Genetic markers may predict disease behavior in patients with ulcerative colitis

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. (Gastroenterology 1997 Jun;112(6):1845-53)     

Lymphangiomyomatosis: CT, chest radiographic, and functional correlations

Eight patients with the diagnosis of lymphangiomyomatosis were evaluated with computed tomography (CT), chest radiography, and pulmonary function tests to determine the relationship between the extent of disease seen on imaging studies and functional status. Chest radiographic assessment included the subjective determination of disease extent and measurements of lung length and the arc of the right hemidiaphragm. Disease extent on CT scans was scored as a percentage of lung that was abnormal on the basis of visual assessment of the degree of cystic replacement of the lung parenchyma. Significant correlations were observed between CT scores and percentages of predicted forced expiratory volume in 1 second/forced vital capacity (r = -.92, P less than .002) and diffusing capacity of the lungs for carbon monoxide (r = -.80, P less than .017). No significant correlations were observed between subjective chest radiographic scores and pulmonary function tests, although measurements of lung length and percentage of predicted total lung capacity were correlated (r = .76, P less than .045). CT was more accurate than chest radiography in defining the presence and extent of parenchymal cysts and provided for greater morphologic-physiologic correlation. CT, particularly high-resolution CT, may be useful in the diagnosis and longitudinal evaluation of patients with this disease and may be more sensitive than pulmonary function tests in the early stages of lung damage.     

间充质干细胞的来源

目的:间充质干细胞具有强大的增殖能力和多向分化潜能,文章对其主要的来源途径予以综述。资料来源:应用计算机检索Medline1991-01/2006-01期间的相关文章,检索词为“mesenchyma stem cells,origin,research progress”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1998-01/2006-10期间的相关文章,检索词为“间充质干细胞,来源,研究进展”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:①间充质干细胞的起源。②间充质干细胞研究进展、干细胞的分离及鉴定。排除标准:重复研究、个案报告或Meta分析类文章。资料提炼:共收集到96篇相关文献,40篇文献符合纳入标准,排除的56篇文献为内容陈旧或重复。符合纳入标准的40篇文献中,分别涉及骨髓、肌肉、脐血、胎盘、外周血、脂肪组织、血管及其他来源的间充质干细胞。资料综合:间充质干细胞是属于中胚层的一类多能干细胞,具有强大的增殖能力和多向分化潜能,动物模型试验和临床应用研究也取得了一定的效果。间充质干细胞来源广泛,易于获得,临床上为神经损伤及其他系统的损伤修复提供了更为广泛的途径。结论:间充质干细胞主要来源于骨髓、肌肉、脐血、外周血、胎盘等组织,具有广阔的应用前景。     

Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody

A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.     

The effect of hemodialysis and C5a des arg on neutrophil subpopulations

Alterations in neutrophil subpopulations during human hemodialysis or following injection of C5a des arg into rabbits were studied. Whereas baseline peripheral blood neutrophils contained approximately 80% of cells that formed rosettes with IgG-sensitized erythrocytes, neutrophils harvested at the granulocyte nadir (20 min after initiating hemodialysis or the injection of C5a des arg) were markedly depleted of this population. This was seen in a change in ratio of rosette-forming neutrophils (RFN) to non-rosette-forming neutrophils (non-RFN) from 4:1 at 0 time to 1:2 at 20 min. Since non-RFN are less active in assays of adherence and chemotaxis, these alterations in circulating neutrophil populations were reflected in abnormal functional capacity of neutrophils harvested at 20 min. To study the mechanism of RFN depletion, we investigated the ability of C5a des arg to aggregate various human neutrophil suspensions. Unfractionated neutrophils and RFN demonstrated prompt in vitro aggregation in response to C5a des arg, whereas this activated complement fragment induced little aggregation in a population enriched for non-RFN. These results may explain the alterations in neutrophil adherence, chemotaxis, phagocytosis, and bactericidal activity, which have been reported to accompany clinical disorders characterized by in vivo complement activation (i.e., hemodialysis or gram-negative sepsis).     

Donor sepsis is not a contraindication to cadaveric organ donation

Systemic donor infection is regarded as being an absolute contraindication to cadaveric organ donation for transplantation. This is largely due to fear of transmitting pathogenic organisms to the immunosuppressed recipient. However, due to the current shortage of organs available for transplantation, clinicians are faced with the option of using organs from 'non-ideal' donors, such as those patients with documented evidence of infection. We report the successful outcome of six orthotopic liver transplants, 11 renal transplants, one combined heart lung transplant and one simultaneous kidney and pancreas transplant with organs from eight donors in whom bacterial meningitis (n = 7) and acute bacterial epiglottitis (n = 1) were the antecedent causes of death.