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Biomedical subjects

A Dobozy

Publications and source records attributed to A Dobozy.

At least 19 recordsLinked to original sources
PubMed2000

Development of a system for detection of circulating antibodies against hemidesmosomal proteins in patients with bullous pemphigoid.

Specific antibodies directed against special hemidesmosomal proteins are involved in the pathogenesis of bullous pemphigoid (BP), and detection of these antibodies is crucial for a correct diagnosis. As the BP autoantigen primary structures are known, the question was addressed as to whether it is possible to demonstrate circulating antibodies against BP autoantigens (BPAG1 and BPAG2) by means of an ELISA system, using antigenic epitopes. With the help of the programs Peptidestructure and Plotstructure, antigenic epitopes of BP antigens were predicted, chemically synthesized and screened using serum from 43 proven BP patients. The coding sequences of the best antigenic epitopes were then chemically synthesized and inserted as monomer and homo- or hetero-oligomer forms into fusion-expression plasmids (PGEX-4T, Pharmacia) in-frame to the C-terminus of glutathione-S-transferase. Fusion products were expressed and purified from Escherichia coli cells by affinity chromatography. The recombinant proteins were used for the detection of antibodies in the serum of 43 BP patients and of 60 controls (including 30 healthy persons, 22 patients with pemphigus vulgaris and 8 patients with other bullous dermatoses). Use of the homo- and hetero-oligomers of the recombinant fusion peptides increased the sensitivity of the disease-specific antibody detection. When a mixture of the best recombinant fusion proteins was used, the sensitivity of the ELISA assays in the case of the BP patients' serum was 0.90. This system could form the basis of a rapid and simple system for the diagnosis of BP.

Aged↗
PubMed2000

Histidine decarboxylase expression in human melanoma.

Histamine has been implicated as one of the mediators involved in regulation of proliferation in both normal and neoplastic tissues. Histidine decarboxylase, the only enzyme that catalyzes the formation of histamine from L-histidine, is an essential regulator of histamine levels. In this study, we investigated the gene and protein expression of histidine decarboxylase in melanoma. Reverse transcriptase polymerase chain reaction and in situ hybridization studies of WM-35, WM-983/B, HT-168, and M1 human melanoma cell lines both resulted in positive signals for histidine decarboxylase messenger RNA. A polyclonal chicken antibody was developed against human histidine decarboxylase and protein expression was confirmed by western blot analysis of the cell lysates, revealing a predominant immunoreactive band at approximately 54 kDa corresponding to monomeric histidine decarboxylase. Protein expression of histidine decarboxylase was also shown by flow cytometric analysis and strong punctate cytoplasmic staining of melanoma cell lines. Moreover, both primary and metastatic human melanoma tissues were brightly stained for histidine decarboxylase. When compared with the very weak or no reactions on cultivated human melanocytes both western blot and immunohistochemical studies showed much stronger histidine decarboxylase expression in melanoma cells. These findings suggest that expression of histidine decarboxylase is elevated in human melanoma.

Blotting, Western↗
PubMed1999

Scleromyxedema.

Scleromyxedema is a sclerotic variant of papular mucinosis, in which lichenoid papules and scleroderma-like features are present. We describe a patient with scleromyxedema with IgG type lambda chain paraprotein, a systemic sclerosis-like illness, and myositis. The patient's serum contained Scl 70 antibodies, characteristic of scleroderma. Electromyography showed signs of acute myositis and the creatine phosphokinase (CPK) level was elevated. Multiply passaged fibroblasts from the patient's skin lesions showed altered growth response in vitro. The patient was treated with cyclosporin (4 mg/kg/day) with improvement.

Cyclosporine↗
PubMed1999

Effects of the neuropeptides substance P, calcitonin gene-related peptide and alpha-melanocyte-stimulating hormone on the IL-8/IL-8 receptor system in a cultured human keratinocyte cell line and dermal fibroblasts.

The neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP) and alpha-melanocyte-stimulating hormone (alpha-MSH) are known to be able to regulate the production of cytokines in the skin. Since IL-8 plays an important role in cutaneous inflammation, the effects of SP, CGRP and alpha-MSH on the IL-8/IL-8 receptor (IL-8RA) systems of these cell types were studied. Cultures of human dermal fibroblasts and an immortalized keratinocyte cell line HaCaT were treated with 10-8 M SP, CGRP or alpha-MSH. The results demonstrated that these neuropeptides have different effects on the IL-8 and IL-8RA expressions of the cells. SP and CGRP upregulated the IL-8RA mRNA expression in HaCaT cells, but had no influence on their IL-8 production, whereas, alpha-MSH had no effect on either the IL-8 or the IL-8RA mRNA expression in HaCaT cells. In contrast, alpha-MSH resulted in a time-dependent induction of the IL-8 mRNA expression in dermal fibroblasts. This induction was already detectable after 6 h, and after 12 h there was a 5-fold change in comparison with the controls. The IL-8 content of the supernatant was also increased, with a maximum at 48 h after alpha-MSH treatment. The data established in the present study support the notion that neuropeptides can directly modulate the IL-8/IL-8RA system of keratinocytes and fibroblasts.

Antigens, CD↗
PubMed1999

Interleukin-10 receptors are expressed by basement membrane anchored, alpha(6) integrin(+) cytotrophoblast cells in early human placenta.

Cytotrophoblast cells produce interleukin (IL)-10 and express IL-10 receptor mRNA in culture. Furthermore, IL-10 dramatically reduces the synthesis of matrix metalloproteinase (MMP)-9 and the invasivity of cytotrophoblast cells in vitro, suggesting that an autocrine regulatory role in vivo is also possible. To test this hypothesis we investigated the expression of IL-10 receptor protein by first trimester cytotrophoblasts both in vitro and in situ, using flow cytometry and immunohistochemistry. Flow cytometric analyses demonstrated that 75-80% of cytotrophoblasts are able to bind labelled IL-10, suggesting that these cells possess IL-10 receptors in vitro. Serial sections of early human placentae stained for either alpha(5) and alpha(6) integrin subunits, or for IL-10 receptors respectively, revealed that placental cytotrophoblasts possess cell surface IL-10 receptors not only in vitro, but also in vivo. IL-10 receptors were present mainly on alpha(6) integrin expressing villous cytotrophoblast cells and on alpha(6)-positive cells of invasive cell columns located nearest the villous stroma. Differentiated trophoblasts (i.e. alpha(5)-positive cells and villous syncytiotrophoblasts) showed no reactivity. This differential expression of IL-10 receptors suggests that IL-10 might suppress the invasivity of undifferentiated cytotrophoblast cells, in vivo, preserving their non-invasive state in an autocrine manner. The possible involvement in cytotrophoblast proliferation and/or differentiation is also discussed.

Antigens, CD↗
PubMed1998

Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study.

BACKGROUND: Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis. OBSERVATIONS: After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group. CONCLUSIONS: There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.

Administration, Cutaneous↗
PubMed1998

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↗
PubMed1998

Juvenile pemphigus foliaceus.

A 7-year-old girl with generalized erythematous, scaling plaques and vesiculobullous lesions on the extremities was diagnosed as having pemphigus foliaceus. Lesional direct immunofluorescence revealed intercellular IgG, IgA and C3 deposition. The patient's serum gave positive reactions against one epitope of desmoglein 3 and the epitope of desmoglein 1 in enzyme-linked immunosorbent assays, but the blood sample for indirect immunofluorescence did not display any circulating antibodies. The patient was successfully treated systemically with prednisolone and dapsone. Currently, she is taking dapsone, 12.5 mg daily. She has been free of lesions for the last 3 years.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

A short-term trial of tacrolimus ointment for atopic dermatitis. European Tacrolimus Multicenter Atopic Dermatitis Study Group.

BACKGROUND: Tacrolimus (FK 506) is an effective immunosuppressant drug for the prevention of rejection after organ transplantation, and preliminary studies suggest that topical application of tacrolimus is effective in the treatment of atopic dermatitis. METHODS: We conducted a randomized, doubleblind, multicenter study that compared 0.03 percent, 0.1 percent, and 0.3 percent tacrolimus ointment with vehicle alone in patients with moderate to severe atopic dermatitis. The ointment was applied twice daily to a defined, symptomatic area of 200 to 1000 cm2 of skin for three weeks. The primary end point was the change in the summary score for erythema, edema, and pruritus between the first and last days of treatment. RESULTS: After three weeks of treatment, the median percentage decrease in the summary score for dermatitis on the trunk and extremities was 66.7 percent for the 54 patients receiving 0.03 percent tacrolimus, 83.3 percent for the 54 patients receiving 0.1 percent tacrolimus, 75.0 percent for the 51 patients receiving 0.3 percent tacrolimus, and 22.5 percent for the 54 patients receiving vehicle alone (P<0.001). The results for the face and neck were similar. The differences among the three tacrolimus groups were not statistically significant. A sensation of burning at the site of application was the only adverse event that was significantly more frequent with tacrolimus than with vehicle alone (P<0.001). Throughout the study, most patients in all three tacrolimus groups had blood concentrations of tacrolimus below 0.25 ng per milliliter. The highest concentration was 4.9 ng per milliliter, which was reported in the group receiving 0.3 percent tacrolimus. CONCLUSIONS: The short-term application of tacrolimus ointment is effective in the treatment of atopic dermatitis, with the sensation of burning being the main side effect.

Administration, Cutaneous↗
PubMed1997

[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↗
PubMed1997

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↗
PubMed1997

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↗