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  • 1
    Digitale Medien
    Digitale Medien
    Preliminary communication: matrix metalloproteinases in Kaposi's sarcoma (2003)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 149 (2003), S. 0 
    Details
    ISSN: 1365-2133
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1046/j.1365-2133.2003.05561.x
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  • 2
    Digitale Medien
    Digitale Medien
    Expression of matrix metalloproteinase (MMP)-7 and MMP-13 and loss of MMP-19 and p16 are associated with malignant progression in chronic wounds (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 152 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Background  The risk of squamous cell carcinoma (SCC) is significantly increased in chronic leg ulcers. Very little is known about the molecular pathogenesis of these tumours, which are often undiagnosed for a long time. As matrix metalloproteinases (MMPs) are implicated at all stages of tumorigenesis, we investigated whether the pattern of epithelial MMP expression can predict development of SCC from pseudoepitheliomatous hyperplasia of chronic wounds.Methods  Samples from nine patients with SCCs that had arisen in chronic wounds and 31 with venous leg ulcers were studied using immunohistochemistry for MMP-7, MMP-8, MMP-9, MMP-13, MMP-19 and the tumour suppressor p16. In situ hybridization was performed for MMP-1, MMP-3, MMP-7, MMP-12 and MMP-13.Results  MMP-7 was expressed by malignantly transformed epithelium, while it was absent from chronic wounds. MMP-9 was detected in the epithelium in both SCCs and chronic wounds. Epithelial MMP-13 expression was strong in SCC, but was absent in chronic wounds. MMP-12 was expressed in the epithelium in two SCCs, while macrophages were positive in chronic wounds. MMP-19 was induced in proliferating epithelium of wounds, but was absent from invasive areas of SCC. p16 was expressed by keratinocytes in half of the chronic wounds and at superficial margins of SCCs, while invasive areas were negative.Conclusions  Our results suggest that epithelial expression of MMP-7, MMP-12 and MMP-13, but not that of MMP-1, MMP-3, MMP-8, MMP-9 and MMP-10, in chronic wounds provides a diagnostic clue for distinguishing SCCs from nonmalignant wounds. The loss of MMP-19 and p16 from the epithelium could aid in making the differential diagnosis between well-differentiated SCCs and nonmalignant chronic wounds.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06447.x
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  • 3
    Digitale Medien
    Digitale Medien
    Epithelial tissue-type plasminogen activator expression, unlike that of urokinase, its receptor, and plasminogen activator inhibitor-1, is increased in chronic venous ulcers (2004)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 151 (2004), S. 0 
    Details
    ISSN: 1365-2133
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Background  The plasminogen activation system represents a potent mechanism of extracellular proteolysis and is an essential component of normal wound healing. It has also been implicated in the pathogenesis of chronic, nonhealing ulcers. Traditionally, urokinase-type plasminogen activator (uPA) has been associated with pericellular proteolytic activity involved in tissue remodelling processes, and tissue-type plasminogen activator (tPA) mainly with intravascular fibrinolysis.Objectives  The present study was conducted to characterize the spatial distribution of the various plasminogen activation system components in chronic ulcers and acute, well-granulating wounds.Methods  The expression of uPA, tPA, urokinase receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and vitronectin was investigated by immunohistochemical staining, in addition to uPA, tPA and PAI-1 expression by in-situ hybridization, in samples from eight chronic venous ulcers, five decubitus ulcers, five well-granulating acute wounds and five normal skin samples.Results  In chronic venous leg ulcers tPA mRNA was detected in basal and suprabasal keratinocytes at the leading wound edge, while in well-granulating wounds and in decubitus ulcers tPA mRNA was expressed only in a few keratinocytes. However, tPA was widely expressed in fibroblast- and macrophage-like cells in the stroma of well-granulating wounds, while less tPA was detected in the granulation tissue of chronic ulcers. tPA mRNA and protein were localized in the superficial granular layers in normal skin. Although no qualitative differences in expression of uPA, PAI-1 or uPAR in the wound edge keratinocytes in chronic ulcers vs. normally granulating wounds were found, their expressions were more pronounced in the granulation tissue of well-granulating wounds.Conclusions  These results suggest that in poorly healing venous leg ulcers, the pattern of tPA expression is altered in keratinocytes at the leading edge of the wound, and the patterns of tPA, uPA and PAI-1 expression are altered in the granulation tissue.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1365-2133.2004.06261.x
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  • 4
    Digitale Medien
    Digitale Medien
    Topical synthetic inhibitor of matrix metalloproteinases delays epidermal regeneration of human wounds (2001)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    Details
    ISSN: 1600-0625
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Matrix metalloproteinases (MMPs) degrade extracellular proteins during epithelialization of wounds. To evaluate the biological significance of MMPs in epidermal healing, the synthetic broad-spectrum MMP inhibitor GM 6001 (also called Galardin and Ilomastat) was applied topically to standardized human wounds. GM 6001 (10 μg/μl) or vehicle alone was applied every second day onto 4 de-roofed 6 mm suction blister wounds on the volar forearm of healthy male volunteers for 12 days. GM 6001 delayed healing by 2–4 days as assessed macroscopically and microscopically. In situ hybridization or immunohistochemistry showed that MMP-1 (interstitial collagenase) was present in and MMP-2 (gelatinase A) close to laterally migrating keratinocytes whereas MMP-9 (gelatinase B) was seen during maturation of new epidermis. MMP-1 was undetectable in blister roofs (normal epidermis) and found in low levels in normal skin. Total MMP-1 activities increased about 100-fold in wounds, independent of treatment, compared to normal skin as analyzed by specific ELISA-based activity assay. By gelatin zymography, MMP-2, but not MMP-9, was detected in blister roofs and wound healing was associated with increased active MMP-2 and latent MMP-9 levels. GM 6001 prevented activation of MMP-2 and increased latent MMP-9 levels. GM 6001 delayed re-appearance of laminin-5, the synthesis of which correlated with epidermal regeneration. Restoration of stratum corneum, measured indirectly by transepidermal water loss, was also impaired (P〈0.05) in the GM 6001 group. In conclusion, pharmacological MMP inhibition delayed epidermal regeneration in vivo, suggesting that MMPs are required to restore epidermis after epidermal ablation in humans.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1034/j.1600-0625.2001.100506.x
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  • 5
    Digitale Medien
    Digitale Medien
    Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and -3, are expressed in psoriatic lesions (2001)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    Details
    ISSN: 1600-0625
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-α, IL-1β, TGF-α, and IFN-γ, also capable of regulating MMP transcription. To investigate the role of stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1034/j.1600-0625.2001.010003175.x
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  • 6
    Digitale Medien
    Digitale Medien
    Ultrastructural features resembling those of harlequin ichthyosis in patients with severe congenital ichthyosiform erythroderma (2001)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 145 (2001), S. 0 
    Details
    ISSN: 1365-2133
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Congenital ichthyoses are a group of heterogeneous disorders of cornification. Autosomal recessive congenital ichthyosis (ARCI) can be clinically subdivided into congenital ichthyosiform erythroderma and lamellar ichthyosis. Ultrastructurally, ARCI is classified into four groups: ichthyosis congenita (IC) types I–IV. The genetic background of the ARCI disorders is heterogeneous, but only one disease gene, transglutaminase 1, has been detected so far. We describe six patients with severe congenital ichthyosis from six different Scandinavian families. They could not be classified ultrastructurally into the four IC groups because of atypical findings of electron microscopy. These included abnormal lamellar bodies, alterations in keratohyalin, remnant organelles and lipid inclusions in the upper epidermal cells, which resembled the ultrastructural findings of harlequin ichthyosis (HI), although the HI phenotype was not present at birth. Some clinical features, such as thick scales, erythroderma, alopecia and ectropion were common to all patients. Ichthyosis was usually accentuated in the scalp and four patients had clumped fingers and toes. None of the patients carried the transglutaminase 1 mutation. We conclude that ultrastructural findings resembling those detected in previous HI cases (type 1 and 2) can also be found in patients who do not have classic clinical features of that rare ichthyosis. This may be due to lack of specificity of ultrastructural markers for HI or to its clinical heterogeneity.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1365-2133.2001.04401.x
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  • 7
    Digitale Medien
    Digitale Medien
    Expression of the anhidrotic ectodermal dysplasia gene is reduced in skin cancer coinciding with reduced E-cadherin (1998)
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 7 (1998), S. 0 
    Details
    ISSN: 1600-0625
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: X-linked anhidrotic ectodermal dysplasia (EDA) is characterized by defects in the development of hair, teeth, and sweat glands. We have recently cloned the gene for EDA by positional cloning. The EDA gene encodes a transmembrane protein with a putative role in epithelial-mesenchymal interactions. Since EDA could play a role in cell-cell or cell-matrix adhesion, acantholytic skin diseases and several types of non-invasive and invasive skin cancers were studied using in situ hybridization. Because of the observation that the promoter region of the EDA gene contains a binding site for LEF-1, which is involved in the signaling through E-cadherin/beta catenin complex, we compared the expression of EDA with immunolocalization for E-cadherin (E-CD). EDA expression during hair growth cycle, in benign adnexal tumors, and neuroectodermderived nevus cells was also examined. Our findings indicate that EDA expression is less abundant in malignant tumors, including basal and squamous cell carcinomas and melanoma, and in acantholytic keratinocytes compared to normal epidermis. The reduction in expression also coincides with diminished E-CD staining in all malignant cell types and in acantholytic cells. Our results suggest that EDA protein functions in the regulation of epithelial cell contacts and that it may be associated with the E-CD signaling pathway.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1111/j.1600-0625.1998.tb00319.x
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  • 8
    Digitale Medien
    Digitale Medien
    Matrix metalloproteinases in tumor progression: focus on basal and squamous cell skin cancer (2003)
    Oxford, UK : Munksgaard International Publishers
    Experimental dermatology 12 (2003), S. 0 
    Details
    ISSN: 1600-0625
    Quelle: Blackwell Publishing Journal Backfiles 1879-2005
    Thema: Medizin
    Notizen: Abstract: Many normal biological processes, such as reproduction, fetal development and wound healing, are critically dependent on controlled degradation of extracellular matrix (ECM) macromolecules. However, excessive degradation of matrix components occurs in pathologic tissue destruction, e.g. in atherosclerosis, rheumatoid arthritis, and cancer. Matrix metalloproteinases (MMPs) are degradative enzymes that play an important role in all aspects of tumor progression by enhancing tumor-induced angiogenesis and destroying local tissue architecture and basement membranes to allow tumor invasion and metastasis. Efficient breakdown of the ECM surrounding invasive cancer islands involves interplay between tumor cells, stromal cells, and inflammatory cells, all of which express a distinct set of MMPs. Besides the classical role of MMPs in degradation of ECM, MMPs may also indirectly influence the tumor microenvironment through the release of growth factors, cryptic sites or angiogenic factors, or through the generation of matrix fragments that inhibit tumor cell proliferation, migration and angiogenesis. This makes the contribution of MMPs to tumorigenesis much more complex than initially thought. Currently, a number of clinical studies have focused on testing MMP inhibitors as potential antineoplastic agents. In this review we discuss the present role of MMPs in the development and progression of cancer, focusing on non-melanoma skin cancers basal (BCC) and squamous (SCC) cell carcinoma, and the possible influence of MMPs in their differences.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1034/j.1600-0625.2003.120201.x
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  • 9
    Digitale Medien
    Digitale Medien
    Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers (1998)
    Springer
    Archives of dermatological research 290 (1998), S. S47 
    Details
    ISSN: 1432-069X
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Controlled proteolysis is needed for cell migration, angiogenesis, and matrix remodeling during normal wound repair. Our objective has been to investigate how chronic leg ulcers differ from normally healing wounds (pinch graft donor sites) with respect to their metalloproteinase expression patterns. Using in situ hybridization and immunohistochemistry, we found that collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and stromelysin-2 (MMP-10) were expressed in keratinocytes bordering both acute and chronic wounds. Unlike MMP-1, signal for collagenase-3 (MMP-13) was not detected in keratinocytes but exclusively in fibroblasts deep in the ulcer bed of chronic wounds, suggesting that while MMP-1 production is important for migration, MMP-13 plays a role in matrix remodeling. Tissue inhibitor of metalloproteinase (TIMP)-1 was not detected in the epidermis of any chronic wound sample while it was expressed in keratinocytes bordering normally healing wounds. TIMP-3 was abundantly expressed in stromal fibroblast- and macrophage-like cells surrounding vessels and sweat glands in both types of wounds. Our results suggest that there are no qualitative differences in the expression of MMPs-1, -3 and -10 in the epidermis of chronic vs normally healing wounds. However, the number of stromal cells expressing MMP-1 and MMP-3 was greater in chronic vs acute wounds, whereas MMP-10 was never detected in the dermis. TIMP-1 expression near the basement membrane in acute, but not in chronic, wounds suggests that the balance between MMPs and their inhibitors may be altered in poorly healing wounds. Analogous to chronic cutaneous wounds, MMP-1 and -3 are abundantly expressed in chronic small and large bowel ulcers, while the migrating surface epithelium is negative for TIMP-1 expression.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/PL00007453
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  • 10
    Digitale Medien
    Digitale Medien
    Psychomotor, respiratory and neuroendocrinological effects of buprenorphine and amitriptyline in healthy volunteers (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 139-146 
    Details
    ISSN: 1432-1041
    Schlagwort(e): buprenorphine ; amitriptyline ; interaction ; psychomotor performance ; respiration ; pituitary hormones ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Actions and interactions of buprenorphine (BUP) and amitriptyline (AMI) on performance and respiration were studied double-blind and cross-over in 12 healthy volunteers. After one-week pretreatments with AMI or placebo, the subjects received on Day 8 placebo, BUP or AMI so that the final treatments were 1) placebo, 2) acute AMI 50 mg, 3) acute BUP, 4) subchronic AMI + acute BUP and 5) subchronic AMI. The subacute treatments were started at two-week intervals. A Mapleson D rebreathing circuit including a pneumotachograph and an infrared capnograph was employed to study drug effects on respiration. Minute volume and end-tidal carbon dioxide as well as psychomotor performance were measured and the blood samples taken on Day 8 before the drug intake and 2 and 4 h thereafter. The performance tests included tracking, choice reaction, flicker fusion, exophoria, nystagmus, digit symbol substitution and the subjective assessment of mood. BUP depressed respiration, and subchronic AMI increased this depression. Both BUP and acute AMI 50 mg each alone impaired various measures of performance and rendered the subjects drowsy, feeble, mentally slow and muzzy but subchronic AMI did not enhance BUP effects. BUP increased plasma prolactin levels similarly after both pretreatments. The results suggest that both BUP and AMI moderately affect psychomotor performance but the interaction between these agents is mild and restricted mainly to respiration.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00544557
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