EBV-positive Hodgkin lymphoma is associated with suppression of p21cip1/waf1 and a worse prognosis

<p>Abstract</p> <p>Background</p> <p>About 30-50% of Hodgkin lymphomas (HLs) harbor the Epstein-Barr virus (EBV), but the impact of EBV infection on clinical outcomes has been unclear. EBV-encoded small RNAs (<it>EBER</it>s) are presented in all EBV-infected cells, but their functions are still less understood.</p> <p>Results</p> <p><it>EBER1 </it>was transfected into two HL cell lines, KMH2 and L428, and microarrays were used to screen for <it>EBER1</it>-induced changes. We found that <it>EBER1 </it>suppressed <it>p21</it>^cip1/waf1transcription in HL cell lines. In addition, positive regulators of <it>p21</it>^cip1/waf1transcription, such as p53, EGR1, and STAT1, were decreased. Suppression of <it>p21</it>^cip1/waf1in the <it>EBER1</it>⁺HL cell lines was associated with increased resistance to histone deacetylase inhibitors or proteasome inhibitors, drugs known to cause apoptosis by increasing p21^cip1/waf1levels. On biopsy specimens, EBV⁺HLs had weaker expression of both p21^cip1/waf1and active caspase 3. Clinically, suppression of p21^cip1/waf1in EBV⁺HLs was associated with a worse 2-year disease-free survival rate (45% for EBV⁺HLs <it>vs</it>. 77% for EBV^-HLs, <it>p </it>= 0.002).</p> <p>Conclusion</p> <p>Although the underlying mechanisms are still relatively unclear, <it>EBER1 </it>inhibits <it>p21</it>^cip1/waf1transcription and prevents apoptosis through down-regulation of p53, EGR1, and STAT1. The anti-apoptotic activity of <it>EBER1 </it>may be important in the rescue of Reed-Sternberg cells from drug-induced apoptosis and in the clinical behaviors of EBV⁺HLs.</p

Canine adipose tissue-derived MSCs engineered with mRNA to overexpress TSG-6 and enhance the anti-inflammatory effects in canine macrophages

BackgroundMesenchymal stem cells (MSCs) are useful agents in the treatment of various inflammatory diseases. The immunomodulatory effects of MSCs are largely related to their secretory properties. mRNA engineering emerged as a safe alternative to enhance the secretory function of MSCs. Optimization of the untranslated region (UTR) sequence is important for enhancing the translational efficiency of exogenous mRNAs. However, research on the optimization of UTR in canine MSCs has not yet been conducted.ObjectivesWe aimed to identify the UTR sequence related to the expression efficiency of in vitro transcription (IVT) mRNA in canine MSCs and investigate whether mRNA-engineered MSCs that overexpress TSG-6 exhibit enhanced anti-inflammatory effects.MethodsCanine adipose tissue-derived (cAT)-MSCs were transfected with green fluorescence protein (GFP) mRNA with three different UTRs: canine hemoglobin subunit alpha-like 1 (HBA1), HBA2, and hemoglobin subunit beta-like (HBB). The translation efficacy of each mRNA was evaluated using relative fluorescence. TSG-6 mRNA was produced with the UTR optimized according to relative fluorescence results. cAT-MSCs were transfected with TSG-6 mRNA (MSCTSG-6), and TSG-6 expression was analyzed using real-time quantitative PCR, ELISA, and western blotting. To evaluate the anti-inflammatory effects of MSCsTSG-6, DH82 cells were co-cultured with MSCsTSG-6 or treated with dexamethasone, and changes in the expression of inflammatory cytokines were analyzed using qPCR.ResultsThe highest fluorescence level was observed in the HBA1 UTR at 24 h post-transfection. TSG-6 mRNA transfection yielded high levels of TSG-6 in the cAT-MSCs. In DH82 cells co-cultured with MSCsTSG-6, the expression of inflammatory cytokines decreased compared to that in co-culturing with naïve MSCs and dexamethasone treatment.ConclusionsOptimization of the HBA1 UTR improved the translation efficiency of IVT mRNA in canine MSCs. cAT-MSCs engineered with TSG-6 mRNA effectively enhanced the anti-inflammatory effects of the MSCs when co-cultured with LPS-activated DH82 cells

Acute Diffuse Phlegmonous Esophagogastritis: A Case Report

Acute phlegmonous infection of the gastrointestinal tract is characterized by purulent inflammation of the submucosa and muscular layer with sparing of the mucosa. The authors report a rare case of acute diffuse phlegmonous esophagogastritis, which was well diagnosed based on the typical chest computed tomographic (CT) findings and was successfully treated. A 48-yr-old man presented with left chest pain and dyspnea for three days. Chest radiograph on admission showed mediastinal widening and bilateral pleural effusion. The patient became febrile and the amount of left pleural effusion is increased on follow-up chest radiograph. Left closed thoracostomy was performed with pus drainage. A CT diagnosis of acute phlegmonous esophagogastritis was suggested and a surgery was decided due to worsening of clinical condition of the patient and radiologic findings. Esophageal myotomies were performed and the submucosal layer was filled with thick, cheesy materials. The patient was successfully discharged with no postoperative complication

Gallbladder pseudolithiasis caused by ceftriaxone in young adult

Ceftriaxone is a commonly used antibiotic due to some of its advantages. Reversible gallbladder (GB) sludge or stone has been reported after ceftriaxone therapy. Most of these patients have no symptom, but the GB sludge or stone can sometimes cause cholecystitis. We experienced two patients who had newly developed GB stones after ceftriaxone therapy for diverticulitis and pneumonia, and this resolved spontaneously 1 month after discontinuation of the drug. Awareness of this complication could help to prevent unnecessary cholecystectomy

Efflux in Acinetobacter baumannii can be determined by measuring accumulation of H33342 (bis-benzamide)

10.1093/jac/dkt052Journal of Antimicrobial Chemotherapy6871594-160

A childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy

Tuberculosis is primarily a pulmonary disease, but extra-pulmonary manifestations are not uncommon, especially in children and adolescents. Ten percent of extra pulmonary tuberculosis localizes to the bones and joints, and 56% of such cases affect the spine. We treated a childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy in a patient without specific constitutional symptoms. We report this case because the patient had an unusual presentation of spinal tuberculosis

Follicular Oocytes Better Support Development in Rabbit Cloning Than Oviductal Oocytes

This study was conducted to determine the effect of rabbit oocytes collected from ovaries or oviducts on the developmental potential of nuclear transplant embryos. Donor nuclei were obtained from adult skin fibroblasts, cumulus cells, and embryonic blastomeres. Rabbit oocytes were flushed from the oviducts (oviductal oocytes) or aspirated from the ovaries (follicular oocytes) of superovulated does at 10, 11, or 12-h post-hCG injection. The majority of collected oocytes were still attached to the sites of ovulation on the ovaries. We found that follicular oocytes had a significantly higher rate of fusion with nuclear donor cells than oviductal oocytes. There was no difference in the cleavage rate between follicular and oviductal groups, but morula and blastocyst development was significantly higher in the follicular group than in the oviductal group. Two live clones were produced in follicular group using blastomere and cumulus nuclear donors, whereas one live clone was produced in the oviductal group using a cumulus nuclear donor. These results demonstrate that cloned rabbit embryos derived from follicular oocytes have better developmental competence than those derived from oviductal oocytes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90481/1/cell-2E2011-2E0030.pd

Safety and feasibility of countering neurological impairment by intravenous administration of autologous cord blood in cerebral palsy

<p>Abstract</p> <p>Backgrounds</p> <p>We conducted a pilot study of the infusion of intravenous autologous cord blood (CB) in children with cerebral palsy (CP) to assess the safety and feasibility of the procedure as well as its potential efficacy in countering neurological impairment.</p> <p>Methods</p> <p>Patients diagnosed with CP were enrolled in this study if their parents had elected to bank their CB at birth. Cryopreserved CB units were thawed and infused intravenously over 10~20 minutes. We assessed potential efficacy over 6 months by brain magnetic resonance imaging (MRI)-diffusion tensor imaging (DTI), brain perfusion single-photon emission computed tomography (SPECT), and various evaluation tools for motor and cognitive functions.</p> <p>Results</p> <p>Twenty patients received autologous CB infusion and were evaluated. The types of CP were as follows: 11 quadriplegics, 6 hemiplegics, and 3 diplegics. Infusion was generally well-tolerated, although 5 patients experienced temporary nausea, hemoglobinuria, or urticaria during intravenous infusion. Diverse neurological domains improved in 5 patients (25%) as assessed with developmental evaluation tools as well as by fractional anisotropy values in brain MRI-DTI. The neurologic improvement occurred significantly in patients with diplegia or hemiplegia rather than quadriplegia.</p> <p>Conclusions</p> <p>Autologous CB infusion is safe and feasible, and has yielded potential benefits in children with CP.</p

Reduced Tomato Bacterial Wilt by Ferrous Chloride Application

Exogenous ferrous chloride (FeCl2) suppressed in vitro growth of Ralstonia pseudosolanacearum, causing bacteria for tomato bacterial wilt. More than 50 µM of FeCl2 reduced the in vitro bacterial growth in dose-dependent manners. Two to 200 µM of FeCl2 did not affect the fresh weight of detached tomato leaves at 3 and 5 days after the petiole dipping without the bacterial inoculation. The bacterial wilt of the detached tomato leaves was evaluated by inoculating two different inoculum densities of R. pseudosolanacearum (105 and 107 cfu/ml) in the presence of FeCl2. Bacterial wilt in the detached leaves by 105 cfu/ml was efficiently attenuated by 10–200 µM of FeCl2 at 3 and 5 days post-inoculation (dpi), but bacterial wilt by 107 cfu/ml was only reduced by 200 µM of FeCl2 at 3 and 5 dpi. These results suggest that iron nutrients can be included in the integrated disease management of tomato bacterial wilt

Recommended immunization schedule for children and adolescents: the Korean Pediatric Society, 2013

This article contains the recommended immunization schedule by the Committee on Infectious Diseases of the Korean Pediatric Society, updated in March 2013, when Haemophilus influenzae type b vaccine is now included in the National Immunization Program in Korea. It also includes catch-up immunization schedule for children and adolescents who are behind the recommended schedule. These schedules are a minor revision of the corresponding parts of Immunization Guideline, 7th edition, of the Korean Pediatric Society, released in 2012. Pediatricians should be aware of these schedules to provide adequate immunization to Korean children and adolescents