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  • 11
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 13 (2004), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Little is known about how eosinophils accumulate in bullous pemphigoid (BP) and why these cells rapidly disappear during immunosuppressive therapy. Eosinophils can produce cytokines such as IL-4, IL-5, IL-6, IL-10 and IL13, which can induce endothelial cells to express cellular adhesion molecules (CAMs) such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) necessary for the recruitment of eosinophils from the bloodstream to the skin. The present aim was to investigate the cellular expression of these three CAMs in serial biopsies before and during oral low-dose methotrexate therapy. Seventy-four biopsy specimens, 37 from active lesions and 37 from normal skin, were taken at different intervals from eight patients with bullous pemphigoid and stained immunohistochemically with specific monoclonal antibodies for these three CAMs. The expression and distribution of CAMs in the biopsies was evaluated and scored with light-microscopic examination. The basal keratinocytes in active lesions expressed ICAM-1. A strong VCAM-1 expression of endothelial cells and pericytes was correlated to a perivascular inflammatory cell infiltrate that also showed intense immunoreactivity to ICAM-1. Endothelial cell/pericytes also expressed E-selectin strongly in the BP patients before therapy. The expression of CAMs faded during therapy and, to the best of our knowledge, this has not been previously reported. Thus we suggest that the rapid reduction of tissue eosinophils may reflect the altered pattern of cell adhesion molecules during immunosuppressive therapy, which could explain the prompt clinical improvement seen in BP patients treated with methotrexate.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract Kalinin is an extracellular adhesion molecule specific to epithelial basement membranes (BM) identified as a component of anchoring filaments of hemidesmosomes. This heterotrimeric protein is synthesized by cultured normal human keratinocytes and is involved in cell attachment. In indirect immunoriuorescence studies, the epidermal BM of patients with junctional epidermolysis bullosa (JEB) of Herlitz's type were found not to be reactive with the anti-kalinin monoclonal antibodies ka146 and K140 and displayed a decreased immunoreactivity to two anti-kalinin antibodies cross-reacting with K-laminin, an anchoring filament component recently described. The intrinsic defect of JEB keratinocytes in the synthesis of kalinin was further documented by indirect immunofiuorescence on in vitro cultures of these cells. In non-Herlitz JEB patients, staining of BM was constantly detected. Impairment of expression of kalinin correlated with the lack of reactivity to the monoclonal antibody GB3, which delects the BM component nicein/BM600. These results clearly demonstrate a defect of kalinin expression in epithelial basement membranes of Herlitz JEB patients and suggest that kalinin may play a role in the pathogencsis of the disease. Further studies are in progress to define possible relationships between kalinin and nicein.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  This report investigates the effect of pimecrolimus cream 1% (Elidel®, Novartis pharma AG, Basel, Switzerland), a nonsteroid, cell-selective, cytokine inhibitor on the course of atopic dermatitis (AD), as assessed by changes in body surface involvement and pattern of drug use over time.Methods  Data from 961 patients in two 1-year double-blind, multicenter, pediatric studies of similar design were analyzed: 250 infants (aged 3–23 months) were randomized 4 : 1 and 711 children (aged 2–17 years) were randomized 2 : 1 to receive pimecrolimus cream 1% or vehicle, respectively. Emollients were used by all patients to alleviate dry skin and, at the first signs or symptoms of AD, pimecrolimus or vehicle was applied twice daily to prevent progression to flares. If flares occurred in either group, moderately potent topical corticosteroids were mandated.Results  Pimecrolimus was applied for 68.4% (infants) and 53.8% (children) of study days, and frequency of use of pimecrolimus decreased over time, reflecting improvement in disease control. The mean total body surface area affected decreased continuously over time. Significantly more patients in the pimecrolimus than control groups were maintained without corticosteroid therapy (infants: 63.7% vs. 34.8%, P 〈 0.001; children: 57.4% vs. 31.6%, P 〈 0.001, respectively).Conclusion  The need for pimecrolimus therapy decreases over time as the patients’ disease improves. Hence, once long-term management of AD with pimecrolimus is established, the burden of disease for both the patient and the caregiver decreases significantly and disease-free periods become more frequent.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of dermatology 19 (1980), S. 0 
    ISSN: 1365-4632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: : A 28-year-old white man had Cowden's disease and multiple gastrointestinal polyps. Of the 56 cases of Cow-den's disease which have been reported so far, esophageal and gastrointestinal involvement have been observed in only 18 patients. Endoscopic, radiologic, and histopathologic features of these lesions were confirmed in the present patients.
    Type of Medium: Electronic Resource
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  • 15
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    British journal of dermatology 146 (2002), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary Melanins are a ubiquitous class of biological pigments, which play an important role in the photoprotection of skin. Recent advances in the chemistry of melanins have demonstrated their diversity. The various types of melanin show different physico-chemical properties, suggesting that their photobiological properties are not unique. In this review, the implications of melanin diversity for the natural photoprotection of skin are discussed.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    British journal of dermatology 146 (2002), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The current state of knowledge of melanoma genetics is reviewed. Mutations in the tumour suppressor gene CDKN2A and in the oncogenes N-ras and H-ras seem to play the most important roles in the development and progression of malignant melanoma. Experimental studies to determine the role of ultraviolet (UV) light in the induction of melanoma have been hampered by a lack of suitable animal models. The commonly used laboratory animals are not susceptible to the induction of melanoma upon exposure to UV radiation (UVR) alone. Recent observations with four different animals have suggested, however, that UVR may be involved in the induction of melanoma. The most recent model consists of human skin grafted onto immunodeficient mice. To date, using this model, only the combination of UVB (280–320 nm) exposure and topical promoter treatment has led to the development of malignant melanoma. The wavelength dependency of the induction of melanoma has been established in the fish model Xiphophorus. The application of such an action spectrum to humans looks possible.
    Type of Medium: Electronic Resource
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  • 17
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    British journal of dermatology 146 (2002), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary The development of actinic keratosis (AK) and squamous cell carcinoma (SCC) is the result of a complex sequence of events initiated by exposure to ultraviolet (UV) light. The application of sunscreens prior to sun exposure has been reported to reduce the incidence of AK. The initial damage takes place in the DNA and most of the UV-induced lesions in the DNA are repaired. However, mutations may occur as a result of base mispairing of the cell and its DNA replicate before the DNA lesion is repaired. The genes involved in the repair process are also potential UV targets. Mutations in the tumour suppressor gene p53 are a common feature of AK and SCC. The hairless mouse is the best available animal model, in which lesions resembling human AK (papillomas), keratoacanthomas and SCCs may be induced. This model of multistage carcinogenesis offers an excellent tool for mechanistic studies. The relative efficacy of UV wavelengths (action spectrum) that induce SCC has been determined using the hairless mouse as a model. The action spectrum has been extrapolated to humans skin and is recognised worldwide.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  SDZ ASM 981 is a selective inhibitor of inflammatory cytokines released from T lymphocytes and mast cells, which has been developed for the treatment of inflammatory skin diseases. Objectives  In the present study, the atrophogenic potential of SDZ ASM 981 1% cream in humans was compared with that of medium and highly potent topical steroids, and vehicle. Methods  Four different preparations, SDZ ASM 981 1% cream, the corresponding vehicle of SDZ ASM 981 1% cream, betamethasone-17-valerate 0·1% cream and triamcinolone acetonide 0·1% cream, were applied to the volar aspect of the forearms of 16 healthy volunteers, twice daily, 6 days a week, for 4 weeks. Skin thickness was evaluated by ultrasound examination, clinical signs of atrophy by stereomicroscopy, and epidermal thickness was assessed by histology. Results  Both topical corticosteroids induced a significant reduction in skin thickness, as compared with SDZ ASM 981 1% cream and vehicle, which were shown to be equivalent. The difference in skin thickness (measured by ultrasound examination) between patients treated with SDZ ASM 981 1% cream and those receiving either of the two topical steroids was significant from day 8 onwards. Histological analysis performed at day 29 showed significant epidermal thinning with topical steroids compared with SDZ ASM 981 1% cream or the vehicle. Conclusion  The lack of atrophogenic properties of SDZ ASM 981 1% cream in this short-term study demonstrates its potential as long-term treatment for inflammatory skin diseases, thus overcoming a major drawback of topical steroids. This may also be important for the treatment of children, and sensitive areas of skin, such as the face and skin-folds.
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Basal cell carcinoma (BCC) is a frequent skin cancer with low metastalic potential. Expression of the anchoring filament proteins, native laminin-5 and its individual α3, β3 and γ2 chains, uncein, and linear IgA antigen was examined by immunostaining in 17 BCC with different histological subtypes. Immunoreactivity of the hemidesmosomal proteins, integrin α6β4. 230-kDa bullous pemphigoid antigen (BP-230 Ag) and plectin/HD-1, and that of dermal-epidermal junction (DEJ) components, integrin α2β1, laminin-1, collagen IV, and collagen VII was also analysed. Around tumour nests, the labelling of laminin-5 was absent or markedly reduced in 12 BCC (comprising eight solid BCC, three adenoid BCC and one keratotic BCC) and strong in five BCC (comprising three adenoid BCC, one keratotic BCC and one adenoid and keratotic BCC). Intriguingly, in tumour cells of 12 BCC including laminin-5 negative tumours, a cytoplasmic reactivity of the laminin 72 chain was detected, but not that of the α3 and β3 chains. In the basement membrane of the epidermis overlying tumour nests, the labelling of laminin-5 was always strong. Uncein, linear IgA disease antigen, and integrin α6β4 were absent in solid BCC and weakly expressed in adenoid or keratotic BCC. For plectin/HD-1 and BP-230 Ag, a cytoplasmic reactivity was detected in the majority of the tumour cells. The labelling of integrin α2β1, laminin-1, collagen IV and collagen VII indicated no alteration in the synthesis of these proteins. In peritumoral lacunae, immunoreactivity of hemidesmosome and anchoring filament proteins was absent, except for plectin/HD-1 on the tumour side and sometimes for laminin-5 on the stromal side, while laminin-1, collagen IV and collagen VII were detected on the stromal side. These findings suggest that the components of the hemidesmosome-anchoring filament complex are not synthetized or assembled properly in BCC, and that the alteration of these adhesion structures may be the cause of peritumoral lacunae.
    Type of Medium: Electronic Resource
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  • 20
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 129 (1993), S. 0 
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A fully differentiated epithelium displaying features of human epidermis was obtained in vitro by culturing second-passage normal human keratinocytes for 14 days in defined medium and on an inert polycarbonate filter substratum at the air-liquid interface.Vertical sections stained for histology and indirect immunofluorescene studies showed that the‘basal’cells synthesize and secrete all major markers of hemidesmosomes and the lamina lucida. Components of the lamina densa are also expressed. Collagen VII is synthesized, but not secreted. Ultrastructural studies showed the presence of hemidesmosomes with major dense plaques and anchoring filaments, and a basement membrane-like structure was clearly identified.These results show that epidermal cells are able to produce hemidesmosomes and to secrete the major components of the dermo-epidermal junction in the absence of serum and dermal factors, suggesting that basement membrane synthesis and hemidesmosome assembly are not dependent on the presence of dermis.
    Type of Medium: Electronic Resource
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