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S Goerdt

Publications and source records attributed to S Goerdt.

At least 19 recordsLinked to original sources
PubMed2007

[Hematogenous contact dermatitis after intravesicular instillation of mitomycin C].

Mitomycin C is an alkylating chemotherapeutic agent which is instilled intravesically to prevent recurrence of superficial bladder carcinomas. After several cycles of mitomycin C, our patient developed a pruritic genital dermatitis and palmar desquamation. Following exclusion of a fungal infection, we performed patch tests using the standard series, the major basic ointment ingredients, disinfectants, and mitomycin C in concentrations of 0.001 to 0.1%; the resulting diagnosis was allergic contact dermatitis due to delayed-type hypersensitivity to mitomycin C. The skin rash rapidly resolved with application of topical steroids, and the intravesical chemotherapy was changed to doxorubicin. Eczematous skin reactions are quite common side effects after intravesical instillation of mitomycin C. In the majority of cases, they are caused by delayed-type hypersensitivity reactions, presumably elicited by hematogenous spread of the allergen, and not by irritation. The sensitization most likely occurs via the bladder mucosa. In order to differentiate between allergic and toxic contact dermatitis, patch tests with the above-mentioned mitomycin C concentrations are useful. In cases of mild allergic contact dermatitis the intravesical chemotherapy might be continued with concomitant topical steroids.

Administration, Intravesical↗
PubMed2006

Highly phagocytic, CD4hi, CD14hi and CD16hi antigen-presenting cells modulated by tumour-conditioned media retain the capacity to mature and induce TH1 T-cell proliferation.

The tumour microenvironment down-modulates antigen-presentation by dendritic cells (DC), presumably due to inhibition of DC maturation. Here, we sought to examine (1) whether monocyte-derived cells cultivated with tumour-conditioned media under conditions that are conducive to DC generation (APCTCM) resemble immature DC (iDC), IL-10-induced regulatory DC (DCIL10) or display other distinctive features; (2) whether APCTCM are convertible to immunostimulatory DC (DCims) upon proper activation and (3) whether APCTCM and activated APCTCM are functionally defective. Four tumour cell lines expressing different cytokines were used to mimic different tumour microenvironments. As compared to iDC, DCims or DCIL10, APCTCM exhibited the highest levels of expression for CD14, CD16 and CD4. These markers and a high phagocytic capacity were unique features of these cells. When APCTCM were activated by a maturation cocktail, CD83, CD86, HLA-DR and CD25 were up-regulated to levels considerably higher than in DCIL10 and comparable to DCims while CD14, CD16, CD4 and dextran-uptake were down-modulated. Activated APCTCM induced 50-60% of the proliferative response of DCims in the allogeneic T-cell proliferation assay while DCIL10 mounted a 20-30% response (iDC elicited approximately 10%). Activated APCTCM induced secretion of almost equal amounts of IFN-gamma, TNF-alpha and IL-2 as DCims indicating induction of Th1 differentiation. When mature DCims were exposed to TCM, their immunostimulatory function was not significantly altered. However, when TCM were added to the co-cultures of DCims and CD4 T-cells the proliferative outcome was dependent on the TCM. In summary, APCTCM display special features but can mature into DCims-like cells.

Antigen-Presenting Cells↗
PubMed2006

Differential expression of a gene signature for scavenger/lectin receptors by endothelial cells and macrophages in human lymph node sinuses, the primary sites of regional metastasis.

Sentinel lymph node biopsy for several cancers has shown that metastatic tumour cells are preferentially arrested in the lymph node sinuses. To study the molecular components of this sinusoidal trap, gene profiling of lymph node (sinuses) versus tonsil (no sinuses) was performed. Among other groups of molecules, an intriguing gene signature of scavenger and lectin-like receptors was identified. Nine of the 13 genes were preferentially expressed in sinusoidal cells by immunohistochemistry. Using stabilin-2 and monoclonal antibody 3A5 as exclusive endothelial cell (EC) and macrophage (Mvarphi) markers, respectively, lymph node sinusoidal ECs (stabilin-2+, LYVE-1+, DC-SIGNR+, MARCO+, stabilin-1+, MMR+) and sinusoidal Mvarphi (MMR+, DC-SIGN+, sialoadhesin+, CD163+, stabilin-1+ ) showed distinct, but overlapping expression patterns of the signature molecules by double labelling immunofluorescence. The number of stabilin-1+ sinusoidal Mvarphi, however, varied considerably between samples, indicating turnover/differentiation dynamics in this sinusoidal cell population. In the hepatic sinuses, LYVE-1 and CD36 were strongly up-regulated on both sinusoidal ECs and Mvarphi, while DC-SIGNR and DC-SIGN were strongly down-regulated; in contrast to lymph node sinusoidal ECs, MARCO was confined to Mvarphi (Kupffer cells) in the liver sinuses. As Mvarphi are not present in the wall and lumen of splenic sinuses, splenic sinuses expressed a considerably reduced repertoire of scavenger/lectin receptors lacking sialoadhesin, CD36, CD163, and MARCO; in addition, DC-SIGNR was absent from splenic sinusoidal ECs, while DC-SIGN and thrombomodulin were strongly expressed. Interestingly, most of the signature molecules are known to mediate tumour cell adhesion in addition to their functions as scavenger or pattern recognition receptors. This study establishes a gene and tissue database platform to test the hypothesis that additive expression of the lymph node sinus signature genes in sinusoidal ECs and Mvarphi may contribute to selective tumour cell metastasis in lymph nodes and liver including organ-specific mechanisms, such as intraluminal retention or transmigration, while sparing the spleen.

Biomarkers↗
PubMed2006

Lymphatic endothelium-specific hyaluronan receptor LYVE-1 is expressed by stabilin-1+, F4/80+, CD11b+ macrophages in malignant tumours and wound healing tissue in vivo and in bone marrow cultures in vitro: implications for the assessment of lymphangiogenesis.

Lymphangiogenesis is a novel prognostic parameter for several cancers that is preferentially quantified by immunohistochemistry of the lymphatic endothelium-specific hyaluronan receptor LYVE-1. Recently, the specificity of LYVE-1 was challenged by serendipitous observations of LYVE-1 expression in rare tissue macrophages. As expression of the hyaluronan receptor-like molecule stabilin-1 is shared by sinusoidal endothelium and macrophages, a thorough analysis of LYVE-1 expression was performed using macrophage-specific markers in vivo and in vitro. In murine tumour models and excisional wound healing, LYVE-1 expression occurred in a subset of CD11b(+), F4/80(+) tissue macrophages that preferentially co-expressed stabilin-1. Upon comparison of single- and double-labelling immunofluorescence, it became apparent that LYVE-1(+) macrophages mimic sprouting and collapsed lymphatic vessels. In vitro, LYVE-1 expression was induced in 25-40% of murine bone marrow-derived macrophages upon exposure to B16F1 melanoma-conditioned medium and IL-4/dexamethasone. By FACS analysis, 11.5% of bone marrow-derived macrophages were LYVE-1(+), stabilin-1(+) double-positive, while 9.9% were LYVE-1(+), stabilin-1(-) and 33.5% were LYVE-1(-), stabilin-1(+). Northern and western analyses confirmed expression of LYVE-1 mRNA and protein in bone marrow-derived macrophages. In the light of the current debate about true endothelial trans-differentiation versus endothelial mimicry of monocytes/macrophages, LYVE-1(+), stabilin-1(+) non-continuous endothelial-like macrophages will require further developmental and functional analyses. In conclusion, the findings imply that LYVE-1 staining must be supplemented by double labelling with macrophage markers in order to differentiate clearly between LYVE-1(+) lymphatics and LYVE-1(+) tumour-infiltrating macrophages. This improved approach will help to clarify the prognostic significance of lymphangiogenesis in malignant tumours.

Animals↗
PubMed2006

[Allergic contact dermatitis from colophony and turpentine in resins of untreated pine wood].

Pine wood is one of the most used raw products in furniture manufacturing in Europe. High concentrations of colophony and turpentine can be extracted from pine resins. A 45-year-old woman developed a contact dermatitis of the face and hands due to a sensitization to colophony and turpentine after she had bought untreated pine chairs. The increased use of untreated pine in the furniture industry might result in an increase of colophony and turpentine-induced contact allergies. Therefore, the slogan "untreated=harmless" should be considered critically in such cases.

Administration, Topical↗
PubMed2006

Paucity of FOXP3+ cells in skin and peripheral blood distinguishes Sézary syndrome from other cutaneous T-cell lymphomas.

Cutaneous T-cell lymphomas (CTCL) are mainly comprised of two variants: mycosis fungoides (MF) with CD4(+) tumor cells confined to the skin and the leukemic Sézary syndrome with tumor cell spread to the blood. In this study, we investigated cutaneous expression of the regulatory T-cell (T(reg)) marker FOXP3 in 30 CTCL patients. Immunohistochemical analysis revealed significantly lower numbers of CD4(+)FOXP3(+) cells within the dermal lymphomononuclear infiltrate of Sézary patients (16% FOXP3(+) cells of CD4(+) cells) in contrast to MF (43% FOXP3(+) cells (P<0.05)) and rare types of CTCL (45% FOXP3(+) cells). Furthermore, CD4(+)FOXP3(+) T cells were also markedly reduced in the CD4(+) population within the peripheral blood of Sézary patients compared to controls as determined by fluorescence-activated cell sorter, quantitative PCR and functional analyses. The data support the conclusion that the neoplastic cells in CTCL do not express the T(reg) marker FOXP3. Our data also identify Sézary syndrome as, to our knowledge, the first reported neoplastic disease with a clear reduction in T(reg) numbers within the CD4(+) population. This lack of T(reg) might account for the more aggressive nature of Sézary syndrome compared with other CTCL.

Adolescent↗
PubMed2005

[Hypereosinophilic dermatitis. An overlooked diagnosis?].

BACKGROUND: The idiopathic hypereosinophilic syndrome is a rare systemic disease characterized by blood and tissue eosinophilia of unknown etiology, in which multiple organs may be affected. In hypereosinophilic dermatitis the only affected organ besides the blood is the skin. PATIENTS: We present a series of seven patients with hypereosinophilic dermatitis who were treated in our hospital between 2002 and 2003. RESULTS: All patients initially showed characteristic, therapy-resistant, polymorphic skin lesions, presenting with a combination of erythematous, pruritic and urticarial papules and plaques. All had blood eosinophilia without evidence of allergic, parasitic or other causes. The histology showed tissue eosinophilia only in half of the cases; the other histological findings were non-specific. We observed a good response to therapy with systemic corticosteroids, dapsone and light therapy, applied as UVA-1 irradiation or as shower photochemotherapy. CONCLUSIONS: The diagnosis "hypereosinophilic dermatitis" should be based primarily on the characteristic clinical picture together with "idiopathic" peripheral eosinophilia, whereas the histological findings are not always indicative. Because of the multiplicity of possible differential diagnoses and the often non-revealing histology, we assume that the diagnosis "hypereosinophilic dermatitis" is often overlooked.

Adult↗
PubMed2005

Interleukin-4 and dexamethasone counterregulate extracellular matrix remodelling and phagocytosis in type-2 macrophages.

Alternatively activated macrophages (Mphi2) are induced by Th2 cytokines and by glucocorticoids (GC), and can be distinguished from classically activated effector macrophages (Mphi1) on the basis of their anti-inflammatory properties. In addition, Mphi2 are involved in Th2/Th1 skewing, enhance antigen uptake and processing and support tissue remodelling and healing. In order to elucidate the heterogeneity of Mphi2 population systematically, we analysed a number of genes involved in extracellular matrix (ECM) remodelling, inflammation and phagocytosis in Mphi2 populations generated with interleukin-4 (IL-4) or GC. Using real-time polymerase chain reaction, we demonstrated that the ECM component, tenascin-C, is stimulated by IL-4, whereas it is suppressed by dexamethasone. The ECM remodelling enzymes--MMP-1 and MMP-12--and tissue transglutaminase (TG) showed a similar regulation pattern. FXIIIa, another putative Mphi2-associated TG, was synergistically regulated by IL-4 and GC. Enzyme-linked immunosorbent assay analysis revealed that the production of Mphi2-associated chemokines, AMAC-1, MCP-4 or TARC, was induced by IL-4 and was modulated by GC. Phagocytosis of opsonized and non-opsonized particles was stimulated by GC, whereas IL-4 had only a modulatory effect, what may be partially explained by the expression pattern of hMARCO, a scavenger receptor for non-opsonized particles, that was strongly and selectively induced by GC. In conclusion, stimulation of Mphi with IL-4 and GC regulate antagonistically the expression of ECM remodelling-related molecules and phagocytosis of opsonized and non-opsonized particles.

Base Sequence↗
PubMed2005

Prognostic factors and prediction of prognosis by the CTCL Severity Index in mycosis fungoides and Sézary syndrome.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a slowly progressive malignancy for which there is no cure. Therefore, accurate prediction of prognosis is important for the conduct of clinical trials and for counselling of individuals. OBJECTIVES: To improve prediction of survival in patients with CTCL. METHODS: Prognostic factors including tumour-node-metastasis (TNM) criteria and the CTCL Severity Index (CTCL-SI) were analysed using a Weibull model for multivariate analysis in a sample of 62 patients with classical CTCL (mycosis fungoides and Sézary syndrome). The Brier score was used to quantify the quality of individual prediction. RESULTS: Estimated 5-year survival rate (SR5) differed according to TNM stage: stage IA, 100% (95% confidence interval 70-100%); IB-III, 86% (73-100%); IVA, 54% (32-91%); IVB, 0% (0-52%). In a multivariate analysis, two independent prognostic factors were identified: lymph node (P = 0.036) and blood involvement (P = 0.015). A probability of survival model showed correlation of CTCL-SI with survival in patients with CTCL-SI > 20 according to the following formula: SR5 = 124-2 x (CTCL-SI)%. Calibration of SR5 against CTCL-SI-independent CTCL subsets revealed underestimation of Sézary syndrome. When CTCL-SI parameters were adjusted accordingly, the probability of survival model did not change significantly, while SR5 values became adequate. In addition, CTCL-SI was shown to be superior to TNM by 30% regarding individual predictive power. CONCLUSIONS: Probability of survival in CTCL can be accurately predicted by a CTCL-SI-based survival rate formula. Careful monitoring of lymph node and blood compartments and quantification by CTCL-SI are reliable tools for follow-up of patients with CTCL and allow progression-adjusted prediction of prognosis.

Adult↗
PubMed2005

Overexpression of c-myb in leukaemic and non-leukaemic variants of cutaneous T-cell lymphoma.

BACKGROUND: The c-myb oncogene is a transcription factor that regulates proliferation, differentiation and apoptosis of haematopoietic cells and activated T cells by binding to promoter sequences of such genes as c-myc or bcl-2 that are expressed in cutaneous T-cell lymphoma (CTCL). OBJECTIVE: Our study was performed in order to evaluate c-myb expression as a quantitative parameter for differential diagnosis in leukaemic and non-leukaemic variants of CTCL. METHODS: c-myb expression was analysed in lesional skin and in the peripheral blood of 21 patients with mycosis fungoides (MF), 15 patients with Sézary syndrome (SS) and 15 patients with inflammatory skin diseases using immunohistochemistry and semiquantitative as well as quantitative RT-PCR. RESULTS: Immunohistochemistry confirmed expression of c-myb in the lesional skin of the majority of CTCL patients with a tendency towards higher expression in SS (1.86 +/- 0.5) versus MF (1.2 +/- 0.7) while c-myb was absent from the lesional skin of patients with inflammatory skin diseases. c-myb was overexpressed in the peripheral blood in all SS patients (100% SS vs. 35.7% MF) at a high expression level (51,335.31 +/- 31,960.32 AU in SS vs. 1,226.35 +/- 1,258.29 AU in MF using semiquantitative RT-PCR, and 5.72 x 10(-2) +/- 2.27 x 10(-2) in SS vs. 0.91 x 10(-2) +/- 1.18 x 10(-2) in MF vs. 0.24 x 10(-2) +/- 0.11 x 10(-2) in inflammatory skin disease using quantitative RT-PCR). CD4+ cells from the peripheral blood of SS patients and cell lines in vitro showed the highest c-myb expression levels upon quantitative RT-PCR (23.27 x 10(-2) and 10.78 x 10(-2) +/- 7.24 x 10(-2)). CONCLUSION: Overexpression of c-myb in skin lesions of both non-leukaemic and leukaemic CTCL independent of the stage of the disease indicates that it acts early in disease development. Nevertheless, if positive, c-myb expression in lesional skin is a clear-cut diagnostic marker for CTCL as compared to inflammatory skin diseases. High-level expression of c-myb in the peripheral blood as assessed by quantitative RT-PCR constitutes an additional diagnostic parameter for SS and may be especially useful in cases in which morphological determination of Sézary cells or FACS analysis of CD7 and CD26 remain inconclusive.

Adult↗
PubMed2004

The receptor for interleukin-17E is induced by Th2 cytokines in antigen-presenting cells.

Interleukin-17E (IL-17E) (IL-25) is a recently identified cytokine capable to induce Th2-associated cytokine production (IL-5 and IL-13) and T helper 2 (Th2)-type pathologies in animal models. The IL-17E-responsive cell population in vivo was described to be a further uncharacterized non-T-, non-B-splenic accessory cell. Despite the identification of IL-17BR as the receptor for IL-17E, the cell population expressing IL-17BR has hitherto not been identified. Here, we show that human monocyte-derived Th2-skewed antigen-presenting cells (APC2) express membrane-bound and soluble forms of IL-17BR on the mRNA and protein level upon stimulation with IL-4, IL-10, IL-13 or transforming growth factor-betain vitro. These results indicate that IL-17BR-expressing APC2s may mediate the development of the IL-17E-mediated immunological reaction patterns observed in vivo.

Alternative Splicing↗
PubMed2003

Nevi flammei affecting two contralateral quadrants and nevus depigmentosus: a new type of phacomatosis pigmentovascularis?

Here, we report on a 64-year-old-woman with nevi flammei affecting two contralateral quadrants, venous insufficiency of the right leg, and asymmetry of the arms, in association with a linear nevus depigmentosus. This combination of vascular and pigmentary abnormalities may represent a novel type of phacomatosis pigmentovascularis caused by non-allelic twin-spotting.

Female↗
PubMed2003

Experience in treating molluscum contagiosum in children with imiquimod 5% cream.

There is a wide variety of topical or surgical treatment options for molluscum contagiosum (MC). However, treatment in young or anxious children is difficult, time-consuming and often painful. We studied the topical efficacy and tolerance of imiquimod, a topical immune-response modifier, which stimulates the production of interferon-alpha and other cytokines in children with MC. In an open-label, follow-up trial, imiquimod 5% cream was applied three times a week for 16 weeks to 15 children aged 4-11 years with multiple MC. Nine of 13 children (69%) who completed treatment responded. Two patients (15%) showed a complete remission, and seven (54%) had a partial response, with a remarkable reduction of the MC lesions. Four children (31%) showed stable or progressive disease. In three children (23%) with partial remission, the number of mollusca were considerably reduced, thus avoiding surgical treatment. In general, the treatment was well-tolerated, without systemic side-effects. Local side-effects included erythema (85%), itching (75%), burning sensations (23%) and pain (11%). Three children (23%) discontinued treatment because of local side-effects. The results of this study suggest that imiquimod 5% cream is a useful new treatment option for MC in children, especially in severe cases. The dosing schedule and length of treatment requires further evaluation.

Adjuvants, Immunologic↗