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Increased Expression (increased + expression)
Terms modified by Increased Expression Selected AbstractsIncreased Expression of p53 Protein Correlates With the Extent of Myocyte Damage in Cardiac Allograft RejectionCONGESTIVE HEART FAILURE, Issue 6 2008Bernadette K. McLaren MD Acute cardiac allograft rejection (ACAR) has been associated with a poor prognosis. The early diagnosis of ACAR necessitates the accurate detection of myocyte damage. Nuclear damage activates p53, a transcription factor that initiates apoptosis and repair. Endomyocardial biopsies (n=25) from 10 cardiac allograft recipients were stained for nuclear p53. The biopsies were divided into rejection groups based on the grading of ACAR: group 1, grade 0; group 2, grade Ia and Ib; group 3, grades II and III. While clinical indices did not correlate with myocyte damage, significantly more myocytes in group 3 stained for nuclear p53 (2.48±0.60/mm2) compared with group 1 (0.22±0.12/mm2) and group 2 (0.43±0.18/mm2). Increased expression of p53 in cardiac myocytes with grade II or grade III rejection provides an objective quantification as an aid in the diagnosis of ACAR. [source] Increased Expression of the Neuronal Glutamate Transporter (EAAT3/EAAC1) in Hippocampal and Neocortical EpilepsyEPILEPSIA, Issue 3 2002Peter B. Crino Summary: ,Purpose: To define the changes in gene and protein expression of the neuronal glutamate transporter (EAAT3/EAAC1) in a rat model of temporal lobe epilepsy as well as in human hippocampal and neocortical epilepsy. Methods: The expression of EAAT3/EAAC1 mRNA was measured by reverse Northern blotting in single dissociated hippocampal dentate granule cells from rats with pilocarpine-induced temporal lobe epilepsy (TLE) and age-matched controls, in dentate granule cells from hippocampal surgical specimens from patients with TLE, and in dysplastic neurons microdissected from human focal cortical dysplasia specimens. Immunolabeling of rat and human hippocampi and cortical dysplasia tissue with EAAT3/EAAC1 antibodies served to corroborate the mRNA expression analysis. Results: The expression of EAAT3/EAAC1 mRNA was increased by nearly threefold in dentate granule cells from rats with spontaneous seizures compared with dentate granule cells from control rats. EAAT3/EAAC1 mRNA levels also were high in human dentate granule cells from patients with TLE and were significantly elevated in dysplastic neurons in cortical dysplasia compared with nondysplastic neurons from postmortem control tissue. No difference in expression of another glutamate transporter, EAAT2/GLT-1, was observed. Immunolabeling demonstrated that EAAT3/EAAC1 protein expression was enhanced in dentate granule cells from both rats and humans with TLE as well as in dysplastic neurons from human cortical dysplasia tissue. Conclusions: Elevations of EAAT3/EAAC1 mRNA and protein levels are present in neurons from hippocampus and neocortex in both rats and humans with epilepsy. Upregulation of EAAT3/EAAC1 in hippocampal and neocortical epilepsy may be an important modulator of extracellular glutamate concentrations and may occur as a response to recurrent seizures in these cell types. [source] SHORT COMMUNICATION: Increased Expression of Glutathione by Estradiol, Tumor Necrosis Factor-Alpha, and Interleukin 1-Beta in Endometrial Stromal CellsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2009Sa Ra Lee Problem, The intracellular antioxidant system, based on glutathione (GSH), plays a key role in endometrial detoxification reactions and has been proposed to be involved in the pathogenesis endometriosis. This study was designed to evaluate whether estradiol (E2) and proinflammatory cytokines have any effects on expression of glutathione in endometrial stromal cells (ESCs). Method of study, Glutathione levels were measured utilizing high-performance liquid chromatography following in vitro culture and treatment of ESCs with estradiol, tumor necrosis factor-alpha (TNF-,) and interleukin 1-beta (IL-1,). Results, The GSH level in E2 (10,8 m) treatment group was significantly higher than in the control group at 48 h (P < 0.05). In vitro treatment of ESCs with TNF-, 10 ng/mL as well as E2 (10,8 m) plus TNF-, 10 ng/mL for 48 hr also led to a significant increase in GSH level (P < 0.05; P < 0.05, respectively). Both IL-1, 10 ng/mL and E2 (10,8 m) plus IL-1, 10 ng/mL for 48 hr increased GSH level significantly (P < 0.05; P < 0.05, respectively) as well. Conclusions, These findings might suggest that increased production of estradiol and proinflammatory cytokines in the peritoneal cavity possibly leads to the establishment of endometriosis through increased level of GSH. [source] Increased Expression of Laminin-5 and Its Prognostic Significance in Hypopharyngeal Cancer,THE LARYNGOSCOPE, Issue 7 2004Meijin Nakayama MD Objectives: We investigated the clinicopathologic significance of laminin-5 ,2 chain (LN,2) expression in 26 surgically removed hypopharyngeal cancers and compared the results with conventional prognostic factors elicited from hematoxylin-eosin (H&E) stained whole-mount laryngeal sections. Study Design: Stainability of LN,2 was mainly evaluated at the invasive front of the cancer nests. Scoring was performed on the basis of a semiquantitative scale defined according to the number of immunopositive cancer cells (score 3, 2, 1, and 0). Stainability of LN,2 was also evaluated macroscopically at different tumor locations such as surface center, interstitial space, and invasive front. Status of cartilage and vascular invasion and patterns of tumor extension were evaluated from H&E stained sections. The results of LN,2 expression correlated with the tumor stages, neck node status, pathologic differentiation, and prognoses. Results: Among the 26 cases, 24 demonstrated positive LN,2 expression. Of these cases, 1, 14, 9, and 0 showed scores of 3, 2, 1, and 0, respectively. Positive expression of LN,2 at the invasive front was more prominent in the high-expression group, and surface center was often positive in the cases of low-expression group. Among the H&E stained prognostic factors, vascular invasion and infiltrative pattern demonstrated significant correlations with clinical outcome. Vascular invasion and infiltrative pattern were also closely related to positive LN,2 expression. Five-year survival rates of patients who showed high LN,2 expression were significantly poorer than in patients with low expression. Conclusion: Hypopharyngeal cancers positive for LN,2 indicate a considerable risk for cancer progression and are closely related to prognosis. Increased LN,2 expression might be a prognostic indicator for squamous cell carcinomas of the hypopharynx. [source] Increased Expression of Regulatory Tr1 Cells in Recurrent Hepatitis C after Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009A. Carpentier Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: ,Treg' and CD49b+CD18+ cells: ,T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management. [source] Increased Expression of Senescence-Associated Cell Cycle Inhibitor p16INK4a in Deteriorating Renal Transplants and Diseased Native KidneyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2005Anette Melk Some features of kidney transplants with dysfunction overlap the lesions of aging, such as tubular atrophy and interstitial fibrosis (TA/IF) without major glomerular abnormalities. Somatic cell limitations could contribute to deterioration in aging and disease states. Since expression of p16INK4a, a cell cycle inhibitor associated with somatic cell senescence in vitro, is induced in aged kidney, we studied whether kidneys with dysfunction and TA/IF manifested increased p16INK4a expression. We performed p16INK4a immunostaining on transplanted kidneys and native kidneys with chronic renal diseases. At implantation, transplants manifested little TA/IF, and nuclear p16INK4a immunostaining was consistent with age. However, transplants biopsied for abnormal function displaying TA/IF showed strong nuclear and cytoplasmic p16INK4a staining, beyond the amount predicted for age. Both atrophic and non-atrophic nephrons displayed increased p16INK4a, suggesting that it was not simply a feature of atrophy. Epithelial p16INK4a staining was not increased in transplants with good function, but was increased in diseased native kidneys. The finding of increased p16INK4a expression in renal transplants and diseased kidneys with TA/IF and impaired function supports the concept that some cell senescence changes that accompany aging are also induced by injury and disease stresses. Thus, aging, injury and disease may share common pathways involving somatic cell senescence. [source] Increased Expression of Cyclin D1, Cyclin E and p21Cip1 Associated with Decreased Expression of p27Kip1 in Chemically Induced Rat Mammary CarcinogenesisCANCER SCIENCE, Issue 12 2000Tae Jung Jang We induced rat mammary tumors in 7-week-old female Sprague-Dawley rats by intragastric administration of 7,12-dimethylbenz(a)anthracene (DMBA), and analyzed by immunohistochemistry the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 in carcinomas, atypical tumors, and benign tumors as well as normal mammary glands from the control group. Proliferation status was assessed by immunohistochemistry using bromodeoxyuridine (BrdU). A sequential increase in cyclin D1-, cyclin E-, and p21Cip1 -positive epithelial cells was observed from normal mammary glands, to atypical tumors, to carcinomas. In contrast, carcinomas showed a significantly lower number of epithelial cells immunoreactive to p27Kip1 when compared with atypical tumors, benign tumors and normal mammary glands. The immunoreactivities of BrdU, cyclin D1, cyclin E, and p21Cip1 were positively correlated, whereas that of p27Kip1 appeared inversely correlated to those of the others. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analysis were also performed to determine the mRNA and protein levels of cyclins and cyclin-dependent kinase inhibitors in tumors and normal mammary glands. The protein levels for cyclin D1, cyclin E and p21Cip1 in carcinomas and atypical tumors were significantly higher than those in benign tumors, while normal mammary glands showed negligible expression. On RT-PCR, tumors showed higher mRNA levels of cyclin D1 and cyclin E than those of normal mammary glands. Our results suggest that rat mammary carcinogenesis involves increased expression of cyclin D1, cyclin E, and p21Cip1, associated with decreased expression of p27Kip1 [source] Increased Expression of p53 Protein Correlates With the Extent of Myocyte Damage in Cardiac Allograft RejectionCONGESTIVE HEART FAILURE, Issue 6 2008Bernadette K. McLaren MD Acute cardiac allograft rejection (ACAR) has been associated with a poor prognosis. The early diagnosis of ACAR necessitates the accurate detection of myocyte damage. Nuclear damage activates p53, a transcription factor that initiates apoptosis and repair. Endomyocardial biopsies (n=25) from 10 cardiac allograft recipients were stained for nuclear p53. The biopsies were divided into rejection groups based on the grading of ACAR: group 1, grade 0; group 2, grade Ia and Ib; group 3, grades II and III. While clinical indices did not correlate with myocyte damage, significantly more myocytes in group 3 stained for nuclear p53 (2.48±0.60/mm2) compared with group 1 (0.22±0.12/mm2) and group 2 (0.43±0.18/mm2). Increased expression of p53 in cardiac myocytes with grade II or grade III rejection provides an objective quantification as an aid in the diagnosis of ACAR. [source] Increased expression of VEGF following exercise training in patients with heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2001T. Gustafsson Background and aims During the last decades several angiogenic factors have been characterized but so far it is unknown whether local muscle exercise training increases the expression of these factors in patients with moderate heart failure. Expression of the major putative angiogenic factor vascular endothelial growth factor (VEGF) at the level of messneger RNA (mRNA) and/or protein was therefore studied before and after 8 weeks of training in patient with chronic heart failure. Methods VEGF mRNA and protein concentrations were determined in skeletal muscle biopsies before and after 8 weeks of one-legged knee extension training in patients with chronic heart failure (New York Heart Association II,III). Results Exercise training increased the citrate synthase activity and peripheral exercise capacity by 46% and 36%, respectively, in parallel with a two-fold increase in VEGF at both the mRNA (P = 0·03) and protein (P = 0·02) levels Conclusion The increase in VEGF gene expression in response to exercise training indicates VEGF to be one possible mediator in exercise-induced angiogenesis and may therefore regulate an important and early step in adaptation to increased muscle activity in patient with chronic heart failure. [source] Increased expression of microRNA-155 in Epstein-Barr virus transformed lymphoblastoid cell linesGENES, CHROMOSOMES AND CANCER, Issue 1 2006Jinmai Jiang First page of article [source] Increased expression of GluR2-flip in the hippocampus of the Wistar audiogenic rat strain after acute and kindled seizuresHIPPOCAMPUS, Issue 1 2010Daniel Leite Góes Gitaí Abstract The Wistar Audiogenic Rat (WAR) is an epileptic-prone strain developed by genetic selection from a Wistar progenitor based on the pattern of behavioral response to sound stimulation. Chronic acoustic stimulation protocols of WARs (audiogenic kindling) generate limbic epileptogenesis, confirmed by ictal semiology, amygdale, and hippocampal EEG, accompanied by hippocampal and amygdala cell loss, as well as neurogenesis in the dentate gyrus (DG). In an effort to identify genes involved in molecular mechanisms underlying epileptic process, we used suppression-subtractive hybridization to construct normalized cDNA library enriched for transcripts expressed in the hippocampus of WARs. The most represented gene among the 133 clones sequenced was the ionotropic glutamate receptor subunit II (GluR2), a member of the ,-amino-3-hydroxy-5-methyl-4-isoxazoleopropionic acid (AMPA) receptor. Although semiquantitative RT-PCR analysis shows that the hippocampal levels of the GluR2 subunits do not differ between naïve WARs and their Wistar counterparts, we observed that the expression of the transcript encoding the splice-variant GluR2-flip is increased in the hippocampus of WARs submitted to both acute and kindled audiogenic seizures. Moreover, using in situ hybridization, we verified upregulation of GluR2-flip mainly in the CA1 region, among the hippocampal subfields of audiogenic kindled WARs. Our findings on differential upregulation of GluR2-flip isoform in the hippocampus of WARs displaying audiogenic seizures is original and agree with and extend previous immunohistochemical for GluR2 data obtained in the Chinese P77PMC audiogenic rat strain, reinforcing the association of limbic AMPA alterations with epileptic seizures. © 2009 Wiley-Liss, Inc. [source] Increased expression of SDF-1/CXCR4 is associated with lymph node metastasis of invasive micropapillary carcinoma of the breastHISTOPATHOLOGY, Issue 6 2009Fangfang Liu Aims:, Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are implicated in tumour chemotaxis and metastasis. The aim was to examine their roles in the metastasis of invasive micropapillary carcinoma (IMPC) of the breast, a tumour with a high propensity for nodal spread. Methods and results:, We compared the expression of SDF-1 and CXCR4 in 103 cases of breast cancer containing IMPC components with a control group of 96 cases of invasive ductal carcinoma (IDC), not otherwise specified type by immunohistochemistry and chemical in situ hybridization (CISH). The results showed that the predominant cytoplasmic expression of both SDF-1 and CXCR4 was greater in tumour cells of the IMPC components than in those of the non-IMPC components and the control IDC cases, and was correlated significantly with the number of positive lymph nodes (P < 0.05). SDF-1 expression on cell membranes was less frequently identified in IMPC than IDC (P = 0.021). Immunohistochemical detection of SDF-1 in endothelial cells of lymphatic vessels was more common in IMPC (P = 0.007) and correlated significantly with lymph node status (P = 0.002), although SDF-1 mRNA was rarely detected by CISH. Conclusions:, This study suggests that up-regulation of cytoplasmic expression of SDF-1/CXCR4 might be one of the molecular mechanisms facilitating lymph node metastasis of IMPC. [source] Increased expression of mRNA encoding interleukin (IL)-4 and its splice variant IL-4,2 in cells from contacts of Mycobacterium tuberculosis, in the absence of in vitro stimulationIMMUNOLOGY, Issue 4 2004Helen A. Fletcher Summary Expression of interleukin (IL)-4 is increased in tuberculosis and thought to be detrimental. We show here that in healthy contacts there is increased expression of its naturally occurring antagonist, IL-4delta2 (IL-4,2). We identified contacts by showing that their peripheral blood mononuclear cells (PBMC) released interferon (IFN)-, in response to the Mycobacterium tuberculosis -specific antigen 6 kDa early secretory antigenic target (ESAT-6). Fresh unstimulated PBMC from these contacts contained higher levels of mRNA encoding IL-4,2 (P=0·002) than did cells from ESAT-6 negative donors (noncontacts). These data indicate that contact with M. tuberculosis induces unusual, previously unrecognized, immunological events. We tentatively hypothesize that progression to active disease might depend upon the underlying ratio of IL-4 to IL-4,2. [source] Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 11 2009Martin A. Storr MD Abstract Background: Activation of cannabinoid (CB)1 receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB2 receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB2 receptor-deficient (CB mice. Methods: Mice were treated with TNBS to induce colitis and then given intraperitoneal injections of the CB2 receptor agonists JWH133, AM1241, or the CB2 receptor antagonist AM630. Additionally, CB mice were treated with TNBS and injected with JWH133 or AM1241. Animals were examined 3 days after the induction of colitis. The colons were removed for macroscopic and microscopic evaluation, as well as the determination of myeloperoxidase activity. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for CB2 receptor was also performed in animals with TNBS and dextran sodium sulfate colitis. Results: Intracolonic installation of TNBS caused severe colitis. CB2 mRNA expression was significantly increased during the course of experimental colitis. Three-day treatment with JWH133 or AM1241 significantly reduced colitis; AM630 exacerbated colitis. The effect of JWH133 was abolished when animals were pretreated with AM630. Neither JWH133 nor AM1241 had effects in CB mice. Conclusions: We show that activation of the CB2 receptor protects against experimental colitis in mice. Increased expression of CB2 receptor mRNA and aggravation of colitis by AM630 suggests a role for this receptor in normally limiting the development of colitis. These results support the idea that the CB2 receptor may be a possible novel therapeutic target in inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] Increased expression of the heterogeneous nuclear ribonucleoprotein K in pancreatic cancer and its association with the mutant p53INTERNATIONAL JOURNAL OF CANCER, Issue 2 2010Renyuan Zhou Abstract The heterogeneous nuclear ribonucleoprotein (hnRNP) K is an essential RNA and DNA binding protein involved in gene expression and signal transduction including DNA transcription, RNA splicing, RNA stability and translation. The role of hnRNP K in cancer is relatively understudied. However, several cellular functions strongly indicate that hnRNP K is involved in tumorigenesis. In this study, we investigated the altered protein expression and the subcellular distribution of the hnRNP K protein using tissue microarrays in pancreatic cancer. We showed an increased cytoplasmic hnRNP K in pancreatic cancer. This increase in hnRNP K protein occurs at the posttranscriptional level. We postulate that the cytoplasmic accumulation of hnRNP K will lead to silenced mRNA translation of tumor suppressor genes and thus contributes to pancreatic cancer development. We also demonstrated that knocking down of hnRNP K expression by siRNA inhibited pancreatic cancer cell growth and colony formation. hnRNP K was identified as a member of the p53/HDM2 pathway. Whether hnRNP K interacts with the mutant p53 is not known. Using two different pancreatic cancer cell lines, we can demonstrate that hnRNP K interacts with the mutant p53. The subcellular distribution and function of the mutant p53 and the interaction of hnRNP K/mutant p53 were affected by the Ras/MEK/ERK pathway, growth factors and the specific p53 mutations in pancreatic cancer cells. Since Kras is activated and p53 is mutated in most pancreatic cancers, these data unveiled an important new signaling pathway that linked by hnRNP K and mutant p53 in pancreatic cancer tumorigenesis. [source] Increased expression of fatty acid synthase in human aberrant crypt foci: Possible target for colorectal cancer preventionINTERNATIONAL JOURNAL OF CANCER, Issue 1 2009Kathleen E. Kearney Abstract Aberrant crypt foci (ACF), the earliest identified monoclonal lesions in the colon, provide insights into changes that promote and/or accompany the transformation of normal colonic epithelial cells to colorectal cancer. Fatty acid synthase (FAS), the primary enzyme involved in de novo lipogenesis from carbohydrates, is expressed at low levels in most normal human tissues but is elevated in several human neoplasms including colorectal adenomas and carcinomas. To determine if this pathway is altered even earlier in colorectal tumorigenesis, 35 human ACF from 21 patients were evaluated for the immunohistochemical expression of FAS. Sections of colon cancer served as positive controls, and normal colonic mucosa distant from cancer or ACF served as negative controls. FAS expression was increased in 30 (86%) ACF compared with that in adjacent normal colonic mucosa. The expression of FAS in ACF was not related to the degree of dysplasia or to the number of crypts in the ACF. The over expression of FAS in a high proportion of ACF suggests that this enzyme plays an important role very early in colorectal tumorigenesis and may be a target for chemoprevention. © 2009 UICC [source] Increased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor in breast cancer cells alters tumorigenic properties in vitro and in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 4 2003Jason S. Lee Abstract The mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF-IIR) is thought to act as a suppressor of tumor growth by binding the mitogenic peptide IGF-II and modulating its extracellular levels via degradation. This receptor has been found to be absent or nonfunctional in a high proportion of breast tumors as a result of LOH and mutation of the gene. In our study, we have examined the effect of increasing expression of M6P/IGF-IIR on breast cancer cell tumorigenicity. MDA-MB-231 breast cancer cells stably transfected with M6P/IGF-IIR cDNA exhibited not only a greatly reduced ability to form tumors but also a markedly reduced growth rate in nude mice. In vitro, increased M6P/IGF-IIR expression resulted in 2-fold reduced uptake of IGF-II and was associated with reduced cellular invasiness and motility. Cells with increased M6P/IGF-IIR expression exhibited reduced phosphorylation of IGF-I receptor and p44/42 MAPK compared to vector transfectants, or wild-type MDA-MB-231 cells. These results therefore suggest that M6P/IGF-IIR levels can modulate breast cancer cell tumorigenicity by a mechanism that may involve altered IGF-I receptor signaling. © 2003 Wiley-Liss, Inc. [source] Induction of Angiogenesis and Inhibition of Apoptosis by Hepatocyte Growth Factor Effectively Treats Postischemic Heart FailureJOURNAL OF CARDIAC SURGERY, Issue 1 2005Vasant Jayasankar M.D. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI. Methods: The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure,volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot. Results: Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 ± 3 vs. control 64 ± 5 mmHg, p < 0.05), maximum dP/dt (3024 ± 266 vs. 1907 ± 360 mmHg/sec, p < 0.05), maximum dV/dt (133 ± 20 vs. 84 ± 6 ,L/sec, p < 0.05), and LV border zone wall thickness (1.98 ± 0.06 vs. 1.53 ± 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 ± 10.0 vs. 90 ± 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 ± 0.3 vs. 8.2 ± 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group. Conclusions: Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure. [source] Increased expression of non-interleukin-2 T cell growth factors and their implications during liver allograft rejection in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2007Wei-Lin Wang Abstract Background and Aim:, Rejection remains a problem in the transplantation field. The aim of this study was to establish acute and chronic rejection models in rats and to investigate the roles of non-interleukin (IL)-2 T cell growth factors such as IL-15, IL-7 and IL-13 during rejection. Methods:, A liver transplant model was established using Dark Agouti and Brown Norway rats. The rats were divided into group A, left without treatment; group B, received cyclosporinee (1 mg/kg/day); and group C, cyclosporinee (4 mg/kg/day). Histopathological, reverse transcriptase-polymerase chain reaction and western blot were performed in liver specimens obtained from different time-points after transplantation in the three groups. Results:, In group A, the livers showed irreversible acute cellular rejection with cell infiltration. In group B, chronic liver rejection was found, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy and liver fibrosis. No apparent histological alterations were observed in group C. IL-15, IL-7 and IL-13 messenger RNA and their protein were all highly expressed in the liver specimens of groups A and B. Upregulated expression was found in IL-15 since the first day after transplantation and in IL-7 and IL-13 since day 6. The extent of IL-15 upregulation was more than that of IL-7 and IL-13. Conclusions:, Liver transplantation in Dark Agouti to Brown Norway rats with low-dose immunosuppression can induce chronic rejection. In the process of acute and chronic allograft rejections, non-IL-2 T cell growth factors such as IL-15, IL-7 and IL-13 play roles. Strategies should pay more attention to regulating these cytokines after liver transplantation. [source] Protective up-regulation of CK2 by mutant huntingtin in cells co-expressing NMDA receptorsJOURNAL OF NEUROCHEMISTRY, Issue 3 2008Mannie M. Y. Fan Abstract Huntington's disease is caused by a polyglutamine expansion in the huntingtin (htt) protein, and previous data indicate that over-activation of NMDA receptors (NMDARs) may be involved in the selective degeneration of cells expressing NR1/NR2B NMDARs. We used KinetworksÔ multi-immunoblotting screens to examine expression of 76 protein kinases, 18 protein phosphatases, 25 heat shock/stress proteins, and 27 apoptosis proteins in human embryonic kidney 293 cells transfected with NR1/NR2B and htt containing 15 (htt-15Q; wild-type) or 138 (htt-138Q; mutant) glutamine repeats. Follow-up experiments revealed several proteins involved in the heat-shock response pathway to be up-regulated in the soluble fraction from cells expressing htt-138Q, including protein phosphatase 5 and cyclin-dependent kinase 5. Increased expression in the soluble fraction of htt-138Q-expressing cells was also noted for the stress- and calcium-activated protein-serine/threonine kinase casein kinase 2, a change which was confirmed in striatal tissue of yeast artificial chromosome transgenic mice expressing full-length mutant htt. Inhibition of casein kinase 2 activity in cultured striatal neurons from these mice significantly exacerbated NMDAR-mediated toxicity, as assessed by labeling of apoptotic nuclei. Our findings are consistent with up-regulation of components of the stress response pathway in the presence of polyglutamine-expanded htt and NR1/NR2B which may reflect an attempt at the cellular level to ameliorate the detrimental effects of mutant htt expression. [source] Increased expression of glial cell line-derived neurotrophic factor protects against oxidative damage-induced retinal degenerationJOURNAL OF NEUROCHEMISTRY, Issue 3 2007Aling Dong Abstract Oxidative damage contributes to retinal cell death in patients with age-related macular degeneration or retinitis pigmentosa. One approach to treatment is to identify and eliminate the sources of oxidative damage. Another approach is to identify treatments that protect cells from multiple sources of oxidative damage. In this study, we investigated the effect of increased expression of glial cell line-derived neurotrophic factor (GDNF) in three models of oxidative damage-induced retinal degeneration. Double transgenic mice with doxycycline-inducible expression of GDNF in the retina were exposed to paraquat, FeSO4, or hyperoxia, all sources of oxidative damage and retinal cell death. Compared to controls, mice with increased expression of GDNF in the retina showed significant preservation of retinal function measured by electroretinograms, reduced thinning of retinal cell layers, and fewer TUNEL-positive cells indicating less retinal cell death. Mice over-expressing GDNF also showed less staining for acrolein, nitrotyrosine, and 8-hydroxydeoxyguanosine, indicating less oxidative damage to lipids, proteins, and DNA. This suggests that GDNF did not act solely to allow cells to tolerate higher levels of oxidative damage before initiation of apoptosis, but also reduced damage from oxidative stress to critical macromolecules. These data suggest that gene transfer of Gdnf should be considered as a component of therapy for retinal degenerations in which oxidative damage plays a role. [source] Advanced glycation endproducts and pro-inflammatory cytokines in transgenic Tg2576 mice with amyloid plaque pathologyJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Gerald Münch Abstract Increased expression and altered processing of the amyloid precursor protein (APP) and generation of ,-amyloid peptides is important in the pathogenesis of amyloid plaques in Alzheimer's disease (AD). Transgenic Tg2576 mice overexpressing the Swedish mutation of human APP exhibit ,-amyloid deposition in the neocortex and limbic areas, accompanied by gliosis and dystrophic neurites. However, murine plaques appear to be less cross-linked and the mice show a lower degree of inflammation and neurodegeneration than AD patients. ,Advanced glycation endproducts (AGEs)', formed by reaction of proteins with reactive sugars or dicarbonyl compounds, are able to cross-link proteins and to activate glial cells, and are thus contributing to plaque stability and plaque-induced inflammation in AD. In this study, we analyze the tissue distribution of AGEs and the pro-inflammatory cytokines IL-1, and TNF-, in 24-month-old Tg2576 mice, and compare the AGE distribution in these mice with a younger age group (13 months old) and a typical Alzheimer's disease patient. Around 70% of the amyloid plaque cores in the 24-month-old mice are devoid of AGEs, which might explain their solubility in physiological buffers. Plaque associated glia, which express IL-1, and TNF-,, contain a significant amount of AGEs, suggesting that plaques, i.e. A, as its major component, can induce intracellular AGE formation and the expression of the cytokines on its own. In the 13-month-old transgenic mice, AGEs staining can neither be detected in plaques nor in glial cells. In contrast, AGEs are present in high amounts in both plaques and glia in the human AD patient. The data obtained in this show interesting differences between the transgenic mouse model and AD patients, which should be considered using the transgenic approach to test therapeutical strategies to eliminate plaques or to attenuate the inflammatory response in AD. [source] Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cellsJOURNAL OF NEUROCHEMISTRY, Issue 6 2002Parmjeet K. Parmar Abstract Neuroserpin is a serine protease inhibitor widely expressed in the developing and adult nervous systems and implicated in the regulation of proteases involved in processes such as synaptic plasticity, neuronal migration and axogenesis. We have analysed the effect of neuroserpin on growth factor-induced neurite outgrowth in PC12 cells. We show that small changes in neuroserpin expression result in changes to the number of cells extending neurites and total neurite length following NGF treatment. Increased expression of neuroserpin resulted in a decrease in the number of cells extending neurites and a reduction in total free neurite length whereas reduced levels of neuroserpin led to a small increase in the number of neurite extending cells and a significant increase in total free neurite length compared to the parent cell line. Neuroserpin also altered the response of PC12 cells to bFGF and EGF treatment. Neuroserpin was localised to dense cored secretory vesicles in PC12 cells but was unable to complex with its likely enzyme target, tissue plasminogen activator at the acidic pH found in these vesicles. These data suggest that modulation of neuroserpin levels at the extending neurite growth cone may play an important role in regulating axonal growth. [source] Increased survivin expression in high-grade oral squamous cell carcinoma: a study in Indian tobacco chewersJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 10 2006C. Jane Background:, Oral cancer is one of the five leading sites of cancer in the Indian population. In the present study we analyzed the expression of apoptosis regulating genes, viz. survivin, Bcl-2, Bax and p53 in precancerous and cancerous lesions of the buccal mucosa of Indian tobacco chewers. Method:, Paraffin-embedded tissue samples from 38 patients with primary oral squamous cell carcinoma (OSCC) and 17 patients with leukoplakia were used. The expression of survivin, Bcl-2, Bax, and p53 was evaluated using immunohistochemical staining method. Results:, Thirty-six percent OSCC were found to be positive for nuclear p53 staining while none of the precancerous lesions showed p53 positivity. Survivin, Bcl-2 and Bax expression was found to increase with increased grade of malignancy. Increase in survivin expression was statistically most significant (P < 0.001). Conclusion:, Increased expression of anti-apoptotic survivin in high-grade tumors suggests that survivin is likely to contribute significantly to apoptosis resistance in response to therapy. [source] Expression of matrix metalloproteinase-9 in predicting prognosis of hepatocellular carcinoma after liver transplantationLIVER TRANSPLANTATION, Issue 5 2010Deniz Nart Matrix metalloproteinases (MMPs) are known to play an important role in cell migration during cancer invasion by degrading extracellular matrix proteins. This study aimed to determine the role of MMP-9 in hepatocellular carcinoma (HCC) carcinogenesis. Eighty-nine cases who underwent liver transplantation for HCC in cirrhotic liver were selected for this study. The tumor characteristics such as nodule number, maximal diameter, portal vein invasion, and the preoperative alpha-fetoprotein levels were reviewed. The intensity of immunostaining and the percentage of immunoreactive cells with MMP-9 were evaluated. All patients were evaluated for HCC recurrence and/or death, and cause of death was noted. There was a lower survival and more recurrence risk among participants with 4 or more nodules exceeding 3 cm in diameter, with poorly differentiated tumor, and with large-vessel involvement. Eleven patients developed recurrent HCC (12.4%). Twelve patients died as a result of HCC (13.5%). Among 89 HCCs, the incidences of a weak (+) and moderate (++) expression of MMP-9 in carcinoma cells were 30.3% (23/89) and 43.8% (39/89), respectively. Increased expression and intensity of MMP-9 were found to be inversely associated with poor tumor differentiation (P = 0.016, P = 0.009, respectively). A significant correlation between expression and intensity of MMP-9 and large vascular invasion (P = 0.01, and P = 0.03) was also observed. As far as prognosis is concerned, increased immunoreactivity and intensity of MMP-9 were found to exert an unfavorable impact on overall survival rates (P < 0.01, P = 0.01, respectively) and recurrences (P = 0.001, P = 0.02). Multivariate analyses revealed that MMP-9 staining percentage (P = 0.007) and portal vein invasion (P = 0.002) were independent predictors of survival, whereas the only independent predictor of recurrences was portal vein invasion (P = 0.007). In this study, our results indicate a positive association between MMP-9 expression and histopathologic parameters that indicate poor prognosis. We conclude that together, MMP-9 staining percentage and portal vein invasion in HCC may aid to predict poor outcome. Nevertheless MMP-9 staining percentage is expected to be a potential predictive marker on survival and needs to be studied more in detail. Liver Transpl 16:621-630, 2010. © 2010 AASLD. [source] Increased expression of aquaporin 3 in atopic eczemaALLERGY, Issue 9 2006M. Olsson Background:, Dry skin in atopic eczema depends on increased water loss. The mechanisms behind this are poorly understood. The aim of this work was to identify genes that may contribute to water loss in eczema. Methods:, Affymetrix DNA microarrays U133A were used to analyse gene expression in skin biopsies from 10 patients with atopic eczema and 10 healthy controls. Results:, DNA microarray analysis showed up-regulation of 262 genes and down-regulation of 129 genes in atopic eczema. The known functions of these genes were analysed using Gene Ontology to identify genes that could contribute to increased water loss. This led to identification of aquaporin 3 (AQP3), which has a key role in hydrating healthy epidermis. Increased expression of AQP3 was found in eczema compared with healthy skin. This was confirmed with real-time polymerase chain reaction (P < 0.001). In healthy skin, epidermal AQP3 immunoreactivity was weak and mainly found in the stratum basale. A gradient was formed with decreasing AQP3 staining in the lower layers of the stratum spinosum. By contrast, in acute and chronic atopic eczema strong AQP3 staining was found in both the stratum basale and the stratum spinosum. Conclusions:, Aquaporin 3 is the predominant aquaporin in human skin. Increased expression and altered cellular distribution of AQP3 is found in eczema and this may contribute to water loss. [source] OmpC and the ,E regulatory pathway are involved in adhesion and invasion of the Crohn's disease-associated Escherichia coli strain LF82MOLECULAR MICROBIOLOGY, Issue 6 2007Nathalie Rolhion Summary Ileal lesions of 36.4% of patients with Crohn's disease (CD), an inflammatory bowel disease in humans, are colonized by pathogenic adherent-invasive Escherichia coli (AIEC), and high levels of antibodies directed against E. coli OmpC are present in 37,55% of CD patients. We therefore investigated the expression of OmpC and its role in the interaction of CD-associated adherent-invasive E. coli strain LF82 with intestinal epithelial cells. High osmolarity induced a significant increase in the ability of LF82 bacteria to interact with Intestine-407 cells, which correlates with increased OmpC expression. Deletion of ompC gene markedly decreased the adhesion and invasion levels of the corresponding mutant. A LF82-,ompR mutant impaired in OmpC and OmpF expression, showed decreased adhesion and invasion, and unlike a K-12-negative OmpR mutant did not express flagella and type 1 pili. Interestingly, the wild-type phenotype was restored when OmpC or OmpF expression was induced in the LF82-,ompR mutant. Overexpression of RpoE in the LF82-,ompR isogenic mutant restored a full wild-type phenotype without restoring OmpC expression. Increased expression of RpoE was observed in wild-type strain LF82 at high osmolarity. Hence, the role of OmpC in the AIEC LF82 adhesion and invasion is indirect and involves the ,E regulatory pathway. [source] Abnormalities of IgA1 production in IgA nephropathyNEPHROLOGY, Issue 2002John FEEHALLY SUMMARY: IgA nephropathy (IgAN) is characterized by the mesangial deposition of polymeric IgA1 (plgA1). the original view that this plgA1 is derived from the mucosal immune system can no longer be sustained. Studies of duodenal mucosa and marrow indicate increased production of plgA1 in the marrow and decreased production in the mucosa. These changes are consistent with immunization studies showing exaggerated and prolonged plgA responses to systemic immunization, and reduced mucosal responses to mucosal neoantigens. However, the IgA1 and IgG systemic responses to mucosal antigen are increased in IgAN, a finding consistent with impairment in oral tolerance, the process by which systemic immune responses, to mucosal antigen challenge are normally suppressed. Both IgA1 production and the induction of oral tolerance are under T-cell control. T-cell populations involved in these processes include ,, T cells, Tr cells and T-helper (Th)3 cells; cytokines with a key role in the control of IgA production include interleukin (IL)-10 and transforming growth factor (TGF)-,. There is evidence of abnormal ,, T-cell V region usage in both mucosa and marrow in IgAN. Increased expression of relevant cytokines has also been reported in circulating T cells in IgAN. the increased O-glycosylation of circulating IgA1 in IgAN may also be further evidence of a shift in the production of mucosal-type plgA1 from the mucosa to marrow. These findings suggest that the specific lymphocyte homing mechanisms that normally maintain oral tolerance and control the site of IgA production require further study in IgAN. [source] Role of heat shock protein 47 on tubulointerstitium in experimental radiation nephropathyPATHOLOGY INTERNATIONAL, Issue 5-6 2002Diange Liu The molecular mechanisms of fibrosis in radiation nephropathy have received scant attention. Heat shock protein 47 (HSP47), a collagen-binding stress protein, helps in the intracellular processing of procollagen molecules during collagen synthesis. We investigated the role of HSP47 in the progression of radiation nephropathy using experimental radiation nephropathy. Experimental rat groups were as follows: (i) group I, sham operated (n = 12); (ii) group II, single doses of irradiation, either 7, 15 or 25 Gy to left kidney (n = 60); and (iii) group III, a similar irradiation procedure as group II after right nephrectomy (n = 60). The rats were followed up until 9 months after renal exposure to radiation. Renal dysfunction (as determined by serum creatinine and blood urea nitrogen) and hypertension were noted in group III rats, along with inflammatory cell infiltration and interstitial fibrosis (as determined by increased deposition of collagens). Compared to control rat kidneys, an increased expression of HSP47 was noted in kidneys obtained from irradiated rats. By double immunostaining, HSP47-expressing cells were identified as ,-smooth muscle actin-positive myofibroblasts and vimentin-positive tubular epithelial cells. Increased expression of HSP47 was closely associated with increased deposition of collagens in the widened interstitium of irradiated rats. Overexpression of HSP47 by phenotypically altered tubulointerstitial cells might play a role in excessive assembly/synthesis of collagens and could contribute to tubulointerstitial fibrosis in radiation nephropathy. [source] Increased expression of cyclooxygenase-2 in human salivary gland tumorsPATHOLOGY INTERNATIONAL, Issue 10 2001Kazunari Sakurai We examined the immunohistochemical localization of cyclooxygenase (COX)-2 in human salivary gland tumors. Thirty salivary gland adenomas (SGA), 40 salivary gland carcinomas (SGC) and 15 normal salivary glands (NSG) were studied. NSG showed restricted COX-2 staining only in the epithelial cells of salivary ducts. In contrast, COX-2 protein was detected in 27 cases of SGA (90%), except for three myoepitheliomas, and in all cases of SGC (100%) at various intensities and in various fashions. Thirteen SGA (43%) and 36 SGC (90%) cases showed strong COX-2 staining predominantly in tumor cells containing ductal components, as did serous and mucous acinic components of acinic cell carcinomas, mucoepidermoid carcinomas and mucinous carcinomas. These findings may suggest that COX-2 in salivary gland tumors is expressed in tumor cells derived from pluripotential ductal epithelium that can histologically develop into either serous or mucinous acinar cells. [source] | |||||||||||||||||||||||||||||||||||||||||||