Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Detection of serum midkine levels in cancer patients using rabbit anti-human midkine monoclonal antibodies

Midkine (MK) is a heparin-binding growth factor and was found to be highly expressed in many types of human carcinomas. MK may become a novel tumor marker. In this study, we used the rabbit specific antibodies against human MK to establish a double antibody sandwich enzyme-linked immunosorbent assay (ELISA) of MK system and applied it to detect serum MK levels in different types of cancer patients. The standard curve, precision and recovery rate were tested, respectively, and serum MK concentration of 102 cancers patients and 102 normal individuals were detected using this method. The detection range of this method was 0.2 to 10 ng/ml (R2 = 0.97). The average intra and intro-assay coefficients of variation (CVs) were 3.6 and 7.9%, respectively. The average recovery rate was 89.9% when some standard antigens were added into the serum. The medians (25th and 75th percentiles) of serum MK levels were 1.35 ng/ml (0.96 and 1.64) in cancer patients and 0.30 ng/ml (0.23 and 0.38) in the controls; the MK levels of the patients were significantly higher than those of the controls (P<0.05). Moreover, 87.2% of the patients showed more than 0.6 ng/ml levels of MK. Serum MK could serve as a general tumor marker with a good potential for clinical application.Key words: Midkine, rabbit monoclonal antibody, sandwich ELISA, tumor marker

Thienoisoindigo-Based Semiconductor Nanowires Assembled with 2-Bromobenzaldehyde via Both Halogen and Chalcogen Bonding

We fabricated nanowires of a conjugated oligomer and applied them to organic field-effect transistors (OFETs). The supramolecular assemblies of a thienoisoindigo-based small molecular organic semiconductor (TIIG-Bz) were prepared by co-precipitation with 2-bromobenzaldehyde (2-BBA) via a combination of halogen bonding (XB) between the bromide in 2-BBA and electron-donor groups in TIIG-Bz, and chalcogen bonding (CB) between the aldehyde in 2-BBA and sulfur in TIIG-Bz. It was found that 2-BBA could be incorporated into the conjugated planes of TIIG-Bz via XB and CB pairs, thereby increasing the pi - pi stacking area between the conjugated planes. As a result, the driving force for one-dimensional growth of the supramolecular assemblies via pi - pi stacking was significantly enhanced. TIIG-Bz/2-BBA nanowires were used to fabricate OFETs, showing significantly enhanced charge transfer mobility compared to OFETs based on pure TIIG-Bz thin films and nanowires, which demonstrates the benefit of nanowire fabrication using 2-BB

The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis

The Triggering Receptors Expressed on Myeloid cells (TREM) are a family of cell-surface molecules that control inflammation, bone homeostasis, neurological development and blood coagulation. TREM-1 and TREM-2, the best-characterized receptors so far, play divergent roles in several infectious diseases. In the intestine, TREM-1 is highly expressed by macrophages, contributing to inflammatory bowel disease (IBD) pathogenesis. Contrary to current understanding, TREM-2 also promotes inflammation in IBD by fueling dendritic cell functions. This review will focus specifically on recent insights into the role of TREM proteins in IBD development, and discuss opportunities for novel treatment approaches

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Clinical and laboratory findings associated with severe scrub typhus

<p>Abstract</p> <p>Background</p> <p>Scrub typhus is a mite-borne bacterial infection of humans caused by <it>Orientia tsutsugamushi </it>that causes a generalized vasculitis that may involve the tissues of any organ system. The aim of this study was to identify factors associated to severe complications from scrub typhus.</p> <p>Methods</p> <p>We conducted this prospective, case-control study on scrub typhus patients who presented to the Department of Internal Medicine at Chosun University Hospital between September, 2004 and December, 2006. Cases were 89 scrub typhus patients with severe complications and controls were 119 scrub typhus patients without severe complications.</p> <p>Results</p> <p>There were significant differences in the absence of eschar, white blood cell (WBC) counts, hemoglobin, albumin, serum creatinine, fibrinogen, C-reactive protein (CRP), and active partial thromboplastin time (aPTT) between the two groups. Multivariate analysis demonstrated that only the following four factors were significantly associated with the severe complications of scrub typhus: (1) age ≥ 60 years (odd ratio [OR] = 3.13, <it>P </it>= 0.002, confidence interval [CI] = 1.53-6.41), (2) the absence of eschar (OR = 6.62, <it>P </it>= 0.03, CI = 1.22-35.8, (3) WBC counts > 10, 000/mm3 (OR = 3.6, <it>P </it>= 0.001, CI = 1.65-7.89), and (4) albumin ≤ 3.0 g/dL (OR = 5.01, <it>P </it>= 0.004, CI = 1.69-14.86).</p> <p>Conclusions</p> <p>Our results suggest that clinicians should be aware of the potential for complications, when scrub typhus patients are older (≥ 60 years), presents without eschar, or laboratory findings such as WBC counts > 10, 000/mm3, and serum albumin level ≤ 3.0 g/dL. Close observation and intensive care for scrub typhus patients with the potential for complications may prevent serious complications with subsequent reduction in its mortality rate.</p

Building the process-drug–side effect network to discover the relationship between biological Processes and side effects

<p>Abstract</p> <p>Background</p> <p>Side effects are unwanted responses to drug treatment and are important resources for human phenotype information. The recent development of a database on side effects, the side effect resource (SIDER), is a first step in documenting the relationship between drugs and their side effects. It is, however, insufficient to simply find the association of drugs with biological processes; that relationship is crucial because drugs that influence biological processes can have an impact on phenotype. Therefore, knowing which processes respond to drugs that influence the phenotype will enable more effective and systematic study of the effect of drugs on phenotype. To the best of our knowledge, the relationship between biological processes and side effects of drugs has not yet been systematically researched.</p> <p>Methods</p> <p>We propose 3 steps for systematically searching relationships between drugs and biological processes: enrichment scores (ES) calculations, t-score calculation, and threshold-based filtering. Subsequently, the side effect-related biological processes are found by merging the drug-biological process network and the drug-side effect network. Evaluation is conducted in 2 ways: first, by discerning the number of biological processes discovered by our method that co-occur with Gene Ontology (GO) terms in relation to effects extracted from PubMed records using a text-mining technique and second, determining whether there is improvement in performance by limiting response processes by drugs sharing the same side effect to frequent ones alone.</p> <p>Results</p> <p>The multi-level network (the process-drug-side effect network) was built by merging the drug-biological process network and the drug-side effect network. We generated a network of 74 drugs-168 side effects-2209 biological process relation resources. The preliminary results showed that the process-drug-side effect network was able to find meaningful relationships between biological processes and side effects in an efficient manner.</p> <p>Conclusions</p> <p>We propose a novel process-drug-side effect network for discovering the relationship between biological processes and side effects. By exploring the relationship between drugs and phenotypes through a multi-level network, the mechanisms underlying the effect of specific drugs on the human body may be understood.</p

Acute epiglottitis as the initial presentation of pediatric Systemic Lupus Erythematosus

We report a case of a 5-year old girl, who initially presented with acute epiglottitis, sepsis and multi-organ failure. She was subsequently diagnosed as having Systemic Lupus Erythematosus. To the best of our knowledge, this article describes the first case of Haemophilus influenzae type f epiglottitis as the initial presentation of SLE in childhood

Construction and Analysis of High-Complexity Ribosome Display Random Peptide Libraries

Random peptide libraries displayed on the ribosome are becoming a new tool for the in vitro selection of biologically relevant macromolecules, including epitopes, antagonists, enzymes, and cell-surface receptors. Ribosome display is a cell-free system of coupling individual nascent proteins (phenotypes) to their corresponding mRNA (genotypes) by the formation of stable protein-ribosome-mRNA complexes and permitting the selection of a functional nascent protein by iterative cycles of panning and reverse transcription-polymerase chain reaction (RT-PCR) amplification in vitro. The complexity of the random peptide library is critical for the success of a panning experiment; greater the diversity of sequences within the library, the more likely it is that the library comprises sequences that can bind a given target with specific affinity. Here, we have used the cell-free system Escherichia coli S30 lysate to construct high-complexity random peptide libraries (>1014 independent members) by introducing strategies that are different from the methods described by Mattheakis et al. and Lamla et al. The key step in our method is to produce nanomole (nmol) amounts of DNA elements that are necessary for in vitro transcription/translation by using PCR but not plasmid DNA. Library design strategies and protocols that facilitate rapid identification are also presented