Early Involvement of the Corpus Callosum in a Patient with Hereditary Diffuse Leukoencephalopathy with Spheroids Carrying the de novo K793T Mutation of CSF1R

We herein report the case of a 41-year-old Japanese man with hereditary diffuse leukoencephalopathy with spheroids (HDLS) who carried the de novo K793T mutation in the colony-stimulating factor 1 receptor gene (CSF1R). He showed a gradual decline of his cognitive and mental functions over the following six months. On brain MRI, a thin corpus callosum with T2- and FLAIR-high signal intensity in the splenium was conspicuous, whereas cerebral deep and periventricular white matter lesions were mild. We propose that a diagnosis of HDLS should be considered in patients with presenile dementia presenting with corpus callosum lesions on MRI, even in cases with a lack of any apparent family history.ArticleINTERNAL MEDICINE. 52(4):503-506 (2013)journal articl

Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

Objective Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. Methods We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. Results All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p < 0.01; with non-CNS group, p < 0.01). Conclusion This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.ArticleINTERNAL MEDICINE. 53(1):21-27 (2014)journal articl

Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

Objective Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. Methods We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. Results All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p < 0.01; with non-CNS group, p < 0.01). Conclusion This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.ArticleINTERNAL MEDICINE. 53(1):21-27 (2014)journal articl

Patients With Refractory Out-of-Cardiac Arrest and Sustained Ventricular Fibrillation as Candidates for Extracorporeal Cardiopulmonary Resuscitation - Prospective Multi-Center Observational Study.

BACKGROUND: We investigated whether patients with out-of-hospital cardiac arrest (OHCA) and sustained ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT) or conversion to pulseless electrical activity/asystole (PEA/asystole) benefit more from extracorporeal cardiopulmonary resuscitation (ECPR). Methods and Results: We analyzed data from the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan, which was a prospective, multicenter, observational study with 22 institutions in the ECPR group and 17 institutions in the conventional CPR (CCPR) group. Patients were divided into 4 groups by cardiac rhythm and CPR group. The primary endpoint was favorable neurological outcome, defined as Cerebral Performance Category 1 or 2 at 6 months. A total of 407 patients had refractory OHCA with VF/pVT on initial electrocardiogram. The proportion of ECPR patients with favorable neurological outcome was significantly higher in the sustained VF/pVT group than in the conversion to PEA/asystole group (20%, 25/126 vs. 3%, 4/122, P\u3c0.001). Stratifying by cardiac rhythm, on multivariable mixed logistic regression analysis an ECPR strategy significantly increased the proportion of patients with favorable neurological outcome at 6 months in the patients with sustained VF/pVT (OR, 7.35; 95% CI: 1.58-34.09), but these associations were not observed in patients with conversion to PEA/asystole. CONCLUSIONS: OHCA patients with sustained VF/pVT may be the most promising ECPR candidates (UMIN000001403)

Structure of human factor VIIa/tissue factor in complex with a peptide-mimetic inhibitor: high selectivity against thrombin by introducing two charged groups in P2 and P4

The crystal structure of human factor VIIa/soluble tissue factor in complex with a highly selective peptide-mimetic factor VIIa inhibitor has been solved at 2.6 Å resolution. This structure suggests that Asp60 and Lys192 are key residues for achieving high selectivity against thrombin inhibition

Variation in Agronomic Traits of Myanmar’s Major Rice Cultivars in Wet Season and Dry Season

In Myanmar, the double cropping area using photoperiod insensitive rice cultivars is gradually expanding with the development of irrigation facilities. However, performance of agronomic traits of these rice cultivars between wet season (WS) and dry season (DS) have not been clarified. The objective of this study is to evaluate variation of heading date, culm length, panicle length, panicle number and paddy yield of rice cultivars in WS and DS, and to identify main components explaining phenotypic variations by genotypes, locations, cropping seasons and year in Myanmar to establish efficient cropping system. We used eight major cultivars (Theedatyin, Manawthukha, Sinthukha, Sinthwelatt, Kyawzeya, Shwewartun, Ayeyarmin and Pawsanyin) and planted in 2014 and 2015 for DS, in 2015 and 2016 for WS. As the results of experiments at three locations; Yezin, Hmawbi and Myaungmya, we found that heading date of all cultivars grown in WS at Yezin and Myaungmya were about 10 to 16 days earlier than those in DS except for Theedatyin, although Yezin is located about 320 km north of Myaungmya. Further, the difference in heading date between WD and DS was larger in middle matured cultivar group than that of middle/late matured cultivar group at Yezin and Myaungmya. On the other hand, heading dates in WS and DS were almost the same in all cultivars grown at Hmawbi which is located about 100 km east of Myaungmya. These variations in heading date could be attributed to difference of day and night temperature in WS and DS at each location. Culm length in WS was longer than that of DS in all cultivars at all locations except for 2015 DS at Myaungmya. An air–dry effect is likely to be a cause do this variation. Analysis of variance revealed that phenotypic variance of heading date and culm length was highly associated to genotype, season and location as well as their interactions. Genotypes and interaction of genotypes by season were significant component of phenotypic variance of yield. In analysis of variance separately conducted in WS and DS showed that genotype, location and interaction between genotypes and location were found to be associated to heading date and yield. The results suggest that the cultivar trials at different locations need to be conducted both in WS and DS to improve the efficiency of selection for widely adopted cultivars as well as to make efficient cropping system in Myanmar