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Biomedical subjects

L Misery

Publications and source records attributed to L Misery.

At least 19 recordsLinked to original sources

Presence of circulating abnormal CD34+ progenitors in adult Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is related to the proliferation of cells, which are similar to Langerhans cells (LC) but possess many abnormal characteristics. Lesions are widespread and this fact suggests that LCH cells or their precursors are present in the blood of patients. In five adult patients, we have isolated and cultured CD34+ blood progenitors of dendritic cells. We studied their phenotype by flow cytometry and their functional properties in mixed culture with heterologous lymphocytes and with autologous lymphocytes in the presence of tri-nitro-phenyl antigen (TNP). The amount of CD34+ precursors was dramatically higher than controls but a high mortality occurred during the in vitro differentiation. The phenotype of surviving cells was similar to LC phenotype (CD1a+, CD83+, Lag+) but some of them expressed CD2. These cells were able to induce T cell proliferation in mixed culture. They could not initiate primary response to TNP, except in a patient treated with thalidomide. In our hands, these CD34+ cells may be precursors of LCH cells.

Adult

Expression of substance P receptors in normal and psoriatic skin.

Recently, substance P receptors (SPR) have been detected in neonatal foreskin. Our purpose was to determine the expression of SPR in other localizations than neonatal foreskin. As SP has been implicated in the pathogenesis of inflammatory cutaneous lesions, we wondered whether SPR localization was modified in psoriatic lesions. In normal skin, SP binding sites were detected using biotinylated SP and abrogated by a specific NK1 antagonist (spantide) on blood vessels, sweat glands and hair follicles. In the normal epidermis, SPR were usually observed on granular layers but may also be observed on other cell layers. The SP binding processed on cultured keratinocytes demonstrated that SPR were expressed in the epidermis, except basal cell layers, confirming that keratinocytes constitutively express SPR. In skin lesions of psoriatic patients, SP binding sites were expressed on the uppermost keratinocytes which are not granular cells, and seem to be overexpressed. Our results raise the question of the role of SPR on psoriatic keratinocytes.

Adult

A case of Schnitzler's syndrome with nodular regenerative hyperplasia of the liver.

Schnitzler's syndrome is a rare condition of urticaria, macroglobulinemia, and sclerotic bone lesions. We report a case in a 70-year-old man in whom inflammatory polyarthralgia was followed by a nonpruritic urticarial eruption with a moderate decline in general health. Laboratory tests showed inflammation and a modest isolated peak of monoclonal IgM kappa. There was no evidence of Waldenström macroglobulinemia. Schnitzler's syndrome was considered. However, an ultrasound scan of the abdomen done because of mild gamma-glutamyl-transferase elevation disclosed multiple hepatic lesions. The liver histology showed incipient nodular regenerative hyperplasia. Only about 30 cases of Schnitzler's syndrome have been reported since the seminal description in 1972. Hepatic involvement was a common but nonspecific finding, and we found no cases with nodular regenerative hyperplasia. However, this abnormality is often found in patients with autoimmune or hematological disorders. The pathogenesis of Schnitzler's syndrome remains unknown, but the possibility of progression to a hematological malignancy requires prolonged follow-up.

Aged

Human normal dermal fibroblasts express somatostatin receptors.

The hormone/neuropeptide somatostatin (SOM) exerts multiple functions in the central nervous system, the immune system, the hypothalamo-pituitary axis, the gastrointestinal tract, and the pancreas. Endogenous SOM occurs in 2 biologically active forms, with 14 or 28 amino acids. Five subtypes of SOM receptors have been cloned. SOM is present in human skin. We have investigated the expression of SOM receptors on human dermal normal fibroblasts. Biotinyl-SOM allowed the visualization of SOM receptors on human dermal fibroblasts. Radioligand binding studies with (3-[125I]iodotyrosyl11)-SOM-14 were performed on these cells and the effect of SOM-14 on the DNA synthesis by fibroblasts was evaluated by measuring [3H]-methyl thymidine incorporation. Saturation curve, and Scatchard plot showed a homogeneous class of receptors with a Bmax of 0.055 +/- 0.023 nM and KD of 2.0 +/- 0.4 nM (values: mean +/- SEM). Fibroblasts expressed 3,317 +/- 1,385 binding sites per cell. Competitive displacement experiments showed that SOM-14 IC50 was 69.3 +/- 4.5 nM (mean +/- SEM), for SOM-28 33.2 +/- 6.0 nM and for octreotide 36.5 +/- 3.3 nM. The KI values calculated from these IC50 were, respectively: 62.4 +/- 4.1 nM; 29.9 +/- 5.4 nM; 32.9 +/- 2.9 nM. We conclude that subtype 2 or 3 SOM receptors is present on human normal dermal fibroblasts. A weak effect of SOM-14 on DNA synthesis was observed with SOM concentrations of 10(-7) and 10(-6) M.

Animals

Langerhans cells in the neuro-immuno-cutaneous system.

Langerhans cells are epidermal antigen presenting cells. They are able to express some neuronal markers. They express many neuropeptide receptors. Neuropeptides are able to modulate Langerhans cell functions. Langerhans cells are closely connected with nerve fibers in the epidermis. Thus, Langerhans cells and the nervous system are anatomically and functionally associated. We suggest that they belong to a neuroimmunocutaneous system. The interactions between nervous and immune system are probably important in the pathophysiogeny of inflammatory dermatoses.

Animals

Modulation of cutaneous SP receptors in atopic dermatitis after UVA irradiation.

Atopic dermatitis is a pruritic inflammatory skin disorder, involving immunological and non-immunological factors. Substance P seems to be involved in the pathogenesis of atopic dermatitis. Substance P-containing nerve fibers are increased in the lesional skin of patients with atopic dermatitis and a reduced weal and flare reaction to intradermal injection of substance P has been observed. We investigated the distribution of substance P receptors in the involved skin of patients before and after single or repetitive UVA irradiations. Our results indicate that substance P receptors of the NK-1 subtype are expressed on blood vessels and on epidermal keratinocytes of involved skin of patients with atopic dermatitis. UVA irradiations did not modify the epidermal distribution of substance P receptors but decreased their expression intensity on blood vessels. UVA irradiations seem to decrease skin inflammation through the modulation of NK-1 receptor expression on endothelial cells.

Dermatitis, Atopic

[Epidermolysis bullosa acquisita and hepatitis C].

INTRODUCTION: Epidermolysis bullosa acquisita is a bullous dermatosis. Its etiology remains unknown and the efficacy of its treatment is low. OBSERVATION: We report the first association between epidermolysis bullosa acquisita, chronic hepatitis C and cryoglobulinemia, healing with interferon alpha and ribavirine. DISCUSSION: We suggest a role for hepatitis C virus in the pathogenesis of epidermolysis bullosa acquisita. We suppose a synthesis of autoimmune antibodies in a dysimmune environment. Interferon alpha and ribavirine might be a new therapeutic avenue but further studies are necessary to confirm it.

Adult

Binding and in vitro modulation of human epidermal Langerhans cell functions by substance P.

Substance P (SP) is distributed in both the central and peripheral nervous system. It has various effects on immunocompetent cells, such as macrophages and lymphocytes. The aim of our study was to search for the presence of SP receptors (SP-R) on human cutaneous Langerhans cells (LC), and to determine the effects of SP on LC immunological functions in a model of mixed epidermal cell-lymphocyte reaction (MELR). Radioligand binding studies showed that LC-enriched epidermal cell suspensions reversibly bound SP, and that the specific binding increased with the percentage of LC. Functional assays showed that SP had no effect when added at concentrations from 10(-6) M to 10(-12) M to the MELR. The addition of SP at concentrations of 10(-4) M and 10(-5) M was able to inhibit the allogeneic T-cell response (98.3 +/- 1.8% and 92.8 +/- 8.9% inhibition, respectively) without modifying the cell viability. This inhibition was through an effect of SP on both T-cell and LC function. We conclude that SP has receptors on LC and may inhibit antigen presentation.

Binding, Competitive

Effect of UVB 311 nm irradiation on normal human skin.

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.

Adult

Presence of somatostatin in normal human epidermis.

Somatostatin (SOM) is a ubiquitous peptide which is responsible for the inhibition of numerous biological functions. SOM is described as an antiproliferative molecule and an inhibitor of exocrine or endocrine secretion from a variety of tissues, including pancreas, gastrointestinal tract, central and peripheral nervous system. Mediation of SOM effects can be indirect or direct, respectively, through other molecules or receptors on target cells. We have searched for the presence of SOM in the epidermis using immunofluorescence, confocal laser scanning microscopy, radioimmunoassay, and chromatography. Immunofluorescence and confocal laser scanning microscopy studies were performed using rabbit antiserum anti-SOM and mouse monoclonal antibody directed to CD1a Langerhans cell (LC) marker disclosed with fluorescein or tetramethylrhodamine isothiocyanate conjugates. SOM was extracted from whole skin or epidermal cell suspension or LC-enriched suspensions and analysed by radioimmunoassay. We used an antiserum which was reactive for the 6-11 portion of native SOM. Chromatographic columns were performed on extracts from whole skin. The epidermis was SOM immunoreactive. LC were immunoreactive for SOM and the staining was membranous. SOM was extracted from the whole skin at about 0.13 +/- 0.02 fmol/mg of tissue (mean +/- SEM). The SOM concentration in epidermal cell suspensions was 1.5 +/- 0.9 fmol/10(6) cells. Data obtained with LC-enriched suspensions showed large variations between donors. Extracts from skin showed one peak with an elution profile like that of 14 amino acid SOM. This study demonstrates that 14 amino acid SOM is expressed in normal human epidermis.

Chromatography, Gel

Skin, immunity and the nervous system.

Connections between nerve fibres and cutaneous cells have been studied using confocal and electron microscopy. In the skin, nerve fibres may secrete neuromediators, i.e. substance P, vasoactive intestinal peptide, somatostatin, calcitonin-gene-related peptide, gastrin-releasing peptide, neuropeptide Y, peptide histidine-isoleucine, neurotensin, neurokinins A and B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melanocyte-stimulating hormone and adrenocorticotrophic hormone are also expressed in the skin. Neuromediators and neurohormones may be secreted by cutaneous cells, which also express receptors. Functions of epidermal and dermal cells are modulated by these substances. Immune cells transiently present in the skin (e.g. macrophages and lymphocytes) are modulated by neuromediators through receptors. During the course of skin disorders, especially inflammatory reactions, the neuroimmunocutaneous system is destabilized. This is particularly true in psoriasis. This destabilization may be secondary, although evidence shows it can also be responsible for the induction and maintenance of the inflammatory process. The skin, the nervous system and immunity are not independent systems but are closely associated and use the same language of cytokines and neurotransmitters. A new concept is suggested: the neuroimmunocutaneous system.

Autocrine Communication