Biomedical subjects

A Valenzuela

Publications and source records attributed to A Valenzuela.

At least 19 recordsLinked to original sources

PubMed2002

Association of the CTLA4 3' untranslated region polymorphism with the susceptibility to rheumatoid arthritis.

Cytotoxic T-lymphocyte antigen 4 (CTLA4) gene polymorphism located in the 3' untranslated region (UTR) was investigated in 141 Spanish patients (38 men and 103 women) with rheumatoid arthritis (RA) and in 194 ethnically-matched healthy controls. Twenty alleles having different numbers of (AT) repeats (from 7 to 32) were found in this population. (AT)7 and (AT)16 were the most frequent alleles, and accounted for almost two-thirds of the allelic frequency in the control population. Consequently, alleles were assigned as L (large: 16 or more AT repeats) or S (short: less than 16 AT repeats). When the L/S distribution in patients and controls were compared, an increase of L alleles was observed among patients (49.9% vs. 39.7%; p = 0.02; p(c) = 0.04, odds ratio [OR] = 1.46; 95% confidence interval [CI], 1.06-2.01). Hence, the frequency of S alleles was decreased among patients (51.1% vs. 60.3%; p = 0.02; p(c) = 0.04; OR = 0.69; 95%CI, 0.50-0.95). Moreover, a statistically significant decrease in the frequency of S/S individuals was observed among RA patients (27.7% versus 40.7%; p = 0.01; p(c) = 0.03; OR = 0.56; 95%CI, 0.34-0.91). These differences were irrespective of the HLA "shared epitope" (SE) status, and were observed similarly among SE+ as well as among SE- patients. After combining these data with other reported previously by us, from studies of CTLA4 49 (A/G) and -318 (C/T) polymorphisms, we conclude that the strongest association between CTLA4 gene polymorphisms and RA susceptibility occurs with the 3' UTR polymorphism.

3' Untranslated Regions↗

PubMed2002

Association of NRAMP1 promoter gene polymorphism with the susceptibility and radiological severity of rheumatoid arthritis.

The natural resistant-associated macrophage protein 1 (NRAMP1) has been proposed as a candidate gene for the susceptibility to autoimmune diseases. In this study, the possible role of the functional polymorphism located at the promoter region of NRAMP1 gene in the susceptibility and clinical outcome of rheumatoid arthritis (RA) was investigated. A total of 141 Spanish RA patients and 194 controls previously typed for HLA-DRB1* were genotyped for the NRAMP1 polymorphism. No significant differences in the distribution of frequencies among RA patients and controls were observed. Nevertheless, when patients and controls were stratified according to their HLA shared epitope (SE) status, an increase of 2/2 genotype among SE-negative (SE-) patients with respect to SE- controls was observed (23% vs 7%, OR = 3.74, 95% CI 1.31-10.72). In addition, the possible role of this polymorphism in the clinical course of RA was investigated in a subgroup of 82 patients who were prospectively followed during a mean of 9 years. After follow-up, an increase of patients with the homozygous 2/2 genotype was detected among those with severe small joint radiological involvement: 73% of patients 2/2 had a severe form in contrast to 37% of patients with the genotype 2/3 and 30% of patients bearing 3/3 OR = 5.45, 95% CI 1.14-34.24). In conclusion, NRAMP1 gene promoter polymorphism could influence the radiological severity of rheumatoid arthritis and disease susceptibility, particularly in individuals lacking HLA-linked risk factors.

Arthritis, Rheumatoid↗

PubMed2001

Association of vitamin D receptor genotypes with early onset rheumatoid arthritis.

The presence of certain vitamin D receptor (VDR) genotypes has been associated with low bone mineral density (BMD) in elderly populations as well as with accelerated bone loss in patients with rheumatoid arthritis (RA). In the present study, VDR genotypes from 120 Spanish patients with RA were investigated. Three VDR gene polymorphisms (BsmI, ApaI and TaqI) were investigated using polymerase chain reaction followed by enzymatic digestion. The distributions of VDR allelic frequencies were similar in patients and controls and therefore no influence of VDR polymorphisms on rheumatoid arthritis susceptibility could be demonstrated. However, in an analysis of the clinical features of the different VDR-related genetic subgroups, the BB/tt genotype, defined by the BsmI and TaqI restriction site polymorphisms, was identified to be weakly associated with an early onset RA in female patients. This VDR genotype has been associated with a low BMD level in various studies. When patients were stratified according to the presence of the shared HLA epitope SE, it was found that SE + female patients bearing the BB/tt genotype showed the earliest disease onset. The mechanisms by which the VDR polymorphism is associated with RA is unknown, but they could be related to the immunoregulatory properties of vitamin D.

Age of Onset↗

PubMed2001

Molecular epidemiology of a multiresistant Pseudomonas aeruginosa outbreak in a paediatric intensive care unit.

After isolation of multiresistant (MR) Pseudomonas aeruginosa from 3 hospitalized patients in a paediatric intensive care unit (PICU), a prospective surveillance programme was established to detect infected and/or colonized patients in the hospital. Isolates were examined by means of outer membrane protein (OMP) profiles, serotyping and DNA genomic analysis using pulsed-field gel electrophoresis (PFGE). Fifty-five P. aeruginosa strains were isolated from 23 hospitalized patients during September and October 1997. The median hospital stay before isolation of P. aeruginosa was 8 d. PFGE demonstrated that the same clone infected 14 patients, 4 of whom were not hospitalized in the PICU. Susceptibility patterns and OMP profiles correlated with PFGE results in 37.8% and 36.4% of cases, respectively. Serotype O11 correlated with pattern A in 77% of cases and serotype O4 correlated with unrelated strains in 75% of cases but did not discriminate between outbreak and unrelated isolates. Extensive investigation of cultures failed to identify a reservoir of P. aeruginosa. PFGE was superior to OMP analysis and serotyping for discriminating between strains. The possible mode of acquisition for most of the patients infected with the same clone was cross-contamination.

Adolescent↗

PubMed2001

Differences in morphological age-related dental changes depending on postmortem interval.

Morphological methods for age estimation from teeth have been developed and applied to samples without taking the postmortem interval into consideration. We studied differences in morphological age-related changes between fresh extracted teeth and teeth from human skeletal remains in order to develop appropriate dental age estimation methods according to the time after death. Forty-three permanent teeth from dental patients were compared to 37 teeth obtained from human skeletal remains with a postmortem interval from 21 to 37 years. Morphological age-related changes were investigated by measuring variables on intact and half-sectioned teeth. A new computer assisted image analysis procedure to avoid subjectivity was developed to measure variables in sectioned specimens. Dental color, translucency length, attrition, cementum apposition, and secondary dentin showed higher values in teeth from human skeletal remains than in fresh extracted teeth. Variables obtained by morphometric analysis of computer-generated images (tooth length, tooth width, root length, and root area) showed higher values in fresh extracted teeth than in teeth from skeletal remains. The postmortem interval affects age-related morphological changes, and therefore different methods should be used for teeth of unknown postmortem interval.

Adult↗

PubMed2001

[Docosahexaenoic acid (DHA) in fetal development and in infant nutrition].

Docosahexanoic acid (C22:6, DHA) is a highly unsaturated omega-3 fatty acid that forms part of the central nervous and visual system structures. DHA is synthesized from its precursor, alfa-linolenic acid, that is also a omega-3 fatty acid and can be obtained from vegetable oils. Marine organisms, specially fish, are good nutritional sources of DHA and eicosapentanoic acid (EPA), another omega-3 fatty acid that has a role in vascular homeostasis. DHA increases membrane fluidity, improving neurogenesis, synaptogenesis and the activity of retinal photoreceptors. The fetus, specially during the last trimester of pregnancy, has high DHA requirements. It is provided by the mother, since fetal DHA synthesis is negligible in this stage of development. Breast feeding provides DHA to the child, but most replacement artificial formulas do not provide this fatty acid. At the present moment, many products for infant nutrition contain DHA.

Brain↗

PubMed2000

The HIV-1 gp120 inhibits the binding of adenosine deaminase to CD26 by a mechanism modulated by CD4 and CXCR4 expression.

HIV-1 external envelope glycoprotein gp120 inhibits adenosine deaminase (ADA) binding to its cell surface receptor in lymphocytes, CD26, by a mechanism that does not require the gp120-CD4 interaction. To further characterize this mechanism, we studied ADA binding to murine clones stably expressing human CD26 and/or human CD4, and transiently expressing human CXCR4. In this heterologous model, we show that both recombinant gp120 and viral particles from the X4 HIV-1 isolate IIIB inhibited the binding of ADA to wild-type or catalytically inactive forms of CD26. In cells lacking human CXCR4 expression, this gp120-mediated inhibition of ADA binding to human CD26 was completely dependent on the expression of human CD4. In contrast, when cells were transfected with human CXCR4 the inhibitory effect of gp120 was significantly enhanced and was not blocked by anti-CD4 antibodies. These data suggest that the interaction of gp120 with CD4 or CXCR4 is required for efficient inhibition of ADA binding to CD26, although in the presence of CXCR4 the interaction of gp120 with CD4 may be dispensable.

Adenosine Deaminase↗

PubMed2000

A new spontaneous mouse mutation in the Kcne1 gene.

A new mouse mutant, punk rocker (allele symbol Kcne1(pkr)), arose spontaneously on a C57BL/10J inbred strain background and is characterized by a distinctive head-tossing, circling, and ataxic phenotype. It is also profoundly and bilaterally deaf. The mutation resides in the Kcne1 gene on Chromosome (Chr) 16 and has been identified as a single base change within the coding region of the third exon. The C to T nucleotide substitution causes an arginine to be altered to a termination codon at amino acid position 67, and predictably this will result in a significantly truncated protein product. The Kcne1(pkr) mutant represents the first spontaneous mouse model for the human disorder, Jervell and Lange-Nielsen syndrome, associated with mutations in the homologous KCNE1 gene on human Chr 21.

Amino Acid Sequence↗

PubMed2000

The application of dental methods of identification to human burn victims in a mass disaster.

This paper deals with the usefulness of dental identification in the case of 28 human burn victims of a bus accident in Spain. Postmortem forensic procedures for identification were used including general external examination, routine photographs and radiographs and complementary biological methods. Dental identification was also used and a description of the method is presented. Dental identification was established in 57% of the cases. When victims were less than 20 years of age, the success rate of identification by dental methods was higher (76% of victims in this age group). The assessment of dental age allowed the establishment of identity of four victims. We recommend that dental procedures be used in human identification after mass disasters. Odontological and radiographic procedures are powerful methods when dealing with burn victims.

Accidents, Traffic↗

PubMed2000

The matrix metalloproteinase gelatinase A in human dentine.

A dentine protein extraction protocol was modified in order to identify matrix metalloproteinase gelatinolytic activities in the non-mineralized and mineralized phases of human dentine. Dentine proteins from 24 individual permanent molars from patients aged 15-73 years were sequentially extracted, first with guanidinium chloride (G1 extract), then EDTA (E extract), and after this demineralization step, again by guanidinium chloride (G2 extract) to dissociate collagen-associated proteins. Extracts were analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and the gels were processed by Western blotting and zymography to detect gelatinolytic activities. Active and latent forms of gelatinase A were identified in the non-mineralized dentine fraction (G1 extract) of 58% of the teeth. Other gelatinolytic species were also detected by zymography with apparent M(r) of 92, 54 and 30 kDa. Although gelatinase A was detected in the G1 extracts of teeth from all ages, indicating more recent synthesis and remodelling of the predentine, gelatinase A was never detected in any E extract or in the G2 extracts of patients older than 41 years. The presence of the active form of gelatinase A in mineralized human dentine implicates this enzyme in dentine mineralization.

Adolescent↗

PubMed2000

Gelatinase A in human dentin as a new biochemical marker for age estimation.

Dentin proteins from 24-individual permanent molars from patients aged 15 to 73 years were sequentially extracted, with guanidinium chloride (G1-extract) and then with EDTA; after demineralization, the material was again extracted with guanidinium chloride (G2-extract). Extracts were analyzed by SDS-PAGE electrophoresis and the gels were processed for zymography to detect gelatinolytic activities. The patterns of gelatinase A distribution differed in the different dentin protein fractions, and the changes varied with age. Significant differences were detected in gelatinase A in G2-extracts between individual younger than 20 years old and the rest of the sample (chi2exp = 19.429; 1 d.f.; p < or = 0.001). The incidence of true and false positives and negatives, and sensitivity and specificity for the presence of gelatinase A in dentin extracts, were calculated. Determination of gelatinase A in human dentin may be a useful marker to estimate age, especially when other morphological methods are of limited usefulness.

Adolescent↗

PubMed1999

Stromal cell-derived factor-1alpha associates with heparan sulfates through the first beta-strand of the chemokine.

Biological properties of chemokines are believed to be influenced by their association with glycosaminoglycans. Surface plasmon resonance kinetic analysis shows that the CXC chemokine stromal cell-derived factor-1alpha (SDF-1alpha), which binds the CXCR4 receptor, associates with heparin with an affinity constant of 38.4 nM (k(on) = 2.16 x 10(6) M(-1) s(-1) and k(off) = 0.083 x s(-1)). A modified SDF-1alpha (SDF-1 3/6) was generated by combined substitution of the basic cluster of residues Lys(24), His(25), and Lys(27) by Ser. SDF-1 3/6 conserves the global native structure and functional properties of SDF-1alpha, but it is unable to interact with sensor chip-immobilized heparin. The biological relevance of these in vitro findings was investigated. SDF-1alpha was unable to bind in a CXCR4-independent manner on epithelial cells that were treated with heparan sulfate (HS)-degrading enzymes or constitutively lack HS expression. The inability of SDF-1 3/6 to bind to cells underlines the importance of the identified basic cluster for the physiological interactions of SDF-1alpha with HS. Importantly, the amino-terminal domain of SDF-1alpha which is required for binding to, and activation of, CXCR4 remains exposed after binding to HS and is recognized by a neutralizing monoclonal antibody directed against the first residues of the chemokine. Overall, these findings indicate that the Lys(24), His(25), and Lys(27) cluster of residues forms, or is an essential part of, the HS-binding site which is distinct from that required for binding to, and signaling through, CXCR4.

Animals↗

PubMed1999

Deoxypyridinoline crosslinks in human dentin and estimation of age.

A new biochemical method for estimation of dental age from human dentin is presented. An adaptation and modification of a dentin protein extraction protocol was developed by which deoxypyridinoline crosslinks were measured using an enzyme immunoassay technique. Deoxypyridinoline, a non-reducible collagen crosslink, was measured in human dentin samples from permanent individual molars. The measurement of this protein in dentin samples from 22 patients with ages ranging from 15 to 73 years old was carried out to obtain an estimate of age at death. By linear regression between deoxypyridinoline values and age, equations for age calculations were computed. The error between the estimated age and the known age at extraction was calculated. Our results show that this method produces an expected associated error on calibration averaging 14.9 years about the mean estimated values, at a 65% level of confidence. Values of sensitivities and specificities were calculated for deoxypyridinoline at different ages. We conclude that determination of deoxypyridinoline in human dentin extracts is a new and reliable procedure, potentially suitable for most forensic laboratories and which could be a useful tool to estimate human dental age. This method could be considered as an alternative method to calculate dental age, contributing to a more accurate estimation of chronological age when used in addition to other morphological or biochemical dental methods.

Adolescent↗

PubMed1999

Chronic renal failure in pediatrics 1996. Chilean survey.

The Nephrology Branch of the Chilean Pediatric Society has greatly influenced the development of government health plans regarding the management and care of patients under 18 years with chronic renal failure (CRF). In order to assess the status of children with CRF in Chile up to 1996, a questionnaire was sent to all pediatric nephrologists in charge of those children. The total sample was of 227 patients under 18 years, giving a national prevalence of 42.5 and an incidence of 5.7 per million inhabitants; of these patients, 50.7% were male, 58.6% over 10 years and 15% younger than 5 years. The most frequent etiologies of CRF were: obstructive uropathy, 18.1%; hypo/dysplasia, 16.7%; reflux nephropathy, 16.7%; and glomerulopathies, 16.3%. Although 48% of patients were on conservative medical treatment, 42.2% of these were in end-stage renal disease, 22.9% were on dialysis, and 29.1% had undergone renal transplantation. Of the dialysis group, 75% were on peritoneal dialysis. Of the transplanted children, 78.8% had normal renal function, but 16.7% returned to dialysis. Three-year graft survival and patient survival were 68% and 94%, respectively.

Adolescent↗

PubMed1999

Association of HLA shared epitope with joint damage progression in rheumatoid arthritis.

A nine years prospective study was performed on 82 Spanish rheumatoid arthritis patients with a disease duration of less than two years at the study entry, in order to evaluate the role of HLA markers in the susceptibility and progression of rheumatoid arthritis. Radiological evaluation of disease severity was performed at the time of diagnosis and 9 years later. High resolution HLA-DR typing demonstrated that the presence of the shared epitope (SE) was more frequent among patients (61% vs. 31% in controls; p = 0.00003; OR = 3.48). Fourteen patients carried two SE+ HLA-DRB1 alleles (SE+/+); 36, one single allele (SE+/-) and 32 were SE negative (SE-/-). HLA-DR4 (particularly DRB1*0401 and DRB 1*0405) and HLA-DR10 were increased among patients. At study entry, the frequencies of locally severe (hands and feet) RA were more frequent among SE+/+ patients (79%) than among SE+/- (47%) and SE-/-(44%) patients (p = 0.05; RR = 1.80). After 9 years of disease these differences disappeared, whereas differences in the extent of the disease arise: 79%, 50% and 32% of SE+/+, SE+/- and SE-/- patients respectively showed large joints involvement (shoulders, elbows, hips and knees) (p = 0.01; RR = 2.44 for SE+/+ vs. SE-/-; and p = 0.04; RR = 1.81 for SE+ vs. SE-). These results suggest that the presence of the shared epitope is associated with the extent and progression of radiological joint damage in rheumatoid arthritis.

Adult↗

PubMed1999

Complex associations between HLA-DRB1 genes and female rheumatoid arthritis: results from a prospective study.

We followed 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis (RA) to analyze whether patient sex influenced the HLA-DRB1 associations with disease susceptibility. Results showed that, although a high increase of the shared epitope (SE) was observed in both genders, distribution of HLA-DRB1 specificities differs from males to females: DR1 was increased among male patients, whereas DR4 as well as DR10 were preferentially associated with female RA. To further explore whether this phenomenon operates either on susceptibility or on disease progression, 82 patients (25 males and 57 females) among the whole group were followed during the first 8 to 10 years of their disease. Results from this prospective study showed that the association of the SE with radiological disease severity was found in both male and female patients, although it was stronger among the latter group. Interestingly, DR1- as well as DR4-related alleles contributed to the high frequency of SE among female patients with early small-joints severe RA and/or long-term large-joint erosions. These results suggest that HLA polymorphism might be involved in RA pathogenesis through two mechanisms: (a) in combination with patient sex, operating in disease induction; and (b) independent of patient sex, influencing disease severity and progression.

Arthritis, Rheumatoid↗

PubMed1999

CTLA4 polymorphisms in Spanish patients with rheumatoid arthritis.

Cytotoxic T-lymphocyte antigen 4 (CTLA4) polymorphisms located in the promotor region at positions -318 (C/T) and in exon 1 (49 A/ G) were investigated in 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis and in 305 ethnically-matched healthy controls. When the allelic and genotypic frequencies corresponding to the CTLA4 -318 position were compared, no significant differences between patients and controls were found. However, when the CTLA4 49 A/G polymorphism was analysed, a significant increase of A/G heterozygous individuals among female patients (48.5% vs. 33.8% in controls; P=0.008; OR=2.0) was observed. This increase was absent among males (37.8%, P=NS). Analysis of the CTLA4 49 polymorphism with respect to HLA-DRB1 typing demonstrated a significant increase of A/G heterozygosity in the HLA-DR3-positive patient group compared with HLA-DR3-negative patient group (14/19, 74% vs. 49/119, 41%; P=0.009, OR=4.0). The increase of A/G genotype among HLA-DR3-positive patients was found in both males (4/6, 67%) and females' (10/13, 77%), although statistical differences were only reached in the female group. These results provide new insight into this complex association, confirm previous data from other studies, and suggest that the CTLA4 gene could be involved in the pathogenesis of rheumatoid arthritis.

Abatacept↗

PubMed1999

Essential fatty acids as determinants of lipid requirements in infants, children and adults.

Essential fatty acids (EFA) are the indispensable component of the lipid supply beyond the provision of energy as a fuel for oxidation. They serve as dietary precursors for the formation of prostanoids and other eicosanoids thus are of great significance in health and modulation of disease conditions. Eicosanoids are powerful autocrine and paracrine regulators of cell and tissue functions: thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, and uterine contraction. Recent attention has focused on the effect of n-3 and n-6 long chain EFAs in normal fetal development. Results from human infant studies suggest that n-3 fatty acids are needed for optimal development of visual and brain function. Human milk is the best and only time proven source of fat and dietary essential fatty acids for infant feeding. International recommendations for n-3 and n-6 EFA dietary intake are reviewed and suggested intakes for long chain EFAs are provided.

Adult↗