Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response

Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-gamma (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed.     

Effects of extracellular matrices on human keratinocyte adhesion and growth and on its secretion and deposition of fibronectin in culture

Extracellular matrices (ECMs) play an important role as components of basement membrane of normal human skin and in migrating epidermal cells in wound healing. We investigated the effects of various ECMs on human keratinocyte adhesion and growth as well as on its secretion and deposition of fibronectin (FN) in vitro using a serum-free, low-calcium culture system. Since cell adhesion is the first step of cell growth, we performed cell adhesion assay for 14 h. Human keratinocytes adhered best on FN and less well on types I/III collagen, type IV collagen, and heparan sulfate proteoglycan (HSPG) as compared with bovine serum albumin (BSA) (control) or laminin (La). Cell growth assayed for 7-8 days on the dishes coated with various extracellular matrices revealed significantly increased keratinocyte growth on FN and on types I/III collagen in comparison with that on type IV collagen, HSPG, BSA (control), or La. Morphology of keratinocytes and of their colonies on FN and types I/III collagen was strikingly different from that of the control; the colonies were not so compact as in the control, but rather loose and larger; each keratinocyte was spread out more on these substrata. These morphologic features seemed to correlate with the increased keratinocyte growth on these extracellular matrices. Both immunofluorescence study for FN with keratinocytes in 8-day culture on various extracellular matrices and enzyme-linked immunosorbent assay for FN measurement on substratum or in conditioned medium with keratinocytes in 5-day culture demonstrated that extracellular matrices modulated the secretion and deposition of FN by human keratinocytes in culture; the keratinocyte growth correlated with the amount of FN detected on substratum but not with that in medium. Based on the results of the present investigation, we think that the growth of human keratinocytes depends on the amount of FN on substratum.     

Functional properties of the surface of the vermilion border of the lips are distinct from those of the facial skin

BACKGROUND: The vermilion border of the lips (lip for short) is the only part on the face where the oral mucosa is persistently exposed to the outside. Despite its prominent presence on the face, constituting not only the target of cosmetics but also the site for various skin diseases, its functional properties remain almost unknown. OBJECTIVES: To elucidate the functional properties of the vermilion border of the lips. METHODS: We studied the biophysical properties of the lip by comparing them with those of the cheek skin in 303 healthy Japanese females aged 21-80 years, in winter. We used a closed-chamber system to measure transepithelial water loss (TEWL) of the lip to avoid the effect of breathing. Moreover, we examined the effects of oral etretinate, a drug that definitely produces dry, scaly lips, on the lips of seven male patients aged 49-89 (average 67) years. RESULTS: TEWL was significantly almost three times as high on the lips as that on the cheek which is a site that shows far higher levels than do other body areas. TEWL decreased with age more remarkably on the lip than on the cheek. High-frequency conductance, a parameter for surface hydration state, was significantly lower on the lip than on the cheek. The mean values obtained were about one-third of those on the cheek, and no age-related changes were observed either on the lip or on the cheek. The superficial epithelial cells on the lip were parakeratotic and larger than those of the cheek skin. Furthermore, we detected a significant increase in TEWL on the lip as well as on the cheek of patients treated with oral etretinate. CONCLUSIONS: It appears that the incomplete corneocyte formation of the lip surface is responsible for the poor barrier function and water-holding capacity.     

Physiological analysis of the facial skin by corneocyte morphology and stratum corneum turnover

In order to clarify the properties of facial skin, we measured corneocyte size and stratum corneum turnover rate on the face of healthy female volunteers in relation to age and compared the data with those from the flexor surface of the forearm. The corneocyte size on the face was found to be significantly smaller and the percentage of nucleated corneocytes was distinctly higher than those on the forearm. Stratum corneum turnover rate on the face was also approximately two times faster than on the forearm. The corneocyte size increased with aging on the forearm, but not on the face. Additionally, turnover rate decreased with aging on the forearm, but not on the face. These findings suggest that the facial skin is apparently influenced by some exogenous or endogenous factors which seem to overcome the influence of intrinsic aging effects.     

Comparison of Sheffield media with standard media for the isolation of Haemophilus ducreyi

Isolation of Haemophilus ducreyi is the only method for the definitive diagnosis of chancroid. Culture on supplemented gonococcal base (GCHgs) or on supplemented Muller-Hinton agar (MHHb) has yielded the best isolation rates. Sheffield media is an alternative to standard media. We compared the isolation rate of H. ducreyi on GCHgs and MHHb to that on the Sheffield media with and without 5% horse blood. Vancomycin (3 mg/L) was added to all media. Of the 87 specimens cultured from patients with genital ulcer disease, 57 (66%) were positive on either GCHgs or MHHb or on both. Twenty six (30%) were positive on GCHgs only, 15 (17%) on MHHb only, and 15 (17%) on both. One culture was positive on Sheffield medium with 5% horse blood; none were positive on Sheffield medium without horse blood. Stock strains showed good growth at 48 hr on GCHgs and MHHb, but no growth at 48 hr and only minimally detectable growth at 72 hr on Sheffield media with horse blood. No growth was detected on Sheffield media without horseblood. Thus optimal culture of H. ducreyi in Kenya requires two media, supplemented gonococcal base and Muller-Hinton agar. Sheffield media is not useful for the primary isolation of H. ducreyi.     

太田痣并发伊藤痣和鲜红斑痣

报告2例太田痣并发伊藤痣及鲜红斑痣.2例患者均为先天发病,例1为左侧面部太田痣并发双侧肩部、背部、腰部、臀部和上肢伊藤痣及左面颈部、左背部鲜红斑痣:例2为左侧面部太田痣并发肩背部伊藤痣及面部、躯干和四肢多处鲜红斑痣.     

我国正常人皮肤表面皮脂和水分含量的研究

目的：了解我国不同年龄、不同性别正常人皮肤角质层含水量、皮肤表面皮脂含量及皮肤皮脂的分泌速度。方法：利用皮肤表面皮脂测量仪和皮肤水分含量测量仪对我国北方325名正常人的前额及前臂屈侧皮肤皮脂量和皮肤含水量进行测量。结果：12岁以前,男女前额皮脂量无差异;13岁以后,男性前额的皮脂量明显高于女性。除36～50岁年龄组外,女性前额的皮脂分泌快于男性。男女前臂的皮脂量无差异。除男性13～35岁组的前额皮肤含水量高于女性外,其他各年龄组各部位男、女皮肤含水量无显著差别。13～35岁组男、女性前额的含水量均高于前臂。其他各年龄组前额和前臂皮肤含水量无明显部位差异。13-35岁组男性前额皮肤含水量最高。结论：正常人皮肤表面含水量和皮脂含量因性别、年龄和部位的不同而有差异。     

Relationship of nevocytic nevi to sun exposure in dysplastic nevus syndrome

In eighty consecutive patients who have the dysplastic nevus syndrome, the concentration of nevocytic nevi on the relatively sun-protected lateral thoracic area was compared to the concentration on the relatively sun-exposed areas of the anterior and posterior thorax. Nevocytic nevi in an area 7 X 20 cm were counted in each location. There was a total of 177 nevi on the lateral thorax (average, 2.2 nevi/person), 361 on the anterior thorax (average, 4.5 nevi/person), and 506 on the posterior thorax (average, 6.3 nevi/person). Men showed no significant difference in the number of nevi on the anterior and posterior thoracic areas, but women had fewer nevi on the anterior than on the posterior thoracic sites. These findings are consonant with the hypothesis that sunlight induces nevocytic nevi in patients who have the dysplastic nevus syndrome.     

Patch testing in patients treated with systemic immunosuppression and cytokine inhibitors

Background: Currently, there is little data available on the reliability of patch testing in patients taking immunosuppressive agents other than systemic corticosteroids. Objectives: We present data from 38 patients who were patch tested whilst taking various immunomodulating agents to determine if positive reactions can be elicited. Patient/materials/methods: Between September 2006 and May 2009, 38 patients attending the St John's Institute of Dermatology were patch tested whilst taking immunosuppressive agents including azathioprine, ciclosporin, infliximab, adalimumab, etanercept, methotrexate, mycophenolate mofetil, and tacrolimus. Results: Positive patch test reactions of varying degrees and significance were elicited in: 2 of 10 patients on azathioprine; 5 of 11 patients on ciclosporin; 1 patient on ciclosporin and Fumaderm^®; 1 patient on infliximab; 1 patient on infliximab and methotrexate; 1 of 2 patients on adalimumab; 1 patient on etanercept and methotrexate; 3 of 4 patients on methotrexate; 1 of 3 patients on mycophenolate mofetil; and 1 patient on mycophenolate mofetil and tacrolimus. Negative patch test reactions occurred in 1 patient on azathioprine and ciclosporin; 1 patient on infliximab and azathioprine; and 1 patient on mycophenolate and ciclosporin. Conclusions: Positive patch test reactions can be elicited in patients taking azathioprine, ciclosporin, infliximab, adalimumab, etanercept, methotrexate, mycophenolate mofetil, and tacrolimus. However, it remains unclear what effect these immunosuppressive drugs may have on suppressing allergic patch test reactions and further studies should be carried out to determine the reliability of testing in these circumstances.     

The histomorphologic spectrum of primary cutaneous diffuse large B-cell lymphoma: a study of 79 cases

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group. In this study, we retrospectively assessed the histomorphologic features of 79 cases of PCDLBCLs, including those of "leg type" and "other" NOS type, to further categorize the histologic spectrum of these unusual cutaneous neoplasms. The histologic diagnosis of PCLBCL usually poses little diagnostic difficulty; however, some cases may adopt unusual or unfamiliar appearances mimicking other lymphoproliferative disorders or other malignant neoplasms. Seventy-nine cases, occurring in 37 men and 42 women, aged 34-94 years, were analyzed. Fifty-three cases were classified as "leg type" and 26 cases were classified as "other" NOS type using the WHO-EORTC classification. Of the 53 cases classified as "leg type," 33 were women and 20 were men; of the 26 cases of "other" NOS type, 9 were women and 17 were men. In the "leg type" category, 31 cases were located on the lower extremities, 5 cases on the face, 5 cases on the arm, 3 cases on the chest, 2 cases on the shoulder, 2 cases on the back, 1 case on the trunk, 1 case on the buttock, 1 case on the supraclavicular area, 1 case on the head, and 1 case on the flank. Of the "other" NOS type category, 8 cases were located on the face, 5 cases on the shoulder, 3 cases on the head, 2 cases on the abdomen, 2 cases on the chest, 1 case on the trunk, 1 on the vulva, 1 on the axilla, 1 on the back, 1 on the neck, and 1 on the hip. Most cases assessed showed the classic morphologic appearance of PCDLBCL, but cases mimicking Burkitt lymphoma (starry-sky pattern), natural killer-cell (NK) lymphoma, mycosis fungoides (epidermotropism), low-grade B-cell lymphomas, epithelial malignancies, and Merkel cell carcinoma were encountered in this series. The high frequency of these rare histologic patterns can be explained by a bias associated with consultation practice. Careful histologic examination and immunohistochemical stains were used to establish the correct diagnosis. The differential diagnosis of PCDLBCL is broad and difficult to define histologically. Knowledge of these rare histologic variants is necessary to avoid misinterpretation of these cases as nonlymphoid malignancies.     

Spitz痣与恶性黑素瘤患者临床特点及P16表达的分析

回顾性分析我院2016-2018年确诊的7例Spitz痣和5例恶性黑素瘤患者资料。 Spitz痣患者中男2例,女5例,年龄9～36岁,中位年龄 29岁,发生部位：上肢2例,手部1例,膝部1例,右耳1例,小腿1例,鼻根部1例;5例恶性黑素瘤患者中男1例,女4例,年龄50～84岁,中位年龄78岁,发生部位：足底4例,下肢1例。在7例Spitz痣中P16弥漫性高表达5例,中等表达1例,低表达1例;5例恶性黑素瘤中,P16阴性3例,低表达2例。     

IMMUNE DEPOSITS IN THE SKIN OF REVERSED PASSIVE ARTHUS REACTION. THE EFFECTS OF THE ADMINISTRATION OF THE CORTICOSTEROID

The effects of corticosteroid administration on the immune deposits in the skin of reversed passive Arthus reaction (RPAR) using horseradish peroxidase as antigen were studied. Immune deposits were seen on vascular walls, on collagen fibers, at the dermo-epidermal junction, at perifollicular regions, on mononuclear cells and in PMN-leukocytes. By corticosteroid administration the amount of these immune deposits was most obviously reduced within the first 30 minutes after the induction of the RPAR. At 1, 4, 8, 24 and 48 hours after induction of the reaction there were no significant differences in the amount and the extent of the immune deposits on the vascular walls, on the collagen fibers and on the mononuclear cells, between the sections treated by corticosteroid and those of non-treated specimens. The infiltration of PMN-leukocytes and their uptake of immune complexes were maximum at 4 hours after the injection and the number of these infiltrated PMN-leukocytes and the amount of immune complexes which were taken by them were slightly reduced by corticosteroid administration.     

Quality of life measurement in atopic dermatitis. Position paper of the European Academy of Dermatology and Venereology (EADV) Task Force on quality of life

There is a need for researchers to have easy reference to the wide spectrum of different types of quality of life (QoL) instruments that can be used in atopic dermatitis (AD). Previous reviews on QoL in AD do not cover the full spectrum of QoL measures used in studies on AD. This study, on behalf of the European Academy of Dermatology and Venereology (EADV) Task Force on QoL, contains information on instruments available for health‐related QoL and family QoL assessment in AD including information on validation, experience of QoL assessment in AD for different purposes, peculiarities of QoL assessment in different age groups, expert analysis of available instruments including data on limitations of their use and recommendations of the Task Force.     

Evaluation of sunscreening agents

Sunscreen preparations are evaluated according to their protection against biological effects of ultraviolet radiation. UV-induced phenomena found on protected skin are compared with those on unprotected skin; thus the sunprotection factor is estimated. In order to assess the photoprotective power of sunscreens, only early UV-induced effects are decisive - such as erythema. PUVA erythema, pigmentation, activation of the ornithine decarboxylase, the influence on Langerhans cells, appearance of 'sunburn' cells, and changes of the DNA metabolism. We report on the various methods to obtain the specific sunprotection factors against UVB and UVA. Water-resistance, photostability, and pharmacokinetics depending on the vehicle are further criteria with regard to the evaluation of sunscreens. We rely on consumers information regarding the following properties of sunscreens: stickness, oily shine, greasiness, discoloration, odor, and tolerance.     

外用维A酸引起小鼠皮肤反应的研究

目的 观察在动物实验中外用0.1%全反式维A酸霜及其基质引起的皮肤反应。方法 小鼠背部每天分别外用0.1%全反式维A酸霜及其基质,连续使用30d,肉眼观察皮肤变化,并用生物学仪器进行红斑和皮屑检测。结果 外用0.1%全反式维A酸霜,肉眼观察第3天左右出现红斑、脱屑反应,第6天左右达高峰,第12天左右消失,继续用药至第30天,未见反应再现;仪器测得红斑值在第1天时已明显升高,第6天时达最高峰,并持续高峰状态至第9天,第11天时降至基本正常,至第30天,均维持在正常范围,皮屑指数在用药第3天时明显升高,第9天时达高峰,然后逐渐下降,第27天时降至正常。外用基质部位与用药前比无差异。结论 在动物实验中,外用0.1%全反式维A酸霜引起的皮肤反应在不停药的情况下,呈现“出现-高峰-消退”的一过性规律。维A酸皮肤反应与基质无关。     

Skin radiance: how to quantify? Validation of an optical method

BACKGROUND/PURPOSE: The aim of this study was to validate an optic device used to measure the quantity of light reflected by the skin, which depends on the brightness of the skin. METHODS: This apparatus gives three parameters, called Complexion/diffusion (Cd), Cr (Complexion/reflection) and Complexion/specular position (Csp). Measurements were carried out on the forehead (slightly rounded surface) and the cheekbone (angular surface). To estimate the repeatability and the reproducibility of each parameter, two female subjects (one with a dull complexion and the other with a glowing complexion) and three operators participated in the study. To investigate repeatability, each operator performed 10 consecutive measurements on both zones. To investigate inter-investigator reproducibility, the operators performed the measurements alternately. To investigate day-to-day reproducibility, these measures were achieved during three visits at a 2-day interval, at D1, D3 and D5. To estimate the sensitivity and the specificity, 30 females participated in the study (15 in the dull complexion group and 15 in the glowing complexion group). RESULTS: Cd was repeatable (variation coefficient <20%), day-to-day reproducible on both sites (generally P>0.05) but not inter-investigators reproducible (generally P<0.05). The sensitivity was 93% on the forehead and 80% on the cheekbone; the specificity was 87% on the forehead and 60% on the cheekbone. Cr was repeatable (variation coefficient <5%), day-to-day reproducible (P>0.05) and not inter-investigators reproducible (generally P<0.05). The sensitivity was 93% on the forehead and 80% on the cheekbone; the specificity was 87% on the forehead and 80% on the cheekbone. Csp was not repeatable (variation coefficient >5%) on both the studied zones and for the three investigators. CONCLUSION: The repeatability and the day-to-day reproducibility were satisfying for the Cd and Cr parameters on both the studied sites. The sensitivity and the specificity were satisfying for both parameters on both sites, except for the specificity of the Cd parameter on the cheekbone. Therefore, this apparatus is suitable to follow-up an evolution on both the studied sites, but we recommend: (a) that the same trained investigator always performs the measurements, (b) to privilege the forehead in particular for a classification (dull or glowing).     

Clinical pharmacology of intravenous paracetamol in perinatal medicine

Clinical pharmacology aims to predict drug-related effects based on compound and population specific pharmacokinetics (PK, concentration-time), and pharmacodynamics (PD, concentration-effect). Consequently, dosing needs to be based on the physiological characteristics of the individual patient. Pregnancy and early infancy hereby warrant focused assessment. The specific characteristics of both subpopulations will be illustrated based on observations on intravenous (iv) paracetamol PK and PD collected in these specific populations. At delivery, there is a significant higher paracetamol clearance (+ 45%, L/h) when compared to non-pregnant observations. This higher clearance is in part explained by a proportional increase in oxidative metabolite production, but mainly an increase in glucuronidation. When focusing on PD, an association between maternal paracetamol exposure and atopy in infancy and fetal gastroshizis has been reported. In early infancy, paracetamol clearance is significantly lower and mainly depends on size (weight 0.75), while also the distribution volume is higher (L/kg). Reports on hepatic tolerance, haemodynamic stability and impact of body temperature have been published while the concentration effect profile for analgesia seems to be similar between neonates and children. Similar to maternal exposure, there are reports on the association with atopy. Studies on the use of paracetamol to close the patent ductus arteriosus are ongoing. At least, these observations provide evidence on the need to study commonly administered anesthetics in such specific subpopulations with specific focus on both population specific PK and PD to further improve patient tailored pharmacotherapy.     

Dorsal sensory impairment in hands and feet of people affected by Hansen's disease in Israel

INTRODUCTION: Sensory testing in people affected by Hansen's disease is usually performed on palms and soles only. In Israel, both palmar/plantar and dorsal aspects of limbs are routinely tested. OBJECTIVES: The aim of this study was to describe the magnitude of dorsal sensory impairment (SI) in limbs and compare the frequency of SI on palms and soles with that on the dorsum of hands and feet. DESIGN: In a cross-sectional study, limbs of 140 patients registered at The Israel Hansen's Disease Centre during the years 1999-2003 were tested for their sensory status. Both palmar/plantar and dorsal aspects were tested using Semmes-Weinstein monofilaments. SI was defined as not feeling stimuli applied with the 2 g monofilament. RESULTS: SI was detected on the dorsum in 43% of sites on hands and only in 27% on palms. 64% of sites on dorsum of feet had SI compared to 53% on the soles. SI was detected in up to 18% in hands with no palmar SI, and in 6% of feet with no plantar SI. Furthermore, SI on palms and soles was found to be accompanied by dorsal SI in all hands and in 97% of feet. CONCLUSION: SI on dorsum of limbs occurs more frequently than SI on palms and soles. Therefore sensory testing should also consider inclusion of the dorsal aspect of hands and feet.     

恶性黑素瘤研究文献的计量学分析

目的：了解全球黑素瘤研究的现状、核心作者群及期刊、研究集中的学科领域,帮助黑素瘤研究者及临床医生更好地把握行业动态.方法：利用web of sci引文分析工具对2000-2012年全球发表的关于恶性黑素瘤研究的科学文献进行分析.结果：自2000年起全球对黑素瘤的研究逐渐增加,美国发表的科技论文占了全部论文的1/3;黑素瘤基因学研究在2000-2002年间有了突破性进展,开拓了新的研究领域.结论：恶性黑素瘤研究在疾病的诊断、治疗等各个方面深入到了基因水平,对肿瘤的生物学特性、病理特征的研究,外科和放射技术的应用以及药物治疗是目前研究的热点领域.     

当下热播婚恋剧对女大学生婚恋观的影响——以上海高校在校女学生为例

有关婚恋观的研究经久不衰,但是关于当下热播的婚恋剧作为一种＂媒介现实＂是否反映真实的普遍婚姻状况,并且是否会影响及如何影响女大学生的婚恋观方面的研究,国内尚为空白。本文通过对上海交通大学在校女大学生进行焦点小组访谈和问卷抽样调查,结合对热播婚恋剧的分析,发现婚恋剧大体反映当下普遍婚姻状况,但其基调要比真实婚姻状况乐观;电视剧、电影作为大众媒介会影响女大学生的婚恋观,婚恋剧接触程度较深的女大学生与婚恋剧接触程度较浅的女大学生在某些具体的婚恋观问题上存在差异。