Differential regulation of the histone chaperone HIRA during muscle cell differentiation by a phosphorylation switch

Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.

Focal-Type Autoimmune Pancreatitis Mimicking Cholangiocarcinoma / 대한내과학회지

Autoimmune pancreatitis (AIP) is a rare pancreatic disorder of autoimmune etiology. It has characteristic clinical features, such as pancreatic parenchymal swelling and irregular narrowing of the main pancreatic duct due to plasma cell infiltration. It occurs mostly in Far East Asia. Although it generally involves whole pancreatic parenchyma, some cases demonstrate focal involvement of the pancreas or adjacent organs, which are often mistaken for cancer. We report a case of AIP that was confused with cholangiocarcinoma of the distal common bile duct (CBD). The patient experienced sudden development of jaundice with vague abdominal discomfort. Abdominal computed tomography revealed a well-enhanced lesion, and positron emission tomography showed high standard uptake value at the distal CBD, indicating malignant disease. However, pathological examination by surgical excision indicated focal-type AIP. This is believed to be the first case of focal-type AIP mimicking cholangiocarcinoma.

Cavernous Sinus Metastasis of Non-Small Cell Lung Cancer / 결핵및호흡기질환

Progressive ptosis and headache developed in a 50-year-old woman with non-small cell lung cancer. Although brain magnetic resonance imaging showed improved cerebellar metastasis after prior radiotherapy without any other abnormality, the follow-up examination taken 6 months later revealed metastasis to the cavernous sinus. The diagnosis of metastasis to the cavernous sinus is often difficult because it is a very rare manifestation of lung cancer, and symptoms can occur prior to developing a radiologically detectable lesion. Therefore, when a strong clinical suspicion of cavernous sinus metastasis exists, thorough neurologic examination and serial brain imaging should be followed up to avoid overlooking the lesion.

Newly Developed Weakness of Lower Extremities Despite Improved Brain Metastasis of Lung Cancer after Radiotherapy / 결핵및호흡기질환

An intramedullary spinal cord metastasis (ISCM) rarely develops in systemic cancer but is indicative of a poor prognosis. A 56-year-old man was admitted due to weakness of the lower extremities. He had received radiotherapy 3 months prior for a brain metastasis that had developed 1 year after achieving a complete response from chemotherapy for extended stage small cell lung cancer. Although the brain lesion had improved partially, ISCM from the cervical to lumbar-sacral spinal cords, which was accompanied by a leptomeningeal dissemination, was diagnosed based on magnetic resonance imaging of the spine and cerebrospinal fluid cytology. Finally, he died of sudden cardiac arrest during treatment. This is the first case of ISCM involving the whole spinal segments. Physicians should be aware of the subsequent development of ISCM in lung cancer patients with a previously known brain metastasis who present with new neurological symptoms.

Radiographic and Magnetic Resonance Imaging of Segond Fracture in the Knee Joint

PURPOSE: Patients with Segond fracture have a high probability of anterior cruciate ligament and meniscal injury. The purpose of this study is to evaluate the site and shape of fragment of Segond fracture on plain radiograph and to analyze associated intraarticular injuries of knee joint on Magnetic Resonance(MR) imaging. MATERIALS AND METHODS: From July. 1994 to June 2002, 10 Segond fractures were reviewed retrospectively on plain radiograph and MR imaging. We confirmed by arthroscopic findings that ligamentous injuries and meniscal injuries were associated in all of the 10 cases. RESULTS: The radiographic findings of Segond fractures were as follows: the elliplical shape was 8 case, the average size 7.2 mm x 2.5 mm (length x width), the location average 4.3mm below tibial articular surface and the displacement average 2.0 mm from original site. Of the 10 patients, 9 (90%) had anterior cruciate ligament (ACL), 2 posterior cruciate ligament, 2 lateral collateral ligament and 4 medial collateral ligament injury. Meniscal injury was also diagnosed in 6. CONCLUSION: In plain radiograph of patients with acute traumatic knee injury, the caution is needed to examine Segond fracture. MR imaging is an useful study because anterior cruciating ligament disruption is often associated with Segond fracure.

The Degradation of Metallurgical Structure of Ti-6A1-4V Alloy after TKA in the Human

PURPOSE: To investigate the causes of structural degradation in Ti-6A1-4V alloy. MATERIALS AND METHODS: We prepared 20 metal specimens by cutting the fringe of 4 screw holes of tibial components taken from 5 cases of MG TKS(unused: 1, 3 years used: 2, 6 years used: 2). The structure and composition of specimens were analyzed by Scanning electron microscope(SEM), Energy dispersive spectrometer(EDS), and hardness tester. RESULTS: In soft tissue, titanium contained giant cells were observed by H-E stain, and Ti and Va peaks were detected by EDS. SEM showed that the unused specimens had normal metal fiber mesh texture, and the texture began to disappear from the surface of specimens after 3 years later. There were no metal fiber mesh, but black deposits were detected in specimens of 6 years. EDS revealed that Ti, Va, and Al peaks were appeared in the unused specimens, whereas 0 and C peaks in specimens of 3 years a#od 0, C, P, S, Ca and Cl peaks in specimens of 6 years were obtained. The hardness was decreased with the used period. CONCLUSION: It seemed that various molecular components of human body including carbon, hydrogen and oxygen influenced the metal elements of alloy to degrade in their structure.