Translational research : the journal of laboratory and clinical medicine
-
Myxedema coma, a rare entity, with a reported 25%-65% mortality had no objective criteria for making the diagnosis when we began our study. We developed an objective screening tool for myxedema coma to more easily identify patients and examine the best treatment method in future prospective studies to reduce the mortality of this entity. We conducted a retrospective chart review to find all patients aged ≥18 years admitted with myxedema coma from January 1, 2005 through June 13, 2010 at Indiana University Health Methodist Hospital. ⋯ However, the overall model was highly significant (P = 0.012), providing strong support for a scoring system that uses these variables simultaneously. This screening tool enables physicians to rapidly diagnose myxedema coma to expedite treatment. A more refined diagnostic tool may be used in future clinical studies designed to determine the optimal treatment.
-
Given the fundamental roles of microRNAs (miRNAs) in physiological, developmental, and pathologic processes, we hypothesized that genes involved in miRNA biogenesis contribute to human complex traits. For 13 such genes, we evaluated the relationship between transcription and 2 classes of complex traits, namely cellular growth and sensitivity to various chemotherapeutic agents in a set of lymphoblastoid cell lines. ⋯ Furthermore, small interfering RNA knockdown of AGO2 resulted in cellular growth inhibition in an ovarian cancer cell line (OVCAR-3), supporting the role of this miRNA biogenesis gene in cell proliferation in cancer cells. Expression quantitative trait loci mapping indicated that genetic variation (in the form of both single-nucleotide polymorphisms and copy number variations) that may regulate the expression of AGO2 can have downstream effects on cellular growth-dependent complex phenotypes.
-
Tumor budding (single tumor cells or small tumor cell clusters) at the invasion front of colorectal cancer (CRC) is an adverse prognostic indicator linked to epithelial-mesenchymal transition. This study characterized the immunogenicity of tumor buds by analyzing the expression of the major histocompatibility complex (MHC) class I in the invasive tumor cell compartment. We hypothesized that maintenance of a functional MHC-I antigen presentation pathway, activation of CD8+ T-cells, and release of antitumoral effector molecules such as cytotoxic granule-associated RNA binding protein (TIA1) in the tumor microenvironment can counter tumor budding and favor prolonged patient outcome. ⋯ No relationship was observed with CIMP, MMR, or BRAF mutation. In conclusion, tumor buds may evade immune recognition through downregulation of membranous MHC-I. A combined profile of MHC-I/CD8/TIA1 improves the prognostic value of antitumoral effector cells and should be preferred to a single marker approach.
-
Clinical Trial
Evidence for metabolic aberrations in asymptomatic persons with type 2 diabetes after initiation of simvastatin therapy.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) prevent vascular events and are widely prescribed, particularly in persons with type 2 diabetes. However, intolerability because of myopathic symptoms often limits their use. We investigated the effects of simvastatin on parameters of mitochondrial function and muscle gene expression in 11 subjects with type 2 diabetes, none of whom had statin intolerance. ⋯ Although statins inhibit an early step in coenzyme Q (CoQ) biosynthesis, we observed no differences in CoQ content within skeletal muscle mitochondria, muscle tissue, or circulating platelets. In summary, we report subtle changes in whole body energetics, mitochondrial citrate synthase activity, and microarray data consistent with subclinical myopathy. Although the benefits of statin therapy are clear, further understanding of muscular perturbations should help guide safety and tolerability.
-
Compared with other types of cancer, thyroid cancer incidence rates have increased rapidly worldwide in the past few decades. In recent years, potential thyroid cancer biomarkers have been studied, but these biomarkers have neither specificity nor good positive predictive value. Exhaled breath analysis is a recently developed convenient and noninvasive method for screening and diagnosing the disease. ⋯ The statistical methods of principal component analysis and partial least-squares discriminant analysis were performed to process the final data. The VOCs exhibited significant differences between nodular goiter patients and normal controls, papillary thyroid carcinoma patients and normal controls, and papillary thyroid carcinoma patients and nodular goiter patients; 7, 7, and 3 characteristic metabolites played decisive roles in sample classification, respectively. Breath analysis may provide a new, noninvasive, and directly qualitative method for the clinical diagnosis of thyroid disease.