Biomedical subjects

Qutayba Hamid

Publications and source records attributed to Qutayba Hamid.

94 records · Page 6Linked to original sources

PubMed2002

Intrasinus administration of topical budesonide to allergic patients with chronic rhinosinusitis following surgery.

OBJECTIVE: Whether instillation into the maxillary sinus of topical budesonide affected the immune response and improved allergic patients with chronic rhinosinusitis that had persistence of symptoms despite appropriate surgical intervention was assessed. STUDY DESIGN: Double-blind placebo-controlled. METHODS: Twenty-six patients with allergy to house dust mites who had previously had surgery and who had persistent symptoms of disabling rhinorrhea or pressure-pain resistant to oral antibiotics and intranasal corticosteroids were recruited. During the double-blind study, patients instilled 256 microg budesonide daily or placebo through an intubation device (maxillary antrum sinusotomy tube) into one of the maxillary sinuses for 3 weeks before clinical assessment and a second biopsy. RESULTS: We found an improvement in the symptom scores in 11 of the 13 patients who received budesonide; we also found a decrease in CD-3 (P = .02) and eosinophils (P = .002), and a decrease in the density of cells expressing interleukin4 (P = .0001) and interleukin-5 messenger RNA (P = .006) after treatment. CONCLUSION: Topical budesonide delivered through a maxillary antrum sinusotomy tube can control chronic rhinosinusitis that persists after surgery.

Administration, Intranasal↗

PubMed2002

CCR3-blocking antibody inhibits allergen-induced eosinophil recruitment in human skin xenografts from allergic patients.

Eosinophil, basophil, and T helper 2 (TH2) cell recruitment into tissues is a characteristic feature of allergic diseases. These cells have in common the expression of the chemokine receptor CCR3, which may represent a specific pathway for their accumulation in vivo. Although animal models of allergic reactions are available, findings cannot always be extrapolated to man. To overcome these limitations, we have developed a humanized mouse model of allergic cutaneous reaction using severe combined immunodeficiency mice engrafted with skin and autologous peripheral blood mononuclear cells from allergic donors. Intradermal injection of the relevant allergen into human skin xenografts from allergic individuals induced a significant recruitment of human CD4(+) T cells, basophils, and TH2-type cytokine mRNA-expressing cells, as well as murine eosinophils. Human skin xenografts, atopic status, and autologous peripheral blood mononuclear cell reconstitution were all mandatory to induce the allergic reaction. Next, we addressed the role of CCR3 in the endogenous mechanisms involved in the inflammatory cell recruitment in this experimental model of allergic cutaneous reaction. In vivo administration of an anti-human CCR3-blocking antibody selectively reduced accumulation of eosinophils but not that of CD4(+) cells, basophils, or cells expressing mRNA for TH2-type cytokines. These findings establish a new in vivo model of humanized allergic reaction and suggest that eosinophil migration is mediated mainly through CCR3. Finally, these results suggest that this model might be useful to test human-specific antiallergic modulators.

Allergens↗

PubMed2002

Expression of activation markers and cytokine mRNA by peripheral blood CD4 and CD8 T cells in atopic and nonatopic childhood asthma: effect of inhaled glucocorticoid therapy.

HYPOTHESIS: Activated CD8 as well as CD4 T cells contribute to the production of asthma-relevant cytokines in both atopic and nonatopic childhood asthma. OBJECTIVES: To measure the percentages of peripheral blood CD4 and CD8 T cells expressing naïve/memory (CD45RA/CD45RO) and activation (HLA-DR, CD25) markers, as well as mRNA-encoding interleukin-4 (IL-4) and interleukin-5 (IL-5) in atopic and nonatopic childhood asthmatics and in nonasthmatic controls matched for age and atopic status; and to study the effects of inhaled glucocorticoid therapy of the asthmatics on these measurements. METHODS: Peripheral blood mononuclear cells were isolated from 17 atopic and 8 nonatopic stable (not acutely ill) asthmatics aged 7 to 16 years with moderate-to-severe disease and from 15 nonasthmatic controls matched for age and atopic status. Activation markers on CD4 and CD8 T cells were measured by flow cytometry, and expression of cytokine mRNA by in situ hybridization with CD4 and CD8 T cells were isolated using magnetic beads. Measurements were repeated in 18 of the asthmatics 4 to 6 months after initiation or escalation of inhaled glucocorticoid therapy for inadequately controlled asthma. RESULTS: The percentages of CD4 T cells expressing CD45RO but not CD45RA were elevated in both asthma groups as compared with the relevant controls and were reduced in association with de novo or augmented inhaled glucocorticoid therapy. The percentages of CD8 T cells expressing both markers were not elevated in asthmatics as compared with controls. The percentages of both CD4 and CD8 T lymphocytes expressing HLA-DR and CD25 were elevated in the asthmatics as compared with controls, and significantly reduced in association with de novo or augmented inhaled glucocorticoid therapy. Elevated percentages of CD4 T cells expressing mRNA encoding IL-4 and IL-5, and CD8 T lymphocytes expressing IL-5, were found in asthmatics as compared with the controls. De novo or augmented inhaled glucocorticoid therapy was associated with significant reductions in the percentages of CD4 T cells expressing IL-5 and IL-4 mRNA, as well as improvements in lung function, symptom scores, and bronchial hyperresponsiveness to metacholine (PD20) in both the atopic and nonatopic asthmatics. CONCLUSIONS: The data are consistent with the hypothesis that both activated CD4 and CD8 T cells are associated with child asthma, and that CD4 T cells make a greater contribution to IL-4 and IL-5 synthesis. Increased dosages of inhaled glucocorticoid resulted in clinical improvement in the asthmatics along with reduced T-cell activation and cytokine mRNA expression, suggesting a possible causal association.

Adolescent↗

PubMedDate not supplied

Toll-like receptors 4 and 2 expression in the bronchial mucosa of patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a lung disease characterized by chronic infection with Gram-negative bacteria Pseudomonas aeruginosa and Gram-positive bacteria Staphylococcus aureus. Recently, toll-like receptor (TLR) 4 has been shown to be responsible for the lipopolysaccharide (LPS)-mediated immune response. While TLR2 mediates responses driven by bacterial lipoproteins and peptidoglycans from Gram-positive bacteria, LPS derived from P aeruginosa may stimulate the immune response in the airways of patients with CF via activation of TLR4. OBJECTIVES: To investigate TLR4 and TLR2 expression in the bronchial mucosa of patients with CF and normal control subjects. PATIENTS AND METHODS: Endoscopic bronchial biopsies from seven patients with CF and six healthy control subjects were obtained. TLR4 and TLR2 expression was assessed using immmunocytochemistry. Real-time polymerase chain reaction was used to detect TLR4 messenger RNA in blood cells from patients with CF and to compare TLR4 expression in CF bronchial epithelial cells with non-CF bronchial epithelial cells. RESULTS: In patients with CF, the number of TLR4-positive cells was significantly increased in their submucosa (P<0.05) but significantly reduced in their epithelium compared with control subjects (P<0.05). The majority of TLR4-positive cells were neutrophils. Patients with CF (n=4) and control subjects (n=4) had a similar percentage of TLR4-expressing neutrophils and monocytes/lymphocytes in peripheral blood. CF cells (IB-3) had significantly decreased basal TLR4 messenger RNA expression compared with non-CF cells (Calu-3) (P<0.05). Although there was a trend toward reduced TLR2 expression in the airway epithelium of patients with CF (P=0.07), there was no significant difference in TLR2 expression in the submucosa of patients with CF compared with that of control subjects. CONCLUSIONS: Both TLR4 and TLR2 expression in the bronchial epithelium of patients with CF were significantly reduced compared with healthy control subjects. In contrast, the number of TLR4-positive neutrophils in the submucosa of patients with CF was higher than in control subjects. This may suggest that the loss of epithelial TLR expression may contribute to the impaired defense against LPS.

Adult↗