Nozu K.,Kobe University |
Iijima K.,Kobe University |
Kanda K.,Kobe University |
Nakanishi K.,Wakayama Medical University |
And 15 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010
Context: Our understanding of inherited salt-losing tubulopathies has improved with recent advances in molecular genetics. However, the terminology of Bartter syndrome and Gitelman syndrome does not always accurately reflect their pathophysiological basis or clinical presentation, and some patients are difficult to diagnose from their clinical presentations. Objective: In the present study,weconducted molecular analysisanddiuretic tests for patients with inherited salt-losing tubulopathies to clarify the pharmacological characteristics of these disorders. Patients: We detected mutations and subsequently conducted diuretic tests using furosemide and thiazide for 16 patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine with CLCNKB; and three with SLC12A3). Results: Patients with SLC12A1 mutations showed no response to furosemide, whereas those with SLC12A3 mutations showed no response to thiazide. However, patients with CLCNKB mutations showed no response to thiazide and a normal response to furosemide, and those with KCNJ1 mutations showed a good response to both diuretics. This study revealed the following characteristics of these disorders: 1) subjects with CLCNKB mutations showed one or more biochemical features of Gitelman syndrome (including hypomagnesemia, hypocalciuria,andfractional chloride excretion insensitivity to thiazide administration); and 2) subjects with KCNJ1 mutations appeared to show normal fractional chloride excretion sensitivity to furosemide and thiazide administration. Conclusions: These results indicate that these disorders are difficult to distinguish in some patients, even when using diuretic challenge. This clinical report provides important findings that can improve our understanding of inherited salt-losing tubulopathies and renal tubular physiology. Copyright © 2010 by The Endocrine Society.
Liu B.,Mie University |
Ohishi K.,Mie University |
Yamamura K.,Mie University |
Suzuki K.,Mie University |
And 7 more authors.
Experimental Hematology | Year: 2010
Objective: Although the anticancer activities of histone deacetylase (HDAC) inhibitors have been studied, a role for HDAC in normal hematopoiesis has not been clearly defined. Previous studies have shown that the potent HDAC inhibitor FK228 stimulates interleukin (IL)-3-mediated erythropoiesis. Here, we examined whether the widely used valproic acid (VPA) affects megakaryopoiesis as well as erythropoiesis. Materials and Methods: CD34+ cells were incubated in serum-free or serum-containing cultures with cytokines, with or without VPA. Results: In the serum-free cultures containing IL-3+stem cell factor (SCF), VPA significantly increased generation of CD61+GPA- megakaryocytic and a CD61+GPA+ mixture of megakaryocytic and erythroid precursors from CD34+ hematopoietic precursors at a pharmacological concentration (100 μg/mL). The increase in generation of megakaryocytic and erythroid precursors by VPA was confirmed by replating cultured cells with thrombopoietin+SCF and erythropoietin+SCF, respectively. VPA was as potent as FK228. In cultures with granulocyte-macrophage colony-stimulating factor+SCF, where CD61-GPA+ erythroid precursors were mostly developed, VPA mainly enhanced the generation of CD61-GPA+ erythroid precursors. In serum-containing cultures, only low numbers of CD61+ or GPA+ cells were developed with IL-3+SCF. Nevertheless, a substantial number of these cells were generated with VPA. Furthermore, these stimulating effects of VPA were observed by incubating CD34+ cells from patients with myelodysplastic syndrome. Quantitative reverse transcription polymerase chain reaction showed that VPA enhanced GATA-2, but not GATA-1, messenger RNA expression with IL-3+SCF. Conclusions: These results indicate a novel role for VPA in enhancing the potential of IL-3 to stimulate megakaryopoiesis as well as erythropoiesis and suggest a new therapeutic approach of epigenetic therapy for hematological disease. © 2010 ISEH - Society for Hematology and Stem Cells.
Ino K.,Matsusaka Chuo General Hospital
[Rinshō ketsueki] The Japanese journal of clinical hematology | Year: 2010
A 46-year-old Japanese man was admitted to our hospital because of prolonged fever. Laboratory examination demonstrated leukopenia, thrombocytopenia, marked liver dysfunction, and elevation of serum ferritin. A bone marrow examination showed several hemophagocytic macrophages, and a diagnosis of hemophagocytic syndrome was made. He was treated using HLH-94 protocol, and his clinical symptoms and laboratory data were rapidly improved. After 5 weeks, fever and liver dysfunction reappeared. A repeat bone marrow examination demonstrated that 28.4% of marrow nucleated cells were atypical lymphocytes, which were positive for CD2, CD7, CD16, CD56, and HLA-DR. Clonality of these proliferating NK cells was confirmed by an analysis of EB virus terminal repeat sequence and cytogenetic analysis, and final diagnosis of aggressive NK-cell leukemia was made. After induction chemotherapy consisting of dexamethasone, etoposide, ifosfamide, and L-asparaginase, the patient achieved partial remission. He received allogeneic peripheral blood stem cell transplantation from his one locus mismatched son, and is alive with no evidence of disease 20 months after transplantation.
Nakatani K.,Molecular and Laboratory Medicine |
Wada H.,Molecular and Laboratory Medicine |
Tanigawa T.,Matsusaka Chuo General Hospital |
Komada F.,Matsusaka Municipal Hospital |
And 5 more authors.
Circulation Journal | Year: 2013
Background: CYP2C19 loss-of-function genotype (*2 and/or *3 alleles) is related to low responsiveness to clopi-dogrel, which is a risk factor for ischemic cardiac events. The contribution of these genotypes to platelet reactivity in Japanese patients in a steady state receiving dual antiplatelet therapy after coronary stenting was evaluated. Methods and Results: A total of 155 Japanese patients were classified according to their CYP2C19 loss-of-function genotype. Platelet reactivity was assayed by plasma levels of soluble P-selectin and platelet-derived microparticles, light transmittance aggregometry induced by ADP (ADP-LTA), shear stress-induced platelet aggregometry, vasodilator-stimulated phosphoprotein phosphorylation (VASP) index and the VerifyNow-P2Y12 assay. Linear and logistic regression models were used to assess the associations between CYP2C19 loss-of-function genotype and high on-treatment platelet reactivity. In total, 62 patients (40.0%) were extensive metabolizers (EMs), 70 (45.2%) were intermediate metabolizers (IMs) and 23 (14.8%) were poor metabolizers (PMs). ADP-specific assays (ADP-LTA, the VASP index and VerifyNow-P2Y12) differed according to CYP2C19 genotype, with a significant gene-dose effect (PMs > IMs > EMs). CYP2C19 loss-of-function carrier status was associated with more frequent high platelet reactivity. CYP2C19 loss-of-function genotype alone could explain 12.2%, 14.3%, and 14.7% of the variability in the ADP-LTA, VASP and VerifyNow-P2Y12 assays, respectively. Conclusions: CYP2C19 loss-of-function genotype is associated with more frequent high platelet reactivity, as assessed by ADP-specific platelet function tests, in Japanese patients.
Katayama Y.,Matsusaka Chuo General Hospital
Kyobu geka. The Japanese journal of thoracic surgery | Year: 2013
A 55-year-old man was admitted to our hospital because of an abnormal shadow in the left upper division on chest computed tomography(CT). Virtual bronchoscopy revealed a displaced anomalous bronchus. Thin sliced CT revealed complete lobulation between the upper division and the lingula. Three dimensional (3D)-CT revealed abnormal distribution of the left pulmonary artery which descended without passing over the left main bronchus. The left upper division was evaluated to be mirror imaged to a right upper lobe. Video assisted thoracoscopic left upper divisionectomy was performed. The tumor was diagnosed as adenocarcinoma( pT1aN0M0:p-stage I A).