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)

Molecular analysis of alpha 1-antitrypsin (alpha 1AT) Wbethesda revealed that it differs from the normal M1 (Ala213) allele by a single base mutation causing an amino acid substitution Ala336 GCT----Thr ACT. Evaluation of alpha 1AT biosynthesis directed by the Wbethesda allele showed that although Wbethesda alpha 1AT mRNA was translated normally in vitro, transfection of the Wbethesda cDNA into COS-I cells was associated with human alpha 1AT secretion of 50% that of cells transfected with a normal alpha 1AT cDNA. The pattern of alpha 1AT biosynthesis was not intracellular accumulation as observed with the common Z alpha 1AT deficiency allele, but reduced intracellular alpha 1AT, suggesting intracellular degradation of the newly synthesized Wbethesda molecule. Together these observations suggest that in heterozygous combination with a Z or Null alpha 1AT allele, the Wbethesda variant causes "alpha 1AT deficiency", thus classifying it as an alpha 1AT "at risk" allele for emphysema.
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PMID:Alpha 1-antitrypsin Wbethesda: molecular basis of an unusual alpha 1-antitrypsin deficiency variant. 239 72

The human protease inhibitor genes alpha 1 antitrypsin (alpha 1-PI) and alpha 1-antichymotrypsin (alpha 1-ACT) are acute-phase proteins which are induced in response to inflammation. These inhibitors function to limit the activity of serine proteases in vivo. alpha 1-PI acts as an inhibitor of neutrophil elastase to protect the elastin fibers of the lung. Genetic deficiencies of alpha 1-PI result in development of chronic pulmonary emphysema. The physiologic role of alpha 1-ACT has not been clearly defined, but it also appears to function in the maintenance of protease-protease inhibitor equilibrium in the lung. Nucleic acid and protein sequence homologies detected between alpha 1-PI and alpha 1-ACT suggested an evolutionary relationship. Gene mapping experiments were performed to determine if these protease inhibitor genes reside at the same chromosomal locus in man. In situ hybridization data demonstrate that both alpha 1-PI and alpha 1-ACT map to the same region, q31-q32.3, on chromosome 14.
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PMID:Regional location of alpha 1-antichymotrypsin and alpha 1-antitrypsin genes on human chromosome 14. 348 24

A 26-year-old Negro male schizophrenic is described with severe bilateral orbital injuries following attempted self-enucleation. Owing to his psychosis there was difficulty in obtaining a visual acuity and in establishing the cause of his fixed, dilated pupils. ACT scan showed bilateral orbital oedema, with surgical emphysema and haemorrhage. The visual evoked potential (VEP) was present in the right eye but absent in the left. High doses of systemic steroids effected rapid resolution of the orbital swelling and recovery of the vision in the right eye. The effects of self-inflicted injury to the orbital content and the value of sophisticated investigation in this unusual case are discussed.
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PMID:Oedipism reviewed: a case of bilateral ocular self-mutilation. 670 64

Alpha 1-antichymotrypsin (alpha 1-ACT) is a serine proteinase inhibitor (serpin) with cathepsin G, mast cell chymase and chymotrypsin as target enzymes. We present the case of a middle-aged man with low plasma levels of alpha 1-ACT, asthma with progression to emphysema, and chronic HCV positive liver disease with selective accumulation of alpha 1-ACT in hepatocytes. This secretory defect is analogous to that seen in Pi Z alpha 1-antitrypsin deficiency. The molecular basis of alpha 1-ACT deficiency in this patient has been characterized by direct sequencing of the alpha 1-ACT genes from the patient and his father. A C-->G transversion in exon III causing a 229Pro-->Ala substitution is proposed to cause a conformational change resulting in abnormal transport through the RER. This mutation was found in one of 20 additional tested patients with chronic obstructive lung disease, but in no control. Two additional polymorphisms of the gene have been identified in unrelated healthy individuals with normal plasma alpha 1-ACT levels. The alpha 1-ACT deficiency state may predispose to obstructive lung disease and influence the course of liver disease. Identification of a specific mutation allows identification of heterozygotes for this deficiency allowing future evaluation of its clinical significance.
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PMID:The molecular basis of alpha 1-antichymotrypsin deficiency in a heterozygote with liver and lung disease. 822 25