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Biomedical subjects

R Alves

Publications and source records attributed to R Alves.

At least 19 recordsLinked to original sources

Lupus erythematosus tumidus: an underestimated entity.

There have been few reports of lupus erythematosus tumidus (LET) in the literature. Most of textbooks of dermatology or dermatopathology mention this entity only briefly, if at all. The authors describe an additional case of this underdiagnosed disorder that further supports its existence as a separate entity in the spectrum of the variants of chronic cutaneous lupus erythematosus. Although most cases are reported in the European countries, to our knowledge, this is the first case documented in Portugal. The clinical, photobiological and histological features as well as differential diagnosis, treatment and prognosis are also discussed.

Dermatologic Agents↗

Responses of IgE, IgG1, and IgG4 to concanavalin A-binding Blomia tropicalis antigens in allergic patients.

Blomia tropicalis (Bt) and Dermatophagoides pteronyssinus (Dp) are the prevalent house dust mites in tropical countries and are associated with allergic diseases. Glycosylated antigens are highly immunogenic and involved in different pathologies. We evaluated the presence of IgE, IgG1, and IgG4 to concanavalin A-binding antigens (Bt-Con-A) isolated from Bt-total extract in sera of allergic and non-allergic subjects. Bt-total and Bt-Con-A extracts were evaluated by SDS-PAGE and ELISA for reacting with IgE, IgG1, and IgG4 in sera of 121 patients with allergic rhinitis and 36 non-allergic individuals. All subjects were skin prick tested with Bt-total extract and inhibition tests were performed for IgE, IgG1, and IgG4 using both extracts (Bt-total and Bt-Con-A). Skin prick test showed that 58% of the patients were sensitized to Bt (Bt+), with 52% reactive to both mites (Bt and Dp) and 6% to Bt only. A broad spectrum of proteins (14-152 kDa) was visualized in Bt-total and components >27 kDa for the Bt-Con-A extract. ELISA showed a similar profile of IgE, IgG1 and IgG4 levels in response to Bt-total and Bt-Con-A extracts in different groups, although Bt+ patients showed a lower IgG4 reactivity to Bt-Con-A extract. Specific IgG1 levels were higher in Bt+ patients than in control subjects, and IgG4 levels showed no significant difference among groups. ELISA inhibition showed a partial IgE and total IgG1 and IgG4 cross-reactivity with Dp extract for Bt-total and Bt-Con-A extracts. We conclude that Con-A-binding components isolated from Bt constitute major allergens and are involved in both allergen sensitization (IgE response) and homeostasis maintenance (IgG1 and IgG4 responses).

Allergens↗

Differential IgE reactivity to Der p 1 and Der p 2 allergens of Dermatophagoides pteronyssinus in mite-sensitized patients.

Several studies have shown that the presence of IgE antibodies to house dust mites (HDM), particularly Dermatophagoides pteronyssinus (Dpt), is an important risk factor for asthma. Allergen immunotherapy is indicated for patients with IgE antibodies to clinically relevant allergens. The aims of this study were to analyze the levels of specific serum IgE to Der p 1 and Der p 2 allergens in mite-sensitized atopic patients and to compare them with both in vivo (skin prick test) and in vitro (IgE-ELISA) sensitizations to Dpt crude extract. Forty-seven atopic patients with allergic rhinitis with or without intermittent or persistent mild asthma and positive skin prick test (SPT) to Dpt total extract were studied. Thirty age-matched healthy subjects with negative SPT to HDM were included as controls. Levels of total IgE and Dpt-, Der p 1- and Der p 2-specific IgE were measured by ELISAs in SPT-positive atopic patients and SPT-negative control subjects. Among 47 symptomatic atopic patients, 27 (57.4%) were double positive IgE to Der p 1 and Der p 2 allergens, 3 (6.4%) were single positive IgE to Der p 1, 4 (8.5%) were single positive IgE to Der p 2, and 13 (27.6%) were double negative IgE to both allergens. There was a significant correlation between Der p 1- and Der p 2-specific IgE levels, but not between Der p 1- or Der p 2-IgE levels and SPT results. The double negative IgE patients had the smallest skin test reactions although they showed high mean levels of total serum IgE. Therefore, the knowledge of specific IgE levels to Der p 1 and Der p 2 major allergens might support physicians for indication or follow-up in mite-sensitized patients under allergen-specific immunotherapy. These approaches might be important for obtaining improved safety and efficacy of the current clinical practice of allergen immunotherapy.

Adolescent↗

Tuberculosis treatment default among Brazilian children.

OBJECTIVES: To study the prevalence and time of tuberculosis (TB) treatment default among children and to compare defaulters with those who completed treatment. METHODS: Retrospective cohort study at the Hospital Municipal Jesus, Rio de Janeiro, Brazil, among TB patients aged <15 years followed from 1998 to 2002. The group that completed treatment was compared with those that defaulted. RESULTS: The records of 248 patients were studied. The default rate was 24.2% and was more frequent in the first 2 months of treatment (43.3%) and among those aged <1 year (42.4%). The following variables were associated with default: previous default (relative risk [RR] 1.99, 95%CI 1.12-3.54, P = 0.035), father not living with the child (RR 1.85, 95%CI 1.06-3.21, P = 0.030) and father using illicit drugs (RR 2.93, 95%CI 1.44-5.97, P = 0.002). CONCLUSIONS: Health professionals responsible for treating children with TB should pay special attention to children aged <1 year, those with a history of previous default, and those whose father is absent or an illicit drug user.

Adolescent↗

IgE, IgG1, and IgG4 antibody responses to Blomia tropicalis in atopic patients.

BACKGROUND: Allergens from house dust mites (HDMs), Dermatophagoides pteronyssinus and Blomia tropicalis are clinically relevant in atopic respiratory diseases in tropical countries. AIMS OF THE STUDY: To evaluate immunoglobulin (Ig)E, IgG1, and IgG4 antibody responses to B. tropicalis in Brazilian atopic patients. METHODS: About 110 patients with allergic rhinitis with/without asthma and 33 control subjects underwent skin prick testing (SPT) with HDM extracts, and their sera were tested for IgE and IgG subclass antibodies to D. pteronyssinus and B. tropicalis by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. RESULTS: Most patients (56%) had positive SPT to B. tropicalis extract (B. tropicalis+ group), although 51% were reactive to both B. tropicalis and D. pteronyssinus and 6% were sensitized to B. tropicalis only. IgE-ELISA detected 43%B. tropicalis positivity with high-specific IgE levels in B. tropicalis+ patients. Specific IgG4 levels were higher in B. tropicalis+ than B. tropicalis- groups and correlated with specific IgE levels. The IgG1 levels to B. tropicalis were higher in patients than controls. The major allergenic B. tropicalis components recognized by B. tropicalis+ patient sera were the 54, 66, and 68 kDa proteins. The IgG4-binding protein profiles closely resembled that of IgE. The IgG1 antibodies recognizing multiple B. tropicalis protein species were detected in sera of all three patient groups. CONCLUSIONS: A large percentage of our allergic patients are B. tropicalis+. They are more frequently sensitized to high-molecular weight (HMW) B. tropicalis components than the major low-molecular weight (11-15 kDa) allergens detected in other studies. The results suggest that HMW B. tropicalis antigenic components are potential candidates for evaluating allergen exposure and sensitization, and for immunotherapy treatment.

Adult↗

Monitoring the active sessile-colonisation of two drinking water distribution systems based on the protein contents in native biofilm samples.

Biofilms are present to a greater or lesser degree in virtually all drinking water distribution systems. In order to investigate the relative intensity and the spatial and temporal distributions of the active sessile-colonization, protein was determined in native biofilm samples from the Oeiras-Amadora (OADS) and the Almada (ADS) distribution systems in Portugal. Samples (25 cm2) were taken from lengths of asbestos cement pipes of different ages and diameters. Protein was detected at levels from 0.3 to 68 microg/cm2 in samples from all analysed pipe diameters and ages. At OADS, protein was found at 0.3 to 1 mg/cm2 in 99% of the samples. At ADS, protein was only found in 30% of the samples, but at significantly higher levels (0.3 to 68 mg/cm2). In addition to displaying a more intense and scattered active colonization, ADS's oldest-pipes (in use for over 30 years) solely exhibited protein at the highest levels found (> 19 mg/cm2), in contrast with the younger pipes where protein levels ranged from 0.3 to 19 mg/cm2. Observed results suggest that the spatial and temporal distribution patterns of the active biofilm colonization may vary significantly among drinking water networks and may have a rather slow evolution, possibly at the decades scale.

Biofilms↗

Irreversibility in unbranched pathways: preferred positions based on regulatory considerations.

It has been observed experimentally that most unbranched biosynthetic pathways have irreversible reactions near their beginning, many times at the first step. If there were no functional reasons for this fact, then one would expect irreversible reactions to be equally distributed among all positions in such pathways. Since this is not the case, we have attempted to identify functional consequences of having an irreversible reaction early in the pathway. We systematically varied the position of the irreversible reaction in model pathways and compared the resulting systemic behavior according to several criteria for functional effectiveness, using the method of mathematically controlled comparisons. This technique minimizes extraneous differences in systemic behavior and identifies those that are fundamental. Our results show that a pathway with an irreversible reaction located at the first step, and with all other reactions reversible, is on average better than an otherwise equivalent pathway with all reactions reversible, which in turn is on average better than an otherwise equivalent pathway with an irreversible reaction located at any step other than the first. Pathways with an irreversible first reaction and low concentrations of intermediates (one of the primary criteria for functional effectiveness) exhibit the following profile when compared to fully reversible pathways: changes in the concentration of intermediates in response to changes in the level of initial substrate are equally low, the robustness of the intermediate concentrations and of the flux is similar, the margins of stability are similar, flux is more responsive to changes in demand for end product, intermediate concentrations are less responsive to changes in demand for end product, and transient times are shorter. These results provide a functional rationale for the positioning of irreversible reactions at the beginning of unbranched biosynthetic pathways.

Homeostasis↗

Effect of overall feedback inhibition in unbranched biosynthetic pathways.

We have determined the effects of control by overall feedback inhibition on the systemic behavior of unbranched metabolic pathways with an arbitrary pattern of other feedback inhibitions by using a recently developed numerical generalization of Mathematically Controlled Comparisons, a method for comparing the function of alternative molecular designs. This method allows the rigorous determination of the changes in systemic properties that can be exclusively attributed to overall feedback inhibition. Analytical results show that the unbranched pathway can achieve the same steady-state flux, concentrations, and logarithmic gains with respect to changes in substrate, with or without overall feedback inhibition. The analytical approach also shows that control by overall feedback inhibition amplifies the regulation of flux by the demand for end product while attenuating the sensitivity of the concentrations to the same demand. This approach does not provide a clear answer regarding the effect of overall feedback inhibition on the robustness, stability, and transient time of the pathway. However, the generalized numerical method we have used does clarify the answers to these questions. On average, an unbranched pathway with control by overall feedback inhibition is less sensitive to perturbations in the values of the parameters that define the system. The difference in robustness can range from a few percent to fifty percent or more, depending on the length of the pathway and on the metabolite one considers. On average, overall feedback inhibition decreases the stability margins by a minimal amount (typically less than 5%). Finally, and again on average, stable systems with overall feedback inhibition respond faster to fluctuations in the metabolite concentrations. Taken together, these results show that control by overall feedback inhibition confers several functional advantages upon unbranched pathways. These advantages provide a rationale for the prevalence of this control mechanism in unbranched metabolic pathways in vivo.

Biophysical Phenomena↗

Comparing systemic properties of ensembles of biological networks by graphical and statistical methods.

MOTIVATION: When dealing with questions that concern a general class of models for biological networks, large numbers of distinct models within the class can be grouped into an ensemble that gives a statistical view of the properties for the general class. Comparing properties of different ensembles through the use of point measures (e.g. medians, standard deviations, correlation coefficients) can mask inhomogeneities in the correlations between properties. We are therefore motivated to develop strategies that allow these inhomogeneities to be more easily detected. RESULTS: Methods are described for constructing ensembles of models within the context of a Mathematically Controlled Comparison. A Density of Ratios Plot for a given systemic property is then defined as follows: the y axis represents the value of the systemic property in a reference model divided by the value in the alternative model, and the x axis represents the value of the systemic property in the reference model. Techniques involving moving quantiles are introduced to generate secondary plots in which correlations and inhomogeneities in correlations are more easily detected. Several examples that illustrate the advantages of these techniques are presented and discussed.

Biometry↗

Systemic properties of ensembles of metabolic networks: application of graphical and statistical methods to simple unbranched pathways.

MOTIVATION: Mathematical models are the only realistic method for representing the integrated dynamic behavior of complex biochemical networks. However, it is difficult to obtain a consistent set of values for the parameters that characterize such a model. Even when a set of parameter values exists, the accuracy of the individual values is questionable. Therefore, we were motivated to explore statistical techniques for analyzing the properties of a given model when knowledge of the actual parameter values is lacking. RESULTS: The graphical and statistical methods presented in the previous paper are applied here to simple unbranched biosynthetic pathways subject to control by feedback inhibition. We represent these pathways within a canonical nonlinear formalism that provides a regular structure that is convenient for randomly sampling the parameter space. After constructing a large ensemble of randomly generated sets of parameter values, the structural and behavioral properties of the model with these parameter sets are examined statistically and classified. The results of our analysis demonstrate that certain properties of these systems are strongly correlated, thereby revealing aspects of organization that are highly probable independent of selection. Finally, we show how specification of a given behavior affects the distribution of acceptable parameter values.

Amino Acids↗

Extending the method of mathematically controlled comparison to include numerical comparisons.

MOTIVATION: The method of mathematically controlled comparison has been used for some time to determine which of two alternative regulatory designs is better according to specific quantitative criteria for functional effectiveness. In some cases, the results obtained using this technique are general and independent of parameter values and the answers are clear-cut. In others, the result might be general, but the demonstration is difficult and numerical results with specific parameter values can help to clarify the situation. In either case, numerical results with specific parameter values can also provide an answer to the question of how much larger the values might be. In contrast, a more ambiguous result is obtained when either of the alternatives can have the larger value for a given systemic property, depending on the specific values of the parameters. In any case, introduction of specific values for the parameters reduces the generality of the results. Therefore, we have been motivated to develop and apply statistical methods that would permit the use of numerical values for the parameters and yet retain some of the generality that makes mathematically controlled comparison so attractive. RESULTS: We illustrate this new numerical method in a step-by-step application using a very simple didactic example. We also validate the results by comparison with the corresponding results obtained using the previously developed analytical method. The analytical approach is briefly present for reference purposes, since some of the same key concepts are needed to understand the numerical method and the results are needed for comparison. The numerical method confirms the qualitative differences between the systemic behavior of alternative designs obtained from the analytical method. In addition, the numerical method allows for quantification of the differences and it provides results that are general in a statistical sense. For example, the older analytical method showed that overall feedback inhibition in an unbranched pathway makes the system more robust whereas it decreases the stability margin of the steady state. The numerical method shows that the magnitudes of these differences are not comparable. The differences in stability margins (1-2% on average) are small when compared to the differences in robustness (50-100% on average). Furthermore, the numerical method shows that the system with overall feedback responds more quickly to change than the otherwise equivalent system without overall feedback. These results suggest reasons why overall feedback inhibition is such a prevalent regulatory pattern in unbranched biosynthetic pathways.

Computational Biology↗

Biological activities of 7-epiclusianone.

7-Epiclusianone, isolated from Rheedia gardneriana, was tested in several biological assays. It was active in vitro against trypomastigotes of Trypanosoma cruzi but inactive in vivo in experimentally infected mice. It was also active against Artemia salina, but inactive against the fungus Cladosporium sphaerospermum and the snail Biomphalaria glabrata.

Animals↗

Two recent cases of tertiary syphilis.

Tertiary syphilis is now a rare disease in Europe, mainly as a result of occasional antibiotherapy for concomitant infections. However early syphilis is rising in USA and Germany, and it is necessary to maintain an high level of knowledge and suspicion to achieve a diagnosis in the tertiary stage of the disease. In this report two patients with benign tertiary syphilis are described. The first one is a 55-year-old female with erythemato-violaceous annular scaling plaques on the right buttock and scapula and on both thighs, which had a negative and then a low VDRL titer. The second case is a 33-year-old mentally handicapped female with erythematous plaques, with psoriasiform scaling in the trunk and well defined crusted ulcers on the face, which also had negative VDRL. Biopsy of the skin lesions revealed plasmocytic infiltrate with endothelial swelling without granulomas and with negative silver stains in both patients. The investigation for cardiovascular and neurological involvement was negative in both patients. Diagnosis of tertiary syphilis can be difficult as clinical pictures can be misleading, similar to other granulomatous diseases, and serological titers can be low or negative. We recall the necessity of ruling out neurological and cardiac involvement in this stage of syphilis. These cases are reported as a reminder of the possibility of syphilis, so that new cases are not misdiagnosed and mistreated as other diseases.

Adult↗