Publications (58) View all
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Article: Retinol palmitate prevents ischemia-induced cell changes in hippocampal neurons through the Notch1 signaling pathway in mice.
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ABSTRACT: Retinol palmitate, an analogue of vitamin A, plays multiple roles in the nervous system, including neural differentiation, axon outgrowth, and neural patterning, and is also an antioxidative agent and thereby potential neuroprotectant for brain ischemia. The present aimed investigated the protective effects of retinol palmitate against ischemia-induced brain injury in a bilateral common carotid artery occlusion (BCCAO) model in mice. Ischemia induced by 20-min BCCAO resulted in significant neuronal morphological changes and reactive astrocyte proliferation in the hippocampus, particularly in the CA1 region, and these changes were accompanied by increased Notch1 expression. Intraperitoneal retinol palmitate administration before ischemia reduced ischemic neurons with Notch1 expression; the differences were statistically significant in both the 1.2 mg/kg group and 12 mg/kg group. These results show that retinol palmitate prevents brain ischemia-induced neuronal injury with Notch1 expression and that Notch1 signaling could be involved in the neuroprotective mechanism. Retinol palmitate could be a treatment option for human brain infarction.Experimental Neurology 05/2013; · 4.70 Impact Factor -
Article: A case-matched study of stereotactic radiosurgery for patients with multiple brain metastases: comparing treatment results for 1-4 vs ≥ 5 tumors.
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ABSTRACT: Object Although stereotactic radiosurgery (SRS) alone for patients with 4-5 or more tumors is not a standard treatment, a trend for patients with 5 or more tumors to undergo SRS alone is already apparent. The authors' aim in the present study was to reappraise whether SRS results for ≥ 5 tumors differ from those for 1-4 tumors. Methods This institutional review board-approved retrospective cohort study used the authors' database of prospectively accumulated data that included 2553 consecutive patients who underwent SRS, not in combination with concurrent whole-brain radiotherapy, for brain metastases (METs) between 1998 and 2011. These 2553 patients were divided into 2 groups: 1553 with tumor numbers of 1-4 (Group A) and 1000 with ≥ 5 tumors (Group B). Because there was considerable bias in pre-SRS clinical factors between Groups A and B, a case-matched study was conducted. Ultimately, 1096 patients (548 each in Groups A and B) were selected. The standard Kaplan-Meier method was used to determine post-SRS survival and the post-SRS neurological death-free survival times. Competing risk analysis was applied to estimate cumulative incidences of local recurrence, repeat SRS for new lesions, neurological deterioration, and SRS-induced complications. Results The post-SRS median survival time was significantly longer in the 548 Group A patients (7.9 months, 95% CI 7.0-8.9 months) than in the 548 Group B patients (7.0 months 95% [CI 6.2-7.8 months], HR 1.176 [95% CI 1.039-1.331], p = 0.01). However, incidences of neurological death were very similar: 10.6% in Group A and 8.2% in Group B (p = 0.21). There was no significant difference between the groups in neurological death-free survival intervals (HR 0.945, 95% CI 0.636-1.394, p = 0.77). Furthermore, competing risk analyses showed that there were no significant differences between the groups in cumulative incidences of local recurrence (HR 0.577, 95% CI 0.312-1.069, p = 0.08), repeat SRS (HR 1.133, 95% CI 0.910-1.409, p = 0.26), neurological deterioration (HR 1.868, 95% CI 0.608-1.240, p = 0.44), and major SRS-related complications (HR 1.105, 95% CI 0.490-2.496, p = 0.81). In the authors' cohort, age ≤ 65 years, female sex, a Karnofsky Performance Scale score ≥ 80%, cumulative tumor volume ≤ 10 cm(3), controlled primary cancer, no extracerebral METs, and neurologically asymptomatic status were significant factors favoring longer survival equally in both groups. Conclusions This retrospective study suggests that increased tumor number is an unfavorable factor for longer survival. However, the post-SRS median survival time difference, 0.9 months, between the two groups is not clinically meaningful. Furthermore, patients with 5 or more METs have noninferior results compared to patients with 1-4 tumors, in terms of neurological death, local recurrence, repeat SRS, maintenance of good neurological state, and SRS-related complications. A randomized controlled trial should be conducted to test this hypothesis.Journal of Neurosurgery 04/2013; · 2.96 Impact Factor -
Article: The expression of CD203c on basophils as a marker of IgE-mediated L-asparaginase allergy.
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ABSTRACT: ABSTRACT Immediate allergy to L-asparaginase (ASP) is a major obstacle in treating lymphoid malignancies. ASP-specific IgG (ASP-IgG) has been used as a surrogate marker. Recently, the CD203c-basophil activation test (BAT) was found to be useful in diagnosing IgE-mediated allergies. We compared the diagnostic utility of the CD203c-BAT to that of ASP- IgG levels in determining ASP allergies in children. Eight ASP allergic reactions occurred over 75 ASP treatment courses. The sensitivity, specificity and area under the receiver operating characteristic curve of CD203c-BAT were similar to the ASP-IgG levels (0.75 vs. 0.85, 0.82 vs. 0.78, and 0.81 vs. 0.85, respectively). Positive skin prick test results in ASP allergy patients with suggested that ASP-IgE was one of the key players in ASP allergy. A combination of the BAT with the ASP-IgG level had the highest specificity (0.95) and positive predictive value (0.62), which permitted us to identify ASP allergy more effectively.Leukemia & lymphoma 04/2013; · 2.40 Impact Factor -
Article: Effects of Pitavastatin in Japanese Patients With Chronic Heart Failure.
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ABSTRACT: Background: Recent clinical trials using rosuvastatin, a hydrophilic statin, did not show beneficial effects on cardiovascular events in patients with heart failure. We examined the cardioprotective effects of pitavastatin, a lipophilic statin, on Japanese patients with chronic heart failure (CHF). Methods and Results: A total of 574 Japanese patients with CHF were randomly assigned to the pitavastatin group (n=288) or the control group (n=286). There was no significant difference between the 2 groups for the primary outcome, which was a composite of cardiac death and hospitalization for worsening HF (adjusted hazard ratio (aHR): 0.922, 95% confidence interval (CI): 0.632-1.345, P=0.672). A strongly significant statistical interaction between the effect of pitavastatin and left ventricular ejection fraction (LVEF) was found (P=0.004). In patients with LVEF ≥30%, a significant reduction in the primary outcome (aHR: 0.525, 95% CI: 0.308-0.896, P=0.018) was observed in the pitavastatin group. Pitavastatin did not show any effects on the primary outcome (aHR: 1.582, 95% CI: 0.890-2.813, P=0.118) in the subgroup of patients with LVEF <30%. Conclusions: Pitavastatin did not reduce cardiac death or hospitalization for worsening HF in Japanese patients with CHF. (UMIN-ID: UMINC000000428).Circulation Journal 03/2013; · 3.77 Impact Factor -
Article: Split hand syndrome in amyotrophic lateral sclerosis: different excitability changes in the thenar and hypothenar motor axons.
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ABSTRACT: BACKGROUND: In amyotrophic lateral sclerosis (ALS), muscle wasting preferentially affects the abductor pollicis brevis (APB) and first dorsal interosseous over the abductor digit minimi (ADM), and this is termed 'split hand'. Previous axonal excitability studies have suggested increased nodal persistent sodium current and reduced potassium current in motor axons in ALS, but the extent of excitability changes in APB and ADM axons in ALS has never been compared. OBJECTIVE: To elucidate the peripheral axonal pathophysiology of split hand. METHODS: In both APB and ADM motor axons of 21 patients with ALS and 17 age-matched normal controls, threshold tracking was used to measure excitability indices such as strength-duration time constant (SDTC; a measure of persistent sodium current) and threshold electrotonus. RESULTS: In normal controls, SDTC was significantly longer for APB than ADM axons, suggesting that axonal excitability is physiologically higher in APB axons. Compared with normal controls, patients with ALS had longer SDTC and greater threshold changes in depolarising threshold electrotonus in both APB and ADM axons. Furthermore, the difference in extent of SDTC prolongation between normal subjects and patients with ALS was greater in APB than ADM axons. CONCLUSIONS: APB axons have physiologically higher excitability than ADM axons, and, in ALS, the hyperexcitability is more prominent in APB axons. Although cortical mechanisms would also be involved, more prominent hyperexcitability of APB axons may contribute to development of split hand, and the altered axonal properties are possibly associated with motor neuronal death in ALS.Journal of neurology, neurosurgery, and psychiatry 03/2013; · 4.87 Impact Factor
