Brain Reorganization in Patients with Brachial Plexus Injury: A Longitudinal Functional MRI Study

The aim of this study is to assess plastic changes of the sensorimotor cortex (SMC) in patients with traumatic brachial plexus injury (BPI) using functional magnetic resonance imaging (fMRI). Twenty patients with traumatic BPI underwent fMRI using blood oxygen level-dependent technique with echo-planar imaging before the operation. Sixteen patients underwent their second fMRI at approximately one year after injury. The subjects performed two tasks: a flexion-extension task of the affected elbow and a task of the unaffected elbow. After activation, maps were generated, the number of significantly activated voxels in SMC contralateral to the elbow movement in the affected elbow task study (Naf) and that in the unaffected task study (Nunaf) were counted. An asymmetry index (AI) was calculated, where AI = (Naf − Nunaf)/(Naf + Nunaf). Ten healthy volunteers were also included in this fMRI study. The AI of the first fMRI of the patients with BPI was significantly lower than that of the healthy subjects (P = 0.035). The AI of the second fMRI significantly decreased compared with that of the first fMRI (P = 0.045). Brain reorganization associates with peripheral nervous changes after BPI and after operation for functional reconstruction

Mutations in Ran system affected telomere silencing in Saccharomyces cerevisiae

The Ran GTPase system regulates the direction and timing of several cellular events, such as nuclear-cytosolic transport, centrosome formation, and nuclear envelope assembly in telophase. To gain insight into the Ran system\u27s involvement in chromatin formation, we investigated gene silencing at the telomere in several mutants of the budding yeast Saccharomyces cerevisiae, which had defects in genes involved in the Ran system. A mutation of the RanGAP gene, rna1-1, caused reduced silencing at the telomere, and partial disruption of the nuclear Ran binding factor, yrb2-Δ2, increased this silencing. The reduced telomere silencing in rna1-1 cells was suppressed by a high dosage of the SIR3 gene or the SIT4 gene. Furthermore, hyperphosphorylated Sir3 protein accumulated in the rna1-1 mutant. These results suggest that RanGAP is required for the heterochromatin structure at the telomere in budding yeast. © 2007 Elsevier Inc. All rights reserved

Evaluation of endometrial thickness in postmenopausal women by using 3.0-T MRI

Background: The accepted threshold for normal endometrial thickness is 5 mm; lesions with endometrial thickness 5 mm areconsidered malignant. However, endometrium ≥ 5 mm on transvaginal ultrasonography inpostmenopausal woman is considered as asymptomatic endometrial thickening. However, recent studies suggest that asymptomatic endometrial thickness of even 8 mm – 11 mm in postmenopausal women may be normal. Objectives: The present study investigated the normal endometrial thickness range in 297 asymptomatic postmenopausal women using 3.0-T magnetic resonance imaging (MRI) T2-weighted sagittal images measured retrospectively by a single radiologist. Method: The data were classified according to patient age and postmenopausal duration, and the medical records and follow-up MR images were reviewed to assess the clinical outcome. Results: The mean endometrial thickness was 2.4 ± 0.1 mm (range: 0.1–11.6). The endometriumin 21 of 297 subjects was ≥ 5 mm thick. Follow-up MR images were obtained in 17 of these 21 women, and their endometrial thickness was found to have decreased in all of them. To date,none of the subjects has been diagnosed with endometrial cancer. Conclusion: Although 5 mm is considered the conservative threshold of normal endometrial thickness on MRI of postmenopausal women, this figure should not, to avoid excessive false-positive diagnoses, be assumed as an indication of malignancy

Truncated KCNQ1 mutant, A178fs/105, forms hetero-multimer channel with wild-type causing a dominant-negative suppression due to trafficking defect

AbstractWe identified a novel mutation Ala178fs/105 missing S3–S6 and C-terminus portions of KCNQ1 channel. Ala178fs/105-KCNQ1 expressed in COS-7 cells demonstrated no current expression. Co-expression with wild-type (WT) revealed a dominant-negative effect, which suggests the formation of hetero-multimer by mutant and WT. Confocal laser microscopy displayed intracellular retention of Ala178fs/105-KCNQ1 protein. Co-expression of the mutant and WT also increased intracellular retention of channel protein compared to WT alone. Our findings suggest a novel mechanism for LQT1 that the truncated S1–S2 KCNQ1 mutant forms hetero-multimer and cause a dominant-negative effect due to trafficking defect

Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization

RBM20 is a major regulator of heart-specific alternative pre-mRNA splicing of TTN encoding a giant sarcomeric protein titin. Mutation in RBM20 is linked to autosomal-dominant familial dilated cardiomyopathy (DCM), yet most of the RBM20 missense mutations in familial and sporadic cases were mapped to an RSRSP stretch in an arginine/serine-rich region of which function remains unknown. In the present study, we identified an R634W missense mutation within the stretch and a G1031X nonsense mutation in cohorts of DCM patients. We demonstrate that the two serine residues in the RSRSP stretch are constitutively phosphorylated and mutations in the stretch disturb nuclear localization of RBM20. Rbm20 S637A knock-in mouse mimicking an S635A mutation reported in a familial case showed a remarkable effect on titin isoform expression like in a patient carrying the mutation. These results revealed the function of the RSRSP stretch as a critical part of a nuclear localization signal and offer the Rbm20 S637A mouse as a good model for in vivo study

Central nervous system post-transplant lymphoproliferative disorder after allogeneic hematopoietic stem cell transplantation: The Nagasaki transplant group experience

A 17-year-old male received allogeneic transplantation for acute lymphoblastic leukemia, and presented with generalized seizures due to a solitary brain lesion with massive necrosis on day +621. Epstein?Barr virus (EBV) DNA copies were below the cut-off value in plasma. Stereotactic biopsy of the cerebral lesion confirmed the diagnosis of post-transplant lymphoproliferative disorder (PTLD) with large atypical cells positive for CD20 and EBER.In order to diagnose primary central nervous system PTLD, the biopsy should be applied as early as possible when brain lesion with necrosis develops in post-transplant patients regardless of EBV-DNA in plasma

Delta-Sarcoglycan Gene Therapy Halts Progression of Cardiac Dysfunction, Improves Respiratory Failure, and Prolongs Life in Myopathic Hamsters

The BIO14.6 hamster provides a useful model of hereditary cardiomyopathies and muscular dystrophy. Previous delta-sarcoglycan (δSG) gene therapy (GT) studies were limited to neonatal and young adult animals, and prevented the development of cardiac and skeletal muscle dysfunction. GT of a pseudo-phosphorylated mutant of phospholamban (S16EPLN) moderately alleviated the progression of cardiomyopathy

Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy

ObjectivesWe sought to explore the relationship between a Tcap gene (TCAP)abnormality and cardiomyopathy.BackgroundHypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) cause severe heart failure and sudden death. Recent genetic investigations have revealed that mutations of genes encoding Z-disc components, including titin and muscle LIM protein (MLP), are the primary cause of both HCM and DCM. The Z-disc plays a role in establishing the mechanical coupling of sarcomeric contraction and stretching, with the titin/Tcap/MLP complex serving as a mechanical stretch sensor. Tcap interacts with the calsarcin, which tethers the calcineurin to the Z-disc.MethodsThe TCAPwas analyzed in 346 patients with HCM (236 familial and 110 sporadic cases) and 136 patients with DCM (34 familial and 102 sporadic cases). Two different in vitro qualitative assays—yeast two-hybrid and glutathion S-transferase pull-down competition—were performed in order to investigate functional changes in Tcap's interaction with MLP, titin, and calsarcin-1 caused by the identified mutations and a reported DCM-associated mutation, R87Q.ResultsTwo TCAPmutations, T137I and R153H, were found in patients with HCM, and another TCAPmutation, E132Q, was identified in a patient with DCM. It was demonstrated by the qualitative assays that the HCM-associated mutations augment the ability of Tcap to interact with titin and calsarcin-1, whereas the DCM-associated mutations impair the interaction of Tcap with MLP, titin, and calsarcin-1.ConclusionsThese observations suggest that the difference in clinical phenotype (HCM or DCM) may be correlated with the property of altered binding among the Z-disc components