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Goodyear OC Dennis M Jilani NY Loke J Siddique S Ryan G Nunnick J Khanum R Raghavan M Cook M Snowden JA Griffiths M Russell N Yin J Crawley C Cook G Vyas P Moss P Malladi R Craddock CF 《Blood》2012,119(14):3361-3369
Strategies that augment a GVL effect without increasing the risk of GVHD are required to improve the outcome after allogeneic stem cell transplantation (SCT). Azacitidine (AZA) up-regulates the expression of tumor Ags on leukemic blasts in vitro and expands the numbers of immunomodulatory T regulatory cells (Tregs) in animal models. Reasoning that AZA might selectively augment a GVL effect, we studied the immunologic sequelae of AZA administration after allogeneic SCT. Twenty-seven patients who had undergone a reduced intensity allogeneic transplantation for acute myeloid leukemia were treated with monthly courses of AZA, and CD8(+) T-cell responses to candidate tumor Ags and circulating Tregs were measured. AZA after transplantation was well tolerated, and its administration was associated with a low incidence of GVHD. Administration of AZA increased the number of Tregs within the first 3 months after transplantation compared with a control population (P = .0127). AZA administration also induced a cytotoxic CD8(+) T-cell response to several tumor Ags, including melanoma-associated Ag 1, B melanoma antigen 1, and Wilm tumor Ag 1. These data support the further examination of AZA after transplantation as a mechanism of augmenting a GVL effect without a concomitant increase in GVHD. 相似文献
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Synthesis,Antioxidant, and Xanthine Oxidase Inhibitory Activities of 5‐[4‐[2‐(5‐Ethyl‐2‐pyridinyl)ethoxy]phenyl]methyl]‐2,4‐thiazolidinedione Derivatives 下载免费PDF全文
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Synthesis and antimicrobial study of novel heterocyclic compounds from hydroxybenzophenones 总被引:1,自引:0,他引:1
Khanum SA Shashikanth S Umesha S Kavitha R 《European journal of medicinal chemistry》2005,40(11):1156-1162
The triazolothiadiazine analogues 6a-e were obtained via a multistep synthesis sequences beginning with the hydroxybenzophenones 1a-e. Hydroxybenzophenones on reaction with ethyl chloroacetate affords ethyl (2-aroylaryloxy)acetates 2a-e which on treatment with hydrazine hydrate yields 2-(2-aroylaryloxy)acetohydrazides 3a-e. Intramolecular cyclization of 3a-e with carbon disulfide affords 5-(2-aroylaryloxy)methyl-1,3,4-oxadiazole-2-(3H)thiones 4a-e, which on treatment with hydrazine hydrate yields 4-amino-5-(2-aroyl aryloxy)methyl-1,2,4-triazole-3-(2H)thiones 5a-e. Condensation of 5a-e with alpha-halocarbonyl compound results in 3-(2-aroylaryloxy)methyl-6-phenyl-1,2,4-triazolo[3,4-b][1,3,4] thiadiazine 6a-e analogues. The compounds 4a-e, 5a-e and 6a-e were tested against variety of fungal and bacterial strains in comparison to fluconazole and chloramphenicol, respectively. 相似文献
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Prytherch DR Ridler BM Ashley S;Audit Research Committee of the Vascular Society of Great Britain Ireland 《The British journal of surgery》2005,92(6):714-718
BACKGROUND: Reducing the data required for a national vascular database (NVD) without compromising the statistical basis of comparative audit is an important goal. This work attempted to model outcomes (mortality and morbidity) from a small and simple subset of the NVD data items, specifically urea, sodium, potassium, haemoglobin, white cell count, age and mode of admission. METHODS: Logistic regression models of risk of adverse outcome were built from the 2001 submission to the NVD using all records that contained the complete data required by the models. These models were applied prospectively against the equivalent data from the 2002 submission to the NVD. RESULTS: As had previously been found using the P-POSSUM (Portsmouth POSSUM) approach, although elective abdominal aortic aneurysm (AAA) repair and infrainguinal bypass (IIB) operations could be described by the same model, separate models were required for carotid endarterectomy (CEA) and emergency AAA repair. For CEA there were insufficient adverse events recorded to allow prospective testing of the models. The overall mean predicted risk of death in 530 patients undergoing elective AAA repair or IIB operations was 5.6 per cent, predicting 30 deaths. There were 28 reported deaths (chi(2) = 2.75, 4 d.f., P = 0.600; no evidence of lack of fit). Similarly, accurate predictions were obtained across a range of predicted risks as well as for patients undergoing repair of ruptured AAA and for morbidity. CONCLUSION: A 'data economic' model for risk stratification of national data is feasible. The ability to use a minimal data set may facilitate the process of comparative audit within the NVD. 相似文献
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