Stem-cell leukemia: p53 deficiency mediated suppression of leukemic differentiation in C3H/He myeloid leukemia

C3H/He mice produce myeloid leukemias after whole body irradiation of 1–3 Gy as compared with non-irradiated controls that produce fewer than 1% of leukemia [Radiatiton Research 127 (1991) 146]. Thus, p53-deficient C57BL/6 strain, a malignant lymphoma prone, was crossed back into C3H/He strain. Lethally irradiated wild-type mice to which p53-deficient bone marrow cells were transplanted (transplantation assay) showed dramatic change in the propensity of leukemia of myeloid lineages, the cells lacking CD3, Thy1.2, sIgM, B220, Mac-1, Gr-1, but being positive for c-Kit and CD44. Furthermore, transplanted mice subjected to 3 Gy irradiation gave rise to a faster development of leukemia and a higher frequency of double-lineage leukemias than the non-irradiated control.     

Systemic overexpression of the alpha 1B-adrenergic receptor in mice: an animal model of epilepsy

PURPOSE: A lack of selective alpha1-adrenergic receptor (alpha1-ARs) agonists and antagonists has made it difficult to clarify the precise function of these receptors in the CNS. We recently generated transgenic mice that overexpress either wild-type or a constitutively active mutant alpha 1B-AR in tissues that normally express the receptor. Both wild-type and mutant mice showed an age-progressive neurodegeneration with locomotor impairment and probable stress-induced motor events, which can be partially reversed by alpha 1-AR antagonists. We hypothesized that the wild-type and mutant mice may exhibit spontaneous epileptogenicity as compared with normal (nontransgenic) mice. METHODS: Normal, wild-type, and mutant mice were studied. Twenty mice (1 year old) underwent prolonged video-EEG monitoring over a 4-week period. Raw EEG data were blindly analyzed by visual inspection for the presence of interictal and ictal epileptic activities. RESULTS: During the acute postoperative period (< or = 3 days), both wild-type (26.1 +/- 8.07 spikes/day) and mutant mice (116.87 +/- 55.13) exhibited more frequent interictal spikes than did normal mice (2.17 +/- 0.75; p value, <0.05), but all three groups showed EEG and clinical seizures. During the later monitoring periods (>3 days), wild-type and mutant mice showed more frequent interictal spikes (15.44 +/- 4.07; p < 0.01; and 6.05 +/- 2.46; p < 0.05, respectively) as compared with normal mice (0.41 +/- 0.41), but only mutant mice had spontaneous clinical seizures (means +/- SEM). CONCLUSIONS: The selective overexpression of the alpha 1B-AR is associated with increased in vivo spontaneous interictal epileptogenicity and EEG/behavioral seizures. These results suggest a possible role (direct or indirect) for the alpha 1B-ARs in the development and expression of epileptogenicity.     

GABA(A) receptor changes in delta subunit-deficient mice: altered expression of alpha4 and gamma2 subunits in the forebrain

The delta subunit is a novel subunit of the pentameric gamma-aminobutyric acid (GABA)(A) receptor that conveys special pharmacological and functional properties to recombinant receptors and may be particularly important in mediating tonic inhibition. Mice that lack the delta subunit have been produced by gene-targeting technology, and these mice were studied with immunohistochemical and immunoblot methods to determine whether changes in GABA(A) receptors were limited to deletion of the delta subunit or whether alterations in other GABA(A) receptor subunits were also present in the delta subunit knockout (delta-/-) mice. Immunohistochemical studies of wild-type mice confirmed the restricted distribution of the delta subunit in the forebrain. Regions with moderate to high levels of delta subunit expression included thalamic relay nuclei, caudate-putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex. Virtually no delta subunit labeling was evident in adjacent regions, such as the thalamic reticular nucleus, hypothalamus, and globus pallidus. Comparisons of the expression of other subunits in delta-/- and wild-type mice demonstrated substantial changes in the alpha4 and gamma2 subunits of the GABA(A) receptor in the delta-/- mice. gamma2 Subunit expression was increased, whereas alpha4 subunit expression was decreased in delta-/- mice. Importantly, alterations of both the alpha4 and the gamma2 subunits were confined primarily to brain regions that normally expressed the delta subunit. This suggests that the additional subunit changes are directly linked to loss of the delta subunit and could reflect local changes in subunit composition and function of GABA(A) receptors in delta-/- mice.     

Cytokine gene expression by alloactivated cells in SCID mice

OBJECTIVES: The severe combined immune deficient (SCID) mouse provides a neutral environment to study human immune responses. We therefore tested human gene expression of Interleukin (IL) 2, 4 and 10, interferon gamma (IFNgamma); transforming growth factor beta 1 (TGFbeta1); and CD40 ligand (CD40L) in splenic extracts of SCID mice after engraftment of PBLs from two persons (direct MLR) or one person plus allopeptides (indirect MLR) in the presence or absence of cyclosporin A (CsA) or FK506. METHODS: Cytokine gene expression was detected by RT and quantitative (for IFN-gamma, TGFbeta1 and CD40L) PCR. All cells, allopeptides, CsA (25 mg/kg/day for 7 days) or FK 506 (0.5 mg/kg/day for 7 days) were administered intraperitoneally (IP). RESULTS: In both direct and indirect MLR the numbers of SCID mice expressing the human cytokine genes varied between 33% for IL4 and 100% for IL10, IFN-gamma, TGFbeta1, and CD40L. There was significant interpersonal variation in levels of gene expression. Concomitant CsA or FK506 administration for 7 days did not abrogate early or late (1 week after discontinuation of CsA or FK506) cytokine gene expression in either the direct or indirect MLR, but paradoxically enhanced levels of IFN-gamma, TGFbeta1 and CD40L gene expression in some experiments. CONCLUSIONS: The results explain late rejection after rapid calcineurin inhibitor withdrawal or reduction, and illustrate the potential use of SCID mice as a surrogate model to study graft outcome by determination levels of gene expression and sensitivity to immunosuppressive agents in the in vivo alloresponse.     

低氧预适应增强小鼠学习记忆能力

目的探讨脑低氧预适应对Balb／C小鼠学习记忆能力的影响，进一步研究低氧预适应的机制。方法选用清洁级成年健康雄性Balb／C交系小鼠，数字表法随机分为3组（n=12）：①对照组（H0）；②1次低氧组（H1）；③4次低氧组印低氧预适应组（H4）。然后行改良的Morris水迷宫测试：在一直径约为1米的圆形水槽边缘等距的四个点（NESW）处做好标记，在一固定位置放一玻璃平台，使槽中水面高于平台1．5厘米，水面覆以泡沫屑，小鼠在水迷宫中训练5日后，进行低氧预适应模型制备，随后分别在低氧处理后1小时、2小时、4小时、1天、2天、3天进行测试，共进行6个时段测试，每个时段4次，分别将小鼠从改良的Morris水迷宫的NESW4个起始点放入水槽中任其游动，寻找平台，记录每次的遗避潜伏期，将4次平均值作为该小鼠在该时段的成绩。然后比较各组测定的小鼠在迷宫中的逃避潜伏期，以确定低氧预适应对小鼠学习记忆能力的影响。结果H4组小鼠在低氧处理后4小时、1、2．3天的逃避潜伏期明显短于H0和H1组（P〈0．05）。结论脑低氧预适应能增强小鼠学习记忆能力，具体的产生机制需要进一步的研究。     

东北铁线莲对小鼠肿瘤的抑制作用

[目的]探讨东北铁线莲乙酸乙酯提取物的抗肿瘤作用.[方法]给小鼠接种S180肉瘤细胞制作S180肉瘤小鼠动物模型,随机分为空白对照组、东北铁线莲乙酸乙酯提取物大、中、小剂量组及环磷酰胺组,实验大、中、小剂量组分别给予0.8,0.4,0.2 g/kg东北铁线莲乙酸乙酯提取物,10 d后观察小鼠体重变化,计算肿瘤抑制率.[结果]东北铁线莲乙酸乙酯提取物大、中、小剂量组肿瘤抑制率分别为66.4%,55.3%,40.6%,与空白对照组比较有显著性差异.[结论]东北铁线莲乙酸乙酯提取物对小鼠S180肉瘤的生长具有抑制作用.     

黄芪对高脂血症小鼠血脂及脂质过氧化的影响

[目的]探讨黄芪对高脂血症小鼠血脂及脂质过氧化的影响.[方法]取小鼠随机分组,除正常组外的其他组小鼠灌胃给予脂肪乳剂,建立高脂血症小鼠模型,分别灌胃给予不同剂量黄芪组小鼠18.0,9.0,4.5 g/kg黄芪水提取物,连续4周,测定各组小鼠血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)含量,谷胱甘肽过氧化物酶(GSH-Px)和超氧化化物歧化酶(SOD)活性,脂质过氧化物(LPO)含量.[结果]不同剂量黄芪组小鼠血清TC,TG,LDL-C含量明显下降,SOD,GSH-Px活性明显增强,血清LPO含量明显下降.[结论]黄芪具有调节小鼠血脂代谢及增强机体抗脂质过氧化的作用.     

海尔福对铅中毒小鼠治疗效果的实验研究

目的探讨海尔福对铅中毒小鼠的治疗效果及作用。方法将30只健康昆明小白鼠随机分为染铅组(腹腔注射醋酸铅40mg/kg.d-1,4周)、治疗组(腹腔注射醋酸铅40mg/kg.d-1+Haierfu 2ml/d)及对照组(腹腔注射等量的生理盐水)。染铅组灌胃4周于第0、4、8周,用水迷宫试验测试学习记忆能力1次。实验结束时处死小鼠,测定小鼠学习记忆情况;取血、肝、肾、股骨、尿液、粪便测定铅含量;取脑组织常规切片,光镜观察。结果染铅组小鼠的学习记忆能力受阻碍,治疗组学习记忆明显改善,铅排泄量明显升高;而治疗组脑组织结构病变比染铅组明显减轻(P均<0.05或0.01)。结论海尔福具有驱铅、改善学习记忆能力、保护脑组织的作用。