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Biomedical subjects

S Magrin

Publications and source records attributed to S Magrin.

At least 37 records · Page 2Linked to original sources
PubMed1991

Hepatitis C virus replication in 'autoimmune' chronic hepatitis.

Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HCV confirmed ELISA results in all patients. HCV-RNA was found in the serum from 10 patients. Institution of alpha-interferon treatment in three steroid non-responsive patients was followed by prompt normalization of transaminases. Thus, a subgroup of autoantibody-positive chronic active hepatitis can be recognized as HCV-related and should be clinically and etiologically distinguished from autoimmune chronic active hepatitis. Trials of alpha-interferon treatment are worthwhile in this condition.

Autoantibodies↗
PubMed1991

Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials.

We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant alpha-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2-6 months, greater than or equal to 2 mega-units thrice weekly) and long-term (9-18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or schedule were accounted for. About 50% of patients originally responding to treatment relapsed within 6 months of either dose reduction or stopping interferon, thus suggesting that only in about one out of four patients is benefit from treatment sustained up to 1 year. We conclude that larger trials are needed to identify an optimal schedule of treatment and to evaluate predictors of interferon effectiveness in patients with non-A, non-B chronic hepatitis.

Alanine Transaminase↗
PubMed1991

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.

Adrenal Cortex Hormones↗
PubMed1991

Smouldering hepatitis B virus replication in patients with chronic liver disease and hepatitis delta virus superinfection.

Hepatitis B virus deoxyribonucleic acid (HBV-DNA) was studied by Southern blot analysis in liver biopsy specimens from 75 HBsAg-positive patients with chronic liver disease living in southern Italy. Twenty-seven of the patients were hepatitis delta virus (HDV) superinfected. Intrahepatic HBV-DNA was detected in 54 (72%) patients, 32 (59%) of them with replicative forms. The presence of replicative forms was directly related to liver HBcAg and inversely related to liver HDAg, as shown by multivariate analysis. However, 14 patients with intrahepatic HBV-DNA non-replicative pattern and about half of HDV-infected patients were liver HBcAg and/or serum HBV-DNA positive, mostly in low amounts. Histological inflammatory activity was strongly related to liver HBcAg expression regardless of HDV superinfection, as confirmed by multivariate analysis. Our results confirm previous studies about the concordance between intrahepatic HBV-DNA replicative pattern and liver HBcAg expression and about inhibition by HDV of high-level HBV replication. However, they suggest that low-level HBV replication may have an important role in causing liver damage also among HDV-infected patients, in a population where the spreading of HBV and HDV is a naturally occurring event.

Adolescent↗
PubMed1991

Autologous blood stem cell (ABSCT) versus purged bone marrow transplantation (pABMT) in standard risk AML: influence of source and cell composition of the autograft on hemopoietic reconstitution and disease-free survival.

Complete and sustained hemopoietic function following myeloablative therapy can be successfully achieved by autologous transfusion of blood derived hemopoietic stem cells. It was the purpose of this study to compare autologous blood stem cell transplantation (ABSCT) in 20 patients with autologous transplantation of a mafosfamide purged marrow (pABMT) in 23 patients; all were transplanted in first complete remission (CR) of acute myelogenous leukemia (AML) using the same pretransplant regimen (14.4 Gy total body irradiation and 200 mg/kg cyclophosphamide). The autografts, mostly differing in source of hemopoietic stem cells, cell composition and CFU-GM number, were evaluated for their ability to reconstitute hemopoiesis and induce long-term disease-free survival (DFS). Prior to harvest, hemopoietic stem cells were mobilized by inducing transient myelosuppression (ara-C 100 mg/m2 every 12 h s.c. days 1-5 and daunorubicin 45 mg/m2, days 3 and 4) followed by an overshooting of peripheral stem cell concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Collection, processing and storage of peripheral blood stem cells (PBSC).

Eight patients with hematological malignancies were treated with autologous blood stem cell transplantation (ABSCT). Hemopoietic precursor cells were mobilized into the peripheral blood (PB) by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem cell concentration. PB CFU-GM showed a 15-20 fold increase on days 15-20 after chemotherapy. Peripheral blood stem cells were collected by 5-8 continuous flow leukaphereses using a Fenwall CS 3000 blood cell separator when platelet and WBC count was rising rapidly (platelet greater than 50 x 10e9/L and WBC greater than 1 x 10e9/L). Mean CFU-GM collected per run by leukapheresis were 10.85 x 10e4/Kg (procedure 3), 10.03 x 10e4/Kg (modified procedure 1). Mononuclear cell suspension in 10% DMSO was frozen at controlled rate freezer (-1 degree C to -4 degrees C) and stored in the liquid phase of nitrogen. After thawing CFU-GM recoveries ranged from 13.8% to 81.5%; 55-70% of recovered cells excluded trypan blue dye.

Adolescent↗
PubMed1991

Hepatitis C virus antibodies in chronic liver diseases of different aetiology.

To define the prevalence of Hepatitis C Virus (HCV) infection in patients with chronic hepatitis or cirrhosis of any aetiology, we tested a group of 372 consecutive subjects with biopsy-proven chronic liver disease (CLD) for anti-HCV antibodies, excluding active drug-addicts and alcoholics. Our results show that in Southern Italy HCV infection is widespread among subjects with cryptogenic chronic liver disease, as well as in liver diseases with features of autoimmunity (71.7% and 66.7% anti-HCV positive, respectively). Anti-HCV is infrequent among non drug-addicted HBsAg positive subjects (4.7%), and bears no relation to hepatitis D superinfection. Subjects with CLD and a history of parenteral exposure are almost always anti-HCV positive (89.2%). Patients with HBV-related CLD and previous drug-addicts are on the average younger than other disease groups, irrespective of their HCV status. Among subjects whose CLD is related to parenteral exposure, cryptogenic or autoimmune no increase in the rate of anti-HCV positivity seems to bear a parallel relationship to age. No known risk factor for parenteral transmission, other than use of blood or blood products and previous drug-addiction, can be clearly related to HCV infection. No trend to familiar clustering of HCV-induced liver disease is apparent. Liver disease severity, as assessed by transaminase levels and liver histology, does not correlate to anti-HCV status.

Adolescent↗
PubMed1989

Activation of the complement system in primary sclerosing cholangitis.

Recent evidence, including the presence of circulating immune complexes, suggests that abnormalities of humoral immunity may be important in the pathogenesis of primary sclerosing cholangitis. The aim of the present study was to determine whether activation of the complement system is present in patients with this disease, as this would be supportive evidence of a role for circulating immune complexes in primary sclerosing cholangitis. Plasma complement fragments C3d and C4d, and serum C3 and C4, their respective parent molecules, have been assayed. Both C3d and C4d were elevated in patients with primary sclerosing cholangitis compared with patients with extrahepatic obstructive cholestasis and normal controls (p less than 0.01 in all instances). C3 was elevated in both patient groups, in whom it was similar, compared with normal controls (p less than 0.001 in both cases), whereas C4 was similar in all groups. Elevated levels of circulating immune complexes were identified in 21 of 24 (88%) patients with primary sclerosing cholangitis, but in none of the normal controls. These findings support the hypothesis that in primary sclerosing cholangitis circulating immune complexes are associated with activation of complement via the classical pathway.

Adult↗
PubMed1989

The relationship between HLA-DR3 and T-cell regulation of immunoglobulin production in primary sclerosing cholangitis.

Immunoglobulin production in vitro, its control by concanavalin A-activated suppressor T-cells, and the relationship between abnormalities in nonantigen-specific suppression and histocompatibility antigens have been studied in 20 patients with primary sclerosing cholangitis (PSC). Suppression of IgG, IgM, and IgA synthesis was impaired in 12 patients with PSC alone, but was normal in 8 with PSC and associated ulcerative colitis (UC). The HLA antigens B8 and DR3 were increased in frequency in both groups of patients, but an association between DR3, and to a lesser extent B8, and defective suppressor T-cell function was only observed in the patients with PSC alone. These results not only provide further evidence of an association between HLA DR3 and impaired nonantigen-specific suppression but also indicate the genetic complexity of this association and its specificity, being found in this study in only one subgroup of patients with PSC.

Adult↗
PubMed1989

Interleukin-2, interleukin-2 receptor and gamma-interferon synthesis by peripheral blood mononuclear cells in chronic hepatitis delta virus infection.

The behaviour of the immune system during liver damage caused by chronic hepatitis delta virus (HDV) infection was evaluated by assessing, in 16 patients with HBsAg+ chronic liver disease and HDV superinfection (15 HBeAg-, 1 HBeAg+), phytohaemagglutinin (PHA)-induced interleukin-2 synthesis and interleukin-2 receptor expression, PHA and staphylococcal enterotoxin B (SEB)-induced gamma-interferon synthesis and, in some cases, the presence of hepatitis B virus DNA (HBV-DNA) within peripheral blood mononuclear cells (PBMC). The results were compared to those obtained in 13 patients without HBV replication (i.e., serum HBV-DNA and liver HBcAg-negative), in 15 with HBV replication (i.e., serum HBV-DNA and/or liver HBcAg-positive) with chronic liver disease without HDV superinfection, and in 15 HBsAg-negative healthy control subjects. The lymphokine pattern in HDV infection was comparable to that of healthy subjects and of HBV non-replicating patients without HDV superinfection. Interleukin-2 receptor expression and gamma-interferon synthesis were however significantly decreased in HDV-negative patients with active HBV replication. HBV-DNA was detected in PBMC from 8 of 23 patients, without any correlation with the lymphokine pattern. Our results suggest that in HDV-related chronic liver disease, immune system alterations are unlikely. HDV superinfection does not affect the occurrence of HBV-DNA sequences within the leukocytes. HBV-DNA in PBMC does not interfere with the interleukin-2 system nor with the gamma-interferon response in HBV- and HDV-related chronic liver disease.

Adult↗
PubMed1988

Differential effect of alpha-interferons on CD4- and CD8-positive lymphocytes in chronic hepatitis B virus carriers.

alpha-Interferons are an effective therapy in a proportion of chronic hepatitis B virus (HBV) carriers. The mode of action is almost certainly dependent upon immune modulation in addition to direct antiviral effects but the precise mechanism is unknown. To investigate whether the aberrant T-cell activation present in HBV carriers was responsive to interferons, we have studied the in vitro effect of alpha-interferons on Tac antigen expression and DNA synthesis as early and late markers of T-cell activation, respectively. At a concentration of 1000 U/ml the effect of alpha-interferons on Tac expression was contrasting in the two major T-cell subsets; there was enhancement of Tac expression on CD4-positive T-cells but inhibition of the CD8-positive subset. However, there was no overall effect on lymphocyte proliferation, perhaps as a consequence of the differential effect of alpha-interferons on the early T-cell activation marker. At higher concentration, however, the enhancement of T-cell activation was less clear, indicating that the concentration range that supports T-cell activation is narrow. Such subtle differential effects on T-cell activation may be accompanied by more profound effects on immune function and this may be one way in which alpha-interferons are of value in chronic HBV infection.

Adult↗
PubMed1988

Echocardiographic recognition of mediastinal masses.

The aim of our study was to assess the ability of echocardiography to recognize mediastinal masses. We studied 50 patients: 25 with acute lymphoblastic leukemia, nine with lymphomas, four with pleural effusion and previously known neoplastic diseases, ten with nonlymphomatous mediastinal masses, and two with compression of the superior vena cava. In 33 of 50 patients, computed tomography (CT) showed mediastinal masses, and in one, an aneurysm of the thoracic descending aorta. All patients had previously had chest x-ray and two-dimensional echocardiographic (2-DE) examinations in order to recognize the presence of masses. Two-DE was found to have similar specificity (94.1 percent) but higher sensitivity (90.9 percent vs 60.6 percent) if related to radiographic examination. The positive predictive value was 96.7 vs 95.2 percent and the negative predictive value was 84.2 percent vs 55.1 percent. In particular, 2-DE was more useful than chest x-ray examination when a concomitant pleural or pericardial effusion was present. Moreover, abnormalities of cardiac function due to compression or infiltration and the follow-up of patients were better evaluated.

Adolescent↗
PubMed1988

Abnormal T-cell activation in chronic hepatitis B viral infection: a consequence of monocyte dysfunction?

The process of T-cell activation in chronic hepatitis B virus (HBV) carriers has been investigated by measurement of membrane expression of lymphocyte-activation markers in response to a variety of mitogenic stimuli in order to delineate further the abnormality of T-cell-mediated immunity present in such patients. A substantial proportion of unstimulated T cells from the peripheral blood of patients but not controls expressed HLA-DR; in contrast the IL-2 and transferrin receptors were rarely expressed spontaneously in either group and there was no difference in spontaneous lymphocyte transformation. After stimulation with monocyte-dependent T-cell mitogens, phytohaemagglutinin (PHA) or anti-T3, patients had significantly reduced expression of the IL-2 and transferrin receptors and of HLA-DR in association with impaired lymphocyte transformations compared to controls. In contrast, lymphocyte activation was normal in response to the monocyte-independent T-cell mitogen phorbol-myristate-acetate (PMA). These data confirm that the process of T-cell activation is abnormal in chronic HBV carriers but suggest that the T cell is intrinsically normal. In allogeneic co-cultures, monocytes from patients inhibited the transformation of normal and patients' lymphocytes in response to PHA, suggesting that defects of T-cell-mediated immunity in chronic HBV carriers may be a consequence of monocyte dysfunction.

Antigens, Surface↗
PubMed1986

In vitro effects of lymphoblastoid interferon on lymphocyte activation and cell-mediated cytolysis in patients with chronic hepatitis B virus infection.

In addition to a direct anti-viral effect, interferons have important immunological properties including effects on cell-mediated immunity and antibody production as well as cell-mediated cytolysis. In chronic hepatitis B virus infection the host immune system is important for the elimination of replicating virus and in addition to directly inhibiting hepatitis B virus replication, interferons may affect host immune responses. We investigated the effect of lymphoblastoid interferon in vitro on lymphocyte activation and cell-mediated cytolysis in patients with chronic hepatitis B virus infection. The proliferative response to the mitogen PHA was significantly impaired in patients compared to controls. In addition supernatants of cultured mononuclear cells from patients stimulated with PHA contained less interleukin-2 activity than controls while the proportion of stimulated mononuclear cells expressing the interleukin-2 receptor was also reduced in patients. Prior incubation with 10(3) U ml-1 lymphoblastoid interferon increased both interleukin-2 activity and interleukin-2 receptor expression in patients and controls, although in patients the response was less marked. In contrast the proliferative response was unaffected. Natural killer cell activity against K562 cells was similar in patients and controls which in both groups was significantly augmented by prior incubation with 10(3) U ml-1 lymphoblastoid interferon; the increase was inversely proportional to baseline activity. In contrast incubation of target or effector cells with interferon did not augment T-cell cytotoxicity against autologous hepatocytes. The effects of lymphoblastoid interferon in vitro, were modest, but subtle changes in immunological status in addition to a direct effect on viral replication may be relevant to eventual clearance of the hepatitis B virus.

Cytotoxicity, Immunologic↗
PubMed1986

Assessment of HBV replicative status by receptors for polymerized human albumin.

Receptors for polymerized human albumin (pHSA-r) are expressed on HBsAg in larger numbers during complete viral replication. We have evaluated the usefulness of pHSA-r as a marker of high-level infection by a comparison with serum HBeAg, liver HBcAg and serum HBV-DNA. One-hundred-and-fifty-seven patients with HBsAg positive chronic liver disease were tested for HBeAg and pHSA-r titre. In 73 of them liver HBcAg was tested by immunofluorescence, while in the remaining 84 serum HBV-DNA was determined. Seventy-three subjects were HBeAg positive, 20/73 were HBcAg positive, and 60/84 had circulating HBV-DNA. The best cut-off for pHSA-r was found at 1:204,800 (sensitivity of 67.6% and specificity of 95.7% in detecting viral replication). At this cut-off the concordance rate between pHSA-r and viral replication (as assessed by HBV-DNA or liver HBcAg) was 83%, a figure similar to that of HBeAg (88%). Three HBeAg negative subjects who were actually complete replicators were identified by the pHSA-r test.

Carrier State↗