Biomedical subjects
Publications and source records attributed to R Sciot.
Cementifying fibroma is the most frequent benign fibro-osseous odontogenic tumor. We found chromosome abnormalities in a second case of this type of benign tumor. The chromosome changes in both cases are different. The chromosome bands involved in our case have not been described before in any benign fibroma so far reported.
HepG2 cell cultures and human hepatocyte primary cultures were used to develop appropriate hepatocytic in vitro models of iron load in order to further understand the pathophysiological mechanisms occurring in the liver of patients with hemochromatosis. The first step of this study was to obtain an efficient iron supply in conditions of minimal toxicity. It was demonstrated that iron complexed to citrate entered efficiently into HepG2 cells and human hepatocytes. This iron load was obtained with minimal toxicity in both culture models as evaluated by the intracellular LDH activity and the total protein content. The second step was to study the effect of iron on ferritin and transferrin receptor expression. In HepG2 cell cultures, intracellular and extracellular ferritin concentrations were strikingly increased by iron in dose- and time-dependent manners. However, the relative amounts of H and L ferritin mRNAs were not significantly affected by iron, suggesting that ferritin regulation occurred at a translational level. On the other hand, in human hepatocyte cultures, the increase of intracellular and extracellular ferritin concentrations was accompanied by an increase in the amounts of H and L ferritin mRNAs. In this model, iron-induced ferritin biosynthesis seemed to be more complex than in HepG2 cells and to be governed by transcriptional and/or post-transcriptional regulatory mechanisms. However, an additional translational level of regulation could not be excluded. In contrast, transferrin receptor expression was decreased by iron in HepG2 cells as well as in human hepatocyte cultures. This decrease was associated with a decrease in the mRNA steady-state level. In both culture models, transferrin receptor regulation seemed to occur at a transcriptional or post-transcriptional level. These results demonstrate that normal human hepatocytes in primary culture respond to iron in a manner close to that observed in vivo and thereby provide a promising experimental model for further understanding pathophysiological mechanisms involved in human hemochromatotic liver.
A typical case of alveolar soft-part sarcoma was examined using ultrastructural, immunohistochemical and cytogenetic methods. Immunohistochemical stains were performed on frozen sections and showed strong desmin expression with the three anti-desmin antibodies used. In addition, the tumour cells were weakly positive for vimentin and myosin. Neural markers were negative. Chromosomal analysis showed consistent involvement of 17q25--an abnormality which has been reported in another alveolar soft-part sarcoma. The histogenesis of alveolar soft-part sarcoma is still debatable but our findings support a myogenic origin. The finding of an apparently identical chromosomal abnormality in two of three thus far examined cases of alveolar soft-part sarcoma is of interest and must await further confirmation, but it may result in the identification of a chromosomal marker for this enigmatic tumour and thus pave the way for further molecular elucidation.
The distribution and the cellular source of the novel extracellular matrix glycoprotein tenascin were studied in normal and fibrotic rat liver. Cryostat sections of normal rat livers, livers of rats treated with intraperitoneal injections of CCl4 and 4-day-old and 8-day-old primary fat-storing cell cultures were stained for tenascin and desmin using an immunoperoxidase procedure or a double-label immunofluorescence technique. Fat-storing cell cultures were metabolically labeled with 3H-proline. Radiolabeled proteins were immunoprecipitated from the supernatant with antitenascin antiserum and subjected to polyacrylamide gel electrophoresis. In normal rat livers, tenascin was detected discontinuously along the sinusoids, whereas portal tracts were devoid of staining. In fibrotic rat livers, tenascin was preferentially expressed in areas of cell damage, in slender septa or at connective tissue-parenchymal interfaces. The middle region of broad septa was negative. Desmin-positive fat-storing cells accumulated in areas strongly immunoreactive for tenascin, and double-label immunofluorescence showed cells positive for both tenascin and desmin. In fat-storing cell cultures, both intracellular positivity for tenascin and staining of extracellular fibers were seen. Gel electrophoresis of immunoprecipitated proteins revealed two major and three minor bands with molecular weights consistent with tenascin. We conclude that tenascin is a component of the extracellular matrix of both normal and fibrotic rat livers. The strong expression of tenascin in areas of cell damage, in "early" septa or at septal-parenchymal interfaces, in contrast to its absence from the middle region of mature septa, suggests a role in early matrix organization. Fat-storing cells synthesize and secrete tenascin.
Skin metastases in the fingertips were the first-presenting symptom of a still occult, giant-cell bronchial carcinoma. We report the presentation, diagnosis and clinical course.
Synovial chondromatosis is extremely rare in small joints. The authors present a case of involvement of the fifth metacarpophalangeal joint, treated by removal of loose bodies and synovectomy.
Hemangiopericytoma is an infrequent vascular tumor that rarely appears in the head and neck. The nasal cavity and the paranasal sinuses are most often involved. Four cases are added to the literature and some important features are stressed. The clinical presentation is aspecific. Diagnosis is made only by careful histological examination with special stainings (reticulin, immunohistochemistry with Ulex Europaeus) and gives an idea about the grading. Treatment with radical surgery, if possible, is effective while preoperative embolisation can reduce the risk of hemorrhage. The median follow-up of the present cases is only 3 years. During this period no recurrence was observed. We suggest that more radical resections can probably reduce the local recurrence rate. However lifetime clinical follow-up is warranted since late recurrences have been reported in almost half of the patients.
The ancient story of Prometheus, chained to a rock for defying Zeus by stealing fire from Mount Olympus and subjected to daily tearing at his liver by an eagle, attests to the early recognition of the extraordinary regenerative capacity of the human liver. This process had remained an intriguing mystery over the millennia. In the last 20 years, following the pioneering work of Bucher (1) and Moolten et al (2), there has been an explosion of research that has clarified some of the mechanisms underlying the process of hepatic regeneration. Regeneration implies proliferation and regeneration. After the fetal and postnatal growth of the liver is completed, hepatocytes no longer proliferate actively, but they can proliferate in response to cell death or loss (3). Hepatocyte growth responses are of particular research interest because they occur in vivo and involve cells that are normally quiescent. Hepatic regeneration constitutes a highly regulated process that is best shown by the arrest of liver growth following a partial hepatectomy precisely at the moment the hepatic mass reaches the mass of the original intact liver (3). This suggests that hepatic regeneration after a partial hepatectomy is a strictly regulated nonautonomous growth process that is controlled by the same factors that are responsible for the determination and maintenance of hepatic mass in a normal individual. In response to a partial hepatectomy, hepatocytes enter the cell cycle and progress to DNA synthesis and replication but only in numbers sufficient to restore the hepatic mass. The regeneration response is both synchronized and universal in that it affects all intrahepatic cell lines, including nonparenchymal cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Human liver parenchymal cells have a very simple cytokeratin composition and express only one cytokeratin pair: cytokeratin 8 (a type II cytokeratin, molecular weight 52 kD) and cytokeratin 18 (a type I cytokeratin, molecular weight 45 kD). Intrahepatic bile duct cells contain in addition to cytokeratins 8 and 18 also cytokeratins 7 (a type II cytokeratin, molecular weight 54 kD) and cytokeratin 19 (a type I cytokeratin, molecular weight 40 kD). The paper deals with the cytokeratin expression in various types of benign and malignant primary liver tumors as assessed by immunohistochemical methods or by the use of gel electrophoresis and immunoblotting of cytoskeletal extracts.
Hepatocytes take up transferrin-bound iron by two mechanisms. One pathway consists in the binding of transferrin to high affinity receptor sites. This process results in receptor-mediated endocytosis and is highly efficient and saturable. The other mechanism involves low affinity, non-specific and non-saturable internalization of transferrin-bound iron, probably through pinocytosis, adsorptive endocytosis or low affinity binding sites. At low transferrin saturation, the first mechanism is quantitatively most important, at high transferrin saturation the latter mechanism becomes more significant. A mechanism whereby transferrin-bound iron is not endocytosed but reduced at and translocated through the plasma membrane has also been invoked and challenges the concept of (receptor-mediated) endocytosis of transferrin. However, this hypothesis remains to be confirmed.
Hepatic transferrin receptors were studied in normal male rats at 1 to 59 wk after weaning, using immunohistochemical and biochemical techniques. The number of transferrin receptors measured and the intensity of the staining in situ decreased rapidly during the first 10 wk of life and more slowly thereafter. Immunohistochemistry further demonstrated changes in the topographical and (sub)cellular localization of the transferrin receptor. In the young rat livers, staining was almost exclusively present on hepatocytes in acinar zone 2 + 3 in a honeycomb to sinusoidal pattern. With aging, a panacinar heterogeneous and mainly sinusoidal staining of hepatocytes was more frequent. Kupffer cell positivity was more obvious as compared with the young rat livers. The observed changes in transferrin receptor expression may partly be explained by age-dependent alterations in DNA synthesis and proliferative potential of the liver cells. A series of rats were iron loaded with carbonyl iron up to 39 wk and "unloaded" by administration of a normal diet during 20 wk. In these animals, serial histochemical studies showed predominantly parenchymal (7 to 14 wk), mixed parenchymal and reticuloendothelial (39 wk) and almost exclusive reticuloendothelial siderosis (59 wk). In the siderotic livers transferrin receptor numbers tended to be lower than in the controls with significant differences after 14 and 39 wk. Immunohistochemistry showed decreased parenchymal but increased reticuloendothelial transferrin receptor expression with iron load. After the period of unloading, parenchymal transferrin receptors were virtually absent despite the negligible siderosis of these cells. In contrast, siderotic reticuloendothelial cells were intensely positive. These findings support down-regulation of parenchymal transferrin receptor resulting from iron storage. However, the positivity of siderotic reticuloendothelial cells and the absence of re-emergence of parenchymal receptors in conditions of minimal parenchymal and prominent reticuloendothelial siderosis need further elucidation.
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Six cases of hepatoblastoma (five epithelial, one mixed epithelial-mesenchymal) were studied on serially cut cryostat sections, using a panel of monoclonal antibodies directed against individual cytokeratins, vimentin, and desmin, in an indirect immunoperoxidase procedure. Embryonic and fetal-type tumor cells expressed the "hepatocellular" cytokeratins no. 8 and 18 but, surprisingly, also expressed the "bile duct type" cytokeratin no. 19. In addition, two cases had a number of tumor cells which were also positive for the "bile duct type" cytokeratin no. 7. Cells embedded in osteoid-like material were immunoreactive for vimentin but also for cytokeratins no. 7, 18, and 19. Gel electrophoresis, and Western blotting of cytoskeletal extracts, confirmed the immunohistochemical data. The implications of these findings for the histogenesis of hepatoblastoma are discussed in this report.
The novel extracellular matrix glycoprotein tenascin was studied immunohistochemically in normal and fibrotic human liver. Its localization was compared to that of laminin, fibronectin and collagen type IV. In the normal liver, a weak staining for tenascin was detected along sinusoids, while portal tracts were negative. In both alcoholic and cholestatic liver disease and acute and chronic hepatitis, sinusoidal immunoreactivity for tenascin was variably increased as compared to the normal liver. Most striking, however, was the preferential accumulation of tenascin at connective tissue-parenchymal interfaces between proliferating ductules and in areas of piecemeal necrosis. As compared to laminin, fibronectin and collagen type IV, tenascin has the most restricted distribution. Our findings indicate that tenascin is a component of the extracellular matrix of the human liver. Its preferential expression at connective tissue-parenchymal interfaces in fibrosing areas in contrast to its absence from mature fibrous septa suggest a transient role in early matrix organization.
It was discovered that eight patients with complications of non-cirrhotic portal hypertension had received an arsenical preparation for psoriasis as Fowler's solution some years age. Seven of them were admitted for bleeding oesophageal varices. Upon admission, splenomegaly and hypersplenism were present. Liver tests were normal and palmar skin keratosis and melanosis were noted. Liver biopsy of six patients showed features of incomplete septal cirrhosis. Malignant skin lesions were present in half of the patients. One patient died from lung carcinoma and another from an ovarium neoplasm. Chronic arsenic intake should be actively looked for in all patients with psoriasis and non-cirrhotic portal hypertension. They should be followed up for many years for development of malignant lesions in skin, lung and liver. Liver abnormalities present in the biopsies are often minor and may escape detection.
Two cases of fibrolamellar carcinoma of the liver, one with lymph node metastasis are reported. Using immunohistochemistry as well as one- and two-dimensional gel electrophoresis and Western blotting, tumour cells of both primary lesions and of the metastasis were found to express cytokeratin polypeptides 8 and 18 and, surprisingly, cytokeratin 7. A small number of cells also expressed cytokeratin 19. This is the first detailed analysis of the cytokeratin expression of fibrolamellar carcinoma, and is also the first to present biochemical evidence that, contrary to what has been suggested, hepatocellular carcinomas do not always preserve the pattern of cytokeratin expression of normal hepatocytes.
To further investigate the possible usefulness of antitransferrin receptor staining in the differential diagnosis between benign and malignant primary liver tumours, we examined the transferrin receptor expression in ten cases of focal nodular hyperplasia, six of nodular regenerative hyperplasia, two adenomas and six hepatoblastomas. In focal nodular hyperplasia, the ductular structures were always positive and the parenchymal cells displayed three staining patterns of moderate intensity. In nodular regenerative hyperplasia there was scattered, relatively weak transferrin receptor staining. The tumour cells in the adenomas were only weakly positive. Three hepatoblastomas showed an intense staining of tumour cells; one was weakly positive and two were negative. A high intensity of transferrin receptor staining, as previously described in hepatocellular carcinomas, was only observed in the hepatoblastomas. This gives further credence to the usefulness of strong transferrin receptor expression in evaluating the malignant nature of tumour foci in liver biopsies.
A cytokeratin immunohistochemical study was performed on 38 liver biopsies from cases of primary biliary cirrhosis, primary sclerosing cholangitis, extrahepatic biliary obstruction or drug-induced liver disease in order to analyse the cytoskeletal changes in detail. On paraffin sections of 27 cases, a variable number of hepatocytes were reactive with a polyclonal anti-cytokeratin antiserum that, in the normal liver, stains bile duct cells only. On cryostat sections of 23 cases, a variable number of hepatocytes were immunoreactive with a monoclonal antibody specifically directed against cytokeratin no. 7 and were most numerous in cases of long-standing cholestasis irrespective of the aetiology. In three cases of primary sclerosing cholangitis and two cases of primary biliary cirrhosis a few hepatocytes were also weakly positive with a monoclonal antibody specific for cytokeratin no. 19. Since cytokeratins no. 7 and no. 19 are, in the normal liver, restricted to bile duct cells, these results further support the concept of 'ductular metaplasia' of hepatocytes, the mechanism of which remains unclear.