Introduction: Nasal polyposis associated with aspirin-intolerant asthma tends to be difficult to control, with frequent recurrences. We examined the effect of intranasal lysine-aspirin administration on resistant nasal polyps of asthmatic, aspirin-intolerant patients, when used in addition to routine therapy.Patients and methods: Thirteen patients with asthma and intolerance to aspirin were recruited. All but one had undergone numerous polypectomies and were uncontrolled on standard therapy with intranasal corticosteroids, leukotriene receptor antagonists and nasal douching. Aspirin treatment involved one drop (100 ml) of 30 mg/ml lysine-aspirin solution to each nostril, initially daily, increased every two or three days up to a maximal of 18 drops (54 mg lysine-aspirin) a day. Nasal symptoms, nitric oxide level, nasal inspiratory peak flow rate, peak expiratory flow rate and nasendoscopic grading were assessed prior to therapy and three months later. We also compared the change in endoscopic polyp scores during three months of lysine-aspirin administration with the changes which had occurred during the three months prior to administration (during which time other therapies had been identical).Results: Nasal blockage symptoms tended to decrease; other nasal symptoms were unchanged. Significant changes were seen in nasal inspiratory peak flow rate (103.3 + 18.9 and 140.0 + 16.7 l/ min before and after aspirin, respectively; p ¼ 0.014), but not in peak expiratory flow rate (438.7 + 33.4 and 440.0 + 28.4 l/min before and after aspirin, respectively; p ¼ 0.700). Nasal nitric oxide levels rose significantly (in both sides, p ¼ 0.028). Expired chest nitric oxide levels did not change. Nasal polyp scores on nasendoscopic examination were significantly reduced (right side, p ¼ 0.027; left side, p ¼ 0.018). Compared with the preceding three months, adding intranasal lysine-aspirin application had the effect on decreasing nasal polyp volume (right side, p ¼ 0.031; left side, p ¼ 0.016).Conclusion: This open study suggests that intranasal lysine-aspirin administration reduces nasal polyp volume in aspirin-intolerant patients, without any adverse affect on concomitant asthma. This was a preliminary study and should be followed by a placebo-controlled, double-blind trial.

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The human interleukin-5 receptor (hIL-5R) consists of a unique α subunit (hIL-5Rα) and a common β subunit (βc) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Rα and βc by immunoprecipitation using anti–hIL-5Rα and anti-βc monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5–responsive cell line, TF-h5Rα. It was observed that IL-5 stimulation induced the recruitment of βc to hIL-5Rα, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Rα and βc, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, βc, and STAT5. Moreover, IL-5–induced dimerization of IL-5R subunits caused JAK2 activation and βc phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Rα revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Rα–associated JAK2 is indispensable for the IL-5 signaling event.

The authors believe that by close collaboration between endovascular therapists and vascular neurosurgeons, high-risk DAVFs in the lateral sinus and the confluence of sinuses can be successfully managed without treatment-related morbidity and mortality.

The JAK (Janus kinase) family of protein tyrosine kinases and the STATs (signal transducers and activators of transcription) have been shown to be activated in response to a number of cytokines and growth factors. In this study, we evaluated the activation of JAK/STAT pathway upon human interleukin-5 (hIL-5) stimulation of two different hIL-5-responsive cell lines, hIL-5 receptor α-subunit (hIL·5Rα) cDNA-transfected TF-1 (TF-h5Rα) and butyric-acid-treated YY-1 (YY-Bu), and peripheral eosinophils. Immunoprecipitation and electrophoretic mobility shift analysis revealed that tyrosine phosphorylation of JAK2 and activation of ST AT 5 were induced upon stimulation with hIL-5 in all three cell types, while STAT1 activation was only observed in eosinophils. These results indicate that JAK2/STAT5 activation is a common JAK/ STAT pathway for hIL-5-mediated signal in these cells.

A 49-year-old woman complained of hearing loss and diminution of left radial arterial pulsation. She had been diagnosed with sudden deafness and treated with corticosteroids. Her audibility deteriorated again after the cessation of the therapy. Angiograms showed stenosis in the bilateral carotid arteries, the left vertebral artery, the left subclavian artery, and the pulmonary arteries. She was diagnosed with Takayasu's arteritis. After steroid therapy was restarted, there were improvements in her audibility, radial arterial pulsation, and levels of inflammatory markers (erythrocyte sedimentation rate, Creactive protein, and gamma-globulin), fibrinogen, interleukin-6, and RANTES (regulated on activation, normal T cell expressed and secreted).

The human interleukin-5 receptor (hIL-5R) consists of a unique α subunit (hIL-5Rα) and a common β subunit (βc) that activate two Janus kinases (JAK1 and JAK2) and a signal transducer and activator of transcription (STAT5). The precise stoichiometry of the hIL-5R subunits and the role of JAK kinases used in IL-5 signaling were investigated. We analyzed the interaction between hIL-5Rα and βc by immunoprecipitation using anti–hIL-5Rα and anti-βc monoclonal antibodies. The binding of JAK1 and JAK2 to each hIL-5R subunit was also evaluated in the hIL-5–responsive cell line, TF-h5Rα. It was observed that IL-5 stimulation induced the recruitment of βc to hIL-5Rα, although in the absence of IL-5 the subunits remain independent. In the absence of IL-5, JAK2 and JAK1 were associated with hIL-5Rα and βc, respectively. IL-5 stimulation resulted in tyrosine phosphorylation of JAK2, JAK1, βc, and STAT5. Moreover, IL-5–induced dimerization of IL-5R subunits caused JAK2 activation and βc phosphorylation even in the absence of JAK1 activation. Furthermore, tyrosine phosphorylation of JAK1 was dependent on the activation of JAK2. Detailed study of the C-terminal truncated cytoplasmic domain of hIL-5Rα revealed that the cytoplasmic stretch at position 346-387, containing the proline-rich region, is necessary for JAK2 binding. These observations suggest that activation of hIL-5Rα–associated JAK2 is indispensable for the IL-5 signaling event.