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Diminished Expression (diminished + expression)
Selected AbstractsMurine TNF,ARE Crohn's disease model displays diminished expression of intestinal Ca2+ transportersINFLAMMATORY BOWEL DISEASES, Issue 6 2008Sylvie Huybers MSc Abstract Background: Patients suffering from Crohn's disease (CD) show increased incidence of low bone mineral density. Investigating this complication is difficult because the exact etiology of CD remains elusive. Mice carrying a deletion in the tumor necrosis factor (TNF) AU-rich elements (ARE) are reported as a model for human CD and are characterized by elevated TNF-, levels and inflammations in the terminal ileum. To evaluate whether these mice have a Ca2+ handling problem, this study analyzed the Ca2+ homeostasis in heterozygous TNF,ARE mice (TNF,ARE/+) in comparison to wildtype littermates. Methods: Beside serum Ca2+ and vitamin D levels, the expression of Ca2+ transporters was analyzed in intestine, kidney and bone using quantitative real-time PCR, Western blot and immunohistochemistry. Bone scans were performed to measure bone parameters. Results: Ca2+ transporters in duodenum (TRPV6, calbindin-D9K, PMCA1b) and kidney (TRPV5, calbindin-D28K, NCX1) showed significantly reduced mRNA expression levels in TNP,ARE/+ mice, except for renal TRPV5. In bone, only calbindin-D9K mRNA displayed a significant down-regulation. These findings were supported by declined duodenal calbindin-D9K and renal calbindin-D28K protein values. Likely, this down-regulation of Ca2+ transporters in TNP,ARE/+ mice is mediated by the 58 ± 9% reduction in serum 1,25(OH)2D3 levels. Diminished expression of Ca2+ transporters combined with unchanged serum Ca2+ levels assumes Ca2+ loss from bone to compensate for the body's overall Ca2+ shortage. Indeed, microcomputed tomography scanning demonstrated reduced trabecular and corticol bone thickness and volume in TNF,ARE/+ mice. This finding is further supported by increased total deoxypyridinoline in serum. Conclusions: Our results imply that TNF,ARE/+ mice have a disturbed Ca2+ homeostasis characterized by reduced duodenal and renal Ca2+ transporters, diminished 1,25(OH)2D3 levels, and increased bone resorption associated with profound bone abnormalities. (Inflamm Bowel Dis 2008) [source] Diminished expression of dihydropteridine reductase is a potent biomarker for hypertensive vesselsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 21 2009Chang-Kwon Lee Abstract To identify the new targets for hypertension, we analyzed the protein expression profiles of aortic smooth muscle in spontaneously hypertensive rats (SHR) of various ages during the development of hypertension, as well as in age-matched normotensive Wistar,Kyoto (WKY) rats, using a proteomic analysis. The expressions of seven proteins were altered in SHR compared with WKY rats. Of these proteins, NADH dehydrogenase 1,, GST,1, peroxi-redoxin I and transgelin were upregulated in SHR compared with WKY rats. On the other hand, the expression of HSP27 and Ran protein decreased in SHR. The diminution of dihydrobiopterin reductase, an enzyme located in the regeneration pathways of tetrahydrobiopterin (BH4), was also prominent in SHR. The results from a PCR analysis revealed that the expression of BH4 biosynthesis enzymes , GTP cyclohydrolase-1 and sepiapterin reductase , decreased and increased, respectively, in SHR compared with WKY rats. The level of BH4 was less in aortic strips from SHR than from WKY rats. Moreover, treatment with BH4 inhibited aortic smooth muscle contraction induced by serotonin. These results suggest that the deficiency in BH4 regeneration produced by diminished dihydrobiopterin reductase expression is involved in vascular disorders in hypertensive rats. [source] Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancerTHE PROSTATE, Issue 3 2006Zheng Fu Abstract BACKGROUND Diminished expression of Raf kinase inhibitor protein (RKIP), an inhibitor of the Raf signaling cascade, promotes prostate cancer (PCa) metastasis in a murine model, suggesting that it is a metastasis suppressor gene. However, the prognostic significance of RKIP expression and its association with metastasis in PCa patients is unknown. METHODS To investigate RKIP protein expression is a prognostic marker in PCa we performed immunohistochemical staining for RKIP expression in tissue microarrays consisting of 758 non-neoplastic prostate tissues, primary tumors and metastases from 134 PCa patients. The Cox proportional-hazards model was used to adjust for covariates including Gleason score, tumor volume, tumor weight, clinical stage, digital rectal exam findings, serum PSA level and surgical margins. RESULTS RKIP expression was low in approximately 5%, 48%, and 89%of non-neoplastic prostate, primary tumors and metastases, respectively. Low RKIP expression in primary tumors was a strong positive predictive factor for PCa recurrence based on PSA levels. In patients whose primary tumors expressed high RKIP levels, the 7-year PSA recurrence rate was <,10%; whereas in patients with tumors with low RKIP expression the recurrence rate was 50% (P,<,0.001). Multivariate analysis revealed RKIP was an independent prognostic factor (P,<,0.001). CONCLUSION In contrast to increased expression of pro-tumorigenic genes, these results demonstrate decreased protein expression of a gene, for example, RKIP, can serve as a prognostic marker in PCa patients. © 2005 Wiley-Liss, Inc. [source] Gene expression and dental enamel structure in developing mouse incisorEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 2 2010Amer Sehic Sehic A, Risnes S, Khan Q-E-S, Khuu C, Osmundsen H. Gene expression and dental enamel structure in developing mouse incisor. Eur J Oral Sci 2010; 118: 118,130. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci At the mouse incisor tip the initially differentiated ameloblasts produce a thin, prism-free enamel, while further apically, in the immediate adjacent segment, the enamel thickness increases and the four-layered enamel of mouse incisor is formed. Comparative gene-expression profiling was carried out on RNA isolated from these two segments of incisor tooth germs at embryonic day (E)17.5 and at postnatal days (P)0, 1, 2, and 10 using microarrays to measure messenger RNA (mRNA) and microRNA (miRNA) species present in the segments. Validation of expression data was achieved using real-time reverse transcription,polymerase chain reaction (RT-PCR) and western blotting. Bioinformatic data suggested enhanced cellular apoptosis in the incisal tip segment, which, together with diminished expression of the Amelx and Enam genes, may contribute to the production of the thin enamel seen in this tooth segment. For genes exhibiting higher levels of expression in the adjacent segment where complex enamel is being formed, bioinformatic analysis suggested significant associations with cellular functions involving the actin cytoskeleton, cellular development, morphology, and movement. This is suggested to reflect that ameloblasts with Tomes' process are being organized in transverse rows, facilitating the transverse movement that results in prism decussation in the inner enamel of the adjacent segment. Bioinformatic analysis of miRNA expression data lends support to these suggestions. [source] Characteristics of testicular dysgenesis syndrome and decreased expression of SRY and SOX9 in Frasier syndromeMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 9 2008Valérie Schumacher Abstract Frasier syndrome (FS) is characterized by chronic renal failure in early adulthood, varying degrees of gonadal dysgenesis, and a high risk for gonadal germ cell malignancies, particularly gonadoblastoma. Although it is known to arise from heterozygous splice mutations in intron 9 of the Wilms' tumor gene 1 (WT1), the mechanisms by which these mutations result in gonadal dysgenesis in humans remain obscure. Here we show that a decrease in WT1,+,KTS isoforms due to disruption of alternative splicing of the WT1 gene in a FS patient is associated with diminished expression of the transcription factors SRY and SOX9 in Sertoli cells. These findings provide the first confirmation in humans of the results obtained by others in mice. Consequently, Sertoli cells fail to form the specialized environment within the seminiferous tubules that normally houses developing germ cells. Thus, germ cells are unable to fully mature and are blocked at the spermatogonial,spermatocyte stage. Concomitantly, subpopulations of the malignant counterpart of primordial germ cells/gonocytes, the intratubular germ cell neoplasia unclassified type (ITGCN), are identified. Furthermore, dysregulated Leydig cells produce insufficient levels of testosterone, resulting in hypospadias. Collectively, the impaired spermatogenesis, hypospadias and ITGCN comprise part of the developmental disorder known as ,testicular dysgenesis syndrome' (TDS), which arises during early fetal life. The data presented here show that critical levels of WT1,+,KTS, SRY and SOX9 are required for normal Sertoli cell maturation, and subsequent normal spermatogenesis. To further study the function of human Sertoli cells in the future, we have established a human cell line. Mol. Reprod. Dev. 75: 1484,1494, 2008. © 2008 Wiley-Liss, Inc. [source] Diannexin, a Novel Annexin V Homodimer, Protects Rat Liver Transplants Against Cold Ischemia-Reperfusion InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2007X.-D. Shen Ischemia/reperfusion injury (IRI) remains an important problem in clinical transplantation. Following ischemia, phosphatidylserine (PS) translocates to surfaces of endothelial cells (ECs) and promotes the early attachment of leukocytes/platelets, impairing microvascular blood flow. Diannexin, a 73 KD homodimer of human annexin V, binds to PS, prevents attachment of leukocytes/platelets to EC, and maintains sinusoidal blood flow. This study analyzes whether Diannexin treatment can prevent cold IRI in liver transplantation. Rat livers were stored at 4°C in UW solution for 24 h, and then transplanted orthotopically (OLT) into syngeneic recipients. Diannexin (200 ,g/kg) was infused into: (i) donor livers after recovering and before reperfusion, (ii) OLT recipients at reperfusion and day +2. Controls consisted of untreated OLTs. Both Diannexin regimens increased OLT survival from 40% to 100%, depressed sALT levels, and decreased hepatic histological injury. Diannexin treatment decreased TNF-,, IL-1,, IP-10 expression, diminished expression of P-selectin, endothelial ICAM-1, and attenuated OLT infiltration by macrophages, CD4 cells and PMNs. Diannexin increased expression of HO-1/Bcl-2/Bcl-xl, and reduced Caspase-3/TUNEL+ apoptotic cells. Thus, by modulating leukocyte/platelet trafficking and EC activation in OLTs, Diannexin suppressed vascular inflammatory responses and decreased apoptosis. Diannexin deserves further exploration as a novel agent to attenuate IRI, and thereby improve OLT function/increase organ donor pool. [source] Muir,Torre syndrome: Diagnostic and screening guidelinesAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2006Brad Jones SUMMARY A 65-year-old man presented with a history of multiple skin coloured papules on his face that were asymptomatic. He had an adenocarcinoma resected from his proximal colon 12 years prior to presentation as well as a family history of colon cancer on the maternal side. Diagnostic biopsies showed the lesions to be sebaceous adenomas and epitheliomas and the diagnosis of Muir,Torre syndrome was made. The sebaceous tumour tissue showed microsatellite instability and immunohistochemical staining indicated diminished expression in the DNA mismatch,repair protein complex MSH2/MSH6. Genetic analysis showed a germline mutation in the MSH2 gene confirming the diagnosis of Muir,Torre syndrome. The patient and his first-degree relatives have been referred for genetic counselling and screening. We review the diagnostic criteria in this syndrome and review the recommended screening guidelines. [source] Vitamin D and Its Analog EB1089 Induce p27 Accumulation and Diminish Association of p27 with Skp2 Independent of PTEN in Pituitary Corticotroph CellsBRAIN PATHOLOGY, Issue 4 2002Wei Liu Disruption of the gene for the cyclin dependent kinase inhibitor (CDKI) p27/kip1 results in pituitary corticotroph hyperplasia while diminished expression of this protein has been described in aggressive human pituitary tumors. We have previously shown that 1,25-vitamin D3 (VD) hypophosphorylates p27 and interferes with the degradation of this CDKI in thyroid carcinoma cells. In this study we investigated whether VD/EB1089 can induce p27 accumulation and cause growth arrest of pituitary corticotroph cells. VD and EB1089 exhibited a significant reduction in AtT20 corticotroph but not PRL235 Iactotroph cell growth. These changes were accompanied by selective accumulation of p27 in AtT20 but not in PRL235 cells. As p27 levels are highly dependent on protein degradation, we examined the effect of VD/EB1089 on p27 association with factors that target this CDKI to the proteasome. VD/EB1089 significantly restricted the association of p27 with Skp2 as well as with cyclin dependent kinase 2 (CDK2). As the tumor suppressor and phosphatase PTEN has been implicated in p27 regulation, we tested whether the effects of VD/EB1089 on p27 accumulation in corticotrophs could be mediated through this pathway. VD/EB1089 did not appreciably alter PTEN expression. Moreover, transfection of PTEN did not influence the effect of VD on p27 accumulation in corticotrophs. We conclude that VD/EB1089 can selectively arrest pituitary corticotroph growth and induce p27 accumulation. This effect is mediated at least partially through diminished p27 association with Skp2 and with CDK2. In contrast to other cell systems, PTEN does not participate in the regulation of corticotroph p27 and is not involved in mediating the effect of VD on p27 in these cells. Our findings highlight p27 and VD analogs as targets for manipulation and drug development respectively in the treatment of inoperable corticotroph adenomas. [source] | ||||||||||