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The influence of ionic strength and composition on the binding and inhibition of human leukocyte elastase by glycosaminoglycans with variable degree and position of sulfation was investigated. The kinetic mechanism of inhibition had a hyperbolic, mixed-type character with a competitive component that was promoted by low ionic strength, reduced by phosphate ions, and which also depended on the substrate and glycosaminoglycan structure. Enzyme binding was a cooperative phenomenon that varied with ionic strength and composition. The inhibition patterns correlated with the cationic character of elastase and with the distribution of arginines on its molecular surface, most notably with residues located in the vicinity of the substrate binding region. The order of affinity for elastase binding was chondroitin 4-sulfate < chondroitin 6-sulfate < dermatan sulfate, iduronate-containing derivatives being superior with respect to the glucuronate-containing counterparts. Additional sulfation at both the 4- and 6- positions or at the N- and 4-positions of the N-acetylgalactosamine moiety decidedly improved the inhibitory efficiency. The results highlight a fundamental physiological role of enzyme-glycosaminoglycan interactions. In the azurophil granule of the human polymorphonuclear neutrophil, elastase and other enzymes are bound to a matrix of chondroitin 4-sulfate because this is the only glycosaminoglycan that simultaneously offers good binding for enzyme compartmentalization together with prompt release from the bound state at the onset of phagocytosis.  相似文献   
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BACKGROUND & AIMS: Arterioportal fistulas (APFs) are rare vascular disorders of the mesenteric circulation. The aim of this study was to determine the etiology, anatomical location, and main symptom at presentation of APFs, and analyze the various modes of treatment. METHODS: The etiology, clinical presentation, radiographs, and treatment of 12 patients with APFs are reported in detail, and another 76 cases published since 1980 are reviewed. RESULTS: APFs result from trauma (n = 25, 28%), iatrogenic procedures (n = 14, 16%), congenital vascular malformations (n = 13, 15%), tumor (n = 13, 15%), aneurysm (n = 12, 14%), and other causes (n = 11, 12%). The origin of APFs is the hepatic artery in the majority of patients (n = 56, 65%). The main symptoms at presentation are lower or upper gastrointestinal bleeding (n = 29, 33%), ascites (n = 23, 26%), heart failure (n = 4.5%), or diarrhea (n = 4.5%). Radiological intervention provides definitive treatment in 42% (n = 33) of patients, whereas the remainder are treated by surgery alone (n = 27, 31%) or a combination of radiological intervention and surgery (n = 8, 9%). CONCLUSIONS: APFs result in a protean syndrome variously combining portal hypertension and other hemodynamic imbalances (heart failure, intestinal ischemia). Single or multiple interventional radiological procedures using arterial and/or venous approaches allow definitive treatment of most APFs. With increasing technological advances, it is anticipated that surgery will only be indicated in rare instances after failure of radiological intervention(s).  相似文献   
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The role of geriatrics and geriatricians in family medicine remains unsettled. Despite a rapidly aging population, a tremendous shortage now exists of faculty with interest and expertise in geriatrics. Relatively few family practice residents choose to enter geriatric fellowship programs, and federal funding for such programs has been reduced. Despite accreditation requirements, residency programs are not always able to provide the range of geriatric experiences needed to properly prepare graduates to provide care for the broad range of older patients. Medical students' exposure to geriatrics remains limited. The Group on Geriatric Education of the Society of Teachers of Family Medicine believes that family medicine faculty must recognize and be committed to the notion that geriatrics is integral to family medicine. Both undergraduate and residency training programs should emphasize experience with geriatric patients in multiple settings. In particular, the nursing home should not be the main focus of geriatric training. The small number of certified geriatric faculty will be able to provide leadership, but a broad range of faculty must become involved in teaching geriatrics. Faculty development activities and continuing education programs to foster the necessary expertise will be essential to the accomplishment of this task.  相似文献   
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