Note on arousing type A persons by depriving them of work

Healthy subjects classified as Type A and Type B persons on the basis of a questionnaire measuring coronary-prone behavior were compared in terms of psychophysiological arousal during periods of inactivity and strenuous mental work. Type B subjects were more aroused during work than during inactivity in terms of catecholamine and cortisol excretion and heart rate, whereas Type As showed a tendency to be equally aroused, or even more aroused, during inactivity. Similarly, self- reports showed that Type As felt more distressed than Type Bs during inactivity. It was suggested that inability to cope with inactivity may add to the health risks associated with Type A behavior.     

Receptor-dependent and -independent immunomodulatory effects of phenol-soluble modulin peptides from Staphylococcus aureus on human neutrophils are abrogated through peptide inactivation by reactive oxygen species

The virulence and pathogenesis mechanisms of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains depend on a newly described group of phenol-soluble modulin (PSM) peptides (the PSMα peptides) with cytolytic activity. These toxins are α-helical peptides with a formyl group at the N terminus, and they activate neutrophils through formyl peptide receptor 2 (FPR2), a function closely correlated to the capacity of staphylococcal species to cause invasive infections. The effects of two synthetic PSMα peptides were investigated, and we show that they utilize FPR2 and promote neutrophils to produce reactive oxygen species (ROS) which in turn trigger inactivation of the peptides. Independently of FPR2, the PSMα peptides also downregulate the neutrophil response to other stimuli and exert a cytolytic effect to which apoptotic neutrophils are more sensitive than viable cells. The novel immunomodulatory functions of the PSMα peptides were sensitive to ROS generated by the neutrophil myeloperoxidase (MPO)-H(2)O(2) system, suggesting a role for this enzyme system in counteracting bacterial virulence.     

急性肝衰竭大鼠血浆D-乳酸、二胺氧化酶和内毒素的变化及其意义

目的探讨血浆D-乳酸、二胺氧化酶（DAO）和内毒素水平在急性肝衰竭大鼠的变化及其意义。方法选取健康雌性SD大鼠40只,随机分为对照组（15只）和实验组（25只）,采用分光光度法检测血浆中D-乳酸、DAO和内毒素水平,分别用HE染色及电镜观察大鼠回肠的组织形态和超微结构。结果 实验组大鼠血浆D-乳酸、DAO和内毒素水平均明显高于对照组（P〈0.05）;实验组大鼠回肠黏膜明显萎缩,部分绒毛断裂、脱落。结论急性肝衰竭大鼠肠黏膜屏障出现明显障碍。     

再生障碍性贫血的骨髓和细胞病理

目的：研究再生障碍性贫血（AA）患者骨髓组织病理及有核细胞的超微结构变化。方法：光镜观察20例AA患者骨髓活检病理,透射电镜分析骨髓有核细胞超微结构。结果：光镜下所有患者骨髓脂肪组织增多,造血面积减小,大部分存在血浆渗出、出血和纤维细胞局灶性增生,血窦血管结构紊乱。电镜观察显示原始和早幼红细胞代偿性不典型增生,中晚幼红细胞核损伤。粒细胞呈活化和损伤状态;巨核细胞显著减少,胞浆灶性坏死;单核细胞异常增生、活化、吞噬和坏死。淋巴细胞大部分结构正常。结论：AA患者骨髓造血细胞减少和炎症反应同时存在,单核巨噬细胞活化和吞噬反应与造血细胞损伤相关。     

Trial of the correlation between cytochrome oxidase CYP3A4 with the susceptibility of paclitaxel-based regimen for advanced gastric cancer

Objective： The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods： Peripheral venous blood sample of 53 advanced gastric cancer patients were enrolled to test the mutation of CYP3A4 gene by denaturing high performance liquid chromatography（DHPLC） and DNA sequencing. The relation between the efficacy of paclitaxel-based regimen and CYP3A4 gene polymorphisms was further analyzed. Results： DHPLC indicated that among the 53 patients, 21 cases showed biomodal type（mutation） and 32 cases were of unimodal type（wild-type）. Sequencing results showed that the deletion mutation was found at the 27 th basic group of C in exon 10 of CYP3A4 gene. The response rate（RR） and disease control rate（DCR） of wild-type group were 40.6% and 84.4%, while in mutation group they were 33.3% and 85.7%, respectively, with no significances between the two groups（P 0.05）. Of all 53 cases, the median progression-free survival（PFS） was 6.5 months（95% CI： 3.576–9.424 months）, and the median overall survival（OS） was 11.0 months（95% CI： 6.955–15.045 months）. The median PFS and OS in wild-type group had no differences compared with those in mutation group（7.0 months vs. 7.0 months, P 0.05; 10.0 months vs. 14.0 months, P 0.05）. Between wild-type and mutation groups, the median PFS of patients applied with oxaliplatin containing regimen and the median OS in patients applied with/without oxaliplatin had no significant differences（P 0.05）, while the median PFS in patients received non-oxaliplatin regime had statistical differences（P = 0.024）. The median PFS and OS in patients receiving 3-drug or 2-drug regimes had no correlation with CYP3A4 gene polymorphisms. The adverse effects in the two groups were mild, mainly in grades 1–2. The common adverse effects were anorexia, nausea/vomiting and leucopenia. Conclusion： Deletion mutation was located in     

Serum amyloid A mediates human neutrophil production of reactive oxygen species through a receptor independent of formyl peptide receptor like-1

Serum amyloid A (SAA) is one of the acute-phase reactants, a group of plasma proteins that increases immensely in concentration during microbial infections and inflammatory conditions, and a close relationship between SAA levels and disease activity in rheumatoid arthritis (RA) has been observed. RA is an inflammatory disease, where neutrophils play important roles, and SAA is thought to participate in the inflammatory reaction by being a neutrophil chemoattractant and inducer of proinflammatory cytokines. The biological effects of SAA are reportedly mediated mainly through formyl peptide receptor like-1 (FPRL1), a G protein-coupled receptor (GPCR) belonging to the formyl peptide receptor family. Here, we confirmed the affinity of SAA for FPRL1 by showing that stably transfected HL-60 cells expressing FPRL1 were activated by SAA and that the response was inhibited by the use of the FPRL1-specific antagonist WRWWWW (WRW4). We also show that SAA activates the neutrophil NADPH-oxidase and that a reserve pool of receptors is present in storage organelles mobilized by priming agents such as TNF-alpha and LPS from Gram-negative bacteria. The induced activity was inhibited by pertussis toxin, indicating the involvement of a GPCR. However, based on FPRL1-specific desensitization and use of FPRL1 antagonist WRW4, we found the SAA-mediated effects in neutrophils to be independent of FPRL1. Based on these findings, we conclude that SAA signaling in neutrophils is mediated through a GPCR, distinct from FPRL1. Future identification and characterization of the SAA receptor could lead to development of novel, therapeutic targets for treatment of RA.