运用彗星试验检测麝香酮对苯并(a)芘致DNA损伤的影响

[目的]研究麝香酮在体内试验条件下 ,对苯并(a)芘致小鼠肝和肺细胞核DNA损伤的影响。[方法]SENCAR雄性成年小鼠灌胃 ,分别单独给予苯并(a)芘125、250、500mg/(kg·bw·d)和用麝香酮250、500mg/(kg·bw·d)预处理后再给予苯并(a)芘125mg/(kg·bw·d) ,处死动物后分离小鼠肝和肺组织细胞核做彗星测试 ,采用CCD成像分析系统分析彗星 ,取尾相 (olivertailmoment,OTM)值判断DNA损伤强度。[结果]苯并(a)芘各浓度组均出现小鼠肝和肺细胞OTM值的明显增加 ,高浓度麝香酮[500mg/(kg·bw·d)]可引起小鼠肝细胞OTM值的轻度增加。用高浓度麝香酮预处理小鼠后再给予苯并(a)芘 ,所观察到的肝、肺的DNA损伤 (肝OTM值为7.6、肺为11)较之苯并(a)芘单独染毒引起的DNA损伤(肝OTM值为5.1、肺为6.9)增加更明显。[结论]麝香酮能明显增强苯并(a)芘所致的DNA损伤作用     

Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival.

PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted.     

Treatment of refractory Hodgkin's lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody.

PURPOSE: Hodgkin's lymphoma (HL) has been demonstrated to be a good target for immunotherapy since lymphocyte activation markers such as CD30 are expressed in high numbers on the malignant cells. Thus, we developed a new radioimmunoconjugate consisting of the murine anti-CD30 monoclonal antibody (MAb) Ki-4 labeled with iodine-131 ((131)I). PATIENTS AND METHODS: The biodistribution of (131)I-Ki-4 was assessed via dosimetry after preinfusion of 5 mg native Ki-4 followed by 250 to 300 MBq (131)I-labeled Ki-4. Whole-body scintigraphy was performed 1 hour, 24 hours, 48 hours, 72 hours, and 6 days after the infusion. Dosimetry was calculated using the programs NucliDose ICON-IDL (version 5.0.2; Siemens, Erlanger, Germany) and MIRDOSE (version 3.1; Oak Ridge National Laboratories; Oak Ridge, TN). The therapeutic dose was given on day 8 after preinfusion of unlabeled Ki-4. RESULTS: We treated 22 patients with relapsed or refractory CD30-positive HL. Preinfusion of 5 mg native Ki-4 was sufficient to bind the soluble CD30. Imaging demonstrated localization of involved areas measuring 5 cm in diameter or more in four patients and 2.5 cm in one patient. Patients received total body doses of 0.035 Gy to 0.99 Gy. Acute toxicity was mild with grade 1 fatigue in 19 of 22 assessable patients. Seven patients experienced grade 4 degrees hematotoxicity 4 to 8 weeks after treatment. Response included one complete remission, five partial remissions, and three minor responses. CONCLUSION: Treatment with (131)I-Ki-4 is effective but can be associated with severe hematotoxicity.     

The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a

The inhibitor cystine knot (ICK) is an unusual three-disulfide architecture in which one of the disulfide bonds bisects a loop formed by the two other disulfide bridges and the intervening sections of the protein backbone. Peptides containing an ICK motif are frequently considered to have high levels of thermal, chemical and enzymatic stability due to cross-bracing provided by the disulfide bonds. Experimental studies supporting this contention are rare, in particular for spider-venom toxins, which represent the largest diversity of ICK peptides. We used ω-hexatoxin-Hv1a (Hv1a), an insecticidal toxin from the deadly Australian funnel-web spider, as a model system to examine the contribution of the cystine knot to the stability of ICK peptides. We show that Hv1a is highly stable when subjected to temperatures up to 75 °C, pH values as low as 1, and various organic solvents. Moreover, Hv1a was highly resistant to digestion by proteinase K and when incubated in insect hemolymph and human plasma. We demonstrate that the ICK motif is essential for the remarkable stability of Hv1a, with the peptide’s stability being dramatically reduced when the disulfide bonds are eliminated. Thus, this study demonstrates that the ICK motif significantly enhances the chemical and thermal stability of spider-venom peptides and provides them with a high level of protease resistance. This study also provides guidance to the conditions under which Hv1a could be stored and deployed as a bioinsecticide.     

Impact of Food Intake on Liver Stiffness Determined by 2-D Shear Wave Elastography: Prospective Interventional Study in 100 Healthy Patients

The aim was to evaluate the influence of food intake on liver stiffness measurement (LSM), performed with 2-D shear wave elastography (Logiq E9, GE Medical Systems, Wauwatosa, WI, USA). One hundred healthy volunteers were prospectively enrolled. Mean age was 25.8 (19–55) y, and mean body mass index was 22.43 (17.3–30.8) kg/m². Patients fasted for at least 3 h and subsequently ingested a liquid meal of 800 kcal. Liver stiffness and portal vein velocity were measured before and after food intake. Food intake resulted in significantly higher LSM values compared with baseline LSM (5.74 ± 0.94 kPa vs. 4.80 ± 0.94 kPa, p < 0.001). On multiple linear regression analysis, body mass index was significantly positively correlated with the LSM increase after food intake (p?=?0.01). No correlation between the increase in LSM and the increase in post-prandial portal vein velocity was observed (r?=?0.09). In summary, food intake has a significant influence on LSM. There is an 11% risk of misclassifying non-fasting, healthy patients as having significant fibrosis.     

Exact Solution of a Constraint Optimization Problem for the Thermoelectric Figure of Merit

In the classical theory of thermoelectricity, the performance integrals for a fully self-compatible material depend on the dimensionless figure of merit zT. Usually these integrals are evaluated for constraints z =  const. and zT =  const., respectively. In this paper we discuss the question from a mathematical point of view whether there is an optimal temperature characteristics of the figure of merit. We solve this isoperimetric variational problem for the best envelope of a family of curves z(T)T.