中国麻风皮肤病杂志2006年第22卷总目次索引

皮肤科基础研究紫外线对皮肤角质形成细胞和成纤维细胞产生MMP-1和MMP-3的影响………………………(11)血小板活化因子乙酰水解酶基因Ile198Thr突变与银屑病的相关研究………………………………(17)石蜡包埋皮肤组织标本中提取RNA进行逆转录PCR的研究…………………………………     

PAF-AH基因突变与银屑病的相关性研究

目的:研究血小板活化因子乙酰水解酶基因突变(Ala379Val)与银屑病的关系.方法:对60例银屑病患者及60例健康对照者,分别用聚合酶链反应技术(PCR)及测序分析基因组DNA的突变等位基因.结果:银屑病组血小板活化因子乙酰水解酶基因突变率(Ala379Val)与健康人群无显著差异(P>0.05).结论:血小板活化因子乙酰水解酶基因突变可能与银屑病的发病无关.     

银屑病患者血小板活化因子乙酰水解酶基因突变的研究

目的 探讨血小板活化因子乙酰水解酶基因突变(Arg92→His)与银屑病的关系.方法 对47例银屑病患者及52例健康对照者,分别用聚合酶链反应技术(PCR)及限制性内切酶片段长度多态性(RFLP)分析血小板活化因子乙酰水解酶基因组DNA的突变等位基因.结果 银屑病组突变率显著高于对照组(P<0.05).结论 血小板活化因子乙酰水解酶基因突变(Arg92→His)与银屑病存在相关性,其突变可能为银屑病的一个发病高危因素.     

血小板活化因子乙酰水解酶基因Val279Phe突变与银屑病的相关性研究

目的 探讨血小板活化因子乙酰水解酶(PAF-AH)在银屑病发病机制中的作用。方法 等位基因特异性聚合酶链反应技术分析银屑病患者及健康对照者PAF-AH基因Val279Phe位点的多态性,并对含有突变等位基因的多态性片段进行DNA测序分析。采用PAF-AH活性检测试剂盒测定血浆PAF-AH的活性。结果 所有研究对象中发现3例Val279Phe突变型杂合子,未发现突变型纯合子;银屑病组的突变等位基因频率与健康对照组差异无统计学意义(P>0.1);银屑病患者血浆PAF-AH活性低于健康献血者,两组比较差异有统计学意义(P<0.01)。结论 本研究结果提示PAF-AH基因的Val279Phe突变与银屑病无明显的相关关系,可能不是银屑病患者血浆PAF-AH活性降低的主要原因。     

血浆型PAF乙酰水解酶与炎性疾病相关性研究进展

血小板活化因子(PAF)是一种强效炎症介质,PAF乙酰水解酶(PAF-AH)作为其信号系统中的关键性调节因子,在银屑病等多种疾病的发病机制中发挥重要作用。本文对血浆型PAF-AH与相关炎性疾病的研究进展做一综述。     

银屑病患者血浆血小板活化因子乙酰水解酶活性变化及其临床意义

目的 探讨银屑病患者血浆血小板活化因子乙酰水解酶(PAF-AH)活性变化在银屑病发病机制中的作用。方法 采用酶水解底物显色法测定银屑病患者血浆PAF-AH活性。结果 银屑病患者血浆PAF-AH活性明显低于健康对照者(P<0.01)。进展期银屑病患者的血浆PHF-AH活性明显低于静止期和退行期患者(P<0.01),静止期组和退行期组的差异不具有显著性(P>0.1)。结论 PAF-AH活性不足可能是银屑病发病的重要内源性因素之一,其活性水平与银屑病的病情活动性具有相关性,在进行病情及预后判断时可能具有一定的参考意义。     

血小板活化因子及其乙酰水解酶与荨麻疹的相关性研究

目的： 明确人体血清血小板活化因子（PAF）及血小板活化因子乙酰水解酶（PAF-AH）水平与荨麻疹发病的相关性。方法： 收集荨麻疹患者及正常对照者的血清样本,对荨麻疹患者进行病情严重程度评分（UAS）,利用ELISA法对样本中PAF及PAF-AH水平进行测定。结果： 共有32例急性和32例慢性荨麻疹患者入选,血清PAF水平分别为430.4 pg/mL及391.6 pg/mL,高于32例正常对照(224.5±31.67pg/mL),差异均具有统计学意义(均P<0.05)。急、慢性荨麻疹患者血清PAF-AH水平与正常对照组相比无统计学差异。血清PAF水平与急、慢性荨麻疹患者UAS评分存在正相关(均P<0.05),PAF-AH水平与急、慢性荨麻疹病情严重程度评分均无明显相关性（均P>0.05）。结论：PAF可能与急、慢性荨麻疹的发病有关。     

板层状鱼鳞病一家系TGM1突变基因检测

目的 报道1例有近亲背景的板层状鱼鳞病患者及其家系,并检测其转谷氨酰胺酶Ⅰ编码基因TGM1的突变。 方法 提取板层状鱼鳞病患者及家族成员的基因组DNA,采用PCR 扩增TGM1 基因所有的15个外显子及其邻近的侧翼序列并进行双向直接测序。结果 该板层状鱼鳞病患者TGM1基因第11个外显子的1666位的碱基存在胞嘧啶（C）→胸腺嘧啶（T）突变,使得529位密码子由ACA→ATA,相应氨基酸由苏氨酸（Thr）变为异亮氨酸（Ile）。结论 患者转谷氨酰胺酶Ⅰ Thr529Ile基因突变可能导致其发病。其父母基因型均为该突变的杂合子,近亲婚配促进基因的纯合,增加后代患病概率。     

应用全外显子测序技术筛查LEOPARD综合征患者致病基因一例

目的:报道一例LEOPARD综合征(LS)患者并检测其基因突变。方法:收集患者临床资料，提取该患者及父亲外周血DNA,应用全外显子组高通量测序检测技术，筛查患者致病基因。结果:全外显子测序结果发现患者PTPN11基因12号外显子第1415位核苷酸发生c.1415C>T杂合突变，导致第472号氨基酸由Thr变为Met(p.Thr472Met)。结论:PTPN11基因12号外显子c.1415C>T (p.Thr472Met)突变为该例LEOPARD综合征的致病突变位点。     

局部应用血小板活化因子拮抗剂治疗寻常型银屑病的作用——临床和免疫组化研究

已证实血小板活化因子存在于免疫性皮肤反应和银屑病皮损中。为探讨血小板活化因子拮抗剂在治疗银屑病中的作用,本研究选择10例慢性斑块型银屑病患者,局部外用血小板活化因子拮抗剂进行双盲对照研究,治疗前、后评价临床反应和通过免疫组化了解局部炎症、分化和增殖程度变化。本研究证实,10％血小板活化因子拮抗剂溶液治疗银屑病4周后,临床和细胞生物学水平显示无效。对于这一阴性结果,最可能的解释是在银屑病发病机理中,血小板活化因子不是一个重要的作用因子。     

Identification of platelet-activating factor acetylhydrolase II in human skin

Platelet-activating factor acetylhydrolases are a family of specialized phospholipase A2 enzymes. They serve an anti-inflammatory function by converting the proinflammatory autocoid, PAF, into biologically inactive lyso-PAF, by the removal of the sn-2 acetyl group of this glycerophospholipid. Similarly, platelet-activating factor acetylhydrolases can also degrade oxidatively modified sn-2 polyunsaturated-fatty-acid-containing phospholipids, which are toxic to cells. Platelet-activating factor acetylhydrolase II is a recently cloned member of this family of specialized phospholipases. Consistent with a potential role of this intracellular enzyme in protecting membrane phospholipids against oxidative stress, platelet-activating factor acetylhydrolase II has been shown to translocate from cytosol to membranes in response to pro-oxidative stressors, and overexpression of this enzyme decreases the cytotoxic effects of these agents. The objective of this study was to assess whether platelet-activating factor acetylhydrolase II is involved in protecting skin against oxidative stress. Platelet-activating factor acetylhydrolase II protein was demonstrated in human skin by immunohistochemistry, with the highest levels of the enzyme found in sebaceous glands and lesser amounts in epidermal keratinocytes. Treatment of epidermal cells with t-butylhydroperoxide or ultraviolet B radiation resulted in platelet-activating factor acetylhydrolase II translocation from cytosol to membranes. To assess the role of this enzyme in epidermal function, a recombinant retroviral strategy was used to overexpress platelet-activating factor acetylhydrolase II in the human keratinocyte-derived cell line HaCaT. Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apop tosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation. Similar levels of apoptosis, however, were seen in both control and platelet-activating-factor-acetylhydrolase-II-over expressing HaCaT cells in response to C2 ceramide. These studies demonstrate the presence of platelet-activating factor acetylhydrolase II in a restricted pattern in human skin, and provide evidence that this specialized phospholipase is involved in protecting this organ against oxidative stress through the degradation of oxidatively modified bioactive phospholipids.     

银杏石榴煎对寻常性银屑病患者血小板活化因子及其受体表达水平的影响

目的 探讨中药银杏石榴煎治疗进行期寻常性银屑病的疗效及其对患者血清中血小板活化因子(PAF)及皮损组织中血小板活化因子受体(PAFR)表达水平的影响。方法 治疗前后对银屑病患者皮损进行PASI评分.采用ELISA法检测患者治疗前后和正常人对照血清中PAF的表达水平,并采用免疫组化方法检测患者治疗前后皮损和正常人皮肤中PAFR的表达变化。结果 ①银杏石榴煎可显著改善患者的临床症状,治疗后(2.86±1.81)PASI评分较治疗前(32.81±14.77)明显下降(P<0.01);②治疗前患者血清中PAF表达水平(15.41±4.28 pg/mL)明显高于正常人对照(5.77±1.47 pg/mL)(P<0.01),治疗后(8.25±2.43 pg/mL)其表达水平较治疗前明显下降(P<0.05),且患者血清中PAF表达水平与PASI评分呈正相关(r=0.46,P<0.05);③治疗前患者皮损表皮及真皮中内皮细胞、炎症细胞可见明显PAFR阳性表达,治疗后阳性细胞表达减少(P<0.05)。结论 进行期银屑病患者血清中PAF及皮损中PAFR呈高表达,且与患者病情严重程度密切相关,银杏石榴煎可明显降低它们的表达水平。     

银屑病患者外周血白细胞磷酸二酯酶活性检测及临床意义

目的通过检测正常人群和银屑病患者外周血白细胞磷酸二酯酶（phosphodiesterase,PDEs）活性,探讨PDEs活性在银屑病发病中的作用。方法对50例银屑病患者及60名健康对照者外周血白细胞应用高效液相色谱法（HPLC）检测PDEs活性。结果银屑病患者外周血白细胞PDEs活性为（10．40±3．54）％,健康对照者为（8．60±2．25）％,两者差异有统计学意义（P〈0．05）。结论外周血白细胞PDEs活性与银屑病的发病可能具有相关性。     

Augmentation of staphylococcal alpha-toxin signaling by the epidermal platelet-activating factor receptor

Staphylococcal alpha-toxin is a cytolytic toxin secreted by many strains of Staphylococcus aureus that has proinflammatory and cytotoxic effects on human keratinocytes. alpha-toxin exerts its effects by forming a transmembrane pore that behaves like an ionophore for ions such as calcium. Because cellular membrane disruption with resultant intracellular calcium mobilization is a potent stimulus for the synthesis for the lipid mediator platelet-activating factor, the ability of alpha-toxin to induce platelet-activating factor production was assessed, and whether the epidermal platelet-activating factor receptor could augment toxin-induced signaling in epithelial cells examined. Treatment of the human keratinocyte-derived cell line HaCaT with alpha-toxin resulted in significant levels of platelet-activating factor, which were approximately 50% of the levels induced by calcium ionophore A23187. alpha-toxin also stimulated arachidonic acid release in HaCaT keratinocytes. Pretreatment of HaCaT cells with platelet-activating factor receptor antagonists, or overexpression of the platelet-activating factor metabolizing enzyme acetylhydrolase II blunted alpha-toxin-induced arachidonic acid release by approximately one-third, suggesting a role for toxin-produced platelet-activating factor in this process. Finally, retroviral-mediated expression of the platelet-activating factor receptor into the platelet-activating factor receptor-negative epithelial cell line KB resulted in an augmentation of alpha-toxin-mediated intracellular calcium mobilization and arachidonic acid release. These studies suggest that alpha-toxin-mediated signaling can be augmented via the epidermal platelet-activating factor receptor.     

CARD15 mutations in patients with plaque-type psoriasis and psoriatic arthritis: lack of association

Psoriasis has a strong genetic component in the development of the disease as indicated by familial occurrence and a high concordance rate among monozygotic twins. In genome-wide scans for psoriasis several susceptibility loci have been detected, but the disease-causing genes have not yet been identified. A recent scan, performed on psoriatic arthritis (PsA), which occurs in about 15% of the psoriasis patients showed a significant locus on chromosome 16 in a region that was already described by genome scan for psoriasis. CARD15, a major susceptibility gene for Crohn’s disease (CD) on chromosome 16q, is an interesting candidate gene for psoriasis, because there is a documented clinical association of CD with psoriasis, and recently the association of CARD15 mutations with PsA was reported in Newfoundland population. We investigated the association of this variant with PsA and the overall psoriasis genotype in 59 independent patients with PsA in comparison with 361 age and sex-matched controls. In addition, a second cohort of 89 independent North American PsA patients was included. The diagnosis of psoriasis was made by a dermatologist based on standard clinical criteria. In these patients, PsA was defined as an inflammatory joint disease, negative rheumatoid factor, and lack of another causative condition for arthritis. Using case-control analysis, the G908R mutation was weakly associated with psoriasis and PsA, but due to the low frequency of this mutation statistical significance was not reached. All other variants including leu1007fsinsC and R702W did not show any association with psoriasis or PsA. In conclusion, a disease-causing role for CARD15 mutations could not be confirmed in German or American subjects with PsA.     

Accelerated proliferation of epidermal keratinocytes by the transgenic expression of the platelet-activating factor receptor

Abstract Transgenic mice overexpressing platelet-activating factor receptor (PAFR) have abnormal pigmentation of the ear and the tail, which can progress to melanocytic tumors as the mice age. Histologically, epidermal hyperproliferation and increases in dermal melanocytes are evident. Examination of these transgenic mice at various ages revealed hyperproliferation of the epidermis even 2 weeks after birth which developed as the mice aged. Dermal melanocytes also increased in number with growth. Expression of the PAFR transgene was found in keratinocytes and not in melanocytes, thereby suggesting that PAF does not play a direct role in proliferation of melanocytes. Topical application of a cream containing WEB2086, a specific PAFR antagonist, to the ear and the dorsal skin significantly suppressed the number of BrdU-positive cells in PAFR transgenic mice. These results suggest that PAF plays a modulatory role in the growth of epidermal keratinocytes. PAFR transgenic mice would be a useful model for investigations of skin diseases related to altered proliferation of epidermal keratinocytes including psoriasis. Received: 26 April 1999 / Received after revision: 5 July 1999 / Accepted: 9 July 1999