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Biomedical subjects

G Burg

Publications and source records attributed to G Burg.

At least 73 records · Page 4Linked to original sources
PubMed2001

Lymphomatoid papulosis and human herpesviruses--A PCR-based evaluation for the presence of human herpesvirus 6, 7 and 8 related herpesviruses.

BACKGROUND: Lymphomatoid papulosis (LyP) is a chronic, recurrent lymphoproliferative disorder of the skin that belongs to the group of primary cutaneous CD30-positive T-cell lymphomas. Ultrastructural and clinical features of LyP suggest that it has a viral etiology. Human herpesviruses have been proposed as causative cofactors for LyP because of their oncogenic potential and their association with other lymphomas. METHODS: LyP skin lesions and a LyP-derived cell line were examined for the presence of the recently discovered oncogenic human herpesvirus 8 (HHV-8) and the two T-lymphotropic human herpesviruses 6 and 7 (HHV-6 and HHV-7) by nested polymerase chain reaction (PCR) using virus-specific oligonucleotide primers. Furthermore, a recently described method involving degenerate PCR primers was applied to detect highly conserved DNA sequences shared by a variety of herpesviruses, especially oncogenic gamma-herpesviruses, in an attempt to identify a yet undiscovered herpesvirus associated with LyP. RESULTS: HHV-6 and 8 could not be found in 26 archival and 11 snap-frozen LyP lesions and a LyP tumor cell line. HHV-7 DNA sequences were detected in 14% (5 of 37) of LyP samples. HHV-6 was found in 23% (3 of 13) and HHV-7 in 8% (1 of 13) of normal skin samples from healthy individuals, respectively. Using degenerate PCR primers to amplify the highly conserved polymerase region of herpesviruses, no DNA sequences related to human herpesviruses could be detected. CONCLUSIONS: LyP is not associated with HHV-6, HHV-7 and HHV-8. In addition, the studies using degenerate PCR primers do not indicate the presence of a previously undescribed human herpesvirus in LyP.

DNA, Viral↗
PubMed2001

Constitutive and interleukin-7- and interleukin-15-stimulated DNA binding of STAT and novel factors in cutaneous T cell lymphoma cells.

On testing cutaneous T cell lymphoma cell lines and skin lesions, we found that the transcription factors STAT2, STAT3, STAT5, and STAT6 (STAT, signal transducer and activator of transcription) were present in the nuclei of these cells and that the binding to their specific DNA binding sites was stimulated by interleukin-7 and interleukin-15. DNA binding studies also revealed the presence of three additional DNA factors in cutaneous T cell lymphoma cells that bound to the same sequences and could also be stimulated by interleukin-7 and interleukin-15. One of these novel factors was also present in the adult T cell leukemia cell line Jurkat and malignant T cells from the blood of Sézary syndrome patients, but not in normal peripheral blood lymphocytes. It may therefore be a marker of T cell leukemia. It seems to interfere with the binding of STAT1 to the sis inducible element, suggesting that the DNA binding activity of STAT1 in cutaneous T cell lymphoma cells is disturbed.

Adult↗
PubMed2001

Cd1d is expressed on dermal dendritic cells and monocyte-derived dendritic cells.

CD1 proteins are a family of cell surface molecules that present lipid antigens to T cells. We investigated skin dendritic cells and monocyte-derived dendritic cells for expression of CD1 molecules using a panel of 10 different monoclonal antibodies focusing on the recently described CD1d molecule. By immunohistochemical analysis, CD1d expression in normal human skin was restricted to dendritic appearing cells in the papillary dermis mainly located in a perivascular localization. Langerhans cells did not show detectable CD1d expression in situ. Epidermal/dermal cell suspensions analyzed by flow cytometry demonstrated distinct subpopulations of HLA-DR positive dermal dendritic cells expressing CD1a, CD1b, and CD1c. CD1d was expressed on HLA-DRbright dermal antigen-presenting cells in dermal suspensions (16% +/- 3.6%), as well as on highly enriched dermal dendritic cells migrating out of skin explants (60.5% +/- 8.0%). Migrated mature dermal dendritic cells coexpressed CD83 and CD1d. Western blot analysis on microdissected skin sections revealed the presence of a 50-55 kDa CD1d molecule in dermis, suggesting that CD1d is highly glycosylated in skin. Both immature and mature monocyte-derived dendritic cells cultured in autologous plasma expressed CD1d molecules. In contrast, culture in fetal bovine serum downregulated CD1d expression. In conclusion, antigen-presenting cells in skin express different sets of CD1 molecules including CD1d and might play a role in lipid antigen presentation in various skin diseases. Differential expression of CD1 molecules depending on culture conditions might have an impact on clinical applications of dendritic cells for immunotherapy.

Animals↗
PubMed2001

Decreased intraindividual HLA class I expression is due to reduced transcription in advanced melanoma and does not correlate with HLA-G expression.

The presentation of endogenously synthesized peptides in association with HLA class I molecules allows the activation of CD8(+) lymphocytes. Tumor cells often fail to present antigenic peptides resulting in the immune escape of metastasizing cells. The aim of this study was to elucidate possible molecular mechanisms leading to reduced antigen presentation in melanoma. Melanoma cell short-time cultures were genotypically and phenotypically HLA-typed by sequence-specific primer polymerase chain reaction and complement-mediated microlymphocytotoxicity assays, respectively. Flow cytometric analysis of HLA-A2 and HLA-A3 allospecificities were performed to confirm typing results. Transcriptional levels of classical HLA-A, HLA-B genes and nonclassical HLA-G genes were detected using quantitative real-time reverse transcriptase polymerase chain reaction (LightCycler). We found loss or downregulation of HLA proteins in 18% (for HLA-A) and 53% (for HLA-B) of all tested metastases. Genomic analysis, however, revealed the presence of the corresponding HLA class I gene in six out of seven cases. On the level of gene transcription we observed a differential regulation of HLA-A, HLA-B, and HLA-G mRNA expression. There was no correlation between classical and nonclassical HLA gene transcription, but the transcriptional levels of classical HLA corresponded to the protein expression levels. Furthermore, an overall reduced amount of HLA class I gene transcription was observed in melanoma metastases during disease progression in three individuals. We postulate that there is a transcriptional regulation of HLA class I gene expression in melanoma cells. These data suggest that treatment approaches aimed at activating specific cytotoxic T lymphocytes are most successful in early disease.

Flow Cytometry↗
PubMed2001

The interferon inhibiting cytokine IK is overexpressed in cutaneous T cell lymphoma derived tumor cells that fail to upregulate major histocompatibility complex class II upon interferon-gamma stimulation.

Cutaneous T cell lymphomas are characterized by an accumulation of malignant clonal lymphocytes in the skin and occasionally in the blood. We compared gene transcription profiles from cultured clonal lymphocytes with autologous healthy blood lymphocytes by microarray hybridization. Cutaneous T cell lymphoma derived cells transcribed high amounts of an interferon inhibiting cytokine factor. The presence of an interferon inhibiting cytokine factor was confirmed in 12 skin biopsies of mycosis fungoides and Sézary syndrome derived blood lymphocytes by reverse transcriptase-polymerase chain reaction. The presence of interferon inhibiting cytokine factor mRNA in Sézary syndrome derived lymphocytes was associated with a lack of HLA class II upregulation after stimulation with interferon-alpha and interferon-gamma. This was not due to a loss of the interferon signaling cascade as the presence of interferon-signaling components was confirmed by reverse transcriptase--polymerase chain reaction on the transcriptional level. The elevated constitutive interferon inhibiting cytokine factor expression observed in cutaneous T cell lymphoma derived cells was insensitive to interferon-gamma stimulation, but was enhanced in normal peripheral blood mononuclear cells. We suggest that interferon inhibiting cytokine factor contributes to the lack of HLA class II upregulation in lymphoma cells. Interferon inhibiting cytokine factor may participate in providing a microenvironment at the tumor site insensitive to interferon-gamma stimulation and thus prevents an efficient local immune response.

Adult↗
PubMed2001

Syringocystadenoma papilliferum: a study of potential tumor suppressor genes.

Syringocystadenoma papilliferum (SP) is a benign tumor most commonly located on the scalp or face, which frequently arises from a nevus sebaceus (NS). Transition of SP to basal cell carcinoma (BCC) and, albeit rarely, to metastatic adenocarcinoma may occur. Allelic deletions of the human homologue of the drosophila patched gene (PTCH) occur in both NS and BCC. To search for genetic changes in SP, a microdissection-based genetic analysis using polymorphic markers at 9q22 (PTCH; D9S15, D9S303, D9S287, D9S252) as well as markers at 9p21 flanking the tumor suppressor gene p16 (IFNA, D9S171) was performed. Glandular epithelium consisting of two rows of cells as well as adjacent normal tissue or inflammatory infiltrates in the stroma, when present, was dissected and subjected to single-step DNA extraction and loss of heterozygosity (LOH) analysis. Two of 10 informative SP cases showed LOH at 9q22 (PTCH). Three of 7 informative SP cases showed allelic deletions at 9p21 (p16). Allelic loss at 9q22 is consistent with the clinical observation of transition of SP to BCC. The finding of frequent allelic loss at 9p21 is unlikely to be related to the rare transition of SP to metastatic adenocarcinoma. Our study supports the hypothesis of a gatekeeper role of the tumor suppressor gene p16 in a variety of benign and malignant tumors, including SP.

Adenocarcinoma, Papillary↗
PubMed2001

Impact of interferons on the expression of melanoma-associated antigens in melanoma short-term cell cultures.

Some immunotherapeutic approaches based on melanoma-associated antigens rely on in vitro cultivation of melanoma cells. A beneficial effect of interferons has been shown in melanoma. This study aimed to determine whether stimulation of patient-derived melanoma short-term cell cultures using interferon-alpha and -gamma changes the expression pattern of melanoma-associated antigens. Lymph node, skin and brain metastases were cultivated for up to 3 weeks and treated with interferon-alpha, interferon-gamma or mock stimulation. Expression of the melanoma-associated antigens MAGE-3, MelanA/MART-1 and tyrosinase was determined by flow cytometry and compared with the expression pattern of HLA class I molecules. We found consistently enhanced expression of HLA class I molecules, whereas the melanoma-associated antigens showed mixed responses, with moderate induction, suppression or no visible effect. The reaction to interferon stimulation was similar for all the antigens examined within a single melanoma cell culture. In contrast to the HLA class I molecules, which showed induced expression with interferon, the melanoma-associated antigens showed a varied response to interferon stimulation. Differential reaction to interferon stimulation is of importance to immunotherapeutic modalities and might influence progression of the disease. We therefore suggest that evaluation of variation in melanoma-associated antigen expression in the clinical setting may help to identify patients who would profit from adjuvant interferon therapy.

Animals↗
PubMed2001

Heterogeneity of allelic deletions within melanoma metastases.

During the initiation and progression of malignant melanoma, a series of different genetic events accumulate on several different chromosomes. The biological heterogeneity of tumour cells presents a major problem, preventing effective treatment of melanoma. To examine the degree of genetic heterogeneity, we searched for allelic losses (loss of heterozygosity; LOH) on chromosomes 9p, 9q, 1p and 17p, examining different areas within human melanoma metastases. All of the examined metastases were informative within at least one dissected area for at least one marker. Out of 29 areas in 11 melanoma metastases, 58% showed LOH with at least one marker. On chromosome 9p21-22, eight out of 26 informative loci (31%) showed LOH at D9S171 (three not informative), two out of 18 (11%) at IFNA (11 not informative) and seven out of 24 (29%) at D9S169 (five not informative). LOH on chromosome 9q22.3 was examined by the microsatellite marker D9S12; three out of 24 areas (12.5%) showed LOH, and five were not informative. Deletions on chromosome 1p were assessed using D1S450. Four out of 25 (16%) showed LOH; four were not informative. Deletions on chromosome 17p13 were examined with TP53; two out of 21 cases (9%) showed LOH, and eight were not informative. Our data demonstrate an impressive heterogeneity of allelic losses in the investigated chromosomal areas within the same metastatic lesion. This suggests that there is not one specific genetic alteration that accounts for melanoma progression to metastases. Rather there seem to be multiple genetic alterations accumulating even on the same chromosome, and progression from melanoma to metastases is paralleled by the accumulation of clones harbouring multiple genetic abnormalities.

Adult↗
PubMed2001

Expression of TCL1 in hematologic disorders.

OBJECTIVE: TCL1, MTCP1 and TCL1b are three members of a new family of oncogenes that are expressed in T cell leukemias of ataxia telangiectasia patients (T-PLL, T-CLL). TCL1 is located at 14q32.1 and activated by juxtaposition to the alpha/delta-locus at 14q11 or beta-locus at 7q35 of the T cell receptor during the reciprocal translocations t(14;14)(q11;q32), t(7;14)(q35;q32), or inversion inv(14)(q11;q32). TCL1 encodes a predominantly cytoplasmic protein of 114 aa (14 kD) of unknown function. Recent studies suggest that TCL1 promotes cell survival rather than stimulating cell proliferation, as previously proposed. METHODS: In an attempt to clarify the contexts in which TCL1 is expressed, we investigated TCL1 expression in 114 lymphoma and leukemia patients by Northern blot, RT-PCR and immunohistochemistry. RESULTS: TCL1 expression is restricted to lymphoid cells, and is found in neoplastic (T and B cell neoplasms, and Hodgkin's disease) and nonneoplastic proliferations (reactive lesions). Out of 114 cases, 18 neoplasms of myeloid and 4 cases of epithelial origin were TCL1-negative. In lesions of the lymphoid system, both low- and high-grade lymphomas were found to express TCL1. CONCLUSIONS: We propose that TCL1 expression especially in high-grade B cell non-Hodgkin's lymphomas might interfere with B cell differentiation and promote the transition from low- to high-grade lymphoma.

Blotting, Northern↗
PubMed2001

Bilateral carpal tunnel syndrome as a clue for the diagnosis of systemic amyloidosis.

A 60-year-old Swiss woman presented with a 1-year history of periorbital hemorrhagic papules, a tendency to develop hematoma due to minor trauma and shortness of breath. The personal medical history included surgery for bilateral carpal tunnel syndrome (CTS) 2 years ago. Clinical and laboratory findings included macroglossia, Bence-Jones proteinuria, reticular lung infiltrates, thickening of the ventricular walls in echocardiography and increase in atypical plasma cells in the bone marrow. The coexistence of the specific symptoms of CTS, macroglossia and cutaneous lesions should immediately alert the physician to the probable existence of plasma-cell-dyscrasia-related systemic amyloidosis.

Amyloidosis↗
PubMed2001

Skin cancers in organ transplant recipients: two cases of virus-induced neoplasms.

Immunosuppression profoundly influences the prevalence of skin disorders in transplant recipients. Skin tumors occur with high incidence and constitute a major part of transplantation-related morbidity and mortality. We report on 2 immunosuppressed patients presenting with rapidly growing epithelial and mesenchymal neoplasms after renal transplantation. The diagnostic approach, differential diagnosis and treatment options are discussed emphasizing the characteristics of cutaneous lesions in immunosuppressed transplant recipients.

Adult↗
PubMed2001

Swiss guidelines for the treatment and follow-up of cutaneous melanoma.

Melanoma is the most common lethal cutaneous neoplasm. There is major controversy over the best management of this malignancy. In order to harmonize treatment and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland have been inaugurated. They have been approved by all Swiss medical societies involved in the care of melanoma patients.

Continuity of Patient Care↗
PubMed2001

[Allergic contact dermatitis to cosmetics containing Melaleuca alternifolia (tea tree oil)].

INTRODUCTION: Melaleuca alternifolia is a coniferous tree found in tropical regions, the needles contain an essential oil that is used in medical and cosmetic products. The essential oil contains turpentines (limonene, alpha-pinene, phellandrene) that are potentially allergenic. PATIENTS AND METHODS: In 1997, 1216 patients were patch tested in our dermatoligic unit. Fourteen of them tested because of eczema used products containing tea tree oil. The patients used creams, hair products and essential oils containing Melaleuca alternifolia for cosmetic reasons and to treat skin affections. They were patch tested for a standard panel of allergens, topical emulgators, perfumes, plants, topical medications, metal, gloves, topical disinfectants and preservatives, dental products and rubber derivatives. Products containing Melaleuca alternifolia were tested concentrated or diluted. RESULTS: We report on 7 cases of patients with an allergic contact dermatitis due to tea tree oil. Two of them also exhibited from a delayed type IV hypersensitivity towards fragrance-mix or colophony suggesting the possibility of cross reaction or an allergic group reaction caused by contamination of the colophony with the volatile fraction of turpentines. DISCUSSION: The allergic potential of low concentrations of Melaleuca alternifolia is presumed to be low on healthy skin. Photoaged Melaleuca alternifolia must be considered to be a stronger sensitizer.

Adult↗