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Biomedical subjects

S Shimodaira

Publications and source records attributed to S Shimodaira.

At least 19 recordsLinked to original sources
PubMed2005

Effect of Helicobacter pylori eradication on ongoing mutation of immunoglobulin genes in gastric MALT lymphoma.

Gastric low-grade mucosa-associated lymphoid tissue (low-grade MALT) lymphomas has been associated with Helicobacter pylori (H. pylori) infection. Although infiltrating T cells with specificity for H. pylori are known to stimulate the development of MALT lymphomas, the effect of H. pylori eradication on rearranged immunoglobulin heavy chain (IgH) genes of low-grade gastric MALT lymphomas is unclear. Gastric biopsies from five cases were investigated by cloning and sequence analysis of rearranged IgH genes before and after the treatment for H. pylori. In all cases, IgH genes were mutated from their germline counterpart. The frequency of intraclonal sequence heterogeneity before the eradication of H. pylori varied from 0.25 to 0.49%. Clones obtained from the tumours before the eradication of H. pylori in cases 1 and 2 showed a tendency to display a mutation pattern by positive antigen selection and their monoclonarity disappeared after the eradication. The frequency of intraclonal sequence heterogeneity of the clones obtained from cases 3, 4 and 5 (0.12% in case 3, 0.10% in 4 and 0.18% in 5) after the eradication of H. pylori was lower than that in tumours before the eradication (0.30% in case 3, 0.49% in 4 and not determined in 5). These findings suggest that low-grade gastric MALT lymphomas expand due to the persistent presence of H. pylori in vivo. The characteristic feature of tumour clones obtained from the tumours after the eradication of H. pylori is a very low intraclonal heterogeneity, which may potentially be independent of H. pylori.

Aged↗
PubMed2005

Significance of chemokine receptor expression in aggressive NK cell leukemia.

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.

Adult↗
PubMed2000

Genetic linkage of Kozak sequence polymorphism of the platelet glycoprotein Ib alpha with human platelet antigen-2 and variable number of tandem repeats polymorphism, and its relationship with coronary artery disease.

The -5 C/T polymorphism of platelet glycoprotein (GP) Ib alpha is a major determinant of the level of GP Ib/V/IX complex surface expression. We investigated the frequency of this polymorphism among Asian populations. The gene frequencies of cytosine (C) in this polymorphism were 0.283 and 0.219 in Japanese and Korean populations respectively. The C allele is linked with human platelet antigen (HPA)-2a and smaller types of variable number of tandem repeats (VNTR). A novel allele, C-HPA-2a-D of VNTR, was found. No association was observed between these alleles and coronary artery disease in this case-control study. The clinical relevance of this polymorphism in the thrombotic status remains undetermined.

Adult↗
PubMed2000

Competitive reverse transcription-polymerase chain reaction assay for quantification of human multidrug resistance 1 (MDR1) gene expression in fresh leukemic cells.

We have analyzed MDR1 gene expression in 69 clinical samples obtained from 64 patients with leukemic hematologic malignancies by using a competitive reverse transcription-polymerase chain reaction assay with a heterologous competitor RNA. To exclude a false-positive result caused by concomitant normal lymphocytes that physiologically express MDR1, in samples we determined a cut-off value of 8 amol MDR1 transcript per microgram of RNA by simultaneous measurement of rhodamine 123 dye efflux either in lymphocyte or gated leukemic cell populations. Consequently, 23 of 69 samples were concluded to be MDR1-positive in leukemic cells per se. The MDR1 expression rate was significantly correlated with factors such as a history of preceding chemotherapy, elder age of the patient, and certain disease types (eg, leukemia progressed from myelodysplastic syndrome). Moreover, the complete response rate after chemotherapy was significantly higher in MDR1-negative patients than in MDR1-positive patients (52% vs 17%, respectively; P = .01). The assay established will enable the quantification of MDR1 gene expression in blood samples from patients with leukemic hematologic malignancies and will be applicable to clinical laboratories as a routine test.

Adolescent↗
PubMed1999

Elliptocytosis in myelodysplastic syndrome associated with translocation (1;5)(p10;q10) and deletion of 20q.

Acquired elliptocytosis is a red blood cell abnormality occasionally associated with myelodysplastic syndrome (MDS). A Japanese male with MDS who presented with elliptocytosis had mild anemia and hypercellular bone marrow with three lineage-dysplasia. He was diagnosed with refractory anemia of MDS. Cytogenetic analysis of bone marrow cells showed 47,XY,+1,der(1;5)(q10;p10),t(1;5) (p10;q10),del(20)(q11) in 70% of the analyzed cells. Analysis of red blood cell membrane proteins by sodium dodecyl sulphate-polyacrylamide gel electrophoresis showed normal electrophoretic patterns with no quantitative abnormalities of each protein. Del(20q) and/or t(1;5)(p10;q10) might be associated with elliptocytosis in this patient.

Aged↗
PubMed1999

Abnormal proliferation of CD4- CD8+ gammadelta+ T cells with chromosome 6 anomaly: role of Fas ligand expression in spontaneous regression of the cells.

We report a case of granular lymphocyte proliferative disorder accompanied with hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted gammadelta+ T cells showed an increase in Fas ligand expression compared with the levels in sorted alphabeta+ T cells. The expression of Fas ligand on these gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia improved along with a decrease in granular lymphocyte count and disappearance of the abnormal karyotype without treatment. The expression of Fas ligand may be involved in spontaneous regression of granular lymphocyte proliferation with hemolytic anemia.

Anemia, Hemolytic↗
PubMed1999

Acute myelogenous leukemia with a t(2;17;4)(p13;q21;p16) aberration: effective treatment with all-trans retinoic acid and granulocyte colony-stimulating factor.

The efficacy of all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL) has been well documented. However, ATRA is not as effective against other types of acute myelogenous leukemia (AML) or myelodysplastic syndromes. We present a patient with AML (FAB: M2) associated with a t(2;17;4)(p13;q21;p16) chromosomal defect in which the 17q21 breakpoint was not within the retinoic acid receptor alpha locus which is typically rearranged in APL. This patient was successfully treated with ATRA and granulocyte colony-stimulating factor and improvement of hematological parameters lasted for 19 months without the use of cytotoxic agents.

Antineoplastic Agents↗
PubMed1999

Polymorphisms of platelet membrane glycoprotein Ib alpha and plasma von Willebrand factor antigen in coronary artery disease.

To examine the relationships of two polymorphisms of platelet glycoprotein (GP) Ib alpha and coronary artery diseases (CAD) in Japanese patients, we conducted a case-control study with 158 Japanese patients and 169 control subjects. The frequencies of HPA-2 polymorphism and the variable number of tandem repeat (VNTR) polymorphisms in the macroglycopeptide region did not significantly differ between CAD patients and control subjects. The polymorphisms of GPIb alpha were not associated with the number of affected vessels in CAD patients. When patients with acute coronary syndrome only were analyzed, the frequencies of the two polymorphisms of GPIb alpha showed no significant difference. Although plasma von Willebrand antigen (vWF:Ag) levels in patients were significantly higher than in controls, no association between vWF concentration and GPIb genotypes was observed. In patient groups with higher or lower vWF:Ag concentrations, no increase in the frequencies of Met145 or larger VNTR polymorphisms was seen in either group. Our findings indicate that no association exists between the frequencies of the two polymorphisms of GPIb alpha and CAD.

Aged↗
PubMed1999

Liver cirrhosis with marked thrombocytopenia and highly elevated serum thrombopoietin levels.

Three patients with liver cirrhosis (LC) and a bleeding tendency due to marked thrombocytopenia of less than 20 x 10(9)/l were admitted to our hospital for further examination. Bone marrow examination revealed megakaryocytic hypoplasia in all three patients. All patients exhibited amegakaryocytic thrombocytopenic purpura, myelodysplastic syndrome, or bone marrow hypoplasia. 111In-labeled platelet kinetic studies revealed decreased platelet production in all patients. Although serum thrombopoietin (sTPO) levels are usually within the normal level in patients with LC, the sTPO levels of our patients were about 10 times higher than the levels of normal subjects (1.22 +/- 0.37 fmol/ml): 13.34, 16.79, and 10.46 fmol/ml, respectively. These sTPO data supported our findings of decreased megakaryopoiesis. Our findings suggest that examination of sTPO levels is useful in determining the etiology of marked thrombocytopenia in LC patients.

Blood Platelets↗
PubMed1998

Changes in serum thrombopoietin levels after splenectomy.

To clarify the role of thrombopoietin (c-Mpl ligand, TPO) in 'hypersplenic' thrombocytopenia, we used an enzyme-linked immunosorbent assay to examine changes in serum TPO levels accompanied with splenectomy in 6 patients with liver cirrhosis, 4 patients with gastric cancer, and 2 patients with lymphoid malignancies. We also measured serum levels of other thrombopoietic cytokines such as interleukin-6 (IL-6) and erythropoietin. Platelet counts reached a maximum at day 14 after splenectomy in all subjects. In patients with liver cirrhosis, a lower elevation of platelet counts was observed compared with that in patients with gastric cancer. Serum TPO levels gradually elevated after splenectomy and reached a maximum 3.5 days after splenectomy in noncirrhotic patients, whereas peak serum TPO levels were delayed until day 7 in the cirrhosis group. IL-6 and erythropoietin showed similar kinetics between cirrhotic and noncirrhotic patients. These findings suggest that transient thrombocytosis after splenectomy may be associated with an alteration in the site of TPO catabolism by platelets from spleen to the blood and that deterioration of TPO production may play a role in thrombocytopenia in liver cirrhosis.

Adult↗
PubMed1997

Internal tandem duplication of FLT3 associated with leukocytosis in acute promyelocytic leukemia. Leukemia Study Group of the Ministry of Health and Welfare (Kohseisho).

FLT3 is a member of receptor tyrosine kinases expressed in leukemia cells, as well as in hematopoietic stem cells. Recently, a somatic alteration of the FLT3 gene was found in acute myeloid leukemia, as an internal tandem duplication (FLT3/ITD) which caused elongation of the juxtamembrane (JM) domain of FLT3. Here we characterized the FLT3/ITD and investigated its clinical significance in acute promyelocytic leukemia (APL). Seventy-four newly diagnosed patients with APL, who were treated with the same protocol in a multi-institutional study, were studied for the FLT3/ITD. Genomic and message sequences of the FLT3 gene were amplified by means of polymerase chain reaction (PCR), and elongated PCR products were sequenced. Fifteen patients (20.3%) had FLT3/ITD, all of which were transcribed in frame. Location of the duplicated fragments (six to 30 amino acids) varied from patient to patient. However, they always contained either Y591 or Y599, but the tyrosine kinase domain was not significantly affected. This finding implied that signal transduction of FLT3 is amplified by the duplication. Clinically, the presence of FLT3/ITD was related to high peripheral white blood cell counts as well as peripheral leukemia cell counts (P < 0.0001), high LDH level (P = 0.04), and low fibrinogen concentration (P = 0.04). These data suggest that FLT3/ITD plays a significant role in progression of APL.

Adult↗
PubMed1997

Resistance to activated protein C and Arg 506 Gln factor V mutation are uncommon in eastern Asian populations.

We investigated the prevalence of the factor V (FV) Arg 506 Gln mutation in healthy subjects from three eastern Asian countries (Japan, n = 270; China, n = 113; and Korea, n = 93) and in 26 Japanese patients showing venous thromboembolic events. The patients were also examined for activated protein C (APC) resistance by using the Coatest APC resistance kit. The FV mutation was investigated by polymerase chain reaction and restricted enzyme digestion with MnlI RFLP assay of the FV gene. None of the patients showed APC resistance, while all subjects examined were homozygous for Arg at position 506 of the FV gene. Our results imply that FV mutation and APC resistance contribute little to venous thrombotic diseases in eastern Asia.

Adult↗
PubMed1997

Eosinophilia associated with clonal T-cell proliferation.

Eosinophilia associated with the expansion of cloned T-cells is reviewed in relation to cytokine production. It has been proved that eosinophilopoiesis is caused by eosinophil-stimulating cytokines, including interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor and interleukin-3, which are secreted from T-cells. Recently, we and other groups have reported several cases of eosinophilia including hypereosinophilic syndrome (HES) accompanied with proliferation of abnormal T-cells with an unusual phenotype CD3- CD4+ or CD3+ CD4- CD8- in the peripheral blood. The T-cells clonally proliferate, as confirmed by clonal rearrangements of the T-cell receptor (TCR) gene, and produce eosinophil-stimulating cytokines, especially IL-5, with or without stimulation in vitro. Although HES is defined by the combination of unexplained prolonged eosinophilia and evidence of organ involvement, these observations suggest that increased production of eosinophil-stimulating cytokines from the abnormal T-cells with phenotype CD3- CD4+ or CD3+ CD4- CD8- may cause eosinophilia, some of which have been diagnosed as HES.

CD3 Complex↗
PubMed1997

[Mantle cell lymphoma with multiple extranodal involvement].

A 79-year-old male was admitted to our hospital because of general fatigue and night sweat. Physical examination showed generalized superficial lymphadenopathy, marked splenomegaly, and tumors in the conjunctiva and the abdomen. Chest X-ray and computed tomography (CT) revealed pleural effusion and intrathoracic lymphadenopathy. Abdominal ultrasonography and CT showed hepatosplenomegaly and intraperitoneal tumors. Upper gastrointestinal fiberscopy revealed multiple polypoid lesions and ulcers in the duodenum and the stomach. Involvement of relatively small-sized lymphocytes with cleaved nuclei was identified in each biopsied specimen from a cervical lymph node, a tumor in the conjunctiva, gastrointestinal polypoid lesions, and the bone marrow. Surface marker analysis of abnormal lymphocytes in the bone marrow revealed that CD5, CD19, and CD20 were strongly positive, but CD23 was weakly positive. Although (11:14)(q13:q32) translocation was not identified by chromosome analysis of bone marrow cells, Northern blot analysis of bone marrow cells revealed overexpression of the PRAD1 oncogene. Diagnosis of mantle cell lymphoma (MCL) was made. Combination chemotherapy by cyclophosphamide and vincristine was not effective, but etoposide perorally given at a dose of 50 mg per day was effective. In MCL, extranodal involvement of a digestive tract and bone marrow is well known. This case suggests that involvement of multiple organs including lacrimal glands and pleura could be characteristic of MCL cells.

Abdominal Neoplasms↗
PubMed1996

Eosinophilia associated with proliferation of CD(3+)4-(8-) alpha beta+ T cells with chromosome 16 anomalies.

We describe a patient with eosinophilia and an abnormal CD(3+)4-(8-) alpha beta+ T-cell population. Chromosomal analysis of sorted CD(3+)4-(8-) cells revealed abnormal karyotypes on chromosome 16. In the presence of IL-2 the production of IL-5 from CD(3+)4-(8-) cells was higher than that from CD(3+)4-(8-) cells. Eosinophil survival-enhancing activity in the patient serum was inhibited by a combination of anti-IL-5 and anti-GM-CSF monoclonal antibodies. These data suggest that increased production of IL-5 and GM-CSF from the abnormal CD(3+)4-(8-) cells might cause eosinophilia.

Antibodies, Monoclonal↗