228 research outputs found
High-Density Single Nucleotide Polymorphism Genome-Wide Linkage Scan for Susceptibility Genes for Diabetic Nephropathy in Type 1 Diabetes: Discordant Sibpair Approach
OBJECTIVE— Epidemiological and family studies have demonstrated that susceptibility genes play an important role in the etiology of diabetic nephropathy, defined as persistent proteinuria or end-stage renal disease (ESRD) in type 1 diabetes
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Plasma kininogen and kininogen fragments are biomarkers of progressive renal decline in type-1 diabetes
The ability of microalbuminuria to predict early progressive renal function decline in type-1 diabetic patients has been questioned. To resolve this, we determined the plasma proteome differences between microalbuminuric patients with type-1 diabetes and stable renal function (controls) and patients at risk for early progressive renal function decline (cases) and asked whether these differences have value as surrogate biomarkers. Mass spectrometry was used to analyze small (less than 3 kDa) plasma peptides isolated from well-matched case and control plasma obtained at the beginning of an 8-12 year follow-up period. Spearman analysis of plasma peptide abundance and the rate of renal function decline during follow-up identified seven masses with a significant negative correlation with early progressive renal function decline. Tandem mass spectrometry identified three fragments of high molecular weight kininogen. Increased plasma high molecular weight kininogen in the cases was confirmed by immunoblot. One peptide, des-Arg9-BK(1-8), induced Erk1/2 phosphorylation when added apically to two proximal tubular cell lines grown on permeable inserts. Thus, we have identified plasma protein fragments, some of which have biological activity with moderate to strong correlation, with early progressive renal function decline in microalbuminuric patients with type-1 diabetes. Other peptides are candidates for validation as candidate biomarkers of diabetes-associated renal dysfunction
Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers
Purpose: To demonstrate the safety and feasibility of leveraging therapeutic antibodies for surgical imaging. Procedures: We conducted two phase I trials for anti-epidermal growth factor receptor antibodies cetuximab-IRDye800CW (n=12) and panitumumab-IRDye800CW (n=15). Adults with biopsy-confirmed head and neck squamous cell carcinoma scheduled for standard-of-care surgery were eligible. For cetuximab-IRDye800CW, cohort 1 was intravenously infused with 2.5 mg/m(2), cohort 2 received 25 mg/m(2), and cohort 3 received 62.5 mg/m(2). For panitumumab-IRDye800CW, cohorts received 0.06 mg/kg, 0.5 mg/kg, and 1 mg/kg, respectively. Electrocardiograms and blood samples were obtained, and patients were followed for 30 days post-study drug infusion. Results: Both fluorescently labeled antibodies had similar pharmacodynamic properties and minimal toxicities. Two infusion reactions occurred with cetuximab and none with panitumumab. There were no grade 2 or higher toxicities attributable to cetuximab-IRDye800CW or panitumumab-IRDye800CW; fifteen grade 1 adverse events occurred with cetuximab-I RDye800CW, and one grade 1 occurred with panitumumab-IRDye800CW. There were no significant differences in QTc prolongation between the two trials (p=0.8). Conclusions: Panitumumab-IRDye800CW and cetuximab-IRDye800CW have toxicity and pharmacodynamic profiles that match the parent compound, suggesting that other therapeutic antibodies may be repurposed as imaging agents with limited preclinical toxicology data
Confirmation of Genetic Associations at ELMO1 in the GoKinD Collection Supports Its Role as a Susceptibility Gene in Diabetic Nephropathy
Primary Defects in β-Cell Function Further Exacerbated by Worsening of Insulin Resistance Mark the Development of Impaired Glucose Tolerance in Obese Adolescents
OBJECTIVE—Impaired glucose tolerance (IGT) is a pre-diabetic state of increasing prevalence among obese adolescents. The purpose of this study was to determine the natural history of progression from normal glucose tolerance (NGT) to IGT in obese adolescents
High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes: Results of a 6-year follow-up
Diabetes in Relation to Serum Levels of Polychlorinated Biphenyls and Chlorinated Pesticides in Adult Native Americans
Genome-Wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes
10.2337/db08-1514Diabetes5861403-1410DIAE
Ablation of AMP-Activated Protein Kinase α2 Activity Exacerbates Insulin Resistance Induced by High-Fat Feeding of Mice
OBJECTIVE—We determined whether muscle AMP-activated protein kinase (AMPK) has a role in the development of insulin resistance
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