Seropositivity and identification of paramyosin for sparganosis in the Kangwon and Incheon provinces of the Republic of Korea.

Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography-mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.

Efficacy of the APACHE II score at ICU discharge in predicting post-ICU mortality and ICU readmission in critically ill surgical patients.

In this study, we evaluated the efficacy of the discharge Acute Physiology and Chronic Health Evaluation (APACHE) II score in predicting post-intensive care unit (ICU) mortality and ICU readmission during the same hospitalisation in a surgical ICU. Of 1190 patients who were admitted to the ICU and stayed >48 hours between October 2007 and March 2010, 23 (1.9%) died and 86 (7.2%) were readmitted after initial ICU discharge, with 26 (3.0%) admitted within 48 hours. The area under the receiver operating characteristics curve of the discharge and admission APACHE II scores in predicting in-hospital mortality was 0.631 (95% confidence interval [CI] 0.603 to 0.658) and 0.669 (95% CI 0.642 to 0.696), respectively (P=0.510). The area under the receiver operating characteristics curve of discharge and admission APACHE II scores for predicting all forms of readmission was 0.606 (95% CI 0.578 to 0.634) and 0.574 (95% CI 0.545 to 0.602), respectively (P=0.316). The area under the receiver operating characteristics curve of discharge APACHE II score in predicting early ICU readmissions was, however, higher than that of admission APACHE II score (0.688 [95% CI 0.660 to 0.714] versus 0.505 [95% CI 0.476 to 0.534], P=0.001). The discharge APACHE II score (odds ratio [OR] 1.1, 95% CI 1.01 to 1.22, P=0.024), unplanned ICU readmission (OR 20.0, 95% CI 7.6 to 53.1, P=0.001), eosinopenia at ICU discharge (OR 6.0, 95% CI 1.34 to 26.9, P=0.019), and hospital length-of-stay before ICU admission (OR 1.02, 95% CI 1.01 to 1.03, P=0.021) were significant independent factors in predicting post-ICU mortality. This study suggests that the discharge APACHE II score may be useful in predicting post-ICU mortality and is superior to the admission APACHE II score in predicting early ICU readmission in surgical ICU patients.

Proteomic analysis of a 120 kDa protein complex in cyst fluid of Taenia solium metacestode and preliminary evaluation of its value for the serodiagnosis of neurocysticercosis.

Cyst fluid (CF) of Taenia solium metacestode (TsM) is an important source of serodiagnostic antigens. We have investigated the molecular characteristics of the 120 kDa protein complex in TsM CF purified by fast performance liquid chromatography. The structure of the purified protein was characterized by a variety of proteomic analyses. The protein was found to consist of 2 major components of 42-46 and 22-28 kDa, and shared 3 subunits of 14, 16 and 18 kDa. The 42-46 kDa component was determined to contain 3 additional subunits of 22, 28 and 38 kDa. These 6 subunits were shown to originate from either the 14 or 18 kDa precursor. We assessed the antibody reactivity of the native protein, its individual subunits and the recombinant 14 and 18 kDa proteins, and found that the 120 kDa protein, particularly 14 and 18 kDa subunits revealed high reliability for differentiation of active and mixed stage NC from chronic NC. The subunits of the 120 kDa protein complex identified herein represent some of the low-molecular weight glycoproteins which have been described in several previous studies. Recognizing and understanding the structural and immunological relationship of these proteins will facilitate the development of new serodiagnostic assays.

Alternative splicing variants of c-FLIP transduce the differential signal through the Raf or TRAF2 in TNF-induced cell proliferation.

In human cancer, despite apoptotic activity, death-ligand promotes the cell cycle progression under certain conditions. In this study, we demonstrated that TNF-alpha-induced cell proliferation is achieved through the c-FLIP. In addition, alternative splicing variants (c-FLIP(L) and c-FLIP(S)) contribute the TNF-alpha-induced cell cycle promotion through distinct pathways. The long form of c-FLIP (c-FLIP(L)) activates the Raf, which enhance the activity of Erk and PI3K, whereas short form (c-FLIPS) are activated by c-jun-N-terminal Kinase (JNK) through the TNF receptor-associated factor (TRAF) 2. Since, however, recruitment of c-FLIP(L) into FADD is later than that of c-FLIP(S), the activation of PI3K and Erk show the late response to activation of JNK. We also show that each c-FLIP variant is regulated by a distinct molecular mechanism at the transcriptional level; c-FLIP(L) is induced by Erk, whereas c-FLIP(S), through the JNK activation, is like an autocrine regulatory loop. Therefore, the induction of c-FLIP(L) in response to TNF-alpha is achieved in a more delayed manner than that of c-FLIP(S). Our present study also implies that other alternative splicing variants perform differential roles in spite of the same pathway.

Immunosuppressant rapamycin inhibits protein kinase C alpha and p38 mitogen-activated protein kinase leading to the inhibition of chondrogenesis.

Immunosuppressants are now known to modulate bone metabolism, including bone formation and resorption. Because cartilage, formed by differentiated chondrocytes, serves as a template for endochondral bone formation, we examined the effects of the immunosuppressant rapamycin on the chondrogenesis of mesenchymal cells and on the cell signaling that is required for chondrogenesis, such as protein kinase C, extracellular signal-regulated kinase-1 (ERK-1), and p38 mitogen-activated protein (MAP) kinase pathways. Rapamycin inhibited the expression of type II collagen and the accumulation of sulfate glycosaminoglycan, indicating inhibition of the chondrogenesis of mesenchymal cells. Rapamycin treatment did not affect precartilage condensation, but it prevented cartilage nodule formation. Exposure of chondrifying mesenchymal cells to rapamycin blocked activation of the protein kinase C alpha and p38 MAP kinase, but had no discernible effect on ERK-1 signaling. Selective inhibition of PKCalpha or p38 MAP kinase activity, which is dramatically increased during chondrogenesis, with specific inhibitors in the absence of rapamycin blocked the chondrogenic differentiation of mesenchymal cells. Taken together, our data indicate that the immunosuppressant rapamycin inhibits the chondrogenesis of mesenchymal cells at the post-precartilage condensation stage by modulating signaling pathways including those of PKCalpha and p38 MAP kinase.