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  • 1
    Electronic Resource
    Electronic Resource
    E- and P-cadherin expression during murine hair follicle morphogenesis and cycling (1999)
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 8 (1999), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The role of adhesion molecules in the control of hair follicle (HF) morphogenesis, regression and cycling is still rather enigmatic. Since the adhesion molecules E- and P-cadherin (Ecad and Pcad) are functionally important, e.g. during embryonic pattern formation, we have studied their expression patterns during neonatal HF morphogenesis and cycling in C57/BL6 mice by immunohistology and semi-quantitative RT-PCR. The expression of both cadherins was strikingly hair cycle-dependent and restricted to distinct anatomical HF compartments. During HF morphogenesis, hair bud keratinocytes displayed strong Ecad and Pcad immunoreactivity (IR). While neonatal epidermis showed Ecad IR in all epidermal layers, Pcad IR was restricted to the basal layer. During later stages of HF morphogenesis and during anagen IV-VI of the adolescent murine hair cycle, the outer root sheath showed strong E- and Pcad IR. Instead, the outermost portion of the hair matrix and the inner root sheath displayed isolated Ecad IR, while the innermost portion of the hair matrix exhibited isolated Pcad IR. During telogen, all epidermal and follicular keratinocytes showed strong Ecad IR. This is in contrast to Pcad, whose IR was stringently restricted to matrix and secondary hair germ keratinocytes which are in closest proximity to the dermal papilla. These findings suggest that isolated or combined E- and/or Pcad expression is involved in follicular pattern formation by segregating HF keratinocytes into functionally distinct subpopulations; most notably, isolated Pcad expression may segregate those hair matrix keratinocytes into one functional epithelial tissue unit, which is particularly susceptible to growth control by dermal papilla-derived morphogens. The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0625.1999.tb00377.x
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  • 2
    Electronic Resource
    Electronic Resource
    Inhibition of cytokine secretion from human leukemic mast cells and basophils by H1- and H2-receptor antagonists (2000)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 9 (2000), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: H1-type antihistamines have recently been reported to inhibit cytokine secretion from human and murine mast cells and basophils. In order to confirm and expand these studies, we have compared several H1-blockers and the H2-blocker ranitidine for their effect on TNF-α, IL-3, 6, 8 and GM-CSF release from human leukemic mast (HMC-1) and basophilic (KU812) cells, compared to dexamethasone. Cells were stimulated for 24 h with phorbol myristate acetate (25 ng/ml) and calcium ionophore A 23187 (2.5×10−7 M) alone or with the drugs added at 10−4 to 10−15 M, and production of cytokines was measured by ELISA. All antihistamines caused a dose-dependent inhibition of TNF-α release from HMC-1 cells, with maximal effects at 10−12 M for azelastine, 10−9 M for loratadine and cetirizine, and 10−8 M for ranitidine. The inhibitory potency of H1-blockers on cytokines from HMC-1 cells was TNF-α 〉IL-8≥IL-6≥IL-3, with no significant effects on GM-CSF. In KU812 cells which failed to secrete TNF-α and GM-CSF, the sequence was IL-6 〉IL-8 after preincubation. Dexamethasone inhibited all cytokines, but ranitidine only TNF-α and IL-3. Antihistamines had no effect on calcium flux in resting or stimulated cells. At the mRNA level, inhibition was only seen with KU812 cells and IL-8 in the presence of azelastine at 10−10 M. These data show thus distinct inhibitory patterns for different antihistamines during cytokine production from human mast cells and basophils which may contribute to the anti-inflammatory effects of these drugs during treatment of allergic diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2000.009002118.x
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  • 3
    Electronic Resource
    Electronic Resource
    Human skin mast cells rapidly release preformed and newly generated TNF-α and IL-8 following stimulation with anti-IgE and other secretagogues (2001)
    Copenhagen : Munksgaard International Publishers
    Experimental dermatology 10 (2001), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Several groups have previously reported that rodent or human leukemic mast cells produce inflammatory cytokines such as TNF-α and IL-8 as well as the pro-allergic cytokines IL-4, IL-5 and IL-13. Comparatively little is known, however, regarding the ability of normal human skin mast cells to secrete these factors following either IgE-dependent or IgE-independent modes of activation. We therefore investigated whether normal human skin mast cells produce these cytokines following stimulation by a variety of secretagogues. Enriched isolated skin mast cells released both TNF-α and IL-8 following activation with either anti-IgE, SCF, substance P, compound 48/80 or A23187. This release was dose- and time-dependent, with maximal levels being reached within 4 h of stimulation involving, in part, the secretion of preformed stores of both cytokines. In accordance with this, using lysates of highly purified (〉90%) skin mast cells, we could demonstrate that both TNF-α and IL-8 mRNA and protein were present in both unstimulated as well as stimulated mast cells. In stark contrast to these results, no significant levels of either IL-4, IL-5 or IL-13 were detected, regardless of the secretagogue used or the period of stimulation. These results show that human skin mast cells are capable of rapidly secreting pro-inflammatory cytokines like TNF-α and IL-8 following IgE-dependent activation and stimulation by the neuropeptide substance P, SCF and the basic polypeptide analogue compound 48/80. In contrast to other types of human mast cells however, human skin mast cells were incapable of secreting IL-4, IL-5 or IL-13 in these settings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1034/j.1600-0625.2001.100503.x
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  • 4
    Electronic Resource
    Electronic Resource
    Alterations in ganglioside expression during the differentiation of human mast cells (1999)
    Oxford, UK : Blackwell Publishing Ltd
    Experimental dermatology 8 (1999), S. 0 
    Details
    ISSN: 1600-0625
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Gangliosides are physiological components of the outer cell membrane. In the present study, the role of ganglioside expression during differentiation of human mast cells was evaluated. After 11 days of culture in medium known to induce mast cell differentiation, 70% of peripheral blood mononuclear cells (PBMC) showed positive staining for the high affinity IgE receptor and tryptase on immunocytochemistry and an associated 20-fold increase of ganglioside GM3 expression. Furthermore, exogenous addition of GM3 during cultivation of PBMC in medium containing low levels of growth factors induced an increase of mast cell specific tryptase. The association of ganglioside expression with mast cell differentiation was confirmed by experiments with the human mast cell line HMC-1. FcɛRI-positive cultured cells enriched with immunobeads exhibited a 3-fold higher expression of GM3, compared to FcɛRI negative HMC-1 cells. Furthermore, measurable amounts of the gangliosides GM2, GM1 and GD1a were found only in the FcɛRI positive cells. A corresponding transient increase of mRNA for GalNAcT, the key enzyme in the production of these latter gangliosides, could be detected preceding the expression of these gangliosides and the FcɛRI by RT-PCR. Taken together, these data point to a functional role of gangliosides in the differentiation of human mast cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0625.1999.tb00386.x
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  • 5
    Electronic Resource
    Electronic Resource
    Optical coherence tomography in dermatology (1999)
    Oxford, UK : Blackwell Publishing Ltd
    Skin research and technology 5 (1999), S. 0 
    Details
    ISSN: 1600-0846
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background/alms: Optical coherence tomography is a new in vivo imaging tool originally developed to investigate the eye. We undertook a preliminary investigation of experimental and clinical dermatological applications.Methods: We obtained optical coherence tomography images of ethnic groups, of cutaneous changes induced by exposure to water and dimethyl sulfoxide, of corticosteroid atrophy and of acne vulgaris.Results: Optical coherence tomography was able to visualize specific structural changes in stratum corneum and viable epidermis in these diverse conditions.Conclusions: The high lateral and axial resolution of 4 urn and 7 μm, respectively, and the image quality of this prototype make optical coherence tomography a promising instrument for clinical and investigative dermatology.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0846.1999.tb00120.x
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  • 6
    Electronic Resource
    Electronic Resource
    Gene expression and regulation of transcription factor activator protein-2 alpha in human mast cells (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The transcription factor activator protein (AP)-2 regulates cell-type specific gene expression during development and differentiation, but its role in mast cell development has so far not been explored.Methods:  Gene expression and regulation of AP2 was assessed in normal skin, diseases with increased mast cell numbers, and in vitro models of mast cell differentiation.Results:  AP-2α-protein was not detectable in normal skin but in mastocytoma lesional mast cells. AP-2α-mRNA and -protein were also detected in leukemic mast cells (HMC-1), in the adherent fraction of peripheral blood (PBMC) and umbilical cord blood mononuclear cells (CBMC), and AP-2α-mRNA at low levels in isolated-purified mast cells. During culture with fibroblast supernatants or SCF, AP-2α-mRNA was de novo expressed in KU812-cells, maintained at about the same level in PBMC and CBMC, and upregulated in HMC-1-cells. On extended culture, a down-regulation was noted at mRNA and/or protein levels. In contrast, tryptase expression increased in all cells throughout culture, as did c-Kit in normal cells, whereas in both leukemic cell lines, c-Kit was maintained unchanged at about the same level.Conclusions:  These findings suggest a continuous activation of AP-2α in mastocytomas and mast cell leukemia and its transient upregulation during c-Kit dependent early steps of normal mast cell differentiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2005.00811.x
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  • 7
    Electronic Resource
    Electronic Resource
    Mast cells and vasculature in atopic dermatitis – potential stimulus of neoangiogenesis (2005)
    Oxford, UK : Munksgaard International Publishers
    Allergy 60 (2005), S. 0 
    Details
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Atopic dermatitis skin lesions are characterized by inflammatory changes and epithelial hyperplasia requiring angiogenesis. As mast cells may participate in this process via bidirectional secretion of tissue-damaging enzymes and pro-angiogenic factors, the present study aimed to assess the occurrence and possible function of mast cells in the papillary dermis and in epidermal layers of atopic dermatitis lesions.Methods:  Semi-thin and serial sections in combination with immunohistochemistry, histochemistry and proliferating cell nuclear antigen (PCNA)-activity assays were used and related to epidermal thickness and targeted gene expression studies.Results:  Mast cells were located in the papillary dermis and migrated through the basal lamina into the epidermis of atopic dermatitis lesions. An increased PCNA-activity in cells of superficial epidermal layers indicated an activation of keratinocytes and stimulation of endothelial growth. Only ∼30% of the papillary mast cells stained with the tryptase were toluidin-blue-positive, and ∼80% were chymase positive. A high number of mast cells expressed c-kit. Most papillary and epidermal mast cells were localized close to endothelial cells. Vascular expression of endoglin (CD105) demonstrated neoangiogenic processes. Mast cells stimulation led to the expression of proangiogenic factors. Also, gene expression of tissue-damaging factors such as matrix metalloproteinases was increased.Conclusions:  These data suggest that in atopic dermatitis, mast cells are abundantly localized close to and within the epidermis where they may stimulate neoangiogenesis. Via the new vessels, inflammatory cells, together with complement components and antibodies, can be transported to the epidermis to aid in the defense against environmental antigens and to maintain chronic inflammation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1398-9995.2004.00628.x
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  • 8
    Electronic Resource
    Electronic Resource
    Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P, identify distinct mast cell subtypes (1995)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 133 (1995), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary In order to identify more specific or selective mast cell markers, the reactivity of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic cell line KU812), in mast cells cultured from blood precursors, in adherent mononuclear cells from peripheral blood, and in mast cells of tissue sections from 1 3 urticaria pigmentosa lesions, live mastocytomas and live normal skin specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated avidin, and immunohistochemical staining (APAAP) with other mast cell reactive monoclonal antibodies, was performed for comparison. Double staining with the APAAP method, using the Ki-antibodies and toluidine blue, was also carried out. Both Ki-antibodies showed reactivity for skin mast cells, but with a different staining pattern. In addition, the Ki-MC1 antibody did not react with the cell lines, and reacted only with a few peripheral blood mononuclear cells and cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all cultured mast cells and blood mononuclear cells, but stained only about one-half of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa. Ki-MC1 antibody can thus be considered as a useful additional marker for normal skin mast cells. In contrast, the Ki-M1 P antibody primarily identifies immature mast cells and monocytes/macrophages, suggesting that these cell types probably originate from the same bone marrow precursor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1995.tb02702.x
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  • 9
    Electronic Resource
    Electronic Resource
    Effect of granulocyte macrophage colony-stimulating factor in a patient with benign systemic mastocytosis (2001)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 145 (2001), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report the in vitro and in vivo effects of granulocyte macrophage colony stimulating factor (GM-CSF), a known inhibitor of in vitro mast cell differentiation, in a patient with benign, adult-onset systemic mastocytosis. In vitro effects of GM-CSF on bone marrow cultures before the start of treatment showed a marked inhibition of mast cell marker expression [tryptase, Kit, and high-affinity IgE receptor (FcεRIα)] at both protein and mRNA levels. Therefore, the patient was treated with daily injections of GM-CSF for 10 weeks. After an initial improvement, increasing worsening of clinical symptoms was noted, and the patient refused further treatment. Lesional skin biopsies showed an increase of toluidine blue-positive mast cells, compared with uninvolved skin, with further significant increase after treatment. Similar results were obtained on staining for mast cell-specific tryptase and Kit, as well as for CD1a and FcεRIα. These findings show that GM-CSF inhibits human bone marrow mast cell differentiation in vitro, and also in mastocytosis. However, GM-CSF apparently enhances recruitment of mast cell as well as dendritic cell precursors into the tissue during systemic treatment. These findings and the observed adverse clinical effects in the present patient make it unlikely that GM-CSF monotherapy will be beneficial for the treatment of mastocytosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2001.04435.x
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  • 10
    Electronic Resource
    Electronic Resource
    Mechanism of proline-specific proteinases: (I) substrate specificity of dipeptidyl peptidase IV from pig kidney and proline-specific endopeptidase from Flavobacterium meningosepticum
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Protein Structure and Molecular 954 (1988), S. 161-169 
    Details
    ISSN: 0167-4838
    Keywords: (Pig kidney) ; Dipeptidyl peptidase IV ; Dipeptidyl-peptide hydrolase ; Proline specific endopeptidase ; Substrate specificity
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://linkinghub.elsevier.com/retrieve/pii/0167-4838(88)90067-2
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