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.      

Infarction of the septomarginal band and tricuspid papillary muscle rupture related to alcohol septal ablation for hypertrophic cardiomyopathy

We presented a 77‐year‐old man with hypertrophic obstructive cardiomyopathy applied with flail tricuspid leaflet and severe tricuspid regurgitation leading to right heart failure 2 months after the failed septal ablation. The ruptured anterior tricuspid papillary muscle resulted from infarction of the base of anterior papillary muscle of the right ventricle (RV) confirmed by magnetic resonance imaging. As the septomarginal band is frequently lit up by intracoronary contrast that particular attention should be paid to the RV papillary muscles. And, if the papillary muscles or the RV free wall is brightened, then the use of that septal artery should be avoided.     

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.     

Evaluation of the congenital supravalvular aortic stenosis by different imaging modalities

A 36‐year‐old female was admitted to hospital exhibiting chest pain, dyspnea, and a heart murmur on the right upper sternal border, radiating to both carotid arteries. The blood pressure of the patient's right arm exceeded the pressure in the left by 25 mm Hg (Coanda effect). In spite of laboratory results that did not fall outside the expected range, the left ventricle was revealed to be hypertrophic following electrocardiography. Transthoracic echocardiography revealed a severe supravalvular aortic stenosis (SVAS) with a peak Doppler velocity of 6.04 cm/s and an estimated mean pressure gradient of 89 mm Hg, with moderate aortic and mitral regurgitation. Contrast‐enhanced computed tomography (CCT) indicated a partial hourglass‐shaped narrowing of the ascending aorta. Lesions associated with supravalvular stenosis of the pulmonary artery, patent ductus arteriosus, and aortic coarctation were ruled out by the CCT. Congenital SVAS is a rare heart condition, and three anatomically distinct forms have been described. The most common type is the “hourglass,” which produces a marked thickening and disorganization of the aortic tissue, producing a constricting annular ridge at the superior margin of the sinuses of Valsalva.     

A rare complication of mechanical aortic valve replacement: Separation in the region of the mitral‐aortic intervalvular fibrosa

A 28‐year‐old man was admitted to our emergency service with a shortness of breath and palpitation. On admission, his blood pressure was high and he was in hypertensive pulmonary edema. His physical examination showed rales in both lungs and pansystolic murmur at mitral focus. His medical history included aortic valve replacement (AVR) because of native aortic valve infective endocarditis. Transthoracic echocardiography (TTE) showed normal functional aortic valve. Color flow imaging demonstrated severe mitral regurgitation with posterior eccentric jet. To examine in detail, transesophageal echocardiography (TEE) and three‐dimensional (3D) echocardiography were performed. TEE disclosed a separation in the subaortic curtain leading to severe mitral regurgitation from the left ventricle to the left atrium. In addition to severe mitral regurgitation with posterior eccentric jet, 26‐mm‐long pouch was seen in mitral‐aortic intervalvular fibrosa (MAIVF) at 120° TEE view. This pouch was separated from the mitral anterior leaflet junction releasing the mitral anterior leaflet and causing prolapse and chorda rupture in the A2 scallop of the mitral anterior leaflet. The MAIVF connects the anterior mitral leaflet to the posterior portion of the aortic annulus. The separation of the MAIVF represents a complication of the aortic valve replacement.