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Biomedical subjects

G Lefranc

Publications and source records attributed to G Lefranc.

At least 37 records · Page 2Linked to original sources
PubMed1998

Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment.

Severe combined immunodeficiency (SCID) comprises a heterogenous group of disorders that are fatal unless treated by bone marrow transplantation (BMT). The most common form of SCID (T-B+ SCID) is due to mutations of either the common gamma chain (gammac) or of gammac-coupled JAK3 kinase. We report an unusual JAK3 defect in a female who was successfully treated > 20 years ago with a BMT using her HLA-identical father as the donor. Persistence of genetically and biochemically defective autologous B cells, associated with reconstitution of cellular and humoral immunity, suggests that integrity of the gammac-JAK3 signalling pathway is not strictly required for immunoglobulin production.

B-Lymphocytes↗
PubMed1998

[Genetic analysis of the South Altaian population of the Mendur-Sokkon village, Altai Republic].

This study was a continuation of complex research on the gene pool of indigenous Siberian populations conducted at the Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences. In the population of South Altaians from the Mendur-Sokkon village, Ust'-Kanskii raion, Altai Republic, polymorphism for the following genetic markers was studied: blood groups ABO, MNSs, Rhesus, Kell, Duffy, and P; erythrocyte acid phosphatase (AcP); phosphoglucomutase 1 (PGM1); haptoglobin (Hp); and transferrin (Tf). The genetic position of South Altaians relative to the populations of the European part of Russia, Siberia, and the Urals was estimated. It was demonstrated that the gene pool of the South Altaian population of Mendur-Sokkon possessed both Caucasoid and Mongoloid genetic characteristics, with the latter prevailing. Genetically, this population is most closely related to Mongols and Nentsis. The genetic distance between South and North Altaians was large; this agreed with earlier genetic data and confirmed anthropological and ethnographic evidence indicating that these two groups had different backgrounds and were at different stages of ethnogenesis.

Adolescent↗
PubMed1997

The IGHG3 gene shows a structural polymorphism characterized by different hinge lengths: sequence of a new 2-exon hinge gene.

Four of the five human IGHG genes (G1, GP, G2, and G4) display a hinge region consisting of a unique exon. In contrast, IGHG3 exhibits a different structure in which the hinge is constituted by four or, less frequently, three exons. We report here the nucleotide sequence of a new 2-exon hinge G3 gene found in a Mandenka individual from Eastern Senegal. A comparison of this sequence with that of 4-exon and 3-exon hinge G3 genes suggests that the 3-exon and 2-exon hinge forms arose independently by deletion events in a 4-exon hinge gene.

B-Lymphocytes↗
PubMed1997

Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins. In addition to the 16 mutations described previously, we report 19 novel mutations. These data indicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support the wide heterogeneity of molecular defects in this rare disease.

Adolescent↗
PubMed1996

DNA analysis of the immunoglobulin IGHG loci in a Mandenka population from eastern Senegal: correlation with Gm haplotypes and hypotheses for the evolution of the Ig CH region.

This study presents restriction fragment length polymorphism (RFLP) and serological analyses of the immunoglobulin CH loci in a sample of 100 individuals from a Senegalese Mandenka population. The RFLP variability is mostly the result of large DNA insertions or deletions in the non-coding flanking regions of the IGHG genes, and to variable number of tandem repeat-like patterns within their 5'-switch sequences. However, part of the IGHG3 polymorphism also corresponds to a variable number of exons coding for the flexible hinge segment of the IgG3 antibody (the 4-exon and 3-exon forms, and a newly described 2-exon form). This diversity presents relevant associations with Gm haplotypes, suggesting that molecular rearrangements of the G3 hinge are related to the evolution of the Gm polymorphism. Non-significant correlation coefficients are found between Gm haplotypes and A2m alleles in the Mandenka, indicating that these loci may have reached equilibrium through recombination. The effect of recombination on linkage disequilibrium is more generally revealed, across the Ig CH genomic region, by a significant decrease of D' values with increasing physical distances between the loci on the chromosome.

Alleles↗
PubMed1996

Salivary IgG subclasses in individuals with and without homozygous IGHG gene deletions.

In this study, the levels of salivary IgG1, IgG2, IgG3 and IgG4 from individuals with and without homozygous immunoglobulin heavy chain constant gene deletions were quantified by enzyme-linked immunosorbent assay (ELISA). To analyse the restriction of salivary IgG subclasses, we used unstimulated whole saliva and sera collected at the same time from individuals with homozygous gene deletions, two with G1 deletion, one with G4 deletion, six with both G2 and G4 deletions and from eight individuals without IGHG gene deletions and expressing all four IgG subclasses. The median values of salivary IgG from individuals with homozygous G1, or G4, or both G2 and G4 deletions, and from individuals expressing all four subclasses were 24.2 mg/l and 23.4 mg/l, respectively. The median values of serum IgG were 13.7 g/l and 15.9 g/l, respectively. Our results show that the salivary and serum IgG levels were both within the normal range in individuals with homozygous gene deletions of either G1, or G4, or both G2 and G4.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

First study of immunoglobulin and T cell receptor gene rearrangements in chronic and acute lymphoblastic leukemias from Tunisia.

We report the first characterization at the immunological and molecular level of 12 cases of chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) from Tunisia. Our results show biallelic IgH gene rearrangement in B-CLL (6/6). A high ratio of T-ALL (4/6) was observed in Tunisian ALL leukemias. One T-ALL expressed CD10 (common ALL) which has already been found in some other cases of T-ALL. We report the occurrence of T cell receptor (TCR) beta and/or gamma gene rearrangements in two precursor B-ALL patients who had normally rearranged Ig genes. In one precursor B-ALL case, multiple rearranged IgH and TCR gamma bands allowed the identification of three clones. Such an oligoclonal ALL is interesting since only rare biclonal TCR beta or gamma gene rearrangements have been described.

Blotting, Southern↗
PubMed1995

Isolation of T cell receptor gamma/delta chain constant genes from minke whale.

The polymerase chain reaction using oligonucleotides based on consensus sequences from other species allowed us to amplify minke whale (Balaenoptera acutorostrata) T cell receptor (TcR) gamma and delta constant genes. Two types of Cgamma clones were obtained which only differ by one mismatch. These minke whale Cgamma clones showed 83% nucleotide and 70% amino acid sequence similarity to the corresponding region of the human TRGC genes. The minke whale Cdelta sequences were all identical, and showed 86% nucleotide and 77.8% amino acid sequence similarity to the human TRDC gene. The whale Cgamma and Cdelta clones were used as probes for Southern blot analysis. The data confirmed that there is a unique Cdelta gene in minke whale. Two different Cgamma genes were detected, one of them also cross-hybridizing with a human Cgamma probe, suggesting that the Cgamma locus in minke whale consists of at least two different constant genes.

Amino Acid Sequence↗
PubMed1994

Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E).

In the human, the order of the immunoglobulin heavy chain constant region (Ig CH) genes is the following: 5'-M-D-G3-G1-EP1-A1-GP-G2-G4-E-A2-3'. Extensive multigene deletions have been described in the Ig CH locus, some of these encompassing up to 160 kb. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their being found: deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly (17 cases out of 18) in the Mediterranean area. So far, deletions I and II have been found in Tunisia, deletions III, IV and V in Italy, and deletion VI in Sweden. In this paper, we show that a Tunisian, T17, previously reported as being homozygous for a deletion of type IV, is, in fact, homozygous for a deletion that encompasses A1-GP-G2-G4-E. Therefore T17 is the first case of a deletion of type III reported in the Tunisian population. Molecular analysis demonstrates that the T17 deletion occurred between highly homologous regions located downstream of IGHEP1 and IGHE, respectively. In contrast to the EZZ deletion, the recombination occurred near or in the switch regions, since the homologous regions involved in the deletion extend over 4.5 kb of DNA and encompass the I alpha 1-S alpha 1 and I alpha 2-S alpha 2 regions, respectively.

Blotting, Southern↗
PubMed1993

Haplotypes of the human immunoglobulin lambda IGLV7S1 and IGLV1S1 genes defined by restriction-site polymorphism and insertion/deletion of a 6-kb DNA fragment.

Haplotypes were defined in the human immunoglobulin lambda locus by using three probes--V lambda VII, V lambda A, and V lambda I--hybridized to BamHI, KpnI, EcoRI, and HindIII digests. Four KpnI alleles were described. Two of them, 13 kb and 16 kb, detected with both the V lambda VII and V lambda A probes, were correlated with 4.6-kb and 10.5-kb KpnI fragments, respectively, which hybridize to the V lambda I probe. The two others (17 kb and 24 kb) were detected with the three probes V lambda VII, V lambda A, and V lambda I. Moreover, we show that two of those haplotypes may reflect an insertion of 6 kb between V lambda A and V lambda 1S1. Familial studies were performed to demonstrate the Mendelian inheritance. Our results demonstrate the absence of association between the C lambda alleles and V lambda haplotypes.

Antibody Diversity↗
PubMed1992

Ultrastructural and cytochemical analysis of Na+, K+, ATPase and H+, K+, ATPase in parietal cells of gastric mucosa in the rabbit.

Rabbit gastric secretion has the physiological peculiarity of being continuous and uninfluenced by food intake. In this respect, ultrastructural analysis of rabbit parietal cells has revealed morphofunctional features situated between states of rest and very active acid secretion. Our cytochemical study shows that Mg2+ ATPase and ADPase activities vary from cell to cell and can even be totally absent. These activities concern either microcanaliculi or laterobasal folds or both, but never tubulovesicles. Application of the technique of Mayahara to K+ pNPP, associated or not with inhibitors (ouabain, vanadate, N-ethyl-maleimide, sodium fluoride), enabled us to confirm the coexistence of H+, K+, ATPase and Na+, K+, ATPase activities in the rabbit and to determine that these activities concern basolateral folds, microcanaliculi, hyaloplasm and tubulovesicles. The global activity of K+, pNPPase varied considerably in intensity. The results of using inhibitors suggest that proton transport ceases completely in certain cells. The signs of functional alternation found in this study are in agreement with physiological data relative to this animal.

Animals↗
PubMed1991

Biological half-life of normal and truncated human IgG3 in scid mice.

The fractional catabolic rate of IgG in the body is regulated with precision in order to maintain appropriate serum concentrations. We have investigated the turnover rate of normal human IgG3, a newly identified, naturally occurring, truncated form of IgG3 and a human-mouse chimeric IgG3 antibody in an immunodeficient mouse strain, C.B-17 (SCID), lacking endogenous Ig. The half-life of non-truncated, normal serum IgG3 as well as the chimeric antibody was about 7 days, whereas truncated IgG3 had a shorter half-life of about 5 days. Due to the inherent immune defect, the SCID mouse could represent a versatile animal model for the determination of turnover rates, inasmuch as an immune response will not be mounted against foreign antigens.

Animals↗