Transgenic rabbits with increased VEGF expression develop hemangiomas in the liver: a new model for Kasabach-Merritt syndrome

Clinical studies have provided ample evidence that high (either systemic or local) levels of vascular endothelial growth factor (VEGF) are associated with several pathophysiological disorders, including hemangiomas. To investigate whether elevated VEGF expression could directly affect these disorders, we created a transgenic (Tg) rabbit model with increased hepatic expression of the human VEGF(165) transgene under the control of the human alpha-antitrypsin promoter. Tg rabbits exhibited marked hepatomegaly, with livers 2.5-fold heavier than those of control rabbits. Histological analysis revealed that the livers of Tg rabbits showed prominent dilation of the sinusoids and formed various-sized blood vessel networks, a feature of diffuse hemangiomas. Immunohistochemical staining revealed that the hepatocytes produced VEGF(165), whereas plasma VEGF(165) was not detected. Furthermore, Tg rabbits suffered from hemolytic anemia, thrombocytopenia and splenomegaly, which was associated with marked extramedullary hematopoiesis. The manifestations of Tg rabbits mimic many of the features of hemangiomatous disorders in humans such as the Kasabach-Merritt syndrome, and therefore this model may be potentially useful for the study of the pathogenesis and complications of hemangiomas as well as the investigation of angiogenesis inhibitors.     

TGFβ1基因对血管内皮细胞细胞外基质表达及与基质黏附的影响

了解TGFβ1基因对血管内皮细胞表达细胞外基质蛋白及与基质黏附力的影响。用DOTAP脂质体转染p MAMneo TGFβ1于原代培养的脐静脉内皮细胞,经G4 18筛选,TGFβ1表达经免疫荧光鉴定。Western blot确定 型胶原、纤黏连蛋白的表达,微管吸吮系统确定内皮细胞与基质的黏附力。结果表明生理情况下的内皮细胞能表达少量的TGFβ1及胶原、纤黏连蛋白。经G4 18筛选,外源性TGFβ1在血管内皮细胞中稳定表达,能显著提高胶原、纤黏连蛋白纤维的表达及细胞与基质的黏附。说明TGFβ1在血管组织工程中促进内皮细胞的黏附具有一定的应用价值。     

Molecular and biochemical mechanisms ofPasteurella haemolyticaleukotoxin-induced cell death

Pasteurella haemolyticaleukotoxin (LKT) is a member of the RTX family of pore-forming toxins that kill bovine immune cells. Several studies have suggested that RTX toxins kill target cells by the induction of apoptosis. In the present study, BL3 bovine leukaemia cells were exposed to LKT and assessed by molecular and flow cytometric techniques that measure different aspects of apoptotic cell death. The intoxicated cells demonstrated morphological, light scatter and Hoechst 33258 staining characteristics consistent with cells undergoing apoptosis. The cells also exhibited internucleosomal DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage, both indicators of apoptosis. LKT-treated cells bound annexin-V-FITC indicating that phosphatidylserine groups were translocated from the inner to the outer leaflet of the cell membrane. The effect of LKT on cells was dose dependent and inhibitable by incubation with anti-LKT monoclonal antibody. Finally, an early step for induction of apoptosis appears to be the binding of LKT to a β2 integrin since pre-incubating cells with anti-β2 integrin antibodies inhibited LKT-induced apoptosis. This study provides new insights into understanding the pathogenesis of bovine pasteurellosis and could lead to the development of both preventative and therapeutic strategies for disease management.     

Induction of a cytotoxic T cell response by co-injection of a T helper peptide and a cytotoxic T lymphocyte peptide in incomplete Freund's adjuvant (IFA): Further enhancement by pre-injection of IFA alone

We have previously demonstrated that it is possible to induce a consistent and strong cytolytic T lymphocyte (CTL) response to synthetic peptides, corresponding to poorly immunogenic malaria CTL epitopes, by co-injecting them with peptides representing defined T helper (Th) epitopes in incomplete Freund's adjuvant (IFA). In this study we have tested different immunization protocols to improve further the elicitation of the CTL response. We show that the CTL response to a mixture of Th + CTL peptides administered in IFA was further enhanced by a previous injection of the Th epitope peptide in IFA. Moreover, we found that the response could be significantly augmented by a pre-injection of IFA alone. This enhancement was observed only if the Th epitope was also present in the second injection. The number of lymph node cells recovered was 2–3-fold higher in mice pre-injected with IFA, but the increase in specific CTL activity, expressed as lytic units per animal, by pre-injection of IFA was at least 10–20-fold. Thus, pre-injection of IFA clearly increases the magnitude of a subsequent CTL response.     

Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex

Numerous protein kinases have been implicated in visual cortex plasticity, but the role of serine/threonine protein phosphatases has not yet been established. Calcineurin, the only known Ca2+/calmodulin-activated protein phosphatase in the brain, has been identified as a molecular constraint on synaptic plasticity in the hippocampus and on memory. Using transgenic mice overexpressing calcineurin inducibly in forebrain neurons, we now provide evidence that calcineurin is also involved in ocular dominance plasticity. A transient increase in calcineurin activity is found to prevent the shift of responsiveness in the visual cortex following monocular deprivation, and this effect is reversible. These results imply that the balance between protein kinases and phosphatases is critical for visual cortex plasticity.     

多发性骨髓瘤患者血清IL-6活性与急性相蛋白浓度的相关性研究

运用敏感的B_9细胞增殖试验检测了81例多发性骨髓瘤(MM)患者血清IL-6活性,同时分析了标本的几种急性相蛋白含量,结果表明,68％MM患者血清中IL-6活性大于5μ/ml(正常对照为5μ/ml以下),几种急性相蛋白中C-反应性蛋白(CRP)在MM时升高(P<0.01),平均达正常对照组的17倍以上,MM患者补体C_4与正常对照组无差异(p>0.05),C_3、白蛋白及转铁蛋白在MM时分别比正常下降24.42％、38.83％和32.80％,且与疾病分期有关,在血清IL-6大于5μ/ml的55例中,IL-6活性与CRP、C_3、白蛋白的相关系数分别为0.46,-0.34和-0.29,IL-6与转铁蛋白浓度相关不明显。本文结果提示:CRP、C_3及白蛋白等含量的变化可作为反映MM病情的简易而敏感的指标。     

领导干部心理健康量表的初步编制

目的编制一套适用于领导干部群体的心理健康量表。方法通过文献研究、个案分析、问卷调查等,确立测验结构并编制成预测量表,通过对127位被试施测结果进行条目分析等形成正式量表,并进行因子分析等考察量表的信度和效度。结果编制成一个含3个量表:心理症状量表、自我概念量表、外界适应量表,共计93个项目的测评系统。项目与其所在量表的题总相关系数在0.445～0.855之间(P<0.001),各条目决断值(CR值)均具有显著性;对自我概念量表和外界适应量表探索性因素分析分别提取4个和3个公因子,累计解释总变异量分别为54.842%,48.365%,因子载荷在0.427～0.814和0.434～0.796之间;各量表的Cronbach'sα系数分别为0.775,0.860,0.952。结论初步研究显示量表的信效度均达到心理学测量标准,具有较好的信效度。     

1 MHz腔内射频加热辐射器在体模和犬颈段食管中的热场分布

目的 在肌肉等效体模及Beagle犬颈段食管中测定ZRL—Ⅱ型食管腔内加热辐射器的温度分布，探讨其热场分布能否满足食管癌加热治疗的临床需要。方法 ①在肌肉等效体模中测定ZRL—Ⅱ型食管腔内射频加热辐射器的温度分布，②Beagle犬用氯胺酮麻醉、固定。将腔内加热辐射器插入食管腔内，加热45min后分层解剖犬的颈部，同时测量食管外壁、气管、食管周围软组织中的温度。结果 ①在肌肉等效体模中距离导管囊表面1cm的环形体内的温度在43．2℃～43．6℃之间；在距离导管囊表面2cm的环形体内的温度在42．6℃～43．3℃之间，在距离导管囊表面3cm的环形体内的温度在42．6℃～42．8℃之间。②测得Beagle犬颈段食管腔内和外壁的温度为43．5℃，气管内为38．0℃，主动脉旁38．0℃，距食管外壁1cm处的软组织温度为40-3℃，距食管外壁2cm处的软组织温度为39．0℃，而颈部皮下的温度是37．5℃。结论 ①ZRL-Ⅱ型射频食管腔内加热辐射器的热场分布满足临床食管腔内加热的需要，②体模测定与活体动物测定，热场分布存在一定差异，需进一步研究。     

Significance of cytogenetic and fluorescence in situ hybridization analysis in evaluating antichronic myeloid leukemia efficacy of different immune effector cells

We report on the antileukemia effect of interleukin 2 (IL2) on different immune cells from 22 patients with chronic myeloid leukemia (CML). Bone marrow cells from these patients were first cultured in modified long-term bone marrow culture medium for several days, then separately cultured with lymphokine activated killer cells (LAK), cytokine-induced killer cells (CIK), and dendritic cell cocultured CIK (DC-CIK) for another 1-2 days. They were then detected for presence of the Philadelphia chromosome (Ph) by cytogenetic analysis and fluorescence in situ hybridization (FISH). The percentage of Ph-chromosome-positive cells in the bone marrow mononuclear cells after culturing with CIK and DC-CIK was significantly lower than that after culturing with IL2 or LAK. Our results demonstrate that cytogenetics and FISH are useful techniques for the evaluation of the anti-CML effect of immune cells and that CIK or DC-CIK can be appropriate candidates for adoptive immune cell therapy in vivo or for leukemia cell purging ex vivo.