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排序方式: 共有850条查询结果,搜索用时 7 毫秒
831.
José F. Muñoz-Valle Yeminia Valle Jorge R. Padilla-Gutiérrez Isela Parra-Rojas Hector Rangel-Villalobos Mónica Vázquez del Mercado Iris Y. Ledezma-Lozano José R. Villafan-Bernal Juan Armendáriz-Borunda Ana Laura Pereira-Suárez 《Clinica chimica acta; international journal of clinical chemistry》2010,411(9-10):725-728
BackgroundThe Cytotoxic T lymphocyte antigen (CTLA-4) is one of the major susceptibility genes associated with autoimmune diseases. Susceptibility to rheumatoid arthritis (RA) is determined by both environmental and genetic factors. The genetic contribution approaches 50–60%. The association between RA with the + 49A>G CTLA-4 polymorphism in the Mexican population was investigated.MethodsThe polymerase chain reaction–restriction fragment was used to amplify the + 49A>G CTLA-4 polymorphism in RA patients and healthy subjects (HS).ResultsWe analyzed the association between the + 49A>G CTLA-4 polymorphism and RA. The G allele frequency was higher in RA patients than HS (46.8 vs 37.7%, OR = 1.45, p = 0.01). RA patients carrying the A/G genotype were significantly more likely to be positive to CRP and RF. There was no evidence of an association between SNP genotypes and the clinical characteristics of rheumatoid arthritis.ConclusionsThe + 49A>G CTLA-4 polymorphism is a genetic marker of susceptibility for RA in western Mexican population. 相似文献
832.
Mercado M González B Sandoval C Esquenazi Y Mier F Vargas G de los Monteros AL Sosa E 《The Journal of clinical endocrinology and metabolism》2008,93(9):3411-3415
Context: Lack of exon 3 of the GH receptor (d3-GHR) has been associated with increased responsiveness to GH therapy. By analogy, we hypothesized that patients with acromegaly bearing the d3-GHR genotype may have a more morbid clinical and biochemical picture. Objective: Our objective was to determine whether the GHR genotype, by modifying tissue sensitivity to GH, influences the clinical/biochemical expression of acromegaly and its outcome after treatment. Setting: The study was conducted at a specialized clinic at a tertiary care hospital. Design, Patients, and Methods: We conducted a prospective genotype investigation and retrospective analysis and correlation with clinical, biochemical, and outcome data from a group of 148 patients. Samples from 175 healthy blood donors were used as controls. GHR genotyping was performed by real-time PCR. Main Outcome Measures: We assessed prevalence of the three GHR genotypes (fl/fl, d3/d3, and d3/fl), associations between the genotypes, and baseline as well as post-therapeutic characteristics. Results: Prevalence of the fl/fl, d3/d3, and d3/fl genotypes was 45, 22, and 32%, respectively, similar to what was found in the controls. Baseline characteristics were similar in carriers of the three genotypes. A positive correlation between IGF-I and log GH concentrations was significant only in homo- or heterozygous d3 carriers. Among d3-GHR carriers, diabetes, but no other comorbidities, was more prevalent (odds ratio = 2.02; 95% confidence interval = 0.96-4.2). d3-GHR carriers had significantly higher IGF-I concentrations after treatment. Multiple regression analysis revealed that the homo- or heterozygous lack of exon 3 was the strongest predictor of persistent biochemical activity (odds ratio = 1.29; 95% confidence interval = 0.65-2.58). Conclusions: The absence of exon 3 of the GHR may be associated with a more morbid acromegalic clinical and biochemical picture and a lower chance of achieving IGF-I normalization after therapy. 相似文献
833.
Marjo Hordijk-Trion Mattie Lenzen William Wijns Peter de Jaegere Maarten L Simoons Wilma J M Scholte op Reimer Michel E Bertrand Nestor Mercado Eric Boersma 《European heart journal》2006,27(6):671-678
AIMS: Revascularization in patients with coronary artery disease changed over the last two decades, favouring the number of patients treated by means of percutaneous coronary interventions (PCI) when compared with coronary artery bypass grafting (CABG). Many randomized controlled trials (RCTs) have been performed to compare these two competing revascularization techniques. Because of the strict enrolment criteria of RCTs in which highly selected patients are recruited, the applicability of the results may be limited in clinical practice. The current study evaluates to what extent patients in clinical practice were similar to those who participated in RCTs comparing PCI with CABG. METHODS AND RESULTS: Clinical characteristics and 1-year outcome of 4713 patients enrolled in the Euro Heart Survey on Coronary Revascularization were compared with 8647 patients who participated in 14 major RCTs, comparing PCI with CABG. In addition, we analysed which proportion of survey patients would have disqualified for trial participation (n=3033, 64%), aiming at identifying differences between trial-eligible and trial-ineligible survey patients. In general, important differences were observed between trial participants and survey patients. Patients in clinical practice were older, more often had comorbid conditions, single-vessel disease, and left main stem stenosis when compared with trial participants. Almost identical differences were observed between trial-eligible and trial-ineligible survey patients. In clinical practice, PCI was the treatment of choice, even in patients who were trial-ineligible (46% PCI, 26% CABG, 28% medical). PCI remained the preferred treatment option in patients with multi-vessel disease (57% in trial-eligible and 40% in trial-ineligible patients, respectively, P<0.001); yet, the risk profile of patients treated by PCI was better than that for patients treated either by CABG or by medical therapy. In the RCTs, there was no mortality difference between PCI and CABG. In clinical practice, however, we observed 1-year unadjusted survival benefit for PCI vs. CABG (2.9 vs. 5.4%, P<0.001). Survival benefit was only observed in trial-ineligible patients (3.3 vs. 6.2%, P<0.001). CONCLUSION: Many patients in clinical practice were not represented in RCTs. Moreover, only 36% of these patients were considered eligible for participating in a trial comparing PCI with CABG. We demonstrated that RCTs included younger patients with a better cardiovascular risk profile when compared with patients in everyday clinical practice. This study highlights the disparity between patients in clinical practice and patients in whom the studies that provide the evidence for treatment guidelines are performed. 相似文献
834.
Victoria Mendoza Ernesto Sosa Ana Laura Espinosa-de-Los-Monteros Mauricio Salcedo Gerardo Guinto Sonia Cheng Carolina Sandoval Moises Mercado 《Growth hormone & IGF research》2005,15(1):28-32
OBJECTIVE: The frequency of activating mutations of the GSPalpha gene as the etiology of GH-secreting pituitary adenomas has been the subject of important ethnogenetic variability. Whereas up to 40% of Caucasian patients with acromegaly have tumors which harbor these somatic mutations, their prevalence among Asian populations is much lower. The correlation between the presence of these mutations and the clinical and biological behavior of these tumors has also been a matter of controversy. In the present study, we investigated the prevalence of GSPalpha mutations in GH-secreting tumors obtained from a genetically homogenous population of Mexican patients with acromegaly. We also sought to establish whether or not the presence of these mutations correlates in any way with the clinical or biochemical characteristics of the disease. STUDY DESIGN AND METHODS: Fifty eight GH-secreting pituitary adenomas were examined for the presence of point mutations in either codon 201 or 227 of the GSPalpha gene, using PCR and direct sequencing of DNA extracted from either fresh or paraffin-embedded tissues. Patients were prospectively followed clinically and biochemically for up to nine years after pituitary surgery. RESULTS: Heterozygous point mutations in exon 8 (codon 201) were found in 11 patients (19%), and no molecular alterations were evident in exon 9. The frequency and severity of the different clinical features of acromegaly did not differ between patients with and without GSPalpha mutations. Patients with and without mutations had pre-operative GH and IGF-I elevations of similar magnitude, and although microadenomas appeared to be more frequent among patients with GSPalpha mutations, this did not reach statistical significance. Upon short-term follow-up, biochemical cure (normal age- and gender-adjusted IGF-I and post-glucose GH below 1 ng/mL) was similarly achieved in both groups. After 3-9 years of post-operative follow up however, a significantly greater proportion of patients with the mutation achieved a "safe" basal GH value (100% vs 33%, p=0.001) as well a lower nadir post-glucose GH (0.53+/-0.5 vs 2.9+/-6.2 ng/mL, p=0.04) although the rate of IGF-1 normalization did not differ between the 2 groups. CONCLUSIONS: Our results show that the prevalence of GSPalpha mutations in Mexican patients with acromegaly is intermediate between that found in Asian and Caucasian populations. In this well-defined genetic population the presence of codon 201 mutations appeared to be associated with a greater probability of achieving a "safe" GH value upon long-term follow-up. 相似文献
835.
Besserer GM Ottolia M Nicoll DA Chaptal V Cascio D Philipson KD Abramson J 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(47):18467-18472
The Na(+)-Ca(2+) exchanger plays a central role in cardiac contractility by maintaining Ca(2+) homeostasis. Two Ca(2+)-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca(2+) binding to these regulatory domains activates the transport of Ca(2+) across the plasma membrane. Previously, we solved the structure of CBD1, revealing four Ca(2+) ions arranged in a tight planar cluster. Here, we present structures of CBD2 in the Ca(2+)-bound (1.7-A resolution) and -free (1.4-A resolution) conformations. Like CBD1, CBD2 has a classical Ig fold but coordinates only two Ca(2+) ions in primary and secondary Ca(2+) sites. In the absence of Ca(2+), Lys(585) stabilizes the structure by coordinating two acidic residues (Asp(552) and Glu(648)), one from each of the Ca(2+)-binding sites, and prevents a substantial protein unfolding. We have mutated all of the acidic residues that coordinate the Ca(2+) ions and have examined the effects of these mutations on regulation of exchange activity. Three mutations (E516L, D578V, and E648L) at the primary Ca(2+) site completely remove Ca(2+) regulation, placing the exchanger into a constitutively active state. These are the first data defining the role of CBD2 as a regulatory domain in the Na(+)-Ca(2+) exchanger. 相似文献
836.
Torres-Carrillo NM Torres-Carrillo N Vázquez-Del Mercado M Delgado-Rizo V Oregón-Romero E Parra-Rojas I Muñoz-Valle JF 《Rheumatology international》2008,28(4):355-360
We assessed whether the −844 G/A polymorphism and mRNA expression of plasminogen activator inhibitor 1 (PAI-1) gene are associated with rheumatoid arthritis (RA). Demographic data, hematological, biochemical parameters, disease activity–disability
indexes, −844 G/A genotypes and mRNA expression levels of the PAI-1 gene were determined in 50 RA patients and 50 healthy subjects (HS). Non-significant differences in genotype and allele frequencies
related to −844 G/A polymorphism in RA versus HS, were found. High mRNA expression of the PAI-1 gene, was demonstrated in RA versus HS (P < 0.05). In addition, A/A genotype carriers showed increase of PAI-1 mRNA expression (3.1-fold) respect to G/G and G/A genotypes in RA patients (P < 0.05). Our finding suggest an association of A/A −844 PAI-1 genotype with high PAI-1 mRNA expression in RA patients. 相似文献
837.
Ruan B Pong K Jow F Bowlby M Crozier RA Liu D Liang S Chen Y Mercado ML Feng X Bennett F von Schack D McDonald L Zaleska MM Wood A Reinhart PH Magolda RL Skotnicki J Pangalos MN Koehn FE Carter GT Abou-Gharbia M Graziani EI 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(1):33-38
Rapamycin is an immunosuppressive immunophilin ligand reported as having neurotrophic activity. We show that modification of rapamycin at the mammalian target of rapamycin (mTOR) binding region yields immunophilin ligands, WYE-592 and ILS-920, with potent neurotrophic activities in cortical neuronal cultures, efficacy in a rodent model for ischemic stroke, and significantly reduced immunosuppressive activity. Surprisingly, both compounds showed higher binding selectivity for FKBP52 versus FKBP12, in contrast to previously reported immunophilin ligands. Affinity purification revealed two key binding proteins, the immunophilin FKBP52 and the beta1-subunit of L-type voltage-dependent Ca(2+) channels (CACNB1). Electrophysiological analysis indicated that both compounds can inhibit L-type Ca(2+) channels in rat hippocampal neurons and F-11 dorsal root ganglia (DRG)/neuroblastoma cells. We propose that these immunophilin ligands can protect neurons from Ca(2+)-induced cell death by modulating Ca(2+) channels and promote neurite outgrowth via FKBP52 binding. 相似文献
838.
Coralith Garcia Omayra Chincha Mey Leon David Iglesias Francesca Barletta Erik Mercado Theresa Ochoa 《The American journal of tropical medicine and hygiene》2010,82(6):1118-1120
Diarrhea is still a prevalent health issue in HIV patients. Our objective was to characterize the different diarrheagenic E. coli (DEC) groups in stools from adult HIV patients. Cross sectional study: We enrolled HIV-positive and -negative patients with and without diarrhea from a tertiary-care center of Lima, Peru. Clinical data was recorded and a stool sample per patient was cultured. Multiplex PCR was used to detect different DECs. One hundred eighty-four participants were enrolled. The frequency of having at least one DEC was more common in HIV-positive than HIV-negative patients with diarrhea (42% versus 20%, P < 0.05). The enterotoxigenic E. coli (ETEC) was the most common DEC in patients with diarrhea, 13% in HIV patients. The diffusely adherent E. coli (DAEC) was only present in HIV positive patients with diarrhea (10.1%). Different types of DEC are frequent in stools from HIV-positive patients.Since the highly active anti-retroviral treatment (HAART) was introduced for acquired immunodeficiency syndrome (AIDS), the incidence of opportunistic infections has decreased and new pathogens, such as diarrheagenic Escherichia coli (DEC) groups,1 are now associated with diarrhea in human immunodeficiency virus (HIV) patients. Because antibiotic therapy may be successful in cases where pathogenic bacteria are identified, studies focusing on bacterial diarrhea in AIDS patients are needed. The DECs have been classified into six groups based on specific genes that determine their virulence factors: enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), Shiga toxin producing E. coli (STEC), enteroagregative E. coli (EAEC), enteropathogen E. coli (EPEC), and diffusely adherent E. coli (DAEC).2 The role of different DECs in causing diarrhea in HIV-infected people in Latin American countries has not been adequately addressed because most studies have not examined for all currently recognized groups of DECs. Our objective was to characterize the different DECs in stools from adult HIV patients in Lima, Perú. 相似文献
839.
840.
Yolik Ramírez-Marín David Eduardo Abad-Contreras Martha Ustarroz-Cano Norma S. Prez-Gallardo Lorena Villafuerte-García Dulce Maria Puente-Guzmn Jorge Luna del Villar-Velasco Leonardo Alejandro Rodríguez-Lpez Gonzalo Torres-Villalobos Miguel ngel Mercado Jesús Tapia-Jurado Francisco Drusso Martínez-García Martin Conrad Harmsen M. Cristina Pia-Barba David M. Giraldo-Gomez 《Materials》2021,14(11)
Reconstruction of bile ducts damaged remains a vexing medical problem. Surgeons have few options when it comes to a long segment reconstruction of the bile duct. Biological scaffolds of decellularized biliary origin may offer an approach to support the replace of bile ducts. Our objective was to obtain an extracellular matrix scaffold derived from porcine extrahepatic bile ducts (dECM-BD) and to analyze its biological and biochemical properties. The efficiency of the tailored perfusion decellularization process was assessed through histology stainings. Results from 4’-6-diamidino-2-phenylindole (DAPI), Hematoxylin and Eosin (H&E) stainings, and deoxyribonucleic acid (DNA) quantification showed proper extracellular matrix (ECM) decellularization with an effectiveness of 98%. Immunohistochemistry results indicate an effective decrease in immunogenic marker as human leukocyte antigens (HLA-A) and Cytokeratin 7 (CK7) proteins. The ECM of the bile duct was preserved according to Masson and Herovici stainings. Data derived from scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) showed the preservation of the dECM-BD hierarchical structures. Cytotoxicity of dECM-BD was null, with cells able to infiltrate the scaffold. In this work, we standardized a decellularization method that allows one to obtain a natural bile duct scaffold with hierarchical ultrastructure preservation and adequate cytocompatibility. 相似文献