Studies on fibronectin in the skin. III. Indirect immunofluorescence studies in lichen planus.

Fibronectin is a glycoprotein which is responsible for a varity of functions in the human organism, such as mediation of contact between cells and between cells and fibres, opsonic qualities, interaction in the stabilization of fibrin, etc. Fibronectin is an important constituent of the ground substance having a special affinity to collagen. In indirect immunofluorescence studies its presence has been abundantly demonstrated in normal human skin, in collagen-rich structures such as the basement membranes, the papillary and reticular dermis, and in the vascular and neural structures, demonstrable by its characteristic staining patterns. Fibronectin is not found in the epidermis. In lichen planus, the distribution in unaffected skin is identical with that in normal skin, whereas in affected skin, changes in the pattern of fibronectin are found. The basement membrane zone becomes broader and hazy, later undergoing disintegration and destruction, concomitant with swelling and homogenization of the reticular distribution of fibronectin in the papillary dermis. Globular structures containing fibronectin are found in the basement membrane area, together with an intensified immunofluorescence in the vascular system. Fibronectin has certain adhesional properties and changes in the distribution of this glycoprotein may result in loss of tissue stability. The pathophysiological significance of the changes of fibronectin in lichen planus is, however, difficult to evaluate at present.     

The incidence of gonorrhoea and the antibiotic sensitivity of gonococci in Australia, 1981-1991. The Australian Gonococcal Surveillance Programme.

OBJECTIVE--To review and analyse the changing incidence of gonorrhoea and the increasing antibiotic resistance in gonococci in Australia from 1981 to 1991. DESIGN--Use of data from the sample of gonorrhoea in Australia examined by the Australian Gonococcal Surveillance Programme (AGSP), a continuing long-term multi-centric study of gonococcal disease and gonococcal susceptibility to antibiotics, over the period 1 July, 1981 to 30 June, 1991. RESULTS--Over 32,000 cases and strains from defined sources were examined in the 10 year study period. The number of cases of gonorrhoea in the sample decline from a peak of 6599 in 1982-1983 to 1121 in the final year under review, a reduction of 83%. Periods when greater than average reductions in incidence occurred in different groups were noted. Ano-rectal gonorrhoea in men decreased sharply in 1985 during an overall decline of 92.5% recorded between 1 July, 1981 to 30 June, 1987. However, the incidence of ano-rectal cases in males rose in subsequent years while gonorrhoea, overall, continued to decrease and at a greater rate after 1985. Antibiotic resistance in gonococci in Australia was manifested both as a progressive increase in the levels of intrinsic resistance to the penicillins and through the appearance and spread of penicillinase-producing N gonorrhoeae (PPNG). At the end of the review period in June, 1991, 8.8% of gonococcal isolates in Australia showed high levels of intrinsic resistance to the penicillins and 13% of strains were PPNG. These separate mechanisms of resistance appeared at different times in different parts of Australia, and their importance also varied throughout the country. Most infections with PPNG were acquired by men overseas whereas most women with PPNG were infected locally. Endemic spread of PPNG was a significant problem in Sydney and Melbourne, but decreased in importance in the later years of the study. CONCLUSIONS--In the past decade a large reduction in the incidence of gonorrhoea and, by implication, other STDs has occurred in the past decade in Australia. In some groups of patients the decline in incidence is continuing while in others a slight increase has been noted. Resistance to antibiotics of gonococci in Australia was mainly restricted to the penicillins, but through both chromosomal and plasmid-mediated mechanisms. This resistance was seen particularly in Sydney and Melbourne where endemic cycles of transmission of PPNG were established, and in infected travellers from S-E Asia in other centres. Valid and comparable, and regionally relevant data are a continuing requirement for assessing and modifying antibiotic treatment regimens for gonococcal disease.     

An educational approach to leprosy control: an evaluation of knowledge, attitudes and practice in two poor localities in Bombay, India.

Based on the hypothesis that a systematic, carefully planned educational approach to leprosy would yield results in terms of knowledge, attitudes and case presentation superior to those of the established and traditional mass survey method, ALERT-India launched a programme in S ward of Bombay in February 1985, to compare the two. An intensive programme of health education, using trained teams, was carried out in one zone of this ward over a period of 12 months. Eight months later, mass survey work (as used routinely in previous years and on a country-wide basis) was carried out in an adjacent zone. In 1987, the Centre for Social and Technological Change in Bombay, in association with the School of Oriental and African Studies, University of London, was requested to evaluate the effect of the above educational approach in terms of knowledge, attitudes and practice in both the trial and control zones. Other aspects of this experimental approach, including its cost and effectiveness in identifying cases of leprosy, will be published separately. The design of the 'KAP' evaluation and the social and environmental controls introduced in the statistical analysis are described. The results pointed to a considerable degree of ignorance about leprosy as a disease (and its treatment) in both the study and the control zones. Knowledge about early symptoms was particularly weak and on all aspects scores for women were invariably lower than men. General education enhanced the absorption of specific knowledge, and the education of children compensated adequately for lack of parental education in this respect. Overall the evaluation indicated that the intensive educational approach was superior to the survey approach in terms of improving knowledge, attitudes and practice.     

Element concentrations in serum, erythrocytes, hair and urine of alopecia patients

The trace element concentrations of Se, Rb, Zn, Fe, Co, Cs, Mg, Ca, F, Cu, Cr and Ag in serum and of Se, Rb, Zn, Fe, Co and Cs in red cells of Finnish alopecia patients were determined. In addition the Cu and Zn content in 24 h urine and Cu, Zn, Cd, Cr and Se concentrations in the hair of these patients were studied. No differences in element concentrations of the samples mentioned above as compared to those of the normal population could be found. In addition, there was no tendency of excesses or deficiences of elements analysed in the samples. Statistically significant difference was found between the copper content of serum in alopecia areata and alopecia universalis patients and also between the copper content of serum in alopecia areata plus alopecia totalis and alopecia universalis patients. The selenium concentration in serum samples of a few patients was low, but this is in agreement with the fact that the selenium content in the Finnish population is low due to the scanty content of selenium in food.     

Pace of leprosy elimination and support teams in Bihar state, India

Despite the extensive implementation of multiple drug therapy (MDT) in most leprosy-endemic countries world-wide since 1982, bringing about a remarkable reduction in prevalence, there are still regions at the sub-national level where the implementation of MDT remains difficult. The state of Bihar (population 86.3 million) in India is a good example of such a region. Previously rated as one of the most highly endemic states, it still contributes about 21% of the total caseload in India and about 12% of the global caseload. For various reasons, case-finding and drug treatment have lagged behind the progress made in most other states in the country and in 1996, the Damien Foundation India Trust (DFIT) volunteered technical support to increase the pace of elimination. Sixteen out of the 39 districts in the state were allocated, with a population of 41.8 million. Support teams, including a Medical Advisor and a Non-Medical Supervisor, both with over 10 years experience of leprosy work and control programmes, were provided to assist and work alongside government staff in case detection, treatment delivery, case-holding and discharge in their respective areas of operation. New case detection by intensive survey increased by 394% and total new case detection by 226% during the year 1996-1997, with similar trends in the following year. Striking improvements were also observed in MDT coverage, treatment regularity, monitoring and discharge of patients and in the training of local staff. This collaboration between a non-government agency (DFIT) and the staff of the National Leprosy Eradication Programme in 16 out of 39 districts in the State of Bihar has clearly been extremely successful. Similar approaches in the remaining districts of Bihar, and in other parts of India, where the infrastructure is available but inadequate, may contribute significantly to achieving the elimination goal at national and sub-national levels.     

Biologic Response Modifiers and Pediatric Psoriasis

The efficacy and safety of biologic response modifiers such as etanercept, adalimumab, infliximab, and ustekinumab have been demonstrated in the treatment of psoriasis in adults, but none are currently approved for the treatment of psoriasis in children in the United States, and only etanercept is approved for the treatment of psoriasis in children in the European Union. Through case reports, case series, and a large clinical trial of the use of etanercept, the literature supports the use of these agents to treat psoriasis in children. Data on the use of the tumor necrosis factor‐α antagonists etanercept, adalimumab, and infliximab in the treatment of other inflammatory diseases in children—namely Crohn's disease, juvenile arthritis, and uveitis—support their safety profile in children.     

PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma

BACKGROUND: Although various studies have shown mutations of the tumor suppressor gene, PTEN/MMAC1, in primary, metastatic, and cultured cutaneous melanoma specimens, little is known about the pattern of PTEN protein expression in early melanocytic tumor progression. OBJECTIVE: To further investigate the role of PTEN in melanocytic tumor development. METHODS: We assessed the level and distribution of PTEN in normal skin, 39 acquired melanocytic nevi, and 30 primary cutaneous melanomas, including lentigo malignas, by immunostaining. RESULTS: We found high levels of PTEN expression in cutaneous muscles, nerves, and muscular arteries, and moderate-to-high amounts of PTEN in the epidermis, follicular epithelium, and sebaceous and eccrine glands. PTEN staining in cutaneous lymphatics, dermal and periadnexal adventitial fibroblasts, and chondrocytes were variably absent. Junctional melanocytes and chondrocytes frequently exhibited preferential nuclear staining. We found uniformly strong PTEN expression in the cytoplasm of almost all benign and dysplastic nevi. However, there was some evidence of nuclear PTEN loss even in the benign melanocytic proliferations. In addition, out of 30 primary cutaneous melanomas and lentigo malignas, we detected diffuse expression of PTEN in 11 (37%) tumors, widespread loss of PTEN in 11 (37%) tumors and mixed PTEN expression in 8 (27%) lesions. In the primary cutaneous melanomas, PTEN was largely localized to the cytoplasm. CONCLUSIONS: The presence of PTEN in benign melanocytic tumors and the absence of PTEN in a significant proportion of primary cutaneous melanomas support a role for PTEN loss in the pathogenesis of melanoma.     

Cytochrome p450: a target for drug development for skin diseases

Enzymes of the cytochrome P450 (P450 or CYP) super family are the most versatile and important class of drug-metabolizing enzymes that are induced in mammalian skin in response to xenobiotic exposure. At the same time, CYP have numerous important roles in endogenous and exogenous substrate metabolism in the skin. For example, they participate in the metabolism of therapeutic drugs, fatty acids, eicosonoids, sterols, steroids, vitamin A, and vitamin D, to name a few. In addition, in some skin diseases, for example in psoriasis, many CYP are elevated. CYP are the target of special interest in the development of drugs for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologists are either substrate, inducer, or inhibitor of this enzyme family. The functional significance of drug metabolism in skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYP, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review discusses some of these perspectives and suggests additional work in this research area with regard to the expression and modulation of CYP in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.     

Epidemiology and Clinical Pattern of Atopic Dermatitis in a North Indian Pediatric Population

Abstract: Various epidemiologic factors and clinical patterns of atopic dermatitis (AD) were evaluated in 672 children. Of these, 210 were infants (up to 1 year) and 462 were children. Mean age at onset and mean duration of the disease were 4.2 months and 3.3 months, respectively, in the “infantile AD” group. In the “childhood AD” group the corresponding figures were 4.1 years and 1.9 years. In both groups, patients from urban areas significantly outnumbered those from rural backgrounds. In the infantile AD group, the disease was aggravated in winter in 67.14%, in summer in 23.36% and in spring in 9.51% of patients. The corresponding figures in the childhood AD group were 58% in winter, 32.92% in summer, 7.43% in spring, and 1.74% in the rainy season. In the infantile AD group, personal and family history of atopy were seen in 0.91% and 36.19% of patients, respectively. No patient had a history of drug allergy. In the childhood AD group, 15.35% had a personal history of atopy, 36.44% had a family history of atopy, and 7.36% had both a personal and family history of atopy. A history of drug allergy was reported in 3.16% of children. In the infantile AD group, 79% had facial involvement, 42% had flexors affected, and 5.70% had both flexors and extensors affected. The types of eczema seen were acute in 52.72%, subacute in 23.35%, chronic in 23.35%, and follicular in 0.46%. In the childhood AD group, 74.50% had facial involvement, 35.53% had flexural involvement, 56.32% had extensor involvement, and 8.24% had both flexors and extensors involved. Acute eczema was seen in 28.79%, subacute in 23.38%, chronic in 47.40%, and follicular in 0.43% of the children.     

Expression of cyclooxygenase isozymes during morphogenesis and cycling of pelage hair follicles in mouse skin: precocious onset of the first catagen phase and alopecia upon cyclooxygenase-2 overexpression

Cyclooxygenase (COX)-1 and -2 catalyze the key reaction in prostaglandin biosynthesis. Whereas COX-1 is found in most tissues, COX-2, with a few exceptions, is not expressed in normal tissues but becomes transiently induced in the course of inflammatory reactions. In many neoplastic epithelia, COX-2 is constitutively overexpressed. Here we show that COX isozymes are spatiotemporally expressed during morphogenesis of dorsal skin epithelium of NMRI mice. COX-1 and COX-2 mRNA and protein were detected in embryonic and postnatal epidermal tissue by RT-PCR, northern blot, and immunoblot analysis indicating that both isoforms may contribute to prostaglandin production. Being barely detectable in interfollicular epidermis and resting hair follicles of adult mice, COX-2 protein appeared in embryonic skin first in epidermal precursor cells and later on in the basal cells and the peridermal layer of the stratified epidermis. In the course of pelage hair follicle morphogenesis, COX-2 remained expressed in the basal interfollicular compartment and, in addition, became apparent in elongated hair germs and hair pegs and later on in the outer root sheath cells of the distal and proximal hair follicles as well as in basal sebaceous gland cells. During the subsequent synchronous phases of hair cycling, COX-2 expression declined in catagen, was barely detectable in telogen, and was reinduced in the basal outer root sheath and basal sebaceous gland cells of anagen hair follicles. COX-1 immunosignals were detected predominantly in the interfollicular spinous and granular layers of the developing, neonatal, and adult epidermis but not in follicular epithelial cells of developing or cycling hair follicles. Dendritic cells in the interfollicular epidermis and distal hair follicles were also COX-1-positive. Transgenic overexpression of COX-2 under the control of a keratin 5 promoter in basal cells of the interfollicular and follicular epidermis induced a precocious entry into the first catagen stage of postnatal hair follicle cycling and a subsequent disturbance of hair follicle phasing. Furthermore, transgenic mice developed an alopecia. Inhibition of transgenic COX-2 activity by feeding the specific COX-2 inhibitor valdecoxib suppressed the development of alopecia, indicating that COX-2-mediated prostaglandin synthesis is involved in hair follicle biology.     

246名女性皮肤老化特征及相关因素的调查分析

目的 探讨女性面部皱纹的发生情况及相关影响因素.方法 采用问卷表调查的方法,将研究对象根据工种及日均日晒时间分为室内组和室外组,使用图像分析仪SIA0612标准化拍照,结合Visioscan VC98定量测量皱纹的结果,将研究对象面部皱纹分0～9级分析.利用SPSS 17.0分析防晒情况、护肤美容、皱纹发生时间、发生部位等并对皱纹产生可能相关因素进行室内外组对比分析.结果 246名19～71岁女性,回顾各不同年龄阶段使用防晒措施的比例是:6～11岁年龄段为11%;12～18岁为13.5%;19～29岁为38.5%;30～39岁为39.2%;40～59岁为44%;60～75岁为0.在近5年阶段的为最多达44.1%.出现皱纹与色素斑时间及情况比较:目前无皱纹的占5.7%,目前无色素斑的占21.7%.发现皱纹时间以30～35岁为最多,发现色素斑时间以25～30岁为最多.室内组人群面部皱纹发生的顺序由多到少依次是眶下、外眦、鼻唇沟区域、眉间;室外组皱纹最多出现的依次顺序依次是:外眦、眶下、眉间、鼻唇沟.室内人群皱纹最常发生于鱼尾纹,至少在45岁达100%.而室外人群的皱纹发生普遍早,鱼尾纹至少在30岁就达100%.结论 皱纹和色素斑均为中国女性皮肤老化的主要表现.色素斑出现时间略早于皱纹.女性皮肤光老化的主要表现依次为肤色灰黄、皮肤干燥、粗糙、皮革样外观、显著的红血丝和(或)严重的色素斑、脆性增加等.室内组女性皱纹出现次序和时间都有别于室外组.

Abstract：

Objective To estimate the prevalence and associated factors of facial wrinkling in females.Methods Questionnaires were designed and delivered to collect related data on volunteers. The subjects were divided into outdoor and indoor groups. Wrinkles were classified into 9 grades based on photos taken by SIA0612 image analyzer and quantification analysis via Visioscan VC 98. SPSS 17.0 software was used to assess the associated factors of wrinkling, including sun-protective measures, skin care and cosmetology, onset age and location of wrinkles in these subjects. Results A total of 246 patients aged 19 - 71 years were recruited in this study. Sun-protective measures were applied in 13.5% of the subjects between 12 and 18 years of age,38.5% of those between 19 and 29 years of age, 39.2% of those between 30 and 39 years of age, 44% of those between 40 and 59 years of age, and in none of those between 60 and 75 years of age, 44.1% of all the subjects in the latest 5 years. Wrinkles were absent in 5.7% of the subjects, and pigmentation macules absent in 21.7%. The first development of wrinkles was mainly observed in subjects aged 30 to 35 years, and that of pigmentation macules in those aged 25 to 30 years. The most common locations of facial wrinkles, in order of decreasing frequency, were infraorbital area, lateral angle of eye, nasolabial fold, glabella in the indoor group,lateral angle of eye, infraorbital area, glabella and nasolabial fold in the outdoor group. Fishtail lines seemed to be the commonest wrinkles with an earliest onset among these wrinkles, and showed a prevalence of 100% in subjects aged 45 years or older in the indoor group, and in those aged 30 years or older in the outdoor group.Conclusions Wrinkles and pigmentation macules are dominate manifestations of skin aging in Chinese females. The onset of pigmentation macules is earlier than that of wrinkles. The main manifestations of skin aging in Chinese females, in order of decreasing frequency, are yellow-grey skin, skin dryness, roughness,leather-like appearance, teleangiectasia, and (or) severe pigmentation macules, increase in skin fragility, etc.The order and age of wrinkle appearance are different between indoor and outdoor females.     

Lamin expression in normal human skin,actinic keratosis,squamous cell carcinoma and basal cell carcinoma

BACKGROUND: Aberrant expression patterns of nuclear lamins have been described in various types of cancer depending on the subtype of cancer, its aggressiveness, proliferative capacity and degree of differentiation. In general, the expression of A-type lamins (lamins A and C) has been correlated with a non-proliferating, differentiated state of cells and tissues. OBJECTIVES: To establish and compare the expression patterns of lamins in normal human skin, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). METHODS: Expression patterns of the individual lamin subtypes were studied immunohistochemically. The proliferation capacity of the tumour cells was detected using a specific antibody to Ki-67, and was related to the A-type lamin expression patterns. RESULTS: In normal skin, lamin A was expressed in the suprabasal cell compartment of the epidermis, whereas the basal cells were mostly unstained. BCCs and SCCs stained positive in most cells, while the epidermis overlying BCC and SCC and the epidermis in AK stained homogeneously and strongly in the basal cells in addition to the suprabasal cells. Lamin C was expressed in some basal cells of normal epidermis while the suprabasal cells stained strongly positive. Both BCCs and SCCs stained strongly positive for lamin C, with the difference that in BCC the staining was predominantly present in nucleolar structures with occasional staining of the nuclear envelope. The epidermis overlying SCC showed strong positivity in the lamina of virtually all cells. The expression of lamin C in the basal cells of AK resembled the expression pattern seen in the epidermis overlying BCC, i.e. a nucleolar staining next to nuclear envelope staining. Lamin B1 and B2 were found in virtually all cells in normal epidermis, AK, BCC, SCC and the epidermis overlying cancer. The percentage of Ki-67-expressing cells was highest in BCC (45%), and gradually decreased via epidermis overlying BCC, AK, SCC, and epidermis overlying SCC, to normal skin (11%). Simultaneous expression of A-type lamins and Ki-67 occurred in approximately 50% of the proliferating (Ki-67 positive) cells in BCC and SCC. CONCLUSIONS: Significant changes occur in the expression patterns of A-type lamins in both premalignant and malignant lesions of the skin. The profound overlap of lamin A and Ki-67 staining patterns indicates that the proliferating tumour cells may obtain a certain degree of differentiation. Finally, lamin A expression in the basal cell layer of the apparently normal epidermis overlying BCC may suggest its involvement in the primary process.     

Hexose sugars differentially alter collagen gene expression and synthesis in fibroblasts derived from granulation tissue,hypertrophic scar and keloid

Clinical observations have suggested that sugar and honey enhance granulation tissue formation and in vitro studies have shown that monosaccharide sugars stimulate mesenchymal and endothelial cells. In this study, the effects of glucose, fructose, galactose and mannose on type I and type III collagen gene expression and synthesis were studied in granulation tissue, hypertrophic scar and keloid fibroblast cultures. Glucose elevated both type I and type III collagen mRNAs in hypertrophic scar fibroblasts. Fructose increased type III collagen mRNA almost sevenfold in granulation tissue fibroblasts. Galactose caused an increase in type I and type III collagen mRNAs in granulation tissue fibroblasts and hypertrophic scar fibroblasts but, in contrast, mannose decreased type I and type III collagen levels in hypertrophic scar and keloid fibroblasts. Analysis of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) revealed that glucose decreased the amount of PINP in granulation tissue and keloid fibroblasts, whilst fructose decreased the amount in all the fibroblast cell lines studied. Galactose caused a decrease in the synthesis of type I collagen in all cell lines but a decrease was seen in type III collagen only in hypertrophic scar fibroblasts. Mannose decreased the amount of PINP in all cell lines but a decrease in the amount of PIIINP was seen only in granulation tissue fibroblasts. The effect of sugars on the ratio type I/type III collagen was negligible or decreasing with the exception of galactose, which increased the ratio in hypertrophic scar fibroblasts. The results suggest that glucose, fructose and galactose have no significant value in the stimulation of collagen synthesis in vitro. Mannose may have value in the prevention or treatment of abnormal scars.     

Keratinocytes in the depigmented epidermis of vitiligo are more vulnerable to trauma (suction) than keratinocytes in the normally pigmented epidermis, resulting in their apoptosis

BACKGROUND: Vitiligo may develop following minor physical trauma. However, in autologous epidermal grafting, depigmentation of the donor (normally pigmented) site from a suction blister is rare, even in cases displaying failure of repigmentation at the recipient (depigmented) site. OBJECTIVES: To examine whether the suction procedure is more likely to damage keratinocytes in the depigmented than in the normally pigmented epidermis of vitiligo, and to determine what kind of damage occurs to the keratinocytes. METHODS: Paired roofs of suction blisters from five patients with generalized vitiligo, five with localized and seven with segmental type, were used for the study. Multiple new lesions developed in two of the five patients with the generalized type. Apoptosis of keratinocytes in the epidermis was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labelling (TUNEL) staining, with immunohistochemistry for Bax and active caspase 3. Expression of Bcl-2, Bax, FLIP and p53, activation of caspases 3, 8 and 9, and cleavage of poly(adenosine diphosphate ribose) polymerase (PARP) in the epidermis were analysed by Western blotting in four patients with each type. RESULTS: Apoptotic keratinocytes, which stained with TUNEL and anti-Bax and antiactive caspase 3 antibodies, were scattered in the blistered epidermis, mainly in the lower portions. The depigmented epidermis displayed significantly more apoptotic keratinocytes than the normally pigmented epidermis. The numerical difference between the paired epidermides was related to the disease activity and not to the type of lesions. The number of apoptotic keratinocytes in the normally pigmented epidermis was as high as that in the depigmented epidermis in the two patients with active generalized type vitiligo. Expression of Bax and p53 in the depigmented epidermis was higher than in the normally pigmented epidermis, whereas expression of FLIP was lower. In addition, the activation of caspases 3, 8 and 9, and cleavage of PARP, were increased in the depigmented compared with the normally pigmented epidermis. The degree of difference in expression and activation was parallel to the results of the TUNEL assay. CONCLUSIONS: The keratinocytes in the depigmented compared with the normally pigmented epidermis of vitiligo may become apoptotic more easily after suction.     

Studies on fibronectin in the skin

Summary Affected and unaffected skin from patients with vulgar psoriasis and normal skin from a control group were investigated for the presence of fibronectin with an indirect immunofluorescence technique. In the control group, fibronectin is missing in the epidermis, but is found in the basement membrane zone of the dermo-epidermal junction area, in the papillary and the reticular dermis, and in the vascular and neural systems of the skin. The same distribution is also found in unaffected psoriatic skin, whereas in affected skin a change in the distribution of fibronectin is found in the dermis and in the basement membranes, together with the presence of fibronectin in the epidermis, mainly in the cornified layers.     

Oestrogen receptor beta is the predominant oestrogen receptor in human scalp skin

Oestrogens play a major role in non-classic target tissues in both sexes, yet there have been few studies on estrogens and skin. Recently a second oestrogen receptor (ERbeta) has been discovered. Therefore, we have compared the expression of oestrogen receptor alpha (ERalpha), beta (ERbeta), the androgen receptor (AR) and a cell proliferation marker in male and female non-balding scalp skin. ERbeta was the major steroid receptor expressed in human skin. It was highly expressed in epidermis, blood vessels and dermal fibroblasts, in contrast to ERalpha and AR. In the hair follicle, ERbeta expression was localized to nuclei of outer root sheath, epithelial matrix and dermal papilla cells, in contrast to ERalpha, and the AR, which was only expressed in dermal papilla cells. Serial sections also showed strong nuclear expression of ERbeta in the cells of the bulge, while neither ERalpha nor AR was expressed. In the sebaceous gland, ERbeta was expressed in both basal and partially differentiated sebocytes. ERalpha exhibited a similar pattern of expression, while the AR was expressed in the basal and very early differentiated sebocytes. There was no obvious difference in the expression of either oestrogen receptor in male or female skin. The wide distribution of ERbeta in human skin suggests that oestrogens may play an important role in the maintenance of skin and in the regulation of the pilosebaceous unit, and provides further evidence for oestrogen action in non-classic target tissues. The differential expression of ERalpha, ERbeta and AR in human skin suggests that the mechanisms by which steroid hormones mediate their effects may be more complex than previously thought.     

Mycetomas in central Tunisia

INTRODUCTION: Mycetomas are inflammatory pseudo-tumors containing fungal or actinomycosic-type grains. They are frequent in tropical and subtropical countries and unknown in Tunisia. PATIENTS AND METHODS: We conducted a retrospective study of 12 cases of mycetoma registered in the Dermatological department of the university hospital in Sousse (central Tunisia) over a period of 27 years, from 1974 to 2001. The diagnosis was confirmed by anatomopathological and/or mycological examination. RESULTS: The mean age at the onset was of 49 years and the sex ratio of 1. A notion of a traumatism was reported in two cases and eight patients had various agricultural activities. The mean duration of progression was of eight years. The localization was the foot in 10 cases. The mycetoma was of actinomycosic origin in 10 cases, due to Actinomadura madurae in nine cases, to Nocardia spp in one case and of fungal origin in 2 cases:Pseudoallescheria boydii in one case and Madurella mycetomi in the other. Antibiotic therapy was associated with surgical exeresis in nine cases and amputation in the other two cases. COMMENTS: Confrontation of our results with those of Tunisian series and a review of the literature, helped to specify the clinico-epidemiological characteristics and progression of mycetoma in Tunisia. These characteristics are: the rareness of the infection, the relative frequency of affection in women, the proximal involvement of the foot, the frequency of agricultural activity and the rareness of traumatic past history, the predominance of the actinomycosic origin due to Actinomadura madurae, and the need to associate surgical exeresis with the medical treatment or amputation in order to stop the progress of the disease.     

Regulated proenkephalin expression in human skin and cultured skin cells

Skin responds to environmental stressors via coordinated actions of the local neuroimmunoendocrine system. Although some of these responses involve opioid receptors, little is known about cutaneous proenkephalin expression, its environmental regulation, and alterations in pathology. The objective of this study was to assess regulated expression of proenkephalin in normal and pathological skin and in isolated melanocytes, keratinocytes, fibroblasts, and melanoma cells. The proenkephalin gene and protein were expressed in skin and cultured cells, with significant expression in fibroblasts and keratinocytes. Mass spectroscopy confirmed Leu- and Met-enkephalin in skin. UVR, Toll-like receptor (TLR)4, and TLR2 agonists stimulated proenkephalin gene expression in melanocytes and keratinocytes in a time- and dose-dependent manner. In situ Met/Leu-enkephalin peptides were expressed in differentiating keratinocytes of the epidermis in the outer root sheath of the hair follicle, in myoepithelial cells of the eccrine gland, and in the basement membrane/basal lamina separating epithelial and mesenchymal components. Met/Leu-enkephalin expression was altered in pathological skin, increasing in psoriasis and decreasing in melanocytic tumors. Not only does human skin express proenkephalin, but this expression is upregulated by stressful stimuli and can be altered by pathological conditions.     

A biochemical study of experimental porphyria. I. The influence of griseofulvin at various concentrations on porphyrin metabolism

In order to determine the lowest concentration of griseofulvin (GF) needed to induce abnormal porphyrin metabolism, D-D strain mice were fed with a feed containing GF in concentrations of 0.1%, 0.5%, and 1.0%. The liver and blood porphyrin levels were analyzed, and the red fluorescence of the liver and blood observed with a fluorescent microscope. In the 0.5% GF and 1.0% GF groups, a swelling of the liver was observed, and coproporphyrin and protoporphyrin levels in the liver and the blood increased markedly. However, the increase in protoporphyrin levels was more prominent than the increase of coproporphyrin levels. The increase in the liver protoporphyrin was more marked than that in the blood porphyrin. Comparisons of the 0.5% GF and 1.0% GF groups revealed that liver swelling was more prominent in the 1.0% GF group. A high degree of metabolic abnormality in blood protoporphyrin was found in 1.0% GF animals whose feeding period was rather short. In the 0.1% GF group, liver swelling was hardly noticeable, and there were no differences between the short feeding and long feeding groups. Although no abnormalities in blood porphyrins were noticed in comparison with the normal group, abnormally high levels of liver porphyrins were found in 3 out of the 34 treated mice. No differences from the normal group were noted in the remaining 31 animals. In the 0.5% GF and 1.0% GF groups, red fluorescence of the liver was seen in all cases, while in the 0.1% GF group, reticular red fluorescence was noted in only one animal. From these findings, it appears that a marked increase in porphyrin occurs at a concentration above 0.5% in D-D strain mice, whereas, at the concentration of 0.1%, the majority of the treated mice remain within normal limits. Only a few showed any abnormality of porphyrin metabolism. We feel that, for this reason, it would be better to use a GF concentration of 0.1% for the lowest concentration experiments involving GF-induced protoporphyria in D-D strain mice and especially for investigations of the interaction of other chemicals with GF, and investigations of initial changes of porphyrin metabolism.