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.     

Cell renewal and gene expression in the trachea of hamster at different ages.

The tracheal mucosa of the Syrian golden hamster has been extensively employed as a model system for respiratory tract cell renewal, injury, and carcinogenesis. However, baseline cell kinetic data are not available for normal juvenile and adolescent animals in which the mucosa and cartilage are rapidly enlarging. The objective of this research was to elucidate alterations in cell kinetics, epithelial morphology, and gene expression in the trachea of hamsters at different ages. Cell kinetics were examined by 3H-thymidine labeling indices, morphology by light and electron microscopic examination, and gene expression by slot blot analysis. Results showed that mucosal epithelium of the young and adolescent hamster undergoes cyclic necrosis and cell shedding, exposing portions of the elastic basal lamina. Epithelial shedding was associated with hyperplasia and squamous metaplasia. Additionally, the labeling indices of mucosal epithelial cells and chondroblasts also exhibited variable patterns which were associated with a cyclic pattern of expression of c-fos and c-erbB2 proto-oncogenes and epidermal growth factor receptor.     

Successful treatment of periungual warts using photodynamic therapy: a pilot study

AIM: The aim of this pilot study was an investigation on photodynamic therapy (PDT) whether it is a good alternative for treating periungual and subungual warts of the hands. STUDY DESIGN: Twenty patients (mean age: 30.5 years) with a total of 40 periungual and subungual warts were treated with PDT. A photosensitizer, 20%delta-aminolevulinic acid was applied on the warts. After a mean incubation time of 4.6 h (SD: 1.2), the warts were irradiated with the VersaLight for 5-30 min (15.2 +/- 4.3 min). RESULTS: After a mean of 4.5 treatments a mean clearance of 100% was achieved in 90% of the patients. One patient (5%) showed a clearance of 50% and another showed no improvement. The subungual or periungual location of the wart had no influence on the number of treatments or end result (P > 0.05). There were two recurrences during the mean follow-up period of 5.9 months (SD: 7.6). Besides mainly pain and hyperpigmentation, most treatments had no side-effects. CONCLUSION: PDT can offer a good alternative for treating periungual warts of the hands. Larger studies are indicated.     

Predictors of mortality and institutionalization after hip fracture: the New Haven EPESE cohort. Established Populations for Epidemiologic Studies of the Elderly.

OBJECTIVES. Hip fractures can have devastating effects on the lives of older individuals. We determined the frequency of occurrence of hip fracture and the baseline factors predicting death and institutionalization at 6 months after hip fracture. METHODS. A representative cohort of 2812 individuals aged 65 years and older was followed prospectively for 6 years. Hip fractures were identified, and the occurrence of death and institutionalization within 6 months of the fracture was determined. Prefracture information on physical and mental function, social support, and demographic features and in-hospital data on comorbid diagnoses, fracture site, and complications were analyzed to determine predictors of death and institutionalization after hip fracture. RESULTS. Of 120 individuals suffering a hip fracture, 22 (18%) died within 6 months and 35 (29%) were institutionalized at 6 months. The predictors of death in multiple logistic regression included fracture site, a high number of comorbid conditions, a high number of complications, and poor baseline mental status. The primary predictor of institutionalization was poor baseline mental status. CONCLUSIONS. The frequency of death, institutionalization, and loss of function after hip fracture should prompt a reevaluation of the current approach to this problem.     

Metastatic thyroid carcinoma presenting as an expansile intraluminal esophageal mass

We report a patient with metastatic thyroid carcinoma invading the esophagus in whom barium and MR examinations revealed an expansile intraluminal mass indistinguishable from that of a primary esophageal malignancy. Metastatic thyroid carcinoma should therefore be included in the differential diagnosis of an expansile esophageal mass. As in our patient, MR imaging may be useful for showing that the mass originates in the thyroid gland.     

Temporomandibular joint: morphology and signal intensity characteristics of the disk at MR imaging

Magnetic resonance (MR) imaging has been used in the temporomandibular joint (TMJ) primarily to define the disk position. This report examines altered morphology and signal intensity characteristics of the TMJ disk as they relate to the severity of internal derangement. Two hundred sixteen joints in 133 patients with a history of such derangement. were imaged with MR. Disk position, signal intensity, morphology, and the presence of osteoarthritis were determined for each joint. The normal disk was not anteriorly displaced and had a normal "bow-tie" shape. A grade 1 disk was anteriorly displaced and had a normal shape; a grade 2 disk was anteriorly displaced and had an abnormal shape. Forty (19%) joints were considered normal; none of these exhibited osteoarthritis. One hundred thirty-nine (64%) joints were grade 1; osteoarthritis was found in 17%. Thirty-seven (17%) were grade 2; osteoarthritis was found in 95%. All forty normal joints had high or intermediate signal intensity in the disk. Osteoarthritic joints had a higher percentage of disks with diminished intensity (P less than .0001). Severe or untreated osteoarthritis is known to be a complication of TMJ internal derangements; hence this grading system seems to correlate with the severity of internal derangement.