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141.
Benitez-Rajal J Lorite MJ Burt AD Day CP Thompson MG 《American journal of physiology. Gastrointestinal and liver physiology》2006,291(5):G977-G986
We have previously provided evidence suggesting that phosphatidic acid, possibly derived from the hydrolysis of phosphatidylcholine by phospholipase D (PLD), is involved in platelet-derived growth factor (PDGF)-mediated increases in extracellular signal-regulated kinase (ERK) activity and DNA synthesis in rat hepatic stellate cells (HSC), the primary fibrogenic cells of the liver. A recent study has shown the presence of P2Y nucleotide receptors on HSC that are coupled to contraction and synthesis of the matrix component, alpha1-procollagen, leading to the suggestion that they may represent a new therapeutic target in the treatment of liver fibrosis. However, although extracellular nucleotides have been shown to stimulate both PLD and ERK, and to elicit proliferation of fibrogenic cells outside the liver, their effect on these parameters in HSC have not yet been investigated. PLD activity was determined by [3H]choline release and [3H]phosphatidylbutanol production, ERK activity by Western blotting, and DNA synthesis by [3H]thymidine incorporation. We report here, for the first time in HSC, that extracellular nucleotides stimulate PLD activity and a sustained activation of ERK. However, in contrast to PDGF, nucleotides had negligible effects on DNA synthesis. Moreover, the effects of PDGF and nucleotides on PLD and ERK were not additive, suggesting activation of the same PLD isoform and pool of ERK. The data demonstrate that nucleotide-stimulated PLD and ERK activities are not coupled to DNA synthesis in HSC. Instead, these responses may be linked to other phenotypic changes associated with activated HSC such as increases in contraction, motility, or extracellular matrix deposition. 相似文献
142.
The effect of the inoculum source on the digestion of linear alkylbenzene sulfonates (LAS) under anaerobic conditions has
been investigated. The potential for primary and ultimate LAS biodegradation of anaerobic sludge samples obtained from wastewater
treatment plants (WWTPs) of different geographical locations was studied applying a batch test system. It was found that only
4–22% of the LAS added to the batch anaerobic digesters was primarily transformed suggesting a poor primary degradation of
the LAS molecule in anaerobic discontinuous systems. Regarding ultimate biodegradation, the addition of LAS to the batch anaerobic
digesters caused a reduction on the extent of biogas production. Significant differences in the inhibition extent of the biogas
production were observed (4–26%) depending on the sludge used as inoculum. Effect of the surfactant on the anaerobic microorganisms
was correlated with its concentration in the aqueous phase. Sorption of LAS on anaerobic sludge affects its toxicity by depletion
of the available fraction of the surfactant. LAS content on sludge was related to the total amount of calcium and magnesium
extractable ions. The presence of divalent cations promote the association of LAS with anaerobic sludge reducing its bioavailability
and the extent of its inhibitory effect on the biogas production. 相似文献
143.
Lasaro MA Rodrigues JF Mathias-Santos C Guth BE Régua-Mangia A Piantino Ferreira AJ Takagi M Cabrera-Crespo J Sbrogio-Almeida ME de Souza Ferreira LC 《FEMS immunology and medical microbiology》2006,48(1):123-131
Production and release of heat-labile toxin (LT) by wild-type enterotoxigenic Escherichia coli (ETEC) strains, isolated from diarrheic and asymptomatic Brazilian children, was studied under in vitro and in vivo conditions. Based on a set of 26 genetically diverse LT(+) enterotoxigenic E. coli strains, cell-bound LT concentrations varied from 49.8 to 2415 ng mL(-1). The amounts of toxin released in culture supernatants ranged from 0% to 50% of the total synthesized toxin. The amount of LT associated with secreted membrane vesicles represented <5% of the total toxin detected in culture supernatants. ETEC strains secreting higher amounts of LT, but not those producing high intracellular levels of cell-bound toxin, elicited enhanced fluid accumulation in tied rabbit ileal loops, suggesting that the strain-specific differences in production and secretion of LT correlates with symptoms induced in vivo. However, no clear correlation was established between the ability to produce and secrete LT and the clinical symptoms of the infected individuals. The present results indicate that production and release of LT by wild-type human-derived ETEC strains are heterogeneous traits under both in vitro and in vivo growth conditions and may impact the clinical outcomes of infected individuals. 相似文献
144.
Elliott JM Carling RW Chicchi GG Crawforth J Hutson PH Jones AB Kelly S Marwood R Meneses-Lorente G Mezzogori E Murray F Rigby M Royo I Russell MG Shaw D Sohal B Tsao KL Williams B 《Bioorganic & medicinal chemistry letters》2006,16(22):5752-5756
Introduction of selected amine containing side chains into the 3-position of N',2-diphenylquinoline-4-carbohydrazide based NK3 antagonists abolishes unwanted hPXR activation. Introduction of a fluorine at the 8-position is necessary to minimize unwanted hI(Kr) affinity and a piperazine N-tert-butyl group is necessary for metabolic stability. The lead compound (8m) occupies receptors within the CNS following oral dosing (Occ(90) 7 mg/kg po; plasma Occ(90) 0.4 microM) and has good selectivity and excellent PK properties. 相似文献
145.
146.
Diaz D Chara L Chevarria J Carballido J Esteban E Navas V Monserrat J Prieto A de la Hera A Alvarez-Mon M 《Cancer immunology, immunotherapy : CII》2009,58(2):235-245
The peripheral blood lymphocytes of eight patients with metastatic renal cell carcinoma, and of eight healthy volunteers were
analyzed by four-color flow cytometry to characterize the immunophenotypic alterations manifested, determine the prevalence
of lymphocyte apoptosis, and detect evidence of the systemic effect of inhaled IL-2. The T, B and NK lymphocytes of untreated
patients were found to have undergone profound changes characterized by an increase in susceptibility to both spontaneous
and mitogen-induced ex vivo apoptosis, a modified distribution of the main lymphocyte populations in the peripheral blood,
and alterations in activation status. An increase in the proportion of regulatory T cells was also seen in these patients.
Treatment with inhaled IL-2, however, normalized the rate of apoptosis in all the lymphocyte subpopulations studied, as well
as their distribution and activation status. These findings demonstrate that inhaled IL-2 has systemic immunomodulatory effects. 相似文献
147.
148.
Hemicentins are conserved extracellular matrix proteins discovered in Caenorhabditis elegans, with orthologs in all vertebrate species including human and mouse. Hemicentins share a single, highly conserved amino-terminal von Willebrand A domain, followed by a long (〉40) stretch of immunoglobulin repeats, multiple tandem epidermal growth factors and a fibulin-like carboxy-terminal module. C. elegans has a single hemicentin gene that has pleiotropic functions in transient cell contacts that are required for cell migration and basement membrane invasion and in stable contacts at hemidesmosome-mediated cell junctions and elastic fiber-like structures. Here, we summarize what is known about the function ofhemicentin in C. elegans and discuss implications for hemicentin function in other species. 相似文献
149.
Francisco Carricondo Mari Cruz Iglesias Fernando Rodríguez Joaquin Poch-Broto Pablo Gil-Loyzaga 《Cell and tissue research》2010,342(1):13-19
The adult mammalian auditory receptor lacks any ability to repair and/or regenerate after injury. However, the late developing
cochlea still contains some stem-cell-like elements that might be used to regenerate damaged neurons and/or cells of the organ
of Corti. Before their use in any application, stem cell numbers need to be amplified because they are usually rare in late
developing and adult tissues. The numerous re-explant cultures required for the progressive amplification process can result
in a spontaneous differentiation process. This aspect has been implicated in the tumorigenicity of stem cells when transplanted
into a tissue. The aim of this study has been to determine whether cochlear stem cells can proliferate and differentiate spontaneously
in long-term cultures without the addition of any factor that might influence these processes. Cochlear stem cells, which
express nestin protein, were cultured in monolayers and fed with DMEM containing 5% FBS. They quickly organized themselves
into typical spheres exhibiting a high proliferation rate, self-renewal property, and differentiation ability. Secondary cultures
of these stem cell spheres spontaneously differentiated into neuroectodermal-like cells. The expression of nestin, glial-fibrillary-acidic
protein, vimentin, and neurofilaments was evaluated to identify early differentiation. Nestin expression appeared in primary
and secondary cultures. Other markers were also identified in differentiating cells. Further research might demonstrate the
spontaneous differentiation of cochlear stem cells and their teratogenic probability when they are used for transplantation. 相似文献
150.
El Bakkouri M Pow A Mulichak A Cheung KL Artz JD Amani M Fell S de Koning-Ward TF Goodman CD McFadden GI Ortega J Hui R Houry WA 《Journal of molecular biology》2010,404(3):456-477
The Clp chaperones and proteases play an important role in protein homeostasis in the cell. They are highly conserved across prokaryotes and found also in the mitochondria of eukaryotes and the chloroplasts of plants. They function mainly in the disaggregation, unfolding and degradation of native as well as misfolded proteins. Here, we provide a comprehensive analysis of the Clp chaperones and proteases in the human malaria parasite Plasmodium falciparum. The parasite contains four Clp ATPases, which we term PfClpB1, PfClpB2, PfClpC and PfClpM. One PfClpP, the proteolytic subunit, and one PfClpR, which is an inactive version of the protease, were also identified. Expression of all Clp chaperones and proteases was confirmed in blood-stage parasites. The proteins were localized to the apicoplast, a non-photosynthetic organelle that accommodates several important metabolic pathways in P. falciparum, with the exception of PfClpB2 (also known as Hsp101), which was found in the parasitophorous vacuole. Both PfClpP and PfClpR form mostly homoheptameric rings as observed by size-exclusion chromatography, analytical ultracentrifugation and electron microscopy. The X-ray structure of PfClpP showed the protein as a compacted tetradecamer similar to that observed for Streptococcus pneumoniae and Mycobacterium tuberculosis ClpPs. Our data suggest the presence of a ClpCRP complex in the apicoplast of P. falciparum. 相似文献