Mathison A.,Chromatin |
Grzenda A.,Chromatin |
Lomberk G.,Chromatin |
Velez G.,Chromatin |
And 11 more authors.
PLoS ONE | Year: 2013
Krüppel-like factor 11 (KLF11) and the highly homologous KLF10 proteins are transcription factors originating from duplication of the Drosophila melanogaster ancestor cabut. The function of these proteins in epithelial cells has been previously characterized. In the current study, we report a functional role for KLF11 in mesenchymal cells and in mesenchymal cell dysfunction, namely, fibrosis, and subsequently perform a detailed cellular, molecular, and in vivo characterization of this phenomenon. We find that, in cultured mesenchymal cells, enhanced expression of KLF11 results in activated extracellular matrix pathways, including collagen gene silencing and matrix metalloproteinases activation without changes in tissue inhibitors of metalloproteinases. Combined, reporter and chromatin immunoprecipitation assays demonstrate that KLF11 interacts directly with the collagen 1a2 (COL1A2) promoter in mesenchymal cells to repress its activity. Mechanistically, KLF11 regulates collagen gene expression through the heterochromatin protein 1 gene-silencing pathway as mutants defective for coupling to this epigenetic modifier lose the ability to repress COL1A2. Expression studies reveal decreased levels of KLF11 during liver fibrogenesis after chemically induced injury in vivo. Congruently, KLF11-/- mice, which should be deficient in the hypothesized anti-fibrogenic brake imposed by this transcription factor, display an enhanced response to liver injury with increased collagen fibril deposition. Thus, KLFs expands the repertoire of transcription factors involved in the regulation of extracellular matrix proteins in mesenchymal cells and define a novel pathway that modulates the fibrogenic response during liver injury. © 2013 Mathison et al.
Van Doesburg M.H.M.,University Utrecht |
Van Der Molen A.M.,University Utrecht |
Journal of Ultrasound in Medicine | Year: 2012
Objectives-Amajor pathologic finding in patients with idiopathic carpal tunnel syndrome is noninflammatory fibrosis and thickening of the subsynovial connective tissue. The objective of this study was to determine the ability of sonography to depict this thickening by comparing subsynovial connective tissue thickness in patients with carpal tunnel syndrome and healthy control participants. Methods-Longitudinal sonograms of the middle finger superficial flexor tendon and subsynovial connective tissue were obtained at 3 levels: at the wrist crease (proximal tunnel), at the hook of the hamate (mid tunnel), and at the distal edge of the transverse carpal ligament (distal tunnel). The thickness of the subsynovial connective tissue perpendicular to the direction of the tendon and the diameter of the flexor digitorum superficialis tendon at the same level were measured. Then, a thickness ratio was created. Results-At all 3 levels, the subsynovial connective tissue was thicker in patients than in controls (P < .0001) with a thickness ranging from 0.60 to 0.63 mm in patients and 0.46 to 0.50 mm in controls. The thickness ratio was significantly greater in patients at the hamate and distal levels (P = .018 and .013, respectively). Conclusions-With this study, we have shown that it is possible to measure subsynovial connective tissue thickness with sonography, and the tissue is thicker in patients with carpal tunnel syndrome than in healthy controls. © 2012 by the American Institute of Ultrasound in Medicine.
Karp D.D.,University of Houston |
Lee S.J.,Dana-Farber Cancer Institute |
Keller S.M.,Montefiore Medical Center |
Wright G.S.,Florida Cancer Specialists |
And 15 more authors.
Journal of Clinical Oncology | Year: 2013
Purpose Selenium has been reported to have chemopreventive benefits in lung cancer. We conducted a double-blind, placebo-controlled trial to evaluate the incidence of second primary tumors (SPTs) in patients with resected non-small-cell lung cancer (NSCLC) receiving selenium supplementation. Patients and Methods Patients with completely resected stage I NSCLC were randomly assigned to take selenized yeast 200
Zhang B.,University of Minnesota |
Iezzi R.,MayoClinic |
Cui T.,University of Minnesota
2013 Transducers and Eurosensors XXVII: The 17th International Conference on Solid-State Sensors, Actuators and Microsystems, TRANSDUCERS and EUROSENSORS 2013 | Year: 2013
The monitoring and controlling of vascular endothelial growth factor (VEGC) are very impnrtant in the treatment of certain cancers and age-related macular degeneration. Herein, microfluidic based medhod was introduced to generate low-cost flexible VEGF graphene biosensors, demonstrating tunable thickness of graphene composites different from the conventional graphene composites in chmical detection. After alternating the surface wetting ability, a PDMS based microfluidic system duplicated from a silicon mold was used to introduce, confine and pattern the graphene films. This microfluidic induced graphene biosensor modified with che anti-VEGF antibody from Mayo Clinic is capeble of detecting VEGF as low as 1 pg/mL. A promising technique be presented to develop the low-cost and high-performance biosensors for the VEGF detection. © 2013 IEEE.
Spoon D.B.,MayoClinic |
Orszulak T.A.,MayoClinic |
Edell E.S.,MayoClinic |
Li Z.,MayoClinic |
Journal of Heart Valve Disease | Year: 2012
Background and aim of the study: Patients with aortic stenosis (AS) and chronic obstructive pulmonary disease (COPD) have been considered at high risk for aortic valve replacement (AVR), which results in some patients being denied this life-saving operation. Hence, the study aim was to assess the operative, 30-day, and long-term mortality in individuals with COPD undergoing AVR for AS in the modern surgical era. Methods: This retrospective cohort of patients had documented COPD (FEV1/FVC <70%), and underwent isolated AVR for severe AS between 1993 and 2007 at the Mayo Clinic in Rochester, MN. Results: Of the 68 patients who met the study criteria, 27 had mild/moderate COPD (FEV 1 >50%), 35 had severe COPD (FEV1 30-50%), and six had very severe COPD (FEV1 <30%). The overall operative and 30-day mortality was 4.8%. More severe COPD was associated with a longer stay in the intensive care unit (42 h for mild/moderate versus 115 h for severe/very severe: p = 0.02), but did not influence the operative or 30-day mortalities. Female gender was associated with an increased length of hospital stay. Long-term mortality was significantly higher in patients with a history of cerebrovascular disease (HR 4.3, p <0.001), NYHA class III or IV heart failure (class III HR 2.79, p = 0.05; class IV HR 3.97, p = 0.03), and increased age (HR 1.06, p = 0.003). The severity of COPD was an independent risk factor for long-term mortality. Conclusion: Patients with severe AS and COPD are at an acceptable risk for AVR (30-day mortality <5%). The severity of COPD is not associated with an increased in-hospital or 30-day mortality, but does influence long-term mortality. © Copyright by ICR Publishers 2012.
PubMed | MayoClinic
Type: Comparative Study | Journal: Psychiatric services (Washington, D.C.) | Year: 2011
This study was a retrospective data-based analysis of health care utilization and costs for patients diagnosed as having bipolar disorder compared with patients with diagnoses of depression, diabetes, coronary artery disease, or asthma.Data were from an employer-based health plan. Consistent diagnosis and continuous enrollment from 2004 to 2007 were used to identify the study population (total N = 7,511), including those with bipolar disorder (N = 122), depression (N = 1,290), asthma (N = 2,770), coronary artery disease (N = 1,759), diabetes (N = 1,418), and diabetes with coronary artery disease (N = 455). Resource utilization quantified as cost (total, specialty care, psychiatric outpatient) and number of visits (specialty care and outpatient psychiatric care) was compared across groups.Patients with bipolar disorder had higher adjusted mean per member per month (PMPM) costs than any other comparison group except for those with both diabetes and coronary artery disease. The cost was predominantly related to pharmacy costs and both inpatient and outpatient psychiatric care. A subset of 20% of patients with bipolar disorder accounted for 64% of the total costs. This subgroup of patients was more likely to be female, to have frequent hospital stays, and to have a higher number of comorbidities. Depressed patients, in contrast to bipolar disorder patients, had higher adjusted mean PMPM costs in primary care and nonpsychiatric inpatient costs.Health care costs for bipolar disorder exceeded those for several common chronic illnesses. These data provide further evidence for employers, insurers, and providers to seek innovative models to deliver effective and efficient care to individuals with bipolar illness.
PubMed | MayoClinic
Type: Journal Article | Journal: Annals of oncology : official journal of the European Society for Medical Oncology | Year: 2013
Several observational studies have shown that statins may modify the risk of gastric cancer (GC). We carried out a systematic review and meta-analysis of studies evaluating the effect of statins on GC risk.We conducted a systematic search of multiple databases up to December 2012. Studies that evaluated exposure to statins, reported GC outcomes and odds ratio (OR) or provided data for their estimation were included in the meta-analysis. Pooled OR estimates with 95% confidence intervals (CIs) were calculated using the random-effects model.Eleven studies (eight observational, three post-hoc analyses of 26 clinical trials) reporting 5581 cases of GC were included. Meta-analysis showed a significant 32% reduction in GC risk with statin use (adjusted OR, 0.68; 95% CI, 0.51-0.91). After exclusion of one study which was contributing to considerable heterogeneity, a significant 16% reduction in GC risk was a more conservative, consistent estimate (adjusted OR, 0.84; 95% CI, 0.78-0.90). This chemopreventive association was present in both Asian (adjusted OR, 0.68; 95% CI, 0.53-0.87) and Western population (adjusted OR, 0.86; 95% CI, 0.79-0.93).Meta-analysis of studies supports a protective association between statin use and GC risk, in both Asian and Western population, in a dose-dependent manner.