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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 163 records · Page 9Linked to original sources
PubMed1994

Long-term use of topical calcipotriol in chronic plaque psoriasis.

BACKGROUND AND DESIGN: A multi-centre, open, prospective study of 12 months duration was performed to assess safety, efficacy and tolerability of topical calcipotriol in the long-term treatment of psoriasis. One hundred and sixty-seven adults with chronic plaque psoriasis who had previously responded to calcipotriol entered the study. Disease activity was monitored using the psoriasis area and severity index (PASI). Calcipotriol ointment 50 micrograms/g was applied twice daily until remission was attained. Treatment was then stopped but reinstituted in the event of relapses. RESULTS: Of the 167 recruited patients, 6 patients did not receive any treatment during the trial. A total of 39 patients were withdrawn: 15 due to inadequate control of their psoriasis, 9 due to irritant reactions, 7 due to defaulting and 8 for miscellaneous voluntary reasons. A further 24 patients either reached the study medication limit of 2,500 g or were considered to have completed the study a few weeks prior to the 12-month period. Accordingly, 98 patients were assessable after 12 months of therapy. Complete clearing was obtained in 26% of subjects, who then used the treatment intermittently. The remaining patients required continuous treatment for 12 months. The mean PASI fell from 8.1 (SD +/- 6.67, n = 167) at baseline to 3.90 (+/- 3.50, 136) at 2 months and 2.71 (+/- 2.12, 98) at 12 months. There was no rise in the mean serum total calcium. CONCLUSION: Calcipotriol ointment was safe, effective and well tolerated.

Administration, Topical↗
PubMed1994

[Abnormal fibrinolysis in Degos disease. A study of 3 cases].

INTRODUCTION: Degos' disease is a rare dermatosis characterized by papular lesions with a porcelain-white central atrophy and histopathological aspect of wedge-shaped infarction necrosis and an endovasculitis in the dermis. Its pathogenesis is unknown but many abnormalities of haemostasis have been reported. PATIENTS AND METHODS: Platelets functions, coagulation and fibrinolysis were estimated in three patients with Degos' disease. For one patient, direct immunoelectron microscopy using an antibody to von Willebrand factor was performed on lesional skin. RESULTS: In all the patients, prolonged euglobulin lysis time, increased plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activities before and after a venous occlusion test were detected and indicated an inhibition of fibrinolysis. Electron microscopy demonstrated in one case an increased number of Weibel-Palade bodies and a raised staining of von Willebrand factor in endothelial cells. Tests for coagulation and circulating anticoagulant were normal. Results of platelets adhesion showed decrease of adhesion in one case and increased adhesion in another. Platelets aggregation studies were normal in two cases and showed hyperactive spontaneous and induced aggregation in one case. CONCLUSION: We showed an inhibition of fibrinolysis in three patients with Degos' disease. These abnormalities could induce a prethrombotic state. The release of PA and PAI from the endothelial cells into the blood stream and the modifications observed with electron microscopy may signify a primary lesion of endothelial cell of still unknown origin.

Atrophy↗
PubMed1994

Reconstruction of human skin in culture.

The possibility of cultivating cells in vitro has been one of the most important technical breakthroughs of the last decades and is the basis of much of the progress in cell biology. The first aim of cell biologists was to find how to stimulate cell growth using more and more sophisticated culture conditions. The success of Rheinwald and Green for long term subcultivation of keratinocytes is a brilliant example of the importance of this approach. When achieving technical conditions which make possible long term subcultivation of normal cells, biologists have looked to chemically defined medium, making possible analytical study of the effect of peptides or drugs on cells growth and differentiation. When comparing cellular response in monolayer culture in vitro, with cells in vivo, it became clear that most of the cell responses observed on dedifferentiated cells in monolayer culture are not at all predictive for the response of the same cells in vivo. These differences seem to be due to cell-cell and cell-matrix interactions existing in vivo which are responsible for cell differentiation and pharmacological responses. In order to develop in vitro cell culture systems predictive for the in vivo cell response, and to make possible alternative model systems for animal drug testing, new sophisticated systems have been developed. These systems attempt to reproduce in vitro the cell to cell and cell-matrix interactions responsible for cell differentiation, with the hope of realizing, step by step, a real organogenesis in vitro. The first human organ for which this concept has been developed, is the skin. We would like to review the most recent development of this technique, making possible the realization in vitro of a living skin equivalent. The work of our Laboratory has been mainly concerned by the investigation of two questions: Are the cells, in the living skin equivalent, in a functional and differentiated state close to the in vivo one? Is it possible, using the skin equivalent system, to obtain, in vitro, cell responses predictive for the in vivo ones?

Cell Differentiation↗
PubMed1994

Differential modulation of human fibroblast and keratinocyte growth by the protein kinase C inhibitor GF 109203X.

Protein kinase C (PKC) is known to be involved in cellular proliferation and differentiation. In this work, we have investigated the effects of a novel PKC inhibitor, GF 109203X, on normal human fibroblast and keratinocyte growth. GF 109203X selectively inhibited PKC activity extracted from either fibroblasts (IC50 = 0.01 microM) or keratinocytes (IC50 = 0.4 microM). The inhibitory effects of GF 109203X on total PKC activity and Ca(2+)-independent PKC activity were similar. Nevertheless, in keratinocytes Ca(2+)-independent PKC activity represented 95% of total PKC activity, whereas in fibroblasts it corresponded to only 32% of total PKC activity. GF 109203X also inhibited a cellular function related to PKC activity in living fibroblasts and keratinocytes; it blocked the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate on 125I-epidermal growth factor binding. GF 109203X inhibited fibroblast growth, in terms of tritiated thymidine incorporation and cell counts, in a dose-dependent manner. We also observed that GF 109203X at 1 microM inhibited serum stimulation of expression of mRNA for c-fos and c-jun, which are usually involved in cellular proliferation. These results suggest that PKC stimulates fibroblast growth. In contrast, GF 109203X stimulated keratinocyte growth. We also observed that GF 109203X inhibited c-fos and c-jun mRNA expression in these cells. In fact, in keratinocytes these proto-oncogenes would be involved in the cellular differentiation process rather than in cellular proliferation. This suggests that the inhibition of PKC favors keratinocyte proliferation probably by inhibiting their differentiation. Thus, using GF 109203X, we show that PKC is involved differently in human fibroblast and keratinocyte growth.

Adolescent↗
PubMed1994

Additive effects of calcipotriol and cyclosporine A: from in vitro experiments to in vivo applications in the treatment of severe psoriasis.

We report that calcipotriol (CPT) is a potent inhibitor of lymphocyte proliferation in mixed epidermal cell lymphocyte reactions. In this model, CPT and cyclosporine A (CsA) have synergistic effects. These results have led to a randomised double-blind therapeutic study protocol in patients with severe psoriasis. In these patients, topical CPT and sub-therapeutic doses of CsA (2mg/kg/d) induce disappearance of cutaneous lesions. This therapeutic association may minimize secondary side effects of both drugs.

Adult↗
PubMed1994

Plasma thrombomodulin level in malignancy varies according to the tumor type.

Plasma thrombomodulin (TM) level was measured by ELISA in patients with either digestive tract cancers or malignant melanomas. A striking difference was seen between tumor types with an increase in the TM level of the former and a decrease in the latter. This finding is in agreement with the classification of tumors previously proposed by Zacharski et al.

Digestive System Neoplasms↗
PubMed1993

Ultraviolet A-induced lipid peroxidation and antioxidant defense systems in cultured human skin fibroblasts.

Cultured human skin fibroblasts from healthy donors were irradiated with 180 kJ.m-2 ultraviolet (UV) A (320-400 nm) and assayed for thiobarbituric acid-reactive substances (TBARS), taken as an indicator of lipid peroxidation. Antioxidant defenses, including total glutathione (GSH) levels, superoxide dismutase (SOD), glutathione peroxidase (GSHPx), and catalase (Cat) activities were simultaneously assayed before and after irradiation. For the various donors, with different activities of these antioxidant systems before irradiation, TBARS correlated positively with SOD activity and negatively with Cat activity, whereas no correlation with GSH level or GSHPx activity was found. These data support the view that O2- is generated by UVA irradiation. They also suggest that H2O2, arising from O2- dismutation by SOD is not completely removed by Cat. Thus, the sensitivity of human fibroblasts to UVA-induced lipid peroxidation depends on a balance between SOD and Cat activities. After UVA irradiation, Cat activity was strongly inhibited, whereas GSH level was slightly decreased. By contrast, GSHPx and SOD activity remained unchanged after UVA irradiation.

Catalase↗
PubMed1993

Umbilical Paget's disease and prostatic carcinoma.

We report a case of umbilical Paget's disease occurring in a patient with a prostatic carcinoma. No other malignancy was found, and the patient was treated by surgical excision of the lesion. To our knowledge, the occurrence of extramammary Paget's disease of the umbilicus has not been reported previously. The clinical presentation, its association with prostatic carcinoma, and the possible pathogenesis are discussed.

Aged↗
PubMed1993

Exposure to long wavelength ultraviolet radiation decreases processing of low density lipoprotein by cultured human fibroblasts.

Exposure of MRC5 human fibroblasts to UVA radiation (365 nm) resulted in a dose-dependent decrease in low density lipoprotein (LDL) uptake and degradation by cells. Following a 25 J/cm2 irradiation dose, about 45% and 70% reduction in 125I-LDL uptake and degradation were observed, respectively. Under the same conditions, the 14C-sucrose uptake was also decreased to about the same extent as LDL uptake. Cell pretreatment with the antioxidants vitamin E and vitamin C did not prevent the UVA-induced fall in LDL degradation. These results point to the possible effects of UVA radiation on receptor-mediated and nonspecific uptake of exogenous molecules. With special regard to the alterations in receptor-mediated processing of exogenous ligands, such a phenomenon could be of importance in UVA-induced skin degenerative processes.

Cell Line↗
PubMed1993

Lovastatin potentiates the photocytotoxic effect of photofrin II delivered to HT29 human colonic adenocarcinoma cells by low density lipoprotein.

A 24 h preculture of HT29-18 human colonic adenocarcinoma cells with the sterol synthesis inhibitor lovastatin at concentrations of 0.1-0.5 microM markedly increased the photocytotoxic effect of photofrin II delivered to cells by low density lipoproteins. Under the same conditions, LDL binding and photofrin II (PII) uptake by HT29 cells increased about 1.8-fold and 1.5-fold, respectively. These results suggest that hydroxymethylglutaryl-coenzyme A reductase inhibitors could be useful for potentiating the photodynamic therapy of tumors by PII.

Adenocarcinoma↗
PubMed1993

Membrane damage induced in cultured human skin fibroblasts by UVA irradiation.

Irradiation of cultured human skin fibroblasts with ultraviolet light from 320 to 400 nm (UVA) leads to a decrease in the membrane fluidity exemplified by an enhanced fluorescence anisotropy of the lipophilic fluorescent probe 1-[4-trimethylamino)-phenyl]-6-phenylhexa-1,3,5-triene. This UVA-induced decrease in fluidity is associated with lactate dehydrogenase leakage in the supernatant. Vitamin E, an inhibitor of lipid peroxidation, exerts a protective effect on both phenomena. Therefore, this UVA-induced damage in membrane properties may be related to lipid peroxidation processes. Moreover, exponentially growing cells are more sensitive to these UVA-induced alterations than confluent cells.

Cell Division↗
PubMed1993

Effects of the Avène spring water on the dynamics of lipids in the membranes of cultured fibroblasts.

In this preliminary report, dealing with the biological properties of Avène spring water, we investigated its effects on membrane properties of cultured human skin fibroblasts used as a model cell system. It is shown that incubation of these cells in the presence of Avène spring water brings about an increase in the fluidity of plasma membrane. This effect was evidenced by a decrease in the fluorescence anisotropy of the lipophilic probe diphenylhexatriene and by a 3-fold increase in the lateral diffusion coefficient of the lipophilic probe 5-(N-hexadecanoyl)-aminofluorescein, as measured through fluorescence recovery after photobleaching experiments. This effect reached a maximum for incubation times longer than 30 min and for a dilution of Avène water in laboratory water to about 20-25%. As discussed, changes in the hydrodynamic properties of cell membranes induced by Avène water provide a plausible explanation for some of the biological events this spring water is known to trigger.

Anisotropy↗
PubMed1993

Evaluation of phototoxic and photogenotoxic risk associated with the use of photosensitizers in suntan preparations: application to tanning preparations containing bergamot oil.

Bases for the elaboration of a standardized protocol are proposed for studying phototoxic effects of skin tanning preparations containing photosensitizing agents. The experimental procedure includes in vivo phototoxicity tests, evaluation of the photogenotoxic risk and determination of the photosensitizer concentration in plasma after topical application. This procedure was carried out with tanning preparations containing a well-known photosensitizer, 5-methoxypsoralen, as a component of bergamot oil. The whole study has been performed using topical application of the commercial suntan product, i.e. containing the sunscreens and all other components. Whereas the exposure to solar simulated radiation never triggered any phototoxic response, a photosensitizing effect was observed for skin type I volunteers exposed to high doses of ultraviolet A. The transepidermal penetration resulted in a 5-methoxypsoralen concentration of 1-4 ng/ml in the suction blister fluid. The photogenotoxicity of this suction blister fluid containing 5-methoxypsoralen and also other ingredients of the tanning preparation was assayed on yeast cells and was found to be rather low. 5-Methoxypsoralen was also detected in plasma after repeated applications but at low concentrations (about 1 ng/ml) which do not present a potential risk for systemic ocular effects.

5-Methoxypsoralen↗
PubMed1993

Sarcoidosis associated with leucocytoclastic vasculitis. A case report and review of the literature.

We report on a patient presenting with cutaneous leucocytoclastic vasculitis in association with sarcoidosis. Detailed investigations did not show evidence of infectious or neoplastic diseases. Vasculitis was therefore considered to be secondary to sarcoidosis. A review of 4 other previously reported cases reveals a common presentation with the association of vasculitic skin lesions with deep cutaneous nodules, mediastinal lymph nodes and arthritis. The role of antibody response in leucocytoclastic vasculitis is discussed.

Female↗
PubMed1993

Fusarium solani cutaneous infection in a neutropenic patient.

A 47-year-old woman with acute myeloblastic leukemia developed disseminated papules and pustules after chemotherapy. A skin biopsy specimen revealed fungal vasculitis and grew Fusarium solani. The patient died despite treatment with amphotericin B. The isolate was resistant to amphotericin B, imidazole and 5-fluocytosine. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients.

Dermatomycoses↗
PubMed1993

Persistent acantholytic dermatosis: sex-related differences in clinical presentation?

We report the case of a 58-year-old man with a chronic papular eruption of 10 years' duration. Histopathology revealed focal acantholytic dyskeratosis. This condition is thought to represent a distinct entity which has been reported under several names and frequently referred to as persistent acantholytic dermatosis. The relationship between this condition and transient acantholytic dermatosis (Grover's disease), emphasizing sex-related presentations, is discussed.

Acantholysis↗
PubMed1993

A CD2+ subset of non-malignant peripheral blood lymphocytes from patients with Sézary syndromes overexpress the low-molecular-weight GTP-binding protein Rab2.

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.

Antigens, Differentiation, T-Lymphocyte↗