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Biomedical subjects

W Sterry

Publications and source records attributed to W Sterry.

At least 235 records · Page 13Linked to original sources

[Persistent pruritus after hydroxyethyl starch infusions. Retrospective long-term study of 266 cases].

In 266 patients receiving hydroxyethyl starch (HES) for otological indications, we retrospectively analysed the incidence of pruritus and its relationship to clinical and therapeutic parameters. We found that 32% of the patients developed pruritus, which characteristically appeared as pruritic crises. In 55% of pruritic patients onset after the HES medication had already been discontinued was reported. The symptoms persisted on average for 8.8 weeks. Pruritus was generalized, but with a predilection for the trunk and genitalia. Coincidental atopic disease or higher age did not promote pruritus. However, the incidence of pruritus correlated well with the cumulative dosage and also depended on the type and molecular weight of HES given (6% or 10%, mol.wt. 40 or 200 kDa). Light and electron microscopic assessment showed deposits of HES, especially within dermal macrophages and endothelial cells and adjacent to nerve fibres. Pathogenetically a histamine-independent pathway is probably responsible for the induction of pruritus. Hence, classic antihistaminic drugs had no therapeutic effect in our patients.

Adolescent↗

SIL-TAL1 deletion in T-cell acute lymphoblastic leukemia.

The TAL1 gene on chromosome 1 encodes a hematopoietic transcription factor. Disruption of TAL1 via chromosomal translocation or a site-specific deletion has been reported in up to 30% of T-cell acute lymphoblastic leukemias (T-ALL). Here we used a polymerase chain reaction (PCR) assay to identify the 90 kb SIL-TAL1 deletion in a group of 19 cutaneous T-cell lymphomas and a series of 142 T-ALL patients (76 children, 66 adults). While none of the T-cell lymphoma exhibited a SIL-TAL1 recombination, seven T-ALL cases showed a type d1 and two patients a type d2 deletion. Of pediatric T-ALL, 9% (7/76) and of adult patients only 3% (2/66) were characterized by this genomic lesion. The deletion correlated with commitment to the T-cell receptor (TCR) alpha beta lineage, but lacked association with a distinct maturation stage. Sequence analysis of SIL-TAL1 breakpoints revealed marked heterogeneity at the junctional region among the nine patients due to random deletion and insertion of N-region nucleotides or templated P-nucleotide addition mediated via illegitimate V(D)J recombinase action. Clonospecific oligomer probes in conjunction with PCR allowed the detection of minimal residual disease in one out of four patients monitored during complete hematologic remission.

Adolescent↗

[Osteoma cutis. Multiple miliary osteoma of the face].

Primary and secondary forms of ossification can be distinguished on the basis of the skin, with osteoma cutis occurring in primary forms. Three entities can be differentiated: solitary and generalized osteoma cutis and multiple miliary osteoma of the face. Clinically, multiple papules 2-3 mm in diameter are present, which histologically consist of bony trabeculae enclosing mature fat cells and, occasionally, marrow cells. We describe the clinical, radiological and histological features of a case of multiple miliary osteoma of the face in an otherwise healthy 55-year-old woman.

Biopsy↗

Therapy with topical corticosteroids.

Therapy with topical corticosteroids has improved greatly in recent years due to both advanced understanding of their mode of action and awareness of their side effects, as well as newly developed derivatives with specifically designed pharmacological properties. Paradoxically, the fear of using corticosteroids has increased on the part of the public during the same period. Treatment of inflammatory or neoplastic skin disorders with topical corticosteroids can be both successful and safe only if certain points are clarified before it is begun. These include (a) specific diagnosis, (b) choice of strength of the compound needed for control of the disease, (c) time schedule for length of therapy and planned patient visits, and (d) choice of vehicle adequate to the skin lesion. Topical corticosteroids of different potency are available today; one can classify these into four groups (weak, medium, strong, very strong) and use them in a patient-tailored treatment. When large areas are to be treated, systemic side effects must be taken into consideration, and compounds that are degraded quickly after absorption are recommended. Finally, the corticophobia of many patients must be addressed by careful information to ensure compliance. Using these guidelines, treatment with corticosteroids is highly effective, easy to use by the patient, and allows a maximum of safety.

Administration, Topical↗

Distribution of adhesion molecules, IgE, and CD23 in a case of angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia developed in a 13-year-old boy. The immune phenotype of infiltrating cells and the distribution of adhesion molecules of the integrin, immunoglobulin, and selectin families were analyzed with monoclonal antibodies. The infiltrate consisted mainly of helper lymphocytes, monocytes, eosinophils, CD1+ dendritic cells, and mast cells. A CD23/Fc epsilon receptor was present on 40% of these cells, and surface bound IgE was present on 30% of these cells. The latter was found on all cell types. A cellular adhesion molecule analysis revealed that the proliferating endothelial cells were expressing constitutive ICAM-1, LFA-3, VLA-1, VLA-3, VLA-5, alpha 6, and beta 3-integrin chain as well as activation-dependent VLA-2, VCAM-1, and human lymphocyte antigen-DR. The infiltrating cells expressed LFA-1 and CD2, the correlating ligands for ICAM-1 and LFA-3. Our studies support previous observations of an unusual IgE-mediated immune reaction, and suggest an additional pathogenic role for adhesion events in the development of the pathognomonic cellular composition in angiolymphoid hyperplasia with eosinophilia.

Adolescent↗

Differential expression of adhesion molecules on infiltrating cells in inflammatory dermatoses.

BACKGROUND: Adhesion molecules and their ligands are involved in coordination of the activities of the immune system. OBJECTIVE: To evaluate whether adhesion molecules are relevant in the pathogenesis of inflammatory dermatoses, we analyzed the expression pattern of many of these molecules. METHODS: The expression of 10 members of the integrin and immunoglobulin superfamilies was mapped by means of immunohistochemical techniques in biopsy specimens of psoriasis (n = 15), pityriasis lichenoides (n = 11), parapsoriasis en plaques (n = 11), contact dermatitis (n = 7), and lichen planus (n = 5). RESULTS: In all investigated skin diseases, almost every infiltrating cell expressed lymphocyte function-associated antigens 1 and 3 as well as very late activation (VLA) antigens 4 and 5. The subepidermal infiltrate differed with regard to the expression of VLA-1, VLA-3, and VLA-6, which was high in lichen planus and moderate or absent in the other dermatoses. The intraepidermal lymphocytes in psoriasis and pityriasis lichenoides were VLA-1 positive, whereas the subepidermal infiltrate lacked this marker. CONCLUSION: The differential upregulation of adhesion molecules in the mononuclear infiltrate and on keratinocytes demonstrates their importance in the pathogenesis of cutaneous inflammation.

Antigens, Differentiation↗

Expression of adhesion proteins involved in cell-cell and cell-matrix interactions in the skin of patients with progressive systemic sclerosis.

BACKGROUND: Lymphocytic infiltration and activation of connective tissue metabolism in the early phase of progressive systemic sclerosis (PSS, scleroderma) may be critically influenced by cellular adhesion molecules (CAMs), which mediate cell-cell and cell-extracellular matrix interactions. OBJECTIVE: The tissue distribution might demonstrate a pathogenetic role of these adhesion molecules in early edematous and chronic fibrotic scleroderma. METHODS: We investigated by immunohistochemical techniques the in situ expression and distribution of beta 1 and beta 2 integrins, selectins, and CAMs of the immunoglobulin superfamily in patients with scleroderma. RESULTS: In the early disease stage a moderate percentage of perivascular CD3+/CD4+/TCR alpha/beta + lymphocytes showed expression of the alpha 3, alpha 5, and beta 1 chains and, to a lesser degree, of the alpha 1, alpha 2, alpha 4 and alpha 6 subunits. In contrast to chronic PSS, LFA-1 alpha, LFA-1 beta and ICAM-1 expression on mononuclear infiltrating cells was seen more frequently in acute scleroderma. Different percentages of fibroblasts expressed alpha 1-, alpha 3-, alpha 5- and beta 1-integrin chains. In acute PSS ICAM-1 was expressed especially by fibroblasts located around perivascular inflammatory infiltrates as well as by endothelial cells (ECs). A few ECs expressed alpha 2 beta 1 integrins. CONCLUSION: Our observations suggest that CAMs are intimately involved in early pathogenetic events in scleroderma, mediating cellular interactions between lymphocytes, ECs, and fibroblasts, as well as homing and tissue targeting of mononuclear infiltrating cells.

Acute Disease↗

Demonstration of clonal disease in early mycosis fungoides.

Cutaneous T-cell lymphomas (CTCLs) are known to show monoclonal T-cell infiltrates late in the course of the disease. However, detection of monoclonal T-cell proliferation in early stages is difficult. To investigate the possibility that clones might appear only as minor subpopulations, we analyzed the proliferative activity of T cells expression certain variable (V) regions of the T-cell receptor (TCR). In biopsy specimens from 27 patients with CTCLs, all T cells expressing the V regions V alpha 2, V beta 5a, V beta 5b, V beta 6, V beta 8 and V beta 12 accounted for less than 5% of the total infiltrate. In the vast majority of the cases, less than 3% of the cells expression one TCR V region proliferated. In one case of mycosis fungoides, however, an epidermotropic clone expressing V beta 8 was detected. This clone was present in two distinct lesions from different anatomic sites and was found in an early relapse 1 year after complete remission following PUVA therapy. The case described here documents the possibility of clonal disease early in the course of mycosis fungoides.

Aged↗

Infiltration of both T cells and neutrophils in the skin is accompanied by the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1): an immunohistochemical and ultrastructural study.

Various inducible adhesion molecules on human endothelial cells like the endothelial leukocyte adhesion molecule-1 (ELAM-1) seem to be the basis of mechanisms that allow peripheral blood leukocytes to enter precisely areas of inflamed tissue. Because in vitro data had shown that ELAM-1 plays a central role in neutrophil as well as memory T-cell endothelium interactions, we analyzed in vivo at the light and electron microscopic level its expression in various benign and malignant skin diseases, which differ in the composition of the cellular infiltrates. The expression of ELAM-1 on endothelial cells at different anatomical sites could be demonstrated independently from the cell type (neutrophils/memory T cells) infiltrating the surrounding tissue. On the ultrastructural level we demonstrate that the expression of ELAM-1 is restricted to certain segments of post-capillary venules exhibiting distinctive morphologic features. The ELAM-1-positive endothelia are identical to those vessels that are currently described to be the preferred sites of lymphocyte trafficking in diseased skin.

Antibodies, Monoclonal↗

Common pathogenetic pathways in allergic and irritant contact dermatitis.

Despite their different pathogeneses, allergic and irritant contact dermatitis show a remarkable similarity with respect to clinical appearance, histology, and immunohistology. To further analyze this apparent contradiction, our study was designed to meticulously compare cellular infiltrates in irritant and allergic patch-test reactions by immunostaining with a broad panel of monoclonal antibodies. For this purpose, skin biopsies from allergic and irritant patch-test reactions of similar inflammatory degree were obtained from the same probands. We found that after 72 h both types of reaction were characterized by an identical dermal infiltrate consisting mainly of memory T cells, many of which were activated, and macrophages. Dermal and epidermal Langerhans cell density and HLA--DR expression of keratinocytes were also virtually identical. Our results show that antigen recognition by specific memory T cells as well as irritants can finally induce the same pattern of inflammation, including activation of T cells obviously independent of exogenous antigen.

Adult↗

HTLV-1-negative pleomorphic T-cell lymphoma of the skin: the clinicopathological correlations and natural history of 15 patients.

The peripheral T-cell lymphomas represent a heterogeneous group and include, besides mycosis fungoides and Sézary syndrome, large-cell anaplastic lymphoma. We report 15 cases from our files that fulfil the histological criteria of pleomorphic T-cell lymphoma with primary skin involvement. Most of the cases were elderly with a male-to-female ratio of 1.5:1. The HTLV-1 serology was negative. The clinical features of these patients differed from those with mycosis fungoides and Sézary syndrome, in that eczematous and precursor lesions such as parapsoriasis en plaque were lacking apart from one exception. All the patients with small-cell pleomorphic T-cell lymphomas were alive, although three of the nine patients with medium-to-large tumour cells have died. Pleomorphic T-cell lymphoma should be regarded as a distinct entity among the lymphoproliferative disorders of the skin.

Adult↗

Expression of adhesion molecules in early allergic patch test reactions.

In order to study the relevance of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial leukocyte adhesion molecule 1 (ELAM-1) for lymphocyte extravasation in the early phase of allergic contact dermatitis, the time courses of lymphocyte infiltration and adhesion molecule expression during initiation of this disorder were determined. Sequential biopsies of positive allergic patch test reactions were obtained 4, 8, 16 and 24 h after antigen application, cryostat sectioned and stained with monoclonal antibodies for ICAM-1, VCAM-1, ELAM-1 and lymphocytes by use of an immunoperoxidase technique. The slides were evaluated semiquantitatively according to appropriate gradation scales that had been defined separately for the staining with each antibody. Our results show that there is a significant upregulation of VCAM-1 and ELAM-1 expression within the first 8 h after antigen application, when lymphocyte extravasation is just beginning. In contrast, ICAM-1 is already expressed in higher levels in normal skin and is hardly enhanced during the first 8 h of patch test reactions. The main influx of lymphocytes occurs 16-24 h after antigen application and is accompanied by a further increase in all three adhesion molecules. We conclude that VCAM-1 and ELAM-1 rather than ICAM-1 may be of particular importance for the start phase of allergic contact dermatitis and that all three of them contribute to an amplification of this inflammation.

Cell Adhesion Molecules↗

Immunophenotypical characterization of inflammatory cellular infiltrates in tinea.

In order to elucidate the still poorly understood pathogenetic pathways of acute tinea, the inflammatory cellular infiltrates in this infection were analyzed. Lesional punch biopsies were cryostat-sectioned and stained with monoclonal antibodies for immunophenotypization of T cells, B cells, macrophages and activation markers. For each antibody the positively stained inflammatory cells in the dermis and in the epidermis were quantified separately. Most of the dermal mononuclear cells in acute tinea were identified as T helper lymphocytes of the memory type. Furthermore, considerable amounts of Langerhans' cells and macrophages were found, but virtually no B cells. A high proportion of cells expressed markers of activation. Within the epidermis, accumulations of Langerhans' cells and LeuM5+ dendritic macrophages were detected near fungal element. In view of the otherwise rather similar cellular infiltrates in acute tinea and different non-infectious dermatoses, acute tinea may be particularly suitable to study the functional relationship of Langerhans cells and LeuM5+ macrophages.

Acute Disease↗

Role of beta 1-integrins in epidermotropism of malignant T cells.

To better understand the molecular mechanisms of epidermotropism, we immunohistochemically analyzed the expression pattern of adhesion molecules belonging to the integrin and immunoglobulin superfamilies in cases of mycosis fungoides (MF) (n = 15), pleomorphic T cell lymphoma (n = 10), and high-grade T cell lymphoma (n = 7). The cutaneous T cell lymphomas (CTCLs) investigated were categorized into cases with or without epidermotropism. Focal neoexpression of ICAM-1 on keratinocytes was restricted to epidermotropic lymphomas. Both LFA-1 and LFA-3 were expressed on infiltrating cells in all cases investigated. In contrast, beta 1-integrins showed differential expression, most prominent in the case of VLA-1 and VLA-6: These molecules were present on infiltrating cells in most cases with epidermotropic MF and absent in most other CTCLs. We conclude that the phenomenon of epidermotropism might involve different sets of adhesion molecules in different entities of CTCL, with VLA-1 being the most influential beta 1-integrin in the case of MF.

Antibodies, Monoclonal↗