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S Fukuhara

Publications and source records attributed to S Fukuhara.

At least 199 records · Page 11Linked to original sources
PubMed1990

[bcl-2 gene involved in Japanese follicular lymphoma].

Using three chromosome 18-specific DNAs, rearrangements of a bcl-2 gene were detected in 20 (44%) of 45 Japanese patients (pts) with follicular lymphoma (FL) and 3 (8%) of 36 pts with diffuse large cell lymphoma. The 21 pts had t (IgH; bcl-2), and of the remaining two who did not display it, one had chromosome t(14; 18). Compared with the findings in American pts, the lower frequency of t(14; 18)-positive lymphoma could reflect a difference in the incidence of overall nodal B lymphoma between Japan and the United States. 11 of 18 pts with t(14; 18)-positive FL expressed CD10 antigen on the cell surface and all 12 pts with t(14; 18)-negative FL did not, and the difference is statistically significant, indicating that t(14; 18)-positive Japanese FL is the same disease entity as most of American FL. Extra 18q- chromosome found in the advanced grade diseases of t(14; 18)-positive lymphoma results in amplification of the rearranged bcl-2 gene on 18q-, suggesting that the change is closely associated with transformation of FL carrying t(14; 18). It is thus possible of international realization to institute the prognostic factors and the treatment strategy for conquering t(14; 18)-positive lymphoma.

Chromosomes, Human, Pair 18↗
PubMed1990

[Cytogenetics on malignant lymphoma].

Translocations involving band q32 on chromosome 14 are commonly identified as a 14q + marker-chromosome and the involvement is the single most frequent abnormality in various types of lymphoid cancer. Based on these findings, we have proposed that the 14q + marker-positive lymphoid cancer should be divided into subclasses according to the precise translocations, each of which is a primary chromosome change, and the subclass initiates serial processing of the karyotype evolution associated with the development of more aggressive lymphoid cancer. The proposal is strongly supported by recent advances in molecular genetics. Genes or unknown DNA sequences, which had evolutionally been conserved, were isolated from the breakpoint on the partner chromosome of the 14q+ translocation, and the DNA sequences identified to juxtapose to the IgH gene locus on chromosome 14 band q32 accompanied by individual translocation. Thus, we can subclassify the lymphoid cancers marked with chromosome changes involving the loci of other functional genes.

Chromosomes, Human, Pair 14↗
PubMed1989

Acute transformation of chronic large granular lymphocyte leukemia associated with additional chromosome abnormality.

A patient with large granular lymphocyte (LGL) leukemia that transformed into an acute or aggressive form after 20 months of the chronic phase is reported. The patient's leukemic cells were mature, medium-sized lymphocytes with sparse azurophil granules and the surface phenotypes of the cells were CD2+, CD3-, CD11+, and CD16+. Molecular analysis showed a germ line configuration in both T-cell receptor beta-chain genes and T-cell receptor tau-chain genes. A clonal anomaly of chromosome (trisomy 8) was demonstrated in peripheral blood cells. LGL after acute transformation of the disease displayed large blastic morphology with prominent nucleoli, intense basophilic cytoplasm, and numerous granules. Karyotypic analysis demonstrated a mosaic of trisomy 8 and trisomy 8 with an additional marker chromosome. Thus, transformation of chronic LGL leukemia into an acute or aggressive form in this patient was associated with morphologic and karyotypic changes of the leukemic cells. Patients with a stable form of chronic LGL leukemia should be examined carefully for the possible acute crisis associated with a clonal evolution.

Adult↗
PubMed1989

Involvement of c-myc oncogene in lymphoma cell lines with no detectable chromosome rearrangement of band 8q24.

Two lymphoma cell lines of B-cell type were established from Japanese patients with diffuse small noncleaved cell lymphoma. Cytogenetic analysis revealed a 14q+ marker chromosome in both cell lines, and a t(8;14)(q24.1;q32.3) seemed most likely to have occurred. The chromosome 8 pair, however, had no abnormalities. Molecular analysis demonstrated c-myc amplification lacking gross rearrangement in one cell line and genetic rearrangement of c-myc at the first intron as well as aberrant sizes of c-myc mRNA in the other cell line. In the latter case, it is possible that a t(8;14)(q24.1;q32.3) was buried in an unrecognized complex translocation. A combination of cytogenetic and molecular studies to determine the precise nature of the 14q32 translocation is discussed.

Aged↗
PubMed1989

Involvement of bcl-2 gene in Japanese follicular lymphoma.

A t(14;18) (q32;q21) chromosome translocation is closely associated with the follicular lymphoma, which is prevalent in the United States, and the t(14;18) causes the juxtaposition of a bcl-2 gene on chromosome 18 with an immunoglobulin heavy-chain gene locus on chromosome 14. Genomic DNAs from 30 Japanese patients with follicular lymphoma were examined for the molecular features by Southern blot hybridization. Using probe b for the major breakpoint cluster region of a bcl-2 gene, the rearrangements were detected in eight patients. Six of the eight patients had breakpoints located within the major breakpoint region, while two had breakpoints outside this cluster region but within the region of the 7.5-kb SstI fragment containing the probe b sequence. In two patients, pFL-2 probe detected the bcl-2 gene rearrangements that occurred near or within the minor breakpoint cluster region. These ten patients had a rearranged JH-containing fragment that migrated with the rearranged bcl-2 fragment. In the other 20 patients, these two chromosome 18-specific DNA probes did not detect the bcl-2 rearrangements. Compared with studies performed in the United States, the statistical analysis indicates a significant difference in frequency of the bcl-2 gene rearrangements near or within the major breakpoint cluster region (P = 0.0027) and the minor breakpoint cluster region (P = 0.029). However, the distribution difference of these events was not significant.

Blotting, Southern↗
PubMed1989

An interindividual variability in the sensitivity of atrioventricular node to diltiazem in patients with paroxysmal supraventricular tachycardia.

To study the sensitivity of atrioventricular (AV) node to diltiazem in seven patients with paroxysmal supraventricular tachycardia (PSVT), we analyzed the plasma concentration-response relationship of this Ca-antagonist using AH interval as an index for assessing its Ca channel blocking effect on the AV node after an IV infusion (0.4 mg/kg). The postdose AH intervals were prolonged compared with the baseline, and their percentage changes correlated significantly (P less than 0.01) with log-diltiazem concentrations in all patients. However, drug concentrations associated with a 20% prolongation of AH interval differed considerably among the patients (range; 65 to 260 ng/ml), indicating a large interindividual variability in the sensitivity of AV node to diltiazem. These results suggest that the interindividual difference in the responsiveness of AV node to diltiazem-induced Ca channel blocking effect may be one of the possible explanations for the therapeutic failure of this Ca-antagonist for terminating PSVT or preventing its recurrences in certain patients.

Adult↗
PubMed1989

Cytogenetic studies on the adult T-cell leukemia in Japan.

Cytogenetic studies were performed on 16 patients with ATL seen in Northern Kyushu island; nine were patients with acute type leukemia, one with crisis type and five with lymphoma type. The serum antibody for HTLV-1 (ATLA) was positive in all patients and the phenotype of ATL cells were ERFC+, OKT3+, OKT4+, OKT6-, OKT8-, OKT10+, OKla1+/- and Tac+. Abnormal findings of chromosomes were observed in 15 patients. Thirteen patients were in near diploid range. One patient was in triploid range and one patient was in tetraploid range. The polyploid karyotypes were found only in lymphoma type patients. Trisomy 3 and trisomy 7 were observed each in three patients with acute type of ATL. The most frequent abnormal rearrangement was observed in the long arm of chromosome 6 and the break occurred at band 6q15 and 6q21 each in four patients in this series.

Acute Disease↗
PubMed1989

Immunohistochemical analysis of peripheral T-cell lymphoma in Japanese patients.

The authors immunohistochemically analyzed the phenotype of 40 cases of peripheral T-cell lymphoma, including 12 adult T-cell leukemia/lymphoma (ATL) cases. Molecular genetic analysis of the T-cell receptor beta-chain and immunoglobulin heavy chain genes were also applied to cases of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)-like lymphoma and so-called Lennert's lymphoma. Twenty non-ATL lymphomas expressed a helper/inducer phenotype, whereas only one extranodal case expressed a suppressor/cytotoxic phenotype. Three cases had a CD4-CD8- phenotype, and two cases a CD4+CD8+phenotype. No specific relationship between morphologic characteristics (LSG classification) and phenotype was found among non-ATL lymphomas. Six of eight AILD-like lymphomas had a helper/inducer phenotype. Monoclonality of neoplastic T-cells was demonstrated in six of the seven cases of AILD-like lymphoma by molecular genetic analysis. Two cases of Lennert's lymphoma also showed a helper/inducer phenotype and rearrangement of the T-cell receptor beta-chain gene. Serologically defined ATL cases had a helper/inducer phenotype except in one case that expressed both CD4 and CD8. None of the ATL cases had the CD7 antigen in this study using WT 1 as a CD7 antibody, which is in contrast with the non-ATL lymphomas in which 13 of 25 cases expressed CD7. CD25, strongly detectable in all ATL cases, was negative or weakly expressed in non-ATL lymphomas. These facts suggest that non-ATL and ATL are in the different biologic state, probably resulting from the integration of human T-cell leukemia virus type I (HTLV-I), although both are derived from helper/inducer T-cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Production of sterile transcripts of C gamma genes in an IgM-producing human neoplastic B cell line that switches to IgG-producing cells.

A human neoplastic B cell line SSK41 that expresses IgM on its surface switches spontaneously to IgG-producing cells. The SSK41 line contains a single immunoglobulin heavy-chain locus, the constant region (C) genes of which retain the germline configuration. The IgG-producing SSK41 line was purified by sorting, and shown to have undergone S-S recombination with deletion of the C mu gene. This line produced secretory and membrane-bound forms of gamma-chain mRNA. From cDNA libraries of a mixed population of IgM+/IgG+ SSK41 cells, we have isolated cDNA clones encoding the mature membrane-bound and secretory forms of the mu and gamma 1 heavy chains, all of which share the same variable region sequence. cDNA clones containing the mature gamma 3 chain were identified as well. We also isolated cDNA clones containing C gamma 1 and C gamma 3 sterile transcripts from the SSK41 line. These sterile transcripts contained additional exon sequences designated 'I' which were localized upstream of the C gamma 1 and C gamma 3 switch regions and homologous to murine counterparts. The I sequences were precisely spliced to the 5' ends of the corresponding C gamma exon sequences. These features of germline CH transcripts, i.e. the isotype specificity to class switching, location of exons, and sequences per se, are highly conserved between man and mouse.

Amino Acid Sequence↗
PubMed1988

Establishment of a peripheral T-cell lymphoma cell line showing amplification of the c-myc oncogene.

A new T-cell lymphoma cell line, designated T34, was established from freshly isolated lymph node tumor cells of a patient with non-Hodgkin's diffuse large cell lymphoma. The T34 cells, as well as the parental lymphoma cells, showed mature helper/inducer immunophenotypes in that they formed spontaneous sheep erythrocyte rosettes and reacted with OKT-3 and OKT-4 monoclonal antibodies. They were negative for OKT-6, OKT-8, terminal deoxynucleotidyl transferase, WT-1, and HLA-DR antigens. Molecular analysis revealed that the T34 cells contained 8- to 16-fold amplified c-myc DNA. The same genetic change was observed in parental lymphoma cells, indicating that the c-myc amplification had occurred in vivo. There was no gross rearrangement of the c-myc DNA. The c-myc gene of the T34 cell line was actively transcribed into normal-sized c-myc mRNA. Cytogenetic analysis showed that both the T34 and the parental lymphoma cells had a near-triploid karyotype with multiple structural chromosome changes. The terminal end of the long arm of chromosome No. 8, the chromosomal locus of single-copy c-myc, was elongated (8q+ chromosome), perhaps reflecting the site of c-myc amplification. These data suggested that amplification of the c-myc oncogene played some role in progression and proliferation of this peripheral T-cell neoplasm.

Aged↗
PubMed1988

Characterization and comparison of two newly established Epstein-Barr virus-negative lymphoma B-cell lines. Surface markers, growth characteristics, cytogenetics, and transplantability.

Two Epstein-Barr virus (EBV)-negative lymphoma B-cell lines, HBL-1 and HBL-2, were established from a pleural effusion and a lymph node biopsy of two patients with diffuse large cell lymphoma. HBL-1 and HBL-2 showed the characteristics of activated B-cells in B-cell lineage, as did original lymphoma cells. Chromosome analyses revealed that HBL-1 exhibiting 14q+ marker-positive lymphoid cancer showed a new subclass of 14q32 translocation resulting from a translocation between chromosomes 14 and 16, which had been masked in a complex translocation involving five chromosomes, and that HBL-2 had a 14q+ marker chromosome, the result of an 11;14 translocation [t(11;14)(q13;32)]. Successful heterotransplantation into athymic nude mice demonstrated tumorigenicity of HBL-1 and HBL-2. The transplantability and tumor growth rate of HBL-2 were higher and more rapid than those of HBL-1. HBL-1 and HBL-2 appear useful for facilitating therapeutic investigations as well as immunologic and oncogenic studies in B-cell lymphomas.

Aged↗
PubMed1988

Dispersed localization of D segments in the human immunoglobulin heavy-chain locus.

We have studied the organization of the human immunoglobulin heavy-chain genes by pulse field gel electrophoresis as well as by isolation of cosmid clones. The total length of the heavy-chain variable region locus was estimated to be approximately 3000 kb. We found that D segments including a recently isolated D5 segment were dispersed among VH segments. We identified a pseudo V segment 18 kb 3' to the D5 segment in isolated cosmid clones. A 300 kb fragment produced by MluI digestion contained VH, D, JH segments and the distance between VH and D was estimated to be approximately 240 kb. Overlapping cosmid clones containing the human D1, D2, D3, D4, JH, Cmu and C delta genes were isolated. Restriction maps of these regions indicated that the distance between D and JH is about 22 kb. A partial restriction map of the VH locus was constructed using the pulse field gel electrophoresis technique and deletion of VH segments in B cells.

Amino Acid Sequence↗
PubMed1988

Phenotypic conversion of T lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts. Molecular genetic evidence of the same clonal origin.

Acute biphenotypic leukemia composed of lymphoblasts and myeloblasts developed in a patient with T lymphoblastic lymphoma (T-LBL) who had an anterior mediastinal mass. A novel myeloid cell line, termed TK-1, has been established from his peripheral blood after the leukemic conversion. The identical rearranged pattern of T cell receptor gamma-chain gene was observed among the DNAs derived from lymph node cells in the lymphoma phase, the myeloid cell line TK-1, and the subclones with different karyotypes (TK-1B and TK-1D), which showed that myeloid cells had been derived from the T-LBL of the same patient. This finding demonstrates that phenotypic conversion occurs in the clonally propagating tumor cells and suggests that some hematopoietic cells retain the capacity to adopt either lineage.

Acute Disease↗
PubMed1988

Establishment and characterization of an Epstein-Barr virus negative B-cell lymphoma cell line and successful heterotransplantation.

An EBV-negative B-cell lymphoma cell line designated as HBL-1 was established from the pleural effusion of a patient with malignant lymphoma, diffuse, large cell. Surface marker studies revealed that HBL-1 cell possessed the same phenotypes of a mature B-cell as the original lymphoma cell from pleural effusion. HBL-1 closely resembled morphologically to the original lymphoma cells observed in the lymph node biopsy and pleural effusion. Chromosome analysis revealed that HBL-1 cells showed chromosomal aberrations of a 14q+ marker chromosome as the result of a translocation between chromosomes 14 and 16. Heterotransplantation to subcutaneous tissue of an athymic nude mouse has succeeded, but intraperitoneal heterotransplantation has failed. Tumors were localized in the subcutaneous tissues and no metastasis was found. This newly established cell line may facilitate immunological and oncogenic studies for human B-cell lymphomas.

Aged↗
PubMed1988

Leukemic cells from some adult T-cell leukemia patients proliferate in response to interleukin-4.

The proliferative response of fresh peripheral blood leukemic cells from eight adult T cell leukemia (ATL) patients to interleukin-4 (IL-4) was studied to determine the possibility that the IL-4-mediated T-cell growth pathway is involved in the cell growth of leukemic cells in ATL. Resting lymphocytes from ten normal individuals did not proliferate in response to IL-4. Leukemic cells from two ATL patients did not respond to interleukin-2 (IL-2) or IL-4. Leukemic cells from two patients did respond to IL-2, but not to IL-4. In contrast, a strong proliferative response was observed in the IL-4 culture, but not in the IL-2 culture in the remaining four patients. Chromosome analysis of mitotic cells, performed in one of four patients, confirmed that the cells dividing in response to IL-4 were leukemic cells, but not activated normal lymphocytes. These results indicate the activation of IL-4/IL-4 receptor system in leukemic cells from some ATL patients and suggest the possible involvement of the system in the proliferation of leukemic cells and the leukemogenesis in ATL.

Adult↗