Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells

Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. In this study, we employed a new proximity biotin-labeling method using promiscuous biotin ligase (pBirA) to identify unknown elements in the rapamycin-induced interactome on the FK506-rapamycin binding (FRB) domain in living cells. FKBP25 showed the strongest biotin labeling by FRB-pBirA in the presence of rapamycin. Immunoprecipitation and immunofluorescence experiments confirmed that endogenous FKBP25 has a rapamycin-induced physical interaction with the FRB domain. Furthermore, the crystal structure of the ternary complex of FRB-rapamycin-FKBP25 was determined at 1.67-angstrom resolution. In this crystal structure we found that the conformational changes of FRB generate a hole where there is a methionine-rich space, and covalent metalloid coordination was observed at C2085 of FRB located at the bottom of the hole. Our results imply that FKBP25 might have a unique physiological role related to metallomics in mTOR signaling.ope

Severe Chronic Active EBV Infection in an Adult Patient: Case Report

Severe chronic active Epstein-Barr virus (EBV) infection is a rare and life-threatening illness. Although the criteria for diagnosis include chronic or recurrent infectious mononucleosis-like symptoms lasting more than 6 months and high titers of anti-EBV antibodies, clinical and laboratory findings may be heterogeneous and flexible application of those criteria is necessary in cases showing typical clinical and pathologic findings. We report a case of severe chronic active EBV infection in a 62-yr-old female patient who showed classical clinical findings with infiltration of EBV-infected T lymphocytes in the bone marrow, spleen, and lymph nodes, and died four months after presentation

Manual Acupuncture at PC6 Ameliorates Acute Restraint Stress-Induced Anxiety in Rats by Normalizing Amygdaloid Noradrenergic Response

Acupuncture improves ethanol withdrawal-induced anxiety in rats in an acupoint-dependent manner. Thus, the present study investigated the effects of acupuncture on acute restraint stress- (ARS-) induced anxiety. Male rats were exposed to ARS for 3 h followed by acupuncture at either PC6 (Neiguan), HT7 (Shenmen), or a nonacupoint (tail) once a day for three consecutive days. Five minutes after the third acupuncture treatment, anxiety-like behavior was evaluated in an elevated plus maze (EPM). Additionally, plasma corticosterone (CORT) levels were measured by radioimmunoassay and the concentrations of norepinephrine (NE) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in the central nucleus of the amygdala (CeA) were determined using high-performance liquid chromatography. Acupuncture at PC6, but not HT7 or a nonacupoint, attenuated anxiety-like behavior, but this attenuation was abolished by a postacupunctural intra-CeA infusion of NE. Acupuncture at PC6 also reduced the oversecretion of plasma CORT and inhibited increases in amygdaloid NE and MHPG induced by ARS. Further, Western blot analyses and real-time polymerase chain reaction assays revealed that acupuncture at PC6 prevented ARS-induced enhancements in the protein and mRNA expressions of tyrosine hydroxylase in the CeA. These results suggest that acupuncture performed specifically at acupoint PC6 reduces ARS-induced anxiety-like behavior by dampening amygdaloid noradrenergic responses

Trends of Presentation and Clinical Outcome of Treated Renal Angiomyolipoma

PURPOSE: The purpose of this study is to set guidelines for the management of renal angiomyolipoma (AML), clinical prognosis according to tumor size, in association with tuberous sclerosis complex (TSC), multiplicity, radiographic finding, and treatment modality. MATERIALS AND METHODS: Between March 1998 and October 2008, 129 out of 254 patients with AML who underwent surgical intervention or angioembolization were enrolled. Diagnosis of AML was determined by the presence of a low attenuated component on CT imaging or by pathological confirmation. Indications of treatment were intractable pain, hematuria, suspicion of malignancy, large tumor size, spontaneous rupture, and radiographically equivocal tumors in which a differential diagnosis was needed to rule out malignancy. Parameters including age, sex, tumor size, multiplicity, radiographic characteristics, association with TSC, and treatment modality were reviewed. RESULTS: Age at presentation was 50.6 years and mean tumor size was 3.5 cm. Presentation symptoms were flank pain, hematuria, spontaneous rupture, and fatigue. 97 (75.2%) patients were incidentally discovered. 100 (77.5%) were females. 68 (52.7%) underwent nephron-sparing surgery (NSS), 35 (27.1%) radical nephrectomy, and 26 (20.2%) angioembolization. TSC was accompanied in 12 (9.3%) patients. No patient developed renal function impairment during the mean follow-up period of 64.8 months. Patients with TSC presented at a younger age, along with larger, bilateral, and multiple lesions. CONCLUSION: Significant differences in clinical manifestations and treatment outcomes were noted in respect to tumor characteristics, association with TSC, and treatment modality. Considering the benign nature of AML, these parameters ought to be considered when deciding upon active surveillance or prophylactic intervention.ope

Prescription Pattern of NSAIDs and the Prevalence of NSAID-induced Gastrointestinal Risk Factors of Orthopaedic Patients in Clinical Practice in Korea

This is a cross-sectional observational study undertaken to explore the current prescription pattern of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of NSAID-induced gastrointestinal (GI) risk factors of orthopaedic patients in real clinical practice in Korea. Study cohort included 3,140 orthopaedic outpatients at 131 hospitals and clinics between January 2008 and August 2008. A self-administered questionnaire was completed by each patient and physician. A simplified risk scoring scale (the Standardized Calculator of Risk for Events; SCORE) was used to measure patients' risk for GI complications. The pattern of NSAIDs prescription was identified from medical recordings. Forty-five percents of the patients belonged to high risk or very high risk groups for GI complications. The cyclooxygenase-2 enzyme (COX-2) selective NSAID showed a propensity to be prescribed more commonly for high/very high GI risk groups, but the rate was still as low as 51%. In conclusion, physician's considerate prescription of NSAIDs with well-understanding of each patient's GI risk factors is strongly encouraged in order to maximize cost effectiveness and to prevent serious GI complications in Korea. Other strategic efforts such as medical association-led education programs and application of Korean electronic SCORE system to hospital order communication system (OCS) should also be accompanied in a way to promote physician's attention