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Biomedical subjects

L Dubertret

Publications and source records attributed to L Dubertret.

At least 127 records · Page 7Linked to original sources
PubMed1996

Lymphocytes, cytokines and adhesion molecules in chronic graft versus host disease.

Aims-To determine which inflammatory and immune pathways are implicated in the development of chronic graft versus host disease (GvHD) and whether differences between these pathways are responsible for the different presentations of chronic GvHD.Methods-Biopsy specimens of diseased and normal skin were obtained from patients presenting with lichen planus-like and sclerodermatous type chronic GvHD. Expression of epidermal cytokines, adhesion molecules and lymphoid surface markers was analysed by means of immunohistochemistry. Apoptosis was detected using the in situ nick endlabelling method.Results-In both GvHD lesion types, CD8+ cells predominated in the epidermis, whereas CD4+ cells were the most prevalentin the dermis. Apoptotickeratinocytes were found in diseased skin only and Fas antibodies labelled a considerable number of keratinocytes. The epidermis in both types of lesions expressed interleukin (IL) 1alpha, tumour necrosis factor (TNF) alpha and intercellular adhesion molecule (ICAM)-1, but dermal vascular cell adhesion molecule (VCAM)-1 expression was restricted to specimens of lichen planus-like GvHD. IL1alpha and E-selectin were expressed in normal looking skin of 55% and 80%, respectively, of patients with lichen planus-like GvHD.Conclusion-The similarity between expression of epidermal cytokines and adhesion molecules (with the exception of VCAM-1) and lymphocyte phenotype in lichen planus-like and sclerodermatous GvHD strongly suggests that the latter occurs as a consequence of the healing process. VCAM-1 distinguishes between lichen planus-like and sclerodermatous lesions. IL1alpha and E-selectin are potential early markers of chronic GvHD.

Journal Article↗
PubMed1996

Long-term safety of cyclosporine in the treatment of psoriasis.

BACKGROUND AND DESIGN: Cyclosporine has proved to be highly effective in the treatment of psoriasis. However, cyclosporine is potentially toxic. Side effects include renal toxic effects, hypertension, and an increased risk of malignant neoplasm. The toxicity of cyclosporine is dose-related, yet the safe duration of treatment is undefined. We studied the hospital records of all patients with psoriasis treated with cyclosporine at Saint Louis Hospital, Paris, France, between January 1, 1987, and December 31, 1993. In total, 122 patients treated for 3 to 76 months were evaluated. RESULTS: The percentage of patients who discontinued treatment because of side effects rose from a mean +/- SD of 14% +/- 2.4% at 12 months to 41% +/- 6.7% at 48 months. An increase in serum creatinine levels to more than 30% above the baseline value occurred in 53 patients after a median treatment time of 23 months. Hypertension developed in 29 patients after a median treatment time of 53 months. Three initial patient characteristics--age older than 50 years (P = .04), initial diastolic pressure higher than 75 mm Hg (P = 0.5), and serum creatinine levels more than 100 mumol/L (1.1 mg/dL) (P = .02, log rank test)--predicted discontinuation of cyclosporine because of side effects. CONCLUSIONS: The risk of cyclosporine-induced toxic effects increases with age of the patient and with preexisting hypertension or high serum creatinine levels. The data suggest that the incidence of side effects increases with time. Thus, cyclosporine is not an acceptable long-term monotherapy for psoriasis.

Adolescent↗
PubMed1996

Disseminated varioliform pustular eruption due to Mycobacterium avium intracellulare in an HIV-infected patient.

Severe disseminated infection due to Mycobacterium avium intracellulare, with unusual cutaneous features, is reported in a patient with acquired immunodeficiency syndrome (AIDS). The eruption appeared as disseminated pustular lesions which showed necrotic features and which led to varioliform scarring. Bacterial culture from the skin, blood, and bone marrow, and ultimately from the bronchoalveolar fluid and sputum, was positive for M. avium intracellulare. The patient was successfully treated using a multiple agent anti-mycobacterial regimen including clarithromycin, which appeared to be the most effective drug. This resulted in resolution of the cutaneous and general symptoms. Our patient illustrates the wide spectrum of skin presentations that may be seen with mycobacterial infections in subjects infected with the human immunodeficiency virus (HIV). Clarithromycin is an important agent for the treatment of these severe infections.

AIDS-Related Opportunistic Infections↗
PubMed1996

UVA-induced immune suppression in human skin: protective effect of vitamin E in human epidermal cells in vitro.

UVA (320-400 nm) radiation damage to membranes, proteins, DNA and other cellular targets is predominantly related to oxidative processes. In the present study, we demonstrated that cutaneous UVA-induced immunosuppression can be related, at least in part, to the appearance of these oxidative processes. The UVA-induced oxidative processes in freshly isolated epidermal cells were monitored by measuring the thiobarbituric acid reactive substances (TBARS) as an index of peroxidation. The in vitro immunosuppressive effects of UVA were demonstrated by measuring the allogeneic lymphocyte proliferation induced by epidermal cells or purified Langerhans cells in the mixed epidermal cell-lymphocyte reaction (MECLR). In addition, the effects of a potent antioxidant (vitamin E) on these two UVA-induced processes were analysed. Our results showed that the antigen-presenting function of Langerhans cells measured in the MECLR is dose-dependently decreased by UVA radiation (up to 20J/cm2). Overnight incubation of epidermal cells with vitamin E (400 mumol/l) before irradiation partially protected epidermal cells from the immunosuppressive effects of UVA radiation, and decreased TBARS release into the supernatant (a decrease of 35% compared with a control without vitamin E). Our results suggest that UVA radiation may alter cell-presenting antigen function partly via the generation of reactive oxygen species which trigger peroxidative processes, and these data contribute to the understanding of the role of oxidative mechanisms in immune suppression induced by UVA radiation. Our in vitro model can be used to quantify UV-mediated epidermal cell damage and the degree of immune photoprotection provided by various agents.

Adolescent↗
PubMed1996

[Contact photoallergic eczema caused by ketoprofen].

INTRODUCTION: Since 1983, several cases of allergy and photoallergic contact dermatitis to ketoprofen gel have been reported in Italy and Spain. In France, this drug has been available for topic applications since 1989 and no cases of photoallergy have been reported. CASE REPORT: We observed two cases of photoallergic contact dermatitis to ketoprofen (Profenid gel, Ketum gel). Imputability was suggested by clinical history and proven by patch-tests showing evidence of crossed photoallergy with fenofibrate in both cases. Photoallergic dermatitis to oxybenzone was associated in one case. COMMENTS: Ketoprofen is the predominant nonsteroid anti-inflammatory drug responsible for allergic and/or photoallergic contact dermatitis resulting from topic applications. Its prevalence is probably underestimated in France in light of the number of cases reported in certain Mediterranean countries. Cross reactive photoallergy to ketoprofen and fenofibrate can be explained by the common benzoly-ketone structure of these compounds. In case of skin reaction, the other drug should not be prescribed and benzophenone-containing cosmetics discouraged.

Adult↗
PubMed1996

Immunohistochemical and virological study of skin in the papular-purpuric gloves and socks syndrome.

The pathogenesis of viral exanthems remains unclear. We have undertaken an immunohistochemical study of lesional skin biopsies in patients with the papular-purpuric gloves and socks syndrome (PPGSS) secondary to parvovirus B19 infection. Intracytoplasmic staining of the dermal endothelial cells, keratinocytes, and sweat glands was shown with an antibody to parvovirus B19. There were perivascular dermal infiltrates with T cells, sometimes with exocytosis. By polymerase chain reaction, virus DNA was detected in all skin biopsies and in one serum sample. The cutaneous manifestations of parvovirus infection seem secondary to infection of the endothelium and epidermis.

Adolescent↗
PubMed1996

Drug-induced pseudolymphoma and hypersensitivity syndrome. Two different clinical entities.

OBJECTIVE: To test the hypothesis that drug-induced pseudolymphoma and hypersensitivity syndrome are 2 distinct clinical entities. DESIGN: Retrospective study from 1980 to 1993. SETTING: Departments of dermatology and medicine of 5 referral universitary hospitals. PATIENTS: Twenty-four patients who met arbitrary criteria selected as being suggestive of lymphoma, with probable drug cause. Patients with other definite cutaneous drug-induced eruptions were excluded. INTERVENTION: None. MAIN OUTCOME MEASURES: Suspect drugs; clinical, biological, and pathological findings; and evolution of each case and of 110 published case reports. RESULTS: Two groups were separated according to their mode of onset and clinical aspect. Three patients (and 15 cases in the literature) had subacute papulonodular or infiltrated plaques, without visceral involvement. Skin biopsy specimens showed a dense lymphocytic infiltrate mimicking lymphoma. Healing was constant when the drug was stopped. The 21 remaining patients (and 95 published cases) had an acute widespread eruption, with fever, enlarged lymph nodes, and multivisceral involvement. Lymphocytosis, atypical lymphocytes, eosinophilia, hepatitis, and high levels of lactate dehydrogenase were frequent. Skin biopsy findings were usually not specific (lymphocytic infiltrate and keratinocyte necrosis) but sometimes mimicked lymphoma. Severe forms and relapses occurred, even after the drug was stopped. The inducing drugs were the same in the 2 groups. CONCLUSIONS: These 2 groups correspond to drug-induced pseudolymphoma and hypersensitivity syndrome. We think that they are 2 distinct entities with different clinical and biological features and outcome, even if the pathological findings are sometimes similar. Prospective studies are needed to confirm these facts, to evaluate the therapy, and to follow up patients.

Adolescent↗
PubMed1996

[Pyogenic granuloma of the tongue in chronic graft versus host disease].

INTRODUCTION: The development of pyogenic granuloma of the tongue is rare. We report such a case in a patient with chronic graft-versus-host disease. CASE REPORT: A 5-year-old girl was treated with allogenic bone marrow transplantation for aplastic anemia. Complications consisted in chronic graft-versus-host disease with cutaneous, mucosal and hepatic involvement. Seven months later, a voluminous pyogenic granuloma of the tongue developed on previous erosive lichenoid lesions of chronic graft-versus-host disease while the patient was under cyclosporin. Surgical resection was done. Relapse occurred and treatment was identical. DISCUSSION: Six cases of pyogenic granuloma of the oral cavity in chronic graft-versus-host disease have been reported in the literature. Pyogenic granuloma must be considered in tumoral lesion of the oral cavity of patients with chronic graft-versus-host disease. All patients had erosive lichenoid lesions and were under cyclosporin; its role in the genesis of these lesions is debated. Treatment relies on surgical resection confirming the diagnosis.

Bone Marrow Transplantation↗
PubMed1995

[Cancers of the skin, relations to ultraviolet rays].

There are three main types of skin cancers: basal cell carcinoma, squamous cell carcinoma and melanoma. They are very different in terms of clinical presentation, evolution, and prognosis. Their frequency is increasing and there is sufficient evidence for the aetiological role of solar ultraviolet radiation (UVR). This evidence is based largely on epidemiological studies, animal models and studies of xeroderma pigmentosum patients. The risk of squamous and basal cell carcinoma increases with chronic solar exposure while the risk of melanoma seems to be more influenced by intermittent exposures. The physiopathological mechanisms of UV carcinogenesis are not yet entirely understood. One of the main factors seems to be mutagenesis due to impaired DNA photoproducts repair. Alteration in immune function and genesis of free radicals induced by exposure to UVR may also play a central role in UV carcinogenesis.

Humans↗
PubMed1995

Lovastatin enhances the photocytotoxicity of UVA radiation towards cultured N.C.T.C. 2544 human keratinocytes: prevention by cholesterol supplementation and by a cathepsin inhibitor.

The effect of the hydroxymethylglutaryl-CoA (HMG-CoA) inhibitor lovastatin on the UVA-induced photocytotoxicity has been investigated in cultured human N.C.T.C. 2544 keratinocytes. In the absence of irradiation, 5 x 10(-7) M lovastatin did not exhibit any significant cytotoxic effect towards this cell line. Although the drug cannot act as a photosensitizer, because it does not absorb in the UVA range, it markedly increased the UVA-induced cellular damage (about 70% reduction in cell viability at 5 x 10(-7) M). This effect was not accompanied by an increase in the lipid peroxidation product content of cells as compared with treatment with UVA alone. Medium supplementation with 0.01 mg/ml free cholesterol totally prevented the enhancement of UVA photocytotoxicity induced by lovastatin. A protective effect was also observed when cells were supplemented with an amount of low-density lipoprotein giving the same cholesterol concentration in the culture medium. Finally, E64 [L-trans-epoxysuccinyl-leucylamido-(4-guanidino)-butane], a lysosomal cathepsin inhibitor, also prevents the cell death induced by UVA in cells treated with lovastatin. These results suggest that HMG-CoA reductase inhibitors could increase the sensitivity of skin cells to UVA radiation, and that this phenomenon is related to lysosomal enzyme release.

Cathepsins↗
PubMed1995

The nitric oxide donors, azide and hydroxylamine, inhibit the programmed cell death of cytokine-deprived human eosinophils.

Azide and hydroxylamine release nitric oxide (NO) enzymatically in biological conditions. We observed that both compounds were able to inhibit in vitro the programmed cell death of human eosinophils from peripheral blood. This protective effect could be mimicked by permeable cGMP analogs and by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Moreover, the soluble guanylate cyclase inhibitor LY-83583 inhibited in a dose-response manner the effects of the NO donors. Consequently, via the increase of eosinophil survival, NO could contribute to the amplification of inflammatory and allergic processes. This effect appears to be mediated, at least in part, by the soluble guanylate pathway.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Exogenous nitric oxide elicits chemotaxis of neutrophils in vitro.

Nitric oxide (NO) has been shown to be both an intercellular and intracellular messenger. We propose here that exogenous NO induces chemotactic locomotion of human neutrophils. Indeed, when human neutrophils were placed in a gradient of a nitric oxide donor (S-nitroso-N-acetylpenicillamine; SNAP), a directed locomotion was induced, as evidenced by experiments of chemotaxis under agarose. Degraded SNAP (i.e., SNAP solution which had previously released NO) did not induce directed locomotion. Moreover, oxyhemoglobin, a scavenger of free NO, suppressed the chemotactic effect of SNAP, whereas LY-83583, a soluble guanylate cyclase inhibitor, inhibited the SNAP-mediated chemotaxis in a dose-response manner. Other unrelated NO donors, SIN-1 and S-nitroso-cysteine--a natural S-nitroso-compound, also induced a directed locomotion of neutrophils. Taken together, these in vitro experiments indicate that exogenous NO could mediate the chemotaxis of neutrophils and thus suggest that NO could contribute to neutrophil recruitment in vivo.

Aminoquinolines↗
PubMed1995

Human eosinophils in culture undergo a striking and rapid shrinkage during apoptosis. Role of K+ channels.

In the absence of appropriate stimulus, eosinophils in vitro rapidly exhibit the features of apoptotic cells (nuclear pycnosis, cell shrinkage, DNA fragmentation). By using electronic cell sizing, we precisely measured the volume distribution of human eosinophils during apoptosis. We observed that apoptosis of eosinophils was accompanied by a marked cell volume decrease (approximately 60%). Moreover, analysis of the volume distribution in different experimental conditions (kinetics of apoptosis, inhibition of apoptosis by cytokines) revealed that the cell shrinkage, once triggered, was a fast process in which the intermediate states between normal and shrunken volume had a short half-life. As a model of apoptosis, the eosinophil model allowed us to test the hypothesis that apoptotic cell shrinkage was linked to osmotic changes due to leakage of internal ions. Indeed, in the presence of K+ channel blockers, the shrinkage was inhibited in a dose-dependent manner. In conclusion, our results suggest that eosinophil shrinkage during apoptosis is a striking and rapid phenomenon and osmotic changes due to K+ efflux could be responsible, at least in part, of the volume decrease.

Apoptosis↗
PubMed1995

Uncoordinate expressions of type I and III collagens, collagenase and tissue inhibitor of matrix metalloproteinase 1 along in vitro proliferative life span of human skin fibroblasts. Regulation by all-trans retinoic acid.

In vitro human skin fibroblasts aging was characterized by a continuous increase of collagenase mRNA levels. On the contrary, TIMP-1 mRNA level decreased only at late passages (> 65% of proliferative life span). Type I and III mRNA levels showed a high variability depending on cell strains studied. However, type I and III collagen expressions varied parallely. All-trans retinoic acid (RA) decreased collagenase expression and stimulated TIMP-1 expression. Under RA action, high variability in mRNAs levels encoding type I and III collagens was observed with HSF passages. However, RA tended to correct variations in collagens expressions observed along HSF life span.

Cell Division↗
PubMed1995

Unusual specific cutaneous lesions in myelodysplastic syndromes.

BACKGROUND: Early diagnosis of leukemia cutis in myelodysplastic syndrome (MDS) is important because these lesions can precede acute peripheral blood or bone marrow transformation. Leukemia cutis is usually easy to recognize, but atypical lesions are not well described. OBJECTIVE: Our purpose was to describe unusual specific lesions in MDS. METHODS: Data from patients with myeloid malignancies and leukemia cutis were reviewed. Only patients with MDS and cutaneous lesions different from typical tumors were included. Clinical features were analyzed. RESULTS: Four patients with MDS and unusual specific cutaneous lesions were found. They had ecchymoses, necrotic plaques or ulcers, and prurigo-like lesions. In three of four patients appearance of these skin lesions heralded or was concomitant with acute transformation. CONCLUSION: Specific cutaneous lesions can display unusual patterns. Early biopsy of cutaneous lesions in MDS is indicated.

Aged↗
PubMed1995

Hyperkeratotic spicules and monoclonal gammopathy.

Hyperkeratotic spicules are a rare disorder that has been associated with different types of malignancies. An association with multiple myeloma raises the question of a relation between the monoclonal component and skin manifestations. We describe hyperkeratotic spicules in a 61-year-old man with a monoclonal gammopathy of undetermined significance. Immunofluorescence and immunoelectron microscopic findings demonstrated the deposition of the monoclonal immunoglobulin at the dermoepidermal junction. Our findings support previous reports that the association between hyperkeratotic spicules and monoclonal gammopathy is not fortuitous and may be related to particular properties of the monoclonal immunoglobulin.

Humans↗
PubMed1995

Autosomal recessive lamellar ichthyosis: identification of a new mutation in transglutaminase 1 and evidence for genetic heterogeneity.

Autosomal recessive lamellar ichthyosis (ARLI) belongs to the group of congenital disorders of cornification. It is characterized by a severe and generalized ichthyosis, and other variable cutaneous signs. The human transglutaminase 1 (TGM1) gene was recently found to be the disease-causing gene. Linkage analysis in 23 families (of which 13 were consanguineous) showed that for 10 of them, the disease was linked to the TGM1 gene. A new deleterious mutation introducing a stop codon in the TGM1 reading frame was found. Nevertheless, for the 13 other ARLI families, TGM1 was found to be unlinked to the disease. The present data show that ARLI is genetically heterogeneous and confirm that TGM1 is one of the responsible genes.

Base Sequence↗