Background-Stem/progenitor cell niches in tissues regulate stem/progenitor cell differentiation and proliferation through local signalling.

The liver has enormous regenerative capacity. Following acute liver injury, hepatocyte division regenerates the parenchyma but, if this capacity is overwhelmed during massive or chronic liver injury, the intrinsic hepatic progenitor cells (HPCs) termed oval cells are activated. These HPCs are bipotential and can regenerate both biliary epithelia and hepatocytes. Multiple signalling pathways contribute to the complex mechanism controlling the behaviour of the HPCs. These signals are delivered primarily by the surrounding microenvironment. During liver disease, stem cells extrinsic to the liver are activated and bone-marrow-derived cells play a role in the generation of fibrosis during liver injury and its resolution. Here, we review our current understanding of the role of stem cells during liver disease and their mechanisms of activation.

Objective: To investigate by high frequency ultrasonography the appearance of calcium pyrophosphate dihydrate (CPPD) calcifications, in the most commonly affected sites in CPPD disease, and the relationship between ultrasonographic CPPD deposits and the presence of CPPD crystals in synovial fluid. Methods: Three ultrasonographic patterns of CPPD calcification were identified and 11 patients enrolled. A control group comprised 13 patients with no evidence of CPPD deposits. Synovial fluid was aspirated from all patients and controls and examined for identification of crystals. All patients underwent a standard radiography examination at the same sites investigated by ultrasound. Results: In all patients with ultrasonographically defined CPPD deposits, CPPD crystals were found in the synovial fluid. In two cases, standard radiographic examination did not show evidence of the calcific deposits that were identified by ultrasonography. CPPD crystals were not found in the synovial fluid of controls. In four control group patients, ultrasonography identified calcifications defined as deposits of another nature. Conclusions: The ultrasonographic pattern used in this study for the diagnosis of CPPD disease demonstrated a very high correlation with the presence of CPPD crystals in synovial fluid. Ultrasonography demonstrated a sensitivity and specificity at least equal to that of radiography in identifying CPPD crystal calcifications. U ntil now, the diagnosis of calcium pyrophosphate dihydrate (CPPD) crystal deposition disease has been based mainly on radiographic or microscopic detection of CPPD crystals.Ryan and McCarty proposed several diagnostic criteria for the diagnosis of CPPD crystal deposition disease, 1 based on the premise that CPPD crystals are the specific feature of the disease and including radiographic clues suggested by Resnick et al 2 and Martel et al. 3 According to these criteria, a case is definite if CPPD crystals are demonstrated in tissues or synovial fluid by definite means (for example, chemical analysis) or if crystals are demonstrated by compensated polarised light microscopy and typical calcifications are seen on radiographs. In this last case, if only one of these criteria is found, a probable diagnosis is made.Ultrasound (US) is a very sensitive and specific technique for detecting calcifications of soft tissues, 4 5 but only a few papers have described sonographic evidence of articular and periarticular changes caused by CPPD disease. [6][7][8][9] In this paper we tried to define the US aspect of CPPD calcifications in order to propose ultrasonographic criteria for the differentiation of CPPD deposits and hyperechoic deposits of another nature. We then tried to verify the relationship between the ultrasonographically defined presence of CPPD calcifications in cartilage and periarticular tissues and the presence of CPPD crystals in the synovial fluid and compare the US findings with the radiographic findings. PATIENTS AND METHODSWe enrolled in this study all patients with US evidence of CP...

In adult skeletal muscles, 2 junctophilin isoforms (JPH1 and JPH2) tether the sarcoplasmic reticulum (SR) to transverse tubule (T-tubule) membranes, generating stable membrane contact sites known as triads. JPHs are anchored to the membrane of the SR by a C-terminal transmembrane domain (TMD) and bind the T-tubule membrane through their cytosolic N-terminal region, which contains 8 lipid-binding (MORN) motifs. By combining expression of GFP-JPH1 deletion mutants in skeletal muscle fibers with in vitro biochemical experiments, we investigated the molecular determinants of JPH1 recruitment at triads in adult skeletal muscle fibers. We found that MORN motifs bind PI(4,5)P2 in the sarcolemma, but do not mediate the selective localization of JPH1 at the T-tubule compartment of triads. On the contrary, fusion proteins containing only the TMD of JPH1 were able to localize at the junctional SR compartment of the triad. Bimolecular fluorescence complementation experiments indicated that the TMD of JPH1 can form dimers, suggesting that the observed localization at triads may result from dimerization with the TMDs of resident JPH1. A second domain, capable of mediating homo- and heterodimeric interactions between JPH1 and JPH2 was identified in the cytosolic region. FRAP experiments revealed that removal of either one of these 2 domains in JPH1 decreases the association of the resulting mutant proteins with triads. Altogether, these results suggest that the ability to establish homo- and heterodimeric interactions with resident JPHs may support the recruitment and stability of newly synthesized JPHs at triads in adult skeletal muscle fibers.

Posttransplantation lymphoproliferative disorders include a wide spectrum of diseases ranging from hyperplastic-appearing lesions to frank non-Hodgkin lymphoma. More than 90% of these disorders are Epstein-Barr virus-associated lesions of B-cell origin that arise in the setting of pharmacologic immunosuppression after transplantation. With the increased use of organ transplantation and intensive immunosuppression, posttransplantation lymphoproliferative disorders are becoming more common. The prognosis is often poor, with most patients dying despite receiving treatment. The aim of this review is to report the most recent knowledge about the clinical features, diagnosis, prophylaxis, and treatment of posttransplantation lymphoproliferative disorders, which can be useful to physicians and health assistants dealing with these life-threatening, posttransplantation clinical entities in clinical practice.

Communicated by Maria Rita Passos-BuenoMalignant hyperthermia (MH) is a dominantly inherited pharmacogenetic condition that manifests as a life-threatening hypermetabolic reaction when a susceptible individual is exposed to common volatile anesthetics and depolarizing muscle relaxants. Although MH appears to be genetically heterogeneous, RYR1 is the main candidate for MH susceptibility. However, since molecular analysis is generally limited to exons where mutations are more frequently detected, these are routinely found only in 30-50% of susceptible subjects. In this study the entire RYR1 coding region was analyzed in a cohort of 50 Italian MH susceptible (MHS) subjects. Thirty-one mutations, 16 of which were novel, were found in 43 individuals with a mutation detection rate of 86%, the highest reported for RYR1 in MH so far. These data provide clear evidence that mutations in the RYR1 gene are the predominant cause of MH.

Obscurin contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity in skeletal muscle fibers.

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