David E. R. Sutherland

sprouty encodes a novel antagonist of FGF signaling that patterns apical branching of the Drosophila airways.

Antagonists of several growth factor signaling pathways play important roles in developmental patterning by limiting the range of the cognate inducer. Here, we describe an antagonist of FGF signaling that patterns apical branching of the Drosophila airways. In wild-type embryos, the Branchless FGF induces secondary branching by activating the Breathless FGF receptor near the tips of growing primary branches. In sprouty mutants, the FGF pathway is overactive and ectopic branches are induced on the stalks of primary branches. We show that FGF signaling induces sprouty expression in the nearby tip cells, and sprouty acts nonautonomously and in a competitive fashion to block signaling to the more distant stalk cells. sprouty encodes a novel cysteine-rich protein that defines a new family of putative signaling molecules that may similarly function as FGF antagonists in vertebrate development.

branchless Encodes a Drosophila FGF Homolog That Controls Tracheal Cell Migration and the Pattern of Branching

The molecular basis for patterning of complex organ structures like the lung and insect tracheal system is unknown. Here, we describe the Drosophila gene branchless (bnl) and demonstrate that it is a key determinant of the tracheal branching pattern. bnl is required for tracheal branching and is expressed dynamically in clusters of cells surrounding the developing tracheal system at each position where a new branch will form and grow out. Localized misexpression of bnl can direct branch formation and outgrowth to new positions. Generalized misexpression activates later programs of tracheal gene expression and branching, resulting in massive networks of branches. bnl encodes a homolog of mammalian fibroblast growth factors (FGFs) and appears to function as a ligand for the breathless receptor tyrosine kinase, an FGF receptor homolog expressed on developing tracheal cells. The results suggest that this FGF pathway specifies the tracheal branching pattern by guiding tracheal cell migration during primary branch formation and then activating later programs of finer branching at the ends of growing primary branches.

An Increased Incidence of Late Acute Rejection Episodes in Cadaver Renal Allograft Recipients given Azathioprine, Cyclosporine, and Prednisone

We studied the incidence of biopsy-proven, acute rejection episodes occurring after 1 year posttransplant in cadaver renal allograft recipients. The 328 patients evaluated were given three immunosuppressive drug protocols. Group I (transplanted 9/80-6/84) (n = 75) received azathioprine, prednisone (P), and antilymphoblast globulin; group II (transplanted 9/80-6/84) (n = 83) received cyclosporine and P; group III (transplanted 7/84-12/86) (n = 170) received ALG, AZA, CsA, and P (sequential therapy). The incidence of first acute rejection episodes occurring up to 1 year posttransplant was 55% in group I and 35% in groups II and III. The incidence of late (greater than 1 year) acute rejection episodes was 6.5% in group I, 2.5% in group II, and 9.5% in group III (group II vs. III, P = 0.02). In group III, 50% of the late rejections were first, 44% second, and 6% third. The primary etiologies of this increased incidence of late acute rejection may have included subtherapeutic CsA levels and lower P doses. Sequential immunosuppressive therapy has been shown to be advantageous in the first posttransplant year. However, unless adequate immunosuppression is maintained, this approach can be associated with a significantly increased incidence of late acute rejection.

Experience with pancreas transplants from living related donors

The rationale to perform transplants of any organ from related donors rather than cadaver donors is twofold: there is a shortage of cadaver (CAD) donors for the number in need of a transplant, and the rejection rate will be less with grafts from living related donor (LRDs). Either of these two alone will justify the use of LRDs, and for kidney transplants both rationales pertain.

Renal Transplantation in Diabetic Patients: The Treatment of Choice

Diabetic patients with end-stage renal disease have been routinely accepted for kidney transplantation at the University of Minnesota since 1968 and now at most transplant centers worldwide. This is not surprising since approximately 25% of all patients accepted for treatment of end-stage renal disease in the United States have diabetes mellitus as the etiology of their renal failure. In earlier years of renal transplantation, results in diabetics were not as good as those in nondiabetics. Nevertheless, the survival rate of diabetic patients treated with transplantation exceeded that of diabetics maintained solely on dialysis.

Living donors in kidney retransplantation

Living donors have been used for a large number of kidney retransplants, but so rarely for extra-renal organs that an analysis is not possible. Hence, the data and discussion presented here on living donors is restricted to the kidney.

International Pancreas Transplantation Registry report

The International Pancreas Transplant Registry (IPTR) has collected information prospectively on all pancreas transplant cases in the world since 1980 (1), and has retrospective information on all cases before 1980 dating back to the first case performed in 1966 (2). Several previous reports of the Registry have been made (3–13). Some of the results of an analysis performed on August 22, 1989, of cases submitted to the Registry as of June 30, 1989, and reported in greater detail elsewhere (14, 15), are summarized here.

Pancreas transplantation in non-uremic diabetic recipients

Most pancreas transplants have been performed in diabetic patients with end-stage nephropathy who also received kidney transplants, either simultaneous with or before the pancreas graft (1). Such patients have been selected for the procedure because they were already obligated to immunosuppression in lieu of the kidney transplant, and the only risk incurred in order to achieve an insulin-independent, normoglycemic state, was that of the surgery itself, a risk that is currently very low (2–8). In addition, in such patients a kidney graft can be used to monitor for rejection episodes that in most instances effect both grafts simultaneously, with a rise in serum creatinine as a manifestation of renal allograft rejection preceding pancreas allograft dysfunction, allowing treatment to be initiated in time to preserve endocrine function. For this reason, pancreas graft survival rates are higher in recipients of simultaneous kidney transplants than in recipients of solitary pancreas transplants (8).

Immunosuppressive Therapy for Diabetics after Renal Transplantation

Uremia is the major cause of death in patients who live more than 20 years after the onset of insulin-dependent diabetes mellitus. Until recently, most uremic diabetics were not treated with dialysis and transplantation.

Pancreas Transplants in Diabetic Nephropathy

Pancreas-transplantation application for the treatment of diabetes mellitus has increased dramatically [1]. More pancreas transplants were performed in the 2 years from January 1, 1982, to December 31, 1983, than during the preceding 16 years [2], following the first transplant performed by Kelly and Lillehei and associates in 1966 [3].