Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again

Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back AgainHistoric Perspectives
HP he discovery of inborn errors of metabolism, although rare in the general population, usually unexpectedly contributes to the understanding of pathogenetic mechanisms operating in disease. Al-phaxantitrypsin (o^AT) deficiency was in this respect no exception to the rule. This inborn error provided the first reasonable explanation of the tissue-destructive element so characteristic of emphysema. We have witnessed an extraordinarily rapid expansion in this field of research and the front line today seems to be in the hands of molecular biologists. In addition to its importance for chest physicians, however, o^AT deficiency also has had a considerable impact in hepatology which I will briefly discuss later. AlphaxAT deficiency was discovered in 1962 at the General Hospital, Malmo, Sweden. This was perhaps not due to a mere chance but could be regarded as one of many spectacular results emerging from a long and strong Swedish research tradition in protein chemistry, in particular the branch dealing with separation techniques. Reading here

Separation of Macromolecules by Ultracentrifugation and Electrophoresis
In the 1920s, Svedberg (Department of Physical Chemistry, Uppsala) devised his ultracentrifuge for protein separation. His pupil, Arne Ttselius, later developed the first separation technique for proteins in an electrical field: electrophoresis. Tiselius published his method of free electrophoresis in a PhD thesis in 1940. Jan Waldenstrom (at that time in Uppsala and later chairman of the Department of Medicine in Malmo) together with the physical chemist Kai Pedersen (Uppsala) realized the potential of these new techniques for the study of plasma protein patterns, particularly in patients with very high erythrocyte sedimentation rates. Use of the sophisticated ultracentrifugation technique was important in evaluation of such well-known entities as Waldenstroms macroglobulinemia and purpura hyperglobulinemia.

Category: Health

Tags: emphysema, lung disease, trypsin inhibitory capacity