No abstract

Monoclonal antibodies for the human insulin receptor were produced following immunization of mice with IM-9 lymphocytes and/or purified placental receptor. Four separate fusions yielded 28 antibodies, all of which reacted with receptor from human placenta, liver and IM-9 cells. Some antibodies cross-reacted to varying degrees with receptor from rabbit, cow, pig and sheep, but none reacted with rat receptor. At least 10 distinct epitopes were recognized as indicated by species specificity and binding competition experiments. All of these epitopes appeared to be on extracellular domains of the receptor as shown by binding of antibodies to intact cells. In some cases the epitopes were further localized to alpha or beta subunits by immunoblotting. Several antibodies inhibited binding of 125I-insulin to the receptor, some had no effect on binding, and others enhanced the binding of 125I-insulin. It is concluded that these antibodies will be valuable probes of receptor structure and function.

No abstract

Since the toxic fraction of cereal flour which damages the small bowel mucosa of patients with coeliac disease has not been fully defined in vivo, we studied the effect of intraduodenal infusions of different doses of unfractionated gliadin and of alpha-, beta-, gamma- and omega-gliadin subfractions on the morphology of multiple jejunal biopsies taken from two patients with treated coeliac disease. A dose-response study with increasing quantities of unfractionated gliadin in one coeliac patient showed that 1000 mg produced marked damaged in serial jejunal biopsies taken 2-3 h after commencing the infusion and that the changes had almost completely disappeared 72 h later. alpha-, beta-, gamma- and omega-gliadin were prepared, checked for purity and investigated for toxicity in two coeliac patients. After an intraduodenal challenge with 1000 mg of the four gliadin subfractions these were shown to have induced damage in the mucosa of jejunal biopsies taken 6 h later. These observations confirm the results of studies in vitro, which suggest that not only alpha-but beta-, gamma- and omega-gliadin are enterotoxic in coeliac disease.