| Pathogenesis of kidney disease in systemic lupus erythematosus.
November 5, 2009 at 10:08 am
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| | Pathogenesis of kidney disease in systemic lupus erythematosus. Curr Opin Rheumatol. 2009 Sep;21(5):489-94 Authors: Bagavant H, Fu SM PURPOSE OF REVIEW: A combination of systemic autoimmunity and tissue response to immune injury underlie renal involvement in lupus erythematosus. In this review, we discuss recent literature investigating pathogenetic mechanisms of lupus glomerulonephritis. RECENT FINDINGS: In lupus glomerulonephritis, glomerular immune complexes were believed to be the primary mediators of renal disease. Recent studies make it apparent that autoantibodies of multiple specificities participate in the formation of immune complexes, deposited in the kidneys. Renal infiltration by T cells, macrophages, and dendritic cells have a dominant role in the progression of lupus glomerulonephritis leading to renal failure. Activation of Toll-like receptors modulates autoantibody production and systemic interferon responses. However, glomerular cell responses to immune injury influence disease outcome. In addition, new insights on the genetics of susceptibility to end-organ damage in lupus glomerulonephritis have been discovered. Differential glomerular responses reflected in gene expression profiles during disease progression provide potential markers for diagnosis of lupus glomerulonephritis progression and flares. In addition, studies of end-organ responses provide new targets for therapeutic interventions. SUMMARY: Lupus glomerulonephritis is a prototype of immune complex disease mediated by autoantibodies of multiple specificities, one of which is anti-DNA. Murine models of spontaneous systemic lupus erythematosus have been critical for understanding the underlying disease. Recent studies demonstrate that in addition to systemic autoimmunity, end-organ responses, and end-organ resistance to damage are also critical in determining disease outcome. This understanding should influence design of novel therapeutic approaches in systemic lupus erythematosus. PMID: 19584729 [PubMed - indexed for MEDLINE] |
| Cadherin and integrin regulation of epithelial cell migration.
November 5, 2009 at 10:08 am
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| | Cadherin and integrin regulation of epithelial cell migration. Langmuir. 2009 Sep 1;25(17):10092-9 Authors: Silvestre J, Kenis PJ, Leckband DE These studies quantified the relative effects of E-cadherin expression and homophilic ligation on the integrin-mediated motility of epithelial cells. Micropatterned proteins were used to quantitatively titrate the ligation of E-cadherin and integrin receptors in order to assess their coordinate influence on the migration velocities of MDA-MB-231 breast tumor epithelial cells. Fibronectin, E-cadherin, and mixtures of fibronectin and E-cadherin were covalently patterned on solid surfaces at defined compositions and mass coverages. The migration velocities of parental epithelial cells and of cells engineered to express E-cadherin under tetracycline control show that E-cadherin expression reduces cell motility by both adhesion-dependent and adhesion-independent mechanisms. Increasing E-cadherin expression levels also suppresses the dependence of cell velocity on the fibronectin coverage. On E-cadherin-containing substrata, the cell velocity decreases both with the E-cadherin expression level and with the immobilized E-cadherin surface density. These studies thus identified conditions under which E-cadherin preferentially suppresses cell migration by adhesion-independent versus adhesion-dependent mechanisms. PMID: 19583181 [PubMed - indexed for MEDLINE] |
| Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer.
November 5, 2009 at 10:08 am
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| | Stromal caveolin-1 levels predict early DCIS progression to invasive breast cancer. Cancer Biol Ther. 2009 Jun;8(11):1071-9 Authors: Witkiewicz AK, Dasgupta A, Nguyen KH, Liu C, Kovatich AJ, Schwartz GF, Pestell RG, Sotgia F, Rui H, Lisanti MP Here, we determined the possible association of stromal caveolin-1 (Cav-1) levels with DCIS recurrence and/or progression to invasive breast cancer. An initial cohort of 78 DCIS patients with follow-up data was examined. As ER-positivity was associated with recurrence, we focused our analysis on this subset of 56 patients. In this group, we observed that DCIS progressed to invasive breast cancer in approximately 14% of the patient population (8/56), in accordance with an expected progression rate of 12-15%. Nearly ninety percent of DCIS patients (7/8) that underwent recurrence to invasive breast cancer had reduced or absent levels of stromal Cav-1. Remarkably, an absence of stromal Cav-1 (score = 0) was specifically associated with early disease progression to invasive breast cancer, with reduced time to recurrence and higher recurrence rate. All DCIS patients with an absence of stromal Cav-1 underwent some form of recurrence (5/5) and the majority (4/5) underwent progression to invasive breast cancer. This represents an overall cumulative incidence rate of 100% for recurrence and 80% for progression. An absence of stromal Cav-1 in DCIS lesions was also specifically associated with the presence of inflammatory cells. Conversely, ninety-seven percent of ER(+) DCIS patients (35/36) with high levels of stromal Cav-1 (score = 2) did not show any invasive recurrence over the duration of follow-up (4-208 mo), and 89% of such patients are estimated to remain free of invasive recurrence, even after 15 y. Thus, determination of stromal Cav-1 levels may be a useful new biomarker for guiding the treatment of ER(+) DCIS patients. PMID: 19502809 [PubMed - indexed for MEDLINE] |
| In vitro effects of nanophase hydroxyapatite particles on proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells.
November 5, 2009 at 10:08 am
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| | In vitro effects of nanophase hydroxyapatite particles on proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. J Biomed Mater Res A. 2009 Sep 15;90(4):1083-91 Authors: Liu Y, Wang G, Cai Y, Ji H, Zhou G, Zhao X, Tang R, Zhang M Coculturing scaffolds with seeded cells in vitro is an indispensable process for construction of engineered tissues. It is essential to understand effects of the constituent particles of scaffold on seeded cells. In this study, we investigated the influence of nano-sized hydroxyapatite (nHAP) particles on the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs). nHAP particles were cocultured with MSCs separated from rabbit. Cellular effects of particles were determined by cell counts, Vonkossa stains, and reverse transcription-polymerase chain reaction (RT-PCR) examinations. Results showed that nHAP particles could promote the MSCs growth when particle concentrations were lower than 20 microg/10(4) cells. This effect disappeared when the particles and the cells were cocultured in serum-free media. Higher particle concentrations could significantly inhibit the cell growth. Under the standard culture condition, the only effect of nHAP particles on osteogenic differentiation of MSCs was to enhance the expression of collagen I. Under the osteogenic-inductive culture condition, nHAP particles could inhibit mineralization of cells but promote their osteogenic differentiation. These cellular effects of particles still existed when the particles and the cells were cultured in indirect coculture system. nHAP particles could decrease calcium and phosphate concentrations of culture media, which possibly contributed to the cellular effects of nHAP particles. PMID: 18671263 [PubMed - indexed for MEDLINE] |
| Designing tailored biomaterial surfaces to direct keratinocyte morphology, attachment, and differentiation.
November 5, 2009 at 10:08 am
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| | Designing tailored biomaterial surfaces to direct keratinocyte morphology, attachment, and differentiation. J Biomed Mater Res A. 2009 Sep 15;90(4):999-1009 Authors: Bush KA, Driscoll PF, Soto ER, Lambert CR, McGimpsey WG, Pins GD Precisely engineering the surface chemistry of biomaterials to modulate the adsorption and functionality of biochemical signaling molecules that direct cellular functions is critical in the development of tissue engineered scaffolds. Specifically, this study describes the use of functionalized self-assembled monolayers (SAMs) as a model system to assess the effects of biomaterial surface properties on controlling fibronectin (FN) conformation and concentration as well as keratinocyte function. By systematically analyzing FN adsorption at low and saturated surface densities, we distinguished between SAM-dependent effects of FN concentration and conformation on presenting cellular binding domains that direct cellular functions. Quantitative image analyses of immunostained samples showed that modulating the availability of the FN synergy site directly correlated with changes in keratinocyte attachment, spreading, and differentiation, through integrin-mediated signaling mechanisms. The results of this study will be used to elucidate design features that can be incorporated into dermal equivalents and percutaneous implants to enhance the rate of re-epithelialization and tissue regeneration. Furthermore, these findings indicate that SAM-based model systems are a valuable tool for designing and investigating the development of scaffolds that regulate the conformation of extracellular matrix cues and cellular functions that accelerate the rate of tissue regeneration. PMID: 18655147 [PubMed - indexed for MEDLINE] |
| [Combination of reconstructive vascular operations with gene-engineering technologies of angiogenesis stimulation: a present-day policy aimed at improving the remote results of treating patients with lower limb chronic ischaemia]
November 5, 2009 at 10:08 am
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| | [Combination of reconstructive vascular operations with gene-engineering technologies of angiogenesis stimulation: a present-day policy aimed at improving the remote results of treating patients with lower limb chronic ischaemia] Angiol Sosud Khir. 2008;14(4):49-53 Authors: Gavrilenko AV, Voronov DA, Konstantinov BA, Bochkov NP The authors have studied therapeutic outcomes in a total of 38 patients diagnosed with occlusions of the femoropopliteal segment. In the Study Group patients (n = 19), the operation of femoropopliteal bypass grafting was supplemented by using gene stimulators of angiogenesis (gene constructions with the genes of vascular endothelial growth factor, and angiogenin). The Control Group patients (n = 19) were subjected to a reconstructive vascular operation alone. The remote results were followed up from six to twenty-six months, having shown reliably better therapeutic outcomes obtained in the Study Group patients, as judged by the distance of pain-free walking, the time of restoration of the baseline parameters of blood flow during the treadmill test, muscular perfusion, and the quality of life indices. A conclusion was made that the use ofangiogenesis-stimulating methods combined with reconstructive vascular operations improves the long-term outcomes in patients presenting with lower limb chronic ischaemia. PMID: 19791552 [PubMed - indexed for MEDLINE] | | | 
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