PubMed Health⌕ Search

Biomedical subjects

N Ghanem

Publications and source records attributed to N Ghanem.

At least 73 records · Page 4Linked to original sources
PubMed1990

[Molecular genetics of 21-hydroxylase deficiency in congenital adrenal hyperplasia].

21-hydroxylase gene analysis was performed on the genomic DNA from patients with congenital adrenal hyperplasia (CAH), their siblings, their parents as well as from a healthy individual serving as control. After digestion by the Taq I and Bgl II restriction enzymes, DNA was hybridized with specific nucleotidic probes: pC21a for the 21-hydroxylase genes, pAT-A for the C4 component Complement genes, closely linked to the 21-hydroxylase genes on the 6 chromosome. Likewise the pFB3B probe was used for the B factor gene located 80 kilobases upstream the 21-hydroxylase gene. From this molecular analysis on 11 families, we report here 4 investigations showing the most frequent genetic abnormalities we have encountered: gene deletions, gene conversions and point mutations. These data show that the molecular approach is a powerful tool for studying this endocrine disease at the clinical, genetic and fundamental point of view.

Adrenal Hyperplasia, Congenital↗
PubMed1990

RFLP of human immunoglobulin genes.

Human immunoglobulin chains are encoded by variable, diversity, joining and constant gene segments localized on chromosomes 2, 22 (light chains) and 14 (heavy chains). An extensive genetic polymorphism exists as revealed by restriction fragment length polymorphism of the different genes. These new markers allow a more precise delineation of the evolution of the immune system and of genes linked to disease susceptibility.

Genes, Immunoglobulin↗
PubMed1990

CYP21B gene conversion and complete CYP21A gene deletion in congenital adrenal hyperplasia.

We studied a family in which one out of two children presented a non-salt wasting form of CAH. Genomic DNA of the patient, his brother, his parents and a normal control were digested by the Taq I and Bgl II restriction enzymes. The fragments were electrophoresed, transferred onto a nitrocellulose membrane and hybridized with two specific probes: pC21a for the CYP21 genes and pAT-A for the C4 genes. We performed simultaneous RFLP analyses of the CYP21 and C4 genes and determined the relative hybridization intensity of the genes using scanning densitometry of the X-ray films. The affected child had a CYP21B gene conversion in the CYP21A pseudogene on one chromosome inherited from his mother and a mutated CYP21B gene on the second chromosome inherited from his father. The second maternal chromosome, inherited by the unaffected brother, presented an unusual CYP21A gene deletion without a C4A or C4B gene deletion. Although CYP21A is a pseudogene, this type of complete CYP21A gene deletion associated with a CYP21B gene conversion has never been previously described.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Limiting dilution cloning of B cells from patients with multiple myeloma: emergence of non-malignant B-cell lines.

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of slowly proliferating malignant plasma cells in the bone marrow (BM). Several reports have shown the existence of an abnormal B-cell compartment including proliferative idiotypic B cells (i.e., B cells bearing the same idiotypic determinants as the myeloma protein) in the BM and peripheral blood (PB) of patients with MM. In order to study whether this abnormal compartment can be grown in vitro, we cultured the PB and BM of 23 patients with MM using limiting dilution methods. Our purpose was to restrict the effect of suppressor cells and the possible overgrowth of the cultures by the more rapidly growing B cells, which occurs in bulk cultures. Spontaneously growing cells were obtained only from patients seropositive for the Epstein-Barr virus (EBV) and all the cultures were composed of B cells carrying the EBV genome. Thus, positive cultures were generated only in the presence of B cells latently infected with EBV in vivo. The mean frequency of these B cells (1 in 25,000 B cells) was as low in MM patients as in healthy donors. This low frequency indicated that malignant cells do not bear the EBV genome in vivo and that the in vivo regulation of the EBV infection is unaffected in patients with MM. No Ig-gene rearrangements, specific of the autologous myeloma cells, were found in the cell lines obtained from BM or PB. Thus, the putative malignant B cells or myeloma cells were not able to generate cell lines in vitro, either spontaneously or after endogenous infection with EBV.

Antibodies, Viral↗
PubMed1989

BamHI and SacI RFLPs of the human immunoglobulin IGHG genes with reference to the Gm polymorphism in African people. Evidence for a major polymorphism.

In this paper, we extend the study of the IGHG gene RFLPs in black African persons and in some other individuals characterized by a Negroid admixture. We demonstrate a polymorphism that is much more important in black Africans, than in Caucasoids, mainly for the IGHG3 and G1 genes, the most 5' members of the IGHG multigene family. These genes encode for the IgG3 and IgG1 subclasses, which are of crucial biological importance.

Alleles↗
PubMed1989

Exon duplication and triplication in the human T-cell receptor gamma constant region genes and RFLP in French, Lebanese, Tunisian, and black African populations.

The human T-cell receptor gamma (TCRG) locus comprises 14 variable genes (TRGV), five joining segments (TRGJ), and two constant region genes (TRGC). The constant gamma 1 gene, TRGC1, consists of three exons, whereas the TRGC2 gene contains four or five exons due to the duplication or triplication of exon 2 and spans 9.5 kb or 12 kb, respectively. In this paper, we define the alleles of the T-cell receptor gamma J2 and C2 genes, and we show that two Hind III allelic fragments, 5.4 kb and 8 kb, characterize unambiguously the C2 gene with duplication or triplication of exon 2. We show also that the cDNA of the HPB-MLT cell line results from the transcription of an allelic TRGC2 gene with duplicated exon 2. We propose a model involving unequal crossing-overs to explain the organization and the evolution of the TRGC locus. Moreover, we analyze the TCRG haplotypes in four different populations (French, Lebanese, Tunisian, and Black African) to underline their interest for population genetics.

Alleles↗
PubMed1989

Deletion, insertion, and restriction site polymorphism of the T-cell receptor gamma variable locus in French, Lebanese, Tunisian, and black African populations.

The human T-cell receptor gamma region spans 160 kb of genomic DNA and is densely populated by coding sequences. Restriction fragment length polymorphisms have been previously documented for the constant region genes, the joining segments, and the variable genes belonging to subgroups I and IV. Here we further define the polymorphism of the V gamma I subgroup genes. based on complete mapping of the Eco RI and Taq I allelic restriction fragments. We describe seven haplotypes; five result from polymorphic restriction sites, the sixth corresponds to a deletion of about 10 kb encompassing V4 and V5, and the seventh results from an insertion of an additional gene, V3P, between V3 and V4. As a consequence of the deletion or insertion polymorphism, the number of V gamma I subgroup genes vary from seven in haplotype TRGVI*3 to ten in haplotype TRGVI*4, whereas the most common haplotype, TRGVI*1, has nine V genes, five of them being functional. Frequencies of the different TRGVI haplotypes in French, Lebanese, Tunisian, and Black African populations are given.

Black People↗
PubMed1989

No detectable malignant B cells in the peripheral blood of patients with multiple myeloma.

Previous studies have reported the presence of idiotypic B lymphocytes in the peripheral blood of patients with multiple myeloma (MM), suggesting that they may belong to the malignant clone. This led us to investigate by Southern blot analyses the presence of tumour-specific immunoglobulin-gene (Ig-gene) rearrangements in the peripheral-blood mononuclear cells of 21 MM patients. This method was shown to detect clonal cells when they represent as little as 2% of the cell population. B-cell-enriched fractions were also studied in nine cases. An occasional contamination by circulating malignant plasma cells was carefully evaluated using immunofluorescence. Clonal rearrangements were observed in only two cases, in which a contamination by myeloma cells was evident. In these cases the use of different endonucleases clearly demonstrated that these Ig-clonal rearrangements involved post-switched cells. No clonal rearrangement was found when contamination by myeloma cells was absent. Our results demonstrate the absence of detectable B cells involved in the myeloma clone in the peripheral blood of patients with MM.

Aged↗
PubMed1989

[Type I and II heart block].

Second degree blocks are divided into type I blocks, with an increment in conduction time for two consecutive conducted impulses, and type II blocks which present with constant conduction times for consecutive conducted impulses. This distinction is not only of theoretical interest but also of practical interest, since type I blocks located in the node are benign as a rule, whereas type I blocks in other locations and type II blocks are of poor natural prognosis and require pacing. Major increments of the PR interval, occurrence at night and young age are in favour of type I blocks. 2/1 blocks without 2 consecutive impulses sometimes raise difficult problems. Carotid massage and change from supine to upright posture may display two consecutive conducted P waves. If this does not happen, Holter recordings will show, in almost every case, two consecutive waves which enable the block to be typed. Whenever a doubt persists, electrophysiological exploration makes it possible to determine the exact location of the block. Type I blocks imply the presence of a decremental conduction and therefore of varying conduction velocities which decrease with consecutive impulses. This is compatible with the normal functioning of the atrioventricular node which has calcium-dependent potentials, b ut everywhere else it implies a pathological state of tissues that have sodium-dependent potentials and give an all-or-nothing response. This explains why extranodal type I blocks, like types II blocks, make it necessary to fit the patients with a pacemaker, whereas type I blocks usually are of good prognosis.

Electrocardiography↗
PubMed1989

BstEII restriction fragment alleles and haplotypes of the human IGHG genes with reference to the BamHI/SacI RFLPs and to the Gm polymorphism.

In previous studies, we have described, for each of the five human immunoglobulin IGHG (C gamma) genes, BamHI, SacI and BamHI/SacI allelic restriction fragments. Further, we have determined BS (BamHI/SacI) linkage groups of alleles for the whole of the IGHG loci and we have demonstrated correlation with the Gm alleles and haplotypes. In this paper we characterize more precisely the polymorphism of the IGHG genes and, consequently, the structure and evolution of this multigene family, using the restriction enzyme BstEII and two different probes, a IGHG (C gamma) probe and a G3 (C gamma 3) specific probe. Alleles and haplotypes of the BstEII restriction fragments have been defined with reference to the BS alleles and haplotypes. New RFLPs of the IGHG genes are described and unambiguous correlations have been established with most of the Gm alleles and haplotypes. Thus, the IGHG gene RFLPs strengthen the Gm polymorphisms as powerful tools for the characterization of populations, disease and genetic marker linkage analyses, forensic medicine and evolution of these IGHG genes.

Alleles↗
PubMed1989

No influence of conversions affecting allotype expression on the IgG subclass restriction of specific antibodies.

Antibodies against any given antigen are usually restricted to a particular class or subclass, a finding which has been suggested to be due to a preferential association between particular VH and CH genes. The DNA sequences regulating this process are as yet entirely unknown. It is likely however that some of these regulatory sequences are located within or in the immediate vicinity of the immunoglobulin genes themselves. We therefore analyzed the IgG subclass pattern of specific antibodies in sera from individuals displaying mutations, duplications, deletions or gene conversions event (replacing parts of the constant region genes of one subclass with that of another) affecting the allotype expression of immunoglobulin heavy chain constant region genes. Marked influences on antibody levels were noted in sera from individuals displaying duplication or deletions of constant region genes. However, in no case of gene conversion or mutation was there any measurable influence on the antibody pattern, clearly suggesting a lack of VH gene regulation by sequences within and possibly also immediately downstream of the constant region genes.

Antibody Specificity↗