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S Goerdt

Publications and source records attributed to S Goerdt.

At least 37 records · Page 2Linked to original sources
PubMed2003

Serum of patients with Behçet's disease induces classical (pro-inflammatory) activation of human macrophages in vitro.

BACKGROUND: Although several immunological abnormalities have been demonstrated in Behçet's disease (BD), the exact mechanism of the inflammatory changes occurring is still unknown. Antigen-presenting cells, such as mononuclear phagocytes, play a major role in the regulation of immune-mediated as well as of non-specific inflammation. OBJECTIVE: To investigate the serum activity of patients with BD on antigen and chemokine expression of human macrophages in vitro. METHODS: Serum of 15 patients (8 women, 7 men; mean age 33 +/- 10 years) with BD was incubated with cultured macrophages isolated from peripheral blood of healthy volunteers. Macrophages maintained in patients' serum, fetal calf serum with/without dexamethasone and interleukin (IL)-4 or gamma-interferon were investigated for alternative macrophage-activation-associated CC-chemokine 1 (AMAC-1) and IL-8 mRNA expression by Northern blotting. In addition, cytocentrifuge macrophage preparations were stained with monoclonal antibodies against proteins indicating alternative (anti-inflammatory) macrophage activation, such as MS-1 high-molecular-weight protein (MS-1-HMWP), RM3/1 antigen (CD163) and 25F9, as well as classical (pro-inflammatory) macrophage activation, such as CD11c, class I receptor binding the Fc part of IgG (FcgammaRI: CD64) and class III receptor binding the Fc part of IgG (FcgammaRIII: CD16). RESULTS: Macrophages treated with patients' serum showed neither AMAC-1 expression nor staining with monoclonal antibodies for MS-1-HMWP, CD163 or 25F9. Concomitant treatment with IL-4/dexamethasone up-regulated significantly the expression of CD163. In contrast, IL-8 mRNA expression and staining for CD11c and CD64 were strongly positive after treatment with serum of patients with BD. CD64 positivity and IL-8 mRNA expression were more prominent in patients with active BD than in patients with inactive disease. CONCLUSION: Taken together, our results indicate that serum of patients with BD induces classical (pro-inflammatory) activation of human peripheral blood macrophages in vitro. Our findings suggest that serum factor(s) may be responsible for inflammatory changes in BD.

Adult↗
PubMed2003

Current status of cutaneous T-cell lymphoma: molecular diagnosis, pathogenesis, therapy and future directions.

Primary cutaneous T-cell lymphomas (CTCL) represent a heterogeneous group of neoplasms characterized by skin-homing malignant T-lymphocytes. In contrast to primary extracutaneous (nodal) lymphomas, CTCL is characterized by a prolonged clinical course with a different clinical behavior and outcome. Disease progression, however, involves the recirculation compartments, i.e. lymph nodes and peripheral blood, and may finally spread to the visceral organs. Advances in T-cell receptor gene rearrangement techniques support the clinical diagnosis in early stages of CTCL by improved sensitivity and specificity of molecular diagnosis. The pathogenesis of CTCL is characterized by an altered immune biology and the accumulation of genetic mutations during disease progression. Although there is an initial response to standard therapy, including photochemotherapy, interferons, and retinoids, all patients will eventually relapse, and therefore treatment of CTCL continues to be palliative. New therapeutic drugs including bexarotene, DAB(389)IL-2 and IL-12 have demonstrated clinical responses; and new experimental therapeutic directions, e.g. stem cell transplantation and vaccination strategies may be applied with the intention to cure.

Cell Transformation, Neoplastic↗
PubMed2003

Jessner's lymphocytic infiltration of the skin: a CD8+ polyclonal reactive skin condition.

BACKGROUND: Jessner's lymphocytic infiltration of the skin (JLIS) is a clinically and histologically distinct disease entity. Conflicting results have been reported concerning its differentiation from cutaneous lupus erythematosus and polymorphous light eruption, its relationship to palpable migratory arciform erythema and its classification as a B-cell or a CD4+ T-cell lymphoproliferative disease. OBJECTIVE: Our study was performed in order to re-evaluate JLIS clinically and by immunohistochemical and molecular analyses. METHODS: Stringent inclusion/exclusion criteria were used to collect a cohort of 34 patients with JLIS that did not overlap with lupus erythematosus or polymorphous light eruption. Clinical data were analysed, and immunohistochemical and molecular studies were performed including TCR-gamma PCR GeneScan software analysis of tissue and peripheral blood samples. RESULTS: In the majority of the patients, the lesions consisted only of papules and plaques while in 12% annular lesions were also seen. The lesions were found on the face (38%), on the trunk and arms (50%) or at both sites (12%). Immunohistochemical analyses revealed a clear predominance of T cells in all patients, and of CD8+ T cells in 77% of the patients. As judged by TCR-gamma PCR GeneScan analysis, 98 and 79% of the tissue and peripheral blood samples, respectively, showed a polyclonal T-cell population; identical T-cell clones were not detected concomitantly in both the skin and the peripheral blood of the same patient. CONCLUSIONS: JLIS occurs at 2 major predilection sites, that is the face and trunk. Therefore introduction of palpable migratory arciform erythema as a separate entity is not justified. The lymphoid infiltrates are dominated immunohistochemically by CD8+ T cells that do not show clonality on molecular analysis. Thus, JLIS represents a characteristic CD8+ polyclonal reactive skin condition.

Adult↗
PubMed2002

[Allergic reaction after contact with Hura crepitans (sandbox tree)].

We describe a 36-year-old female patient with angioedema-like swellings and rhinoconjunctivitis for 1 year occurring exclusively at her home. The clinical history revealed no correlation with foods, food additives, drugs, or aeroallergens. The complaints always started immediately after contact with the sandbox tree (Hura crepitans) placed in her apartment. Scratch testing resulted in a two-fold positive reaction towards leaves and stem, while five controls remained negative. Thus we suggest the reaction of the patient to be allergic in nature. Hura crepitans belongs to the family of Euphorbiaceae, whose largest genera are Euphorbia and Croton. The toxic reactions to the milky sap, the so-called latex, of these plants are caused by ingredients such as phorbol esters, croton oil, lectins, and terpens. Various terpens are also well known as allergens. Phytotoxic and phytoallergic reactions are growing increasingly important and should therefore be included in the differential diagnosis in dermatology.

Adult↗
PubMed2002

Cutaneous large B-cell lymphoma of the leg masquerading as a chronic venous ulcer.

We report on a 74-year-old female patient with a primary cutaneous CD20+, diffuse large cell B-cell lymphoma of the lower leg resembling a chronic non-healing leg ulcer. There was no evidence of systemic involvement on computed tomography (CT) scans of the chest, abdomen and pelvis; a slightly enlarged lymph node in the right groin showed dermatopathic lymphadenopathy on histology and immunohistochemistry. Involvement of the bone marrow and peripheral blood was ruled out by punch biopsy and fluorescent activated cell sorter (FACS) analysis of the blood, respectively. Therapeutic anti-CD20 monoclonal antibody rituximab was given at 375 mg m(-2) i.v. once weekly for 7 weeks, without adverse effects, resulting in a minor improvement in the centre of the ulcerated tumour. Unfortunately, the response was not maintained, and after 7 weeks of treatment the patient started to develop new tumour lesions at the border of the ulcer. Local radiotherapy was started and combined photon and electron beam irradiation induced complete remission of the B-cell lymphoma.

Aged↗
PubMed2002

Familial lymphocytic infiltration of the skin: histochemical and molecular analysis in three brothers.

BACKGROUND: Lymphocytic infiltration of the skin (Jessner and Kanof) is a T cell pseudolymphoma characterized by the occurrence of recurrent asymptomatic papules and plaques and by a coat-sleeve-like perivascular lymphoid infiltrate. Rarely, familial cases have been reported. OBJECTIVES: Our study was performed to address the question of a genetic predisposition in a case of familial lymphocytic infiltration by histochemical and molecular analysis. RESULTS: We report on 3 brothers with typical clinical and histological features of Jessner's lymphocytic infiltration of the skin. Immunohistochemical analysis revealed a mixed lymphocytic infiltrate with a predominance of CD8+ T cells in all 3 patients. Molecular determination of T cell clonality by PCR-based GeneScan analysis of the T cell receptor (TCR)-gamma-chain showed oligoclonal, pseudomonoclonal or polyclonal TCR-gamma rearrangement patterns in lesional skin and in peripheral blood of all 3 brothers, while no common TCR idiotype was detected. CONCLUSION: Inherited deviations in TCR usage seem unlikely as a special cause of familial Jessner's lymphocytic infiltration of the skin; lack of clonality furthermore supports the notion that this variant of the disease is as true a pseudo-T-cell lymphoma as are the spontaneous cases.

Adult↗
PubMed2001

[Alternative activation of antigen-presenting cells: concepts and clinical relevance].

Lymphocytes do not just act as immunological effector cells, but also play an important role in the regulation of the immune response. They are able to induce or suppress inflammatory reactions and this balancing function is reflected in the well-known Th1/Th2 concept. Lymphocytes depend on antigen presenting cells (APC) for induction of differentiation and specific activation mediated by antigen capture, processing and presentation. Thus, APC represent a link between innate and acquired immunity. In parallel to the Th1/Th2 dichotomy, APC may be subdivided into (a) pro-inflammatory, classically activated APC such as mature dendritic cells and IFN-gamma-activated effector macrophages, and (b) into anti-inflammatory, alternatively activated APC such as IL-10-activated immature dendritic cells and IL-4-induced suppressor macrophages. Alternatively activated APC may mediate induction and maintenance of tolerance towards allergens and environmental substances, control the course of inflammatory reactions, and participate in healing processes by enhancing angiogenesis. Malignant tumors and certain infectious agents may misuse alternatively activated APC for their purposes, thereby requiring counter-action by Th1 lymphocytes and classically activated APC. The concept of alternative activation thus confirms the important role of APC in maintaining the balance between induction and suppression of both inflammation and immunity and it opens new perspectives for the development of specific immunotherapeutic approaches.

Animals↗
PubMed2001

Nodular and bullous cutaneous mastocytosis of the xanthelasmoid type: case report.

Severe generalized nodular and bullous mastocytosis of the xanthelasmoid type is described in a 7-month-old boy. Reddish to yellowish-brown xanthelasmoid papules and nodules first developed in the inguinal region a few weeks after birth and then progressively spread to cover nearly the entire body surface. There was severe pruritus and recurrent episodes of blistering. The diagnosis of cutaneous mastocytosis of the xanthelasmoid type with subepidermal bullae was confirmed by skin biopsies showing solid and deeply penetrating infiltrates of metachromatic mast cells under light and electron microscopy. Systemic involvement of other organs, however, was excluded by bone scintigraphy, abdominal ultrasound, bone marrow aspiration and echocardiography. The extensive skin involvement was reflected in highly elevated urinary levels of histamine (263.4 microg L(-1)) and its metabolite N-methylimidazole acetic acid (20.8 mg L(-1)). The patient was systematically well and received only symptomatic treatment. Over a period of 1 year, the condition gradually improved, and the skin lesions began to flatten and regress.

Biopsy↗
PubMed2001

Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein betaIG-H3.

Alternative activation of macrophages, induced by Th2 cytokines and glucocorticoids, is essential for the proper functioning of anti-inflammatory immune reactions. To this end, alternatively activated macrophages (aaMPhi) express a not yet fully unravelled set of genes including cytokines such as alternative macrophage activation-associated CC-chemokine (AMAC)-1 and pattern recognition molecules such as the scavenger receptor CD163. In order to further characterize the molecular repertoire of aaMPhi, differential gene expression was analyzed by combining subtractive suppression cloning and differential hybridization. We show here that aaMPhi induced by interleukin (IL)-4 overexpress the prototype extracellular matrix (ECM) protein fibronectin on the mRNA and protein level. This overall increase is accompanied by a shift in fibronectin splice variants from an embryonic to a mature pattern. In addition, the expression of another ECM protein, betaIG-H3, is also upregulated by IL-4 in aaMPhi. In contrast to IL-4 and in line with its inhibitory effect on wound healing, dexamethasone exerts a strongly suppressive effect on fibronectin and betaIG-H3 expression. In conclusion, overexpression of ECM proteins induced by IL-4 in macrophages suggests that aaMPhi may be involved in ECM deposition and tissue remodelling during the healing phase of acute inflammatory reactions and in chronic inflammatory diseases.

Alternative Splicing↗
PubMed2001

Make PEEC, not war: does evasive transdifferentiation protect from carcinogenesis?

DNA repair and immune surveillance are established mechanisms that secure a programmed escape from the evolution of cancer (PEEC) by healing and elimination, respectively. Evasive transdifferentiation, i.e. silencing of carcinogenic events, is an emerging concept with potentially broad applicability that paradigmatically includes the claim that common acquired melanocytic nevi represent a programmed rescue from malignity for initiated melanocytes. This hypothesis is difficult to test. Research into the molecular mechanisms that govern the development of acquired melanocytic nevi, however, should result in the identification of a molecular master switch and an associated set of genes that - beyond the processes involved in apoptosis - may help bypass carcinogenesis and may be of therapeutic benefit in the future.

Adaptation, Physiological↗
PubMed2000

High detection rate of T-cell receptor beta chain rearrangements in T-cell lymphoproliferations by family specific polymerase chain reaction in combination with the GeneScan technique and DNA sequencing.

The distinction between benign polyclonal and malignant monoclonal lymphoid disorders by morphology or immunophenotyping is frequently difficult. Therefore, the demonstration of clonal B-cell or T-cell populations by detecting identically rearranged immunoglobulin (Ig) or T-cell receptor (TCR) genes is often used to solve this diagnostic problem. Whereas the detection of rearranged Ig genes is well established, TCR gamma (gamma) and beta (beta) gene rearrangements often escape detection with the currently available polymerase chain reaction (PCR) assays. To establish a sensitive, specific, and rapid method for the detection of rearranged TCR-beta genes, we developed a new PCR approach with family-specific Jbeta primers and analyzed the resulting PCR products by high-resolution GeneScan technique. The superior efficiency of this new method was demonstrated by investigating 132 DNA samples extracted from lymph node and skin biopsy specimens (mostly formalin fixed) and blood samples of 62 patients who had a variety of T-cell lymphomas and leukemias. In all but 1 of the tumor samples (98.4%) a clonal amplificate was detectable after TCR-beta PCR and the same clonal T-cell population was also found in 15 of 18 (83%) of the regional lymph nodes and in 7 of 11 (64%) of the peripheral blood samples. Direct comparison of these results with those obtained currently by the most widely applied TCR-gamma PCR revealed an approximate 20% lower detection rate in the same set of samples than with the TCR-beta PCR method. These results indicate that the new TCR-beta PCR is most suitable for a rapid and reliable detection of clonal T-cell populations. (Blood. 2000;96:640-646)

Clone Cells↗
PubMed2000

Pseudoexons and regulatory elements in the genomic sequence of the beta-chemokine, alternative macrophage activation-associated CC-chemokine (AMAC)-1.

Recently, the authors reported the cloning of a novel human CC chemokine of alternatively activated macrophages (AMAC-1), whose expression is induced by Th2-associated cytokines such as interleukin 4 (IL-4), IL-13 and IL-10; vice versa, AMAC-1 expression is inhibited by Th1-associated cytokines such as interferon gamma (IFN-gamma). In order to study the genomic organization and transcriptional regulation of the AMAC-1 gene, genomic clones were isolated by screening a human lambda genomic library. Sequencing of a clone with a 1.7-kb insert gave a partial genomic sequence for the AMAC-1 gene. The complete AMAC-1 genomic sequence was obtained by bioinformational methods and the whole region spanning the AMAC-1 gene was verified by PCR amplification of subfragments and sequencing. The AMAC-1 gene consists of three exons. Whereas exons 2 and 3 were separated by a small intron of 411 bp, exon 1 and exon 2 were separated by 6 kb of non-translated genomic sequence containing two pseudoexons that are not expressed although they feature intact exon/intron boundaries and complete open reading frames. In order to allow a detailed analysis, a 2.7-kb fragment containing the promoter region and the first exon of AMAC-1 gene was cloned into a reporter gene construct. In the AMAC-1 promoter, two possible transcription start points were identified. In addition, several putative regulatory sequences for IL-4- and IFN-gamma-dependent transcriptional pathways were found including STAT6 and STAT1 binding sites as well as several AP-1 and C/EBP elements. Interestingly, a combined STAT6/STAT1 binding element is located in the direct vicinity of the first putative transcription start point. Competitive binding of IL-4-induced STAT6 versus IFN-gamma-induced STAT1 to this site may explain the antagonistic effects these cytokines exert on AMAC-1 expression.

Amino Acid Sequence↗
PubMed2000

[Radiation-induced acne].

Radiation-induced acne is a rare, clinically and pathogenetically ill-defined acneiform dermatosis with special features that may occur in irradiated skin areas especially after high doses of deeply penetrating radiation. We report on a patient with an oropharyngeal carcinoma who developed severe radiation-induced acne including comedones and cysts as well as few inflammatory papules and pustules in a skin area irradiated with up to 63 gray of a 6 MeV photon beam. Acnegenic drugs may precipitate the disease; our patient was on longterm therapy with carbamazepine whose acnegenic potency is less well documented than that of testosterone or glucocorticoids. Treatment of radiation-induced acne is comedolytic; topical retinoids are especially valuable.

Acne Vulgaris↗