Allergy and Immunology – serie

This work is concerned with Cystic Fibrosis (CF), the most common fatal genetic disease in the Caucasian population. The decade of the 1980s was one of spectacular progress in understanding the genetic and molecu­ lar basis of CF. The research breakthroughs of the decade began with the first fundamental insights, published in 1981-1983, into the basic cellular pathophysiology of CF with demonstrations of altered ion transport in spe­ cialized exocrine epithelial tissues (1-3). Research progress shifted into a triumph of "reverse genetics," using restriction-fragment-Iength polymor­ phism DNA technology (4), with the localization of the CF gene to a region of chromosome 7 (5-7). Understanding, accelerated by an explOSion of in vitro methodologies for epithelial cell culture and transformation, allowed and physiological studies (8-11); these focused, controlled biochemical with increasing precision, on the molecular pathology of distal steps in the regulatory pathways for epithelial ion transport (12-19). Finally, the "end of the beginning" occurred in late 1989 with one of the great achievements of molecular genetics, the isolation and cloning of the CF gene (20). As a result, we now have a CF gene product, the cystic fibrosis transmembrane regulator (CFfR), possessing predicted amino acid sequence, suggested tertiary structure, and possible transmembrane transport function (21). These amazing developments have set the stage for the next round of advances, which surely will include: 1.

It has been little more than a century since Emil von Behring and his colleagues (1890) showed that the blood of tetanus-immune rabbits contained a factor that could be transferred to nonimmune animals to protect them against tetanus. These observations, together with the work of Paul Ehrlich, started scientists on the long and complex path to our present understanding of the humoral, or B-cell, immune system. These early studies led to Nobel prize awards for von Behring (1901 ) and Ehrlich (1908), each of whom contributed much to our knowledge of the B-cell immune system. In the early 20th century it was recognized that the serum of individuals who had recently suffered an infection contained a protective humoral factor that could be transferred to a nonimmune person, thereafter affording that individual protection against the infectious agent that had caused disease. In 1933 McKhann and Chu reported that a placental extract containing the globulin fraction could modify measles. However, it was not until 1939 that Tiselius and Kabat demonstrated that the antibodies responsible for protection against these infectious disorders resided within the gammaglobulin plasma fraction. In a major step forward, Cohn in 1944 established a method for the fractionation and purification of this plasma gammaglobulin fraction. These procedures, which are based on cold ethanol precipitation of plasma, produce a readily adaptable, large-scale fractionation procedure that is still utilized to this day in the preparation of commercial gammaglobulin.

Leading clinical experts survey the latest information available on the key rheumatic and allergic issues that physicians face in treating the HIV-infected patient.

It has been little more than a century since Emil von Behring and his colleagues (1890) showed that the blood of tetanus-immune rabbits contained a factor that could be transferred to nonimmune animals to protect them against tetanus. These observations, together with the work of Paul Ehrlich, started scientists on the long and complex path to our present understanding of the humoral, or B-cell, immune system. These early studies led to Nobel prize awards for von Behring (1901 ) and Ehrlich (1908), each of whom contributed much to our knowledge of the B-cell immune system. In the early 20th century it was recognized that the serum of individuals who had recently suffered an infection contained a protective humoral factor that could be transferred to a nonimmune person, thereafter affording that individual protection against the infectious agent that had caused disease. In 1933 McKhann and Chu reported that a placental extract containing the globulin fraction could modify measles. However, it was not until 1939 that Tiselius and Kabat demonstrated that the antibodies responsible for protection against these infectious disorders resided within the gammaglobulin plasma fraction. In a major step forward, Cohn in 1944 established a method for the fractionation and purification of this plasma gammaglobulin fraction. These procedures, which are based on cold ethanol precipitation of plasma, produce a readily adaptable, large-scale fractionation procedure that is still utilized to this day in the preparation of commercial gammaglobulin.

This work is concerned with Cystic Fibrosis (CF), the most common fatal genetic disease in the Caucasian population. The decade of the 1980s was one of spectacular progress in understanding the genetic and molecu­ lar basis of CF. The research breakthroughs of the decade began with the first fundamental insights, published in 1981-1983, into the basic cellular pathophysiology of CF with demonstrations of altered ion transport in spe­ cialized exocrine epithelial tissues (1-3). Research progress shifted into a triumph of "reverse genetics," using restriction-fragment-Iength polymor­ phism DNA technology (4), with the localization of the CF gene to a region of chromosome 7 (5-7). Understanding, accelerated by an explOSion of in vitro methodologies for epithelial cell culture and transformation, allowed and physiological studies (8-11); these focused, controlled biochemical with increasing precision, on the molecular pathology of distal steps in the regulatory pathways for epithelial ion transport (12-19). Finally, the "end of the beginning" occurred in late 1989 with one of the great achievements of molecular genetics, the isolation and cloning of the CF gene (20). As a result, we now have a CF gene product, the cystic fibrosis transmembrane regulator (CFfR), possessing predicted amino acid sequence, suggested tertiary structure, and possible transmembrane transport function (21). These amazing developments have set the stage for the next round of advances, which surely will include: 1.