Modulation of neutrophil oxidative responses to soluble stimuli by platelet-activating factor

The role of platelet activating factor (PAF) as a regulator of human neutrophil superoxide (O2-) generation in response to soluble and particulate stimuli was examined. At concentrations greater than 10(-7) mol/L, PAF alone induced a brief burst of O2- production. When cells were exposed to PAF and either the chemotactic peptide n-formyl- methionyl-leucyl-phenylalanine (FMLP 10(-7) mol/L) or the tumor promoter phorbol myristate acetate (PMA 10 ng/mL), a marked synergistic augmentation of O2- release was noted when compared to control cells stimulated with FMLP or PMA alone. Mean percentage of enhancement by 10(-5) mol/L of PAF was 297% +/- 35% (n = 9) of control responses to FMLP and 185% +/- 16% (n = 3) of control responses to PMA. Consistent enhancement occurred with PAF concentrations of as low as 10(-9) mol/L. Enhancement could be demonstrated when neutrophils were exposed to PAF either at the same time as, or up to 60 minutes prior to, the second stimulus, and was neither reversed by removal of PAF from the medium prior to addition of FMLP or PMA nor dependent on the presence of extracellular divalent cations. Continuous recordings revealed that the enhancement was due to an increased maximal rate of O2- production. In contrast, PAF concentrations up to 10(-5) mol/L had only a minimal effect on the response to neutrophils to opsonized zymosan. Analysis of the enhancing properties of lipids structurally related to PAF revealed that the critical moiety was the saturated fatty acid at position 1. These results indicate the presence of a PAF-mediated positive feedback loop whereby the oxidative burst induced by some soluble stimuli is augmented. Modulation of neutrophil O2- production by PAF may serve to amplify neutrophil oxidative responses at sites of inflammation.     

Economic evaluation of specialist cancer and palliative nursing: a literature review

Little progress has been made in economic evaluation of specialist cancer and palliative care nursing. A literature review of economic studies of clinical nurse specialists (CNSs) was undertaken to assess how the measurement of economic outcomes has been tackled in the literature to date. The initial search found 400 studies. Abstracts from all the studies were reviewed but only 17 studies met the basic criteria for inclusion, reporting primary cost and outcomes data, and clearly specifying the role of a CNS. All of the studies but one focused on direct patient care rather than other CNS roles and were undertaken alongside effectiveness studies. The economic evaluations considered only a narrow range of costs, but a wide range of outcomes. Specific nursing outcomes were only reported in a minority of studies. None of the studies reported cost-effectiveness ratios. However, CNS interventions were reported to be both less costly and more effective than alternative forms of care, negating the need for further cost-effectiveness analysis. Overall, the papers were not of good quality, reducing the validity of the findings. Robust economic evaluations of the CNS role need to be undertaken. These should involve nursing researchers and practitioners so that evaluations reflect the complex and multidimensional nature of CNS care and meet the required standard of evidence to influence practice.     

大鼠、兔和人关节软骨组织形态学的比较

目的:观察比较大鼠、兔和人正常关节软骨组织学结构和关节炎软骨病理变化的差异。方法:实验于2006-08/2007-04在北京大学运动医学研究所完成。取大鼠、兔和人正常的关节滑车软骨和关节炎的滑车软骨,人关节软骨来源告知患者并征得同意,进行苏木精-伊红和甲苯胺蓝组织学染色,观察正常关节软骨的形态结构及关节炎软骨的病理变化。结果:关节软骨具有明显的分层,3者的主要区别在于软骨的第三层和潮线。大鼠软骨的第三层是典型的肥大细胞,无潮线;兔软骨的第三层是典型的柱状细胞层,潮线明显;人的软骨第三层为深层带,细胞较大,形态不规则,有多核细胞存在,有明显的潮线。正常软骨甲苯胺蓝染色均匀。关节炎软骨变化从表面开始,大鼠表现为表层软骨纤维样变,肥大细胞消失;兔和人表现为表层软骨细胞坏死,深层细胞排列紊乱。甲苯胺蓝染色失染或染色不均。结论:大鼠、兔和人的关节软骨结构不尽相同,主要差别在第三层和潮线的有无。关节炎软骨的变化也各有异同,但兔的软骨变化更接近于人。     

Activation of the contact system in insect-sting anaphylaxis: association with the development of angioedema and shock

A postulated role of the contact system in anaphylactic reactions to insect stings was investigated. During prospective, in-hospital sting challenge, we collected serial blood samples from five normal volunteers and 16 patients with a history of insect-sting anaphylaxis. Activation of the contact system was assessed by measuring plasma levels of factor XIIa-C1-inhibitor and kallikrein-C1-inhibitor complexes as well as those of cleaved high molecular weight kininogen (HK). In addition, antigenic levels of (pre)kallikrein, factor XII, and HK were measured. No significant changes in contact system parameters were observed in any of the five volunteers or the four patients who did not develop an anaphylactic reaction after sting challenge. In contrast, significant changes in contact system parameters occurred in 7 of the 12 patients with anaphylactic symptoms after challenge. Peak levels of either C1-inhibitor complex were found 5 minutes after the onset of anaphylactic symptoms. The increase in C1-inhibitor was most pronounced in the 4 patients with angioedema, 2 of which also developed shock. However, activation of HK was observed in all four patients with angioedema, the two patients with shock but no angioedema, as well as in 1 of the remaining 6 patients with anaphylactic symptoms other than angioedema or shock. Thus, activation products of the contact system may be involved in the pathogenesis of angioedema and shock in insect- sting anaphylaxis.     

The putative factor IX gene promoter in hemophilia B Leyden

Hemophilia B Leyden is characterized by low levels of factor IX antigen and activity before the age of 15, whereas after puberty factor IX levels rise at a rate of about 5% per year. A single base substitution (-A----T) at position -20 was identified in the putative promoter of the gene cloned from a patient with hemophilia B Leyden. This nucleotide change was confirmed in a second patient from the same pedigree and was also found in a patient from a second Dutch pedigree with the same hemophilic phenotype. The results indicate that the two Dutch kindreds are related and point to the functional significance of the -20 position for the expression of the human factor IX gene.     

High‐resolution MALDI‐FT‐ICR MS imaging for the analysis of metabolites from formalin‐fixed,paraffin‐embedded clinical tissue samples

We present the first analytical approach to demonstrate the in situ imaging of metabolites from formalin‐fixed, paraffin‐embedded (FFPE) human tissue samples. Using high‐resolution matrix‐assisted laser desorption/ionization Fourier‐transform ion cyclotron resonance mass spectrometry imaging (MALDI‐FT‐ICR MSI), we conducted a proof‐of‐principle experiment comparing metabolite measurements from FFPE and fresh frozen tissue sections, and found an overlap of 72% amongst 1700 m/z species. In particular, we observed conservation of biomedically relevant information at the metabolite level in FFPE tissues. In biomedical applications, we analysed tissues from 350 different cancer patients and were able to discriminate between normal and tumour tissues, and different tumours from the same organ, and found an independent prognostic factor for patient survival. This study demonstrates the ability to measure metabolites in FFPE tissues using MALDI‐FT‐ICR MSI, which can then be assigned to histology and clinical parameters. Our approach is a major technical, histochemical, and clinicopathological advance that highlights the potential for investigating diseases in archived FFPE tissues. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.