Deployment of an Autonomous Underwater Vehicle in Ice-covered Sea of Okhotsk : The First Japanese Challenge

第3回極域科学シンポジウム/第35回極域気水圏シンポジウム 11月29日（木） 国立国語研究所 ２階多目的

A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy

BACKGROUND: Deficiency of 4-aminobutyrate aminotransferase (GABA-T) is a rare disorder of GABA catabolism, with only a single sibship reported. We report on a third case, a Japanese female infant with severe psychomotor retardation and recurrent episodic lethargy with intractable seizures, with the diagnosis facilitated by proton magnetic resonance (MR) spectroscopy ((1)H-MRS). METHODS: Neuroimaging was performed at the first episode of lethargy. For (1)H-MRS, locations were placed in the semioval center and the basal ganglia. Quantification of metabolite concentrations were derived using the LCModel. We confirmed the diagnosis subsequently by enzyme and molecular studies, which involved direct DNA sequence analysis and the development of a novel multiplex ligation-dependent probe amplification test. RESULTS: (1)H-MRS analysis revealed an elevated GABA concentration in the basal ganglia (2.9 mmol/l). Based on the results of quantitative (1)H-MRS and clinical findings, GABA-T deficiency was suspected and confirmed in cultured lymphoblasts. Molecular studies of the GABA-T gene revealed compound heterozygosity for a deletion of one exon and a missense mutation, 275G>A, which was not detected in 210 control chromosomes. CONCLUSIONS: Our results suggest that excessive prenatal GABA exposure in the central nervous system (CNS) was responsible for the clinical manifestations of GABA transaminase deficiency. Our findings suggest the dual nature of GABA as an excitatory molecule early in life, followed by a functional switch to an inhibitory species later in development. Furthermore, quantitative (1)H-MRS appears to be a useful, noninvasive tool for detecting inborn errors of GABA metabolism in the CNS

Distribution of intraperitoneally administered deuterium-labeled water in aquaporin-4-knockout mouse brain after middle cerebral artery occlusion

IntroductionAs the movement of water in the brain is known to be involved in neural activity and various brain pathologies, the ability to assess water dynamics in the brain will be important for the understanding of brain function and the diagnosis and treatment of brain diseases. Aquaporin-4 (AQP4) is a membrane channel protein that is highly expressed in brain astrocytes and is important for the movement of water molecules in the brain.MethodsIn this study, we investigated the contribution of AQP4 to brain water dynamics by administering deuterium-labeled water (D2O) intraperitoneally to wild-type and AQP4 knockout (AQP4-ko) mice that had undergone surgical occlusion of the middle cerebral artery (MCA). Water dynamics in the infarct region and on either side of the anterior cerebral artery (ACA) was monitored with proton-density-weighted imaging (PDWI) performed on a 7T animal MRI.ResultsD2O caused a negative signal change quickly after administration. The AQP4-ko mice showed a delay of the time-to-minimum in both the contralateral and ipsilateral ACA regions compared to wild-type mice. Also, only the AQP4- ko mice showed a delay of the time-to-minimum in the ipsilateral ACA region compared to the contralateral side. In only the wild-type mice, the signal minimum in the ipsilateral ACA region was higher than that in the contralateral ACA region. In the infarct region, the signal attenuation was slower for the AQP4-ko mice in comparison to the wild-type mice.DiscussionThese results suggest that AQP4 loss affects water dynamics in the ACA region not only in the infarct region. Dynamic PDWI after D2O administration may be a useful tool for showing the effects of AQP4 in vivo

Association between serum calcium levels and prognosis, hematoma volume, and onset of cerebral hemorrhage in patients undergoing hemodialysis

Background: High serum calcium levels should be avoided in patients on hemodialysis (HD) because they can induce cardiovascular diseases and worsen the patient\u27s prognosis. In contrast, low serum calcium levels worsen the prognosis of patients with cerebral hemorrhage in the general population. So far, whether serum calcium levels in patients on HD are associated with cerebral hemorrhage remains unknown. This study aimed to reveal the association between serum calcium and cerebral hemorrhage in patients on HD, including in-hospital death, volume of hematoma, and onset of cerebral hemorrhage. Methods: This cross-sectional case-control study included 99 patients on HD with cerebral hemorrhage at a single center between July 1, 2007 and December 31, 2017. Controls included 339 patients on HD at a single HD center between July 1, 2011 and June 30, 2012. Data on serum calcium level, patient demographics, and comorbid conditions were collected, and associations between cerebral hemorrhage and subsequent death were evaluated by multivariate logistic regression analysis. Further, the association of these backgrounds and hematoma volume was evaluated by multiple regression analysis. Results: Of the 99 patients, 32 (32%) died from cerebral hemorrhage. The corrected serum calcium level (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.43-4.35; P < 0.001) and antiplatelet drug use (OR, 3.95; 95% CI, 1.50-10.4; P = 0.005)had significant effects on the prognosis. Moreover, the corrected serum calcium (P = 0.003) and antiplatelet drug use (P = 0.01) were significantly correlated with hematoma volume. In the patients, the corrected serum calcium level (OR, 1.54; 95% CI, 1.07-2.22; P = 0.02) was associated with the onset of cerebral hemorrhage, as was pre-hemodialysis systolic blood pressure (per 10 mmHg) (OR, 1.40; 95% CI, 1.23-1.59; P < 0.001). Conclusions: Although the precise mechanisms remain unknown, a high serum calcium level is associated with cerebral hemorrhage in patients on HD. Thus, we should pay attentions to a patient\u27s calcium level

Spatial Frequency-Based Analysis of Mean Red Blood Cell Speed in Single Microvessels: Investigation of Microvascular Perfusion in Rat Cerebral Cortex

BACKGROUND: Our previous study has shown that prenatal exposure to X-ray irradiation causes cerebral hypo-perfusion during the postnatal development of central nervous system (CNS). However, the source of the hypo-perfusion and its impact on the CNS development remains unclear. The present study developed an automatic analysis method to determine the mean red blood cell (RBC) speed through single microvessels imaged with two-photon microscopy in the cerebral cortex of rats prenatally exposed to X-ray irradiation (1.5 Gy). METHODOLOGY/PRINCIPAL FINDINGS: We obtained a mean RBC speed (0.9±0.6 mm/sec) that ranged from 0.2 to 4.4 mm/sec from 121 vessels in the radiation-exposed rats, which was about 40% lower than that of normal rats that were not exposed. These results were then compared with the conventional method for monitoring microvascular perfusion using the arteriovenous transit time (AVTT) determined by tracking fluorescent markers. A significant increase in the AVTT was observed in the exposed rats (1.9±0.6 sec) as compared to the age-matched non-exposed rats (1.2±0.3 sec). The results indicate that parenchyma capillary blood velocity in the exposed rats was approximately 37% lower than in non-exposed rats. CONCLUSIONS/SIGNIFICANCE: The algorithm presented is simple and robust relative to monitoring individual RBC speeds, which is superior in terms of noise tolerance and computation time. The demonstrative results show that the method developed in this study for determining the mean RBC speed in the spatial frequency domain was consistent with the conventional transit time method

Negative Correlation between Brain Glutathione Level and Negative Symptoms in Schizophrenia: A 3T 1H-MRS Study

BACKGROUND: Glutathione (GSH), a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients. METHODS AND FINDINGS: Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE (1)H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test). Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS) in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A. CONCLUSION: These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia