1,721,151 research outputs found
Direct contribution of epithelium to organ fibrosis : epithelial-mesenchymal transition
No full textFibrosis of epithelial parenchymal organs and end-stage organ failure represent the final common pathway of many chronic diseases and are a major determinant of morbidity and mortality worldwide. Fibrosis is a complex response initiated to protect the host from an injurious event; nevertheless, it leads to serious organ damage when it becomes independent from the initiating stimulus. It involves massive deposition of matrix by an expanded pool of fibrogenic cells, disruption of the normal tissue architecture, and parenchymal destruction. Fibroblasts, the effector cells of matrix production, when engaged in fibrogenesis, display the highly activated phenotype characteristic of myofibroblasts. These cells are present in a large number in sites with ongoing inflammation, reparative reaction, and fibrosis, but their origin has not yet been definitely elucidated. Although proliferation of preexisting stromal fibroblasts and, probably, recruitment of bone marrow-derived fibrogenic cells may account for a portion of them, emerging evidence seems to indicate that an important number of matrix-producing fibroblasts/myofibroblasts arises through a mechanism of epithelial-mesenchymal transition. Through this process, epithelial cells would lose intercellular cohesion and would translocate from the epithelial compartment into the interstitium where, gaining a full mesenchymal phenotype, they could participate in the synthesis of the fibrotic matrix. Epithelial-mesenchymal transition is induced by the integrated actions of many stimuli including transforming growth factor-beta and matrix-generated signals that are also known to be implicated in inflammation, repair responses, and fibrosis. The consequences of epithelial-mesenchymal transition in chronic fibrosing diseases could be two-fold as follows: on one hand, by supplementing new mesenchymal cells, it might feed the expanding pool of interstitial fibroblasts/myofibroblasts responsible for the matrix accumulation; on the other hand, it could cause loss of epithelial cells, thus, contributing to the parenchyma destruction seen in advanced fibrosis. Markers of epithelium undergoing epithelial-mesenchymal transition include loss of E-cadherin and cytokeratin; de novo expression of fibroblast-specific protein 1/S100A4, vimentin, and alpha-smooth muscle actin; basement membrane component loss; and production of interstitial-type matrix molecules such as fibronectin and type I/III collagen. Evidence of epithelial-mesenchymal transition has been reported in the kidney, lung, liver, eye, and serosal membranes suggesting that epithelial-mesenchymal transition could be involved in the pathogenesis of fibrotic disorders in these organs. Thus, because of its fibrogenic potential, the detection of epithelial-mesenchymal transition in biopsy specimens could be useful diagnostically and represent a new biomarker of progression in chronic fibrosing diseases
Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load
Full text linkThe natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as "elite controllers (EC) or suppressors" and do not develop disease in the absence of anti-retroviral therapy. Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and EC
Eradication of Helicobacter pylori, improvement of gastritis, and the normalization of the hyperproliferative state of gastric mucosa did not prevent a case of gastric cancer
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VZV fulminant necrotizing encephalitis with concomitant EBV-related lymphoma and CMV ventriculitis: report of an AIDS case
No full textA case of AIDS with varicella zoster virus fulminant necrotizing encephalitis associated with cytomegalovirus ependymitis-subependymitis and a periventricular Epstein-Barr virus-related lymphoma is described. The patient had no herpes zoster cutaneous eruptions and died three days after the onset of symptoms. Varicella zoster virus and cytomegalovirus antigens were found by immunohistochemistry in the same area around a necrotic periventricular lesion; a periventricular lymphoma, large B cell type, was also observed. In situ hybridization with Epstein-Barr virus-encoded- RNAs probe was positive in about 40% of the neoplastic cells. The association of herpes-related lesions in the same cerebral region should be consistent in AIDS cases with acute neurological symptom
Structural elucidation of the Rifaximin Ph. Eur. Impurity H
No full textRifaximin, a semisynthetic, rifamycin-based non-systemic antibiotic is used in the treatment of acute and chronic gastrointestinal disorders. The aim of this study was the elucidation of the molecular structure of the 802 Dalton impurity which was found in Rifaximin industrial batches and reported with an erroneous structure in European Pharmacopoeia 6.5 (2009) [7] monograph as Rifaximin Impurity H. This impurity was isolated from Rifaximin by preparative HPLC and purified by column chromatography. The molecular structure was evidenced by means of 1H and 13C NMR spectroscopy, mass spectrometry and FT-IR
A new and sensitive approach for immunohistochemical analysis on formalin fixed murine tissues
No full textBackground. Immunohistochemistry (IHC) is the localization of antigens in different tissues using specific primary and secondary antibodies. IHC is widely used in basic research and surgical pathology, both in human and animal models. Frozen and fixed tissues can be used but fixation and paraffin embedding offer the best option for preserving the specimen morphology. Unfortunately, the most common fixative (10% buffered formalin) may alter the biochemistry of the proteins and mask antigens. For this reason, antigen retrieval is required to allow antigen-antibody binding and different types of digestive enzymes or heat-induced methods can be used.
Murine models have always been a challenge for IHC due to low sensitivity of mouse antibodies binding mouse tissues and limited availability of immunohistochemical reagents for formalin fixed tissues. In fact, most of the mouse-specific antibodies are only functional on frozen tissues but the quality of frozen sections is not good enough for morphological evaluation.
Aim. To propose a new and sensitive approach, based on heat-antigen retrieval, for IHC on formalin fixed-paraffin embedded murine tissues in order to provide a useful panel of antibodies for immunology research.
Methods. Tissues: murine colon, small bowel, lung, spleen. Fixative: 10% buffered formalin (24 hour at room temperature). We used a pressure cooker specifically designed for antigen retrieval (temperature of 125 C degrees and 20 psi, unmasking buffer at pH 6.00 which turns during boiling to 7.00) and tested a panel of 31 antibodies to identify leukocytes, endothelial and epithelial cells, cytoskeleton molecules, proliferation markers, and cytokines. These antibodies either cross-reacted with murine antigens or were mouse-specific. Immunohistochemical staining was carried out on an automated immunostainer. We compared several dilutions of the antibodies, and used various detection systems.
Results. See table 1. Overall, 21 of the tested antibodies showed specific positivity (highlighted in white), 4 antibodies failed to work (highlighted in red) and 6 produced a strong background which made it difficult to analyze the results (highlighted in yellow). The morphology of the cells and tissues was entirely preserved in all of the samples. In table 1 we reported the technical characteristics of the antibodies and our results in terms of: recommended concentration, recommended detection system for each antibody.
Conclusions. We demonstrated the useful application of an innovative method for immunohistochemical analysis on formalin fixed murine tissues: the decloaking chamber. This method will guarantee to deliver a clear and specific staining compared to other well recognized technique
Fabry disease: the role of renal biopsy in three females with mild clinical symptoms
No full textFabry's diseases (FD) is a rare X-linked lipid storage disorder due to a deficient lysosomal a-galactosidase A (a-GAL) activity. In males with the classic phenotype this metabolicleads to the intracellular accumulation of neutral GL throughout the body, mainly in kidney, heart and brain causing severe multisystemic failure. Heterozygous females are generally asymptomatic carriers and reanl biopsy is rarely performed. Conclusions: In female carriers of the Fabry's gene, renal biopsy should be considered if there is persistent proteinuria
Challenging diagnosis of an unusual solitary pulmonary nodule
No full textWe describe the case of a 64-year-old woman with a solitary pulmonary nodule and a previous breast carcinoma whose diagnosis of histoplasmoma was established only after surgical resection and appropriate stains. It is important not to confuse these two diseases as this will prevent inappropriate medical treatment. Limited surgery is indicated for the treatment of these circumscribed lesion
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