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Biomedical subjects

J Granados

Publications and source records attributed to J Granados.

At least 73 records · Page 4Linked to original sources
PubMed1997

Relationship of anticardiolipin antibodies and antiphospholipid syndrome to HLA-DR7 in Mexican patients with systemic lupus erythematosus (SLE).

We studied IgG and IgM anticardiolipin antibodies (aCL) by an ELISA method in 80 Mexican systemic lupus erythematosus (SLE) patients and 378 of their first degree relatives. Sixty five percent of SLE patients and 16% of their relatives were positive for aCL. We also determined allele and haplotype frequencies of Major Histocompatibility Complex (MHC) genes (classes I, II and III) in both patients and relatives. MHC allele and haplotype frequencies of aCL positive and negative individuals were compared to those of normal ethnically matched controls. SLE patients with aCL had statistically significant increased corrected frequencies of HLA-DR3 (pC = 0.04, RR = 2.78); DR7 (pC = 0.005), RR = 3.42) and DQ2 (pC = 0.003, RR = 2.58) antigens. Their first degree relatives positive for aCL also had increased frequency of HLA-DR7 but it did not remain significant after correcting the P value. On the other hand, SLE patients negative for aCL had a moderate increased frequency of DR3 and DQ2 but not of DR7. These results suggest that DR7 associates with the presence of aCL. The distribution of MHC alleles in SLE patients positive for aCL resembles that found in their aCL positive first degree relatives. Since the presence of the antibody is not sufficient to predict a clinical outcome, we studied those patients with reliable clinical data regarding the presence of the antiphospholipid syndrome (aPLS). SLE patients with aPLS had significantly increased frequency of DR7 (pC = 0.004), as did those with probable aPLS (pC = 0.05), while the frequency of DR7 in SLE patients in the doubtful or negative aPLS categories was no different from normal controls. These data support a possible role of DR7 in the development of aCL in SLE patients and their relatives and suggest a contribution of this class II MHC antigen to the development of aPLS within SLE.

Alleles↗
PubMed1997

HLA class I and class II alleles and haplotypes in Mexican mestizos established from serological typing of 50 families.

We describe new information on the frequency and association of class II antigens (HLA-DR and HLA-DQ) of the major histocompatibility complex (MHC) in Mexicans. The study includes HLA-B typing and its association with the HLA-DR antigens determined in 50 families, which included 100 individuals. This family study allowed the establishment of the precise composition of the 200 HLA haplotypes, which cannot be obtained from unrelated individuals. The predominant antigens in decreasing order of frequency were B35, B39, and B61 at the B locus; DR4, DR5, and DR8 at the DR locus; and DQ3 at the DQ locus. The most common HLA-B,HLA-DR haplotype (considering broad specificities) was B16,DR4, with a frequency of 8.0%. Five HLA-B,HLA-DR haplotypes showed significant delta values (observed vs. expected frequencies) after correcting for the number of comparisons. On the other hand, the most common HLA-DR,HLA-DQ haplotypes were DR4,DQ3 and DR5,DQ3 with a frequency higher than 10%. Ten of the 17 HLA-DR,HLA-DQ haplotypes had significant postcorrection delta values.

Ethnicity↗
PubMed1996

HLA-DR6 (possibly DRB1*1301) is associated with susceptibility to Takayasu arteritis in Mexicans.

Takayasu arteritis is characterized by a "pulseless" condition and occurs frequently in young females from Asian and South American countries. This disease has been found to be linked with major histocompatibility complex (MHC) antigens in Japanese individuals. In the present study we compared gene frequencies of class I, class II, and class III MHC genotypes in patients with Takayasu arteritis and ethnically matched healthy controls. Serological typing was confirmed by molecular typing at the DNA level. We found significant increases in the frequencies of human leucocyte antigen (HLA)-DR6 and HLA-B62 in patients compared to the healthy controls (P corrected [C] = 0.0007, relative risk [RR] = 5.08; PC = 0.05, RR = 3.13 respectively). However, since the number of patients was considerably lower than the number of controls this can be considered as a tendency and not a true association. On the other hand, we found a significantly decreased frequency of HLA-DR4 in patients compared to healthy controls (PC = 0.04, RR = 0.34). At the DNA level, all DR6-positive individuals were HLA-DRB1*1301 whereas controls were HLA-DRB1*1301 (4.2%). Takayasu arteritis in Mexicans is probably associated with the HLA-DR6 (DRB1*1301) gene.

Adult↗
PubMed1996

Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua Aztec descent.

A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent. Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp changes, respectively, in the corresponding HLA molecule at the peptide-binding site. These substitutions may have originated from a DNA stretch donation from an allele belonging to the B15 group, enabling HLA-B*3514 to cope with the presentation of a new set of antigenic peptides. The high frequency of serologic B35 in Amerindians, together with the variety of B35 alleles detected by DNA sequencing in these populations, suggest that a frequent B35 subtype was present in the founder population and that several B35 subtypes may have been recently generated, probably due to the abrupt arrival of new pathogens following European invasions.

Alleles↗
PubMed1996

Surgical treatment of Brucella endocarditis.

Between April 1987 and October 1992, six cases of Brucella endocarditis were operated on in the authors' hospital for valve replacement. They were five men and one woman with a mean(s.d.) age of 52(15) years (range 30-71 years). Three patients were in New York Heart Association (NYHA) class III and three in class IV. Two patients had previous history of rheumatic fever, one was a drug abuser, two had peripheral embolism and one constrictive pericarditis. Most were living in rural areas. Echocardiographic diagnoses were: severe aortic regurgitation in two patients, mixed disease in two and double valve involvement in two. Valve vegetations were demonstrated in two patients, valve calcification in two and annulus abscess in two others. Serological tests were positive in all patients. All patients had valve replacements and three were operated on as emergencies. Surgical findings were: valve vegetations in two patients, cusp perforation in two annulus abscess in two and prosthetic leak in two. Mean(s.d.) cardiopulmonary bypass time was 123(77) min with a mean ischaemic time of 79(43) min. All patients were given specific antibiotic treatment after surgery. There was no intraoperative mortality and the 5-year survival rate was 100%. Early reoperations were needed in three patients, two because of prosthetic leakage causing severe regurgitation and one for tamponade. The results suggests that Brucella endocarditis is rare, but still occurs in Mediterranean areas. Surgical replacement is needed in spite of antibiotic treatment and recurrences with prosthetic leaks are usual.

Adult↗
PubMed1996

Increased frequency of HLA-DR3 and complotype SCO1 in Mexican mestizo children with amoebic abscess of the liver.

The increase of HLA-DR3 and complotype SCO1 previously found in Mexican mestizo adults with E. histolytica amoebic abscess of the liver, was also found in Mexican mestizo children of either sex with the same disease, when compared to the healthy control population (adults and/or children) of the same ethnic and socioeconomic background. This HLA and complotype pattern was not found in Mexican Mestizo patients with amoebic rectocolitis. No linkage disequilibrium was found between these and the other MHC determinants tested in this survey. Thus, HLA-DR3 and SCO1 may constitute primary, independent risk factors, not for any kind of amoebic tissue invasion (i.e. amoebic rectocolitis), but specifically for amoebic liver abscess, irrespective of age or sex. The possibility of linkage disequilibrium with other factors (i.e. the TNF family) within or close to the MHC that were not tested in this study, is discussed. Children with amoebic liver abscess revealed a significant increase in HLA-DR5, and the absence of HLA-DR6 when compared to adults with amoebic liver abscess, suggesting that at least in this ethnic group these class II HLA traits may contribute to some of the peculiarities of pediatric amoebic liver abscess as opposed to the adult version of this disease. HLA-DR3, SCO1, but also HLA-DR5 and HLA-DR6 have all been associated with certain forms of immune-dysfunction, and may thus contribute to some of the clinical and immunological features of this parasitic disease.

Adolescent↗
PubMed1996

The role of HLA-DR alleles and complotypes through the ethnic barrier in systemic lupus erythematosus in Mexicans.

Alleles of the major histocompatibility complex (MHC) have been recognized as genetic factors for the development of SLE. The [HLA-B8; SC01; DR3] extended haplotype seems to be relevant in patients from white European descent, pertinent alleles, however, are difficult to select on haplotypes with linkage disequilibrium. Studies in non-Caucasian patients are therefore mandatory. Admixture estimates in Mexicans have shown a proportion of 56% of Indian genes, 40% of Caucasian genes and from 4 to 12% of Black genes. In order to determine the relevant MHC loci in the genetic susceptibility for SLE we studied Class I, II and III alleles in 102 Mexican SLE patients and 350 of their first degree relatives and compared these two groups to another one composed by 200 ethnically matched normal individuals. We found significantly increased frequencies of HLA-DR3 (pC = 0.03, RR = 2.56) and DR7 (pC = 0.004, RR = 3.08) in SLE patients as compared to controls. On the other hand, first degree relatives had a significantly increased frequency of HLA-DR7 (pC = 0.01, RR = 2.98). There were 21 out of 33 HLA-DR3 haplotypes with complotypes other than SC01 and 25 out 37 SC01 haplotypes with DR alleles other than DR3. Nevertheless, [SC01; DR3] haplotypes were also increased (pC = 0.01, RR = 12.4). After removing [HLA-B8; SC01; DR3] haplotypes, DR3 was the only allele that remained significantly increased (p = 0.04, RR = 2.1). We also found in SLE patients significantly decreased frequencies of the autochthonous Mexican alleles (A30, B39 and DR4) and no deviation from normality of any of the HLA-DQ alleles. These data suggest a fundamental role of the HLA-DR3 allele in the predisposition to SLE in Mexican patients which might be hightened by genes located around the class III MHC region. They also substantiate the pertinence of ethnic admixture estimates in modern human populations.

Alleles↗
PubMed1995

Valvuloplasty in traumatic aortic insufficiency due to subtotal tear of the intima.

Aortic regurgitation is one of the usual pathologic findings necessitating valve replacement in cardiac surgery. Several diseases may result in leaflet incompetence. Circumferential intimal tear of the aortic root with prolapse of the aortic valve commissures is a rare cause of aortic incompetence. We report the repair of the aortic wall and valve in 1 patient with such a tear 6 months after an important thoracic trauma. Three months after the aortic valve reconstruction the patient is in good condition and fully asymptomatic.

Aged↗
PubMed1995

Extended HLA haplotypes among the Bari Amerindians of the Perija Range. Relationship to other tribes based on four-loci haplotype frequencies.

Extended HLA haplotypes among Bari Amerindians living at the Perija Range on the limits between Colombia and Venezuela have been defined using serology for class I, electrophoresis and immuno-fixation for Bf and C4, and PCR-SSO for class II loci typing. Haplotypes were assigned based on family studies and gene frequencies were calculated using a subset of less related subjects selected from the genealogy. No rare class III variants were observed, but the characteristic low HLA diversity of isolated Amerindians populations present also in the Bari extends to Bf and C4. Thus there were only 22 different haplotypes segregating in families when nine loci were considered. All of them except three carried Bf*S, C4A*3, C4B*1. The null allele C4A*Q0 reached a frequency of 0.147 and was predominantly present in A24 Cw7 B39 DRB1*0411 haplotypes. In contrast to what has been reported using HLA alleles or class I haplotype frequencies and other isolated South American tribes, genetic distance estimates based on A-Cw-B-DR haplotype frequencies show a closer relationship between the two linguistically but geographically distant Venezuelan tribes, the Bari and the Warao, as compared to two culturally different Brazilian populations. The information reported here will be useful for identifying ancestral haplotypes in native peoples of America, for population comparison, and for discussing the differential influence of MHC haplotype diversity and population survival when similar data on other Amerindian tribes becomes available.

Alleles↗
PubMed1994

Immunogenetic aspects in primary open-angle glaucoma in family members of Mexican mestizo glaucomatous patients.

We determined antigens of the major histocompatibility complex classes I, II, and III in 25 families of Mexican mestizo glaucomatous patients. Patients and family members were examined, and the predisposition of first-degree relatives to a corticosteroid-provocative test was determined. The results showed a high frequency of the HLA-DR3 antigen in patients with primary open-angle glaucoma compared with controls (32.5% vs 4.0%, P = .001, odds ratio = 10.25). We suggest that the increased presence of the HLA-DR3 antigen could be an important factor in the genetic susceptibility to glaucoma.

Biomarkers↗
PubMed1994

The syndrome of presumed ocular histoplasmosis in Mexico: a preliminary study.

A study to screen for the syndrome of presumed ocular histoplasmosis (SPOH) among native populations from three Mexican states was performed. Two of these states, Guerrero and Querétaro, were selected as histoplasmosis is endemic there, whereas Tlaxcala was considered a control, due to the absence of reported cases. A total of 253 individuals were submitted to ocular fundus examination to obtain evidence of SPOH. A high percentage of positive reactors to histoplasmin skin test (ST) was observed in Guerrero (83%) and Querétaro (53%), whereas in Tlaxcala positive ST were almost absent (2.04%). Only five individuals had retinal lesions, although these lesions were not characteristic of the syndrome. Stimulation of these individual's cells showed different patterns in the histoplasmin-induced lymphocyte transformation response, and two out of five individuals with retinal lesions presented a stimulated response, as well as three controls without lesions. Histocompatibility antigens (HLA) were determined in a sample of each population and no particular allele, including HLA-B7, was found to be related to SPOH as reported in the USA; however, HLA-B22 was found in three individuals who developed pulmonary histoplasmosis. Results do not provide clinical evidence or data on specific HLA risk factors, for the presence of SPOH in the population studied.

Alleles↗