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Biomedical subjects

A R Sousa

Publications and source records attributed to A R Sousa.

9 recordsLinked to original sources
PubMed1996

The effects of prednisolone on the cutaneous tuberculin response in patients with corticosteroid-resistant bronchial asthma.

We have used the classical tuberculin cutaneous delayed hypersensitivity immune response to investigate the effects of corticosteroids on mononuclear cell function in nine subjects with corticosteroid-resistant asthma (CRA) and six subjects with corticosteroid-sensitive asthma (CSA), who demonstrated sensitivity to intradermal purified protein derivative (PPD) of Mycobacterium tuberculosis. In a double-blind, crossover, placebo-controlled study, patients were given oral prednisolone or placebo, starting on day 0, and a predetermined intradermal dose of PPD on day 7. On day 9 the site of the induration was measured and biopsied for immunohistochemical analysis. There was no difference in skin induration between the CSA and CRA groups during the placebo arm of the study (p = 0.38). Prednisolone significantly suppressed the cutaneous induration (p, 0.003) in the CSA group but not in the CRA group. As compared with placebo, the number of macrophages (p = 0.018), eosinophils (p = 0.009), and T memory cells (p = 0.009) was suppressed by prednisolone in the CSA group but not in the CRA group. No significant suppression of the number of neutrophils or monocytes/immature macrophages was induced by prednisolone in either group. There was no difference in intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial leukocyte adhesion molecule-1 expression in blood vessels or epidermis between the CSA and CRA groups, with no suppression by prednisolone in either group. These findings suggest a defect in the responsiveness of cellular immune mechanisms to the suppressive effects of corticosteroids in steroid-resistant asthma. The differential suppressive effects of corticosteroids on cellular recruitment in the PPD response between the individuals with CSA and those with CRA are not due to modulation of expression of endothelial adhesion molecules.

Adrenal Cortex Hormones↗
PubMed1996

Effect of endobronchial aspirin challenge on inflammatory cells in bronchial biopsy samples from aspirin-sensitive asthmatic subjects.

BACKGROUND: The aspirin-induced bronchoconstriction in patients with aspirin-sensitive asthma is caused by cysteinyl leukotriene release. The cellular source of the leukotrienes is unknown. The inflammatory cell infiltrate in bronchial biopsy samples from seven aspirin-sensitive asthmatic (ASA) subjects and eight non-ASA subjects before and after local challenge with lysine aspirin was therefore examined. METHODS: Using flexible bronchoscopy, airway mucosal biopsy samples were taken and lysine aspirin solution was placed directly onto a carina of the contralateral lung. Twenty minutes later a second series of biopsy samples was taken from the site of the local endobronchial lysine aspirin challenge. The biopsy samples were double immunostained with a rabbit polyclonal antibody to the enzyme 5-lipoxygenase and monoclonal antibodies to mast cells (AA1), neutrophils (NP57), macrophages (EBM11), T lymphocytes (anti-CD3), and total (BMK13) and activated eosinophils (EG2). RESULTS: A decrease in both absolute mast cell numbers staining with mast cell tryptase (AA1) and the percentage of mast cells co-immunostaining with 5-lipoxygenase was seen in the ASA patients after lysine aspirin challenge compared with the non-ASA control group. There was also an increase in the numbers of activated eosinophils (EG2) in the ASA subjects compared with the non-ASA group. No changes were observed in the total numbers of macrophages (EBM11), neutrophils (NP57), total eosinophils (BMK13), and T lymphocytes (anti-CD3) after challenge with lysine aspirin. CONCLUSIONS: The decrease in numbers of mast cells staining for tryptase and the increase in activated eosinophils after endobronchial challenge with lysine aspirin may represent degranulation of these cell types, and may be an early event associated with aspirin-sensitive reactions in ASA subjects.

Administration, Topical↗
PubMed1996

Inflammatory cell populations in bronchial biopsies from aspirin-sensitive asthmatic subjects.

The inflammatory cell infiltrate in bronchial biopsies of 12 aspirin-sensitive asthmatic (ASA) subjects and eight non-aspirin-sensitive (non-ASA) control subjects have been compared. Biopsies were taken from a right middle or lower lobe segmental carina using fiberoptic bronchoscopy. The biopsies were snap-frozen in OCT, and sections 5 microns thick were doubled immunostained using a rabbit polyclonal antibody to the enzyme 5-lipoxygenase (5-LO) and with a monoclonal antibody to neutrophils (NP57), macrophages (EMB11), and total (BMK13) and activated eosinophils (EG2), mast cells (AA1), and T-lymphocytes (anti-CD3). There was no significant difference in the total numbers of cells staining for 5-LO between the two groups of subjects. As a percentage of total 5-LO cells, there were significantly more mast cells (12.9 +/- 3.8% versus 3.4 +/- 3.1%; p = 0.039) and total eosinophils (34.7 +/- 9.4% versus 11.1 +/- 3.8%; p = 0.044) and significantly fewer macrophages (23.3 +/- 6.1% versus 39.8% +/- 5.3; p = 0.041) in the bronchial biopsies from ASA subjects as compared with non-ASA patients. The numbers of neutrophils, T-lymphocytes, and activated eosinophils were similar for the two groups. The increased numbers of eosinophils and mast cells identified in the bronchial tissue from aspirin-sensitive asthmatic subjects may be the source of the enhanced cysteinyl leukotriene production observed in these subjects.

Administration, Inhalation↗
PubMed1996

Expression of interleukin-1 beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra) on asthmatic bronchial epithelium.

Accumulating evidence suggests that the cytokine network is central to the immunopathology of bronchial asthma and recent findings have suggested that naturally occurring cytokine antagonists may also be involved. In this study we looked at the expression of interleukin-1 beta (IL-1beta) and its naturally occurring receptor antagonist, IL-1ra, in the normal and asthmatic bronchial wall. Frozen bronchial biopsies from 12 normal and 18 asthmatic individuals were double stained with EBM11 (a CD68 macrophage marker) and either a rabbit anti-IL-1beta or a rabbit anti-IL-1ra. Hue-saturation-intensity color image analysis (HSI) was used to quantify the brown immunoperoxidase reaction product present on the bronchial epithelium. There was an increased expression of both IL-1beta and IL-1ra in the asthmatic bronchial epithelium, p < 0.0002 and p < 0.0001, respectively. Additionally, the numbers of macrophages, of IL-1beta producing cells, and the percentage of macrophages producing IL-1beta were significantly increased in the asthmatic submucosa (p < 0.004, p < 0.002, and p < 0.008, respectively).

Adult↗
PubMed1994

Increased expression of the monocyte chemoattractant protein-1 in bronchial tissue from asthmatic subjects.

The expression of the monocyte chemoattractant protein (MCP-1), a member of the chemokine family of low molecular weight cytokines, was assessed by immunohistochemistry in bronchial biopsies from 12 asthmatic and 12 normal subjects. Both a monoclonal antibody (F9) and a polyclonal antibody were employed to detect MCP-1, while the mouse myeloma protein (MOPC21) was used as a negative control. Strong positive reactions for MCP-1 were seen in the bronchial epithelium. Subepithelial macrophages, blood vessels, and bronchial smooth muscle were also stained. Hue-saturation-intensity color image analysis was used to quantify reactions of the monoclonal antibody in the epithelial and subepithelial layers. With the monoclonal antibody, asthmatic biopsies showed 51.8 +/- 3.7% (mean +/- SEM) of the epithelium staining positively, whereas normal subjects reacted much less, with 6.4 +/- 1.9% of the epithelium staining (P < 0.0001); there was no overlap between the two groups. Likewise, staining was increased in the subepithelium of asthmatic airway biopsies, with 11.5 +/- 3.1% and 2.0 +/- 1.0% staining positively in asthmatic and normal subepithelium, respectively, (P < 0.002). There was a significant correlation between staining of the epithelium and subepithelium (r = 0.77, P < 0.001). The polyclonal anti-MCP-1 antibody also gave strong reactions in the epithelium and subepithelium, with 34.0 +/- 7.8% of the asthmatic and 1.6 +/- 1.0% of the normal bronchial epithelium staining positively (P < 0.0001). These increased levels of MCP-1 in the asthmatic airways suggest that they may play a role in macrophage recruitment and activation and thereby contribute to the inflammatory pathology of bronchial asthma.

Adult↗
PubMed1993

Detection of GM-CSF in asthmatic bronchial epithelium and decrease by inhaled corticosteroids.

The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) in airway epithelial cells in vivo was assessed in 15 asthmatic and 9 normal subjects. GM-CSF was analyzed using immunohistochemistry with a polyclonal and a monoclonal antibody. Hue saturation intensity color image analysis was used to quantify staining. Asthmatic airway epithelial cells stained significantly more with anti-GM-CSF than those from normal subjects (p = 0.0013 and p = 0.0003 for the polyclonal and monoclonal antibodies, respectively). Additionally, 8 asthmatic individuals inhaled 1,000 micrograms beclomethasone diproprionate per day for 8 wk and 6 asthmatic patients inhaled matching placebo. There was a significant reduction of GM-CSF in the epithelium in the patients who were given corticosteroids (p = 0.014), whereas the group of subjects who were given placebo showed no significant change in GM-CSF staining. There was a correlation between the percentage suppression of GM-CSF staining by inhaled corticosteroids and the percentage increase in FEV1 (r = 0.61, p < 0.05) and percentage decrease in carbachol responsiveness (r = 0.80, p < 0.01). These findings suggest that GM-CSF may play a role in the inflammatory processes of bronchial asthma and that the epithelial cell may be a target cell for drug action.

Administration, Inhalation↗
PubMed1990

[Aorto-left ventricular tunnel arising from the left sinus of Valsalva].

Aortic-left ventricular tunnel (ALVT) is a rare congenital anomaly in which an abnormal communication connects the ascending aorta with the left ventricle, bypassing the aortic valve. Usually the ALVT takes its origin from the right aortic sinus. We report a patient with an ALVT arising from the left sinus of Valsalva who underwent surgery at five months of age. The diagnosis was first established by two-dimensional echocardiography.

Aorta↗
PubMed1983

Subclavian flap aortoplasty for treatment of coarctation of the aorta in infants less than 3 months of age.

Over a period of 3 years, 21 infants under 3 months of age were operated upon for coarctation of the aorta by subclavian flap aortoplasty. Associated intracardiac defects were present in 13 patients (62%), VSD being the most frequently encountered (10 patients, 48%). In 8 patients coarctation of the aorta, with or without patent ductus arteriosus, was the only cardiovascular malformation. The indication for surgical treatment was intractable congestive heart failure despite intensive medical treatment. Eight patients were on mechanical ventilatory support prior to surgery. There was no early operative mortality. One patient died in congestive heart failure due to valvular aortic stenosis 3 months after surgery for correction of the coarctation. During a follow-up of from 2 months to 3 years, 5 patients underwent a second operation for correction of intracardiac defects. Nineteen of the surviving 20 patients are in good clinical condition. One patient has clinical evidence of residual coarctation; a blood pressure difference of more than 10 mmHg between right arm and leg is presented in 4 patients. Early subclavian flap aortoplasty is recommended for patients with coarctation of the aorta, with or without associated intracardiac defects, who remain in congestive heart failure despite medical therapy.

Aortic Coarctation↗