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Our findings lead us to strongly recommend that (i) genetic analysis should be performed in patients with polyneuropathy of unknown etiology, and (ii) that RNAi therapy should be started as early as possible in patients with genetically confirmed ATTRv amyloidosis. In contrast, excessive amyloid deposits were visible in the heart and sympathetic ganglia, and moderate amyloid deposits were found in several organs even after the periodic administration of patisiran for 21 months, likely because therapy was initiated at a late stage of the disease. Sural nerve biopsy showed no amyloid deposits in the endoneurium or perineurium, but a small amount of amyloid deposition was visible on the vessel wall by Congo red staining (Supplementary Figure S2). Although TTR synthesis in hepatocytes was significantly reduced, massive amyloid deposits were found in some organs, even after RNAi therapy, likely because of the late initiation of the therapy. [Extracted from the article]

Right temporal variant frontotemporal dementia, also called right-predominant semantic dementia, often has an unclear position within the framework of the updated diagnostic criteria for behavioral variant frontotemporal dementia or primary progressive aphasia. Recent studies have suggested that this population may be clinically, neuropathologically, and genetically distinct from those with behavioral variant frontotemporal dementia or left-predominant typical semantic variant primary progressive aphasia. Here we describe a Japanese case of right temporal variant frontotemporal dementia with novel heterozygous MAPT mutation Adenine to Thymidine in intervening sequence (IVS) 9 at position -7 from 3ʹ splicing site of intron 9/exon 10 boundary (MAPT IVS9-7A > T). Postmortem neuropathological analysis revealed a predominant accumulation of 4 repeat tau, especially in the temporal lobe, amygdala, and substantia nigra, but lacked astrocytic plaques or tufted astrocytes. Immunoelectron microscopy of the tau filaments extracted from the brain revealed a ribbon-like structure. Moreover, a cellular MAPT splicing assay confirmed that this novel variant promoted the inclusion of exon 10, resulting in the predominant production of 4 repeat tau. These data strongly suggest that the MAPT IVS9-7 A > T variant found in our case is a novel mutation that stimulates the inclusion of exon 10 through alternative splicing of MAPT transcript and causes predominant 4 repeat tauopathy which clinically presents as right temporal variant frontotemporal dementia. [ABSTRACT FROM AUTHOR]

The Escherichia coli yqgF gene is highly conserved across a broad spectrum of bacterial genomes. The gene was first identified as being essential for cell growth during screening for targets for broad-spectrum antibiotics. YqgF is structurally similar to RuvC, a Holliday junction resolvase, but its function has not been established. This study describes the isolation of a temperature-sensitive yqgF mutant, the growth of which was inhibited by rho or nusA multicopy plasmids, indicating that YqgF is involved in transcription. Rho is a global transcription termination factor that acts at Rho-dependent terminator sites, which exist not only at the ends of genes but also within genes. The transcription of genes possessing intragenic, or upstream, Rho-dependent terminators was reduced in temperature-sensitive yqgF mutants. This transcription inhibition was sensitive to the Rho inhibitor, bicyclomycin. In addition, the transcription of mutant tnaA genes defective for upstream Rho-dependent termination was not significantly affected by the yqgF mutation. Taken together, these results suggest that YqgF is involved in anti-termination at Rho-dependent terminators in vivo. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic performance of the kinetic parameter maximum slope (MS) in breast lesions obtained by ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) of the contrast wash-in period with that of the washout index (WI) derived from standard DCE MRI and that of the Breast Imaging Reporting and Data System (BI-RADS) category.Materials and Methods: In total, 138 contrast enhanced lesions (90 malignant, 48 benign) were evaluated. Ultrafast DCE MRI images were acquired using a k-space-weighted image contrast (KWIC), obtained 0-1 min after gadolinium injection (3.75 s/frame; 16 frames) and followed by standard DCE MRI (60 s/frame, 3 frames). MS was calculated for the KWIC time series as percentage relative enhancement per second (%/s). As a semi-quantitative parameter for the standard DCE MRI time series, WI was evaluated using the change in signal intensity between early and delayed phases. The diagnostic performance (malignant/benign differentiation) of MS, WI, and BI-RADS category was compared by ROC analysis using the area under the curve (AUC).Results: The AUC of MS was as good as that of WI (0.81 vs. 0.79, respectively; P = 0.81), yet inferior to the BI-RADS category (0.81 vs. 0.96, respectively; <0.001). MS tended to have higher sensitivity (91.1% [82/90]) compared with WI (87.8% [79/90]) with same specificity (62.5% [30/48]).Conclusions: MS obtained by ultrafast DCE MRI of the breast is a promising kinetic parameter in the differential diagnosis of malignant and benign breast lesions with decreased scanning time. [ABSTRACT FROM AUTHOR]

We prospectively examined the variability of non-Gaussian diffusion magnetic resonance imaging (MRI) and intravoxel incoherent motion (IVIM) measurements with different numbers of b-values and excitations in normal breast tissue and breast lesions. Thirteen volunteers and fourteen patients with breast lesions (seven malignant, eight benign; one patient had bilateral lesions) were recruited in this prospective study (approved by the Internal Review Board). Diffusion-weighted MRI was performed with 16 b-values (0–2500 s/mm2 with one number of excitations [NEX]) and five b-values (0–2500 s/mm2, 3 NEX), using a 3T breast MRI. Intravoxel incoherent motion (flowing blood volume fraction [fIVIM] and pseudodiffusion coefficient [D*]) and non-Gaussian diffusion (theoretical apparent diffusion coefficient [ADC] at b value of 0 sec/mm2 [ADC0] and kurtosis [K]) parameters were estimated from IVIM and Kurtosis models using 16 b-values, and synthetic apparent diffusion coefficient (sADC) values were obtained from two key b-values. The variabilities between and within subjects and between different diffusion acquisition methods were estimated. There were no statistical differences in ADC0, K, or sADC values between the different b-values or NEX. A good agreement of diffusion parameters was observed between 16 b-values (one NEX), five b-values (one NEX), and five b-values (three NEX) in normal breast tissue or breast lesions. Insufficient agreement was observed for IVIM parameters. There were no statistical differences in the non-Gaussian diffusion MRI estimated values obtained from a different number of b-values or excitations in normal breast tissue or breast lesions. These data suggest that a limited MRI protocol using a few b-values might be relevant in a clinical setting for the estimation of non-Gaussian diffusion MRI parameters in normal breast tissue and breast lesions. [ABSTRACT FROM AUTHOR]