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991.
992.
Martin R Bielekova B Gran B McFarland HF 《Journal of neural transmission. Supplementum》2000,(60):361-373
Multiple Sclerosis (MS) is considered a T cell-mediated autoimmune disease of central nervous system myelin. Based on elegant experiments in an animal model of MS, experimental allergic encephalomyelitis (EAE), a number of myelin proteins and peptides derived from these can induce inflammatory demyelinating lesions. Recent studies with transgenic mice expressing human HLA-DR molecules and a myelin basic protein (MBP)-specific T cell receptor as well as data from a phase II clinical trial with an altered peptide ligand based on MBP peptide (83-99) provide convincing evidence that the pathogenetic concepts which largely stem from the above EAE studies are valid in MS, too. 相似文献
993.
ZENG Hui Eckart Mayr KANG Bin XIONG Ao XIN Feng Michael Nogler Martin Krismer 《华中科技大学学报(医学英德文版)》2006,26(3)
Ziel ist die Analyse der Neigungslage des Beckens im Liegen und im Stehen bzw.die Beobachtung der Stabilit(a)t der Beckenfl(a)che als Beckenfl(a)che für die Acetabulum-Prothese Transplantation. 72 Testpersonen wurden je nach Status ihres Pfannengelenks in 3 Gruppen eingeteilt:Gruppe 1 "mit gesundem Pfannengelenk", Gruppe 2 "mit Arthritis" und Gruppe 3 "nach Implantation der Hüftendoprothese". Unter dem Einsatz von 3D- Digital-Instrument wurde die Fl(a)chen-Neigung vor dem Becken jeweils im Liegen und im Stehen gemessen und die Messwerte wurden verglichen. Die Fl(a)chen-Neigungen vor dem Becken bei allen 3 Gruppen (mit gesundem Pfannengelenk/mit Arthritis/nach Operation) im Liegen sind: 6.37°± 3.70°, 6. 47°± 3.52° und 4.56°±2.39°. Im Stehen sind es 7.33°±3.08°, 6.60°±3.45° und 6.74°±3.43°. Der Fl(a)chen-Neigungsunterschied vor dem Becken im Liegen und im Stehen hat keine grosse Bedeutung (P>0.05).Die (A)nderung der Fl(a)chen-Neigung vor dem Becken vom Liegen bis zum Stehen ist kleiner als 2.5°.Die Fl(a)che vor dem Becken (pelvic anterior plane, PAP) als Bezugsfl(a)che für Hüftpfanne-Prothese Transplantation bei klinischer Operation ist stabil und verlaβlich. 相似文献
994.
995.
Simpson PB Woollacott AJ Pillai GV Maubach KA Hadingham KL Martin K Choudhury HI Seabrook GR 《Journal of neuroscience methods》2000,99(1-2):91-100
To facilitate the discovery of novel compounds that modulate human GABA(A) receptor function, we have developed a high throughput functional assay using a fluorescence imaging system. L(tk-) cells expressing combinations of human GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a robust and persisting acidification response to addition of GABA, which was antagonised by the GABA(A) receptor antagonist bicuculline. The concentration-response relationship for GABA was modulated by allosteric ligands, including benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site ligands on the pH response to GABA for receptors containing alpha1beta3gamma2, alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results from electrophysiological studies on the same receptor subunit combinations expressed in Xenopus oocytes. Most modulatory compounds tested were found to be relatively unselective across the three subunit combinations tested; however, some showed subtype-dependent efficacy, such as diazepam, which had highest agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism on alpha1beta3gamma2 and still substantial but the least agonism on alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant receptor expressed in L(tk-) cells can affect the efficacy of the response to some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked acidification, indicating that multiple transporters are involved in the GABA-evoked pH change. This novel fluorescence-based high throughput functional assay allows the rapid characterization of allosteric ligands acting on human GABA(A) receptors. 相似文献
996.
nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice 总被引:5,自引:0,他引:5
Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity. 相似文献
997.
The potential causes, immunopathology, and treatment of multiple sclerosis (MS) are summarized in this article. Findings from a well-examined animal model for MS, experimental allergic encephalomyelitis (EAE), are described and used to illustrate the paths of research in MS. Data from a recent clinical trial with a modified myelin peptide provide support for concepts deduced from EAE. The authors stress that the complexity of the disease requires new techniques to capture the influence of single or combined treatment approaches. 相似文献
998.
Risperidone-associated weight gain in children and adolescents: a retrospective chart review 总被引:1,自引:0,他引:1
Martin A Landau J Leebens P Ulizio K Cicchetti D Scahill L Leckman JF 《Journal of child and adolescent psychopharmacology》2000,10(4):259-268
OBJECTIVE: Risperidone use has been associated with substantial weight gain in children and adolescents. Reports available to date have consisted of small case series evaluated without standardized indices of developmentally normative weight increase. The purpose of this study was to evaluate age- and gender-adjusted weight changes linked to risperidone use in a juvenile psychiatric inpatient population. METHOD: Thirty-seven child and adolescent inpatients treated with risperidone for 6 consecutive months were compared to a group of 33 psychiatric inpatients with no atypical neuroleptic exposure. Weight, height, and body mass index (BMI) were recorded on at least a monthly basis, and Tanner staging was completed on admission. Percent change from baseline weight, changes in standardized z scores of weight for age and gender, and proportion of subjects experiencing a < or = 7% weight increase from baseline were compared among groups. RESULTS: Subjects in both groups were comparable at baseline except for gender distribution (more males were in the risperidone group, p < 0.05). Risperidone-treated children and adolescents experienced significant weight gain between baseline and endpoint (paired t test, p < 0.001) that was first evident within 2 months of starting treatment, progressed steadily at an average rate of 1.2 kg/month, and did not reach a clear plateau during 6 months of observation. Significant increases in standardized weight were noted at 3 and 6 months for risperidone-treated subjects. Risperidone use conferred a substantial risk of gaining over 7% from baseline weight (odds ratio = 3.5, 95% confidence interval = 1.8-6.6, p < 0.001). CONCLUSIONS: Six-month exposure to risperidone was associated with clinically significant weight gain in 78% of treated children and adolescents (as opposed to 24% of those in the comparison group, p < 0.001). Risperidone dosage, concomitant medication use, and other demographic characteristics such as age, pubertal status, gender, and baseline weight and BMI were not associated with an increased risk of morbid weight gain. Standardized z scores offer advantages for the assessment of weight change among developing children and adolescents. 相似文献
999.
1000.
Farah I Pénillon S Sessa C Bosson JL Martin M Chichignoud B Magne JL Guidicelli H 《Annales de chirurgie》2000,125(5):450-456
STUDY OBJECTIVE: The objective of this retrospective study was to report the long-term results of distal revascularization at the ankle in patients with critical ischemia. PATIENTS AND METHODS: From January 1989 to November 1999, 50 inframalleolar bypasses were performed in 49 patients (35 males and 14 females with a mean age of 75 years [range: 51 to 95 years]). Twenty-five patients (50%) were diabetics. All patients presented with critical ischemia of the lower limb. Distal anastomosis was performed at the retromalleolar posterior tibial artery in 28 cases (56%), pedal artery in 20 cases (40%) and distal fibular artery in two cases (4%). Bypasses were performed using a greater saphenous vein (n = 38), a cryopreserved arterial allograft (n = 9), or a PTFE graft (n = 2). A composite graft with greater saphenous vein and arterial allograft was performed in two cases. RESULTS: There were two early postoperative deaths. One patient presented a blow-out of the distal anastomosis that required bypass ligation and subsequent leg amputation. Early thrombosis of the graft occurred in four cases, leading to major amputation in three cases. No patients were lost to follow-up and mean follow-up was 26.7 months (range: 1 to 86 months). Graft thrombosis occurred in 15 patients and led to amputation in 6 cases. Bypass graft patency rate was 72% and 61% at 1 year and 3 years, respectively, yielding a 80% limb salvage rate at 3 years. The 3-year actuarial survival rate was 53%. CONCLUSION: Inframalleolar bypasses are a valuable tool in patients with critical ischemia. The lower limb salvage rate is satisfactory in this elderly population. Based on this experience, angiography with good run-off and, when necessary, a surgical approach to verify patency of the arteries at the ankle should always be performed before undertaking a major amputation. 相似文献