Kidney transplant patients at Ullevål Hospital 1963-83. / Pasienter nyretransplantert ved Ullevål sykehus 1963­83.

BACKGROUND: In the period November 1963 to July 1983, 118 patients received a kidney transplant at Ullevål Hospital. All future kidney transplants were subsequently performed at Oslo University Hospital, Rikshospitalet. The purpose of our study is to present demographic data and show patient and graft survival from the first patient cohort of kidney transplant recipients in Norway. MATERIAL AND METHOD: The patients were identified in surgical protocols from Ullevål Hospital and the Norwegian Renal Registry using follow-up data up to December 2016. We recorded the patients' age and sex, cause of renal failure, donor characteristics, patient and graft survival, number of retransplants and cause of death. RESULTS: 118 patients: 38 women and 80 men, aged 14-67 years, received a transplant during the reference period. The most common indicators for transplantation were chronic glomerulonephritis (n = 61), chronic pyelonephritis (n = 20) and polycystic kidney disease (n = 14). Seventy-two patients (61 %) received a kidney from a deceased donor. After one year, 94 of the patients were still living (80 %), after five years, 66 of the patients (56 %) were still living, and after twenty years, the figure was 34 (29 %). Cardiovascular disease was the most common cause of death. The median graft survival was 3.8 years (quartile range 14.4 years). Thirty-two patients underwent retransplantation. INTERPRETATION: Even in this pioneering era, patient survival rates and the functional life of donated kidneys were acceptable.

Co-chaperones TIMP2 and AHA1 Competitively Regulate Extracellular HSP90:Client MMP2 Activity and Matrix Proteolysis.

The extracellular molecular chaperone heat shock protein 90 (eHSP90) stabilizes protease client the matrix metalloproteinase 2 (MMP2), leading to tumor cell invasion. Although co-chaperones are critical modulators of intracellular HSP90:client function, how the eHSP90:MMP2 complex is regulated remains speculative. Here, we report that the tissue inhibitor of metalloproteinases-2 (TIMP2) is a stress-inducible extracellular co-chaperone that binds to eHSP90, increases eHSP90 binding to ATP, and inhibits its ATPase activity. In addition to disrupting the eHSP90:MMP2 complex and terminally inactivating MMP2, TIMP2 loads the client to eHSP90, keeping the protease in a transient inhibitory state. Secreted activating co-chaperone AHA1 displaces TIMP2 from the complex, providing a "reactivating" mechanism for MMP2. Gene knockout or blocking antibodies targeting TIMP2 and AHA1 released by HT1080 cancer cells modify their gelatinolytic activity. Our data suggest that TIMP2 and AHA1 co-chaperones function as a molecular switch that determines the inhibition and reactivation of the eHSP90 client protein MMP2.