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Zimmermann N Doepker MP Witte DP Stringer KF Fulkerson PC Pope SM Brandt EB Mishra A King NE Nikolaidis NM Wills-Karp M Finkelman FD Rothenberg ME 《American journal of respiratory cell and molecular biology》2005,32(5):428-435
Asthma is a complex inflammatory pulmonary disorder that is on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in the pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known to be involved in epithelial differentiation but not allergic disease. In situ hybridization revealed induction of SPRR2 signal in a subset of bronchial epithelial cells and mononuclear cells associated with inflammation after allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression was significantly decreased in IL-13-deficient mice. Studies in gene-targeted mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we aimed to determine if the induction of SPRR2 by allergen was tissue specific. Notably, SPRR2 was markedly increased in the small intestine after induction of allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology. 相似文献
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We reviewed the long-term results of 25 patients who had localized soft tissue resections for refractory anterior retinacular knee pain. Patients completed visual analog scales to determine their activity and pain level changes, subjective assessment of their results, and whether they would have the surgery again under the same circumstances. Five of the 25 patients (20%) had had no knee surgery before the soft tissue excision, with the rest having had an average of two prior operations (range, 1 to 6). Subjectively, 22 patients (88%) noted moderate-to-substantial improvement after surgery; 3 patients (12%) declared no long-term benefit. All 25 patients stated that they would repeat the surgery under the same circumstances. Five patients (20%) noted a decrease in their results over time, but only two patients (8%) decreased their job level after surgery because of their knee pain. The average activity level dropped 60% after knee symptoms developed and increased 40% after surgery. Pain levels decreased 50% after surgery. The patients with the best overall results had lesions that were in the medial, inferomedial, or inferolateral retinaculum. The histologic results of the specimens included fibrosis, vascular proliferation, and small nerves with decreased myelin (neuromata). Our results show that specific soft tissue excision of painful tissue can often lead to successful clinical outcomes. 相似文献
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Robert H. Hunsaker Phillip K. Fulkerson Fred J. Barry Richard P. Lewis Carl V. Leier Donald V. Unverferth 《The American journal of medicine》1982,73(2):235-238
The purposes of this study were to: (1) evaluate the progression of cardiac involvement in Duchenne's muscular dystrophy using systolic time intervals (PEP/LVET); (2) determine if the degree of cardiac involvement bears a relation to the severity of skeletal muscle disease; and (3) describe the M-mode and two-dimensional echocardiographic findings. In 1970, systolic time intervals were studied in 16 patients. During the 10-year interim, two patients were lost to follow-up study, and five patients died. Nine remaining patients were re-studied in 1980 with M-mode and two-dimensional echocardiography as well as systolic time intervals. The PEP/LVET value of these nine patients increased from 0.37 ± 0.05 (X? ± SD) in 1970 to 0.47 ± 0.07 (p < 0.005) in 1980. Three patients remained ambulatory, and their PEP/LVET value (0.41 ± 0.04) was significantly better than that of the nonambulatory patients (0.50 ± 0.07, p < 0.05). The M-mode echocardiography percentage diameter change was also worse in the nonambulatory group (21 ± 4 percent versus 34 ± 7 percent, p < 0.02). The five patients who were nonambulatory in 1970 died in the intervening 10 years. This study demonstrated that the heart disease of Duchenne's muscular dystrophy is progressive and that the severity of skeletal muscle disease is probably associated with the degree of cardiac dysfunction. 相似文献
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