The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

GD3 Accumulation in Cell Surface Lipid Rafts Prior to Mitochondrial Targeting Contributes to Amyloid-beta-induced Apoptosis

Neuronal apoptosis induced by amyloid beta-peptide (A beta) plays an important role in the pathophysiology of Alzheimer's disease (AD). However, the molecular mechanism underlying A beta-induced apoptosis remains undetermined. The disialoganglioside GD3 involves ceramide-, Fas- and TNF-alpha-mediated apoptosis in lymphoid cells and hepatocytes. Although the implication of GD3 has been suggested, the precise role of GD3 in A beta-induced apoptosis is still unclear. Here, we investsigated the changes of GD3 metabolism and characterized the distribution and trafficking of GD3 during A beta-induced apoptosis using human brain-derived TE671 cells. Extracellular A beta induced apoptosis in a mitochondrial-dependent manner. GD3 level was negligible in the basal condition. However, in response to extracellular A beta, both the expression of GD3 synthase mRNA and the intracellular GD3 level were dramatically increased. Neosynthesized GD3 rapidly accumulated in cell surface lipid microdomains, and was then translocated to mitochondria to execute the apoptosis. Disruption of membrane lipid microdomains with methyl-beta-cyclodextrin significantly prevented both GD3 accumulation in cell surface and A beta-induced apoptosis. Our data suggest that rapidly accumulated GD3 in plasma membrane lipid microdomains prior to mitochondrial translocation is one of the key events in A beta-induced apoptosis.

Biomechanical Comparison of the Modified ML (Mattress Locking) Suture and the Modified MA (Mason-Allen) Suture in Rotator Cuff Repairs / 대한정형외과학회잡지

PURPOSE: In arthroscopic rotator cuff repairs, there is generally a weak link in the tendon suture interface, and arthroscopic rotator cuff repairs can have higher retear rates than open repairs. The purpose of this study was to compare the strength of modified ML (Mattress Locking) suture vs. the modified MA (Mason-Allen) suture when the suture is anchored into bone. MATERIALS AND METHODS: Paired human supraspinatus tendons were harvested and split in half, producing four tendons per one cadaver, for a total of 24 specimens. Two suture configurations (ML, MA) were randomized and checked for each set of tendons. Specimens were cyclically loaded under force control between 5 and 30 N at 0.25 Hz for fifty cycles. Each specimen was loaded to failure under displacement control at 1 mm/sec. Cyclic elongation, peak to peak displacement, stiffness, ultimate tensile load, and mode of failure were checked. RESULTS: No significant difference was found between the two suture configuration with respect to peak to peak displacement, cyclic elongation, and stiffness. With regard to ultimate failure load, there were no statistically significant differences between the modified ML suture and the modified MA suture (223.18N, 220.82N). The most common mode of failure between both sutures was suture pullout. CONCLUSION: The modified ML suture and the modified MA suture have similar biomechanical properties. The modified ML suture may be a simple and clever method and similar biomechanical alternative to the modified Mason-Allen suture in arthroscopic rotator cuff repair.

A Case of Adult-onset Metachromatic Leukodystrophy with Normal Nerve Conduction Studies

Adult-onset metachromatic leukodystrophy (MLD) is very rare with a combination of cognitive and behavioral symptoms and peripheral polyneuropathy. A 47-year-old man was admitted due to memory impairment, gait disturbance, dysarthria and personality changes for a period of 3 years. The arylsulfatase A level in his leukocytes was decreased. A brain MRI showed bilateral symmetrical demyelination but nerve conduction velocities (NCV) were normal. We report a very rare case of adult-onset MLD with normal NCV.

Efficacy of ENaP(ESTHETIC NaP)-line for orthognathic surgery of korean mandibular prognathism

As the most of dentofacial deformity patients indicated to orthognathic surgery have strong desire for esthetic improvement as well as functional improvement, ideal esthetic evaluation should be made at surgical prediction. Lateral cephalographs has been commonly used for surgical prediction, however, remarkable discrepancy between esthetic viewpoint by simple looking and analysis on lateral cephalographs often found on evaluation of sagittal position of the upper and lower jaws especially in cases of mandibular prognathism of Koreans. In these cases, we have been employed Esthetic NaP(ENaP)-line for corrective evaluation and ideal surgical pre-diction on lateral cephalographs, but the efficacy of ENaP-line has not been evaluated. This is a study on efficacy of ENaP-line for orthognathic surgery of Korean mandibular prognathism. 170 Korean patients who had been diagnosed as mandibular prognathism and planned for orthognathic surgery at Department of Oral and Maxillofacial Surgery, College of Dentistry, Yonsei University during last 10 years are studied. The obtained results are as followings; among 170 patients of mandibular prognathism, 132 patients(77.6%) had not discrepancy in evaluation of sagittal position of the maxilla between cephalometric and esthetic evaluation(they are classified as Group I), however, 38 patients(22.4%) had definite discrepancy(they are classified as Group II). ENaP-line was employed in all cephalometric analysis of Group II. The proportions of male and female were similar in both Groups. Sixteen vertical reference lines perpendicular to 16 horizontal reference lines were obtained as followings; Each of the representative degree of SN/AFH, SN/CFH and AFH/CFH obtained at Group I was applied to SN plane, AFH plane and CFH plane of Group II each other, and so 16 horizontal reference lines could be obtained individually according to each of the applied degree to each plane. And then their reliability to coincide with ENaP-line of Group II was evaluated. A vertical reference line perpendicular to a horizontal line made by application of the representative degree of AFH/CFH in Group I to AFH line in Group II had the most highest coincidence with ENaP-line of Group II, however, its agreement was 42% in male and 47% in female. From this results, the rest of them should be determined their corrective jaw position definitely depend on

Primary Left Atrial Myxosarcoma: One case Report / 대한흉부외과학회지

Primary cardiac myxosarcoma is extremely rare, which is uncommon in primary cardiac tumors. We report a primary cardiac myxosarcoma in a 40-year-old female patient who was admitted to the hospital because of exertional dyspnea and palpitation. The patient underwent emergency operation immediately after the intracardiac (left atrium) tumor was discovered by an echocardiography. Palliative tumor removal was done and final pathologic diagnosis was primary cardiac myxosarcoma. She was discharged without complications.

Immunohistochemical Expression of p53, E-cadherin, and nm23 Proteins in Metastatic Carcinoma of Neck Lymph Node and Corresponding Primary Carcinoma

This study was carried out to evaluate the immunohistochemical expressions of p53, E-cadherin, and nm23 proteins in 114 cases of metastatic carcinoma of the neck lymph node (MTLNCA) and corresponding primary carcinoma (PRCA). The positive expressions of p53, E-cadherin, and nm23 proteins were 62.3%, 58.8% and 64.0%, respectively in PRCA, and 40.4%, 38.6%, and 43.9%, respectively in MTLNCA with significant down-regulation from PRCA to MTLNCA (p<0.05). The down-regulation was correlated with female gender, moderate and poor differentiation, and adenocarcinoma in p53 protein, female gender, respiratory and gastrointestinal carcinoma in E-cadherin protein, and female gender, respiratory carcinoma, moderate differentiation, and squamous cell carcinoma in nm23 protein (p<0.05). There was no significant relationship among expressions of p53, E-cadherin, and nm23 proteins (p<0.05). In conclusion, these results suggest that the expressions of p53, E-cadherin, and nm23 proteins seem to be down-regulated from PRCA to MTLNCA and this down-regulation may play a role in invasion and metastasis.