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排序方式: 共有271条查询结果,搜索用时 31 毫秒
71.
Blum A Tremont G Donahue J Tung G Duncan J Buchbinder B Gascon G 《Epilepsy & behavior : E&B》2007,10(3):495-503
A 39-year-old man, who presented at age 312 with Landau-Kleffner syndrome, had persisting oral and written language deficits into adulthood. Seizures were easily controlled in childhood, but reemerged in adulthood as medication-refractory complex partial seizures. Abnormal T2 signal hyperintensity was seen in the left mesial temporal area on brain MRI. Later, left temporal lobectomy revealed focal cortical dysplasia in the lateral temporal neocortex and gliosis plus neuronal loss in the hippocampus. This case suggests that focal cortical microdysgenesis may be a cause of the Landau-Kleffner syndrome. Persistent seizures in this illustrative case may have led to the evolution of dual-temporal-lobe pathology with mesial temporal sclerosis. 相似文献
72.
Ahmed Al-Jarallah Jay David Cook Generoso Gascon Imaduddin Kanaan Edir Sigueira 《Journal of surgical oncology》1994,55(2):126-131
We report 3 patients, ages 5, 9 and 13 years, with mutism following posterior fossa surgery (PFS). All presented with headache of 10–180 days duration, excellent premorbid learning performance and paucity of neurologic signs. Radiographic studies demonstrated large posterior fossa tumor occupying the fourth ventricle, and hydrocephalus, leading to gross total resection of the tumor. Within 24–48 hr, all patients were mute. None had problems with swallowing and coughing. AH were able to nod “yes or no,” follow commands, point to body parts, and make their wants known by gestures. Jaw, gag, snout and palmomental reflexes were normal. CT scan and MRI Brain showed no cerebral hemispheric lesions. All children regained speech although dysarthric, within 5–12 weeks. Twenty-two previously reported cases are similar to ours. We conclude that this post-surgical mutism syndrome is unique and must be differentiated from aphemia, Broca's aphasia, hysterical mutism and elective mutism. The cerebellum, in a way not yet understood, does play a role in speech production. © Wiley-Liss, Inc. 相似文献
73.
Serum protein s-100 predicts clinical outcome in patients with melanoma treated with adjuvant interferon--comparison with tyrosinase rt-PCR 总被引:2,自引:0,他引:2
Domingo-Domènech J Molina R Castel T Montagut C Puig S Conill C Martí R Vera M Auge JM Malvehy J Grau JJ Gascon P Mellado B 《Oncology》2005,68(4-6):341-349
OBJECTIVE: To study the clinical value of the determination of serum S-100 protein as a single tumor marker or in combination with tyrosinase RT-PCR in patients with melanoma receiving adjuvant interferon. PATIENTS AND METHODS: Patients were tested for serum S-100 protein luminoimmunometric assay and for blood tyrosinase mRNA (RT-PCR), before starting interferon and every 2-3 months thereafter. RESULTS: One hundred and six patients (stage IIA, 27; IIB, 19; III, 49; and IV, 11) were included in the study. Median follow-up was 51 months (range 2-76). In the univariate analysis, under treatment S-100 > or =0.15 microg/l and a positive RT-PCR correlated with a lower disease-free survival and overall survival (OS). In the multivariate analysis, clinical stage, under therapy positive RT-PCR and S-100 levels > or =0.15 mug/ml, were independent prognostic factors for OS. The hazard ratio for OS was 3.9 (95% CI, 1.67-9.15; p = 0.004) and 2.2 (95% CI, 1.05-4.6; p = 0.016) for S-100 > or =0.15 microg/l and positive RT-PCR, respectively. When both techniques where combined, a positive RT-PCR indicated a poorer clinical outcome only in patients with S-100 <0.15 microg/l. CONCLUSIONS: S-100 > or =0.15 microg/l and a positive RT-PCR during adjuvant interferon therapy indicate a high risk of death in resected melanoma patients. S-100 determination has a higher positive predictive value than RT-PCR, while tyrosinase RT-PCR adds prognostic information in patients with S-100 <0.15 microg/l. 相似文献
74.
Zhang R Gascon R Miller RG Gelinas DF Mass J Hadlock K Jin X Reis J Narvaez A McGrath MS 《Journal of neuroimmunology》2005,159(1-2):215-224
Sporadic amyotrophic lateral sclerosis (sALS) is a progressive neuroinflammatory disease of spinal cord motor neurons of unclear etiology. Blood from 38 patients with sALS, 28 aged-match controls, and 25 Alzheimer's disease (AD) patients were evaluated and activated monocyte/macrophages were observed in all patients with sALS and AD; the degree of activation was directly related to the rate of sALS disease progression. Other parameters of T-cell activation and immune globulin levels showed similar disease associated changes. These data are consistent with a disease model previously suggested for AD, wherein systemic immunologic activation plays an active role in sALS. 相似文献
75.
Preclinical and clinical development of the proteasome inhibitor bortezomib in cancer treatment 总被引:4,自引:0,他引:4
Montagut C Rovira A Mellado B Gascon P Ross JS Albanell J 《Drugs of today (Barcelona, Spain : 1998)》2005,41(5):299-315
The proteasome is a ubiquitous enzyme complex that plays a critical role in the degradation of many proteins involved in cell cycle regulation, apoptosis and angiogenesis. Since these pathways are fundamental for cell survival and proliferation, particularly in cancer cells, the inhibition of proteasome is an attractive potential anticancer therapy. The present review will focus on the proteasome inhibitor bortezomib (Velcade, formerly PS-341; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA). Bortezomib is an extremely potent and selective proteasome inhibitor that shows strong activity in in vitro and in vivo laboratory studies against many solid and hematologic tumor types. Moreover, bortezomib, mainly by inhibition of the NF-kappaB pathway, has a chemosensitizing effect when administered together with other antitumoral drugs. Based on these results, bortezomib entered clinical phase I trials, alone or in combination with chemotherapy, that showed good tolerance at doses that achieved a desired degree of proteasome inhibition. Phase II studies showed high response rates in refractory multiple myeloma patients, which led to the accelerated approval of bortezomib by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) for this indication. A phase III trial comparing bortezomib with dexamethasone in refractory/ relapsed multiple myeloma patients had to be halted due to a survival advantage in the bortezomib arm. Additional studies are focusing on the potential benefit of bortezomib in newly diagnosed multiple myeloma patients. In other solid and hematological malignancies, phase II studies with bortezomib alone or in combination with other agents are ongoing. Encouraging results, particularly in lung cancer and lymphoma, have been observed. The critical molecules or genes responsible for tumor sensitivity to bortezomib continue to be evaluated using novel technologies. 相似文献
76.
77.
Functionally active monoclonal antibody that recognizes an epitope on the O side chain of Pseudomonas aeruginosa immunotype-1 lipopolysaccharide. 总被引:5,自引:8,他引:5
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A murine monoclonal antibody (MAb) was prepared against Pseudomonas aeruginosa immunotype-1 (It-1) lipopolysaccharide (LPS). The MAb bound It-1 LPS in the enzyme-linked immunosorbent assay and in the immunodiffusion and immunoblotting assays, agglutinated and opsonized It-1 bacteria, and protected against challenge with live It-1 organisms in a murine burn infection model. All of these activities were immunotype specific. Correlation of the opsonic and protective properties of the MAb with its recognition site on the LPS O side chain confirmed that such immunotype-specific determinants are important targets for protective antibodies in Pseudomonas disease. The functional equivalence of this MAb and polyclonal antibodies from hyperimmune plasma underscores the therapeutic potential of single MAbs which recognize critical determinants in the LPS O side chain. 相似文献
78.
Summary The biotransformation of midazolam is mediated by a cytochrome P-450 isozyme (P-450 IIIA) whose activity is highly variable. The kinetics of the 1- and 4-hydroxylation of midazolam, the major routes of midazolam oxidation, by human liver microsomes have been examined to characterize further the cytochrome isozyme(s) catalysing these reactions, and to screen for drugs that might interfere with them.In hepatic microsomal preparation from two kidney donors (extensive and poor metabolisers of debrisoquine) KM values for 1-hydroxylation were 4.2 and 6.1 M (extensive and poor metabolisers, respectively), and for the 4-hydroxylation they were 14.7 and 18.1 M, respectively. The corresponding Vmax values were 25.8 and 29.8 and 17.0 and 18.1 nmolsdmg P–1·h–1. Both reactions appeared to be catalysed by the same or by coregulated isozymes.Midazolam hydroxylations in vitro are inhibited by many drugs, including nifedipine and other dihydropyridine-type calcium channel blockers, ergot alkaloids, cyclosporine, erythromycin and phenothiazine-type neuroleptics.A clinical case report illustrates the consequence of such a drug-drug interference with hepatic biotransformation; midazolam-induced sleep in a patient lasted for 6 days (t1/2=25 h).Presented in part at the Fifty-seventh Annual Meeting of the Swiss Society for Internal Medicine, Interlaken, May 1989, and at the Fourth World Conference on Clinical Pharmacology and Therapeutics, Mannheim, July 1989. 相似文献
79.
Josep Domingo-Domenech Cristina Oliva Ana Rovira Jordi Codony-Servat Marta Bosch Xavier Filella Clara Montagut Marian Tapia Clara Campás Lenny Dang Mark Rolfe Jeffrey S Ross Pere Gascon Joan Albanell Bego?a Mellado 《Clinical cancer research》2006,12(18):5578-5586
PURPOSE: To investigate whether nuclear factor kappaB (NF-kappaB)/interleukin 6 (IL-6) was linked to docetaxel response in human prostate cancer cell lines, and whether inhibition of NF-kappaB sensitized tumor cells to docetaxel. We also aimed to correlate IL-6 (as a surrogate marker of NF-kappaB) and docetaxel response in hormone-independent prostate cancer (HIPC) patients. EXPERIMENTAL DESIGN: Hormone-dependent (LNCaP) and hormone-independent (PC-3 and DU-145) prostate cancer cell lines were exposed to docetaxel alone or combined with the NF-kappaB inhibitor PS-1145 (an inhibitor of IkappaB kinase-2). Effects of dose, exposure time, and schedule dependence were assessed. Activation of NF-kappaB was assayed by electrophoresis mobility shift assay and luciferase reporter assay, IL-6 levels by ELISA, and cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle and apoptosis were assessed by fluorescence-activated cell sorting analysis. Apoptosis was also measured by detection of cleavage of poly(ADP-ribose) polymerase. In patients with metastatic HIPC receiving docetaxel-based chemotherapy, IL-6 serum levels were assayed before chemotherapy and every 3 to 4 weeks thereafter. RESULTS: PC-3 and DU-145 cells had higher NF-kappaB activity, secreted more IL-6, and were more resistant to docetaxel than LNCaP cells. NF-kappaB activity was induced by docetaxel. Cotreatment with docetaxel and PS-1145 prevented docetaxel-induced NF-kappaB activation, reduced IL-6 production, and increased docetaxel effects on cell viability in PC-3 and DU-145 cells but not in LNCaP. Synergism with docetaxel and PS-1145, as assayed by median-effect principle, was observed in DU-145 and PC-3. In HIPC patients, pretreatment IL-6 serum levels correlated to prostate-specific antigen (PSA) response: median IL-6 level was 10.8+/-9.5 pg/mL in PSA responders versus 36.7+/-20.8 pg/mL (P=0.006) in nonresponders. A PSA response was also linked to a decline in IL-6 levels during treatment. Median overall survival was 6.8 months in patients with high IL-6 versus 16.6 months in those with low IL-6 (P=0.0007). On multivariate analysis, pretreatment IL-6 (P=0.05) was an independent prognostic factor for time to disease progression and survival. CONCLUSIONS: Inhibition of NF-kappaB emerges as an attractive strategy to enhance docetaxel response in prostate cancer. The interest of this view is further supported by a significant association between high IL-6 in sera of HIPC patients and decreased response to docetaxel. 相似文献
80.
G G Gascon P T Ozand A Mahdi A Jamil A Haider J Brismar M al-Nasser 《Neurology》1990,40(12):1876-1882
We studied 14 Arab infants with infantile spongy degeneration, 13 of whom were products of consanguineous marriages. They presented in infancy with macrocephaly, poor visual behavior or blindness, and axial hypotonia with appendicular spasticity. Brain CT and MRI showed diffuse symmetric leukoencephalopathy, even before neurologic symptoms. There were relatively normal EEGs. The visual evoked responses (P100) were either absent or delayed early in the course. The brainstem auditory evoked responses showed milder abnormalities, with loss of later components before the earlier ones. Deficient aspartoacylase activity in cultured fibroblasts or brain biopsy confirmed the diagnosis in all patients. 相似文献