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K Degitz

Publications and source records attributed to K Degitz.

54 records · Page 3Linked to original sources
PubMed1993

Differentiation driven by granulocyte-macrophage colony-stimulating factor endows microglia with interferon-gamma-independent antigen presentation function.

The antigen presentation function of microglial cells was analyzed after differentiation in neonatal mouse brain cell cultures supplemented either with macrophage (M) or granulocyte/macrophage (GM) colony-stimulating factor (CSF). The cells separated from concomitant astrocytes in both culture systems turned out to exhibit cytological characteristics of macrophages and bore MAC-1 and F4/80 markers in a similar way. When comparatively tested for accessory cell function, only microglia developed with GM-CSF were able to efficiently induce antigen-directed proliferation of a series of helper T cell lines representing both the TH1 and TH2 subtype. Antigenic T cell activation by this microglia population was performed without prior stimulation and exceeded that of M-CSF-dependently grown microglial cells, even if those had been pretreated with interferon-gamma (IFN-gamma). In contrast to such difference in function, low cell surface expression of MHC class II or intercellular adhesion molecule-1 determinants proved to coincide in both populations. Correlating with the capacity for antigen presentation, expression of membrane-bound interleukin-1 (IL1)--a costimulatory signal for TH2 cells--was augmented significantly in GM-CSF-grown microglia. In parallel, the interaction only of this microglia population with a selected TH1 cell line was accompanied by maximal release of T cell-stimulating factor, a cytokine recently identified as an IL1-analogous second signal for TH1 cells. Thus, a developmental process is suggested which produces a form of microglia specialized in antigen presentation and thereby acting uncoupled from IFN-gamma.

Animals↗
PubMed1993

The polymerase chain reaction. Method and applications in dermatopathology.

Since it was first reported in 1985, the polymerase chain reaction (PCR) has revolutionized the way molecular studies are performed, and has developed into one of the most powerful tools in molecular pathology. By use of a cyclic change of temperature, a specific and exponential in vitro amplification of a target DNA sequence can be achieved within hours. As a template for PCR reactions, total genomic DNA is used; this can be readily extracted from clinical specimens. Very low quantities of DNA, as well as DNA degraded by fixation, can also be used as a template for PCR reactions, allowing formalin-fixed, paraffin-embedded tissue to become amenable to detailed molecular analysis. Sequences specific for certain viruses and other microorganisms, as well as molecular marker sequences associated with various types of human cancer, can be readily detected in paraffin-embedded tissue sections. The methodology of PCR, along with various applications in dermatopathology, are reviewed.

DNA↗
PubMed1993

A 5' portion of the ICAM-1 gene confers tissue-specific differential expression levels and cytokine responsiveness.

Intercellular adhesion molecule-1 (ICAM-1), a cell-adhesion molecule critically involved in leukocyte trafficking and adherence, displays tissue-specific and cytokine-specific expression profiles. Although human dermal microvascular endothelial cells (HDMEC) constitutively express ICAM-1, keratinocytes (HK) do not. Interleukin-1 (IL-1) upregulates ICAM-1 expression in HDMEC, but fails to do so in either HK or A431, a human squamous carcinoma cell line, even though both have IL-1 receptors and express ICAM-1 on exposure to other cytokines. We have previously characterized a human ICAM-1 genomic clone that contains the 5' flanking transcriptional regulatory region. To test the hypothesis that tissue- and cytokine-specific ICAM-1 gene expression results from the interaction of constitutive and inducible tissue-specific trans-acting factors with distinct cis-elements of the ICAM-1 gene, various ICAM-1-based reporter gene (CAT) plasmids were constructed. Transcriptional activity of these various constructs was assessed after transient transfection into HDMEC and A431. A critical ICAM-1 region was identified that conferred enhanced expression of CAT in HDMEC and suppressed expression of CAT in A431. This same region further enhanced CAT expression in transfected HDMEC treated with IL-1 alpha, yet no such enhancement was seen with IL-1 treatment of identically transfected A431. However, treatment of A431 transfectants with IFN gamma did result in enhanced CAT expression, demonstrating reversal of A431 cell context suppression of the ICAM-1-based reporter gene construct. These data implicate the existence of both tissue- and cytokine-specific responsive elements in the 5' flanking region of the ICAM-1 gene and demonstrate that regulatory effects directed by such elements are dependent upon their cellular context. Moreover, they provide the basis for identification of specific cis-acting genetic elements, the trans-acting factors with which they interact, and the molecular mechanisms by which they regulate transcription of the ICAM-1 gene.

Base Sequence↗
PubMed1993

Lupus vulgaris confirmed by polymerase-chain reaction.

We report a case of lupus vulgaris with typical clinical and histological findings. Mycobacterium tuberculosis was not only identified by a conventional culture technique, but also by a recently established system which has been designed to detect mycobacterial DNA in formalin-fixed, paraffin-embedded tissue by polymerase-chain reaction (PCR). Because results can be obtained within days, the PCR-based technique may markedly facilitate the diagnosis of skin tuberculosis.

DNA, Bacterial↗
PubMed1992

Human intercellular adhesion molecule-1 gene and its expression in the skin.

Cell adhesion molecules are cell-surface proteins that allow specific cell-cell interactions among leukocytes, as well as between leukocytes and other cells. Recent studies have shown that the differential expression of selected cell-adhesion molecules plays a critical role in cutaneous inflammation, immunologic responses, and wound repair. Intercellular adhesion molecule-1 (ICAM-1) is a cell-adhesion molecule that is constitutively expressed on human dermal microvascular endothelial cells (HDMEC) and is inducible on human keratinocytes (HK). Its regulated expression is vital to the initiation and evolution of localized inflammatory processes in the skin. ICAM-1 serves as a specific ligand for lymphocyte function-associated antigen-1 (LFA-1), a cell-surface protein expressed on all leukocytes. The regulated expression of ICAM-1 allows leukocytes to bind to endothelial cells at sites of inflammation and, after exiting into the tissue, to interact with specific target cells, such as HK. Furthermore, specific cytokines are capable of differentially regulating ICAM-1 expression on HDMEC, HK, and other cells. The biologic relevance of ICAM-1 expression in cutaneous inflammation is further supported by functional studies demonstrating the critical role of ICAM-1/LFA-1 interactions in mediating the binding of peripheral blood leukocytes to HDMEC and to HK--cells known to be participants and targets in specific cutaneous immunologic responses. Thus, the delineation of precise molecular mechanisms that regulate the tissue-specific and cytokine-specific expression if ICAM-1 is important to both our understanding of the biology of localized inflammation and to the development of directed anti-inflammatory therapeutic strategies. Current evidence indicates that ICAM-1 expression is regulated at the level of gene transcription. Recently our laboratory has isolated and characterized a human genomic clone that contains the 5' regulatory region of the ICAM-1 gene. In the current studies, we further describe the genomic ICAM-1 clones isolated to date and demonstrate the presence of consensus regulatory elements located within the 5' flanking region of the ICAM-1 gene that are potentially involved in regulating ICAM-1 gene transcription.

Animals↗
PubMed1992

[Cutaneous lupus erythematosus and cardiolipin antibodies. Incidence and clinical significance].

In recent years, the importance of antiphospholipid antibodies in systemic lupus erythematosus and various other dermatological and internal diseases has been recognized. Characteristic symptoms associated with these antibodies are venous and arterial thrombosis, recurrent fetal loss, thrombocytopenia, and haemolytic anaemia. Two antiphospholipid antibody subgroups that are clinically relevant can be discerned: anticardiolipin antibodies and lupus coagulant. In this study, 51 clinically well-characterized patients with predominantly cutaneous lupus erythematosus were screened for the presence of anticardiolipin antibodies. Anticardiolipin antibodies could be detected in only three patients. These data suggest that, in patients with cutaneous lupus erythematosus, anticardiolipin antibodies should be measured only in the presence of symptoms associated with antiphospholipid antibodies.

Antiphospholipid Syndrome↗
PubMed1991

Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene.

Cell-cell adhesion is critical in the generation of immunologic responses and is dependent upon expression of a variety of cell surface receptors. While intercellular adhesion molecule 1 (ICAM-1), a specific receptor for lymphocyte function-associated antigen 1, is constitutively expressed by some cell types, its de novo or increased expression by various cells has been associated with the initiation of inflammatory responses and appears to be transcriptionally regulated. The 5' region of the human ICAM-1 gene has been cloned and both structurally and functionally analyzed. A 17.3-kilobase genomic clone containing three exonal regions encoding the N-terminal third of the ICAM-1 protein was isolated. A 2.05-kilobase subclone, containing the 5' most exon, was utilized to determine an interferon-gamma-induced transcription initiation site via primer extension and S1 nuclease protection assays. Analysis of the 5'-flanking region revealed consensus sequences for appropriately located basal promoter elements, as well as numerous potential cis-acting enhancer elements. When subcloned into a reporter gene construct, the putative promoter subregion functioned as a potent promoter. However, in accord with biologically observed expression of ICAM-1 in specific cell types, when additional 5'-flanking sequences were included in reporter gene constructs, tissue appropriate repression of transcription was observed.

Amino Acid Sequence↗
PubMed1991

[ICAM-1 and immunological cell adhesion in the skin].

The adhesion molecule ICAM-1 mediates cell contact among leukocytes and between leukocytes and various non-lymphoid cells. A substantial body of experimental evidence indicates a crucial role of ICAM-1 in the biology of cutaneous inflammation. The current status of knowledge on ICAM-1 is reviewed and discussed with regard to the pathophysiology of inflammatory and neoplastic disorders of the skin.

Antigens, CD↗
PubMed1990

Characterization and functional analysis of interferon-gamma-induced intercellular adhesion molecule-1 expression in human keratinocytes and A-431 cells.

Human intercellular adhesion molecule-1 (ICAM-1) is a cell-surface glycoprotein that serves as one of the major ligands for lymphocyte function-associated antigen-1 (LFA-1), a member of the integrin supergene family of adhesion molecules that is involved in cell-cell adhesion. Homotypic and heterotypic conjugate formation between leukocytes and between leukocytes and target cells via the LFA-1/ICAM-1 interaction has been demonstrated to be a critical event in numerous immunologic and inflammatory processes. While LFA-1 is expressed by all leukocytes, ICAM-1 is not normally expressed by all tissues with which leukocytes interact, but ICAM-1 may be induced de novo by various cytokines, including interferon-gamma (IFN-gamma). The constitutive and IFN-gamma-induced expression and function of ICAM-1 in human keratinocytes (HK) and A-431 cells in culture has been analyzed. While A-431 cells constitutively express ICAM-1 when assessed by northern blotting, by biosynthetic labeling and immunoprecipitation, and by flow cytometry, HK do not. When these two cell types are exposed to recombinant human (rh-) IFN-gamma at 1000 U/ml for 24 h, A-431 cells upregulate ICAM-1 and HK express ICAM-1 to an equal degree when assessed by these same parameters. Furthermore, in an in vitro adhesion assay, rh-IFN-gamma treatment of the HK or A-431 cells greatly increases the specific adherence of radiolabeled T cells to these cells. These data provide further evidence for the potential role of the regulated expression of ICAM-1 by keratinocytes in immunologic and inflammatory responses occurring in the skin.

Cell Adhesion↗
PubMed1990

T-cell antigen receptors.

We have reviewed the knowledge of the human TCR and its implications in dermatology. The TCR has been shown to be the molecule responsible for specific cellular immunity in the same way that immunoglobulins confer humoral immunity. Much has been learned about the complex genomic organization of the TCR chains and how the great diversity of TCR proteins is created by somatic rearrangement of the genes. Most peripheral T cells carry an alpha/beta TCR heterodimer; these cells account for the major T-cell-associated functions such as cytolysis and the modulation of immune responses. The gamma/delta TCR is found on a minor population of T cells, and its functional significance needs further characterization. With respect to dermatology, the knowledge of TCR genetics, along with the application of recombinant DNA methodology, has provided a major improvement in the diagnosis and management of mycosis fungoides. Sezary's syndrome, and other lymphoproliferative diseases of the skin.

DNA, Recombinant↗
PubMed1989

Immunological alterations inducible by mercury compounds. II. HgCl2 and gold sodium thiomalate enhance serum IgE and IgG concentrations in susceptible mouse strains.

We determined the levels of total IgE, IgG and IgM in the sera of HgCl2 and gold sodium thiomalate (GST) treated A.SW, C57Bl/6, and DBA/2 mice. In HgCl2 treated A.SW mice, IgE and IgG levels increased up to 30 times above normal. In C57Bl/6 mice HgCl2 induced a slight IgE increase, but no change in IgG. Strain DBA/2, by contrast, did not show significant increases in either IgE or IgG. A.SW mice also proved susceptible to the immunostimulatory effects of GST in that they responded by significant increases in IgE, IgG, and IgM. C57Bl/6 mice responded to GST by an increase in IgM alone, and DBA/2 mice again, were resistant. The same strain-specific responses have been reported with respect to the autoimmunizing effects inducible by HgCl2 and GST.

Adjuvants, Immunologic↗
PubMed1989

[Livido racemosa in detection of anti-phospholipid antibodies].

Livedo reticularis and antiphospholipid antibodies have previously been found to be associated with a subgroup of patients with systemic lupus erythematosus. We present a case of livedo reticularis accompanied by antiphospholipid antibodies, in which no other signs of any systemic or cutaneous disease could be detected.

Adult↗