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Biomedical subjects

M Omine

Publications and source records attributed to M Omine.

At least 37 records · Page 2Linked to original sources
PubMed1998

Expression analysis of human Rhesus blood group antigens by gene transduction into erythroid and non-erythroid cells.

Rh blood group antigens are associated with non-glycosylated human erythrocyte membrane proteins encoded by two closely related genes, RHCE and RHD, and with a glycoprotein, a critical co-expressing factor encoded by the RH50 gene. The sequence analysis of RHCE transcripts has revealed that RhE/e and C/c serological phenotypes are associated with a nucleotide substitution in exon 5 and six substitutions in exons 1 and 2 of RHCE gene, respectively. Smythe et al. have shown that the full length transcript of RhcE gene expressed c and E antigens and the transcript of RhD gene expressed D and G antigens, using retroviral-mediated gene transduction into K562 cells. We performed an epitope analysis of Rh antigen by constructing retroviral gene coding six RH cDNAs, which contain RhcE, ce, CE and D cDNAs, and CE-D, D-CE chimera cDNAs. The cDNAs were introduced into KU812E cells and the expressed antigens were analyzed by flow cytometry. These studies revealed that the C/c and E/e associated substitutions actually participated in respective polymorphic epitopes. However, the C antigen was not detected on the KU812E cells introduced with CE cDNA, despite E antigen being expressed. The study with the chimera gene between CE and D cDNAs also indicated that the Rh epitopes were not constructed with short polymorphic exofacial peptide loops only but also with other peptide fragments and membrane components. Co-expression studies of Rh50 and RhD or cE gene in non-erythroid cells, 293, and expression studies of Rh50 in another erythroid cell, HEL, did not show any Rh antigens on the transduced cells, despite the Northern blot study showing both transcripts in the cells. It was suggested that at least a second co-expressing factor was needed to express RhCE or D antigens on the plasma membrane.

Cell Line↗
PubMed1998

Immunoblastic lymphadenopathy-like T cell lymphoma evolving into a massive plasma cell proliferation with biclonal paraproteinemia.

We present a case of immunoblastic lymphadenopathy-like T cell lymphoma (IBL-T) who subsequently developed a massive proliferation of plasma cells. At diagnosis of IBL-T, the patient had polyclonal hypergammaglobulinemia and subsequently, while on chemotherapy, developed paraproteinemia with biclonal peaks and the IBL-T lesion was replaced with a massive proliferation of CD38-positive plasma cells. The evolution was not likely to be attributed to a new neoplastic proliferation of B cells. It appeared that two B cell clones possibly had a growth advantage among the polyclonal B cells due to a depletion of suppressor T cells or to a disturbance in the immune system.

ADP-ribosyl Cyclase↗
PubMed1997

Coagulation patterns of disseminated intravascular coagulation in acute promyelocytic leukemia.

Coagulation patterns of 19 newly-diagnosed acute promyelocytic leukemia (APL) patients with disseminated intravascular coagulation (DIC) at presentation were studied. Seventeen patients had hemorrhagic complications, of which four were fatal. Fatal hemorrhages were related with lower fibrinogen level and lower platelet count. DIC of the APL patients without infection was characterized by low fibrinogen and normal antithrombin III (ATIII) level. Thrombin-ATIII complex level was elevated in all patients examined. Patients with infection had higher fibrinogen levels than those without infection and some patients had reduced ATIII level. Ten remission inductions were tried with multidrug chemotherapy and seven with all-trans retinoic acid (ATRA). Complete remission was achieved in seven of ten inductions with chemotherapy and in all seven inductions with ATRA. Two patients treated with chemotherapy had fatal hemorrhage after starting therapy but none treated with ATRA.

Adolescent↗
PubMed1997

Case report: primary hepatic lymphoma associated with chronic liver disease.

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle-aged males. Presenting symptoms and physical findings were non-specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

Adult↗
PubMed1997

[All-trans retinoic acid-induced myelomonocytoid differentiation in acute promyelocytic leukemia].

A 30-year-old man with a diagnosis of acute promyelocytic leukemia (APL) was admitted. Laboratory findings were as follows: WBC 32,900/microliter with 88% promyelocytes, Hb 10.4 g/dl, platelets 2.6 x 10(4)/microliter. Coagulation tests revealed DIC. Bone marrow was hypercellular with 91.8% promyelocytes which were strongly positive for peroxidase and positive for alpha-naphthyl butyrate esterase. Cytogenetic study revealed 46, XY, t(15;17) (q22:q11). He was treated with all-trans retinoic acid (ATRA) along with hydroxyurea (HU) and low-molecular weight heparin (LMH). Because his WBC increased to 93,700/microliter on day 6 of ATRA therapy, DCMP chemotherapy was given, while ATRA was withheld. He developed enterocolitis due to myelosuppression. ATRA was restarted along with granulocyte-colony stimulating factor (G-CSF). His WBC rose to 10,400/microliter with a marked, but temporary predominance of myelomonocytes both in peripheral blood and in bone marrow. These myelomonocytoid cells were positive for specific and nonspecific esterase double stainings. Then he entered complete remission. It was of interest that myelomonocytoid differentiation of APL cells was induced by ATRA. The etiology was discussed.

Adult↗
PubMed1997

[Blast crisis accompanied by severe DIC of Ph negative chronic myeloid leukemia showing t(9;16) and positive M-BCR/ABL rearrangement].

A 66-year-old woman complained of chest discomfort in January 1995. In March the accelerated phase of chronic myeloid leukemia (CML) was diagnosed. Chromosomal analysis demonstrated negative Ph and positive t(9;16) (q34;p11) with positive major BCR/ABL chimeric mRNA. Administration of hydroxycarbamide was initiated, but in May she developed high fever and severe left hypochondralgia. Her WBC was 62,100/microliter (blast 64%), and LDH was 3,590 IU/l. Bone marrow examination showed 78.6% blasts, with a nucleated cell count of 74 x 10(3)/microliter. Blasts were negative for esterase stain and partially positive for both peroxidase stain and PAS reaction. Surface marker analysis revealed that blasts were positive for CD13, CD19, CD33, CD34, and HLA-DR. A diagnosis of blast crisis was made and she was treated with the VDS-CP regimen with heparin for DIC. After temporary improvement her disease recurred rapidly with severe DIC. Treatment with low molecular weight heparin and fresh frozen plasma failed to control DIC and she died of subarachnoid hemorrhage on the 48th hospital day. This is the first veprted of case Ph-negative, M-BCR/ABL-positive CML with t(9;16) accompanied by severe DIC.

Aged↗
PubMed1996

A novel quantitative 'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias.

Telomerase activation is important for carcinogenesis. However, the timing and magnitude of the activation during cancer development are unknown. In this study, a new PCR-based method for measuring telomerase activity was developed and shown to be very useful for quantitative analysis of human telomerase. Using this assay, blood or bone marrow cells from healthy donors, and patients with chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) were examined as to their relative activity. Telomerase activity present in normal peripheral blood cells was generally very low. However, significant activity was detected occasionally in samples derived from younger healthy donors. Striking telomerase activation was observed at the time of the blastic crisis in CML: no samples from chronic phase cases showed significant activity, while all cases with a well established crisis showed strong activity. Most AML cases were telomerase-positive. Quantitative analyses revealed that the relative titer varied among the AML patients, from as low as found in normal cells to as high as found in cell lines. However, a tendency that the activity was higher in relapsed cases than in fresh ones was suggested. In summary, telomerase was activated during the progression of the clinical stages in leukemias. This observation suggests that shortened telomeres and increased telomerase activity might be necessary for cancer cells to undergo clonal evolution towards more malignant phenotypes in advanced stages.

Adult↗
PubMed1996

The majority of T lymphocytes are polyclonal during the chronic phase of chronic myelogenous leukemia.

To clarify the extent of cell lineage involvement in chronic myelogenous leukemia (CML), we investigated the bcr gene rearrangement and clonality using the X-chromosome-linked restriction fragment length polymorphism (RFLP) methylation method in T lymphocytes and granulocytes. We examined the granulocyte and T-cell fractions from the peripheral blood of seven female patients with CML during the chronic phase; patients were heterozygous for RFLPs at the phosphoglycerate kinase (PGK) or the hypoxanthine phosphoribosyltransferase (HPRT) gene. RFLP-methylation analysis of granulocytes demonstrated a monoclonal pattern in six of the seven patients and a rearranged bcr gene in all seven patients. In contrast, T lymphocytes exhibited a polyclonal pattern in six cases; in one case, a faint band was observed following methyl-sensitive enzyme cleavage. The bcr gene analysis in T lymphocytes showed the germline in every case. Our results indicate that the majority of T lymphocytes are polyclonal during the chronic phase of CML and confirm previous reports based on glucose-6-phosphate dehydrogenase, cytogenetic, and bcr rearrangement analyses.

Adult↗
PubMed1996

Detection of c-myc oncogene amplification in a CML blastic phase patient with double minute chromosomes.

Double minute chromosomes (dmin) are relatively rare in leukemias. Cytogenetic analysis of blood cells from a woman with blastic phase chronic myelogenous leukemia (BC-CML) showed numerous dmin chromosomes and complex abnormalities including a Philadelphia (ph(1))-chromosome. Oncogene amplification in hematopoietic malignancies is also rare. Using PCR, we retrospectively investigated the extent of c-myc gene amplification in DNA extracted from stored blood smears from the patient. To qualify the PCR products, the beta-globin gene was used as the internal reference gene and it was co-amplified with the c-myc gene. The extent of amplified c-myc was about 6.8-fold. This finding suggests that the c-myc gene was amplified in dmin and that the gene amplification contributes to the progression to acute leukemia or rapid growth of leukemic cells.

Base Sequence↗
PubMed1996

Elevated deoxyuridine triphosphate nucleotidohydrolase (dUTPase) activity in the cobalamin-deficient megaloblastic bone marrow cells.

The biochemical basis underlying the pathogenesis of megaloblastic anemia due to vitamin B12 deficiency was examined. Megaloblastic bone marrow cells show a marked imbalance in the deoxynucleoside triphosphate pools. If cellular dUTP concentration is elevated due to metabolic block in a similar way to dCTP, ensuing uracil misincorporation into DNA would result in deranged DNA composition and impaired cell function. Therefore, dUTP-degrading activity was measured in blood cells from various diseases. dUTPase (dUTP nucleotidohydrolase) activity of bone marrow cells was, on average, 4.4 times higher in 8 patients with untreated megaloblastic anemia than that of other normoblastic conditions. Such elevated dUTPase may help lower cellular dUTP levels in megaloblastic anemia. However, it is not clear whether the observed increase of dUTPase in megaloblastic cells is sufficient to suppress uracil misincorporation below the harmful level.

Anemia, Megaloblastic↗
PubMed1996

Effect of recombinant human granulocyte colony-stimulating factor on combination therapy with aztreonam and clindamycin for infections in neutropenic patients with hematologic diseases.

The present multicenter study was performed to evaluate the effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on combination therapy using aztreonam (AZT) and clindamycin (CLDM) to treat severe infection in neutropenic patients with hematologic diseases. Forty-three neutropenic patients with infections (rhG-CSF group) were treated with AZT (2 g) and CLDM (600 mg) 2-3 times daily as well as rhG-CSF (Lenograstim or Filgrastim: 2-5 mu/kg/day). The clinical efficacy of this regimen was compared to that obtained in 44 febrile neutropenic patients, with hematologic diseases, who received only AZT and CLDM in a previous study (historical control group). The overall efficacy rate was 69.8% (30/43) in the rhG-CSF group and 65.9% (29/44) in the historical control group. Although the neutrophil count was significantly increased and C-reactive protein tended to be lower in the rhG-CSF group, the daily maximum body temperature profiles of the 2 groups were nearly the same. These results suggest that rhG-CSF is of little benefit in the treatment of single infectious episodes in neutropenic patients, and that appropriate antibiotic therapy is more important.

Acute Disease↗
PubMed1996

Hypocomplementemia and hematological abnormalities in immunoblastic lymphadenopathy and immunoblastic lymphadenopathy-like T cell lymphoma.

Serum complement levels and hematological data were evaluated in five patients with immunoblastic lymphadenopathy (IBL) and four with IBL-like T cell lymphoma (IBL-T). Anemia with Hb values below 10.0 g/dl was seen in four patients. A direct Coombs test was positive in five patients and the bone marrow of two of these showed features of pure red cell aplasia. Seven patients were thrombocytopenic with platelet counts below 100 x 10(9)/l. Six of the seven patients had splenomegaly. Platelet-associated IgG was elevated in all three thrombocytopenic patients examined. Whole complement activity (CH50) was reduced in eight patients (89%) at presentation and subsequently normalized in five who were treated either with prednisolone (two patients with IBL) or with multidrug combination chemotherapy (three with IBL-T). One patient achieved complete remission and four partial remission. Remission was accompanied by normalization of hematological abnormalities and elevation of complement activity to the normal range in all cases. These results suggested that complement-mediated mechanisms are responsible, at least in part, for some of the hematological abnormalities observed in IBL and IBL-T and that hypocomplementemia is a common abnormality with significance as a laboratory marker for the disease activity.

Aged↗
PubMed1996

Prognostic implications in myelodysplastic syndromes: A review of 62 cases.

We retrospectively reviewed 62 MDS patients (15 RA, 3 RARS, 10 CMML, 20 RAEB, 14 RAEBT) to clarify the current problems in their management. Median survival of RA and RARS patients was 67.9 months and significantly longer than that of CMML, RAEB, or RAEB-T patients with median survivals of 16.1, 16.8, and 9.5 months, respectively. Karyotypic abnormalities were observed in 58% of the patients examined. Forty-two patients died, 16 (38%) of leukemic transformation and 21(50%) of bone marrow failure. While most of the RAEB-T patients of all ages and all the RAEB patients diagnosed below 60 years of age died of transformation, 70% of the older RAEB patients died of infection. Prognosis after transformation was poor and 12 patients died within two months. These results indicate that management after transformation and treatment against infection in RAEB patients with advanced age are crucial to improve the prognosis in MDS.

Adult↗
PubMed1996

[Percutaneous endoscopic gastrostomy in patients with swallowing difficulties--home care and long-term result].

We studied the possibility of home care of patients who are unable to swallow. Postsurgical complications during the short term (within a week), medium term (within a month) and long term (more than a month) were recorded along with survival time. We also retrospectively studied the number of patients who were discharged after percutaneous endoscopic gastrostomy from November 1989 to March 1995. The percentage of patients with short-term postsurgical complications was 12.1%. Vomiting was the most frequent complication during the medium term and the long term. The weekly rate of complication development (total complications number/total survival time) was highest in the short term and decreased year by year. It was lower in those who were discharged from the hospital than in those who were not discharged. The average survival time was 460.2 days (544.7 days: home care group, 419.0 days: hospital group). The one-year survival rate was 58%, and the two-year survival rate was 36%. One third (32.8%) of patients were cared for at home after gastrostomy (average duration of care at home: 338.5 days) and the average duration of care at home as a percentage of survival time was 58.8%. We conclude that Percutaneous endoscopic gastrostomy can improve the quality of life of patients who are unable to swallow, and may allow them to be cared for at home.

Activities of Daily Living↗
PubMed1996

Expression of costimulatory molecules in human leukemias.

In order to determine the indication of B7 (B7-1 and B7-2) molecules-mediated immuno-gene therapy for human leukemias, we investigated 94 human leukemic samples for the expression of MHC molecules required for tumor antigen-specific signals and of B7-1, B7-2, and ICAM-1 molecules required for non-specific costimulatory signals. All samples were strongly positive for MHC class I and 84% for class II antigen. B7-1, B7-2 and ICAM-1 were expressed in 5%, 22% and 16% of the total cases, respectively. Especially in 54 AML samples, B7-1 was only expressed in one case, while B7-2 was detected in as many as 15 cases (28%). We have also examined 13 human myelo/monocytic cell lines for the expression of class II and costimulatory molecules and found that significant expression of costimulatory molecules was induced in human leukemic cells by some suitable drugs, among which interferon-gamma (IFN-gamma) was the most potent inducer. Our results indicate that when the B7-mediated immuno-gene therapy was applied to human leukemias, especially to AML, B7-1 was rather preferable to B7-2 in that the latter was more widely expressed on human leukemic cells. Furthermore, since gene-transfer systems occasionally accompany serious problems, it should be taken into account that costimulatory molecules on human myelo/monocytic leukemic cells could be induced ex vivo without the introduction of exogenous genes.

Antigens, CD↗