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C Gorodezky

Publications and source records attributed to C Gorodezky.

At least 37 records · Page 2Linked to original sources
PubMed1997

Development of PCR-SSOP for the identification of HLA-A*02 subtypes and determination of HLA-A*02 frequencies within different ethnic populations.

A PCR-SSOP typing method, involving a single PCR amplification in conjunction with 19 digoxigenin labelled oligonucleotide probes, has been developed for the identification of 17 known HLA-A*02 alleles. The method has been applied to four populations (Northern Ireland, Singapore Chinese, Shetland Island and Mexican) and percentages of HLA-A*02 alleles determined within each population.

Alleles↗
PubMed1997

Interactions of HLA-B*4801 with peptide and CD8.

Functional properties of the B*4801 allotype were investigated using HLA class I-deficient 221 cells transfected with B*4801 cDNA. From pool sequence analysis of endogenously bound peptides, B*4801 was shown to select for nonamer peptides having glutamine or lysine at position 2 and leucine at the carboxyl-terminus. In an in vitro cell-cell binding assay, B*4801 binds CD8 alpha homodimers weakly due to the presence of a threonine residue at position 245 in the alpha 3 domain. A mutant B*4801 molecule in which alanine replaces threonine 245, binds CD8 alpha homodimers at levels comparable to those of other HLA class I allotypes. Despite the low affinity of B*4801 for CD8 alpha, alloreactive T-cells that recognize B*4801 molecules expressed by the 221 transfectant are inhibited by anti-CD8 monoclonal antibodies. Analysis of 25 B*48-expressing individuals from various populations showed threonine 245 was encoded by every B*48 allele.

Alleles↗
PubMed1997

The LMP2 polymorphism is associated with susceptibility to acute anterior uveitis in HLA-B27 positive juvenile and adult Mexican subjects with ankylosing spondylitis.

INTRODUCTION: An association between polymorphism of the HLA linked LMP2 locus and the development of acute anterior uveitis (AAU) has previously been described in B27 positive white subjects with ankylosing spondylitis (AS). This study evaluated LMP2 alleles in two HLA-B27 positive Mexican populations of patients with spondyloarthropathy known to have a different clinical spectrum of disease from white people. PATIENTS AND METHODS: The study populations consisted of 90 AS patients from Guadalajara with predominantly adult onset disease and 80 AS patients from Mexico City with predominantly juvenile onset disease. LMP2-CfoI amplified fragment length polymorphisms were determined after polymerase chain reaction amplification and digestion with CfoI restriction enzyme. RESULTS: There was an increased LMP2A allelic frequency in patients who had had AAU in both Guadalajara (31.8%) and Mexico City (33.3%) when compared with non-AAU patients (15.2% and 17.7% of Guadalajara and Mexico City populations, respectively). The odds ratio relating LMP2A allelic frequency and AAU for the combined population, stratified by age at onset of disease, was 2.51 (p = 0.01). LMP2 alleles did not influence the age at onset of disease or the development of peripheral arthritis. CONCLUSIONS: These data support the view that polymorphism at the LMP2 locus is associated with the development of AAU in B27 positive subjects with AS. The requirement for both the less common LMP2 allele and HLA-B27 is consistent with the low prevalence of AAU in Mexican patients with spondyloarthritis.

Acute Disease↗
PubMed1997

HLA-DRB1*08 influences the development of disease in Mexican Mestizo with spondyloarthropathy.

OBJECTIVE: HLA class II encoded factors may influence the phenotype of ankylosing spondylitis (AS). These include HLA DRB1*07 for peripheral arthritis, and polymorphism of the HLA-linked LMP2 locus and HLA DRB1*08 for acute anterior uveitis (AAU). We studied the relationship between DRB1*08 and disease phenotype in additional populations of individuals with AS. METHODS: The patient population included 385 unrelated HLA-B27 positive individuals with AS. These included 204 Caucasians and 2 populations of Mexican Mestizo with AS: 106 with predominately adult onset disease from Guadalajara and 75 with predominately juvenile onset disease from Mexico City. The control population of 428 individuals included 210 random and 36 HLA-B27 positive unrelated Canadian Caucasians and 173 random and 9 HLA-B27 positive Mexican Mestizo from Mexico City. DRB1*08 typing was by sequence specific polymerase chain reaction. RESULTS: A significantly higher prevalence of DRB1*08 was observed in Mexican patients with juvenile onset disease (44.9%) and especially those with undifferentiated spondyloarthropathy (55.6%) compared to normal unrelated Mexican Mestizo (25.4%) (p < 0.01 for both) and in patients with undifferentiated spondyloarthropathy versus B27 controls (11.1%) (p = 0.03), although no significant differences were observed in within patient group comparisons based on phenotypic features of disease such as AAU and age at onset. No significant relationship between DRB1*08 and disease phenotype was evident in Caucasian individuals. CONCLUSION: Our data suggest DRB1*08 may influence the phenotype of spondyloarthritis in Mexican Mestizo, but do not support the view that DRB1*08 influences the development of AAU, as reported in a Japanese population.

Adolescent↗
PubMed1997

[Global and historical development of the IMETAF (International Molecular Epidemiology Task Force) in Mexico].

IMETAF or International Molecular Epidemiology Task Force was created upon the enthusiasm of Janice Dorman, molecular epidemiologist at Pittsburgh University. Also, she was in charge of the WHO type I Diabetes world project called DIAMOND. As a result of this project done with Mexican scientists. The Scientific Committee of IMETAF was formed on July 28, 1993. The activities began. A national infrastructure survey was done to analyze the epidemiology and molecular biology capabilities; a directory of scientist in epidemiology and molecular biology was elaborated; a theoric and practical course on molecular epidemiology was organized during 1996 and a second one will be held in 1997; and a series of Workshops were done: cancer and leukemias; bacterial diseases; trypanosomiosis and leishmaniosis and viral diseases. The results of these academic activities were brought to the National Academy of Medicine to a 2 days workshop and to an International Symposium called Projection of molecular epidemiology in medicine, held on April 17, 1996. The papers are published in this number. The goal of IMETAF will continue promoting transfer of technology, stimulating formal training in molecular epidemiology and helping getting funds for collaborative projects.

Child↗
PubMed1997

[National survey of the infrastructure of research centers in advanced biotechnology and molecular epidemiology in Mexico].

An International Molecular Epidemiology Task Force group (IMETAF) was established in 1993, where the Mexican group include as their objectives: the evaluation of the main public health problems that could be improvement through molecular epidemiology; the analysis of the interaction between molecular biology and epidemiology; development of international nets of collaboration and the establishment of surveys toward the prevention and control of some diseases. As part of a general strategy the Mexican scientific committee developed the first national infrastructure survey of the centers of biotechnology and molecular epidemiology. This survey obtained data trough a questionnaire of the general characteristics the development of the molecular epidemiology, the main tools of surveys, equipment, material and reagents, the personnel trained in biotechnology, epidemiology and public health, the needs of training, the national and international nets, how to develop molecular epidemiology and areas to be considered. The results give a general idea of the possibilities to develop the field in Mexico. More than 50% are currently working in this theme. The majority in infectious diseases. The centers have the equipment, material reagents and human resources well trained to incorporate the molecular epidemiology in their usual work. They reported the need of technology transfer to develop collaborations and courses, symposia or congresses. We conclude that Mexico has the capability and the infrastructure to develop molecular epidemiology. A survey is needed on animals.

Academies and Institutes↗
PubMed1997

[High- and low-risk molecular sequences in autoimmune diseases. An analysis of type I diabetes in Latin America].

Type I diabetes is an autoimmune and a polygenic disease, in which MHC-class II genes contribute to 48% of the disease. The aim of the present study, is to provide a guideline to understanding the molecular association of these genes, through the immunogenetic analysis of 3 Latin american mestizo populations. We included 606 individuals, 349 patients with DMDI and 257 healthy controls coming from 3 geographical areas: Mexico City, Mexico; Caracas, Venezuela and Medellin, Colombia. The results clearly indicate that in mestizo groups, the diabetogenic haplotypes are from mediterranean ancestry, while protection is due to Amerindian genes. It was demonstrated that the relevant sequences for IDDM expression are located to DRB1 and DQB1 loci with a minimal contribution of DQA1 residues. The sequences determining peptide recognition and the induction of TH1 cells mediating the cellular autoimmune response are in positions DRB1-57 and 74 (an aspartic acid and a glutamic acid respectively, confer protection), modulated by D-57 in the DQ, 8 chain. These data show that DRB1-DQB1 haplotypes are central for IDDM expression and open new pathways for the disease management.

Adolescent↗
PubMed1995

Characterization of B27 haplotypes by oligotyping and genomic sequencing in the Mexican Mestizo population with ankylosing spondylitis: juvenile and adult onset.

The aim of this study was to investigate the contribution of the different B27 subtypes in the Mexican Mestizo population with juvenile and adult AS. No differences in the distribution of B27 subtypes were found between both populations, B*2705 being the predominant subtype followed by B*2702. Transracial gene mapping was performed in order to find out the origin of the B27 alleles of the Mexican Mestizos. A PCR with SSOPs was used to analyze the polymorphism in exons 2 and 3 of HLA-B27 and HLA-C related alleles. This population shares with the Spanish Caucasians B*2705 and B*2702, which are absent in Central and South American Indians. AS and healthy Mexican mestizo donors were analyzed to ascertain B27/Cw haplotypes. The B27/Cw linkage arrangements seen in mestizos are similar to those reported for Caucasian Spaniards with three different haplotypes positively associated with AS in both populations, B*2705/Cw*0102, B*2705/Cw*02022, and B*2702/Cw*02022, suggesting that B27 in Mexicans may be due to a recent Caucasoid admixture with the Spanish genes. Finally, a strategy for sequence analysis of exons 2 and 3 from genomic DNA of HLA-B27 alleles was developed. A novel HLA-B27-like allele typed serologically as B27 was identified and sequenced by this method in a healthy Mexican mestizo, corresponding to the B*7301 variant found with low frequency in different populations. Analysis of the association of B*7301 to AS would require an extensive study in different populations and could provide insights into the molecular structure of the alleles involved in the disease.

Adolescent↗
PubMed1995

Allelic heterogeneity of HLA-B35 subtypes in different populations as assessed by DNA typing.

HLA-B35, a class I antigen differentially associated to several diseases in different ethnic groups, comprises at least eight alleles which differ among them by one to six amino acids. In the present work a rapid DNA typing procedure was used to investigate the distribution of the various HLA-B35 alleles in different populations. The approach is based on a group-specific PCR amplification of a set of closely related HLA-B alleles sharing a Thr in position 45 of the alpha-1 domain. The amplified DNA was then hybridized to a panel of sequence-specific oligonucleotide (SSO) probes designed to recognize the polymorphic residues in previously reported HLA-B35 subtypes. This methodology was successfully tested in 100 individuals of four different populations, previously typed by serology as HLA-B35, and in six reference panel cells of the 10th International Histocompatibility Workshop. HLA-B*3501 was the predominant subtype in all populations. B*3502, B*3503 and, to a lesser extent B*3508, were also found. Among Mexican Mestizos, thirteen individuals had patterns of SSO hybridization suggestive of new B35 alleles. The evolutionary considerations on the different B35 alleles and their extended B35,Cw4 haplotypes are discussed.

Alleles↗
PubMed1991

The HLA system and T-cell subsets in Bell's palsy.

The etiology of Bell's palsy (BP) is still unknown, but infectious, immunological and genetic factors have been suggested to play a role in the pathogenesis of the disease. We analyzed blood samples of 92 Mexican Mestizo patients diagnosed as having BP according to established international criteria, and the results were compared to a group of apparently healthy controls of the same ethnic origin. HLA class I (A, B, C) and Class II (DR, DQ) products of the major histocompatibility complex (MHC), and the percentages of CD3, CD4 and CD8 T-cell subsets were investigated. The number of family antecedents was surprisingly high (46%), supporting a genetic basis. There was a slight increase of DRw13, suggesting a possible susceptibility class II-linked gene. A significant decrease of DR4 (pc = 0.001) was detected, which may indicate the existence of a resistance DR-linked gene. Thus, a non DR4 carrier may be in high risk of expressing BP. In the acute phase of the disease, the T-cell subsets showed a decrease in CD3 and CD4 cells when compared to controls. CD8 cells were increased in the same stage. A transient T-cell imbalance was thus observed which recovered in the convalescent phase. None of the patients with CD4 lower than 40% were DR4, suggesting that the DR-linked resistance gene may predispose to the T-cell defect.

Adult↗
PubMed1991

Genetic pattern of the HLA system: HLA A, B, C, DR, and DQ antigens in Mexican patients with parenchymal brain cysticercosis.

The distribution of HLA class I and class II determinants was investigated in 48 patients with parenchymal neurocysticercosis and in 295 healthy controls of the same ethnic group, the Mexican Mestizo population. Two antigens, A28 and DQw2, showed significantly differences in frequency between patients and controls; HLA A28 was increased (39.6% versus 15.6%; pc = 0.008), and HLA DQw2 was decreased (4.2% versus 31.7%; pc = 0.004) in neurocysticercosis patients. The relative risk for developing the disease in HLA A28 positive individuals was 3.55. Our results show that the major histocompatibility complex plays some role in the susceptibility and resistance to parenchymal neurocysticercosis, but the HLA genetic background of patients with neurocysticercosis does not seem to influence the severity of inflammatory response against cysticerci, nor is the disease sex related.

Adolescent↗
PubMed1990

HLA-DQ alpha allele and genotype frequencies in various human populations, determined by using enzymatic amplification and oligonucleotide probes.

Allele and genotype frequencies at the HLA-DQ alpha locus have been determined by the use of polymerase chain reaction (PCR) amplification and nonradioactive oligonucleotide probes. The probes define six alleles and 21 genotypes in a dot-blot format. A total of over 1,400 individuals from 11 populations has been typed by two different laboratories using this method. In contrast to some variable-number-of-tandem-repeat markers that have been used for identity determination, DQ alpha genotype frequencies do not deviate significantly from Hardy-Weinberg equilibrium in all populations studied. The distribution of alleles varies significantly between most of these populations. In Caucasians, the allele frequencies range from 4.3% to 28.5%. In this population, the power of discrimination is .94, and, for paternity determination, the power of exclusion is .642. These population data will allow the use of the HLA-DQ alpha marker in paternity determination, the analysis of individual identity in forensic samples, and anthropological studies.

Alleles↗
PubMed1989

What is the significance of the presence of MHC molecules on the surface of parasites in human neurocysticercosis?

Sixteen cysticerci excised from 15 surgery patients were examined for the presence of HLA molecules on their surface, to confirm the role of these molecules in parasite damage and to investigate if HLA products are host specific or perhaps host-like antigens synthesized by the parasite. MoAbs against monomorphic and polymorphic HLA were chosen according to the patients HLA phenotypes. MoAbs against host and non-host antigens were selected and tested on cyst slides by indirect immunofluorescence assays. Host molecules were present in 43.7% of the cysts, but non-host antigens were also apparent in 62.5%. These results suggest mimicry as a possible mechanism to explain the presence of MHC products on the surface of the parasite; inflammation may also induce the expression of HLA that could become associated with the parasite. In vitro cellular immune response to specific antigens was also performed and positive responses correlated with the presence of HLA molecules on the cyst's surface. Moreover, damaged parasites had host molecules as well. Parasites from responder patients had all kind of HLA molecules or at least, antigenic determinants while the cysts from non-responders did not have molecules on their surface. These data support the role of HLA in cyst destruction.

Adult↗