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S Hirosawa

Publications and source records attributed to S Hirosawa.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Lymphomatoid granulomatosis (LYG) occurring in a patient with follicular lymphoma during remission].

A 49 years-old man presented with dry cough, low grade fever, and abnormal shadow on a chest X-ray. He had suffered from follicular lymphoma of the liver 5 years previously. He received irradiation therapy in combination with chemotherapy for approximately three years and had been in complete remission. Physical and radiological examination revealed pleural effusion and softly dense masses in the right lung. The laboratory data were within normal limits. He was diagnosed as having lymphomatoid granulomatosis (LYG) by open lung biopsy. The lung lesion was mainly infiltrated with T cells. The patient received prednisolone and the lung lesions disappeared. However, when a lung mass was noted two months later, he started to receive combination chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisolone every three months. He has not shown relapse of LYG so far. To investigate the association between the preceding follicular lymphoma and subsequent LYG at this time, DNA analysis using the PCR technique was carried out. The LYG lesion did not show a rearranged band for the JH probe, while the paraffin-embedded specimen of the preceding follicular lymphoma had shown rearranged band for the JH band. Southern blot analysis of the LYG lesion, showed no rearrangement for TCR beta, gamma or JH probe. These findings indicate that the LYG was different from the preceding follicular lymphoma in terms of origin. LYG is considered to be induced in the immunosuppressive state due to lymphoma.

Combined Modality Therapy↗
PubMed1990

Functional characterization of the 5'-regulatory region of human factor IX gene.

Functional characterization of the 5'-regulatory region of the human factor IX gene was carried out by a series of gene dissection analyses. The region extending from -175 to -274 of the 5' end flanking sequence is required for the expression of this gene. Within this region, sequence elements AGCCACT at -238 and TCAAAT at -187 were assigned as the functional CAAT box and TATA box, respectively. The transcription initiation site was found to be at -150 for the factor IX chloramphenicol acetyltransferase chimeric gene. A negative regulatory (silencer) activity was located in the region spanning from 1.4 to 1.7 kilobases upstream of the promoter region. This region contains a short sequence element (ATCCTCTCC) known to have such activity. A strong promoter on the opposite strand was also located about 500 base pairs upstream of the promoter. The expression of factor IX gene was highly liver specific, as assessed by Northern blot analysis. Short sequence elements (TGGACC and CTTTGGACT) homologous to the known liver-specific elements were located in the vicinity of the defined promoter region.

Base Sequence↗
PubMed1990

Structural and functional basis of the developmental regulation of human coagulation factor IX gene: factor IX Leyden.

Hemophilia B Leyden is characterized by unusual developmental regulation of factor IX synthesis in affected individuals. One family affected with the hemophilia B Leyden phenotype was found to have a specific single-base mutation (G----A) at nucleotide -6 of the factor IX gene. The mutation site was found in a small region of the 5'-untranslated sequence designated the Leyden-specific region (LS region). This region, approximately 40 base pairs in length, contains the unique mutation sites of all the known factor IX Leyden genes (five families) analyzed to date. This fact strongly suggests that the LS region is directly or indirectly involved in the developmental regulation of factor IX biosynthesis. Base changes at nucleotide -20 as well as at nucleotide -6 and deletions of the 3' half of the LS region reduced expression activity of the factor IX gene to approximately 15-31% that of the normal control, as assessed in a cultured cell (HepG2) expression system. The LS region binds at least two proteins. Androgen significantly increased the transcriptional activities of both mutant and normal factor IX genes in a concentration-dependent manner.

Aging↗
PubMed1989

Restriction fragment length polymorphism caused by a deletion involving Alu sequences within the human alpha 2-plasmin inhibitor gene.

A restriction fragment length polymorphism within the human alpha 2-plasmin inhibitor gene has been detected by Southern blot hybridization using an alpha 2-plasmin inhibitor cDNA probe. This restriction fragment length polymorphism can be attributed to the presence of two alleles, A and B, that are distributed in Hardy-Weinberg equilibrium with frequencies of 73.5% and 2.65%, respectively, in 66 unrelated Caucasian individuals or with frequencies of 51.0% and 49.0%, respectively, in 50 unrelated Japanese individuals. The minor allele, B, is due to a deletion of about 720 base pairs in intron 8 of the alpha 2-plasmin inhibitor gene. Sequence analysis of the deletion junction in allele B and the corresponding regions of allele A demonstrated the presence of oppositely oriented Alu sequences at the 5' and 3' deletion boundaries. These data suggest that this restriction fragment length polymorphism was caused by intrastrand recombination between Alu sequences.

Alleles↗
PubMed1989

Molecular basis for congenital deficiency of alpha 2-plasmin inhibitor. A frameshift mutation leading to elongation of the deduced amino acid sequence.

The present study was designed to elucidate the molecular genetic basis of a familial deficiency of alpha 2-plasmin inhibitor (alpha 2PI). Southern blot hybridization analysis with human alpha 2PI cDNA and genomic DNA probes demonstrated no gross deletion or rearrangement of the gene. By sequencing all the coding exons and exon-intron boundaries of the gene of a homozygote, we identified a single cytidine nucleotide insertion in the exon coding for the carboxyl-terminal region. This frameshift mutation leads to an alteration and elongation of the carboxyl-terminal portion of the deduced amino acid sequence. Synthetic oligonucleotide probes confirmed this frameshift mutation in all the affected family members including both heterozygous parents. In a transient expression assay, the alpha 2PI level in the culture medium of the cells transfected with the mutated alpha 2PI expression vector was very low and only 4% of that of the cells transfected with the normal vector, although the transcript levels and the cellular contents of alpha 2PIs did not differ significantly. Elongation of amino acid sequence in the mutant alpha 2PI was confirmed by an analysis of alpha 2PI in a transient expression experiment. These data indicate that this mutation is the cause of alpha 2PI deficiency in this pedigree.

Amino Acid Sequence↗
PubMed1989

[CD8+ agranular lymphocyte proliferative disorder with T-cell receptor beta-chain gene rearrangement associated with thymoma and neutropenia].

A 58-year-old male with a 10-years history of thymoma was admitted to our hospital because of the respiratory infection. Hepatosplenomegaly and systemic lymphadenopathy were revealed on physical examination. Chest roentgenogram showed a large anterior mediastinal tumor and a right pleural effusion. Blood examination showed Hb 11.5 g/dl, leucocyte count 1,600/microliters (1% neutrophils, 34% monocytes, 65% lymphocytes) and platelet count 11.2 x 10(4)/microliters. The lymphocytes in the peripheral blood and pleural fluid were mostly small agranular mature lymphocytes and CD2+ 3+ 4- 8+. A monoclonal rearrangement of TCR beta chain gene was found using Southern blot analysis of the lymphocytes in the peripheral blood and pleural fluid. The CFU-GM colony formation by bone marrow cells was normal, and not suppressed by the patient's serum or peripheral blood lymphocytes. Neutrophil-associated IgG was increased with a direct immunofluorescence test. Serum IgG level was slightly decreased. Radiation therapy for thymoma exerted no effect. Treatment with prednisolone 60 mg daily resulted in complete disappearance of the pleural effusion and partial improvement of hepatosplenomegaly, thymoma and neutropenia. Histological examination of the thymoma revealed predominantly spindle cell type. He is still in good condition 21 months after diagnosis. This case seems to represent neoplastic proliferation of mature CD8+ T cells associated with thymoma.

Agranulocytosis↗
PubMed1988

Undetectable bcr-abl rearrangements in some CML patients are due to a deletion mutation in the bcr gene.

Most patients with chronic myelogenous leukemia (CML) have Philadelphia (Ph) chromosome. Breakpoints on chromosome 22 in CML occur in a small region designated as the breakpoint cluster region (bcr). More than 90 percent of CML patients have breakpoints in the bcr; the remaining patients had no detectable rearrangement. In our study, a commercially available 1.2 kb HindIII-BglII (1.2 HBg) bcr probe was used to locate breakpoints in the bcr, which were found in 22 of 24 patients. Furthermore, using a probe upstream from the 1.2 HBg probe, rearranged bands were clearly detected in the two patients in whom no extra bands had been found with the 1.2 HBg probe. These results strongly suggest that these two patients carry a deletion at the acr-abl recombination point encompassing the area of the 1.2 HBg probe. Therefore, in our series, all CML patients eventually had breakpoints in the bcr, and the involvement of rearrangement was demonstrated to be highly specific for CML. Our data indicate that hybridization of CML cellular DNA with several bcr probes is important in examining accurately the frequency of bcr-abl rearrangements in CML, as some cases contain a deletion within the region.

Chromosome Aberrations↗
PubMed1988

Organization of the human alpha 2-plasmin inhibitor gene.

We have isolated overlapping phage genomic clones covering an area of 26 kilobases that encodes the human alpha 2-plasmin inhibitor. The alpha 2-plasmin inhibitor gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA. To our knowledge, the number of introns is the highest yet reported for a member of the serine protease inhibitor (serpin) superfamily. All introns are located in the 5'-half of the corresponding mRNA. The 5'-untranslated region and the leader sequence are interrupted by 3 introns totaling approximately equal to 6 kilobases. A "TATA box" sequence is located 17 nucleotides upstream from the proposed transcription initiation site. Multiple "GC box" sequences, G + C-rich sequences, and "CCAAT box"-like sequence, the hepatitis B virus enhancer element-like sequence and the human immunodeficiency virus enhancer-like sequence appear in the 5'-flanking region. The NH2-terminal region, which implements factor XIII-catalyzed cross-linking of alpha 2-plasmin inhibitor to fibrin, is encoded by the 4th exon. The reactive site and plasminogen-binding site, both located in the COOH-terminal region, are encoded by the 10th exon. When similar amino acids of alpha 2-plasmin inhibitor and other members of the serpin gene superfamily are aligned, the position of the 7th intron of the alpha 2-plasmin inhibitor gene aligns precisely with that of the second intron of the genes for rat angiotensinogen and human alpha 1-antitrypsin genes and is misaligned by only one nucleotide with that of the third intron of antithrombin III, suggesting that the alpha 2-plasmin inhibitor gene originates from the common ancestor of these serine protease inhibitors.

Amino Acid Sequence↗
PubMed1988

Human genes for complement components C1r and C1s in a close tail-to-tail arrangement.

Complementary DNA clones for human C1s were isolated from cDNA libraries that were prepared with poly(A)+ RNAs of human liver and HepG2 cells. A clone with the largest cDNA insert of 2664 base pairs (bp) was analyzed for its complete nucleotide sequence. It contained 202 bp of a 5' untranslated region, 45 bp of coding for a signal peptide (15 amino acid residues), 2019 bp for complement component C1s zymogen (673 amino acid residues), 378 bp for a 3' untranslated region, a stop codon, and 17 bp of a poly(A) tail. The amino acid sequence of C1s was 40.5% identical to that of C1r, with excellent matches of tentative disulfide bond locations conserving the overall domain structure of C1r. DNA blotting and sequencing analyses of genomic DNA and of an isolated genomic DNA clone clearly showed that the human genes for C1r and C1s are closely located in a "tail-to-tail" arrangement at a distance of about 9.5 kilobases. Furthermore, RNA blot analyses showed that both C1r and C1s genes are primarily expressed in liver, whereas most other tissues expressed both C1r and C1s genes at much lower levels (less than 10% of that in liver). Multiple molecular sizes of specific mRNAs were observed in the RNA blot analyses for both C1r and C1s, indicating that alternative RNA processing(s), likely an alternative polyadenylylation, might take place for both genes.

Amino Acid Sequence↗
PubMed1987

A variant Burkitt-type translocation (2p-;8q+) in a patient with diffuse large cell lymphoma.

A case of diffuse large cell lymphoma with t(2p-;8q+) is reported. Immunologically the lymphoma cells were shown to be of B-cell origin and positive for surface gamma and kappa chains, B4, CALLA, and Ia1 markers. Karyotypically three major clones were detected: 47,XX, + 12,t(2;8)(p11-13;q24) (52%); 47,XX, + 12 (26%); and 46,XX,t(2;8)(p11-13;q24) (15%). A t(2p-;8q +) has been exclusively reported in cases of Burkitt's lymphoma or Burkitt-type acute lymphocytic leukemia. The present case is the first one with t(2p-;8q +) observed in non-Burkitt-type lymphoid malignancy of the B-cell lineage. The t(2p-;8q +) may play a primary role in the early stage of transformation of B cells, and trisomy 12 may provide them secondarily with an advantage for tumor progression. The phenotypic pictures provided by 8q24 rearrangements seem to be heterogeneous, as previously suggested.

Adult↗
PubMed1987

Breakpoints in Philadelphia chromosome (Ph1)-positive leukemias.

We studied chromosome 22 breakpoints in 24 Philadelphia (Ph1)-positive leukemias. Nineteen of 21 patients with chronic myelogenous leukemia (CML) possessed a chromosomal break within the 5.8 kilobase (kb) breakpoint cluster region (bcr). Furthermore, in one of three cases of acute lymphocytic leukemia (ALL), we found a chromosomal rearrangement in the bcr locus. No chromosomal rearrangements were found in two cases of CML and two cases of ALL using several restriction enzymes. The bcr rearrangement is highly specific for CML. Further analyses will be necessary to determine whether some cases without bcr rearrangement have another specific locus of rearrangement. Two of three cases of CML with blastic crisis had rearrangement of the immunoglobulin gene and T-cell receptor gene. One CML patient with blastic crisis, who achieved complete remission but relapsed thereafter, was found to have the same immunoglobulin gene rearrangement in the blastic crisis and relapse phases, suggesting that the same clone was involved in both crisis and relapse.

Bacterial Proteins↗
PubMed1984

Flow cytometric analysis of deoxyribonucleic acid (DNA) content in adult leukemia.

Flow cytometric analysis of the bone marrow cellular DNA content was performed in 40 adult patients with acute leukemia. Twenty-eight had AML (29 previously untreated and 9 relapse) and 12 ALL (8 previously untreated and 4 relapse). For the whole series, the mean G1/0-phase compartment was 82 +/- 1.3%, the mean S-phase compartment 14 +/- 1%, and the mean G2 +M-phase compartment 4 +/- 0.7%. The percentage of cells in the S-phase had a positive correlation with the LDH level, but not with other parameters. Patients at relapse had significantly lower percentages of cells in the S-phase in AML and significantly higher in ALL. The changes of the S-phase size of the same patients at the first and relapse phases varied. Patients who obtained complete remission had significantly higher percent S phase than patients who did not. This difference was more significant in ALL. Percent cytoreduction had no correlation with the remission rate or S-phase size. Therefore, we analyzed changes of cells in the S-phase of patients with untreated AML during chemotherapy. The reduction rate of cells in the S-phase of patients who obtained complete remission was significantly higher than that of patients who did not.

Adolescent↗