End-to-side portacaval shunts were carried out in three children with the liver disease of alpha-1-antitrypsin deficiency and complications of portal hypertension. Their clinical courses have been stable for 3 1/2 to almost 7 years. Postoperative liver biopsy material from two of the patients showed the typical histopathological changes caused by portal diversion, as well as an apparent reducti...

We were all taught that proteins have to fold correctly to be active and that the primary sequence of amino acids acts as the ’blueprint‘ for successful, productive folding. in recent years, we have also learnt how sensitive that blueprint is to change. For example, a single amino-acid change in the protein sequence, or a subtle change in temperature at which folding takes place, can lead to th...

Alpha-1 antitrypsin deficiency is a recently identified genetic disease that occurs almost as frequently as cystic fibrosis. It is caused by various mutations in the SERPINA1 gene, and has numerous clinical implications. Alpha-1 antitrypsin is mainly produced in the liver and acts as an antiprotease. Its principal function is to inactivate neutrophil elastase, preventing tissue damage. The muta...

Alpha1-antitrypsin deficiency is a genetic disorder which contributes to the development of chronic obstructive pulmonary disease, bronchiectasis, liver cirrhosis and panniculitis. The discovery of alpha1-antitrypsin and its function as an antiprotease led to the protease-antiprotease hypothesis, which goes some way to explaining the pathogenesis of emphysema. This article will review the clini...

The S variant of the human alpha 1-antitrypsin with E-264----V, is responsible for a mild alpha 1-antitrypsin deficiency quite common in the European population. S protein specifically cleaved at the susceptible peptide bond was crystallized and its crystal structure determined and refined to 3.1 A resolution. The S variant crystallizes isomorphous to the normal M variant. The difference Fourie...

Cystic fibrosis (CF) is characterized by progressive and ultimately fatal pulmonary disease although there are notable variations in clinical features. This heterogeneity is thought to lie outside the cystic fibrosis transmembrane regulator (CFTR) gene locus and may stem from deficiencies in the antiproteinase screen that protects the lung from proteolytic attack. One hundred and fifty seven pa...