Hepatocellular expression of a dominant-negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis

The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by redu…

Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice

Background/Aims In hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice. Methods Transgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed an…

Hepatic over-expression of TGF-beta1 promotes LPS-induced inflammatory cytokine secretion by liver cells and endotoxemic shock.

Transforming growth factor-beta (TGF-beta) is an important suppressor of inflammation. However, TGF-beta has also been found to promote secretion of inflammatory cytokines, and transgenic mice, which constitutively express TGF-beta in liver, have been found to be more susceptible to endotoxemia. To approach this apparent paradox, we investigated the role of hepatic TGF-beta1 in endotoxemia by utilising inducible TGF-beta1-transgenic mice that express TGF-beta1 under control of the C-reactive protein promoter. In contrast to non-transgenic littermates, administration of lipopolysaccharide (LPS) induced strongly increased expression of TGF-beta and acute phase proteins in the TGF-beta1-transg…

Inherited semisterility for control of harmful insects. II. Degree of sterility and types of translocations in the mosquito Culex pipiens L.

Fur die Anwendung von Semisterilitat infolge von Translokationen zur Bekampfung schadlicher Insekten ist der Grad der Semisterilitat und die Art der zugrundeliegenden Translokation von Bedeutung. Von den bisher untersuchten 124 Translokationen hatten 101 einen Sterilitatsgrad zwischen 10 und 50%, 23 uber 50 bis zu 85%. Mit dem mannlichen Geschlechtsfaktor M gekoppelte Translokationen sind zur Zeit die fur die Praxis am nutzlichsten. Sie treten nicht so haufig auf als erwartet, machen aber doch rund 1/4 aller getesteten Translokationen aus. Es werden Grunde angefuhrt, weshalb M-gekoppelte Translokationen nutzlicher sind.

Liver-specific overexpression of matrix metalloproteinase 9 (MMP-9) in transgenic mice accelerates development of hepatocellular carcinoma.

Matrix metalloproteinase-9 (MMP-9) plays a central role in tumor invasion and development of metastases. Expression of MMP-9 had been shown in human hepatocellular carcinomas (HCCs). However, it remained unclear whether MMP-9 could influence development of HCC. In order to address this issue, we generated transgenic mice overexpressing MMP-9 in the liver. In order to avoid embryonic lethality a Cre-lox system was utilized for conditional overexpression of MMP-9 under control of an albumin enhancer and promoter. Induction of MMP-9 overexpression in transgenic mice was achieved by i.v. injection of an adenovirus coding for the Cre recombinase. Initiation of liver carcinogenesis was achieved b…

TGF-β superfamily signaling is essential for tooth and hair morphogenesis and differentiation

Members of the transforming growth factor beta (TGF-beta) superfamily of signaling molecules are involved in the regulation of many developmental processes that involve the interaction between mesenchymal and epithelial tissues. Smad7 is a potent inhibitor of many members of the TGF-beta family, notably TGF-beta and activin. In this study, we show that embryonic overexpression of Smad7 in stratified epithelia using a keratin 5 promoter, results in severe morphogenetic defects in skin and teeth and leads to embryonic and perinatal lethality. To further analyze the functions of Smad7 in epithelial tissues of adult mice, we used an expression system that allowed a controlled overexpression of …

Ecophysiological and morphological features of glacier-dwelling Collembola

Collembola predominantly live in soil, and on the soil surface and its neighboring strata. Some species also dwell in extreme habitats in the arctic and antarctic regions and in the high alpine zones.1–8 Collembola constitute 14–22% of all arctic insect species,9,10 and in tundra and northern forest regions with snow and frost prevailing for the best part of the year they constitute an essential part of the winter-active fauna.11–15 Snow Collembola are reported to occur in masses also in the temperate climate zones of central Europe with species like Hypogastrura socialis, Isotomurus palustris und Isotoma hiemalis frequently among them.16,17 According to Zettel,18 the surface activity of I.…

Phosphororganische verbindungen XLVIII ermittlung der absoluten konfiguration von optisch aktiven methyl-(n)-propyl-benzyl-phenyl-arsonium- bzw. ammonium-salzen mit hilfe von S(+) methyl-(n)-propyl-benzyl-phenyl-phosphoniumsalz als bezugssubstanz

Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study

The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The followi…