BACKGROUND & AIMS: :Accumulation of lipid-laden macrophages is a hallmark of atherosclerosis. The relevance of the key transcription factor nuclear factor kappaB (NF-kappaB) for macrophage-derived foam-cell formation has not been unequivocally resolved. Transgenic mice lines were generated in which NF-kappaB activation is specifically inhibited in macrophages by overexpressing a trans-dominant, non-degradable form of IkappaBalpha (IkappaBalpha (32A/36A)) under control of the macrophage-specific SR-A promoter. Alanine substitution of serines 32 and 36 prevents degradation and retains the inactive NF-kappaB/IkappaBalpha (32A/36A) complex in the cytoplasm. Similarly, stable human THP1 monocytic cell lines were generated with integrated copies of IkappaBalpha (32A/36A) cDNA. Upon treatment with oxidized low-density lipoprotein (ox-LDL), murine peritoneal macrophages from transgenic IkappaBalpha (32A/36A) mice, as well as THP1/IkappaBalpha (32A/36A) clones, display decreased lipid loading after differentiation into macrophages. This is accompanied by increased expression of the transcription factors PPARgamma and LXRalpha as well as of the major cholesterol-efflux transporter ABCA1. Paradoxically, mRNA expression of the 'lipid-uptake' receptor CD36 is also increased. Since the net result of these changes is reduction of foam-cell formation, it is proposed that under specific inhibition of NF-kappaB activation, ABCA1-mediated cholesterol efflux prevails over CD36-mediated lipid influx.

背景与目标： : 富含脂质的巨噬细胞的积累是动脉粥样硬化的标志。关键转录因子核因子kappaB (NF-kappaB) 与巨噬细胞衍生的泡沫细胞形成的相关性尚未明确解决。产生了转基因小鼠品系，其中在巨噬细胞特异性SR-a启动子的控制下，通过过表达反式显性，不可降解形式的IkappaBalpha (32A/36A))，在巨噬细胞中特异性抑制NF-kappaB的激活。丝氨酸32和36的丙氨酸取代可防止降解，并在细胞质中保留无活性的NF-kappaB/IkappaBalpha (32A/36A) 复合物。同样，用IkappaBalpha (32A/36A) cDNA的整合拷贝生成了稳定的人THP1单核细胞系。用氧化的低密度脂蛋白 (ox-LDL) 处理后，来自转基因IkappaBalpha (32A/36A) 小鼠的鼠腹膜巨噬细胞以及THP1/IkappaBalpha (32A/36A) 克隆在分化为巨噬细胞后显示出降低的脂质负荷。这伴随着转录因子PPARgamma和LXRalpha以及主要胆固醇外排转运蛋白abca1的表达增加。矛盾的是，“脂质摄取” 受体CD36的mRNA表达也增加。由于这些变化的最终结果是减少了泡沫细胞的形成，因此提出在NF-κ b活化的特异性抑制下，ABCA1-mediated胆固醇外排优于CD36-mediated脂质内流。

BACKGROUND & AIMS: A 38-year-old man, blood group A+, was allotransplanted for multiple myeloma from his fully matched sister, blood group O+. Anti-A antibodies IgG and IgM titres of the donor were low. Allogeneic peripheral blood stem cells were harvested by leukapheresis after subcutaneous administration of G-CSF. Rapid engraftment occurred since 5.6 x 10(9)/l leukocytes were achieved on day +9 post-transplant. At this time a severe immune haemolytic syndrome occurred and direct antiglobulin test was positive (IgG and C3d). Elution showed an anti-A specificity. Evolution was rapidly unfavourable related to multiorgan failure. The patient died on day +20 post-transplant.

背景与目标： 一名38岁的A血型男子从其完全匹配的姐姐O血型中同种异体移植了多发性骨髓瘤。供体的抗A抗体IgG和IgM滴度较低。皮下给予g-csf后，通过白细胞分离术收集异基因外周血干细胞。由于在移植后第9天实现了5.6 × 10(9)/l白细胞，因此发生了快速植入。此时发生了严重的免疫溶血综合征，直接抗球蛋白试验呈阳性 (IgG和C3d)。洗脱显示出抗A特异性。进化与多器官衰竭迅速不利。患者在移植后第20天死亡。

BACKGROUND & AIMS: :We have translated RNAs for the two rat asialoglycoprotein receptor polypeptides together in a cell-free system containing dog pancreatic microsomes and immunoprecipitated the products with antibodies that distinguish the two proteins. In this system the proteins oligomerize, as judged by their coprecipitation with either of the subunit-specific antisera. Oligomerization does not occur between subunits synthesized without microsomes or between subunits synthesized on separate microsomes mixed during detergent solubilization. Thus, oligomerization occurs within the microsomal membrane. We calculate that oligomerization proceeds with an efficiency of approximately 85%. The receptor complex appears to represent a specific oligomer because it excludes a third membrane glycoprotein synthesized in the same reaction. Oligomerization of the asialoglycoprotein receptor in vitro should provide a useful system to study the assembly of a membrane-protein complex.

背景与目标： : 我们已经在包含狗胰腺微粒体的无细胞系统中将两种大鼠去唾液酸糖蛋白受体多肽的rna翻译在一起，并用区分这两种蛋白质的抗体免疫沉淀了产物。在该系统中，蛋白质寡聚，根据它们与亚基特异性抗血清中的任何一种的共沉淀来判断。在没有微粒体的情况下合成的亚基之间或在洗涤剂增溶过程中混合的单独的微粒体上合成的亚基之间不会发生低聚。因此，低聚发生在微粒体膜内。我们计算低聚化以约85% 的效率进行。受体复合物似乎代表特定的寡聚体，因为它排除了在同一反应中合成的第三种膜糖蛋白。体外去唾液酸糖蛋白受体的寡聚化应为研究膜蛋白复合物的组装提供有用的系统。

BACKGROUND & AIMS: The mammalian transcription factor LSF (CP2/LBP-1c) binds cellular promoters modulated by cell growth signals. We demonstrate here that LSF-DNA-binding activity is strikingly regulated by induction of cell growth in human peripheral T lymphocytes. Within 15 min of mitogenic stimulation of these cells, the level of LSF-DNA-binding activity increased by a factor of five. The level of LSF protein in the nucleus remained constant throughout this interval. However, a rapid decrease in the electrophoretic mobility of LSF, attributable to phosphorylation, correlated with the increase in DNA-binding activity. pp44 (ERK1) phosphorylated LSF in vitro on the same residue that was phosphorylated in vivo, specifically at amino acid position 291, as indicated by mutant analysis. As direct verification of the causal relationship between phosphorylation and DNA-binding activity, treatment in vitro of LSF with phosphatase both increased the electrophoretic mobility of the protein and decreased LSF-DNA-binding activity. This modulation of LSF-DNA-binding activity as T cells progress from a resting to a replicating state reveals that LSF activity is regulated during cell growth and suggests that LSF regulates growth-responsive promoters.

背景与目标： 哺乳动物转录因子LSF (CP2/LBP-1c) 结合由细胞生长信号调节的细胞启动子。我们在此证明，LSF-DNA结合活性通过诱导人外周血T淋巴细胞中的细胞生长而显着调节。在有丝分裂刺激这些细胞的15分钟内，lsf-dna结合活性水平增加了5倍。在整个间隔内，细胞核中LSF蛋白的水平保持恒定。然而，由于磷酸化，LSF的电泳迁移率迅速降低与DNA结合活性的增加有关。pp44 (ERK1) 在体内磷酸化的相同残基上体外磷酸化LSF，具体地在氨基酸位置291，如突变体分析所示。作为磷酸化与DNA结合活性之间因果关系的直接验证，用磷酸酶体外处理LSF既增加了蛋白质的电泳迁移率，又降低了LSF-DNA结合活性。随着T细胞从静止状态发展为复制状态，LSF-DNA结合活性的这种调节表明LSF活性在细胞生长过程中受到调节，并表明LSF调节生长反应性启动子。

BACKGROUND & AIMS: :Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.

背景与目标： : 依那西普是一种重组人可溶性肿瘤坏死因子 (TNF-α) 受体融合蛋白，可抑制TNF-α，TNF-α 是移植物抗宿主病 (GVHD) 发病机理中的主要介质。我们研究的目的是评估依那西普治疗21例类固醇难治性急性GVHD (aGVHD) (n = 13) 和慢性GVHD (cGVHD) (n = 8) 患者的安全性和有效性。依那西普25 mg，每周皮下注射两次，持续4周，然后每周注射25 mg，持续4周。在开始使用依那西普时，14例患者有皮肤，13例有胃肠道，5例有肝脏，5例有肺部，4例有口腔受累。12名患者 (57%) 完成12剂治疗。总体而言，21例患者中有11例 (52%) 对依那西普治疗有反应，其中6例 (46% 例) aGVHD [n = 4完全缓解 (CR)，n = 2部分缓解 (PR)] 和5例 (62%) cGVHD (n = 1 CR，n = 4 PR)。临床反应最常见于难治性肠道aGVHD患者，其中55% 患者具有CR，9% 患者具有PR。48% 患者发生CMV再激活，14% 患者发生细菌感染，19% 患者发生真菌感染。自依那西普开始以来，中位随访429天 (范围71-1007天) 后，有14名患者 (67%) 还活着。7例患者死亡，3例感染，2例难治性aGVHD，2例疾病进展。总之，我们的初步数据表明，依那西普具有良好的耐受性，并且可以在类固醇难治性aGVHD和cGVHD患者中诱导高反应率，尤其是在GI受累的情况下。

BACKGROUND & AIMS: :The mechanism by which T cells signal other T cells is not well defined. This was investigated by studying the ability of circulating T cells to induce the proliferation of autologous T cell clones. Peripheral blood T cells activated by cross-linking of the CD3/T cell receptor complex, which increased the expression of cell adhesion molecules LFA-1, LFA-3 and ICAM-1, induced the proliferation of autologous T cell clones. Irradiated antigen-activated peripheral blood T cells could also induce the proliferation of T cell clones which could not recognize that antigen. T-T cell activation required cell contact, was not major histocompatibility complex (MHC) restricted and was blocked by monoclonal antibodies directed against adhesion molecules CD2 and LFA-3 but was not blocked by antibody to class II MHC determinants. As CD2 is the natural ligand for LFA-3, increased expression of T cell surface adhesion molecules LFA-1, ICAM-1 and particularly LFA-3 during an inflammatory response may rapidly recruit T cells that are activated through the CD2 pathway. These results allow a simplified model to explain how relatively few antigen/MHC-specific T cells can recruit large numbers of non-antigen-specific T cells in the generation of an inflammatory response and postulates a novel role of the CD2 molecule in T cell immune function.

背景与目标： : T细胞向其他T细胞发出信号的机制尚不明确。通过研究循环T细胞诱导自体T细胞克隆增殖的能力进行了研究。通过CD3/T细胞受体复合物交联激活的外周血T细胞，增加细胞粘附分子LFA-1、LFA-3和ICAM-1的表达，诱导自体T细胞克隆增殖。辐照的抗原激活的外周血T细胞也可以诱导无法识别该抗原的T细胞克隆的增殖。T-t细胞活化需要细胞接触，不受主要组织相容性复合物 (MHC) 的限制，并被针对粘附分子CD2和LFA-3的单克隆抗体阻断，但未被针对II类MHC决定簇的抗体阻断。由于CD2是LFA-3的天然配体，因此在炎症反应期间LFA-1、ICAM-1并且特别是LFA-3的T细胞表面粘附分子的表达增加可以快速募集通过CD2途径激活的T细胞。这些结果允许一个简化的模型来解释相对较少的抗原/MHC特异性T细胞如何在炎症反应的产生中募集大量非抗原特异性T细胞，并假设CD2分子在T细胞免疫功能中的新作用。

BACKGROUND & AIMS: Cardiac troponin T (cTnT) and troponin I (cTnI) have been suggested as new, more specific markers of myocardial cellular damage. The objective of this study was to examine how the distributions of cTnI and cTnT were affected in postinfarction left ventricular remodeled (LVR) myocardium. At 2 months postinfarct in a porcine heart failure model, both Western blot and biochemical assay analyses were performed on left ventricular myocardium remote from the infarct zone in ligation animals (n = 8). Results were compared with data from the left ventricular myocardium from similar sized healthy (control) pigs (n = 7). Autoradiograms from Western blot analysis showed that the protein mass for cTnI and cTnT in LVR hearts decreased 80% (P < 0.001) and 40% (P < 0.02), respectively, when compared with nondiseased tissue. Similarly, the concentrations for cTnI and cTnT in LVR hearts decreased 42% (P < 0.05) and 70% (P < 0.001), respectively, compared with nondiseased normal tissue. The clinical assumption is that the appearance of cTnI and cTnT in the blood is proportional to chronic loss of cTnI and cTnT from injured myocardium associated with left ventricular remodeling.

背景与目标： 心肌肌钙蛋白T (cTnT) 和肌钙蛋白I (cTnI) 已被认为是新的，更特异的心肌细胞损伤标志物。这项研究的目的是研究梗死后左心室重塑 (LVR) 心肌中cTnI和cTnT的分布如何受到影响。在猪心力衰竭模型中，在梗塞后2个月，对结扎动物 (n = 8) 远离梗塞区的左心室心肌进行了Western印迹和生化测定分析。将结果与类似大小的健康 (对照) 猪 (n = 7) 的左心室心肌数据进行了比较。来自Western blot分析的放射自显影图显示，与未患病组织相比，LVR心脏中cTnI和cTnT的蛋白质质量分别降低了80% (P < 0.001) 和40% (P <0.02)。同样，与未患病的正常组织相比，LVR心脏中cTnI和cTnT的浓度分别降低了42% (P < 0.05) 和70% (P <0.001)。临床假设是血液中cTnI和cTnT的出现与与左心室重构相关的受损心肌的cTnI和cTnT的慢性损失成正比。

BACKGROUND & AIMS: The involvement of antigen-specific T cells in the pathogenesis of collagen diseases is still controversial. The final stages of collagen diseases are usually characterized by the dominance of inflammation. Therefore, antigen non-specific factors, such as inflammatory cytokines, probably play an important role in this process. On the other hand, the methods available to analyze the antigen-specific aspects of the immune response are still limited. Here we review our novel system of T cell clonality analysis based on the idea that activated antigen-specific T cells should form accumulating clones among the lymphocyte population. Using this method, dynamic changes of clonal accumulation of T cells could be evaluated during antigenic stimulation in vivo and in vitro. The significance of antigen-specific T cell clones in collagen diseases is discussed using data obtained from patients with rheumatoid arthritis and systemic lupus erythematosus.

背景与目标： 抗原特异性T细胞参与胶原疾病的发病机理仍存在争议。胶原蛋白疾病的最后阶段通常以炎症为主。因此，抗原非特异性因子 (如炎性细胞因子) 可能在这一过程中起重要作用。另一方面，用于分析免疫应答的抗原特异性方面的方法仍然有限。在这里，我们基于激活的抗原特异性T细胞应在淋巴细胞群体中形成累积克隆的想法，回顾了我们的新型T细胞克隆分析系统。使用该方法，可以在体内和体外评估抗原刺激过程中T细胞克隆积累的动态变化。使用类风湿关节炎和系统性红斑狼疮患者获得的数据讨论了抗原特异性T细胞克隆在胶原疾病中的意义。

BACKGROUND & AIMS: Inflammatory cell infiltration of the lung is a predominant histopathological change that occurs during radiation pneumonitis. Emigration of inflammatory cells from the circulation requires the interaction between cell adhesion molecules on the vascular endothelium and molecules on the surface of leukocytes. We studied the immunohistochemical pattern of expression of cell adhesion molecules in lungs from mice treated with thoracic irradiation. After X-irradiation, the endothelial leukocyte adhesion molecule 1 (ELAM-1; E-selectin) was primarily expressed in the pulmonary endothelium of larger vessels and minimally in the microvascular endothelium. Conversely, the intercellular adhesion molecule 1 (ICAM-1; CD54) was expressed in the pulmonary capillary endothelium and minimally in the endothelium of larger vessels. Radiation-mediated E-selectin expression was first observed at 6 h, whereas ICAM-1 expression initially increased at 24 h after irradiation. ICAM-1 and E-selectin expression persisted for several days. P-selectin is constitutively expressed in Weibel-Palade bodies in the endothelium, which moved to the vascular lumen within 30 min after irradiation. P-selectin was not detected in the pulmonary endothelium at 6 h after irradiation. The radiation dose required for increased cell adhesion molecule expression within the pulmonary vascular endothelium was 2 Gy, and expression increased in a dose-dependent manner. These data demonstrate that ICAM-1 and E-selectin expression is increased in the pulmonary endothelium following thoracic irradiation. The pattern of expression of E-selectin, P-selectin, and ICAM-1 is distinct from one another.

背景与目标： 肺炎性细胞浸润是放射性肺炎期间发生的主要组织病理学变化。炎症细胞从循环中迁移需要血管内皮上的细胞粘附分子与白细胞表面的分子之间的相互作用。我们研究了经胸部照射治疗的小鼠肺中细胞粘附分子表达的免疫组织化学模式。X射线照射后，内皮白细胞粘附分子1 (ELAM-1; E-选择素) 主要在较大血管的肺内皮中表达，而在微血管内皮中表达最少。相反，细胞间粘附分子1 (ICAM-1; CD54) 在肺毛细血管内皮中表达，而在较大血管的内皮中表达最少。首先在6小时观察到辐射介导的E-选择素表达，而ICAM-1表达最初在辐射后24小时增加。ICAM-1和E-选择素表达持续数天。P-选择素在内皮的Weibel-Palade体中组成性表达，在照射后30分钟内移至血管腔。照射后6小时，在肺内皮中未检测到P-选择素。肺血管内皮细胞粘附分子表达增加所需的辐射剂量为2 Gy，并且表达以剂量依赖性方式增加。这些数据表明，胸部照射后，肺内皮中ICAM-1和E-选择素的表达增加。E-选择素，P-选择素和ICAM-1的表达模式彼此不同。

BACKGROUND & AIMS: OBJECTIVE:The aim of this study was to assess the potential contribution of HLA-class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell arteritis (GCA). METHODS:Ninety-eight biopsy-proven GCA patients and 225 ethnically matched controls from Lugo, Northwest Spain, were genotyped for the MICA-TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probes system. RESULTS:A significant difference in the distribution of the alleles of MICA between patient and control groups (P = 0.005) was found. This was due to an increased frequency of the MICA A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; P(C) = 0.0005; OR 2.2, 95% CI 1.4-3.4). In addition, the HLA-B*15 allele showed a higher frequency in GCA patients compared with controls (P = 0.004; P(C) = 0.04; OR 2.7, 95% CI 1.3-5.7). Interestingly, the association observed with the MICA A5 allele seems to be independent of linkage disequilibrium with HLA-B, as well as independent of that previously described with HLA-DRB1*04. Remarkably, simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers leads to an increase in the OR obtained for each individual genetic marker (MICA A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8). CONCLUSIONS:Our results provide the first evidence that the MICA and HLA-B genes are independently associated with the genetic susceptibility to GCA, and suggest that several genes within the MHC might have independent effects in the susceptibility to this systemic vasculitis.

背景与目标：

BACKGROUND & AIMS: :We present the case of an 80-year-old lady known to be sensitive to chlorocresol (4-chloro-3-methyl phenol) who developed severe erythrodermic exfoliative dermatitis with atypical features 2 weeks after commencing subcutaneous insulin. All medications except insulin were stopped, without major improvement. It was noted that the insulin contained m-cresol (m-methyl phenol) so a parabens-based insulin was substituted. There was a significant improvement in her clinical condition within 72 hr. Further patch and intradermal testing to the insulin and m-cresol was planned, but she developed a nosocomial infection and died. We hypothesize that the adverse cutaneous reaction was a systemic manifestation of cresol sensitivity, given the rapid clinical resolution on changing insulins and the previously demonstrated sensitivity to chlorocresol, particularly as cross-reactivity between different low molecular weight methyl phenols is documented. Local injection site reactions and systemic side-effects including nausea, diarrhoea and vomiting have previously been reported with cresol-containing insulins, although to our knowledge, this is the first reported case of a severe cutaneous reaction. It is important to be aware of m-cresol as a potential allergen, as it is contained in most commercially available insulins.

背景与目标： : 我们介绍了一位对氯甲酚 (4-氯-3-甲基苯酚) 敏感的80岁女士的病例，该女士在开始皮下胰岛素治疗2周后出现了严重的红皮病剥脱性皮炎，具有非典型特征。除胰岛素外，所有药物均停止，无明显改善。注意到胰岛素含有间甲酚 (间甲基苯酚)，因此取代了基于对羟基苯甲酸酯的胰岛素。她的临床状况在72小时内有明显改善。计划对胰岛素和间甲酚进行进一步的贴剂和皮内测试，但她发生了医院感染并死亡。我们假设不良皮肤反应是甲酚敏感性的全身性表现，因为临床上对胰岛素的快速反应以及先前证明的对氯甲酚的敏感性，尤其是在记录了不同低分子量甲基酚之间的交叉反应性时。含甲酚的胰岛素以前曾报道过局部注射部位反应和全身副作用，包括恶心，腹泻和呕吐，尽管据我们所知，这是首次报道的严重皮肤反应病例。重要的是要意识到间甲酚是一种潜在的过敏原，因为它包含在大多数市售的胰岛素中。

BACKGROUND & AIMS: CD4+ anti-tumor T cells reactive with rat adenocarcinoma 13762 kill tumor in vitro and cause regression of tumor in vivo. The role of various host immune cells in CD4+ T-cell-mediated tumor elimination in vivo was investigated by adoptive transfer of anti-tumor T cell clones to recipients that were selectively depleted of individual immune cell types. By these means, macrophages and NK cells were found to be required for tumor killing. Depletion of host CD4+ T cells, CD8+ T cells, or neutrophils was without effect on tumor elimination by anti-tumor T cells. An essential role for antigen receptor-negative NK cells is likely dependent upon secretion of IFN-gamma from NK cells since treatment of tumor recipients with anti-IFN-gamma antibody prior to adoptive transfer and tumor challenge abrogated T cell killing, resulting in progressive tumor growth. Viability of adenocarcinoma 13762 or anti-tumor T cells was unaffected by treatment with either IFN-gamma or anti-IFN-gamma antibody in vitro, but cell surface MHC class II expression was induced in tumor cells by exposure to IFN-gamma. In addition, tumor cells were isolated from tumor-bearing animals by absorption using anti-MHC class II antibody, demonstrating that 13762 tumor expresses cell surface MHC class II antigens in situ. However, if hosts were depleted of NK cells before tumor challenge, MHC class II+ tumor was not recovered. Collectively these results suggest that adenocarcinoma 13762 is eliminated by MHC class II-restricted CD4+ T cells by direct tumor killing.

背景与目标： 与大鼠腺癌反应的CD4 + 抗肿瘤T细胞13762在体外杀伤肿瘤并在体内引起肿瘤的消退。通过将抗肿瘤T细胞克隆过继转移到选择性耗尽个体免疫细胞类型的受体，研究了各种宿主免疫细胞在体内CD4 T细胞介导的肿瘤消除中的作用。通过这些方法，发现巨噬细胞和NK细胞是杀死肿瘤所必需的。宿主CD4 T细胞，CD8 T细胞或中性粒细胞的耗竭对抗肿瘤T细胞消除肿瘤没有影响。抗原受体阴性NK细胞的重要作用可能取决于NK细胞中IFN-γ 的分泌，因为在过继转移和肿瘤挑战之前用抗IFN-γ 抗体治疗肿瘤接受者消除了T细胞杀伤，导致进行性肿瘤生长。腺癌13762或抗肿瘤T细胞的活力在体外不受IFN-γ 或抗IFN-γ 抗体治疗的影响，但细胞表面mhcii类表达通过暴露于IFN-γ 在肿瘤细胞中诱导。此外，通过使用抗MHC II类抗体吸收从荷瘤动物中分离肿瘤细胞，证明13762肿瘤原位表达细胞表面MHC II类抗原。但是，如果宿主在肿瘤激发之前耗尽了NK细胞，则MHC II类肿瘤将无法恢复。这些结果共同表明，通过直接杀伤肿瘤，MHC II类限制性CD4 T细胞消除了腺癌13762。

BACKGROUND & AIMS: The thymic microenvironment plays a key role in the intrathymic T-cell differentiation. It is composed of a tridimensional network of epithelial cells whose physiology is controlled by extrinsic circuits such as neuroendocrine axes. Herein we show that the expression of extracellular matrix ligands and receptor by cultured thymic epithelial cells is upregulated by prolactin (PRL) and growth hormone (GH), the latter apparently occurring via insulin-like growth factor I (IGF-I). Thymocyte release from the lymphoepithelial complexes, thymic nurse cells, as well as the reconstitution of these complexes are enhanced by PRL, GH or IGF-I. Treatment of a mouse thymic epithelial cell line with these hormones induced an increase in thymocyte adhesion, an effect significantly prevented in the presence of antibodies to fibronectin, laminin or respective receptors VLA-5 and VLA-6. Our data suggest that the in vitro changes in thymocyte/thymic epithelial cell interactions induced by pituitary hormones are partially mediated by the enhancement of extracellular matrix ligands and receptors.

背景与目标： 胸腺微环境在胸腺内T细胞分化中起关键作用。它由上皮细胞的三维网络组成，其生理受外部回路 (例如神经内分泌轴) 控制。在本文中，我们显示培养的胸腺上皮细胞的细胞外基质配体和受体的表达被催乳素 (PRL) 和生长激素 (GH) 上调，后者显然通过胰岛素样生长因子I (igf-i) 发生。PRL，GH或igf-i增强了从淋巴上皮复合物，胸腺护士细胞的胸腺细胞释放以及这些复合物的重建。用这些激素处理小鼠胸腺上皮细胞系诱导胸腺细胞粘附的增加，在存在针对纤连蛋白，层粘连蛋白或相应受体VLA-5和VLA-6的抗体的情况下，这种作用被显着阻止。我们的数据表明，垂体激素诱导的胸腺细胞/胸腺上皮细胞相互作用的体外变化部分是由细胞外基质配体和受体的增强介导的。

BACKGROUND & AIMS: :Assessment of wound healing is a complex task, especially when the lesion is associated to significant (full thickness) loss of the skin. The clinical observation, essentially subjective and highly dependent on the observer's experience, creates difficulties in the comparison of results. Scoring scales were introduced in the clinical practice to create comparable semi-quantitative data and promote better management of resources, but its usefulness in a clinical perspective is still limited. New non-invasive biometric methodologies, although infrequently used, have opened new possibilities. While complementing the clinical observation and contributing to therapeutic decisions and prognosis, they may also help to look further into the pathophysiological mechanisms of scarring drugs rehabilitation. Following previous work in this arena, the authors review, the state-of-the-art of cutaneous wound healing clinical and biometric follow up, proposing a diagnosis correlation for the most relevant descriptors found in both strategies in order to fully characterise the different stages of the healing process.

背景与目标： : 评估伤口愈合是一项复杂的任务，尤其是当病变与皮肤的显着 (全层) 损失相关时。临床观察本质上是主观的，并且高度依赖于观察者的经验，因此在比较结果方面造成了困难。在临床实践中引入了评分量表，以创建可比较的半定量数据并促进更好的资源管理，但其在临床方面的实用性仍然有限。新的非侵入性生物识别方法虽然很少使用，但开辟了新的可能性。在补充临床观察并有助于治疗决策和预后的同时，它们也可能有助于进一步研究疤痕药物康复的病理生理机制。在这个领域的先前工作之后，作者回顾了皮肤伤口愈合的最新技术，临床和生物特征随访，提出了两种策略中最相关的描述符的诊断相关性，以便充分表征不同的特征愈合过程的阶段。

BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.

背景与目标： : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术，跟踪畸形疾病的过程，然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠，该小鼠经过工程改造以过表达golli J37，Golli-mbp基因复合物的产物，特别是在少突胶质细胞中。从21天到75天大，在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹，我们认为这是同类研究中的首次纵向研究。microMRI数据表明，在髓鞘形成峰值期间 (21-42天)，明显的整体髓鞘减少，与对照组相比，JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处具有很好的相关性。In: Ransom B，Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社，伦敦，pp 555-570] 髓磷脂染色，[Campagnoni AT，macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤，在以后的年龄减弱，并且 [Lees MB，Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社，pp 197-224] VEPs，所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。总体而言，这些非侵入性技术能够在空间上解决正常发育和发育延迟的小鼠大脑中髓鞘形成的增加。