Longitudinal correlations between MRE,MRI-PDFF,and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

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The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options

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The Arabidopsis repressor of light signaling, COP1, is regulated by nuclear exclusion: mutational analysis by bioluminescence resonance energy transfer

Bioluminescence resonance energy transfer (BRET) between Renilla luciferase and yellow fluorescent protein has been adapted to serve as a real-time reporter on protein-protein interactions in live plant cells by using the Arabidopsis Constitutive photomorphogenesis 1 (COP1) protein as a model system. COP1 is a repressor of light signal transduction that functions as part of a nuclear E3 ubiquitin ligase. COP1 possesses a leucine-rich nuclear-exclusion signal that resides in a domain implicated in COP1 dimerization. BRET was applied in conjunction with site-directed mutagenesis to explore the respective contributions of the nuclear-exclusion and dimerization motifs to the regulation of COP1 activity in vivo. One specific mutant protein, COP1(L105A), showed increased nuclear accumulation but retained the ability to dimerize, as monitored by BRET, whereas other mutations inhibited both nuclear exclusion and COP1 dimerization. Mutant rescue and overexpression experiments indicated that nuclear exclusion of COP1 protein is a rate-limiting step in light signal transduction.     

Renal fractional flow reserve: a hemodynamic evaluation of moderate renal artery stenoses.

The objective of this study was to perform a hemodynamic evaluation of moderate (50-90%) renal artery stenosis (RAS) under conditions of rest and maximum hyperemia. Identifying patients with RAS who have hemodynamically significant stenoses and are most likely to benefit from revascularization is clinically important. Current methods used to evaluate RAS, including angiography, have limitations. Physiologic evaluation of RAS may have a role in identifying patients with hemodynamically significant stenosis. Patients with suspected renovascular hypertension due to aorto-ostial RAS were included in the study. Hyperemia was induced by administration of intrarenal papavarine. Translesional pressure gradients were measured and renal fractional flow reserve (FFR) was calculated using a 0.014' pressure guidewire. Thirteen patients and 14 arteries with moderately severe (50-90%) RAS were studied. The mean translesional pressure gradient rose from a baseline of 6.3 +/- 3.9 to 17.5 +/- 10.8 mm Hg with maximal hyperemia. The renal FFR ranged from 0.58 to 0.95. There was a poor correlation between angiographic stenosis measurement and the renal FFR (r = -0.18; P = 0.54) and the hyperemic translesional mean pressure gradient (r = 0.22; P = 0.44). There was an excellent correlation between renal FFR and the resting mean translesional pressure gradient (r = -0.76; P = 0.0016) and the hyperemic mean translesional pressure gradient (r = -0.94; P < 0.0001). Selective renal arterial papavarine administration induces maximum hyperemia, permitting the calculation of renal FFR in renal arteries with aorto-ostial stenoses. The renal FFR correlates well with other hemodynamic parameters of lesion severity, but poorly with angiographic measures of lesion severity.     

Valve injury and repair in balloon aortic valvuloplasty

Aortic valves 0.5, and 4.5 months after successful percutaneous balloon aortic valvuloplasty (BAV) were examined. BAV caused macroscopic and microscopic fractures in calcific deposits. An inflammatory response was identified that may lead to valvular scarring. This process may be an important factor in the development of restenosis after BAV.     

Vivax and falciparum malaria seen at an Indian service hospital

The cases of 740 adult males with vivax and/or falciparum malaria managed in a military hospital in north-eastern India during the period from June 1978 to March 1981 were analysed. Four hundred and nine (55.3%) were infected with Plasmodium falciparum, 237 (32.0%) with P. vivax and the remaining 94 (12.7%) with both P. vivax and P. falciparum. The majority of cases were chloroquine sensitive and did not pose diagnostic or therapeutic problems. Of 381 patients subjected to an extended field test, 82 (21.5%) exhibited a variable degree of chloroquine resistance. Cerebral and haemopoietic involvement were the commonest of the pernicious syndromes observed in 92 (12.4%) patients. Atypical presentations, variable chloroquine resistance and presentation with complications call for timely recognition and institution of a specific supportive therapeutic regime.     

Mechanism of topology simplification by type II DNA topoisomerases

Type II DNA topoisomerases actively reduce the fractions of knotted and catenated circular DNA below thermodynamic equilibrium values. To explain this surprising finding, we designed a model in which topoisomerases introduce a sharp bend in DNA. Because the enzymes have a specific orientation relative to the bend, they act like Maxwell's demon, providing unidirectional strand passage. Quantitative analysis of the model by computer simulations proved that it can explain much of the experimental data. The required sharp DNA bend was demonstrated by a greatly increased cyclization of short DNA fragments from topoisomerase binding and by direct visualization with electron microscopy.