Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221-442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C (84%) (P < 0.0001), 221-442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The competition pattern in type 1 diabetic patients differed from that in GAD65Ab-positive late autoimmune diabetes in adults (LADA) patients (n ‫؍‬ 44), first-degree relatives (n ‫؍‬ 38), and healthy individuals (n ‫؍‬ 14). Whereas 87 and 72% of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively, only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and 28% of healthy individuals showed competition (P < 0.0001). These findings support the view that type 1 diabetes is associated with disease-and epitope-specific GAD65Abs and supports the notion that the middle epitope is disease associated. These GAD65-specific rFabs should prove useful in predicting type 1 diabetes and in the study of conformational GAD65Ab epitopes. Diabetes

No abstract

No abstract

No abstract

A total of 659 consecutive patients underwent venography for the evaluation of idiopathic left varicocele before sclerotherapy. In 484 cases no valves of the left spermatic vein could be demonstrated, while 172 patients demonstrated competent valves or absent insertions of the left spermatic vein at the typical point on the left renal vein plus retrograde flow over persistent intercardinal anastomoses. Stenosis of the renal vein occurred in 103 patients (15.7%). In only 3 patients was stenosis observed in the course of the left iliac vein, suggestive of the so-called distal nutcracker phenomenon. We propose that during embryogenesis disturbances in the development of the secondary venous system may result in the idiopathic left varicocele.