Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

BACKGROUND: Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. OBJECTIVES: This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. RESULTS: While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. CONCLUSION: The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.     

Laparoscopy and Peripancreatic Neoplasia

Since its inception laparoscopy has been a valuable tool for diagnosis, and more recently it has become widely accepted as a medium for surgical intervention. In this light, the addition of minimally invasive techniques to the management of peripancreatic cancer has gained notable attention. Although most practitioners agree that there is some role for minimally invasive therapy, opinions vary as to the extent and significance these applications carry to the overall management of peripancreatic malignancies.     

Identification of Equine Arteritis Virus Immunodominant Epitopes Using a Peptide Microarray

Using the commercially available PEPperCHIP^® microarray platform, a peptide microarray was developed to identify immunodominant epitopes for the detection of antibodies against Equine arteritis virus (EAV). For this purpose, the whole EAV Bucyrus sequence was used to design a total of 1250 peptides that were synthesized and spotted onto a microarray slide. A panel of 28 serum samples representing a selection of EAV strains was tested using the microarray. Of the 1250 peptides, 97 peptides (7.76%) showed reactivity with the EAV-positive samples. No single peptide was detected by all the positive serum samples. Seven peptides repeatedly showed reactivity above the cut-off and were considered to have diagnostic potential. Five of these peptides were within the immunodominant GP5 protein and two were within the replicase polyprotein regions NSP2 and NSP10, located in ORF1. The diagnostic sensitivity of the seven peptides selected was low, ranging from 5% to 55%; however, the combined diagnostic sensitivity and specificity of the seven peptides was 90% and 100%, respectively. This data demonstrate that multiple peptide sequences would be required to design a comprehensive serological test to cover the diversity of the EAV strains and the individual immune responses of horses.     

原发性高血压的基因治疗前瞻

目的:综合分析目前原发性高血压基因治疗的前景及其面临的主要问题。资料来源:应用计算机检索Pubmed数据库1996-01/2006-01有关原发性高血压基因治疗的文章,检索词“hypertension,genetherapy”,限定文章种类为“English”。同时检索万方数据2000-01/2006-01有关原发性高血压基因治疗的文章,检索词“原发性高血压,基因治疗/疗法”。资料选择:纳入标准:①关于原发性高血压基因治疗策略的研究。②关于基因治疗正义及反义基因的研究。③关于原发性高血压基因治疗载体的研究。排除标准:陈旧或重复性研究及综述。资料提炼:共收集到195篇与原发性高血压基因治疗相关的文献,其中30篇符合纳入标准。资料综合:①原发性高血压基因治疗目前有两种策略,即反义抑制策略和过度表达策略。反义抑制策略减少原发性高血压和心血管病理生理相关的基因转录和翻译;过度表达策略使血压降低相关基因的表达都增加,从而增加舒血管物质的生成使血管舒张。②原发性高血压基因治疗要选择高效转染分裂和非分裂细胞,易于大量制造,无免疫原性,无毒副作用,可载入大分子DNA,能整合进入宿主基因组,且不影响其他基因的载体。③目前面临着原发性高血压靶基因的界定、载体的选择等问题。结论:靶基因的界定,载体的构建和基因转移法是原发性高血压基因治疗的关键,基因治疗可减少传统药物治疗带来的副作用,降低原发性高血压的发病率,甚至治愈原发性高血压。     

Serum interleukin-10 in non-Hodgkin's lymphoma: a prognostic factor

Serum interleukin-10 (IL-10) was measured retrospectively in 153 patients with a fully documented history of non-Hodgkin's lymphoma (NHL) using an enzyme-linked immunosorbent assay (ELISA) detecting both human IL-10 and the Epstein-Barr virus (EBV) molecule BCRF1/viral IL- 10. IL-10 was detectable in 47 (46%) of the 101 patients with active NHL, 3 of 52 (6%) patients in first partial or complete response, and none of the 60 healthy blood donors. Serum IL-10 was detectable with a similar frequency in all subtypes of NHL and in all clinical stages, as well as in EBV-seropositive and EBV-negative patients. In patients with intermediate or high-grade NHL, the presence of detectable serum IL-10 at diagnosis was correlated to a significantly shorter overall (P = .025) and progression-free (P = .030) survival. Patients with stage IV disease and detectable serum IL-10 had a particularly poor prognosis (4 years of survival: 0%). Multivariate analysis showed that IL-10 was an independent prognosis factor. These results indicate that IL-10 is detectable in a subgroup of patients with active NHL and correlates to a poor survival in patients with intermediate or high-grade NHL.     

静息状态脑功能网络的研究及应用

目的:对静息状态网络的研究方法、初步的研究成果等作以介绍,并结合静息状态网络在阿尔茨海默病早期预警中的应用,介绍静息状态脑网络的应用。资料来源:应用计算机检索PubMed1980-01/2006-12与静息状态网络相关的文献,检索词“restingstate,functional connectivity”,并限定文献语言种类为“English”;同时计算机检索万方数据库1995-01/2006-12有关方面的文献,检索词为“静息,功能连接,阿尔茨海默病”,并限定语言种类为中文。资料选择:对资料进行初审,选取包括静息状态的相关文献,开始查找原文。纳入标准:①有关静息状态脑网络和功能连接的研究。②有关阿尔茨海默病的研究。排除标准:重复研究。资料提炼:共收集到53篇有关静息状态网络方面的研究,排除23篇重复性研究,30篇符合要求。资料综合:近年来,研究者发现大脑处于无任务的静息状态时,仍然存在着某种功能活动。这些现象表明大脑在静息状态时可能存在有组织的网络。这有助于对人脑高级意识和某些认知疾病的研究,因此,有关这方面的工作越来越受到人们的重视。结论:对静息状态网络的本质和规律的研究还很有限,对这个网络所支持的精确的功能还有待于进一步研究。     

Urine leukotriene E4 levels are elevated in patients with active systemic lupus erythematosus.

The peptidoleukotrienes, leukotriene (LT) C4 and its metabolites LTD4 and LTE4, cause diverse physiologic effects and have been implicated in several disease processes. A potential role for enhanced peptidoleukotriene synthesis in the pathogenesis of autoimmune disease in general and systemic lupus erythematosus (SLE) in particular has been suggested by animal studies. Therefore, we measured the urinary levels of LTE4 in patients with active and inactive SLE as well as in patients with rheumatoid arthritis (RA), scleroderma (Scl), and in healthy controls. Comparisons were made to other standard clinical tests in assessing individual patient disease activity. A marked increase in urinary LTE4 levels in patients with active SLE was noted (319 +/- 49 pg/mg creatinine, n = 20) relative to patients with inactive SLE (80 +/- 8 pg/mg creatinine, n = 7 [p less than 0.02]), patients with RA (86 +/- 8 pg/mg creatinine [p less than 0.01]), and healthy controls (68 +/- 4.3 pg/mg creatinine, n = 6 [p less than 0.01]). Patients with Scl also had elevated urinary LTE4 levels (188 +/- 33 pg/mg creatinine, n = 7) relative to controls (p less than 0.02), while values from patients with RA were not significantly different from controls. Using the Systemic Lupus Activity Measurement as a gauge of clinical activity, a rise in urinary LTE4 levels was noted during stages of active disease with a subsequent decline following the resolution of these symptoms. Our data indicate that increased synthesis of leukotrienes is associated with active SLE and Scl and suggest that these leukotrienes may mediate certain symptoms associated with these diseases.