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Biomedical subjects

J L Diaz

Publications and source records attributed to J L Diaz.

At least 19 recordsLinked to original sources
PubMed2005

Psychometric field study of the new haemophilia quality of life questionnaire for adults: the 'Hemofilia-QoL'.

Although there is a worldwide interest in the assessment of health-related quality-of-life (HRQoL) in haemophilia patients, no non-disease specific instruments (for adults) are readily available. In this paper, a haemophilia-specific quality-of-life assessment measure for adults (the Hemofilia-QoL questionnaire) has been developed and tested for psychometric properties in 121 adults with haemophilia living in Spain. The Hemofilia-QoL questionnaire is a self-report modular instrument that assesses nine relevant HRQoL domains for patients with haemophilia (e.g. physical health, daily activities, joint damage, pain, treatment satisfaction, treatment difficulties, emotional functioning, mental health, relationships and social activity). Psychometric examination involved the assessment of data quality, scaling assumptions, reliability (internal consistency and test-retest) and validity (concurrent; external clinical criterion and sensitivity). The Hemofilia-QoL 36-item version questionnaire had acceptable internal consistency and retest reliability values. The questionnaire shows excellent concurrent validity (with the SF-36 Health Survey) and external clinical criterion validity (haemophilia clinical status) and sensitivity (health status changes) as well. The Hemofilia-QoL is now available for adult assessment and is ready for use in clinical research in Spain.

Adolescent↗
PubMed2005

Autoimmune rheumatic diseases in the intensive care unit: experience from a tertiary referral hospital and review of the literature.

Autoimmune rheumatic diseases (AIRD) are not uncommon in the general population and up to one third of hospitalized patients with AIRD may need admission to intensive care unit (ICU). This paper describes the causes of admission, the clinical features and outcome of 24 AIRD patients admitted to a medical ICU from a third level hospital. Thirteen patients had systemic lupus erythematosus (54.2%), three rheumatoid arthritis (12.5%), three pulmonary renal syndrome (12.5%), two dermatopolymyositis (8.3%), two scleroderma (8.3%) and one antiphospholipid syndrome (4.2%). The main causes for ICU admission were rheumatic disease flare-up (37.5%), infection (37.5%) and complications derived from rheumatic disease (29.1%). Mortality during ICU stay was 16.7% (four patients). Excluding shock requiring vasopressor support, no statistical difference was found between survivors and nonsurvivors; although there was a trend to higher test severity scores (APACHE II, ODIN) in nonsurvivors. Our results reveal a lower mortality rate in AIRD patients admitted to the ICU than reported previously. Severity scores such as APACHE II are predictors of mortality in patients with AIRD in the ICU.

Adolescent↗
PubMed1998

Smoking and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liées à l'Age.

OBJECTIVE: To assess the associations between age-related macular degeneration (ARMD) and smoking. METHODS: The POLA study is a population-based study taking place in the town of Sète, located on the French Mediterranean Sea border. The presence of early and late ARMD was assessed in 2196 participants on the basis of 50 degrees color fundus photographs using an international classification system. RESULTS: After adjustment for age and sex, current and former smokers showed an increased prevalence of late ARMD (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-12.4; OR = 3.2, 95% CI = 1.3-7.7, respectively). An increased risk was present in participants who smoked more than 20 pack-years (OR = 3.0, 95% CI = 0.9-9.5 for 20-39 pack-years; OR = 5.2, 95% CI = 2.0-13.6 for 40 pack-years and more). In addition, the risk of late ARMD remained increased until 20 years after cessation of smoking (OR = 9.0, 95% CI = 3.0-27.0 for 1-9 years; OR = 4.0, 95% CI = 1.3-12.0 for 10-19 years; OR = 1.3, 95% CI = 0.4-4.3 for 20 years and more). Smoking was not significantly associated with early signs of ARMD. CONCLUSIONS: This study further confirms the adverse effect of tobacco on late ARMD. Former smokers seem to remain at high risk for ARMD.

Aged↗
PubMed1997

Dimerization properties of human BAD. Identification of a BH-3 domain and analysis of its binding to mutant BCL-2 and BCL-XL proteins.

Bad, an inducer of programmed cell death, was recently isolated from a mouse cDNA library by its ability to bind to the anti-apoptotic protein BCL-2. Sequence analysis suggested that Bad was a member of the BCL-2 gene family that encodes both inducers and inhibitors of programmed cell death. To further analyze the role of BAD in the network of homo- and heterodimers formed by the BCL-2 family, we have cloned the human homologue of BAD and assessed its biological activity and its interactions with wild type and mutant BCL-2 family proteins. Our results indicate that the human BAD protein, like its mouse homologue, is able to induce apoptosis when transfected into mammalian cells. Furthermore, in yeast two-hybrid assays as well as quantitative in vitro interaction assays, human Bad interacted with BCL-2 and BCL-XL. Sequence alignments of human BAD revealed the presence of a BH-3 homology domain as seen in other BCL-2 family proteins. Peptides derived from this domain were able to completely inhibit the dimerization of BAD with BCL-XL. Thus, as previously shown for BAX, BAK, BCL-2, and BCL-XL, the BH3 domain of BAD is required for its dimerization with other BCL-2 family proteins. BAD was further analyzed for its ability to bind to various mutants of BCL-2 and BCL-XL that have lost the ability to bind BAX and BAK, some of which retain biological activity and some of which do not. Surprisingly, all of the mutated BCL-2 and BCL-XL proteins analyzed strongly interacted with human BAD. Our data thus indicate that mutations in BCL-2 and BCL-XL can differentially affect the heterodimeric binding of different death-promoting proteins and have implications concerning the relationship between heterodimerization and biological activity.

Amino Acid Sequence↗
PubMed1997

Structural and functional complementation of an inactive Bcl-2 mutant by Bax truncation.

Interactions among proteins in the Bcl-2 family regulate the onset of programmed cell death. Previous work has shown that the death-inhibiting family members Bcl-2 and Bcl-xL form heterodimers with the death-promoting homologue Bax and that certain site-directed mutants of Bcl-2 and Bcl-xL lose both biological activity and the ability to bind Bax. To better understand the structural basis of heterodimer formation, we have used a yeast two-hybrid assay to screen for mutants of Bax that regain the ability to bind to these inactive Bcl-2(G145A) and Bcl-xL(G138A) mutants. This screen identified a series of C-terminally truncated Bax molecules that contain complete BH3 (Bcl-2 homology domain 3) domains but that have lost BH1 and BH2 sequences. These results indicate that while the Bcl-2 and Bcl-xL mutants fail to bind full-length Bax, they still retain a binding site for the critical BH3 domain. This suggests that conformational constraints in full-length Bax regulate its ability to bind to other Bcl-2 family members. Furthermore, we demonstrate that the normally inert Bcl-2(G145A) mutant effectively blocks apoptosis induced by a C-terminally truncated Bax molecule, but does not block apoptosis induced by wild-type Bax. This demonstrates that cell protection can be effected by directly binding pro-apoptotic members of the Bcl-2 family.

Amino Acid Sequence↗
PubMed1997

A common binding site mediates heterodimerization and homodimerization of Bcl-2 family members.

Bcl-2 inhibits apoptosis induced by a wide variety of stimuli. In contrast, the Bcl-2 homologue, Bax, antagonizes Bcl-2's death protecting function. Bcl-2 forms protein-protein homodimers with itself and heterodimers with Bax, and previous experiments have shown that point mutations in Bcl-2 can abrogate Bax binding while leaving homodimerization intact. These mutagenesis results can be interpreted to suggest that Bcl-2 has separate binding sites that are responsible for homodimer and heterodimer formation. Results from yeast two-hybrid studies have also suggested that homodimerization and heterodimerization reflect distinct modes of interaction. However, using quantitative plate binding assays, we now show that Bax as well as peptides derived from the BH3 domains of Bax and Bak block both Bcl-2/Bax binding and Bcl-2/Bcl-2 binding. Similar assays demonstrate that Bcl-xL can form both homodimers and heterodimers and that these interactions are also inhibited by Bax and the BH3-derived peptides. These results demonstrate that the same binding motifs are responsible for both homodimerization and heterodimerization of Bcl-2 family members.

Amino Acid Sequence↗
PubMed1996

Tyloxapol inhibits NF-kappa B and cytokine release, scavenges HOCI, and reduces viscosity of cystic fibrosis sputum.

Cystic fibrosis (CF) patients develop progressive cytokine-mediated inflammatory lung disease, with abundant production of thick, tenacious, protease- and oxidant-rich purulent airway secretions that are difficult to clear even with physiotherapy. In the search for a potential treatment, we have tested tyloxapol, an alkylaryl polyether alcohol polymer detergent previously used as a mucolytic agent in adult chronic bronchitis. Tyloxapol inhibits activation of the transcription factor nuclear factor-kappa B (NK-kappa B), reduces resting secretion of the cytokine interleukin-8 (IL-8) in cultured human monocytes, and inhibits lipopolysaccharide (LPS)-stimulated release of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and the eiconsanoids thromboxane A2 and leukotriene B4 (LTB4). We have previously shown that tyloxapol is a potent antioxidant for hydroxyl radicals ( OH). Tyloxapol (0.05 to 0.1% wt/vol) effectively scavenges the oxidant hypochlorous acid (HOCl; 1 to 7.5 mM) in vitro, and protects from HOCl-mediated lung injury in rats. Tyloxapol also reduces the viscosity of CF sputum (from 463 +/- 133 to 128 +/- 52 centipoise). We conclude that tyloxapol is potentially useful as a new antiinflammatory therapy for CF lung disease, and could possibly promote clearance of secretions in the CF airway.

Adult↗
PubMed1992

T-lymphocyte lines specific for glutamic acid decarboxylase (GAD) the 64K beta-cell antigen of IDDM.

Insulin-dependent diabetes mellitus (IDDM) is viewed as a thymus-dependent autoimmune disease, although the specific beta-cell autoantigen or autoantigens remain unknown. The recent identification of the beta-cell 64K antigen as the enzyme glutamic acid decarboxylase (GAD) permits investigation of GAD as a candidate for the autoantigen associated with beta-cell destruction, mediated by T-lymphocytes, in susceptible individuals. In this study, we describe the isolation of GAD-specific T-lymphocyte lines from BB rats, an animal model of IDDM. GAD (Escherichia coli) was inoculated into the footpads of diabetes-resistant BB rats, and after 10 days, a popliteal lymph node cell culture suspension was prepared. GAD-specific T lymphocytes were obtained by culture with interleukin 2 and repeated stimulation with GAD in the presence of BB rat thymic antigen-presenting cells. Four stable, CD4+, MHC (RT1u)-restricted T-lymphocyte lines were isolated. They proliferate selectively in the presence of GAD and secrete interleukin 2 and interferon-gamma. T-lymphocyte lines such as these could be important in the definition of pathogenetic epitopes associated with GAD.

Animals↗
PubMed1991

Synergistic effects of kinship, sex and rank in the behavioural interactions of captive stump-tailed macaques.

In almost all non-human primate species kinship, sex and rank bias the patterning of interactions among subjects, seemingly in a way that favours the individual's fitness. A number of studies have been done in order to study separately the effects of these variables, concluding that an adequate model of interactions cannot be developed assuming preponderance of a single variable. The 'willingness' of one animal to interact with another can be explained as the result of assessing the possible outcomes (proximate and/or ultimate) of the interaction. The interrelationship of variables such as kinship, sex and rank, among others, provides the actors with a basis for deciding their rates of social interactions. The following study was done to assess whether kinship, rank and sex exerted independent, additive effects in the within-group distributions of eight social behaviour categories of captive groups of stump-tailed macaques. We found that the three variables synergistically affected the patterning of all behavioural categories. This suggests that the pay-offs of social interactions do not vary linearly, being intrinsically correlated with the actors' attributes so that uncertainty in the choice of a potential partner is minimized.

Aggression↗
PubMed1991

The relationship between insulin autoantibodies and islet cell histology in the diabetes prone BB rat.

The relationship between insulin autoantibodies (IAA) and pancreatic islet cell histology was examined in 71 diabetes prone BB rats from the Toronto colony. Twenty-seven of the 71 became diabetic and of these, 18 (67%) were IAA positive by ELISA. IAA were also detected in 39/44 (89%) which did not develop diabetes, but in none of six control animals at 50-140 days of age. All 27 which became diabetic showed some evidence of lymphocytic infiltration scored + to ++++ histometrically and 26/27 evidence of beta cell degranulation. The frequency of diabetes increased with both intensity of insulitis and degree of beta cell degranulation, but there was no correlation between either and IAA. IAA are a marker for the BB strain of Wistar rat, but do not correlate with islet cell histology and do not predict clinical diabetes.

Animals↗
PubMed1990

Delayed disappearance of human compared to porcine insulin in a patient with the insulin autoimmune syndrome.

The insulin autoimmune syndrome is characterised by high titres of autoantibody to insulin, a high circulating concentration of total insulin and later, reactive hypoglycaemia. We have studied a patient with this syndrome whose insulin autoantibody bound exclusively human insulin. This permitted us to investigate the disappearance of bound (human) and unbound (porcine) insulin in the same patient, using i.v. injections of 0.075 U/g of each insulin on separate days. The peak plasma free insulin concentration following porcine insulin was four times greater than that following the same dose of human insulin. The plasma disappearance half-time of porcine insulin following injection was 11 min compared with 32 min following human insulin injection, and the area beneath the disappearance curve of free insulin during the 120 min of sampling was greater for porcine insulin by a factor of 3.15. The nadir in plasma glucose occurred at 45 min following porcine insulin and at 90 min following human insulin injection. The restoration of basal glucose concentration was correspondingly slower following human insulin, but the absolute fall in glucose achieved was no different. There was no evidence of insulin resistance. Insulin autoantibodies can seriously disturb the kinetics and effect of free insulin.

Animals↗
PubMed1989

Systematic variation and differences in insulin-autoantibody measurements.

Insulin autoantibodies (IAAs) are currently the subject of intensive investigation as potential markers for autoimmune insulitis. However, the results of different reports vary widely. In an attempt to elucidate the reasons for the discrepant reports and to initiate standardization procedures, the International Diabetes Workshop (IDW) undertook two studies in which 22 centers worldwide measured IAA in coded samples. The variance in binding signal from the 49 sera in study 1 was considerable, even when results were standardized, but was largely systematic and attributable to basic differences in assay type (liquid phase versus solid phase) and to differences in the ligand used (human vs. nonhuman insulin). In study 2, 5 sera were prepared and presented blindly to compare dilution curves, insulin-species specificity, interference from irrelevant serum proteins, precision, and dose-dependent displaceability. Many assays, both liquid and solid phase, were influenced by marked and unpredictable nonspecific binding, revealed by loss of parallelism between dilution curves in pooled normal serum and buffer, by variable binding signals with different normal sera, and by difficulty in distinguishing human insulin-specific from cross-reactive IAA sera. It was concluded from the experience of both studies that variance could probably be reduced by using a standard curve with derived common units, a single species of ligand, and methodology to minimize the effect of nonspecific binding. Variation related to assay type was probably due to liquid- versus solid-phase systems being differentially more sensitive to certain aspects of antigen-antibody binding; this issue will be addressed in future serum exchanges and workshops.

Autoantibodies↗
PubMed1989

The time course of insulin autoantibodies (IAA) in the diabetes prone BB rat.

The BB rat is a widely used animal model for the study of insulin dependent diabetes. An enzyme linked immunosorbent assay, using purified rat insulin, was used to measure serial insulin autoantibodies (IAA) levels in coded sera from the BB/W/D rat colony in order to establish the time course of IAA. The animals included 26 diabetes-prone BB rats, six diabetes-resistant BB rats and six Wistar controls. There was an increase in both IAA frequency and titre with time in the diabetes-prone group: none were positive at 45 days, 17/19 (89%) were positive by day 90 and all were positive thereafter. Similar results were observed in the diabetes-resistant BB group (0/6 positive at day 51, 6/6 positive at day 90). None of the Wistar controls were positive at 105 days, although occasional positive sera were observed at 120 days. IAA seem to be acquired early on in the majority of BB rats, both diabetes-prone and diabetes-resistant, and much later, if at all, in controls. A clear homology of the MHC genes exists in both BB rat sublines, thus IAA appear to be a strain related phenomenon rather than a marker for IDDM.

Animals↗
PubMed1988

Behavioral effect of scopolamine in cats.

An ethological study was performed on a colony of cats. Their spontaneous behavior was observed following the chronic administration of scopolamine hydrobromide (0.3 mg/kg/day). Forty-four behavioral units grouped under four categories--resting postures, individual actions, grooming and social interactions--were coded. A general decrease of the frequency of the tested behaviors was observed; this was particularly true of those behaviors in response to individual or social stimulus of an affiliative or agonistic type. The results were consistent with former reports in other species suggesting the changes in attention underlie this lack of response.

Animals↗
PubMed1988

Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies.

Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important.

Adult↗