Development of an immunochemical method for determination of human kepsinogen isozynogens and its clinical application

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1. Human pepsinogen A genes were clones and analyzed. The results showed that there exist at least three different genes and that at least two of them are tendemly aligend on a human chromosomal DNA.2. Rat prpsinogen C gens was cloned and the base sequences of all the exons and their veicnities were elucidated.3. Human pepsinogen C gene was cloned and the base suquences of all the xons and their vicinities were elucidated. 4. Restrriction nuclease difests of human blood cell DNA from 92 Japanese subjects were analyzed by Southern-blot analysis, demonstrating the presence of three different pepsinogen A genes in Japanese.5. The activation mechamisms of human, monkey and pocine pepsinogens A were investigated. The results showed that the mechanism differs significantly among species and that among human pepsinogen isozymogens the mechanism also differs significantly.6. An enzyme-linked immunsorbent assay (ELISA) for human pepsinogen A (of I) was developed by using a hybridoma monoclonal antibody against the zymogen. The concentration range of serum pepsinogen A in gealthy controls was 15-100 ug/1. Serum pepsinogen Levels were significantly higher in the subjects who developed active duodenal ulcer or active gastric ulcer, but significantly lower in those who had gastric cance, than in control subjects. This assay is thought to be useful in the screening work to identify subjects at incrteased tisk for gastric cancer of duodenal and gastric ulce.7 The serum level of pepsinogen A (PGA) and pepsinogen C (PGC) and the PGA/PGC ratio were compared with the surface area of the fundic mucosa, as determined endoscopically by the Congo red method. The PGA velue as well as the PGA/PGA ratio were shown to be useful in detection of chronic gastritis and gastric cancer.