Young Jin Ko

Merlin Neutralizes the Inhibitory Effect of Mdm2 on p53

The stability of p53 tumor suppressor is regulated by Mdm2 via the ubiquitination and proteasome-mediated proteolysis pathway. The c-Abl and PTEN tumor suppressors are known to stabilize p53 by blocking the Mdm2-mediated p53 degradation. This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function. The results showed that merlin increased the p53 stability by inhibiting the Mdm2-mediated degradation of p53, which accompanied the increase in the p53-dependent transcriptional activity. The stabilization of p53 by merlin appeared to be accomplished through Mdm2 degradation, and the N-terminal region of merlin was responsible for this novel activity. This study also showed that overexpression of merlin-induced apoptosis of cells depending preferentially on p53 in response to the serum starvation or a chemotherapeutic agent. These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.

Motor branch of the rectus femoris: anatomic location for selective motor branch block in stiff-legged gait

OBJECTIVE To determine the ideal target point for selective motor branch block of the rectus femoris to treat stiff-legged gait. DESIGN Descriptive study. SETTING Anatomic institute of a university school of medicine in Korea. CADAVERS Twenty-two preserved adult cadavers. INTERVENTION The anterior thigh of the cadaver was dissected below the inguinal ligament. The motor branches of the 4 heads of the quadriceps were identified and traced from just below the inguinal ligament to the motor points. MAIN OUTCOME MEASURES The point T, where the motor branch of the rectus femoris is divided into smaller subbranches, was identified. Its location in relation to the surface anatomic landmarks was determined on the basis of the 2 anatomic lines that connect the anterior superior iliac spine to the medial femoral condyle, and the issuing spot of the femoral nerve below the inguinal ligament to the middle of the superior pole of the patellar. RESULTS The motor branch of the rectus femoris was divided into 2 subbranches at point T just before it reached the muscle. It nearly touched the medial margin of the rectus femoris at a proximal one-fourth to one-fifth point on 2 anatomic lines. The superior subbranch penetrated the muscle fascia at the posterior surface of the proximal one third of the muscle, whereas the inferior subbranch penetrated the muscle fascia at the medial border of the muscle. CONCLUSION The point T is the most suitable target point to selectively block the motor branch of the rectus femoris without affecting the other 3 motor branches of the femoral nerve in the treatment of stiff-legged gait.

A molecular basis for the efficacy of magnesium treatment following traumatic brain injury in rats.

Magnesium ions have been shown to be a promising treatment for brain lesions caused by traumatic brain injury (TBI), as well as for the associated acute neurodegeneration and progressive functional deficits. This study investigated the effects of magnesium on the expression of the cell death/survival related proteins following TBI. Male Sprague-Dawley (SD) rats (n = 66, 280-320 g body weight) were subjected to sham surgery alone (n = 14), or to the surgery followed by a lateral fluid percussion brain injury of moderate severity (n = 52, 2.4-2.7 atm). The injured rats were randomly treated with an intravenous bolus of magnesium chloride (n = 26, 125 micromol) or saline vehicle (n = 26). The coronal brain sections were quantitatively analyzed for cell apoptosis and the expression of p53-related proteins, Bcl-2, cyclin D1 and PCNA at 1, 2, and 4 days post-injury by immunohistochemistry or in situ hybridization. Tissue damage was observed primarily in the ipsilateral cortex of the injured region with the induction of apoptosis and p53 mRNA level at 2 days after TBI. The expression of p53 and responding proteins (p21(WAF1/CIP1), Mdm2 and Bax) showed a temporal pattern similar to the apoptotic events in the time course experiments. They were induced in the early time points of days 1-2, decreasing by day 4 after TBI. In contrast, the expression of the cell survival related proteins - Bcl-2, cyclin D1, and PCNA - was most significant at day 4 post-injury, when the rate of apoptosis decreased. Magnesium treatment resulted in a reduction in apoptosis and expression of p53-related proteins. However, it had only a slight additive effect on the expression of the survival related proteins in the same time-course. These results provide a molecular basis for the efficiency of magnesium in treating TBI-induced tissue damage.

Accuracy of the glenohumeral injection using the superior approach: a cadaveric study of injection accuracy.

Kim J-S, Yun JS, Kim JM, Ko YJ, Rhee WI, Ha NK, Kim M-W: Accuracy of the glenohumeral injection using the superior approach: a cadaveric study of injection accuracy. Objective:The glenohumeral joint can be accessed by anterior, posterior, or superior approach. Blind shoulder injections using anterior or posterior approach have been often inaccurate and infiltrated untargeted structures. The aim of this study was to investigate the success rate of injections in the glenohumeral joint using the superior approach. Design:Nineteen shoulders from 12 adult cadavers were anatomically dissected after a dye injection had been performed, with cadavers in the supine position. A clinician rated injection confidence scores. The dissectors rated injection accuracy scores and investigated untargeted structures penetrated. Results:The clinicians confidence scores were the highest in 18 of 19 shoulders. Superior glenohumeral injections were successful in 18 of 19 (94.7%) shoulders; however, in 3 of these 18 shoulders, the long heads of biceps tendons were penetrated. Conclusions:The glenohumeral joint injection using the superior approach is accurate and clinically useful, but caution for the likelihood of penetrating the long head of biceps tendon should be considered.

Inhibition of NF-κB activation by merlin☆

Abstract The neurofibromatosis type 2 (NF2) gene encodes an ezrin–radixin–moesin (ERM) related protein, referred to as either merlin or schwannomin, that is known to be a tumor suppressor. NF-κB signaling is known to be important for controlling cellular proliferation and protecting against apoptosis. In this report, merlin was demonstrated to be effective in suppressing the NF-κB signaling pathway in NIH3T3 and C6 cells. In addition, merlin blocked the tumor necrosis factor-α (TNF-α)-induced NF-κB–DNA binding mediated via the inhibition of degradation of IκBα and blocked the activation of NF-κB-dependent transcription. A reporter gene assay using deletion mutants of NF2 showed that the N-terminus (amino acids 1–130) of merlin may be important for its inhibition of NF-κB activation. These results show that merlin acts as a negative regulator of the NF-κB signaling pathway.

The quantitative assessment of functional impairment and its correlation to infarct volume in rats with transient middle cerebral artery occlusion

The purpose of this study was to quantitatively assess motor activity and sensory functions and to determine their relationships to infarct severity by measuring infarct volume in rats with transient ischemic stroke. Male Sprague-Dawley rats (11 weeks old, n = 42) were randomly divided into 4 separate groups; a sham operation group, and 1-h, 2-h and 3-h middle cerebral artery occlusion (MCAO) groups. Percent weights borne on paretic hind limbs were measured consecutively for 7 days starting from the day before the induction of ischemia. Fifty percent withdrawal threshold values of forepaws and hindpaws were measured using von-Frey hairs. Infarct volumes in the three ischemic groups, which were significantly different (p < 0.01) from each other, were found to increase in size with ischemic time. The percent weight borne on paretic hind limb in the three MCAO groups were significantly lower than that in the sham group, and this functional deficit remained significant throughout the observational period (p < 0.01). A significant correlation was found between infarct volumes and percent weight borne on paretic hind limbs after ischemia (-0.7 < rho < -0.4, p < 0.05). In contrast the 50% withdrawal threshold values of paretic forepaws and hindpaws in the three ischemic groups were not significantly different from those of the sham controls. Motor test findings, which were used to assess reductions in paretic hind limb weightbearing, were shown to be correlated with infarct volume. The present study shows that this test could be used as a tool to objectively and quantitatively assess functional outcome in MCAO rats.

Prevalence of pre-stroke low bone mineral density and vertebral fracture in first stroke patients.

PURPOSE After stroke, many factors contribute to the loss of bone mineral density (BMD) and fracture. Pre-stroke low BMD and vertebral fracture may pose a greater risk of fractures and further contribute to additional functional loss. The purposes of this study were to assess pre-stroke BMD and vertebral fracture in patients with first stroke. METHODS Forty-eight patients with first stroke events were included. To reflect pre-stroke BMD, the patients who underwent bone densitometry tests within 30 days from stroke onset were selected. BMD was checked at the lumbar spine and both femurs (total hip and femoral neck). Thoracic and lumbar spine X-rays were performed. RESULTS Of the 48 stroke patients, 21 (43.8%) had osteoporosis and 19 (39.6%) had osteopenia. X-ray evaluation showed that 12 (25.0%) had one or more lumbar or thoracic vertebral fractures and 8 (16.7%) had two or more vertebral fractures. Of the 12 patients who had one or more vertebral fractures, 4 (33.3%) were previously aware of the fact that they had a vertebral fracture. CONCLUSION Results showed a high prevalence of pre-stroke low BMD and vertebral fracture in patients experiencing first stroke. Bone loss progresses rapidly in the acute stages of stroke, and such a high prevalence of pre-stroke low BMD and vertebral fracture may pose a greater risk of fractures and further contribute to additional functional loss. Therefore, early screening and active management of osteoporosis from the acute stages of stroke is critical.

Detection of knee effusion by ultrasonography.

Hong BY, Lim SH, Cho YR, Kim HW, Ko YJ, Han SH, Lee JI: Detection of knee effusion by ultrasonography. Objectives:The purpose of this study was to assess which scan view was sensitive in detecting knee effusion by ultrasonography while infusing normal saline in cadaveric specimens. Design:Intraarticular injection of normal saline with contrast dye was done in increments (5, 10, 15, and 20 ml) into the knee joint of eight fresh cadavers. After infusion of each amount, sonographic images were obtained with five different scans: medial, midline, and lateral on longitudinal scans, and medial and lateral on transverse scans. When 20 ml had been injected, the knee was flexed at 30 degrees and serial images were taken. Results:After infusion of 10 ml, effusion of more than 2 mm depth with ultrasonography was most frequently seen in lateral transverse scans (14/14), and the next most frequent view was a lateral longitudinal scan (11/14). After knee flexion, the amount of effusion was increased on medial and middle longitudinal scans and was decreased on transverse scans. Conclusions:For detecting knee effusion by ultrasonography, lateral transverse and longitudinal scans were the most sensitive in the knee extension posture. With knee flexion at 30 degrees, effusion was more readily detected on the medial and midline longitudinal scans than with knee extension.

Correlating ultrasound findings of carpal tunnel syndrome with nerve conduction studies

Introduction: The aim of this study was to make correlations between ultrasonographic measurements of thenar muscle and flexor retinaculum and nerve conduction studies (NCS) in carpal tunnel syndrome (CTS). Methods: Ultrasound and NCS were performed on 92 wrists with CTS and on 40 wrists from healthy individuals. Ultrasound of thenar and hypothenar muscles, flexor retinaculum, and median nerve were assessed. The ultrasonographic findings were compared between the 2 groups, and correlation analyses between median latency and ultrasonographic findings were performed. Results: Motor latency correlated positively with flexor retinaculum thickness (FRT) and negatively with the ratio of thenar to hypothenar muscle. FRT and motor latency were found to be increased significantly in CTS. The ratio of thenar to hypothenar muscle was found to be decreased significantly in CTS compared with controls. Conclusions: The ultrasonographic findings of FRT and thenar muscle reflect the severity of disease in patients with CTS and are valuable for the diagnosis of CTS. Muscle Nerve 48: 905–910, 2013

Relapsed spontaneous spinal epidural hematoma associated with aspirin and clopidogrel

An acute spontaneous spinal epidural hematoma (SSEH) is a rare spinal pathology. A 57-year-old man who had hypertension and had been on dual antiplatelet therapy with aspirin and clopidogrel for primary prevention presented with the sudden onset of mid back pain and monoplegia of the left lower extremity. Magnetic resonance imaging revealed an epidural hematoma, and the patient underwent emergency hemilaminectomy for evacuation. However, the symptoms worsened, and complete paraplegia developed. A second procedure to remove the recurrent hematoma was performed. No vascular malformation or other possible cause for SSEH was found other than the aspirin and clopidogrel medication. This case report describes relapsed SSEH caused by the combination of aspirin and clopidogrel medication and urges caution in prescribing dual antiplatelet agents.