脱氢表雄酮对人脐静脉内皮细胞CD40/CD40L表达的影响

目的:探讨脱氢表雄酮(DHEA)对干扰素-γ(I NF-γ)刺激下的人脐静脉内皮细胞(HUVECs)CD40/CD40L表达的影响。方法:原代培养人脐静脉内皮细胞,给予I NF-γ刺激和不同浓度DHEA干预。采用流式细胞术检测CD40/CD40L在细胞表面的表达,通过反转录-聚合酶链反应(RT-PCR)检测CD40/CD40L mRNA的表达。结果:I NF-γ刺激HUVECs表达CD40/CD40L,DHEA下调I NF-γ诱导的HUVECs表面CD40/CD40L的表达,同时对I NF-γ刺激下的CD40/CD40L mRNA的表达有抑制作用,并且呈剂量依赖性。结论:DHEA能减轻I NF-γ刺激下的人脐静脉内皮细胞CD40/CD40L的表达。     

Word-specific cortical activity as revealed by the mismatch negativity

Neurophysiological brain activity evoked by individual spoken words and pseudowords was recorded and the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was calculated. Consistent with earlier reported results, the MMN response to word-final syllables was enhanced compared with that elicited by the same syllables placed in a pseudoword context. Here we now demonstrate that the enhancement of the MMN elicited by two individual words showed different scalp topographies. The early word-specific brain activity is consistent with the assumption that the memory traces activated by individual words are carried by large neuronal ensembles that differ in their distributions over the cortex. Current source estimates localized the between-word differences in the right hemisphere and in parieto-occipital left-hemispheric areas. The differential brain responses to individual words appeared as early as ∼100 ms after the recognition points of the words, suggesting that their specific memory traces become active almost immediately after the information in the acoustic input is sufficient for word identification.     

Hepatic lysosomal enzymes activity and liver morphology after short-time omeprazole administration

The aim of the study was to establish the influence of short-time omeprazole administration on liver function and morphology. Omeprazole was administered intraperitoneally, twice daily, for 3 days to male Wistar rats in two doses: 0.571 mg/kg and 5.71 mg/kg. Control animals were treated with physiological saline. Half of the animals were sacrificed 12 hours after the last injection. The remaining rats were raised for another 6 weeks, without any xenobiotics, and sacrificed on the 47th day of the experiment. The activity of free and bound fractions of hepatic acid phosphatase, beta-galactosidase, beta-N-acetyl-glucosaminidase, cathepsin B, D and L, lipase, and sulphatase were determined spectrophotometrically in homogenates of the liver. The liver sections were examined by light microscopy with hematoxylin-eosin, azan, and periodic acid-Schiff stains. Marginally significant (p < 0.1) differences in activity of free sulphatase fraction, and free and bound fractions of beta-galactosidase were found in animals exposed to the higher dose of omeprazole and sacrificed 12 hours after the last injection. Enzymatic profiles were normalised during the next 6 weeks. Histological evaluation revealed small degenerative and adaptive changes in all examined groups. It could be concluded that observed differences of hepatic lysosomal enzyme activities were the result of accompanied chemical-induced peritonitis as previously reported, and not a direct drug-toxic effect.     

B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors

The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function.     

Dissecting the complexity of the memory T cell response

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.     

负性刺激分子PD-L对T细胞介导小鼠L929肿瘤细胞免疫效应的影响

目的：探讨负性刺激分子在肿瘤细胞逃避免疫效应中的作用.方法：以L929细胞为靶细胞,体内致敏C57BL/6小鼠,注入PD-L1、PD-L2抗体阻断,并设立未致敏对照组.分离小鼠脾细胞,体外采用3H-TdR掺入法、荧光标记双染色FCM以及PI染色FCM法分别检测淋巴细胞增殖反应、活化诱导的细胞凋亡以及脾细胞及其培养上清对肿瘤细胞的杀伤效应.结果：L929细胞表达PD-L1,而不表达PD-L2.体内与体外联合应用PD-L1抗体,能显著增强L929肿瘤细胞诱导的致敏组小鼠脾细胞的增殖活性和特异性杀伤效应,并可抑制活化诱导的T细胞凋亡;PD-L1抗体亦可增加L929细胞诱导的未致敏组小鼠脾细胞的增殖活性和促进其脾细胞培养上清对L929细胞的杀伤效应.结论：PD-L1抗体可通过阻断PD1/PDL途径促进初始T细胞和致敏T细胞介导的抗瘤效应.     

红细胞分化调节因子对体外培养的L929和KB细胞的生长抑制作用

从兔网织红细胞提纯的红细胞分化调节因子(erythroid differentiation factor,EDF),能对体外培养的自发转化成纤维细胞系L929及人鼻咽癌细胞系KB产生作用。当EDF剂量为0.10μg/ml时,可引起L929细胞形态发生改变,并有细胞核固缩现象。第2d的细胞生长抑制率为64.86％,软琼脂集落形成率为0;第5d时细胞增殖为负值。~3H-TdR掺入率明显降低。EDF剂量为0.15μg/ml时,对KB细胞生长已有抑制作用。EDF剂量达0.30μg/ml时,生长抑制明显。以上结果证明了EDF对恶性细胞具有增殖抑制作用。这种作用对不同种类细胞敏感性不同,并且与剂量呈正相关。     

表面磁性膜医用316L不锈钢支架的生物相容性

目的 对表面磁性膜血管内支架进行生物相容性研究,为该支架的临床应用提供实验依据.方法 通过溶血实验、动态凝血时间实验、急性全身毒性实验、皮内刺激实验、细胞毒性实验、热源实验、过敏实验、体内植入实验综合评价表面磁性膜血管内支架的生物相容性.结果 表面磁性膜血管内支架无溶血反应及凝血功能的改变,无急性全身毒性反应,无热源反应,支架材料中不存在致敏性物质;支架材料动物体内植入在初期有轻度的炎性反应,12周后炎性反应基本消失,未见炎性细胞浸润积聚现象.结论 表面磁性膜血管内支架具有良好的生物相容性,其应用于临床具有可行性和安全性.     

股骨粗隆间骨折采用改良L形钢板内固定的生物力学原理与临床应用

作者自1994年始采用自行设计L形钢板内固定治疗不稳定股骨粗隆间骨折60例，平均随访25个月，X线片显示骨折愈合时间6～13周，平均8．9周，伤肢功能在3个月内基本恢复正常，无骨折延迟愈合及髋内翻现象。为论证改良L形钢板的优点，本文采用8具新鲜尸股骨沿着它的外侧、内侧骨皮质粘贴6个应变片，观察股骨近端应变和位移分布，以检验改良L形钢板固定粗隆间骨折的效果。在实验前后将股骨粗隆造成二部分或四部分骨折。利用实验结果给制成应变和位移图，并与鹅头打固定组相比较。在载荷加至1800N时比较两种内固定器械的生物力学性能。结果表明，在治疗不稳定粗隆间骨折中，L形钢板比鹅头钉更具有生物力学的优势。     

Biochemical characterization of I-Ak proteins from mutant antigen-presenting B-cell--B-lymphoma hybridomas

Chemically induced mutants of an I-Ak,d expressing antigen-presenting B-cell--B-lymphoma hybridoma have recently been generated by immunoselection in vitro and were found to possess alterations in some of their serologically and functionally defined I-Ak region dependent functions. In order to identify at the structural level the origin of the differences in serological and functional properties of these mutants, I-Ak molecules from several of these mutant hybridomas were compared biochemically to wild-type I-Ak polypeptides by two-dimensional gel electrophoresis and high-pressure liquid chromatographic tryptic peptide analyses. Two-dimensional gel electrophoresis indicated that no major structural alterations, resulting in changes in mol. wt or charge, had occurred in the Ak alpha or Ak beta polypeptides from the mutant cells. Likewise, Ak alpha peptide maps of the mutants were indistinguishable from the normal Ak alpha peptide maps. However, two of the three mutants studied did exhibit one additional peptide in their Ak beta peptide maps. These results suggest that the major deficiencies in T-cell-activating functions of these mutants are a result of a limited alteration in the Ak beta polypeptide primary structure.