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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 109 records · Page 6Linked to original sources
PubMed1997

Langerhans' cells are depleted in chronic graft versus host disease.

AIMS: To measure Langerhans' cells in skin of patients treated by bone marrow transplantation who developed chronic graft versus host disease (GvHD); to determine whether the reduction in Langerhans' cells resulted directly from the GvHD or from other factors, such as the immunosuppressive regimens used in bone marrow transplant patients. PATIENTS AND METHODS: Lesional and nonlesional skin specimens from nine patients with lichen planus-like lesions and three patients with sclerodermoid lesions were studied. Control skin specimens were taken from three patients undergoing breast reduction surgery. The number of Langerhans' cells/mm2 and the area of Langerhans' cells as a percentage of total epidermis were measured by counting cells labelled with antihuman CD1a. RESULTS: A significant reduction in Langerhans' cell area and number were found in specimens with lesions (area 3.5%; number 507/mm2) compared with specimens without lesions (8.42%; 2375/mm2). In contrast, Langerhans' cell area and number in skin without lesions were similar to controls (10.26%; 2968/mm2). CONCLUSIONS: Langerhans' cells were significantly reduced in skin with lesions of chronic GvHD but not in skin without lesions from the same patient, suggesting that the reduction is a direct consequence of GvHD and not linked to immunosuppressive drugs or late effects of conditioning regimens. In long term bone marrow transplant recipients, Langerhans' cells are derived mainly from the donor cells; therefore, this result suggests the occurrence of autoreactive phenomenon in chronic GvHD.

Adolescent↗
PubMed1997

Biafine applied on human epidermal wounds is chemotactic for macrophages and increases the IL-1/IL-6 ratio.

Using a model of pure epidermal wounds in normal human volunteers, we have studied the effects of Biafine emulsion firstly on inflammatory cell migration, vascular permeability and cytokine release during the first 24 h, and secondly on epidermal wound healing by measuring transepidermal water loss from day 1 to day 7. Under these conditions, Biafine does not improve epidermal healing, in contrast to what is observed with bleeding dermoepidermal wounds. Our results suggest that the effects of Biafine are essentially at the dermis level. The analysis of epidermal wound exudates leads to the same conclusion. As a matter of fact, we demonstrated that Biafine is chemotactic for macrophages and increases the IL-1/IL-6 ratio, chiefly by reducing the secretion of IL-6. This study permits to progressively clarify the mode of action of Biafine, that seems to be located at the level of granulation tissue formation and not at the epidermal level.

Adolescent↗
PubMed1997

Epstein-Barr virus-associated lymphoproliferative disease during methotrexate therapy for psoriasis.

BACKGROUND: Epstein-Barr virus (EBV)-associated lymphoproliferative disorders have recently been observed during treatment of rheumatoid arthritis and dermatomyositis with low-dose methotrexate. OBSERVATION: A patient with psoriasis developed a B-cell lymphoproliferative disorder during long-term treatment with low-dose methotrexate. The lymphoid cells expressed EBV latent membrane protein 1, and the EBV viral genome was present as demonstrated by in situ hybridization. Evaluation for EBV clonality showed that the lymph node contained clonal EBV DNA. Polymerase chain reaction studies confirmed that the B-cell lymphoproliferative disorder was mainly monoclonal, suggesting that the disorder arose from a single EBV-infected B-cell clone. CONCLUSIONS: Lymphoproliferative disorders associated with Epstein-Barr virus in which the clinicopathological presentation is similar to those occurring in patients after transplantation may be observed in patients with psoriasis treated with methotrexate. While it is impossible to rule out a fortuitous occurrence of an EBV-associated lymphoproliferative disorder and psoriasis treated with methotrexate in the same patient, EBV appears to be critical in the pathogenesis of the lymphoproliferative disorder in this patient.

Antigens, Viral↗
PubMed1997

Malignant melanoma and granulomatosis.

Sarcoidosis or granulomatous reactions have rarely been reported in association with malignant melanoma (MM). We describe seven patients who presented with both granulomatous disease and MM, and discuss the physiopathological and prognostic significance of this association. In three patients, the granulomatosis was diagnosed as true sarcoidosis and in one patient, as tumour-associated granuloma. In three cases, designated here as atypical tumour-associated granulomatoses, the presence of clear-cut pulmonary granulomatous nodules was typical neither for sarcoidosis nor for tumour-associated granuloma and was highly suggestive of melanoma metastases. Mediastinal lymphadenopathy was present in every patient. In all seven patients, the question of mediastinal or pulmonary involvement or relapse of the MM was raised, but could be confirmed in only one patient. MM can be associated with granulomatous disease. Knowledge of this association has implications in the management of patients with MM.

Adult↗
PubMed1997

[BCG-induced mycobacterium infection induced by alternative medicine].

INTRODUCTION: Mesotherapy is an alternative medical process defined by the intradermal injection of small amounts of pharmacological substances. It has been associated with the development of mycobacterial infections. CASE REPORT: A 80-year-old woman presented with a Mycobacterium bovis infection of the face following mesotherapy. Genome analysis of the mycobacterial strain isolated from a skin lesion using pulse-field gel electrophoresis demonstrated the presence of a vaccinal strain identical to the one employed by the same physician to vaccinate a child two hours before. DISCUSSION: Given the severity of mycobacterial infections following mesotherapy and given the lack of evidence about its efficacy, mesotherapy should not be performed on the face. Standardisation of aseptic measures in the daily medical practice could prevent such infectious complications.

Aged↗
PubMed1996

Ultraviolet-A induces activation of AP-1 in cultured human keratinocytes.

UV-A irradiation induces a time-dependent activation of AP-1 in NCTC 2544 human keratinocytes. 4 h after irradiation, a 2-3-fold increase in AP-1 activity is observed in human keratinocytes and fibroblasts. Activation is still detectable 24 h later. The UV-A induced AP-1 binding complex is shown to contain c-Fos and c-Jun proteins. Lipophilic vitamin E impedes UV-A induced lipid peroxidation but does not prevent AP-1 activation which is inhibited by N-acetylcysteine, a hydrophilic antioxidant. This finding suggests that UV-A-dependent AP-1 activation is sensitive to the cellular redox state but is not related to membrane lipid peroxidation.

Acetylcysteine↗
PubMed1996

Binding of autoantibodies is not restricted to desmosomes in pemphigus vulgaris: comparison of 14 cases of pemphigus vulgaris and 10 cases of pemphigus foliaceus studied by western immunoblot and immunoelectron microscopy.

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases characterized by a loss of cell-cell adhesion and by autoantibodies directed against epidermal cadherins. PF antigen has been established as desmoglein I which is located strictly on the desmosome, whereas the precise ultrastructural localization of PV antigen remains unclear and controversial to date. To further investigate this question, we compared the location of immune deposits in 14 patients with PV and 10 patients with PF by both direct and indirect immunoelectron microscopy (IEM). Inclusion criteria were based upon clinical features, histological level of cleavage and characterization of circulating antibodies by Western blot on epithelial bovine tongue extracts. IEM was performed on unfixed 0.7-mm slices of skin for the direct technique or on normal skin for the indirect technique using peroxidase labelling. In PF, by both direct and indirect IEM, immune deposits were located on the extracellular part of desmosomes (desmoglea) in all the samples studied. In PV, by both direct and indirect IEM, deposits were situated on the desmoglea and along large portions of the keratinocyte membrane without desmosomal structures in 15 of the 18 samples studied and only on the desmoglea in 3 samples. These results suggest that, in contrast to PF, the target antigen in PV is not always restricted to desmosomes. As various types of adherens junctions have been reported to mediate cell adhesion in the epidermis, the PV antigen could be a component of desmosomes and of other focal adhesions.

Adult↗
PubMed1996

Effect of human basic fibroblast growth factor on fibroblast proliferation, cell volume, collagen lattice contraction: in comparison with acidic type.

Human recombinant basic fibroblast growth factor (bFGF) is a potent mitogen for normal human dermal fibroblasts in the presence of heparin which binds to and stabilizes it. The optimal mitotic response is obtained with a concentration of 1 ng/ml of bFGF in monolayer cultures (non-differentiated fibroblasts) as well as in the better-differentiated fibroblasts obtained through the 'collagen lattices' culture system (fibroblasts embedded in a 3-dimensional collagen gel) achieving a doubling of the cell number in 8 days. Despite increasing the number of cells, bFGF decreases the ability of fibroblasts to contract collagen fibers. This inhibition is concentration-dependent and reaches a plateau at a dose of about 1 ng/ml. This effect is associated with a bFGF-induced decrease of fibroblast volume. Various dosing regimens indicate that although the highest response was obtained by daily dosing nearly optimal response was obtained either by early daily dosing or short intermittent treatment. Interestingly, the fibroblast mitotic response to bFGF decreases steadily when fibroblasts mature in collagen gels. The mitogenic properties of bFGF associated to its ability to inhibit fibroblasts contraction, if demonstrated in vivo, may be of interest in the management of wound healing.

Cell Division↗
PubMed1996

Alteration of lipoproteins of suction blister fluid by UV radiation.

Suction blister fluid is a good representative of the interstitial fluid feeding the epidermal cells. Lipoproteins contained in the suction blister fluid of healthy volunteers are readily photo-oxidized by UV radiation in the wavelength range 290-385 nm. Absorbed light doses equivalent to one minimal erythemal dose absorbed by skin exposed to UVB (e.g. 290-320 nm) are sufficient to induce lipid peroxidation and modification of apolipoproteins A-I, A-II and B. Albumin, which is known to protect serum fully from oxidative stresses, is not so effective against photo-oxidation. Although tryptophan (Trp) residues of proteins contained in the suction blister fluid are photo-oxidized, apolipoprotein A-II, which does not contain any chromophoric Trp residue, is also altered by the UV radiation. With regard to results obtained with a model reconstituted fluid, it is suggested that the radical chain reaction of the lipid peroxidation can transfer the initial photodamage at sites not directly susceptible to photo-oxidation. The biological implications of these results are discussed.

Apolipoprotein A-I↗
PubMed1996

Mapping of a second locus for lamellar ichthyosis to chromosome 2q33-35.

Lamellar ichthyosis (LI) is an inherited autosomal recessive disorder of cornification. It was recently demonstrated to result from deleterious mutations in the transglutaminase 1 (TGM1) gene. However, the disease was shown to be genetically heterogeneous, since some families were found to be unlinked to TGM1. Homozygosity mapping on three consanguinous families originating from Morocco shows (i) absence of linkage with TGM1 and other regions of the genome containing genes involved in cornification, and (ii) location of a second disease-causing gene on chromosome 2q33-35. A maximum two-point lodscore of 7.60 was obtained with D2S157 for theta = 0. The analysis of recombination events places the gene within a 7-8 cM interval. Additional consanguinous pedigrees were also demonstrated to be unlinked both to TGM1 and to 2q33-35, suggesting the existence of at least a third disease-causing gene.

Chromosome Mapping↗
PubMed1996

Cell survival and shuttle vector mutagenesis induced by ultraviolet A and ultraviolet B radiation in a human cell line.

Although it is known that sunlight is carcinogenic,few molecular data are available concerning the mutagenic effects of ultraviolet (UV) B (290-320 nm) and UVA (320-400 nm) radiation in human cells. To analyze the biologic effects of UVA and UVB, we irradiated the 293 human cell line, derived from adenovirus-transformed human embryonic kidney cells, in which we had stably introduced a shuttle vector harboring the lacZ' bacterial gene as the mutagenesis target. Identical cell survival occurred after UVA doses 700-fold higher than UVB. This comparable to the UVA/UVB ratio that reaches the basal cell layer of the skin after sunlight exposure with UVB sunscreen. The frequency of UVA- and UVB- induced mutations increased with the UV dose as cell survival decreased. At cell survival levels greater than 10%, UVA and UVB induced similar frequencies of mutations in the episomal lacZ gene, whereas for cell survival lower than 10%, UVA induced twice as many mutations as UVB. Sequence analysis of 81 independent lacZ mutants (36 UVA- and 45 UVB-induced) revealed specific characteristics for some UV-induced-mutations, particularly for UVB. Mutations at A/T base pairs were induced more frequently by UVA than by UVB. The UVA-induced mutation spectrum that we have observed in human cells may help help to elucidate the mechanism of skin carcinogenesis.

Amino Acid Sequence↗
PubMed1996

Heparin induces fibroblast proliferation, cell-matrix interaction and epidermal growth inhibition.

We have examined the effect of heparin on fibroblasts cultivated in monolayer or in a 3-dimensional culture system: the so-called collagen lattices. Thereafter, we have investigated the effect of heparin on the kinetics of epidermal growth on the collagen lattices. In monolayer culture, heparin stimulated the fibroblast growth with an optimal response at 0.01 mg/ml. The volume of treated fibroblasts was smaller than that of untreated controls. In the collagen lattices, heparin stimulated the fibroblast growth with an optimal response at 0.1 mg/ml. The volume of treated fibroblasts was greater than that of untreated controls, the opposite to the result observed in monolayer culture. The beginning of the contraction of the collagen lattices was inhibited by heparin. Heparin inhibited epidermal growth on the immersion as well as on the emersion collagen lattices. These effects of heparin should be the consequences of heparin-induced modifications of cell-matrix interactions.

Biopsy↗