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P Bioulac-Sage

Publications and source records attributed to P Bioulac-Sage.

At least 19 recordsLinked to original sources
PubMed1998

[Familial autoimmune hepatitis and C4 deficiency].

INTRODUCTION: Familial auto-immune hepatitis is unusual. We report a case in which hepatitis was associated with a deficiency in the C4 component of the complement. EXEGESIS: Type 1 auto-immune hepatitis A was diagnosed in a 38-year-old woman presenting with systemic lupus erythematosus. Her daughter had to undergo a splenectomy for immunologic thrombocytopenic purpura when she was 9 years old. When she turned 13, she further developed type 1 autoimmune hepatitis. During follow-up (4 and 8 years, respectively), both patients had a mild deficiency in C4. CONCLUSION: C4 deficiency is not only frequently observed in relatives of patients with auto-immune hepatitis, but also in familial systemic lupus. This abnormality may have had a crucial pathogenic role in these two patients.

Adolescent↗
PubMed1998

Case report: secondary biliary cirrhosis possibly related to congenital hepatic fibrosis. Evidence for decreased number of portal branch veins and hypertrophic peribiliary vascular plexus.

A 30-year-old man with presinusoidal portal hypertension was transplanted for cryptogenic cirrhosis. On the explanted liver, few intrahepatic stones, biliary cirrhosis, chronic cholangitis of the large bile ducts and a peculiar proliferation of small dilated bile ducts at the periphery of the portal tracts led to the diagnosis of secondary biliary cirrhosis and cholangitis, possibly linked to ductal plate malformation, including congenital hepatic fibrosis associated with a minor form of Caroli's disease. Ex vivo portogram and histology showed the paucity of portal vein branches and the hypertrophy of the peribiliary vascular plexus. This hypertrophy, which has been reported in livers with presinusoidal hypertension, is another indirect argument to suggest the diagnosis of congenital hepatic fibrosis.

Adult↗
PubMed1998

[Langerhans-cell histiocytosis and Erdheim-Chester disease: probably not a fortuitous association].

BACKGROUND: Erdheim Chester disease (MEC) is a rare non-Langerhans cell histiocytosis characterized by multi-visceral involvement. We report a case of MEC associated with Langerhans cell histiocytosis (HCL). CASE REPORT: A 46-year-old women presented skin and vulvar localization of HCL associated with typical MEC bone involvement. Despite chemotherapy (vinblastine) and prednisone, the disease progressed to involve the central nervous system, leading to fatal outcome. Post-mortem examination showed HCL in skin, MEC in bones and central nervous system, and intermediate histiocytic proliferation in the encephalon. DISCUSSION: Usually, MEC and HCL are considered as distinct entities. MEC is characterized by a xanthogranulomatous proliferation of CD 68+ foamy histiocytes nested in fibrosis, and HCL by a proliferation of PS 100+ and CD1a+ Langerhans cells. However, our observation, as well as previous reports, suggests that MEC is part of the HCL spectrum.

Bone Diseases↗
PubMed1998

[Lichen planus in children: role of the campaign for hepatitis B vaccination].

INTRODUCTION: Cutaneous lichen planus in children is a rare entity. To study its specific clinical and therapeutic features, we report on 8 cases seen in 5 years in a pediatric dermatology clinic. In parallel, this study addresses the role of HBV immunization campaigns in childhood lichen planus. OBSERVATIONS: Six boys and two girls with a diffuse form of lichen planus were studied. The mean age was 11 years. Four children were of skin types V and VI. Lesions followed Blaschko's lines in two children. One case was associated with atopic dermatitis. In half the cases--the most recent--the eruption was noted after HBV immunization. Biopsy specimens from seven children were reviewed and confirmed the diagnostic of lichen planus. Oral retinoids or corticosteroids were used successfully in six cases. DISCUSSION: Half of our cases confirmed the atypical features of lichen planus in childhood. This study confirms the predominance of lichen planus in children with pigmented skin suggesting a genetic predisposition. The eruption following Blaschko's lines suggests that a clonal keratinocytic population is the target of lichenoid inflammation. HBV immunization could be a stimulus triggering a cytotoxic lymphocyte-mediated reaction. The proportion of affected children was low in comparison with all children immunized. So lichen planus arises probably in predisposed children. This justifies surveillance in the pediatric and dermatologic medical communities.

Adolescent↗
PubMed1997

Concerted nonsyntenic allelic losses in hyperploid hepatocellular carcinoma as determined by a high-resolution allelotype.

Although the occurrence of loss of genetic material in hepatocellular carcinoma (HCC) has been documented both by cytogenetic analysis and by monitoring of allelic losses, a global overview of the extent and frequency of deletion occurring throughout the genome is not yet available. To contribute to this information, DNAs extracted from flow-sorted aneuploid nuclei from HCC and matched normal DNAs were typed for 275 microsatellite loci that were distributed along the autosomes. An average of 190 (69%) informative loci per case were generated on 48 HCC. Complete loss of heterozygozity in the tumor DNA was observed for 15.6% of the typed loci. The chromosome segments that were most frequently affected by deletion were: 8p (60%), 17p (48%), 1p (44%), 4q (42%), 16p (40%), 16q (39%), 6q (35%), 9p (30%), and 13q (29%). On average, 8 of the 39 chromosome segments studied per tumor carried at least one locus that demonstrated loss of heterozygosity (ie., the fractional allelic loss was 0.21). Groups of concerted nonsyntenic losses were observed for 16p and 1p and for 16p and 4q. The location of putative tumor suppressor genes on the most frequently deleted regions was confirmed and, in some cases, refined.

Adult↗
PubMed1997

Extracellular matrix composition and integrin expression in early hepatocarcinogenesis in human cirrhotic liver.

Extracellular matrix (ECM) plays a major role in cell differentiation, proliferation, and gene expression, both in physiological and in pathological conditions. Immunohistochemistry has been used to investigate modifications of ECM and related receptors, the integrins, in 26 small nodular lesions developed in human cirrhotic livers, on the basis that these lesions could represent sequential steps of hepatocarcinogenesis: the lesions were 16 macroregenerative nodules (MRNs), either of ordinary (n = 5) or atypical (n = 11) type, and ten small (< 15 mm) hepatocellular carcinomas (HCCs). Data were compared with those obtained in the surrounding cirrhotic tissue, in large HCCs, and in normal liver. The results indicate similarities between ordinary MRNs and cirrhosis, on the one hand, and between atypical MRNs and small HCCs, on the other. Strong and homogeneous deposition of collagen type IV and laminin in sinusoids and overexpression of alpha 6 integrin by sinusoidal cells and hepatocytes were especially noticeable in dysplastic areas characteristic of atypical MRNs, as in small HCCs. In addition, the staining of alpha 2 and alpha 6 integrins in MRNs revealed the presence of widespread atypical ductular proliferation expanding from periportal and perinodular areas, containing epithelial cells with transitional (hepato-biliary) phenotype. These findings suggest a transition from atypical MRNs to small HCCs and a possible role for liver epithelial precursor cells ('stem cells') in the development and evolution of MRNs.

Carcinoma, Hepatocellular↗
PubMed1997

Prevalence of liver cell dysplasia and association with HCC in a series of 100 cirrhotic liver explants.

BACKGROUND/AIMS: Liver cell dysplasia of large (LLCD) and small (SLCD) cell types may represent a premalignant change. We sought to evaluate their prevalence, relationship with the gross type of cirrhosis, aetiology of liver disease, and the presence of hepatocellular carcinoma in a series of cirrhotic livers. METHODS: The presence and pattern of SLCD and LLCD were evaluated by careful histological analysis in 100 consecutive cirrhotic livers of viral (49%) or non viral (51%) aetiology, and with or without hepatocellular carcinoma. Prevalences were compared using Chi-square or Fisher's tests; relative risk for hepatocellular carcinoma was evaluated by the odds ratio. RESULTS: Dysplasia was found in 82/100 of livers. Eighty-one had LLCD, with (n=49) or without (n=32) associated SLCD. SLCD alone was found in only one case. LLCD and SLCD tended to be more frequent and extensive in mixed or macronodular cirrhosis than in micronodular cirrhosis. LLCD was significantly more frequent and extensive in cirrhosis due to hepatitis B, as was SLCD in cirrhosis due to hepatitis B virus or biliary diseases, where it showed a different pattern (focal vs diffuse, respectively). LLCD and SLCD were both significantly associated with the presence of hepatocellular carcinoma, even of small size. Small foci of SLCD and widespread LLCD were the two conditions which showed the strongest association with hepatocellular carcinoma, with odds ratios of: 6.33 and 3.88, respectively. Widespread SLCD was not relevant for hepatocellular carcinoma in biliary diseases. CONCLUSIONS: Liver cell dysplasia may be considered an additional risk factor for hepatocellular carcinoma in patients with cirrhosis and should be looked for in biopsies. Widespread LLCD and SLCD with a focal pattern are particularly relevant for hepatocellular carcinoma, whereas widespread small cell changes found in biliary diseases seem to have a different biological significance.

Carcinoma, Hepatocellular↗
PubMed1997

Human hepatic myofibroblasts increase invasiveness of hepatocellular carcinoma cells: evidence for a role of hepatocyte growth factor.

The stroma of hepatocellular carcinomas (HCC) is infiltrated with myofibroblasts (MFs). Preliminary in vivo data have suggested that liver MF express hepatocyte growth factor (HGF), a cytokine that has been implicated in several tumor models. Our aim was to investigate the role of MF and HGF in HCC. Cultured liver MF expressed HGF messenger RNA (mRNA) and secreted HGF in their medium, as shown by Western blot, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA). Addition of MF-conditioned medium to the HepG2 HCC cell line induced cell scattering. This was associated with a decrease in cell proliferation. MF also increased about 100-fold the ability of HepG2 to invade Matrigel. Increased invasiveness was also shown for HuH7 cells, but no scattering was observed and cell proliferation was stimulated. All the effects of MF on both tumor cell types were blocked by addition of an antibody to HGF and they all could be reproduced by adding recombinant HGF to the tumor cells. RT-PCR and Western blot analysis confirmed that both tumor cell lines expressed c-met, the receptor for HGF. The effects of MF-conditioned medium were not reproduced by acidic fibroblast growth factor, basic fibroblast growth factor, epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1), or platelet-derived growth factor (PDGF-BB). Reverse transcription-polymerase chain reaction (RT-PCR) analysis confirmed that HGF was expressed in human HCC. Our data show that human liver MF act on HCC cells to increase their invasiveness and suggest that MF-derived HGF could be involved in the pathogenesis of HCC.

Actins↗
PubMed1997

Case report: incomplete septal cirrhosis with liver cell dysplasia.

A 60-year-old woman was transplanted for end-stage alcoholic cirrhosis. The diagnosis of cirrhosis was made 13 years earlier on the basis of features of portal hypertension and a wedge liver biopsy. Liver function tests were subnormal except for a low prothrombin time. Unproven possible alcohol abuse was the only aetiological factor. Her condition remained unchanged until transplantation, despite complete abstinence. Histological examination of the explant showed incomplete septal cirrhosis associated with distal obstructive portal venopathy, cirrhotic nodules predominantly in the subcapsular areas and nodular regenerative hyperplasia with septal fibrosis elsewhere. In addition, there were areas of large and small liver cell dysplasia. This observation shows the difficulty in making a diagnosis of incomplete septal cirrhosis and the hypothetical link between liver cell dysplasia (which has never been reported in incomplete septal cirrhosis but is well known to be associated with hepatocellular carcinoma in cirrhosis) and rare cases of liver adenomas and carcinomas reported in patients presenting with liver vascular disorders.

Female↗
PubMed1997

Characterization of a new human liver myofibroblast cell line: transcriptional regulation of plasminogen activator inhibitor type I by transforming growth factor beta 1.

Myofibroblasts (MF) are a major effector cell type in liver fibrogenesis, where they are thought to derive from the activation of hepatic stellate cells. Cultured human MF, grown from liver explants, retain most of the in vivo characteristics of liver MF but are in limited supply. A continuous MF cell line would therefore be valuable in studying human liver fibrogenesis. For this purpose, we sought to immortalize human liver MF with polyoma virus large T antigen. MF were obtained from explants of human liver and transfected with a plasmid containing the coding sequence of polyoma virus large T antigen. This procedure yielded an activity growing cell line, designated GREF-X, which did not express large T antigen. Nevertheless, this cell line has been passaged repeatedly for almost 1 year and is thus likely immortalized. The morphology of GREF-X resembles that of primary liver MF. These cells have a doubling time of approximately 72 hours and are density-inhibited, and their growth is serum-dependent. Moreover, GREF-X cells do not grow in soft agar or induce tumors in nude mice, suggesting that they are not transformed. They stain positively for MF markers, such as smooth muscle alpha-actin and vimentin; express collagens type I, IV, V, and VI, fibronectin, and laminin: and secrete matrix-metalloproteinase-2. In addition, GREF-X cells are able to take up and esterify [3H]retinol, suggesting that they actually derive from hepatic stellate cells. Finally, these cells respond to transforming growth factor-beta 1, a major mediator of liver fibrogenesis, by increasing secretion of fibronectin and plasminogen activator-inhibitor type 1. Transient transfection experiments showed that plasminogen activator-inhibitor type 1 regulation, by transforming growth factor-beta 1, was transcriptional. We believe, therefore, that GREF-X would be a useful tool for studying the pathophysiology and pharmacology of liver fibrogenesis.

Actins↗
PubMed1997

Osteonectin (SPARC) expression in human liver and in cultured human liver myofibroblasts.

Osteonectin/SPARC is a glycoprotein involved in the regulation of cell shape, adhesion, migration, and proliferation. It also has complex effects on extracellular matrix synthesis and turnover. We found that osteonectin mRNA was very abundant in a human liver myofibroblast library. Using Northern and Western blot, immunoprecipitation, and radioimmunoassay, we found that cultured liver myofibroblasts actively secreted osteonectin. Myofibroblasts are very rare in normal liver but proliferate during liver fibrosis where they synthesize extracellular matrix components. Thus, we studied the distribution of osteonectin in normal and fibrotic human liver using in situ hybridization. Osteonectin mRNA expression was weak in normal liver but very high in fibrotic liver within fibrous septae and scattered sinusoidal cells. Serial sectioning and double staining experiments with an antibody to smooth muscle alpha-actin showed that osteonectin transcripts were mostly co-localized with myofibroblasts. In conclusion, osteonectin is highly expressed in human liver myofibroblasts in culture as well as in human liver fibrosis in vivo. The many biological properties of osteonectin make it a candidate effector of human liver fibrogenesis.

Actins↗
PubMed1996

Longitudinal melanonychia in children. A study of eight cases.

BACKGROUND AND DESIGN: Longitudinal melanonychia is rare in white children and represents a difficult clinical challenge. Because of the fear of malignant melanoma, a surgical excision is usually performed, sometimes with definitive aesthetic and functional consequences. Eight children with longitudinal melanonychia who were between the ages of 2 and 14 years underwent follow-up. Surgical excision was performed in five cases. For three children, a wait-and-see policy was adopted, because their longitudinal melanonychia had been unchanged for years at the time of their examination. RESULTS: Melanoma was never observed in our cases (follow-up, 5.5 years). Histologic examinations performed in five cases showed junctional nevi of the nail matrix, often with dysplasia as commonly seen in juvenile nevi. Two children had postoperative nail dystrophy. CONCLUSION: In white children, longitudinal melanonychia rarely disappears. Since an ungual melanocytic band can appear at the age when other nevi appear, surgical excision should not be undertaken on different grounds than for other congenital or acquired nevi in children.

Adolescent↗
PubMed1996

Cystic smooth-muscle tumor of the liver and spleen associated with Epstein-Barr virus after renal transplantation.

Immunosuppression is known to favor the development of various types of tumors. After organ transplantation, the risk of lymphoproliferative disease, whether clonal or not, is particularly increased and clearly associated with Epstein-Barr virus infection. We report a case of an unusual large cystic tumor of the liver with satellite hepatic and splenic nodules occurring 4 years after renal transplantation. Radiologic examination showed a rich vascularization of the tumor. Light and electron microscopy of a surgical liver biopsy, completed by an immunohistochemical study, demonstrated a well-differentiated tumor of smooth-muscle origin. Using in situ hybridization, we showed large amounts of Epstein-Barr virus messenger RNAs within the tumor cells. In addition, Southern blot analysis revealed that viral DNA was present in the form of a single monoclonal episome within the tumor. The polymerase chain reaction analysis of the genomic DNA of tumoral cells also indicated a monoclonal pattern. At last, the tumor was shown to be of host origin. Six months later, and despite three courses of chemotherapy, the tumoral lesions were unchanged. This case underlines the role of Epstein-Barr virus infection in the development of unusual and clonal smooth-muscle tumors after organ transplantation. The evolution of these rare tumors is uncertain.

Female↗