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European Journal of Clinical... Jan 2019
Topics: Animals; Cell Nucleus; Hepatocytes; Rats; Rifabutin
PubMed: 30368739
DOI: 10.1007/s10096-018-3411-7 -
Veterinary Pathology Nov 2022We performed a retrospective examination of spontaneous hepatocellular carcinomas (HCCs) (primary and metastatic tumors) in 14 captive prosimians brought to the...
We performed a retrospective examination of spontaneous hepatocellular carcinomas (HCCs) (primary and metastatic tumors) in 14 captive prosimians brought to the Veterinary Medical Diagnostic Laboratory in North Carolina State University over a period of 11 years (2003 to 2014) to characterize the tumors. These animals are endangered primates; a better understanding of the main fatal neoplasms is crucial. In addition to the histologic evaluation, an immunohistochemical study was also performed, using a hepatocyte marker (hepatocyte paraffin 1 [HepPar-1]) and 2 cholangiocyte markers (keratin 7 [K7] and keratin 19 [K19]), in an attempt to identify a specific profile for HCCs with metastatic behavior. Six of the 14 HCCs had pulmonary metastases. The most frequent histopathological findings were a trabecular pattern (14/14, 100%), presence of multinucleated cells (12/14, 85.7%), and foci of extramedullary hematopoiesis (9/14, 64.3%). The mitotic count was significantly higher in the metastatic HCCs ( < .05). HepPar-1 was detected in all primary and metastatic HCCs, with a strong intensity of staining. Labeling for K7 and K19 was positive in 12 HCCs (85.7%) and 1 HCC (7.1%), respectively. Contrary to the less aggressive HCCs, most of the metastatic HCCs (5/6) expressed K7 in more than 15% of cells. The percentage of K7-positive neoplastic hepatocytes was significantly higher in metastatic HCCs. This study suggests that K7 might be a prognostically relevant marker in HCCs of captive prosimians.
Topics: Animals; Biomarkers, Tumor; Carcinoma, Hepatocellular; Immunohistochemistry; Keratin-19; Keratin-7; Liver Neoplasms; Paraffin; Retrospective Studies; Strepsirhini
PubMed: 35876312
DOI: 10.1177/03009858221114471 -
World Journal of Hepatology Apr 2021Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically... (Review)
Review
Giant cell hepatitis (GCH) is characterized by large and multinucleated (syncytial) hepatocytes in the context of liver inflammation. Infantile GCH is typically associated with autoimmune hemolytic anemia in the absence of any other systemic or organ-specific autoimmune comorbidity. The etiology is unknown; concomitant viral infections (as potential trigger factors) have been identified in a few patients. The pathogenesis reportedly relies upon immune-mediated/ autoimmune mechanisms. This condition should be considered in any infant developing Coombs-positive anemia; indeed, anemia usually precedes the development of hepatitis. The clinical course is usually aggressive without the appropriate immunosuppressive therapy, which may include steroids, conventional immunosuppressors (, azathioprine and cyclophosphamide as first-line treatments), intravenous immunoglobulin, and biologics (rituximab). Improvements in medical management (including the availability of rituximab) have significantly reduced the mortality of this condition in the last decade.
PubMed: 33959224
DOI: 10.4254/wjh.v13.i4.411 -
Frontiers in Physiology 2017Polyploidy, the existence of cells containing more than one pair of chromosomes, is a well-known feature of mammalian hepatocytes. Polyploid hepatocytes are found either...
Polyploidy, the existence of cells containing more than one pair of chromosomes, is a well-known feature of mammalian hepatocytes. Polyploid hepatocytes are found either as cells with a single polyploid nucleus or as multinucleated cells with diploid or even polyploid nuclei. In this study, we evaluate the degree of polyploidy in the murine liver by accounting both DNA content and number of nuclei per cell. We demonstrate that mouse hepatocytes with diploid nuclei have distinct metabolic characteristics compared to cells with polyploid nuclei. In addition to strong differential gene expression, comprising metabolic as well as signaling compounds, we found a strongly decreased insulin binding of nuclear polyploid cells. Our observations were associated with nuclear ploidy but not with total ploidy within a cell. We therefore suggest ploidy of the nuclei as an new diversity factor of hepatocytes and hypothesize that hepatocytes with polyploid nuclei may have distinct biological functions than mono-nuclear ones. This diversity is independent from the well-known heterogeneity related to the cells' position along the porto-central liver-axis.
PubMed: 29163206
DOI: 10.3389/fphys.2017.00862 -
Veterinary Pathology Nov 2014Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is...
Multinucleated hepatocytes (MNHs) have been occasionally reported in macaques, as well as chimpanzees and gorillas, as an incidental finding. However, information is sparse on variations in incidence in the cynomolgus macaque (Macaca fascicularis). A survey was conducted to assess the occurrence of MNHs in the liver of stock (nonstudy) animals from SNBL SRC (Alice, TX) and SNBL USA (Everett, WA) submitted for diagnostic purposes. A total of 215 cynomolgus monkeys originally from Cambodia (61), China (5), Indonesia (125), and Mauritius (24) were used for this investigation. From each animal, usually 2 liver samples were processed for histopathology with 2 sections in each slide. An MNH was defined as a hepatocyte with 3 or more nuclei. A threshold of 3 MNHs was selected for the Multinucleated Hepatocyte Grading System: 0 = not remarkable (≤3 MNHs counted from 2-4 liver sections), minimal = 4 to 15 MNHs, mild = 16 to 30 MNHs, moderate = 31 to 59 MNHs, and severe ≥60 MNHs. The incidence of MNHs was 60 of 86 (70%) in males and 72 of 129 (56%) in females for a total overall incidence of 132 of 215 animals (61%). Affected hepatocytes were frequently observed close to the capsule and generally had 3 to 8 nuclei per hepatocyte but as many as 15 occurred in a single cell. Awareness of the incidence of MNHs in cynomolgus monkeys is important for potential use as background data in preclinical safety and toxicity evaluation studies.
Topics: Animals; Cell Nucleus; Female; Hepatocytes; Liver; Macaca fascicularis; Male
PubMed: 24395914
DOI: 10.1177/0300985813516641 -
In Vivo (Athens, Greece) 2009Muscle injury induces strong changes in muscle cells and extracellular matrix. Muscle regeneration after injury has similarities to muscle development during... (Review)
Review
Muscle injury induces strong changes in muscle cells and extracellular matrix. Muscle regeneration after injury has similarities to muscle development during embryogenesis and seems to follow the same procedure. The initial phase of muscle repair is characterized by inflammation and degeneration of the damaged tissue. Almost simultaneously, previous quiescent myogenic cells, called satellite cells, are activated, proliferate, differentiate and fuse to form multinucleated myofibers. Other non-muscle stem cells may also take part in this process. Secreted factors, such as hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor-betas (TGF-betas), insulin-like growth factors (IGFs), tumour necrosis factor alpha (TNFalpha) and others, are released during muscle repair and guide muscle regeneration, however, their exact functions and effects on muscle remodeling remain unknown. Intensive research is currently addressing the regenerative mechanisms which are involved in acute muscle injuries and chronic muscle diseases.
Topics: Animals; Cell Differentiation; Cytokines; Extracellular Matrix; Humans; Muscle Development; Muscle Fibers, Skeletal; Muscle, Skeletal; Regeneration; Satellite Cells, Skeletal Muscle; Stem Cells; Wound Healing
PubMed: 19779115
DOI: No ID Found -
Human Pathology Apr 2009Progress in liver histopathology continues to be made, as evidenced by recent publications in all areas of hepatobiliary disease. Multinucleated giant hepatocytes, known... (Review)
Review
Progress in liver histopathology continues to be made, as evidenced by recent publications in all areas of hepatobiliary disease. Multinucleated giant hepatocytes, known to be associated with autoimmune and drug hepatitis, now have been seen in chronic hepatitis C with or without HIV infection and in patients with infection by human herpesvirus-6A. The new term Mallory-Denk body (formerly the Mallory body) recognizes the substantial contributions to this field by Professor Helmut Denk of Austria. The problems of fatty liver and hepatic iron overload have been addressed in studies highlighting their complex pathogenesis. Genomic and immunohistochemical analysis of liver tumors provides important diagnostic information, particularly regarding the use of glypican-3 in the diagnosis of hepatocellular carcinoma.
Topics: Humans; Liver Diseases
PubMed: 19289183
DOI: 10.1016/j.humpath.2008.12.014 -
Veterinary Microbiology Feb 2004Porcine circovirus type 2 (PCV2) is now recognised as the causal agent of porcine multisystemic wasting syndrome (PMWS), an economically important wasting disease of... (Review)
Review
Porcine circovirus type 2 (PCV2) is now recognised as the causal agent of porcine multisystemic wasting syndrome (PMWS), an economically important wasting disease of young pigs [J. Vet. Diagn. Invest. 12 (2000) 3]. Gross lesions of PMWS include generalised lymphadenopathy, hepatitis, nephritis and pneumonia and typical histological lesions include lymphocytic depletion and multinucleated giant cell formation in lymph nodes, degeneration and necrosis of hepatocytes, and multifocal lymphohistocytic interstitial pneumonia. This communication will review the results of experimental infections of gnotobiotic (GN), colostrum-deprived (CD) and colostrum-fed (CF) pigs within our group, and elsewhere, with PCV2 and the conclusions that can be drawn from this work.
Topics: Animals; Circoviridae Infections; Circovirus; Colostrum; Germ-Free Life; Parvoviridae Infections; Parvovirus, Porcine; Swine; Swine Diseases; Wasting Syndrome
PubMed: 14741129
DOI: 10.1016/j.vetmic.2003.10.009 -
Journal of the South African Veterinary... Jun 2005A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to...
A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA) origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell) hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.
Topics: Amyloidosis; Animals; Blood Chemical Analysis; Fatal Outcome; Female; Kidney Diseases; Kidney Medulla; Lions; Liver; Serum Amyloid A Protein
PubMed: 16108528
DOI: 10.4102/jsava.v76i2.404 -
Histology and Histopathology Mar 2009Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The... (Review)
Review
Physiological and pathological bone resorption is mediated by osteoclasts, multinucleated cells which are formed by the fusion of monocyte / macrophage precursors. The canonical pathway of osteoclast formation requires the presence of the receptor activator for NFkappaB ligand (RANKL) and macrophage colony stimulating factor (M-CSF). Non-canonical pathways of osteoclast formation have been described in which cytokines / growth factors can substitute for RANKL or M-CSF to induce osteoclast formation. Substitutes for RANKL include LIGHT, TNFalpha and interleukins 6, 11 and 8. M-CSF substitutes include vascular endothelial growth factor (VEGF), placental growth factor (PlGF), FLt-3 ligand and hepatocyte growth factor (HGF). These growth factors can also influence canonical (RANKL / M-CSF-induced) osteoclast formation. Both canonical and non-canonical pathways of osteoclast formation play a role in the formation of osteolytic lesions where there is increased osteoclast formation and activity, such as in giant cell tumour of bone.
Topics: Cytokines; Humans; Macrophage Colony-Stimulating Factor; Models, Biological; Osteoclasts; Osteolysis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Tumor Necrosis Factor-alpha
PubMed: 19130404
DOI: 10.14670/HH-24.337