Massive hepatic necrosis is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague.We examined 13 explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis, and three-dimensional reconstruction of serial sections were applied.Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed α-fetoprotein. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules.Regeneration of human livers following massive hepatic necrosis can occur in two ways-either through proliferation of α-fetoprotein-positive acinary-arranged hepatocytes or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration and hence have therapeutic implications.
In our Department, between 1991 and 1996, 132 patients, there of 87 male-45 female, average age of 48.2 years underwent surgery because of stage 1 (T2) to stage 3 melanoma that was located on the skin. None of patients suffered from early or in situ melanoma. Our retrospective study was based on those 94 patients who had been followed up by Department or dermatology-oncology in our medical centre. Surgery is still the primary treatment for cutaneous malignant melanoma. Thin melanomas (up to 2 mm in thickness) can be excised with 2 cm margins. Whether this is also true for thicker melanomas is not known and the only way to obtain more knowledge is to participate in prospective randomised studies. Elective lymph node dissection is associated with significant morbidity which includes lymphedema, wound complications and paresthesias of the extremity. For this reason we use an alternative operative approach uses selective lymphadenectomy with identification of the sentinel node.
Transforming growth factor (TGF)-β-1 is a very efficient inhibitor of hepatocyte proliferation in various in vivo and in vitro experimental systems. However, there are no data on whether it can influence the mitogenic response induced by primary hepatocyte mitogens.In this study, we compared the proliferative response in the liver between wild-type and transgenic mice, overexpressing active TGF-β-1 in their liver following the treatment by a primary hepatocyte mitogen TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene).The proliferative response was characterized by the immunohistochemical examination of pulse and cumulative bromodeoxyuridine labelling and by quantitative real-time polymerase chain reaction analysis of cell cycle-related genes.Neither of the applied techniques revealed significant differences between the two groups of mice; furthermore, we observed the upregulation of TGF-β-1 expression following the mitogenic treatment.TGF-β-1 does not inhibit the primary mitogen-induced proliferative response of the hepatocytes. This observation may provide an explanation for the divergent consequences of hepatic proliferations induced by partial hepatectomy or primary mitogenic treatment.
The canals of Hering or biliary ductules have been described to connect the bile canaliculi with the interlobular bile ducts, and thus forming the distal part of the biliary tree. Studies in the last two decades suggested that the cells constructing these ductules could behave as hepatic progenitor cells. The canals of Hering are confined to the periportal space in the rat, while they have been reported to spread beyond the limiting plate in human liver. The distribution of the distal biliary ductules in normal human hepatic tissue has been investigated in our recent experiments. We could demonstrate the presence of interlobular connective tissue septa in a rudimentary form in healthy livers. The canals of Hering run in these septa in line with the terminal branches of the portal vein and hepatic arteries. This arrangement develops in the postnatal period but regresses after early childhood. The canals of Hering can be identified by the unique epithelial membrane antigen (EMA)-/CD56+/CD133+ immunophenotype. The canals of Hering leave the periportal space and spread into the liver parenchyma along rudimentary interlobular septa outlining the hepatic lobules. Our observations refine the original architectural description of the intraparenchymal portion of the canals of Hering in the human liver. The distinct immunophenotype supports their unique biological function.
Marfan syndrome is a genetic disorder of the connective tissue, which affects approximately 2000–3000 individuals in Hungary. Given its multi-systemic manifestations, this disorder is often difficult to diagnose. To date, the National Marfan Register system contains approximately 250 cases, and this number is dynamically increasing. Aims: Collection of data from biological samples, clinical parameters, and lifestyle factors in Hungarian patients with Marfan syndrome. Methods: In terms of the criteria used for selection, those cases were chosen where the disorder could be clearly diagnosed on the basis of the patients’ cardiovascular and systemic symptoms, as well as of their family history, in line with the guidelines set by the Revised Ghent Nosology. Results: For the purposes of developing the biobank used for the research, 102 cases were selected from the Marfan Register (cDNA from 55 patients, genomic DNA and serum from 102 patients). In addition to the samples, data have been obtained by using internationally validated surveys to further examine the role of physical activity, nutrition and various psychological factors. Conclusions: The establishment of the Marfan Biobank enables scientists to effectively carry out research based on genetic, gene-expression and protein analysis. The biobank also provides new opportunities to study Hungarian patients with Marfan syndrome. Orv. Hetil., 2012, 153, 296–302.
The Solt-Farber protocol, in the absence of an initiating agent, was used to examine the precursor-product relationship between oval cells and hepatocytes in rat liver. The animals were administered 2-acetylaminofluorene (AAF) by gavage for 2 wk combined with partial hepatectomy 1 wk after administering AAF Two dose levels of AAF were used: 9- and 21-mg total dose for animals in Groups I and II, respectively. [3H]Thymidine was administered i.p. to one-half of the animals at Day 6 post-partial hepatectomy. Animals were sacrificed 7, 9, 11, and 13 days after surgery. Only oval cells became labeled on Day 7 in both groups. On Day 9 both labeled oval cells and labeled basophilic hepatocytes were present in Group I, whereas in Group II only oval cells remained labeled. On Days 11 and 13 both oval cells and basophilic hepatocytes were labeled in both groups. The total amount of radioactivity in Group II livers remained the same on Day 9 when only labeled oval cells were present and on Days 11 and 13 when both labeled oval cells and labeled basophilic hepatocytes were present. The calculated half-life for basophilic hepatocytes was about 50 h. The differentiation of oval cells into basophilic hepatocytes was delayed in Group II as compared to Group I, and the higher dose of AAF also induced the formation of both intestinal metaplasia and bile duct formation. In situ hybridization with an alpha-fetoprotein probe showed a strong expression in groups of typical oval cells and in cells arranged in duct-like structures. In addition a transient expression of AFP was also observed in the areas of basophilic hepatocytes 9 to 11 days after partial hepatectomy. Administration of AAF decreased the level of albumin mRNA in preexisting hepatocytes and caused a significant decrease of serum albumin. In contrast, oval cells showed a strong albumin expression, and basophilic hepatocytes formed islands of albumin-expressing cells. Oval cells and the foci of early basophilic hepatocytes lacked glucose-6-phosphatase activity. At Day 13 significant numbers of basophilic hepatocytes were positive for glucose-6-phosphatase. Oval cells were strongly gamma-glutamyltranspeptidase positive, whereas the foci of basophilic hepatocytes were negative for gamma-glutamyltranspeptidase. Only occasionally were transiently gamma-glutamyltranspeptidase-positive hepatocytes observed in basophilic foci. In summary our data indicate that oval cells can differentiate to hepatocytes and may have an important physiological function as a source of major serum proteins when hepatocytes are unable to synthesize these proteins.
