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81.
Ana Paula F Trombone Celio L Silva Luciana P Almeida Rogerio S Rosada Karla M Lima Constance Oliver Maria C Jamur Arlete AM Coelho-Castelo 《Genetic vaccines and therapy》2007,5(1):1-8
Background
Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of the mucopolysaccharidoses. The disease is caused by a deficiency of the lysosomal enzyme sulphamidase and results in the storage of the glycosaminoglycan (GAG), heparan sulphate. MPS IIIA is characterised by widespread storage and urinary excretion of heparan sulphate, and a progressive and eventually profound neurological course. Gene therapy is one of the few avenues of treatment that hold promise of a sustainable treatment for this disorder.Methods
The murine sulphamidase gene cDNA was cloned into a lentiviral vector and high-titre virus produced. Human MPS IIIA fibroblast cultures were transduced with the sulphamidase vector and analysed using molecular, enzymatic and metabolic assays. High-titre virus was intravenously injected into six 5-week old MPS IIIA mice. Three of these mice were pre-treated with hyperosmotic mannitol. The weight of animals was monitored and GAG content in urine samples was analysed by polyacrylamide gel electrophoresis.Results
Transduction of cultured MPS IIIA fibroblasts with the sulphamidase gene corrected both the enzymatic and metabolic defects. Sulphamidase secreted by gene-corrected cells was able to cross correct untransduced MPS IIIA cells. Urinary GAG was found to be greatly reduced in samples from mice receiving the vector compared to untreated MPS IIIA controls. In addition, the weight of treated mice became progressively normalised over the 6-months post-treatment.Conclusion
Lentiviral vectors appear promising vehicles for the development of gene therapy for MPS IIIA. 相似文献82.
Cliona delitrix is a very destructive coral-excavating sponge in Caribbean coral reef systems, particularly for Montastraea species. Little is known about how these excavating sponges propagate across coral reefs. In this study a hypothesis was tested that coral breakage caused by the bioeroding activity facilitates the asexual propagation of this sponge and in turn favors the spread of the most aggressive sponge genotypes. An allozyme analysis, involving 12 loci systems of 52 sponge individuals from a total of 13 Montastraea heads, found that no two sponges possessed identical multi-locus genotypes. Contrary to the pattern expected for fragmenting species, the incidence of clonality and asexual propagation at the population level was minimal. The lack of correlation between genetic and physical distances for the studied sponges also suggests that population maintenance appears to derive from larval dispersal, with a spatial range of dispersal larger than the average distance between the coral heads (10–102 m). 相似文献
83.
84.
Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides 总被引:2,自引:0,他引:2
Background
The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.Results
EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.Conclusion
DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress. 相似文献85.
Yongping Gao Christopher M. Gillen Michele G. Wheatly 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2009,152(3):216-225
Calmodulin (CaM) is a highly conserved calcium (Ca2+) binding protein that transduces Ca2+ signals into downstream effects influencing a range of cellular processes, including Ca2+ homeostasis. The present study explores CaM expression when Ca2+ homeostasis is challenged during the mineralization cycle of the freshwater crayfish (Procambarus clarkii). In this paper we report the cloning of a CaM gene from axial abdominal crayfish muscle (referred to as pcCaM). The pcCaM mRNA is ubiquitously expressed but is far more abundant in excitable tissue (muscle, nerve) than in any epithelia (gill, antennal gland, digestive) suggesting that it plays a greater role in the biology of excitation than in epithelial ion transport. In muscle cells the pcCaM was colocalized on the plasma membrane with the Ca2+ ATPase (PMCA) known to regulate intracellular Ca2+ through basolateral efflux. While PMCA exhibits a greater upregulation in epithelia (than in non-epithelial tissues) during molting stages requiring transcellular Ca2+ flux (pre- and postmolt compared with intermolt), expression of pcCaM exhibited a uniform increase in epithelial and non-epithelial tissues alike. The common increase in expression of CaM in all tissues during pre- and postmolt stages (compared with intermolt) suggests that the upregulation is systemically (hormonally) mediated. Colocalization of CaM with PMCA confirms physiological findings that their regulation is linked. 相似文献
86.
Corry-Anke Brandsma Machteld N Hylkema Marie Geerlings Wouter H van Geffen Dirkje S Postma Wim Timens Huib AM Kerstjens 《Respiratory research》2009,10(1):108
There is increasing evidence that a specific immune response contributes to the pathogenesis of COPD. B-cell follicles are present in lung tissue and increased anti-elastin titers have been found in plasma of COPD patients. Additionally, regulatory T cells (Tregs) have been implicated in its pathogenesis as they control immunological reactions. We hypothesize that the specific immune response in COPD is smoke induced, either by a direct effect of smoking or as a result of smoke-induced lung tissue destruction (i.e. formation of neo-epitopes or auto antigens). Furthermore, we propose that Tregs are involved in the suppression of this smoke-induced specific immune response.The presence of B cells, memory B cells and Tregs was assessed by flow cytometry in peripheral blood of 20 COPD patients and 29 healthy individuals and related to their current smoking status.COPD patients had lower (memory) B-cell percentages and higher Treg percentages in peripheral blood than healthy individuals, with a significant negative correlation between these cells. Interestingly, current smokers had higher percentages of (class-switched) memory B cells than ex-smokers and never smokers, irrespective of COPD.This increase in (class-switched) memory B cells in current smokers is intriguing and suggests that smoke-induced neo-antigens may be constantly induced in the lung. The negative correlation between B cells and Tregs in blood is in line with previously published observations that Tregs can suppress B cells. Future studies focusing on the presence of these (class switched) memory B cells in the lung, their antigen specificity and their interaction with Tregs are necessary to further elucidate the specific B-cell response in COPD. 相似文献
87.
Jiang X Gillen S Esposito I Giese NA Michalski CW Friess H Kleeff J 《Histology and histopathology》2010,25(12):1497-1506
Spectrins are members of the superfamily of F-actin cross linking proteins that are important as scaffolding proteins for protein sorting, cell adhesion, and migration. In addition, spectrins have been implicated in TGF-beta signaling. The aim of the present study was to analyze the expression and localization of beta1-spectrin (SPTBN1) in pancreatic tissues. mRNA levels of SPTBN1 in cultured pancreatic cancer cell lines, as well as in normal pancreatic tissues (n=18), chronic pancreatitis (n=48) and pancreatic cancer tissues (n=66) were analyzed by real time quantitative RT-PCR. Localization of SPTBN1 in pancreatic tissues was determined by immunohistochemistry. SPTBN1 staining was assessed semi-quantitatively in 55 cancer tissues and survival analysis was carried out using the Kaplan-Meier method. Median SPTBN1 mRNA levels were 6.0-fold higher in pancreatic cancer tissues compared to the normal pancreas (p<0.0001) and 2.2-fold higher compared to chronic pancreatitis tissues (p=0.0002). In the normal pancreas, SPTBN1 was present in the cytoplasm of normal ductal cells and occasionally in pancreatic acinar and centroacinar cells. In pancreatic cancer tissues, SPTBN1 was present in the cytoplasm of pancreatic cancer cells. Low SPTBN1 protein expression indicated a tendency for worsened prognosis with a median survival of 14.0 months, versus 23.8 months for patients whose tumors expressed moderate/high levels of SPTBN1. In conclusion, reduced SPTBN1 expression correlated with shorter survival of pancreatic cancer patients, suggesting a tumor suppressor function of this gene, as has already been shown for other malignancies of the gastrointestinal tract. 相似文献
88.
A Luquita L Urli MJ Svetaz AM Gennaro ME Giorgetti G Pistone R Volpintesta S Palatnik M Rasia 《Journal of biomedical science》2010,17(1):8
Background
Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology. 相似文献89.
Arianna Tavanti Lambert AM Hensgens Selene Mogavero László Majoros Sonia Senesi Mario Campa 《BMC microbiology》2010,10(1):203
Background
Candida parapsilosis is known to show limited genetic variability, despite different karyotypes and phenotypes have been described. To further investigate this aspect, a collection of 62 sensu strictu C. parapsilosis independent isolates from 4 geographic regions (Italy, n = 19; New Zealand, n = 15; Argentina, n = 14; and Hungary, n = 14) and different body sites (superficial and deep seated) were analysed for their genetic and phenotypic traits. Amplification fragment length polymorphism (AFLP) analysis was used to confirm species identification and to evaluate intraspecific genetic variability. Phenotypic characterisation included clinically relevant traits, such as drug susceptibility, in vitro biofilm formation and aspartyl protease secretion. 相似文献90.
Corry-Anke Brandsma Wim Timens Marie Geerlings Henrike Jekel Dirkje S Postma Machteld N Hylkema Huib AM Kerstjens 《BMC pulmonary medicine》2010,10(1):1-10