Antitumor effects of human recombinant interleukin-1α and etoposide against human tumor cells: mechanism for synergismin vitro and activityin vivo

Recombinant human interleukin 1α (rh IL-1α) and etoposide (VP-16) synergize for direct growth inhibition of several human tumor cell linesin vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also enhanced the internalization of receptor-bound rh IL-1α. The purposes of this study were to test our hypothess that these events were critical to the synergy between rhIL-1α and VP-16, to determine whether rhIL-1α and VP-16 synergize to increase superoxide (SO) anion radical productionin vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combinaton against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist (IL-1ra) before exposure to rhIL-1α, VP-16 and rhIL-1α plus VP-16. The synergistic or antagonistic effects were assessed by MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were treated by rhIL-1α, VP-16, and rhIL-1α+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1α and VP-16. The production of SO radical by A375/C6 cells was increased 2.5 fold by the combination of rhIL-1α and VP-16, and the addition of exogenous SOD blocked the synergy between rhIL-1α and VP-16. However, when A375/S0D15 cells which over-expressed manganese superoxide dismutase (MnSOD) after MnSOD cDNA transfecton were exposed to rhIL-1α and VP-16, in vitro antagonism was observed. In vivo studies demonstrated that the combination of rhIL-1α and VP-16 delayed tumor growth better than either agent alone, although long-term survival was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1α and VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combnation of IL-1α and VP-16 might prove useful for the treatment of malignant diseasein vivo, if the increased toxicity can be reduced or managed. The US Government’s right to retain a non-exclusive royalty-free license on and to any copyright is acknowledged.     

Plant growth and reproduction along CO2 gradients: non-linear responses and implications for community change

The effects of rising atmospheric CO₂ concentrations on natural plant communities will depend upon the cumulative responses of plant growth and reproduction to gradual, incremental changes in climatic conditions. We analysed published studies of plant responses to elevated CO₂ to address whether reproductive and total biomass exhibit similar enhancement to elevated vs. ambient CO₂ concentrations, and to assess the patterns of plant response along gradients of CO₂ concentrations. In six annual plant species, mean enhancement at double ambient vs. ambient CO₂ was 1.13 for total biomass and 1.30 for reproductive biomass. The two measures were significantly correlated, but there was considerable scatter in the relationship, indicating that reproductive responses cannot be consistently predicted from enhancement of total biomass. Along experimental CO₂ gradients utilizing three concentrations, there was a great diversity of response patterns, including positive, negative, non-monotonic and non-significant (flat) responses. The distribution of response patterns differed for plants grown in stands compared to those grown individually. Positive responses were less frequent in competitive environments, and non-monotonic responses were more frequent. These results emphasize that interpolation of plant response based on enhancement ratios measured at elevated vs. ambient CO₂ concentrations is not sufficient to predict community responses to incremental changes in atmospheric conditions. The consequences of differential response patterns were assessed in a simulation of community dynamics for four species of annual plants. The model illustrates that the final community composition at a future point in time depends critically on both the magnitude and the rate of increase of atmospheric CO₂.     

Genetic conflict and evolution of mammalian X-chromosome inactivation

The existence of parentally imprinted gene expression in the somatic tissues of mammals and plants can be explained by a theory of intragenomic genetic conflict, which is a logical extension of classical parent-offspring conflict theory. This theory unites conceptually the phenomena of autosomal imprinting and X-chromosome inactivation. We argue that recent experimental studies of X-chromosome inactivation and andro-genetic development address previously published predictions of the conflict theory, and we discuss possible explanations for the occurrence of random X-inactivation in the somatic tissues of eutherians. © 1995 Wiley-Liss, Inc.     

畜禽遗传资源系统保存的理论与模拟实验研究──I．畜禽遗传资源系统保存的理论分析

本文提出了畜禽遗传资源系统保存的概念、基本思想及其群体遗传结构变化的数学模型。该理论是将一定时空内某一畜种所拥有的全部基因作为保存对象,既将活体保存作为基本方法,又将其有机地与高新生物技术结合在一起;既追求系统地保存控制畜种特性的基因资源,又可达到保存地方品种的目的。在假定无世代重叠,群体内存在选择、突变、迁移,且考虑漂变效应的情况下,本文所构建的两个数学模型可分别用来描述一个座位上多个主基因频率或数量性状群体均数的动态变化。     

使用MUG培养基定量检测植物药中大肠杆菌时荧光猝灭现象的发生与克服方法

实验中观察到,用ＭＵＧ培养基对植物药中的大肠杆菌定量时多发生荧光猝灭现象,影响检测结果。本文对此现象产生的原因与克服方法进行了系统的考察,发现以一种简便的转接方法可排除植物药介质对菌检的干扰。该方法由两组检验系列构成,当怀疑正常稀释系列（第一系列）４０ｈ培养液的荧光结果可能因猝灭现象呈假阴性时,立即分别将该系列的１—３号管培养液以０．５ｍｌ的接种量转接入新鲜的ＭＵＧ培养基（第二系列）,重新培养２４ｈ,荧光猝灭现象即可克服。综合两系列的荧光、产气和吲哚三项生化特征得出检品中大肠杆菌含量。实际应用表明,此法能显著提高使用该培养基时菌检结果的可靠性。     

Influence of 50 Hz electric and magnetic fields on the pulse rate of human heart

This investigation studied the effects of 50 Hz electric and magnetic fields on the pulse rate of the human heart. The ECG (electrocardiograms) of 41 male volunteers were recorded with a Holter recorder. Twenty-six subjects were measured in and outside real fields, and 15 subjects were measured in and outside “sham” fields. The blood pressure and EEG (electroencephalogram) were also measured, but this article presents only the results of ECG recordings. The measurements took 3 h. The subjects were first sitting for 1 h outside the fields, then 1 h in the real or “sham” fields, and then, again, 1 h outside the fields. The electric field strength varied from 3.5 to 4.3 kV/m and the magnetic flux density from 1.4 to 6.6 μT. An analysis of the ECG recordings showed that the subjects' pulse rates were the same in and outside the fields. No response occurred when the subjects were exposed to real or “sham” fields. © 1994 Wiley-Liss, Inc.     

Assessment of five cultivars of potato (Solatium tuberosum L.) in a competition diallel

In 1992 and 1993, potato cultivars Cara, Estima, Pentland Dell, Pentland Javelin and Torridon were assessed in all possible pairings in three consecutive drills, such that one member of the pair (the cultivar) was the centre-drill, and the other member (the neighbour) was in the two adjacent drills. Each year the trial was a randomised complete block design with four replicates. Inter-cultivar competition was present for height, total tuber yield, ware yield and dry matter content, but not for emergence and maturity. Cultivar heights and dry matter contents under inter-cultivar competition and in pure-stands were highly correlated, whereas for total and ware yields, the rankings of cultivars in pure-stands were different from those under competition. Pure-stand yields were predicted for the two years separately because of year × cultivar and year × neighbour interactions. When the average total yield of the outer-drills was used as a covariate to adjust centre-drill yields to pure-stands, predicted yields were closer to those observed than were yields under competition, but there was little improvement in the correlations. In contrast, not only were the predicted values even closer to the observed ones when based on individual neighbour effects, the correlations were much higher (r = 0.76–0.94). Unfortunately, in plant breeding trials with large numbers of entries, precise estimation of individual neighbour effects would require an unrealistically large number of replicates. Hence, for the final stages of yield assessment of new cultivars, it is still desirable to use multiple-drill plots and to discard the outside drills where inter-cultivar competition can occur.     

SEXUAL SELECTION IN THE BARN SWALLOW (HIRUNDO RUSTICA). IV. PATTERNS OF FLUCTUATING ASYMMETRY AND SELECTION AGAINST ASYMMETRY

The patterns of variation in fluctuating asymmetry were studied in four morphological characters of the barn swallow Hirundo rustica. The level of absolute and relative asymmetry was larger in the secondary sexual character “outer tail length” than in three nonsexual morphological traits (wing, central tail, and tarsus length). The extent of individual asymmetry in outer tail length was negatively correlated with tail-ornament size, whereas the relationship between asymmetry of all other morphological characters and their size was flat or U-shaped. Asymmetry in outer tail length was unrelated to asymmetry in other morphological characters, whereas asymmetries in the length of wing, central tail, and tarsus were positively correlated. Male bam swallows exhibited larger asymmetry in outer tail length than females. Asymmetry of most morphological traits exhibited intermediate repeatabilities between years, with the exception of male and female outer tail length, which were highly repeatable. Tail asymmetry of offspring weakly, though significantly, resembled that of their parents. Asymmetry in wing and outer tail length was also significantly related to several fitness components. Male barn swallows that acquired a mate were less asymmetric in wing and outer tail length than unmated males. Females with more asymmetrical tails laid eggs significantly later. Annual reproductive success was unrelated to fluctuating asymmetry. Male barn swallows that survived were less asymmetric in wing and outer tail length than nonsurvivors, whereas female survivors were less asymmetric in outer tail length than nonsurvivors. These results suggest that levels of fluctuating asymmetry in barn swallows are associated with differences in fitness.     

The ‘World Prodigy’ oil spill in Narragansett Bay,Rhode Island: acute effects on macrobenthic crustacean populations

On June 26,1989, the tanker World Prodigy ran aground just outside the mouth of the West Passage of Narragansett Bay, Rhode Island, USA. About 922 metric tons of No. 2 fuel oil were released into the water and drifted over a total area of about 120 sq miles. Three days after the spill only a small fraction of the oil remained.The effects on macrobenthic crustaceans within the first five weeks after the spill were studied at five stations with a varying degree of oil exposure, including one control site never reached by oil from the spill. Significant differencies between these stations were noted for total amphipod abundance, the amphipod genus Ampelisca and ostracods (retained on a 0.3 mm mesh), but not for amphipods of the genus Corophium. At the most heavily impacted station (23 µg oil g^–1 sediment dry weight), the total amphipod abundance, dominated by Ampelisca verrilli, decreased by 86% within the first two weeks after the spill. Decreases in total amphipod abundance significantly larger than at the control site were noted also at two other stations, one of which with only trace amounts of oil detected in the sediment. The amphipod populations at these sites were dominated by juvenile specimens.These findings confirm the extreme sensitivity to oil pollution of amphipods and ostracods, noted in earlier field and experimental studies.     

The effects of prolonged emersion and submersion by tidal manipulation on marine macrobenthos

Effects of tidal manipulation, resulting in prolonged periods of emersion and submersion or in protracted tidal cycles, on estuarine benthic animals are reviewed.Prolonged submersion periods did not show effects on mortality of most benthic animals tested, with the exception of the crumb-of-bread sponge Halichondrea panicea, which, at low water-flow rates, was covered with a layer of bacteria and subsequently died.Protracted low-water periods of 18 hours during several weeks hardly caused any mortality. However, protracted low-water periods of 30 hours during some weeks or emersion during several days caused a strong increase in mortality, depending on: the duration of emersion, temperature, condition of the animals, species and age. At temperatures below –1 °C and above 24 °C mortality was generally high. Animals with a low glycogen content were more sensitive to emersion than those with a high content. Species with a shell and those that are relatively big were less sensitive than those without a shell or of small size.The reproductive cycle of benthic animals could be delayed or accelerated by both emersion and submersion.