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Biomedical subjects

C Chapuis-Cellier

Publications and source records attributed to C Chapuis-Cellier.

At least 19 recordsLinked to original sources

Oligo-monoclonal immunoglobulins frequently develop during concurrent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients after renal transplantation.

In the present study we report that the appearance of oligo-monoclonal immunoglobulins (oligoM-Igs) in the sera of transplanted individuals is concurrent with the detection of coincident active CMV infection and EBV replication. Eighty-four renal allograft patients were monitored with respect to CMV isolation, to CMV conventional serology and humoral response against the EBV trans-activator ZEBRA (an immediate-early antigen also called BZLF1). Titration of anti-ZEBRA antibodies (IgG and IgM) and amount of EBV DNA in serum were evaluated. Using the combination of four techniques (agarose gel electrophoresis, analytical isoelectric focusing, high resolution immunoelectrophoresis, immunofixation electrophoresis), oligoM-Igs were found in 25% of patients after allografting and significantly associated with rejection episodes (P < 0.001). Twenty out of 23 (86%) concurrent CMV/EBV infections were associated with serum oligoM-Igs (P < 0.001). One can thus reasonably assume that a sustained EBV replication following iatrogenic immunosuppression can promote the immunoglobulin heavy chain expression in EBV-infected B lymphocytes. The proliferation of immunoglobulin-secreting clones might occur after active CMV infection, through a transient over-immunosuppression or via immune subversion.

Antibodies, Viral↗

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

PURPOSE: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded. METHODS: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible. The other biologic variables studied were related to tumor burden (plasmacytosis, hemoglobin, serum levels of monoclonal immunoglobulin, albumin) or to kidney function (creatinine). beta 2-microglobulin (beta 2-M), C-RP, lactic dehydrogenase (LDH), and calcemia were also assessed. RESULTS: No correlation was found between LI and serum C-RP. LDH was the sole variable significantly correlated to C-RP (P < 0.01). Besides the biologic parameters used for the staging according to the Durie and Salmon classification, beta 2-M, albumin and LI were significantly different between stages (P < 0.0002, < 0.0004, < 0.00001). LDH and C-RP showed no significant difference. Results were similar when patients with and without bone lesions were analyzed separately. Multivariate analysis ranked these variables as follows with respect to prognostic value: beta 2-M, LI, and age. CONCLUSION: Among the variables analyzed, LI is the sole true reflector of cell proliferation. We confirm its diagnostic and prognostic value.

Adult↗

Tobacco smoking and other factors in relation to serum alpha-1-antitrypsin.

Serum levels of alpha-1-antitrypsin were measured by radial immunodiffusion, and phenotypes were determined by electrofocusing in acrylamide gel in 160 subjects who were used as controls in a case-control study of hepatocellular carcinoma (HCC). The results were studied in relation to age, sex, diagnostic category, tobacco smoking, consumption of alcoholic beverages, presence of hepatitis B surface antigen (HBsAg), and serum levels of alphafetoprotein (AFP) by modeling the data through multiple regression. There was no relation of serum alpha-1-antitrypsin values with sex, HBsAg, AFP, consumption of alcoholic beverages, and diagnostic category (p > 0.25). By contrast, there were statistically significant dose-dependent positive associations of serum alpha-1-antitrypsin with age and tobacco smoking (p < 0.01 in both instances). The positive association of serum alpha-1-antitrypsin with tobacco smoking and the previously reported excessive elevation of serum alpha-1-antitrypsin in hepatitis B-negative tobacco-related cases of HCC suggest that alpha-1-antitrypsin is intimately related to the pathogenetic process linking tobacco smoking to HCC.

Age Factors↗

Epstein-Barr virus associated lymphoproliferative diseases (B cell lymphoma) after transplantation.

We report 12 cases of lymphomas which occurred among 1670 patients with kidney or combined renal and pancreatic transplantation. Group 1 comprised nine patients presenting with the diffuse form of the disease where immunoblasts or mature plasma cells massively infiltrated all organs. The first symptom was a viral syndrome, associated with a restriction of heterogeneity of immunoglobulins; oligoclonal to monoclonal peaks of immunoglobulins appeared about 50 days after transplantation. All patients received antilymphocyte globulins (ALG), and seven were treated with cyclosporin. EBV infection could be demonstrated in almost all patients; three EBV lymphoblastoid cell lines were established, their HLA phenotype being the same as the recipient of the graft. All patients finally died with renal and hepatic failure. Group 2 comprises three patients who presented solid B cell tumours of tonsils, lungs, and spleen at onset, extending to liver, kidney graft, lymph nodes, and brain. All received cyclosporin; two patients were treated with ALG, and one with OKT3. Immunoglobulins were polyclonal, oligoclonal, or decreased. Cell surface immunoglobulins were monoclonal on two tumours. EBV-DNA was positive within two tumours. Two patients presented EBV and CMV primary infection. CD4+T lymphocytes subsets were diminished at onset, and increased after cessation of immunosuppressive therapy. One patient died because of brain involvement; the two others are alive, one with perfect graft function. Therapy consisted of stopping immunosuppressive treatment, Acyclovir, and in two patients of group 2, monoclonal antibodies to pan-B and EBV receptor antigens.

Acyclovir↗

Alpha 1-antitrypsin.

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Chromatography, Affinity↗

Oligoclonal "fingerprint" of CSF IgG in multiple sclerosis patients is not modified following intrathecal administration of natural beta-interferon.

The IgG pattern in CSF was studied in 11 patients with multiple sclerosis who exhibited an oligoclonal banding upon thin-layer polyacrylamide gel isoelectric focusing followed by silver stain of unconcentrated CSF. Each patient received beta-interferon intrathecally during a 2 month period. No modification was observed over a 6 month period. In addition, the oligoclonal pattern was remarkably unique for each individual representing a typical "fingerprint" which allowed the identification of any single CSF.

Electrophoresis, Polyacrylamide Gel↗

Alpha 1-antitrypsin levels and phenotypes and hepatitis B serology in liver cancer.

Serum levels of alpha 1-antitrypsin (alpha 1 AT) were measured by radial immunodiffusion and phenotypes were determined by electrofocusing in acrylamide gel in 39 patients with hepatocellular carcinoma (HCC) positive for serum hepatitis B surface antigen (HBsAg), 41 patients with HCC negative for serum HBsAg, and 160 age- and sex-matched hospital controls. There was no difference between the control series and either of the two HCC groups with respect to alpha 1 AT phenotype pattern; also, there was no evidence of association between HCC and either the M2 allele or any of the alpha 1 AT deficiency phenotypes. However, HCC cases negative for HBsAg had significantly higher serum alpha 1 AT values (mean 665 +/- 26 mg 100 ml-1) than HCC cases positive for HBsAg (mean 571 +/- 23 mg 100 ml-1), who in turn, had significantly higher alpha 1 AT values than hospital controls (mean 434 +/- 13 mg 100 ml-1). These results indicate that in Greece, as in other high HCC incidence countries, genetically determined alpha 1 AT deficiency is not aetiologically important; the increase of serum alpha 1 AT is an important correlate of HCC with possible aetiologic significance and diagnostic potential and HBsAg-positive HCC and HBsAg-negative HCC are manifest differently as well as being aetiologically distinct.

Aged↗

Interaction of group-specific component (vitamin D-binding protein) with immobilized Cibacron blue F3-GA.

Group-specific component (vitamin D-binding protein) was purified to homogeneity from human plasma by a three-step procedure involving pseudo-ligand affinity chromatography on immobilized Cibacron blue F3-GA followed by gel filtration and ion-exchange chromatography. Upon pseudo-ligand chromatography, Gc globulin was separated into two peaks. The first, which represented approx. 4% of the total Gc globulin, was eluted together with other alpha-globulins of similar Mr and/or pI, and the second (96% of Gc globulin) was clearly retarded. Collection of the latter provided a fraction 10-fold enriched in Gc globulin, with yields higher than 90%. Incubation of plasma with trace amounts of radioactively-labeled 25-OH vitamin D3 showed that the radioactivity coeluted with the first peak. In addition, after saturation with 25-OH vitamin D3, all the Gc globulin was eluted in the first peak. This indicates that the two peaks correspond to the holo and the apo forms of the protein, respectively, and suggests that either the interaction of the apo form with the Cibacron blue dye involves the binding site for vitamin D metabolites, or that the holo-protein undergoes a conformational change as a consequence of formation of the complex.

Carrier Proteins↗

Pi-Gm linkage: evidence for linkage in males but not in females and for an effect of the S allele of the Pi system.

Linkage between the Pi (alpha 1-antitrypsin) and Gm (immunoglobulin heavy chain) loci was studied in thirty-four families including forty-one informative parents and 142 children. In females, the results did not provide evidence for linkage (posterior probability of non-linkage 0.98). In contrast, in males, there was strong evidence for linkage (peak lod 3.9 at theta = 0.18, posterior probability of linkage 0.98). The two populations appeared to be significantly different (0.001 less than P less than 0.01) with respect to the heterogeneity criterion of Morton. In addition, the effect of the possession of the S allele (associated with significantly decreased serum alpha 1-antitrypsin levels) was studied in fifteen informative parents and fifty-three children of the same group. No evidence for or against linkage was found in females, but in males close linkage between Pi S and Gm was demonstrated (peak lod 7.7 at theta = 0.05, posterior probability of linkage 0.9999). These data indicate significant linkage between Pi and Gm in males but not females and close linkage between the Pi S and Gm markers in males.

Alleles↗

Preferential transmission of the Z deficient allele of alpha 1-antitrypsin.

The transmission of the Z deficient allele of alpha 1-antitrypsin was studied in 23 families, each with a single parent heterozygous for this allele. When the mother carried the Z allele, the distribution of phenotypes in the children did not differ significantly from the expected frequency. In contrast, when the father was the carrier, a significant increase of heterozygous phenotypes was observed in the children. This observation suggests that a selective advantage is associated with the expression of the Z allele in male gametes.

Alleles↗

Genetic polymorphism of serum alpha-1-protease inhibitor (alpha-1-antitrypsin): Pi i, a deficient allele of the Pi system.

The microheterogeneity of the I allele of the Pi system of APi (alpha-1-antitrypsin) was studied in 43 individuals with the new PAGIF technique. The unique aspect of the I allele product (unequal distribution of bands 4 and 6), previously demonstrated with acid-starch gel, was confirmed. In addition, two subtypes of the Pi I allele--I1 and I2--were clearly distinguished. Serum concentrations of APi associated with the expression of the I allele were significantly decreased (68% of normal values) and thus very similar to those associated with the expression of the S allele. This indicates that the I allele can be considered as a "deficient" allele of the Pi system.

Alleles↗

Alpha-1-antitrypsin phenotypes in Lyon, France.

Alpha-1-antitrypsin Pi phenotyping was performed by thin-layer isoelectric focusing on samples from 1653 healthy white blood donors. The variants were confirmed by the acid-starch gel technique and crossed immunoelectrophoresis, with complete agreement between the two methods. The allele frequencies in this population were PiM, 0.9019; PiS, 0.0713;PiZ,0.0142; PiI, 0.0036; PiF, 0.0036; PiV, 0.0024. In addition, some rare phenotypes (MX, IS, LM) were noted. No difference was noted in the distribution of the variant alleles between males and females. The significance of the high frequency of the S allele is related to the ethnic origin of this population. The agreement of the results obtained by our technique and by acid-starch gel electrophoresis confirms the validity of Pi determination by thin-layer isoelectric focusing.

Adolescent↗