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1.
The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation 总被引:7,自引:10,他引:7
Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV-specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T-cell-depleted (TCD) grafts from EBV-seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV- specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T-cell populations that occurred contemporaneously with the clinical regression of disease. 相似文献
2.
胎儿和新生儿溶血病(HDFN)可导致严重的围产期疾病,包括高胆红素血症及其引起的核黄疸。血红素分子解离为胆红素并产生免疫介导的溶血。它与白蛋白结合后转运到肝细胞,再由尿苷二磷酸葡萄糖醛酸转移酶(UGT)酶家族作用而葡萄糖醛酸化。对于人类,这种代谢途径中主要的酶是胆红素- 相似文献
3.
Outcomes in splenic marginal zone lymphoma: analysis of 107 patients treated in British Columbia 下载免费PDF全文
Katharine H. Xing Amrit Kahlon Brian F. Skinnider Joseph M. Connors Randy D. Gascoyne Laurie H. Sehn Kerry J. Savage Graham W. Slack Tamara N. Shenkier Richard Klasa Alina S. Gerrie Diego Villa 《British journal of haematology》2015,169(4):520-527
Splenic marginal zone lymphoma (SMZL) accounts for less than 2% of all non‐Hodgkin lymphomas. We identified 107 cases diagnosed with SMZL between 1985 and 2012 from the British Columbia Cancer Agency Centre for Lymphoid Cancer and Lymphoma Pathology Databases. Patient characteristics were: median age 67 years (range 30–88), male 40%, stage IV 98%, splenomegaly 93%, bone marrow involvement 96%, peripheral blood involvement 87%. As initial treatment, 52 underwent splenectomy (10 with chemotherapy), 38 chemotherapy alone (21 chemoimmunotherapy containing rituximab, 1 rituximab alone), two antivirals for hepatitis C, and 15 were only observed. The 10‐year overall survival for first‐line splenectomy versus chemotherapy was 61% and 42%, respectively [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·26–0·88, P = 0·017]. The 10‐year failure‐free survival (FFS) after first‐line splenectomy vs chemotherapy was 39% and 14%, respectively (HR 0·48, 95% CI 0·28–0·80, P = 0·004). Among the 38 patients who received first‐line chemotherapy, FFS was similar between those receiving rituximab (n = 22) and those who did not (n = 16) (HR 0·64, 95% CI 0·31–1·34, P = 0·238). Fifteen patients transformed to aggressive lymphoma with median time to transformation of 3·5 years (range 6 months to 12 years) and the 10‐year transformation rate was 18%. In conclusion, splenectomy remains a reasonable treatment for patients with SMZL. 相似文献
4.
Adhesion of platelets to surface-bound fibrinogen under flow 总被引:2,自引:2,他引:2
After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain. 相似文献
5.
6.
Shenkier TN Voss N Chhanabhai M Fairey R Gascoyne RD Hoskins P Klasa R Morris J O'Reilly SE Pickles T Sehn L Connors JM 《Cancer》2005,103(5):1008-1017
BACKGROUND: The objective of this study was to evaluate the clinical outcome of a population-based cohort of immunocompetent patients with primary central nervous system lymphoma (PCNSL) treated with 3 different strategies over 13 years. METHODS: One hundred twenty-two consecutive patients (median age, 66 years) with PCNSL were identified. Three treatment strategies were employed: 1) whole-brain irradiation with (from January, 1990, to June, 1991) or without (from April, 1995, to December, 1999) cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-type chemotherapy (n=50 patients); 2) combined-modality therapy, including 1 g/m2 methotrexate plus whole-brain irradiation (from July, 1991, to March, 1995; n=34 patients); and 3) 8 g/m2 methotrexate alone (from January, 2000, to March, 2003) with whole-brain irradiation reserved for those with progressive disease (n=38 patients). Treatment failure was defined as progressive disease, disease recurrence, death from toxicity or lymphoma, or toxicity that necessitated a change in primary treatment. RESULTS: The median failure-free survival was 7 months, and the median overall survival (OS) was 17 months. The median OS was similar in all 3 eras. In this population-based analysis, one-third of patients did not receive the treatment strategy of the era. Therefore, the data also were analyzed by treatment received. On multivariate analysis (including era of treatment), 3 factors-age > 60 years, lactate dehydrogenase > normal, and omission of methotrexate-were associated significantly with poorer OS (hazard ratio: 2.3, 2.2, and 2.3, respectively). CONCLUSIONS: Outcomes for a general population with PCNSL remained constant despite different treatment strategies over three eras. For the two-thirds of patients who could receive potentially curative treatment, age, lactate dehydrogenase level, and receipt of > or = 1 g/m2 methotrexate appeared to be important determinants of OS. 相似文献
7.
Lester R Li C Phillips P Shenkier TN Gascoyne RD Galbraith PF Vickars LM Leitch HA 《Leukemia & lymphoma》2004,45(9):1881-1885
8.
Background The contribution of dysmotility to dysphagia in oesophageal cancer is unclear.
Aim To examine oesophageal motility in patients with oesophageal carcinoma and to assess the effect of chemoradiotherapy on motility.
Methods Stationary manometry and 24-hour pH-metry were performed in 12 patients with oesophageal carcinoma and one week following
completion of chemoradiotherapy using 5-fluorouracil (5-FU), cisplatin and 40Gy radiotherapy.
Results All patients had abnormal motility prior to treatment. Peristalsis was impaired in 11 patients with a mean (SD) of 25% (9)
of waves normally propagated. Eight patients had 20% or more simultaneous waves. Following chemoradiotherapy, the percentage
of waves normally propagated increased from 25% (9) to 52% (10) (p < 0.03) and normal peristalsis was restored in four patients.
The percentage of simultaneous waves decreased from 38% (11) to 21.6% (10) (p=0.129) while the percentage of dropped or increased
waves decreased from 20% (11) to 8.3% (4) (p=0.264).
Conclusions Oesophageal motility is disturbed in oesophageal cancer. Dysphagia in oesophageal cancer may be partly explained by oesophageal
dysmotility. This is improved by chemotherapy. 相似文献
9.
Five cases of penile metastases are presented. Axial and sagittal T1-weighted and T2-weighted scans were performed in all patients. In some, coronal images were also obtained. The penile metastases were most often seen as discrete masses in the corpora cavernosa or corpus spongiosum. An atypical pattern of diffuse infiltration is also illustrated. Limitations of cavernosography, ultrasound (US) and computed tomography (CT) are discussed. The magnetic resonance (MR) features of penile metastases and possible role MR may have in the management of these patients are described. 相似文献
10.
Williams TN; Maitland K; Phelps L; Bennett S; Peto TE; Viji J; Timothy R; Clegg JB; Weatherall DJ; Bowden DK 《QJM : monthly journal of the Association of Physicians》1997,90(12):751-757
We studied the aetiology of malnutrition in a cohort of 1511 children <
10 years old in Espiritu Santo, Vanuatu. Malnutrition was categorized using
standard anthropometric criteria as: underweight [weight-for-age (WA) Z
score < -2], wasting [weight-for-height (WH) Z < -2], or stunting
[height-for-age (HA) Z < -2]. On multiple logistic regression analysis,
the only factors significantly associated with wasting were age < 5
years [OR (95% CI) 1.8 (1.2-2.9), p = 0.01] and having suffered one or more
episodes of clinical P. vivax malaria in the 6 months preceding nutritional
assessment [OR 2.4 (1.3-4.4), p = 0.006]. The incidence of P. vivax
infection was significantly higher during the 6 months preceding assessment
in underweight vs. non-underweight children [incidence rate ratio (IRR) 2.6
(1.5-4.4), p < or = 0.0001). These groups had similar incidences of
clinical P. falciparum infection during the same period [IRR 1.1 (0.57-2.1)
p = 0.8] and of either species during the 6 months following assessment
[IRR P. vivax 1.3 (0.9- 2.0) p = 0.2; IRR P. falciparum 1.3 (0.9-1.9) p =
0.2]. In these children, P. vivax malaria was a major predictor of acute
malnutrition; P. falciparum was not. Wasting neither predisposed to nor
protected against malaria of either species. Although P. vivax malaria is
generally regarded as benign, it may produce considerable global mortality
through malnutrition.
相似文献