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Results for “Proliferation”

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At least 325 records · Page 18Linked to original sources

PubMed1996

Peroxisome proliferator-activated receptor alpha inhibits hepatic S14 gene transcription. Evidence against the peroxisome proliferator-activated receptor alpha as the mediator of polyunsaturated fatty acid regulation of s14 gene transcription.

The peroxisome proliferator-activated receptor (PPARalpha) has been implicated in fatty acid regulation of gene transcription. Lipogenic gene transcription is inhibited by polyunsaturated fatty acids (PUFA). We have used the PUFA-sensitive rat liver S14 gene as a model to examine the role PPARalpha plays in fatty acid regulation of hepatic lipogenic gene transcription. Both PPARalpha and the potent peroxisome proliferator, WY14643, inhibit S14CAT activity in transfected primary hepatocytes. WY14643 and PPARalpha target the S14 T3 regulatory region (TRR, -2.8 to -2.5 kilobases), a region containing 3 T3 response elements (TRE). Transfer of the TRR to the thymidine kinase (TK) promoter conferred negative control to the TKCAT gene following WY14643 and PPARalpha treatment. Gel shift analysis showed that PPARalpha, either alone or with RXRalpha, did not bind the S14TRR. However, PPARalpha interfered with TRbeta/RXRalpha binding to a TRE (DR+4). Functional studies showed that co-transfected RXRalpha, but not T3 receptor beta1 (TRbeta1), abrogated the inhibitory effect of PPARalpha on S14 gene transcription. These results suggest that WY14643 and PPARalpha functionally interfere with T3 regulation of S14 gene transcription by inhibiting TRbeta1/RXR binding to S14 TREs. Previous studies had established that the cis-regulatory targets of PUFA control were located within the proximal promoter region of the S14 gene, i.e. between -220 and -80 bp. Finding that the cis-regulatory elements for WY14643/PPARalpha and PUFA are functionally and spatially distinct argues against PPARalpha as the mediator of PUFA suppression of S14 gene transcription.

Animals↗

PubMed1998

Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. Implications for peroxisome proliferator-activated receptor alpha natural ligand metabolism.

Peroxisomal beta-oxidation system consists of four consecutive reactions to preferentially metabolize very long chain fatty acids. The first step of this system, catalyzed by acyl-CoA oxidase (AOX), converts fatty acyl-CoA to 2-trans-enoyl-CoA. Herein, we show that mice deficient in AOX exhibit steatohepatitis, increased hepatic H2O2 levels, and hepatocellular regeneration, leading to a complete reversal of fatty change by 6 to 8 months of age. The liver of AOX-/- mice with regenerated hepatocytes displays profound generalized spontaneous peroxisome proliferation and increased mRNA levels of genes that are regulated by peroxisome proliferator-activated receptor alpha (PPARalpha). Hepatic adenomas and carcinomas develop in AOX-/- mice by 15 months of age due to sustained activation of PPARalpha. These observations implicate acyl-CoA and other putative substrates for AOX, as biological ligands for PPARalpha; thus, a normal AOX gene is indispensable for the physiological regulation of PPARalpha.

Acyl-CoA Oxidase↗

PubMed2000

Proliferation of intimal smooth muscle cells. Attenuation of basic fibroblast growth factor 2-stimulated proliferation is associated with increased expression of cell cycle inhibitors.

Basic fibroblast growth factor (FGF2) is a potent mitogen for medial smooth muscle cells and is necessary for their proliferation after balloon catheter injury; however, intimal smooth muscle cells do not require FGF2 for their proliferation, and they respond only weakly to exogenous FGF2. The present study examined the activation of extracellular signal-regulated kinase (ERK) signaling as well as the expression and activity of cell cycle proteins in FGF2-stimulated intimal smooth muscle cells. FGF2 activates ERKs 1 and 2, and Western blot analysis showed that cyclin D, cyclin E, and cyclin-dependent kinase (CDKs) 2 and 4 were expressed in intimal smooth muscle cells after FGF2 infusion. FGF2 stimulation, however, did not lead to phosphorylation of the retinoblastoma protein (Rb), CDK 2 activation, or expression of cyclin A. Western blot analysis showed that intimal smooth muscle cells express elevated levels of the cell cycle inhibitors p15(INK4b) and p27(Kip1), compared with medial smooth muscle cells, and that FGF2 stimulation does not reduce the level of these inhibitors. These studies suggest that despite activation of ERKs 1 and 2 and expression of the cell cycle activators, cyclin D and cyclin E, high levels of cell cycle inhibitors may inhibit cell cycle transit in FGF2-stimulated intimal smooth muscle cells.

Animals↗

PubMed2000

Peroxisome proliferator-activated receptor delta (PPARdelta )-mediated regulation of preadipocyte proliferation and gene expression is dependent on cAMP signaling.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a key regulator of terminal adipocyte differentiation. PPARdelta is expressed in preadipocytes, but the importance of this PPAR subtype in adipogenesis has been a matter of debate. Here we present a critical evaluation of the role of PPARdelta in adipocyte differentiation. We demonstrate that treatment of NIH-3T3 fibroblasts overexpressing PPARdelta with standard adipogenic inducers led to induction of PPARgamma2 expression and terminal adipocyte differentiation in a manner that was strictly dependent on simultaneous administration of a PPARdelta ligand and methylisobutylxanthine (MIX) or other cAMP elevating agents. We further show that ligands and MIX synergistically stimulated PPARdelta-mediated transactivation. In 3T3-L1 preadipocytes, simultaneous administration of a PPARdelta-selective ligand and MIX significantly enhanced the early expression of PPARgamma and ALBP/aP2, but only modestly promoted terminal differentiation as determined by lipid accumulation. Finally, we provide evidence that synergistic activation of PPARdelta promotes mitotic clonal expansion in 3T3-L1 cells with or without forced expression of PPARdelta. In conclusion, our results suggest that PPARdelta may play a role in the proliferation of adipocyte precursor cells, whereas activation of endogenous PPARdelta in 3T3-L1 cells appears to have only minor impact on the processes leading to terminal adipocyte differentiation.

1-Methyl-3-isobutylxanthine↗

PubMed2001

Differential gene regulation in human versus rodent hepatocytes by peroxisome proliferator-activated receptor (PPAR) alpha. PPAR alpha fails to induce peroxisome proliferation-associated genes in human cells independently of the level of receptor expresson.

We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) alpha agonist (compound 1). Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric acid or compound 1 in rat hepatocytes. In addition, apolipoprotein CIII mRNA was decreased by both fenofibric acid and compound 1 in rat hepatocytes. Both agonists decreased apolipoprotein CIII mRNA in human hepatocytes; however, very little change in FACO activity or mRNA was observed. Furthermore, other peroxisome proliferation (PP)-associated genes including peroxisomal 3-oxoacyl-CoA thiolase (THIO), peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), peroxisomal membrane protein-70 (PMP-70) were not regulated by PPAR alpha agonists in human hepatocytes. Moreover, other genes that are regulated by PPAR alpha ligands in human hepatocytes such as mitochondrial HMG-CoA synthase and carnitine palmitoyl transferase-1 (CPT-1) were also regulated in HepG2 cells by PPAR alpha agonists. Several stably transfected HepG2 cell lines were established that overexpressed human PPAR alpha to levels between 6- and 26-fold over normal human hepatocytes. These PPAR alpha-overexpressing cells had higher basal mRNA levels of mitochondrial HMG-CoA synthase and CPT-1; however, basal FACO mRNA levels and other PP-associated genes including THIO, HD, or PMP-70 mRNA were not substantially affected. In addition, FACO, THIO, HD, and PMP-70 mRNA levels did not increase in response to PPAR alpha agonist treatment in the PPAR alpha-overexpressing cells, although mitochondrial HMG-CoA synthase and CPT-1 mRNAs were both induced. These results suggest that other factors besides PPAR alpha levels determine the species-specific response of human and rat hepatocytes to the induction of PP.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1997

Cell proliferation enhances entry of Listeria monocytogenes into intestinal epithelial cells by two proliferation-dependent entry pathways.

Bacterial entry into intestinal host cells is the result of a fairly sophisticated manipulation of host cell machinery by the pathogens. To study further the potential cell target of Listeria spp., the in-vitro entry of L. monocytogenes strains into intestinal cells was examined in relation to the metabolism, proliferation and differentiation of the cells by the alamarBlue assay, [3H] thymidine incorporation, and brush border-associated enzyme activities, respectively. The study showed that cell metabolism was not involved in the entry of L. monocytogenes in three cell models (two human and one porcine). On the other hand, entry was closely related to the proliferation process and poorly related to the differentiation state of the cells. The use of L. monocytogenes mutants lacking invasion proteins showed that InlA and InlB acted in synergy to mediate the entry of L. monocytogenes into proliferative cells, whereas InlA alone seemed to be involved in the entry into non-proliferative cells. These two entry pathways could correspond to the two cellular processes used by L. monocytogenes to enter proliferative and non-proliferative cells, as suggested by the use of cytochalasin D, nocodazole, chloroquine and monodansylcadaverine. Taken together, we propose a hypothesis in which the entry of L. monocytogenes is mediated by interaction between randomly distributed E-cadherin on the surface of proliferative cells. In contrast, the entry into non-proliferative cells may involve pp60c-src, a proto-oncogenic tyrosine kinase signal that modifies E-cadherin localisation. In conclusion, these results suggest that L. monocytogenes may preferentially enter crypt cells in vivo by a microfilament-dependent process, whereas the few bacteria that infect villus cells enter by an E-cadherin-internalin interaction that mediates microtubule-dependent endocytosis.

Animals↗

PubMed1975

Proliferating and non-proliferating compartments in cervical dysplasia and carcinoma in situ.

The existence of proliferating and non-proliferating compartments in atypical cervical epithelium is suggested by autoradiographical investigations and studies on the topographical distribution of mitosis performed on human cervical cones and on cervices of mice following carcinogenic treatment.

Animals↗

PubMed1997

Transduction potential of human retroviruses in highly proliferating small-cell lung cancer cells as well as non-proliferating hematopoietic stem cells.

Direct gene transfer to solid tissues or metastatic cancer cells requires vectors capable of in vivo transduction to specific cells. The predominant retroviral vectors of murine origin are inactivated by human complement, which precludes their use in vivo. Such inactivation does not take place with vectors based on human retroviruses. Murine retroviral vectors are also limited to proliferating cells, which human retroviruses are not. In this study we examined whether or not a vector using components from the human retroviruses HIV-1 and HTLV-1 could infect small-cell lung cancer cells and resting CD34+ hematopoietic stem cells. While HIV-1 itself was unable to infect cells lacking the CD4-membrane molecule, chimeric viral particles (pseudotype virus) with HIV-1 genome and HTLV-1 envelope components were able to infect both CD4-containing lymphocytic cells, CD4-negative tumour cells and hematopoietic stem cells. After infection with the pseudotype vector, the RNA genome was reverse transcribed and integrated. Transduction efficiency and gene expression under the HIV-1 LTR promoter in both tumour and stem cells were found to be of a similar or greater magnitude than in lymphocytic cells. These results suggest that gene transfer targeting proliferating as well as resting cells in vivo may be realized using components from human retroviruses.

Antigens, CD34↗

PubMed2003

Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation.

Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteries that have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (Ki 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org.

Angioplasty, Balloon↗

PubMed1998

Tissue-specific induction of 17 beta-hydroxysteroid dehydrogenase type IV by peroxisome proliferator chemicals is dependent on the peroxisome proliferator-activated receptor alpha.

The 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) family of proteins regulates the levels of the active 17 beta-hydroxy forms of sex steroids. The expression of 17 beta-HSD type IV is induced by peroxisome proliferator chemicals (PPC) in rat liver. In order to characterize more generally the impact of PPC on 17 beta-HSD expression, we determined (1) if expression of other members of the 17 beta-HSD family was coordinately induced by PPC exposure, (2) the tissues in which 17 beta-HSD was induced by PPC, and (3) whether the induction of 17 beta-HSD by PPC was dependent on the peroxisome proliferator-activated receptor alpha (PPAR alpha), the central mediator of PPC effects in the mouse liver. The mRNA levels of 17 beta-HSD I, II, and III were not altered in the liver, kidney, and testis or uterus of rats treated with PPC. The mRNA or 80 kDa a full-length protein levels of 17 beta-HSD IV were strongly induced in liver and kidney, but not induced in adrenals, brown fat, heart, testis, and uterus of rats treated with diverse PPC. In liver and kidneys from treated rats, additional proteins of 66 kDa, 56 kDa, and 32 kDa were also induced which reacted with the anti-17 beta-HSD IV antibodies and were most likely proteolytic fragments of 17 bega-HSD IV. Treatment of mice which lack a functional form of PPAR alpha with PPC, demonstrated that PPC-inducibility of 17 beta-HSD IV mRNA or the 80 kDa protein was dependent on PPAR alpha expression in liver and kidney. Our results demonstrate that 17 beta-HSD IV is induced by PPC through a PPAR alpha-dependent mechanism and support the hypothesis that exposure to PPC leads to alterations in sex steroid metabolism.

17-Hydroxysteroid Dehydrogenases↗

PubMed2003

Activation of peroxisome proliferator-activated receptors alpha and gamma1 inhibits human smooth muscle cell proliferation.

Atherosclerotic lesions occur as a result of excess lipid deposition within the vascular tissues. The peroxisome proliferator-activated receptors (PPARs) present in adipose and hepatic tissues have been shown to promote fatty acid oxidation and lipid storage. An immunohistochemical assessment of PPARalpha and PPARgamma revealed both proteins were also present in the medial and intimal layers of human arteries, predominately in regions containing smooth muscle cells. In agreement with this observation, smooth muscle cells isolated from these vessels were found by RT-PCR to express both PPARalpha and PPARgamma1. The functionality of these receptors was tested with selective PPAR agonists. Mitogenic stimulation of smooth muscle cell proliferation was blocked by 15d-PGJ2, a PPARgamma agonist, as well as by WY14643, a PPARalpha agonist. These data indicate PPAR activation by selective agonists could influence lesion progression directly, as well as indirectly through reductions in serum lipoprotein and triglyceride levels.

Arteriosclerosis↗

PubMed1992

In situ demonstration of proliferating cells in the rat central nervous system during experimental autoimmune encephalomyelitis. Evidence suggesting that most infiltrating T cells do not proliferate in the target organ.

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats and the bromodeoxyuridine (BrdU)-incorporating cells were demonstrated immunohistochemically in lesions in the central nervous system (CNS) to assess the extent of T cell proliferation during EAE. In active EAE, BrdU+ cells were most numerous on day 12 postimmunization, when both clinical signs and inflammation detected by histologic examination were most severe; they declined thereafter although a considerable number of inflammatory foci remained in some rats. In passive EAE, BrdU+ cells were most numerous 2 days before the full-blown EAE and then rapidly decreased in number. On day 6 post-transfer, the CNS showed the most severe histologic changes but virtually no inflammatory cells in the lesions were labeled with BrdU. Double immunofluorescence staining with T cell (OX52) and macrophage/microglia (OX42) markers showed that about half of the BrdU+ cells were labeled with OX52 at the peak of EAE. The proportion of BrdU+OX52+ T cells at later stages was about 20%. BrdU+OX42+ cells ranged between 50 and 80% throughout the course of the disease. Furthermore, serial pulsing experiments during passive EAE revealed that inflammatory cells that had been labeled with BrdU outside the CNS and found later in the CNS were 15 times more numerous than those labeled in situ in the CNS. Taken together, these findings indicate that the majority of T cells involved in EAE undergo DNA synthesis outside the CNS and then infiltrate into the CNS, and that T cells labeled in situ in the CNS are few, and decrease rapidly in number. Since interleukin-2-receptor-positive cells detected by mAb OX39 outnumbered BrdU+ T cells at these later stages, we postulate that an unresponsive state instead of T-cell proliferation was induced in the CNS.

Animals↗

PubMed1991

Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. Inhibition of long chain acyl-CoA synthetase by triacsins caused inhibition of Raji cell proliferation.

Triacsins A, B, C, and D are new inhibitors of long chain acyl-CoA synthetase (EC 6.2.1.3) and possess different inhibitory potencies against the enzyme (Tomoda, H., Igarashi, K., and Omura, S. (1987) Biochim. Biophys. Acta 921, 595-598). Acyl-CoA synthetase activity in the membrane fraction of Raji cells was also inhibited by triacsins. The same hierarchy of inhibitory potency as that against the enzyme from other sources, triacsin C greater than triacsin A much greater than triacsin D greater than or equal to triacsin B, was observed. When Raji cells were cultivated in the presence of triacsins, cell proliferation was inhibited in a dose-dependent fashion. The drug concentrations required for 50% inhibition of cell growth at day 2 were calculated to be 1.8 microM for triacsin A, much greater than 20 microM for triacsin B, 1.0 microM for triacsin C, and much greater than 15 microM for triacsin D, demonstrating a hierarchy for inhibitory potency of triacsins similar to that against the acyl-CoA synthetase activity. To understand the role of long chain acyl-CoA synthetase in animal cells, the effect of triacsins on the lipid metabolism of Raji cells was studied. When intact Raji cells were incubated with [14C]oleate in the presence of individual triacsins, the incorporation of [14C]oleate into each of the lipid fractions such as phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol was inhibited to an analogous extent. A common hierarchy, triacsin C greater than triacsin A much greater than triacsin D greater than triacsin B, was shown for the inhibition in each synthesis of the three lipids, which was identical with that for acyl-CoA synthetase. These findings indicate that the inhibition of acyl-CoA synthetase is well correlated with the inhibition of lipid synthesis. Taken together, the data strongly suggest that the inhibition of acyl-CoA synthetase by triacsins leads to the inhibition of lipid synthesis and eventually to the inhibition of proliferation of Raji cells.

Cell Division↗

PubMed1989

IL-2-induced polyclonal proliferation of human peripheral blood lymphocytes: functional and phenotypic characteristics of proliferating cells.

Unstimulated human peripheral blood lymphocytes (HPBL) were found to proliferate when cultured in vitro with interleukin-2 (IL-2). In bulk long-term cultures of HPBL cultured with IL-2, cell numbers usually doubled after 8-11 days of culture, and a 10-fold increase in cell number occurred between the second and third weeks of culture. These cells retained their ability to respond to a panel of T-cell dependent antigens, phytomitogens and allogeneic cells up to Day 21 of culture. The proliferating cells predominantly expressed the T-cell antigens (CD3, CD4 and CD8), but not antigens of natural killer (NK) cells, B cells or mononuclear phagocytic cells. The proportion of cells expressing CD3 and CD4 antigens progressively increased with length of culture. Purified lymphocytes expressing either CD4 or CD8 antigens were also found to be capable of showing a proliferative response to IL-2, especially when provided with autologous accessory cells. However, purified human peripheral blood B cells expressing the Leu 12 antigen did not respond with or without autologous accessory cells. Unlike the responses to phytomitogen, soluble antigens or allogeneic cells, the proliferative responses of HPBL to IL-2 were not inhibited by a monoclonal antibody (OK-Ia-1) to the non-polymorphic part of human class II histocompatibility antigens.

Antibodies, Monoclonal↗

PubMed1986

Disappearance of upward proliferation and persistence of downward basal cell proliferation in rat forestomach papillomas induced by butylated hydroxyanisole.

The reversibility of forestomach lesions induced in rats by butylated hydroxyanisole (BHA) was examined. F344 rats were given BHA for 24 weeks, followed by the basal diet, and their forestomach lesions at weeks 24 and 96 were compared histopathologically. Hyperplasias and papillomas showing upward proliferation were found in week 24 but not in week 96. However, downward proliferation of basal cells persisted after the discontinuation of BHA administration. This finding suggests that downward growth of basal cells is not reversible and is important in the development of BHA-induced forestomach tumors in rats.

Animals↗

PubMed1988

Antigen as a positive and negative regulator of proliferation in cytotoxic lymphocytes. A model for the differential regulation of proliferation and lytic activity.

The goal of these experiments has been to capitalize on the functionally distinct responses of heteroclitic CTL to cross-reactive Ag to explore the role of Ag in regulating CTL proliferation and lytic function. The experiments here have examined one of these clones in detail but several such clones appear similar. The principal findings were: 1) proliferation and lysis may be optimally stimulated by quantitatively different interactions, 2) Ag can have negative as well as positive effects on the proliferative potential of the responding cell, and 3) both positive and negative effects on lysis can be mimicked by agents which are similar to the second messengers produced by stimulating the TCR.

Animals↗

PubMed1985

Biochemical fractionation of conditioned media containing factors which support in vitro proliferation of high proliferation potential colony forming cells.

Synergistic activity (SA), which is the capacity to support the in vitro proliferation of High Proliferation Potential Colony Forming Cells (HPP-CFC's), has been fractionated from conditioned media by standard biochemical techniques. On fractionation of both Wehi conditioned medium (Wehi CM) or human placental conditioned medium (HPCM) by several techniques, multiple peaks of SA were observed. Protein from HPCM expressing SA, ranged from 9,000-28,000 in molecular weight as determined by gel filtration. Chromatofocusing crude HPCM separated two activities possessing isoelectric points of 5.7 and 5.3. In crude Wehi CM, inhibitors or toxicity occasionally masked SA which partially adsorbed to Con-A sepharose and could be eluted with competing sugar. Further fractionation of this material on DEAE-sepharose separated three peaks of activity. Pooling the active fractions from the first two peaks gave a preparation that was up to 179 fold more active than the crude material.

Animals↗

PubMed1983

Phenotypic characterization of hepatic proliferation. Antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver.

Different forms of hepatocellular proliferation are seen in fetal livers, massive hepatic necrosis, and nodular transformation (nodular regenerative hyperplasia) of the liver. In an attempt to characterize the proliferating cells in these conditions, we studied the expression of several antigens by immunohistochemical methods. Alpha-fetoprotein (AFP), alpha 1-antitrypsin (AAT), a hepatocellular export protein, carcinoembryonic antigen (CEA), a marker of bile duct epithelial cells, and hepatitis B virus antigens (HBsAg, HBcAg), were localized by the peroxidase-antiperoxidase method in 11 fetal livers, 10 cases of nodular transformation, and 7 cases of massive hepatic necrosis. AFP was the most prevalent antigen in fetal hepatocytes. Many hyperplastic hepatocytes in nodular transformation contained AAT, but not oncofetal antigens, supporting the differentiated hepatocellular nature of these cells. A similar staining pattern was seen in two-cell-thick plates of hepatocytes in massive hepatic necrosis. In contrast, the ductlike structures at the periphery of necrotic lobules contained both AAT and CEA, suggesting that these cells exhibit features of hepatocytes and bile duct epithelial cells. Therefore, the appropriate term for these regenerating cells appears to be "ductular" or "biliary hepatocytes".

Adult↗