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M Alizadeh

Publications and source records attributed to M Alizadeh.

26 records · Page 2Linked to original sources
PubMed1995

TAP2 gene polymorphism contributes to genetic susceptibility to multiple sclerosis.

MS is an autoimmune demyelinating disease that has been known to be associated with the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype. TAP1 and TAP2, two genes encoded within the MHC class II region between HLA-DP and -DQ loci, display genetic variability and are involved in the transport of antigenic peptides from the cytoplasm to the endoplasmic reticulum. Comparison of 116 MS patients with Caucasoid controls did not reveal any significant correlation between the previously described alleles of the TAP1 and TAP2 genes and MS. We report here an additional TAP2 dimorphism at codon 386, called I and J, corresponding to a silent mutation. An increased frequency of the J variant was observed in the patient population. The J mutation was not found in linkage disequilibrium with the HLA-DRB1*1501 allele and can be considered an additional genetic susceptibility marker of the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

HLA-E is the only class I gene that escapes CpG methylation and is transcriptionally active in the trophoblast-derived human cell line JAR.

Polymorphic as well as HLA-F and -G genes are repressed in the human cell line JAR, derived from a tumor of trophoblast origin. By contrast, the HLA-E gene as well as the non-HLA novel coding-sequence, R1, located 5' to HLA-E, both remain transcriptionally active. We first demonstrated the role of DNA methylation in the repression of class I genes (except HLA-E) in JAR by the use of the 5-Azacytidine demethylating agent. Following treatment, JAR clones reexpressed polymorphic class I transcripts and cell surface alpha chains. Using methylation-sensitive rare cutter enzymes on JAR genomic DNA, followed by classical or pulse field gel electrophoresis and hybridization with HLA locus-specific probes, we found methylated CpG islands in the 5' region of all class I genes, except for HLA-E. These results, establishing an inverse relationship between states of methylation and transcriptional activity within the MHC class I chromosomal region in JAR, and the observations that the HLA-E and R1 genes were ubiquitously expressed, suggest that the HLA-E chromosomal domain might have functional importance including the presence of housekeeping genes.

Azacitidine↗
PubMed1993

Evidence for a polymorphism of HLA-G gene.

HLA-G gene polymorphism was analyzed by RFLP using seven restriction enzymes and an HLA-G locus-specific probe. Hybridization of 55 DNAs digested with three enzymes (Taq I, Pst I, and Bgl II) revealed two polymorphic bands in each case. RFLP patterns obtained with Taq I and Pst I corresponded to the same allelic polymorphism and differed from the Bgl II polymorphism. Combining both polymorphisms enabled determination of four alleles. Allelic frequencies were calculated: 40% of the subjects tested had allele 1, 36% had allele 2, 22% had allele 3, and 2% had allele 4. Analyzing the complete HLA class I phenotype revealed strong linkage disequilibrium with the HLA-A locus. The polymorphism described is located in the 3' flanking region of the gene. Moreover, extended HLA-A haplotypes were constructed by combining the HLA-G polymorphism with other class-I-sequence polymorphisms.

Base Sequence↗
PubMed1985

Mechanism for the reductive activation of diaziquone.

In order to understand the redox properties of diaziquone (AZQ) and the reductive alkylation role of its one-electron reduced free radical anion AZQ- in biological systems, we investigated the electrochemical and structural properties of AZQ and its reduced species by cyclic voltammetry, controlled potential electrolysis, optical absorbance spectroscopy and 1H NMR. This study was carried out in aqueous media as well as in Me2SO. In aqueous media AZQ can be reduced by 2 electrons to the dianion AZQ2- which is oxidized back to AZQ- and AZQ. In Me2SO, 1 - e- reduction or oxidation steps are possible. This allowed the characterization of AZQ and its 1 or 2 - e- reduced species by UV-visible absorbance spectroscopy. The redox properties of the aziridine rings were observed by cycle voltammetry. Using 1H NMR, it was possible to follow the structural dependence of AZQ on the nature of the medium. Protonation of the aziridine rings at low pH may facilitate the opening of the ring leading to the carbonium ion, the required species for alkylation. Cyclic voltammetry data indicate that reduction of the quinone facilitates the aziridine ring opening.

Antineoplastic Agents↗
PubMedDate not supplied

Quantitation of chemokines (MDC, TARC) expression in mucosa from Crohn's disease and ulcerative colitis.

Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.

Adolescent↗
PubMedDate not supplied

DRB1*15 and DRB1*03 extended haplotype interaction in primary Sjögren's syndrome genetic susceptibility.

OBJECTIVE: Sjögren's syndrome (SS) is a chronic autoimmune disease with a genetic component. Among the genetic factors, the role of HLA class II genes has been suggested and a positive association with DRB1*03 allele has been described. However, there is no consensus on a unique HLA locus for this disease nor on the role of the HLA gene product in the disease. The aim of this study was to analyse prospectively MHC region involvement in the genetic susceptibility to SS by studying DRB1, DQB1, DPB1, TAP1, TAP2 genes and TNF microsatellites in a population of 45 primary SS patients. METHODS: All the polymorphisms studied were analysed at the genomic level using PCR-based methodologies. RESULTS: Concerning HLA class II alleles, the highest relative risk to develop the disease was associated with the DRB1*15-DRB1*0301 heterozygous genotype (17.8% vs 3.5% in controls - pc < 0.005, OR = 5.96). Analysing other genes located on the same region allowed us to further determine the DRB1 haplotypes at risk. For instance, the DRB1*0301 haplotype involved in the genetic susceptibility to SS was more often associated with the DPB1* 0201 and TNF-a2 alleles in SS patients than in controls. Moreover, all the DRB1*15-DRB1*0301 SS patients were TAP1-0101, TAP2-0101 homozygous, allowing us to deduce the extended genotype at risk as DRB1*15, TAP1-0101, TAP2-0101/DRB1*0301, TAP1-0101, TAP2-0101 which was carried by only 3 controls out of the 130 tested (p < 0.01, OR = 6.68). CONCLUSION: This study confirmed the role of the MHC region in the susceptibility to Sjögren's disease, and for the first time suggests a synergistic interaction between two HLA-DRB1 extended haplotypes in the genetic mechanisms controlling the disease.

ATP Binding Cassette Transporter, Subfamily B, Mem↗