Biomedical subjects

V Mielke

Publications and source records attributed to V Mielke.

24 records · Page 2Linked to original sources

PubMed1990

Detection of neutrophil-activating peptide NAP/IL-8 and NAP/IL-8 mRNA in human recombinant IL-1 alpha- and human recombinant tumor necrosis factor-alpha-stimulated human dermal fibroblasts. An immunocytochemical and fluorescent in situ hybridization study.

A neutrophil-activating peptide (NAP)/IL-8 produced by LPS-stimulated human peripheral blood monocytes was biochemically purified and functionally characterized by different investigators. Work conducted in our laboratory showed that NAP/IL-8 as well as variants of this peptide are produced by a variety of cells (e.g., monocytes, T lymphocytes, endothelial cells) and that lesional psoriatic scales contain large amounts of biologically active NAP/IL-8. We now investigated human dermal fibroblasts for production of NAP/IL-8. The peptide was detected by immunocytochemistry by using the mAb 46E5. NAP/IL-8 mRNA was visualized by high resolutive fluorescent in situ hybridization with biotinylated antisense/sense RNA probes. Among the various stimuli used [human (h)rIL-1 alpha, hrTNF-alpha, hrIL-3, hr-granulocyte-macrophage-CSF, LPS, FMLP, and platelet-activating factor (PAF)] only hrIL-1 alpha (100 U/ml) and hrTNF-alpha (100 ng/ml) induced the transcription and translation of NAP/IL-8. In contrast to monocytes, LPS was without effect in cultured human dermal fibroblasts. Both NAP/IL-8 and NAP/IL-8 mRNA were found in the cytoplasm adjacent to the nucleus, but interestingly NAP/IL-8 mRNA was not restricted to the cytoplasm. In positive cells only two small bright spots were randomly distributed in the nucleus. Most likely these spots represent transcription sites where NAP/IL-8 mRNA is accumulated during gene expression. Our observations show that stimulation of dermal fibroblasts with the cytokines hrIL-1 alpha and hrTNF-alpha results in expression of IL-8.

Cell Compartmentation↗

PubMed1990

Dominance of memory over naive T cells in contact dermatitis is due to differential tissue immigration.

CD4+ T cells include a naive (CD4-, CD45RO-, CD29-, CD45RA+) as well as a memory subpopulation (CD4+, CD45RO+, CD29+, CD45RA-). These subpopulations represent different stages in T-cell development and function. Recently, it has been shown that inflammatory and neoplastic CD4+ T-cell infiltrates are dominated by the memory subpopulation, whereas both subpopulations are about the same size in the peripheral blood. This was thought to be the result of in situ maturation of naive into memory T cells. We analysed early positive patch-test reactions 1-2 days after antigen challenge and found that most of the CD4+ T cells that had freshly immigrated into the tissue carried the memory phenotype. Their preferential migration may be mediated by at least five adhesion molecules expressed on their cell surface. This observation has important pathogenetic implications, since memory T cells can be rapidly activated by antigens and secrete a wide variety of pro-inflammatory cytokines.

Antigens, CD↗

PubMed1989

Adhesion molecule mapping in normal human skin.

Adhesion molecules are a rapidly growing group of cell surface receptors providing cell-cell and cell-matrix interactions. Their physiological role in tissue homeostasis as well as cellular migration and differentiation is increasingly appreciated. In the present study we have analyzed the expression pattern of most adhesion molecules of the integrin family as well as of adhesion molecules belonging to the immunoglobulin superfamily in normal human skin. We provide evidence that expression of adhesion molecules in the various cutaneous cell systems follows a constant distribution. Moreover, the physiological mononuclear infiltrate of the skin also expresses a variety of adhesion molecules enabeling these cells to migrate or to reside within the skin. Furthermore, our results indicate that intercellular adhesion molecule-1 is not a prerequisite for lymphocyte epidermotropism as frequently stated. Our data provide a rational basis to analyze changing adhesion molecule expression in inflammatory and neoplastic skin diseases.

Adult↗

PubMed1989

CD4+ cutaneous T-cell lymphomas show the phenotype of helper/inducer T cells (CD45RA-, CDw29+).

CD4+ T cells are heterogenous and include at least two subsets that differ in their influence to immunoglobin synthesis, cytokine secretion pattern and immunophenotype. Among others these subsets have been designated as suppressor/inducer or naive T cells (CD45RA+, CDw29-) and helper/inducer or memory T cells (CD45RA-, CDw29+). Current theories suggest that these CD4+ T-cell subsets either reflect sequential stages of maturation before and after activation (antigen contact) or represent distinct lineages. In this study, we systematically analyzed the participation of both suppressor/inducer (CD45RA+) and helper/inducer (CDw29+) T cells in the dermal lymphohistiocytic infiltrate of various CD4+ cutaneous T-cell lymphomas. Although in peripheral blood both subsets are equally distributed, we present evidence that all CD4+ cutaneous T-cell lymphomas are of the helper/inducer T cell phenotype. These findings are of importance both for pathogenetic and clinical considerations: the presence of plasma cells in dermal infiltrates and the elevation of serum immunoglobulins in patients of mycosis fungoides may be the consequence of interleukin-4 secretion of the neoplastic CD4+ helper/inducer cells. The exclusive memory T cell phenotype of cutaneous T-cell lymphomas may be due to a general predominance of this subset in the skin, or be the consequence of cellular activation during malignant transformation.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

Localized and disseminated pagetoid reticulosis. Diagnostic immunophenotypical findings.

Pagetoid reticulosis (PaRet) is a rare skin disease with an intraepidermal infiltrate of atypical lymphocytes. We performed phenotypic studies on two patients with classic localized PaRet (Woringer-Kolopp disease) and one patient with the disseminated type (Ketron-Goodman disease) and compared these with all published reports of cases; both variants show intraepidermal, highly activated, proliferating T cells with variable loss of pan-T-cell antigens, contrasting with nonactivated dermal reactive T cells. This pattern is unique among cutaneous lymphomas and can be used for diagnosis. Despite the fact that localized PaRet does not show a malignant course, recent genotypic analysis of one patient showed monoclonality. Comparable constellations are found in other diseases like lymphomatoid papulosis, which also represent monoclonal disorders of activated T cells with a benign course. To unify these seeming discrepancies, we introduce the concept of "benign cutaneous lymphomas."

Adult↗

PubMed1987

Selective recognition of rat follicular dendritic cells (dendritic reticulum cells) by a new monoclonal antibody Ki-M4R in vitro and in vivo.

Using unstimulated rat peritoneal cells as immunogen a new monoclonal antibody Ki-M4R was produced. Ki-M4R recognizes follicular dendritic cells (dendritic reticulum cells) in germinal centers of lymphoid follicles in lymphatic tissue. In addition, sinus lining cells, endothelia of postcapillary venules, as well as mesangial cells of the renal glomerula immunoreact with Ki-M4R in vitro as well as in vivo. This antibody might be useful for studying the interaction of follicular dendritic cells and B-cell immune response.

Animals↗