Objective: To apply a computerized morphometric model to evaluate and quantify the morphologic features, including hepatic progenitor cells, in large regenerative nodules (LRN) and high grade dysplastic nodules (DN) in hepatitis C virus (HCV)-related cirrhosis.
Study Design: Thirty-two cirrhotic nodules; 10 LRN; and 8 DN were identified in cirrhotic livers with HCV-related cirrhosis removed at transplantation. All specimens were stained for routine diagnosis with hematoxylin-eosin and immunohistochemically for CD31, CD34, cytokeratin 7 (CK7) and reticulin. We determined by a computerized morphometric model on hematoxylin-eosin slices the volume fractions occupied by hepatocyte nuclei and cytoplasm, sinusoids, portal triads, fibrosis and centrilobular veins. We also investigated volume fraction of hepatocytes expressing CK7, and volume fractions of capillary units and of sinusoid capillarization expressing CD31 and CD34, respectively, and surface fraction of reticulin.
Results: Compared to LRN, DN showed higher volume fraction of hepatocyte nuclei, higher number of hepatocytes in unit volume, higher nuclear/cytoplasmic ratio, higher volume fractions of capillarized sinusoids, capillary units and CK7 positive hepatocytes and lower mean hepatocyte volume and surface reticulin fraction.
Conclusion: Our morphometric model is an objective method of quantification of the morphologic changes of LRN and DN, including the hepatic progenitor compartment.
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J Physiol
January 2025
Center for Developmental Health, Oregon Health & Science University, Portland, OR, USA.
Robust preclinical models of asymmetric ventricular loading in late gestation reflecting conditions such as hypoplastic left heart syndrome are lacking. We characterized the morphometry and microvascular function of the hypoplastic left ventricle (LV) and remaining right ventricle (RV) in a sham-controlled late gestation fetal lamb model of impaired left ventricular inflow (ILVI). Singleton fetuses were instrumented at ∼120 days gestational age (dGA; term is ∼147 days) with vascular catheters, an aortic flow probe and a deflated left atrial balloon.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Background: Close to 80 to 90% of subjects with AD also present cerebral amyloid angiopathy (CAA) a disease in which amyloid accumulation damages the vasculature an impairs blood flow. Since current AD therapies are targeting the disease focusing on amyloid, we are interested on determine how to decrease the accumulation of amyloid in the vasculature observed in CAA and our aim is to determine the impact of tau reduction in CAA pathogenesis.
Method: We crossed the Tg-FDD mice CAA model with Mapt mice to decrease tau levels and analyzed the disease pathogenesis in the different genotypes though behavioral tests, histological and morphometric assays and transcriptomic analysis using the nCounter neuroimmflamation panel from Nanostring.
Pathologica
December 2024
Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy.
HPV status is an important prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), with HPV-positive tumors associated with better overall survival. To determine HPV status, we rely on the immunohistochemical investigation for expression of the P16 protein, which must be associated with molecular investigation for the presence of viral DNA. We aim to define a criterion based on image analysis and machine learning to predict HPV status from hematoxylin/eosin stain.
View Article and Find Full Text PDFNat Cardiovasc Res
January 2025
Department of Physiology, Anatomy & Genetics, University of Oxford, Oxford, UK.
During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps of differentiation to form functionally distinct subtypes of ECs. A key example is the formation of lymphatic ECs (LECs), which are thought to arise largely through transdifferentiation from venous endothelium. Opposing this model, here we show that the initial expansion of mammalian LECs is primarily driven by the in situ differentiation of mesenchymal progenitors and does not require transition through an intermediate venous state.
View Article and Find Full Text PDFIntroduction: Chronic kidney disease (CKD) and heart failure with preserved ejection fraction (HFpEF) are more prevalent in the elderly. There is a lack of large animal models that allow the study of the impact of age on CKD and HFpEF in a translational fashion. This manuscript reports the first large preclinical model of CKD-HFpEF and metabolic derangements in naturally aged swine.
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