Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0729233 (Thoracic)
 6,478 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this comprehensive review, two very closely related interstitial pneumonias are discussed: the cryptogenic form of organizing pneumonia (COP); and secondary forms of organizing pneumonia (OP), which occur in association with identifiable medical conditions. Some newer and lesser known of these associated conditions are described, most importantly post-radiation OP.Rapidly progressive, corticosteroid-resistant and poor prognostic forms of OP have been described. These types purportedly occur more frequently in secondary OP. However, OPs frequently coexist with other interstitial pneumonias, especially when associated with connective tissue diseases. Therefore, tissue sampling error or an incorrect morphologic diagnosis can be the basis for the occurrence of clinically aggressive OPs. By using the 2002 American Thoracic Society/European Respiratory Society diagnostic criteria, some pre-2002 cases reported as OP would be re-classified today.Although COP is considered to have a good prognosis and to be corticosteroid responsive, approximately 70% of patients, treated with corticosteroids, relapse even during initial treatment. Multiple and late relapses occur in about one-third of the patients. We performed a meta-analysis of second-line treatment options for corticosteroid-refractory forms of OP. Three alternative nonsteroid agents - cyclophosphamide, azathioprine, and cyclosporin - have been used in combination with corticosteroids. On careful review, in a number of cases reported as secondary OP, other histologic interstitial patterns besides OP were described. The need for second-line therapy in these patients might have been dictated by the non-organizing pneumonic component. Most of the scant number of reports come from outside the US. World experience with these is limited, but good clinical outcomes have been noted, even in patients with interstitial patterns in addition to OP.The initiation of the OP tissue response in the bronchiolar and sub-bronchiolar location may be due to the presence of bronchiolar-associated lymphoid tissue found at the bifurcations of the bronchioles. Inhaled antigens stimulate granulocyte colony stimulating factor-mediated airway inflammation, followed later by CD44-mediated clearance. Repair requires intrabronchiolar formation of granulation tissue and a favorable ratio of matrix metalloproteinase to tissue inhibitors of metalloproteinase (MMP : TIMP) within the stroma. This reparative milieu allows extracellular matrix degradation and re-synthesis to occur. MMP-expressing fibroblasts then phagocytose the collagen fibrils and microfibrils produced earlier in repair, reversing the initial fibrosis.
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PMID:The organizing pneumonias : a critical review of current concepts and treatment. 1669 89

Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgical treatment of TAAs usually involves a major operation, which conveys many risks to the patient. Better knowledge of the cellular events that lead to aneurysm formation may elucidate less morbid treatment options for this condition. A number of recent studies have identified that the relative abundance and activity of extracellular matrix (ECM) proteolytic systems are increased with TAAs. Specifically, the matrix metalloproteinases (MMPs) have been linked through numerous studies to TAA formation. MMPs comprise a family of ECM-degrading proteinases. Endogenous tissue inhibitors (TIMPs) normally regulate MMP activity, and the activation of MMPs is complex and tightly controlled. Aneurysm formation may be related to relative changes in the balance between MMP/TIMP abundance favoring proteolysis. Through ECM degradation, the medial layer will undergo structural remodeling and a loss of structural integrity, leading to TAA formation. The goals of this review are to examine the structure of the normal and aneurysmal thoracic aorta and to place the new findings regarding ECM proteolysis in perspective with regard to TAA formation and progression. Through an integration of basic and clinical studies regarding the underlying molecular basis for proteolysis of the thoracic aorta, improved diagnostic, prognostic, and therapeutic strategies for this disease process are likely to be realized.
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PMID:Proteinase systems and thoracic aortic aneurysm progression. 1729 15