Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine.

Context: Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients.

Objective: To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification.

Methods And Results: This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials.

Detection of new biallelic polymorphisms in the human MxA gene.

The interferon-inducible human MxA protein plays an important role in innate defense against an array of viruses. One might expect allelic diversity at the MxA locus to influence the timing and magnitude of its expression or even the range of viruses whose biological cycle is inhibited by the encoded product. Here we have collected 267 samples of genomic DNA from three distinct populations (European, Asian, and African) and have systematically sequenced the promoter of the MxA gene and its 17 exons in order to inventory its allelic variants.

Human/bovine chimeric MxA-like GTPases reveal a contribution of N-terminal domains to the magnitude of anti-influenza A activity.

Type I interferons (IFN-α/β) provide powerful and universal innate intracellular defense mechanisms against viruses. Among the antiviral effectors induced by IFN-α/β, Mx proteins of some species appear as key components of defense against influenza A viruses. The body of work published to date suggests that to exert anti-influenza activity, an Mx protein should possess a GTP-binding site, structural bases allowing multimerisation, and a specific C-terminal GTPase effector domain (GED).

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis.

Background: Disorganized angiogenesis is associated with several pathologies, including cancer. The identification of new genes that control tumor neovascularization can provide novel insights for future anti-cancer therapies. Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new genes.

Influenza A strain-dependent pathogenesis in fatal H1N1 and H5N1 subtype infections of mice.

To determine if fatal infections caused by different highly virulent influenza A viruses share the same pathogenesis, we compared 2 different influenza A virus subtypes, H1N1 and H5N1. The subtypes, which had shown no pathogenicity in laboratory mice, were forced to evolve by serial passaging. Although both adapted viruses evoked diffuse alveolar damage and showed a similar 50% mouse lethal dose and the same peak lung concentration, each had a distinct pathologic signature and caused a different course of acute respiratory distress syndrome.

A non-cytosolic protein of Trypanosoma evansi induces CD45-dependent lymphocyte death.

In a recent study dealing with a mouse model of Trypanosoma evansi-associated disease, a remarkable synchrony between the parasitaemia peak and the white-blood-cell count nadir was noticed. The present study was designed to establish whether there is a direct causal link between the parasite load during its exponential phase of growth and the disappearance of peripheral blood leukocytes. In vitro experiments performed with trypanosomes and purified peripheral blood mononucleated cells revealed the existence of a lymphotoxin embedded in the T.

[Medical policies, state and religious missions in Rwanda (1920-1940). An authoritative design of colonial medicine?].

The Belgian health policy set up in mandated Rwanda after the First World War was mainly centred on some campaigns taking specifically yaws as a target. The struggle against this endemic disease (not fatal, but most disabling) was organized in a very systematic and authoritarian way. This article looks into two of those yaws campaigns, questions their runnings and alterations, and finally brings to light the intra-colonial tensions between the health services and the administration on the one hand, between the colonizers and the African populations on the other hand.

Pre- and post-transplant monitoring of granzyme B enzyme-linked immunosorbent spot assay in pediatric liver recipients.

Unlabelled: This study aims to investigate potential role of granzyme B enzyme-linked immunosorbent spot (GrB ELISPOT) for immunological monitoring in pediatric liver transplantation.

Patients And Methods: Peripheral blood mononuclear cells from 28 pediatric recipients were serially tested for GrB-producing donor-reactive cells at day 0 pre-transplantation (baseline) and days 7, 14, and 28 post-transplantation.

Results: At baseline, no difference of GrB value was found in acute rejection (14/28) compared to normal graft function patients (day 0: 4(3.

Inhibition of tumor growth and metastasis establishment by adenovirus-mediated gene transfer delivery of the antiangiogenic factor 16K hPRL.

Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic therapy, therefore, holds potential as an attractive strategy for inhibiting metastasis development.

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.

Early immunological monitoring after pediatric liver transplantation: cytokine immune deviation and graft acceptance in 40 recipients.

Cytokine deviation may be a factor contributing to graft acceptance. We analyze, in the context of liver transplantation, circulating cytokine levels and their mRNA precursors in liver biopsy samples to study a putative correlation with early immunologic outcome. Forty primary pediatric liver recipients were submitted to a prospective immune monitoring protocol, including 8 of 40 patients with an early, biopsy-proven acute rejection episode.

Prolactin/growth hormone-derived antiangiogenic peptides highlight a potential role of tilted peptides in angiogenesis.

Angiogenesis is a crucial step in many pathologies, including tumor growth and metastasis. Here, we show that tilted peptides exert antiangiogenic activity. Tilted (or oblique-oriented) peptides are short peptides known to destabilize membranes and lipid cores and characterized by an asymmetric distribution of hydrophobic residues along the axis when helical.

Anti-CD2 monoclonal antibody and tacrolimus in adult liver transplantation.

Background: Blockade of costimulation and adhesion signaling is an attractive approach to interfere with graft rejection

Methods: Between January 1997 and May 1999, forty adults having benign liver diseases were included in a prospective, randomized study comparing tacrolimus plus low-dose short-term steroids without (n=20, TAC group) or with a 10-day course of antihuman CD2 monoclonal antibody (n=20, BTI group).

Results: At day 7, histological rejection expressed by mean Banff scores (2.3+/-1.

The antiangiogenic factor, 16-kDa human prolactin, induces endothelial cell cycle arrest by acting at both the G0-G1 and the G2-M phases.

The 16-kDa N-terminal fragment of human prolactin (16K hPRL) is a potent antiangiogenic factor that has been shown to prevent tumor growth in a xenograph mouse model. In this paper we first demonstrate that 16K hPRL inhibits serum-induced DNA synthesis in adult bovine aortic endothelial cells. This inhibition is associated with cell cycle arrest at both the G(0)-G(1) and the G(2)-M phase.

New features in the treatment of androgen-independent prostate cancer.

Prostate cancer develops from clones that are already present as early as thirty-five years of age, when circulating concentrations of androgens are high. The progression of the disease is low and the cancer is diagnosed at a more advanced age. Prostate cancer evolves from an androgen dependant stage to stage where it escapes from all anti-androgenic treatments.

Prostatic androgen repressed message-1 (PARM-1) may play a role in prostatic cell immortalisation.

Background: Prostatic androgen-repressed message-1 (PARM-1) has been cloned from the prostate. The transcript of the PARM-1 gene is overexpressed during regression of the prostate after androgen withdrawal. The regulation of PARM-1 by androgens is limited to this organ.

Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition.

We herein report on our efforts to improve the mapping resolution of a QTL with major effect on milk yield and composition that was previously mapped to bovine chromosome 20. By using a denser chromosome 20 marker map and by exploiting linkage disequilibrium using two distinct approaches, we provide strong evidence that a chromosome segment including the gene coding for the growth hormone receptor accounts for at least part of the chromosome 20 QTL effect. By sequencing individuals with known QTL genotype, we identify an F to Y substitution in the transmembrane domain of the growth hormone receptor gene that is associated with a strong effect on milk yield and composition in the general population.