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Biomedical subjects

G Blaison

Publications and source records attributed to G Blaison.

12 recordsLinked to original sources
PubMed2004

[Update of pernicious anemia. A retrospective study of 49 cases].

PURPOSE: The aim of this study was to describe the present clinical characteristics of the pernicious anemia (PA). METHOD: It is a retrospective (1996-2002) multicenter (five departments of internal medicine) study of 49 patients presenting an established cobalamin deficiency related to PA. RESULTS: The median age of the patients was 74 years (25-93), the female/male ratio 2:9. Several autoimmune disorders were noted in 35% of the patients. Various clinical manifestations, mainly neurological, cutaneous and thrombotic, were found in 65.4% of the patients, at least one hematological abnormalities in 100%. Average serum vitamin B12 and homocystein levels were with 73 pg/ml (20-1960) and 42.9 micromol/l (7, 8-124). Anti-intrinsic factor or anti-parietal gastric cells antibodies were found in 87.5% and 62% of the patients (at least one antibody, in 96%) abnormal Schilling's test results in 86%. All the followed patients were successful treated with intramuscular (n = 27) or oral crystalline cyanocobalamin (n = 5). CONCLUSIONS: PA was associated with several autoimmune disorders; PA may be responsible of various clinical manifestations or biological abnormalities; and oral crystalline cyanocobalamin treatment may be successful.

Adult↗
PubMed1999

[Left branch portal vein thrombosis associated with hyperhomocysteinemia].

A 34 year-old man, who was a smoker, was hospitalised because of severe epigastric and right upper quadrant pain. An isolated left branch portal vein thrombosis was diagnosed using ultrasonography and arteriography. Two thrombogenic pathologies were found: i) a latent myeloproliferative syndrome with spontaneous presence of erythroid colony forming unit (CFU-E) in bone marrow culture, normal blood cell count, platelet count and medullogram; ii) a hyperhomocysteinemia associated with low serum folate levels and a methyl tetrahydrofolate reductase mutation. The association of these two factors probably resulted in portal vein thrombosis. This is the first adult case of a portal vein thrombosis associated with hyperhomocysteinemia. Increased homocysteine serum levels could be a previously unrecognized factor for portal vein thrombosis. Homocysteinemia should be systematically investigated in patients with idiopathic portal vein thrombosis since folate supplements could prevent deleterious vascular effects of hyperhomocysteinemia.

Adult↗
PubMed1994

[Granulomatous mastitis, erythema nodosa and oligoarthritis. Apropos of a case].

The authors report a case of granulomatous mastitis associated with erythema nodosum and oligoarthritis. The skin and joint symptoms improved with potassium iodide. The breast lesion clinically simulated a tumor of high malignant grade. Granulomatous mastitis is a benign and rare disease. Its interest lies in the possible association with systemic manifestations and in its steroid responsiveness. This condition has been recently described as a distinct entity. When associated with systemic manifestations, sarcoidosis should be considered.

Adult↗
PubMed1994

Evidence that the V kappa III gene usage is nonstochastic in both adult and newborn peripheral B cells and that peripheral CD5+ adult B cells are oligoclonal.

There is evidence that in certain situations the expressed antibody repertoire is dominated by small subsets of V gene segments. They include fetal, CD5+, and autoantibody-forming B cells as well as low grade B cell malignancies. For instance, inside the V kappa III family of approximately 10 members, only 3 (humkv325, 328, and Vg) are used recurrently for autoantibody production. However, the significance of this recurrence is difficult to interpret without a clear vision of the actual repertoire in normal subjects. To address this, we have sequenced and compared two sets of rearranged V kappa III genes generated by cDNA PCR amplification from a normal newborn, a normal adult, and from CD5+ B cells of the same adult donor. The results show that: (a) only four V kappa III gene segments are used by neonatal and total adult B cells (humkv325, humkv328, Vg, and kv305), humkv325 being overexpressed in both repertoires; (b) there is no significant difference in terms of V kappa III gene usage between the adult and newborn repertoires; (c) regarding the junction regions, there is a favored use of the most 5' JK gene segments (Jk1-Jk2); approximately 20% of the newborn and adult junction sequences was characterized by one or two additional codons, most probably resulting from a nontemplate addition of nucleotides; (d) adult clones, in contrast to most newborn clones, show sequence divergences from prototype sequences with patterns which suggest antigen-driven diversity; (e) regarding the adult CD5+ B cell library, it is most probable that the 78 clones analyzed derived from no more than nine different VK-JK rearrangements. Humkv325 is used by at least six of them, and most of the expressed V genes were in exact or very near germline configuration. Collectively these results suggest that the expressed antibody V kappa III repertoire in the adult represents only a fraction of the potential genetic information and that it resembles the preimmune repertoire of the neonate. The data, which also suggest that the adult peripheral blood CD5+ B cell population may be dominated by a small number of B cell clones, are discussed with regards to the V kappa III usage in pathological situations.

Adult↗
PubMed1993

A minor group of rheumatoid factors isolated from a patient with rheumatoid arthritis is derived from somatically mutated Vk1 genes further evidence that rheumatoid factors during autoimmune diseases undergo an antigen driven maturation.

To better understand the structural basis for rheumatoid factor [RF] activity and the origin of autoantibodies in human autoimmune diseases, we isolated the RF producing B cells from the peripheral blood and from the synovial fluid of a patient suffering from rheumatoid arthritis [RA]. We previously demonstrated that a significant fraction of these RF were derived from three V kappa III genes known to encode most of the monoclonal RF light chain variable regions. To get more insight into the actual repertoire of RF-V kappa genes during RA, we analyzed the nucleotide sequences of RF light chain variable regions of other V kappa families. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from RF producing cells from the same patient KRA, we isolated only three different rearranged V kappa-J kappa complexes: slkv5, slkv7 and bkv42, all derived from V kappa I germ-line genes not previously known to be associated with RF activity; this suggests that the repertoire of VL genes coding for RF during RA is more diverse than the one involved in the generation of paraprotein RF during monoclonal lymphoid proliferations, although there remains a possible bias in favor of the V kappa III family. Moreover, each of these genes is somatically mutated with a pattern suggesting a selective pressure of the antigen. Particularly interesting is the additional proline residue at the V kappa-J kappa junction of bkv42, an unorthodox feature that we found previously in more than 50% of RF V kappa III-J kappa gene complexes. Finally, the homogeneity of some non conservative mutations suggests the existence of a restricted set of pathogenic epitopes driving the production of RF during RA.

Amino Acid Sequence↗
PubMed1992

Molecular analysis of the V kappa III-J kappa junctional diversity of polyclonal rheumatoid factors during rheumatoid arthritis frequently reveals N addition.

Much interest was stirred in recent years by the evidence that rheumatoid factors (RF) variable regions are encoded by a restricted set of V genes, with little or no somatic mutations, that are often overexpressed in the fetal repertoire. This is reminiscent of what has been observed for natural autoantibodies. However, these data come from studies of monoclonal RF (mRF) isolated from patients with lymphoproliferative disorders who usually do not present autoimmune symptoms. The molecular characterization of RF during autoimmune diseases such as rheumatoid arthritis (RA) has been hampered for some time because of their polyclonality; recently using the polymerase chain reaction method, we have demonstrated that RF kappa variable regions from a patient with RA were encoded by V kappa III genes known to code for mRF but that these genes had undergone somatic mutations with a pattern suggesting an antigen-driven maturation. Because an important role of the light chain third complementarity-determining region (CDR3) in anti-IgG reactivity and idiotype expression has already been suspected for RF, we now report the molecular characterization of the junction regions of these rearranged V kappa gens. Surprisingly, our data show that in 55% of the cases there is addition of a proline and/or glycine amino acid residue at the recombination site between V kappa and J kappa. The sequence analysis of our patients' germ-line Vg and J kappa 4 genes segments and their flanking regions demonstrates that the additional codons are not readily explicable by recombination between germ-line sequences and probably result from an N addition process. Since we could not find such an additional codon in 15 previously published mRF kappa chains we suggest that "pathogenic" RF during RA and mRF derive from different, although overlapping, B cell subsets. Moreover, since additional codons at the recombination site of V kappa and J kappa seem exceptional in expressed human kappa chains and because the resulting amino acid residue is a proline in most cases, we think that RF kappa chain CDR3 is under a very strong selective pressure during RA.

Amino Acid Sequence↗
PubMed1992

[Rheumatoid factors].

Rheumatoid factors (RF), which are auto-antibodies recognising the Fc fragment of IgGs, are the commonest auto-antibodies in man. They are present in polyclonal form in a large number of auto-immune disorders as well as in certain inflammatory states. In monoclonal form, they are frequently the product of "mature" malignant (chiefly Waldenström's macroglobulinemia and chronic lymphoid leukemia) and allegedly benign (such as cryoglobulinemias) lymphoid proliferations. In addition, RF account for a significant part of the normal antibody repertory, notably during the fetal and neonatal periods, suggesting that they may play an important role in the development and regulation of the immune system. As a result, RF are an excellent model for the analysis of auto-immunity in man. Thus many indirect (analysis of antigens recognised and of idiotopes carried) and, more recently, direct (protein or nucleotide sequencing of their various regions) studies have now provided the following conclusions. RF are coded by a very limited repertory of V genes. These genes are present in the normal genome and appear to be highly preserved in the human species. They are used with very few somatic mutations by monoclonal B proliferations (which opens up valuable therapeutic possibilities) as well as probably by RF producing B lymphocytes in normal individuals. In contrast, in the context of auto-immune disorders, these same genes have many somatic mutations suggesting maturation governed by the antigen and/or escape from idiotype control.

Autoimmune Diseases↗
PubMed1991

Molecular analysis of V kappa III variable regions of polyclonal rheumatoid factors during rheumatoid arthritis.

We report the first molecular characterization of V kappa regions of the main human autoantibodies occurring during rheumatoid arthritis, the polyclonal rheumatoid factors. Using two sets of polymerase chain reactions in order to amplify the cDNA derived from both peripheral blood and synovial fluid rheumatoid factor-secreting cells, nucleotide analysis of the V kappa III family usage shows the following: (a) at least three different V kappa III genes are used to encode polyclonal rheumatoid factors in a single patient, (b) each one of these genes seems more or less somatically mutated (from 1 to 14 mutations), (c) the mutation process preferentially affects the complementarity determining regions suggesting a selective pressure of antigen and (d) there is no clear difference between the mutation rates affecting the synovial fluid and peripheral blood rheumatoid factor-secreting cells. These results are able to explain some of the known idiotypic differences between monoclonal and polyclonal rheumatoid factors in humans. They also provide evidence that polyclonal autoantibodies arising during an autoimmune disease can be the products of multiple somatically mutated genes and suggest that this process is antigen driven, whether this antigen is the Fc piece of IgG or another unknown antigen.

Amino Acid Sequence↗
PubMedDate not supplied

[Rhabdomyolysis caused by simvastatinin a patient following heart transplantation and cyclosporine therapy].

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are cholesterol-lowering agents which may induce rhabdomyolysis. The authors present a case of rhabdomyolysis attributed to simvastatin in a heart-transplant recipient. They stress the probability of a dose-dependent muscular toxicity and the risk of overdosage in patients already under treatment with drugs that interfere with the pharmacokinetics of HMG-CoA reductase inhibitors, notably ciclosporine.

Anticholesteremic Agents↗