Cooperate concept of metastasis: site-specific requirement of activated differentiation and dynamic deterioration

Cancer metastasis results from positive and negative cellular events such as constitutive activation of oncogenes (cOA) or genetic losses (GL) being modulated by downstream signals of epithelial-mesenchymal or mesenchymal-epithelial transition, thus constituting master programs of metastatic phenotype and site specificity. To address the complex nature of these programs, we introduced clinical and phenotypic markers like tumor size, grade, cellular shape, or expression of E-cadherin in 27 colon cancer (CC) patients (cOA and GL), and 41 patients with gastrointestinal stromal tumors (GIST, cOA) to produce scores of cOA and GL. Scores of cOA were highest in case of hepatic and lower in case of an isolated peritoneal spread (GIST), or (CC) of both, cOA and GL, highest in case of a combined hepatic and peritoneal spread and lower in case of an isolated peritoneal spread; but in case of an isolated hepatic spread, scores of cOA were high and low of GL. This indicates a differential contribution of cellular dissociation and recognition in site-specific metastasis, of cOA predominantly in production of hepatic and in the case of GL of serosal spread.     

Reactivity of intraosseous femoral head arteries after long term glucocorticoid treatment: An experimental study in immature pigs

In the pathogenesis of steroid induced femoral head necrosis only intra- and extravascular factors have been discussed. Vasoreactivity of intraosseous femoral head arteries has not previously been investigated. This study investigates the effect of long term glucocorticoid treatment on reactivity of intraosseous femoral head arteries in a porcine model. From 24 immature female Danish Landrace pigs from 12 litters, 12 animals received 100 mg methyl-prednisolone (orally) daily for 3 months. Their 12 sister pigs served as controls and received no corticosteroid. After sacrificing the animal, resistance arteries (diameter approximately 250 µm) were isolated from the femoral head epiphyseal cancellous bone and mounted as ring preparations on a small vessel myograph for measurement of isometric force development. The vasocontractory response to increasing doses of noradrenaline was not altered by methylprednisolone treatment. After submaximal precontraction by noradrenaline, vasorelaxation by sodium nitroprusside was not altered by methylprednisolone treatment. Only part of both experimental groups showed vasorelaxation to substance P and increasing doses of bradykinin. Increasing dose of endothelin-1 evoked vasoconstriction in both experimental groups. Sensitivity to endothelin-1 was increased after 3 months of methylprednisolone treatment. The response of isolated intraosseous femoral head arteries to endothelin-1 after long term glucocorticoid treatment in the pig is enhanced and appears to be unchanged for other physiologic vasoactive substances.Presented in part as a Young Investigator Award Competition of the 42^nd Annual World Congress International College of Angiology, San Diego, California, June 2000.     

Zinc-α2-Glycoprotein Exerts Antifibrotic Effects in Kidney and Heart

Zinc-α2-glycoprotein (AZGP1) is a secreted protein synthesized by epithelial cells and adipocytes that has roles in lipid metabolism, cell cycling, and cancer progression. Our previous findings in AKI indicated a new role for AZGP1 in the regulation of fibrosis, which is a unifying feature of CKD. Using two models of chronic kidney injury, we now show that mice with genetic AZGP1 deletion develop significantly more kidney fibrosis. This destructive phenotype was rescued by injection of recombinant AZGP1. Exposure of AZGP1-deficient mice to cardiac stress by thoracic aortic constriction revealed that antifibrotic effects were not restricted to the kidney but were cardioprotective. In vitro, recombinant AZGP1 inhibited kidney epithelial dedifferentiation and antagonized fibroblast activation by negatively regulating TGF-β signaling. Patient sera with high levels of AZGP1 similarly attenuated TGF-β signaling in fibroblasts. Taken together, these findings indicate a novel role for AZGP1 as a negative regulator of fibrosis progression, suggesting that recombinant AZGP1 may have translational effect for treating fibrotic disease.     

An investigation of multidisciplinary complex health care interventions - steps towards an integrative treatment model in the rehabilitation of People with Multiple Sclerosis

ABSTRACT: BACKGROUND: The Danish Multiple Sclerosis Society initiated a large-scale bridge building and integrative treatment project to take place from 2004-2010 at a specialized Multiple Sclerosis (MS) hospital. In this project, a team of five conventional health care practitioners and five alternative practitioners was set up to work together in developing and offering individualized treatments to 200 people with MS. The purpose of this paper is to present results from the six year treatment collaboration process regarding the development of an integrative treatment model. DISCUSSION: The collaborative work towards an integrative treatment model for people with MS, involved six steps: 1) Working with an initial model 2) Unfolding the different treatment philosophies 3) Discussing the elements of the Intervention-Mechanism-Context-Outcome-scheme (the IMCO-scheme) 4) Phrasing the common assumptions for an integrative MS program theory 5) Developing the integrative MS program theory 6) Building the integrative MS treatment model. The model includes important elements of the different treatment philosophies represented in the team and thereby describes a common understanding of the complexity of the courses of treatment. SUMMARY: An integrative team of practitioners has developed an integrative model for combined treatments of People with Multiple Sclerosis. The model unites different treatment philosophies and focuses on process-oriented factors and the strengthening of the patients' resources and competences on a physical, an emotional and a cognitive level.     

A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1

An important characteristic of autoimmune polyendocrine syndrome type 1 (APS 1) is the existence of neutralizing autoantibodies (nAbs) against the type I interferons (IFN) -α2 and -ω at frequencies close to 100%.     

CASE: a framework for computer supported outbreak detection

Background  

In computer supported outbreak detection, a statistical method is applied to a collection of cases to detect any excess cases for a particular disease. Whether a detected aberration is a true outbreak is decided by a human expert. We present a technical framework designed and implemented at the Swedish Institute for Infectious Disease Control for computer supported outbreak detection, where a database of case reports for a large number of infectious diseases can be processed using one or more statistical methods selected by the user.     

Plasma cytokines eotaxin,MIP‐1α, MCP‐4, and vascular endothelial growth factor in acute lower respiratory tract infection

Major overlaps of clinical characteristics and the limitations of conventional diagnostic tests render the initial diagnosis and clinical management of pulmonary disorders difficult. In this pilot study, we analyzed the predictive value of eotaxin, macrophage inflammatory protein 1 alpha (MIP‐1α), monocyte chemoattractant protein 4 (MCP‐4), and vascular endothelial growth factor (VEGF) in 40 patients hospitalized with acute lower respiratory tract infections (LRTI). The cytokines contribute to the pathogenesis of several inflammatory respiratory diseases, indicating a potential as markers for LRTI. Patients were stratified according to etiology and severity of LRTI, based on baseline C‐reactive protein and CURB‐65 scores. Using a multiplex immunoassay of plasma, levels of eotaxin and MCP‐4 were shown to increase from baseline until day 6 after admission to hospital. The four cytokines were unable to predict the etiology and severity. Eotaxin and MCP‐4 were significantly lower in patients with C‐reactive protein ≥100, and MIP‐1α was significantly higher in the patients with CURB‐65 > 3, but the predictive power was low. In conclusion, further evaluation, including more patients, is required to assess the full potential of eotaxin, MCP‐4, MIP‐1α, and VEGF as biomarkers for LRTI because of their low predictive power and a high interindividual variation of cytokine levels.