Neutrophil lysis after phagocytosis is a process potentially important in the pathogenesis of community-associated methicillin-resistant S. aureus (CA-MRSA) infection. The mechanism for this process is not currently known. Therefore, to better understand CA-MRSA virulence we used human oligonucleotide microarrays to investigate the mechanism underlying enhanced PMN lysis that occurs after phagocytosis of CA-MRSA.
Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus.
Specimen part, Treatment
View SamplesWith advances in supportive therapy in the last two decades, mortality rates from ALI/ARDS have improved somewhat, but remain around 30 to 40% with significant morbidity in survivors. Several promising treatments are in various stages of evaluation, but many have failed to prove beneficial in large randomized clinical trials (RCT). The first definitive step forward in ALI therapeutics occurred recently as a result of a large RCT demonstrating a mortality decrease from 40 to 31% with the use of low-volume ventilation strategies. From this, it is clear that the opportunity for successful intervention in ALI exists. However, therapeutic advances remain frustrated by the lack of complete understanding of ALI pathophysiology. This stresses the importance of integrating basic and clinical research of the molecular pathogenesis of this disease. The conclusions of a recent National Heart, Lung, and Blood Institute (NHLBI) Working Group on ALI support this type of research as a priority for future investigations of ALI. One of the areas of research given priority by this ALI Working Group is the issue of ALI severity progression and the role of cells of innate immunity in this process. Currently, the processes that determine which ALI patients progress to ARDS and which do not are unclear. As with many phenotype differences, there is most likely a genetic component involved. The basis for this has been demonstrated. For example, a surfactant protein B (SP-B) polymorphism appears to increase a patients risk of developing ALI from pneumonia. Additionally, a polymorphism in the promoter region of the gene for interleukin-6 (IL-6) has been associated with a poor prognosis in patients with ARDS. Understanding the intracellular processes of these genes and the cells expressing them in ALI progression could lead to the identification of molecular markers of ALI severity and eventually to the development of targeted therapies. An examination of genetically uniform animals will provide a clearer insight into the interaction between immune cells in ALI progression as well as guide future human experiments.
Sepsis alters the megakaryocyte-platelet transcriptional axis resulting in granzyme B-mediated lymphotoxicity.
Specimen part
View SamplesGlucose intolerance and diabetes mellitus are classical parts of endogenous Cushings syndrome (CS), and insulin resistance is a feature of cortisol excess. CS patients display characteristics including hyperglycemia, abdominal obesity, reduced high-density lipoprotein cholesterol levels and elevated triglycerides, and arterial hypertension. Hypercortisolism is a well known cause of bone loss, and patients with CS frequently display low bone mass and fragility fractures. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut, and affects the secretion of several hormones, cytokines, and growth factors with potential influence on bone metabolism. Bone biopsies from nine CS patients, before and mean 3 months after surgery, were screened for expressional candidate genes using Affymetrix human Gene Plus 2.0 Arrays. Analyses were performed to identify genes in glucocorticoid-induced osteoporosis and genes in glucose metabolism and energy homeostasis.
The glucocorticoid-induced leucine zipper gene (GILZ) expression decreases after successful treatment of patients with endogenous Cushing's syndrome and may play a role in glucocorticoid-induced osteoporosis.
Sex, Age, Specimen part
View SamplesAim of this project was the evaluation of the effect of flushing (intraportal and intraoperative) hepatic allografts with tacrolimus before transplantation. Group A was administered tacrolimus, 20ng/ml in 1500ml albumin solution; and Group B was administered only albumin solution. Wedge biopsie of the allograft were harvested after 15 min flushing time and the gene expression profile were determined.
Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial.
Specimen part, Treatment
View SamplesWe used microarrays to investigate the transcriptome of 6 days old male flies exposed to either 15 or 25 C development at either constant or fluctuating temperatures. Further, we investigated gene expression at benign (20C) and high (35C) temperatures
Thermal fluctuations affect the transcriptome through mechanisms independent of average temperature.
Sex
View SamplesThe present work aimed to identify reference genes for RT-qPCR studies of hypoxia in cervical cancer. From 422 candidate reference genes selected from the literature, we used Illumina array-based expression profiles to identify 182 genes not affected by hypoxia treatment in eight cervical cancer cell lines or correlated with the hypoxia-associated dynamic contrast-enhanced magnetic resonance imaging parameter ABrix in 42 patients. Among these genes, we selected nine candidates (CHCHD1, GNB2L1, IPO8, LASP1, RPL27A, RPS12, SOD1, SRSF9, TMBIM6) that were not associated with tumor volume, stage, lymph node involvement or disease progression in array data of 150 patients, for further testing by RT-qPCR. geNorm and NormFinder analyses of RT-qPCR data of 74 patients identified CHCHD1, SRSF9 and TMBIM6 as the most suitable set of reference genes, with stable expression both overall and across patient subgroups with different hypoxia status (ABrix) and clinical parameters. The suitability of the three candidates as reference genes were validated in studies of the hypoxia-induced genes DDIT3, ERO1A, and STC2. After normalizing with CHCHD1, SRSF9 and TMBIM6, the RT-qPCR data of these genes showed a significant correlation with Illumina expression (P<0.001, n=74) and ABrix (P<0.05, n=32), and the STC2 data were associated with clinical outcome, in accordance with the Illumina data. Thus, CHCHD1, SRSF9 and TMBIM6 seem to be suitable reference genes for studying hypoxia-related gene expression in cervical cancer samples by RT-qPCR. STC2 might be a useful prognostic hypoxia biomarker in cervical cancer that warrants further investigation.
Identification and Validation of Reference Genes for RT-qPCR Studies of Hypoxia in Squamous Cervical Cancer Patients.
Specimen part, Cell line
View SamplesAim of the study was to characterize the transcriptional response of human primary renal proximal tubule epithelial cells (RPTEC) to low oxygen stress.
The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesWe used microarrays to assess gene expression profiling of 6 patients with a mutation (Arg1174Gln) in the tyrosine kinase domain of the insulin receptor gene (INSR) and 10 matched healthy controls
A PGC-1α- and muscle fibre type-related decrease in markers of mitochondrial oxidative metabolism in skeletal muscle of humans with inherited insulin resistance.
Specimen part
View SamplesThe response to nitrogen starvation was studied in S. pombe. This experiment contains expression data from Affymetrix Yeast 2.0 arrays.
Nitrogen depletion in the fission yeast Schizosaccharomyces pombe causes nucleosome loss in both promoters and coding regions of activated genes.
No sample metadata fields
View SamplesEmerging biomarkers based on medical images and molecular characterization of tumor biopsies open up for combining the two disciplines and exploiting their synergy in treatment planning. We compared pretreatment classification of cervical cancer patients by two previously validated imaging- and gene-based hypoxia biomarkers, evaluated the influence of intratumor heterogeneity, and investigated the benefit of combining them in prediction of treatment failure. The imaging-based biomarker was hypoxic fraction, determined from diagnostic dynamic contrast enhanced (DCE)-MR images. The gene-based biomarker was a hypoxia gene expression signature determined from tumor biopsies. Paired data were available for 118 patients. Intratumor heterogeneity was assessed by variance analysis of MR images and multiple biopsies from the same tumor. The two biomarkers were combined using a dimension-reduction procedure. The biomarkers classified 75% of the tumors with the same hypoxia status. Both intratumor heterogeneity and distribution pattern of hypoxia from imaging were unrelated to inconsistent classification by the two biomarkers, and the hypoxia status of the slice covering the biopsy region was representative of the whole tumor. Hypoxia by genes was independent on tumor cell fraction and showed minor heterogeneity across multiple biopsies in 9 tumors. This suggested that the two biomarkers could contain complementary biological information. Combination of the biomarkers into a composite score led to improved prediction of treatment failure (HR:7.3) compared to imaging (HR:3.8) and genes (HR:3.0) and prognostic impact in multivariate analysis with clinical variables. In conclusion, combining imaging- and gene-based biomarkers enables more precise and informative assessment of hypoxia-related treatment resistance in cervical cancer, independent of intratumor heterogeneity.
Combining imaging- and gene-based hypoxia biomarkers in cervical cancer improves prediction of chemoradiotherapy failure independent of intratumour heterogeneity.
Specimen part
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