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51.
Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease 总被引:7,自引:2,他引:7
Gruss HJ; Hirschstein D; Wright B; Ulrich D; Caligiuri MA; Barcos M; Strockbine L; Armitage RJ; Dower SK 《Blood》1994,84(7):2305-2314
CD40 was originally described as a B-cell-restricted antigen and was subsequently found to be a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 is also expressed on dendritic cells, thymic epithelium, monocytes, and some carcinoma cell lines, and plays a critical role in cell contact-dependent activation. Primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells, the presumed malignant cells of Hodgkin's disease (HD); were found to express high levels of cell surface CD40. We found that recombinant CD40 ligand (CD40L) induced interleukin-8 (IL-8) secretion and enhanced IL-6, TNF, and lymphotoxin-alpha (LT-alpha/TNF-beta) release from cultured H-RS cells. These cytokines play a significant role in the clinical presentation and pathology of HD, a tumor of cytokine-producing cells. CD40L had no mitogenic activity for HD-derived cell lines. In contrast, CD40L enhanced expression of costimulatory molecules intracellular adhesion molecule-T and B7-1 on cultured H-RS cells, both of which are overexpressed on primary H-RS cells. In addition, CD40L induced a 40% to 60% reduction of the expression of the HD-associated CD30 antigen, another member of the TNF receptor superfamily. Primary and cultured H- RS cells express not only CD30, but also CD40. CD40L has pleiotropic biologic activities on H-RS cells, and the CD40-CD40L interaction might be a critical element in the deregulated cytokine network and cell contact-dependent activation cascade typical for HD. 相似文献
52.
Payal P. Khincha Ingrid M. Wentzensen Neelam Giri Blanche P. Alter Sharon A. Savage 《British journal of haematology》2014,165(3):349-357
Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome and telomere biology disorder characterized by dysplastic nails, reticular skin pigmentation and oral leucoplakia. Androgens are a standard therapeutic option for bone marrow failure in those patients with DC who are unable to undergo haematopoietic stem cell transplantation, but there are no systematic data on its use in those patients. We evaluated haematological response and side effects of androgen therapy in 16 patients with DC in our observational cohort study. Untreated DC patients served as controls. Seventy percent of treated DC patients had a haematological response with red blood cell and/or platelet transfusion independence. The expected age‐related decline in telomere length was noted in androgen‐treated patients. All treated DC patients had at least one significant lipid abnormality. Additional treatment‐related findings included a significant decrease in thyroid binding globulin, accelerated growth in pre‐pubertal children and splenic peliosis in two patients. Liver enzymes were elevated in both androgen‐treated and untreated patients, suggesting underlying liver involvement in DC. This study suggests that androgen therapy can be effectively used to treat bone marrow failure in DC, but that side effects need to be closely monitored. 相似文献
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Jada G. Hamilton PhD MPH Sadie P. Hutson PhD RN WHNP BC Richard P. Moser PhD Sarah C. Kobrin PhD MPH Amy E. Frohnmayer MA Blanche P. Alter MD MPH Paul K. J. Han MD MA MPH 《Annals of behavioral medicine》2013,46(2):204-216
Background
Effects of different sources of medical uncertainty on people’s health-related cognitions, emotions, and decision making have yet to be systematically examined.Purpose
The aim of this study is to examine how uncertainties arising from different sources are associated with decision making regarding stem cell transplantation in Fanconi anemia, a rare, inherited bone marrow failure syndrome that typically presents during childhood.Methods
Data were collected through a cross-sectional survey of 178 parents of 126 Fanconi anemia patients.Results
Two distinct sources of uncertainty were associated with decision outcomes: probability was associated with a lower likelihood of choosing stem cell transplantation, and ambiguity due to conflicting expert opinions was associated with greater decision-making difficulty. Concern about transplantation may mediate these associations.Conclusions
Different sources of uncertainty have different effects on Fanconi anemia treatment decisions, which may be mediated by parents’ emotional reactions. Further research is needed to elucidate these effects and help Fanconi anemia families cope with uncertainty. 相似文献57.
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Patients with biallelic mutations in BRCA2 are in Fanconi anaemia group D1. We analysed the severity of the mutations in 27 cases, classified according to their association with breast cancer in heterozygotes, and their predicted functional effect. Twenty mutations were frameshifts or truncations, three involved splice sites, five were missense variants of unknown severity and two were benign polymorphisms. Five patients had VACTERL-H association. Leukaemia was reported in 13 patients, and solid tumours in 15; 6 patients had two or more malignancies. The cumulative probability of any malignancy was 97% by age 5.2 years. IVS7+1G-->A and IVS7+2T-->G were associated with AML, and 886delGT and 6174delT with brain tumours. However, patients with other alleles remained at very high risk of these events. Missense mutations formed a distinct cluster in a highly conserved region of the BRCA2 protein. The small group of patients with biallelic mutations in BRCA2 is distinctive in the severity of the phenotype, and early onset and high rates of leukaemia and specific solid tumours, and may comprise an extreme variant of Fanconi anaemia. Several of the alleles were not associated with cancer in presumed carriers, and thus counselling presents more uncertainties than usual. 相似文献
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60.
Retroperitoneal varices simulating masses 总被引:1,自引:0,他引:1
Howard R. Gould M.D. Sacha Benjamin Albert J. Alter Andrew B. Crummy David T. Atwell 《Abdominal imaging》1982,7(1):335-339
Retroperitoneal varices in portal hypertension may simulate the appearance of neoplastic masses or adenopathy. Contrast-enhanced CT scans clarify the diagnosis of large vascular channels. Three patients with large retroperitoneal varices demonstrated on CT had confirmation by angiography. 相似文献