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Biomedical subjects

J Martín

Publications and source records attributed to J Martín.

At least 19 recordsLinked to original sources
PubMed2003

Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma.

We have taken advantage of a recently described technique of transformation and immortalization of T lymphocytes using the lymphotropic Herpesvirus saimiri, to achieve long-lasting T-cell lines from gastric cancer patients and healthy volunteers. Blood samples were drawn and T lymphocytes were transformed. Once sustained growth was observed, lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. Cytofluorometric analysis revealed that CD3 and CD45 were found at lower proportion in primary cells from patients than from control individuals (54% vs 75%, p<0.001, 90% vs 96%, p<0.05, respectively), and in HVS-derived T-cell lines (90% vs 98%, p<0.05, 97% vs 100%, p<0.05, respectively). Proliferative analyses showed that primary isolated cells were unable to respond adequately to CD3-, CD2-, and PHA-mediated stimulation, as compared to controls. Similarly, T-cell lines from patients proliferated to a lesser extent when CD3- and CD2-mediated stimuli were considered, especially when simultaneous stimulation via CD3 and CD2 molecules was carried out (47,824 counts per minute [cpm] vs 121,478 cpm, p<0.05). Altogether these results show that the defects reported in T cells from patients with cancer are not exclusively due to tumour-derived factors, since the alterations persist in long-lasting, HVS-transformed, T-cell lines, suggesting that this model seems a suitable one to disclose them.

Adenocarcinoma↗
PubMed2003

A poly(ADP-ribose) polymerase haplotype spanning the promoter region confers susceptibility to rheumatoid arthritis.

OBJECTIVE: To investigate the association of the poly(ADP-ribose) polymerase 1 (PARP-1) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition. METHODS: An association study with 213 Spanish RA patients and 242 healthy subjects was carried out to investigate the association of all known PARP-1 gene promoter polymorphisms, i.e., a CA microsatellite repeat, a poly(A)(n), and 3 single point mutations (C410T, C1362T, and G1672A), with disease susceptibility. Additionally, we analyzed the distribution of PARP-1 polymorphisms in 58 Spanish families with 1 or more affected members. RESULTS: Upon complete genotyping of the panel of 455 samples, strong linkage disequilibrium was observed among the 5 PARP-1 polymorphisms. Only 2 PARP-1 haplotypes were detected: haplotype A (410T-[A](10)-[CA](10-12)-1362C, which includes short PARP-1 CA alleles) and haplotype B (410C-[A](11)-[CA](13-20)-1362T, always paired with long PARP-1 CA variants). Regarding the G1672A variation, although linkage disequilibrium was detected, it did not seem to be part of the conserved haplotypes described. Haplotype B was statistically overrepresented in the RA patient group compared with the healthy subjects (odds ratio 1.42, 95% confidence interval 1.06-1.91, P = 0.019). In addition, a significant dose effect of PARP-1 haplotype carriage on disease predisposition was observed. Of note, within haplotype B, the PARP-1 CA 97-bp allele was found to be the RA-predisposing marker (odds ratio 2.17, 95% confidence interval 1.27-3.72, P = 0.003, corrected P < 0.05). CONCLUSION: Our results demonstrate the existence of 2 unique PARP-1 haplotypes in the Spanish population and provide the first evidence that PARP-1 haplotypes play a role in susceptibility to RA.

Arthritis, Rheumatoid↗
PubMed2003

The inducible nitric oxide synthase promoter polymorphism does not confer susceptibility to systemic lupus erythematosus.

OBJECTIVE: There is increasing evidence that nitric oxide (NO) may be important in the pathogenesis of systemic lupus erythematosus (SLE). One possible explanation for the differences observed in NO production between SLE patients and controls is variation in the 5' promoter region of the NOS2 gene, which controls NOS2 transcription. We studied the possible contribution of (CCTTT)(n) microsatellite polymorphism in the NOS2 promoter region to susceptibility to SLE and the clinical outcome of the disease. METHODS: We analysed the distribution of the multiallelic (CCTTT)(n) repeat within the 5' upstream promoter region of the NOS2 gene, by a polymerase chain reaction-based method, in 117 SLE patients and 199 healthy subjects from southern Spain. RESULTS: No statistically significant differences between SLE patients and healthy controls were observed with regard to the frequency of (CCTTT)(n) microsatellite repeats of any given length. Similarly, no associations were found with any of the clinical characteristics tested. CONCLUSION: We conclude that polymorphism in the NOS2 gene promoter does not play a relevant role in the pathogenesis of SLE in our population.

Adolescent↗
PubMed2003

Association of MICA-A5.1 allele with susceptibility to celiac disease in a family study.

OBJECTIVE: The aim of this study was to analyze the role of the major histocompatibility complex class I chain-related gene A (MICA) transmembrane polymorphism in celiac disease (CD) susceptibility. METHODS: Sixty-one celiac Spanish families were genotyped for MICA transmembrane polymorphism by a polymerase chain reaction method combined with fluorescent technology. A transmission disequilibrium test was performed to investigate the preferential transmission of MICA alleles to the affected offspring. RESULTS: The MICA A5.1 allele was shown to be significantly transmitted to the affected siblings. This association was independent of the CD-predisposing DQ2 haplotype. Additionally, we classified our celiac families into typical and atypical groups as we found a significant association with MICA A5.1 in typical celiac families. There was also an association tendency with atypical families. CONCLUSIONS: Our data suggest that the MICA A5.1 allele is associated with CD development independently of DQ2-extended haplotype and clinical forms of CD.

Alleles↗
PubMed2002

Theoretical study of the morphologically originated noise associated with the transmittance of a precipitation system.

In this paper we present the results of a computational study that analyses the relationship between the noise associated with the optical transmittance of a system of particles and the morphology of such particles. Computational algorithms have been developed in order to represent the different morphologies within a wide range of sizes. By using this methodology, it has been possible to study the morphology of particles in a virtual system, therefore avoiding the distortions that would inevitably be present in a real system. As a consequence of this study, a classification of the morphologies observed has been made according to the amount of noise they would add to the transmittance of a system of particles. The theoretical results obtained are in good agreement with the available experimental data obtained in real systems.

Journal Article↗
PubMed2002

No evidence for association of the inducible nitric oxide synthase promoter polymorphism with Trypanosoma cruzi infection.

The purpose of the present study was to address the possible contribution of the (CCTTT)n microsatellite polymorphism in the NOS2 promoter region to the susceptibility to chronic Trypanosoma cruzi infection and to Chagas' disease related cardiomyopathy. We determined the (CCTTT)n genotypes in a sample of 76 serologically positive chagasic individuals and in 78 healthy controls. No statistically significant differences were observed between total chagasic patients and healthy controls with regard to frequency of the (CCTTT)n microsatellite repeat of any given length. Likewise, we found no differences in the distribution of the (CCTTT)n microsatellite repeats between seropositives without manifestations of the disease and those with chagasic cardiomyopathy. Our data suggest that the NOS2 promoter pentanucleotide microsatellite polymorphisms analyzed do not play a major role in the pathogenesis of chronic T. cruzi infection in this Peruvian sample.

Animals↗
PubMed2002

A new allele within the transmembrane region of the human MICA gene with seven GCT repeats.

Major histocompatibility complex class I chain-related genes (MIC) belong to a multicopy gene family located within the HLA class I region of chromosome 6. They encode for proteins that have a completely different organization, expression, and products from classical HLA class I gene products. One member of this family is the MICA gene, which is characterized by its high degree of polymorphism, with over 50 MICA alleles described. Moreover, MICA exon 5 presents a microsatellite polymorphism consisting of a variable number of GCT repeats that encode for 4, 5, 6, 9, or 10 alanine residues, and a variant (MICA A5.1) that includes a nucleotide insertion (GCT-->GGCT). In this study, we report a novel allele in the transmembrane region of the MICA gene consisting of seven GCT repeats found in a family based study of MICA polymorphism in celiac disease.

Base Sequence↗
PubMed2002

Genetic determinants of rheumatoid arthritis: the inducible nitric oxide synthase (NOS2) gene promoter polymorphism.

An association study and a linkage analysis were carried out in parallel in order to investigate the association of the inducible nitric oxide synthase (NOS2) gene promoter polymorphism with rheumatoid arthritis (RA) predisposition and/or outcome including a -954G-C mutation, a di-allelic (TAAA)(n) marker and the highly polymorphic (CCTTT). The -954G-C point mutation occurred non-polymorphic and the di-allelic (TAAA)(n) marker was not associated with RA predisposition. The (CCTTT)(n)locus showed a trend for RA association in the case-control study, however, stratification data by Class II status did not yield significant effect and overall, the family study showed no significant association nor linkage for any of the markers under study using TDT and non-parametric linkage respectively. Finally, no influence was detected regarding any of the clinical parameters tested. After evaluating for the first time the influence of NOS2 promoter polymorphism in RA, it seems to have no major effect on disease susceptibility and/or outcome.

Alleles↗
PubMed2002

Complete characterization of the DQB1 first exon polymorphism.

Here we report an additional source of variation resulting from genetic polymorphism in HLA-DQbeta1 genes, namely, allelic diversity in the first exon of the HLA-DQB1 locus, which encodes the leader peptide sequence. Six different variants, including a novel polymorphic site, were detected among the DBQ1 haplotypes.

Exons↗
PubMed2001

Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors.

We have introduced a point mutation in the first coding exon of the locus encoding the cyclin-dependent kinase 4 (Cdk4) by homologous recombination in embryonic stem cells. This mutation (replacement of Arg24 by Cys) was first found in patients with hereditary melanoma and renders Cdk4 insensitive to INK4 inhibitors. Here, we report that primary embryonic fibroblasts expressing the mutant Cdk4R24C kinase are immortal and susceptible to transformation by Ras oncogenes. Moreover, homozygous Cdk4(R24C/R24C) mutant mice develop multiple tumors with almost complete penetrance. The most common neoplasia (endocrine tumors and hemangiosarcomas) are similar to those found in pRb(+/-) and p53(-/-) mice. This Cdk4 mutation cooperates with p53 and p27(Kip1) deficiencies in decreasing tumor latency and favoring development of specific tumor types. These results provide experimental evidence for a central role of Cdk4 regulation in cancer and provide a valuable model for testing the potential anti-tumor effect of Cdk4 inhibitors in vivo.

3T3 Cells↗
PubMed2001

The -174/-597 promoter polymorphisms in the interleukin-6 gene are not associated with susceptibility to multiple sclerosis.

Interleukin-6 (IL-6) has been implicated in the etiology of experimental autoimmune encephalomyelitis (EAE) in transgenic animals and contributes to neuropathology in humans. A single nucleotide polymorphism (SNP) at position -174 in the IL-6 gene promoter (IL-6pr) appears to influence IL-6 expression. Complete linkage disequilibrium was observed between the -174 and the -597 alleles. The aim of this study was to investigate the possible influence of -174/-597 IL-6pr polymorphisms on susceptibility to multiple sclerosis (MS). Genotyping of the -597 variant was performed by an RFLP method in 131 MS patients [88 relapsing-remitting (RR-MS), 43 secondary progressive (SP-MS)] and 157 healthy subjects. No differences were found between MS patients and controls with respect to the distribution of -597 IL-6pr genotypes. Neither was found when genotypes were analyzed according to the clinical course of the disease (RR-MS or SP-MS). Future studies focusing on complex transcriptional interactions between the IL-6pr and 3' flanking region polymorphic sites will be necessary to determine the IL-6 haplotype influence on susceptibility to MS.

Adult↗
PubMed2001

Rheumatoid arthritis in southern Spain: toward elucidation of a unifying role of the HLA class II region in disease predisposition.

OBJECTIVE: To evaluate the contributions of HLA-DQ and -DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II region's contribution to RA predisposition. METHODS: One hundred sixty RA patients and 153 healthy controls were typed for HLA-DRB1 and -DQB1 using high-resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA-positive DRBI alleles according to the RAP model. RESULTS: DQ3 (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3-homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB1*1001-carrying haplotype; no DRB1*1001-homozygous patients were observed. DRBI*0401 played a unique role in the contribution of DQ3-DR4 haplotypes to RA, in spite of its low frequency in southern Spain. CONCLUSION: The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3-DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA-DQ and -DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.

Alleles↗
PubMed2001

Experimental study of precipitating systems; computerised analysis of the optical transmittance and associated noise.

The change of the transmittance in a precipitant system has been measured by using a focused laser beam into a precipitation cell in which the precipitate was generated by an injection technique. We have monitored the evolution of the transmittance on several precipitation processes with different chemicals (PbI2, PbSO4, BaSO4 and BaC2O4) and quantities of precipitated mass (20.0, 17.5, 15.0, 12.5 and 10.0 mg). The noise associated to the transmittance signal has been obtained by a numerical procedure based on computer analysis, finding that it provides information about particle shape features and nucleation kinetics.

Journal Article↗
PubMed2001

Study of precipitant systems by computerised simulation. Influence of optical elements on the noise associated with the transmittance.

The transmittance signal of a precipitant system measured with a focused laser beam carries associated noise coming from several sources. In this work, we have studied the influence of the focal parameters (wavelength, focal length and prefocused radius of the beam) on the maximum noise reached in equivalent nucleation processes. For this purpose, a simulation program of precipitating systems, designed in FORTRAN 90, has been developed. The program generates simulated transmittances, which are processed by another computer program to extract associated noise. Wide ranges of values of the focal parameters have been analysed, finding relationships between the maximum noise and the focal parameters. They have been justified in connection with the changes observed in the radial parameters, which define the size and shape of the focused path.

Journal Article↗
PubMed2001

[Polyps of the biliary tract: is their preoperative diagnosis possible?].

Bile duct polyps are a very uncommon cause of obstructive jaundice. We present our experience of three patients diagnosed in the last 10 years. Initial presentation usually takes the form of obstructive jaundice associated with abdominal pain, which simulates biliary lithiasis. The diagnosis is usually surgical. Although in some cases radiological studies and endoscopic retrograde cholangiopancreatography (ERCP) may sometimes detect bile duct polyps, exact diagnosis before surgery is very unusual. The radiological signs that suggest the existence of a bile duct polyp in the ERCP seem to be the presence of repletion defects, fixed unilaterally to the biliary conduit, without meniscus and without circumferential stenosis of the affected conduit. The most frequently found polyps are fibroinflammatory, and less frequently adenomatous.

Adult↗
PubMed2001

Lack of association between NRAMP1 gene polymorphisms and Trypanosoma cruzi infection.

Genetic analysis in mice and humans have established the key role of the human natural resistance-associated macrophage protein 1 (NRAMP1) in resistance to intracellular infections. In the present study we investigated whether four NRAMP1 polymorphisms (5'(GT)n, -236 C-->T, D543N, and 3'UTR deletion) were important in determining the susceptibility to Trypanosoma cruzi infections as well as in the development of chagasic cardiac disease. Genotyping for these variants was assessed in 83 seropositive (asymptomatic, n=51, cardiomyopathic, n=32) and 85 seronegative individuals from a Peruvian population where T. cruzi is endemic. No statistically significant differences either between patients and controls or between asymptomatic and cardiomyopathic individuals were observed with respect to NRAMP1 variants. Our data suggest that the NRAMP1 genetic polymorphism analysed do not play a major role in the pathogenesis of T. cruzi infection in this Peruvian sample.

Adolescent↗