PubMed Health⌕ Search

Biomedical subjects

R Vidal

Publications and source records attributed to R Vidal.

At least 19 recordsLinked to original sources
PubMed2002

Influence of deficient alpha1-anti-trypsin phenotypes on clinical characteristics and severity of asthma in adults.

Severe alpha1-anti-trypsin (AAT) deficiency implies a high risk of pulmonary emphysema development. The possible relationship between partial deficiencies of this enzyme and bronchial asthma remains controversial. The objective of this study was to ascertain the distribution of AAT phenotypes in a non-selected asthmatic patient population. Across-sectional study on a sample of 111 patients with asthma was carried out. Demographic and clinical variables were collected with serum IgE concentrations, plasma eosinophil number and serum AAT concentrations determined, together with the Pi phenotype. Asthma was mild in 36 (32.4%) patients, moderate in 45 (40.5%) and severe in 30 (27%). No differences were observed in eosinophil count or serum IgE or AAT concentrations among patients with different degrees of severity. Twenty-two (19.8%) asthmatics with deficient phenotypes for AAT were identified, distributed equally in all severity stages of the disease. No significant differences were found in clinical and functional characteristics, or in asthma morbidity between PiMM and PiMS patients or the heterozygote group (PiMS and PiMZ). Eosinophil count and IgE concentrations did not differ significantly between asthmatics with normal phenotype and heterozygotes. In conclusion, the distribution of AAT phenotypes in asthmatic patients did not differ from that found in the general population. Heterozygote phenotypes for the deficiency do not appear to confer greater severity or different clinical expression of asthma in adults.

Adult↗
PubMed2001

Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide.

Inheritance of apoE4 is a strong risk factor for the development of late-onset sporadic Alzheimer's disease (AD). Several lines of evidence suggest that apoE4 binds to the Alzheimer Abeta protein and, under certain experimental conditions, promotes formation of beta-sheet structures and amyloid fibrils. Deposition of amyloid fibrils is a critical step in the development of AD. We report here that addition of melatonin to Abeta in the presence of apoE resulted in a potent isoform-specific inhibition of fibril formation, the extent of which was far greater than that of the inhibition produced by melatonin alone. This effect was structure-dependent and unrelated to the antioxidant properties of melatonin, since it could be reproduced neither with the structurally related indole N-acetyl-5-hydroxytryptamine nor with the antioxidants ascorbate, alpha-tocophenol, and PBN. The enhanced inhibitory effects of melatonin and apoE were lost when bovine serum albumin was substituted for apoE. In addition, Abeta in combination with apoE was highly neurotoxic (apoE4 > apoE3) to neuronal cells in culture, and this activity was also prevented by melatonin. These findings suggest that reductions in brain melatonin, which occur during aging, may contribute to a proamyloidogenic microenvironment in the aging brain.

Alzheimer Disease↗
PubMed2001

Systemic amyloid deposits in familial British dementia.

Familial British dementia (FBD) is an early onset inherited disorder that, like familial Alzheimer's disease (FAD), is characterized by progressive dementia, amyloid deposition in the brain, and neurofibrillary degeneration of limbic neurons. The primary structure of the amyloid subunit (ABri) extracted from FBD brain tissues (Vidal, R., Frangione, B., Rostagno, A., Mead, S., Revesz, T., Plant, G., and Ghiso, J. (1999) Nature 399, 776-781) is entirely different and unrelated to any previously known amyloid protein. Patients with FBD have a single nucleotide substitution at codon 267 in the BRI2 gene, resulting in an arginine replacing the stop codon and a longer open reading frame of 277 amino acids instead of 266. The ABri peptide comprises the 34 C-terminal residues of the mutated precursor ABriPP-277 and is generated via furin-like proteolytic processing. Here we report that carriers of the Stop-to-Arg mutation have a soluble form of the amyloid peptide (sABri) in the circulation with an estimated concentration in the range of 20 ng/ml, several fold higher than that of soluble Abeta. In addition, ABri species identical to those identified in the brain were also found as fibrillar components of amyloid deposits predominantly in the blood vessels of several peripheral tissues, including pancreas and myocardium. We hypothesize that the high concentration of the soluble de novo created amyloidogenic peptide and/or the insufficient tissue clearance are the main causative factors for the formation of amyloid deposits outside the brain. Thus, FBD constitutes the first documented cerebral amyloidosis associated with neurodegeneration and dementia in which the amyloid deposition is also systemic.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Sequence, genomic structure and tissue expression of Human BRI3, a member of the BRI gene family.

The BRI3 gene is a member of the BRI gene family, made up of at least three different genes (BRI1-3). Previous studies established the cDNA sequence and structure of the human and mouse BRI1 and BRI2 genes and we recently reported that mutations in the BRI2 isoform, located on chromosome 13, are associated with dementia in humans. In the present work, we determine the complete cDNA sequence and genomic organization of the human BRI3 gene. BRI3 codes for a polypeptide of 267 amino acids, with a Mr of 30 KDa and a pI of 8.47. The amino acid sequence is 43.7% identical to the sequence of the human BRI2, and 38.3% identical to that of human BRI1, with the highest percentage of amino acid identity being concentrated on the C-terminal half of the molecules. In Northern blots, BRI3 cDNA hybridizes only one message of approximately 2.1 kilobases, which is predominantly present in the human brain. The BRI3 gene is localized on chromosome 2 and consists of six exons spanning more than 20 kb. Homology search of EST data banks retrieved a Caenorhabditis briggsae homolog of BRI, indicating that the BRI gene belongs to a strongly conserved gene family. These studies, aimed at characterizing the members of the BRI gene family, may provide valuable clues to the understanding of their normal function and how mutations in BRI2 can cause neurodegeneration and dementia similar to Alzheimer's disease.

Alternative Splicing↗
PubMed2001

Regional distribution of amyloid-Bri deposition and its association with neurofibrillary degeneration in familial British dementia.

Familial British dementia (FBD), pathologically characterized by cerebral amyloid angiopathy (CAA), amyloid plaques, and neurofibrillary degeneration, is associated with a stop codon mutation in the BRI gene resulting in the production of an amyloidogenic fragment, amyloid-Bri (ABri). The aim of this study was to assess the distribution of ABri fibrillar and nonfibrillar lesions and their relationship to neurofibrillary pathology, astroglial and microglial response using immunohistochemistry, confocal microscopy, and immunoelectron microscopy in five cases of FBD. Abnormal tau was studied with immunoblotting. We present evidence that ABri is deposited throughout the central nervous system in blood vessels and parenchyma where both amyloid (fibrillar) and pre-amyloid (nonfibrillar) lesions are formed. Ultrastructurally amyloid lesions appear as bundles of fibrils recognized by an antibody raised against ABri, whereas Thioflavin S-negative diffuse deposits consist of amorphous electron-dense material with sparse, dispersed fibrils. In contrast to nonfibrillar lesions, fibrillar ABri is associated with a marked astrocytic and microglial response. Neurofibrillary tangles and neuropil threads occurring mainly in limbic structures, are found in areas affected by all types of ABri lesions whereas abnormal neurites are present around amyloid lesions. Immunoblotting for tau revealed a triplet electrophoretic migration pattern. Our observations confirm a close link between ABri deposition and neurodegeneration in FBD.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Detection of Helicobacter pylori DNA in human feces by PCR: DNA stability and removal of inhibitors.

In this study, the stability of Helicobacter pylori DNA in human feces and the effect of a diet lacking in plant material, the suspected source of PCR inhibitors in human feces, were investigated. In addition, a method to remove these inhibitors was developed. Stools inoculated with H. pylori were used as a model. For this purpose, a H. pylori suspension (10(8) CFU/ml) was used to spike stool samples obtained from four healthy adults known to be H. pylori negative. The evaluation of the stability of H. pylori DNA in feces showed that DNA was degraded after 3 days of contact with fecal material at 37 degrees C. A 2-day diet completely free of plant material was sufficient to eliminate PCR inhibitors from human feces. However, inhibitors were detected 48 h after a normal diet was resumed. A new technique consisting of agarose blocks containing embedded DNA as a template for PCR amplification was used for removal of inhibitors, following DNA extraction by a modified QIAamp tissue method (Qiagen, Hilden, Germany). When this method was applied to inhibiting stool samples known to have an inhibitory effect and spiked with H. pylori (5.10(8) CFU/g), a positive PCR was obtained showing that inhibitors present in the original DNA samples were completely removed. The agarose embedded DNA block method is highly efficient and provides clean, high quality template DNA for PCR purposes avoiding long and fastidious conventional extraction methods. In conclusion, this study confirms that H. pylori DNA degrades with time in stools. A diet free of plant material or a special DNA preparation can be used to remove inhibitors and to allow the detection of H. pylori.

Adult↗
PubMed2001

Development of a DNA-based method aimed at identifying the fish species present in food products.

Analysis of restriction fragment length polymorphism (RFLP) profiles of a 464 bp amplicon obtained from the mitochondrial cytochrome b gene was used to differentiate between several different fish species. The method was tested by a collaborative study in which 12 European laboratories participated to ascertain whether the method was reproducible. Each laboratory was required to identify 10 unknown samples by comparison with RFLP profiles from authentic species. From a total of 120 tests performed, unknown samples were correctly identified in 96% of cases. Further work attempting to use the method to analyze mixed and processed fish samples was also performed. In all cases the species contained within mixed samples were correctly identified, indicating the efficacy of the method for detecting fraudulent substitution of fish species in food products.

Animals↗
PubMed2001

Identification of Hake species (Merluccius Genus) using sequencing and PCR-RFLP analysis of mitochondrial DNA control region sequences.

The use of DNA-based methodologies in identification of hake species belonging to the Merluccius genus was shown to be successful. A short fragment of the left hypervariable domain of the mitochondrial control region was amplified, sequenced, and digested from 11 hake species. The hake-specific PCR product, due to its limited size, was obtained in a variety of tissue samples with different levels of DNA concentration and degradation, including sterilized food products. On the basis of this phylogenetically informative 156-bp sequence were selected four restriction enzymes (ApoI, DdeI, DraIII, and MboII) that allow the hake species discrimination. Species identification by phylogenetic analysis of sequences or by PCR-RFLP methodologies is useful in a variety of scenarios including authentication of thermally processed food, detection of food components, and species determination of individuals whose morphological characters are removed.

Animals↗
PubMed2001

Amyloid and nonfibrillar deposits in mice transgenic for wild-type human transthyretin: a possible model for senile systemic amyloidosis.

The human serum protein transthyretin (TTR) is highly fibrillogenic in vitro and is the fibril precursor in both autosomal dominant (familial amyloidotic polyneuropathy [FAP] and familial amyloidotic cardiomyopathy [FAC]) and sporadic (senile systemic amyloidosis [SSA]) forms of human cardiac amyloidosis. We have produced mouse strains transgenic for either wild-type or mutant (TTRLeu55Pro) human TTR genes. Eighty-four percent of C57BI/6xDBA/2 mice older than 18 months, transgenic for the wild-type human TTR gene, develop TTR deposits that occur primarily in heart and kidney. In most of the animals, the deposits are nonfibrillar and non-Congophilic, but 20% of animals older than 18 months that bear the transgene have human TTR cardiac amyloid deposits identical to the lesions seen in SSA. Amino terminal amino acid sequence analysis and mass spectrometry of the major component extracted from amyloid and nonamyloid deposits revealed that both were intact human TTR monomers with no evidence of proteolysis or codeposition of murine TTR. This is the first instance in which the proteins from amyloid and nonfibrillar deposits in the same or syngeneic animals have been shown to be identical by sequence analysis. It is also the first time in any form of amyloidosis that nonfibrillar deposits have been shown to systematically occur temporally before the appearance of fibrils derived from the same precursor in the same tissues. These findings suggest, but do not prove, that the nonamyloid deposits represent a precursor of the fibril. The differences in the ultrastructure and binding properties of the deposits, despite the identical sizes and amino terminal amino acid sequences of the TTR and the dissociation of deposition and fibril formation, provide evidence that in vivo factors, perhaps associated with aging, impact on both systemic precursor deposition and amyloid fibril formation.

Aging↗
PubMed2001

Occurrence and antimicrobial susceptibility of Ureaplasma parvum (Ureaplasma urealyticum biovar 1) and Ureaplasma urealyticum (Ureaplasma urealyticum biovar 2) from patients with adverse pregnancy outcomes and normal pregnant women.

A recent phylogenetic analysis of Ureaplasma urealyticum resulted in the proposal to divide their 2 biovars into species. We used PCR to compare the distribution of species and the presence of the tet(M) and int-Tn resistance determinants in 63 strains of Ureaplasma spp. isolated from the amniotic fluid of patients with an adverse pregnancy outcome and in 22 strains obtained from the lower genital tract of healthy pregnant women. We also determined the antimicrobial susceptibility of the organisms to erythromycin and tetracycline. U. parvum was the most frequent Ureaplasma species detected in our study. Thus, 50/63 (79.4%) invasive isolates and 17/22 (77.3%) lower genital tract isolates corresponded to U. parvum, whereas 12/63 (19%) invasive isolates and 4/22 (18.2%) non-invasive strains corresponded to U. urealyticum. A mixture of species was found in 2 women. We found no significant differences in the antimicrobial susceptibility of isolates according to species or origin of isolation. Sixty-two strains of Ureaplasma spp. (74.7%) were susceptible to erythromycin, and 21 strains (25.3%) were intermediately susceptible. Sixty-eight isolates (81.9%) were susceptible to tetracycline, 2 strains (2.4%) were intermediate and 13 strains (15.7%) were resistant. DNA sequences related to the tet(M) determinant and the int-Tn gene were found in all tetracycline-resistant isolates.

Amniotic Fluid↗
PubMed2001

Integrated analysis for pre-sorting and waste collection schemes implemented in Spanish cities.

Over recent years, European cities have been questioning their traditional pre-sorting and waste collection practices and looking for new schemes to improve environmental problems generated by waste disposal. This paper presents an integral methodology for four pre-sorting practices that are beginning to be implemented in Spanish cities. A great effort has been made to compile information to be able to estimate a large number of valuation indexes. Based on this information, the methodology is supported by the forecasting of waste generation, the use of GIS techniques, the definition of objectives and their evaluation taking into account legal, social, performance, environmental and economic issues. Special attention is given to environmental impact, for which life cycle assessment methodology is used.

Cities↗
PubMed2001

Chromosome 13 dementia syndromes as models of neurodegeneration.

Two hereditary conditions, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with amyloid deposition in the central nervous system and neurodegeneration. The two amyloid proteins, ABri and ADan, are degradation products of the same precursor molecule BriPP bearing different genetic defects, namely a Stop-to-Arg mutation in FBD and a ten-nucleotide duplication-insertion immediately before the stop codon in FDD. Both de novo created amyloid peptides have the same length (34 amino acids) and the same post-translational modification (pyroglutamate) at their N-terminus. Neurofibrillary tangles containing the classical paired helical filaments as well as neuritic components in many instances co-localize with the amyloid deposits. In both disorders, the pattern of hyperphosphorylated tau immunoreactivity is almost indistinguishable from that seen in Alzheimer's disease. These issues argue for the primary importance of the amyloid deposits in the mechanism(s) of neuronal cell loss. We propose FBD and FDD, the chromosome 13 dementia syndromes, as models to study the molecular basis of neurofibrillary degeneration, cell death and amyloid formation in the brain.

Amino Acid Sequence↗
PubMed2001

Familial cerebral amyloid angiopathy related to stroke and dementia.

The term cerebral amyloid angiopathy (CAA) refers to the specific deposition of amyloid fibrils in the walls of leptomeningeal and cortical arteries, arterioles and, although less frequently in capillaries and veins. It is commonly associated with Alzheimers disease, Down's syndrome and normal aging, as well as with a variety of familial conditions related to stroke and/or dementia: hereditary cerebral hemorrhage with amyloidosis of Icelandic type (HCHWA-I), various inherited disorders linked to Abeta mutants (including the Dutch variant of HCHWA), and the recently described chromosome 13 familial dementia in British and Danish kindreds. This review focuses on four different types of hereditary CAA, emphasizing the notion that CAA is not only related to stroke but also to neurodegeneration and dementia of the Alzheimer's type.

Alzheimer Disease↗
PubMed2000

Measurement of the decay amplitudes of B0 --> J/psiK*0 and B(s)(0) --> J/psistraight phi decays

An angular analysis of B0-->J/psiK(*0) and B(0)(s)-->J/psistraight phi has been used to determine the decay amplitudes with parity-even longitudinal ( A0) and transverse ( A( parallel)) polarization and parity-odd transverse ( A( perpendicular)) polarization. The measurements are based on 190 B0 and 40 B(0)(s) candidates obtained from 89 pb(-1) of &pmacr;p collisions at the Fermilab Tevatron. The longitudinal decay amplitude dominates with |A0|(2) = 0.59+/-0. 06+/-0.01 for B0 and |A0|(2) = 0.61+/-0.14+/-0.02 for B(0)(s) decays. The parity-odd amplitude is found to be small with |A( perpendicular)|(2) = 0.13(+0.12)(-0.09)+/-0.06 for B0 and |A( perpendicular)|(2) = 0.23+/-0.19+/-0.04 for B(0)(s) decays.

Journal Article↗
PubMed2000

Dijet production by double pomeron exchange at the fermilab tevatron

We report the first observation of dijet events with a double Pomeron exchange topology produced in &pmacr;p collisions at sqrt[s] = 1800 GeV. The events are characterized by a leading antiproton, two jets in the central pseudorapidity region, and a large rapidity gap on the outgoing proton side. We present results on jet kinematics and production rates, compare them with corresponding results from single diffractive and inclusive dijet production, and test factorization.

Journal Article↗
PubMed2000

Direct measurement of the W boson width in p&pmacr; collisions at radicals = 1.8 TeV

This Letter describes a direct measurement of the W boson total decay width, gamma(W), using the Collider Detector at Fermilab. The measurement uses an integrated luminosity of 90 pb(-1), collected during the 1994-1995 run of the Fermilab Tevatron p&pmacr; collider. The width is determined by normalizing predicted signal and background distributions to 49 844 W-->enu candidates and 21 806 W-->&mgr;nu candidates in the transverse-mass region M(T)<200 GeV and then fitting the predicted shape to the 438 electron events and 196 muon events in the high- M(T) region, 100<M(T)<200 GeV. The result is gamma(W) = 2.04+/-0.11(stat)+/-0.09(syst) GeV.

Journal Article↗
PubMed2000

Search for second and third generation leptoquarks including production via technicolor interactions in p&pmacr; collisions at radicals = 1.8 TeV

We report the results of a search for second and third generation leptoquarks using 88 pb(-1) of data recorded by the Collider Detector at Fermilab. Color triplet technipions, which play the role of scalar leptoquarks, are investigated due to their potential production in decays of strongly coupled color octet technirhos. Events with a signature of two heavy flavor jets and missing energy may indicate the decay of a second (third) generation leptoquark to a charm (bottom) quark and a neutrino. As the data are found to be consistent with standard model expectations, mass limits are determined.

Journal Article↗