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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The skin is the only tissue yet known in which the complete UVB-induced pathway from 7-dehydrocholesterol (7-DHC) to hormonally active calcitriol (1α,25-dihydroxyvitamin D3) occurs under physiological conditions. It is well known that both calcitriol and UVB radiation exert potent antipsoriatic effects. We speculate that the therapeutic effect of UVB radiation can be attributed to UVB-triggered cutaneous synthesis of calcitriol for which the optimum wavelength was a range of 300 ± 3 nm in vitro and in vivo. On the other hand, the narrowband Philips TL-01 lamp which is commonly used as UVB source for therapeutical treatment of psoriasis, has a maximum spectral irradiance at around 311 nm. The aim of this study was to investigate the calcitriol-inducing potential of the TL-01 lamp in organotypic cultures of keratinocytes supplemented with 25 μM 7-DHC at different radiant exposures (125–1000 mJ/cm2). We found that the maximum calcitriol-generating capacity of the TL-01 lamp at 500 mJ/cm2(corresponding to 2.1 SED [Standard Erythema Dose]) and 16 h after irradiation still amounts to approximately 45 percent of that of monochromatic radiation at 300 nm and 30 mJ/cm2. We conclude from our findings that irradiation with the narrowband TL-01 lamp in therapeutic dose range can affect calcitriol synthesis in epidermal keratinocytes. Thus, the antipsoriatic effect observed after TL-01 lamp exposures may be, at least partially, explained by the known action of newly-synthesized calcitriol on the epidermal cell proliferation and differentiation.
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  • 2
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 1,25-Dihydroxyvitamin D3, 1,25(OH)2D3) and analogs have been shown to inhibit proliferation and to induce differentiation in various cell types, including human melanocytes. There are two principal enzymes involved in the formation of circulating 1,25(OH)2D3 from vitamin D, the hepatic microsomal or mitochondrial vitamin D 25-hydroxylase (25-OHase) and the renal mitochondrial enzyme 25-hydroxyvitamin D3-1α-hydroxylase (1α-OHase) for vitamin D and 25(OH)D3, respectively. Recently, extra-renal activity of 1α-OHase has been reported in various cell types including macrophages, keratinocytes, prostate and colon cancer cells. Increasing evidence indicates that extra-renal 1α-OHase may act in many tissues via the local production of 1,25(OH)2D3 as a major regulator of cell growth in an autocrine or paracrine fashion. In human malignant glioma we have demostrated a correlation between amplification of the gene and its overexpression. Using Reverse transcription (RT)-PCR with primers amplifying a part of the 1α–OHase sequence, we have shown now for the first time several splice variants, including transcripts encoding truncated proteins in melanoma cell lines. To arrive at a more complete description of 1α–OHase expression we developed and employed a highly specific approach that combinded nested and touchdown PCR to clone full length 1α-OHase. In addition, we identified several new splice variants in human melanoma. The new splice variants that were termed Hyd-V5, -V6, -V7 and -V8 were cloned and sequenced. All but one of the new variants showed an insertion of intron 1 leading to a premature termination signal and to truncated proteins without ferredoxin and haem-binding site of the P450 protein. In conclusion our findings indicate that (1) local synthesis of 1,25(OH)2VitD3 mediated via 1α-OHase may be of high importance for growth characteristics of melanoma cells and (2) 25(OH)VitD3 or other percusors of biologically active vitamin D metabolites may be effective in the palliative treatment of metastasizing melanoma.
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pathogenesis of chronic disabling inflammatory diseases (CDIDs) is partly understood. The presently used concepts focus mainly on abnormalities of the immune system but this view is incomplete. The presented concept is a new framework for the pathogenesis of CDIDs. It integrates evolutionary theories with the classical immunological standpoint, which is further linked with a neuroendocrine immune view of erroneous homeostatic adaptation of the other supersystems (nervous system, endocrine system, reproductive system): 1. In CDIDs, the loss of tolerance against self and harmless foreign antigens leads to continuous immune aggression which is dependent on a multifactorial genetically polymorph background (the initiation). 2. However, advantageous or disadvantageous adaptation to CDIDs were not evolutionary conserved because CDIDs severely impaired reproduction or appeared after the reproductive phase and, thus, imply a strong negative selection pressure. 3. Reactions of all supersystems are evolutionary conserved for transient inflammatory reactions such as the elimination of infectious agents, wound healing, foreign body reaction and many others. 4. The sum of the false reactions of all supersystems – conserved for transient inflammation – provide the pathogenetic background for the chronification of CDIDs because a continuous aggressive situation is created (the chronification). The human disease of rheumatoid arthritis is used as a prototypic CDID to illustrate the integrated view point. The synovial tissue innervation is in the focus of this concept.
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Oxysterols stimulate keratinocyte differentiation, which involves the formation of the cornified envelope on the inner plasma membrane by transglutaminase crosslinking of several constituent proteins. Oxysterols increase the expression of one of these crosslinked proteins, involucrin, which can be abolished by mutations of the distal activator protein (AP)-1 response element in the involucrin promoter. Here, we show that oxysterols increase AP-1 binding in electrophoretic gel mobility shift assays and that oxysterols induce the expression of an AP-1 reporter. We further describe the individual components of the AP-1 complex, which are involved in the oxysterol-mediated AP-1 activation and stimulation of keratinocyte differentiation. We identified Fra-1 within the AP-1 DNA binding complex by super shift analysis of nuclear extracts from oxysterol-treated, cultured keratinocytes. Western blot analysis demonstrated that oxysterol treatment increased the levels of Fra-1 and Jun-D, while Northern analysis revealed that oxysterols increased mRNA levels for Fra-1, c-Fos and Jun-D. Together these data indicate that oxysterols stimulate involucrin expression by increasing the levels of specific proteins of the AP-1 complex, indicating that oxysterols regulate keratinocyte differentiation by inducing the AP-1 factors, which in turn activate the genes required for epidermal differentiation. The presence of LXREs within the promoter regions of individual AP-1 proteins suggests that these oxysterol effects may be mediated by LXR.
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Vanilloids and endogenous cannabinoids mediate their actions via the vanilloid receptor subtype 1 (VR1/TRPV1), a non-selective cation channel, which is widely distributed in the central and peripheral nervous system. Only recently, VR1 has been shown to be expressed in keratinocytes in vitro and in vivo. However, a precise description of VR1 localization in epithelial cells was missing. To determine this, we investigated VR1-immunoreactivity as well as mRNA and protein expression in a series of biopsies from normal, diseased, and capsaicin-treated human skin. VR1 was found in epidermal keratinocytes, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands upon immunohistochemistry, RT-PCR and Western blot analysis. Interestingly, in diseased skin such as prurigo nodularis, psoriasis vulgaris, and atopic dermatitis, VR1 expression in keratinocytes correlated with the degree of epidermal differentiation. Enhanced VR1 immunoreactivity and protein content was found in prurigo nodularis in which epidermal keratinocytes are highly differentiated. Under effective capsaicin therapy of prurigo nodularis, the epidermis thinned and the distribution pattern of VR1 on epidermal keratinocytes normalized. In psoriasis vulgaris, a disease with disturbed epidermal differentiation, less intense immunostaining for VR1 was observed. This could be confirmed by western blot analysis showing less VR1 protein amount in comparison to prurigo nodularis although histologically both showed a thickened epidermis. In atopic dermatitis, which is characterized by a moderate epidermal hyperplasia only and regular differentiated keratinocytes, VR1 immunoreactivity was unchanged in comparison to normal skin. These findings suggest that VR1 may contribute to regular differentiation of keratinocytes. VR1 activation opens non-selective cation channels with high permeability to calcium, a ion that is crucially important for the synthesis of cornification proteins such as involucrin, fillagrin and loricrin. The role of VR1 in other epithelial cells of appendage structures remains to be determined. In summary, VR1 is widely distributed in the skin suggesting a central role for this receptor not only in nociception but also maturation and function of epithelial cells.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Extraneuronally, acetylcholine (Ach) is synthesized, stored and secreted in the tegumental cells covering the inner and outer surfaces of the body. It acts via nicotinic (nAchR) and muscarinic (mAchR) receptors in a paracrine and autocrine fashion influencing various keratinocyte functions. Using in vitro studies, we present evidence that effects of cholinergic agonists and antagonists on cutaneous biology are dependent upon specific Ach-R, localised in the different compartments of the skin. Using immunohistochemistry on frozen section of normal skin we could previously demonstrate a differential distribution of alpha 3*, alpha 7, alpha 9 and beta 1 nAchR and m1, m3–5 mAchR in human epidermis. Here we show the functional significance of AchR blockage using organotypical keratinocytes cultures. Cholinergic agonists and antagonists were added on the day of the lift to the air-liquid interface. After 5 days, blockage of all AchR using mecamylamine and atropine resulted in complete inhibition of terminal differentiation. Mecamylamine and atropine alone had only a retarding effect suggesting an additive mechanism of nAchR and mAchR blockage. Specific inhibition of α9 homooligomers with strychnine produced the strongest effects leaving behind only a keratinocytes monolayer. Stimulation of AchR with either nicotine or muscarine in short term organotypic cultures did not produce dramatic changes of epidermal morphology. We conclude that alpha 9 AchR that are located in the basal and lower suprabasal layers of the epidermis, are crucially involved in terminal differentiation of keratinocytes. The functional significance of other nAchR expressed in the epidermis remains unclear, due to the lack of specific agonists and antagonists.
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sexual hormones are important in the maintenance of human skin. Being the endocrine “brain” of the skin, the sebaceous gland is a major target of sexual hormones. While androgens stimulate sebocyte proliferation, estrogens do not to affect sebaceous gland growth. Regarding differentiation, androgens are expected to stimulate and estrogens to suppress sebaceous lipid synthesis, while estrogens, in vivo, enhance sebaceous lipogenesis in aged skin. The latter results have been disputed by current in vitro data indicating no direct effect of sexual hormones on sebocyte differentiation. To elucidate these contradictions we have investigated possible pathways which may be used by sexual hormones to modulate sebocyte differentiation in vitro. It has been postulated that androgen induction of lipogenesis requires the concomitant presence of peroxisome proliferator-activated receptor (PPAR) ligands. We found that arachidonic acid (AA), the direct precursor of leukotriene B4, a natural PPARα ligand, and linoleic acid (LA), a natural PPARδ ligand, induce sebocyte enlargement, accumulation of lipid droplets in the cytoplasm, and nuclear fragmentation. The combined administration of testosterone and AA or LA slightly increased sebaceous lipogenesis. In contrast, synthetic PPAR ligands were unable to enhance sebaceous lipogenesis. Interestingly, AA synthesis in human sebocytes was significantly stimulated by the prostaglandins (PG) E2 and Δ15-J2. On the other hand, PPARγ expression was downregulated by the phytoestrogen genistein. Interestingly, 17β-estradiol has previously been shown to induce the metabolism of PGD2 to Δ12-PGJ2, a natural PPARγ ligand. In addition, we found that 17β-estradiol increases IGF-I synthesis (+28%) and down-regulates IGF-IR expression (−37 to −48%), whereas IGF-I significantly induces sebaceous lipogenesis. In conclusion, sexual hormones are not directly active but are likely to utilize complex mechanisms, including modified known pro-inflammatory pathways, to modulate sebocyte differentiation.
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Association of locally increased androgen activity and skin disorders is obvious in acne and androgenetic alopecia in males. In addition, testosterone was unexpectedly found to perturb the epidermal barrier. Blockade of androgen action via androgen receptor (AR) antagonism accelerates wound healing in aged individuals. Androgen activity on skin can classically be inhibited by systemic administration of compounds, which have strong affinity for AR and antagonize androgen binding to AR molecules. In this study we applied a new technology to realize the same purpose: We tested the activity of antisense oligonucleotides against the AR in primary human foreskin keratinocytes, human non-foreskin keratinocytes from young (30 y) and older (60 y) female donors, and reconstituted human epidermis (SkinEthic model). Reconstituted human epidermis is similar to in vivo human epidermis and features a functional permeability barrier. To transfer the antisense oligonucleotides into human keratinocytes an optimum liposome-mediated transfection system with Poly-L-ornithine (12 μg/ml) over 4 h was used. The transfection efficiency was assessed using FITC-labeled (ACTG)5 random oligonucleotides, which were localized in cytoplasmic structures of the keratinocytes. AR expression on the protein level was investigated by Western blotting. Transient transfection of foreskin keratinocytes with phosphorothioate antisense oligonucleotides (PTO) revealed a reduction of AR expression (≈25%) compared to native keratinocytes after 14 h recovery time. The AR knock down in epidermal keratinocytes of the compared women was stronger in the older, more differentiated keratinocytes. After 24 h, AR expression level have returned back to the level of non-transfected cells. The effect could be reestablished by repetition of transfection. PTO and 2?O-methylribosyl (MRO) antisense oligonucleotides decreased AR expression at levels varying between 46% and 70% in the air-lifted reconstituted human epidermis after 18 h recovery time. The successful inhibition of AR expression in human keratinocytes and reconstituted human epidermis is the first step to develop topically efficient compounds with oligonucleotides.
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The prototypic pineal hormone, melatonin reputedly exerts many functional effects on mammalian skin and/or its isolated cell populations in culture (e.g., melanogenesis inhibition, melanocyte growth inhibition, regulation of seasonal changes in the pelage), and is recognized as a potent free radical scavenger. In mammals, two types of high-affinity membrane melatonin receptors, MT1 and MT2 have been identified, which inhibit adenylate cyclase activity to decrease the intracellular level of cAMP. Low-affinity membrane receptor MT3/QR2 have also been identified, though the mechanism has not been cleared yet. Melatonin is also a natural ligand of nuclear transcription factor ROR(α and β), which is suggested to regulate cell cycle negatively via target gene such as p21WAF/CIP1. Due to its lipophilic structure, melatonin also enters through both the plasma and nuclear membrane, and acts as a potent free radical scavenger to protect macromolecules, in particular DNA. Melatonin demonstrates differential – and often still confusing seemingly contradictory– effects on cell activity in many different systems, which may be explained by this multitude of signaling pathways that are modulated by melatonin bioactivity. Recently, cultured epidermal and follicular melanocytes, keratinocytes, and fibroblasts, have also been found to display the enzymatic activity of arylalkylamine N-acetyltransferase and hydroxyindole -O- methyltransferase for melatonin synthesis. However, little is known about the cutaneous expression and regulation of melatonin and its receptors in situ, and the functional role of melatonin in normal skin and hair follicle biology is still obscure. In order to study whether murine hair follicles in situ are indeed direct peripheral melatonin targets, the follicular expression of MT1, MT2 and/or RORα are investigated. Immunohistochemistry revealed that C57BL/6 mouse hair follicle keratinocytes in situ show prominent MT1-like immunoreactivity (IR), which changed substantially in a hair cycle-dependent manner. RORα-like IR was also detected in murine hair follicles, and also displayed hair cycle dependence. RT-PCR of MT1 and MT2, and real time PCR for MT1, MT2 and RORα on C57BL/6 mice skin cDNA revealed that all three genes are transcribed in normal mouse skin, and demonstrated that their expression/transcription is hair cycle-dependent. In conclusion, normal murine hair follicles are indeed a prominent, direct target for melatonin bioregulation, through MT1, MT2 and RORα melatonin receptors and that at least some of these regulators are functionally active in situ. The observed hair cycle dependence of melatonin receptor expression suggests a role of melatonin in hair cycle control.
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  • 10
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Through their ability to modulate the expression of extracellular matrix (ECM) components and ECM-degrading enzymes, cytokines and growth factors orchestrate the balance between ECM destruction and neosynthesis and therefore play an important role in the control of tissue homeostasis and repair. Disruption of the fragile equilibrium between anabolic and catabolic cytokines in favor of TGF-β may lead to excessive collagen deposition, the hallmark of fibrotic conditions. TGF-β elicits its effects on target genes through Smad proteins, which transduce signals from TGF-β receptors into the nucleus where they bind directly to specific promoter sequences. Using an artificial Smad3/4 dependent reporter construct, we show that synthetic cAMP, prevents TGF-β-induced Smad-specific gene transactivation in human dermal fibroblasts. Activation of adenylate cyclase by forskolin mimics the shown Smad opposing effect. Northern blot studies reveal that cAMP inhibits TGF-β/SMAD-dependent α(2) type I collagen and type 1 plasminogen activator inhibitor gene expression. In addition, TGF-β-induced C-terminal propeptide of type I procollagen secretion into cell supernatants is significantly inhibited by cAMP. Together these results demonstrate the suppression of TGF-β-induced expression of ECM components by increased intracellular cAMP levels. Our data support the notion that various hormones and neuropeptides, which signal via the cAMP pathway, may function as antagonists of fibrosis.
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  • 11
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: After the initial discovery that, in vivo, mammalian skin both transcribes and translates the proopiomelanocortin (POMC) gene, and processes its product into melanocortins (Slominski et al., Experientia 1992), it has become increasingly appreciated that the hair follicle – including the human one – is a prime source and target not only of POMC-derived “pituitary” hormones, e.g. alpha-MSH, ACTH and ß-endorphin, but also expresses the most proximal control element of the hypothalamic-pituitary-adrenal (HPA) axis, corticotropin-releasing hormone (CRH) and its receptor (e.g. Roloff et al. FASEB J 1998, Ito et al. J Invest Dermatol 2004). However, while all proximal elements of the HPA are expressed in both murine and human hair follicles (CRH, CHR-R, POMC, ACTH and ACTH-R), it has neither been shown that these are functionally linked (i.e., is CRH actually capable of modulating intrafollicular POMC gene expression and ACTH production?), nor has it been known whether the most distal HPA component – cortisol synthesis – is also present in the hair follicle. Therefore, we have investigated whether the stimulation of microdissected, organ-cultured human hair follicles with CRH or ACTH elicits responses inside this peripheral miniorgan that imitate a functional HPA – in the absence of any systemic or neural connections and under serum-free culture conditions. Here, we show that CRH stimulation of organ-cultured human scalp hair follicles in the anagen VI stage of the hair cycle indeed results in significant upregulation of POMC transcription, and of alpha-MSH, ACTH, MC1, MC2 and glucocorticoid receptor (GR) immunoreactivity in situ (immunofluorescence). ACTH stimulation, in turn, significantly up-regulates the – already constitutively present!– cortisol-immunoreactivity as well as cortisol secretion into the culture medium. This represents the first available evidence that normal human skin (more precisely: the hair follicle) can actually synthesize the “adrenal” steroid hormone cortisol in situ, and that this acticity is regulated by the same “hypothalamic” and “pituitary” hormones that operate as key controls of adrenal cortisol synthesis. Moreover, we show that cortisol stimulation exerts classical feedback responses inside the human anagen hair follicle recognized for the central HPA: cortisol up-regulates GR, while it down-regulates CRH expression. Given that the HPA operates as the major system for coordinating stress-responses of the mammalian organism and for integrating them into changing metabolic demands and neuro-endocrine-immune signaling circuits, it has fascinating implications (e.g. for general skin physiology and dermatological therapy), and raises most intriguing questions, that human hair follicles are utilizing a fully functional peripheral equivalent of the central HPA.
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  • 12
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The availability of neuropeptides or neuroendocrine hormones as important modulators of innate and adaptive immune responses is effectively controlled by neuropeptide-specific peptidases. In previous studies, drug inhibition or genomic deletion of neutral endopeptidase (NEP, CD10) or of angiotensin-converting enzyme (ACE, CD143) resulted in a profound augmentation of murine allergic contact dermatitis responses. Likewise, we have identified dermal microvascular endothelial cells (EC) as both source and target of the proopiomelanocortin (POMC) peptides ACTH and α-melanocyte-stimulating hormone (α-MSH), in particular. EC express melanocortin receptor (MC-) 1 and α-MSH is capable of profoundly downregulating LPS- or cytokine-induced expression of adhesion molecules in vitro and of endotoxin-induced cutaneous vasculitis in vivo. In this study, we have tested the hypothesis that NEP or ACE expressed by EC may influence the local bioavailability of POMC peptides. Cell membranes prepared from the high NEP/low ACE expressing human microvascular endothelial cell line 1 (HMEC-1) or from low NEP/high ACE expressing primary human dermal EC (HDMEC) were incubated for 30–480 min with ACTH1–39 in the presence or absence of NEP or ACE inhibitors, respectively. Analysis of membrane supernatants for ACTH and α-MSH by radioimmunoassay revealed a decrease in ACTH immunoreactivity (IR) over time that could be partially blocked with NEP inhibitors. In parallel, α-MSH IR increased peaking after 60 min. Fragments generated by incubation of HMEC-1 or HDMEC membranes with ACTH1–39, ACHT1–24 or α-MSH for 1–120 min were further analyzed by Matrix-assisted-LASER desorption time-of-flight (MALDI-TOF) spectroscopy. HMEC-1 membranes generated main peptide products with molecular masses of 2007, 1057 and 945, respectively, from ACTH1–39, and 1057 from ACTH1–24. Inhibition with NEP, but not ACE inhibitors altered the fragmentation profile indicating that NEP is involved in degradation of both ACTH1–39 and ACTH1–24. Likewise, HDMEC membranes fragmented ACTH similar to HMEC-1 membranes in the presence of NEP inhibitors. Both HMEC-1 and HDMEC membranes were also capable of slowly degrading α-MSH suggesting that EC proteolytic peptidases are important for the local control of ACTH/α-MSH bioavailability, which may play a significant role in controlling local cutaneous inflammatory responses.
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  • 13
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 14
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 15
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  For a long time, the mantra of acne pathogenesis debates has been that acne vulgaris lesions develop when (supposedly largely androgen-mediated) increased sebum production, ductal hypercornification, and propionibacteria come together with local inflammatory process in the unlucky affected individual. And yet, the exact sequence, precise interdependence, and choreography of pathogenic events in acne, especially the ‘match that lights the fire’ have remained surprisingly unclear, despite the venerable tradition of acne research over the past century.However, exciting recent progress in this – conceptually long somewhat stagnant, yet clinically, psychologically, and socioeconomically highly relevant – everyday battlefield of skin pathology encourages one to critically revisit conventional concepts of acne pathogenesis. Also, this provides a good opportunity for defining more sharply key open questions and intriguing acne characteritics whose underlying biological basis has far too long remained uninvestigated, and to emphasize promising new acne research avenues off-the-beaten-track – in the hope of promoting the corresponding development of innovative strategies for acne management.
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  • 16
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 17
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 18
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Vascular endothelial growth factor (VEGF) is a powerful agent that causes hyperpermeability of blood vessels as well as endothelial cell proliferation. Recent investigations have revealed that production of VEGF increases in epidermis of psoriatic lesions, and the overproduced VEGF plays an important role in the pathogenesis of psoriasis. In this study, we used immunohistochemical staining as well as extraction of stratum corneum with physiological saline to further analyse VEGF produced in psoriatic lesions. Biological activity of VEGF in the psoriatic scales was assayed by cultured human umbilical vein endothelial cells in vitro. The immunohistochemical examination confirmed an increased production of VEGF in the keratinocytes of psoriatic lesions. In addition, we found that the content of VEGF contained in the psoriatic scales was approximately 50 times greater than that in normal stratum corneum. We also found that VEGF 121 isoform, which has an exclusive ability to cause hyperpermeability of blood vessels, was predominantly detected in psoriatic scales, suggesting a major role of VEGF 121 isoform on the altered structure of microvessels in psoriatic lesions.
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  • 19
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 20
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  With the exception of vitamin D production, virtually all epidermal functions can be considered as protective, or more specifically, as defensive in nature (1). Yet, the term “barrier function” of the stratum corneum (SC) is often used synonymously with only one such defensive function, although arguably its most important, i.e., permeability barrier homeostasis. Regardless of their hierarchy of relative importance, these critical protective functions largely reside in the SC. In this short review, we explore the ways in which the multiple defensive functions of the SC are linked and interrelated, either by their shared localization or by common biochemical processes.
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  • 21
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Cytokines are produced as a consequence of photo-damaged DNA and oxidative stress in ultraviolet (UV)-exposed keratinocytes. A soybean Kunitz trypsin inhibitor (KTI) down-regulates the expression of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) in tumor cells and inflammatory cells.Aim:  The effect of KTI on TNF-α production in UV-exposed primary human keratinocytes was analyzed.Results:  We show (i) UV induced up-regulation of TNF-α mRNA and protein expression in keratinocytes; (ii) cells treated with KTI before UV irradiation showed a significantly lower accumulation of TNF-α protein in a dose-dependent manner and a reduced UV-induced up-regulation of TNF-α mRNA expression; (iii) KTI inhibited the induction of TNF-α target molecules interleukin-1β (IL-1β) and IL-6 proteins; (iv) UV irradiation transiently activated c-Jun N-terminal kinase (JNK) and Akt signaling but only weakly activated extracellular signal-regulated kinase (ERK) and p38; (v) KTI specifically inhibited UV-induced activation of ERK, JNK, and p38, but not Akt; (vi) treatment of cells with SP600125, a pharmacological inhibitor of JNK, predominantly suppressed UV-induced up-regulation of TNF-α expression; and (vii) KTI did not enhance suppression of UV-induced JNK phosphorylation by SP600125.Conclusions:  KTI specifically inhibited UV-induced up-regulation of cytokine expression predominantly through suppression of JNK signaling pathway.
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  • 22
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 23
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 24
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 25
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 26
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  A patient, who presented with abdominal pain and severe photosensitivity that resulted in scarring and mutilation of the fingers, nose and ears, was referred for biochemical assessment of porphyria and DNA screening. Although these clinical manifestations were suggestive of both acute porphyria and congenital erythropoietic porphyria, the biochemical profile was consistent with variegate porphyria (VP). Analysis of the protoporphyrinogen oxidase (PPOX) gene underlying VP resulted in the identification of the founder mutation R59W in a heterozygous state in this patient. Despite extensive mutation analysis, no other potential disease-causing genetic alterations could be detected in the PPOX gene or the uroporphyrinogen III synthase gene. Slight overrepresentation of the mutant PPOX allele was however, observed repeatedly in DNA of the proband compared to other R59W heterozygotes, including his mother who also tested positive for mutation R59W using restriction enzyme analysis and direct DNA sequencing. Confirmation of this phenomenon by real-time polymerase chain reaction analysis and microsatellite analysis, using highly informative markers flanking the PPOX gene, raised the possibility of partial homozygosity for VP in this patient. This study represents the first report of overrepresentation of mutation R59W in a patient with a severe form of VP. A homozygote for the R59W mutation has never been detected, and the severe clinical manifestation observed in our patient is consistent with the hypothesis that such a genotype will not be compatible with life.
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  • 27
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  CD34+ progenitor cells carrying human herpesvirus-8, Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV), have been described in the peripheral blood of AIDS patients suffering from Kaposi's sarcoma (KS). In this study, we investigated the influence of HHV-8 on the differentiation of CD34+ progenitor cells. Native CD34+ cells derived from cord blood could be infected by a laboratory strain of HHV-8, as shown by immunofluorescence staining and polymerase chain reaction, but no significant initial maturation/differentiation effects were observed. In addition, these infected cells were differentiated into immature and mature dendritic cells (DCs) using cytokine induction with recombinant human granulocyte-macrophage colony-stimulating factor (rhGm-CSF), recombinant human tumor necrosis factor (rhTNF-α) and recombinant human stem cell factor (rhSCF). Double immunofluorescence and flow cytometry studies demonstrated that virus infection did not impair the development of immature and mature DC populations. Subsequently, the immunostimulating capacity of DC populations was tested in a mixed lymphocyte reaction using allogeneic T-cells. The HHV-8-infected CD34+ progenitor cell-derived mature DC population showed a significantly enhanced antigen-presenting capacity, compared to non-infected DCs, which was not observed with the immature DCs. This suggests stimulation of DC function by HHV-8 infection. Because there are only a small percentage of HHV-8-positive DCs in the preparations and because it is not clear whether infection is abortive or productive to some extent, this seems to be most likely due to an indirect viral effect.
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  • 28
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Decreased production of T helper type 1 (Th1) cytokines, such as interferon-γ (IFN-γ) or interleukin-2 (IL-2), is a hallmark of atopic diseases. While accessory signals from antigen-presenting cells may be missing, T cells themselves may be suppressed in their ability to produce substantial amounts of Th1 cytokines. We show, in this study, that T cell receptor (TCR)-activated T cells from atopic dermatitis (AD) patients proliferate less than control T cells and produce lower amounts of IFN-γ and IL-2, but comparable amounts of IL-4. Because mice lacking the nuclear factor kappa B (NF-κB) transcription factors – p65 or c-Rel – show reduced Th1, but undisturbed Th2 responses, we investigated the role of c-Rel and p65 for Th1 cytokine production in T cells from healthy and severe AD patients. TCR-activated primary T cells from healthy donors treated with c-Rel antisense oligonucleotides produced lower levels of IL-2 and IFN-γ and proliferated less efficiently than the corresponding control T cells. Moreover, transfection of primary T cells with c-Rel or p65 enhanced proliferation and production of IL-2 and IFN-γ. Nuclear extracts of activated primary T cells from AD donors bound weakly to NF-κB-specific oligonucleotides, compared to extracts from healthy control T cells. Western blotting studies revealed that nuclear, but not cytosolic, extracts from T cells of AD patients lacked significant amounts of c-Rel and p65. T cell clones derived from AD patients failed to sufficiently translocate c-Rel and p65 into the nucleus following activation. Thus, impaired nuclear translocation of c-Rel and p65 may determine an impaired Th1 cytokine response in AD.
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  • 29
    Electronic Resource
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Given that an important functional attribute of stem cells in vivo is their ability to sustain tissue regeneration, we set out to establish a simple and easy technique to assess this property from candidate populations of human keratinocyte stem cells in an in vivo setting. Keratinocytes were inoculated into devitalized rat tracheas and transplanted subcutaneously into SCID mice, and the epithelial lining regenerated characterized to establish the validity of this heterotypic model. Furthermore, the rate and quality of epidermal tissue reconstitution obtained from freshly isolated unfractionated vs. keratinocyte stem cell-enriched populations was tested as a function of (a) cell numbers inoculated; and (b) the inclusion of irradiated support keratinocytes and dermal cells. Rapid and sustained epidermal tissue regeneration from small numbers of freshly isolated human keratinocyte stem cells validates the utilization of this simple and reliable model system to assay for enrichment of epidermal tissue-reconstituting cells.
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  • 30
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  A major area of research in regenerative medicine is the potential application of stem cells in skin grafting and tissue engineering. This would require well defined and efficient protocols for directing the commitment and differentiation of stem cells into the keratinocyte lineage, together with their selective purification and proliferation in vitro. The development of such protocols would reduce the likelihood of spontaneous differentiation of stem cells into divergent lineages upon transplantation, as well as reduce the risk of teratoma formation in the case of embryonic stem cells. Additionally, such protocols could provide useful in vitro models for studying skin tissue biology, as well as facilitate the genetic manipulation of stem cells for therapeutic applications. The development of pharmacokinetic and cytotoxicity/genotoxicity screening tests for skin-related biomaterials and drugs could also utilize protocols developed for the commitment and differentiation of stem cells into the keratinocyte lineage. Hence, this review critically examines the various strategies that could be employed to direct the commitment and differentiation of stem cells into the keratinocyte lineage in vitro.
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  • 31
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  In view of the central pathogenic importance of leukocyte extravasation in inflammatory skin diseases, therapeutic interference with this – surprisingly complex – process is clearly a promising new approach for treating these dermatoses. Despite some disappointments during the clinical use of these agents and despite their crippling price tag, the recent incorporation of biologicals that target defined molecular controls of leukocyte extravasation into dermatological and rheumatological practise, consequently, has greatly enriched our therapeutic options for battling major, chronic, inflammatory dermatoses such as psoriasis. However, the – as yet unresolved and still rather controversially discussed – critical question is: Which of the multiple steps that control leukocyte extravasation in the human system really offer the most promising, most pragmatic, and safest molecular targets for therapeutic intervention for which disease entity? The current debate intends to stimulate public and rational debate of this crucial issue, beyond the evident commercial interests that are touched by whatever stand one takes.
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  • 32
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Mitochondrial dysfunction might play a role in the pathogenesis of liver damage in erythropoietic protoporphyria (EPP). Changes in mitochondrial respiratory chain activities were evaluated in the Fechm1pas/Fechm1pas mouse model for EPP.Mice from different strains congenic for the same ferrochelatase germline mutation manifest variable degrees of hepatobiliary injury. Protoporphyric animals bred into the C57BL/6J background showed a higher degree of hepatomegaly and liver damage as well as higher protoporphyrin (PP) accumulation than those bred into the SJL/J and BALB/cJ backgrounds. Whereas mitochondrial respiratory chain activities remained unchanged in the liver of protoporphyric mice C57BL/6J, they were increased in protoporphyric mice from both SJL/J and BALB/cJ backgrounds, when compared to wild-type animals. Mitochondrial respiratory chain activities were increased in Hep G2 cell line after accumulation of PP following addition of aminolevulinic acid. As a direct effect of these elevated mitochondrial activities, in both hepatic cells from mutant mouse strains and Hep G2 cells, adenosine 5′-triphosphate (ATP) levels significantly increased as the intracellular PP concentration was reduced.These results indicate that PP modifies intracellular ATP requirements as well as hepatic mitochondrial respiratory chain enzymatic activities and further suggest that an increase of these activities may provide a certain degree of protection against liver damage in protoporphyric mice.
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  • 33
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 34
    Electronic Resource
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 35
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract – Astroblepus ubidiai (Actinopterygii; Siluriformes), which is the only native fish of the highlands of the Province of Imbabura, Ecuador, was abundant in the past in the Imbakucha watershed and adjacent drainages but currently it is restricted to a few isolated refuges. Population viability analysis (PVA) was used to detect critical aspects in the ecology and conservation biology of this unique fish. The annual population growth rate (λ) was estimated for six remnant populations of this Andean catfish using a deterministic matrix population model. Sensitivity and elasticity analyses complemented the PVA by providing constructive insights into vital rates affecting projections and extinction probabilities. Positive population growth rates were found in all the study populations. The high contributions of juvenile survival to the variance of λ and its high elasticity indicated that A. ubidiai population dynamics are highly sensitive to the transition values of this vital rate, which can promptly respond to management or antagonistic perturbations. Allowing fish to survive until the age of first reproduction and permitting the successful reproduction of these individuals will facilitate positive population growth rates, however the very small areas of occupancy, small extent of occurrence and severe fragmentation may still contribute to the extinction risk.
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  • 36
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  In past dietary studies kokanee Oncorhynchus nerka were prominent in the diet of Pend Oreille Lake's large piscivores: native bull trout Salvelinus confluentus, cutthroat trout O. clarki and northern pikeminnow Ptychocheilus oregonensis, and introduced lake trout S. namaycush and Kamloops rainbow trout O. mykiss gairdneri. However, kokanee have declined to 10–20% of their former abundance. We therefore initiated this study to understand current predation demands on kokanee and diet overlap among piscivores, using gut content samples and analysis of stable nitrogen (δ15N) and carbon (δ13C) isotopes from the lake's fish and invertebrate community. In gut content samples, kokanee were the main prey item of large [i.e., ≥400 mm total length (TL)] bull and lake trout; a conclusion that was affirmed by stable isotope analysis. Rainbow trout 〉500 mm TL consumed mostly kokanee, thus there was a high degree of diet overlap among large bull, lake and rainbow trout. Small (i.e., 〈400 mm TL) rainbow and cutthroat trout diets overlapped, and were composed mostly of littoral benthic invertebrates. However, gut content and stable isotope analysis did not accord for 400–500 mm TL rainbow trout, small lake trout, and large cutthroat trout. In these instances, a linear mixing model using stable isotope results predicted kokanee consumption for each species, but no kokanee were identified in rainbow or lake trout gut content. Gut content and stable isotope analysis of native northern pikeminnow indicated a diet of mostly littoral benthic invertebrates at smaller (100–150 mm TL) lengths, with kokanee becoming more prominent in the diet of individuals 〉300 mm TL. Percent of kokanee in the diet of northern pikeminnow has declined from a prior study; otherwise piscivore diets have apparently remained unchanged. In this study, judgments as to the feeding of some piscvores, based on gut content alone, would be tenuous because of small sample sizes, but stable isotope analysis provided an efficient means for confirming diets.
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  • 37
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract – Positively phototactic vendace larvae may be vulnerable to enhanced springtime UV levels unless they are able to avoid them. Experimental results, however, suggested that UV avoidance can exist. In this study field data from eight Finnish lakes with different characteristics were analysed. The aim of the study was to determine whether vendace larvae stayed deeper in the water column during sunny than during cloudy periods because thick cloud cover considerably reduces UV irradiance. In addition, avoidance behaviour of larvae was studied in acrylic tubes placed in a lake and under laboratory conditions. The avoidance of high UV-B exposure existed both in the littoral and pelagic zone of the lakes and in laboratory with low UV attenuation. In the lakes with high UV attenuation, avoidance behaviour did not exist. Vendace larvae may use visible light as an indirect indicator of harmful UV-B irradiance.
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  • 38
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  The objectives of this study were, first, to assess the usefulness of otolith microstructure analysis to examine winter size-selective mortality of young-of-the-year (YOY) Atlantic salmon and, secondly, to validate various hypotheses relating to the dynamics of two populations with different winter survival. By examining otolith microstructure, we back-calculated body size at hatching and at emergence of YOY salmon sampled in fall 2000 and in early summer 2001 on the Petite Cascapédia River and the Bonaventure River (Québec, Canada). The results of the study did not reveal any size-selective mortality of YOY salmon in the Petite Cascapédia River, while in the Bonaventure River, size-selective mortality of the smaller individuals of the cohort was detected. This case study allowed not only a better comprehension of the population dynamics of those rivers but demonstrated the usefulness of otolith analysis to detect winter size-selective mortality under a natural environment.
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  • 39
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  Three sympatric whitefish (Coregonus lavaretus (L.)) forms, one being pelagic and two benthic, segregate available habitat and food resources in subarctic Lake Muddusjärvi, northern Finland. Zooplankton availability in the lake, food composition, diet-overlap and growth of densely rakered (DR) whitefish were examined during June to September to explore the reasons for the small individual size of the pelagic form. DR whitefish used zooplankton as main food item and prey selection followed zooplankton species density proportions in the lake. Zooplankton density and water temperature was highest in July–August. The average lengths of Bosmina spp., Daphnia spp., Calanoida and Cyclopoida in DR whitefish stomach were higher than in zooplankton sample during June–September, except Calanoida in June. Diet-overlap between DR whitefish age groups was high at all months indicating intercohort resource competition. DR whitefish reached sexual maturity at 3 years of age and at the length of 12 cm, after which somatic growth almost ceased. Reason for the small average size and slow growth of DR whitefish were connected to high diet-overlap between age groups and early sexual maturation.
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  • 40
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  Along a stream, we investigated whether the abundance of stone loach (Barbatula barbatula, L.) was related to the presence of brown trout (Salmo trutta, L.) and instream habitat variables. First, a field survey was carried out where different habitat variables and the densities of both species were quantified and subjected to principal components analysis. Then the abundance of stone loach was related to the scores of the retained axes (eigenvalues 〉1). The abundance of stone loach was positively correlated to substrate particle size, amount of shade, temperature, discharge and current velocity, but negatively correlated to brown trout abundance. Secondly, a month-long field enclosure experiment in a stream was performed to test for any negative effects of brown trout on stone loach growth. Four treatments were used: intraspecific competition (stone loach at double density), interspecific competition (stone loach + small trout), predation (stone loach + large trout) and a control (stone loach alone). The results showed that large trout tended to have negative effects on final stone loach biomass. The absence of a negative effect of large trout on resource density suggests that nonlethal effects rather than resource competition caused this trend.
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  • 41
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  This study aimed to evaluate otter predation on stocked trout. Large hatchery-reared trout (16–30 cm) were stocked into two Danish rivers with different fish populations. Otter diet before and after trout stocking was determined by analysing 685 spraints, collected regularly during the 35-day study period. Fish composition in the rivers before stocking was assessed by electrofishing. In River Trend, a typical trout river, the proportion of trout in the otter diet increased from 8% before stocking to 33% a few days after stocking. Moreover, trout lengths in the diet changed significantly towards the lengths of stocked trout, indicating that newly stocked trout were preferred to wild trout. In River Skals, dominated by cyprinids, there was no change in otter diet after stocking of hatchery trout, i.e., these were ignored by otter. Otter predation should be taken into account together with fish and bird predation, when stocking is used as a measure for conserving endangered salmonid populations.
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  • 42
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract – During 6 November to 24 December 2000, 23 tigerfish [(Hydrocynus vittatus), 30–54 cm] were tagged with radio transmitters in the Zambezi River (Namibia) to record habitat utilisation during low, rising and high water levels. The fish were tracked, on average, every fourth day during 23 November to 18 May. Two movement patterns were detected. Approximately 50% of the fish moved 〈1000 m among tracking surveys, staying within ‘defined’ home ranges. The remaining fish showed consistent site fidelity for periods, with long distance movements (〉1000 m) to new areas among residency periods. Overall, mean distance moved between tracking surveys was 1447 m. Home range size varied among individuals, with a 95% probability of localisation within an average area of 276,978 m2. The fish utilised a mean river stretch of 18,836 m (range = 90–71,840). All the fish were recorded in the main stem, and on average, 95% of the fixes were in the main stem during low water. However, the fish used temporary flooded areas to an increasing extent during the rising and high water period, but did not undertake long-distance migrations into the floodplains. Fish were sometimes near vegetation, but were never recorded into or under vegetation.
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  • 43
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract – The objective was to compare juvenile salmon density in 20 streams throughout the very large River Tana, northern Norway, and to relate variation in density to a suite of environmental factors. Four sampling sites were electrofished in each stream (one at the mouth of the stream and three within the stream) in August and October 2000, 2001, 2002. 0+ salmon parr were absent from seven streams, present at the mouth of 11 streams, and present within only two streams, both of which were probably spawning streams. Older parr migrated upstream into most streams and their highest densities were usually found in streams flowing directly into the spawning habitat in the three largest tributaries of the Tana or the river itself. Juvenile salmon were sparse or absent in streams flowing into smaller tributaries. Most streams with high parr densities were those of dense riparian vegetation that provided terrestrial invertebrates as drift food for the salmon parr, cover for fish, cooler stream temperatures in summer, and food for benthic stream invertebrates that were also a source of food for the parr.
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  • 44
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract – The size structure of a predator population can cause differences in the relative survival of different prey length classes whereby the biggest prey may reach a safe size because of the size-dependent character of predation. In the present study, the diet of European catfish was investigated to examine if catfish feeding can prevent cyprinids from reaching such a size refuge. In the lake studied, catfish was stocked for biomanipulation purposes to reduce unwanted roach and bream populations. Crayfish and roach were the most important prey items of catfish. If only species composition in the diet was considered, no clear changes were recorded in relation to catfish size. However, the length of roach as prey significantly increased with catfish length. Catfish were significantly larger than the other piscivorous fish in the lake, but took relatively smaller roach in comparison with similar-sized pike or pikeperch. Nevertheless, because of the high mean length of catfish, roach cannot reach a size refuge. For unknown reasons, the expected and intended predation on bream was not observed. Catfish took smaller prey than could be expected from mouth gape data. By extending the relationship between catfish as predator and roach as prey beyond the predator length range currently found in the lake, it could be shown that even catfish of 150 cm length will probably feed upon only 65% of all available bream length classes. Therefore, stocking with catfish cannot prevent a size refuge for the bream.
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  • 45
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  We examine patterns in fish species assemblages in the Toxaway and Horsepasture rivers, two high elevation streams in North Carolina, USA. This region is noted for extreme topographical relief, high cumulative annual rainfall and many rare and endemic plants and animals. The study area encompasses a portion of the Blue Ridge Escarpment and the associated Brevard Fault Zone. We hypothesise that major waterfalls and cascade complexes have acted to limit invasion and colonisation by fishes from downstream. This hypothesis is supported by longitudinal fish assemblage patterns in our study streams. Fish species richness in Toxaway River increased from 4 to 23 between Lake Toxaway and Lake Jocassee, a distance of 10 river km. We found similar discontinuities in neighbouring Horsepasture River and Bearwallow Creek. We found no instances of species replacement along this elevation gradient, and the trend in increased diversity downstream showed discontinuities coincident with sharp elevation breaks. With regard to theories posited to explain community formation in headwater stream fish communities (especially in those characterised by high topographical relief), we suggest coloniser ‘access’ may be more important than other factors including competitive interactions.
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  • 46
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    Oxford, UK : Munksgaard International Publishers
    Ecology of freshwater fish 14 (2005), S. 0 
    ISSN: 1600-0633
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract –  The timing of the smolt migration of Atlantic salmon, Salmo salar L., was investigated during 1972–2002 in the Simojoki, a river flowing into the northern Baltic Sea. The onset of the smolt run was positively correlated with the river water temperature; a rise in water temperature above 10 °C being the main proximate environmental triggering factor. There was also a weaker correlation between the decreasing river discharge in the spring and the onset of the smolt migration. The duration of the main run was shorter in the years when the onset of the smolt run was delayed. No differences were found in the onset timing or in the duration of the smolt run between wild smolts and semi-wild smolts released into the river as parr. A polynomial equation fitted to the annual data on the survival of Carlin-tagged wild smolts and the sea surface temperature (SST) in June off the river mouth appeared to follow a dome-shaped pattern. Survival was lower in cold early summers (SST 〈9 °C) than in those with an average SST (9–11.9 °C), and lower again, although not significantly, in warm early summers (SST ≥12 °C). Too low and probably also too a high water temperature in early summer could thus be one of the underlying reasons for the fluctuations observed in postsmolt survival in the Baltic Sea.
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  • 47
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Clinical evidence of correlations between menopause and endogenous skin aging gave input to various studies investigating the relevance of estrogens for skin functions that are associated with skin aging and their possible therapeutic effects. Skin thickness and bone density are significantly decreased already six months after menopause and are increased after the same period of hormone replacement (HRT). Fibroblast and keratinocyte function is stimulated by estrogen application, and among other effects significant increases of collagen fibres have been demonstrated six months after the onset of HRT (1). Topical use of estrogen compounds was found to diminish skin aging symptoms. The effects of conjugated estrogens (0,625% Premarin) were studied in 60 postmenopausal women (2). In another study the effects of estradiol 0,01% and estriol 0,3% were compared (3). Both studies documented significant reductions of wrinkles without any systemic side effects of the treatments. Recently significant increases of epidermal thickness during estradiol have been described (4). For cosmetic purposes phytoestrogens seem a promising alternative to the medical treatment. Isoflavone containing cosmetical creams were shown to improve skin dryness and wrinkles (5). In various studies mainly beneficial effects of systemic HRT on skin aging parameters have been documented. Although skin aging is certainly no indication for systemic hormone supplementation the beneficial action of such treatment on aging symptoms of the skin are a positive side aspect of such treatment.
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  • 48
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previously it has been demonstrated that the human epidermis synthesizes and degrades acetylcholine and expresses both muscarinic and nicotinic receptors. These cholinergic systems have been implicated in the development of the epidermal calcium gradient and differentiation in normal healthy skin. In vitiligo severe oxidative stress occurs in the epidermis of these patients with accumulation of H2O2 in the 10−3M range together with a decrease in catalase expression/activity due to deactivation of the enzyme active site. It was also shown that the entire recycling of the essential cofactor (6R)-L-erytho 5, 6, 7, 8 tetrahydrobiopterin via pterin-4a-carbinolamine dehydratase (PCD) and dihydropteridine reductase (DHPR) is affected by H2O2 oxidation of Trp/Met residues in the enzyme structure leading to deactivation of these proteins. Using fluorescence immunohistochemistry we now show that epidermal H2O2 in vitiligo patients yields also almost absent epidermal acetylcholinesterase (AchE) in association with accumulation of epidermal acetylcholine. This result was confirmed by Fluorescence excitation spectroscopy following the Trp fluorescence at λmax 280 nm. A kinetic analysis using pure recombinant human AchE revealed that low concentrations of H2O2(10−6M) activate this enzyme by increasing the Vmax 〉 2 fold, meanwhile high concentrations of H2O2(10−3M) deactivate the enzyme with a significant decrease in Vmax. Molecular modelling based on the established 3D structure of human AchE supported that H2O2-mediated oxidation of Trp432, Trp435 and Met436 moves and disorients the active site His440 of the enzyme, thus explaining the deactivation of the protein. To our knowledge these results identified for the first time H2O2 regulation of AchE. Moreover, it was shown that H2O2-mediated oxidation of AchE contributes significantly to the well established oxidative stress in vitiligo.
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  • 49
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Melanocortin receptors (MC-Rs) mediate the biological actions of the members of melanocortin family, e.g. of α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin. We recently reported that human dermal fibroblasts derived from newborn foreskin express MC-1R. In these cells and in a newborn mouse model of cutaneous fibrosis, α-MSH suppressed collagen synthesis induced by the profibrotic cytokine transforming growth factor-β1(Böhm et al., J. Biol. Chem. 2004). Here, we show that MC-1R expression is maintained in various fibroblastic skin cell types established from adult human skin. In vitro, expression of MC-1R at the RNA level was detected by RT-PCR analysis in dermal fibroblasts, dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle, as well as in HT1080 fibrosarcoma cells. In all of the latter cell types except in HT1080 cells, MC-1R immunoreactivity could be visualized on the cell surface as demonstrated by immunofluorescence studies using an antibody against the amino acids 2–18 of the N-terminal domain of human MC-1R. In situ, MC-1R expression was detectable in interfollicular dermal fibroblasts only by immune electron microscopy. In contrast, MC-1R expression was detectable in dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle by conventional immunohistochemistry. To further assess the relevance of MC-1R being expressed in fibroblastic cells of the skin we treated human dermal fibroblasts in vitro with the proinflammatory cytokine interferon-γ(IFN-γ). α-MSH significantly suppressed the upregulating effect of this cytokine on the expression of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule crucially involved in recruitment of activated leukocytes into the hair follicle. In summary, our findings form a basis upon which MC-1R expression can be investigated in inflammatory disorders affecting the connective tissue compartment of the skin. Moreover, our preliminary data on the modulation of IFN-γ-driven upregulation of ICAM-1 by α-MSH suggest additional functions of melancortins in fibroblasts beyond collagen synthesis.
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  • 50
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 51
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 52
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 53
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 54
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 55
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Mast cells (MCs) have been intensely investigated over the past two decades, e.g. the numbers of PubMed-listed reports on MCs have steadily increased and doubled over the past twenty years. Surprisingly, many recent findings that have fundamentally changed our understanding of MC biology and functions have yet to be sufficiently recognized by scientists interested in cutaneous biology and clinical dermatologists. The aim of this study is to review recent hallmark contributions to the field of MC research, to outline the development of our current knowledge of MCs, and to predict the outcome of future MC research efforts. The development of straightforward rodent in vivo models has allowed for the identification and characterization of various novel MC functions. MC effects are not limited to the induction of pathology, but can serve important functions in maintaining health and preventing disease. Attempts to better define the role of MCs in the human system may lead to novel strategies for treating inflammatory disorders and could eventually allow us to utilize MCs for improving responses to environmental danger signals.
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  • 56
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Autoimmune diseases are characterized by defined self-antigens, organ specificity, autoreactive T cells and/or autoantibodies that can transfer disease. Autoimmune blistering diseases are organ-specific autoimmune diseases associated with an immune response directed to structural proteins mediating cell–cell and cell–matrix adhesion in the skin. While both autoreactive T and B cells have been detected and characterized in patients with autoimmune blistering diseases, current evidence generally supports a pathogenic role of autoantibodies for blister formation. The immunopathology associated with blisters induced by autoantibodies relies on several mechanisms of action. Autoantibodies from patients with pemphigus diseases can exert a direct effect just by binding to their target mediated by steric hindrance and/or by triggering the transduction of a signal to the cell. In most subepidermal autoimmune blistering conditions, in addition to the binding to their target antigen, autoantibodies need to interact with factors of the innate immune system, including the complement system and inflammatory cells, in order to induce blisters. Generally, decisive progress has been made in the characterization of the mechanisms of blister formation in autoimmune skin diseases. However, various aspects, including the exact contribution of steric hindrance and signal transduction for pemphigus IgG-induced acantholysis or the fine tuning of the inflammatory cascade triggered by autoantibodies in some subepidermal blistering diseases, still need to be addressed. Understanding the mechanisms by which autoantibodies induce blisters should facilitate the development of more specific therapeutic strategies of autoimmune blistering diseases.
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  • 57
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  The goal of this study was to compare the effects of the Q-switched 1064-nm Nd:YAG laser and the 1320-nm Nd:YAG laser non-ablative treatments on mouse skin in vivo. Skin elasticity measurements were carried out with a Reviscometer, and skin samples were taken for histological study, hydroxyproline content assay and estimation of collagen type I and III. By the second month after non-ablative treatments, the 1064-nm laser treatment resulted in an average of 25% greater improvement of skin elasticity, 6% more increase of dermal thickness, and 11% higher synthesis of hydroxyproline than the 1320-nm laser. Collagen type III increased markedly after the 1064-nm laser treatment whereas more collagen type I was elicited by the 1320-nm laser. Our results demonstrated that the 1064-nm laser was more effective than the 1320-nm Nd:YAG laser in non-ablative treatments, but the results needed to be confirmed in humans. It appeared that photo-mechanic reaction could cause more collagen type III synthesis whereas the photo-thermal effect was in favor of the formation of collagen type I.
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  • 58
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Lipoid proteinosis (LP) (OMIM 247100) is a rare, autosomal recessive disorder. Recent studies have shown that LP is the result of reduced expression of the extracellular matrix protein gene (ECM-1), in which loss-of-function mutations have been described. In the present report, we describe a large consanguineous family with LP. We identified a homozygous splice-site mutation in intron 1 (IVS1 + 1G→C) in three clinically affected patients. This is the first splice-site mutation reported in LP and is the most 5′ of all ECM-1 mutations described thus far. It is predicted to result in the removal of the translation initiation site, thus ablating all three known ECM-1 isoforms (ECM-1a, ECM-1b, and ECM-1c). In addition, we found a novel splicing variant that is not associated with the disease (DQ010946) and results in the generation of a short, prematurely terminating transcript. This case further emphasizes the role of ECM-1 in LP and highlights the unresolved genotype–phenotype correlation in this disease.
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  • 59
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 60
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    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
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  • 61
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Primary human keratinocytes (PHKs) are known to express the EP3 subtype of prostaglandin E2 receptor. To better understand the role of EP3 receptors in regulating epidermal function, we characterized their expression, localization, and signaling effects in human skin. Three different splice variants of the EP3 receptor (EP3A1, EP3C, and EP3D) were found to be expressed. Immunohistochemical analysis of human skin demonstrated that EP3 receptors were most prominently expressed in the basal and lower spinous layers of the epidermis. The EP3 receptor agonist sulprostone was then used to examine EP3 receptor-dependent keratinocyte signaling pathways and functional effects. We observed that sulprostone inhibits keratinocyte growth at doses between 0.02 and 2 nM and induces sn-1,2-diacylglycerol (DAG) and ceramide production. Concurrent expression of the cell-cycle inhibitory protein p21WAF1 also occurred. These data suggest that EP3 receptors produce epidermal growth inhibition through the action of DAG and ceramide second messengers.
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  • 62
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  NC/Nga mice have pathological and behavioral features similar to those seen in human atopic dermatitis. There are two known dermatitis models in NC/Nga mice, one being spontaneous-induced dermatitis under conventional conditions and the other 2,4,6-trinitrochlorobenzene (TNCB)-induced allergic contact dermatitis. However, there are significant differences in time course on development of dermatitis. We studied the role of scratching behavior (sign of itch) on the development of dermatitis on spontaneous- and TNCB-induced dermatitis. We measured scratching counts, transepidermal water loss (TEWL), and skin inflammation score, under conventional conditions or by applying 5% TNCB once a week for 6 weeks in NC/Nga mice. In spontaneous-induced dermatitis, scratching counts increased with the passage of time. The scratching counts were significantly increased only 1 week after housing the mice under conventional conditions, but no changes were observed in cases of TNCB-induced dermatitis. In spontaneous-induced dermatitis, TEWL and skin-inflammation score were gradually increased, time-dependently. On the other hand, in TNCB-induced dermatitis, these dependent values rapidly increased and reached a maximum only after 24 h TNCB application. These data suggest that pathogenesis of spontaneous- and allergic contact-induced dermatitis was clearly different. It will be of major interest to identify the pruritic mediators causing profound scratching behavior and scratching-induced aggravation of inflammation in the spontaneous-induced dermatitis, as opposed to the inflammatory mediators that cause contact allergic dermatitis without major scratching.
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  • 63
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    Topics: Medicine
    Notes: Abstract:  To identify differentially expressed genes which play causal roles in pathogenesis and maintenance for psoriasis, we used BodyMapping and introduced amplified fragment length polymorphism approaches. From the BodyMap database, we selected 2007 genes which specifically expressed in epithelial tissues. Among 2007 genes, we surveyed genes which differentially expressed in involved or uninvolved psoriatic lesional skin samples compared with atopic dermatitis, mycosis fungoides, and normal skin samples. As a result of surveying 2007 genes, 241 genes were differentially expressed only in involved psoriatic skin but not in the other samples. Hierarchical cluster analysis of gene expression profiles showed that 13 independent psoriatic-involved skin samples clustered tightly together, reflecting highly similar expression profiles. Using the same 2007 gene set, we examined gene expression levels in five serial lesions from distal uninvolved psoriatic skin to involved psoriatic plaque. We identified seven genes such as alpha-1-microglobulin/bikunin precursor, calnexin, claudin 1, leucine zipper down-regulated in cancer 1, tyrosinase-related protein 1, Yes-associated protein 1, and unc-13-like protein (Coleonyx elegans) which show high-expression levels only in uninvolved psoriatic lesions. These seven genes, which were reported to be related to apoptosis or antiproliferation, might have causal roles in pathophysiology in psoriasis.
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  • 64
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    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  An amphiphilic tetracationic derivative of Zn(II)-phthalocyanine (RLP068) was prepared by means of chemical synthesis and was showed to possess efficient photophysical and photosensitizing properties against model biological substrates. RLP068 was incorporated into a gel formulation, which allowed its ready penetration into the epidermal layers, but not into the dermis, of both Balb/c and hairless SKH1 mice after 1–2 h of topical deposition. Pharmacokinetic studies showed that the phthalocyanine thus formulated does not enter the general blood circulation. The epidermis-associated amount of phthalocyanine was sufficient to cause an important cutaneous damage upon irradiation with red light (600–700 nm; 100–180 mW/cm2, 160 J/cm2); the latter was confined to the epidermal area with no apparent diffusion to the underlying dermal layers or appearance of photosensitivity in distal skin areas. A systematic investigation of the interplay among the different parameters (deposition time of the formulated phthalocyanine on mouse skin, irradiation fluence rate and total light fluence) allowed us to identify the minimal phototoxic dose, as well as to define irradiation protocols allowing the repeatability of the phototherapeutic treatment. The potential of RLP068 to act as a PDT agent for cutaneous diseases is briefly discussed.
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  • 65
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Three variants of the living skin equivalent cultures were compared in order to determine the most suitable to grow human differentiated epidermis to test beneficial properties of nutrients. Criteria of culture quality were mitotic index and transepidermal water loss (TEWL) assayed by means of a ServoMed Evaporimeter EP-2TM (ServoMed, Kinna, Sweden). Standards were donor skin mean mitotic index 11.1% and TEWL of living subjects mean 6.4 g/m2/h. Cultures (i) in 5% serum, 10 ng/ml of epidermal growth factor (EGF) at 37°C and 95% relative humidity (RH); mitotic index on day 14, 19.2%, but on day 21, 1.8% and TEWL 9.5 g/m2/h on day 18. (ii) In 1% serum, no EGF, 33°C and 95% RH, mitotic index on day 21, 9.1% and TEWL, 9.5% on day 18. (iii) Culture in same medium, 33°C and 60% RH, mitotic index on day 28, 9.5% and TEWL 6.1 g/m2/h on day 18 as in vivo. Incubation in 60% RH was achieved using a novel chamber and dishes exposing only the corneum, sealing the medium. Vitamins C and E were used as model test nutrients. Culture conditions were 1% serum, no EGF at 33°C and 95% RH. Vitamin C at 142 and 284 µM increased the mitotic index after 10- and 15-day treatment, but at 586 µM it was weakly toxic. Vitamin E at 20 and 40 µM did not. Both vitamins reduced TEWL providing functional data in support of previous reports on barrier properties. These are functional biomarkers of skin benefit relevant to skin in vivo.
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  • 66
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Epimorphin is representative of a unique class of stromal membrane-anchored proteins that plays distinct functions depending on its membrane topology. When exposed extracellularly, this molecule acts as a morphoregulator for various tissues including hair follicle epithelia. Previous study identified its functional domain (the pep7 domain: SIEQSCDQDE) for hair follicular morphogenesis followed by the successful generation of a chemically modified active peptide. Here, we report optimization of this peptide by the introduction of sequential mutations and subsequent structural determination. We found that three residues from the C-terminus are dispensable, and alternation of the seventh amino acid to an Alanine residue enhanced activity. To favour the biologically active conformation, ε-Acp (NH(CH2)5CO) linked to a Cysteine residue was connected at the N-terminus followed by the introduction of an intramolecular disulphide bridge, the modification process of which could be included in the peptide synthesis. The obtained modified peptide, termed ‘EPM (epimorphin-derived) peptide’, has a Mw of 950 Da and exerts an inductive effect on hair follicle regeneration at a concentration of approximately 0.00001% or even lower. The action of this EPM peptide was more apparent in mice treated with 1% minoxidil, suggesting its potential clinical benefit as a new type of hair-regenerating agent.
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  • 67
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    Topics: Medicine
    Notes: Abstract:  CD44 and l-selectin (CD62L) are major adhesion receptors that mediate leucocyte recruitment at inflammatory sites and lymph nodes, by supporting cell rolling under blood flow. Both CD44 and CD62L have been implicated in inflammatory skin disorders, but their specific involvement in an immediate-type allergic reaction remains uncertain. We used mice deficient in CD44 or CED62L or both in order to determine whether one or both of these molecules were required for leucocyte extravasation in an atopic dermatitis-like allergic response. Wild-type (WT) mice and mice deficient in CD44, CD62L or both were immunized with ovalbumin (OVA). Inflammatory reaction in the ear was elicited once by means of intradermal injection of OVA. Effective sensitization of CD62L knockout (KO) mice required intraperitoneal antigen injection; however, OVA-specific T helper 2 (Th2)-type immune responses and IgE production in mice lacking CD44, CD62L or both were comparable to those in WT mice following intraperitoneal immunization. We employed intravital videomicroscopy to monitor the recruitment of fluorescence-labelled leucocytes to the ear tissue following challenge with OVA. The number of adherent leucocytes was significantly reduced in CD44 KO and CD44/CD62L double KO mice, indicating that CD44 was involved in firm adhesion, the committed step of leucocyte extravasation. Histology of the OVA-challenged ears showed a diminished leucocyte infiltration in the ears of CD44 KO and double KO mice. The results of our study demonstrate that CD44, but not CD62L, is required for leucocyte extravasation during a Th2-type inflammatory response.
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  • 68
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Lymphocyte trafficking through the dermal compartment is part of the physiological surveillance process of the adaptive immune system. On the other hand, persistent or recurrent lymphocyte infiltrates are hallmarks of both types of chronic inflammatory skin diseases, Th1-type such as psoriasis or Th2/allergic-type like atopic dermatitis. A better understanding of the mechanisms underlying lymphocyte movements is one of the key prerequisites for developing more effective therapies. In this review, we introduce a range of simple-to-sophisticated experimental in vitro and in vivo approaches to analyze lymphocyte migration. These methods start from static in vitro adhesion and chemotaxis assays, include dynamic endothelial flow chamber, intravital dual photon, and transcutaneous live-video microscopy, and finally encompass specific genetically deficient or engineered animal models. Discussing pros and cons of these assay systems hopefully generates both state-of-the-art knowledge about the factors involved in most common chronic skin diseases as well as an improved understanding of the limitations and chances of new biologic pharmaceuticals that are currently introduced into clinical practice.
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  • 69
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Tumor–stroma interactions play a decisive role in the growth and metastasis of solid tumors, and involve signalling either by soluble mediators or direct cell–cell interaction. Here, we report the isolation and characterisation of a novel cDNA (MEL4B3), which is induced in cultured dermal fibroblasts exposed to supernatants of melanoma cell lines. MEL4B3 shares high homology with two predicted cDNA sequences for which no activity has so far been described. In situ hybridisation revealed the expression of MEL4B3 in malignant melanoma increasing with tumor depth; in basal cell carcinoma and in squamous cell carcinoma. MEL4B3 was barely detectable in normal skin or non-malignant melanocytic naevi. Furthermore, MEL4B3 was expressed at high level in the epidermis of psoriatic skin. In vitro, the expression of MEL4B3 was found to be induced by the exposure of human dermal fibroblasts to melanoma cell culture supernatants or to transforming growth factor-β, interleukin-1 and tumor necrosis factor-α. The expression MEL4B3 therefore reflects closely cell activation occurring during tumor growth, metastasis and inflammation.
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  • 70
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  In a previous study, we reported that α-hydroxy acids (AHA), such as glycolic acid and lactic acid, did not induce any significant changes in transepidermal water loss for normal murine skin. The ultrastructural observations, however, showed that the extent of lamellar body exocytosis significantly increased. Because AHA can theoretically decrease the calcium ion concentration by chelation, topical AHA may induce the loss of epidermal calcium gradient by lowering the calcium ion concentration in the granulocytes and, subsequently, induce lamellar body secretion. The aim of this study is to verify that glycolic acid could modulate the epidermal calcium gradient and increase lamellar body exocytosis. Seventy per cent of glycolic acid aqueous solution was applied to the normal skin of hairless mice and biochemical and morphological studies were performed. The loss of epidermal calcium gradient was observed in glycolic-acid-applied skin of hairless mice and subsequent barrier function recovery processes, such as an increase in lamellar body secretion, were observed. The extracellular glycolic acid was found to inhibit the change in intracellular calcium ion concentration in response to extracellular calcium ion concentration changes in the cultured mouse keratinocyte in vitro. The protein and mRNA expressions of tumour necrosis factor-α and interleukin-1α in the murine epidermis were significantly increased after glycolic acid application. An in vitro study using cultured keratinocytes suggested that glycolic acid could lower the calcium ion concentration, at least in part, through the chelating effects of the glycolic acid on the cationic ions.
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  • 71
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Pemphigus foliaceus (PF) is a severe autoimmune bullous disorder, characterized by autoantibodies (autoAb) against desmoglein 1 (Dsg1). As T cells may be critical in the pathology of PF, the aim of the present study was to identify and characterize autoaggressive T-helper cells reactive to Dsg1 in PF patients and healthy individuals. Eight patients with the clinical diagnosis of PF and six HLA class II-matched healthy individuals were examined. By magnetic cell-sorting (MACS) cytokine-secretion assay, Dsg1-responsive T-helper (Th) 1 and Th2 cells were isolated and cloned by limiting dilution. The generated T-cell clones (TCC) were characterized regarding proliferative response, TCR Vβ-chain usage, and cytokine profile upon in vitro stimulation with Dsg1. Both Dsg1-reactive Th1 and Th2 cells were detected in PF patients and controls at similar frequencies. A total of 15 Th1 and Th2 clones were isolated from patients and 27 TCC from healthy controls. Analysis of TCR Vβ-chain usage of autoreactive T cells from both groups revealed no predominance of a specific Vβ chain. Noteworthy, the isolated TCC showed a polarized Th1- or Th2-like phenotype upon in vitro culture and stable expression of Th1 or Th2 cytokines during long-term in vitro culture. In summary, our data demonstrate that T-cell autoreactivity against Dsg1 is not restricted to patients with PF. Moreover, both Th1 and Th2 cells were present in patients and healthy donors, suggesting that the loss of B-cell tolerance against Dsg1 in PF is not exclusively determined by the presence of autoaggressive T cells.
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  • 72
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    Experimental dermatology 14 (2005), S. 0 
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Studies of human hair follicle (HF) induction by follicle-derived cells have been limited due to a lack of suitable test systems. In this study, we established a skin organ culture system which supports HF formation by follicle-derived cells. Long-term skin organ cultures were set up from human retroauricular skin specimens and maintained in culture for up to 8 weeks. In vitro expanded human HF-derived cells from the dermal papilla (DP) and the outer root sheath (ORS) were injected together into the skin specimens and evaluated for their ability to induce reorganization of HFs. Macroscopic analysis of the cultured skin specimens demonstrated the growth of velus-like hair after 4 weeks in culture. Histologic evaluation of the cultured skin specimens after 8 weeks of culture revealed multiple miniaturized HFs with sebaceous glands. In addition, cell clusters of various differentiation stages could be demonstrated in serial sections of the cultured skin specimens. Labeling of HF-derived cells with the fluorescence dye CFDA-1 prior to injection suggested a de novo reorganization of HFs out of the injected cells. In conclusion, the study demonstrated HF formation by HF-derived cells in an in vitro skin organ culture model.
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  • 73
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Munksgaard International Publishers
    Experimental dermatology 14 (2005), S. 0