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Biomedical subjects

I Aguilera

Publications and source records attributed to I Aguilera.

At least 19 recordsLinked to original sources
PubMed2006

Chronic bronchitis and urban air pollution in an international study.

OBJECTIVES: The chronic effects of urban air pollution are not well known. The authors' aim was to investigate the association between the prevalence and new onset of chronic bronchitis and urban air pollution. METHODS: Subjects from the general population randomly selected for the European Community Respiratory Health Survey (ECRHS I) during 1991-93 in 21 centres in 10 countries were followed up from the years 2000 to 2002 (n = 3232 males and 3592 females; average response rate = 65.3%). PM2.5 and elements, with the same equipment at centre level, and home outdoor NO2 in 1634 individuals were measured. Hierarchical models were used. RESULTS: The prevalence and new onset of chronic phlegm during follow up were 6.9% and 4.5%, respectively, 5.3% in males and 3.5% in females. Smoking, rhinitis, poor education, and low social class were associated with (prevalence and new onset of) chronic phlegm in both genders, and occupational exposures in males and traffic intensity (adjusted odds ratio for constant traffic, OR = 1.86; 95% CI 1.24 to 2.77) as well as home outdoor NO2 (OR > 50 microg/m3v < 20 microg3 = 2.71; 95% CI 1.03 to 7.16) among females. PM2.5 and S content at centre level did not show any association with prevalence or new onset of chronic phlegm. Similar results were obtained with chronic productive cough. CONCLUSION: Individual markers of traffic at household level such as reported intensity and outdoor NO2 were risk factors for chronic bronchitis among females.

Adult↗
PubMed2006

De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis.

De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It appears in patients with liver transplants for non-AIH etiology. The few cases in the literature make it a little known entity due to mechanisms that are unclear. We present the case of a woman with a liver transplant whose graft developed de novo AIH. Diagnosed with primary biliary cirrhosis, the patient underwent liver transplantation for refractory pruritus. Sixteen months after transplantation, we detected alterations in the hepatic profile with hypertransaminasemia and elevated alkaline phosphatase, together with elevated antinuclear antibodies. IgG levels were normal. Histological findings indicated AIH. The patient responded rapidly to treatment with prednisolone and azathioprine. De novo AIH in patients transplanted for PBC may cause graft dysfunction. This report also analyzes the case with respect to the other four reported cases, discussing etiologic hypotheses.

Biopsy↗
PubMed2005

Antibodies against the donor antigen glutathione S-transferase T1 after renal transplantation.

The aim of the present study was to determine whether a kidney graft expressing the glutathione S-transferase T1 enzyme (GSTT1) could cause an alloimmune response in a recipient with the null GSTT1 genotype that was similar to that observed in liver transplant. We have found anti-GSTT1 antibodies in the sera of a number of patients and confirmed that only one of the four possible genetic combinations--positive donor/null receptor--could lead to the production of these antibodies. Nevertheless, the main finding of this study is that in kidney transplantation, this mismatch was not sufficient to trigger an immune reaction. Longer follow-up of the posttransplant evolution of the patients is required in order to clarify the contribution of the factors involved in this process.

Adult↗
PubMed2005

Lack of association of recipient MCP-1 gene promoter polymorphism with acute graft rejection after orthotopic liver transplantation.

Acute graft rejection after orthotopic liver transplantation (OLT) is associated with leukocyte infiltration of the graft. Monocyte chemoattractant protein-1 (MCP-1) is a beta-chemokine involved in the attraction and accumulation of mononuclear granulocytes toward sites of inflammation. A biallelic polymorphism (G/A) at position -2518 of the MCP-1 gene has been described. Cells obtained from individuals with the GG or AG genotypes have been found to produce more MCP-1 than those obtained from individuals with the AA genotype. The goal of this study was to assess the possible association between this polymorphism and susceptibility to acute graft rejection after OLT. One hundred fifty Caucasian liver transplant recipients from the South of Spain underwent genotyping using a polymerase chain reaction (PCR) amplification followed by restriction fragment length polymorphism (RFLP). No significant differences were observed when patients with versus without acute rejection episodes were compared for the distribution of -2518 MCP-1 genotypes. The present study supports the lack of involvement of polymorphism at position -2518 (A/G) of the MCP-1 gene on the susceptibility to acute allograft rejection among OLT recipients.

Base Sequence↗
PubMed2005

Glutathione S-transferase T1 genetic mismatch is a risk factor for de novo immune hepatitis in liver transplantation.

Glutathione S-transferase T1 (GSTT1) is a drug metabolizing enzyme abundantly expressed in liver and kidney cells; it is encoded by a single gene that is absent in 20% of the Caucasian population. Our group found that some liver transplantation patients developed de novo immune hepatitis (IH) and that all of them had anti-GSTT1 antibodies. The main objective of this study was to analyze the influence of a GSTT1 mismatch between donor and recipient in the immune response and the outcome of the graft. We confirmed that only under one of the four possible genetic combinations (null recipient/positive donor) is an alloimmune response triggered with production of anti-GSTT1 antibodies. Therefore, we conclude that this genetic mismatch can be considered a risk factor for de novo IH.

Autoantibodies↗
PubMed2004

[The productive sector].

In the last 25 years, the production sector in Spain has undergone important changes. Among these changes, the important growth of the services sector at the expense of the primary sector, the increasing flexibility of the labour market, and the rise in the female workforce could be considered as the most relevant ones. Spanish women have higher rates of unemployment, temporary jobs and part time contracts than Spanish men. Moreover, job access and work conditions are highly related to gender and social class. Because women are forced to compensate for the scarcity of social services for caring for young children and for dependent elderly, they become informal and socially unrecognised caregivers, preventing them from getting or holding a job, and significantly limiting their opportunities for professional development. These social conditions are closely related with the fact that work conditions for women involve higher temporality rates and shorter contracts than those of men, given the sectors and jobs in which they tend to work (due to segregation). Similarly, workers of the less privileged social classes have poorer work conditions. Thus, women of the lower income class are mainly suffering the worst job contracts and the poorest work conditions. More social services are needed to make it possible to attend to family needs and still be able to access and maintain a job contract. Policies tending to conciliate labour and family life are indispensable and should incorporate measures to equally distribute the house keeping activities between women and men.

Family↗
PubMed2001

Mitochondrial DNA point mutation in the COI gene in a patient with McArdle's disease.

We studied a 57-year-old female patient with clinical and biochemical evidences of McArdle's disease. Her muscle biopsy also revealed signs of mitochondrial proliferation, scattered RRF, and a deficit in complex I of the respiratory chain. Molecular genetic analysis showed that the patient was heterozygous for the most common mutation at codon 49 in the myophosphorylase gene. Mitochondrial DNA analysis of muscle tissue revealed an additional G-to-A transition at nucleotide position 7444 in the cytochrome c oxidase subunit I (COI) gene.

Codon↗
PubMed2001

Antibodies against glutathione S-transferase T1 (GSTT1) in patients with de novo immune hepatitis following liver transplantation.

Four patients of 283 liver-transplant recipients (1.4%) developed de novo immune-mediated hepatitis approximately 2 years after transplantation. Antibodies showing an unusual liver/kidney cytoplasmic staining pattern were detected in the sera of all four patients and one of them was used to screen a human liver cDNA expression library with the aim of identifying the antigenic target of these newly developed antibodies. After cloning and sequencing the gene, it was identified as the gene encoding the glutathion-S-transferase T1 (GSTT1), a 29-kD molecular weight protein, expressed abundantly in liver and kidney. Sera from the other three patients also contained anti-GSTT1 antibodies, two of them demonstrated by immunoblot analysis against the recombinant antigen and the other, which was negative by immunoblot, gave a positive reaction when used directly to screen the same library, suggesting it to be directed to a conformational epitope. The GSTT1 enzyme is the product of a single polymorphic gene that is absent from 20% of the Caucasian population. When we analysed the GSTT1 genotype of the four patients described above, we found that this gene is absent from all of them. Three donor paraffin embedded DNA samples were available and were shown to be positive for GSSTT1 genotype. In accordance with these results, we suggest that this form of post-transplant de novo immune hepatitis, that has been reported as autoimmune hepatitis by others, could be the result of an antigraft reaction in individuals lacking the GSTT1 phenotype, in which the immune system recognizes the GSTT1 protein as a non-self antigen, being the graft dysfunction not the result of an autoimmune reaction, but the consequence of an alo-reactive immune response.

Base Sequence↗
PubMed2001

Molecular structure of eight human autoreactive monoclonal antibodies.

The heavy (H) and light (L) chain V-region sequences of eight human autoreactive immunoglobulin M (IgM) monoclonal antibodies (mAbs: BY-4, BY-7, BY-12, IRM-3, IRM-7, IRM-8, IRM-10 and CDC-1) were determined at the cDNA level. All VH and VL families were identified. Four different VH families were represented, VH3 being the most common as five of the mAbs (BY-7, BY-12, IRM-3, IRM-8 and CDC-1) used genetic elements of this family, whereas VH1, VH2 and VH4 were only present in IRM-7, BY-4 and IRM-10, respectively. BY-4, BY-7, BY-12, IRM-7 and IRM-10 reacted with a variety of self as well as non-self antigens, thus exhibiting polyreactive behaviour. Comparison of the gene segments utilized by these mAbs with their germline counterparts revealed that the gene segments were close to germline configuration. The length of H-CDR3 was found to be relatively long (27-60 nucleotides) among the polyreactive mAbs and the presence of Tyr and Trp residues in this region seems to be of vital importance for polyreactivity. We have analysed the utilization of gene elements and the presence of amino acid residues in regions particularly important for antigen binding, such as CDR. Common molecular features relating to the function of the mAbs are discussed.

Amino Acid Sequence↗
PubMed2001

Mitochondrial disease and stroke.

BACKGROUND AND PURPOSE: It is well known that some mitochondrial disorders are responsible for ischemic cerebral infarction in young patients. Our purpose was to determine, in this prospective ongoing study, whether ischemic stroke is the only manifestation of a mitochondrial disorder in young patients. METHODS: Patients aged </=50 years, admitted to the Stroke Unit from January 1999 to May 2000 with a diagnosis of ischemic stroke of unknown origin, were included in the study. All of them had full biochemical and hematologic tests, neuroimaging studies, transesophageal echocardiography, and extracranial and transcranial Doppler sonography. Patent foramen ovale was ruled out. Lactic acid concentrations were measured after anaerobic exercise of the forearm, and a morphological, biochemical, and molecular study after biceps muscle biopsy was performed. RESULTS: Of the 18 patients so far included, 3 (17%) presented lactic acid hyperproduction after physical exercise, and 6 (33%) showed deficit of the mitochondrial respiratory chain complexes. The molecular analyses have confirmed mitochondrial mutations at base pairs 3243 (characteristic of mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes [MELAS]), 4216, and 15 928. CONCLUSIONS: These results suggest that ischemic stroke may be the only manifestation or the initial manifestation of a mitochondrial disorder.

Adolescent↗
PubMed2000

Lipomatosis, proximal myopathy, and the mitochondrial 8344 mutation. A lipid storage myopathy?

Multiple symmetric lipomatosis (MSL) has been related in some cases to the 8344 point mutation of the tRNA-lysine gene of the mitochondrial DNA, mainly in the context of families with classic myoclonic epilepsy with ragged-red fibers (MERRF) and exceptionally in patients with proximal myopathy as the only manifestation of mitochondrial disease. We report on two families harboring the 8344 mutation. The patients presented with MSL and myopathy, expressed as limb girdle weakness in index cases and as exercise intolerance in the others. All muscle biopsies performed showed lipid storage apart from RRF and respiratory chain complexes deficiency. A possible explanation for both adipose proliferation and lipid storage myopathy in these cases is a disturbance in intermediary lipid metabolism secondary to mitochondrial respiratory chain deficiency that could be related via carnitine deficiency.

Adolescent↗
PubMed1999

Identification of cation-independent mannose 6-phosphate receptor/insulin-like growth factor type-2 receptor as a novel target of autoantibodies.

Two human monoclonal autoantibodies, B-33 and B-24, were generated from the B cells of a patient with scleroderma. Both monoclonal antibodies (mAbs) were composed of mu and lambda chains, and recognized cytoplasmic vesicular structures by indirect immunofluorescence on Hep-2 cell line slides, although mAb B-24 showed an additional diffuse cytoplasmic staining pattern. By Western blot, mAb B-24 exhibited a polyreactive-like binding pattern, whereas mAb B-33 failed to recognize any electroblotted Hep-2 antigen. The polyreactive versus monospecific behaviour of mAbs B-24 and B-33 was further confirmed by enzyme-linked immunosorbent assay (ELISA) with a variety of foreign and autoantigens. The N-terminal sequence of a protein band isolated by affinity chromatography with mAb B-33 was identical to that of cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the insulin-like growth factor type-2 receptor (IGF-2R). Immunofluorescence experiments on Hep-2 cell line slides demonstrated a striking co-localization between the staining pattern exhibited by these mAbs and the pattern obtained using a goat anti-CI-MPR serum, indicating the recognition by B-24 and B-33 of a structure located predominantly in late endosomes. Sequence analysis of the V-region gene segments of B-33 and B-24 showed both to be identical, except for the existence of a point mutation in B-33 located in the H-complementarity-determining region 3 (H-CDR3) (position 100D), which produces a non-conservative replacement of Gly by Ser. This single replacement appears to be responsible for the dramatic change in reactivity of human mAb B-33. The data shown here provide new evidence of the critical role played by the H-CDR3 region in distinguishing a polyspecific from a monospecific antibody. A population study demonstrated the existence of immunoglobulin G (IgG) reactivity against CI-MPR/IGF-2R in serum specimens from five individuals with different pathological conditions, thus indicating that this molecule is a potential target for the human autoimmune response.

Amino Acid Sequence↗
PubMed1999

The rough deal protein is a new kinetochore component required for accurate chromosome segregation in Drosophila.

Mutations in the rough deal (rod) gene of Drosophila greatly increase the missegregation of sister chromatids during mitosis, suggesting a role for this gene product in spindle or kinetochore function. The activity provided by rod also appears to be necessary for the recruitment of two known kinetochore components, Zw10 and cytoplasmic dynein. In this paper we describe the cloning of rough deal and an initial cytological characterization of its product. The Rod protein shares no identifiable structural motif with other known proteins, although apparent homologs exist in the genomes of nematode and man. By immunocytochemistry we show that Rod displays a dynamic intracellular staining pattern, localizing first to kinetochores in prometaphase, but moving to kinetochore microtubules at metaphase. Early in anaphase the protein is once again restricted to the kinetochores, where it persists until the end of telophase. This behavior is in all respects similar to that described for Zw10, and suggests that the proteins function together.

Amino Acid Sequence↗
PubMed1999

[Mitochondrial encephalomyopathy of late presentation with progressive ophthalmoplegia, tremor and diffuse leukoencephalopathy].

A 60-year-old woman had developed ptosis, progressive external ophthalmoplegia and action tremor over the last ten years. Physical examination also revealed short stature and retinal pigmentation. Anaerobic forearm exercise test showed increase of basal lactate and rise of lactate/piruvate index. Biceps biopsy displayed numerous ragged red fibers. Respiratory chain studies were consistent with complex I deficiency. Point mutations or deletions in mitochondrial DNA were not found. MR identified a diffuse leukoencephalopathy over both cerebral hemispheres, mesencephalon, pons and cerebellum. The late and sporadic onset of a progressive external ophthalmoplegia outlining a Kearns-Sayre syndrome is striking. A leukoencephalopathy associated with mitochondrial encephalomyopathy is an infrequent finding. The action tremor of this patient could be symptomatic of her mitochondrial disfunction.

Biopsy↗