Mutsuko Miyazaki

DOC2b is a SNARE regulator of glucose-stimulated delayed insulin secretion

Insulin secretion is precisely regulated by blood glucose with unique biphasic pattern. The regulatory mechanism of the second-phase insulin release is unclear. In this study, we report that DOC2b (double C2 domain protein isoform b), a SNARE related protein, was associated with insulin vesicles and translocated to plasma membrane within several minutes upon high-glucose stimulation followed by an interaction with syntaxin4, but not syntaxin1. This binding specificity and the time course of DOC2b translocation were suitable for the regulation of second-phase insulin release. Increased DOC2b expression enhanced glucose-stimulated insulin secretion. In contrast, silencing DOC2b inhibited delayed release of insulin, without affecting rapid (approximately 7min) phase secretion. Interestingly, DOC2b had no effects on KCl-triggered insulin release. These data suggest that DOC2b may be a regulator for delayed (second-phase) insulin secretion in MIN6 cells.

Identification of Glypican3 as a novel GLUT4-binding protein

Insulin stimulates glucose uptake in fat and muscle primarily by stimulating the translocation of vesicles containing facilitative glucose transporters, GLUT4, from intracellular compartments to the plasma membrane. Although cell surface externalization of GLUT4 is critical for glucose transport, the mechanism regulating cell surface GLUT4 remains unknown. Using a yeast two-hybrid screening system, we have screened GLUT4-binding proteins, and identified a novel glycosyl phosphatidyl inositol (GPI)-linked proteoglycan, Glypican3 (GPC3). We confirmed their interaction using immunoprecipitation and a GST pull-down assay. We also revealed that GPC3 and GLUT4 to co-localized at the plasma membrane, using immunofluorescent microscopy. Furthermore, we observed that glucose uptake in GPC3-overexpressing adipocytes was increased by 30% as compared to control cells. These findings suggest that GPC3 may play roles in glucose transport through GLUT4.

F-18 FDG PET/CT findings in a case of T-cell lymphoma-associated hemophagocytic syndrome with liver involvement.

Abstract:This is a report of fluoro-deoxy-glucose positron emission tomography/computed tomography (F-18-FDG PET/CT) findings in a case of T-cell lymphoma-associated hemophagocytic syndrome, with “periportal low attenuation” and edematous gall-bladder wall thickening. FDG PET/CT showed diffuse inten

Therapy-related erythroleukemia caused by the administration of UFT and mitomycin C in a patient with colon cancer

Abstract. A 54-year-old man with colon cancer underwent hemicolectomy. He received postoperative adjuvant chemotherapy with UFT (tegafur/uracil at a 1 : 4 molar ratio) and mitomycin C (MMC) for 3 years. Three years and 4 months after the start of chemotherapy, pancytopenia was noted. Bone marrow aspiration smear demonstrated an increased number of immature erythroblasts, including megaloblasts and myeloblasts. Chromosomal analysis demonstrated structural and numerical abnormalities of 5, 7, 15, and 17. Therapy-related erythroleukemia, acute myeloid leukemia (AML), M6, was diagnosed. The disease progressed after 5 months, and the patient was received chemotherapy with cytosine arabinoside, aclacinomycin, and granulocyte colony-stimulating factor (CAG), and showed a partial hematological response. Careful monitoring for the generation of therapy-related leukemia is needed when UFT and MMC are used for postoperative adjuvant chemotherapy for colorectal cancer.

Two Cases of Acute Myeloblastic Leukemia Evolving from Aplastic Anemia

Two cases of acute myeloblastic leukemia (AML) evolving from aplastic anemia are presented. The first case was diagnosed 18 years ago, and treatment with bolus methylprednisolone, prednisolone, and androgens resulted in partial hematological response. Severe pancytopenia recurred, and AML M0 by French-American-British classification developed. The second case was diagnosed 7 years ago. The patient had HLA DRB1*1501, and treatment with granulocyte colony-stimulating factor (G-CSF), cyclosporine, and methenolone resulted in complete hematological response. Thrombocytopenia recurred and did not respond to cyclosporine and methenolone or to later treatment with antithymocyte globulin, and AML M1 developed. Cytogenetic studies demonstrated 7q— in the first patient and +8 in the second patient. No mutations of N-ras or p53 were observed in either patient. These patients were treated with cytosine arabinoside, aclacinomycin, and G-CSF (CAG) chemotherapy, and the number of leukemic cells decreased substantially. However, pancytopenia after CAG chemotherapy persisted, and the first patient died of pneumonia and the second patient of cerebral hemorrhage.Int J Hematol. 2003;77:471-475.

A novel t(11;14)(q23;q32) in a case of myelodysplastic syndrome

A 65-year-old Japanese man was referred to our hospital in November 2007 because of hemorrhagic tendency. Physical examination revealed pallor and purpura on the lower extremities. Neither lymphadenopathy nor hepatosplenomegaly were observed. He was treated at another hospital for schizophrenia. On admission, the complete blood count findings were hemoglobin 87 g/L; white blood cell count 3.0 10/L (blasts 0%; neutrophils 43.4%; lymphocytes 50.7%; monocytes 3.8%; eosinophils 0.8%; and basophils 1.3%); and platelet count 164 10/L. Serum lactate dehydrogenase was 397 IU/L (normal, 100e200 IU/L). Disseminated intravascular coagulation (DIC) was present with fibrinogen level 0.64g/L; D-dimer level 23.2mg/L; plasmin-a2 plasmin inhibitor complex (PIC) level 11.5mg/L; and thrombin-antithrombin III complex (TAT) level 60.0mg/L (normal values: fibrinogen level 1.5e3.5g/L; D-dimer level !1mg/L; PIC level !0.8mg/L; and TAT level !4.0 mg/L). Bone marrow aspiration revealed the following: hypercellular marrow with myelodysplasia, myeloblasts accounting for 1% of the marrow cells, increase of myelocyte-like cells with fine eosinophilic cytoplasm up to 60%, hypogranulation in neutrophils, and decreased megakaryocytes.