Lethal paraneoplastic pemphigus following treatment of chronic lymphocytic leukaemia with fludarabine.
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Antineoplastic Agents↗
Biomedical subjects
L Dubertret
Publications and source records attributed to L Dubertret.
Expression of V beta gene segments by Sezary cells.
The T-cell receptor V beta repertoire expressed by Sezary cells was determined in a series of 16 patients whose samples have been shown to contain a majority of tumor cells. By using anti-V beta monoclonal antibodies, polymerase chain reaction analysis of expressed V beta, and, in selected cases, nucleotide sequencing, we have shown that the expressed V beta segments belong to five V beta families (V beta 5, V beta 6, V beta 8, V beta 13, and V beta 18), which contain a large fraction of the T-cell receptor V beta repertoire and do not share significant similarities in complementary determining region 4. V beta segments from these five families were also found to be strongly expressed by CD4 + CD7- peripheral blood cells obtained by fluorescence-activated cell sorting from two healthy donors. The diversity of the V beta repertoire expressed by Sezary cells appears to be similar to that expressed by circulating non-neoplastic T cells. These data do not support the hypothesis that a common superantigen is involved in the initiation of this form of cutaneous T-cell lymphoma.
Antigens, CD↗
Polyunsaturated fatty acid enrichment increases ultraviolet A-induced lipid peroxidation in NCTC 2544 human keratinocytes.
The influence of cell enrichment with fatty acids with increasing degree of unsaturation on the ultraviolet A-induced formation of lipid-peroxidation products (thiobarbituric acid reactive substances [TBARS]) has been investigated in NCTC 2544 human keratinocytes. A 48-h preculture of cells in controlled medium supplemented with unsaturated fatty acids resulted in a marked increase in TBARS appearance under ultraviolet A exposure. This effect was dependent upon the degree of unsaturation of the fatty acids, with the following order of efficiency: arachidonic > linolenic > linoleic > oleic acid. For arachidonic acid (AA), the potentiating effect on ultraviolet A-induced lipid peroxidation was dependent upon the fatty acid concentration, with about a 2.5-fold increase in TBARS formation in cells pre-cultured with 5 x 10(-5) M AA, then exposed to a UVA dose of 13 J/cm2. The increase in TBARS formation by AA was almost totally prevented by supplementation of cells with 5 x 10(-5) M vitamin E, whereas buthionine sulfoximine, a chemical which depletes cell glutathione, potentiated lipid peroxidation. These results suggest that the nature of the fatty acids of cellular lipids could influence the response of keratinocytes to ultraviolet A, and especially the ultraviolet A-induced lipid peroxidation.
Antimetabolites↗
Bacillary angiomatosis in HIV-infected patients: report of three cases with different clinical courses and identification of Rochalimaea quintana as the aetiological agent.
Three cases of cutaneous bacillary angiomatosis in HIV-infected patients are reported. They differed profoundly with respect to the extent of the lesions and the clinical course. In two cases, Rochalimaea quintana was identified by direct sequencing of the DNA amplified with the polymerase chain reaction (PCR), whereas an easy, rapid method based on the restriction length of polymorphism analysis of PCR products (PCR-RFLP) was used in the third case. This report illustrates the variations in clinical presentations and evolutive profiles in patients with bacillary angiomatosis, and confirms the causal role of R. quintana in this disease.
Adult↗
Subcellular localization of and photosensitization by protoporphyrin IXhuman keratinocytes and fibroblasts cultivated with 5-aminolevulinic acid.
The subcellular localization of protoporphyrin (PP) has been studied by microspectrofluorometric techniques in NCTC 2544 keratinocytes incubated with 5-aminolevulinic acid (ALA) for times up to 42 h. Whereas the plasma membrane shows strong staining, fluorescent spots are observed within the cytoplasm especially in the perinuclear region. Although the topographic pattern of the PP distribution does not change much with the incubation time with ALA, the fluorescence spectra suggest that the PP microenvironments are quite different at short and long incubation times. Addition of 18 microM desferrioxamine almost doubles the ALA-induced PP concentration. Colocalization experiments with rhodamine 123, a mitochondrial probe, and lucifer yellow (LY) or neutral red (NR), two lysosome probes, demonstrate that at least some of these spots are of lysosomal origin. Study of the time evolution of the NR fluorescence under irradiation with visible light in the presence and absence of ALA demonstrates that lysosomes are damaged cells that have synthesized PP. No PP fluorescence can be detected in mitochondria after incubation with ALA. However, photosensitization of mitochondria occurs under irradiation with visible light. Very little formation of lipofuscins by photosensitization with exogenous PP or ALA-induced PP is observed with the NCTC 2544 keratinocytes, as compared to normal human fibroblasts.
Aminolevulinic Acid↗
Effects of selenium on UVA-induced lipid peroxidation in cultured human skin fibroblasts.
The effect of selenium on the lethal action of ultraviolet radiations and on the lipid peroxidation induced by exposures to ultraviolet A (320-400 nm; 360 kJ.m-2) and ultraviolet B (290-320 nm; 2 kJ.m-2) have been measured in cultured human skin fibroblasts. The experiments have been performed with either pure selenium or a spring water containing selenium and other trace elements (zinc and strontium). For cells cultured in a standard medium containing 10% fetal calf serum, no effect of selenium or spring water addition to the culture medium was observed on the lethality or on the peroxidative process induced by ultraviolet A and B radiations. Concurrently, there was no detectable increase of the seleno-dependent glutathione peroxidase activity. For cells previously depleted in selenium by a culture in a medium containing only 2% serum, a protective effect of selenium can be detected. Depending on the fibroblast donor, we observed (1) a protective effect on lethality of dividing fibroblasts induced by ultraviolet A radiations, (2) a protective effect on lipid peroxidation induced by ultraviolet A radiations on dividing or quiescent fibroblasts and (3) an increase in glutathione peroxidase activity in fibroblasts.
Adolescent↗
Neutrophilic dermatoses during granulocytopenia.
BACKGROUND AND DESIGN: Noninfectious cutaneous neutrophilic lesions can occur during granulocytopenia, but their mechanism remains unknown. We undertook a retrospective study of the neutrophilic dermatoses that developed during granulocytopenia induced by chemotherapy for acute myelogenous leukemia. RESULTS: Seven men and one woman were included (2.6% of treated cases of acute myelogenous leukemia); half had acute myelogenous leukemia subtypes 4 and 5. The male-to-female ratio was 7:1. Neutrophilic eccrine hidradenitis was diagnosed in five cases, Sweet's syndrome in two cases, and difficult-to-classify neutrophilic dermatoses in one case. Cutaneous lesions appeared 12.5 days after the start of chemotherapy, and the mean leukocyte count was 0.426 x 10(9)/L. Three patients needed corticosteroids systemically. CONCLUSION: Neutrophilic dermatoses during chemotherapy-induced granulocytopenia seem to occur more frequently in men with acute myelogenous leukemia subtypes 4 and 5.
Adult↗
Detection of clonal T-cell receptor gamma gene rearrangements with the use of the polymerase chain reaction in cutaneous lesions of mycosis fungoides and Sézary syndrome.
BACKGROUND AND DESIGN: We used the amplification of junctional V (variable)-J joining sequences of the rearranged T-cell receptor gamma (TCR gamma) genes by polymerase chain reaction for rapid and sensitive detection of a clonal T-cell population in a total of 51 skin specimens obtained from 45 patients with mycosis fungoides, five patients with Sézary syndrome, and 29 patients with chronic inflammatory dermatoses. RESULTS: A clonal TCR gamma gene rearrangement was present in all tumors (3/3, 100%) and in most infiltrated plaques (16/22, 73%) and erythrodermas (10/12, 83%). In the patch stage, a clonal subset was found in more than half of the cases (8/14, 57%), whereas no clonality was observed in the controls. We also amplified the V-J sequences of the Igh locus coding for the heavy chain of immunoglobulins, without evidence of clonal rearrangement. These data were compared with those from in situ immunophenotypic analysis. Moreover, by using the same assay with successive dilutions of standard clonal T-cell DNA, a semiquantitative study of the T-cell clone was carried out in some cases. The highest ratios of clonal DNA were observed in advanced stages. CONCLUSIONS: These data validate polymerase chain reaction V gamma-J gamma as a rapid, sensitive tool that can be used in the routine analysis of clonality in cutaneous lesions of mycosis fungoides and in the early diagnosis of mycosis fungoides and Sézary syndrome. Semiquantitative studies suggest that the malignant T-cell clone follows a selective process during the course of the progressive form of mycosis fungoides.
Clone Cells↗
[In vitro cutaneous organogenesis (application to skin grafts)].
The culture of cutaneous fibroblasts in an environment of collagen results in a resistant, three-dimensional culture in which fibroblasts are differentiated. This dermal sheet can be covered with an epidermal cell layer which will allow to rebuild an in vitro human skin equivalent. This in vitro organogenesis technique was used since 1983 to treat burns and children suffering from severe cutaneous malformations (giant naevi). The results which were obtained after 33 grafts on 16 patients show that, if the epidermal graft is essential to preserve patients' lives the dermal constituent is also important in the long-term since it induces the synthesis, 3 to 6 months later, of numerous elastic fibers which give to the graft mechanical properties close to that of the normal skin as well as the recovery of a normal micro relief. These cutaneous reconstructions can be completed in one or, even better, two stages which enable the successive graft of reconstructed dermis and epidermal sheets, the latter obtained in great quantity thank's to Grenn's method. The conditions of preparation of these living biomaterials require rigorous quality controls. Their further development is of great interest since it will improve skin replacement and will be a very interesting tool for gene therapy.
Adult↗
[Hypopigmented mycosis fungoides].
INTRODUCTION: Isolated areas of hypopigmented skin can be a manifestation of mycosis fungoides. This is a rare clinical form with a particular clinical course and histology which has been described only in black subjects. CASE REPORT: Over a 10-year period, a 28-year-old woman from Mali developed non-infiltrated hypopigmented and discretely squamous macules involving the entire body. The diagnosis of mycosis fungoides was made on pathology evidence of epidermotropic lymphocyte infiltration with a few small nests. PUVA led to rapid regression of the lesions. DISCUSSION: Hypopigmented mycosis fungoides has been described in young black subjects (mean age 19 years). The diagnosis is usually made late because benign skin affection is usually the first diagnosis (pityriasis alba, pityriasis versicolor). The pathogenesis of these hypopigmented lesions is not known. PUVA appears to be effective in most cases.
Adult↗
Inhibition of diphosphatidylglycerol synthesis by u.v. A radiations in N.C.T.C. 2544 human keratinocytes.
The effects of u.v. A radiations on phospholipid synthesis were studied in the N.C.T.C. 2544 human keratinocyte cell line, by using [14C]arachidonic acid, [14C]oleic acid or sodium [32P]orthophosphate as precursors. Cells were irradiated in Hanks' medium with 365 nm light at doses up to 19 J/cm2, and then phospholipid synthesis from the three precursors was studied. Under these conditions, only small alterations in the incorporation pattern of [14C]arachidonic into phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)] were observed, for u.v. A irradiation doses up to 19 J/cm2. In contrast, with [14C]oleic acid as precursor, two additional spots were observed, which co-migrate with pure phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG) standards. The incorporation of [14C]oleic acid into PG and DPG was decreased in a dose-dependent manner after u.v. A exposure, with about 50% and 75% decreases at 9.5 J/cm2 and 19 J/cm2 respectively. As for arachidonic acid incorporation, no significant differences in the synthesis of the major phospholipids (PC, PE, PI) were noted upon u.v. A exposure. The dramatic and selective decrease in PG and DPG syntheses was confirmed with [32P]orthophosphate as precursor. As DPG is a specific component of the mitochondrial inner membrane, it appears that one of the early kinds of damage induced by u.v. A irradiation could be the impairment of mitochondrial functions.
Cardiolipins↗
Molecular characterization of a human tyrosinase-related-protein-2 cDNA. Patterns of expression in melanocytic cells.
Pigmentation in mammals is under complex genetic control. Amongst the genes involved in this process, those encoding tyrosinase and the tyrosinase-related-proteins 1 and 2 have been well characterized and share a number of features. Recently, the murine tyrosinase-related-protein-2 gene was shown to encode dopachrome-tautomerase activity and was mapped to the slaty locus. Human tyrosinase and tyrosinase-related-protein-1 genes have been isolated and demonstrate a high degree of similarity with their murine counterparts. However, there has been limited data regarding the existence of a human homologue for tyrosinase-related-protein-2 and its relationship to the other tyrosinase-related proteins. In this study, we report the molecular isolation of a cDNA encoding a human homologue of the murine tyrosinase-related-protein-2/dopachrome tautomerase. We have characterized its expression in human melanocytic cells and have analyzed the relationship between dopachrome tautomerase and tyrosinase activities with the level of visible pigmentation in these cells. TYRP2 has been mapped to the chromosomal region 13q32, thus extending a region of synteny with mouse-chromosome 14.
Animals↗
Internalization of surface HLA-DR molecules by human epidermal Langerhans cells: analysis by flow cytometry and confocal microscopy.
Langerhans cells (LC) play a pivotal role in antigen processing and presentation to T cells during delayed-type hypersensitivity reaction in the skin. Antigen presentation involves the interaction between the class II molecules of MHC (HLA-DR) expressed by LC and T receptor of CD4+ T lymphocytes. It is now recognized that class II molecules are internalized into LC and can be associated with processed immunogenic peptides. This process involves receptor-mediated endocytosis. The aim of this study was to investigate the time-course of endocytosis of HLA-DR by freshly isolated human LC. Epidermal cells, obtained from normal skin samples, were labeled by indirect immunofluorescence using anti-HLA-DR monoclonal antibodies (MAb). The cell suspension was incubated at 37 degrees C for different periods (15, 30, 45, 60 and 90 min) and then analyzed by flow cytometry and confocal microscopy. Flow cytometry analysis showed decreased HLA-DR molecule expression by LC after incubation at 37 degrees C. Confocal microscopic analysis showed different strain patterns depending on the incubation time: (1) T = 0, continuous peripheral staining; (2) T = 15 min, patchy peripheral staining; (3) T = 30 min, patches or intracellular vesicular staining; (4) T = 45 min, intracellular vesicular staining; (5) T = 60 min, diffuse intracellular staining; (6) T = 90 min, aggregated staining. In our study model, flow cytometry provides quantitative information for the HLA-DR endocytosis, whereas confocal microscopy provides qualitative results concerning the intracellular distribution of internalized HLA-DR molecules.(ABSTRACT TRUNCATED AT 250 WORDS)
Cells, Cultured↗
Focal epithelial hyperplasia and multifocal human papillomavirus infection in an HIV-seropositive man.
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AIDS-Related Opportunistic Infections↗
Ultraviolet A decreases epidermal growth factor (EGF) processing in cultured human fibroblasts and keratinocytes: inhibition of EGF-induced diacylglycerol formation.
The binding, uptake, and degradation of epidermal growth factor (EGF) has been studied in MRC5 human fibroblasts and NCTC 2544 human keratinocytes following ultraviolet A (UVA) irradiation at doses up to 18.9 J/cm2, which are not lethal to cells under our experimental conditions. A dose-dependent reduction in EGF binding was observed, with an approximately 75% decrease at the maximal studied UVA dose. At lower doses (6 to 12 J/cm2), EGF binding was more affected by ultraviolet A in fibroblasts than in keratinocytes. In both cell types, this effect of UVA appeared to be related to a reduction of the affinity of the EGF receptor for EGF. Kinetic studies by pulse-chase experiments indicated that EGF is more rapidly internalized by keratinocytes than by fibroblasts, and that UVA exposure resulted in a slower decay of EGF intracellular content. A 24-h pretreatment of cells with 5 x 10(-5) M vitamin E strongly reduced the appearance of light-induced lipid peroxidation products, measured via assay of thiobarbituric acid reactive substances formation, but only partially prevented the UVA-induced alterations of EGF processing by cells. Finally, UVA exposure almost completely abolished the EGF-induced increase in diacylglycerol production from 14C-arachidonic acid-labeled lipids in both cell types. These results demonstrate that UVA radiation induces important changes in EGF processing and could participate in the light-induced degenerative processes of the skin.
Antioxidants↗
Efficacy and safety of oral cyclosporin A (CyA; Sandimmun) for long-term treatment of chronic severe plaque psoriasis.
The value of oral cyclosporin A (CyA; Sandimmun) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation. The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2.5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months). Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the end-point was significantly higher in the group on 5.0 mg/kg/day (92%) than in that on 2.5 mg/kg/day (52%; P < 0.001). A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose. One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine > 30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine > 30% above baseline was dose-related. The results of this study show that 5.0 mg/kg/day of CyA is significantly more effective than 2.5 mg/kg/day in the treatment of chronic plaque psoriasis.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Oral↗
Simultaneous occurrence of two rare cutaneous markers of poor prognosis in myelodysplastic syndrome: erythema elevatum diutinum and specific lesions.
We report the concomitant occurrence of erythema elevatum diutinum and specific skin lesions in a patient with a myelodysplastic syndrome (MDS). This patient's course, and review of other reported cases, support the opinion that neutrophilic dermatoses are associated with a poor prognosis of MDS. The simultaneous appearance of these manifestations could be the consequence of a particular chemotactism of myeloid cells, expressed after acute transformation.
Aged↗
Early alterations of actin in cultured human keratinocytes and fibroblasts exposed to long-wavelength radiations. Possible involvement in the UVA-induced perturbations of endocytotic processes.
Exposure of cultured MRC5 human fibroblasts or NCTC 2544 human keratinocytes to mild doses of ultraviolet A (UVA: 320-400 nm) radiations markedly decreased the actin reactivity with fluorescein-labeled phalloidin. This indicates a change in the degree of polymerization of actin and thus in the organization of actin filaments. Such a phenomenon might be involved in the previously reported UVA-induced inhibition of specific and nonspecific endocytotic processes.
Actins↗