PubMed Health⌕ Search

Biomedical subjects

A Freitas

Publications and source records attributed to A Freitas.

At least 19 recordsLinked to original sources
PubMed2006

Heme oxygenase/carbon monoxide-biliverdin pathway down regulates neutrophil rolling, adhesion and migration in acute inflammation.

BACKGROUND AND PURPOSE: Heme oxygenase (HO) activity is known to down-regulate inflammatory events. Here, we address the role of HO and its metabolites, carbon monoxide (CO) and biliverdin (BVD), in leukocyte rolling, adhesion and neutrophil migration during inflammatory processes. EXPERIMENTAL APPROACH: Intravital microscopy was used to evaluate leukocyte rolling and adhesion in the mesenteric microcirculation of mice. TNFalpha and IL-1beta were determined by ELISA and HO-1 protein expression by Western blot. KEY RESULTS: Intraperitoneal challenge with carrageenan enhanced HO-1 protein expression in mesentery and bilirubin concentration in peritoneal exudates. Pretreatment of mice with a non-specific inhibitor of HO (ZnDPBG) or with a HO-1 specific inhibitor (ZnPP IX) enhanced neutrophil migration, rolling and adhesion on endothelium induced by carrageenan. In contrast, HO substrate (hemin), CO donor (DMDC) or BVD reduced these parameters. The reduction of neutrophil recruitment promoted by HO metabolites was independent of the production of chemotactic cytokines. Inhibitory effects of CO, but not of BVD, were counteracted by treatment with a soluble guanylate cyclase (sGC) inhibitor, ODQ. Furthermore, inhibition of HO prevented the inhibitory effect of a nitric oxide (NO) donor (SNAP) upon neutrophil migration, while the blockade of NO synthase (NOS) activity by aminoguanidine did not affect the CO or BVD effects. CONCLUSIONS AND IMPLICATIONS: Metabolites of HO decreased leukocyte rolling, adhesion and neutrophil migration to the inflammatory site by a mechanism partially dependent on sGC. Moreover, inhibition by NO of neutrophil migration was dependent on HO activity.

Animals↗
PubMed2006

Statistical, computational and visualization methodologies to unveil gene primary structure features.

OBJECTIVES: Gene sequence features such as codon bias, codon context, and codon expansion (e.g. trinucleotide repeats) can be better understood at the genomic scale level by combining statistical methodologies with advanced computer algorithms and data visualization through sophisticated graphical interfaces. This paper presents the ANACONDA system, a bioinformatics application for gene primary structure analysis. METHODS: Codon usage tables using absolute metrics and software for multivariate analysis of codon and amino acid usage are available in public databases. However, they do not provide easy computational and statistical tools to carry out detailed gene primary structure analysis on a genomic scale. We propose the usage of several statistical methods--contingency table analysis, residual analysis, multivariate analysis (cluster analysis)--to analyze the codon bias under various aspects (degree of association, contexts and clustering). RESULTS: The developed solution is a software application that provides a user-guided analysis of codon sequences considering several contexts and codon usage on a genomic scale. The utilization of this tool in our molecular biology laboratory is focused on particular genomes, especially those from Saccharomyces cerevisiae, Candida albicans and Escherichia coli. In order to illustrate the applicability and output layouts of the software these species are herein used as examples. CONCLUSIONS: The statistical tools incorporated in the system are allowing to obtain global views of important sequence features. It is expected that the results obtained will permit identification of general rules that govern codon context and codon usage in any genome. Additionally, identification of genes containing expanded codons that arise as a consequence of erroneous DNA replication events will permit uncovering new genes associated with human disease.

Algorithms↗
PubMed2004

Complete two-loop electroweak fermionic corrections to the effective leptonic weak mixing angle sin2theta(lept)eff and indirect determination of the Higgs Boson Mass.

We present a complete calculation of the contributions to the effective leptonic weak mixing angle, sin((2)theta;(lept)(eff), generated by closed fermion loops at the two-loop level of the electroweak interactions. This quantity is the source of the most stringent bound on the mass M(H) of the standard model Higgs boson. The size of the corrections with respect to known partial results varies between -4 x 10(-5) and -8 x 10(-5) for a realistic range of M(H) from 100 to 300 GeV. This translates into a shift of the predicted (from sin((2)theta;(lept)(eff) alone) central value of M(H) by +19 GeV, to be compared with the shift induced by a recent change in the measured top quark mass which amounts to +36 GeV.

Journal Article↗
PubMed2001

Impaired regeneration of the peripheral B cell repertoire from bone marrow following lymphopenia in old mice.

Aging is associated with a decreased production of B cells by the bone marrow and an increased life-span of peripheral B cells. To determine whether the decreased bone marrow B cell production is linked to the increased life-span of B cells in old mice, B cell regeneration following lymphopenia was studied in young and old mice. The rate of bone marrow pre-B cell and of splenic B cell regeneration is slower in irradiated, old compared to irradiated, young recipients of young, congeneic bone marrow. This finding reflects an age-associated defect in the bone marrow microenvironment. As the bone marrow is the only source of a diverse population of B cells, we measured the diversity of the splenic B cell repertoire regenerated following drug-induced lymphopenia in old and young mice. The heterogeneity of mRNA size from IgH complementarity determining region 3 (CDR3) was more restricted in splenic B cells from old compared to young mice providing additional evidence for an age-associated impairment in B cell production by the bone marrow.

Aging↗
PubMed2001

CTLA-4 up-regulation plays a role in tolerance mediated by CD45.

Cytolytic T lymphocyte-associated antigen 4 (CTLA-4) is a critical down-regulatory molecule in T cells that plays a major role in peripheral tolerance. Although the CD45 protein tyrosine phosphatase is a potent immunomodulatory target, the mechanisms by which antibody against CD45RB isoforms (anti-CD45RB) induces allograft tolerance remain unclear. We show here that anti-CD45RB treatment alters CD45 isoform expression on T cells, which is associated with rapid up-regulation of CTLA-4 expression. These effects appear specific and occur without up-regulation of other activation markers. Administration of a blocking monoclonal antibody to CTLA-4 at the time of transplantation prevents anti-CD45RB therapy from prolonging islet allograft survival. In addition, treatment with cyclosporin A blocks anti-CD45RB-induced CTLA-4 expression and promotes acute rejection. These data suggest that anti-CD45RB acts through mechanisms that include CTLA-4 up-regulation and demonstrate a link between CD45 and CTLA-4 that depends on calcineurin-mediated signaling. They demonstrate also that CTLA-4 expression may be specifically targeted to enhance allograft acceptance.

Abatacept↗
PubMed2000

Mediastinitis after cardiac transplantation.

OBJECTIVE: Assessment of incidence and behavior of mediastinitis after cardiac transplantation. METHODS: From 1985 to 1999, 214 cardiac transplantations were performed, 12 (5.6%) of the transplanted patients developed confirmed mediastinitis. Patient's ages ranged from 42 to 66 years (mean of 52.3 +/- 10.0 years) and 10 (83.3%) patients were males. Seven (58.3%) patients showed sternal stability on palpation, 4 (33.3%) patients had pleural empyema, and 2 (16.7%) patients did not show purulent secretion draining through the wound. RESULTS: Staphylococcus aureus was the infectious agent identified in the wound secretion or in the mediastinum, or both, in 8 (66.7%) patients. Staphylococcus epidermidis was identified in 2 (16.7%) patients, Enterococcus faecalis in 1 (8.3%) patient, and the cause of mediastinitis could not be determined in 1 (8.3%) patient. Surgical treatment was performed on an emergency basis, and the extension of the débridement varied with local conditions. In 2 (16.7%) patients, we chose to leave the surgical wound open and performed daily dressings with granulated sugar. Total sternal resection was performed in only 1 (8.3%) patient. Out of this series, 5 (41.7%) patients died, and the causes of death were related to the infection. Autopsy revealed persistence of mediastinitis in 1 (8.3%) patient. CONCLUSION: Promptness in diagnosing mediastinitis and precocious surgical drainage have changed the natural evolution of this disease. Nevertheless, observance of the basic precepts of prophylaxis of infection is still the best way to treat mediastinitis.

Adult↗
PubMed1999

[Importance of multiplane transesophageal echocardiography in the diagnosis of pulmonary embolism].

Pulmonary thromboembolism (PTE) is a clinical entity difficult to diagnose, its setting is often confused with other pathological entities. The inexistence of isotopic techniques in most centres and the difficulty and delay in performing a pulmonary angiography leads transesophageal echocardiography (TEE) to be, a method of increasing importance for its diagnosis. From January 1996 to November 1997, echocardiographic evaluation was requested for 33 patients due to clinical suspicion of pulmonary thromboembolism. A transthoracic assessment was made previously in 21 patients (average ages 58.3 years, 52% males) which had signs of right overload (dilatation of the right cavities, anomalous movement of the intraventricular septum and pulmonary hypertension) a TEE was performed. The TEE was negative in 10 patients (TEEn) without evidence of thrombi in the trunk and main branches of the pulmonary artery (PA); there was one death on this group for repeated pulmonary microembolisms confirmed by necropsy. The TEE was positive in 11 patients (TEEp) with evidence of thrombi in the PA trunk in 3 patients, bilaterally in both branches in 3 patients and in the right branch in 5 patients. There were dilatations of the right cavities in all patients, paradoxal movement of the interventricular septum and bulging of the intra-auricular septum to the left atria. Foramen ovale was detected in 2 patients. The best visualisation of the PA was achieved in the intermediate planes between 30-70 degrees and between 90-130 degrees (plane for transverse slice of the right branch of the pulmonary artery). In 7 patients with TEEp, PTE was confirmed by CT-scan (visualisation of the thrombi in the trunk and main branches of the PA) and/or ventilation-perfusion scintigraphy and/or pulmonary angiography. In three cases of massive pulmonary embolism in young patients, with severe pulmonary hypertension, thrombolysis was performed with rTPA, under TEE control before and after rTPA in one of the cases. In conclusion, transesophageal echocardiography is an easy technique to be performed in the case of clinical suspicion of PTE. The existence of a negative examination does not invalidate the existence of PTE since only the trunk and the main branches of the PA are accessible by this technique. The detection of thrombi at this level in patients with clinical suspicion of massive pulmonary embolism confirms the diagnosis and supports the indication of thrombolysis.

Adult↗
PubMed1999

[Influence of the equality of ventricular pressure in the echocardiographic determination of the ejection fraction of the left ventricle].

OBJECTIVES: Limited data have been reported concerning the influence of right ventricular systolic overload on the accuracy of the 2D echocardiographic (echo) determination of left ventricular (LV) ejection fraction (EF). The normal newborn at birth (high pulmonary peak systolic pressure) and just after the fall of pulmonary pressure, represent an in vivo model to study this influence. This study compares the LVEF determined by recommended 2D echocardiographic algorithms with that by 3D echo, in newborns at birth and just after the normal fall of right ventricular systolic pressure. METHODS: 100 echocardiographic studies (50 at 2 to 6 hours after birth--group I; and 50 at 7 to 14 days old--control group) were performed in 82 normal newborns, to determine LVEF by 4 geometric models (cylinder hemiellipsoid; ellipsoid biplane; single plane area length, in 4- and 2-chamber view; biplane method of discs) and visual estimation, using 3D echocardiography as the reference method. RESULTS: In group I, the correlation between 3D echo and cylinder hemiellipsoid was r = 0.62 (SEE = 4.5%); ellipsoid biplane, r = 0.69 (SEE = 4.1%); single plane area length, 4 chambers, r = 0.66 (SEE = 5.1%) and, 2 chambers, r = 0.72 (SEE = 4.0%); biplane method of discs, r = 0.83 (SEE = 3.6%), and, visual estimation, r = 0.78 (SEE = 3.5%). In the control group, the correlation between 3D echo and cylinder hemiellipsoid was r = 0.70 (SEE = 3.4%); ellipsoid biplane, r = 0.63 (SEE = 3.4%); single plane area length, 4 chambers, r = 0.79 (SEE = 3.5%) and, 2 chambers, r = 0.76 (SEE = 4.1%); biplane method of discs, r = 0.90 (SEE = 2.3%), and, visual estimation, r = 0.64 (SEE = 3.9%). IN CONCLUSION: These data suggest that the biplane method of discs and single plane area length using 2-chamber view allows a more accurate LVEF determination when significant right ventricular pressure overload is present.

Algorithms↗
PubMed1998

[Microsurgical reconstruction of the head and neck: experience of 63 free flaps].

The authors present the experience of 63 clinical cases of microsurgical reconstruction of the head and neck. These reconstructions were accomplished by different microvascular free flaps which were selected according to the type, size and location of the defects. Fasciocutaneous, osteofasciocutaneous, adipofascial, myo, myocutaneous, myosseous, jejunum and great omentum flaps were applied. The etiology was traumatic in 10 cases, tumoral in 41 cases, congenital in 7 cases, iatrogenic in 3 cases and infectious in 2 cases. The reconstructed anatomical regions were the scalp in 6 cases, the skull base in 1 case, the orbit in 3 cases, the nose in 1 case, the hemiface in 7 cases, the lips in 1 case, the intraoral cavity in 21 cases, the mandible in 8 cases, the intraoral cavity plus mandible in 11 cases and the cervical esophagus in 1 cases. An analysis was made of surgical times, selection and survival rate of the free flaps and the morphofunctional quality of the reconstructions. Considering the good quality of reconstructions, the amelioration of quality of life and the low morbidity in these patients, microvascular free flaps are considered a first choice technique for head and neck reconstruction when the size and location of the defect prevents the use of local flaps.

Adult↗
PubMed1998

Functional aspects of cord blood lymphocytes response to polyclonal and allogeneic activation.

With the purpose of contributing to a better knowledge of the phenotypic characteristics and functional activity of umbilical cord blood (UCB) lymphocytes, we have carried out extensive immunophenotyping of these cells, evaluated their immune response to polyclonal and allogeneic activation and then compared these results with those obtained with peripheral blood lymphocytes of healthy donors (PBHD). Our results showed, in CD4+ UCB lymphocytes, an increase of CD38 and CD45RA and a decrease of CD11a (S6F1), CD54 and HLA-DR double positive cells. An increase of CD38, CD45RA and CD56, and a decrease of CD28, CD57 and HLA-DR were observed in CD8+ UCB lymphocytes. Most natural killer UCB cells are CD16+, CD56+, CD57-, and among the UCB cells there is a lower number of CD8+ and TCRgammadelta+ (either CD8- or CD8+), and higher number of CD4+ lymphocytes. After allogeneic stimulus the majority of these phenotypic differences disappeared, which seems to be in agreement with the normal allogeneic response (assessed through MLR, frequency of CTL and helper T lymphocytes precursors) presented by UCB lymphocytes. Regarding the response to polyclonal activation, among the mitogens used, only PHA induced a different result: a lower IFNgamma production by UCB cells.

ADP-ribosyl Cyclase↗
PubMed1997

Comparison of left ventricular ejection fraction in congenital heart disease by visual versus algorithmic determination.

Two-dimensional (2D) echocardiographic visual estimation of left ventricular (LV) ejection fraction (EF) in patients with acquired heart disease yields results that are comparable to those obtained by recommended algorithms. However, there is no information concerning its accuracy in congenital heart disease. This study compares applicability, accuracy, and reproducibility of LVEF by visual estimation with that by currently used algorithms (cylinder hemiellipsoid, ellipsoid biplane, and biplane method of disks) in 92 consecutive patients with congenital heart disease but unrepaired complete atrioventricular septal defect, univentricular heart, and hypoplastic left ventricle, using 3D echocardiography as the reference method. Visual estimation of LVEF could be applied in all cases. Because of technically inadequate 2D echocardiographic images for volume measurement, analysis for comparison could be performed in 71 patients (77%), aged 1 day to 47 years. The correlation between 3D echocardiographic and visual estimation was 0.91 (SEE 3.3%), cylinder hemiellipsoid, 0.86 (SEE 3.9%), ellipsoid biplane 0.87 (SEE 3.9%), and biplane method of disks 0.93 (SEE 3.2%). Intraobserver variability was similar for all 2D echo methods. Interobserver variability was greater for visual estimation. In conclusion, visual estimation of LVEF is applicable to most patients with congenital heart disease, yielding results that are comparable to those obtained by currently used 2D echocardiographic algorithms.

Adolescent↗
PubMed1997

Is mitral valve prolapse a congenital or acquired disease?

The prevalence of mitral valve prolapse (MVP) at birth was studied in 1,734 consecutive newborns without congenital structural heart disease. We have not identified any case of an unequivocal pattern of MVP using auscultatory and echocardiographic diagnostic criteria. Our data argue for the concept that MVP is an acquired disease.

Echocardiography↗