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排序方式: 共有520条查询结果,搜索用时 109 毫秒
1.
Leonidas JC; Berdon WE; Valderrama E; Neveling U; Schuval S; Weiss SJ; Hilfer C; Godine L 《Radiology》1996,198(2):377
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I. Litvan R. Blesa K. Clark P. Nichelli J. R. Atack M. M. Mouradian J. Grafman T. N. Chase 《Annals of neurology》1994,36(1):55-61
Severe cholinergic loss occurs in the brains of patients with progressive supranuclear palsy. To evaluate the functional implications of this neuronal deficit, dose-response curves were obtained in patients with progressive supranuclear palsy and normal control subjects undergoing intravenous cholinergic blockade (scopolamine) and stimulation (physo-stigmine). Physostigmine had no significant neurobehavioral effects at any does in patients with progressive supranuclear palsy. Scopolamine, at low and medium doses, significantly impaired memory performance of both groups, but worsened the gait of only the patients. High-dose scopolamine, which could not be tolerated by the patients, resulted in gait deterioration among control subjects. Thus, patients with progressive supranuclear palsy have increased sensitivity to cholinergic blockade compared to control subjects. Since loss of cholinergic neurons appears to contribute to the pathogenesis of certain cognitive and motor deficits found in progressive supranuclear palsy, the use of oral anticholinergics should ordinarily be avoided in this disorder. On the other hand, physostigmine at clinically tolerated dose levels seems to be terapeutically ineffective. 相似文献
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J M Davis A Chadburn J A Mouradian 《Archives of surgery (Chicago, Ill. : 1960)》1988,123(11):1349-1352
Twenty-one male homosexuals were followed up by repeated lymph node biopsy for a mean (+/- SEM) follow-up of 99 +/- 18 weeks. Four histologic patterns were seen on biopsy: explosive follicular hyperplasia (EFH), follicular involution (FI), a mixed pattern of EFH with FI in the same node, and lymphocyte depletion. Patients with FI and lymphocyte depletion had mean survival times that were significantly less than those for the subjects with EFH. The percentage of lymph node follicles with suppressor cell clusters (T8) in EFH lymph nodes was significantly higher (43% vs 8%) than in nodes from patients without risk for human immunodeficiency virus infection. Helper/suppressor T-cell ratios in control nodes were 1.6; in EFH nodes, 0.97; and in FI nodes, 0.88. A remarkable 33% of patients in this lymphadenopathy group ultimately developed large-cell (B-cell) lymphoma, suggesting that the follicular stimulation noted histologically played a role in the development of this neoplasm. These data show that there is a progressive destruction of lymph node follicles that correlates with the progression of the disease and that lymph node histologic features may provide important prognostic information. 相似文献
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Normal and diseased isolated lungs: high-resolution CT 总被引:8,自引:0,他引:8
8.
MRL/lpr-->severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells.
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D Ashany J J Hines A E Gharavi J Mouradian J Drappa K B Elkon 《Clinical and experimental immunology》1992,90(3):466-475
MRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent graft-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or old lpr mice or with lpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from old lpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described for lpr spleen-->+/+ chimeras. SCID mice engrafted with spleen cells from young lpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr-->SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr-->SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoantibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice. 相似文献
9.
OBJECTIVE: To examine the effect of 17beta-estradiol on the severity of the cardinal signs of PD in postmenopausal women. BACKGROUND: Although the impact of estrogens on the manifestations of PD has not been subjected to rigorous study, their use is generally thought to be associated with a detrimental antidopaminergic effect. METHODS: A double-blind, placebo-controlled, two-arm crossover study of high-dose transdermal 17beta-estradiol was conducted in eight postmenopausal women with mild to moderate PD, all but one of whom exhibited levodopa-induced dyskinesias. Patients were randomized initially to either hormonal treatment or placebo for 2 weeks, followed by a 2-week washout period, and then another 2-week crossover treatment period. Active treatment employed four skin patches each releasing 0.1 mg of estradiol daily, replaced every 2 to 3 days. RESULTS: After 10 days of treatment a significant reduction was observed in the antiparkinsonian threshold dose of IV levodopa. Mean duration and magnitude of the antiparkinsonian response to threshold or high doses of levodopa were unchanged, and dyskinesia scores were unaltered during 17beta-estradiol treatment compared with placebo. No worsening in "on" time or motor ratings with estrogen treatment was documented. CONCLUSIONS: 17beta-estradiol appears to display a slight prodopaminergic (or antiparkinsonian) effect without consistently altering dyskinesias. Standard postmenopausal replacement therapy with transdermal 17beta-estradiol is likely to be well tolerated by many female parkinsonian patients. 相似文献
10.
Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death 总被引:10,自引:0,他引:10
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Junn E Taniguchi H Jeong BS Zhao X Ichijo H Mouradian MM 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(27):9691-9696
Investigations into the cellular and molecular biology of genes that cause inherited forms of Parkinson's disease, as well as the downstream pathways that they trigger, shed considerable light on our understanding the fundamental determinants of life and death in dopaminergic neurons. Homozygous deletion or missense mutation in DJ-1 results in autosomal recessively inherited Parkinson's disease, suggesting that wild-type DJ-1 has a favorable role in maintaining these neurons. Here, we show that DJ-1 protects against oxidative stress-induced cell death, but that its relatively modest ability to quench reactive oxygen species is insufficient to account for its more robust cytoprotective effect. To elucidate the mechanism of this cell-preserving function, we have screened out the death protein Daxx as a DJ-1-interacting partner. We demonstrate that wild-type DJ-1 sequesters Daxx in the nucleus, prevents it from gaining access to the cytoplasm, from binding to and activating its effector kinase apoptosis signal-regulating kinase 1, and therefore, from triggering the ensuing death pathway. All these steps are impaired by the disease-causing L166P mutant isoform of DJ-1. These findings suggest that the regulated sequestration of Daxx in the nucleus and keeping apoptosis signal-regulating kinase 1 activation in check is a critical mechanism by which DJ-1 exerts its cytoprotective function. 相似文献