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101.
AM Fietta AM Bardoni R Salvini I Passadore M Morosini L Cavagna V Codullo E Pozzi F Meloni C Montecucco 《Arthritis research & therapy》2007,8(6):R160
Lung fibrosis is a major cause of mortality and morbidity in systemic sclerosis (SSc). However, its pathogenesis still needs
to be elucidated. We examined whether the alteration of certain proteins in bronchoalveolar lavage fluid (BALF) might have
a protective or a causative role in the lung fibrogenesis process. For this purpose we compared the BALF protein profile obtained
from nine SSc patients with lung fibrosis (SScFib+) with that obtained from six SSc patients without pulmonary fibrosis (SScFib-) by two-dimensional gel electrophoresis (2-DE). Only spots and spot-trains that were consistently expressed in a different
way in the two study groups were taken into consideration. In total, 47 spots and spot-trains, corresponding to 30 previously
identified proteins in human BALF, showed no significant variation between SScFib+ patients and SScFib- patients, whereas 24 spots showed a reproducible significant variation in the two study groups. These latter spots corresponded
to 11 proteins or protein fragments, including serum albumin fragments (13 spots), 5 previously recognized proteins (7 spots),
and 4 proteins (3 spots) that had not been previously described in human BALF maps, namely calumenin, cytohesin-2, cystatin
SN, and mitochondrial DNA topoisomerase 1 (mtDNA TOP1). Mass analysis did not determine one protein-spot. The two study groups
revealed a significant difference in BALF protein composition. Whereas levels of glutathione S-transferase P (GSTP), Cu–Zn
superoxide dismutase (SOD) and cystatin SN were downregulated in SScFib+ patients compared with SScFib- patients, we observed a significant upregulation of α1-acid glycoprotein, haptoglobin-α chain, calgranulin (Cal) B, cytohesin-2,
calumenin, and mtDNA TOP1 in SScFib+ patients. Some of these proteins (GSTP, Cu–Zn SOD, and cystatin SN) seem to be involved in mechanisms that protect lungs
against injury or inflammation, whereas others (Cal B, cytohesin-2, and calumenin) seem to be involved in mechanisms that
drive lung fibrogenesis. Even if the 2-DE analysis of BALF did not provide an exhaustive identification of all BALF proteins,
especially those of low molecular mass, it allows the identification of proteins that might have a role in lung fibrogenesis.
Further longitudinal studies on larger cohorts of patients will be necessary to assess their usefulness as predictive markers
of disease. 相似文献
102.
103.
The ability of Fusarium species isolated from bananas to produce mycotoxins was studied with 66 isolates of the following species: F. semitectum var. majus (8 isolates), F. camptoceras (3 isolates), a Fusarium sp. (3 isolates), F. moniliforme (16 isolates), F. proliferatum (9 isolates), F. subglutinans (3 isolates), F. solani (3 isolates), F. oxysporum (5 isolates), F. graminearum (7 isolates), F. dimerum (3 isolates), F. acuminatum (3 isolates), and F. equiseti (3 isolates). All isolates were cultured on autoclaved corn grains. Their toxicity to Artemia salina L. larvae was examined. Some of the toxic effects observed arose from the production of known mycotoxins that were determined by thin-layer chromatography, gas chromatography, or high-performance liquid chromatography. All F. camptoceras and Fusarium sp. isolates proved toxic to A. salina larvae; however, no specific toxic metabolites could be identified. This was also the case with eight isolates of F. moniliforme and three of F. proliferatum. The following mycotoxins were encountered in the corn culture extracts: fumonisin B(inf1) (40 to 2,900 (mu)g/g), fumonisin B(inf2) (150 to 320 (mu)g/g), moniliformin (10 to 1,670 (mu)g/g), zearalenone (5 to 470 (mu)g/g), (alpha)-zearalenol (5 to 10 (mu)g/g), deoxynivalenol (8 to 35 (mu)g/g), 3-acetyldeoxynivalenol (5 to 10 (mu)g/g), neosolaniol (50 to 180 (mu)g/g), and T-2 tetraol (5 to 15 (mu)g/g). Based on the results, additional compounds produced by the fungal isolates may play prominent roles in the toxic effects on larvae observed. This is the first reported study on the mycotoxin-producing abilities of Fusarium species that contaminate bananas. 相似文献
104.
Background
Metabolically versatile soil bacteria Burkholderia cepacia complex (Bcc) have emerged as opportunistic pathogens, especially of cystic fibrosis (CF). Previously, we initiated the characterization of the phenylacetic acid (PA) degradation pathway in B. cenocepacia, a member of the Bcc, and demonstrated the necessity of a functional PA catabolic pathway for full virulence in Caenorhabditis elegans. In this study, we aimed to characterize regulatory elements and nutritional requirements that control the PA catabolic genes in B. cenocepacia K56-2. 相似文献105.
Meilyn Rodríguez Lincidio Pérez Jorge V. Gavilondo Greta Garrido Mónica Bequet‐Romero Ignacio Hernández Vivian Huerta Gleysin Cabrera Marlene Pérez Osmani Ramos René Leyva Mariela León Pedro Luis Ramos Ada Triguero Abel Hernández Belinda Sánchez Marta Ayala Jeny Soto Ernesto González Osmani Mendoza Kenia Tiel Merardo Pujol 《Plant biotechnology journal》2013,11(1):53-65
A broad variety of foreign genes can be expressed in transgenic plants, which offer the opportunity for large‐scale production of pharmaceutical proteins, such as therapeutic antibodies. Nimotuzumab is a humanized anti–epidermal growth factor receptor (EGFR) recombinant IgG1 antibody approved in different countries for the treatment of head and neck squamous cell carcinoma, paediatric and adult glioma, and nasopharyngeal and oesophageal cancers. Because the antitumour mechanism of nimotuzumab is mainly attributed to its ability to interrupt the signal transduction cascade triggered by EGF/EGFR interaction, we have hypothesized that an aglycosylated form of this antibody, produced by mutating the N297 position in the IgG1 Fc region gene, would have similar biochemical and biological properties as the mammalian‐cell‐produced glycosylated counterpart. In this paper, we report the production and characterization of an aglycosylated form of nimotuzumab in transgenic tobacco plants. The comparison of the plantibody and nimotuzumab in terms of recognition of human EGFR, effect on tyrosine phosphorylation and proliferation in cells in response to EGF, competition with radiolabelled EGF for EGFR, affinity measurements of Fab fragments, pharmacokinetic and biodistribution behaviours in rats and antitumour effects in nude mice bearing human A431 tumours showed that both antibody forms have very similar in vitro and in vivo properties. Our results support the idea that the production of aglycosylated forms of some therapeutic antibodies in transgenic plants is a feasible approach when facing scaling strategies for anticancer immunoglobulins. 相似文献
106.
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107.
Claudia Sola Ricardo O Lamberghini Marcos Ciarlantini Ana L Egea Patricia Gonzalez Elda G Diaz Vanina Huerta Jose Gonzalez Alejandra Corso Mario Vilaro Juan P Petiti Alicia Torres Ana Vindel Jose L Bocco 《Annals of clinical microbiology and antimicrobials》2011,10(1):1-6
Background
There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA) which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin) against reference strains of Staphylococcus aureus.Methods and Results
The activity of the standard antibiotics and compounds on reference methicillin-sensitive and resistant strains of S. aureus were determined using the macrodilution broth method. The minimum inhibitory concentration (MIC) of the compounds was compared with that of the standard antibiotics. The interaction between any two antimicrobial agents was estimated by calculating the fractional inhibitory concentration (FIC index) of the combination. The various combinations of antibiotics and compounds reduced the MIC to a range of 0.05 to 50%.Conclusion
Pentacyclic triterpenoids have shown anti-staphylococcal activities and although individually weaker than common antibiotics produced from bacteria and fungi, synergistically these compounds may use different mechanism of action or pathways to exert their antimicrobial effects, as implicated in the lowered MICs. Therefore, the use of current antibiotics could be maintained in their combination with plant-derived antibacterial agents as a therapeutic option in the treatment of S. aureus infections. 相似文献108.
109.
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
Background
Despite recommendations for outpatient management, low risk patients with lower respiratory tract infections (LRTIs) are often hospitalized. This survey analyzed perceptions of physicians, nurses, patients and relatives about feasibility of outpatient management and required duration of hospital stay.Methods
We performed a prospective, observational questionnaire survey in hospitalized patients with LRTI as part of a multicenter trial. Treating physicians and nurses, patients and their relatives were asked on admission and before discharge about feasibility of outpatient treatment over 5 dimensions (medical, nursing, organizational factors, and patients' and relatives' preferences) using continuous scales.Results
On admission, 12.6% of physicians, 15.1% of nurses, 18.0% of patients and 5.2% of relatives believed that outpatient treatment would be possible. Before hospital discharge, 31.1% of physicians, 32.2% of nurses, 11.6% of patients and 4.1% of relatives thought that earlier discharge would have been feasible. Medical factors were the most frequently perceived motives for inpatient management. These perceptions were similar in all LRTI subgroups and independent of disease severity and associated expected mortality risks as assessed by the Pneumonia Severity Index (PSI).Conclusion
Independent of type and severity of respiratory tract infection, the misperceived high severity and expected mortality and morbidity were the predominant reasons why treating physicians, nurses, patients and their relatives unanimously believed that inpatient management was necessary. Better assessment and communication about true expected medical risks might contribute to a pathway to shorten in-hospital days and to introduce a more risk-targeted and individually tailored allocation of health-care resources.Trial Registration
NCT00350987 相似文献110.
Martín-Hidalgo A Huerta L Alvarez N Alegría G Del Val Toledo M Herrera E 《Journal of lipid research》2005,46(4):658-668
We examined the presence of hormone-sensitive lipase (HSL) in mammary glands of virgin, pregnant (12, 20, and 21 days), and lactating (1 and 4 days postpartum) rats. Immunohistochemistry with antibody against rat HSL revealed positive HSL in the cytoplasm of both alveolar epithelial cells and adipocytes. In virgin rats, immunoreactive HSL was observed in mammary adipocytes, whereas diffuse staining was found in the epithelial cells. Positive staining for HSL was seen in the two types of cells in pregnant and lactating rats. However, as pregnancy advanced, the staining intensity of immunoreactive HSL increased in the epithelial cells parallel to their proliferation, attaining the maximum during lactation. An immunoreactive protein of 84 kDa and a HSL mRNA of 3.3. kb were found in the rat mammary gland as in white adipose tissue. Both HSL protein and activity were lower in mammary glands from 20 and 21 day pregnant rats than from those of virgin rats, although they returned to virgin values on days 1 and 4 of lactation. Mammary gland HSL activity correlated negatively to plasma insulin levels. Immunoreactive HSL and HSL activity were found in lactating rats' milk. The observed changes indicate an active role of HSL in mammary gland lipid metabolism. 相似文献