Thymopoietin pentapeptide treatment of sarcoidosis.
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Biomedical subjects
Publications and source records attributed to M Faure.
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Using a monoclonal antibody against human HLA-DR antigens and OKT6, we investigated by indirect immunofluorescence the distribution of Langerhans cells in normal human skin and involved and uninvolved skin from patients with psoriasis before, during, and after systemic aromatic retinoid administration. In parallel, enumeration of HLA-DR and of OKT6+ cells was also performed. In involved psoriatic epidermis the distribution of positive cells was disturbed; OKT6+ cells were reduced in number, as were HLA-DR+ cells which were seen in clusters. In control skin sections, a regular pattern of fluorescent dendritic epidermal cells was noted. In normal-appearing human skin, in nonlesional psoriatic skin, but not in diseased psoriatic skin, the number of OKT6+ cells per epidermal section surface unit was higher than that of HLA-DR expressing cells. Changes in the number and distribution of OKT6 and HLA-DR+ cells in psoriatic involved epidermis were corrected by oral retinoid treatment.
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Since the first demonstration of skin antibodies in sera of pemphigus patients by IF (Beutner & Jordon 1964), the scope of skin diseases in which immunologic findings may be of interest has enormously enlarged and dermatology remains one of the leading clinical specialities applying IHC in both diagnosis and research. Immunohistological techniques and, to a lesser degree, immunocytological techniques, have been developed to include not only IF, but also immunoenzymatic methods. Even if not all immunological findings may be disease specific and diagnostic, immunohistological techniques have become a very useful tool for studying skin biopsies in connection with serological methods. Their importance could be increased with rapid development of a new field: the study of normal skin constituents; e.g. Ag, collagen, keratin, with the help of specific polyclonal and monoclonal antibodies.
Rat aortic smooth muscle cells were isolated and maintained in primary culture. After 2-3 days, cells recovered their contractile phenotype and could be induced to contract in response to vasopressin and angiotensin II. Vasopressin- and angiotensin-specific binding sites were detected on these cells, using tritiated Lys8-vasopressin, Asn1-Val5-angiotensin II, and Sarc1-Ile8-angiotensin II. Vasopressin binding sites had Kd values of 30 and 12 nM for Lys8-and Arg8-vasopressin, respectively, and a maximal binding capacity of 25,000 sites/cell. They displayed several of the expected characteristics of vasopressin receptors involved in the vasopressor response in vivo. A highly significant correlation was found between the relative agonistic or antagonistic vasopressor potencies of a series of vasopressin structural analogues and their relative abilities to inhibit [3H]vasopressin binding to aortic smooth muscle cells. Specific binding sites for Asn1-Val5-angiotensin II and Sarc1-Ile8-angiotensin II had the following characteristics: Kd = 2.3 and 1.3 nM, respectively; maximal capacity: 50,000 sites/cell. Vasopressin and angiotensin did not modify the intracellular cyclic AMP content of aortic smooth muscle cells.
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A monoclonal gammopathy was observed in 3 adult patients with long-term and widespread scleredema (Buschke's disease). There was no evidence of multiple myeloma in any patient. The monoclonal immunoglobulin was in every case of the IgG-kappa type. Bence Jones proteinuria was noted in 1 case (kappa). Deposition of monoclonal IgG-kappa in the skin was not detected by immunofluorescence microscopy. These findings and previous reports of 5 cases suggest that diffuse scleredema may be frequently associated with paraproteinemia, but the role of monoclonal immunoglobulins in the pathogenesis of the disease remains to be clarified.
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The distribution of intracellular keratins was investigated in normal bronchial epithelium and in several morphologically distinct forms of respiratory tract carcinomas. This study was performed with two different experimentally produced antisera against normal human stratum corneum keratin and against keratin protein of MW 67,000 dalton, using indirect immunofluorescence and immunoperoxidase methods on tissue sections and cell suspensions. In normal bronchial epithelium, the basal cells were strongly labelled by both antisera. The ciliated columnar cells appeared devoid of cytokeratins in tissue sections but were strongly labelled with both antisera in cell suspensions. The goblet cells remained negative in every case. In squamous metaplasia of the bronchus, all epithelial cells were unevenly stained with both antisera. Among tumours, only the squamous cell carcinomas were strongly labelled by both antisera. Primary lung adenocarcinoma appeared weakly positive, whereas metastatic lung carcinomas, undifferentiated lung carcinomas, oat cell tumours, carcinoid tumours were negative. The immunocytochemical determination of keratins appeared to be of value in the study of normal and abnormal epithelial differentiation, in the diagnosis of poorly differentiated carcinomas and in their distinction from metastatic tumours of the lung.
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The expression of sugar residues on human epidermal cells was investigated by means of lectin binding, as a way of determining membrane structural changes occurring during the differentiation of the epidermis. Fourteen lectins of different sugar specificity were conjugated with fluorescein isothiocyanate (FITC-lectins) and tested in fluorescence microscopy on frozen sections of normal human epidermis. In parallel, FITC-lectins were tested on psoriatic-involved epidermis to visualize differences in the expression of sugar residues that might occur during abnormal epidermal differentiation. No labelling could be obtained with lectins from Bandeira simplicifolia I, Dolichos biflorus, Limulus poyphemus, Tetragonolobus purpureas, Ulex europeus I, and Triticum vulgaris (group 1 lectins). A "pemphigus-like" intercellular labelling of the whole epidermis, except the stratum corneum, was obtained with lectins from Canavalia ensiformis. Maclura pomifera, Phaseolus vulgaris, and Ricinus communis I (group 2 lectins). A selective intercellular labelling of the stratum spinosum and the stratum granulosum was seen in normal epidermis with lectins from Arachis hypogaea, Glycine max, Helix pomatia, and Sophora japonica (group 3 lectins). In psoriatic epidermis, not only the basal cell layer, but also cells from the adjacent lower stratum spinosum were found to be negative, using FITC-lectins of group 3. These data indicate that the expression of lectin binding sites in normal epidermis differs according to the maturation of the cell from the basal cell to the more mature keratinocyte in the stratum granulosum. They suggest that lectins may be used as markers of epidermal cells in various stages of normal and abnormal differentiation.
Peripheral blood lymphocytes frm 16 patients with sarcoidosis (9 patients with skin sarcoids, 7 patients with erythema nodosum and bilateral hilar adenopathy) and cutaneous anergy and from 23 age-matched healthy controls were characterized by reactivity with monoclonal antibodies OKT3, OKT4, OKT8 directed to surface antigens of T lymphocytes, helper-inducer and suppressor-cytotoxic T cell subsets, respectively. In contrast to healthy controls, patients with sarcoidosis had reduced percentages of OKT3+, OKT4+ and OKT8+ cells and a major decrease in the OKT8+ (suppressor) subset. However, these changes were significant only in the group of patients with acute sarcoidosis (erythema nodosum). This abnormal T cell distribution correlates with the alterations in cell-mediated immunity previously observed and suggests the presence of a defective circulating suppressor T cell activity in acute sarcoidosis.
Three cases of skin reactions that occurred in patients under oral administration of Piroxicam are reported here: one erythema-multiforme-like reaction and two cases of acute, pruriginous erythemato-papulous dermatitis, one of which with intraepidermal blister formation. No past history of skin disease could be formed; lesions spontaneously improved when the drug was stopped. Only in one patient, receiving Piroxicam and Fenoprofene, an acute nephritis was observed. The role of Piroxicam, a new non-steroid antiinflammatory agent in the pathogenesis of the skin reactions observed is discussed. However, the renal involvement formed in one case is likely due to Fenoprofene, as in previously reported cases.
Peripheral blood mononuclear cells obtained from patients with various skin disorders were studied by indirect immunofluorescence using the monoclonal antibodies OKT3, OKT4, and OKT8 which react with human T cells (OKT3+ cells), helper-inducer (OKT4+) and suppressor-cytotoxic (OKT8+) T cell subsets, respectively. In parallel, the balance between peripheral blood helper and suppressor subsets was established by the determination of OKT4+/OKT8+ ratios (helper/suppressor ratios). In patients with the Sézary syndrome, but not in patients with mycosis fungoides or parapsoriasis "en plaques," highly significant increases in the helper/suppressor ratios accompanied by decreased levels of suppressor cells were found compared to controls. T cell imbalance with high helper/suppressor ratios and low percentages of circulating OKT8+ suppressor cells were also observed in patients with atopic dermatitis, lichen planus, or acute sarcoidosis (i.e. patients with erythema nodosum sarcoidosis and bilateral hilar adenopathy). In patients with cutaneous manifestations of chronic graft vs. host diseases, low helper/suppressor ratios and elevated OKT8+ cell levels were observed. T cells and T cell subset enumerations and related helper/suppressor ratios were found to be within normal range in patients with psoriasis, systemic lupus, erythematosus, discoid lupus erythematosus, bullous disorders (bullous pemphigoid, dermatitis herpetiformis, pemphigus vulgaris), and miscellaneous diseases.
The nature of normal human epidermal cells (EC) and peripheral blood (PB) cells that react in vitro in allogeneic mixed skin cell lymphocyte culture reaction (MSLR) was investigated using monoclonal antibodies (MCAB) specific for cell subpopulations. T cells and helper-inducer and suppressor-cytotoxic T cell subsets were defined by OKT3, OKT4, OKT8 MCAB, respectively, whereas, among EC, Langerhans cells were characterized by reactivity with OKT6 or anti-HLA-DR MCAB. MSLR were conducted with untreated cell suspensions as controls and cells suspensions depleted of various functionally active cell subset(s). Two approaches were used for cell depletion: (1) complement (C')-mediated lysis by MCAB of T cells, T cell subsets, HLA-DR or OKT6 positive cells; (2) panning of PB cells or EC after pre-incubation with the appropriate MCAB to deplete or enrich (OKT6) cell suspensions with the respective cell subset. Responses in MSLR were abolished after treatment of PB cells with OKT3 + C' or OKT4 + C', significantly reduced with OKT8 + C'; they were abolished after incubation of EC with anti-HLA-DR + C' and significantly reduced with OKT6 + C'. After panning, OKT3 and OKT4 depleted populations did not proliferate in MSLR while OKT8 depleted populations respond as controls. OKT6 depleted EC were not able to stimulate PB cells, yet proliferation rates were increased after stimulation by OKT6 enriched EC. Data show that helper-inducer T cells (OKT3+; OKT4+) play the major role in MSLR and that the presence of Langerhans cells is necessary for the stimulation of PB cells. They also suggest that co-operation between helper and suppressor cells is necessary for an optimal response. Differences in results using either OKT6 or anti-HLA-Dr-C'-mediated treatment of EC may be related to differences in the cellular expression of these markers by EC.
The ability of human normal skin epidermal cells (EC) to induce the proliferation of allogeneic and autologous lymphocytes was investigated in vitro in mixed skin cell-lymphocyte culture reaction (MSLR) as an in vitro approach of the lympho-epidermal interactions that are suspected to be involved in the pathogenesis of cutaneous inflammatory skin diseases and T cell lymphomas in man. Normal human EC were able to stimulate either allogeneic or autologous lymphocytes in MSLR in culture conditions similar to that previously reported in animals. The stimulation was higher in allogeneic than in autologous MSLR. MSLR did not appear to be affected by the trypsin treatment used to obtain EC in suspensions. Lymphocytes proliferation was maximal with a lymphocytes/EC ratio of 1:1. This suggests that autologous and allogeneic MSLR in man depends upon in vitro conditions similar to that studied in animals, and that MSLR may provide an useful tool for the study and the understanding of lympho-epidermal interactions in man.
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