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91.
Petrus J. Pauwels Thierry Wurch Christiane Palmier Francis C. Colpaert 《Naunyn-Schmiedeberg's archives of pharmacology》1996,354(2):136-144
5-Hydroxytryptamine (serotonin, 5-HT), essentially known as a neurotransmitter and vasoactive agent, also functions as a mitogen in various cell types through several different second messenger systems. Stimulation of cloned human 5-HT1D receptor sites by sumatriptan in stably transfected rat C6-glial/5-HT1D cells promotes cell growth (Pauwels et al. (1996) Naunyn-Schmiedeberg's Arch Pharmacol 353:144–156). In the present study, the pharmacology of this growth response was investigated using a broad series of 5-HT receptor ligands. The data were compared with the responses obtained by measuring inhibition of forskolin-stimulated cAMP formation. 5-HT (EC50: 25 nM) promoted cell growth of C6-glial/5-HT1D cells, and this in contrast to the absence of any measurable effect in pcDNA3-plasmid transfected and non-transfected C6-glial cells. The 5-HT effect could be mimicked by the following compounds (EC50 in nM): zolmitriptan (0.41), 2-methyl-4-(5-methyl[1,2,4] oxadiazol-3-yl)biphenyl-4-carboxylic acid [4-methoxy-3-(4-methylpiperazin-1-yl)phenyl]amide (GR 127,935; 0.86), naratriptan (0.92), metergoline (1.9), sumatriptan (2.9), (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-y)]ethylamine (MK-462; 3.0), and R(+)-8-hydroxy-2-(di-n-propylamino)tetralin (R(+)-8-OH-DPAT; 30.7). These EC50-values correspond to the compounds binding affinities at the human 5-HT1D receptor site and, with the exception of GR 127,935 and metergoline, also to the EC50-values found by measuring over 5 min inhibition of forskolin (100 M)-stimulated cAMP formation. Prolonged exposure of GR 127,935 (3 h) and metergoline (30 min) to cells yielded EC50 values in the cAMP assay more close to those measured in the mitogenic response. The growth response to sumatriptan, 5-HT, GR 127,935 and metergoline was blocked by the apparently silent antagonists methiothepin, ritanserin and ketanserin with potencies similar to blockade of inhibition of stimulated CAMP formation. The 8-OH-DPAT effect also is likely mediated by 5-HT1D receptors; stereoselectivity was found with its enantiomers at this receptor site and the effect was blocked by ketanserin (1 M) but not by spiperone (1 M). Micromolar concentrations of the 5-HT1B receptor agonist 3-(1,2,5,6-tetrahydro)-4-pyridil-5-pyrrolo[3, 2-b]pyril-5-one (CP 93,129) and of the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) induced cell growth with a potency that accorded with the affinity of these compounds for the human 5-HT1D receptor site. These effects were sensitive to ketanserin (1 M) antagonism, but not to blockade by -adrenergic blockers and the 5-HT2 receptor antagonist 2-anilino-N-[2-(3-chlorophenoxy)-propyl] acetamidine hydroiodide (BW 501-C-67). The findings suggest that 5-HT1A, 5-HT1B and 5-HT2 receptors are not implicated in 5-HT-stimulated C6-glial/5-HT1D cell growth. In conclusion, human 5-HT1D receptors are involved in the growth of C6-glial/5-HT1D cells. This cellular response is highly sensitive to the intrinsic activity of compounds at 5-HT1D receptors. 相似文献
92.
Parieto-occipital hypoperfusion in late whiplash syndrome: first quantitative SPET study using technetium-99m bicisate (ECD) 总被引:2,自引:0,他引:2
Andreas Otte Thierry Ettlin Lukas Fierz Jan Mueller-Brand 《European journal of nuclear medicine and molecular imaging》1996,23(1):72-74
Brain single-photon emission tomography (SPET) withN,N-1,2-ethylene-diylbis-l-cysteine diethyl ester dihydrochloride (ECD) was performed on ten patients with a clinically high grade late whiplash syndrome and on 11 controls. Two independent readers blinded to the clinical diagnosis were able to separate the ten patients from normal controls. All these patients had qualitative bilateral parieto-occipital hypoperfusion. To confirm this, the perfusion rate of parieto-occipital over global (perfusion index) was calculated after drawing elliptical regions of interest in transversal-oblique slices. The perfusion indices in patients were significantly lower than in controls as tested by the Mann-WhitneyU test. This quantitative study proves our recent qualitatively analysed observation (Lancet 1995; 345: 1513–1514). 相似文献
93.
Thierry Humbert Cuong Luu-Duc Michel Comet Pierre Demenge 《European journal of nuclear medicine and molecular imaging》1991,18(11):870-878
Previous studies led us to hypothesize that a fatty acid analogue, 15-p-iodophenyl--methyl pentadecanoic acid (IMPPA or BMIPP), which is taken up but not quickly metabolized by heart cells, would be a more suitable tracer of cellular viability than thallium-201. Biodistribution studies of 1-14C-IMPPA in conscious, freely moving rats showed that the concentration ratio of radioactivity in the heart with respect to the blood was about 8 for at least 60 min after intravenous administration, permitting its use as a putative tracer in these conscious, freely moving rats. Thereafter, the myocardial uptake of14C-IMPPA was studied in isoproterenol-treated rats (daily treatment for 10 days in order to induce cardiac hypertrophy and necrotic foci) with respect to control ones. Comparison of myocardial localizations by quantitative autoradiography of the uptake of201Tl and14C-IMPPA with that of triphenyltetrazolium chloride (TTC) staining enabled comparative evaluation of nutritional blood flow, localization and uptake of14C-IMPPA and necrotic foci size. Distributions of14C-IMPPA and2011 T1 in control rats' hearts were homogeneous, like TTC staining. In infarcted hearts, areas of decreased14C-IMPPA uptake were nearly the same (100%±5%) as those unstained by TTC. These areas were larger than those showing a decrease in thallium uptake (about 70%±5% of the total scar size). Therefore, IMPPA seems to be a more accurate and sensitive indicator of necrosis localization compared with thallium. It may be a useful agent for assessment of myocardial viability by single photon emission tomography (SPET) imaging. 相似文献
94.
95.
Meurisse M Gollogly L Degauque C Fumal I Defechereux T Hamoir E 《World journal of surgery》2000,24(11):1377-1385
Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones.
In most instances thyrotoxicosis is due to hyperthyroidism, a term reserved for disorders characterized by overproduction
of thyroid hormones by the thyroid gland. Nevertheless, thyrotoxicosis may also result from a variety of conditions other
than thyroid hyperfunction. The present report focuses on the etiologies, pathophysiology, and treatment of iatrogenic thyrotoxicosis. Iatrogenic thyrotoxicosis may be caused by (1) subacute thyroiditis (a result of lymphocytic infiltration,
cellular injury, trauma, irradiation) with release of preformed hormones into circulation; (2) excessive ingestion of thyroid
hormones (“thyrotoxicosis factitia”); (3) iodine-induced hyperthyroidism (radiologic contrast agents, topical antiseptics,
other medications). Among these causes of iatrogenic thyrotoxicosis, that induced by the iodine overload and cytotoxicity
associated with amiodarone represents a significant challenge. Successful management of amiodarone-induced thyrotoxicosis
requires close cooperation between endocrinologists and endocrine surgeons. Surgical treatment may have a leading yet often
underestimated role in view of the potential life-threatening severity of this disease, whereas others kinds of iatrogenic
thyrotoxicosis are usually treated conservatively. 相似文献
96.
Thierry Andre Philippe Colin Christophe Louvet Erik Gamelin Olivier Bouche Emmanuel Achille Nicolas Colbert Catherine Boaziz Pascal Piedbois Nicole Tubiana-Mathieu Arnaud Boutan-Laroze Michel Flesch Marc Buyse Aimery de Gramont 《Journal of clinical oncology》2003,21(15):2896-2903
PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer. PATIENTS AND METHODS: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. RESULTS: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001). CONCLUSION: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations. 相似文献
97.
Analysis of the p21 gene in gliomas 总被引:4,自引:0,他引:4
Li You-Jun Hoang-Xuan Khê Hoang-Xuan Khê Zhou Xiao-Ping Sanson Marc Mokhtari Karima Faillot Thierry Cornu Philippe Poisson Michel Thomas Gilles Hamelin Richard 《Journal of neuro-oncology》1998,40(2):107-111
The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas. 相似文献
98.
Thierry Conroy Bernard Paillot Eric Fran?ois Roland Bugat Jacques-Henri Jacob Ulrich Stein Salvador Nasca Jean-Philippe Metges Olivier Rixe Pierre Michel Emmanuelle Magherini Aliette Hua Gael Deplanque 《Journal of clinical oncology》2005,23(6):1228-1236
PURPOSE: To evaluate response rate and toxicity of irinotecan and oxaliplatin plus fluorouracil (FU) and leucovorin (Folfirinox) in advanced pancreatic adenocarcinoma (APA). PATIENTS AND METHODS: Chemotherapy-naive patients with histologically proven APA and bidimensionally measurable disease were treated with Folfirinox therapy every 2 weeks, which comprised oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) plus leucovorin 400 mg/m(2) followed by bolus FU 400 mg/m(2) on day 1, then FU 2,400 mg/m(2) as a 46-hour continuous infusion. Quality of life (QOL) was assessed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). RESULTS: Forty-seven patients were entered, and 46 received treatment. Thirty-five patients (76%) had metastatic disease. A total of 356 cycles were delivered, with a median of eight cycles per patient (range, one to 24 cycles). All patients were assessable for safety. No toxic death occurred. Grade 3 to 4 neutropenia occurred in 52% of patients, including two patients with febrile neutropenia. Other relevant toxicities included grade 3 to 4 nausea (20%), vomiting (17%), and diarrhea (17%) and grade 3 neuropathy (15%; Levi's scale). The confirmed response rate was 26% (95% CI, 13% to 39%), including 4% complete responses. Median time to progression was 8.2 months (95% CI, 5.3 to 11.6 months), and median overall survival was 10.2 months (95% CI, 8.1 to 14.4 months). Between baseline and end of treatment, patients had improvement in all functional scales of the EORTC QLQ-C30, except cognitive functioning. Responders had major improvement in global QOL. CONCLUSION: With a good safety profile, a promising response rate, and an improvement in QOL, Folfirinox will be further assessed in a phase III trial. 相似文献
99.
Thierry M Muanza Ana P Cotrim Mathew McAuliffe Anastasia L Sowers Bruce J Baum John A Cook Felix Feldchtein Paul Amazeen C Norman Coleman James B Mitchell 《Clinical cancer research》2005,11(14):5121-5127
PURPOSE: Optical coherence tomography (OCT) imaging was evaluated to determine if radiation-induced mucosal damage could be noninvasively monitored in real time and correlated with histopathologic findings. EXPERIMENTAL DESIGN: Female C3H mice, ages 7 to 9 weeks, four per group, were immobilized in a custom-made Lucite jig and received 0, 15, 22.5, and 25 Gy in a single fraction to their oral cavity. OCT images were acquired of proximal, middle, and distal aspects of the dorsum of the tongue on days 0, 1, 3, 5, and 7 post-irradiation. Animals were sacrificed on day 7 and samples taken for histologic evaluation. OCT images were visually examined and also quantified by image analysis and compared with histologic findings. RESULTS: Tongues removed 7 days post-irradiation showed no visible damage; however, upon staining with toluidine blue, ulcers at the base of the tongue became visible (100% for 25 Gy, 75% after 22.5 Gy, and 0% after 15 Gy). Visual inspection of OCT images qualitatively compared with histologic findings and quantitative image analysis of the OCT images (effective light penetration depth) revealed significant changes 7 days post-irradiation compared with unirradiated controls for the base of the tongue. CONCLUSIONS: OCT allows for direct noninvasive real-time acquisition of digitally archivable images of oral mucosa and can detect radiation-induced changes in the mucosa before visual manifestation. OCT may be a useful technique to quantify subclinical radiation-induced mucosal injury in experimental chemoradiation clinical trials. 相似文献
100.
Xavier Leleu Ga?lle Le Friec Thierry Facon Laurence Amiot Renée Fauchet Bernadette Hennache Valérie Coiteux Ibrahim Yakoub-Agha Sylvain Dubucquoi Hervé Avet-Loiseau Claire Mathiot Régis Bataille Jean-Yves Mary 《Clinical cancer research》2005,11(20):7297-7303
Serum beta2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HLA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 microg/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage II and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (> or =2.1 microg/mL) was predictive of short survival (P = 0.017). For each given level of beta2-microglobulin, the relative risk of death was higher for patients with HLA-Is > or = 2.1 microg/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta2-microglobulin produced an efficient prognostic score (P < 0.0001). HLA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta2-microglobulin. 相似文献