Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is an autosomal-dominant neurodegenerative disorder characterized by widespread fasciculations, proximal-predominant muscle weakness, and atrophy followed by distal sensory involvement. To date, large families affected by HMSN-P have been reported from two different regions in Japan. Linkage and haplotype analyses of two previously reported families and two new families with the use of high-density SNP arrays further defined the minimum candidate region of 3.3 Mb in chromosomal region 3q12. Exome sequencing showed an identical c.854C>T (p.Pro285Leu) mutation in the TRK-fused gene (TFG) in the four families. Detailed haplotype analysis suggested two independent origins of the mutation. Pathological studies of an autopsied patient revealed TFG- and ubiquitin-immunopositive cytoplasmic inclusions in the spinal and cortical motor neurons. Fragmentation of the Golgi apparatus, a frequent finding in amyotrophic lateral sclerosis, was also observed in the motor neurons with inclusion bodies. Moreover, TAR DNA-binding protein 43 kDa (TDP-43)-positive cytoplasmic inclusions were also demonstrated. In cultured cells expressing mutant TFG, cytoplasmic aggregation of TDP-43 was demonstrated. These findings indicate that formation of TFG-containing cytoplasmic inclusions and concomitant mislocalization of TDP-43 underlie motor neuron degeneration in HMSN-P. Pathological overlap of proteinopathies involving TFG and TDP-43 highlights a new pathway leading to motor neuron degeneration.

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The water solubility (Sw) in the temperature range from 283 to 308 K and 1-octanol/water partition coefficient (Kow) for the nonionic form of brominated phenols (BPhs) of varying bromine content (4-bromophenol, 2,4-dibromophenol, 2,4,6-tribromophenol, and pentabromophenol) were measured by the generator-column or shake-flask method and by the high-performance liquid chromatography method, respectively. The temperature dependence of Sw, namely enthalpy of solution (deltaHsolution), was calculated using the van't Hoff Equation. To determine the activity coefficients in water (gammaw) of BPhs from the Sw data, enthalpy of fusion (deltaHfusion) and melting point (Tm) were measured by a differential scanning calorimetry method. The gammaw was used for evaluating data consistency as well as for predicting other physico-chemical properties, such as the Henry's law constant (Hw). The present work systematically reports, to our knowledge for the first time, the experimental values of Sw, Kow, deltaHsolution, deltaHfusion, Tm, and gammaw for BPhs with one to five bromines, and it discusses the effects of bromine content on these physico-chemical properties. Finally, the overall physico-chemical characteristics of BPhs are compared with those of polychlorinated phenols, polycyclic aromatic hydrocarbons, and brominated benzenes with the same solubility level as BPhs.

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Despite some limitations, 16-slice MSCT is sufficiently useful for assessment of various coronary stents in patients and can detect in-stent restenoses of assessable stents with high accuracy in comparison to CAG.