Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma.

BACKGROUND: Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. OBJECTIVE: To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS: From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. RESULTS: The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). CONCLUSION: In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.     

Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel

Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts and most other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp (RGD) sequence and then crosslinked with polyethylene glycol (PEG) diacrylate (PEGDA) to create a biomaterial that supported cell attachment, spreading, and proliferation. The hydrogels were evaluated in vitro and in vivo in three assay systems. First, the behavior of human and murine fibroblasts on the surface of the hydrogels was evaluated. The concentration and structure of the RGD peptides and the length of the PEG spacer influenced cell attachment and spreading. Second, murine fibroblasts were seeded into HA-DTPH solutions and encapsulated via in situ crosslinking with or without bound RGD peptides. Cells remained viable and proliferated within the hydrogel for 15 days in vitro. Although the RGD peptides significantly enhanced cell proliferation on the hydrogel surface, the cell proliferation inside the hydrogel in vitro was increased only modestly. Third, HA-DTPH/PEGDA/peptide hydrogels were evaluated as injectable tissue engineering materials in vivo. A suspension of murine fibroblasts in HA-DTPH was crosslinked using PEGDA plus PEGDA peptide, and the viscous, gelling mixture was injected subcutaneously into the flanks of nude mice; gels formed in vivo following injection. After 4 weeks, growth of new fibrous tissue had been accelerated by the sense RGD peptides. Thus, attachment, spreading, and proliferation of cells is dramatically enhanced on RGD-modified surfaces but only modestly accelerated in vivo tissue formation.     

Synergistic antiviral activity of human interferon combinations in the hepatitis C virus replicon system.

The use of type I interferon (IFN), in combination with ribvirin, to treat chronic hepatitis C virus (HCV) infection has many drawbacks that prevent widespread application, ultimately leading to a significant unmet clinical need. Potential improvements in IFN therapy through targeted delivery, molecular alteration, and combination with other agents are ongoing in an attempt to decrease adverse effects and increase efficacy. In this report, the HCV replicon cell culture system was used to assess potential synergistic antiviral effects of multiple IFN species when administered in combination. Quantitative analysis of HCV replicon RNA by TaqMan (PE Applied Biosystems, Foster City, CA) and qualitative analysis of HCV protein expression were used to measure the antiviral efficacy of individual and combination IFN treatments, and synergistic responses of IFN combinations were determined through statistical analysis of the TaqMan results. We found that when administered simultaneously, type I/II IFN combinations (IFN-alpha2b + IFN-gamma or IFN-beta + IFN-gamma) resulted in dramatic antiviral synergy, whereas a type I/I combination (IFN-alpha2b + IFN-beta) demonstrated a slightly antagonistic profile. The synergistic effect is likely due to differential cell surface receptors and signaling pathways employed by types I and II IFNs. Conversely, all type I IFN species bind the same receptor and signal through similar pathways, possibly accounting for the nearly additive response observed. In support of this hypothesis, IFN treatment resulted in differential induction of Stat1 phosphorylation at Tyr 701. In conclusion, simultaneous type I/II IFN combination treatment may allow an overall decreased effective IFN dose, which may reduce the side effect profiles that hinder current therapy.     

金属表面TiO2薄膜的溶胶-凝胶法制备及其血液相容性研究

通过溶胶 凝胶法制备TiO2 薄膜对 316L不锈钢和NiTi形状记忆合金进行表面改性处理。研究发现 ,经 5 0 0℃处理 1h的薄膜结构致密 ,膜层均匀平滑 ,薄膜主要由锐钛矿相TiO2 构成 ,随热处理温度的提高 ,锐钛矿相逐渐转变为金红石相。电化学腐蚀和动态凝血时间及溶血率测试表明 ,通过溶胶 凝胶法制备TiO2 膜进行表面改性的 316L不锈钢和NiTi合金的抗模拟体液腐蚀性提高 ,动态凝血时间延长 ,溶血率下降 ,说明溶胶 凝胶法制备TiO2 膜可以提高金属植入物的血液相容性     

A comparison of two data analyses from two observer performance studies using Jackknife ROC and JAFROC

The authors compared two methodological approaches, Jackknife ROC and JAFROC, in analyzing data ascertained during FROC (free-response receiver operating characteristics) type studies. Observer rating data obtained from two observer performance studies were analyzed. During the first study, seven radiologists interpreted 120 mammography examinations depicting 57 masses under five different conditions with and without the results of computer-aided detection (CAD). In the second study, eight radiologists interpreted 110 examinations depicting 51 masses under six different display conditions with and without CAD results. Readers rated the detection task in a FROC type response. Jackknife ROC (using the software of LABMRMC with the highest rating per case) and JAFROC were used to compute differences, if any, in summary performance levels among all reading modes in each study as well as for all paired data sets. The results of the different analytical approaches are compared. The overall results for all modes were significantly different for the first study (p < 0.05) and not significant (p > 0.05) for the second study using either analytical approach. In the first study, the performance levels represented by three paired data sets were significantly different (p < 0.05) when computed using LABMRMC and four pairs were significantly different (p < 0.05) using JAFROC. In eight of ten pairs, JAFROC produced lower p values than LABMRMC. In the second study, LABMRMC showed no significant differences for any paired data sets and JAFROC showed a significant difference for one pair. In 15 of 16 pairs, p values computed by JAFROC were lower than those computed by LABMRMC.     

Collagen-coated polylactide microspheres as chondrocyte microcarriers

Polylactide (PLA) microspheres were coated with collagen for cell culture and injectable cell carriers. Utilizing a method of emulsion-solvent evaporation, PLA microspheres with diameter ranging from 180 to 280 microm were prepared, followed with aminolysis in hexanediamine/n-propanol solution to introduce free amino groups on their surfaces. After the amino groups were transferred into aldehyde groups by a treatment of glutaraldehyde, collagen type I was covalently coupled via Schiff base formation between the aldehyde groups and the amino groups on collagen molecules. Meanwhile, physically entangled collagen molecules were retained following a grafting-coating protocol to yield microspheres coated with larger amount of collagen. Aminolysis resulted in weight loss of the microspheres following a linear relationship with the aminolysis time. The NH2 and collagen contents existed on the microsphere surface were quantitatively determined by ninhydrin and hydroproline (Hyp) analyses, respectively. Larger amount of collagen was immobilized on the microspheres with higher content of NH2. In vitro chondrocyte culture revealed that the cells could attach, proliferate and spread on these PLA microspheres, in particular on the ones having higher content of collagen. These results show that the collagen-coated PLA microspheres are promising candidate as cell microcarriers.     

补肾宁心方对人单核-血管内皮细胞粘附的影响

目的:探讨补肾宁心方对人单核-血管内皮细胞粘附的影响及机理。方法:以培养人脐静脉内皮细胞(HUVECs)作为靶细胞,在内皮细胞培养基中加入氧化的低密度脂蛋白(ox-LDL)或在试验体系中加入灌服补肾宁心方的兔血清,以孟加拉玫瑰红活细胞染色法测定人单核细胞系U937与HUVECs的粘附,并用流式细胞仪检测内皮细胞表面粘附分子细胞间粘附分子-1(ICAM-1)、血管细胞粘附分子-1(VCAM-1)以及E-选择素的表达。结果:ox-LDL显著增强单核U937细胞与内皮细胞之间的相互粘附,如在试验体系中加入灌服补肾宁心方的动物血清,则粘附率明显降低(P＜0.01)。流式细胞仪分析结果显示ox-LDL能明显促进内皮细胞表面ICAM-1、VCAM-1以及E-选择素的表达,补肾宁心方中药灌服血清可显著下调内皮细胞表面ICAM-1、VCAM-1以及E-选择素的表达(P＜0.01)。结论:补肾宁心方含药血清可能通过下调内皮细胞表面粘附分子的表达抑制单核-血管内皮细胞粘附,从而发挥对血管内皮细胞的保护作用。     

基于基因免疫制备抗人绒毛膜促性腺激素β亚基单克隆抗体及其特性研究

用真核表达人绒毛膜促性腺激素β亚基((human chorionic gonadotrophinβ,hCGβ)的重组质TR421-hCGβ免疫BALB/c小鼠,采用B淋巴细胞杂交瘤技术进行细胞融合,ELISA法筛选阳性细胞株,经过多次的克隆化培养,最终获得10株持续、稳定分泌抗hCGβ单克隆抗体的杂交瘤细胞株。随机抽取6H1杂交瘤细胞进行抗体的制备、纯化及免疫学特性的分析。间接ELISA法证明6H1单抗属于IgG2a亚类。Western blot证明6H1单克隆抗体可以特异性结合hCGβ,间接免疫荧光和流式细胞仪等结果表明,6H1单克隆抗体能够不同程度的结合不同来源的肿瘤细胞膜上表达的hCGβ分子,为进一步研究其生物学功能奠定了物质基础。     

家兔喉淋巴管的微细分布

目的进一步明确家兔喉淋巴管的微细分布。方法采用5′-核苷酸酶-碱性磷酸酶双重染色法(5′-Nase-ALP),半薄切片光镜观察,超薄切片电镜观察。结果喉壁除韧带和软骨层外,其粘膜层、粘膜下层、肌层和外膜均可见毛细淋巴管和淋巴管,其分布的密度不同。喉各分区淋巴管分布具有显著差异,其中以会厌喉面分布密度最高,声襞淋巴管的分布密度最低。在喉的三个间隙即会厌前间隙、声门旁间隙和任克氏间隙中均存在淋巴管,但检出率较低。结论喉壁除韧带和软骨层外,其余各层均存在毛细淋巴管和淋巴管,喉各分区淋巴管分布密度不同。