Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Separation of Macromolecules by Ultracentrifugation and Electrophoresis

Free electrophoresis permitted the separation of plasma proteins into albumin and a-, β- and 7-globulins but was a complicated, expensive and very time-consuming procedure. It became evident that the electrophoretic technique must be simplified in order to be useful in clinical routine. The first attempt to use filter paper as a solid support was performed by Bennhold in Germany in his studies on bisalbumi-nemia. In the early 1950s, paper electrophores was used at the Department of Clinical Chemistry in Uppsala for studies of glycoproteins and immunoglobulins. Carl-Bertil Laurell (Head, Department of Clinical Chemistry, Malmtt since 1954), clearly stimulated by the clinicans’ interests in serum protein-related problems, saw the potential value of the paper electrophoretic technique as a diagnostic tool in clinical medicine. read

He, therefore, refined, improved and made the technique semiquantitative (Fig 1). Globulins could be distinctly separated into a1, a2-, β, p2- and 7-globulins. The paper electrophoretic serum protein pattern interpreted in relation to clinical findings and questions could provide valuable information in a variety of clinical settings. It was of great value for detection of monoclonal or polyclonal hypergammaglobulinemia, to judge disease activity in many chronic disease states, to detect lipid abnormalities, the nephrotic syndrome, etc. As a diagnostic tool in the evaluation of elevated erythrocyte sedimentation rates, paper electrophoresis gained increasing popularity among Swedish physicians. The clinical chemistry laboratory in Malmti became a referral center for serum protein analyses. Samples were sent for analyses from many hospitals throughout the country.
The First Cases of a XAT Deficiency
Swedish chest clinics had, for many years, concentrated on problems related to tuberculosis and became relatively isolated from general internal medicine. The importance of tuberculosis waned in the early sixties and the interests of chest physicians in Sweden gradually turned towards obstructive lung disease and cancer. The chief physician at the chest clinic in Eksjtt (in southern Sweden) sent samples from such patients to Malmtt for paper electrophoretic analysis.

Figure 1. Serum protein electrophoresis pH 8.6. Anode to the left. Normal serum.

Figure 1. Serum protein electrophoresis pH 8.6. Anode to the left. Normal serum.

Category: Health

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