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排序方式: 共有415条查询结果,搜索用时 15 毫秒
1.
B Lal R R Indurti P O Couraud G W Goldstein J Laterra 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(21):9695-9699
The delivery of therapeutic genes to primary brain neoplasms opens new opportunities for treating these frequently fatal tumors. Efficient gene delivery to tissues remains an important obstacle to therapy, and this problem has unique characteristics in brain tumors due to the blood-brain and blood-tumor barriers. The presence of endothelial mitogens and vessel proliferation within solid tumors suggests that genetically modified endothelial cells might efficiently transplant to brain tumors. Rat brain endothelial cells immortalized with the adenovirus E1A gene and further modified to express the beta-galactosidase reporter were examined for their ability to survive implantation to experimental rat gliomas. Rats received 9L, F98, or C6 glioma cells in combination with endothelial cells intracranially to caudate/putamen or subcutaneously to flank. Implanted endothelial cells were identified by beta-galactosidase histochemistry or by polymerase chain reaction in all tumors up to 35 days postimplantation, the latest time examined. Implanted endothelial cells appeared to cooperate in tumor vessel formation and expressed the brain-specific endothelial glucose transporter type 1 as identified by immunohistochemistry. The proliferation of implanted endothelial cells was supported by their increased number within tumors between postimplantation days 14 and 21 (P = 0.015) and by their expression of the proliferation antigen Ki67. These findings establish that genetically modified endothelial cells can be stably engrafted to growing gliomas and suggest that endothelial cell implantation may provide a means of delivering therapeutic genes to brain neoplasms and other solid tumors. In addition, endothelial implantation to brain may be useful for defining mechanisms of brain-specific endothelial differentiation. 相似文献
2.
Mice immunized against anti-substance P (anti-SP) monoclonal antibodies produced anti-SP anti-idiotypic antibodies (SPAb2). In a previous report. SPAb2 antibodies were found to have in vitro biological activity i.e. to behave either as agonists or as antagonists for substance P (SP) depending on the biological test. In this study, the involvement of SPAb2 in vivo biological activity has been tested. Because of the possible implication of SP in the generation and transmission of nociceptive information, we have tested the responsiveness of SPAb2 responding mice in behavioral nociceptive tests. SPAb2 mice showed very small behavioral variations in the hot plate test as compared with a control group of mice immunized against an unrelated monoclonal antibody. In the formalin test, however, SPAb2 mice displayed a significant increase in paw licking time, which was significantly correleted with SPAb2 serum concentration. These results are discussed in terms of the use of SPAb2 as pharmacological tools for studying the biological properties of SP receptors and more generally of auto anti-idiotypic antibodies in modulating behavior responses. 相似文献
3.
F Couraud N Martin-Moutot A Koulakoff Y Berwald-Netter 《The Journal of neuroscience》1986,6(1):192-198
Fetal mouse brain cells were investigated by 22Na+ flux assays with the aim to determine the ontogenetic time course of appearance of functional voltage-sensitive sodium channels. Their pharmacological properties were assessed by measurement of the response to known neurotoxins, acting at site 1, 2, or 3 of the Na+ channel. Brain cell suspensions, prepared at 11-19 d of prenatal development in vivo, and fetal brain neurons in culture were explored. In vivo neurotoxin-sensitive Na+ influx becomes detectable at 12 d of gestation, in concordance with the time of appearance of saturable binding sites for alpha-scorpion toxin (alpha-ScTx) and saxitoxin. Progression in fetal age or in time in vitro is accompanied by an increase in the initial rate and in the amplitude of Na+ uptake stimulated by batrachotoxin or veratridine. The general pharmacological properties of developing Na+ channels are very similar to the known properties of voltage-dependent Na+ channels in adult nerve: Batrachotoxin acts as a full channel agonist and veratridine as a partial agonist. Their respective apparent affinities are increased in presence of alpha-ScTx, in agreement with the known positive cooperativity of toxins acting at sites 2 and 3 of the Na+ channel. alpha-ScTx alone induces a small increase in Na+ permeability; its effect is greatly amplified in the presence of batrachotoxin or veratridine. The apparent affinity of alpha-ScTx is reduced by cell depolarization. Tetrodotoxin and saxitoxin block the increase in Na+ permeability induced by batrachotoxin, veratridine, and alpha-ScTx.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
4.
Jean-Franois Rual Tomoko Hirozane-Kishikawa Tong Hao Nicolas Bertin Siming Li Amlie Dricot Ning Li Jennifer Rosenberg Philippe Lamesch Pierre-Olivier Vidalain Tracey R. Clingingsmith James L. Hartley Dominic Esposito David Cheo Troy Moore Blake Simmons Reynaldo Sequerra Stephanie Bosak Lynn Doucette-Stamm Christian Le Peuch Jean Vandenhaute Michael E. Cusick Joanna S. Albala David E. Hill Marc Vidal 《Genome research》2004,14(10B):2128-2135
The advent of systems biology necessitates the cloning of nearly entire sets of protein-encoding open reading frames (ORFs), or ORFeomes, to allow functional studies of the corresponding proteomes. Here, we describe the generation of a first version of the human ORFeome using a newly improved Gateway recombinational cloning approach. Using the Mammalian Gene Collection (MGC) resource as a starting point, we report the successful cloning of 8076 human ORFs, representing at least 7263 human genes, as mini-pools of PCR-amplified products. These were assembled into the human ORFeome version 1.1 (hORFeome v1.1) collection. After assessing the overall quality of this version, we describe the use of hORFeome v1.1 for heterologous protein expression in two different expression systems at proteome scale. The hORFeome v1.1 represents a central resource for the cloning of large sets of human ORFs in various settings for functional proteomics of many types, and will serve as the foundation for subsequent improved versions of the human ORFeome. 相似文献
5.
Fawzia Zeraria Olivier Dry Jacqueline Fischer Yveline Frobert Jean-Yves Couraud Marie Conrath 《Journal of chemical neuroanatomy》1995,9(1):65-77
A monoclonal antibody directed against a peptide (PS5) specified by RNA complementary to the mRNA coding for substance P (SP), was used to label SP receptors in the rat spinal cord as demonstrated by light and electron microscopy. An immunocytochemical method (avidin-biotin-peroxidase) was used on vibratome sections from rats perfused with paraformaldehyde. Immunoreactivity was observed principally in the two superficial layers of the dorsal horn, in lamina X and the region of motoneurons. The labeling was absent when the antibody was preincubated with the complementary peptide (PS5) used as immunogen. Competition between the anti-complementary peptide antibody and different ligands was tested by preincubation of tissue sections with the ligand in the presence of peptidase inhibitors before addition of the antibody. A specific agonist (SP) or antagonist (spantide, RP 67580) at 10−6M led to total absence of labeling. These results indicate that under our experimental conditions, the anti-complementary peptide antibody recognizes a SP binding site in the rat spinal cord. Electron microscopic study of the two superficial laminae of the dorsal horn showed that immunolabeling was mainly localized extracellularly at apposing neuronal plasma membranes. It was mostly associated with axodendritic or axosomatic appositions. Occasionally labeling was observed between two axon terminals. In all cases, these appositions were non junctional. Generally, neuronal processes involved in these appositions did not contain large granular vesicles. These observations suggest that SP may act in a diffuse, nonsynaptic manner probably on targets distant from SP release sites. 相似文献
6.
C. Le Page S. Bourdoulous E. Béraud P. O. Couraud M. Rieu A. Ferry 《European journal of applied physiology》1996,73(1-2):130-135
The aim of the study was to determine whether different programmes of exercise influence adoptive monophasic experimental auto-immune encephalomyelitis (adoptive EAE), a paralytic disease mediated by T-cells. Adoptive EAE was induced by the transfer of activated encephalitogenic T-lymphocytes into syngeneic recipients (Lewis rats, n = 85) and its development was followed by two independent observers. The results showed that 2 days of severe exercise (250 and 300 min) performed after the adoptive transfer of EAE slightly delayed the onset of the disease (P < 0.008) and the day of its maximal severity (P < 0.016) without affecting the overall severity of the disease. When this programme of exercise was performed before the cell transfer, it had no effect (P > 0.05). Two more moderate exercise programmes (5 × 120 min of running at constant speed or 5 × 60 min of running at variable speed, 5 consecutive days) performed between the adoptive transfer and the onset of the disease did not modify the development of the clinical signs of adoptive EAE (P >0.05). These results showed that severe exercise slightly influenced the effector phase of monophasic EAE and confirmed that physical exercise performed before the onset of experimental auto-immune diseases did not exacerbate the clinical signs. 相似文献
7.
Karine Titier Pierre-Olivier Girodet Hélène Verdoux Mathieu Molimard Bernard Bégaud Wilhelm Haverkamp Malcolm Lader Nicholas Moore 《Drug safety》2005,28(1):35-51
Syncope and sudden death are features of schizophrenia that can be attributed to ischaemic heart disease, the use of antipsychotics (because of proarrhythmia or other reasons such as pharyngeal dyskinesia) or the psychiatric disease itself. Cases have been described with most antipsychotics and have led to the withdrawal, temporary suspension from the market or restricted use of antipsychotics, such as sultopride, droperidol, sertindole or thioridazine. Reviewing the available data shows that all antipsychotics tested affect the cardiac potassium channel, with the concentration that produces 50% inhibition (IC50) ranging from 1 nmol/L (haloperidol) to 6 micromol/L (olanzapine). Experimental in vitro or in vivo electrophysiological studies have shown a dose-dependent increase in the duration of the action potential with various degrees of indicators of serious arrhythmogenicity. However, this does not always translate clinically into an increased duration of the QT interval or increased risk of torsade de pointes or sudden death in clinical trials or pharmacoepidemiological studies. In turn, QT prolongation in clinical trials does not always translate to an increased risk of torsade de pointes or sudden death. The reasons for these apparent discrepancies are unclear and could be related to insufficiently powered field studies, low plasma and tissue drug concentrations with reference to in vitro data or drug effects on other receptors or ion channels that have a protective effect. Alternatively, risks that were not apparent from preclinical or clinical data could be related to the use of the drug in high-risk patients, metabolic interactions or other factors that would only be encountered in large postmarketing populations. The assessment of cardiovascular safety, both preclinical and during premarketing clinical trials, needs to be supported by appropriately powered pharmacoepidemiology studies. 相似文献
8.
Nikolaos Samaras Dimitrios Samaras Pierre-Olivier Lang Alexandre Forster Claude Pichard Emilia Frangos Patrick Meyer 《Maturitas》2013,74(3):213-219
Age related male hypogonadism, or “andropause”, is increasingly recognized as of frequent occurrence in older patients. Diagnosis requires both the presence of clinical symptoms and low testosterone levels. However, diagnosing andropause in this age group may be challenging since symptoms are frequently non specific and testosterone levels are influenced by a multitude of parameters such as lifestyle factors and chronic diseases. In this article we discuss the pathophysiology, definition and diagnostic difficulties of andropause in geriatric patients. Moreover, we review the relation between testosterone levels and frequent geriatric syndromes such as falls, osteoporosis, cognitive and mood disorders, anemia and cardiovascular disease. Finally, we examine the potential benefits and risks of testosterone replacement therapy in this age group. 相似文献
9.