A system for tissue-specific gene targeting: transgenic mice susceptible to subgroup A avian leukosis virus-based retroviral vectors.

Avian leukosis viruses (ALVs) have been used extensively as genetic vectors in avian systems, but their utility in mammals or mammalian cell lines is compromised by inefficient viral entry. We have overcome this limitation by generating transgenic mice that express the receptor for the subgroup A ALV under the control of the chicken alpha sk-actin promoter. The skeletal muscles of these transgenic animals are susceptible to efficient infection by subgroup A ALV. Because infection is restricted to cell lineages that express the transgene, the method has utility for studies of development and oncogenesis and will provide models for tissue-specific gene therapy.     

苯丙胺诱发小鼠激怒反应及其机制

苯丙胺15mg/kg ip能诱发小鼠激怒反应,使小鼠出现攻击和殴斗行为。强安定药、弱安定药和利血平有明显拮抗效果。镇静剂如巴比妥类、抗胆碱药及抗肾上腺素药均无拮抗作用。金刚胺、左旋多巴和阿扑吗啡均能增强苯丙胺的激怒效应。因苯丙胺激怒小鼠的方法简便易行,可作为筛选抗精神病药的动物模型。苯丙胺产生激怒作用的机制与增强多巴胺能神经的功能有关,推测可能是促进边缘系统多巴胺释放的结果。     

Characterization of the major neutrophil-stimulating activity present in culture medium conditioned by Staphylococcus aureus-stimulated mononuclear leucocytes.

Culture medium conditioned by stimulating human mononuclear leucocytes (MNL) with killed Staphylococcus aureus (Scm) was found to contain a substantial amount of tumour necrosis factor-alpha (TNF-alpha) but no detectable tumour necrosis factor-beta (TNF-beta). Culture medium conditioned by MNL in the absence of bacteria contained no TNF-alpha activity. When Scm was fractionated by high-performance liquid chromatography (HPLC) on Bio-Sil TSK 250, TNF-alpha co-eluted with neutrophil-stimulating activity measured by chemiluminescence. Similarly, the ability of neutrophils to kill opsonized S. aureus was enhanced in fractions that contained this neutrophil-stimulating activity. The stimulating activity could be almost completely removed by pretreatment of the Scm with a TNF-alpha-specific monoclonal antibody (mAb). The ability of neutrophils to kill S. aureus in response to Scm was also substantially reduced by mAb to TNF-alpha. These results demonstrate that bacterial interaction with MNL leads to the release of neutrophil-stimulating activity that consists predominantly of TNF-alpha.     

Cyclic AMP inhibits increased collagen production by cyclically stretched smooth muscle cells

Rabbit arterial smooth muscle cells, grown on elastin membranes which were cyclically elongated and relaxed, responded by increasing their rates of synthesis of protein and, in particular, of collagen, compared to stationary controls. Raising intracellular cyclic AMP (cAMP) levels by adding theophylline or dibutyryl cAMP to the culture medium prevented the synthetic response to cyclic stretching, but did not alter the rates of protein or collagen synthesis by stationary controls. Both synthesis and degradation of collagen by cyclically stretched cells increased in parallel such that the proportion of synthesized collagen that was degraded was similar to that found in the stationary cultures. Collagen degradation was not affected by theophylline administration to stationary cell cultures but the drug increased degradation of collagen by cyclically stretched cells. We conclude that the net production of protein, and in particular of a structural protein, collagen, by arterial smooth muscle cells subjected to the mechanical force of stretching was inhibited when intracellular levels of cAMP were raised. The results suggest that cAMP may play a role in the modulation of structural protein content of artery walls in response to changes in tensile stress.