyses were restricted to first primary tumors diagnosed among residents of the cities or surrounding areas with Dosimetry System 1986 dose estimates between 0 and 4 Gy kerma (231 leukemias, 208 lymphomas and 62 myelomas). Analyses focused on time-dependent models for the excess absolute risk. Separate analyses were carried out for acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML), chronic myelocytic leukemia (CML) and adult T-cell leukemia (ATL). There were few cases of chronic lymphocytic leukemia in this population. There was strong evidence of radiation-induced risks for all subtypes except ATL, and there were significant subtype differences with respect to the effects of age at exposure and sex and in the temporal pattern of risk. The AML dose-response function was nonlinear, whereas there was no evidence against linearity for the other subtypes. When averaged over the follow-up period, the excess absolute risk (EAR) estimates (in cases per 10(4) PY Sv) for the leukemia subtypes were 0.6, 1.1 and 0.9 for ALL, AML and CML, respectively. The corresponding estimated average excess relative risks at 1 Sv are 9.1, 3.3 and 6.2 respectively. There was some evidence of an increased risk of lymphoma in males (EAR = 0.6 cases per 10(4) PY Sv) but no evidence of any excess in females. There was no evidence of an excess risk for multiple myeloma in our standard analyses.

Adolescent↗
PubMed1993

Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone marrow stromal cells.

Recent immunophenotypic analysis has shown that the heterogeneous expression of the adhesion molecule VLA-5 classifies myeloma cells into VLA-5+ mature and VLA-5- immature subpopulations. To further clarify the two myeloma subpopulations, we generated a monoclonal antibody, MPC-1, by immunizing mice with an adherent human myeloma cell line, KMS-5. The MPC-1 antibody recognized a 48-Kd surface antigen on KMS-5 but not on U-266, a nonadherent human myeloma cell line. Specificity characterization showed that MPC-1 antigen was expressed on mature myeloma cells, normal plasma cells, and mature B cells, whereas pre-B cells and germinal center B cells lacked its expression. Monocytes and a human bone marrow stromal cell line, KM102, also expressed this antigen. Two subclones of MPC-1+ VLA-5+ (KMS-5Ad) and MPC-1-VLA-5+ (KMS-5NAd) were separated from the KMS-5 cell line. The KMS-5NAd adhered to KM102 more tightly than did the KMS-5NAd, and the U-266 (MPC-1-VLA-5-) displayed almost no adherence to the KM102. The adhesion of the KMS-5Ad was partially inhibited by the MPC-1 antibody. These results, taken together, suggest that the MPC-1 antigen serves as a differentiation marker for B-lineage cells, including plasma cells, and may function as an adhesion molecule involved in the interaction of mature myeloma cells with bone marrow stromal cells.

Animals↗
PubMed1993

Identification of immature and mature myeloma cells in the bone marrow of human myelomas.

With regard to the expression of adhesion molecules, human myeloma cells freshly isolated from bone marrow were heterogeneous. By two-color analysis with anti-VLA-5 antibody (PE staining) and FITC-labeled anti-CD38 antibody, we found all myeloma cells located at CD38-strong positive (CD38++) fraction and identified two subpopulations among these myeloma cells: CD38++ VLA-5-(VLA-5-) myeloma cells and CD38++ VLA-5+ (VLA-5+) myeloma cells. To clarify the biologic character of these two subpopulations, the morphology, in vitro proliferative activity and in vitro M-protein secretion were examined in each fraction isolated by the purification procedure or a cell sorter. Morphologic examination showed that VLA-5- myeloma cells were mostly immature or plasmablastic and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL-6), a growth factor for myeloma cells, while VLA-5+ myeloma cells showed very low uptakes of 3H-thymidine and no responses to IL-6 but secreted higher amounts of M-protein (immunoglobulin) in vitro significantly. Therefore, we could clarify here heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA-5, one of integrin adhesion molecules; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells.

ADP-ribosyl Cyclase↗
PubMed1993

Phenotypic difference of normal plasma cells from mature myeloma cells.

We have recently shown that two-color analysis with fluorescein isothiocyanate (FITC)-anti-CD38 antibody could clearly distinguish myeloma cells (plasma cells) from other hematopoietic cells in the bone marrow. Myeloma cells (plasma cells) alone were located at CD38strong positive (++) fractions. To further distinguish normal plasma cells from mature myeloma cells phenotypically, we examined immunophenotypes of normal plasma cells and myeloma cells by two-color flow cytometry with FITC-anti-CD38 antibody and phycoerythrin staining with antibody to VLA-4, MPC-1, CD44, CD56, CD19, CD20, CD24, or CD10. Normal plasma cells were all VLA-4+VLA-5+MPC-1+CD44+ CD19+CD56- in the bone marrows from seven healthy donors, tonsils from four patients with chronic tonsillitis, a spleen from one patient with idiopathic thrombocytopenic purpura, and lymph nodes from two patients with chronic lymphadenitis, respectively. On the other hand, mature myeloma cells (12 of 20 cases), VLA-4+VLA-5+MPC-1+, were all CD19- and most of them CD56+, and there were no myeloma cells with the CD19+CD56- phenotype in the 20 cases of myelomas we tested. Thus, as for the expression of CD19 and CD56, normal plasma cells from various tissues are all CD19+CD56-, whereas no myeloma cells have the CD19+CD56- phenotype. According to this finding, we investigated the expression of CD19 and CD56 on plasma cells (CD38++ fractions) in monoclonal gammopathy of undetermined significance (MGUS). Both CD19+CD56- and CD19-DC56+ plasma cells were found in all five cases of MGUS we tested, suggesting that MGUS consists of phenotypically normal plasma cells and myeloma cells. Therefore, it is reasoned that phenotypic analysis of plasma cells with anti-CD19 and anti-CD56 antibodies can distinguish normal plasma cells from malignant plasma cells (myeloma cells), and can detect malignant plasma cells even in MGUS or premyeloma states.

Aged↗
PubMed1993

Chronic lymphocytic leukemia associated with bone marrow fibrosis: possible role of interleukin 1 alpha in the pathogenesis.

B-cell chronic lymphocytic leukemia (B-CLL) associated with bone marrow fibrosis is described. The conditioned medium of the CLL cells contained a high quantity of interleukin 1 alpha (IL-1 alpha), and showed growth promoting activity for marrow fibroblasts which was partially inhibited by anti IL-1 alpha antibody. In addition, the conditioned medium as well as IL-1 alpha stimulated the growth of marrow fibroblasts from the patient. These results strongly suggested the marrow fibrosis occurred by the secretion of IL-1 alpha from the CLL cells and its growth stimulation of marrow fibroblasts. As far as we know, this is the first case in which B-CLL was associated with marrow fibrosis, and its mechanism was investigated.

Antigens, CD↗
PubMed1993

Detection of high incidence of H-RAS oncogene point mutations in acute myelogenous leukemia.

We have been analyzing RAS p21 proteins and the DNA sequence of leukemic cells. We report here that these cells have high expression of H-RAS p21, which originates from point mutations of RAS oncogenes. The leukemic cells from six patients with acute myelogenous leukemia were separated from heparinized whole blood and bone marrow by a density gradient technique. The expression of RAS oncogenes was analyzed by a fluorescence-activated cell sorting with a panel of monoclonal antibodies. The high expression of DWP, which was reported to recognized activated RAS oncogene, was found in two patients and was associated with high levels of H-RAS expression. These facts prompted us to analyze the DNA sequence of RAS genes with an automated DNA sequencer. Unexpectedly, various kinds of H-RAS point mutations were found in all six cases, including two cases of hot-spot point mutation at codon 12, whereas K-RAS point mutation (no hot-spot point mutations) was found in six cases. The same H-RAS point mutations, at codons 10, 11, and 15, were found in all six cases. To our knowledge, there is no report on H-RAS point mutation in human leukemias. On the basis of these findings, we suggest that H-RAS point mutation together with p53 gene mutation may play an important role in leukemogenesis.

Base Sequence↗
PubMed1993

Primary squamous cell carcinoma of the breast after cured Hodgkin's disease.

An unusual case of primary squamous cell carcinoma of the breast occurring after cured Hodgkin's disease is reported herein. A 27-year-old woman developed a left breast mass 2 years after chemotherapy and radiation for nodular sclerosing stage IIB Hodgkin's disease. Excisional biopsy revealed squamous cell carcinoma of the breast and a modified radical mastectomy was performed, however, no metastasis was found in the axillary nodes. She received etoposide, mitomycin-C, and doxifluoridine as adjuvant chemotherapy, and remains well without any evidence of recurrent Hodgkin's disease or breast cancer. To our knowledge, this is the first reported case of primary squamous cell carcinoma of the breast associated with Hodgkin's disease. The risk of patients treated for Hodgkin's disease developing breast cancer as a second malignant neoplasm is discussed following the report of this case.

Adult↗