Biomedical subjects

F Andrade

Publications and source records attributed to F Andrade.

23 records · Page 2Linked to original sources

PubMed1994

HLA-B alleles and complotypes in Mexican patients with seronegative spondyloarthropathies.

OBJECTIVES: To analyse major histocompatibility complex (MHC) haplotypes in Mexican mestizo patients with seronegative spondyloarthropathies (SSpA) and normal controls, to discover if there are other antigens, besides B27, in the HLA region that might show association with the disease. METHODS: The study included 100 Mexican mestizo patients with SSpA and 200 of their first degree relatives. These groups were compared with 85 ethnically matched controls. The class I and class III MHC antigens were obtained by standard methods. The significance of differences between patients and controls was tested by chi 2 analysis; linkage disequilibrium among the different alleles in each haplotype was estimated by computing delta values. RESULTS: We found a significantly increased frequency of the HLA-B27 antigen (pcorr. = 1 x 10(-5), odds ratio (OR) = 33.4, 95% confidence interval (CI) = 9.3-142.0). In the group of 45 SSpA patients negative for the B27 antigen, independent increased frequencies of HLA-B49 antigen (pcorr. = 0.03, OR = 6.5, 95% CI = 1.5-32.8)) and the FC31 complotype (pcorr. = 0.04, OR = 3.7, 95% CI = 1.2-11.1) were found. Significant delta values were obtained for the [B27;SC30] haplotype (p = 0.0005) but not for haplotypes marked by the FC31 complotype. HLA-B antigens on the homologous chromosome in B27 positive patients were mainly HLA-B51 (18%) and HLA-B60 (16%); however, the observed genotypes B27/B51 and B27/B60 were not significantly different than expected from the allele frequencies alone. CONCLUSIONS: These data suggest that in Mexicans additional genes within the MHC region besides the HLA-B27 antigen, might be related to the genetic susceptibility for developing SSpA. Relevant antigens included the HLA-B49 and the FC31 complotype.

Adult↗

PubMed1994

Buthionine sulfoximine treatment impairs rat diaphragm function.

Activation of the glutathione (GSH) redox cycle with production of glutathione disulfide (GSSG) has been shown to occur in the diaphragm during inspiratory resistive loading (RB). Buthionine sulfoximine (BSO) lowers tissue GSH by irreversibly inhibiting the rate-limiting synthesis enzyme gamma-glutamylcysteine synthetase. We investigated the effects of BSO on rat diaphragm function, both at rest and after a period of RB. Rats in the RB groups underwent inspiratory RB until they were unable to sustain 70% of their maximal airway pressure. A portion of the diaphragm was analyzed for GSH and GSSG levels, and measurements of in vitro contractile properties included contraction times, maximal tetanic tension (Po), maximal twitch tension (Pt), and force frequency curves. BSO treatment produced a profound depletion of diaphragmatic GSH. Neither BSO nor RB alone significantly altered diaphragm contractile properties at this load of RB. But, in BSO-RB rats, there was a significant decrease in Pt, Po, and tetanic tension at all frequencies of stimulation compared with those in other groups. These data reveal that animals treated with BSO followed by inspiratory resistive loading exhibit marked diaphragm impairment, suggesting that GSH may play an important role in protecting the diaphragm from the stress induced by this resistive breathing protocol.

Analysis of Variance↗

PubMed1993

Diethylmaleate produces diaphragmatic impairment after resistive breathing.

Formation of oxygen-derived free radicals and activation of the glutathione (GSH) redox cycle has been associated with impaired rat diaphragm performance. Diethylmaleate (DEM) given intraperitoneally irreversibly conjugates with GSH, resulting in marked decreases in tissue concentrations of GSH. We have investigated the effects of acute GSH depletion by DEM on diaphragmatic function during resistive breathing (RB) in the rat. The experimental groups were 1) control, 2) DEM alone, 3) RB, and 4) DEM with RB (DEM + RB). RB was obtained by inspiratory RB until the rats were unable to sustain 70% of maximum airway opening pressure. A portion of the diaphragm was frozen for biochemical assays, and the rest of the diaphragm was prepared for measurement of in vitro contractile properties, including maximum tetanic tension, twitch tension, force-frequency curves, and contraction times. DEM treatment produced a profound depletion of GSH in the DEM and DEM + RB groups. Neither DEM nor RB alone significantly altered diaphragm contractile properties. In DEM + RB rats, however, there was a significant decrease in maximum tetanic tension, twitch tension, and tetanic tension. These data reveal that DEM produced an acute depletion of GSH in the diaphragm without impairment of the muscle in nonstressed rats. In the presence of DEM-induced GSH depletion, RB did result in marked diaphragm impairment. The depletion of GSH and the subsequent impairment in diaphragm contractility after RB suggest that GSH may play an important role in protecting the diaphragm against oxidative stress associated with RB.

Animals↗

PubMedDate not supplied

Immunogenetics of mixed connective tissue disease in a Mexican Mestizo population.

OBJECTIVE: The aim of this study was to determine the HLA antigens in Mexican Mestizo patients with mixed connective tissue disease (MCTD). METHODS: We studied 30 patients with MCTD and 99 healthy controls. HLA-A, -B, and -DQ antigens were typed by microlymphocytotoxicity assays. DRB1, DQA1 and DQB1 alleles were oligotyped. RESULTS: HLA-A2 and HLA-B35 were the most frequent MHC class I alleles in MCTD patients, although they were not statistically more frequent than in the controls. According to serological tests, the most frequent DQ allele in the patients was DQ1, which was statistically increased when compared with controls (p = 0.0051). By oligotyping, the DR1 allele and the DQB1*0501 specificities were significantly increased in the patients vs. controls (p = 0.032 and 0.027, respectively). CONCLUSION: The elevated levels of DQ1 found in Mexican MCTD patients, although weak, may indicate a particular genetic susceptibility, since there are previous reports of associations of other alleles (such as DR4) with MCTD in other populations. The increase in DQB1*0501 may account for the increase in DQ1. DQB1*0501 has also been reported in black patients with anti-RNP autoantibodies, compared with black patients without anti-RNP or anti-Sm.

Adult↗

PubMedDate not supplied

Linkage disequilibrium of HLA-DR3 and HLA-DR4 with HLA-B alleles in Mexican patients with rheumatoid arthritis.

OBJECTIVE: We studied the gene frequencies of classes I, II and III antigens of the Major Histocompatibility Complex (MHC) in 32 Mexican mestizo patients with rheumatoid arthritis (RA) and compared them with those obtained from 110 of their first degree relatives and 100 Mexican mestizo controls. Furthermore, we analyzed the observed and expected frequencies of the haplotypes and calculated the delta values in the three groups. METHODS: The class I and class II MHC antigens were determined by the microlymphocytotoxicity test; class III MHC antigens were obtained by high voltage agarose gel electrophoresis and immunofixation. The significance of differences among the three groups was tested by chi-square analysis; linkage disequilibrium among the different alleles in each haplotype was estimated by computing the delta values (observed vs expected frequencies). RESULTS: Patients showed a significantly increased frequency of HLA-A1 (corrected p = 10(-5)), DR3 (corrected p = 0.04) and DQ2 (corrected p = 10(-4)) and a decreased frequency of A31 (corrected p = 0.003) as compared to the normal controls. First degree relatives compared to patients and controls showed a decreased frequency of HLA-DR4 (corrected p = 0.02 and 0.008 respectively); consequently, DQ3 was also diminished (corrected p = 10(-4)). Analysis of MHC haplotypes within families revealed in the patients seven MHC haplotypes with significant differences between the observed and expected frequencies (statistically significant delta values). These haplotypes were: [HLA-B8; DR3], [HLAB44; FC31], [HLA-B8; SC42], [HLA-DR4; SC31], [HLA-B35; SC32], [HLA-DR7; FC31] and [HLA-DR2; SC31]. On the other hand, the control haplotypes showed significant delta values in only one of these haplotypes ([HLA-DR4; SC31]), whereas first degree relatives showed none. Analysis of all the class I, II and III alleles, either alone or as part of specific haplotypes, showed two B-DR haplotypes with higher relative risks than their alleles alone. These haplotypes were: [B44; DR4] (RR = 6.0, p = 0.005), and [B8; DR3] (RR = 8.3, p = 0.010). CONCLUSION: The results suggest that a specific combination of antigens in the same haplotype (for instance between HLA-B and HLA-DR) could contribute to increasing the genetic susceptibility to develop RA.

Alleles↗