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W Sterry

Publications and source records attributed to W Sterry.

At least 253 records · Page 14Linked to original sources
PubMed1992

[Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings].

We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma-chain genes revealed multiple amplification products favouring a polyclonal T-cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient.

Diagnosis, Differential↗
PubMed1991

Cell trafficking in positive and negative patch-test reactions: demonstration of a stereotypic migration pathway.

The cellular and molecular events taking place during epidermal antigen exposure in sensitized individuals are principally well understood. Epidermal Langerhans cells (LC) are supposed to take up, process, and express a given foreign substance on their cell surface. The antigen is then recognized by T cells bearing the appropriate T-cell receptor (TCR). Because LC do not bear variable antigen (Ag)-specific binding sites, one could postulate that the epidermal exposure of any substance should activate LC and other cells of the skin immune system. To test this hypothesis, we analyzed immunophenotypically the cellular trafficking events in positive (n = 5) and negative epicutaneous patch-test reactions (n = 10), using a panel of monoclonal antibodies against CD1a, CD11c (Ki-M1, LeuM5), CD68 (Ki-M6), Ki-M8, and CD3 (Leu4). We can demonstrate that irrespective of whether or not an antigen will be responded to by the immune system (i.e., positive or negative test reaction), epidermal antigen exposure causes a decrease of LC density in the epidermis and simultaneously causes an increase of LC in the dermis. Moreover, monocytes and T cells immigrate into the dermis both in positive and negative patch-test reactions. As is to be expected, the degree of this cellular traffic is more pronounced in positive test reactions, which may be due to amplification mechanisms caused by antigen recognition of sensitized T cells. This finding demonstrates that human skin contains cell migration programs that ensure that any foreign substance will be accessible to the skin immune and phagocytic system.

Antibodies, Monoclonal↗
PubMed1991

Type I and type II psoriasis show a similar usage of T-cell receptor variable regions.

In nonpustular psoriasis, principally two forms can be distinguished [Christophers E. Henseler T: Patient subgroups and the inflammatory pattern in psoriasis. Acta Dermatol Venereol 69(suppl 151):88-92, 1989): Type I frequently shows positive family history, linkage disequilibrium for human leucocyte antigens (HLAs) Cw6, B13 and Bw57 as well as an early onset. Type II manifests itself around the 5th decade, it is more frequently than normal associated with Cw2 and B27. In the light of this association with HLAs an autoimmune pathogenesis has been discussed. In order to investigate the pathogenetic function of T cells we obtained biopsies from patients with type I (n = 10) and type II (n = 10) psoriasis. Three-step peroxidase staining was performed using a panel of monoclonal antibodies directed against five variable (V) regions of the beta chain (V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12) and one of the alpha chain (V alpha 2) of the T cell receptor (TCR). Positive or negative selection of a particular TCR V region could not be detected in the demonstrable repertoire. Furthermore, the usage of the V regions under investigation revealed a similar pattern in the two forms of psoriasis.

Adult↗
PubMed1991

Overexpression of extracellular matrix receptors (VLA-3, 5 and 6) on psoriatic keratinocytes.

The potential role of adhesion molecules in the pathophysiology of psoriasis was investigated and the pattern of expression of the cell-surface receptors ICAM-1, LFA-3, and VLA-1, 2, 3, 4, 5 and 6 was determined in biopsies of skin from patients with psoriasis (n = 12) and from normal skin (n = 12). There were no differences in the intensity or localization of the adhesion molecules VLA-1, 2 and 4 and LFA-3. In contrast, VLA-3 and VLA-6, which are restricted to the basal keratinocytes in normal skin, were overexpressed in the spinous cells in psoriatic skin. ICAM-1 and VLA-5, which are not expressed by keratinocytes in normal skin, were focally induced, especially in cells above elongated rete ridges and where there was an infiltrate with intraepidermal granulocytes and lymphocytes.

Antibodies, Monoclonal↗
PubMed1991

Loss of leucocyte common antigen (CD45) on atypical lymphocytes in the localized but not disseminated type of Pagetoid reticulosis.

Atypical intraepidermal T cells in Pagetoid reticulosis did not express CD45RO, the low molecular isoform of CD45. These cells did express other CD45 isoforms in the disseminated aggressive variant (Ketron-Goodman type). The complete CD45 family was lost from the cell surface in the benign localized variant (Woringer-Kolopp type). Because the presence of CD45 is crucial for the function of the lymphocyte-specific tyrosine kinase p56lck, which is associated with lymphocyte growth and transformation, this may be the molecular basis for the non-aggressive nature of this clonal T-cell proliferation.

Adult↗
PubMed1991

CD4+ memory T cells in peripheral blood are not decreased in patients with atopic dermatitis.

Atopic dermatitis (AD) is a severe and chronic eczematous skin disease, to which increased IgE levels and imbalances of CD4+ T cells are related. CD4+ T cells, however, are heterogeneous and include at least two subpopulations being designated as CD4+ naive and memory T cells. They represent sequential maturational stages (naive into memory) in CD4+ T cell development differing in function and phenotype. Of these two subpopulations the CD4+ memory T cell compartment is a potent producer of gamma-interferon which suppresses IgE synthesis in B cells. Therefore, we speculated whether an inborn maturation defect of CD4+ memory T cells causes the increased IgE production in AD. In patients with AD and age- and sex-matched controls (both n = 10) we analyzed the distribution of both subpopulations in peripheral blood by two-color flow cytometry using monoclonal antibodies against the CD4, CD45RA and CD29 antigen. We provide evidence that the numerical values of CD4+ memory T cells and CD4+ naive T cells are equivalent in both groups. This supports the view that functional disturbances of lymphocytes or lymphocyte subsets are responsible for IgE excess and the pathogenesis of AD.

Adolescent↗
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

A family study of atopic dermatitis. Clinical and genetic characteristics of 188 patients and 2,151 family members.

The history of 188 caucasian patients with atopic dermatitis (AD) and of 2,151 family members has been analyzed. Of the AD patients 48% suffered from respiratory atopy (36% rhinitis, 28% asthma, and 15% both). AD showed by far the earliest onset of all atopic diseases: 50% of our patients had skin lesions before the age of 2 years and 60% before the age of 5 years. In contrast, symptoms of allergic asthma developed in 40% of AD patients before the age of 5 years in comparison with only 25% who had allergic rhinitis. AD affects females more frequently than males (male to female ratio 1:1.5), regardless of whether additional respiratory atopies are present or not. In contrast, respiratory atopies develop more frequently in males than in females (male to female ratio 1.5:1). Mothers with respiratory atopy more often have atopic children (26%) than do fathers with respiratory atopy (13%). Finally, risk figures for genetic counselling are given. In short, the general risk of developing AD (3%) and atopy (7%) increases by a factor of two with each first-degree family member already suffering from atopy.

Adolescent↗
PubMed1990

T-cell receptor and immunoglobulin gene rearrangements in cutaneous T-cell-rich pseudolymphomas.

T-cell rich, small lymphoid infiltrates of the skin may cause considerable problems in the differential diagnosis of reactive versus neoplastic lymphoproliferations, particularly when they lack the morphologic and immunophenotypical criteria for a malignant lymphoma. We did histologic, immunohistologic, and gene rearrangement studies on 10 biopsies from patients with persistent nodular T-cell-rich skin lesions refractory to topical therapy. Based on clinical and immunohistochemical findings, no discrimination was possible between reactive lesions and malignant lymphoproliferations. Histologically, most of the cases contained T-lymphocytic infiltrations that were assumed to be reactive; however, in four biopsies a neoplastic infiltration could not be excluded. Although the T-cell receptor (TCR) beta chain and the immunoglobulin heavy chain (IgH) genes were in germ-line configuration in nine of 10 cases, indicating a predominantly polyclonal lymphocellular infiltrate, in one patient without clinical evidence of malignant lymphoma at presentation a clonally rearranged TCR beta chain gene with the IgH gene in germ-line configuration was detected. One year later, the patient developed a cutaneous pleomorphic T-cell lymphoma and subsequently a large cell anaplastic (CD30+) T-cell lymphoma in an inguinal lymph node. We conclude that clonal T-cell proliferations can be detected by molecular genetic analysis of T-cell-rich, small lymphoid infiltrates of the skin. This finding may precede development of an overt malignant T-cell lymphoma.

Adult↗
PubMed1990

Organization of the monocyte/macrophage system of normal human skin.

Monocytes and macrophages are known to be important for a variety of functions; however, whereas epidermal Langerhans cells have been studied in great detail, few data are available for the dermal monocyte/macrophage system. Therefore we investigated the density, distribution, and phenotype of dermal macrophages in normal human skin using a panel of monoclonal antibodies for single and double labeling. We demonstrate here that within normal human dermis macrophages reside with a remarkable density. Principally, these cells exhibit the phenotype of the phagocytic macrophage system (CD11c+, KiM8+), whereas members of the immune phagocyte system (CD11c+, KiM8-) are absent from normal dermis with the exception of a few Langerhans cells in the papillary body. Within the dermal phagocytic macrophage system we uncover an unexpected phenotypical and morphologic heterogeneity, which correlates with the tissue localization. This study provides a basis for investigating the participation and change of the dermal macrophage system in cutaneous disorders.

Adult↗
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↗
PubMed1990

Induction and upregulation of adhesion receptors in oral and dermal lichen planus.

The expression pattern of well-defined cell surface adhesion receptors called VLA-family, LFA-1 and ICAM-1 was determined semiquantitatively in biopsies of oral (n = 12) and dermal lichen planus (n = 5) and compared to normal uninvolved human oral mucosa (n = 12) and skin (n = 12) using an indirect immunoperoxidase technique. In both oral and dermal lichen planus, an induction of the beta 1-integrins VLA-1 and VLA-3 and an upregulation of VLA-6 was found in T cells infiltrating the basement membrane zone. These cell surface molecules function as receptors for collagen, fibronectin and laminin. A focal induction of ICAM-1 on basal keratinocytes could be detected at sites of intramucosal T cells. These results suggest that investigated adhesion receptors are crucially involved in the aggregation of T cells in both conditions. Further investigations have to be done to determine the functional role of these adhesion receptors in lichen planus.

Antigens, CD↗
PubMed1990

[Formalin-resistant leukocyte differentiation antigens in dermatohistopathology].

The diagnosis of cutaneous leucocytic and particularly lymphocytic infiltrates with a considerable degree of reliability, has become possible owing to the use of monoclonal antibodies against leucocyte differentiation antigens. This method of diagnosis depends heavily on the availability of frozen biopsies, however, since most antigens are destroyed by the routine tissue processing, including formol fixation, paraffin embedding and alcohol dehydration. In recent years an increasing number of antibodies has become available that allow the detection of formalin-resistant leucocyte differentiation antigens and thus can be used on conventional paraffin sections. When using such antibodies, which will be invaluable in routine diagnosis and, furthermore, will allow the investigation of old biopsies, the dermatopathologist must be familiar with the exact distribution of the detected antigen and should be aware of crossreactivities with other structures. This review presents the most important antibodies and gives hints on their rational and economical use.

Antibodies, Monoclonal↗
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↗