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Biomedical subjects

P Bedossa

Publications and source records attributed to P Bedossa.

At least 19 recordsLinked to original sources
PubMed1997

Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups.

BACKGROUND: Our aim was to assess the natural history of liver fibrosis progression in hepatitis C and the factors associated with this progression. METHODS: We recruited 2235 patients from the Observatoire de l'Hépatite C (OBSVIRC) population, the Cohorte Hépatite C Pitié-Salpétrière (DOSVIRC) population, and the original METAVIR population. All the patients had a biopsy sample compatible with chronic hepatitis C as assessed by the METAVIR scoring system (grades the stage of fibrosis on a five-point scale, F0 = no fibrosis, F4 = cirrhosis, and histological activity on a four-point scale, A0 = no activity, A3 = severe activity). No patient had received interferon treatment before the liver biopsy sample was obtained. We assessed the effect of nine factors on fibrosis progression: age at biopsy; estimated duration of infection; sex; age at infection; alcohol consumption; hepatitis C virus C (HCV) genotype; HCV viraemia; cause of infection; and histological activity grade. We defined fibrosis progression per year as the ratio between fibrosis stage in METAVIR units and the duration of infection (1 unit = one stage, 4 units = cirrhosis). FINDINGS: The median rate of fibrosis progression per year was 0.133 fibrosis unit (95% CI 0.125-0.143), which was similar to the estimates from previous studies (0.146 to 0.154). Three independent factors were associated with an increased rate of fibrosis progression: age at infection older than 40 years, daily alcohol consumption of 50 g or more, and male sex. There was no association between fibrosis progression and HCV genotype. The median estimated duration of infection for progression to cirrhosis was 30 years (28-32), ranging from 13 years in men infected after the age of 40 to 42 years in women who did not drink alcohol and were infected before the age of 40. Without treatment, 377 (33%) patients had an expected median time to cirrhosis of less than 20 years, and 356 (31%) will never progress to cirrhosis or will not progress for at least 50 years. INTERPRETATION: The host factors of ageing, alcohol consumption, and male sex have a stronger association with fibrosis progression than virological factors in HCV infection.

Adult↗
PubMed1997

Malignant transformation of nontrophoblastic cells is associated with the expression of chorionic gonadotropin beta genes normally transcribed in trophoblastic cells.

The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta allelic genes beta7 and beta6, which possess a GCC codon corresponding to an alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and beta3 and its allele beta9, which possess a GAC codon corresponding to an aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by type II CGbeta genes, whereas normal nontrophoblastic tissues of differing histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands, thyroid, colon, and uterus) express only type I CGbeta genes. We studied the expression of CGbeta genes in 86 tumor specimens collected from patients with breast, bladder, prostate, and thyroid cancer and found that up to 61% of these nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on tumor tissues and their normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CGbeta genes. These findings provide the basis for a simple test (the CG117 assay) that may be useful for the diagnosis of the most frequent malignancies.

Cell Line↗
PubMed1996

Effect of polymeric nanoparticle administration on the clearance activity of the mononuclear phagocyte system in mice.

We investigated the consequences of acute and subacute administration of mice with polyisobutylcyanoacrylate (PIBCA), polyisohexylcyanoacrylate (PIHCA), poly(D,L-lactic) acid (PLA), and polystyrene (PS) nanoparticles on the mononuclear phagocyte system phagocytic function. This was done by measuring the clearance rate of colloidal carbon. Single administration of PIBCA and PIHCA (but not PLA and PS) nanoparticles reduced carbon clearance in both a time- and dose-dependent fashion. Since clearance of preopsonized carbon was normal, it was assumed that PIBCA and PIHCA nanoparticles deplete opsonins specific for carbon recognition. A decrease in plasma fibronectin levels resulting from nanoparticle administration suggested its implication in their removal from blood. However, fibronectin does not seem to be responsible for PIBCA and PIHCA blockade. Phagocytic function was preserved after repeated treatment with nanoparticles, probably as a result of increased Kupffer cell phagocytic activity and the contribution of spleen macrophages. Neither toxicity nor effects due to nanoparticle hepatic accumulation were observed.

Animals↗
PubMed1996

Quantification of apolipoprotein A-I and B messenger RNA in heavy drinkers according to liver disease.

It has previously been shown that, in heavy drinkers, serum apolipoprotein A-I (ApoA-I) levels are closely related to the degree of liver injury: they are at a maximum in patients with steatosis, begin to decrease in patients with fibrosis, and reach a minimum in patients with severe cirrhosis. In contrast with serum ApoA-I variations, serum apolipoprotein B (ApoB) levels are stable. The assessment of messenger RNA (mRNA) levels of ApoA-I and ApoB using a quantitative competitive polymerase chain reaction (PCR) method was performed in 18 alcoholic patients: 8 with normal livers or steatosis (group I), 6 with fibrosis or nonsevere cirrhosis (group II), and 4 with severe cirrhosis (group III). For ApoA-I, group I had higher serum levels (208.4 +/- 37.6 mg/dL mean +/- SE) and mRNA levels (0.51 +/- 0.12) than group II (serum 116 +/- 19 mg/dL, P < .01, mRNA 0.40 +/- 0.11, P < .09) or group III (serum 56.5 +/- 28.6 mg/dL, P < .01, mRNA 0.27 +/- .02, P = .008). For ApoB, the three groups had similar serum ApoB levels: 129.9 +/- 37.7, 121 +/- 51, 120.7 +/- 57.4 mg/dL. Group I presented higher levels of ApoB mRNA than those of group III (0.68 +/- 0.21 vs. 0.41 +/- 0.18, P < .06). There was a significant correlation between serum and mRNA levels of ApoA-I (r = .65, P = .003) but no correlation between serum and mRNA levels of ApoB (r = .19, NS). We suggest that (1) steatosis is associated with increased ApoA-I mRNA; (2) fibrosis is associated with decreased serum ApoA-I, probably caused by a posttranscriptional mechanism; (3) severe alcohol-induced cirrhosis is associated with a nonspecific decrease in ApoA-I and ApoB mRNA; and (4) in contrast to ApoA-I mRNA, the ApoB mRNA level makes a slight contribution to the ApoB serum concentration.

Adult↗
PubMed1996

An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group.

Histological activity reflects the global assessment of basic necroinflammatory lesions and is a criterion of major importance in chronic hepatitis C. The aim of this study was to propose and test the accuracy of a simple algorithm that generates a single activity score based on basic pathological features. A panel of 10 pathologists reviewed 363 chronic hepatitis C liver biopsies and graded the activity of hepatitis according to their own experience (reference activity). Then, a consensual algorithm on the grading of activity was established by the 10 experts in a panel discussion. Finally, stepwise discriminant analysis was performed to define which basic features had been intuitively used in the reference activity (statistical activity). To test the accuracy of the algorithm, concordance between the activity defined by the algorithm and the reference activity was assessed. It was compared with concordance between the activity defined by the statistical model and the reference activity. The algorithm proposed by the panel for the grading of activity included piecemeal necrosis and lobular necrosis. Concordance between reference activity and activity defined by the algorithm was substantial (305 cases, 84%, kappa = .75). Discriminant analysis showed that piecemeal necrosis, lobular necrosis, and portal inflammation were independently used to grade the activity. Concordance between reference activity and activity defined by the statistical model was substantial (300 cases, 83%, kappa = .73), virtually identical to the concordance between reference activity and activity defined by algorithm. This study proposes a simple algorithm for the grading of activity in chronic hepatitis. Its accuracy is as high as that obtained using a statistical approach.

Algorithms↗
PubMed1996

Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver.

BACKGROUND & AIMS: Cadherins and their associated molecules, such as alpha-catenin, have been shown recently to play a pivotal role in epithelial carcinogenesis. METHODS: The expression of E-cadherin, N-cadherin, and alpha-catenin in 10 normal samples, 28 focal nodular hyperplasias, 9 liver cell adenomas, 65 hepatocellular carcinomas, and 9 cholangiocarcinomas was studied by immunohistochemistry and Western blotting. RESULTS: In the normal liver, hepatocytes expressed E-cadherin and a 129-kilodalton cadherin identified by the anti-N-cadherin antibody GC4. The expression level of alpha-catenin was low. Bile duct cells expressed only E-cadherin and showed high levels of alpha-catenin. The expression of cadherins and alpha-catenin was preserved in focal nodular hyperplasia. In liver cell adenomas, cadherins and alpha-catenin were heterogeneously expressed. In hepatocellular carcinomas, cadherin and alpha-catenin expression was frequently reduced or absent. Alterations in cadherin expression correlated with large tumor size, low grade of histological differentiation, and occurrence of capsular and vascular invasion. In cholangiocarcinomas, neoplastic cells inconstantly expressed E-cadherin and alpha-catenin. CONCLUSIONS: Alterations of cadherin and alpha-catenin expression are frequent in liver cell adenomas and primary liver carcinomas. Their incidence in hepatocellular carcinomas is of prognostic significance.

Adenoma, Liver Cell↗
PubMed1996

Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone.

BACKGROUND & AIMS: Corticosteroids have been shown to significantly decrease short-term mortality in patients with severe alcoholic hepatitis. However, independent factors associated with a favorable outcome and long-term survival are unknown. The aim of this study was to examine prognostic factors and long-term survival in patients with biopsy-proven severe alcoholic hepatitis. METHODS: Of 183 patients studied, 61 had been randomized in a previous trial; 32 of them were treated with prednisolone (group I) and 29 were not treated (group II); 61 were treated from the end of this randomized trial (group III); and 61 were simulated (group IV). RESULTS: At 1 year, survival in group I (69%; confidence interval [CI], 57%-81%) and group III (71%; CI, 55%-87%) was better than in the nontreated groups (group II, 41%; CI, 23%-59%; P = 0.01) (group IV, 50%; CI, 37%-63%; P = 0.05). At 2 years, survival was not significantly different. Treated patients with marked liver polymorphonuclear infiltrate had better 1-year survival (76%; CI, 64%-88%) than the others (53%; CI, 35%-71%; P = 0.05). Treated patients with polymorphonuclear counts of > 5500/mm3 had better 1-year survival (77%; CI, 65%-89%) than the others (40%; CI, 14%-66%; P = 0.003). In the 93 treated patients, liver polymorphonuclear infiltrate (P < 0.03) and polymorphonuclear count (P < 0.001) were independently correlated with 1-year survival. CONCLUSIONS: Prednisolone reduced mortality by at least 1 year. Liver polymorphonuclear infiltrate and polymorphonuclear count were independent prognostic factors.

Female↗
PubMed1996

Binding of apolipoprotein A-I and acetaldehyde-modified apolipoprotein A-I to liver extracellular matrix.

Apolipoprotein A-I (Apo A-I), a protein produced mainly by hepatocytes, is decreased in the sera of alcoholic patients with liver fibrosis and cirrhosis. To explain this decrease, we investigated possible interactions between liver extracellular matrix (ECM) and Apo A-I. Using a solid-phase binding assay, we evaluated the binding of Apo A-I to the different liver matrix components. Apo A-I bound significantly to fibronectin (FN) (optical density [OD] = 1.11 +/- .26, P = .01) and collagen (C) I (OD = 0.91 +/- 0.22, P = .02) in comparison with bovine serum albumin (BSA) (OD = 0.26 +/- 0.16). Binding of Apo A-I to fibronectin was concentration dependent and saturable. Apo A-I bound also to ECM in vivo because Apo A-I was detected by immunofluorescence on fibrous septa in liver biopsy specimens of alcoholic patients. Because a negative correlation between Apo A-I and liver fibrosis is amplified in alcoholic patients, we investigated whether the in vitro formation of Apo A-I/acetaldehyde complex (adducts) increased the binding of Apo A-I to the ECM. We showed that the amount of Apo A-I that bound to FN was significantly higher with acetaldehyde-modified Apo A-I (OD = 2.18 +/- 0.19, P = .01) than with native Apo A-I. This increase was probably related to the formation and binding of Apo A-I dimers, because immunoblot of in vitro acetaldehyde-modified Apo A-I showed the formation of dimeric Apo A-I. In conclusion, FN binds both native and acetaldehyde-modified Apo A-I. Because FN is deposited early and in excess during liver fibrosis, a storage mechanism of Apo A-I on newly deposited fibronectin would explain, in part, the decrease observed in alcoholic patients with liver fibrosis.

Acetaldehyde↗
PubMed1996

Histological features predictive of liver fibrosis in chronic hepatitis C infection.

AIMS: To assess which pathological features are associated with a sensitive marker of liver fibrogenesis and thus of the potential development of fibrosis in hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by quantification of type I collagen mRNA and transforming growth factor (TGF) beta 1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28 patients with chronic hepatitis C and five controls, using a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA quantification were correlated with histological lesions scored semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more strongly expressed in patients than in controls and correlated with the degree of fibrosis, but not with any of the necro-inflammatory lesions (portal inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA concentration was higher in patients than in controls and correlated with histological grade of activity and lobular necrosis. This result was confirmed by in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION: This study shows that fibrosis, rather than necro-inflammatory lesions or activity scores, is associated with fibrogenesis and thus with potential aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an important predictor of prognosis in chronic hepatitis C, as shown by its strong association with TGF beta 1 mRNA expression.

Adult↗
PubMed1996

Cellular and subcellular localization of acetaldehyde-protein adducts in liver biopsies from alcoholic patients.

Acetaldehyde, the first product of ethanol in hepatocytes, can react with protein to form acetaldehyde-protein adducts (APAs). Because it has been suggested that these adducts could be involved in the pathogenesis of ethanol-induced hepatic lesions and in fibrogenesis, we performed an ultrastructural immunohistochemical study to precisely define the cellular and subcellular localization of APAs. A preembedding technique of indirect immunoperoxidase was performed in liver biopsy specimens from eight patients with alcoholic liver disease, using a specific antiserum against APAs. In all specimens, APAs were detected in the rough endoplasmic reticulum, in some peroxisomes, and in the cytosol of hepatocytes. In four patients with steatofibrosis or cirrhosis, labeling of Ito cells was also observed. In these cases, the same staining pattern was observed in the cytoplasmic processes of myofibroblasts in areas of fibrogenesis. When isolated rat Ito cells were incubated in the presence of acetaldehyde, APAs were also detected in the cytoplasm. These results show that APA formation occurs in hepatocytes at the sites of acetaldehyde production. Detection of APAs in human and rat Ito cells strongly suggests that acetaldehyde can diffuse into Ito cells and bind to cytoplasmic proteins to form local APAs. Because Ito cells are the main effector cells of liver fibrosis, detection of APAs in these cells points to their possible involvement in liver fibrogenesis.

Acetaldehyde↗
PubMed1996

Role of liver extracellular matrix in transcriptional and post-transcriptional regulation of apolipoprotein A-I by hepatocytes.

Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.

Animals↗
PubMed1995

A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. Multicenter Study Group.

BACKGROUND: We studied the effects of long-term treatment with interferon on histologic features of the liver and serum alanine aminotransferase concentrations in patients with chronic non-A, non-B hepatitis. METHODS: Consecutive patients who met the inclusion criteria were enrolled in the study. The diagnosis of chronic non-A, non-B hepatitis was established on the basis of the liver-biopsy findings and an abnormal serum alanine aminotransferase value (greater than 1.5 times the normal value) for at least one year. All patients were treated for six months with 3 million units of interferon alfa-2b given subcutaneously three times a week and were then randomly assigned to the same treatment for an additional 12 months (group 1), a regimen of 1 million units three times a week for 12 months (group 2), or no further treatment (group 3). Patients in group 3 who had elevated serum alanine aminotransferase concentrations for three consecutive months underwent the initial regimen once again. Follow-up continued for two years after the discontinuation of treatment. Histologic improvement was defined as a decrease of at least one grade in the score for necroinflammatory activity (0, no activity; 1, mild; 2, moderate; or 3, severe) between the first liver biopsy and a biopsy performed at 18 months. RESULTS: Of the 329 patients initially treated, 303 were randomized: 103 to group 1, 101 to group 2, and 99 to group 3. Of the 286 patients tested, 252 (88.1 percent) had antibodies to hepatitis C virus. In an intention-to-treat analysis, 46 of the patients in group 1 (44.7 percent) had normal serum alanine aminotransferase values at 18 months, as compared with 27 of the patients in group 2 (26.7 percent, P = 0.008) and 30 of those in group 3 (30.3 percent, P = 0.04). Between 19 and 42 months, 23 of the patients in group 1 (22.3 percent) continued to have normal serum alanine aminotransferase values (measured every six months), as compared with 10 of the patients in group 2 (9.9 percent, P = 0.02) and 8 of those in group 3 (8.1 percent, P = 0.005). Among the 176 patients with repeated liver biopsies at 18 months, more patients in group 1 had improved histologic-activity scores (69.6 percent) than in group 2 (47.6 percent, P = 0.02) or group 3 (38.6 percent, P < 0.001). CONCLUSIONS: Among patients with chronic non-A, non-B hepatitis, a regimen of 3 million units of interferon alfa-2b given three times a week for 18 months produced better histologic findings and serum alanine aminotransferase values than regimens involving a lower dose or a shorter duration of treatment.

Alanine Transaminase↗
PubMed1995

[Benign thyroid oncocytomas. Outcome after more than 4 years].

OBJECTIVES: Occasional malignant transformation after partial thyroidectomy for Hürthle cell tumours has led certain authors to propose total thyroidectomy in all cases. The aim of this retrospective study was to evaluate outcome 4 years after partial thyroidectomy in patients with Hürthle cell tumours. METHODS: Ten patients (9 females, 1 male; mean age 45 years; age range 21-65 years) underwent thyroid surgery for Hürthle cell tumours from 1980 to 1989. Lobectomy was performed in 7, subtotal thyroidectomy in 2 and tumourectomy in 1. The extemporaneous pathology examination reported 4 apparently benign vesicular lesions, 2 apparently benign oncocyte lesions, 2 fetal adenomas, 1 thyroiditis, 1 trabecular adenocarcinoma. Pathology examination of the surgical specimen reported isolated benign oncocyte tumours in 4 cases and benign oncocyte tumours with associated vesicular adenomas in 5. In 1 case it was not possible to confirm whether the oncocyte lesion was benign or malignant. All 10 patients were seen again 6 months later for consultation and thyroid hormone assays and thyroid echography in doubtful cases. RESULTS: All patients were seen for follow-up (mean 88 months; range 47-148 months). New thyroid nodules were observed in 2 but did not require surgery. No cervical lymph node enlargement was found. CONCLUSION: The diagnosis of Hürthle cell tumour was confirmed intraoperatively in 8 of the 10 cases. No malignant transformation was observed. These findings demonstrate that total thyroidectomy cannot be indicated intraoperatively and would not appear to be indicated after partial thyroidectomy.

Adenoma, Oxyphilic↗
PubMed1995

Nonhereditary colonic angiodysplasias: histomorphometric approach to their pathogenesis.

The pathogenesis of colonic angiodysplasias, more accurately termed vascular ectasias (VE) has not been definitely established. The aim of this study was to assess that the VE of noncirrhotic patients are not associated with diffuse abnormalities of the colonic mucosal microvasculature unlike the VE of cirrhotic patients. Three groups of nine consecutive patients were studied: group I, control patients with an irritable bowel syndrome; group II, noncirrhotic patients with VE; and group III, alcoholic cirrhotics with VE. A histomorphometric analysis of normal-appearing colonic mucosa was achieved from biopsies taken at six predetermined sites. Noncirrhotics with VE had a significantly lower mean number of mucosal capillaries and a significantly lower mean cross-sectional area of mucosal capillaries than alcoholic cirrhotics with VE. Alcoholic cirrhotics with VE had a significant increase of all the vascular parameters compared to the control group. There was no difference between the control patients and the noncirrhotic patients with VE. These results suggest that the VE of noncirrhotic and cirrhotic patients are entities of distinct pathogenesis.

Angiodysplasia↗
PubMed1995

Molecular analysis of TCR junctional variability in individual infiltrated islets of non-obese diabetic mice: evidence for the constitution of largely autonomous T cell foci within the same pancreas.

Insulitis develops in non-obese diabetic (NOD) mice as a multicentric and asynchronous process. In an effort to understand how this T cell mediated process expands within each islet and propagates between the islets of the same pancreas, we have analyzed the junctional diversity of TCR V beta 6 and V beta 8.2 transcripts cloned from infiltrated islets. The material examined was obtained from individual islets of 8 and 12 week old NOD mice or from pooled islets of 4 week old individual mice. Compared with spleen transcripts, where every V beta 6 or V beta 8.2 clone displays a different junction, islet transcripts are considerably less diverse. Each islet harbors from one to a maximum of six independent CDR3 sequences out of 10 or more analyzed colonies. On the other hand, there is an overall diversity of sequences when comparing the islets of the same pancreas or individual mice at 4 weeks. Altogether, these results support the idea that TCR repertoires are already divergent at the very early onset of insulitis and that each islet-centered infiltrate develops rather autonomously from the oligoclonal expansion of a limited set of precursors. Recirculation between islets is limited and does not seem to be the main mode of propagation of insulitis. Finally, a close analysis of J beta usage and N additions in beta chain transcripts from infiltrating cells reveals definite biases suggestive of an ongoing selective process imposed upon intra-pancreatic T lymphocytes.

Amino Acid Sequence↗
PubMed1995

Prevalence of cholelithiasis according to alcoholic liver disease: a possible role of apolipoproteins AI and AII.

Moderate alcohol intakes decreases the risk of gallstones; in contrast, the prevalence of gallstones is increased in patients with alcoholic cirrhosis. The aims of this prospective study were to assess the prevalence of cholelithiasis among drinkers according to the histological severity of liver disease, and to estimate the importance of serum apolipoproteins AI and apolipoprotein AII as risk factors for gallstones. Among the 320 drinkers included, 53 patients had cholelithiasis. The prevalence increased (p < 0.0001) from 5% in patients with normal liver (1 of 22) and 6% in patients with steatosis only (3 of 47) to 13% in patients with fibrosis (7 of 54), reaching 27% among patients with biopsy-proven cirrhosis (28 of 103). Among patients with clinically obvious cirrhosis on whom biopsy was not performed mainly because of the severity of liver disease, the prevalence of cholelithiasis reached a maximum of 46% (6 of 13). Among drinkers with nonsevere liver disease, patients with cholelithiasis were older (59 +/- 9 years, mean +/- SD vs. 45 +/- 11, p = 0.003) with lower apolipoprotein AI (118 +/- 37 vs. 163 +/- 45 mg/dl; p = 0.002) and apolipoprotein AII (30 +/- 12 vs. 53 +/- 20 mg/dl; p = 0.0002) in comparison with patients without cholelithiasis. These differences persisted after considering by multiple logistic regression analysis, sex, and ideal body weight. Alcohol consumption during the last 5 years was lower in patients with cholelithiasis (83 g/day) in comparison with patients without cholelithiasis (142 g/day; p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Fibronectin of human liver sinusoids binds hepatitis B virus: identification by an anti-idiotypic antibody bearing the internal image of the pre-S2 domain.

Anti-idiotypic antibodies (anti-Ids) have been successfully used to characterize and isolate receptors of several cell ligands. To prepare an immunological probe for identification of cellular components interacting with the hepatitis B virus (HBV), polyclonal antisera against a panel of five HBV-specific monoclonal antibodies (MAbs) were produced in syngeneic BALB/c mice. MAbs to HBV used for immunization (Ab1) recognized biologically important and potentially neutralizing epitopes, located in the pre-S1, pre-S2, or S region-encoded domains of HBV proteins. All the anti-Ids (Ab2) were specific to idiotopes of the homologous Ab1 and inhibited their interaction with the corresponding viral epitopes, suggesting that they recognized unique determinants on the paratope of each immunizing Ab1. Therefore, all five generated polyclonal anti-Ids were of the Ab2 beta type and could represent internal images of viral epitopes. Ab2 raised against the pre-S2 region-specific MAb F124 bound to the extracellular matrix fibronectin of human liver sinusoids. Immunohistochemical studies demonstrated the attachment of viral and recombinant (S, M) hepatitis B surface antigen particles with the pre-S2 region-encoded epitopes to the fibronectin of human liver sinusoids. In contrast, recombinant (S, L*) hepatitis B surface antigen particles, in which the epitope recognized by F124 MAb was not expressed, did not show any binding capacity. These findings suggest that human liver fibronectin may bind HBV in vivo by the pre-S2 region-encoded epitopes in a species-restricted manner. Furthermore, binding of the circulating virus to liver sinusoids could facilitate its subsequent uptake by hepatocytes.

Animals↗