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F Ballester

Publications and source records attributed to F Ballester.

71 records · Page 4Linked to original sources

The pathogenesis of Alport syndrome involves type IV collagen molecules containing the alpha 3(IV) chain: evidence from anti-GBM nephritis after renal transplantation.

Mutations in the COL4A5 collagen gene have been implicated as the primary defect in Alport syndrome, a heritable disorder characterized by sensorineural deafness and glomerulonephritis that progresses to end-stage renal failure. In the present study, the molecular nature of the defect in Alport glomerular basement membrane (GBM) was explored using anti-GBM alloantibodies (tissue-bound and circulating) produced in three Alport patients subsequent to renal transplantation. The alloantibodies bound to the alpha 3(IV)NC1 domain of type IV collagen and not to any other basement membrane component. In tissue sections, the alloantibodies bound specifically to peripheral GBM in normal kidney and the affected renal transplant but not to that of Alport kidney. These results establish that: the alpha 3 chain in type IV collagen molecules, the Goodpasture autoantigen, is the target alloantigen in post-transplant anti-GBM nephritis in patients with Alport syndrome, and that a molecular commonality exists in the pathogenesis of anti-GBM nephritis causing loss of renal allografts in patients with Alport syndrome and renal failure in patients with Goodpasture syndrome. These findings implicate: (1) defective assembly of type IV collagen molecules containing the alpha 3(IV) chain in Alport GBM; and (2) the existence of a mechanism linking the assembly of molecules containing the alpha 3(IV) chain with those containing the alpha 5(IV) chain.

Adult↗

Glomerular basement membrane. Identification of dimeric subunits of the noncollagenous domain (hexamer) of collagen IV and the Goodpasture antigen.

The noncollagenous (NC1) domain hexamer of glomerular basement membrane (GBM) collagen is composed of a multiplicity of monomeric and dimeric subunits, and specific subunits are the targets for anti-GBM autoantibodies of patients with Goodpasture (GP) syndrome. The identity of GBM monomers has been established and the alpha 3(IV)NC1 monomer identified as the one that binds GP antibodies (Gunwar, S., Saus, J., Noelken, M. E., and Hudson, B. G. (1990) J. Biol. Chem. 265, 5466-5469). In the present study, the chain origin of 25 dimeric components and the identity of those that bound the anti-GBM antibodies from two GP patients were determined. This was accomplished by NH2-terminal sequence analysis and immunoblotting analysis of dimeric components that were resolved by two-dimensional electrophoresis in combination with high pressure liquid chromatography. The results revealed that (a) the components are mainly homodimers of the NC1 domains of alpha 1, alpha 2, alpha 3, alpha 4, and probably alpha 5 chains of collagen IV, reflecting a specificity of promoter-promoter association and (b) each homodimer had several size and charge isoforms. The GP antibodies bound exclusively to both alpha 3(IV)NC1 monomers and dimers and not to other basement membrane constituents. These findings provided new insights about the structure of GBM collagen and together with our previous findings firmly established the alpha 3(IV) chain as the target for the anti-GBM antibodies that mediate glomerulonephritis and pulmonary hemorrhage in patients with Goodpasture syndrome.

Adult↗

The oxidation of ubiquinol by the isolated Rieske iron-sulfur protein in solution.

The pre-steady-state redox reactions of the Rieske iron-sulfur protein isolated from beef heart mitochondria have been characterized. The rates of oxidation by c-type cytochromes is much faster than the rate of reduction by ubiquinols. This enables the monitoring of the oxidation of ubiquinols by the Rieske protein through the steady-state electron transfer to cytochrome c in solution. The pH and ionic strength dependence of this reaction indicate that the ubiquinol anion is the direct reductant of the oxidized cluster of the iron-sulfur protein. The second electron from ubiquinol is diverted to oxygen by the isolated Rieske protein, and forms oxygen radicals that contribute to the steady-state reduction of cytochrome c. Under anaerobic conditions, however, the reduction of cytochrome c catalyzed by the protein becomes mechanicistically identical to the chemical reduction by ubiquinols. The present kinetic work outlines that: (i) the electron transfer between the ubiquinol anion and the Rieske cluster has a comparable rate when the protein is isolated or inserted into the parent cytochrome c reductase enzyme; (ii) the Rieske protein may be a relevant generator of oxygen radicals during mitochondrial respiration.

Animals↗

Prospective study on the etiology of community-acquired pneumonia in children and adults in Spain.

The cause of primary pneumonia was diagnosed in 157 of 198 children and 165 of 207 adults seen as inpatients or outpatients in a 12-month period. In children Mycoplasma pneumoniae and pneumococcus were identified in 79 and 29 cases respectively. Twenty-nine of 53 cases of viral infection in children were caused by respiratory syncytial virus, two-thirds of the cases occurring in children under three years of age. No children died of pneumonia. In adults pneumococcus was the most common pathogen, accounting for 81 cases. The overall mortality in adults was 7.7%. A high mortality was found in patients with Haemophilus influenzae and other gram-negative bacilli infections, and in elderly patients with pneumococcal pneumonia. Coagglutination was more sensitive than counterimmunoelectrophoresis for the detection of pneumococcal antigen in respiratory samples (p less than 0.001). Counterimmunoelectrophoresis was the only useful technique for detection of pneumococcal antigen in urine specimens, concentration, overnight storage at 4 degrees C and specific staining significantly increasing positivity (p less than 0.001).

Adult↗

The circular-dichroic properties of the 'Rieske' iron-sulphur protein in the mitochondrial ubiquinol: cytochrome c reductase.

We have studied the c.d. spectra of the 'Rieske' iron-sulphur protein isolated from the ubiquinol: cytochrome c reductase (bc1 complex) of bovine heart mitochondria. Both the oxidized and the reduced form of the 'Rieske' protein display a series of well-resolved c.d. features resembling those reported for the 'Rieske'-type iron-sulphur protein purified from the bacterium Thermus thermophilus [Fee, Findling, Yoshida, Hille, Tarr, Hearshen, Dunham, Day, Kent & Münck (1984) J. Biol, Chem. 259, 124-133]. In particular, the difference spectra, reduced minus oxidized, of both proteins have a distinctive negative band at 497 nm. The c.d. features characteristic of the isolated 'Rieske' protein were found in the dichroic spectra of the whole bc1 complex in the region between 450 and 520 nm. The reduction of the enzyme by ascorbate or ubiquinol is accompanied by the formation of a negative band at about 500 nm that corresponds, in all its c.d. properties, to the specific dichroic absorption of the reduced 'Rieske' iron-sulphur protein.

Animals↗

[Estimate of daily cases of influenza from the cases notified to the Reportable Disease System: usefulness in time series studies].

In time series analyses assessing the relationship between risk factors and respiratory diseases or mortality, influenza incidence is a potential cofounder and, therefore, must be controlled. Available influenza data come from weekly compulsory notifiable disease (EDO system). Furthermore, its graphical distribution, suggests that information may be underestimated in holiday periods. We have applied a procedure for estimate daily influenza series from the weekly cases, using less, a non-parametric local fit. Findings show that smoothing could avoid stepping and sudden peaks in the original series.

Humans↗

[Particulate air pollution and health in Valencia [Spain] 1994-1996].

OBJECTIVE: To estimate the short-term association between levels of air pollution due to suspended particulates and several indicators of morbidity and mortality in the city of Valencia, Spain. METHODS: We performed an ecological time-series study. Daily levels of air pollution from black smoke were related to indicators of mortality, hospital admissions, and visits to emergency departments in the city of Valencia between 1994 and 1996. The magnitude of the association was estimated through Poisson autoregression using generalized additive models. The form of the relationship, the delayed effect of pollution, and the possible modification of this effect by other pollutants or periods of the year were assessed. RESULTS: A significant association was found between levels of suspended particulates and several of the indicators analyzed in Valencia. The form of this relationship was linear. An increment of 10 microg/m3 in the daily levels of black smoke was associated with an increase of 1.8% (95% confidence interval: 0.9-2.7%) in the number of deaths on the following day. The same increment in pollutant levels was associated with an increase of 1.5% (0.1-2.8%) in deaths from all cardiovascular causes, an increase of 1.3% (0.0-2.6%) in admissions for all cardiovascular diseases and in an increase of 5.4% (0.6-10.4%) in the number of emergency visits for asthma. This association was not confounded by levels of other pollutants. Black smoke was not associated with mortality from respiratory diseases, with hospital admissions for cerebrovascular diseases, or with emergency visits for chronic obstructive pulmonary disease. CONCLUSIONS: This study provides evidence that levels of suspended particles in Valencia are associated with emergency visits for asthma, hospital admissions for cardiovascular diseases, and daily deaths. The association found is consistent with the results of previous studies and fits with recent knowledge of psychopathological mechanisms.

Air Pollution↗

[Comparison of two methods in the analysis of the short-term effect of air pollution on health].

OBJECTIVE: We compare two methods to analyse the relationship between air pollution and health. One of them (ME) is based on a generalized linear model, while the other one (MN) incorporates a generalized additive model (GAM). Besides the statistical model used, both methods schow additional discrepancies for the type and number of variables used in the control of confounding. METHOD: An analysis was carried out for each lag of black smoke (0 to 5) and several health indicators from the city of Valencia (Spain) following both methods. Results were compared examining the sequence and the lag of the higher coefficient. The ratio between confidence intervals width and the percent difference in the estimates were also obtained. RESULTS: The discrepancies in results according to the methodology were small. The sequence shaped and the lag of higher coefficient generally remained invariant. Coefficients were similar (percent difference of MN over ME was not greater than 10%). Confidence intervals were more precise for MN, although the reduction was not very strong (the width ratio was around 90%). CONCLUSIONS: The short variation of the results guarantees the applicability of both MN and ME methods, although the systematic reduction of the standard error of MN supports its use as a more efficient procedure to control for confounding.

Air Pollution↗

[Time series methods in epidemiological studies on air pollution].

The time series methods in the epidemiological studies on air pollution are reviewed, illustrated by means of an autoregressive Poisson regression which was employed in the APHEA and EMECAM Projects. A listing is provided of the variations in the daily number of deaths of people over age 70 (all causes, CIE-9:001-799) in Barcelona, 1991-1995, with the average variations in the daily smog pollution levels. A Poisson regression is used insofar as the dependent random variable presumably follows such a probability distribution. As variable possibly leading to confusion, the impact of weather variables (daily temperature and relative humidity averages), seasonal, tendency-related behaviours and day of the year on the death rate are taken into account (all estimated on a determinist basis), in addition to any other variable which behaves in a way that it can be related to the dependent variable (i.e. flu epidemics). The relationship between the death rate and the confusing-causing variables is modelled on a non-linear basis, and the foreseeable lag times are also taken into account (i.e. by using explicative variable time lags). However, due to control not being perfect, it has been decided to opt for estimating an autoregressive Poisson model (adding in some different explicative variables time giving rise to a lag in the death rate) offsetting the residual autocorrelation. The main advantage of the method of analysis described above is that of making it possible to control confusing variables from a determinist standpoint with a software to which all of the groups taking part in this Project had access. This also affords the possibility of using this method in a set, standardized manner, facilitating the comparison of results and making an objective point analysis possible.

Age Factors↗

[Non-specific differences in neurocognitive performance in psychotic disorders?].

INTRODUCTION: In the last years, there has been a growing interest in the study of cognitive functioning, not only in schizophrenia but also in other psychoses and psychiatric disorders. Attention, memory and information processing deficits may have great relevance as predictors of social adjustment and quality of life. OBJECTIVE AND METHODS: [corrected] We revised literature concerning comparative studies of neuropsychological performance in schizophrenia and affective disorders, mainly bipolar disorders. RESULTS: Studies analyzed show contradictory results. Some authors report a more global dysfunction or a more limited and concrete dysfunction in schizophrenia. However, most of the studies, especially those with homogeneous samples of psychotic affective disorders do not find any difference in cognitive functioning between schizophrenic and bipolar patients. DISCUSSION: Although some factors as sample selection, clinical state, course of the disorder, make difficult the interpretation of results, it would not exist specific deficits in any of the diagnostic groups studied.

Bipolar Disorder↗