Hip joint replacement surgery for idiopathic osteoarthritis aggregates in families

In order to determine whether there is a genetic component to hip or knee joint failure due to idiopathic osteoarthritis (OA), we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses, and we used logistic regression to identify independent risk factors for hip and knee arthroplasty in the siblings. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.     

饲喂黄曲霉毒素B_1大鼠肝中AFB_1-DNA加合物的免疫组织化学研究

应用免疫组织化学ＳＰ法对４例饲喂黄曲霉毒素Ｂ１的Ｗｉｓｔａｒ大鼠肝组织中ＡＦＢ１－ＤＮＡ加合物的染色及常规ＨＥ染色发现,４例肝细胞核均出现异型性,但未见肝细胞坏死、增生灶及肝细胞癌;免疫组化揭示部分肝细胞核出现棕黄色、不均质状的ＡＦＢ１－ＤＮＡ加合物,阳性细胞数占１０～８５％。结果提示免疫组织化学方法可作为一种ＡＦＢ１的定位方法,ＡＦＢ１在动物致癌过程中ＡＦＢ１－ＤＮＡ加合物可能具有启动作用     

Encounter with New Resources Causes Polarized Growth of the Cord-Forming Basidiomycete Phanerochaete velutina on Soil

Abstract The development and physiology of cord-forming saprotrophic basidiomycetes, which form extensive and persistent mycelial networks in woodland ecosystems, can be conveniently studied on non-sterile soil in laboratory microcosms mimicking field conditions. Morphological responses of Phanerochaete velutina mycelial systems to resource encounters, and decay partitioning following encounters, varied according to whether simulated woody litter was unsterile or autoclaved and on whether encounter took place at the mycelial foraging front or behind the margin (simulating litter fall onto established systems in the field). Results show that encounter of discrete resources by P. velutina is rapidly communicated to the entire mycelial system; that resource capture takes high priority at the expense of continued system extension and decay-derived carbon reallocation; and that polarized growth toward newly encountered resources, previously considered to occur infrequently with this species, may be readily detected using image analysis techniques. Potential advantages of polarized development of P. velutina are discussed.     

Biomarker Development for the Clinical Activity of the mTOR Inhibitor Everolimus (RAD001): Processes,Limitations, and Further Proposals

The mTOR inhibitor everolimus (RAD001, Afinitor) is an orally active anticancer agent. Everolimus demonstrates growth-inhibitory activity against a broad range of tumor cell histotypes in vitro and has the capacity to retard tumor growth in preclinical tumor models in vivo through mechanisms directed against both the tumor cell and the solid tumor stroma components. These properties have rendered it to be a clinically active drug, with subsequent registration in renal cell carcinoma (Motzer et al. [2008]. Lancet 372, 449–456) as well as showing strong potential as a combination partner (André F et al. [2008]. J Clin Oncol 26. Abstract 1003). Although everolimus has a high specificity for its molecular target, the ubiquitous nature of mTOR and the multifactorial influence that mTOR signaling has on cell physiology have made studies difficult on the identification and validation of a biomarker set to predict and monitor drug sensitivity for clinical use. In this review, a summary of the preclinical and clinical data relevant to biomarker development for everolimus is presented, and the advantages and problems of current biomarkers are reviewed. In addition, alternative approaches to biomarker development are proposed on the basis of examples of a combination of markers and functional noninvasive imaging. In particular, we show how basal levels of pAKT and pS6 together could, in principle, be used to stratify patients for likely response to an mTOR inhibitor.     

Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis

Introduction  

Recent evidence suggests that uric acid (UA), regardless of crystal deposition, may play a direct pathogenic role in renal disease. We have shown that UA is an independent predictor of hypertension and cardiovascular disease (CVD), and that CVD risk factors associate with renal dysfunction, in patients with rheumatoid arthritis (RA). In this study we investigated whether UA associates with renal dysfunction in patients with RA and whether such an association is independent or mediated through other comorbidities or risk factors for renal impairment.     

Physiological responses to folate overproduction in <Emphasis Type="Italic">Lactobacillus plantarum</Emphasis> WCFS1

Background  

Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells.     

Hypercholesterolemia boosts joint destruction in chronic arthritis. An experimental model aggravated by foam macrophage infiltration

Objective

The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.

Methods

Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-α and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone.

Results

Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-α and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups.

Conclusions

This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process.     

Impacts of yeast metabolic network structure on enzyme evolution

A comment on D Vitkup, P Kharchenko and A Wagner: Influence of metabolic network structure and function on enzyme evolution. Genome Biol 2006, 7:R39.