Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

Research Fund for the Control of Infectious Diseases: Research Dissemination Reports (Series 2)1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.published_or_final_versio

Ethnic differences in the association of fat and lean mass with bone mineral density in the Singapore population

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Functional role of ICAM-3 polymorphism in genetic susceptibility to SARS infection.

Key Messages 1. Severe acute respiratory syndrome (SARS) patients who are homozygous for intercellular adhesion molecule-3 (ICAM-3) Gly143 showed significant association with higher lactate dehydrogenase levels and lower total white blood cell counts on admission. 2. In vitro functional studies demonstrated low level binding of ICAM-3 to DC-SIGN and a wide variation in T-cell response of the wild-type ICAM-3 genotype.published_or_final_versio

Association of a single nucleotide polymorphism in the CD209 (DC-SIGN) promoter with SARS severity.

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MRI in multiple myeloma : a pictorial review of diagnostic and post-treatment findings

Magnetic resonance imaging (MRI) is increasingly being used in the diagnostic work-up of patients with multiple myeloma. Since 2014, MRI findings are included in the new diagnostic criteria proposed by the International Myeloma Working Group. Patients with smouldering myeloma presenting with more than one unequivocal focal lesion in the bone marrow on MRI are considered having symptomatic myeloma requiring treatment, regardless of the presence of lytic bone lesions. However, bone marrow evaluation with MRI offers more than only morphological information regarding the detection of focal lesions in patients with MM. The overall performance of MRI is enhanced by applying dynamic contrast-enhanced MRI and diffusion weighted imaging sequences, providing additional functional information on bone marrow vascularization and cellularity. This pictorial review provides an overview of the most important imaging findings in patients with monoclonal gammopathy of undetermined significance, smouldering myeloma and multiple myeloma, by performing a 'total' MRI investigation with implications for the diagnosis, staging and response assessment. Main message aEuro cent Conventional MRI diagnoses multiple myeloma by assessing the infiltration pattern. aEuro cent Dynamic contrast-enhanced MRI diagnoses multiple myeloma by assessing vascularization and perfusion. aEuro cent Diffusion weighted imaging evaluates bone marrow composition and cellularity in multiple myeloma. aEuro cent Combined morphological and functional MRI provides optimal bone marrow assessment for staging. aEuro cent Combined morphological and functional MRI is of considerable value in treatment follow-up

Association of ICAM3 genetic variant with severe acute respiratory syndrome

Genetic polymorphisms have been demonstrated to be associated with vulnerability to human infection. ICAM3, an intercellular adhesion molecule important for T cell activation, and FCER2 (CD23), an immune response gene, both located on chromosome 19p13.3, were investigated for host genetic susceptibility and association with clinical outcome. A case-control study based on 817 patients with confirmed severe acute respiratory syndrome (SARS), 307 health care worker control subjects, 290 outpatient control subjects, and 309 household control subjects unaffected by SARS from Hong Kong was conducted to test for genetic association. No significant association to susceptibility to SARS infection caused by the novel coronavirus (SARS-CoV) was found for the FCER2 and the ICAM3 single nucleotide polymorphisms. However, patients with SARS homozygous for ICAM3 Gly143 showed significant association with higher lactate dehydrogenase levels (P = .0067; odds ratio [OR], 4.31 [95% confidence interval {CI}, 1.37-13.56]) and lower total white blood cell counts (P = .022; OR, 0.30 [95% CI, 0.10-0.89]) on admission. These findings support the role of ICAM3 in the immunopathogenesis of SARS. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses