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101.
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IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates 总被引:14,自引:3,他引:11
Fry TJ Moniuszko M Creekmore S Donohue SJ Douek DC Giardina S Hecht TT Hill BJ Komschlies K Tomaszewski J Franchini G Mackall CL 《Blood》2003,101(6):2294-2299
Interleukin-7 (IL-7) is important for thymopoiesis in mice and humans because IL-7 receptor alpha (IL-7Ralpha) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis. Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)-infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4(+) and CD8(+) subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC(+)) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4- depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4(+) and CD8(+) T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination. 相似文献
103.
Spinal injuries in motorcycle crashes: patterns and outcomes 总被引:4,自引:0,他引:4
Robertson A Giannoudis PV Branfoot T Barlow I Matthews SJ Smith RM 《The Journal of trauma》2002,53(1):5-8
BACKGROUND: The purpose of this study was to determine patterns of spinal injury and clinical outcomes resulting from motorcycle crashes. METHODS: We analyzed data collected on 1,121 motorcyclists involved in road traffic accidents (from 1993-2000) and identified those who had sustained a spinal injury. RESULTS: Spinal injury occurred in 126 (11.2%) riders (112 male riders [88.9%] and 14 female riders [11.1%]), with a mean age of 30.2 years (range, 16-61 years) and Injury Severity Score of 18.8 (range, 4-66). Isolated injuries to the spine occurred in 30 (23.8%) riders. The thoracic spine was injured in 69 (54.8%), the lumbar spine in 37 (29.4%), and the cervical spine in 34 (27.0%) cases. Multiple vertebral levels were affected in 54 (42.9%). Neurologic injury occurred in 25 riders (19.8%), with complete distal neurologic injury in 14 (4 cervical, 9 thoracic, and 1 lumbar). Eleven (8.7%) patients required spinal surgery. There were 13 (10.3%) deaths. CONCLUSION: The thoracic spine is the most commonly injured spinal region in motorcycle crashes. Multiple level injuries are common. Protocols concentrating on the radiographic clearance of the cervical region may miss a significant number of spinal injuries. Vigilance is required in assessing these patients, who often have multiple injuries. 相似文献
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N. A. Andrews A. S. Jones T. R. Helliwell A. R. Kinsella 《British journal of cancer》1997,75(10):1474-1480
Reductions in cell-cell adhesion and stromal and vascular invasion are essential steps in the progression from localized malignancy to metastatic disease. In this study, changes in the expression of the components of the E-cadherin-catenin cell adhesion complex have been investigated using immunohistochemical techniques in primary tumours and nodal metastases from 36 patients with squamous cell carcinoma of the head and neck. For 14 patients the corresponding primary and nodal metastases samples were available. None of the 51 samples showed normal E-cadherin expression when compared with either the adjacent normal squamous epithelium or with normal colonic epithelium that was used as positive control material. In 88% of primary tumours fewer than 50% of cells exhibited normal membranous E-cadherin expression. Loss of membranous E-cadherin expression was more extensive in poorly differentiated carcinomas while, in individual carcinomas, membranous E-cadherin expression was stronger in those parts of the neoplasm that expressed the differentiation marker involucrin. Expression of beta-catenin generally paralleled that of E-cadherin, but in 12 cases there was strong membranous beta-catenin expression in samples that exhibited predominantly cytoplasmic E-cadherin labelling. Expression of alpha-catenin was generally weak and did not correlate with the expression of either beta-catenin or E-cadherin. Marked intratumoral heterogeneity for protein expression was evident for all antibodies, and the abnormal expression of the catenins is a novel finding. E-cadherin is expressed more intensely in cells with greater squamous differentiation, but there was no correlation between the decreased expression of any of the adhesion molecules of the E-cadherin complex tested and local recurrence, metastasis or survival. The loss of expression of components of the E-cadherin complex is a common abnormality in squamous carcinomas and, while it may be permissive for metastasis, it does not appear to be the only determinant of this process. 相似文献
107.
The authors report a female with full-blown hypohidrotic ectodermal dysplasia and survey the literature concerning cases of the complete syndrome in females. The condition is ordinarily inherited as an X-linked recessive trait but evidence suggests that other patterns of inheritance may occur. There are several examples of probable autosomal recessive inheritance. The syndrome appears to be an example of genetic heterogeneity.This study was made possible in part by U.S.P.H.S. Program Grant in Oral Pathology, DE-1770. 相似文献
108.
Toby Gelfand 《Canadian Medical Association journal》1978,118(11):1374
109.
A.Bleakley Chandler MD Irving Chapman MD Leif R. Erhardt MD William C. Roberts MD FACC Colin J. Schwartz MD D. Sinapius MD David M. Spain MD FACC Sol Sherry MD FACC Paul M. Ness MD Toby L. Simon MD 《The American journal of cardiology》1974,34(7):823-833
In recent years the widely held concept that coronary thrombi cause myocardial infarcts has been seriously questioned. On the basis of pathologic studies, several reports have suggested that coronary thrombi do not cause infarcts but instead are the result of infarction. Should these findings become generally substantiated, the antithrombotic approach to the prevention and therapy of ischemic heart disease must be revised. This workshop was organized to examine more closely this issue and to sort out reasons for such divergent views of the role of thrombosis in the pathogenesis of myocardial infarction. 相似文献
110.