Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteinase-3 (PR-3) and neutrophil elastase (NE) are polymorphonuclear leukocyte serine proteinases that degrade extracellular matrix proteins including elastin and appear to be involved in the pathogenesis of several diseases characterized by tissue destruction most notably emphysema and Wegener's granulomatosis. In this report we characterize and compare the mouse PR-3 and NE genes and establish by FISH analysis a common location on mouse chromosome 10C2. Each gene consists of five exons and four introns conserving the typical granule-associated serine proteinase gene structure. The mouse PR-3 gene (Prtn3) is approximately 3.7 kb and is within 2.2 kb of the smaller (1.7 kb) NE gene (Ela2). The larger size of Prtn3 is accounted for by differences in intron sizes. A comparison between the mouse and human PR-3 cDNA reveals 73% homology, however, this drops to 60% when the amino acid sequences are compared. Homology between the mouse and human NE cDNA is 77% for both the cDNA and amino acid sequences. The catalytic triad and its placement are conserved among the four genes. The proximal promoter of mouse Prtn3 contains a TATA box, c-myb and an ets transcriptional site. As these are functional elements in the mouse Ela2 promoter they may also be important in the expression of Prtn3.
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PMID:Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and neutrophil elastase (Ela2). 992 46

Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls. The extent of telomere shortening correlated with the age at diagnosis as well as the short telomere syndrome phenotype. Extremely short TL caused bone marrow failure and immunodeficiency in children and young adults, while milder defects manifested as pulmonary fibrosis-emphysema in adults. We prospectively examined whether TL altered treatment decisions for newly diagnosed idiopathic bone marrow failure patients and found abnormally short TL enriched for patients with mutations in some inherited bone marrow failure genes, such as RUNX1, in addition to telomerase and telomere maintenance genes. The result was actionable, altering the choice of treatment regimen and/or hematopoietic stem cell donor in one-fourth of the cases (9 of 38, 24%). We conclude that TL measurement by flowFISH, when used for targeted clinical indications and in limited settings, can influence treatment decisions in ways that improve outcome.
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PMID:Diagnostic utility of telomere length testing in a hospital-based setting. 2968 93