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.     

Hypoxemia with air breathing periods in U.S. NAVY Treatment Table 6.

Air breathing is used to lessen hyperbaric oxygen (HBO2) toxicity. Hypoxemia could occur during hyperbaric air breathing in patients with lung dysfunction, although this has not been previously reported. We report two cases of hypoxemia during air breathing with two patients treated with the US Navy Table 6. Patient 1 was an 11-year-old male with cerebral gas embolism (during cardiac transplantation), patient 2 was a 66-year-old female with cerebral gas embolism from a central venous catheter accident. Both were mechanically ventilated. We monitored arterial blood gas (ABG) during therapy. In both patients, ABG measurements showed hypoxia during the first air breathing period at 1.9 atm abs (192.5 kPa). If patients require > or = 40% inspired oxygen before HBO2 therapy, oxygenation monitoring is advisable during air breathing periods, especially at lower chamber pressures (< or = 2.0 atm abs).     

INTRA-AORTIC BALLOON RUPTURE CAUSING FEMORAL ENTRAPMENT

Rupture of an intra-aortic balloon counterpulsator (IABCP) demands immediate removal. We report a case of thrombus formation within a Datascope IABCP secondary to IABCP rupture, necessitating surgical exploration for removal. There is a disturbing pattern of balloon ruptures with this type of IABCP.     

Ureteral duplication, ectopy and ureteroceles

These entities pose some of the most challenging diagnostic and therapeutic objectives involving the urinary system. The clinical presentations are varied, and involve children from prenatal to adolescent age groups. The diagnostic and therapeutic alternatives are presented, along with a classification for the more complex clinical settings.