Myofibroblastic conversion of mesothelial cells

Myofibroblastic conversion of mesothelial cells.BackgroundThe continuous chemical, physical, and inflammatory insults of prolonged continuous ambulatory peritoneal dialysis (CAPD) incite mesothelial cell responses, which may result in peritoneal fibrosis. The transforming growth factor-β (TGF-β), especially the isoform TGF-β1, has long been known to play crucial role in the fibrogenic process. Although several studies have implicated TGF-β in peritoneal fibrosis, the underlying mechanism has not been completely elucidated.MethodsTo test the effects of exogenous TGF-β1 on mesothelial cells, we assessed cytoarchitectural changes of human peritoneal mesothelial cells (HPMC) in in vitro culture by light, immunofluorescent, electron and immunoelectron microscopy, and differential gene expression analysis using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and cDNA expression array assays.ResultsThe TGF-β1–induced myofibroblastic conversion was a transdifferentiation process resulting in characteristic myofibroblastic phenotype that included prominent rough endoplasmic reticuli (rER) with dilated cisternas, conspicuous smooth muscle actin (SMA) myofilaments, frequent intercellular intermediate and gap junctions, and active deposition of extracellular matrix (ECM) and formation of fibronexus. The gene expression array analysis revealed complex modulation of gene expression involving cytoskeletal organization, cell adhesion, ECM production, cell proliferation, innate immunity, cytokine/growth factor signaling, cytoprotection, stress response, and many other essential metabolic processes in mesothelial cells.ConclusionThis report describes myofibroblastic conversion of mesothelial cells, a previously undefined, yet frequently speculated, cell adaptive or pathogenic process. Our study helps to elucidate the complex molecular and cellular events involved in myofibroblastic conversion of mesothelial cells. We propose that differentiated epithelial cells of mesothelium convert or transdifferentiate into myofibroblasts, which implies the recruitment of fibrogenic cells from mesothelium during serosal inflammation and wound healing

Correlation of histopathologic and dynamic tissue perfusion measurement findings in transplanted kidneys

BACKGROUND: Cortical perfusion of the renal transplant can be non-invasively assessed by color Doppler ultrasonography. We performed the Dynamic Tissue Perfusion Measurement (DTPM) of the transplant’s renal cortex using color Doppler ultrasonography (PixelFlux technique), and compared the results with the histopathological findings of transplant biopsies. METHODS: Ninety-six DTPM studies of the renal transplant’s cortex followed by transplant biopsies were performed in 78 patients. The cortical perfusion data were compared with the parameter of peritubular inflammatory cell accumulation (PTC 0 to 3) based on Banff-classification system. RESULTS: A significant decrease of cortical perfusion could be demonstrated as the inflammatory cells accumulation in peritubular capillaries increased. Increasing peritubulitis caused a perfusion loss from central to distal layers of 79% in PTC 0, of 85% in PTC 1, of 94% in PTC 2, and of 94% in PTC 3. Furthermore, the perfusion loss due to peritubular inflammation was more prominent in the distal cortical layer. The extent of perfusion decline with increasing peritubulitis (from PTC 0 to PTC 3) was 64% in proximal 20% cortical layer (p20), 63% in proximal 50% cortical layer (p50), increased to 76% in distal 50% cortical layer (d50), and peaked at 90% in the distal 20% cortical layer (d20). For those without peritubulitis (PTC 0), the increase in the the Interstitial Fibrosis/Tubular Atrophy (IF/TA) score was accompanied by a significantly increased cortical perfusion. A Polyomavirus infection was associated with an increased cortical perfusion. CONCLUSIONS: Our study demonstrated that the perfusion of the renal transplant is associated with certain pathological changes within the graft. DTPM showed a significant reduction of cortical perfusion in the transplant renal cortex related to peritubular capillary inflammation

Expression of c-Kit, Flk-1, and Flk-2 Receptors in Benign and Malignant Tumors of Follicular Epithelial Origin

BackgroundVascular endothelial growth factor (VEGF) is a key regulator of physiologic as well as pathologic angiogenesis. The response of VEGF to endothelial cell mitogenesis and survival, as well as angiogenesis and microvascular permeability, is mainly mediated through its receptor-2, VEGFR2 (kinase domain receptor or fetal liver kinase-1, KDR or Flk-1). This study aimed to detect the expression of VEGFR2 in various forms of thyroid tumors. In addition, the expression of Flk-2 (receptor for Flt-3) and c-Kit (receptor for steel locus factor), which shows strong similarity to Flk-1, was also examined in thyroid tumors.MethodsRT-PCR analyses of c-Kit and immunohistochemical staining of c-Kit, Flk-1, and Flk-2 were performed in archived samples of 18 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), 12 follicular adenoma (FA), and 7 nodular goiter (NG) samples. The data were correlated to clinicopathologic features.ResultsBy RT-PCR analyses, c-Kit expression was detected in 22% (4/18) of PTC, 22% (2/9) of FTC, 25% (3/12) of FA, and 57% (4/7) of NG samples. However, positive immunostaining signals of c-Kit were only observed in 17% (3/18) of PTC samples, and not in the others. Similarly, Flk-1 expression was only detected by immunohistochemistry in 67% (12/18) of PTC and 43% (3/7) of NG samples, and not in the others. Interestingly, the expression of Flk-2 was found in 89% (16/18) of PTC, 89% (8/9) of FTC, 75% (9/12) of FA, and 29% (2/7) of NG samples. An inverse relationship of thyroid cancer size with Flk-2 expression was found.ConclusionFlk-2 expression was detected in various forms of thyroid tumors and increased Flk-2 expression was correlated with thyroid tumors with increased transforming activity, suggesting that Flk-2 is involved in pathogenic development of thyroid malignancy. Similarly, Flk-1 expression was also found in some thyroid tumors, while the expression of c-Kit-mediated pathways may not play a major role in thyroid tumorigenesis

Ξc−Ξc′\Xi_c-\Xi_c^{\prime} mixing From Lattice QCD

In heavy quark limit, the lowest-lying charmed baryons with two light quarks can form an SU(3) triplet and sextet. The $\Xi_c$ in the SU(3) triplet and $\Xi_c'$ in the sextet have the same $J^{PC}$ quantum number and can mix due to the finite charm quark mass and the fact the strange quark is heavier than the up/down quark. We explore the $\Xi_c$-$\Xi_c'$ mixing by calculating the two-point correlation functions of the $\Xi_c$ and $\Xi_c'$ baryons from lattice QCD. Based on the lattice data, we adopt two independent methods to determine the mixing angle between $\Xi_c$ and $\Xi_c'$. After making the chiral and continuum extrapolation, it is found that the mixing angle $\theta$ is $1.2^{\circ}\pm0.1^{\circ}$, which seems insufficient to account for the large SU(3) symmetry breaking effects found in weak decays of charmed baryons

Isospin Effect on the Process of Multifragmentation and Dissipation at Intermediate Energy Heavy Ion Collisions

In the simulation of intermediate energy heavy ion collisions by using the isospin dependent quantum molecular dynamics, the isospin effect on the process of multifragmentation and dissipation has been studied. It is found that the multiplicity of intermediate mass fragments $N_{imf}$ for the neutron-poor colliding system is always larger than that for the neutron-rich system, while the quadrupole of single particle momentum distribution $Q_{zz}$ for the neutron-poor colliding system is smaller than that of the neutron-rich system for all projectile-target combinations studied at the beam energies from about 50MeV/nucleon to 150MeV/nucleon. Since $Q_{zz}$ depends strongly on isospin dependence of in-medium nucleon-nucleon cross section and weakly on symmetry potential at the above beam energies, it may serve as a good probe to extract the information on the in-medium nucleon-nucleon cross section. The correlation between the multiplicity $N_{imf}$ of intermediate mass fragments and the total numer of charged particles $N_c$ has the behavior similar to $Q_{zz}$, which can be used as a complementary probe to the in-medium nucleon-nucleon cross section.Comment: 18 pages, 9 figure