Transient elastography improves detection of liver cirrhosis compared to routine screening tests

AIM:To investigate the diagnostic significance oftransient elastography(TE) in a daily routine clinical setting in comparison to clinical signs,laboratory parameters and ultrasound.METHODS:TE,ultrasound,laboratory parameters and cutaneous liver signs were assessed in 291 consecutive patients with chronic liver disease of various aetiologies who underwent liver biopsy in daily routine.RESULTS:Sensitivity of TE for the detection of liver cirrhosis was 90.4%,compared to 80.1% for ultrasound,58.0% for platelet count and 45.1% for cutaneous liver signs(P < 0.0001 for comparisons with histology).AUROC for TE was 0.760(95%CI:0.694-0.825).Combination of TE with ultrasound increased sensitivity to 96.1% and AUROC to 0.825(95%CI:0.768-0.882).TE correlated with laboratory parameters of cirrhosis progression like albumin(r =-0.43),prothrombin time(r =-0.44),and bilirubin(r = 0.34; P < 0.001 for each).Particularly,in patients with Child Pugh score A or normal platelet count TE improved sensitivity for the detection of liver cirrhosis compared to ultrasound by 14.1%(P < 0.04) and 16.3%(P < 0.02),respectively.CONCLUSION:Transient elastography is superior to routine diagnostic tests allowing detection of liver cirrhosis in additional 10%-16% of patients with chronic liver disease that would have been missed by clinical examinations.     

Adult c‐Kit(+) progenitor cells are necessary for maintenance and regeneration of olfactory neurons

The olfactory epithelium houses chemosensory neurons, which transmit odor information from the nose to the brain. In adult mammals, the olfactory epithelium is a uniquely robust neuroproliferative zone, with the ability to replenish its neuronal and non‐neuronal populations due to the presence of germinal basal cells. The stem and progenitor cells of these germinal layers, and their regulatory mechanisms, remain incompletely defined. Here we show that progenitor cells expressing c‐Kit, a receptor tyrosine kinase marking stem cells in a variety of embryonic tissues, are required for maintenance of the adult neuroepithelium. Mouse genetic fate‐mapping analyses show that embryonically, a c‐Kit(+) population contributes to olfactory neurogenesis. In adults under conditions of normal turnover, there is relatively sparse c‐Kit(+) progenitor cell (ckPC) activity. However, after experimentally induced neuroepithelial injury, ckPCs are activated such that they reconstitute the neuronal population. There are also occasional non‐neuronal cells found to arise from ckPCs. Moreover, the selective depletion of the ckPC population, utilizing temporally controlled targeted diphtheria toxin A expression, results in failure of neurogenesis after experimental injury. Analysis of this model indicates that most ckPCs reside among the globose basal cell populations and act downstream of horizontal basal cells, which can serve as stem cells. Identification of the requirement for olfactory c‐Kit–expressing progenitors in olfactory maintenance provides new insight into the mechanisms involved in adult olfactory neurogenesis. Additionally, we define an important and previously unrecognized site of adult c‐Kit activity. J. Comp. Neurol. 523:15–31, 2015. © 2014 Wiley Periodicals, Inc.     

One-Step Identification of Five Prominent Chicken Salmonella Serovars and Biotypes

Based on bacterial genomic data, we developed a one-step multiplex PCR assay to identify Salmonella and simultaneously differentiate the two invasive avian-adapted S. enterica serovar Gallinarum biotypes Gallinarum and Pullorum, and the most frequent, specific, and asymptomatic colonizers of chickens, serovars Enteritidis, Heidelberg, and Kentucky.     

Dynamics of different functional parts of bacteriorhodopsin: H-2H labeling and neutron scattering

We show that dynamics of specific amino acids within a protein can be characterized by neutron spectroscopy and hydrogen–deuterium labeling, and we present data on the motions of a selected set of groups within bacteriorhodopsin (BR), the retinal-based proton pump in the purple membrane of halophilic Archaea. Elastic incoherent neutron scattering experiments allow the definition of motions in the nano- to picosecond time scale and have revealed a dynamical transition from a harmonic to a softer, anharmonic atomic fluctuation regime in the global behavior of proteins. Biological activity in proteins is correlated with this transition, suggesting that flexibility is required for function. Elastic incoherent neutron scattering is dominated by H atom scattering, and to study the dynamics of a selected part of BR, fully deuterated purple membrane with BR containing H-retinal, H-tryptophan, and H-methionine was prepared biosynthetically in Halobacterium salinarum. These amino acids cluster in the functional center of the protein. In contrast to the protein globally, the thermal motions of the labeled atoms were found to be shielded from solvent melting effects at 260 K. Above this temperature, the labeled groups appear as more rigid than the rest of the protein, with a significantly smaller mean square amplitude of motion. These experimental results quantify the dynamical heterogeneity of BR (which meets the functional requirements of global flexibility), on the one hand, to allow large conformational changes in the molecule and of a more rigid region in the protein, on the other, to control stereo-specific selection of retinal conformations.     

Apoptosis in the liver: a matter of ion fluxes and oxidative stress: Third International Conference of the Collaborative Research Center 'Experimental Hepatology' (SFB-575), Düsseldorf, Germany, 13-14 October 2006.

The cell death of hepatocytes is a characteristic feature of liver damage triggered by viral infection, drug abuse, fat overload or autoimmunity. Apoptosis is currently the best-understood form of cell death; however, the precise mechanisms leading to apoptosis in liver disease are largely unknown. Several cellular processes including alterations in cell hydration and ion homeostasis, osmotic and oxidative stress, lysosomal permeabilization as well as alternate forms of cell death may contribute to liver damage. The intriguing complexity and relevance of these processes for liver failure were addressed at the Third International Conference of the Collaborative Research Center 'Experimental Hepatology' (SFB-575),which was held in Düsseldorf, Germany, in 13-14 October 2006. The aim of this symposium was to bring together leading researchers studying cell death pathways in the liver and other systems and to share ideas and recent research findings. This report covers some of the salient and stimulating contributions of the meeting and gives an updated survey of the advances in this burgeoning field of translational medicine.     

Scintigraphy for risk stratification of iodine-induced thyrotoxicosis in patients receiving contrast agent for coronary angiography: a prospective study of patients with low thyrotropin

The risk of iodine-induced thyrotoxicosis in euthyroid patients receiving iodine-containing contrast agents is known to be low, but data on this risk in patients with latent hyperthyroidism are scarce. We investigated the role of thyroid scintigraphy using Tc-99m preceding the application of iodine-containing contrast material to estimate the risk of iodine-induced thyrotoxicosis in patients with low levels of TSH. In a prospective study on 91 patients, thyroid scintigraphy was performed before coronary angiography (CA). In patients with technetium thyroid uptake (TCTU) less than 1%, CA was done without prophylactic drugs (n = 56). Patients with TCTU greater than 1% were treated either with 900 mg of perchlorate or, depending on the autonomous volume, combined with 20 to 60 mg thiamazole. In the 56 patients with TCTU less than 1%, no case of iodine-induced hyperthyroidism occurred within 4 wk after CA. In the patients who received prophylactic drugs, two cases of mild thyrotoxicosis were observed. Our data suggest that in patients with low levels of TSH, the risk of hyperthyroidism after application of iodine-containing contrast media is negligible if TCTU is less than 1%. In these patients, CA can be performed without administration of prophylactic drugs.     

Granzyme B delivery via perforin is restricted by size, but not by heparan sulfate-dependent endocytosis

How granzymes gain entry into the cytosol of target cells during killer cell attack has been the subject of several studies in the past, but the effective delivery mechanism during target cell encounter has not been clarified. Here we show that granzyme B (GzmB) mutants lacking binding to negatively charged, essentially heparan-sulfate-containing membrane receptors are poorly endocytosed yet are delivered to the cytosol with efficacy similar to that of WT GzmB. In a cell-based system GzmB-deficient natural killer cells provided perforin (pfn) by natural polarized secretion and synergized with externally added GzmB. Whereas receptor (heparan sulfate)-dependent endocytosis was dispensable, delivery of larger cargo like that of GzmB fusion proteins and GzmB–antibody complexes was restricted by their size. Our data support the model in which granzymes are primarily translocated through repairable membrane pores of finite size and not by the disruption of endocytosed vesicles. We conclude that structurally related translocators, i.e., perforin and cholesterol-dependent cytolysins, deliver deathly cargo across host cell membranes in a similar manner.