Immunointervention in psoriasis with anti-CD4 antibodies.
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Biomedical subjects
J Thivolet
Publications and source records attributed to J Thivolet.
Pemphigus: past, present and future.
Pemphigus remains the archetype of the autoimmune bullous diseases with circulating and skin antibodies in patients as well as in animal models. Pemphigus antigens are desmosomal-associated glycoproteins of 130 kD in pemphigus vulgaris (desmoglein 3) and of 160 kD (desmoglein 1) in pemphigus foliaceus (fogo selvagem in Brazil, pemphigus seborrheicus in other countries). Pemphigus may be associated to drugs and/or immune system related tumors (e.g. thymoma). Two new forms of pemphigus have been described: IgA pemphigus and paraneoplastic pemphigus. Targets of the autoantibodies are various desmosomal and cellular adhesion molecules. Even if each main pemphigus variant corresponds to specific antibodies, association of various antibodies may be found, leading to the concept of dysimmunoreactivity.
Animals↗
Immunohistopathological study of autoimmune pemphigus. Lack of strictly specific histological and indirect immunofluorescence criteria for paraneoplastic pemphigus.
Paraneoplastic pemphigus (PNP) is a form of pemphigus considered to bear characteristic immunohistopathological features (vacuolar-interface dermatitis, keratinocyte dyskeratosis and reactivity of patients' sera with transitional epithelia). The present study was undertaken in order to investigate whether these criteria are specific enough so as to allow the diagnosis of PNP in the absence of clinical data. A retrospective study of 66 biopsies of pemphigus revealed that one third of them comprised histological signs of PNP; one of the corresponding sera reacted with mouse bladder epithelium. However, no evidence of a neoplastic disease was present in any of the patients, and Western blotting further excluded the diagnosis of PNP. These results suggest that some of the features considered characteristic of PNP are not strictly specific for this variety of pemphigus; hence this diagnosis cannot be reliably established by histology or immunofluorescence but requires biochemical studies.
Acantholysis↗
Potentializing effect of ketoconazole on cyclosporin A-induced inhibition of keratinocyte DNA synthesis.
Keratinocyte growth in vitro and DNA synthesis by epidermal cells in vivo are inhibited by therapeutic doses of cyclosporin A (CsA). This effect may be potentialized by topical treatment with ketoconazole, since this drug has been shown to inhibit CsA metabolism. Normal human skin grafts on nude mice receiving intraperitoneal injections of CsA were treated with ketoconazole cream or its placebo for 3 weeks. The keratinocyte DNA synthesis rate was evaluated through the rates of bromodeoxyuridine (BrdU) incorporation, and the trough blood levels of CsA were checked at the end of the experiment. Counting of the BrdU-labelled nuclei in human tissue sections confirmed a dose-dependent inhibition of BrdU incorporation by keratinocytes exposed to CsA. This CsA-induced inhibition was further increased in the animals treated with ketoconazole cream. This effect was best seen in the groups treated with the low-to-medium doses of CsA (12.5 and 25 mg/kg/day). However, the simultaneous increase in the circulating CsA levels was also observed in these animals. Based on our results, we speculate that the potentializing effect of ketoconazole on CsA-induced inhibition of keratinocyte DNA synthesis is systemic rather than local.
Animals↗
[Treatment of psoriasis by oral calcitriol].
Explore the source record for details and available documents.
Administration, Oral↗
Association of skin malignancies with various and multiple carcinogenic and noncarcinogenic human papillomaviruses in renal transplant recipients.
BACKGROUND: Organ transplant recipients receiving immunosuppressive treatment are prone to skin carcinomas on sun-exposed areas, and the frequency of such carcinomas in the long term reaches 40%. These carcinomas primarily are squamous cell carcinomas (SCC), which often are preceded by viral warts and premalignant keratoses. Human papillomaviruses (HPV) with other cocarcinogenic factors have been reported to play a role in the development of carcinomas in these patients. METHODS: Five hundred renal-graft recipients referred to our department were examined for the presence of warts, precancerous keratoses, Bowen disease, keratoacanthomas, and basal and squamous cell carcinomas. Adequate material for histologic and virologic examination was obtained from 24 patients. An in situ molecular hybridization technique was performed using biotinylated DNA probes for HPV types 1a, 2a, 5, 16, and 18 under stringent conditions. RESULTS: HPV DNA was detected in 44 of 86 specimens, including 14 of 17 warts, 4 of 17 premalignant keratoses, 1 of 4 Bowen disease lesions, 8 of 12 keratoacanthomas, 3 of 4 tumors in which distinction between keratoacanthomas and SCC was difficult, and 14 of 30 SCC. Twenty-six of 44 positive specimens contained several HPV types, whereas 30 specimens contained oncogenic types. Benign types 1 or 2 were detected alone in five SCC. HPV types 16 and 18 (usually detected in genital lesions) were found in 26 samples from sun-exposed areas. CONCLUSIONS: Our results show that oncogenic and benign HPV often are detected within premalignant keratoses and SCC in organ transplant recipients, which suggests that HPV may play a role in the development of cutaneous malignancies.
Adult↗
Contact sensitivity in mice: differential effect of vitamin D3 derivative (calcipotriol) and corticosteroids.
Vitamin D3 derivatives are new compounds used topically for the treatment of psoriasis. To get better insights into the mechanisms of action of these compounds, we studied the effect of local treatment with calcipotriol (vitamin D3 synthetic analogue) and compared it to that of betamethasone dipropionate in a murine contact sensitivity (CS) test, the Mouse Ear Swelling Test. Two haptens were used: oxazolone and paraphenylenediamine. Betamethasone and calcipotriol exerted a differential effect on the delayed-type hypersensitivity response. When drugs were applied to the abdomen (sensitization site) before sensitization, no effect was observed. When betamethasone was applied to the abdomen for 4 consecutive days after epicutaneous sensitization, a diminution of the CS response to the relevant hapten was observed, whereas calcipotriol given in the same conditions did not affect the reaction. Ointments were then administered to the ear (elicitation site) either for 4 consecutive days prior to the challenge, or for 4 days before and 2 days after the challenge. In both conditions, calcipotriol and betamethasone exerted a differential effect on elicitation, the latter inhibiting and the former increasing the CS response to oxazolone and paraphenylenediamine. From these results we conclude: (1) that vitamin D3 derivatives are devoided of immunosuppressive effects when applied topically, and (2) that clinical improvement of chronic inflammatory dermatoses observed with topical vitamin D3 derivatives and corticosteroids is due to different mechanisms.
Adrenal Cortex Hormones↗
In-situ preferential usage of V alpha 8 T-cell receptor gene segments in a patient with bullous pemphigoid.
Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with the occurrence of autoantibodies directed to a limited series of antigens located at the basement membrane zone of the dermo-epidermal junction. Previous studies have demonstrated the presence of activated T cells in BP lesions although their actual contribution to the pathogenesis of the disease has remained unclear. One approach to better understanding the significance of these T-cell infiltrates is to study the diversity of the recognition receptors (TCRs) expressed at the lesion sites. We report here an extensive analysis, performed in one patient with typical BP, where 187 TCR in frame transcripts from a lesional area, from clinically normal skin or from peripheral blood lymphocytes have been sequenced and compared. The data show preferential usage of the V alpha 8 subfamily gene segments in the lesion. It is therefore suggested that T-cell infiltration in BP may not simply reflect a non-specific inflammatory process but include antigen-specific responses.
Amino Acid Sequence↗
Modified epidermal lipid composition in air-exposed culture of non-bullous congenital ichthyotic erythroderma (NBCIE) keratinocytes.
Emerged epidermal cultures on dead de-epidermized dermis (DED) constitute an excellent model for in vitro reproduction of dermatoses linked to a keratinocyte defect. We used such cultures for studies of non-bullous congenital ichthyotic erythroderma (NBCIE). Keratinocytes of normal and pathological origin were expanded in submerged cell cultures and frozen keratinocytes from the resulting cell bank were subsequently used for seeding on DED. Lipid extracts from 14 day emerged cell cultures were assayed qualitatively and quantitatively using thin layer chromatography and compared with the neutral and non-polar lipid profiles obtained from normal epidermis extracts and with those from the plantar stratum corneum of healthy donors and untreated NBCIE patients. The ichthyotic cultures were found to contain significantly elevated levels of n-alkanes, as were the lipid extracts from the patients' plantar horny layer. Our results demonstrate that a major marker of the NBCIE epidermis can be reproduced under the emerged culture conditions. They also indicate that the characteristic n-alkane increase in NBCIE is indeed endogenous and not merely related to possible contamination from topical treatments.
Air↗
Ultrastructural study of chronic lesions of erythema elevatum diutinum: "extracellular cholesterosis" is a misnomer.
Erythema elevatum diutinum (EED) is a rare disease of unknown origin that belongs to the spectrum of leukocytoclastic vasculitis. Chronic lesions of EED contain lipid deposits, for which the term extracellular cholesterosis has been coined. We studied a typical case of EED with long-standing lesions. Findings of electron microscopic examination revealed a heavy, exclusively intracellular lipid deposition that consisted of lipid droplets, myelin figures, and rare cholesterol clefts within histiocytes but also within epidermal keratinocytes, mast cells, pericytes, and lymphocytes. These findings are in keeping with the results of previous ultrastructural studies and suggest that the term extracellular cholesterosis is a misnomer; intracellular lipidosis would more accurately describe the lipid deposition.
Chronic Disease↗
Remission of Langerhans cell histiocytosis with thalidomide treatment.
Explore the source record for details and available documents.
Aged↗
Dissociation of allergenic and immunogenic functions in contact sensitivity to para-phenylenediamine.
Contact sensitivity to para-phenylenediamine (PPD) is a frequent delayed-type hypersensitivity resulting in contact dermatitis. The aim of the present study, conducted in 16 patients allergic to PPD (as assessed by a positive patch test), was to get better insight into the mechanism of T-cell activation in PPD contact sensitivity. PPD was unable to induce significant proliferation of T cells from a first set of 9 patients. In 7 further patients, lymphocyte proliferation was assessed using PPD and 2 PPD metabolites, namely Brandrowski's base (BB) and benzoquinone (BQ). BB specifically stimulated T-cell proliferation in a dose-dependent fashion in all 7 patients whereas BQ, like PPD, was ineffective. The peripheral blood mononuclear cells (PBMC) of 8 PPD nonallergic individuals did not respond to either PPD, BB or BQ. We concluded from this study that: (1) the immunogenic hapten in PPD hypersensitivity is not PPD itself, and (2) BB might be the oxidative derivative of PPD endowed with T-cell-activating properties. Further support to this statement was provided by the observation that a T cell line derived from PBMC of a PPD-allergic patient in the presence of PPD responded to BB but not to PPD. Our in vitro results suggest that PPD is a prohapten which when applied on the skin is metabolized and converted into products (such as BB) which are the immunogenic haptens able to activate specific T cells.
Benzoquinones↗
Alpha interferon treatment in atopic dermatitis.
Eight patients suffering from atopic dermatitis were treated with interferon alpha 2b. They received low or intermediate doses (9-15 x 10(6) U/week) for a short period of time (4-8 weeks), with a moderate improvement of skin lesions in 4 of them and no change or an exacerbation of the disease in the other 4. Among the 4 patients who slightly improved at 4 weeks, 3 did not show any beneficial effect of interferon after 8 weeks. Serum IgE levels, which were increased in all patients before treatment, were not reduced under interferon therapy. This study shows that intermediate doses of interferon alpha 2b are not effective in the short-term treatment of atopic dermatitis.
Adult↗
Evidence of increased keratinocyte proliferation in air-liquid interface cultures of non-bullous congenital ichthyosiform erythroderma.
Modern pharmacological and dermatological research requires the use of appropriate in vitro models which permit a faithful reproduction of various aspects of the in situ situation. The air-exposed culture of keratinocytes on dead de-epidermized dermis is one of the best models of in vitro epidermal differentiation known at the moment. In this study, we verified the model's validity for the reproduction of a hyperproliferative genodermatosis: non-bullous congenital ichthyosiform erythroderma. We used subcultured epidermal keratinocytes originating from normal and ichthyotic patients. Light and electron microscopy of pathological cultures disclosed, on day 14, a terminally differentiated epidermis with a marked granular layer and hyperkeratosis which, however, was not dramatically different from the normal controls. On day 25, the normal cultures displayed an even more pronounced hyperkeratosis and hypergranulosis, whereas the reconstructed epidermis of pathological origin presented a considerable reduction of the viable non-keratinized compartment and a focal parakeratosis. Indirect immunofluorescence revealed the expression of several differentiation markers which were not observed in the immersed culture models (e.g. the desmosome- and differentiation-related antigens KM48 and G36-19). Abundant keratohyalin granules were stained with AKH1 antibody and observed even in the deep epidermal layers, but no profilaggrin-filaggrin conversion could be detected biochemically.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Cutaneous mesenchymal tumour with haemangiopericytoma-like features.
A case of cutaneous mesenchymal haemangiopericytoma-like tumour affecting a 17-year-old male is presented. Clinical features were non-specific. The tumour was studied by light, electron microscopy and immunohistochemistry. The results of these studies suggested the diagnosis of a mesenchymal, poorly-differentiated tumour showing features of haemangiopericytoma. The clinical course after surgery was uneventful after a 9-month follow-up period.
Adolescent↗
Keratinocyte proliferation in epidermal keratinocyte disorders evaluated through PCNA/cyclin immunolabelling and AgNOR counting.
The assessment of cell proliferation is important to our understanding of hyperproliferative disorders. In this work we evaluated the proliferation characteristics of epidermal keratinocytes in diseases with abnormal keratinization by two different methods (immunostaining for the proliferating cell nuclear antigen--PCNA and histochemical staining for nucleolar organizer region--associated argyrophilic proteins--AgNORs). Twenty-seven specimens from diseases with an abnormal keratinization were studied and compared with specimens of normal human skin. As compared with the latter, the numbers of PCNA-positive epidermal keratinocytes were increased in psoriasis, congenital non-bullous ichthyosiform erythroderma, epidermolytic hyperkeratosis and chronic dermatitis and decreased in ichthyosis vulgaris, X-linked ichthyosis and pityriasis rubra pilaris. In most cases a parallel modification of AgNORs was found. We conclude that although PCNA immunolabelling and AgNOR staining do not provide strictly correlated values, both appear as useful markers for the assessment of keratinocyte proliferation in epidermal disorders.
Autoantigens↗
[Immunointervention in psoriasis. Pathogenic consequences].
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
[Accidents caused by iontophoresis].
Ionophoresis is a well-established treatment for idiopathic hyperhidrosis. Modern apparatuses are reliable as long as the electrical equipment is used correctly. The authors present five cases of cutaneous incidents resulting in burns and secondary necrosis. Two of the cases could be explained by defective protection and the other three were apparently of the same type although non confirmation could be established. In comparison with uneventful incidences (pruritus, erythematous reactions, dysaesthesia) these spectacular burns should not exist. Machines must be regularly check and only electrodes with optimal protection should be used.
Adult↗