Reporter constructs with low background activity utilizing the cat gene

Reporter plasmids utilizing the cat gene for the analysis of promoter and enhancer sequences in vertebrate cells, were constructed. These plasmids minimize the background of transcription derived from cryptic promoters or cryptic regulatory elements within the vecto

A cyclic AMP response element mediates repression of tyrosine aminotransferase gene transcription by the tissue-specific extinguisher locus Tse-1

Tyrosine aminotransferase (TAT) gene expression is liver specific and inducible by glucocorticoids and via the cAMP signaling pathway. In fibroblasts and other nonliver cells the gene is subject to negative control by the trans-dominant tissue-specific extinguisher locus Tse-1. We identified a hepatocyte-specific enhancer that is repressed by Tse-1. Two distinct sequence motifs are absolutely essential for function of this enhancer: a cAMP response element (CRE), which is the target for repression by Tse-1, and a hepatocyte-specific element. The specificity of the enhancer is generated by the combination of these two essential elements, which are fully interdependent. In vivo footprinting indicates that Tse-1 acts by affecting protein binding at the CRE. A direct antagonism between Tse-1 and the cAMP signaling pathway suggests that Tse-1 plays a role in control of developmental activation of the TAT gene

Using Business Intelligence Tools to Support Medical Validation of Laboratory Tests

Modern clinical laboratories have to confirm that the procedures used for specific tests are reliable and valid. There are several sources of errors and interferences that can invalidate the results. Medical validation refers to the plausibility check of the test results. Implausible results indicate that something might went wrong with a sample retrieved from the patient, e.g., the blood sample got contaminated with another fluid, which requires re-examination. Here, we describe how an integrated R-based business intelligence (BI) tool can be developed that increase the efficiency of the medical validation at the Institute of Clinical Chemistry (ICC) of the University Hospital Zurich. A BI software environment allowed us to digitalize steps in the validation process that were manually done in Excel worksheets, e.g., importing the data, calculating percentiles, and producing graphical outputs

Enhancement of fibrinogen-triggered pro-coagulant activation of monocytes in vitro by matrix metalloproteinase-9

<p>Abstract</p> <p>Background</p> <p>Interaction of fibrinogen with specific leukocyte integrins of monocytes may link coagulation and inflammation, however, the precise mechanism of fibrinogen leading to the pro-inflammatory and pro-coagulatory response on monocytes is yet unknown.</p> <p>Results</p> <p>Fibrinogen and its digestion fragment D induced pro-coagulant activation of monocytes as assessed in a cellular coagulation assay by reductions in clotting times. Pro-coagulant activation was reversed by blocking antibodies against Mac-1 or LFA-1. Pre-exposure of monocytes to the p38 MAPK inhibitor SB 202190 and the MEK1.2 inhibitor U0126 led to significant increasees in coagulation times whereas blocking JNKII with its inhibitor had no such effect. Blocking NFκB with MG-132 also inhibited pro-coagulant activation of monocytes by fibrinogen. A selective inhibitor of matrix metalloproteinase-9 increased times to clot formation whereas other matrix metalloproteinase inhibitors did not significantly interfere with fibrinogen-augmented clot formation in this assay. Treatment of monocytes with fibrinogen increased concentrations of matrix metalloproteinase-9 immunoreactivity in their supernatants.</p> <p>Conclusions</p> <p>Fibrinogen induces monocyte pro-coagulant activation in an integrin-, nuclear factor κB-, p38 MAPK-, and MEK1.2-dependent manner. Activation of monocytes by fibrinogen increases metalloproteinase-9 secretion, metalloproteinase-9 itself enhances monocyte coagulation by an autocrine mechanism. Results provide further evidence that mediators of hemostasis have a profound impact on cells of the immune system and are closely related to inflammatory pathways.</p

Sites of Failure in Breast Cancer Patients with Extracapsular Invasion of Axillary Lymph Node Metastases: No Need for Axillary Irradiation?!

Background and Purpose:: Extracapsular spread (ECS) is frequent, but the specific sites of relapse are seldom given in the literature. In this study it was evaluated, if ECS might be an indicator for axillary irradiation. Patients and Methods:: After a retrospective review of pathology reports, the information about ECS was available in 254 lymph node-positive patients: ECS was absent in 34% (ECS-negative; n = 87) and present in 66% (ECS-positive; n = 167). All patients were irradiated locally, 78 patients got periclavicular and 74 axillary irradiation (median total dose: 50.4 Gy). 240/254 patients (94.5%) received systemic treatment/s. Mean follow-up was 46 months. Results:: The regional relapse rate was 4.6% without ECS versus 9.6% with ECS. The 5-year axillary relapse-free survival was 100% in ECS-negative and 90% in ECS-positive patients (p = 0.01), whereas corresponding values for periclavicular relapse-free survival (with ECS: 91% ± 4%; without ECS: 94% ± 3%; p = 0.77) and local relapse-free survival (with ECS: 86% ± 4%; without ECS: 91% ± 3%; p = 0.69) were not significantly different. χ2-tests revealed a high correlation of ECS with T-stage, number of positive lymph nodes and progesterone receptor status, comparisons with estrogen receptor, grade, or age were not significant. In multivariate analysis number of positive lymph nodes was solely significant for regional failure. Dividing the patients into those with one to three and those with four or more positive lymph nodes, ECS lost its significance for axillary failure. Conclusion:: ECS was accompanied by an enhanced axillary failure rate in univariate analysis, which was no longer true after adjusting for the number of positive lymph node

Entwicklung der Unterbeschäftigung im Bereich des SGB II nach Formen der Aufgabenwahrnehmung: Quartalsbericht Februar 2008

"Der Quartalsbericht erscheint im Rahmen der regelmäßigen Berichterstattung des IAW in Untersuchungsfeld 1 der Evaluation der Experimentierklausel des Paragraph 6c SGB II im Auftrag des BMAS. Die inhaltliche Besonderheit des vorliegenden Quartalsberichts besteht darin, dass erstmals das für den gesamten Forschungsverbund wichtige Thema der regionalen Unterbeschäftigung im Rechtskreis des SGB II im Vergleich der unterschiedlichen Formen der Aufgabenwahrnehmung beleuchtet werden kann. Bei der erstmaligen Betrachtung des Ausmaßes, der Struktur und der Entwicklung der SGB II-Unterbeschäftigung im Vergleich der Regionen mit unterschiedlichen Formen der Aufgabenwahrnehmung wird ergänzend auch nach Typen des regionalen Arbeitsmarkthintergrunds vor Einführung des SGB II differenziert." (Textauszug