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Biomedical subjects

R Dummer

Publications and source records attributed to R Dummer.

At least 145 records · Page 8Linked to original sources
PubMed1997

[Kaposi sarcoma in cyclosporin A therapy of actinic reticuloid].

A 76 year old patient with actinic reticuloid was treated with Cyclosporin A. 11 months after beginning the immunosuppressive therapy, he developed lymphoedema and livid nodular skin lesions of the right leg, which histologically showed Kaposi's sarcoma. After stopping the Cyclosporin A and intralesional therapy with Interferon alpha, no regression of the Kaposi sarcoma could be seen. The characteristics of Kaposi sarcoma arising during immunosuppressive therapy and the differences in incidence, risk groups and distribution pattern compared to the classic sporadic and the AIDS-related Kaposi sarcoma will be described. The development of Kaposi sarcoma during immunosuppressive therapy for actinic reticuloid has not been previously described.

Aged↗
PubMed1997

[Elastosis perforans serpiginosa in Down syndrome].

Elastosis perforans serpiginosa can arise as a rare complication in patients with Down syndrome. It is one of the primary perforating disorders characterized by transepithelial elimination of abnormal elastic fibers. This may reflect an immunological reaction aquist elastic fibers. We describe a 40-year-old woman with Down's syndrome whose skin lesions were histologically mistaken for lupus vulgaris for a long time.

Adult↗
PubMed1997

Adjuvant immunotherapy in malignant melanoma: impact of antibody formation against interferon-alpha on immunoparameters in vivo.

In an adjuvant clinical trial for high-risk patients with malignant melanoma by using recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha 2b (rIFN-alpha 2b), we monitored the development of antibodies against rIFN-alpha and various immunoparameters as biologic markers for IFN activity in vivo. Thirty-one patients (22 men, nine women) with high-risk malignant melanoma received eight 6-week cycles of rIL-2 and rIFN-alpha. Serum samples of all patients were screened for the presence of antibodies against IFN-alpha by a solid enzyme immunoassay (EIA). Specimens testing positive in the EIA were assessed for their ability to neutralize the antiviral effects of IFN-alpha in vitro in an antibody-neutralizing bioassay (ANB). Furthermore, serum levels of neopterin, beta 2-microglobulin, soluble IL-2 receptor (sIL-2R), anticardiolipin and antithyroglobulin were evaluated. Of 31 patients, 11 (36%) developed binding antibodies; three (27%) of them had antibodies with neutralizing capacities (range, 350-28,000 INU/ml). Of male patients, 8 (36%) of 22 versus 1 (11%) of nine female patients developed antibodies. Statistical analysis (unpaired t test) revealed that all patients with antibody titers showed significant (p < 0.04) lower serum levels of beta 2-microglobulin and reproducible decreases in sIL-2R levels, whereby those with neutralizing antibodies showed significantly (p < 0.0001) lower values than did those with binding antibodies. Elevations of anticardiolipin (17 of 31) and antithyroglobulin (one of 31) were not correlated to the presence of IFN antibodies. Our results show the in vivo significance of antibodies against rIFN-alpha, especially of those with neutralizing capacities. Monitoring of antibody formation as well as immunoparameters like beta 2-microglobulin in clinical trials can contribute to identifying patients who, if necessary, might benefit from alternative IFN treatment, for instance, by using natural IFNs.

Adjuvants, Immunologic↗
PubMed1997

D1 dopamine receptors are not expressed in human melanoma.

D1 dopamine receptor mRNA has been demonstrated in mouse melanoma cells, and the expression of these G-protein-coupled receptors in human melanoma was therefore presumed when dopamine receptor binding radiopharmaceuticals were found to be useful for the detection of metastases in whole-body scintigraphy. The aim of this study was thus to investigate if D1 dopamine receptor mRNA or protein could be directly demonstrated in melanoma cells. The presence of D1 dopamine receptor mRNA was investigated in six human melanoma cell lines from metastases using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, in vitro binding assays with the D1 dopamine receptor agonist 125I-Sch 23982 were performed in 19 melanoma metastases. No D1 dopamine receptor mRNA could be detected by RT-PCR. All melanotic metastases were found to accumulate 125I-Sch 23982, with the presence of binding sites and intensity of 125I-Sch 23982 labelling correlating to the amount of melanin present in the metastases. Two amelanotic melanomas did not accumulate 125I-Sch 23982. D1 dopamine receptors could not be detected by means of RT-PCR or in vitro binding assays in human melanomas. Detection of antagonists is best explained by non-specific binding to melanin.

Animals↗
PubMed1997

Ca(2+)-binding proteins S100A6 and S100B in primary cutaneous melanoma.

PURPOSE: Commercially available polyclonal antibodies against a mixture of bovine brain S100 proteins have become an established marker for immunohistochemical characterization of malignant melanoma. However, the commercially available antibodies used are undefined and to date, 13 different human S100 proteins are known. The purpose of this study was to examine the expression of 4 newly available polyclonal antibodies against the human recombinant Ca(2+)-binding S100 proteins, S100A1, S100A2, S100A4 and S100A6, in cutaneous melanoma and to correlate these findings with the standard S100 staining as well as with the metastatic potential of the primary. METHODS: 39 formalin-fixed paraffin-embedded primary cutaneous melanomas were incubated with polyclonal antibodies against recombinant human S100 proteins using the APAAP method. The extent of staining was qualitatively assessed and a staining index was calculated. Findings were correlated to the metastatic potential and the overall survival in all patients. RESULTS: Staining with antibodies against human S100A6 as well as with antibodies against conventional bovine S100 proteins was positive in all specimens. No correlation was found between the extent of protein expression and patients' outcome for standard S100 staining as well as for S100A6. S100A1, S100A2 and S100A4 staining could not be used for statistical analysis due to their low expression in melanoma. CONCLUSION: Staining was positive using S100A6 antibodies in all specimens, the quality being inferior to the commercially available S100 antibody. Highly specific and well characterized antibodies against the individual S100 proteins are now available for future immunohistochemical characterization studies in melanomas.

Adult↗
PubMed1997

A realistic approach to the sensitivity of PCR-DGGE and its application as a sensitive tool for the detection of clonality in cutaneous T-cell proliferations.

The practical value of the detection of clonality within the T-cell receptor gamma locus by polymerase chain reaction for the diagnosis of cutaneous T-cell lymphomas is well known. However, studies dealing with this subject so far, with special emphasis on the sensitivity of the technique in comparison to, for example, Southern blotting have used mixtures of DNA in various concentrations instead of using mixtures of the cells involved, which would reflect the in vivo situation in a more realistic scope. The purpose of this study was therefore to determine the sensitivity and the limitations of the PCR assay by dilution experiments, using mixtures of cells. Furthermore we studied its applicability to cutaneous T-cell proliferative disorders. Two clonal T-cell lines (MyLa and Jurkat) served as positive control. Dilutions of MyLa cells, cultured normal human keratinocytes and peripheral blood mononuclear cells from lymphoma negative volunteers were used to assess the sensitivity of the PCR-DGGE assay. Skin samples from 4 patients with cutaneous T-cell lymphoma, 1 lesional lymph node, 2 blood samples from a patient with Sézary syndrome and 4 lymphoma-negative tissue samples were analysed. Two samples were uncertain for diagnosis of lymphoma. The PCR-DGGE assay consisted of a 2-round nested PCR with consensus primers within the TCR-gamma locus followed by electrophoretic separation of the product along a denaturing urea/formamide gradient gel. PCR-DGGE sensitivity was, to our knowledge, for the first time investigated for mixtures of lymphocytes (clonal and polyclonal) and keratinocytes. Clonal T-cells were detected in a concentration between 1-0.1% in keratinocytes, whereas the sensitivity was generally lower upon dilution in peripheral blood mononuclear cells or in a mixture of keratinocytes and peripheral blood mononuclear cells. Nevertheless, T-cell clonality was detected in 2 blood samples of a patient with Sézary syndrome, which were negative by Southern blot analysis. The crucial point of this work was the new approach to establish the sensitivity of the PCR-DGGE, in a way which more closely mimics the condition of clinical specimens. Instead of mixing and amplifying DNA extracted from clonal T-cell lines and polyclonal bone marrow cells, we amplified DNA from clonal and polyclonal cells which had been mixed in various ratios before DNA extraction. Polymerase chain reaction in conjunction with denaturing gradient gel electrophoresis is a sensitive and versatile molecular tool for the assessment of clonality of suspect cutaneous lesions. The determination of sensitivity using DNA extracted from premixed cells more closely corresponds to the actual test situation when testing skin samples.

Blotting, Southern↗
PubMed1997

Unilateral agminated angiofibromas: a segmental expression of tuberous sclerosis?

We present a case of acquired unilateral agminated angiofibromas in a 26-year-old patient with onset at the age of 18. He developed over 100 pigmented dome-shaped papules on the left side of his nose, cheek and chin. Histological examination showed acanthosis and dermal capillary proliferations, fibrosis and lymphohistiocytic infiltrates. Staining with CD-31 showed increased vascular formation in the dermis. Staining for S-100 protein, HMB-45, NKIC-3 and Masson-Fontana staining showed no nevocytes or melanocytes in the dermal tissue, suggesting that the lesions are a segmental expression of tuberous sclerosis. However, multiple agminated angiofibroma without a relationship to tuberous sclerosis or a nevocytic or melanocytic formation cannot be ruled out for certain.

Adult↗
PubMed1997

Serum S100--a marker for disease monitoring in metastatic melanoma.

BACKGROUND: S100 proteins are low-molecular-weight calcium-binding proteins and appear to play an important role in various cellular processes such as cell division and differentiation. In histopathology, S100 is widely accepted as the marker of choice for immunohistochemical identification of malignant melanoma. When S100 was detected in the serum of patients with malignant melanoma, it was suggested that serum S100 may be a useful marker for the stage of disease. OBJECTIVE: The aim of this study was to examine serum S100 concentrations of patients with different stages of malignant melanoma and to determine the value of serum S100 in the follow-up of melanoma patients during treatment. METHODS: Sera were obtained from 73 melanoma patients in different stages of the disease. The control group consisted of 130 healthy subjects. In 4 patients with metastatic melanoma, serum S100 was measured serially. Serum levels were measured by a commercially available immunoradiometric assay. RESULTS: While only 1 out of 25 stage I/II patients and 3 of 14 patients with lymph node metastases (stage III, 21.4%) showed detectable serum S100 levels, 27 of 34 patients with disseminated disease (stage IV, 79.4%) had elevated serum S100. Interestingly, rising levels of serum S100 in the serial measurement indicated progression of the disease, and a complete decline reflected 2 patient remissions. CONCLUSION: The data support the value of serum S100 as a clinical marker for progression of metastatic melanoma and serological monitoring during systemic therapies.

Adult↗
PubMed1997

Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

PURPOSE: The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS: One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION: The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

Antineoplastic Agents↗
PubMed1997

No evidence of HTLV-I proviral integration in lymphoproliferative disorders associated with cutaneous T-cell lymphoma.

Several recent studies have reported detection of HTLV-I genetic sequences in patients with cutaneous T-cell lymphoma (CTCL) including mycosis fungoides and Sezary syndrome. The purpose of this study was to determine whether HTLV-I was detectable in lesional tissues of patients suffering from diseases known to be associated with CTCL. Thirty-five cases were obtained from diverse geographical locations including Ohio, California, Switzerland, and Japan. Six of them had concurrent CTCL. Cases were analyzed using a combination of genomic polymerase chain reaction (PCR)/ Southern blot, dot blot, and Southern blot analyses. All assays were specific for HTLV-I provirus. Sensitivity ranged from approximately 10(-6) for PCR-based studies to 10(-2) for unamplified genomic blotting. Lesional DNA from patients with lymphomatoid papulosis (fourteen cases), Hodgkin's disease (twelve cases), and CD30+ large-cell lymphoma (nine cases) was tested for the HTLV-I proviral pX region using a genomic PCR assay followed by confirmatory Southern blot analysis with a nested oligonucleotide pX probe. All cases were uniformly negative. All of the Hodgkin's disease cases, eight of the large-cell lymphoma cases, and six of the lymphomatoid papulosis cases were then subjected to dot blot analysis of genomic DNA using a full-length HTLV-I proviral DNA probe that spans all regions of the HTLV-I genome. Again, all cases were negative. Finally, eleven of the Hodgkin's disease cases were also subjected to Southern blot analysis of EcoRI-digested genomic DNA using the same full-length HTLV-I probe. Once again, all cases were negative. These findings indicated that, despite utilization of a variety of sensitive and specific molecular biological methods, HTLV-I genetic sequences were not detectable in patients with CTCL-associated lymphoproliferative disorders. These results strongly suggest that the HTLV-I retrovirus is not involved in the pathogenesis of these diseases.

Blotting, Southern↗
PubMed1997

Radioiodine-labelled alpha-methyl-tyrosine in malignant melanoma: cell culture studies and results in patients.

Tyrosine is a precursor of melanin synthesis and might thus present a valuable marker for melanoma. The aim of this study was to evaluate the uptake of alpha-methyl-tyrosine (AMT) in melanoma cell cultures and to assess its usefulness as a radiopharmaceutical for staging melanoma patients with whole-body scintigraphy. Melanoma (M19-cell lines) and fibroblast (negative control) cell cultures were incubated with 125I-AMT and the radioactive uptake in the cell lines was measured in a gamma-counter over 24 h. For in vivo studies, planar whole-body scintigraphy and single photon emission computed tomography (SPECT) of the tumour region was performed following injection of 250-350 MBq 123I-AMT in six patients with known melanoma metastases. Findings were compared with results of whole-body positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) as a standard of reference. Fibroblasts showed an unchanged uptake of (mean +/- SD) 0.56 +/- 0.09% 15 min and 0.066 +/- 0.09% 24 h, respectively, after incubation of 125I-AMT, whereas there was an increased uptake in melanoma cell cultures over time from 0.9 +/- 0.05% to 7.5 +/- 1.6%. In staging melanoma patients, the sensitivity of whole-body AMT-scintigraphy compared with FDG-PET was 37% (10 of 27 metastases). AMT is transported and metabolized to a high extent in melanoma cells and 123I-AMT is accumulated in melanoma metastases. Owing to its low sensitivity, however, the clinical use of whole-body AMT scintigraphy cannot be recommended.

Adult↗
PubMed1997

MAGE-3 immunoreactivity in formalin-fixed, paraffin-embedded primary and metastatic melanoma: frequency and distribution.

Monoclonal antibody 57B specifically detects MAGE-3 gene protein expression. MAGE-derived peptides are recognized by CD8+ T cells and applied in immunotherapy. We examined formalin-fixed, paraffin-embedded tissue of 61 melanoma (primary, n = 40; metastatic, n = 21) and 46 control cases (junctional, dermal, compound, Spitz, Reed, and balloon-cell nevi) by immunohistochemistry using the alkaline phosphatase anti-alkaline phosphatase method after antigen retrieval. Immunoreactivity was rated positive at 20 positive cells per tumor or more. Staining pattern was homogeneous, scattered, or focal. All control samples and internal controls were immunonegative. Staining with monoclonal antibody 57B showed a specificity of 100% with a sensitivity of 44%. Immunopositivity (overall, 44% of melanomas) increased along with tumor, node, and metastasis stage; pT1 showed 13%, pT2 22%, pT3a 29%, pT3b 45%, pT4 100%, pTxN1 60%, and pTxNxM1a 63% of samples positive. The staining pattern was homogeneous on pT1 to pT3a tumors, homogeneous or focal in pT3b and pT4a, and homogeneous, focal, or scattered in pTxN1 and pTxNxM1a. The frequency of immunopositivity relates well to data on mRNA expression using reverse transcriptase polymerase chain reaction in a subgroup analyzed by both methods. Monoclonal antibody 57B can be used to allow profiling of melanomas using routine archival tissue, when considering immunotherapeutic approaches involving MAGE-3-derived epitopes.

Animals↗
PubMed1997

Lack of expression of the recombination activating genes RAG-1 and RAG-2 in cutaneous T-cell lymphoma: pathogenic implications.

Analyses of the karyotype and genome of cutaneous T-cell lymphoma (CTCL) cells have shown that they contain chromosome breaks and translocations. The sequence analyses of such DNA breakpoints found in various kinds of leukaemias have suggested that some of the observed translocations have been caused by illegitimate V(D)J (v = Variability; D = diversity; J = joining) recombination. To study whether illegitimate V(D)J recombination is responsible for the continuously increasing number of DNA breaks in CTCL, we used reverse transcriptase polymerase chain reaction (RT-PCR) to analyse three CTCL cell lines and biopsies from 14 CTCL patients for the expression of the RAG-1 and RAG-2 genes which are essential for V(D)J recombination. We found no RAG gene expression in any of the 17 samples analysed, indicating that illegitimate V(D)J recombination may not be the reason for the increased number of chromosomal aberrations and translocations in CTCL cells.

Aged↗
PubMed1996

[Modern tumor therapy as seen in melanoma].

Modern therapy of melanoma should always consider the prognosis of the disease. Primary low-risk melanomas with tumor-thickness below 1 mm can be treated by surgery with a safety margin of 1 cm. If the tumor-thickness is more than 2 mm the safety margin should be at least 3 cm. After the resection of lymph node metastases adjuvant treatment using Interferon-alpha should be considered. Palliative therapy of metastases includes surgery, radiotherapy and chemoimmunotherapy. Recent progress in understanding the immunobiology of melanoma and the development of gene therapy has offered new perspectives for future therapeutical intervention.

Chemotherapy, Adjuvant↗