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.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

Effect of age on left ventricular systolic function in humans: a study of systolic isovolumic acceleration rate

The aim of this study was to examine the effect of age on left ventricular (LV) systolic function in normal healthy adults. Eighty consecutive subjects without cardiovascular disease underwent standard and tissue Doppler (TD) echocardiographic imaging. LV systolic function was assessed by load-dependent indices as ejection fraction (EF) and myocardial systolic velocities by TD as well as by the load-independent index, systolic isovolumic acceleration rate (IVA). None of the echocardiographic measurements of systolic function declined with age (mean IVA for the group, 286 +/- 123 cm s(-2); IVA vs. age, r = 0.21, P = 0.1). Likewise, LV end diastolic dimension, wall thickness, mass and left atrial maximum volume were not significantly related to age. On the other hand, as previously reported, echocardiographic indices of diastolic function showed a significant decline with age (P < 0.05). When the group was stratified by gender, isovolumic velocity and acceleration were higher in men than women, but the differences were not significant (P = 0.12 and 0.37, respectively). No significant relation was observed between age and measurements of LV systolic function by regression analysis in women (P > 0.1). However, in men, a positive correlation was noted between average IVA and age (r = 0.63, P = 0.007). In conclusion, age is not associated with a change in cardiac structure and LV systolic function, but is accompanied by a decline in echocardiographic indices of diastolic function. With respect to gender, age does not appear to influence LV systolic function in women, but is associated with an increase in IVA and septal systolic ejection in men.     

How to use a nasopharyngeal prong in Pierre Robin sequence

Pierre Robin sequence (PRS) describes a small mandible with retrognathia, an elevated and posteriorly positioned tongue, and an associated U-shaped cleft palate. The retracted tongue may obstruct the airway leading to respiratory failure, with failure to thrive and adverse neurodevelopmental outcomes if not addressed. If the airway obstruction cannot be overcome with conservative measures, there are non-surgical and surgical options. A nasopharyngeal prong (NPP) is a non-surgical, temporary treatment that avoids the complications inherent in an operation, especially given the natural history of mandibular growth and improved airway obstruction in PRS. Although the use of a prong requires training, support, and follow up, it effectively bypasses the obstruction in the majority of children with PRS, and allows the child to outgrow the airway obstruction until the prong is no longer required. On average, the prong can be removed between 6 and 12 months of age.     

A prospective follow-up of alcohol septal ablation for symptomatic hypertrophic obstructive cardiomyopathy--the Baylor experience (1996-2002)

BACKGROUND: There is a paucity of data on the long-term outcome of alcohol septal ablation (ASA) for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). HYPOTHESIS: The study was undertaken to evaluate the longer-term outcome of ASA therapy for symptomatic HOCM. METHODS: In all, 137 patients were enrolled consecutively (1996-1999) and 130 (95%) (74 men, 56 women, aged 51 +/- 17 years) underwent ASA and had serial prospective follow-up for up to 5 years (mean follow-up 3.6 +/- 1.4 years). Evaluation included angina (Canadian Cardiovascular Society [CCS] score), dyspnea (New York Heart Association [NYHA] class), duration of exercise on treadmill, and echocardiographic indices. RESULTS: Ethanol (3.5 +/- 1.5 cc), injected into 1.5 +/- 0.6 arteries, induced a mean peak plasma creatine kinase (CK) of 1676 +/- 944 units. Complications of procedures included death 1.5% (2/130), heart block requiring permanent pacemaker 13% (17/130), and coronary dissection 4.4% (6/130). Baseline versus last follow-up visit: NYHA class decreased from 3.0 +/- 0.4 to 1.2 +/- 0.6 (p < 0.01); CCS angina score from 2.0 +/- 0.8 to 0.08 +/- 0.4 (p < 0.01); and duration of exercise increased from 322 +/- 207 to 443 +/- 200 s (p < 0.01). Resting left ventricular outflow tract gradient at baseline versus last follow-up visit showed a decrease from 74 +/- 30 to 4 +/- 13 (p < 0.01), and the dobutamine-provoked gradient of 88 +/- 29 decreased to 21 +/- 21 (p < 0.01) mmHg. All-cause mortality over the duration of follow-up was 7.7% (10) giving an annual rate of 2.1%, and cardiac mortality was 2.3% (3) reflecting an annual rate of 0.6%. CONCLUSIONS: Alcohol septal ablation decreased symptoms and improved exercise performance, indicating that it is an effective procedure for symptomatic HOCM.