The role of the diffusion sequence in magnetic resonance imaging for the differential diagnosis between hepatocellular carcinoma and benign liver lesions.

BACKGROUND AND AIM: To assess the role of diffusion weighted imaging sequence (DWI), routinely used in hepatic magnetic resonance imaging (MRI) for the differentiation of hepatocellular carcinoma (HCC) from benign liver lesions. METHODS: A number of 56 liver MRI examinations were retrospectively analyzed independently by two experienced radiologists, blinded to each other results. A total number of 70 Focal Liver Lesions (FLLs) assessed by liver MRI in 56 patients were included in the present study. All lesions were retrospectively analyzed by two experienced radiologists, independently from each other and who were not aware of the previous results given by using different imaging techniques. All included FLLs had a final histological diagnosis, or the final diagnosis was based on consensus reading by two experienced radiologists. The signal of the included FLLs was qualitatively appreciated on the b-800 sequences and on the apparent diffusion coefficient (ADC) map. The ADC value of each FLL was measured and the ADC ratio between the ADC value of the assessed FLL and that of the surrounding liver parenchyma was calculated. RESULTS: The mean ADC value for benign FLLs as assessed by the two independent readers was 1.75 × 10(-3) and 1.72 × 10(-3). The mean ADC value for HCC nodules was 0.92 × 10(-3) for the first reader and 0.91 × 10(-3) for the second reader respectively. The mean ADC ratio for benign FLLs was 1.81 and 1.84 for the two readers, respectively. The ADC ratio for HCC nodules was 0.91 and 0.91, respectively. The ADC value is an indicator which is less prone to interobserver variability (correlation of 0.919→1). The ADC ratio has, as the analysis of the ROC curve shows, the best predictive value for differentiation between benign FLLs and HCC nodules. Analysis of the signal intensity on the DWI b-800 image alone is of no significance in differentiating benign FLLs from HCC nodules (p>0.005). CONCLUSIONS: The ADC value and the ADC ratio assessed on liver DWI are useful diagnostic tools in the differential diagnosis of benign FLLs vs HCC nodules. Quantitative methods such as calculating the ADC value or ADC ratio have better diagnostic value than qualitative techniques.

How does Mg(2+) affect the binding of anhydrotetracycline in the TetR protein?

The binding of anhydrotetracycline (atc) in wild-type TetR(D), TetR(B), and four single tryptophan mutants of TetR(B) was investigated by UV/vis absorption, steady state, and time-resolved fluorescence spectroscopy. From absorption titration experiments with Mg2+, we conclude that binding of one [atc-Mg]+ complex in the homodimer causes changes in the protein conformation around the second binding pocket. In the presence of absence of Mg2+, several different groups of atc-protein arrangements must exist, each with a characteristic atc fluorescence decay time. Taking into account the results of molecular dynamics (MD) simulations, we propose as one possible origin for such a differentiation teh extent of hydrogen bonding between atc and the surrounding amino acids. Binding of Mg2+ should change the arrangement of the surrounding amino acids such that some of the excited atc molecules do not undergo the relaxation process typical for free atc. The MD simulations also show that the pattern of intra- and intermolecular hydrogen bonding in the two monomeric units is no correlated, thereby leading to different fluorescence kinetics for atc in the two monomeric units. Furthermore, it is suggested that hydrogen bonding between Arg104 and O10 of anhydrotetracycline could regulate the relaxation processes of excited anhydrotetracycline.

Pressure effect on the structure of the Tet repressor protein TetR(B).

The fluorescence of two single tryptophan (trp) mutants of the TetR(B)dimer protein was monitored for hydrostatic pressures 0.1 MPa < p < 300 MPa. In mutant W170, in which trp interacts with segments of both subunits, the fitted fluorescence lifetimes vary both with pressure and observation wavelength. In contrast, the lifetimes are fairly independent of both parameters in the case of W171, in which trp is completely solvent exposed. This difference in fluorescence behaviour is in agreement with the fact that only trp 170 experiences a strong alteration of its direct environment upon a movement of alpha-helix 9 induced by increasing static pressure. The conformational changes induced by pressure in this protein region are only partly reversible. After pressure release, the originally more solvent exposed trp 171 ends up, at least in part, in a more solvent shielded environment and the originally protein embedded trp 170 ends up in a more solvent exposed conformation. These observations provide evidence for heterogeneity in chromophore-protein arrangement under normal, biologically relevant conditions. Furthermore, they indicate that no complete dissociation into monomers occurs at pressures below 300 MPa.