Dermatitis herpetiformis

The multifactorial pathogenesis of dermatitis herpetiformis is reviewed in light of current experimental data. Genetic background, gluten consumption, and abnormal immune and autoimmune reactions are the most important pathogenetic factors, but other agents also participate in the disease development. The predisposing and inducing factors are summarized, while the pathophysiological steps leading to the development of skin symptoms are detailed.     

神话文化中的性规则

人类的性行为,不仅具有作为基础的生物性特点,而且要遵循社会和文化的规则。人类性行为所遵循的规则是历史发展的产物。神话作为世界性的原始文化,从特定的侧面记载了人类性规则的发展历程。健康的性规则是人类长期实践智慧的结晶。挖掘记载人类性规则发生和发展的神话文化的侧面,有益于我们对人类性行为规则的理解。     

Tight junction properties change during epidermis development

In terrestrial animals, the epidermal barrier transitions from covering an organism suspended in a liquid environment in utero, to protecting a terrestrial animal postnatally from air and environmental exposure. Tight junctions (TJ) are essential for establishing the epidermal permeability barrier during embryonic development and modulate normal epidermal development and barrier functions postnatally. We now report that TJ function, as well as claudin‐1 and occludin expression, change in parallel during late epidermal development. Specifically, TJ block the paracellular movement of Lanthanum (La³⁺) early in rat in vivo prenatal epidermal development, at gestational days 18–19, with concurrent upregulation of claudin‐1 and occludin. TJ then become more permeable to ions and water as the fetus approaches parturition, concomitant with development of the lipid epidermal permeability barrier, at days 20–21. This sequence is recapitulated in cultured human epidermal equivalents (HEE), as assessed both by ultrastructural studies comparing permeation of large and small molecules and by the standard electrophysiologic parameter of resistance (R), suggesting further that this pattern of development is intrinsic to mammalian epidermal development. These findings demonstrate that the role of TJ changes during epidermal development, and further suggest that the TJ‐based and lipid‐based epidermal permeability barriers are interdependent.     

Cutaneous Malignancies in Pediatric Solid Organ Transplant Recipients

Pediatric organ transplant recipients (POTRs) are at risk of developing malignancies due to a combination of immunosuppression, impaired DNA damage repair, and infection with oncogenic viruses. The most commonly developed malignancies in this population are skin cancers, which include nonmelanoma skin cancer, melanoma, Kaposi's sarcoma, and anogenital carcinoma. The literature shows that skin cancers account for 13% to 55% of all cancers that occur after transplantation. Given the increasing number and life expectancy of POTRs, prevention and management of skin cancer in these patients is essential, but there is a substantial knowledge gap in our understanding of the differences in skin cancer development, prevention, and management between POTRs and adult organ transplant recipients (AOTRs), for whom more data are available. Substantial differences have been observed in the patterns of malignancy development between POTRs and AOTRs, and data specific to pediatric populations are needed. The objective of this review is to provide updated information on posttransplantation skin cancer development in POTRs, including epidemiologic research on transplant patients and disease development, medication management, surveillance, and education efforts.     

Immunosuppression: A cause of porokeratosis?

Two patients are reported in which the development of porokeratosis occurred following chemotherapy for systemic malignancy. Immunosuppression associated with malignancy and chemotherapy may exacerbate or initiate the development of porokeratosis in patients predisposed to alterations of cutaneous growth dynamics.     

Distribution of epidermal growth factor receptors in rat tissues during embryonic skin development, hair formation, and the adult hair growth cycle

In a previous study on neonatal rat skin (Green MR, Basketter DA, Couchman JR, Rees DA: Dev Biol 100:506-512, 1983) a close positive correlation was found between epidermal growth factor (EGF) receptor tissue distribution and areas of potential epithelial cell proliferation. We now report on the binding distribution of [125I]EGF, representing the tissue localization of available EGF receptors, during embryonic rat skin development including hair follicle formation and the adult hair growth cycle. At 16 days embryonic development a relatively low receptor density is seen over all the epidermal cell layers but by 17 days, with the onset of very rapid epidermal proliferation, labeling increases and becomes restricted to the basal epidermal cells. Between 17 and 20 days embryonic development, available receptors for EGF are consistently absent from epidermal basal cells overlaying the dermal condensates marking the first stage of hair follicle development. This restricted and temporary loss of EGF receptors above these specialized mesenchymal condensates implies a role for the EGF receptor and possibly EGF or an EGF-like ligand in stimulating the epithelial downgrowth required for hair follicle development. In the anagen hair bulb, receptors for EGF are detected over the outer root sheath and the epithelial cell layers at the base of the follicle and show a correlation with the areas of epithelial proliferation in the hair bulb. During the catagen and telogen phases of the hair cycle, receptors are observed in high numbers on all the undifferentiated or dedifferentiating cells of the degenerating epithelial strand and secondary hair germ. Dermal cells are, in general, less heavily labeled than the basal epithelial cells of skin except for the developing striated muscle (panniculus carnosus) in embryonic skin which is more heavily labeled. The data are discussed in terms of a possible role for the EGF receptor and associated EGF or EGF-like ligands in specific areas of epithelial tissue morphogenesis during embryonic skin maturation, hair follicle development, and hair cycling.     

Developing clinical guidelines: issues and challenges

Clinical guidelines are viewed as an important tool in the quest to promote evidence based practice. Consequently, there has been a proliferation in guideline development at a national and local level. This paper describes what clinical guidelines are and how they have been developed by a national organisation--the Royal College of Nursing (RCN). Drawing on the development of two tissue viability guidelines: The Management of Patients with Venous Leg Ulcers and Risk Assessment and Prevention of Pressure Ulcers, some challenges inherent in guideline development are outlined. Certain desirable attributes that a clinical guideline should exhibit in order for it to be utilisable and effective in practice are outlined as these provide a standard for guideline developers. In reality the practice of guideline development will depend upon the topic, the experience of the guideline group, the purpose of the guidelines and the evidence available. Our experience suggests that producing a clinically valid and utilisable guideline is a labour and resource intensive process. It is also time consuming. An alternative strategy to developing local guidelines from scratch would be to adapt an existing guideline to local circumstances. A stepwise process is presented in the paper to assist people with this process.     

A case of nodular scleroderma

Nodular scleroderma is a rare complication of systemic sclerosis; the pathogenetic implications are still unknown, although many factors are supposed to play a role in lesion development. We report the case of a young woman suffering from systemic sclerosis, who developed nodular lesions during therapeutic management with D-penicillamine and plasmapheresis. In order to better understand the essence of this disease, we examined all the possible pathogenetic mechanisms that could be implicated in nodular lesion development.     

Acne vulgaris

Acne vulgaris is worldwide the most common skin disease. Acne is an inflammatory disorder in whose emergence androgens, PPAR ligands, the IGF-1 signaling pathway, regulating neuropeptides and environmental factors are probably involved. These factors interrupt the natural cycling process in the sebaceous gland follicle and support the transition of microcomedones to comedones and inflammatory lesions. Proinflammatory lipids and cytokines are mediators for the development of acne lesions. Bacterial antigens can potentate the inflammatory phenomena. Acne is predominantly treated with combination therapy. Selecting a treatment regimen depends on the exact classification of acne type and severity. The development of scars is the main criterion for the choice of systemic therapy. Retinoids for mild comedonal acne and the combination of retinoids with antibiotics and/or benzoyl peroxide for mild to moderate papulopustular acne are the drugs of first choice for topical treatment. The use of topical antibiotics is not recommended any more because of the development of resistant bacterial strains. Systemic antibiotics, in combination with topical retinoids and/or benzoyl peroxide, for moderate papular/nodular acne and isotretinoin for severe nodular/conglobate acne are the columns of systemic acne treatment. Systemic anti-androgens are used in women against moderate papulopustular acne. Due to advances in the understanding of the underlying inflammatory mechanisms in recent years the development of new therapeutic agents with good efficacy and better side effect profile should be expected in the future.     

In vivo function of desmosomes

Desmosomes are morphologically and biochemically defined cell-cell junctions that are required for maintaining the mechanical integrity of skin and the heart in adult mammals. Furthermore, since mice with null mutations in desmosomal plaque proteins (plakoglobin and desmoplakin) die in utero, it is also evident that desmosomes are indispensable for normal embryonic development. This review focuses on the role of desmosomes in vivo. We will summarize the effects of mutations in desmosomal genes on pre- and post-embryonic development of mouse and man and discuss recent findings relating to the specific role of desmosomal cadherins in skin differentiation and homeostasis.     

Interrogating the integument: the role of the epidermis in hair induction

Hair follicle development is driven by interactions between the epithelium and underlying mesenchyme. These reciprocal interactions are essential for development, as a lack of response from either the mesenchyme or epithelium results in arrested growth. A large body of research has focused on the role of mesenchymal cells during hair follicle development and their inductive properties for hair neogenesis. In this commentary, the role of the epidermis during hair follicle induction will be discussed.     

The role of facial sebum secretion in acne pathogenesis: facts and controversies

Increased sebum secretion has been known as one of the major pathogenic factors in the development of acne; however, objective sebum measurement methods have been developed only recently. We have limited information about the association of sebum secretion, and the development of acne. There continues to be controversy about the role of sebum in the development of acne. This contribution will discuss sebum measurement techniques and the results of recent studies on the relationship of sebum, facial cosmetic skin type, and acne. New therapeutic modalities for inflammatory acne aim to control seborrhea. Superficial chemical peels, laser treatment for inflammatory acne, and photodynamic therapy are used as adjunctive therapies for acne; however, their sebosuppressive effects are only temporary.     

Clinical development of dermatologics

Dermatologic drugs are considered in the same scope as other pharmacologic agents. They have chemical structures, specific mechanisms of action, in vitro activity, in vivo effects, and beneficial effects as well as adverse reactions in clinical use. Dermatologic drug development therefore follows the same general theme as for other drug product classes. Logical and well-planned clinical development programs are required for careful evaluation of the safety and efficacy of the product in its intended use, whether this be a topical or systemically administered drug.     

Spiradenoma arising in a nevus sebaceus of Jadassohn: case report and literature review.

Nevus sebaceus (NS) of Jadassohn is usually a verrucous plaque on the scalp or face that arises secondary to disordered development of epithelial, pilar, sebaceous, and apocrine structures. The emergence of neoplasia is a late stage in the natural history of NS. Although most neoplastic proliferations are benign, several malignant tumors have arisen in this lesion. We describe the first case of a benign spiradenoma arising in an NS on the scalp in a 72-year-old Caucasian woman. Reexcision was recommended to prevent the development of a second neoplastic process and to avoid the rare occurrence of a malignant transformation of the existing neoplasia. The patient declined reexcision and remains under observation. The spectrum of tumors arising in NS are described and are categorized according to behavior. Syringocystadenoma papilliferum is the most commonly observed benign growth, whereas basal cell carcinoma is the most frequently seen malignant process. The signs of tumor development (benign or malignant) within an NS are reviewed, and treatment recommendations are provided. The clinical course of rare and unique aggressive neoplasms originating in NS is summarized.     

The role of Smads in skin development

Smads are a group of signaling mediators and antagonists of the transforming growth factor-beta (TGF-beta) superfamily, responding but not limited to signaling from TGF-beta, Activin, and bone morphogenetic proteins (BMPs). As all of these three signaling pathways play important roles in skin development, we have been actively pursuing studies assessing the role of Smads in skin development. Our studies revealed that Smad-4 affects hair follicle differentiation primarily by mediating BMP signaling. Smad-7 significantly affects hair follicle development and differentiation by blocking the TGFbeta/Activin/BMP pathway and by inhibiting WNT/beta-catenin signaling via ubiquitin-mediated beta-catenin degradation. In contrast, other Smads may have redundant or dispensable functions in skin development. Here, we review the work that shows the emergence of Smad functions in skin development via traditional and novel signaling pathways.     

The molecular basis of hair growth

For a long time, hair follicle development could be studied on the morphological level only. Now that molecular genetics is coming of age, we are beginning to understand the molecular basis of hair follicle development. The study of inherited hair disorders and basic research have both contributed to our insights and exciting developments can be expected in the near future. Here, we present a compact overview of the essential players in hair development and propose a simple model of the genetic interactions in the hair follicle.     

Epidermal differentiation: transgenic/knockout mouse models reveal genes involved in stem cell fate decisions and commitment to differentiation

Epidermal development and differentiation are similar processes and therefore the study of one is likely to provide insight into the other. The signaling cascades required for epidermal differentiation are largely unknown. Recent evidence, however, has implicated two proteins, p63 and c-Myc, in different stages of epidermal development and differentiation. p63 was shown to be required for embryonic epidermal development. Mice lacking p63 do not develop stratified epithelia and appendages suggesting a role for p63 in the commitment to squamous epithelial lineages. Subsequent stem cell fate decisions are required to form the different structures of stratified epithelia including hair follicles, sebaceous glands, and epidermis. Several genes of the Wnt signaling pathway have been implicated in this process, including c-Myc, a downstream target of the Wnt pathway. Interestingly, targeted overexpression of c-Myc in the basal layer of the epidermis results in an increase in sebaceous gland size and number at the expense of hair follicles. This suggests that c-Myc promotes differentiation of epidermal stem cells into sebaceous glands. In this review, we discuss transgenic/knockout mouse models that have provided evidence linking c-Myc and p63 to different stages of epidermal development and differentiation.     

Setting up regional audit in genitourinary medicine and HIV: the south east Thames experience.

Audit at regional level is a useful complement to local audit, especially in small specialties. Regional audit can reduce professional isolation and lead to the development of uniformly high standards in the care given by a variety of providers. The development of regional audit in genitourinary medicine in South East Thames (UK), and of HIV medicine in South Thames, is described. Meetings are held quarterly, and concentrate on standard setting and development of guidelines. Information about the practice of individual units is collected by questionnaire, the results presented, and guidelines developed. Participation in completing questionnaires and attending the meetings is good. Regional guidelines in eleven topics have been produced, and methods of auditing changes in practice are now being assessed. A regional common data-set is being developed to assist in the audit process.     

Prophylactic and therapeutic vaccines for genital papillomavirus infection

The development of potential therapeutic and prophylactic vaccines for human papillomavirus (HPV) infection is a very exciting area of HPV research. There are a number of features of HPV biology that makes the development of a vaccine particularly difficult, although there are several examples of vaccines that have had spectacular success in the prevention of other viral diseases. Our poor understanding of the immune response to HPV infection is the first problem. We do not understand the mechanism by which spontaneous clearing of warts is generated and therefore cannot particularly target this pathway in the development of a vaccine. Furthermore, there is no in vitro culture system nor an animal model for HPV. Another problem is that there is no ready source of live virus that might be exploited for a live attenuated viral vaccine, such as was used with poliovirus. Although most other viruses spend a portion of their life cycle in the systemic circulation where they are vulnerable to neutralizing antibodies, HPV remain exclusively in the epithelium and thus antibodies must transverse the basement membrane and reach the other layers of the skin or mucosa to be effective in preventing infection. Significant progress is being made in the development of potential vaccine candidates despite these and other confounding factors.