Microinjection of alpha-MSH followed by UV-irradiation blocks HSP 72 in human keratinocytes.
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Cell Survival↗
Biomedical subjects
C Bayerl
Publications and source records attributed to C Bayerl.
Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin.
Expression of prostaglandin-H-synthase (PGHS) isozymes was analyzed in 50 biopsies of normal human skin and of pre-malignant and malignant skin lesions, by means of quantitative RT-PCR, immunoprecipitation and Western blotting, as well as immunohistochemistry. Normal skin constitutively expressed PGHS-1 in all cell layers of the epidermis, in endothelial cells of small blood vessels and in sweat-gland epithelium. PGHS-2 expression was very low and restricted to a few keratinocytes of the interfollicular and follicular epidermis. Steady-state concentrations of PGHS-1 and PGHS-2 mRNA were similar in normal skin and in basal-cell carcinomas, but PGHS-1 mRNA was reduced and PGHS-2 mRNA was elevated in actinic keratoses, squamous-cell carcinomas and keratoacanthomas. PGHS-1 protein was detected in all tumor biopsies, being occasionally increased in basal-cell carcinomas. High amounts of PGHS-2 protein were found in actinic keratoses, squamous-cell carcinomas and keratoacanthomas, but not in basal-cell carcinomas. Four malignant melanomas included in this study contained PGHS-1 but no PGHS-2 protein. Immunohistochemical analysis of the biopsies identified keratinocytes, in addition to cells of inflammatory infiltrates and of dendritic morphology, as the major PGHS-expressing cell types. PGHS-2-specific signals were spread throughout the epidermal part of actinic keratoses and squamous-cell carcinomas. These data suggest that constitutive up-regulation of PGHS-2 expression is a consistent pre-malignant event in squamous-cell cancer development in man, as it is in animal models of skin carcinogenesis. Thus, pre-cancerous lesions such as actinic keratoses present a likely target for chemoprevention of skin cancer by selective PGHS-2 inhibitors.
Aged↗
Langerhans cells enclosing sunburn cells in acute UV erythema in vivo.
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Adult↗
Association of heparin-induced skin lesions, intracutaneous tests, and heparin-induced IgG.
BACKGROUND: Cutaneous heparin-induced allergic reactions to subcutaneous heparin may begin 2-5 days after administration. The relation of the delayed-type hypersensitivity and a systemic immunologic response is controversial. The present investigation aimed to analyze the occurrence of thromboembolic complication, pathologic heparin-induced platelet activation (HIPA), and the presence of circulating heparin-induced IgG in patients with heparin-induced skin reactions. METHODS: Intracutaneous tests, HIPA assay, and heparin-heparin IgG antibodies were performed in nine patients with heparin-induced skin lesions. RESULTS: Six of eight patients showed positive intracutaneous tests to heparin and to four low-molecular-weight heparins. Three of six heparin-positive patients presented hypersensitivity to a heparinoid, too. Two of three patients had a positive HIPA test and elevated heparin-induced IgG antibodies. Both patients developed complications presenting as heparin-induced skin necrosis or arterial thrombosis. Two of nine patients were treated with danaparoid, 4/9 patients received r-hirudin, and 1/9 received oral coumarin. In 2/9 patients, anticoagulant therapy was stopped, but these patients will receive r-hirudin if indicated. CONCLUSIONS: On the basis of the coincidence of local and systemic hyperreactivity to heparin and danaparoid, patients with heparin-induced skin lesions should receive r-hirudin, a nonheparin compound, for anticoagulant treatment.
Adult↗
Heat shock protein HSP 27 is expressed in all types of basal cell carcinoma in low and high risk UV exposure groups.
HSP 27, a marker of differentiation and proliferation, helps the cell in repair processes after environmental stress such as heat, UV-irradiation and oxidative stress. So far, its role on carcinogenesis is not yet understood. HSP 27 was studied immunohistochemically in different types of primary, untreated basal cell carcinoma (BCC) in two populations with different UV exposure habits: descendents from Germany, "Pommern", living in Brazil (Pommeranos, n = 15), rural workers with high UV exposure and Germans from the region Baden-Württemberg with indoor jobs (n = 14). Age distribution and type of BCC were similar between the Pommeranos and the Germans. Specimens of BCC (n = 15 solid, n = 6 keratotic, n = 4 adenoid, n = 4 fibrotic) were evaluated in cryostat and paraffin sections for HSP 27, HSP 72 and bcl-2. In Pommeranos in Brazil (UV high risk group) versus (vs) inhabitants from Baden-Württemberg (UV low risk group), HSP 27 was expressed in 93% vs 79% in all histological subclasses, HSP 72 in 20% vs 21% and bcl-2 in 93 % in both groups. Antibodies against HSP 27, but not HSP 72, labeled BCC of all types. In contrast to the lack of HSP 27 in squamous cell carcinoma reported in the literature, we found HSP 27 and bcl-2 positive cells in BCC which might characterize the tumour as relatively benign and slow progressing.
Aged↗
Microinjection of an antibody against HSP 72 in keratinocytes to study acute UV injury.
First, a method of microinjection of antibodies in primary human keratinocytes in culture was established. Second, in acute UV irradiation, the physiological role of heat shock protein (HSP) 72 in keratinocytes was studied with this method. Primary human keratinocytes in culture were injected with "controls" as fluorescent dyes, phosphate buffered saline (PBS), an irrelevant secondary antibody and an antibody against a protein with known protective function in UV erythema, HSP 72. UV irradiation was applied and survival, colony forming and immunohistochemistry for injected and non-injected keratinocytes were evaluated in a time course. Puncturing the plasma membrane with injections of "controls" as FITC, PBS and the IgG anti-mouse antibody did not result in reflux of injected material or any alteration in morphology or colony-forming ability for 24 h. Keratinocytes injected with an mAb to HSP 72 without UV irradiation survived microinjection for up to 12 days, while surprisingly, more than double of injected and irradiated ones died after 12 h compared to not injected and irradiated ones. Moreover, microinjection of the antibody to HSP 72 in the nucleus resulted in a loss of the immunohistochemical labeling for HSP 72 in these cells after 12 h. Microinjection of the "controls" did not harm the survival, forming of colonies and expression of HSP 72 in keratinocytes for 24 h. In contrast, microinjection of an mAb against HSP 72 led to an increase in cell death after UV irradiation, confirming that HSP 72 is important for UV protection. Microinjection of antibodies in human keratinocytes in culture might allow the study of the physiological role of some proteins.
Antibodies, Monoclonal↗
Expression of heat shock protein 27 in chromomycosis.
We report on a 58-year-old woman with long-lasting (36 years) chromomycosis on the foot and secondary self-inoculation from foot to hand 4 years ago. Mycological classification was performed after culture on Sabouraud glucose agar. We used haematoxylin and eosin and Giemsa staining and an antibody to heat shock protein (HSP) 27 (Stress Gen, Clone G3.1) on paraffin-embedded and cryostat specimens of chromomycosis. The mycological culture revealed the fungus Fonsecaea pedosoi. Histopathology revealed dermal fibrosis with persistent fungi (Medlar bodies), numerous mast cells and pseudoepitheliomatous hyperplasia. Immunohistochemically, HSP 27 was positively identified in F. pedrosoi. Moreover, in differentiating keratinocytes in the pseudoepitheliomatous lesions of chromomycosis, HSP 27 was increasingly expressed from basal layers to stratum spinosum in the epidermis but not in keratinocytes directly bordering Medlar bodies. In chromomycosis, HSP 27 is expressed, in accordance with its role as a marker of differentiation and proliferation, in keratinocytes and also in F. pedrosoi. It remains unknown if these results might explain the therapeutic efficacy of hyperthermic treatment.
Adult↗
Immunohistochemical characterization of HSP, alpha-MSH, Merkel cells and neuronal markers in acute UV dermatitis and acute contact dermatitis in vivo.
OBJECTIVE: To study the immunoneurocrine network in inflammatory dermatoses, we investigated histochemically acute UV and acute contact dermatitis. METHODS: Antibodies were applied to frozen and paraffin specimens of human skin after irradiation (n = 10), to positive patch tests (n = 10) and controls (n = 10) against: HSP 70, 72, 27, neuronal polypeptides (alpha-MSH, NSE, bombesin, PGP 9.5, NGF, NGF-R) and intermediate filaments (peripherin, NF 200, CK 19, 20). RESULTS: HSPs and alpha-MSH were upregulated in UV dermatitis in the epidermis compared to contact dermatitis and normal skin. Sunburn cells did not express HSPs or alpha-MSH in UV dermatitis. Neuronal markers and HSP 27 labeled more nerve fibers in UV than in contact dermatitis, except the increased staining for NGF, NGF-R and alpha-MSH in nerve fibers in contact dermatitis. In UV dermatitis, 50% of Merkel cells were suprabasal, but in contact dermatitis, basal, rounded and reduced in number. CONCLUSIONS: Merkel cells, HSPs and markers of neuroinflammation are of different importance in UV and contact dermatitis in vivo.
Apoptosis↗
[Cellular adhesion molecules and components of the extracellular matrix as target structures of autoimmunity].
Cell-cell and cell-matrix adhesion molecules as well as extracellular matrix components are target structures of antibody-mediated autoimmunity that have recently been well characterized at the molecular biological level. Pathogenic autoantibodies against these molecules are causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. Desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, exhibiting intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins. (IgA pemphigus) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestationis with subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments, while epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII constituting the anchoring fibrils. In addition, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.
Autoantibodies↗
Allergic contact stomatitis from aristochol, a phytotherapeutic cholagogue.
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Cholagogues and Choleretics↗
[Cell adhesion molecules and extracellular matrix components as target structures of autoimmunity].
A number of cell-cell and cell-matrix adhesion molecules as well as several extracellular matrix components represent target structures of antibody-mediated autoimmunity which recently have been extensively characterized at the molecular biological level. Pathogenic autoantibodies against these molecules have been found to be causally related to disturbances of cell and tissue adhesion that become apparent as various (muco-)cutaneous blistering diseases. In desmosomes, desmosomal cadherins (desmogleins and desmocollins) mediate epidermal intercellular adhesion. Among these, desmoglein 1 and desmoglein 3 are the autoantigens of pemphigus foliaceus and pemphigus vulgaris, respectively, being characterized by intraepidermal blistering. The pathogenic relevance of autoantibodies against desmocollins (IgA pemphigus and other pemphigus types) and desmoplakins (paraneoplastic pemphigus) still remains unclear. Hemidesmosomes contain the plaque protein BPAG1 and the partly collagen-like transmembrane protein BPAG2, representing the autoantigens of bullous pemphigoid and pemphigoid gestations which show subepidermal blistering. A certain subtype of cicatricial (benign mucous membrane) pemphigoid is characterized by autoantibodies against laminin 5 present in the subhemidesmosomal anchoring filaments. Both epidermolysis bullosa acquisita and bullous SLE exhibit autoantibodies against collagen type VII which constitutes the anchoring fibrils. Besides, autoantibodies against a particular collagen type IV chain of the glomerular basement membrane are responsible for the manifestation of Goodpasture's syndrome. These recent molecular biological findings might be the basis for the development of novel therapeutic strategies.
Animals↗
Characterization of sunburn cells after exposure to ultraviolet light.
Sunburn cells (SBCs) appear in the epidermis shortly after acute UV damage, especially after exposure to UVB light. As yet, the mode of their formation remains to be satisfactorily elucidated. In order to characterize these cells, the expression of various markers of epidermal differentiation following UV exposure was investigated using immunhistochemical procedures. These were applied to paraffin-embedded (microwave technique) and frozen specimens of human skin 24 h after irradiation with 4 times the minimal erythema doses(MED). Normal nonirradiated skin without irradiation served as the control. We used a battery of antibodies directed against the following: cytokeratins (CKs) 5, 10, 17, and 19, actin, cell-adhesion proteins (desmoplakins, desmogleins), markers of terminal epidermal differentiation (filaggrin, involucrin and loricrin), markers of proliferation (PCNA, MIB, K6,16), a marker of endocytosis (clathrin) and markers of cell growth, (transforming growth factor [TGF-alpha]) and B-cell leukemia/lymphoma-2 [bcl-2]. After UV irradiation it was found that CK 5, which is typically confined to basal keratinocytes, was also expressed in suprabasal keratinocytes. The CKs 1 and 10/11 exhibit a normal suprabasal localization, but suprisingly, SBCs were negative for these CKs. Although CK 6,16, and 17 are not usually found in normal epidermis, UVB exposure induced their expression in suprabasal keratinocytes, but again failed to elicit their expression in SBCs. Antibodies specific for markers of late epidermal differentiation (filaggrin, involucrin and loricrin), cell-junction proteins (desmogleins, desmoplakins), proliferation (PCNA and MIB), and endocytosis (clathrin) also failed to produce positive staining of SBCs. Even though TGF-alpha immunoreactivity became detectable in most keratinocytes after UV exposure, this was not the case for SBCs. The number of basally located dendritic cells, most probably melanocytes, exhibiting bcl-2 staining was markedly reduced 6 and 12 h after irradiation as compared with normal skin. SBCs do not express any late differentiation markers, but they do contain proteins typical of basal keratinocytes (CK 5). It can be concluded that SBCs do not develop beyond a more basal-like differentiation pattern, probably as a result of cell death and migration through the epidermis.
Actins↗
Acral persistent papular mucinosis (APPM) with pruritus. A case report and mast cell quantification.
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Adult↗
[Striped nail pigmentation with Hutchinson signs in a boxer].
We present a 68-year-old male patient, who had had longitudinal melanonychia with Hutchinson sign for 4 years. Melanocytic proliferation was ruled out by biopsy. Friction and pressure had been acting on this patient's nails during boxing for the past 40 years. These mechanical factors are discussed under the entity of "frictional longitudinal melanonychia". In addition, cellular and non-cellular mechanisms for longitudinal melanonychia are reviewed.
Aged↗
[Hair casts in lichen ruber].
We present a 59-year old male patient, who had small plant cylinders 1-2 mm in length adhering to the hair shafts and easily moved up and down along them. We found hair casts together with lichen ruber follicularis and pseudopelade of the Brocq type. The presence of hair casts is often misdiagnosed as pediculosis capitis, piedra alba or trichorrhexis nodosa. The case report and the literature are discussed.
Antifungal Agents↗
[Metabolism of antipsoriatic anthrone derivatives].
The metabolisation of the antipsoriatically active molecules 1,8,9-triacetoxy-anthracene und 1,8-diacetoxy-9-anthrone by serum is described. Under these conditions 1,8-dihydroxy-9-anthrone, 1-hydroxy-8-acetoxy-9-anthrone, 1,8,1',8'-tetrahydroxy-bisanthrone, 1,8-dihyroxy-anthraquinone, 1,8-diacetoxy-anthraquinone and 1-hydroxy-8-acetoxy-anthraquinone arise from both educts. Quantitative determinations of these metabolites indicate that hydrolytic reactions occur prior to oxidation. Contrary to 1,8-dihydroxy-9-anthrone, 1,8,9-triacetoxyanthracene and 1,8-diacetoxy-9-anthrone are effective against psoriatic lesions without accompanying inflammations of the skin. 1,8,9-Trimethoxy-anthracene, however, is ineffective, also indicating that at least 1,8,9-triacetoxy-anthracene is a prodrug.--In agreement with Krebs' hypothesis 10,10-dialkylated 1,8-dihydroxy-9-anthrones described in this paper are ineffective against psoriasis.
Anthracenes↗
Parental understanding of basic infant nutrition: misinformed feeding choices.
To assess mothers' knowledge of good infant nutritional practices, a survey was conducted by the Institute of Pediatric Nutrition. The survey addressed issues related to breast-feeding, the use of iron-fortified formula, frequent spitting up, the introduction of cow's milk into the infant diet, and the nutritional value of fruit juice. Mothers who responded to the survey had difficulty identifying the most appropriate choices. This article presents the survey results and discusses the implications for health care providers who care for children and their families.
Adult↗
Meloxicam in acute UV dermatitis--a pilot study.
The non-steroidal anti-inflammatory drug (NSAID) meloxicam is a preferential cyclooxygenase-2 (COX-2) antagonist. The UV protective potential of this drug was studied to compare it with the reported beneficial effects of such preferentially COX-1 specific NSAIDs as indomethacin and acetylsalicylic acid in the literature. In a pilot study (open-label, non-randomized, non-controlled, unblinded), 10 patients received UV irradiation with the minimal erythema dose (MED), first with meloxicam (7.5 mg/die) to reduce post-operative pain and second without ingestion of meloxicam. The factor of UV protection was evaluated. In six of ten patients meloxicam showed no benefit, whereas four of ten patients had a 1.3- up to 3-fold UV protection. In this study, the benefit in UV protection of meloxicam as a preferential COX-2 antagonist was not above the reported benefit of the "old" COX-1 inhibiting NSAIDS.
Acute Disease↗