Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.

Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic, tumor spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

Dynamic and static magnetic resonance angiography of the supra-aortic vessels at 3.0 T: intraindividual comparison of gadobutrol, gadobenate dimeglumine, and gadoterate meglumine at equimolar dose.

PURPOSE: The purpose of this study was the intraindividual comparison of a 1.0 M and two 0.5 M gadolinium-based contrast agents (GBCA) using equimolar dosing in dynamic and static magnetic resonance angiography (MRA) of the supra-aortic vessels. MATERIALS AND METHODS: In this institutional review board-approved study, a total of 20 healthy volunteers (mean ± SD age, 29 ± 6 years) underwent 3 consecutive supra-aortic MRA examinations on a 3.0 T magnetic resonance system. The order of GBCA (Gadobutrol, Gadobenate dimeglumine, and Gadoterate meglumine) was randomized with a minimum interval of 48 hours between the examinations. Before each examination and 45 minutes after each examination, circulatory parameters were recorded. Total GBCA dose per MRA examination was 0.1 mmol/kg with a 0.03 mmol/kg and 0.07 mmol/kg split for dynamic and static MRA, respectively, injected at a rate of 2 mL/s. Two blinded readers qualitatively assessed static MRA data sets independently using pairwise rankings (superior, inferior, and equal). In addition, quantitative analysis was performed with signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) evaluation as well as vessel sharpness analysis of static MRA using an in-house-developed semiautomated tool. Dynamic MRA was evaluated for maximal SNR. Statistical analysis was performed using the Cohen κ, the Wilcoxon rank sum tests, and mixed effects models. RESULTS: No significant differences of hemodynamic parameters were observed. In static MRA, Gadobutrol was rated superior to Gadoterate meglumine (P < 0.05) and equal to Gadobenate dimeglumine (P = 0.06) with good to excellent reader agreement (κ, 0.66-0.83). In static MRA, SNR was significantly higher using 1.0 M Gadobutrol as compared with either 0.5 M agent (P < 0.05 and P < 0.05) and CNR was significantly higher as compared with Gadoterate meglumine (P < 0.05), whereas CNR values of Gadobutrol data sets were not significantly different as compared with Gadobenate dimeglumine (P = 0.13). Differences in CNR between Gadobenate dimeglumine and Gadoterate meglumine were not significant (P = 0.78). Differences in vessel sharpness between the different GBCAs were also not significant (P > 0.05). Maximal SNR in dynamic MRA using Gadobutrol was significantly higher than both comparators at the level of the proximal and distal internal carotid artery (P < 0.05 and P < 0.05; P < 0.05 and P < 0.05). CONCLUSIONS: At equimolar doses, 1.0 M Gadobutrol demonstrates higher SNR/CNR than do Gadobenate dimeglumine and Gadoterate meglumine, with superior image quality as compared with Gadoterate meglumine for dynamic and static carotid MRA. Despite the shortened bolus with Gadobutrol, no blurring of vessel edges was observed.

Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS.

The mechanistic understanding of how membrane-embedded sensor kinases recognize signals and regulate kinase activity is currently limited. Here we report structure-function relationships of the multidomain membrane sensor kinase DcuS using solid-state NMR, structural modeling and mutagenesis. Experimental data of an individual cytoplasmic Per-Arnt-Sim (PAS) domain were compared to structural models generated in silico. These studies, together with previous NMR work on the periplasmic PAS domain, enabled structural investigations of a membrane-embedded 40-kDa construct by solid-state NMR, comprising both PAS segments and the membrane domain. Structural alterations are largely limited to protein regions close to the transmembrane segment. Data from isolated and multidomain constructs favor a disordered N-terminal helix in the cytoplasmic domain. Mutations of residues in this region strongly influence function, suggesting that protein flexibility is related to signal transduction toward the kinase domain and regulation of kinase activity.

In vitro analysis of the two-component system MtrB-MtrA from Corynebacterium glutamicum.

The two-component system MtrBA is involved in the osmostress response of Corynebacterium glutamicum. MtrB was reconstituted in a functionally active form in liposomes and showed autophosphorylation and phosphatase activity. In proteoliposomes, MtrB activity was stimulated by monovalent cations used by many osmosensors for the detection of hypertonicity. Although MtrB was activated by monovalent cations, they lead in vitro to a general stabilization of histidine kinases and do not represent the stimulus for MtrB to sense hyperosmotic stress.