1,721,192 research outputs found
Vasculitis and organ pathology: a practical approach to histological diagnosis and clinical-pathologic correlations
Full text linkVasculitides are a complex and pleomorphic group of diseases, involving all types of vessels and, potentially, all organs, with heterogeneous clinical manifestations. The clinical diagnosis can be challenging due to the diverse clinical manifestations, variable disease course, and overlapping features with other conditions. Overall, the histopathologic diagnosis is a crucial component in the clinical workup and plays a central role in guiding treatment decisions and prognosis estimation. However, reaching a diagnosis can be challenging, due to the complexity of the disease, and the variability in histological findings of these disorders, often caused by the development of secondary changes that may obscure the diagnostic features. Moreover, vasculitides are relatively rare, and many pathologists are unfamiliar with the disease and their diagnostic criteria, both in the biopsy and autopsy setting. This monographic issue collects papers focused on the updated classification of vasculitis, recommendations for sample histologic processing, and clues to the histopathologic diagnosis in diverse organs and systems, providing a practical approach to this complex disease. We also want to take this opportunity to honor the memory of our friend and colleague G. Rossi with the editorial written by some of his best friends. His great commitment as a pathologist and as a researcher, his personality, full of generous outbursts, and his ability to put himself completely at the service of the institutions in which he served professionally, are a legacy that helps all of us in our daily lives and professions
[Cardiomyopathies due to defective energy metabolism: morphological and functional features].
No full textCardiomyopathies are defined as diseases of the myocardium associated with cardiac dysfunction and are classified by morphological characteristics as hypertrophic (HCM), dilated (DCM) arrhithmogenic right ventricular (ARVC) and restrictive cardiomyopathy. These were once considered as specific diagnoses but there is now considerable evidence that many different gene mutations can cause these pathologies. In recent years, big emphasis has been given to the possibility that deregulation of cardiac metabolism may play a role in the mechanisms that lead to cardiac maladaptive remodelling. Cardiac energy metabolism is tightly controlled in mammalian organisms during development and in response to diverse dietary, physiologic, and pathologic conditions. The cardiac phenotype of many genetic diseases caused by mutations in proteins involved in mitochondrial energy production and/or homeostasis, underscores the importance of energetic pathway on cardiac function. For example, inborn errors in nuclear-encoded mitochondrial fatty acid oxidation (FAO) pathway enzymes and defects in fatty acid uptake are an important cause of childhood HCM and sudden death. Abnormalities in mitochondrial respiratory chain function, particularly those caused by mitochondrial DNA (mtDNA) mutations, are responsible for a heterogeneous group of clinical disorders, including isolated HCM. Mitochondrial cardiomyopathies (MCM) are characterized by an adverse clinical course with biventricular dilation and failure, even at a young age. Mutations in genes encoding the gamma2 subunit of AMP-activated protein kinase (PRKAG2), alpha-galactosidase A (GLA) and lysosome-associated membrane proteine-2 (LAMP2) can cause profound myocardial hypertrophy in association with electrophysiological defects. Unlike HCM due to sarcomere gene mutations, which is characterized by myofiber disarray and fibrosis, large cytosolic vacuoles characterize cardiomyopathy due to defect in energy metabolism. Ultrastructural analysis revealed massive mitochondrial proliferation in MCM and glycogen in complexes with protein and/or lipids in cardiomyopathy due to PRKAG2, GLA and LAMP2 mutations
Zidovudine causes early increases in mitochondrial ribonucleic acid abundance and induces ultrastructural changes in cultured mouse muscle cells
No full textBACKGROUND: Zidovudine (azidothymidine, AZT) causes a toxic mitochondrial myopathy in AIDS patients with changes in mitochondrial (mt) DNA and mitochondrial structure. To determine early subcellular events in AZT myopathy in vitro we examined C2C12 myotubes treated with AZT (0.2, 2, 10 μg/ml) for up to 4 weeks. We identified AZT-induced effects on muscle intracellular compartments by determining the comparative abundance of selected myotube cytoplasmic and mtRNAs and mtDNA. EXPERIMENTAL DESIGN: RNA and DNA were extracted from cultured C2C12 myotubes, blotted and probed with cDNAs specific for the mitochondrial gene products cytochrome b and cytochrome c oxidase I, nuclear-encoded sarcomeric troponin C, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase. Transmission electron microscopy was performed on parallel samples. RESULTS: After 4 weeks of AZT, cytochrome b and cytochrome c oxidase I mtRNA abundance increased to 64% and to 31% above respective control levels. No change occurred in mtDNA abundance or nuclear encoded glyceraldehyde-3-phosphate dehydrogenase mRNA compared with the nuclear encoded sarcomeric troponin C control. Transmission electron microscopy showed focal disruption of mitochondrial cristae with intramyocytic lipid droplets after 14 days of AZT treatment. CONCLUSIONS: Increased mtRNA abundance in absence of changes in mtDNA abundance suggests that early AZT toxicity to mitochondria may relate to defects in mtDNA replication or mtRNA transcription
Endomyocardial biopsy findings in patients with ventricular arrhythmias of unknown origin
No full textDiagnosis of Myocarditis Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy The Role of Endomyocardial Biopsy Guided by Electroanatomic Voltage Map
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Evaluation of gastrointestinal mtDNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).
No full textMitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease characterized by severe gastro-intestinal (GI) dysmotility caused by mutations in the thymidine phosphorylase gene. Thymidine phosphorylase (TP) is involved in the control of the pyrimidine nucleoside pool of the cell. Reduced TP activity induces nucleotide pool imbalances that in turn affect both the rate and fidelity of mtDNA replication, leading to multiple deletions and depletion of mtDNA. By using laser capture microdissection and quantitative real-time-polymerase chain reaction technique, we showed that depletion of mitochondrial DNA (mtDNA) is the most prominent molecular defect in the gut wall of MNGIE patients. Depletion affects severely the smooth muscle cells of muscularis propria and the skeletal muscle component of the upper esophagus, while ganglion cells of the myenteric plexus show only a milder mtDNA reduction
PATHOLOGICAL EVIDENCE OF EXTENSIVE LEFT-VENTRICULAR INVOLVEMENT IN ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY
No full textArrhythmogenic right ventricular cardiomyopathy (also known as arrhythmogenic right ventricular dysplasia) is characterized by adipose or fibroadipose tissue replacement of the right ventricular myocardium, whereas the left ventricle is substantively spared. Two cases of the disease with evidence of extensive left ventricular involvement at pathologic examination are described. Hearts from two patients who died suddenly showed full-thickness right ventricular fatty infiltration associated with extensive left ventricular involvement (greater than 50% of myocardial thickness). These findings might explain the reported clinical features of left ventricle dysfunction in a subset of patients with arrhythmogenic right ventricular cardiomyopathy. In view of the biventricular involvement of the disease, it should simply be termed "arrhythmogenic cardiomyopathy.
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