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Biomedical subjects

P Kaudewitz

Publications and source records attributed to P Kaudewitz.

67 records · Page 4Linked to original sources

Epidermal synthesis and expression of HLA-DR on keratinocytes in lupus erythematosus.

It has been suggested that aberrant expression of HLA-DR plays an important role in the induction of an autoimmune reaction. In lupus erythematosus (LE), skin represents a major target for autoimmune attack. We therefore tested lesional and nonlesional skin from 11 patients with different clinical subtypes of LE for the presence of HLA-DR molecules on keratinocytes using a monoclonal antibody against a non-polymorphic HLA-DR determinant. In all lesions tested, HLA-DR-positive keratinocytes were present, whereas in nonlesional skin, these cells remained HLA-DR negative. To exclude the possibility of passive absorption of DR molecules, the de novo synthesis of HLA-DR was demonstrated by the presence of cytoplasmic HLA-DR gamma chains in keratinocytes. If aberrant HLA-DR expression is a primary event, it could facilitate the recognition of autoantigens on keratinocytes by immunocompetent cells. Alternatively, the synthesis of DR molecules could be induced as a secondary event by mediators derived from the inflammatory infiltrate.

Adult↗

Significance of non-lymphoid ('accessory') cells in malignant lymphomas and pseudolymphomas of the skin.

We investigated the co-distribution of lymphocyte subpopulations and non-lymphoid 'accessory' cells in 35 cases of cutaneous lymphoproliferative diseases (T-cell lymphoma, 10 cases; B-cell lymphoma, 17 cases; pseudolymphoma, 8 cases) using immunohistochemical methods. T-zone histiocytes and particularly Langerhans cells were abundant in all cutaneous T-cell lymphomas, but were also found in B-cell lymphomas. T-zone histiocytes were associated with T-lymphocytes, especially T-helper cells, but not with T-suppressor cells. Dendritic reticulum cells were essentially confined to well differentiated germinal centres. Macrophages occurred in both lymphomas and pseudolymphomas without definite relationship with either B- or T-cells. In malignant lymphomas of high grade malignancy, macrophages represented the only non-lymphoid cell type. Our results indicate that malignant lymphoid cells, like normal lymphocytes, require definite micro-environments which are, at least in part, maintained by certain non-lymphoid cells.

Antigen-Presenting Cells↗

Monoclonal antibody patterns in lymphomatoid papulosis.

Atypical cells resembling Reed-Sternberg cells are a characteristic histologic feature of lymphomatoid papulosis. Thus far no consistent data are available on the nature of these cells, or a possible antigenic relationship between them and Reed-Sternberg cells. Twenty-four biopsy specimens from 14 patients with lymphomatoid papulosis were immunolabeled with antibodies against Ki-1 and other Reed-Sternberg cell-associated antigens. In all cases a proportion of the large, atypical cells expressed the Ki-1 antigen. In contrast, in 20 biopsy specimens of benign inflammatory skin lesions or mycosis fungoides, Ki-1-positive cells were absent or only occasionally present. Furthermore, the large atypical cells of lymphomatoid papulosis also expressed other antigens (for example, T3, T4, HLA-DR, IL-2 receptors) that have previously been demonstrated on Reed-Sternberg cells. Our findings, together with the observation that the Ki-1 antigen can be induced on peripheral blood lymphocytes after prolonged phytohemagglutinin stimulation, suggest that the Ki-1-positive cells in lymphomatoid papulosis are activated T cells closely related to the Reed-Sternberg cells of Hodgkin's disease.

Antibodies, Monoclonal↗

Cutaneous B-cell lymphoma.

The various morphologic and functional subtypes of nodal B-cell lymphomas can also be found in the skin. These reflect the various steps of lymphocyte differentiation including maturation from the pre-B lymphocyte to the well-differentiated B2 lymphocyte or plasma cell in the peripheral blood. The subtypes of cutaneous B-cell lymphomas have been discussed (Kiel classification); the percentages indicate the frequencies of the subtypes among a total of 736 cutaneous lymphomas of both T-cell and B-cell origin: Lymphocytic lymphoma (7 per cent). Immunoglobulin-producing lymphomas, including the rate plasmacytoma of the skin, lymphoplasmacytoid immunocytoma, which represents the largest group of cutaneous B-cell lymphoma (12 per cent), and immunoblastic lymphoma, which is the most aggressive form in this group (8 per cent). Cutaneous B-cell lymphoma arising from or related to follicular center cells, including centrocytic lymphoma (7 per cent), mantle-cell lymphoma, centroblastic/centrocytic lymphoma (6 per cent), the highly malignant centroblastic lymphoma (4 per cent), and lymphoblastic lymphoma, Burkitt type. The Ann Arbor staging system is not applicable to cutaneous B-cell lymphoma; therefore, a TNM staging system has been proposed. The diagnosis of cutaneous B-cell lymphoma is based primarily on cytomorphologic features. Differentiation of cutaneous B-cell lymphoma from pseudolymphoma of the skin cannot be based on a single criterion; a spectrum of characteristic features must be evaluated. Analysis of the infiltrating cells in cutaneous B-cell lymphoma using monoclonal antibodies demonstrates that the proliferation of the neoplastic clone is accompanied by a mixture of accessory cells of various origins, including T cells, macrophages, and dendritic reticulum cells. As in nodal B-cell lymphomas, several factors may be involved in the generation of cutaneous B-cell lymphoma, including persistent antigenic stimulation and loss of regulatory mechanisms for lymphocyte proliferation and differentiation in conjunction with environmental and other factors.

B-Lymphocytes↗

Distribution of T-cell subsets as defined by monoclonal antibodies in skin lesions of psoriasis vulgaris.

Cryostat tissue sections from skin lesions of 16 patients suffering from chronic stationary psoriasis vulgaris were assayed for the presence of distinct T-cell subpopulations with monoclonal antibodies. Using two pan-T surface markers (M-T 4-11 and Lyt 3) the total number of infiltrating T-cells was measured. This cell population was further dissected into Leu 3a (helper/inducer) and M-T 8-11 (cytotoxic/suppressor) positive subsets. Percentages of T-cell subpopulations were within the ranges found in healthy peripheral blood and were thus regarded as normal.

Antibodies, Monoclonal↗

Immunoenzymatic typing of lymphoplasmacytoid skin infiltrates.

Monoclonal immunoglobulin-producing lymphomas (immunocytomas, plasmacytomas, and immunoblastomas) constitute 15 to 20% of all cutaneous lymphomas. Their differentiation from polymorphous lymphoplasmacytoid inflammatory or pseudolymphomatous infiltrates may be difficult if sections are stained for a single light chain only. It was the aim of the study to elucidate the ratio of the kappa- to lambda-positive cells in 10 lymphoproliferative, 5 pseudolymphomatous, and 42 inflammatory lymphoplasmacytoid cutaneous infiltrates and to characterize them by the type of Ig (alpha, gamma, mu, kappa, or lambda) synthesized intracellularly. An indirect immunoenzymatic double-labeling method (alkaline phosphatase and peroxidase) was used for the simultaneous demonstration of kappa and lambda light chains and alpha, gamma, and mu heavy chains in paraffin sections. Ig-producing lymphomas of the skin show patchy monoclonal proliferations of cells synthesizing kappa IgM in almost 50% of the cases (5 of 10). Monoclonality is claimed if the ratio of lambda- to kappa-positive cells is at least 1:10, or vice versa. In polyclonal inflammatory and pseudolymphomatous infiltrates, the lambda/kappa ratio never exceeds 1:5. The most common cell type found in these reactive infiltrates produces gamma heavy chain; some produce alpha chain, but only a few produce mu chain. In high-grade malignant lymphomas, the tumor cells may lose their capacity for Ig production.

B-Lymphocytes↗

Genetic influence on natural cytotoxicity and interferon production in multiple sclerosis studies in monozygotic discordant twins.

A dysfunction in natural killer (NK) cell activity has been assumed to play a substantial role in the pathogenesis of multiple sclerosis (MS). To investigate whether such a defect is genetically determined and thus in combination with a certain HLA status may represent an additional risk factor for contracting MS, spontaneous and interferon (IFN) induced NK cells activity against the K562 target cell were analyzed in nine pairs of monozygotic twins discordant for MS. In addition, IFN production was tested in nonadherent lymphocytes stimulated with PHA, influenza virus or leukemia cells. When compared to healthy controls, NK function appeared to be normal in healthy twins, whereas some MS patient displayed decreased activity. No difference in IFN induced NK cell activity and IFN production could be detected between normal controls, healthy twins, and MS patients. These data argue against a genetically determined dysfunction within the NK-IFN system in patients with MS.

Adult↗

Treatment of non-hodgkin's lymphoma of low-grade malignancy with human fibroblast interferon.

10 patients with advanced non-Hodgkin's lymphoma of low malignancy were treated with partially purified HulFN-beta. They received daily i.v. infusions of 4.5 X 10(6) IU for 4 weeks, followed by 9 X 10(6) IU daily for 2 weeks. Patients with stable disease during this period received consolidation therapy with 4.5 X 10(6) IU three times per week for a maximum of 20 weeks. Six out of 10 patients had progressive disease after the initial 6 week treatment and 4 had stable disease. Two of the latter developed progressive disease during consolidation therapy, one had a complete remission of minimal bone marrow involvement, and one was in partial remission with a loss of bone marrow infiltration but unchanged lymph node enlargement.

Adult↗