Seung Ro Lee

The effect of PARP inhibitor on ischaemic cell death, its related inflammation and survival signals

Poly(ADP‐ribose) polymerase (PARP) plays an important role in ischaemic cell death, and 3‐aminobenzamide (3‐AB), one of the PARP inhibitors, has a protective effect on ischaemic stroke. We investigated the neuroprotective mechanisms of 3‐AB in ischaemic stroke. The occlusion of middle cerebral artery (MCA) was made in 170 Sprague–Dawley rats, and reperfusion was performed 2 h after the occlusion. Another 10 Sprague–Dawley rats were used for sham operation. 3‐AB was administered to 85 rats 10 min before the occlusion [3‐AB group (n = 85) vs. control group without 3‐AB (n = 85)]. Infarct volume and water content were measured, brain magnetic resonance imaging, terminal deoxynucleotidyltransferase (TdT)‐mediated dUTP‐biotin nick end‐labelling (TUNEL) and Cresyl violet staining were performed, and immunoreactivities (IRs) of poly(ADP‐ribose) polymer (PAR), cleaved caspase‐3, CD11b, intercellular adhesion molecule‐1 (ICAM‐1), cyclooxygenase‐2 (COX‐2), phospho‐Akt (pAkt) and phospho‐glycogen synthase kinase‐3 (pGSK‐3) were compared in the peri‐infarcted region of the 3‐AB group and its corresponding ischaemic region of the control group at 2, 8, 24 and 72 h after the occlusion. In the 3‐AB group, the infarct volume and the water content were decreased (about 45% and 3.6%, respectively, at 24 h), the number of TUNEL‐positive cells was decreased (about 36% at 24 h), and the IRs of PAR, cleaved caspase‐3, CD11b, ICAM‐1 and COX‐2 were significantly reduced, while the IRs of pAkt and pGSK‐3 were increased. These results suggest that 3‐AB treatment could reduce the infarct volume by reducing ischaemic cell death, its related inflammation and increasing survival signals. The inhibition of PARP could be another potential neuroprotective strategy in ischaemic stroke.

Changes in the seroprevalence of IgG anti-hepatitis A virus between 2001 and 2013: experience at a single center in Korea.

Background/Aims The incidence of symptomatic hepatitis A reportedly increased among 20- to 40-year-old Korean during the late 2000s. Vaccination against hepatitis A was commenced in the late 1990s and was extended to children aged <10 years. In the present study we analyzed the changes in the seroprevalence of IgG anti-hepatitis A virus (HAV) over the past 13 years. Methods Overall, 4903 subjects who visited our hospital between January 2001 and December 2013 were studied. The seroprevalence of IgG anti-HAV was analyzed according to age and sex. In addition, the seroprevalence of IgG anti-HAV was compared among 12 age groups and among the following time periods: early 2000s (2001-2003), mid-to-late 2000s (2006-2008), and early 2010s (2011-2013). The chi-square test for trend was used for statistical analysis. Results The seroprevalence of IgG anti-HAV did not differ significantly between the sexes. Furthermore, compared to the seroprevalence of IgG anti-HAV in the early 2000s and mid-to-late 2000s, that in the early 2010s was markedly increased among individuals aged 1-14 years and decreased among those aged 25-44 years (P<0.01). We also found that the seroprevalence of IgG anti-HAV in individuals aged 25-44 years in the early 2010s was lower than that in the early 2000s and mid-to-late 2000s. Conclusions The number of symptomatic HAV infection cases in Korea is decreasing, but the seroprevalence of IgG anti-HAV is low in the active population.

Hypereosinophilia with Multiple Thromboembolic Cerebral Infarcts and Focal Intracerebral Hemorrhage

We report a case of hypereosinophilia causing multiple areas of cerebral infarcts. A 52-year-old Korean man presented with dysarthria and weakness in both arms. A brain MRI revealed multiple acute infarcts in the distal border zone with focal intracerebral hemorrhage, whereas a cerebral angiogram was not remarkable. The eosinophil count was 5,500/µL and was accompanied by elevated cardiac enzyme levels. The pattern of cerebral infarcts and laboratory results suggest a thromboembolic infarction associated with hypereosinophilia.

Decreased SMG7 expression associates with lupus-risk variants and elevated antinuclear antibody production

Objectives Following up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150 kb flanking regions containing NMNAT2 and SMG7 in a 15 292 case–control multi-ancestry population and tested functions of identified variants. Methods We performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA. Results We confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10−8, OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10−3 and 6.8×10−8, respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=−0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10−5 and 2.0×10−4, respectively). Conclusion We confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis.

Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study:

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01–1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03–2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24–0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85–1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03–9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12–28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

Polymicrobial Purulent Pericarditis Probably caused by a Broncho-Lymph Node-Pericardial Fistula in a Patient with Tuberculous Lymphadenitis

Purulent pericarditis is a rare condition with a high mortality rate. We report a case of purulent pericarditis subsequently caused by Candida parapsilosis, Peptostreptococcus asaccharolyticus, Streptococcus anginosus, Staphylococcus aureus, Prevotella oralis, and Mycobacterium tuberculosis in a previously healthy 17-year-old boy with mediastinal tuberculous lymphadenitis. The probable route of infection was a bronchomediastinal lymph node-pericardial fistula. The patient improved with antibiotic, antifungal, and antituberculous medication in addition to pericardiectomy.

Pure intrasellar meningioma located under the pituitary gland: case report.

Most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae. Subglandular meningiomas located under the pituitary gland are extremely rare. Intrasellar meningiomas in the subdiaphragmatic and subglandular region probably originate from the dura in the sellar floor. We report a case of a subglandular meningioma along with a review of the literature.