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121.
122.
Background
The selection of optimal donor is crucial for successful hematopoietic stem cell transplantation (HSCT). Thereby, it is appropriate to know, in addition to basic human leukocyte antigen (HLA) gene matches, other immunogenic or nonimmunogenic parameters predicting the outcome of transplant.Objective
A unified approach is necessary to provide a comprehensive view of the patient-donor compatibility characterization outside of standard HLA genes. The approach should be applicable as a tool for optimizing procedures for extended donor typing and/or verification typing of a donor.Methods
The study used the summary, unification, and innovation of existing practical knowledge and experience of the Czech National Marrow Donor Registry of various factors beyond HLA matching with impact on transplant outcome.Results
An information technology system–implemented procedure (a verification algorithm) is presented as the decision support approach for prematurely discarding less suitable donors from the transplantation process. It is intended primarily for the transplant specialist to help establish optimal procedures for verifying and determining donor critical factors.Conclusions
A process defining HLAs, killer cell immunoglobulin–like receptors, and cytokine typing strategies was proposed to provide support to a transplant specialist in refining the choice of a suitable donor. 相似文献123.
Sutter TR He XR Dimitrov P Xu L Narasimhan G George EO Sutter CH Grubbs C Savory R Stephan-Gueldner M Kreder D Taylor MJ Lubet R Patterson TA Kensler TW 《Molecular cancer therapeutics》2002,1(14):1283-1292
Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds. 相似文献
124.
Analysis of the third‐ and fourth‐generation cephalosporin use for the treatment of infections caused by Gram‐negative bacteria in hospital settings
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125.
Martin?Dimitrov Pencho?Venkov Margarita?PeshevaEmail author 《Archives of toxicology》2011,85(1):67-74
In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility
of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased
level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration
and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene,
ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium,
lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment
with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic,
glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1
retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide
anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased
hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with
carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary
and key role in determination the selective response of Ty1 test to carcinogenic genotoxins. 相似文献
126.
127.
Lin R Buijse L Dimitrov MR Dohmen P Kosol S Maltby L Roessink I Sinkeldam JA Smidt H Van Wijngaarden RP Brock TC 《Ecotoxicology (London, England)》2012,21(5):1550-1569
The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks). 相似文献
128.
Arsova-Sarafinovska Z Matevska N Eken A Petrovski D Banev S Dzikova S Georgiev V Sikole A Erdem O Sayal A Aydin A Dimovski AJ 《International urology and nephrology》2009,41(1):63-70
Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative
damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low
GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations.
Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte
GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective
effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk
of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20–0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group
was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90
subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate
cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may
play an important role in prostate carcinogenesis. 相似文献
129.
Cholestasis protects the liver from ischaemic injury and post-ischaemic inflammation in the mouse 总被引:2,自引:0,他引:2
Georgiev P Navarini AA Eloranta JJ Lang KS Kullak-Ublick GA Nocito A Dahm F Jochum W Graf R Clavien PA 《Gut》2007,56(1):121-128
BACKGROUND AND HYPOTHESIS: Cholestasis is associated with high morbidity and mortality in patients undergoing major liver surgery, but the mechanisms responsible remain elusive. Increased ischaemic liver injury and inflammation may contribute to the poor outcome. METHODS: Common bile duct ligation (biliary obstruction with hyperbilirubinaemia) or selective ligation of the left hepatic duct (biliary obstruction without hyperbilirubinaemia) was performed in C57BL/6 mice before 1 h of hepatic ischaemia and 1, 4 or 24 h of reperfusion. Infection with the intracellular hepatic pathogen Listeria monocytogenes for 12 and 48 h was used to study ischaemia-independent hepatic inflammation. RESULTS: Cholestatic mice showed considerable protection from ischaemic liver injury as determined by transaminase release, histological liver injury and neutrophil infiltration. In cholestatic mice, reduced injury correlated with a failure to activate nuclear factor kappaB (NFkappaB) and tumour necrosis factor alpha (TNFalpha) mRNA synthesis, two key mediators of post-ischaemic liver inflammation. After selective bile duct ligation, both the ligated and the non-ligated lobes showed blocked activation of NFkappaB as well as reduced induction of TNFalpha mRNA synthesis and neutrophil infiltration. By contrast, infection with L monocytogenes showed comparable activation of NFkappaB and hepatic recruitment of neutrophils 12 h after infection. CONCLUSION: Cholestasis does not increase but rather dramatically protects the liver from ischaemic injury and inflammation. This effect is mediated by a systemic factor, but not bilirubin, and is associated with a preserved capacity to trigger an inflammatory response to other stimuli such as a bacterial pathogen. 相似文献
130.