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Biomedical subjects

L Musset

Publications and source records attributed to L Musset.

At least 55 records · Page 3Linked to original sources

Cryoglobulinemia in chronic liver diseases: role of hepatitis C virus and liver damage.

BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with liver diseases. The respective role of hepatitis C virus (HCV) and liver damage in the pathogenesis of cryoglobulinemia is investigated in this study. METHODS: The prevalence of cryoglobulinemia in 226 consecutive patients with chronic liver diseases (hepatitis C, 127; hepatitis B, 40; other diseases, 59) was studied, and the epidemiological, biological, histological, and virological features in these three groups were analyzed. Anti-HCV antibodies, HCV proteins, and HCV RNA were searched in the cryoprecipitates. RESULTS: The prevalence of mixed cryoglobulinemia was high (41.5%) in patients with liver diseases and higher in patients with hepatitis C (54.3%) than in patients with hepatitis B (15%) or other causes of liver disease (32%). Patients with cryoglobulinemia had cirrhosis more frequently and had a longer history of hepatitis. In patients with hepatitis C, HCV RNA sequences and HCV proteins were detected in the cryoprecipitate. Cryoglobulins became undetectable in 21 of 43 patients treated with interferon. CONCLUSIONS: These findings suggest that HCV is a major cause of cryoglobulinemia. Besides viral infection itself, multiple factors appear to be responsible for the production of cryoglobulins, including cirrhosis and duration of liver disease.

Adult↗

Electrophoretic study of the physico-chemical characteristics of Bence-Jones proteinuria and its association with kidney damage.

AIM: To identify a physico-chemical criterion, or set of criteria, explaining and possibly predicting the nephrotoxic behaviour of Bence-Jones proteins (BJP). METHODS: The electrophoretic mobility and isoelectric point (pI) of 92 BJP isolates were determined using various electrophoresis procedures on polyacrylamide gel. The proportions of monomers and dimers were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) in 58 cases. PAGE data for 10 BJP isolates were used to construct Ferguson plots and titration curves. RESULTS: The distribution of electrophoretic mobility and pI values was bimodal and showed a positive correlation when the pI was above 6. The values of these two parameters in 22 patients with renal impairment were not significantly different from those in the patients without renal impairment, and the statistical analysis showed no predictive value for the onset of renal impairment. However, patients excreting the lambda light chain isotype had a 2.8-fold higher risk of developing renal impairment compared with the other patients. Studies of the charge variation of the protein with pH indicated three types of behaviour, suggesting that the charge of BJP is highly variable at physiological pH. CONCLUSION: It is important to study not only the positivity or negativity of the BJP charge at a given pH, but also its intensity. The study of the BJP titration curves in patients with renal impairment suggests that a low charge at physiological urinary pH could predict renal impairment.

Aged↗

[Multicenter study of commercial kits for the determination of human IgG subclasses, using the ELISA technique].

We evaluated two commercially available sandwich type Elisa procedures for the measurement of IgG subclasses in human serum. Assay kits from The Binding Site and the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service were tested in six laboratories. The performance of spectrophotometers, pipettes and dilutors were assessed at each center. Within-run precision was estimated according to the Valtec method (Société Française de Biologie Clinique). The overall coefficient of variation ranged from 4 to 50% depending on subclass and kit. We also evaluated the IgG2 and IgG4 specificity using four sera containing a monoclonal IgG2 or IgG4 (kappa or lambda type). Using total IgG and immunoelectrophoresis as a comparative technique, IgG2 kappa and IgG4 kappa were both underestimated, IgG2 lambda was overestimated while IgG4 lambda compared favorably. Polyclonal IgG subclasses were frequently overestimated in these sera suggesting cross-reactions with either monoclonal IgG or other polyclonal IgG. Antigen excess was investigated and not encountered with either kit. Our results demonstrate that these procedures are insufficiently accurate or precise for routine clinical use.

Enzyme-Linked Immunosorbent Assay↗

[Western blotting analysis of cryoglobulins associated with chronic hepatitis C].

In a prospective study, a monoclonal component was found in 29/89 (33%) of mixed cryoglobulinemia (MC) associated with hepatitis C virus (HCV) infection, with a IgM in 87% of cases and a Kappa/Lambda ratio at 1.8. HCV RNA anti-HCV antibodies were demonstrated in both MC with and without monoclonal component.

Blotting, Western↗

Hepatitis C virus and essential mixed cryoglobulinaemia.

Clinical and laboratory evidence of liver involvement are frequently found in essential mixed cryoglobulinaemia (EMC). We looked for evidence of hepatitis C virus (HCV) infection in 37 patients with EMC. Anti-HCV antibodies (Ab) were found in 16/37 (43%) patients with EMC using the ELISA 2 test and the RIBA 2 test. The 16 anti-HCV-Ab positive patients (group 1) were compared to the 21 anti-HCV-Ab negative patients (group 2). Group 1 patients had more frequent cutaneous involvement (P = 0.02), clinical, biological and histologic hepatic involvement (P < 0.01), higher serum cryoglobulin and lower CH50 levels (P < 0.001). Serum hepatitis B virus markers were infrequent in both groups and no patient from either group had detectable serum HBV DNA. These preliminary results suggest that HCV may be another cause of mixed cryoglobulinaemia.

Adult↗

Time-resolved immunofluorometric assay of complement C3: application to cerebrospinal fluid.

Complement components have a role in various neurological disorders. Complement C3 can be measured by immunochemical methods, but only radioimmunoassays and electroimmunodiffusion assays (EIDs) are sufficiently sensitive to be applied to biological fluids in which the C3 concentration is low, especially cerebrospinal fluid (CSF). We report a sandwich-type time-resolved immunofluorometric assay (TR-IFMA) for C3 in CSF. The linearity (0.7-3650 micrograms/L) and intra- (CV < 4.8%) and inter-assay (CV < 10.9%) precision were satisfactory and the results agreed with those of EID. The assay is extremely sensitive (< 1 microgram/L) and its analytical range is large and well suited to clinical applications. This simple TR-IFMA is thus a nonisotopic alternative to radioimmunoassay for the quantification of complement C3 in CSF.

Adult↗

Isotypic and allotypic analysis with monoclonal antibodies and jacalin of 309 serum monoclonal IgA from French and Japanese myeloma patients.

The subclass and allotype distribution of serum monoclonal IgA from myeloma patients was determined by ELISA with monoclonal antibodies in two French and one Japanese laboratory. In addition, the French sera were tested for their reactivity with the lectin jacalin. No significant difference in the isotypic distribution between French and Japanese series could be demonstrated: kappa/lambda ratios were 0.99 and 1.17, and the IgA1 subclass accounted for 93.9% and 91% of cases in the French and Japanese studies, respectively. Five out of 7 myeloma IgA2 from Japan and only one of the 12 IgA2 from France belonged to the A2m(2) allotype (P less than 0.01). All 219 IgA1 tested reacted with jacalin by immunoelectrophoresis (IEP), although with variable intensities. Among IgA2 proteins, only one (of the A2m(1) allotype) yielded a precipitating line with jacalin by IEP. Molecular analysis demonstrated that this protein was an IgA1-IgA2 hybrid bearing most of the A2m(1) epitopes.

Antibodies, Monoclonal↗

Characterization of cryoglobulins by immunoblotting.

We adapted an immunoblotting technique for the immunochemical characterization of cryoglobulins. We first compared the results from 157 samples with results obtained by immunofixation and immunoelectrophoresis and then with clinical observations in 125 cases. Full identification was possible in 98% of the cases by immunoblotting, in 54% by immunofixation, and in 28% by immunoelectrophoresis. Novel microheterogeneity aspects were observed by immunoblotting and immunofixation in 13% and 6% of the cases studied, respectively. Our results confirm the frequency of autoimmune and infectious diseases associated with mixed cryoglobulinemias, whereas a lymphoproliferative syndrome was observed only in cases of cryoglobulinemia with a monoclonal constituent or a microheterogeneity aspect, which was not always revealed by immunofixation or immunoelectrophoresis. The pathophysiological importance and classification of microheterogeneity aspects is not clear. These observations justify using a sensitive and specific method for identifying cryoglobulins, even when present at low concentrations, and call for long-term studies of these patients.

Autoimmune Diseases↗

Renal effects of S10036 in man.

The renal hemodynamic and tubular effects of S10036 (fotemustine) were evaluated in seven patients with advanced malignancy. Initial evaluation carried out prior to treatment and repeated 1 day after the first fotemustine infusion and 7 days after the second included clinical, haematological parameters, liver-function tests, and determination of the glomerular filtration rate, renal blood flow and enzymuria. The glomerular filtration rate was 108 +/- 3.7 ml/min before treatment and remained stable after the first (117 +/- 5 ml/min) and second (124 +/- 6 ml/min) fotemustine infusions. Renal blood flow and urinary beta 2-microglobulin and N'-acetylglucosaminidase excretion were also not modified by fotemustine administration. We conclude that fotemustine does not acutely alter renal haemodynamics, nor does it have direct tubular toxicity.

Acetylglucosaminidase↗

[Contribution of immunoenzymatic technics to the assay of anti-native DNA antibodies in the biological diagnosis of lupus erythematosus disseminatus].

Anti native DNA antibodies (anti nDNA Ab), which are a highly specific feature of systemic lupus erythematosus (SLE) were measured by 3 methods: an enzyme linked immunosorbent assay (ELISA), an indirect immunofluorescence test on Crithidia luciliae (IFCL) and the Farr assay (reference test). 114 sera from patients with SLE or another connective tissue disease or without autoimmune rheumatic disease were tested. This study showed that ELISA seemed to be a more sensitive and specific test than IFCL (classical test). ELISA was also as sensitive as the Farr assay. ELISA should replace IFCL for the diagnosis and the follow up of patients with SLE. In other connective tissue diseases, ELISA might give more positive results. Thus these had to be confirmed, especially in the case of low antibodies levels, by using another method (e.g., the Farr assay).

Antibodies, Antinuclear↗

The effects of diltiazem on methotrexate-induced nephrotoxicity.

We have tested the effects of calcium channel blockade with diltiazem on methotrexate-induced nephrotoxicity in patients with biopsy-proven malignant disease. The patients were randomized in a cross-over fashion to receive MTX (4 g.m-2 body surface area) with or without Diltiazem (360 mg per day orally) during two consecutive periods separated by a 3-week interval. Methotrexate caused reversible acute renal failure, with an increase in serum creatinine from 89 (7)mumol.l-1 on day 0 to 150 (6)mumol.l-1 on Day 6. The patterns of beta 2-microglobulin and N-acetyl glucosaminidase urinary excretion were similar, with a sharp increase from Day 0 to Day 3. Urinary beta 2-microglobulin excretion increased from 161 (57) micrograms.l-1 on Day 0 to 1160 (840) micrograms.l-1 on Day 3 and fell to 918 (530) micrograms.l-1 on Day 10. Urinary N-acetyl glucosaminidase excretion increased from 250 (100) mmol.h-1 per mg of creatinine on Day 0 up to 655 (261) on Day 3 and fell to 285 (82) on Day 10. The evolution of renal function was not influenced by diltiazem. In patients receiving diltiazem, serum creatinine increased from 93 (0) mumol.l-1 on Day 0 to 151 (68) mumol.l-1 on Day 6 (p = NS when compared with control values). Urinary enzyme excretion also markedly increased from Day 0 to Day 3 to the same extent as in the group not receiving diltiazem. Our data indicate that acute deterioration in renal function caused by methotrexate is accompanied by tubular damage. Diltiazem was ineffective in preventing the acute renal failure induced by methotrexate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

[Analysis of nine autoantibodies associated with systemic autoimmune diseases using the Luminex technology. Results of a multicenter study].

UNLABELLED: Luminex technology allows simultaneous detection of several analytes in a single well. Applications have been recently developed for the detection of autoantibodies. PURPOSE: To evaluate the performances and convenience of the Fidis analytical system (BioMedical Diagnostics, Marnes-la-Vallee, France) for the detection of nine autoantibodies associated with connective diseases: SS-A, SS-B, Sm, RNP, Scl-70, Jo-1, CENP-B, P ribosomal and double stranded DNA antibodies. MATERIALS AND METHODS: Three hospital laboratories analysed 366 samples taken from their serum banks and corresponding to the main systemic autoimmune diseases. Control samples included 120 sera from blood donors and 42 sera from patients with dysglobulinemia. RESULTS: In each laboratory, handling of this new analytical system was easy. Results are readily obtained: nine autoantibodies are quantitated in fourty-four sera in less than two hours. A clear-cut discrimination between negative and positive results was observed, due to very low backgrounds. Intra-assay and inter-assay variations were low: coefficients of variation were under 10% in 80 and 64% of the cases, respectively. Results obtained with Fidis correlated satisfactorily with those obtained with the numerous routine techniques used in each laboratory. The overall concordance exceeded 93%. CONCLUSION: Fidis is a reliable and time-saving analytical system for the detection of autoantibodies associated with systemic autoimmune diseases.

Autoantibodies↗

Hepatitis C virus infection and cryoglobulinaemia.

Mixed cryoglobulins (CG) are serum proteins that precipitate at low temperature and are commonly classified into two types according to the presence (type II) or not (type III) of monoclonal immunoglobulins. Mixed CG are observed in a wide variety of diseases. Some mixed cryoglobulinaemia occurs without evidence of an underlying disease and is considered as essential mixed cryoglobulinaemia (EMC). Many studies have underlined the possible involvement of liver diseases in the pathogenesis of cryoglobulinaemia and particularly viral hepatitis. Recently, it has been shown that 50 to 80% of patients with EMC are in fact infected with HCV. It has also been shown that CG may be found in about 50% of patients infected with HCV. HCV-RNA genomic sequences are specifically concentrated in CG as well as IgG reactive with HCV-related proteins, and monoclonal IgM with rheumatoid factor (RF) activity. The monoclonal IgM RF detected in HCV infected patients is highly restricted to the same cross-idiotype OWAO. In addition to hepatocytes, HCV-RNA has been found in both peripheral blood and BM mononuclear cells. These cells could represent a reservoir of virus and may play a major role in viral persistence; they also could act as effectors of tissue injury in various organs. HCV shows high genomic variability. It is not clear whether these genetic variations have a significant clinical impact (i.e. severity of the disease) but there is evidence that they may influence both the efficacy of the host immune response and the interferon treatment response. The role of viral factors has been studied but a clear relationship between the presence of cryoglobulinaemia, the viral load or the HCV genotype have not been demonstrated. The frequency of clinical symptoms related to mixed cryoglobulinaemia reported in the literature is extremely variable according to the series. The striking association between HCV infection and mixed type II CG (usually considered as a benign lymphoproliferative disorder) and the occurrence of HCV infection in patients with NHL suggest that HCV could be involved in the pathogenesis of some malignant lymphoproliferative disease. The progression to malignancy probably involves the accumulation of multiple mutations facilitated by chronic antigenic stimulation. The efficacy of anti-viral treatment on both CG levels and related symptoms argue strongly that HCV is involved in the production of CG.

Antigens, Viral↗