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61.
Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training 总被引:11,自引:0,他引:11
Sriwijitkamol A Christ-Roberts C Berria R Eagan P Pratipanawatr T DeFronzo RA Mandarino LJ Musi N 《Diabetes》2006,55(3):760-767
Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training. 相似文献
62.
Summary Vero cells grown in Leighton tubes were infected with blood taken from Argentine Hemorrhagic Fever patients. In 11 out of 12 cases, and between the 2nd–8th days p.i. of the monolayers, Junin viral antigen was detected by the PAP method.With 1 Figure 相似文献
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Peppoloni S Colombari B Neglia R Quaglino D Iannelli F Oggioni MR Pozzi G Blasi E 《Medical microbiology and immunology》2006,195(1):21-28
Microglial cells, the resident phagocytes in the brain, share many phenotypical and functional characteristics with peripheral macrophages, suggesting that they may participate in an innate immune response against microorganisms invading the central nervous system (CNS). In this study, we demonstrate that the microglial cells constitutively exhibit antibacterial activity in vitro against Streptococcus pneumoniae. By using a Pneumococcal surface protein C (PspC)-deleted strain and its wild-type counterpart, we found that the extent of such an activity is significantly influenced by the presence of a PspC molecule on the bacterial surface. The PspC– mutant FP20 is indeed more susceptible than the PspC+ strain HB565 to microglial killing. Interestingly, this phenomenon is observed when using a medium supplemented with heat-inactivated foetal bovine serum (FBS). Electron microscopy studies indicate that the microglial cells interact more efficiently with PspC– than with PspC+ pneumococci. Moreover, upon infection with the PspC– mutant, microglial cells produce levels of TNF-, MIP-2, IL-10 and nitric oxide, significantly higher than those observed with PspC+ bacteria. These findings indicate that the lack of PspC significantly enhances the susceptibility of S. pneumoniae to both bactericidal activity and secretory response by the microglial cells, suggesting that this molecule may play an important role in the invasion of CNS by pneumococcus. 相似文献
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Elena Ardini Roberta Bosotti Andrea Lombardi Borgia Cristina De Ponti Alessio Somaschini Rosaria Cammarota Nadia Amboldi Laura Raddrizzani Andrea Milani Paola Magnaghi Dario Ballinari Daniele Casero Fabio Gasparri Patrizia Banfi Nilla Avanzi Maria B. Saccardo Rachele Alzani Tiziano Bandiera Eduard Felder Daniele Donati Enrico Pesenti Andrea Sartore-Bianchi Marcello Gambacorta Marco A. Pierotti Salvatore Siena Silvio Veronese Arturo Galvani Antonella Isacchi 《Molecular oncology》2014,8(8):1495-1507
67.
Giovanna Ferrari-Amorotti Claudia Chiodoni Fei Shen Sara Cattelani Angela Rachele Soliera Gloria Manzotti Giulia Grisendi Massimo Dominici Francesco Rivasi Mario Paolo Colombo Alessandro Fatatis Bruno Calabretta 《Neoplasia (New York, N.Y.)》2014,16(12):1047-1058
Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates with a propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs and is associated with reduced E-cadherin expression and aggressive disease. The effects of Slug depend, in part, on the interaction of its N-terminal SNAG repressor domain with the chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor of LSD1 that blocks its interaction with Slug, suppresses the migration, invasion, and metastatic spread of TNBC cell lines. We show here that PCPA treatment induces the expression of E-cadherin and other epithelial markers and markedly suppresses migration and invasion of TNBC cell lines MDA-MB-231 and BT-549. These effects were phenocopied by Slug or LSD1 silencing. In two models of orthotopic breast cancer, PCPA treatment reduced local tumor growth and the number of lung metastases. In mice injected directly in the blood circulation with MDA-MB-231 cells, PCPA treatment or Slug silencing markedly inhibited bone metastases but had no effect on lung infiltration. Thus, blocking Slug activity may suppress the metastatic spread of TNBC and, perhaps, specifically inhibit homing/colonization to the bone. 相似文献
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Guglieri M Magri F D'Angelo MG Prelle A Morandi L Rodolico C Cagliani R Mora M Fortunato F Bordoni A Del Bo R Ghezzi S Pagliarani S Lucchiari S Salani S Zecca C Lamperti C Ronchi D Aguennouz M Ciscato P Di Blasi C Ruggieri A Moroni I Turconi A Toscano A Moggio M Bresolin N Comi GP 《Human mutation》2008,29(2):258-266
Limb girdle muscular dystrophies (LGMD) are characterized by genetic and clinical heterogeneity: seven autosomal dominant and 12 autosomal recessive loci have so far been identified. Aims of this study were to evaluate the relative proportion of the different types of LGMD in 181 predominantly Italian LGMD patients (representing 155 independent families), to describe the clinical pattern of the different forms, and to identify possible correlations between genotype, phenotype, and protein expression levels, as prognostic factors. Based on protein data, the majority of probands (n=72) presented calpain-3 deficiency; other defects were as follows: dysferlin (n=31), sarcoglycans (n=32), alpha-dystroglycan (n=4), and caveolin-3 (n=2). Genetic analysis identified 111 different mutations, including 47 novel ones. LGMD relative frequency was as follows: LGMD1C (caveolin-3) 1.3%; LGMD2A (calpain-3) 28.4%; LGMD2B (dysferlin) 18.7%; LGMD2C (gamma-sarcoglycan) 4.5%; LGMD2D (alpha-sarcoglycan) 8.4%; LGMD2E (beta-sarcoglycan) 4.5%; LGMD2F (delta-sarcoglycan) 0.7%; LGMD2I (Fukutin-related protein) 6.4%; and undetermined 27.1%. Compared to Northern European populations, Italian patients are less likely to be affected with LGMD2I. The order of decreasing clinical severity was: sarcoglycanopathy, calpainopathy, dysferlinopathy, and caveolinopathy. LGMD2I patients showed both infantile noncongenital and mild late-onset presentations. Age at disease onset correlated with variability of genotype and protein levels in LGMD2B. Truncating mutations determined earlier onset than missense substitutions (20+/-5.1 years vs. 36.7+/-11.1 years; P=0.0037). Similarly, dysferlin absence was associated with an earlier onset when compared to partial deficiency (20.2+/-standard deviation [SD] 5.2 years vs. 28.4+/-SD 11.2 years; P=0.014). 相似文献
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Cloning and comparative mapping of recently evolved human chromosome 22-specific alpha satellite DNA
Rocchi Mariano Archidiacono Nicoletta Antonacci Rachele Finelli Palma D'Aiuto Leonardo Carbone Roberta Lindsay Elizabeth Baldini Antonio 《Somatic Cell and Molecular Genetics》1994,20(5):443-448
We have isolated and characterized a new alphoid probe, named p190.22. Its chromosomal location was investigated using fluorescence in situ hybridization. Under high stringency conditions p190.22 recognizes specifically the centromere of chromosome 22. A chromosome 22-specific alphoid subset has been previously reported in the literature (p22/12.1). The partial sequence and the genomic organization comparison strongly suggests that they recognize distinct subsets both specific for chromosome 22. The comparative mapping of probes p190.22 and p22/12.1 on chimpanzee (PTR and PPA) and gorilla (GGO) chromosomes was investigated. The two probes showed different hybridization results. p190.22, in particular, did not show any hybridization signal in these three species, suggesting a recent evolution. 相似文献