GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Estimated radiation doses to different organs among patients treated for ankylosing spondylitis with a single course of X rays

A follow-up study of over 14,000 patients treated with a single course of X rays for ankylosing spondylitis demonstrated a substantial excess risk of developing cancer. Previously the excess risk of leukaemia has been related to the estimated mean radiation dose to the active bone marrow but detailed estimates were not made of the radiation doses to other organs. In the present work, data extracted from the original treatment records of a random sample of one in 15 patients have been used to make dose estimates, using Monte Carlo methods, for 30 specific organs or regions of the body and 12 bone marrow sites. Estimates of the mean and median organ doses, standard deviations and ranges have been tabulated. Detailed distributions are presented for six organs (lung, bronchi, stomach, oesophagus, active bone marrow and total body). Comparison with the earlier bone marrow estimates and more recent theoretical estimates shows good agreement.     

Air accidents, pilot experience, and disease-related inflight sudden incapacitation

The epidemiology of sudden death, the etiology of inflight sudden incapacitation, and the influence of pilot age and experience on air accident rates are reviewed in order to determine the aeromedical emphasis needed to minimize accidents. Sudden deaths in men over age 35 are nearly all due to coronary artery disease, whereas in those under 35 years they are mostly due to hypertrophic cardiomyopathy. The incidence of fatal accidents from human error is, however, far greater than that from physical illness. Since inexperienced pilots have a 2-3 times increased incidence of mishaps due to pilot error, the estimated risk of disease related in-flight sudden incapacitation should be balanced by consideration of pilot experience. Therefore, it may be preferable to grant waivers to experienced pilots with an increased incidence of disease-related inflight sudden incapacitation than to replace them with novices. We conclude that overly strict medical criteria may paradoxically increase accident rates.     

New approach to management of intraaortic balloon pumps in patients with peripheral vascular disease: Case reports of four patients requiring urgent IABP insertion

Four selected cases of emergent IABP insertion in PV patients are presented. After angiographic documentation of critical iliac stenosis, conservative peripheral angioplasty was performed prior to IABP insertion. No patient experienced a peripheral ischemic event associated with IABP use. © 1992 Wiley-Liss, Inc.