Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.

Gastrointestinal stromal tumor (GIST) is a newly defined clinical and pathologic entity. This study examines the whole populationbased incidence of GIST as well as pathologic risk stratification schemes. All patients diagnosed in Iceland with a gastrointestinal mesenchymal tumor over the years 1990-2003 were evaluated with an immunohistochemical panel including staining for c-kit. The age-adjusted incidence of GIST was calculated. Size, mitotic rate per 50 HPF and various other pathologic parameters were evaluated. Each tumor was categorized into 1 of 4 recently defined NIH risk stratification categories. Fifty-seven of the mesenechymal gastrointestinal tumors were positive for c-kit and therefore categorized as GIST. The annual incidence for the study period is 1.1 per 100,000. The median age of patients was 65.8 years and median tumor size was 4.6 cm. Only 2 of 35 gastric tumors fall into the NIH high-risk category while half of the nongastric tumors (11 of 22) fall into this high-risk category. Eight of the 57 tumors (14%) metastasized, 7 of which were nongastric. The positive predictive value for malignant behavior of the high-risk category is 46%. The negative predictive value of low-and very-lowrisk NIH category is 100%. Pathologic predictors of malignant behavior are tumor size, mitotic rate, mucosal disruption, necrosis and high cellularity. Nongastric GISTs are clearly at much higher risk of a malignant behavior than gastric GISTs. This populationbased GIST study estimates the incidence of GISTs at 1.1 per 100,000 and furthermore supports the NIH consensus categories for the prediction of malignant behavior of GISTs. ' 2005 Wiley-Liss, Inc.Key words: gastrointestinal stromal tumor; incidence; pathology; epidemiology; GIST For the past few years, there has been a surging interest in mesenchymal gastrointestinal tumors after a long period of neglect. The interest arose following the clinicopathologic definition of gastrointestinal stromal tumors (GISTs). The subsequent discovery of an activating mutation of the c-kit tyrosine kinase in nearly all GIST tumors and the recent clinical breakthrough of being able to target these mutations therapeutically with the specific tyrosine kinase inhibitor imatinib mesylate have caused a marked surge in interest in these tumors.GIST is a relatively newly discovered and defined clinical and pathologic entity previously grouped together with tumors of smooth muscle or neural derivation of the gut, such as leiomyoma, leiomyosarcoma, or schwannoma. The cells in gastrointestinal stromal tumors share some phenotypic characteristics with the interstitial cell of Cajal and are characterized by strong immunostaining for the receptor tyrosine kinase c-kit (CD-117). 1 In 1998, Hirota et al. 2 discovered an activating mutation in the c-kit gene in gastrointestinal stromal tumors and subsequently it was shown that this mutation is present in the majority of GISTs. 3 Imatinib mesylate is a specific tyrosine kinase inhibitor targeting the tyrosine kinases ABL, ARG, PDGFR (a and b) an...

In our porcine model, and increasing the IAP by means of instillation of Ringer's solution, a reliable estimation of the IAP was obtained by measuring the pressure in the urinary bladder, the femoral vein or the inferior caval vein. The IAP estimated indirectly as the urinary bladder pressure is affected by the amount of fluid in the bladder, which should not exceed 10-15 ml. The decrease in femoral vein blood flow reflects the changes in inferior caval vein flow during increased IAP.