PubMed Health⌕ Search

Biomedical subjects

P Bedossa

Publications and source records attributed to P Bedossa.

At least 109 records · Page 6Linked to original sources
PubMed1995

Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 1 receptors in normal, cirrhotic, and neoplastic human livers.

Transforming growth factor-Beta 1 (TGF-beta 1) is an important mediator of control of liver cell proliferation and replication. The aim of the current study was to compare TGF-beta 1 gene expression, protein synthesis, and cell membrane receptors in normal liver, cirrhotic nodules, and neoplastic human livers. Five surgical resections for metastasis in an otherwise normal liver and 25 resections for hepatocellular carcinoma with cirrhosis were included in this study. Messenger RNA (mRNA) and TGF-beta 1 protein were detected on serial tissue sections of normal, cirrhotic, and tumoral livers using in situ hybridization and immunohistochemistry. TGF-beta 1 type II receptors were detected on tissue sections using immunohistochemistry. In normal livers, TGF-beta 1 mRNA and protein were not significantly expressed. In cirrhotic nodules, a few sinusoidal cells and mesenchymal cells of fibrous septa displayed TGF-beta 1 mRNA. By immunohistochemistry, protein was detected in the extracellular matrix along the fibrous septa. Hepatocytes from normal and cirrhotic livers did not express TGF-beta 1. In contrast, the cytoplasm of hepatocytes in neoplastic nodules showed intense staining for TGF-beta 1 mRNA and protein. Although TGF-beta 1 receptor II was expressed on the plasma membrane of normal liver cells, tumoral hepatocytes no longer displayed membrane labeling but rather diffuse intracytoplasmic staining with perinuclear accumulation. This study suggests that the escape of tumoral hepatocytes from control of cell proliferation by TGF-beta 1, despite its overexpression by these cells, might be related to a defect in TGF-beta 1 receptor II processing on the liver cell membrane.

Carcinoma, Hepatocellular↗
PubMed1995

[Reliability of the anatomopathological diagnosis by static image transfer].

50 hepatic biopsies and 50 prostatic biopsies were submitted for diagnostic to an expert by the mean of static images previously digitalized by a consulting pathologist. Accuracy of diagnosis was obtained in 2 minutes with 4 images in 86% of cases. Additional data such as new images, several power fields, permitted accuracy of diagnosis in 98% of the cases. The experiences showed clearly that the quality of the transferred static images is sufficient to allow diagnoses. It pointed out the importance of the different actors involved in the consultation. It illustrates the possible use of this system as a training tool.

Female↗
PubMed1995

[Liver fibrosis].

Explore the source record for details and available documents.

Extracellular Matrix↗
PubMed1994

Alpha-2-macroglobulin and hepatic fibrosis. Diagnostic interest.

Alpha-2-macroglobulin (A2M) is a proteinase inhibitor. Cells synthesizing A2M are in first-order hepatocytes and in second-order activated Ito cells (in culture starting at day 4-5 after seeding). This study was undertaken in 525 alcoholic patients with different histological stages of alcoholic liver disease to assess if the A2M could improve the diagnostic value of PGA index for detection of cirrhosis or fibrosis among drinkers, particularly in patients without clinical symptoms of liver failure and portal hypertension, and to assess the specific correlation of serum A2M with the score of liver fibrosis adjusted for steatosis and alcoholic hepatitis and thereafter adjusted for GGT, PT, and ApoA1, the three components of the PGA index. In 525 alcoholic patients, we have demonstrated the independent diagnostic value of A2M. The predictive values of the weighted score, using linear discriminant function combining PT, GGT, ApoA1 and A2M of the PGAA score and of the PGA score were assessed in a training step and validated in a second step. Then, 316 alcoholic clinically asymptomatic patients were studied. In these patients, the discriminant function permitted correct classification of 72% of patients. The PGAA index had comparable diagnostic value with 70% of patients correctly classified. On the other hand, the PGA index including only PT, GGT, and ApoA1 had classified correctly less patients (65%) than the discriminant function and the PGAA index (P < 0.01). For a value of 7, PGAA had 79% specificity and 89% sensitivity for the diagnosis of cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗
PubMed1994

TGF-beta and collagen-alpha 1 (I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload.

We have shown that lipid peroxidation stimulates collagen-alpha 1 (I) gene transcription in cultured cells. Because iron is a transitional metal known to induce lipid peroxidation, we investigated whether hepatic lipid peroxidation modulates collagen gene expression in iron-overloaded rats. In this animal model of hemochromatosis, we show colocalization with iron in the hepatic acinar zone 1 of both lipid peroxidation and increased collagen-alpha 1 (I) transcripts, using immunohistochemistry for malondialdehyde-protein adducts and in situ hybridization, respectively. Iron overload stimulated the expression of the cytokine transforming growth factor-beta (TGF-beta) in acinar zone 1, in spite of the minor degree of hepatocellular necrosis and inflammation. The formation of reactive aldehydes and TGF-beta, both inducers of collagen gene expression, may play a role in the stimulation of hepatic collagen production in iron overload. These mechanisms could be a link between iron overload and fibrosis in genetic hemochromatosis.

Animals↗
PubMed1994

Acetaldehyde-modified epitopes in liver biopsy specimens of alcoholic and nonalcoholic patients: localization and association with progression of liver fibrosis.

Acetaldehyde, the first product of ethanol oxidation, has been shown to stimulate collagen gene expression and to form protein-acetaldehyde adducts. Because little is known about these adducts in human liver tissue, we assessed, with an immunohistochemical procedure, the presence and location of acetaldehyde-protein adducts in liver biopsy specimens of alcoholic patients. In addition, we correlated the presence of adducts with the progression or subsequent occurrence of liver fibrosis. The group included 106 patients with high alcohol consumption (> 90 gm ethanol/day for the last 5 yr), 10 nonalcoholic patients with normal livers and 23 patients with other liver diseases. Sixty-four of the 106 alcoholic patients had a second liver biopsy, whose specimen was used to assess the progression of liver fibrosis. Polyclonal antibodies were produced against homologous low-density lipoprotein purified from rabbit serum and modified in vitro in the presence of acetaldehyde. Protein-acetaldehyde adducts could be detected by immunohistochemistry in biopsy specimens of 90 alcoholic patients (85%), in none of the 10 nonalcoholic patients with normal livers and in 65% of the patients with nonalcoholic liver disease. Acetaldehyde-modified epitopes were detected in the intracellular and extracellular compartment. Intracellular protein-acetaldehyde adducts were localized in the cytoplasm of hepatocytes with a more intense staining in zone 3. No correlation existed between the intensity of intracellular staining and the histologically assessed severity of liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1994

Stimulation of collagen alpha 1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: a link to tissue fibrosis?

We have shown that lipid peroxidation stimulates collagen alpha 1(I) gene transcription in cultured cells. Because increased lipid peroxidation and collagen production coexist in many hepatic disorders, including experimental carbon tetrachloride intoxication, we investigated whether lipid peroxidation modulates collagen gene expression in rats treated with carbon tetrachloride. In this animal model, we show colocalization of increased collagen alpha 1(I) mRNA with lipid peroxidation by means of in situ hybridization and immunohistochemical study for malondialdehyde and 4-hydroxynonenal protein adducts, respectively. However, allyl alcohol treatment, which induced a similar degree of hepatocellular injury but without aldehyde-protein adducts, did not increase collagen alpha 1(I) gene expression, suggesting that hepatocyte necrosis is not sufficient to induce the expression of collagen type I. Furthermore, in the absence of an inflammatory response, coculture experiments of hepatocytes and Ito cells treated with carbon tetrachloride indicate that hepatocytes exert a "paracrine" stimulation of both lipid peroxidation and collagen gene expression in Ito cells. These experiments suggest that hepatocyte lipid peroxidation plays a major role in the regulation of collagen alpha 1(I) gene expression by Ito cells and that it may be a link between hepatocyte injury and hepatic fibrosis.

1-Propanol↗