间充质干细胞移植治疗缺氧缺血性脑损伤

缺氧缺血性脑损伤(hypoxie-ischaemie brain injury,HIBI)是导致新生儿死亡和儿童神经功能障碍的主要原因,目前临床尚无有效的治疗方法.间充质干细胞(mesenchymal stem cells,MSC)移植治疗为减少缺氧缺血性脑损害带来了希望.     

丹参对缺氧缺血新生大鼠脑皮质氧化还原因子-1蛋白和凋亡细胞的影响

目的研究丹参对缺氧缺血性新生大鼠脑皮质氧化还原因子-1(redoxfactor-1,Ref-1)蛋白和凋亡细胞的影响.方法将新生7日龄SD大鼠制成缺氧缺血性脑损伤(HIBD)动物模型,采用免疫组织化学方法及原位缺口末端标记(TUNEL)法分别观察假手术组、缺氧缺血组及丹参治疗组脑皮质Ref-1蛋白及神经细胞凋亡变化.结果与缺氧缺血组比较,丹参治疗组Ref-1蛋白表达Ref-1阳性细胞数增加(由36.1±6.3上升至76.3±5.4,t=2.43,P＜0.05);而凋亡细胞显著减少(由68±2降至12±5,t=7.02,P＜0.01).结论丹参作为自由基清除剂可能通过促进缺氧缺血后脑神经细胞Ref-1蛋白的表达,从而抑制了细胞凋亡,为治疗新生儿缺氧缺血性脑病提供新的理论依据.     

亚低温对新生鼠缺氧缺血性脑损伤保护作用的实验研究

为研究亚低温对新生鼠缺氧缺血性脑损伤的保护作用,应用7日龄大鼠制成缺氧缺血性脑损伤模型.动物随机分组假手术组(C组),缺氧缺血正常温度组(HI组),缺氧缺血后30分钟亚低温治疗组(亚低温组).脑皮质细胞匀浆用于测定丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,应用原位缺口末端标记(TUNEL)及免疫组化bax基因表达,观察神经细胞凋亡情况.结果显示,HI组MDA含量明显高于C组(P＜0.01),亚低温组MDA含量明显低于HI组(P＜0.01);亚低温组凋亡细胞明显少于HI组(P＜0.01).因此,亚低温可以通过减少自由基的产生,抑制细胞凋亡的机制发挥对缺氧缺血性脑损伤的保护作用.     

新生儿缺氧缺血性系列疾病的探讨

目的　 分析窒息致新生儿缺氧缺血性系列疾病 (HID)临床资料和预后 ,探讨改善预后的措施。 方法 　对 72例HID进行资料分析。 结果 　在 72例HID中 ,新生儿缺氧缺血性脑病 (HIE) 64例 ,新生儿缺氧缺血性肾脏损害 (HIR) 40例 ,新生儿缺氧缺血性心脏损害 (HIM ) 2 4例 ,经治疗 ,存活 60例 ,死亡 7例 ,放弃治疗 5例 ;胎儿期缺氧缺血较出生后缺氧致脏器损害多而重 ( χ2 =8 974,P <0 0 1) ,且预后差 ( χ2 =4 816,P <0 0 5 ) ;保持患儿血糖在正常的高值 ,预后明显优于低值正常血糖的患儿( χ2 =6 0 3 8,P <0 0 5 1,而中值正常水平血糖患儿预后与低值正常水平血糖患儿无显著差异 χ2 =1 3 0 2 ,P <0 0 5 )。 结论 　胎儿期缺氧缺血性HID和血糖在正常的低值的HID预后均差 ,保持血糖在正常的高值预后佳     

脑活素治疗新生儿缺氧缺血性脑病38例疗效分析

新生儿缺氧缺血性脑病(简称HIE)是新生儿死亡及儿童神经系统发育障碍的重要原因,已越来越受到儿科医师的重视。本文对38例缺氧缺血性脑病新生儿在常规治疗基础上加用脑活素治疗,取得     

缺氧诱导因子-1与心血管疾病

缺氧诱导因子(HIF)是一种在体内广泛存在的由缺氧、钴、镁、镍等诱导细胞产生的具有转录活性的核蛋白,由α和β亚基组成,两者属碱性螺旋-环-螺旋-PAS家族蛋白.近年研究发现,HIF-1参与心血管发育的调控,与缺血性心脏病、肺动脉高压、先天性心血管疾病等关系密切.进一步探讨HIF-1在机体缺氧、缺血稳态中的作用,对研究缺氧、缺血性心血管疾病的治疗有指导意义.     

别嘌呤醇对缺氧缺血性脑损伤的保护作用

别嘌呤醇为次黄嘌呤异构体,是临床上治疗痛风的主要用药.随着氧自由基学说的不断拓展,别嘌呤醇的抗氧化作用越来越受到重视.近年来新生儿缺氧缺血性脑病的危害受到高度重视,抗氧化治疗成为一种新的治疗方法.该文主要探讨了别嘌呤醇的药理作用及其对新生儿缺氧缺血性脑病保护作用的可能机制,包括减少氧自由基的产生、直接清除氧自由基、改善脑血管内皮细胞功能、抑制缺氧缺血性脑细胞凋亡、扩张血管改善脑血流等途径,为临床上应用别嘌呤醇治疗新生儿缺氧缺血性脑病提供参考.     

黄体酮对新生儿缺氧缺血性脑病作用的研究进展

新生儿缺氧缺血性脑病病死率和致残率较高,且缺乏有效的治疗方法,所以至今仍为医学界的难题.黄体酮作为神经类固醇激素已经证实对新生儿缺氧缺血性脑病有保护作用,且已经应用于Ⅱ期临床试验.该文综述黄体酮对新生儿缺氧缺血性脑病的治疗进展.     

高压氧治疗新生儿缺氧缺血性脑病前后血浆内皮素和一氧化氮的变化

目的　探讨高压氧 (HBO)治疗缺氧缺血性脑病 (HIE)的疗效及治疗HIE前后血浆内皮素 (ET)和一氧化氮 (NO)含量的变化和ET、NO临床应用价值。方法　将 6 0例HIE患儿随机分为一般治疗组、高压氧组各 30例 ,比较其疗效 ,并在治疗前后检测血浆ET、NO含量 ,同时以 30例正常新生儿组作对照。结果　一般治疗组和高压氧组治疗前血浆ET、NO明显高于正常新生儿组 (P <0 0 5 ) ;治疗后两组ET、NO均较治疗前明显降低 (P <0 0 5 )。但高压氧组较一般治疗组降低明显 ,两组间有显著性差异 ;两组近期有效率分别为 73%、93 3% ,有显著性差异。结论　一般治疗组与高压氧组都有疗效 ,但高压氧组疗效更显著 ,本研究说明高压氧治疗缺氧缺血性脑病可能通过降低ET、NO而减轻继发性缺氧缺血性炎症反应与脑细胞的破坏 ,说明ET、NO可以作为评价高压氧治疗缺氧缺血性脑病的客观生化指标     

神经节苷脂对缺氧缺血新生大鼠脑组织SOD、MDA影响的研究

新生儿缺氧缺血性脑病(HIE)是新生儿期危害最大的常见病,至今尚无满意的治疗措施.神经节苷脂(GM-1)存在于哺乳类动物神经组织,对中枢神经系统损伤后有一定的治疗和保护作用.本实验通过观察(GM-1)对缺氧缺血新生鼠脑组织中超氧化酶歧化酶(SOD),丙二醛(MDA)水平的影响,探讨GM-1对HIE的保护作用及其机制.     

The role of mast cells in eosinophilic esophagitis

Eosinophilic esophagitis (EE) is a chronic inflammatory disease of the esophagus which is characterized by the presence of dense infiltrate of eosinophilic leukocytes restricted to this organ mucosa. Accumulating published evidence suggests a strong role of mast cells in the inflammatory infiltrate in the physiopathology of EE. We have reviewed published articles with relevant information about the presence and possible role of mast cells in EE. Although mast cells have been studied indirectly in EE, reported data allow us to confirm that the number of mast cells infiltrating the esophageal epithelium in adult and child patients with EE is higher with respect to the normal state and in gastroesophageal reflux disease. Mast cells linked to IgE, which are not found in other conditions, have been identified in EE. Despite that fact, an anaphylactic reaction history after exposure to allergens is not common in these patients. Therefore, the mast cells’ function in EE could be dependent on T lymphocytes, as suggested by a mast cell gene expression analysis. Bi‐directional crosstalk is established between mast cells and eosinophils, hence establishing interesting hypotheses regarding their relationship to EE physiopathology. Mast cells’ function as an immune response leader seems to substitute for their effector functions in EE, while at the same time opening new research pathways for consideration of these cells as a therapeutic target in EE. However, the inefficiency of therapies that inhibit mast cell functions while they are effective in other respiratory tract diseases results in the need for specific studies to identify the real function of such complex cells in the physiopathology of EE. There is indirect proof of the role of mast cells in EE, while many doubts exist about their activation mechanism, which does not seem to be IgE‐mediated. Specific approach studies are needed to clarify the function of these cells in the physiopathology of EE, which could be a possible therapeutic target.     

Effect of high doses of intravenously administered immune globulin on natural killer cell activity in peripheral blood.

Because Kawasaki disease is a disorder characterized by lymphocyte activation and immune complex destruction of endothelial cells, we examined the effect of administration of high doses of intravenously administered immune globulin (IVIG) on a lymphocyte population with affinity for endothelial cells: the natural killer cells. We found that administration of high doses of IVIG resulted in a significant increase in the activity of natural killer cells and in the numbers of circulating CD16+ cells. Furthermore, a study of patients treated with IVIG for seizure disorders suggests that this effect of IVIG on circulating NK cells is not unique to patients with Kawasaki disease. The beneficial effect of IVIG in the treatment of Kawasaki disease may be due to the ability of IVIG to inhibit interaction between natural killer cells and endothelial cells.     

IL-21及其受体在自身免疫性疾病中的作用

白细胞介素21(IL-21)是IL-2家族中的新成员,主要由活化的CD4+T细胞和自然杀伤(NKT)细胞合成和分泌。白细胞介素21受体(IL-21R)主要表达在T、B及NK细胞上。IL-21与其受体结合后主要通过激活JAKs-STATs信号通路,调节T、B及NK细胞的活化和增殖发挥生物学功能。作为新型的免疫调节因子,IL-21及其受体在多种自身免疫性疾病的发生发展中扮演着重要的角色,调节IL-21和IL-21R的表达水平或应用阻断剂阻断它们的信号传导通路可作为自身免疫性疾病新的治疗方法。     

T AND B LYMPHOCYTE SUBPOPULATIONS AND LEUKOCYTE TERMINAL DEOXYNUCLEOTIDYL-TRANSFERASE IN ENERGY-PROTEIN UNDERNUTRITION

Abstract. Children with energy-protein undernutrition showed a reduction in the number of circulating T lymphocytes identified on the basis of their ability to form rosettes with sheep red blood cells. T cells with a receptor for IgM (T_μ) were decreased whereas T cells with a receptor for IgG (T_γ) were increased. Surface immunoglobulin bearing B cells were comparable in well nourished and malnourished subjects but the proportion of B_α was increased in the latter. "Null" cells without the conventional markers of T or B cells were proportionately increased. Leukocyte terminal deoxynucleotidyltransferase activity was elevated in the majority of undernourished children and correlated with the proportion of "null" cells. The significance of these observations is discussed and it is suggested that "null" cells represent immature undifferentiated T lymphocytes.     

Connective Tissue Growth Factor Expression in Pediatric Myofibroblastic Tumors

Human connective tissue growth factor (CTGF) is a secreted cysteine-rich peptide and a member of the peptide family that includes serum-induced immediate gene products such as a v-src-induced peptide and a putative proto-oncogene, c-src. CTGF is secreted by endothelial cells, fibroblasts, smooth muscle cells, and myofibroblasts. Its expression is increased in various human and animal fibrotic diseases. We hypothesized that tumors with significant fibrous and vascular components would exhibit increased expression of CTGF. We examined the expression of CTGF mRNA by in situ hybridization in 12 pediatric tumors and tumor-like conditions, including angiofibroma, malignant fibrous histiocytoma, infantile myofibromatosis, and malignant hemangiopericytoma. All the tumors showed moderate to intense CTGF expression in tumor cells and/or endothelial cells of the associated vasculature. Angiofibromas expressed CTGF only in factor VIII–positive endothelial cells and vascular smooth muscle cells. In contrast, infantile myofibromatosis, malignant hemangiopericytomas, and fibrous histiocytomas expressed CTGF in both endothelial cells and in vimentin-positive tumor cells, particularly those around the blood vessels. CTGF mRNA was not detected in the inflammatory cells observed in many of the tumors. The presence of CTGF in the endothelial cells and tumor cells around blood vessels raises the possibility that CTGF is involved in the pathogenesis of these myofibroblastic tumors. Received December 13, 1999; accepted May 23, 2000.     

The pancreatic duct cell: proliferative capabilities, specific characteristics, metaplasia, isolation, and culture

The pancreatic duct cell, although a minor cell type of the pancreas, plays an important role in fluid/electrolyte and mucin secretion, and has been implicated in the development of pancreatic cancer, alcoholic pancreatitis, and cystic fibrosis. In the normal pancreas, the duct cell has the same low proliferative rate as acinar and endocrine cells. Under certain pathological circumstances, duct cells, as well as acinar and islet cells, may be stimulated to proliferate more rapidly. Pancreatic duct cells exhibit certain features not shared by acinar and/or endocrine cells, including a variety of antigens, mucins, enzymes, and morphological features. Adult duct cells resemble fetal pancreatic duct-like cells morphologically, but they have differentiated to at least a limited extent from their precursor cell type. Although there is no evidence that duct cells differentiate into acinar cells after pancreatic morphogenesis is complete, some islet cells develop from duct epithelium in the early postnatal period. Some pathological conditions may lead to the postnatal formation of islet cells from duct cells and may cause acinar cells to become duct-like in morphology or to die and be replaced by duct cells. A better understanding of duct cells is now possible because of the development of techniques for their isolation and culture free from other cell types. Several such techniques are reviewed.     

Pathogenesis and immunologic findings in AIDS

As the numbers of children suffering from AIDS are slowly increasing in West Germany it is essential for pediatricians to be aware of events leading to clinically overt disease. This review summarizes events involved in viral attachment to CD4-bearing cells, intracellular replication, and destruction of both HIV-infected and non-infected cells. As a consequence of HIV-infection a profound and complex immunodeficiency is observed which is only partially explained by the loss of circulating CD4-bearing cells. Functions of antibodies, cytotoxic T-cells, natural killer cells, killer cells, as well as non-specific immune functions are discussed not only with respect to defense mechanisms in general but also with respect to the control of HIV-infection itself. Detailed understanding of these events seems to be a prerequisite for understanding the occurrence of infections and tumours in AIDS.     

Recent research on chimeric antigen receptor T cells in children with refractory/relapsed acute lymphoblastic leukemia北大核心CSCD

目前儿童复发难治性急性淋巴细胞白血病的治疗仍处于困境,即使提高化疗强度或联合造血干细胞移植,仍有部分患儿预后差,生存期短。嵌合抗原受体T细胞(chimeric antigen receptor T-cell,CAR-T)免疫疗法通过基因工程修饰T细胞,并利用不依赖于人类白细胞抗原途径识别肿瘤特异性抗原,靶向结合目标抗原细胞,触发免疫反应,从而发挥持续的抗白血病效应。作为发展最为迅速的肿瘤免疫疗法,CAR-T细胞在多种血液肿瘤的治疗中取得了突破性的进展,但目前国内尚未建立全面的CAR-T细胞研发生产体系和规范的临床诊治方案。该文就CAR-T细胞在儿童复发难治性急性淋巴细胞白血病中的研究进展作一综述。     

An Immunological Study on Mucocutaneous Lymph Node Syndrome: Activation of Tg Suppressor Cells

We analyzed the lymphocyte function of MCLS in pokeweed mitogen-induced immunoglobulin production. T cell suppressor activity was activated in the acute phase adn normalized in convalescence. T cells showing suppressor activity in this system were identified to be Tg cells, and they seemed to be activated as suppressor by a certain factor in the serum. the sera of patients whose T cells showed suppressor activity could induce the suppresoor activity of normal control Tg cells. The suppressor inducing factor in sera is likely to be circulating immune complexes, since T_g cells usually show suppressor activity when they interact with immune complexes. The induction of the suppressor activity of Tg cells by immune complexes may provide a kind of negative feedback suppression mechanism feedback mechanism on the antibody formation and it may be related to the self-limiting characteristics of MCLS. MCLS is different from collagen diseases such as rheumatoid arthritis in that Tg cells do not usually work as suppressor cells in the later diseases.     

Enrichment of Residual Tumor Cells in Bone Marrow Or Peripheral Blood Cells in a Neuroectodermal Tumor Model

To enrich a small population of malignant cells contaminating human bone marrow or peripheral blood, a method of immunomagnetic depletion of the normal nucleated cells was developed. In a model using neuroectodermal cell lanes, contaminations between 0.1% and 1.4% of tumor cells could be increased by a factor of 7.5 (median; range, 3.8 to 18.0; n = 10). Because incubation with antibodies is restricted to the magnetic beads in this method, th cell population after removal of the beads has not been incubated with antibodies. The risk of unspecific staining of the tumor cells during the enrichment procedure is minimal. This simple method is therefore well suited to the study of the characteristics of a minimal residual disease population.