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Ichinomiya, Japan

Kitamura K.,Ichinomiya Municipal Hospital
[Rinshō ketsueki] The Japanese journal of clinical hematology

This study investigated the clinical value of monitoring peripheral blood (PB) WT1 mRNA levels in acute myeloid leukemia (AML) patients. We evaluated the correlation between PB and bone marrow (BM) WT1 mRNA levels in the follow-up period of the clinical course of 17 AML patients. The levels of fusion gene transcripts in PB were also monitored when detected before chemotherapy. Patients with sustained complete remission (CR) showed a trend toward a higher WT1 mRNA reduction rate by induction therapy than patients who relapsed after CR (p=0.09). Correlation between the WT1 levels of PB and BM samples obtained on the same day was relatively strong (R=0.87). Among the four fusion transcript-positive patients, the levels of fusion transcripts and WT1 showed a similar transition pattern. These findings suggest that WT1 mRNA is a useful marker to improve risk-stratification for post-induction therapy and to guide management of individual AML patients by monitoring minimal residual disease, especially for patients with no disease-specific marker. Since WT1 monitoring via PB sampling is simple and less invasive than BM sampling, the use of this marker also improves patient management. Source

Nishimura J.-I.,Osaka University | Yamamoto M.,Osaka University | Hayashi S.,Tokyo Medical and Dental University | Ohyashiki K.,Tokyo Medical University | And 19 more authors.
New England Journal of Medicine

BACKGROUND: Eculizumab is a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement-mediated hemolysis associated with paroxysmal nocturnal hemoglobinuria (PNH). The molecular basis for the poor response to eculizumab in a small population of Japanese patients is unclear. METHODS: We assessed the sequences of the gene encoding C5 in patients with PNH who had either a good or poor response to eculizumab. We also evaluated the functional properties of C5 as it was encoded in these patients. RESULTS: Of 345 Japanese patients with PNH who received eculizumab, 11 patients had a poor response. All 11 had a single missense C5 heterozygous mutation, c.2654G→A, which predicts the polymorphism p.Arg885His. The prevalence of this mutation among the patients with PNH (3.2%) was similar to that among healthy Japanese persons (3.5%). This polymorphism was also identified in a Han Chinese population. A patient in Argentina of Asian ancestry who had a poor response had a very similar mutation, c.2653C→T, which predicts p.Arg885Cys. Nonmutant and mutant C5 both caused hemolysis in vitro, but only nonmutant C5 bound to and was blocked by eculizumab. In vitro hemolysis due to nonmutant and mutant C5 was completely blocked with the use of N19-8, a monoclonal antibody that binds to a different site on C5 than does eculizumab. CONCLUSIONS: The functional capacity of C5 variants with mutations at Arg885, together with their failure to undergo blockade by eculizumab, account for the poor response to this agent in patients who carry these mutations. (Funded by Alexion Pharmaceuticals and the Ministry of Health, Labor, and Welfare of Japan.) Copyright © 2014 Massachusetts Medical Society. Source

Katahira M.,Aichi Prefectural University | Ogata H.,Ichinomiya Municipal Hospital
Internal Medicine

Objective The recurrence rate associated with antithyroid drug (ATD) treatment for Graves' disease (GD) is high compared with that for radioiodine therapy or surgery. It is important to identify patients in whom remission is unlikely, so that they are not given treatment that is destined to fail. The objective of this study was thus to evaluate factors influencing the prognosis of GD patients treated with ATDs. Patients One hundred and sixty-one patients were divided into two groups: 100 patients who could not discontinue ATDs for eight years or more (refractory group) and 61 patients who achieved remission within eight years after starting ATD treatment (nonrefractory group). The groups were compared in terms of age, thyroid function and thyroid-related autoantibodies at diagnosis, and the durations to the recovery of thyroid function and thyroid-related autoantibodies. Results The baseline levels of free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating antibodies (TSAbs) and thyroid-stimulating hormone (TSH) receptor antibodies (TRAbs) were high, and the age at diagnosis and the baseline level of thyroglobulin autoantibodies (TgAbs) were low in the refractory group compared with those in the nonrefractory group. The durations to the recovery of TSH, free T4, TRAb and TSAb levels were longer in the refractory group than in the nonrefractory group. No significant difference was observed with regard to thyroid peroxidase autoantibodies. Conclusion We compared the clinical features of these two groups in order to identify factors influencing the prognosis of GD patients treated with ATDs. A low baseline level of TgAbs is associated with the refractoriness of GD to ATD treatment. © 2016 The Japanese Society of Internal Medicine. Source

Kitano M.,Nagoya University | Iwano S.,Nagoya University | Hashimoto N.,Nagoya University | Matsuo K.,Ichinomiya Municipal Hospital | And 2 more authors.
International Journal of COPD

Background: We investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images.Methods: We retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 - NLVE/NLVI) × 100%. Associations between lobar vol­umes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis.Results: NLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P<0.01), whereas this correlation was not significant for the upper lobes (P=0.05). FEV1%P results were also moderately correlated with inspiratory, expiratory ELV (ELVI,E) for the lower lobes (P<0.05). In contrast, the ratio of the diffusion capacity for carbon monoxide to alveolar gas volume, measured as percent of predicted (DLCO/VA%P) results were strongly correlated with ELVI for the upper lobes (P<0.001), whereas this correlation with NLVCR values was weaker for upper lobes (P<0.01) and was not significant for the lower lobes (P=0.26).Conclusion: FEV1%P results were correlated with NLV collapsibility indices for lower lobes, whereas DLCO/VA%P results were correlated with NLV collapsibility indices and ELV for upper lobes. Thus, evaluating lobar NLV collapsibility might be useful for estimating pulmonary function in COPD patients. © 2014 Kitano et al. Source

Yamada M.,Health Science University | Takano K.,Saku Central Hospital Advanced Care Center | Kawai Y.,Ichinomiya Municipal Hospital | Kato R.,Health Science University
Magnetic Resonance in Medical Sciences

The use of compact magnetic resonance (MR) systems for the neuroimaging of small animals is spreading. We investigated the potential of such systems in functional MR imaging (fMRI) of somatosensory cortex activity elicited by forepaw stimulation in medetomidine-sedated rats. Using a 1.5-tesla compact imager, we detected maximum activity with an electrophysiologically optimized frequency of 9Hz in 3 appropriately sedated rats. With this compact system, we successfully mapped neural activity by combining optimum stimulation for a large hemodynamic response with appropriate anesthesia, thus demonstrating the utility of such systems in hemodynamic-based fMRI in preclinical and translational research. © 2015 Japanese Society for Magnetic Resonance in Medicine. Source

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