Urine metabolome profiling of immune-mediated inflammatory diseases

Background: Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most prevalent IMIDs: rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn?s disease, and ulcerative colitis. Methods: Using nuclear magnetic resonance, we analyzed the urine metabolome in a discovery cohort of 1210 patients and 100 controls. Within each IMID, two patient subgroups were recruited representing extreme disease activity (very high vs. very low). Metabolite association analysis with disease diagnosis and disease activity was performed using multivariate linear regression in order to control for the effects of clinical, epidemiological, or technical variability. After multiple test correction, the most significant metabolite biomarkers were validated in an independent cohort of 1200 patients and 200 controls. Results: In the discovery cohort, we identified 28 significant associations between urine metabolite levels and disease diagnosis and three significant metabolite associations with disease activity (PFDR < 0.05). Using the validation cohort, we validated 26 of the diagnostic associations and all three metabolite associations with disease activity (PFDR < 0.05). Combining all diagnostic biomarkers using multivariate classifiers we obtained a good disease prediction accuracy in all IMIDs and particularly high in inflammatory bowel diseases. Several of the associated metabolites were found to be commonly altered in multiple IMIDs, some of which can be considered as hub biomarkers. The analysis of the metabolic reactions connecting the IMID-associated metabolites showed an overrepresentation of citric acid cycle, phenylalanine, and glycine-serine metabolism pathways. Conclusions: This study shows that urine is a source of biomarkers of clinical utility in IMIDs. We have found that IMIDs show similar metabolic changes, particularly between clinically similar diseases and we have found, for the first time, the presence of hub metabolites. These findings represent an important step in the development of more efficient and less invasive diagnostic and disease monitoring methods in IMIDs

Transhepatic intravascular ultrasound for evaluation of portal venous involvement in patients with cancer of the pancreatic head region.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to evaluate the ability of intravascular ultrasound to diagnose tumor involvement of the portal and the superior mesenteric veins using the preoperative percutaneous, transhepatic approach, and to compare the findings with those made at concomitant direct portography, surgery, and histopathological examination. Ten patients with a preoperative diagnosis of a resectable tumor in the pancreatic head region were examined with percutaneous transhepatic portography (PTP) and intravascular ultrasound (IVUS). The surgeon's intraoperative evaluation and the histopathological examination in combination revealed tumor involvement of the portal or superior mesenteric veins in six of the ten patients. Percutaneous transhepatic portography suggested tumor involvement of the veins in six patients but two of the examinations were false positive and another two were false negative. Intravascular ultrasound showed signs of tumor involvement in eight patients. The examination was, however, false positive in two patients, but there were no false negatives. Complications of the percutaneous transhepatic procedure occurred in six patients including severe pain, bleeding, and related death. Percutaneous transhepatic IVUS of the portal vein may be a useful tool in the preoperative selection of the subgroup of patients with tumor of the pancreatic head region that could benefit from surgery. There is a need for technical improvement as well as studies with larger patient series to definitely decide the role of the technique

Distribution of beta-enolase in normal and tumor rat cells.

Enolase - a glycolytic enzyme is also expressed on the surface of eukaryotic cells such as macrophages, neutrophils, endothelial, neuronal, tumor cells. Surface enolase as plasminogen receptor plays an important role in myogenesis, tumorgenesis and angiogenesis. Determination of enolase localization in the cell lines may give rise to the elucidation of its receptor function in tumor cells. The cellular localization of the muscle-specific isoform of the enolase in normal rat cardiomyocytes (H9c2, an embryonic rat heart-derived cell line) and a rat sarcoma (R1) cell line is reported here. Immunocytochemical assays showed that this enolase isoform is freely diffused in the sarcoplasm of rat cells. The evident location of enolase molecules on the perinuclear surface is observed in immunofluorescence assays. Enolase localization on the surface of some intact normal rat cardiomyocytes was also observed. This surface protein maintains enolase catalytic activity

Distribution of beta-enolase in normal and tumor rat cells.

Enolase - a glycolytic enzyme is also expressed on the surface of eukaryotic cells such as macrophages, neutrophils, endothelial, neuronal, tumor cells. Surface enolase as plasminogen receptor plays an important role in myogenesis, tumorgenesis and angiogenesis. Determination of enolase localization in the cell lines may give rise to the elucidation of its receptor function in tumor cells. The cellular localization of the muscle-specific isoform of the enolase in normal rat cardiomyocytes (H9c2, an embryonic rat heart-derived cell line) and a rat sarcoma (R1) cell line is reported here. Immunocytochemical assays showed that this enolase isoform is freely diffused in the sarcoplasm of rat cells. The evident location of enolase molecules on the perinuclear surface is observed in immunofluorescence assays. Enolase localization on the surface of some intact normal rat cardiomyocytes was also observed. This surface protein maintains enolase catalytic activity

Entrance to Grand Arch, Jenolan Caves, New South Wales [picture] /

Inscription: "The Caves Entrance to Grand Arch"--In pencil below image.; Title devised by cataloguer from inscription below image.; "C. Bayliss Photo. Sydney."--Blind stamp lower left corner.; Condition: Discoloration all around edge of photograph.; In: New South Wales.; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4198483