?1-antitrypsin deficiency is characterised by the misfolding and intracellular polymerisation of mutant protein within endoplasmic reticulum (ER) hepatocytes. Small molecules that bind stabilise Z were identified via a DNA-encoded library screen. A subsequent structure based optimisation led to series highly potent, selective cellular active correctors.

Binding curves for the adsorption of plasma fibronectin, alpha-1-antitrypsin, alpha-2-macroglobulin, ceruloplasmin, transferrin and bovine serum albumin to plain and to hydroxylated polystyrene surfaces were measured. These curves were correlated with the adhesion of BHK cells and leucocytes to these adsorbed protein surfaces in protein-free culture media. Hydroxylated polystyrene adsorbed less...

1- Deoxynojirimycin is a specific inhibitor of glucosidases I and II, the first enzymes that process N-linked oligosaccharides after their transfer to polypeptides in the rough endoplasmic reticulum. In a pulse-chase experiment, 1- deoxynojirimycin greatly reduced the rate of secretion of alpha 1-antitrypsin and alpha 1-antichymotrypsin by human hepatoma HepG2 cells, but had marginal effects on...

Hydrogen peroxide is a component of cigarette smoke known to be essential for inactivation of alpha(1)-antitrypsin, the primary inhibitor of neutrophil elastase. To establish the molecular basis of the inactivation of alpha(1)-antitrypsin, we determined the sites oxidized by hydrogen peroxide. Two of the nine methionines were particularly susceptible to oxidation. One was methionine 358, whose ...

Unlike most globular proteins, the native form of serine protease inhibitors (serpins) is strained. Previous studies of human alpha(1)-antitrypsin, a prototype plasma serpin, revealed that various unfavorable interactions, such as overpacking of side chains, buried polar groups and cavities, are the structural basis of the strain. The local strain could be relieved by various stabilizing single...

This report draws attention to the alpha 1 antitrypsin deficiency in newborns presented as a cholestatic syndrome. Its sub-diagnosis constitutes a major constraint for recognition and appropriate treatment. Good outcomes occur in approximately 50% of patients. It is associated in most cases, to extra and intra-hepatic involvement and the absence of clinical signs that indicate its diagnosis. Th...

The behaviour of alpha 1 antitrypsin in fever stress condition had been investigated on a lot of 51 males and females subjects. 76.4% of them had adaptative reaction by increasing the alpha 1 antitrypsin; 23.5% with basal normal values had no significant reaction in the fever phase and only one subject was deficiently in both conditions. The significance of the non-reactive subjects supports di...

Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Pulmonary and Critical Care Medicine, Cleveland Clinic Foundation, Cleveland, Ohio; Department of Pulmonary and Critical Care Medicine, Oregon Health Sciences University, Portland, Oregon; Division of Pulmonary and Critical Care Medicine, The New York Hospital/Cornell University, New York, ...

C3, factor B, and alpha-1-antitrypsin were determined in newborn infants with septicaemia and sclerema, associated with suspected infections, ABO or Rh incompatibility, and hyperbilirubinaemia of unknown origin, during and after treatment with exchange transfusion. Activation products from C3 and factor B, the clearance of the transfused C3, and its synthesis by the recipient were determined al...

A 47-year-old Caucasian male presented to the chest clinic with a 4-week history of exertional dyspnea. A chest radiograph showed mild hyperinflation without any focal pathology and spirometry showed a mild obstructive defect. In view of symptoms being disproportionate to spirometric and radiologic abnormalities, a thoracic CT scan was obtained. It revealed that there was evidence of bronchiect...