An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications

To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.     

Signaling effects of α-thrombin and SFLLRN in rat glioma C6 cells

Effects of thrombin on brain cells, including change of neurite outgrowth and astrocyte shape, are described, but the molecular mechanisms are unclear. We investigated the effects of human α-thrombin and a six amino acid thrombin receptor activating peptide (TRAP-6, SFLLRN) on [Ca²⁺]₁, phosphoinositide hydrolysis, and protein kinase C in rat glioma C₆ cells. Stimulation of C₆ cells with both α-thrombin and TRAP-6 resulted in [Ca²⁺]₁ mobilization, [³H]Inositol phosphate response, and enhanced immunoreactivity of the protein kinase C (PKC) isoenzymes α, β, γ, δ, and ϵ. Results suggest that α-thrombin and TRAP-6 activate at least partially the same intracellular signaling pathways in rat glioma C₆ cells, which is evidence for involvement of “tethered ligand” receptor in thrombin induced signaling in glioma C₆ cells. © 1996 Wiley-Liss, Inc.     

ArF-excimer laser–induced secondary radiation in photoablation of biological tissue

Secondary radiation, emitted during and after the irradiation of corneal, dermal, and dental tissue by an ArF-excimer laser (193 nm), was qualitatively and quantitatively characterized. Emission of secondary radiation was found in the range of 200–800 nm. The intensity of secondary radiation in the range of 200–315 nm (UVC and UVB) is ∼20% of the total intensity at high laser fluences (>2 J/cm²), and ∼50% at moderate laser fluences (<500 mJ/cm²); 10 μJ/cm² in the UVC and UVB were measured at the sample surface, at fluences (<1J/cm²) which are of relevance for clinical procedures on soft tissues. In dental tissue processing, very high fluences (>5 J/cm²) are required. As a consequence, laser–induced plasma formation can be observed. Secondary radiation can be used as a visible guide for selective removal of carious altered tissue. The data we have found might be of assistance in estimating potential hazards for future mutagenic studies in the field. © 1994 Wiley-Liss, Inc.     

地高辛抗血清对老龄大鼠心肌缺氧复氧损伤影响的体外实验

目的:观察内洋地黄素水平在老龄大鼠心肌细胞缺氧复氧损伤中的变化以及地高辛抗血清的保护作用。方法:实验于2005-04/05在皖南医学院病理生理教研室完成。取10只24月龄和10只6月龄雄性普通级SD大鼠,分别制备青年和老龄大鼠心肌细胞匀浆,老龄和成年大鼠为两大组,每组分为7小组,即每只大鼠心肌随机分到各小组中,共计14小组,每组10支试管。正常对照组:给予CO2和O2的混合气体(1∶19)通气40min;缺氧复氧组:CO2,O2,N2混合气体(5∶4∶91)通气20min后换成CO2和O2的混合气体(1∶19)通气20min;阴性对照组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性灭活兔血清;地高辛抗血清组:同缺氧复氧组,但于再给氧前加入0.1mL的非特异性地高辛抗血清(分别为1∶90000,60000,30000,10000)。观察大鼠心肌细胞钠-钾-三磷酸腺苷酶活性和线粒体内钙聚集程度,分析其剂量-效应关系。结果:①缺氧复氧时,青年组和老龄组大鼠心肌分泌内洋地黄素均显著升高,但老龄组显著低于青年组[(0.081±0.03),(0.153±0.06);(0.074±0.04),(0.125±0.05)ng/g;P<0.05]。②缺氧复氧时,老龄组与青年组心肌细胞钠-钾-三磷酸腺苷酶活性显著受抑制[(0.239±0.015),(0.778±0.050);(0.350±0.047),(0.836±0.044)μkat/g;P<0.05],老龄组与青年组相比,其抑制效应显著增强(P<0.05)。③缺氧复氧时,老龄组线粒体内钙与青年组比较明显增强[(0.082±0.011),(0.495±0.095);(0.075±0.008),(0.412±0.084)mmol/L,P<0.05]。④老龄组和青年组相比,地高辛抗血清呈剂量依赖性的恢复钠-钾-三磷酸腺苷酶活性(r=0.695,0.797,n=5,P<0.05),减轻线粒体内钙聚集(r=-0.565,-0.649,n=5,P<0.05);经直线回归分析发现,老龄鼠回归系数大于青年组(酶活性抑制K=1.50,0.94,线粒体内钙K=-7.43,-6.46)。结论:心肌细胞缺氧复氧时,老龄鼠损伤较青年大鼠更显著,其机制与老龄大鼠心肌细胞钠-钾-三磷酸腺苷酶对内洋地黄素敏感性增加有关,地高辛抗血清对老龄大鼠心肌细胞缺氧复氧保护作用更有效。     

Pharmacological evaluation of the stress-induced social avoidance model of anxiety

We have shown earlier that mild electric shocks induce a lasting social avoidance in male rats. Here we investigated whether shock-induced social avoidance can be developed into a laboratory model of stress-induced anxiety. The putative new model would assess sub-chronic, stress-induced anxiety (as opposed to tests based on natural fear) in a heterologous context (as opposed to classical fear conditioning). A single exposure to mild electric shocks induced a robust social avoidance that lasted more than 5 days. Low doses of chlordiazepoxide (0.5, 1 mg/kg), diazepam (0.5, 1, 5 mg/kg), buspirone (0.3, 1 mg/kg), and fluoxetine (1, 3, 5 mg/kg) abolished this effect, whereas the anxiogenic compound m-chlorophenylpiperazine (0.5-3 mg/kg) induced social avoidance in unshocked rats. These effects were produced at doses that did not affect locomotion in the open field. Haloperidol (0.05, 0.1, 1, 5 mg/kg) influenced social avoidance at sedative doses only. The sensitivity of the model to anxiolytic agents was compromised at high (sedating) doses. Taken conjointly, these data show that shock-induced social avoidance can be used to assess the anxiolytic potential of compounds. In addition to predictive validity, the model appears to show construct and face validity as well: stress is among the etiological factors of, whereas social avoidance simulates the social deficits seen in, a variety of anxiety disorders. The model may be used to study the effects of anxiolytics on sub-chronic states of stress-induced anxiety.     

Life satisfaction and active coping style are important predictors of recovery from surgery

OBJECTIVE: The objectives of this study were to investigate the influence of psychological factors on the recovery of surgical patients and to explore whether there are any psychological variables other than anxiety that have a significant influence on recovery from surgery. METHODS: The participants were 112 adult patients undergoing a variety of surgical procedures. On the day prior to surgery, the Freiburg Personality Questionnaire, the State-Trait Anxiety Inventory, a coping schedule and the Questionnaire of Social Support were used to measure psychological parameters including personality, anxiety, coping and social support. The quality of the surgical outcome was rated by two independent and blinded surgeons by the length of hospital stay and analgesia and sedation requirements. The ratings controlled for the diagnosis, type of operation, intraoperative complications, postoperative medical problems and health limitations independent of the surgical procedure. RESULTS: Patients who had a complicated recovery were found to have reduced life satisfaction and lower situation-specific self-control expectations. Structural equation modeling revealed direct relationships between recovery from surgery and personality dimensions with the strongest correlations to life satisfaction, extraversion and attainment orientation. CONCLUSION: The data from this study suggests that valid predictions of the course of postoperative recovery need to take into account personality and coping behaviour orientated data as well as clinical variables. No direct influence on recovery could be predicted from preoperative state anxiety, but it seems likely that state anxiety may influence coping behaviour and that it is this that appears to have a significant impact to surgical recovery.