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M Masuya

Publications and source records attributed to M Masuya.

At least 37 records · Page 2Linked to original sources

Detection and geometric modeling of molecular surfaces and cavities using digital mathematical morphological operations.

We developed a digital method based on mathematical morphological operations to obtain three types of surfaces: van der Waals surface, solvent-accessible surface, and molecular surface, to extract the cavities on the surface and interior part of the molecule and to extract the ligand portions in contact with the cavities. The molecular surface, the cavities and the portions, and the heme region are visualized using solid modeling. The method enables us to obtain the volumes of the cavities and inhibitor portions and the areas of the surfaces. Solid modeling enables us to obtain cross-sections at arbitrary positions. This will have considerable utility in docking studies.

Computer Graphics↗

Non-Hodgkin's lymphomas with chromosomal translocations involving 3q27 band and immunoglobulin gene loci: report of two cases.

Two cases of non-Hodgkin's lymphoma (NHL) of B-cell origin with reciprocal chromosome translocations involving the 3q27 band and loci for the immunoglobulin genes are described. In case 1, [t(3;14)(q27;q32)], the 14q32 band for the immunoglobulin heavy chain gene was involved, and in case 2, [t(3;22)(q27;q11)], the reciprocal breakpoint was the 22q11 band where the immunoglobulin lambda light chain gene is located. Although the two patients shared some clinical features, the lymphomas varied in histologic phenotypes; in case 1, the lymphoma being a diffuse large cell subtype, whereas in case 2, the lymphoma being the high grade small noncleaved cell lymphoma. Thus, the consistent association of the 3q27 translocation with a specific subtype of NHL remains to be determined. Southern blot analysis of the lymphoma cells from the two patients showed rearrangements and deletions in immunoglobulin genes with features which cannot be explained by normal immunoglobulin-generating mechanisms and which suggest that the translocations involved these loci at the molecular level. Cloning of the breakpoint using DNA probes from the immunoglobulin genes would prove a novel oncogene at the 3q27 band.

Adult↗

Biologic characteristics of acute leukemia after myelodysplastic syndrome.

Ten patients with acute leukemia after primary myelodysplastic syndrome (MDS-AL) were examined to clarify the biologic nature of the leukemic cells in comparison with that of de novo acute myelocytic leukemia (AML). The morphologic and cytochemical features of the leukemic cells from all these patients corresponded well to those of de novo AML, and they were diagnosed with MDS-AML. Phenotypically, the frequent expression of the lymphocyte activation antigens, CD25 and CD30, was characteristic in MDS-AML. The in vitro response of MDS-AML cells to various growth factors was similar to that of de novo AML cells. Transforming growth factor beta 1 (TGF beta 1) suppressed growth factor-dependent colony formation by normal bone marrow cells, MDS bone marrow cells, and de novo AML cells, but did not inhibit colony formation by MDS-AML cells. The number of TGF beta 1 high-affinity binding sites of MDS-AML samples (< 5 to 47 sites/cell) was markedly lower than that in de novo AML samples (120 to 221 sites/cell). Our results indicate that the reduced TGF beta 1 may represent disregulation of the proliferation system in MDS-AML cells. This is thought to occur during the MDS phase, and may be related to the poorer response shown to conventional chemotherapy of AML.

Adult↗

Acute lymphoblastic leukemia associated with a t(1;19)(q23;p13) in an adult.

A cytogenetic study of a 38-year-old patient with acute lymphoblastic leukemia (ALL) revealed a t(1;19)(q23;p13), which is a characteristic translocation of childhood ALL. The leukemic cells were positive for the CD10, CD19, HLA-DR, TdT and cytoplasmic mu-chain. Both of the immunoglobulin heavy chain gene loci were rearranged and the RNA-based polymerase chain reaction demonstrated the E2A/PBX1 fusion transcript which is the result of the t(1;19). This finding suggests that the t(1;19) is implicated not only in childhood ALL but also in adult ALL patients.

Adult↗

Cellular characteristics of chronic myelocytic leukemia basophilic crisis cells: phenotype, responsiveness to and receptor gene expression for various kinds of growth factors and cytokines.

Leukemic cells from a patient with chronic myelocytic leukemia (CML) basophilic crisis were examined in an in vitro clonogenic assay using recombinant human hematopoietic growth factors to elucidate the proliferative and differentiative behaviors. More than 90% of the leukemic cells showed the morphologic characteristics of basophils and were positive for CD11b and CD13. The phenotype of the leukemic cells was different from that of mast cells. In the clonogenic assay using various recombinant growth factors, the leukemic cells were responsive to interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not to granulocyte-CSF (G-CSF), erythropoietin (Epo), or IL-4. IL-5 showed synergistic effects on colony formations induced by both IL-3 and GM-CSF. Transcripts of the GM-CSF receptor alpha chain gene were detected in the leukemic cells, but transcripts of the IL-4 receptor gene were not. Furthermore, c-kit and IL-7 receptor genes were expressed in the leukemic cells. Our results suggest that the differentiation pathway of basophils is different from that of mast cells, even though the receptor gene for stem cell factor (c-kit) was expressed on the basophilic leukemic cells, as it was on mast cells.

Antigens, CD↗

Phenotypical characteristics of acute myelocytic leukemia associated with the t(8;21)(q22;q22) chromosomal abnormality: frequent expression of immature B-cell antigen CD19 together with stem cell antigen CD34.

Twenty-three acute myelocytic leukemia (AML) patients with t(8;21) chromosomal abnormality, all classified as M2 (French-American-British [FAB] classification), were investigated. Blastic cells from all patients were positive for the stem cell-associated antigens, CD34 and HLA-DR, and the immature myeloid antigens, CD13 and CD33. The nonblastic leukemic cells expressed the more mature myeloid antigens, CD11b and CD15, with loss of the immature phenotype. The incidence of positivities for the stem cell-associated antigens, CD34 and HLA-DR, in t(8;21) AML cells was significantly higher in comparison with those in other AML showing granulocytic differentiation (M2 or M3). AML cells with t(8;21) also showed some phenotypic abnormalities. Frequent expression of CD19 was found in the blastic population of t(8;21) AML (18 of 23 cases) without other B-cell antigens and Ig gene rearrangements. CD19 expression was confirmed by immunocytochemistry and Northern blotting. The CD19+ blastic cells coexpressed both CD34 and HLA-DR. In addition, CD33+ cells among the blastic fraction in t(8;21) AML cells were fewer in number than in those of M2 or M3 AML without t(8;21). Our findings indicate that leukemic blasts of t(8;21) AML commonly express CD19 while preserving the stem cell-associated antigens, and differentiate into the granulocytic pathway with discordant maturation such as low CD33 expression.

Adult↗

Structural alterations of the p53 gene in human leukemias.

We have investigated alterations of the p53 gene in human leukemias by polymerase chain reaction-mediated restriction fragment length polymorphism analysis. This method detects the codon 72 polymorphism of the p53 gene, allowing identification of loss of heterozygosity (LOH) of the p53 gene. In this study, at least two specimens were obtained from each patient to compare the allele status at different points of clinical course. Of 21 cases examined 7 were heterozygous at this polymorphic site and were evaluable for LOH study. Only one patient of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) lost the heterozygosity in the specimen of her last relapse. Leukemic cells from her repeated relapses including the last one revealed to have the clonally rearranged immunoglobulin H chain gene of the same size, indicating that alteration of the p53 gene in this patient might account for the lethal relapse as a clonal evolution event. Northern-blot analysis of the p53 gene showed that one case of CD7(+) ALL had altered p53 mRNA. Overall, it is demonstrated that alterations of the p53 gene might be involved in the pathogenesis or progression of at least some human leukemias, although the alterations in leukemias seemed to be not as frequent as in solid tumors.

Base Sequence↗

c-kit gene expression in CD7-positive acute lymphoblastic leukemia: close correlation with expression of myeloid-associated antigen CD13.

Expression of human c-kit proto-oncogene and interleukin-7 receptor (IL-7R) in acute lymphoblastic leukemia (ALL) cells expressing CD7 was examined by Northern-blot analysis and reversed transcription polymerase chain reaction (RT-PCR) assay in relation to the phenotypes. Leukemic cells from four out of 12 CD7+ ALL patients, all of which fulfilled the criteria of ALL in the FAB classification, expressed c-kit genes. Surface CD3 (sCD3) was absent in all of these cases, while cytoplasmic CD3 (cCD3) was found in the two sCD3- cases. CD3 epsilon transcripts were detected in one of the sCD3- cCD3- cases. IL-7R genes were transcribed in the three cases with c-kit gene expression. In addition, there was a good correlation between c-kit gene expression and myeloid associated antigen CD13 positivity of the leukemic cells. None of the patients with c-kit gene expression had mediastinal tumor. Our results show that leukemic cells in a proportion of CD7+ ALL express receptors for cytokines that are secreted by bone marrow stromal cells. Ligands for c-kit genes and IL-7 could play an important role for the regulation of proliferation and differentiation of T-cell progenitors in bone marrow.

Antigens, CD↗

Rearrangement patterns of immunoglobulin heavy chain (IgH) and light chain genes in acute lymphoblastic leukemia and chronic myelocytic leukemia lymphoid crisis cells showing oligoclonal IgH gene rearrangements.

We investigated leukemic cells with multiple immunoglobulin heavy chain (IgH) gene rearrangements from nine B-precursor cell acute lymphoblastic leukemia (ALL) patients and three chronic myelocytic leukemia lymphoid crisis (CML.Ly-BC) patients in order to determine detailed recombination patterns of the variable (V), diversity (D), and joining (J) region genes. Southern blot study, using DNA probes for DQ52 and 5'D region genes, was useful to distinguish VDJ recombination from DJ recombination at the level of each allele. Leukemic cells from seven out of eight CD10-positive ALL patients showed biallelic VDJ recombinations. Rearrangements of Ig kappa genes were found in only one case. Leukemic cells from all of the CML.Ly-BC patients had a DJ/(V)DJ IgH genotype. These findings suggest that the multiple IgH gene rearrangements in B-precursor cell ALL occurred as a consequence of continuing V-(V)DJ rearrangements after neoplastic transformation, and were closely related to the stage of bone marrow B-precursor cell differentiation. Multiple IgH gene rearrangements in CML.Ly-BC might take place earlier in the process of IgH gene rearrangements than is the case in B-precursor cell ALL. In this sense, the genotypic oligoclonality observed in ALL and CML.Ly-BC should be regarded not as 'true', but as 'pseudo' oligoclonal leukemia.

Blast Crisis↗

[Molecular diagnosis of leukemia and lymphoma].

Diagnosis of leukemia and lymphoma has been made by morphological, cytochemical, and immunophenotypical methods. Recently molecular biological approaches have been introduced to clarify the cellular lineage of the tumor cells and to demonstrate the monoclonality. Southern blot analysis using immunoglobulin (Ig) and T cell receptor (TcR) genes revealed the presence of monoclonal components in some cases of angioimmunoblastic lymphadenopathy (AILD), in which demonstration of monoclonality was difficult by conventional methods. In preB-ALL, many cases had rearranged IgH and TcR genes simultaneously. These "dual genotype" cases were found to be of accidental involvement of TcR gene in the process of making effective IgH gene rearrangements by the precise analysis of rearranged IgH gene structures. The rearranged TcR gene which was detected in initial lymphoblastic lymphoma cells, was observed in relapsed blasts after lineage conversion to myeloid leukemia, which indicates the same clonal origin. Diagnosis and detection of minimal residual disease by the polymerase chain reaction (PCR) are now recognized as sensitive methods. PCR using oligonucleotides common to each VH and JH gene detects the rearranged IgH gene sensitively. PCR using primers located on the translocation boundary, such as bcr and abl in CML, is very useful in the diagnosis and pursuit of the disease course. PCR study also can be applied to the detection of alteration of some particular genes such as tumor suppressor genes.

Base Sequence↗

[Immunegene rearrangements of acute undifferentiated leukemia (AUL)].

Acute unclassified/undifferentiated leukemia (AUL) is classified into following 3 subgroups; 1) cases with coexpression of myeloid and lymphoid antigens on a single blast, 2) cases with coexistence of heterogenous subpopulations, 3) cases showing lineage-switch during the clinical course. Most cases in the groups 2 and 3 were not different from those in group 1 because of the presence of one or more common antigen (s) on the blasts. Accordingly, AUL can be considered as a candidate of leukemia arising form multipotential stem cells and the phenotype and genotype are represent a potential for myeloid and lymphoid differentiation. We should recognize that dual genotypes of IgH and TCR genes in B-precursor cell leukemia differ from such multipotentiality of leukemic cells, because the genotype occurs in re-arrangement process for IgH gene diversity after malignant transformation.

Acute Disease↗

[The changes in von Willebrand factor multimer in a course of thrombotic thrombocytopenic purpura].

A 51 year-old woman with severe thrombocytopenia, hemolytic anemia, renal failure and loss of consciousness, and significant decrease in plasma large multimer of von Willebrand Factor (vWF) was diagnosed as having thrombotic thrombocytopenic purpura (TTP). She was treated with plasma exchange, anti-platelet agents and steroids. Although she showed temporary improvement and return of vWF multimer to a normal level, her symptoms reappeared, vWF large multimer level showed a remarkable increase, and she died because of pulmonary bleeding. It would be important that the vWF multimer bands changed in the course of TTP.

Female↗

[Syncytial variant of nodular sclerosing Hodgkin's disease expressing T-cell antigens].

A case of syncytial variant of nodular sclerosing Hodgkin's disease in a 34-year-old woman is reported. Histologically, numerous Reed-Sternberg (RS) cells and their variants were seen in sheets. They were positive for CD30, CD15, CD25, and HLA-DR antigens. In addition, they expressed CD45 antigen and T-cell antigens (CD2, CD4). Molecular genetic analysis showed that this case had a germ line configuration for T-cell receptor (TCR) beta chain, TCR gamma chain, and immunoglobulin heavy chain genes. The percentage of the neoplastic cells in the specimen identified by CD30 positive cells was about 20% which was far above sensitivity of the molecular genetic analysis. Such analysis is reliable as to judgement of the results. Thus, these findings suggest that the RS cells and their variants in the present case are not derived from mature T cell in spite of their T-cell antigens expression.

Adult↗

[Clinical analysis on thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, with plasma level of cytokine].

We studied 10 patients with thrombotic thrombocytopenic purpura (TTP) and 5 patients with hemolytic uremic syndrome (HUS). Common cold symptoms were observed in 2 with TTP and 3 with HUS, and SLE was noted or suspected in 3 with TTP, and the onset was after operation in on with TTP and one with HUS. All TTP patients had coma and high fever. Renal failure was noted in 3 with TTP and their prognosis was poor. Seven patients with TTP and 4 patients with HUS survived. Autoantibody was highly positive in TTP but slightly positive in HUS. High molecular weight multimer of von Willebrand factor was decreased in 3 of 6 with TTP, platelet aggregating factor was positive in 4 of 6 with TTP, and microthrombus was observed in 7 of 8 with TTP. Tumor necrosis factor was increased in 5 of 9 with TTP and HUS, Interleukin-1 beta was increased in all TTP and HUS patients, and soluble interleukin 2 receptor and interferon alpha were also increased. Although plasma exchange was generally effective, some patients required combination therapy with steroids. We speculated that an autoimmune mechanism was involved in the on onset of TTP.

Adolescent↗

[Burkitt's lymphoma of the stomach associated with macroglobulinemia].

We report a 35-year-old male with leukemic change and gastric involvement of Burkitt's lymphoma. A monoclonal immunoglobulin (Ig), IgM-kappa, was detected in the serum by means of immunoelectrophoresis. Immunophenotypical analysis showed that the neoplastic cells were CD20+, OKIal+, CD10-, CD21-, surface Ig+ (M-kappa), and cytoplasmic Ig-. The neoplastic cells did not secret Ig by using of protein A plaque forming cell assay. Active transcription of Ig heavy chain genes was not detected by cell dot analysis of the neoplastic cells. These findings support the possibility that the presence of the monoclonal Ig in the serum does not result from secretion of Ig from the neoplastic cells. The shedding of surface Ig from the neoplastic cells might result in the occurrence of monoclonal Ig in the serum.

Adult↗

Intensive chemotherapy followed by autologous bone marrow transplantation for a patient having wide-spread embryonal carcinoma in the central nervous system.

A patient with an intracranial embryonal carcinoma, which was resistant to cisplatin-based combined chemotherapy and radiotherapy, developed spinal seeding. Alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) and the beta chain of HCG (NCG beta) in serum or cerebrospinal fluid immediately returned to elevated levels despite sequential chemotherapy and resection. Accordingly, we treated this patient with spinal irradiation and intensive combination chemotherapy (cisplatin etoposide, vinblastine, cyclophosphamide and actinomycin D) followed by autologous bone marrow transplantation. With this treatment, the clinical manifestations showed a tendency to improve and, furthermore, the serum levels of AFP and HCG returned to normal. These findings suggest autologous bone marrow transplantation to be a potential approach to the treatment of patients with embryonal carcinomas.

Adult↗