Artikler, rapporter og annet (medisinsk biologi)

Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study

Waaseth, Marit — Fri, 31 Dec 2010 23:00:00 GMT

Waaseth, Marit; Olsen, Karina Standahl; Rylander, Charlotta; Lund, Eiliv; Dumeaux, Vanessa

In HPA 1a-immunized women the decrease in anti-HPA 1a antibody level during pregnancy is not associated with anti-idiotypic antibodies

Kjeldsen-Kragh, J — Wed, 31 Dec 2008 23:00:00 GMT

Kjeldsen-Kragh, J; Killie, Mette Kjær; Kim, Michael; Husebekk, Anne; Freedman, J; Semple, John W

Biosynthesis of Promatrix Metalloproteinase-9/Chondroitin Sulphate Proteoglycan Heteromer Involves a Rottlerin-Sensitive Pathway

Malla, Nabin — Fri, 31 Dec 2010 23:00:00 GMT

Malla, Nabin; Berg, Eli; Moens, Ugo; Uhlin-Hansen, Lars; Winberg, Jan-Olof
Background: Previously we have shown that a fraction of the matrix metalloproteinase-9 (MMP-9) synthesized by the macrophage cell line THP-1 was bound to a chondroitin sulphate proteoglycan (CSPG) core protein as a reduction sensitive heteromer. Several biochemical properties of the enzyme were changed when it was bound to the CSPG.
Methodology/Principal Findings: By use of affinity chromatography, zymography, and radioactive labelling, various macrophage stimulators were tested for their effect on the synthesis of the proMMP-9/CSPG heteromer and its components by THP-1 cells. Of the stimulators, only PMA largely increased the biosynthesis of the heteromer. As PMA is an activator of PKC, we determined which PKC isoenzymes were expressed by performing RT-PCR and Western Blotting. Subsequently specific inhibitors were used to investigate their involvement in the biosynthesis of the heteromer. Of the inhibitors, only Rottlerin repressed the biosynthesis of proMMP-9/CSPG and its two components. Much lower concentrations of Rottlerin were needed to reduce the amount of CSPG than what was needed to repress the synthesis of the heteromer and MMP-9. Furthermore, Rottlerin caused a minor reduction in the activation of the PKC isoenzymes d, e, h and u (PKD3) in both control and PMA exposed cells.
Conclusions/Significance: The biosynthesis of the proMMP-9/CSPG heteromer and proMMP-9 in THP-1 cells involves a Rottlerin-sensitive pathway that is different from the Rottlerin sensitive pathway involved in the CSPG biosynthesis. MMP-9 and CSPGs are known to be involved in various physiological and pathological processes. Formation of complexes may influence both the specificity and localization of the enzyme. Therefore, knowledge about biosynthetic pathways and factors involved in the formation of the MMP-9/CSPG heteromer may contribute to insight in the heteromers biological function as well as pointing to future targets for therapeutic agents.

Acquired loss of renal nuclease activity is restricted to DNase I and is an organselective feature in murine lupus nephritis

Seredkina, Natalya — Fri, 31 Dec 2010 23:00:00 GMT

Seredkina, Natalya; Rekvik, Ole Petter
An acquired loss of renal DNaseI has recently been shown to promote transformation of mild mesangial lupus nephritis into membrano-proliferative end-stage organ disease. In this study, we analyzed expression profiles of DNaseI in other organs of lupus-prone (NZBxNZW)F1 mice during disease progression to determine if silencing of the renal DNaseI gene is an organ specific feature or if loss of DNaseI reflects a systemic error in mice with sever lupus nephritis. Our results demonstrate normal or elevated levels of DNaseI mRNA and enzyme activity in liver, spleen and serum samples of (NZBxNZW)F1 mice throughout all stages of lupus nephritis. DNaseI activity was dramatically reduced only in kidneys of mice with sever nephritis and was the only nuclease that was down-regulated, while 6 other nucleases (DNaseIl1-3, caspase activated deoxyribonuclease, Dnase2a, and endonuclease G) were largely normally expressed in kidneys, liver and spleen. Loss of renal DNaseI was not accompanied by changes in serum DNaseI activity, suggesting an independent mechanism of DNaseI regulation in circulation and in kidneys, and an absence of compensatory upregulation of serum DNaseI activity in case of renal DNaseI deficiency. Thus, silencing of renal DNaseI is a unique renal feature in membrano-proliferative lupus nephritis. Determination of mechanism(s) responsible for DNaseI down-regulation is a future step in generation of new therapeutic targets to treat and prevent progressive lupus nephritis.
Accepted manuscript version, reprinted with permission (Elsevier).
Published version available at http://dx.doi.org/10.1016/j.ajpath.2011.05.011
This article is part of Natalya Serdkina's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/3563

MYCN-regulated miRNAs Inhibit Secretion of the Tumor Suppressor DICKKOPF-3 (DKK3) in Neuroblastoma

Haug, Bjørn Helge — Fri, 31 Dec 2010 23:00:00 GMT

Haug, Bjørn Helge; Henriksen, Jørn Remi; Buechner, Jochen; Kogner, Per; Martinsson, Tommy; Flægstad, Trond; Sveinbjørnsson, Baldur; Einvik, Christer
The MYCN oncogene is frequently amplified in neuroblastoma. It is one of the most consistent markers of a bad prognosis for this disease. Dickkopf-3 (DKK3) is a secreted protein of the Dickkopf family of Wnt regulators. It functions as a tumor suppressor in a range of cancers, including neuroblastoma. MYCN was recently found to downregulate DKK3 mRNA. In this study, we show that MYCN knockdown in MYCN-amplified (MNA) neuroblastoma cell lines increases secretion of endogenous DKK3 to the culture media. MiRNAs are ~20-nt-long RNAs encoded by the genome that downregulate mRNAs by targeting the 3`untranslated region (3’UTR). Many miRNAs regulate genes involved in the pathogenesis of cancer and are extensively deregulated in different tumors. Using miRNA target prediction software, we found several MYCN-regulated miRNAs that could target the 3’UTR sequence of DKK3, including mir-92a, mir-92b and let-7e. Luciferase expression from a reporter vector containing the DKK3-3`UTR was decreased when this construct was cotransfected with mir-92a, mir-92b and let-7e in HEK293 cells. Mutation of the mir-92 seed sequence in the 3’UTR completely rescued the observed decrease in reporter expression when cotransfected with mir-92a and mir-92b. Antagomir and miRNA-mimic transfections in neuroblastoma cell lines confirmed that DKK3 secretion to the culture media is regulated by these miRNAs. Consistent with reports from other cancers, we found DKK3 to be expressed in the endothelium of primary neuroblastoma samples and to be absent in tumors with MYCN amplification. These data demonstrate a previously unknown tumor promoting mechanism for MYCN-regulated miRNAs.
Accepted manuscript version, reprinted with permission (Carciongenesis). Published version available at http://dx.doi.org/10.1093/carcin/bgr073
This article is part of Jørn Remi Henriksen's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/2966
This article is part of Jochen Büchner's doctoral thesis which is available in Munin at http://hdl.handle.net/10037/3653

Therapy of chronic wounds with water-filtered infrared-A (wIRA)

von Felbert, Verena — Mon, 31 Dec 2007 23:00:00 GMT

von Felbert, Verena; Mercer, James; Schumann, Hauke; Strasser, Wolfgang; Daeschlein, Georg; Hoffmann, Gerd

Low Sensitivity of the Formol-Ethyl Acetate Sedimentation Concentration Technique in Low-Intensity Schistosoma japonicum Infections

Lier, Tore — Wed, 31 Dec 2008 23:00:00 GMT

Lier, Tore; Wang, TC; Lu, D; Simonsen, Gunnar Skov; Haukland, Hanne H; Haukland, HH; Vennervald, BJ; Johansen, MV

A prospective study of maternal anti-HPA1a antibody level as a potential predictor for alloimmune thrombocytopenia in the newborn

Killie, Mette Kjær — Mon, 31 Dec 2007 23:00:00 GMT

Killie, Mette Kjær; Husebekk, Anne; Skogen, Bjørn Ragnar; Kjeldsen-Kragh, Jens

Researching complementary and alternative treatments : the gatekeepers are not at home

Grimsgaard, sameline — Sun, 31 Dec 2006 23:00:00 GMT

Grimsgaard, sameline; Fønnebø, Vinjar; Walach, Harald; Norheim, Arne Johan; Launsø, Laila; Ritenbaugh, Cheryl; MacPherson, Hugh; Lewith, George; Koithan, Mary; Falkenberg, Torkel; Boon, Heather; Aickin, Mikel

Anti-dsDNA Antibodies Promote Initiation, and Acquired Loss of Renal Dnase1 Promotes Progression of Lupus Nephritis in Autoimmune (NZBxNZW)F1 mice

Fenton, Kristin Andreassen — Wed, 31 Dec 2008 23:00:00 GMT

Fenton, Kristin Andreassen; Fismen, Silje; Hedberg, Annica; Seredkina, Natalya; Fenton, Christopher Graham; Mortensen, Elin; Rekvik, Ole Petter
This article is part of two doctoral theses available in Munin:
1. Natalya Seredkina's thesis, available in Munin at http://hdl.handle.net/10037/3563
2. Silje Fismen's thesis, available in Munin at http://hdl.handle.net/10037/3721