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T Krieg

Publications and source records attributed to T Krieg.

At least 217 records · Page 12Linked to original sources
PubMed1988

Evidence for LTB4/12-HETE binding sites in a human epidermal cell line.

We identified leukotriene B4 (LTB4)/12-hydroxyeicosatetraenoic acid (12-HETE) binding sites in a squamous cell cancer-derived human epidermal cell line. Analysis of the binding data revealed a single class of binding sites with a dissociation constant of 0.16 microM and a Bmax of 3.8 x 10(6) sites per cell. Competitive binding assays with various eicosanoids at 37 degrees C showed nearly equal binding of 12(S)-HETE, 12(R)-HETE and LTB4. 5(S)-HETE and LTB4-analogs bound with lesser affinity. Specific LTB4 binding at 37 degrees C could also be demonstrated in freshly isolated normal human keratinocytes. Since lipoxygenase-derived eicosanoids are thought to play an important role in hyperproliferative and inflammatory skin diseases, the identification of LTB4/12-HETE binding sites in keratinocytes could have implications for the development of new drugs controlling these disease processes.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1988

Systemic scleroderma. Clinical and pathophysiologic aspects.

Systemic scleroderma is a generalized disease of connective tissue involving mainly the skin, the gastrointestinal tract, the lungs, the heart, and the kidneys. It can be present in different forms, of which acroscleroderma, with limited cutaneous and extracutaneous involvement, and diffuse scleroderma within a more rapid progression are most characteristic. Circulating antibodies against antinucleolar antigens are present in most patients with systemic scleroderma. They are helpful for establishing a classification and for determining the prognosis of the disease; their involvement in the pathogenesis, however, is still unclear. Alterations of the blood vessels and induction of fibroblasts by potent mediators are thought to play an important role in the early phase of scleroderma. Therefore early diagnosis is required, which then can initiate vasoactive therapy. In patients with systemic scleroderma, who also suffer from additional myositis, interstitial lung diseases, or arthritis, anti-inflammatory treatment with prednisolone and azathioprine is suggested. Development and progression of fibrosis cannot yet be influenced sufficiently. Only D-penicillamine affecting cross-linking of collagen has been widely used in scleroderma and has some beneficial effect.

Anti-Inflammatory Agents↗
PubMed1988

A defective cell surface collagen-binding protein in dermatosparactic sheep fibroblasts.

Fibroblasts from dermatosparactic sheep fail to contract collagen gels and show a reduced attachment to collagenous substrates. By comparing collagen-binding membrane proteins of normal (+/+), homozygote (-/-), and heterozygote (+/-) fibroblasts, we present evidence that the interaction of normal fibroblasts with native type I collagen involves a protein of apparent Mr = 34,000 which is absent from dermatosparactic fibroblasts and seems to be related to anchorin CII. This conclusion was reached from the following experiments: (a) On a blot of membrane proteins from normal fibroblasts radioactively labeled type I collagen bound predominantly to a protein band of 34 kD; dermatosparactic membranes revealed only a small amount of binding to a component with a molecular mass of 47 kD. (b) After separation of normal fibroblast membrane proteins on type I collagen-Sepharose, a collagen-binding component of 34 kD was found which was absent from the corresponding fraction of dermatosparactic membranes. (c) Antibodies to anchorin CII stained the surface of normal (+/+), but not of dermatosparactic (-/-) fibroblasts and labeled a 34-kD component after immunoblotting of normal fibroblast membrane proteins. (d) After metabolic labeling of fibroblasts with [35S]methionine and immunoprecipitation with anti-anchorin CII, 40- and 34-kD components were precipitated from extracts of normal fibroblasts, while the latter component was absent from affected cells. Similar differences were found after immunoblotting of membranes from whole normal or affected skin. These data indicate that dermatosparaxis of sheep involves a molecular defect of a collagen-binding protein. Therefore this disease represents a model to study the complex interaction of cells with the extracellular matrix on a molecular level.

Animals↗
PubMed1988

Localization of collagen mRNA in normal and scleroderma skin by in-situ hybridization.

Scleroderma is a fibrotic disease occurring in a localized or systemic form. Disturbed regulation of connective tissue metabolism plays an important role in its pathogenesis. However, until now, most of the data available were obtained from studies of fibroblasts in culture and there is considerable doubt that fibroblasts in a monolayer reflect the in-vivo situation. Using in-situ hybridization with specific antisense RNAs on frozen sections of skin, cells were detected displaying enhanced messenger RNA levels for type I and type III collagen in patients with localized and systemic scleroderma. Activated fibroblastic cells were often located near blood vessels in the deep dermis of patients with early stages of the disease and were mostly surrounded by mononuclear cells. These findings are in agreement with the concept that the interaction of fibroblasts with 'immunocompetent cells' is crucial in the initial activation of connective tissue metabolism in fibrosis.

Adult↗
PubMed1988

[Local recurrent centroblastic lymphoma of the skin].

A 57-year-old patient suffered from a cutaneous centroblastic polymorphic non-Hodgkin lymphoma. This tumour first occurred 6 years ago and showed local relapses after two surgical excisions without any internal manifestations. The tumour had unusual morphological features with a sarcomatous growth pattern and numerous multilobated nuclei, which first led to the diagnosis of a malignant fibrous histiocytoma. Additional immunohistological studies of both the primary tumour and the lesions demonstrated the presence of lymphocytic marker proteins and allowed the definitive classifications as a high-grade malignant non-Hodgkin lymphoma of the B-cell type.

Biomarkers, Tumor↗
PubMed1988

[Angiosarcoma of the scalp].

A 57-year-old male patient suffering from angiosarcoma of the scalp is reported. The clinical picture was highly characteristic, showing an ulcerated reddish tumour without clear demarcation. However, the histological characterization was more difficult and a final diagnosis could only be established with immunohistochemistry using antibodies directed against several endothelial cell antigens.

Biomarkers, Tumor↗
PubMed1988

[Pathophysiology of fibroses. Progressive systemic scleroderma as a model disease].

Fibrosis is characterized by excessive deposition of connective tissue in the involved organs. Although the prime event in the pathogenesis is still poorly understood, several mechanisms are discussed, which finally result in the activation of fibroblasts. Recent studies have demonstrated that immunocompetent cells play a crucial role during the initial phases of the development of fibrosis. Therefore, several mediators have been characterized, which are secreted by platelets, lymphocytes and macrophages and which can attract fibroblasts, induce proliferation and collagen synthesis in mesenchymal cells. These include PDGF, EGF, TGF--beta and many others. In addition, gamma-interferon has been shown to inhibit chemotaxis of fibroblasts and to reduce collagen mRNA levels. A controlled interaction of all the different mediators is required to guarantee a normal functioning of connective tissue. Alterations in these regulation steps can result in excessive deposition of connective tissue and the development of fibrotic processes.

Collagen↗
PubMed1988

[Polychondritis recidivans et atrophicans].

A typical case of chronic atrophic polychondritis with chondritis of the ear and episcleritis is presented. The inflammation subsided on treatment with colchicine. This entity is rare. It has an uncertain prognosis and causes a wide variety of symptoms. Accordingly, the spectrum of conditions that need to be considered in the differential diagnosis is also wide.

Aged↗
PubMed1988

Levels of type IV collagen and laminin fragments in serum from patients with progressive systemic sclerosis.

Sera from patients with progressive systemic sclerosis (PSS) were studied using immuno-assays for laminin P1 fragment and the carboxyterminal NC1 domain from type IV collagen. Compared to healthy controls, patients with PSS showed elevated serum levels of both fragments derived from basement membrane proteins. However, there was no difference when patients with and without Raynaud's phenomenon were compared and no correlation could be established with the activity of the disease or clinically defined types of scleroderma. Our data indicate that the metabolism of basement membrane proteins is involved in the course of scleroderma; however, it remains questionable whether these assays could become useful as diagnostic or prognostic tools.

Collagen↗
PubMed1987

Inhibition of fibroblast chemotaxis by recombinant human interferon gamma and interferon alpha.

Interferons have recently been recognized as potent mediators in inflammatory processes, exerting profound effects on fibroblasts. The influence of interferons gamma and alpha on the chemotactic movement of fibroblasts toward various attractants was, therefore, investigated. Normal human adult and embryonal dermal fibroblasts, fibrosarcoma-derived fibroblasts and SV40-transformed fibroblasts were tested against conditioned medium from fibroblasts, the chemotactic peptide C-140 of fibronectin, platelet-derived growth factor, and leukotriene B4 as attractants in the presence or absence of the interferons. Interferons gamma and alpha inhibited chemotaxis in a dose-dependent manner and at concentrations at least as low as 10(-2) ng/ml. Inhibition was noticeable when the cells were exposed to interferon for as short a period as 60 minutes, and the effect was not readily reversible. Inhibition occurred when the cells came from sparse or dense cultures, but when platelet-derived growth factor was the attractant and the cells had been grown at low density there was no inhibition. It is concluded that this is a specific effect, not to be wholly explained by overall increase in membrane rigidity. Inhibition of fibroblast chemotaxis by interferons may be an important regulatory mechanism during wound healing or fibrosis and metastatic spread of tumor cells.

Adult↗
PubMed1987

Basement membrane formation by malignant mouse keratinocyte cell lines in organotypic culture and transplants: correlation with degree of morphologic differentiation.

Six malignant C3H mouse epidermal cell lines (HEL-30, HEL-37, HELP I, HELP IV, HD II, H3L), with different capacities for epidermal differentiation, were analyzed for their organized growth behavior and basement membrane (BM) formation in organotypical cultures in vitro and after transplantation into syngeneic mice. Expression and deposition of five BM components (type IV collagen, laminin, bullous pemphigoid antigen, fibronectin, heparan sulfate proteoglycan) were determined on frozen sections by indirect immunofluorescence. Additionally, synthesis and secretion of BM components by the line HEL-30 (in submersed cultures) were identified by metabolic labeling and immunoprecipitation. Morphologic differentiation features and formation of a structured BM were studied by electron microscopy. All cell lines were tumorigenic and invasive but nevertheless able to synthesize BM constituents in vitro and in vivo, although pronounced variations in the expression and the polarity and continuity of deposition were found. Irrespective of the amount of BM components synthesized, none of the cell lines formed a structured BM in organotypical cultures in vitro. After transplantation the production of BM components was improved and the newly formed epithelia were separated from the mesenchyme by a structured BM. The formation of BM occurred whether the epithelial cells were in immediate contact with the mesenchyme or separated by a 1 to 2 mm thick native collagen gel. Deposition of BM constituents and formation of BM structures occurred both at the superficial epithelium and around invading cell cords. The studies clearly demonstrated that malignant epidermal cells maintain their capacity to synthesize BM components. The extent of production and the polarity of deposition of the constituents and the quality of BM formation were usually higher in well differentiated cell lines and obviously correlated well with their preserved degree of differentiation. Comparable to normal keratinocytes, formation of structured BM requires interaction with living mesenchyme but occurs independently of direct epidermal-mesenchymal contact.

Animals↗
PubMed1987

Compositional analysis of collagen from patients with diverse forms of osteogenesis imperfecta.

Collagen was extracted by pepsin treatment from various tissues and skin fibroblasts of 23 patients belonging to different types of osteogenesis imperfecta (OI), and characterized by molecular sieve and ion exchange chromatography, gel electrophoresis, and amino acid analysis. We found an elevated collagen III/I ratio in the skin of one patient with OI type I but almost normal values in skin fibroblasts of two other patients of this OI type. Five patients with OI type II had a normal collagen III/I ratio in their skin and skin fibroblasts, but the degree of hydroxylation of lysine residues in collagen I and III from their skin, bone, calvarium, and noncalcified calvarial tissue was increased. Patients belonging to OI types II, III, and IV had also considerable amounts of collagen III in their long bones, while bone tissue from controls contained only type I collagen. The content of type V in calcified tissues was virtually the same in controls and patients.

Adolescent↗
PubMed1987

Nidogen and heparan sulfate proteoglycan: detection of newly isolated basement membrane components in normal and epidermolysis bullosa skin.

The epidermal basement membrane zone comprises various biochemical constituents, some of which may be affected or involved in certain forms of mechanobullous diseases. Recently, nidogen and a low density form of heparan sulfate proteoglycan--two ubiquitous, noncollagenous components of basement membranes--were isolated and characterized, and affinity-purified antibodies to each component were prepared. These antibodies were used to study the distribution of both antigens in normal and diseased human skin. By immunofluorescence, both nidogen and heparan sulfate proteoglycan were linearly distributed along the basement membrane of the dermal-epidermal junction, adnexal structures, and blood vessels of normal human skin. On suction-induced blisters of normal skin, both antigens were found at the base of the blister, indicating that each was within or below the lamina lucida. By indirect immunoelectron microscopy, both antigens were ultrastructurally located within the lamina densa. The staining patterns for nidogen and heparan sulfate proteoglycan were examined in 11 patients with either junctional, dominant dystrophic, or recessive dystrophic epidermolysis bullosa, and were found to be not different from the patterns observed in normal skin.

Antibodies, Monoclonal↗
PubMed1987

Inhibition of fibroblast chemotaxis by superoxide dismutase.

Superoxide radicals are known to be important mediators in chronic inflammatory and fibrotic processes, in which accumulation of fibroblasts is thought to play a major role in the pathogenetic events. The enzyme superoxide dismutase removes these radicals by a catalytic reaction. Chemotactic response of human fibroblasts and fibrosarcoma-derived cells (HT-1080) to fibroblast conditioned medium, fibronectin and platelet-derived growth factor was inhibited in a dose-dependent manner in the presence of superoxide dismutase, while random migration, cell proliferation, cell viability and synthesis of collagen and non-collagenous proteins was not altered. In contrast, phorbol myristate acetate, an inducer of superoxide generation, stimulated the chemotactic movement of fibroblasts to the attractants. Evidence for the formation of superoxide is provided by the reduction of tetrazolium salt by activated fibroblasts which could be inhibited by superoxide dismutase. Thus, it is concluded that superoxide in small amounts is involved in the mechanism of fibroblast chemotaxis. Superoxide dismutase may, therefore, reduce fibroblast migration into sites of injury or inflammation.

Catalase↗