The rhGM-CSF-EPO hybrid protein MEN 11300 induces anti-EPO antibodies and severe anaemia in rhesus monkeys

A recombinant human GM-CSF-EPO hybrid protein named MEN 11300 was administered biweekly for a total of 6 weeks to rhesus monkeys in order to evaluate its pharmacokinetic behaviour, tolerability and immunogenicity. In this primate species a strong antibody response was induced which neutralized the in vitro biological activity of human EPO while no antibody response could be detected against human GM-CSF. A severe drop in reticulocyte counts at approximately 2 weeks after initiation of treatment was followed by a dramatic decrease in the number of erythrocytes. No effects were observed on GM-CSF-dependent hematopoietic lineages and the clinical chemistry analyses did not reveal signs of general toxicity. Reticulocyte and erythrocyte counts started to recover 3-4 weeks after discontinuation of treatment in concert with a decline in anti-EPO antibody titres. Nevertheless, cell numbers remained below basal levels up to 50 days after the last MEN 11300 administration. Haematological impairment indicates that the administration to non-human primate of human EPO fused to human GM-CSF, induces neutralizing autoantibodies to the self EPO. Present data do not allow prediction of the immunogenic potential of the fusion protein in humans and a dose-escalating phase I study should be addressed to investigate the safety of the product.     

恒河猴日需蛋白质量的研究

本文报道了恒河猴(Macaca mulatta)日需蛋白质量的实验研宄。四组未成年恒河猴(共36只)分别饲喂蛋白质含量为15％、20％、24％的配合饲料和玉米加蚕豆,为时90天。四组动物的平均增重依次为0.3、0.6、0.6和0.2公斤。猴子日食蛋白质含量力20％的饲料,氮在体内的平均沉积率是57±13.5％。实验期间,各组动物血红蛋白,血清总蛋白和血总脂的含量无显著变化。以上结果和在本所试用的饲养效果表明,在我们的饲养条件下,配合饲料中蛋白质含量以20％较有利于恒河猴的生长发育和节约费用。     

EXPOSURE TO 50 HZ ELECTROMAGNETIC FIELDS INDUCES THE PHOSPHORYLATION AND ACTIVITY OF STRESS-ACTIVATED PROTEIN KINASE IN CULTURED CELLS

Protein phosphorylation is one of the important processes of cell signal transduction pathways. To study the effects of 50 Hz electromagnetic field (EMF) on the cell signal transduction process, the phosphorylation of stress-activated protein kinase (SAPK/JNK) extracted from Chinese hamster lung (CHL) cells exposed to 0.4 and 0.8 mT 50 Hz EMF for various durations was measured. A solid-phase kinase assay was used to measure the enzymatic activity of SAPK extracted from cells exposed to 50 Hz EMF at the same magnetic flux density and for only 15 min. The results showed that both 0.4 and 0.8 mT could induce the phosphorylation of SAPK, the phosphorylation of SAPK presented a time-dependent course, and there was a difference between the two intensities. The phosphorylated SAPK enhanced its enzymatic activity. All the data indicated that 50 Hz EMF could activate SAPK in a time- and intensity-dependent manner. The biological effects caused by 50 Hz EMF maybe related to the SAPK signal transduction pathway.     

PKC激动剂佛波醇酯诱导大鼠伤害性感受并促进脊髓NO产生

目的:观察PKC激动剂PMA诱导大鼠伤害性感受作用及对脊髓NOS表达和NO生成的影响.方法:采用行为学方法观察大鼠痛反应;热甩尾法测定大鼠痛阈变化;采用NADPH-d组织化学法和硝酸还原酶法分别测定大鼠脊髓内NOS表达和NO含量.结果:鞘内注射PMA后,大鼠出现伤害性感受反应及痛阈降低,脊髓后角浅层和中央管周围灰质内NOS阳性细胞数目、阳性细胞胞体及突起的染色深度明显增加,脊髓NO含量亦明显增加.给予PKC选择性抑制剂CH预处理可阻断鞘内注射PMA诱导的上述改变.结论:脊髓神经元内PKC激活可诱导大鼠产生伤害性感受及热痛觉过敏,并可促进NO产生,其对NO产生的促进作用可能是其诱导痛觉过敏产生的机制之一.     

PARTIAL CLONING AND CHARACTERIZATION OF THE cDNA OF GENERAL ODORANT BINDING PROTEIN 1 GENE IN THE ANTENNA OF HELICOVERPA ARMIGERA (HÜBNER)*

Abstract Using RT‐PCR and RACE techniques, part of the cDNA encoding the general odorant binding protein 1 gene (named as GOBP1‐Harra) from the antenna of Helwoverpa armigera (Hubner) has been cloned. The cDNA length of GOBP1‐Harm is 876 bp. The results of sequencing and structural analysis showed that the mature protein reading frame of GOBPl‐Harm is 435 base pairs in length and 145 amino acids encoded. The predicted MW and pl are 17.0 kD and 4.89, respectively. The deduced amino acid sequence showed a highly similarity to the sequence of GOBP1 from different moth species and shared several common structural features with odorant binding proteins from other insects.     

THE LANDE–KIRKPATRICK MECHANISM IS THE NULL MODEL OF EVOLUTION BY INTERSEXUAL SELECTION: IMPLICATIONS FOR MEANING,HONESTY, AND DESIGN IN INTERSEXUAL SIGNALS

The Fisher‐inspired, arbitrary intersexual selection models of Lande (1981) and Kirkpatrick (1982) , including both stable and unstable equilibrium conditions, provide the appropriate null model for the evolution of traits and preferences by intersexual selection. Like the Hardy–Weinberg equilibrium, the Lande–Kirkpatrick (LK) mechanism arises as an intrinsic consequence of genetic variation in trait and preference in the absence of other evolutionary forces. The LK mechanism is equivalent to other intersexual selection mechanisms in the absence of additional selection on preference and with additional trait‐viability and preference‐viability correlations equal to zero. The LK null model predicts the evolution of arbitrary display traits that are neither honest nor dishonest, indicate nothing other than mating availability, and lack any meaning or design other than their potential to correspond to mating preferences. The current standard for demonstrating an arbitrary trait is impossible to meet because it requires proof of the null hypothesis. The LK null model makes distinct predictions about the evolvability of traits and preferences. Examples of recent intersexual selection research document the confirmationist pitfalls of lacking a null model. Incorporation of the LK null into intersexual selection will contribute to serious examination of the extent to which natural selection on preferences shapes signals.