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L Dubertret

Publications and source records attributed to L Dubertret.

At least 55 records · Page 3Linked to original sources
PubMed2001

UV-A irradiation induces a decrease in the mitochondrial respiratory activity of human NCTC 2544 keratinocytes.

UV-A irradiation caused a dose-dependent decrease in cellular oxygen consumption (56%) and ATP content (65%) in human NCTC 2544 keratinocytes, one hour after treatment. This effect was partially reversed by maintaining the irradiated cells in normal culture conditions for 24 h. Using malate/glutamate or succinate as substrates for mitochondrial electron transport, the oxygen uptake of digitonin-permeabilised cells was greatly inhibited following UV-A exposure. These results strongly suggest that UV-A irradiation affects the state 3 respiration of the mitochondria. However, under identical conditions, UV-A exposure did not reduce the mitochondrial transmembrane potential. The antioxidant, vitamin E inhibited UV-A-induced lipid peroxidation, but did not significantly prevent the UV-A-mediated changes in cellular respiration nor the decrease in ATP content, suggesting that these effects were not the result of UV-A dependent lipid peroxidation. UV-A irradiation also led to an increase in MnSOD gene expression 24 hours after treatment, indicating that the mitochondrial protection system was enhanced in response to UV-A treatment. These findings provide evidence that impairment of mitochondrial respiratory activity is one of the early results of UV-A irradiation for light doses much lower than the minimal erythemal dose.

Adenosine Triphosphate↗
PubMed2001

Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus.

We investigated 33 patients affected with chilblain lesions following a persisting course of more than 1 month. We focused on the incidence of an underlying connective tissue disease, mostly lupus erythematosus (LE), and we analyzed features of idiopathic chilblains compared with those of chilblain lesions associated with connective tissue disease. We also carried out a prospective follow-up of patients. Eleven patients included in the study were free of any clinical and/or laboratory abnormality suggestive of connective tissue disease, while 22 of 33 patients showed 1 or several abnormalities raising suspicion for connective tissue disease, and among them 8 had a diagnosis of systemic lupus erythematosus (SLE) established at initial evaluation based on the American College of Rheumatology revised criteria. The comparative analysis of patients with idiopathic chilblains and patients with chilblains associated with LE showed that female sex and persistence of lesions beyond cold seasons were significantly associated with chilblain LE. Histopathologic studies of chilblain lesions did not reveal features typical of LE in any case, but revealed a higher incidence of a deep perisudoral infiltrate in idiopathic chilblains. In patients showing signs of connective tissue disease, positive cutaneous immunofluorescence was correlated with the presence of circulating antinuclear antibodies. Two patients had an ascertained diagnosis of SLE with severe manifestations during prospective follow-up, requiring treatment with oral steroids in both cases. Chilblains following a chronic course may reveal connective tissue disease, and patients affected with chilblains associated with autoimmune abnormalities may develop severe SLE. Accordingly, long-term follow-up of these patients is warranted.

Adolescent↗
PubMed2001

[Cutaneous lupus erythematosus following argon laser treatment].

BACKGROUND: It is well known that exposure to ultraviolet light can trigger lupus manifestations. Other light sources may have the same effect. We report a case of argon laser-induced lupus erythematosus. CASE REPORT: A 59-year-old women developed an erythematous edematous infiltrated and sensitive lesion over the right cheek ten days after an argon laser treatment of the retina. The lesion spread towards the chin despite antibiotic treatment. Histology examination of a biopsy specimen and direct immunofluorescence suggested the diagnosis of cutaneous lupus erythematosus. The lesions regressed in one month with hydroxychloroquine (400 mg/d) treatment. DISCUSSION: Our patient developed argon laser induced cutaneous lupus erythematosus. It is known that ultraviolet light and non-ultraviolet frequencies (x-rays, visible light) can induce lupus manifestations. One case of discoid lupus erythematosus after argon laser has been reported. In our case, due to a technical error the laser beam was directed onto the ipsilateral cheek during the laser treatment of the retina. The low-energy beams used in ophthalmology would explain the absence of local burn but would be sufficient to trigger lupus. This case demonstrates that argon laser, a visible blue or green beam, can provoke cutaneous lupus erythematosus even if there is no heat-induced burn. It is important to be aware of this adverse effect due to the widespread use of lasers in dermatology, particularly for the treatment of cutaneous lupus lesions.

Argon↗
PubMed2000

Association between INK4a-ARF and p53 mutations in skin carcinomas of xeroderma pigmentosum patients.

BACKGROUND: The INK4a-ARF locus encodes two tumor suppressor proteins, p16(INK4a) and p14(ARF), that act through the Rb-CDK4 and p53 pathways, respectively. Data from murine models and sporadic human skin carcinomas implicate p16(INK4a) and p14(ARF) in the development of skin carcinomas. We examined the frequency of INK4a-ARF, p53, and CDK4 mutations in skin carcinomas from patients with xeroderma pigmentosum (XP), a rare autosomal disease that is associated with a defect in DNA repair and that predisposes patients to skin cancer. METHODS: DNA from skin cancers of 28 unrelated XP patients was screened for mutations in p53, INK4a-ARF, and CDK4 coding exons by single-strand conformation polymorphism analysis and automated sequencing. Data were evaluated with the use of the exact unconditional test derived from Fisher's test. All statistical tests were two-sided. RESULTS: Eight of 28 XP-associated tumors had mutations in the INK4a-ARF locus. Three XP-associated tumors had multiple mutations at this locus. In all, 13 mutations in the INK4a-ARF locus were detected in XP-associated tumors, of which seven (54%) were signature UV radiation-induced mutations, i.e., tandem CC : GG-->TT : AA transitions. p53 mutations, mostly of the type induced by UV radiation, were present in 12 tumors (43%). Statistically significant positive associations were found between the frequency of mutations in p53 and in p16(INK4a) (P =.008) and between the frequency of mutations in p53 and in p14(ARF) (P<.001). No mutations were detected within the CDK4 gene. CONCLUSIONS: We have demonstrated for the first time the occurrence of UV radiation-induced mutations in INK4a-ARF in XP-associated skin carcinomas. The simultaneous inactivation of p53 and INK4a-ARF may be linked to the genetic instability caused by XP and could be advantageous for tumor progression.

Africa, Northern↗
PubMed2000

Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire.

The T-cell-reactive (eg, tuberculoid and reversal) forms of leprosy represent a well-defined granulomatous reaction pattern against an invading pathogen. The immune response in cutaneous sarcoidosis is a granulomatous condition that pathologically is very similar to T-cell reactive leprosy. However, it lacks a defined causative agent. In view of the role of NKT cells in murine granulomas induced by mycobacterial cell walls, we have searched for the presence of NKT cells in the cutaneous lesions of both leprosy and sarcoidosis. These cells were present in T-cell-reactive leprosy but were undetectable in cutaneous sarcoidosis. We have also studied the TCR Valpha repertoire in the two diseases. In addition to Valpha24(+) NKT cells, all patients with T-cell-reactive leprosy showed a very restricted T-cell-reactive Valpha repertoire with a strong bias toward the use of the Valpha6 and Valpha14 segments. Valpha6 and Valpha14(+) T cells were polyclonal in terms of CDR3 length and Jalpha usage. In contrast, most sarcoidosis patients showed a diverse usage of Valpha chains associated with clonal or oligoclonal expansions reminiscent of antigen-driven activation of conventional T cells. Thus the origin and perpetuation of the two kinds of granulomatous lesions appear to depend on altogether distinct T-cell recruiting mechanisms.

Adolescent↗
PubMed2000

[Skin and environment].

The human skin is one of the major human organs in perpetual interaction with environmental factors. Permanent micro-aggressions by light, mechanical factors or chemical factors are useful for the maintenance of healthy skin. For example light is necessary for vitamin D synthesis and for the control of skin inflammation. If the aggression is too strong, repair mechanisms are involved such as wound healing or DNA repair. Accumulation of aggressions could induce acute or chronic diseases such as sunburn, photoageing or skin carcinoma. On specific individuals with genetic predisposition environmental aggressions can induce frequent diseases such as atopic dermatitis, present in 20% of children or psoriasis, present in 2-3% of the European population. Chemical aggressions are responsible for irritant dermatitis or allergic dermatitis, which are among the most frequent professional diseases. Aggression by UV light is one of the best examples of the interaction between environment and health. At a low dose UV light is very good for the health. At a high dose it is responsible for photoageing and skin carcinoma. To improve the control of environmental factors important for health, two approaches are essential: 1) research into epidemiology to discover the causal relationships and into biology to discover the mechanisms involved; 2) education from childhood to explain the results of research and to propose effective behaviours. For each aggression individuals at risk have to be identified.

Environmental Exposure↗
PubMed2000

Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions.

Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.

Administration, Oral↗
PubMed2000

Humoral and cellular responses to histamine and pollen allergen in a skin chamber model: effect of mizolastine.

BACKGROUND: Mizolastine is a new non-sedative antihistamine and antiallergic drug proven to be effective and safe in the treatment of allergic rhinitis and urticaria. OBJECTIVE: To quantitatively explore the time course of mediator release and cell recruitment during allergen challenge and the effects of mizolastine on the event, using the skin chamber model. METHODS: Twelve pollen-sensitive patients (23+/-6 years) were included in a double-blind crossover study. Patients received 10 mg mizolastine or placebo once daily in the first 4-day period and, after a 3-week washout period, vice-versa in the crossover period. On day 4 of each period, a non-invasive in vivo skin chamber technique was used to determine the alteration of vascular permeability, mast cell mediator release, the release of soluble intercellular adhesion molecule -1(sICAM-1) in skin sites challenged with exogenous histamine or grass pollen allergen extract, over an 8-hour period. RESULTS: Challenge with allergen-induced significant mast cell activation, as indicated by the release of histamine, tryptase and LTC4, in chamber fluids 2 hours after initiation of the allergic reaction and during the following 6 hours. Both exogenous histamine and allergen induced significant vasodilatation, which was sustained during the 8-hour challenge, as indicated by the accumulation of protein in the chamber fluids. Likewise, both histamine and allergen induced the release of significant amounts of ICAM-1 throughout the 8-hour period. Mizolastine significantly inhibited the histamine- and allergen-induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2 hours, P = .044; after 8 hours, P = .003 respectively) and the histamine- and allergen-induced--ICAM-1 release (after 2 hours, P = .004; after 8 hours, P = .05; after 2 hours, P = .03 respectively). CONCLUSION: Mizolastine strongly inhibited the local response to histamine in this skin chamber model with, of interest, inhibition of the release of the soluble adhesion-molecule ICAM-1.

Adolescent↗
PubMed2000

Refined localization of the gene for Clouston syndrome (hidrotic ectodermal dysplasia) in a large French family.

Hidrotic ectodermal dysplasia (HED) or Clouston syndrome is a rare autosomal dominant disorder characterized by nail dystrophy, alopecia and palmoplantar hyperkeratosis, which maps to chromosome 13q11-q12.1. We confirmed linkage of HED to this region in a large French family. To define the critical region for HED, detailed haplotypes were constructed with new pericentromeric polymorphic markers. A recombination event in the family indicates that the HED locus maps centromeric to D13S1832. Our French family does not share a common haplotype with other pedigrees previously published (particularly French-Canadian), indicating that the mutations in these families are likely to be of different origin.

Chromosomes, Human, Pair 13↗
PubMed2000

Quantitative and kinetic evolution of wound healing through image analysis.

To define a healing function based on parameters measured on digitized images of wounds, and to use it to compare the rate of healing of two skin graft donor sites, one treated with petrolatum gauze (Pg) and the other with a topical preparation containing alginates (A). Digital photographs of donor sites (depth 0.6 mm) taken every two days between day 6 and day 12 were analyzed blind using the same algorithm, following changes in color and homogeneity. Analysis of variance was used to identify those parameters that changed during healing. The healing function was constructed using measurements made in six patients (group 1) randomly chosen from ten requiring skin grafts, and was applied and validated using data from the remaining four patients (group 2). The results given by this healing function were compared with those provided by principal component analysis. The most significant healing parameters were those measuring wound homogeneity, and our healing function reflects how these change with time. The time-dependent curves of the function calculated for groups 1 and 2 matched well enough to be considered as being derived from the same set of measurements. The results given by this healing function explained, by analogy, the meaning of the first principal component of principal component analysis. From day 6 to day 12, the healing function followed the same time-course for the Pg and A treatments, but healing was achieved significantly earlier (4 days, p < 0.03) with A. This suggests that the effect of A on wound healing is achieved in the first six days, before the visual changes from epidermalization are analyzable.

Administration, Topical↗
PubMed2000

[Thalidomide and thrombosis].

BACKGROUND: Teratogenicity and neuropathy are the well known serious side effects induced by thalidomide. We describe 5 cases of thrombotic events occurring within a brief delay after the onset of thalidomide in a manner that suggests that thalidomide could have acted as a precipiting or as a starting factor in these events. OBSERVATIONS: Five patients including 4 patients with lupus erythematosus (1 discoid lupus, 1 subacute lupus and 2 systemic lupus erythematosus) and one patient with a severe atopic dermatitis, all without previous history of vascular events, developed an arterial thrombosis (2 cases) or a venous thrombosis (3 cases), severe in 4 cases, few days or weeks after the onset of thalidomide treatment (50 to 100 mg daily). DISCUSSION: All the patients had risk factors of thrombosis: the presence of antiphospholipids and/or anticardiolipin antibodies in lupus erythematosus patients and a trauma in the atopic case. However the absence of a previous story of thrombosis, its rapid occurrence after the onset of thalidomide and its severity are intriguing. In addition, recent studies demonstrate that thalidomide has various effects that would act, among other things, on angiogenesis. Thus, we think that a doubt exists on a negative effect of thalidomide in thrombosis risk factors patients and that this hypothesis has to be confirmed.

Adult↗
PubMed2000

[Renal function during long-term cyclosporin treatment of psoriasis].

INTRODUCTION: The goal of this retrospective study was to evaluate the effects of cyclosporin A on renal function in patients treated for five years or more. PATIENTS AND METHODS: Two hundred twenty-four psoriasis patients were treated with cyclosporin at St. Louis Hospital, in Paris, from 1988 to 1997. Eleven patients (5 p. 100 of the total) took cyclosporin for at least five years. Nine case histories were available for the analysis. RESULTS: The group studied consisted of eight men and one woman, ranging in age from 28 to 48 with an average age of 38 years. The average cyclosporin dosage was 3.6 mg/kg/day (2.0-5.0 mg/kg/day). The changes in renal function were not significant as compared to the baseline level. The patients did not show persistent increases of serum creatinine more than 30 p. 100 of the pre-treatment value. Two patients had to discontinue treatment after 6 years because of a 20 p. 100 decrease in glomerular filtration rate. DISCUSSION: Previous studies have shown that cyclosporin A is not a suitable long-term continuous monotherapy for psoriasis. However, with precise and regular monitoring of kidney function, a minority of patients can benefit from prolonged treatment without experiencing side effects.

Adult↗
PubMed1999

P16 UV mutations in human skin epithelial tumors.

The p16 gene expresses two alternative transcripts (p16alpha and p16beta) involved in tumor suppression via the retinoblastoma (Rb) or p53 pathways. Disruption of these pathways can occur through inactivation of p16 or p53, or activating mutations of cyclin dependant kinase 4 gene (Cdk4). We searched for p16, Cdk4 and p53 gene mutations in 20 squamous cell carcinomas (SSCs), 1 actinic keratosis (AK), and 28 basal cell carcinomas (BCCs), using PCR-SSCP. A deletion and methylation analysis of p16 was also performed. Six different mutations (12%) were detected in exon 2 of p16 (common to p16alpha and p16beta), in five out of 21 squamous lesions (24%) (one AK and four SCCs) and one out of 28 BCCs (3.5%). These included four (66%) ultraviolet (UV)-type mutations (two tandems CC : GG to TT : AA transitions and two C : G to T : A transitions at dipyrimidic site) and two transversions. P53 mutations were present in 18 samples (37%), mostly of UV type. Of these, only two (one BCC and one AK) harboured simultaneously mutations of p16, but with no consequence on p16beta transcript. Our data demonstrate for the first time the presence of p16 UV induced mutations in non melanoma skin cancer, particularly in the most aggressive SCC type, and support that p16 and p53 are involved in two independent pathways in skin carcinogenesis.

Alternative Splicing↗
PubMed1999

UV-A-induced decrease in nuclear factor-kappaB activity in human keratinocytes.

Previous reports have demonstrated an increase in nuclear factor-kappaB (NF-kappaB) activity in response to UV radiation. These studies have essentially focused on the DNA-damaging fraction of solar UV radiation (UV-B and UV-C). In contrast, the effects of UV-A radiation (320-400 nm) on NF-kappaB are not well known. In this study, we present evidence that UV-A radiation induces a marked decrease in NF-kappaB DNA-binding activity in NCTC 2544 human keratinocytes. In addition, NCTC 2544 keratinocytes pretreated with UV-A fail to respond to NF-kappaB inducers. Moreover, UV-A radiation induces a decrease in NF-kappaB-driven luciferase reporter gene expression in NCTC 2544 keratinocytes. The expression of the gene encoding IkappaBalpha (IkappaB is the NF-kappaB inhibitor), which is closely associated with NF-kappaB activity, is also reduced (3-fold) upon UV-A treatment. Our results indicate that the UV-A-induced decrease in NF-kappaB DNA-binding activity is associated with a decrease in the levels of the p50 and p65 protein subunits. This is the first evidence that an oxidative stress, such as UV-A radiation, may induce a specific decrease in NF-kappaB activity in mammalian cells, probably through degradation of NF-kappaB protein subunits. These findings suggest that UV-A could modulate the NF-kappaB-dependent gene expression.

Antioxidants↗