Dermato-venereology: An historical perspective⋆

Although, at present dermatology and venereology in the United Kingdom and Eire are practiced separately, the influence of the European Economic Community may cause certain changes. This article refers to events over the course of centuries which have caused the disciplines to develop separate paths.     

Italian multicenter study⋆ on Epiquick®, Rapid Patch Test® and TRUE TestTM

Using 3 different ready-to-apply patch test systems (Epiquick^®= EPI; Rapid Patch Test^®= RPT; TRUE Test^TM= TT), 316 patients sensitive to at least one allergen were studied in order to investigate the reproducibility of these tests in comparison with the Finn Chamber ^®(FC) technique. Each patient was tested with a different ready-to-use system. Each test was compared to the same allergen applied with FC to either side of the upper back. Comparisons were made using EPI, RPT, and TT in 93 (183 tests), 119 (262 tests), and 104 (242 tests) patients respectively. When a positive test result occurred on only one side of the back, the concordance was defined as negative. Similarly, doubtful reactions on either side corresponding to positive or negative results were considered as non concordant. The concordance of positive reactions was 80.9% between the EPI and the FC technique, 77.5% between the RPT and the FC technique, and 72.3% between the TT and the FC technique. The frequency of questionable (+?) and irritant reactions (IR) was about the same for the different tests. Nevertheless, when comparing the positive reactions vs +?, IR, or negative reactions in paired tests, positive results were more frequently obtained with the FC technique. Our data suggest that the standard method with FC allows a better detection of contact allergy than the new ready-to-use systems tested in this study.     

Obesity exacerbates imiquimod‐induced psoriasis‐like epidermal hyperplasia and interleukin‐17 and interleukin‐22 production in mice

Psoriasis is a chronic inflammatory skin disorder that is accompanied by an imbalance between the proliferation and differentiation of keratinocytes. A number of studies have suggested an association between obesity and severe psoriasis; however, it remains to be clarified whether obesity exacerbates psoriasis. To address this unsolved question, we induced psoriasiform dermatitis in mouse models for obesity. We found that obesity exaggerated the severity of psoriasiform dermatitis induced by topical application of the Toll‐like receptor (TLR) 7 agonist, imiquimod. Ear swelling and epidermal hyperplasia were more prominent in the obese mice than in the control mice. When compared to imiquimod‐treated control mice, imiquimod‐treated obese mice expressed higher levels of psoriasis mediators, interleukin‐17A (IL‐17A) and IL‐22 in the skin. Food intake restriction partially abrogated enhanced ear swelling and cytokine overproduction in obese mice. Furthermore, the obesity environment and imiquimod treatment synergistically induced an IL‐17A downstream molecule, regenerating islet‐derived 3γ (Reg3γ), which is a critical molecule for psoriatic epidermal hyperplasia. Palmitic acid, one of the fatty acids released by subcutaneous adipocytes, increased the expression of REG3A (a human homologue of mouse Reg3γ) in both the HaCaT keratinocyte cell line and normal human keratinocytes. Taken together, these results strongly suggest that obesity exacerbates psoriasiform dermatitis in mice by upregulating IL‐17A, IL‐22 and Reg3γ.     

Animal‐type melanoma – tumor cell invasion of dermal lymphatics and molecular identification of lymph node metastasis

Animal‐type melanoma (ATM) represents a rare subtype within the wide spectrum of melanocytic tumors. Clinically, ATM lesions appear as sharply demarcated, brown, black and dark blue pigmented nodules, which show grey‐white surface elements on dermatoscopy. The tumor is restricted to the dermis and arranged in irregular fascicles, which are composed of spindle‐shaped and epithelioid melanocytes. Moderate tumor cell pleomorphism, mitoses and apoptotic cells all suggest a malignant process. Abundant, finely dispersed melanin pigment within tumor cells as well as numerous melanophages are strongly suggestive of ATM. Even though locoregional lymph node metastases are frequently found at diagnosis, the course of ATM is generally benign. Specific molecular changes may be detected in melanocytes from lesions and lymph nodes on fluorescence in situ hybridization (FISH). Such findings strongly indicate the malignant potential of ATM. The peculiar biology of ATM, as a moderately malignant tumor, is reflected in a new histopathological classification within the spectrum of dermal borderline melanocytic tumors (BMT).     

Polymorphisms in the PTPN22 region are associated with psoriasis of early onset

BACKGROUND: Psoriasis, a chronic inflammatory skin disease, affects approximately 2% of the population worldwide. Although the aetiology of psoriasis is poorly understood, patients with disease of early onset (Type I, age of onset相似文献   

Lateral displacement of the nipples and unilateral renal hypoplasia: another mammo-renal syndrome?⋆

Background of study Polythelia is a cutaneous marker of congenital diseases of the kidneys. Lateral displacement of the nipples (e.g. laterally located to their respective midclavicular lines) is considered a further sign of renal disorders, particularly of bilateral renal hypoplasia, as reported by Fleisher in a detailed study on seven infants. Subject We observed a 45-year-old white man with his morphologically normal nipples displaced on the lateral aspects of the trunk without any other consistent clinical features such as accessory nipples or areolae, gonadal dysgenesis, face or car anomalies. Aims and methods In order to reveal congenital abnormalities of the kidneys and the urinary collecting systems the following investigations were undertaken: renal ultrasound, intravenous pyelography. abdomen CT and NMR scans, urethrocystography, transurethral cystoscopy, urinalysis, laboratory tests including karyotype, ECG and cardiovascular evaluation. Results Instrumental findings disclosed a hypoplastic left kidney in an ectopic site, located below the right kidney (cross type of renal ectopy) without any connection between their urinary- collecting systems. Complex malformations of the urinary tract such as an orthotopic narrow right ureteral orifice and ridge, a large-sized diverticulum on the left wall of the bladder were also present. Moreover, a tumour on the upper pole of the right kidney, 20 mm in diameter, with a histological picture of renal-cell carcinoma was detected. Conclusions A lateral displacement of the nipples is a clue for the presence of renal hypoplasia both bilateral and unilateral. The significance of this association is unclear and its occurrence is probably underestimated.     

原癌基因c-fos及c-jun在银屑病皮损中的异常表达

目的为了探索ｃ ｆｏｓ、ｃ ｊｕｎ与银屑病的关系。方法运用原位杂交技术并通过图像定量分析,对３６例寻常性银屑病患者及１５例正常人皮肤中ｃ ｆｏｓ及ｃ ｊｕｎ的表达进行观察。结果银屑病进行期皮损中,ｃ ｆｏｓ、ｃ ｊｕｎ表达全层减少（Ｐ＜０．０１）,恢复期皮损中ｃ ｆｏｓ、ｃ ｊｕｎ的表达与正常皮肤差异无显著性意义Ｐ＞０．０５）。结论提示ｃ ｆｏｓ、ｃ ｊｕｎ可能与银屑病角朊细胞分化受阻及表现型异常密切有关。     

皮肤三维CT在寻常性银屑病诊断中的应用

目的探讨皮肤三维CT在寻常性银屑病诊断中的应用。方法用皮肤三维CT分析40例寻常性银屑病患者及45例其他皮肤病患者皮损部位的影像学特征,探讨Munro微脓肿、角化不全、银屑病样增生、真皮乳头血管扭曲扩张等皮肤三维CT影像学表现对寻常性银屑病的诊断价值。结果 Munro微脓肿、角化不全、银屑病样增生、真皮乳头血管扭曲扩张对诊断寻常性银屑病的敏感性分别为92.50%,95.00%,75.00%和75.00%;特异性分别为97.78%,57.78%,84.44%和75.56%。结论 Munro微脓肿对寻常性银屑病的诊断具有较高的敏感性和特异性,可以作为皮肤三维CT诊断寻常性银屑病的重要依据。     

寻常性银屑病患者外周血Th22细胞及血清中IL-22的水平

目的检测寻常性银屑病患者外周血Th22细胞及其效应因子IL-22在血清中的水平,探讨Th22细胞与银屑病的关系。方法分别采用流式细胞术和酶联免疫吸附法(ELISA)检测23例寻常性银屑病患者(进行期12例,稳定期11例)和11例对照者外周血Th22细胞及血清中IL-22的水平。结果 Th22细胞的水平比较,病例组(1.90±1.73)%高于对照组(1.47±0.96)%,进展期组(2.30±1.63)%高于稳定期组(1.75±1.29)%,但差异均无统计学意义(P均>0.05);而且病例组Th22细胞水平与PASI评分无相关性(P>0.05)。IL-22水平比较,病例组(8.46±6.23)高于对照组(5.28±2.66),进展期组(8.75±4.58)高于稳定期组(6.35±2.46),差异均有统计学意义(P均<0.05);且病例组IL-22的水平与PASI评分呈正相关(P<0.05)。结论 IL-22可能参与银屑病的发病,但外周血Th22细胞水平与银屑病发生和发展无直接相关性。     

Increased prevalence of herpes viruses in high grade CIN and carcinoma of the cervix: the potential for synergistic effect⋆

Objective To assess the prevalence of human papillomavirus (HPV) type 16 and 18, herpes simplex virus (HSV) and human cytomegalovirus (HCMV) in cervical biopsies in order to evaluate their relationship in cervical intraepithelial neoplasia (CIN) and cancer. Setting Colposcopy clinic; Service de Gynécologic-Obstétrique I, Hôpital de Hautepierre. Hôpitaux Universities de Strasbourg and Laboratoire Commun ULP/Synthélabo et U74 INSERM. Institut de Virologie dc la Faculté de Medecine de Strasbourg, France. Subjects Forty-two women with low grade and high grade CIN, twenty women with cervical squamous cancer and twenty-two women with normal cervix assessed by cytological, colposcopical and histological analysis. Methods Viral DNA was detected by PCR technique in colposcopically directed biopsies. Results The prevalence of HPV16 and/or HPV18 with HSV and/or HCMV was significantly higher in cancers (25%) or high grade CIN (29%) than in normal cervices (0%). On the contrary, when only HPV DNA was found, there was no significant difference between cancers (3O%). high grade CIN (29%) and normal cervices (9%). Conclusions The results support the hypothesis of a role of herpes viruses (HSV and HCMV) as cofactors in cervical carcinogenesis.     

Hyaluronan and CD44 in psoriatic skin. Intense staining for hyaluronan on dermal capillary loops and reduced expression of CD44 and hyaluronan in keratinocyte-leukocyte interfaces

The distributions of hyaluronan (HA) and its presumptive receptor, CD44, were studied in skin samples from 13 psoriasis vulgaris patients, using an HA-specific probe (HABC), and monoclonal antibodies, respectively. The general distribution of HA and CD44 in psoriatic lesional epidermis resembled that in normal epidermis. However, areas of epidermis invaded by leukocytes showed a local depletion of HA and CD44, particularly at the contact areas of keratinocytes to lymphocytes and neutrophils. Removal by cellular uptake or extracellular degradation of CD44 and HA may be required for tight adherence between a keratinocyte and a leukocyte. On the dermal side, the tips of the prolonged dermal papillae in psoriatic lesions were intensively stained with HABC. The dilated capillaries and the space below the tip basal lamina, in particular, were heavily covered with HA. Occasionally, a similar intense staining was seen around an enlarged capillary in uninvolved psoriatic skin. CD44-positive leukocytes were found around the affected capillaries. The accumulation of HA in the dermal papillae may support the growth of psoriatic lesions, since HA stimulates the growth of capillaries as well as attracting inflammatory cells.     

白细胞介素22对HaCaT细胞CCL28表达的影响

目的探讨白细胞介素(IL-22)对HaCaT细胞黏膜相关上皮趋化因子(CCL28)表达的影响。方法培养HaCaT细胞,将其分为6组:4个IL-22组(分别用12.5、25、50、100μg/L的IL-22进行干预处理);阻断剂组(50μmol/L PD98059阻断干预,2 h后加入50μg/L IL-22);对照组(用PBS处理)。24 h后,用CCK-8检测细胞的增殖;用实时荧光定量RT-PCR检测CCL28 mRNA的水平变化;用蛋白免疫印迹法、酶联免疫吸附法和免疫荧光检测CCL28蛋白水平的变化。结果CCK-8检测显示,上述浓度的IL-22作用于HaCaT细胞24 h后,对细胞的增殖有明显的促进作用,且这种促进作用能被PD98059抑制,差异具有统计学意义(P<0.05)。实时荧光定量RT-PCR检测显示,上述浓度的IL-22作用于HaCaT细胞,细胞中CCL28 mRNA逐渐升高,均较对照组升高,差异有统计学意义(P<0.01);通路阻断剂组较50μg/L IL-22组降低,差异有统计学意义(P<0.05)。用蛋白免疫印迹法和酶联免疫法检测到CCL28蛋白水平变化的趋势与实时荧光定量RT-PCR检测到的CCL28 mRNA的水平变化的趋势一致,且差异有统计学意义(P<0.05)。免疫荧光检测显示,HaCaT细胞内CCL28蛋白主要表达在细胞质。结论IL-22可剂量依赖促进HaCaT细胞增殖和CCL28的表达,其可能通过MAPK-ERK1/2通路作用。     

窄谱中波紫外线对银屑病患者白细胞介素17、22水平的影响

目的 探讨窄谱中波紫外线（NB-UVB）在银屑病治疗中的作用机制。 方法 42例银屑病患者仅用NB-UVB照射治疗20次,治疗前及治愈患者分别进行标本采集及皮损面积和严重程度指数（PASI）评分;采用酶联免疫吸附试验（ELISA）测定患者治疗前后外周血IL-17和IL-22水平的变化情况,并与20例健康对照比较,同时利用RT-PCR法检测10例患者治疗前后皮肤组织中IL-17和IL-22 mRNA表达水平的差异,并与10例健康对照进行对比分析。 结果 银屑病患者外周血中IL-17（34.26 ± 10.05 ng/L） 和IL-22（13.72 ± 4.45 ng/L）水平明显高于健康对照组（分别为16.34 ± 4.73 ng/L和5.03 ± 1.84 ng/L）,均P < 0.01。患者皮损IL-17 mRNA（13.43 ± 2.12）和IL-22 mRNA（16.53 ± 2.65）表达水平明显高于健康对照组（分别为5.26 ± 0.87和7.72 ± 2.13）,均P < 0.01。银屑病患者PASI与外周血中IL-17和IL-22水平呈正相关（r值分别为0.76和0.70,均P < 0.05）,与皮损中IL-17和IL-22水平亦呈正相关（r值分别为0.65和0.68,均P < 0.05）。42例银屑病患者经NB-UVB照射治疗20次后,15例治愈,且治愈后外周血及皮损中IL-17和IL-22 mRNA及蛋白水平、PASI均明显低于治疗前组,均P < 0.05。 结论 NB-UVB照射治疗银屑病有效的机制之一可能与抑制患者外周血及皮损组织中IL-17及IL-22水平有关。     

寻常性银屑病患者外周血Th22细胞及其白细胞介素22的表达

目的 探讨寻常性银屑病患者外周血Th22细胞及相关因子白细胞介素22（IL-22）表达水平与疾病严重程度及病程的相关性。 方法 抽取40例寻常性银屑病患者和30例健康对照者外周血,流式细胞仪检测外周血Th22细胞比例,ELISA法检测血清中IL-22的表达。采用t检验、Pearson相关分析法进行分析。 结果 寻常性银屑病患者外周血Th22细胞百分比（0.65% ± 0.48%）高于健康对照组（0.33% ± 0.15%）,两组差异有统计学意义（t = 3.89,P < 0.01）;银屑病患者Th22细胞与银屑病病情严重度评分（PASI）呈正相关（r = 0.38,P < 0.05）,但与病程无相关性（r = 0.20,P > 0.05）。银屑病患者血清中IL-22表达水平［（67.96 ± 14.32） ng/L］高于健康对照组［（40.59 ± 9.91） ng/L］,两组差异有统计学意义（t = 9.45,P < 0.01）;银屑病患者血清IL-22表达水平与PASI呈正相关（r = 0.94,P < 0.01）,与病程无相关性（r = 0.10,P > 0.05）。 结论 Th22细胞及IL-22在寻常性银屑病外周血中有高表达,且Th22细胞及IL-22水平均与疾病严重程度相关。     

The skin blanching assay with halcinonide,influence of halcinonide concentration and application time ⋆

Objective Instrumental colour readings (Minolta Chromameter CR200) were performed in order to quantify corticosteroid induced skin blanching. Methods Different Halcinonide concentrations in the same vehicle ranging from 0.005% to 0.200% were tested on the volar part of the forearms. Besides dose-response relationships we studied the influence of application time by applying the formulations under occlusion during 2, 12 and 18 h. Results All evaluated formulations provoked a discernible blanching as indicated by the significant increase of the L* parameter and the decrease of the a* parameter. Discrimination between the different Halcinonide concentrations was possible only in the 2 h application experiment. With longer application times a similar blanching was recorded for all Halcinonide concentrations. Conclusion Our results indicate that a shorter application time may lead to a more sensitive skin blanching assay.     

Changes in the distribution of actin-associated proteins in psoriatic keratinocytes. Immunohistochemical study using confocal laser scanning microscopy

Recent studies support the presence of adherens junctions at the dermal–epidermal interface in addition to hemidesmosomes. In this area the integrin/actin-containing cytoskeleton connection occurs by means of a complex of proteins called actin-associated proteins (talin, vinculin, α-actinin). As previous studies have demonstrated the presence in psoriatic lesions of marked alterations in both the basement membrane molecular composition and the polarized expression of integrins, we decided to determine whether alterations in the behaviour of the actin-associated proteins could be demonstrated. We thus undertook an immunolocalization study with monoclonal antibodies directed against talin, vinculin, and α-actinin in cutaneous biopsies taken from involved and uninvolved skin of 12 patients with extensive chronic plaque psoriasis. The findings showed an almost total lack of reaction against talin and vinculin in the basal layer and an increased positivity against the proteins in the suprabasal layers. Similar, though less marked, alterations were present in uninvolved psoriatic skin. These results, in agreement with those of previous studies, confirm serious alterations in the matrix protein/cytoskeleton connection system, and support the hypothesis that this condition may play a key role in the pathogenesis of the disease. Received: 13 May 1996     

HLA risk haplotype Cw6,DR7, DQA1*0201 and HLA-Cw6 with reference to the clinical picture of psoriasis vulgaris

Received: 24 May 1995     

Two‐photon microscopy of dermal innervation in a human re‐innervated model of skin

When skin is injured, innervation can be severely disrupted. The subsequent re‐innervation processes are poorly understood notably because of the inability to image the full meandering course of nerves with their ramifications and endings from histological slices. In this letter, we report on two‐photon excitation fluorescence (TPEF) microscopy of entire human skin explants re‐innervated by rodent sensory neurons labelled with the styryl dye FM1‐43. TPEF imaging of nerve fibres to a depth up to roughly 300 μm within the dermis was demonstrated, allowing three‐dimensional reconstruction of the neural tree structure. Endogenous second‐harmonic imaging of type I fibrillar collagen was performed in parallel to TPEF imaging using the same nonlinear microscope, revealing the path of the nerves through the dermis.     

染料木黄酮对预防成纤维细胞光化学损伤的影响

目的 探讨染料木黄酮在PUVA所致体外培养真皮成纤维细胞光老化模型中的保护作用。 方法　运用PUVA联合构建体外培养真皮成纤维细胞光老化模型,噻唑蓝比色法（MTT法）确定染料木黄酮最适光保护作用浓度,倒置显微镜下观察细胞形态,酶组织化学法观察细胞衰老相关-β-半乳糖苷酶（SA-β-Gal）表达,流式细胞仪检测细胞活性氧（ROS）含量,实时荧光定量PCR检测细胞基质金属蛋白酶1（MMP-1）mRNA表达等。 结果　UVA照射后24 h,正常对照组、光老化组及染料木黄酮组SA-β-Gal阳性细胞率分别为（0.67 ± 0.58）%、（96.67 ± 1.53）%、（51.67 ± 2.08）%,各组间差异有统计学意义（P ＜ 0.01）。光老化组、染料木黄酮组ROS含量分别为正常对照组的（1.88 ± 0.24）和（1.62 ± 0.02）倍（均P ＜ 0.01）。光老化组MMP-1 mRNA表达上调为正常对照组的10倍,染料木黄酮组表达量仅为正常对照组的6倍,各组间差异有统计学意义（P ＜ 0.05）。结论　染料木黄酮对PUVA所致体外培养真皮成纤维细胞光老化具有一定的保护作用。 【关键词】 染料木黄酮; PUVA疗法; 成纤维细胞; 光; 细胞衰老