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Biomedical subjects

L Kemény

Publications and source records attributed to L Kemény.

At least 19 recordsLinked to original sources

[Vulvar melanosis and vitiligo].

Clinically it is impossible to make difference between the vulvar melanosis the harmless brown spotty change of the vulva and melanoma malignum, that is one of the most dangerous malignancies. Even the dermatoscopical examination was not efficient to exclude the melanoma surely. A small, representative biopsy was enough for the diagnosis, which has exempted the patient from the unjustified mutilating resections. On the patient's skin they detected also a few relatively small disseminated hypopigmented spots. Electronmicroscopically they could observe plenty of melanosomes and big melanosoma-complexes in the lower keratinocyte layers of the vulvar melanotic macules. Melanocytes could not be recognised in the hypopigmented spots.

Biopsy

Identification of a soluble interleukin-8 inhibitor in the supernatant of polymorphonuclear leukocytes.

Interleukin-8 (IL-8) plays a crucial role in the pathogenesis of inflammatory and hyperproliferative diseases in various organs. The purpose of the present investigation was to establish whether there is any naturally occurring inhibitor of IL-8. Here we demonstrate that an IL-8 inhibitor (IL-8INH) is present in the supernatant of polymorphonuclear (PMN) leukocytes. The release of IL-8INH could be increased by stimulating the PMN leukocytes by concanavalin A. IL-81NH blocks the IL-8-induced chemotaxis and Candida albicans killing activity of PMN leukocytes and epidermal cells in vitro, and IL-8-induced neutrophil infiltration in the mouse ear in vivo. The mechanism of action of IL-8INH involves blocking of 125I-IL-8 binding to the IL-8 receptor. Binding of 125I-IL-8 to neutrophils could not be displaced by the IL-8INH, however, preincubation of 125I-IL-8 with IL-8INH increased binding inhibition, suggesting an interaction between IL-8 and the inhibitor. Crosslinking of 125I-IL-8 to IL-8INH shows that IL-8INH binds specifically to 125I-IL-8, and the IL-8INH protein has an apparent molecular weight of 52 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The partial purification of the IL-8INH on DEAE-Sephadex anion-exchange chromatography column also suggests a 50-60-kDa inhibitor protein which blocks IL-8-induced effects on neutrophils by binding to IL-8.

Animals

Demonstration and functional analysis of IL-10 receptors in human epidermal cells: decreased expression in psoriatic skin, down-modulation by IL-8, and up-regulation by an antipsoriatic glucocorticosteroid in normal cultured keratinocytes.

The chronic skin disease psoriasis is characterized by epidermal hyperproliferation and inflammation. The exact etiology of the disease is still unknown. At the molecular level, overexpression of growth factors and proinflammatory cytokines such as IL-8 and the corresponding receptor has been described in psoriatic plaques. On the other hand, the loss of inhibitory control mechanisms is involved in the pathogenesis of the disease, as exemplified by the reduced mRNA levels for the cell cycle inhibitor p53 found in lesional skin. Here we extend these findings to a cytokine with negative regulatory functions, IL-10. Only under certain conditions are human keratinocytes able to synthesize IL-10. In skin, pathological overexpression of IL-10 was described om atopic dermatitis. IL-10 exerts its effects via a specific receptor (IL-10R). We show here for the first time the presence and functionality of IL-10R in epidermal cells and its dramatically decreased expression in acute exanthematic psoriatic epidermis by in vitro and in situ binding studies. These results were substantiated using semiquantitative reverse transcriptase-PCR, demonstrating decreased expression of the IL-10R gene in psoriatic skin, its down-modulation by the proinflammatory cytokine IL-8, and its pharmacological induction in cultured cells. Biological responsiveness of epidermal cells toward IL-10 could also be demonstrated by a reduction of the growth rate and inhibition of IFN-gamma-induced HLA-DR expression. Our results provide the first evidence for a role of the IL-10R gene in the homeostasis of the epidermis and substantiate the concept of a loss of negative regulatory peptides as a step in the eruption of psoriasis.

Acute Disease

[Kaposi sarcoma-associated herpesvirus; human herpesvirus 8].

The discovery of a new human herpesvirus in Kaposi's sarcoma tissues of AIDS patients has opened up new facts in virology and oncology. This herpesvirus was first descriptively named Kaposi's sarcoma-associated herpesvirus, but was recently renamed human herpesvirus 8. Human herpesvirus 8 DNA has been consequently found in all forms of Kaposi's sarcoma, suggesting that it might be involved in the pathogenesis of the disease. Additionally, human herpesvirus 8 can be detected in both malignant and benign lymphoproliferative diseases, such as body-cavity-based B-cell lymphomas and multicentric Castleman disease. The virus was also recently found in rare vascular tumors in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the viral DNA has been sequenced, it has become evident that the new herpesvirus is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission, and also for the development of serologic tests.

AIDS-Related Opportunistic Infections

Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8: a new virus in human pathology.

The discovery of a new human herpesvirus in Kaposi's sarcoma (KS) tissue of patients with AIDS has opened up new vistas in virology and oncology. This herpesvirus was first descriptively named KS-associated herpesvirus (KSHV), but was recently renamed human herpesvirus 8 (HHV8). KSHV/HHV8 DNA has been found in all forms of KS, suggesting that it might be involved in the pathogenesis of KS. In addition, KSHV/HHV8 can be detected in both malignant and benign lymphoproliferative disease. KSHV/HHV8 was also found in patients with angiosarcoma of the face and angiolymphoid hyperplasia with eosinophilia. Although only a limited portion of the virus has been sequenced, KSHV/HHV8 is equipped with genes that could confer oncogenic potential. The virus can now be cultured, providing the possibility for studies of viral replication and the mode of transmission. The recently developed serologic assays for antiviral antibodies suggest that infection with KSHV/HHV8 is not ubiquitous because KSHV/HHV8 seropositivity is limited to a small proportion of the population.

Acquired Immunodeficiency Syndrome

Pyodermatitis-pyostomatitis vegetans.

A 43-year-old woman developed annular and pustular cutaneous lesions preceded by tiny yellow pustules coating the surface of the oral mucosa. The clinical, histological and immunopathological evidence clearly showed that the patient had pyodermatitis-pyostomatitis vegetans. It is suggested that this disease is a distinct entity which should be differentiated from pemphigus vegetans.

Diagnosis, Differential

Antioncogene P53 and mitogenic cytokine interleukin-8 aberrantly expressed in psoriatic skin are inversely regulated by the antipsoriatic drug tacrolimus (FK506).

Uncontrolled proliferation of epidermal cells is the most prominent characteristic of psoriasis. This widespread skin disease can be effectively treated with the microbial substance FK506, which acts by modulating gene expression. We, therefore, asked if the drug changes the expression of genes involved in growth regulation (the mitogenic cytokine interleukin-8 (IL-8) and p53, a negative cell cycle regulator) and signal transduction (protooncogenes c-ras, c-raf, and HER-2). Gene expression was monitored by semiquantitative mRNA-PCR and for p53 by immunocytochemistry in cultured primary keratinocytes (KC). In addition, p53 expression was analysed in skin biopsies of psoriatic patients. After 1-3 hr, IL-8 mRNA levels were dose-dependently decreased in tacrolimus (FK506)-treated cells. Protooncogene expression was not significantly altered. Interestingly, p53 transcription was clearly induced by FK506 treatment. This tendency could be verified on the protein level by immunocytochemistry. In contrast, p53 expression was decreased in lesional psoriatic as compared to normal skin, providing evidence that not only posttranslational modification of the p53 protein, but also transcriptional modulation of the p53 gene, are involved in pathological processes and pharmacological drug action in skin. Together with earlier results showing downmodulation for IL-8 receptor type A expression in cultured KC treated with FK506, these results suggest that both the mitogenic IL-8/IL-8R system and the cell cycle inhibitor p53 represent potential targets for the antipsoriatic action of the drug, whereas protooncogenes acting downstream in mitogenic signal transduction cascades are unaffected. The differential modulation of an entire set of genes provides evidence for the specificity of the drug effects and rules out nonspecific toxic effects on KC.

Dose-Response Relationship, Drug

Human herpesvirus 8 in classic Kaposi sarcoma.

Recent studies suggest the role of a new human herpesvirus (HHV8) in the pathogenesis of different forms of Kaposi sarcoma (KS). In the present work we investigated the presence of HHV8 sequences in KS tumour tissues from patient with classic KS. Since clear evidences point to the role of immune suppression in the development of AIDS-associated KS or patients receiving immunosuppressive therapy, immunological investigations were also performed. We could show a highly consequent association of HHV8 sequences with classic KS in the large series of patients supporting our previous findings that this virus might be in some way involved in the pathogenesis of this tumour. In addition immunological examination of the patients revealed a mild decrease in the CD4 positive cell number, a significantly reduced CD4/CD8 ratio, a diminished PHA reactivity and leukocyte migration factor production of lymphocytes. The changes observed in the present study are similar, but much less pronounced than those may be observed in HIV infection.

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