In patients given a diagnosis of chronic spontaneous urticaria (CSU), there are no obvious external triggers, and the factors that initiate the clinical symptoms of wheal, flare, and itch arise from ...within the patient. Most patients with CSU have an autoimmune cause: some patients produce IgE autoantibodies against autoantigens, such as thyroperoxidase or double-stranded DNA, whereas other patients make IgG autoantibodies against FcεRI, IgE, or both, which might chronically activate mast cells and basophils. In the remainder of patients with CSU, the nature of the abnormalities has not yet been identified. Accumulating evidence has shown that IgE, by binding to FcεRI on mast cells without FcεRI cross-linking, can promote the proliferation and survival of mast cells and thus maintain and expand the pool of mast cells. IgE and FcεRI engagement can also decrease the release threshold of mast cells and increase their sensitivity to various stimuli through either FcεRI or other receptors for the degranulation process. Furthermore, IgE-FcεRI engagement potentiates the ability of mast cells to store and synthesize de novo inflammatory mediators and cytokines. Administration of omalizumab, by virtue of its ability to deplete IgE, attenuates the multiple effects of IgE to maintain and enhance mast cell activities and hence reduces the ability of mast cells to manifest inflammatory mechanisms in patients with CSU.
Background Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). ...Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs. Objectives We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions. Methods Labeled staphylococcal enterotoxin (SE) A, SED, and SEE were used to isolate single SAE-specific B cells from the nasal polyps of 3 patients with aspirin-exacerbated respiratory disease by using fluorescence-activated cell sorting. Recombinant antibodies with “matched” heavy and light chains were cloned as IgG1 , and those of high affinity for specific SAEs, assayed by means of ELISA and surface plasmon resonance, were recloned as IgE and antigen-binding fragments. IgE activities were tested in basophil degranulation assays. Results Thirty-seven SAE-specific, IgG- or IgA-expressing B cells were isolated and yielded 6 anti-SAE clones, 2 each for SEA, SED, and SEE. Competition binding assays revealed that the anti-SEE antibodies recognize nonoverlapping epitopes in SEE. Unexpectedly, each anti-SEE mediated SEE-induced basophil degranulation, and IgG1 or antigen-binding fragments of each anti-SEE enhanced degranulation by the other anti-SEE. Conclusions SEEs can activate basophils by simultaneously binding as antigens in the conventional manner to CDRs and as superantigens to framework regions of anti-SEE IgE in anti-SEE IgE-FcεRI complexes. Anti-SEE IgG1 s can enhance the activity of anti-SEE IgEs as conventional antibodies through CDRs or simultaneously as conventional antibodies and as “superantibodies” through CDRs and framework regions to SEEs in SEE–anti-SEE IgE-FcεRI complexes.
Objectives The purpose of this study was to provide direct evidences that rotor ablation suppresses atrial fibrillation (AF) inducibility. Background Micro–re-entrant wavefronts have been suggested ...to serve as sources of rapid activations during AF. Whether AF inducibility is suppressed by elimination of rotors remains unknown. Methods We used optical mapping to study Langendorff-perfused left pulmonary vein (PV)–left atrium (LA) preparations from 13 dogs with pacing-induced heart failure. Atrial arrhythmias were induced by pacing and mapped during acetylcholine infusion (1 μmol/l). Rotors were identified from optical recordings. Epicardial ablation was performed targeting the rotor anchoring sites in preparations with sustained (>10 min) or incessant spontaneous AF. Non-rotor ablation was performed in 4 preparations. Repeated pacing was performed to test the AF inducibility after ablation. Results Sustained AF (n = 12) and incessant spontaneous AF (n = 1) were induced after acetylcholine infusion. Pulmonary vein focal discharge was found in 9 preparations (9.2 ± 4.2 beats/s), and rotor anchoring was found at the left superior PV-LA junction in 13 preparations (9.1 ± 4.6 beats/s) and at the ligament of Marshall-PV-LA junction in 1 preparation. Epicardial rotor ablation successfully inhibited the inducibility of sustained AF in 12 of 13 preparations (p < 0.01), including 4 with the maximal dominant frequency sites located on the PV-LA junctional rotor zones (direct elimination of mother rotors). The longest AF duration was shortened significantly by rotor ablation (Wilcoxon Z = 3.60, p = 0.002, n = 13), but not by non-rotor ablation (Wilcoxon Z = 1.00, p = 0.317, n = 4). Conclusions Epicardial ablation of the rotor anchoring sites suppresses AF inducibility. The arrhythmogenicity at the maximal dominant frequency sites is directly/indirectly suppressed by the rotor ablation.
Abstract Background Bicycle-related head injury is an important public health issue. A paucity of statistical data on bicycle accidents exists in Taiwan. The purpose of this study was to report the ...characteristics of bicycle-related head injuries among school-aged children in Taipei, Taiwan. Methods Between 2001 and 2002, basic patient information of those with bicycle-related head injuries was collected from the Trauma Data Registry in 5 hospitals of the Taipei area. Telephone interviews were conducted to collect specific information surrounding bicycle accidents. Results Of 324 patients with bicycle-related head injuries, 90 (27.8%) had severe head injuries. Boys compared with girls had a higher proportion of severe head injuries (34.1% vs 23.4%; P = .048). Children aged 5 to 9 years had a higher proportion of severe head injuries compared with ages 10 to 14 years (65.2% vs 6.4%; P = .043). Bicycles without reflectors had a higher proportion of severe head injuries compared to bicycles with reflectors (69.0% vs 5.7%; P = .004). Bicyclists carrying goods (such as backpacks or weighted toward the road) and speeding were associated with severe head injury ( P < .05). Collisions with vehicles of a larger size resulted in a higher rate of severe head injury compared with collisions with pedestrians (76.9% vs 3.6%; P = .043). Conclusions For children whose main mode of transport is bicycles, the enforcement of helmet legislation, educational programs in bicycling safety and equipment, and improving the infrastructure for bicycling in urban areas are needed in Taiwan to reduce potentially debilitating or life-threatening injuries.
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