寻常性银屑病患者皮肤和血清中肿瘤坏死因子α受体p75测定

目的探讨肿瘤坏死因子(TNF)α受体75 000(p75)在寻常性银屑病中的作用机制。方法采用免疫组化和ELISA 方法对寻常性银屑病患者皮损、皮损周围“正常”皮肤p75表达及其在血清中的含量进行检测。结果正常人皮肤表皮基底细胞散在表达p75;银屑病患者皮损周围“正常”表皮、皮损表皮、真皮内浸润单一核细胞(MNCs)均表达p75;银屑病皮损表皮角质形成细胞p75表达强度与真皮内MNCs数呈显著正相关(r's = 0.73,P<0.05);银屑病患者血清中p75的含量与对照组比较差异有显著性(t=3.98,P<0.05);银屑病皮损表皮角质形成细胞p75表达强度与其血清中p75含量呈显著正相关(r's = 0.62,P<0.05)。结论银屑病患者皮肤和血清中TNFα受体p75的异常上调可能是造成银屑病发生和发展的原因之一。     

p27、细胞周期素E、p21在角化棘皮瘤皮损中的表达

p27是一种细胞周期蛋白依赖性激酶抑制物(cyclin-dependent-kinasein-hibitor,cki),对结肠癌、乳腺癌、肺癌、子宫内膜癌和HPV感染性皮肤病及恶性角质形成细胞肿瘤的研究发现,p27蛋白表达与肿瘤的发生、分化、转移及预后等有密切关系^[1～5]。为探讨p27在角化棘皮瘤的发生、发展、消退中的作用,我们采用免疫组化方法检测p27在进展期和消退期角化棘皮瘤皮损中的表达,及与细胞周期素E、同种抑癌基因p21间存在何种关系。     

IL-23在寻常型银屑病皮损角质形成细胞中的表达

目的：探讨IL-23在寻常型银屑病患者角质形成细胞中的表达。方法：分离培养正常人表皮组、银屑病皮损组和银屑病非皮损组中角质形成细胞,给予混合刺激物处理。用RT-PCR方法比较培养的上述各组角质形成细胞在刺激后IL-23p19亚单位的mRNA水平,并用ELISA方法检测刺激前后培养液上清中的IL-23 p19浓度。结果：刺激前,银屑病皮损组角质形成细胞中IL-23水平均高于正常人表皮组和银屑病非皮损组;刺激后,银屑病皮损组角质形成细胞中IL-23 p19 mRNA和IL-23水平均明显高于正常人表皮组和银屑病非皮损组。结论：IL-23在银屑病皮损角质形成细胞中刺激前后的表达均增加,IL-23可能在银屑病的发生中发挥重要作用。     

寻常型银屑病皮损中Th17细胞相关因子的表达

目的:研究Th17细胞相关因子在银屑病发病机制中的作用.方法:用逆转录-聚合酶链反应法(RT-PCR)半定量分析寻常型银屑病患者皮损区、非皮损区及正常人皮肤组织中Th17细胞相关因子IL-17和IL-23(p19/p40)、IL-6 mRNA的表达.结果:银屑病患者皮损中IL-17、IL-23p19、IL-23p40和IL-6的 mRNA平均相对表达量分别为1.231±0.843、1.166±0.142、1.125±0.104和1.186±0.222.皮损组织中该4种细胞因子mRNA表达水平均高于非皮损组和正常皮肤组,非皮损组四者表达高于正常对照组,差异均有统计学意义(均P<0.05).结论:Th17细胞相关因子在银屑病患者皮损中过度表达,提示Th17型细胞因子在银屑病的免疫发病机制中可能起着非常重要的作用.     

特应性皮炎患者皮损中热休克蛋白60、Toll样受体4和核因子-KB p65的表达

目的:研究热休克蛋白60(HSP60)、Toll样受体4(TLR4)、核因子-kB p65(NF-KB p65)在特应性皮炎(AD)患者皮损中的表达水平及其与疾病发生的关系.方法:采用SP免疫组化法检测17例AD患者急性或亚急性期炎性皮损及12份正常皮肤石蜡标本中HSP60、TLR4、NF-kB p65的表达.结果:HSP60、TLR4、NF-kB p65在重度患者皮损角质形成细胞中均过度表达,与正常对照及中度组比较,差异有统计学意义(P＜0.05);HSP60及NF-kB p65在中度患者组中的表达明显高于正常对照,差异具有统计学意义(P＜0.05);HSP60、TLR4、NF-kB p65在AD皮损中的表达水平与湿疹面积及严重度指数(EASI)评分间存在正相关(P＜0.05).结论:HSP60、TLR4、NF-kB p65在AD患者皮损中存在过度表达.HSP60的表达上调可能与AD发病有关.     

异位性皮炎——细胞介导和IgE介导的免疫病理反应

异位性皮炎(AD)患者皮损及对吸入性变应原产生的湿疹样反应中,真皮的浸润细胞主要是活化的TH细胞和郎格罕细胞(LC),故认为细胞介导的免疫反应参与了AD皮损的发生.最近发现,AD患者表皮LC结合IgE分子,并认为对AD提供了特异的诊断依据.由此可见,AD可能是IgE介导和细胞介导的混合反应.     

IL-31及其受体在特应性皮炎发病中的作用

特应性皮炎是一种慢性复发性、瘙痒性、炎症性皮肤病,该病发病机制不清,涉及遗传、免疫、感染等多种因素.近年来发现浸润到皮损局部的T细胞,其产生的细胞因子在该病的发生发展过程中起着重要作用,尤其是新发现有四个螺旋结构的细胞因子白介素-31.它主要由Th2细胞产生,与特应性皮炎瘙痒的发生有密切联系.     

有皮肤表现的成人T细胞白血病/淋巴瘤患者的皮肤组织短期培养后可表达嗜人T淋巴细胞病毒Ⅰ型的基因产物

成人 T 细胞白血病/淋巴瘤(ATLL)的发生与嗜人 T 淋巴细胞病毒Ⅰ型(HTLV-Ⅰ)感染有关,本病临床已可分为急性、慢性、危象、淋巴瘤及隐匿型五型,各型中皮肤受累很常见。根据该病特征性的临床表现和皮损内 ATLL 细胞的 Southern 印迹分析,提出了皮肤型 ATLL 这一新病名。但皮损内 HTLV-Ⅰ型病毒感染的病理学及病毒学诊断标准尚未建立。作者首次对 ATLL病人皮损组织进行短期培养以检查 HTLV-Ⅰ型病毒表达。患者70岁,男性。双侧腹股沟肿物2个     

银屑病角质形成细胞p14ARF基因甲基化的研究

目的:检测银屑病皮损角质形成细胞p14ARF基因启动子区甲基化,探讨其与银屑病发病的关系。方法:利用甲基化特异性PCR技术检测37例银屑病及35例正常人角质形成细胞p14ARF基因启动子区甲基化状态。结果:37例银屑病皮损角质形成细胞p14ARF基因启动子区甲基化阳性率为43.2%(16/37),显著高于正常对照(χ2=13.5,P<0.05)。结论:p14ARF基因启动子区甲基化与银屑病角质形成细胞过度增殖具有一定的关系。     

58例毛母质瘤临床病理学分析

58例毛母质瘤临床特点为发生在青少年最多,皮损部位以头颈部居多,表现为皮下单发之园形硬结,肿瘤实质部分由嗜硷细胞和影细胞组成,这二种细胞的比例与肿瘤生长时间长短有一定的关系。影细胞和嗜碱细胞是该病的特征性细胞。     

p73蛋白在正常人皮肤和表皮肿瘤中的表达

目的 探讨p73蛋白在正常人皮肤和不同表皮肿瘤皮损中的表达及意义。方法 应用免疫组化方法检测19例脂溢性角化病、16例基底细胞癌、11例Bowen病、5例鳞状细胞癌及10例正常人皮肤p73、p53、Ki67的表达。结果 在正常人表皮基底层、毛囊外毛根鞘最外层基底样细胞和皮脂腺生发细胞有p73的表达;在基底细胞癌和脂溢性角化病的基底样细胞、Bowen病中异形性明显的瘤细胞p73呈高表达,鳞状细胞癌和脂溢性角化病中的鳞状细胞呈弱阳性或不表达。脂溢性角化病、Bowen病、基底细胞癌、鳞状细胞癌之间p73蛋白表达差异有统计学意义(H=12.71,P<0.01),其中基底细胞癌的表达最强。Ki67在皮肤肿瘤之间差异也有统计学意义(H=14.12,P<0.01),但p53差异无统计学意义(H=2.058,P>0.05)。在各组样本中,p73的表达与p53、Ki67无显著相关性(P>0.05)。结论 p73蛋白可能在皮肤分化中起重要作用。     

日光性角化病P53蛋白的定量分析

应用流式细胞免疫技术 ,对 2 7例日光性角化病 (SolarkeratosisSK)及 8例高分化皮肤鳞癌皮损细胞的P53蛋白进行了定量分析。SK的P53蛋白荧光指数 (FluerescenceIndexFI)高于正常皮肤 ,低于高分化鳞癌 ,P值均 <0 .0 5。SK及高分化鳞癌的P53蛋白阳性表达率分别为 4 0 .74 %、87.50 % ,正常皮肤为阴性表达。提示SK皮损细胞中有P53蛋白的异常堆积     

Epidermal growth factor receptors in human epidermal tumours

Immunolocalization studies using the strepavidin/biotin peroxidase system were used to identify epidermal growth factor receptors in 10 samples of normal skin, 13 seborrhoeic warts (SW), five lesions of Bowen's disease (BD), 11 solar keratoses (SK), 22 basal cell carcinomas (BCC) and five squamous cell carcinomas (SCC). The intensity of cell membrane staining was assessed using the 10-cm visual analogue scale technique and the results analysed using non-parametric statistics. The cell membranes in BCC showed significantly less intense staining when compared to normal epidermal cells (P less than 0.001) and the constituent cells of SW (P less than 0.001), SK (P less than 0.001), BD (P less than 0.01), and SCC (P less than 0.001). Classification of the specimens into normal, benign, premalignant and malignant indicated that cell membranes of malignant tumours showed significantly less staining than the other groups (P less than 0.001). The observed reduction in the epidermal growth factor receptors in malignant tumours may be due to occupation and down regulation in response to autocrine secretion of growth factors.     

Acantholytic variant of seborrheic keratosis

From among 524 histologic specimens of seborrheic keratosis (SK), 29 showed acantholysis, not related to pemphigus, Darier's disease, actinic keratosis or acantholytic squamous cell carcinoma. Acantholysis was found in 24 (23.3%) of the irritated type of SK, almost exclusively in the squamous cell nests showing dyskeratosis and spongiosis between and around squamous eddies or horn cysts. Clinically, 65.5% of the lesions were located on the face and scalp, 20.7% on the trunk and 13.8% on the limbs. It was speculated that dyskeratotic, degenerative changes of the keratinocytes together with spongiosis were responsible for the acantholysis.     

脂溢性角化病96例和日光性角化病28例临床与病理分析

目的观察脂溢性角化病(SK)与日光性角化病(AK)的临床及病理差异。方法回顾性分析本科门诊2006年1月-2011年7月经病理确诊的96例SK和28例AK患者的临床及病理资料,对数据用Excel整理与分析。结果①SK好发于中老年人,而AK好发于老年人;②SK皮损好发于头面、躯干及四肢,而AK好发于头、面和颈等光暴露部位;③组织病理:SK以角化型和棘层肥厚型为主,而AK以原位癌型和萎缩型为主;④SK临床与组织病理的诊断符合率为70.83%,而AK临床与组织病理的诊断符合率仅为46.43%,临床上易将AK误诊为SK。结论 AK发病晚于SK,临床上AK误诊率高于SK,两者鉴别诊断主要依赖组织病理。     

脂溢性角化病的皮肤高频超声及皮肤镜特征分析

目的 描述脂溢性角化病（SK）的常见皮肤高频超声及皮肤镜特征。方法 收集2017年8 - 12月在北京协和医院皮肤科门诊就诊的46例SK患者,对其50处SK皮损行50 MHz和20 MHz皮肤高频超声和皮肤镜检查。对SK皮肤高频超声和皮肤镜特征进行总结分析。采用χ2检验比较50 MHz和20 MHz超声对SK的评估结果差异,并对SK皮肤高频超声和皮肤镜下特征的对应关系通过简单匹配系数进行分析。结果 SK皮损特征自上而下50 MHz和20 MHz超声表现分别为增强高回声（48处和39处,P = 0.007）、角质层块状或点状增强高回声（22处和11处,P = 0.019）、伴后方声影（34处和13处,P < 0.001）、皮损形态规则且边界清晰（46处和41处,P = 0.137）、皮损内不均质低回声（50处和47处,P = 0.079）和点状高回声（25处和2处,P < 0.001）、基底位于同一水平面（40处和36处,P = 0.349）、皮损下方真皮回声减低（50处和28处,P < 0.001）。50 MHz超声对SK皮损的8个皮肤高频超声特征整体评价显著优于20 MHz超声（P = 0.002）。50处SK皮损常见皮肤镜下特征为边界清楚（50处）,粉刺样开口（45处）,沟嵴/脑回状模式（31处）,发卡样血管（30处）,多发粟粒样囊肿（24处）,虫蚀状边缘（21处）和亮白色条纹（3处）。50 MHz和20 MHz超声下,SK皮损角质层块状或点状增强高回声与皮肤镜下粉刺样开口的简单匹配系数分别为42%（21处）和20%（10处）,皮损内点状高回声与皮肤镜下多发粟粒样囊肿（> 3个）的简单匹配系数分别为58%（29处）和48%（24处）。结论 皮肤高频超声和皮肤镜对SK皮损评估具有较好的应用价值,且50 MHz超声比20 MHz超声对SK的皮损成像更具优势。     

Apoptosis in the areas of squamous differentiation of irritated seborrheic keratosis

Seborrheic keratosis (SK) consists of a localized proliferation of basaloid keratinocytes, often accompanied by hyperkeratosis and hyperpigmentation. In irritated SK, these features are associated with areas of squamous differentiation with larger keratinocytes and squamous cell eddies. This work is concerned with the evaluation of apoptosis, as demonstrated by the TUNEL method, in the different varieties of SK. Apoptosis was highly expressed in the areas of squamous differentiation of irritated SK, but only mildly increased in the other varieties of SK. These data support the hypothesis that apoptosis has a role in the squamous differentiation of irritated SK. In consideration also of previous data showing that irritated SK is associated with downregulation of EGF-R expression and 125I-EGF binding, we postulate that the morphologic features of irritated SK could correspond to an involution phase of the disease, characterized by altered cell balance with inadequate cell renewal and increased cell loss.     

Enhanced expression of p16 in seborrhoeic keratosis; a lesion of accumulated senescent epidermal cells in G1 arrest

BACKGROUND: Seborrhoeic keratosis (SK) is a common skin disease associated with skin ageing and photoageing, but only limited studies have been performed on SK and the senescence of keratinocytes. OBJECTIVES: We sought to clarify the genetic basis of SK and the senescence of keratinocytes. METHODS: Expression of p16, cyclins A, D and E, p21, p53, retinoblastoma (Rb) gene product and telomerase-associated protein 1 (TP1) in SK was examined by immunohistochemistry. DNA fragmentation in SK was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling method. We cultured keratinocytes from SK lesions and non-lesional epidermis and examined expression of p16, observed morphology of the cultured cells by light and electron microscopy and measured survival time. RESULTS: p16, a cyclin-dependent kinase inhibitor, was expressed in all cells from SK lesions, whereas normal keratinocytes expressed p16 only in the granular cells. Other factors such as cyclins A, D and E, p21, p53, Rb gene product, and TP1, were not expressed in SK cells. These results suggest that p16 expression is a marker of SK and that p16 has a role in the pathogenesis of SK. DNA fragmentation was not detected in four of five SK tissue samples; one of the SK tissue samples showed DNA fragmentation only in the superficial upper layer of an SK lesion, suggesting that apoptosis was inhibited in SK cells. In contrast, normal epidermis showed DNA fragmentation in the granular and squamous layers. Immunohistochemical examination of cultured SK cells also revealed the presence of p16. A greater number of SK cells survived after 3 weeks of culture in comparison with normal keratinocytes. Features of senescence, such as a balloon-like appearance after lengthy culture and increased amounts of tonofilaments in cytoplasm, were observed in SK cells in culture. CONCLUSIONS: These results suggest that SK is a benign neoplasm where keratinocytes in a senescent condition and G1 arrest are accumulated.     

Are all seborrheic keratoses benign? Review of the typical lesion and its variants

BACKGROUND: Seborrheic keratosis (SK) is one of the more common benign epidermal neoplasms seen in adult and middle-aged patients. OBJECTIVE: As little is written in the literature about the variants of SK, this article aims to categorize and discuss the different subtypes and their important associations. METHODS: An in-depth literature search using OVID Medline and PubMed was conducted to classify the various subtypes of SK. Clinical variants were photographed and used to help document the subtypes. The pathology is described for each. RESULTS: Six subtypes of SK were identified: dermatosis papulosa nigra, stucco keratosis, inverted follicular keratosis, large cell acanthoma, lichenoid keratosis, and flat seborrheic keratosis. Although the etiology and pathogenesis of SKs are still largely debatable, several underlying mechanisms and contributing factors have been identified. All subtypes represent benign lesions, and treatment is usually done for cosmetic reasons. Several of the subtypes may act as cutaneous markers for internal malignancy and should be monitored closely for any atypical changes. CONCLUSION: Although all subtypes of SK are benign, their association with other malignant lesions and ability to serve as cutaneous markers of internal malignancy emphasize the importance of correctly identifying all variants.