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N Kamada

Publications and source records attributed to N Kamada.

At least 91 records · Page 5Linked to original sources
PubMed1998

A long term follow-up of a randomized trial comparing interferon-alpha with busulfan for chronic myelogenous leukemia. The Kouseisho Leukemia Study Group.

To evaluate the long-term effectiveness of interferon-alpha (IFN-alpha) therapy in patients with chronic myelogenous leukemia (CML) in chronic phase, we examined the updated outcomes of 159 patients who had been enrolled between 1988 and 1991 into a randomized trial comparing IFN-alpha with busulfan. At a median follow-up of 73 months, the median survival was 71 months in the IFN-alpha group and 55 months in the busulfan group (P=0.0563), and the median time of remaining in chronic phase was 58 months in the IFN-alpha group and 39 months in the busulfan group (P=0.4676). Landmark analysis showed a significant advantage in survival (P=0.009) and duration of chronic phase (P=0.0001) in patients with any cytogenetic response among the IFN-alpha group. About half patients were discontinued IFN-alpha administration in spite of cytogenetic response in this study. It appears that continuation of IFN-alpha might possibly confer a survival advantage. Pretreatment factors associated with cytogenetic response included high hemoglobin level, low percentage of peripheral basophils and low leukocyte counts. Multivariate analysis identified lower percentage of bone marrow basophilia (P=0.007) for survival advantage. If a group with a very good prognosis is predicted by a new prognostic model, it might be an option to wait for bone marrow transplantation.

Adult↗
PubMed1998

Establishment of a novel cell line (TS-2) of pre-B acute lymphoblastic leukemia with a t(1;19) not involving the E2A gene.

The t(1;19)(q23;p13) translocation involving the E2A gene on chromosome 19p13.3 is a nonrandom translocation that is often seen in childhood pre-B-cell acute lymphoblastic leukemia (ALL). However, recent studies have demonstrated the presence of immunophenotypic and molecular heterogeneity among patients with the cytogenetically identical chromosome translocation. Here we report a novel pre-B ALL cell line, TS-2, with t(1;19) translocation not involving the E2A gene. The breakpoint of t(1;19) in TS-2 was demonstrated to be at 19p13.3, a region indistinguishable from the locus of the E2A gene, by cytogenetic study and fluorescence in situ hybridization. However, rearrangement of the E2A gene was not detected in TS-2 by Southern blot analysis. Moreover, the expressions of PBX1 or E2A/PBX1 fusion genes were not detected by an extensive study with Northern blot analysis and reverse transcription-polymerase chain reaction. These findings suggest that TS-2 may have a genetic abnormality involving uncharacterized gene(s) at 19p13.3 distinct from the E2A gene and, therefore, may be useful for investigating the heterogeneity of molecular pathogenesis in leukemias with t(1;19)(q23;p13) translocation.

Adenovirus E2 Proteins↗
PubMed1998

Isodicentric chromosome 21: a novel aberration in acute myeloid leukemia.

We present here a 78-year-old female patient with acute myeloid leukemia (AML), French-American-British classification M2, exhibiting isodicentric chromosome 21, idic(21)(q22), at the time of diagnosis. The patient had three idic(21)(q22), besides the del(5)(q13q32), add(21)(q22), dic(21;22) (q22;q13), and +22. Fluorescence in situ hybridization studies with whole-chromosome painting and centromere-specific probes for chromosome 21 verified the diagnosis of idic(21)(q22). There were no distinct clinicohematological characteristics of AML with isodicentric 21. The patient was treated with remission-induction therapy followed by consolidation therapy. Two years later, the patient showed the disappearance of isodicentric 21 but retained del(5)(q13q32) and gained other chromosomal abnormalities, +add(17)(p11) and -16. To our knowledge, this is the first report of AML with acquired idic(21)(q22).

Aged↗
PubMed1998

Frequent expression of human Thy-1 antigen on pre-B cell acute lymphoblastic leukemia with t(9;22).

Thy-1 (CDw90) is a phosphatidylinositol-anchored protein, and is expressed on human pluripotential hematopoietic stem cells. The expression pattern of this antigen on leukemia cells is still controversial. In this study, 72 adult patients with pre-B cell acute lymphoblastic leukemia (pre-B ALL) were examined for the expression pattern of Thy-1 by using indirect immunofluorescence and reversed transcription polymerase chain reaction (RT-PCR) methods. Twelve cases were judged positive on the basis of conventional immunophenotype criteria. Thirteen cases showed a weak clonal shift on the fluorogram, even though their positive percentages were from 6.7% to 14.9%. Thy-1 gene transcripts were detected in all of the 13 cases showing a weak clonal shift. The study of antibody binding capacity, which was calculated by the mean fluorescence intensity of the test sample on the basis of a calibration curve using standard beads, showed that cases with more than 150 sites/cell could be positive. Thy-1 positivity in pre-B ALL was not associated with the expression of B-cell differentiation antigens. Thy-1 expression was significantly higher in pre-B ALL cases with karyotypic abnormalities than in those with normal karyotype (p = 0.0071). The t(9;22) abnormality was found in 18 of the 25 Thy-1+ cases. Simultaneous expression of transcriptional factors, GATA-2 and SCL, was frequently detected in the Thy-1+ cases. bcr-abl and GATA-2 are thought to play important roles in the proliferation of immature hematopoietic cells. Indeed, cell-cycle analysis showed that the cell population in the S/G2/M phase of the present Thy-1+ cases was less than that in the Thy-1- cases (p = 0.001770). Our data suggest that Thy-1 expression indicates the proliferative status of the leukemia cells, not their phenotypic immaturity.

Adolescent↗
PubMed1998

Biphasic expression of CD4 in acute myelocytic leukemia (AML) cells: AML of monocyte origin and hematopoietic precursor cell origin.

In 227 of 495 (45.9%) Japanese adult patients with acute myelocytic leukemia (AML), leukemic cells expressed CD4. Incidence of CD4 expression in each FAB subtype was as follows: M1 37.4%, M2 33.7%, M3 35.4%, M4 65.0%, and M5 78.3%. The typical expression pattern of myelomonocytic differentiation antigens and cytokine receptors in CD4+ AML was CD34lowCD33high CD11bhighGM-CSFRhigh. AML cases with 11q23 abnormalities and with inv(16) were frequently CD4-positive. These data collectively indicate that CD4 expression in AML cells is associated with monocytic characteristics. However, CD4+CD34high AML cases appear to have unique immature characteristics including low expression of myelomonocytic differentiation antigens (ie CD33 and CD11b), and accumulation of chromosome abnormalities (ie t(8;21) in CD4lowCD34high AML and chromosome 7 abnormalities in CD4highCD34high AML). We speculate that these leukemia subsets originate from CD4+ hematopoietic precursor cells, therefore then should be considered separately from most of the CD4+ AML as represented by CD34lowCD33high CD11bhighGM-CSFRhigh. Overall survival of patients with CD4+ AML in our series was worse than that of those with CD4 AML (P = 0.0202).

Adult↗
PubMed1998

Identification of a commonly deleted region at 17p13.3 in leukemia and lymphoma associated with 17p abnormality.

Fluorescence in situ hybridization (FISH) was performed in 17 myeloid leukemia patients and seven lymphoid leukemia/ lymphoma patients who exhibited chromosomal abnormalities on the short arm of chromosome 17, in order to detect a commonly deleted region on chromosome band 17p13. Twenty-four leukemia/lymphoma patients studied cytogenetically at our institution over a period of 10 years had detectable 17p abnormalities such as translocation (six patients), addition (11 patients) and deletion of 17p13 (seven patients). A 17p abnormality was the only abnormality present in three patients. Most of the patients had additional complex cytogenetic abnormalities. The diagnosis was acute myeloid leukemia (AML) in 10 patients, two each with chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome (MDS) and the remaining three with malignant lymphoma (ML). Seven cosmid probes (D17S34, cCI17-624, cCI17-453, D17S379, cCI17-636, cCI17-732 and TP53) which mapped on 17p13 were used to analyze the allelic deletion. Eighty percent (19 out of 24) of the informative leukemia patients exhibited allelic loss in 17p13.3 at cC17-624. The smallest region of an overlapping deletion was observed on chromosome band 17p13.3 between cCI17-624 and cCI17-453. Patients with translocation involving 17p also showed deletion at cCI17-624 and cCI17-453. We hypothesize that this region contains a novel tumor suppressor gene(s) that is involved in leukemogenesis.

Adult↗
PubMed1998

Expression, localization and functional interactions of Ku70 subunit of DNA-PK in peripheral lymphocytes and Nalm-19 cells after irradiation.

PURPOSE: To investigate the changes in expression, localization and functional interaction of Ku70 subunit of DNA-PK after irradiation. MATERIALS AND METHODS: Protein expression by Western blotting, cellular localization by immunofluorescence and functional interactions by immunoprecipitation were investigated after gamma-irradiation in two different cell systems: (1) quiescent human peripheral lymphocytes (0, 2 and 4 Gy) stimulated to proliferate with PHA; and (2) in a proliferating Nalm-19 cell line (0 and 2 Gy). Cell cycle analysis was performed by FACS. Immunofluorescence on extended chromatin fibres was also performed to show close association of Ku70 with the chromatin fibre. RESULTS: Gamma-irradiation induced dose-dependent expression of Ku70 in both cell systems. Confocal microscopy on immunostained cells and cell cycle analysis showed that Ku70 protein translocates to the cytoplasm after the G1 phase. There was a delay in the cytoplasmic shift of Ku70 in the irradiated group, corresponding with the G1 delay. The cytoplasmic localization was supported by ultracentrifugation studies. Immunofluorescence with Ku70 antibody on an extended chromatin fibre showed that Ku70 is closely associated with the chromatin fibre, and irradiation produced many spots of intense fluorescence on it. Ku70 coprecipitated with c-ABL and p21 after irradiation. The c-ABL was coprecipitated throughout the time course of observation, whereas p21 was transiently (0.2 h) associated with Ku70 and only in the lower dose groups. CONCLUSIONS: These studies have demonstrated new biological characteristics of Ku70 in the cellular response to irradiation.

Antigens, Nuclear↗
PubMed1998

Human leukotriene B4 omega-hydroxylase (CYP4F3) gene: molecular cloning and chromosomal localization.

Leukotriene B4 (LTB4) omega-hydroxylase catalyzes the conversion of LTB4 into a biologically less active product, 20-hydroxy-LTB4. In a preceding paper (Kikuta et al., 1993), we showed human polymorphonuclear leukocyte (PMN) LTB4 omega-hydroxylase to be a novel form of cytochrome P450, designated CYP4F3, on the basis of its cDNA cloning and expression in yeast cells. Here, we have isolated the gene encoding CYP4F3 and determined its genomic organization and chromosomal localization. The CYP4F3 gene contained 13 exons and spanned approximately 22.2 kb. The cDNA of CYP4F3 contained 5050 nucleotides excluding the poly(A) tail. The translation initiation codon (ATG) was present in exon II. Primer extension and S1 mapping analyses indicated that the transcription initiation site is 49 nucleotides upstream from the 3' end of exon I, and no other initiation sites were detected. A TATA-box-like sequence (TACAT) and 120-b GC-rich sequence were observed just before transcription initiation site. Several putative regulating elements recognized by the GATA family, MZF-1, CACCC binding protein, and C/EBP, were identified in its 5' flanking region. Genomic DNA screening for CYP4F3 and Southern blot analysis suggested the existence of other CYP4F genes in addition to CYP4F3 and CYP4F2 in the human genome. Fluorescence in situ hybridization demonstrated that the CYP4F3 gene is located at 19p13.2.

Amino Acid Sequence↗
PubMed1998

A case of cutaneous Ki-1 positive anaplastic large cell lymphoma in a hemodialysed patient.

A 66-year-old woman who suffered from chronic glomerulonephritis had been undergoing hemodialysis for about 10 years. A reddish papule on her waist developed gradually into a nodule (1.9 x 1.4 cm). Histopathological findings showed that the tumor cells had oval to reniform nuclei; multinucleated neoplastic cells and erythrophagocytosis were also present. Immunohistochemical analyses revealed that the membranes of the tumor cells stained for Ber-H2 (Ki-1) and epithelial membrane antigen (EMA), Vimentin was partially positive, but keratin, S-100, chromogranin, leukocyte common antigen (LCA), UCHL-1, MT-1, L-26, MB-1 and C3D-1 were all negative. Anti-human T-cell leukemia virus-1 (HTLV-1) was also negative. No gene rearrangement of the T-cell receptors beta-, gamma- and delta-chain could be detected. From these results, we diagnosed cutaneous Ki-1 anaplastic large cell lymphoma (ALCL), but the origin could not be determined. The relationship between lymphoma and chronic renal failure and/or hemodialysis was far from clear.

Aged↗
PubMed1998

A case of bullous pemphigoid in a patient on hemodialysis.

We describe a case of bullous pemphigoid (BP) in a patient with chronic renal failure maintained on hemodialysis. We diagnosed BP by histopathological and immunofluorescence studies. The relationship between BP and chronic renal failure and/or hemodialysis is not clear, but we believe that immune disarrangement due to chronic renal failure and/or hemodialysis may have influenced the pathogenesis of BP in our case.

Aged↗
PubMed1998

Fluorescence in situ hybridization analysis of 12;21 translocation in Japanese childhood acute lymphoblastic leukemia.

Fluorescence in situ hybridization (FISH) analysis was applied to detect t(12;21) using two yeast artificial chromosome probes and cosmid probes covering the TEL(ETV6) and the AML1 gene to clarify the incidence of abnormality of t(12;21) in Japanese childhood acute lymphoblastic leukemia (ALL). We detected seven TEL/AML1 fusion positive patients (9.5%), all of whom were diagnosed as B-lineage ALL, among 74 childhood ALL. On the other hand, no TEL/AML1 fusion positive patients were found among 37 adult ALL. The incidence among Japanese seemed to be lower than that among other nations. Of the seven patients with the TEL/AML1 fusion, five exhibited normal karyotype, one was t(8;12)(q11;p13), i(21q) and the remaining one exhibited a near-triploid karyotype in conventional G-banding. The FISH method clearly demonstrated that all patients with the TEL/AML1 fusion had subpopulations of leukemic cells with deletion of the normal TEL allele, which is significant for understanding the progression of leukemia with t(12;21).

Blotting, Southern↗
PubMed1998

Segmental jumping translocation in leukemia and lymphoma with a highly complex karyotype.

In order to identify the oncogene associated with malignant transformation 141 leukemia and malignant lymphoma patients were studied by FISH. Specific chromosome regions were translocated onto structurally abnormal chromosomes, resulting in partial tri-, tetra-, or pentasomy of these regions. We designated this type of chromosomal translocation as a "segmental jumping translocation (SJT)". These SJTs were found in several chromosomal regions such as 8q24, 9q34, 11q13, 11q23, 13q14, 14q24-q32, 21q22 and 22q11. The SJT at 9q34, which involved the ABL oncogene, was found in three of nine secondary leukemia patients who were treated with anticancer drugs and radiation. Non-Hodgkin's lymphoma and acute myeloid leukemia (AML) patients had 3-7 copies of SJT at 11q13 or 11q23. SJT at 14q32 and 21q22 were predominantly detected in the acute type of adult T-cell leukemia (8 of 27 patients) and in AML (5 of 17 patients). The size of the SJT regions varied among the patients. The overlapping region within the SJT could involve oncogene(s) associated with transformation to the advanced stage in leukemia and lymphoma patients. The SJT provides evidence of a new mechanism for gene amplification and formation of unidentified marker chromosomes in the advanced disease stage.

Adult↗
PubMed1998

[Therapy-related MDS/leukemia carrying dup(11) (q21q23) with MLL gene tandem duplication].

A 42-year-old woman had been given a diagnosis of malignant lymphoma, follicular, small cleaved cell. She had undergone chemotherapy including etoposide (1,500 mg/total) and was in her second complete remission. Four years and 4 months later, refractory anemia with excess of blasts (RAEB) with dup(11) (q21q23) x 2 developed in the patient and progressed to acute myeloid leukemia (AML-M5b). Despite regression of the AML to RAEB, a clone with the additional abnormality of del(20) (q11q13.1) appeared and transformed the RAEB into AML-M6. Rearrangement of the MLL gene was observed, and FISH analysis demonstrated that the signal sequences from the gene's 5' and 3'-terminal regions had detached. RT-PCR techniques detected a tandem duplication of MLL gene exons 2 through 8. This was considered to be one of the mechanisms behind the formation of the 11q23 abnormality observed in this patient.

Adult↗
PubMed1998

Multiple possible sites of BRCA2 interacting with DNA repair protein RAD51.

To investigate the biological consequences of aberrant BRCA2 protein during mammary carcinogenesis, we attempted to identify proteins that normally interact with BRCA2. By using a yeast two-hybrid system with a hybrid protein that contained residues 639-1,508 of BRCA2 protein fused to the GAL4 DNA-binding domain, we isolated five independent cDNA clones that encoded parts of RAD51 protein, a human homolog of bacterial RecA. In vitro experiments using anti-RAD51 antibody confirmed interaction of BRCA2 with RAD51. The RAD51-binding region of BRCA2 detected in the present study was distinct from the region reported recently. Further studies using smaller portions of BRCA2 defined at least two additional RAD51-binding domains, residues 982-1,066 and 1,139-1,266. Our results suggest that BRCA2 can interact with RAD51 through multiple sites of BRCA2 and that control of mitotic and meiotic recombination and/or of genomic integrity through binding to RAD51 may be a crucial mechanism by which BRCA2 suppresses abnormal proliferation of mammary cells.

Amino Acid Sequence↗
PubMed1997

Administration of exogenous interleukin-2 abrogates spontaneous rat liver allograft acceptance but does not affect long-term established graft survival.

BACKGROUND: Spontaneous tolerance to the orthotopic liver allograft uniformly occurs in the DA (RT1a) to PVG (RT1c) rat combination despite a fully allogeneic barrier. METHODS: To assess whether spontaneous acceptance might be the consequence of a T cell help deficit at the time of the first exposure of alloantigens to the host, we studied the effect of exogenous interleukin (IL)-2 injections at the time of liver transplantation and during long-term follow-up. RESULTS: Although spontaneous acceptance of the liver allograft constantly ensued in the DA to PVG combination, a daily injection of recombinant IL-2 (3 x 10(5) U) uniformly provoked acute cellular rejection of the liver allograft and consequently the death of animals by postoperative day 5-6. Simultaneous to the graft loss, hepatic enzymes (alanine aminotransferase) increased more than 50-fold in IL-2-treated recipients, whereas similar IL-2 treatment did not produce any hepatic dysfunction in syngeneic animals. By immunohistology, the expression of the alpha chain of the IL-2 receptor, usually undetectable in untreated animals, was evident on CD4 and CD8 lymphocytes infiltrating the liver graft. In contrast, a similar IL-2 regimen and even higher IL-2 doses (x 10(6) U) did not abrogate the liver allograft survival during long-term follow-up. CONCLUSIONS: Our results demonstrate that spontaneous rat liver allograft acceptance may be abolished by exogenous IL-2 injections, which suggests that an "inherent T cell help deficit" might be implicated in the spontaneous acceptance mechanisms of DA to PVG liver allografts.

Alanine Transaminase↗
PubMed1997

Identification of translocational breakpoints within the intron region before the last coding exon (exon 12) of the EVI1 gene in two cases of CML-BC with inv(3)(q21q26).

We have previously shown that the EVI1 gene at chromosome 3q26 is transcriptionally activated by chromosomal rearrangements in acute myelogenous leukemias (AMLs) with inv(3)(q21q26) or t(3;3)(q21;q26). The breakpoints in t(3;3) cases were 15 to 330 kb upstream of the EVI1 gene, while those in inv(3) cases were 150 to 200 kb downstream and outside of the EVI1 coding region. The EVI1 gene is also activated in chronic myelogenous leukemia-blastic crisis (CML-BC) with inv(3)(q21q26); however, the molecular mechanism of EVI1 activation in CML-BC is still unclear. In this paper, we have analyzed chromosomal rearrangements in two leukemia cell lines derived from CML-BC with inv(3)(q21q26) and have identified the breakpoints within the EVI1 coding area. The EVI1 gene spans over 100 kb with 12 exons (10 coding exons), and the chromosomal breakpoints are clustered in the intron region before the last coding exon (exon 12). The nucleotide sequence of EVI1 cDNA clones from MOLM-1 cells was truncated at exon 11, and a novel sequence of 681 nucleotides was added at the 3' end of the EVI1 transcripts. The novel sequence was derived from a readthrough intron sequence 3' to the coding exon 11 adjacent to the breakpoint. The breakpoints at 3q21 were within the breakpoint cluster area downstream of the ribophorin I gene, suggesting that the activation mechanism of the EVI1 gene in CMLs with inv(3) is the same as that in AMLs with inv(3). These results indicate that expression of a truncated EVI1 gene is an important factor in the progression of CML.

Amino Acid Sequence↗
PubMed1997

The inv(11)(p15q22) chromosome translocation of de novo and therapy-related myeloid malignancies results in fusion of the nucleoporin gene, NUP98, with the putative RNA helicase gene, DDX10.

The inv(11)(p15q22) is a recurrent chromosomal abnormality associated with de novo and therapy-related myeloid malignancies. Here we report the molecular definition of this chromosomal aberration in four patients. Positional cloning showed the consistent rearrangement of the DDX10 gene on chromosome 11q22, which encodes a putative RNA helicase. The translocation targets the NUP98 gene on 11p15, a member of the FG peptide repeat nucleoporin family. In DDX10 and NUP98, the inv(11) breakpoints occurred within two introns of each gene and the two genes merged in-frame to produce the chimeric transcripts characteristic of this translocation. Although two reciprocal chimeric products, NUP98-DDX10 and DDX10-NUP98, were predicted, only NUP98-DDX10 appears to be implicated in tumorigenesis. DDX10 is predicted to be involved in ribosome assembly. NUP98 has been identified as a nuclear pore complex protein and a target of chromosomal translocation in acute myeloid leukemia through the t(7;11)(p15;p15) translocation. The predicted NUP98-DDX10 fusion protein may promote leukemogenesis through aberrant nucleoplasmic transport of mRNA or alterations in ribosome assembly.

Amino Acid Sequence↗