Proteolytic activity and expression of the 20S proteasome are increased in psoriasis lesional skin.

BACKGROUND: Deregulation of the proteasome pathway has been shown to be involved in the pathogenesis of several inflammatory disorders. To date limited information exists on proteasome and immunoproteasome expression and activity in psoriasis skin. OBJECTIVES: To investigate the potential role of proteasomes in the pathogenesis of psoriasis. METHODS: Thirty-six patients with psoriasis and 40 healthy subjects were included. The protein and mRNA expression levels and proteolytic activity of proteasome and immunoproteasome subunits were determined using immunohistochemistry, quantitative polymerase chain reaction and fluorogenic peptide substrate in lesional and nonlesional psoriasis skin. We additionally measured the plasmatic proteasome (p-proteasome) levels using enzyme-linked immunosorbent assay. RESULTS: We reveal an increased expression of proteasome and immunoproteasome subunits but stable mRNA levels in lesional psoriasis skin as compared with nonlesional psoriasis skin (n = 19), suggesting that proteasome and immunoproteasome expression is regulated post-transcriptionally. This proteasome overexpression was associated with a significant increase of the proteasomal chymotrypsin-like activity that was threefold higher in lesional skin than in nonlesional skin (n = 3). p-Proteasome levels were enhanced in patients with psoriasis (mean ± SEM 3960 ± 299 ng mL(-1) , range 1484-8987) when compared with controls (2535±187 ng mL(-1) , range 654-6446, P<0·001) and were significantly higher in psoriatic arthritis (4937±572 ng mL(-1) , range 2600-8987). In addition, they were correlated to the body surface area involved and appeared thus as a new biomarker of psoriasis severity. CONCLUSIONS: Altogether these results strongly suggest the involvement of the proteasome system in the pathogenesis of psoriasis and support the relevance of proteasome inhibitors in local or systemic treatment of psoriasis.

The enhancer in an MHC class II gene, in vitro and in mouso.

The E alpha class II gene of the major histocompatibility complex is expressed in a variety of immunocompetent cells. Part of the control of tissue-specific expression is mediated by a block of sequences found far upstream of the transcriptional startsite; this stretch is necessary for expression in the B lymphocytes of transgenic mice, but largely dispensable elsewhere. We review the evidence for the role of this region in E alpha transcription in transgenic animals, as well as data from transfections into tissue-culture cells, which indicate that this region has non-specific enhancer activity. We discuss possible models to explain how a non-specific enhancer can participate in cell-specific control.

[Peritoneal splenosis disclosed by infectious mononucleosis in an adolescent. Contribution of scintigraphy]. / Splénose péritonéale révélée par une mononucléose infectieuse chez un adolescent. Apport de la scintigraphie.

This article does not deal with the general problem of splenosis, but with the pathology of splenic nodules implanted in the peritoneum. This condition is uncommon, and chiefly hematological and infectious in the index case. Although this issue is debated, functional activity of these nodules is substantiated, leading to consider therapeutical applications in some exceptional cases.

[Should thalidomide be rehabilitated?]. / Faut-il réhabiliter la thalidomide?

Thalidomide (alpha-N-phtalimido-glutarimide) was withdrawn from sale in 1961 since it was held responsible for the birth of hundreds of phocomelus children. Despite this teratogenic potential, thalidomide remains a useful tool in the treatment of erythema nodosum leprosum, as well as in discoid lupus erythematosus when antimalarial drugs are ineffective or contraindicated. In addition, good results have been reported in several diseases such as actinic prurigo, polymorphous light eruption, Behçet syndrome, Weber-Christian disease, prurigo nodularis, pyoderma gangrenosum and ulcerative colitis. The mechanism of action is under debate but it is likely that thalidomide has immunomodulating properties by controlling T-suppressor lymphocytes, and anti-inflammatory effects, particularly an inhibition of neutrophil chemotaxis. Several attempts at synthesis of effective thalidomide derivatives devoid of teratogenic effects are ongoing.

[Verrucous carcinoma. Apropos of a case report with palpebral localization]. / Le carcinome verruqueux. A propos d'une observation de localisation palpébrale.

The authors present a case of "verrucous carcinoma" of the eyelid. Such a location never seems to have been described in the literature. As the histological features of the tumor are highly differentiated the exact diagnosis can be ascertained, only upon examination of a large biopsy specimen or of the operative specimen. Clinical, histological and evolutional features are recalled. The therapeutic means of curing this locally malignant and potentially recurrent lesion are discussed. In most cases, recovery depends on early treatment, particularly on surgery.

[Mediterranean boutonneuse fever. Apropos of 154 recent cases]. / La fièvre boutonneuse méditerranéenne. A propos de 154 cas récents.

The Mediterranean spotted fever is always present in the south of France. The actual incidence is unknown. The disease appears in summer. The diagnostic is based on the association of fever, "black spot" and exanthema and/or a seroconversion. Indirect immunofluorescence is the most used technique. Some patients have severe complications: neurologic, cardiovascular, renal, thrombopenia. These cases look like Rocky Mountain Spotted Fever. The treatment is based on tetracycline.

[Hormonotherapy in acute, idiopathic hirsutism, and seborrheic alopecia (author's transl)]. / Place de l'hormonothérapie dans le traitement de l'acné, de l'hirsutisme idiopathique et des alopécies séborrheiques.

It has been established that, through skin responds to circulating androgens, it can also produce androgens from precursors. Therapy can address either of the two following physiopathological steps: the secretory step can be countered by replacement or suppressive therapy which is now fairly well mastered; the target-organ step opens new possibilities concerning receptor abnormalities and receptor control. The medical literature was reviewed for data on hormonal therapy for women with acne, idiopathic hirsutism and seborrheic alopecia, three conditions which are usually only partially improved by cosmetic treatment.

[Lymphomatoid granulomatosis with mesenteric localization. Nosologic problems (author's transl)]. / Localisation abdominale de la granulomatose lymphomatoïde. Problèmes nosologiques.

The authors report the case of a 70-year-old woman with a mesenteric tumor, apparently isolated. Histologic examination led to the diagnosis of lymphomatoid granulomatosis. A review of the literature found four previously published cases of lymphomatoid granulomatosis with mesenteric localization, and with or without pulmonary involvement. The general features of this affection are recalled. Special attention is given to forms without pulmonary involvement (Liebow granulomatosis) as well as to their relationship with polymorphic reticulosis. Separation of these two disorders, which depended mainly on a strict distribution of the various lesions, seems questionable. The authors tend to consider that both conditions belong to the same nosologic group, sincea pathological features are similar and borderline cases exist.

[Cutaneous manifestations of mediterranean periodic disease. Concerning an observation. Review of the literature (author's transl)]. / Manifestations cutanées de la maladie périodique. A propos d'une observation: revue de la littérature.

Méditerranean Periodic Disease is frequently encountered in non-aschenazic Jews and in Armenians. Aside from the classic triad of pseudo-palustral febrile crises, paroxysms of abdominal and articular pain, and a biological syndrome of inflammation; cutaneous manifestations were noted in 25 to 35% of the cases according to various authors. The most commonly encountered lesions consisted of erysipel-like plaques and subcutaneous nodules. We observed the case of a 47 years old Armenian male, afflicted with Mediterranean Periodic Disease for 30 years in which the dermatologic symptoms are quite classic aside from a vitiligo having progressively appeared since 15 years. Possibly a coincidental association, but to the best of our knowledge, which has not as yet been reported.

[Tetralogy of Fallot, congenital coronary aneurysms with the histology of periarteritis nodosa: nosologic problems]. / Tétralogie de Fallot, Anévrysmes coronariens congénitaux avec histologie de périartérite noueuse: problèmes nosologiques.

Coronary lesions of periarteritis nodosa are detected in a newborn suffering from a Fallot's tetrad. The authors remind us of the present concept of infantile P.A.N. similar to adults' and of the notion of Kawasaki's syndrom that is almost the same as the infant's serious P.A.N. The reported case, original in many a detail, seems to represent the later expression monosymptomatic of Kawasaki's syndrom as if this one had been amputated at that stage of the greater part of its elements and then, casually developed in utero upon a congenital cardiopathy.