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Biomedical subjects

R Stadler

Publications and source records attributed to R Stadler.

At least 19 recordsLinked to original sources
PubMed2007

Mycosis fungoides: a dermatological masquerader.

Mycosis fungoides (MF), a low-grade lymphoproliferative disorder, is the most common type of cutaneous T-cell lymphoma. Typically, neoplastic T cells localize to the skin and produce patches, plaques, tumours or erythroderma. Diagnosis of MF can be difficult due to highly variable presentations and the sometimes nonspecific nature of histological findings. Molecular biology has improved the diagnostic accuracy. Nevertheless, clinical experience is of substantial importance as MF can resemble a wide variety of skin diseases. We performed a literature review and found that MF can mimic >50 different clinical entities. We present a structured framework of clinical variations of classical, unusual and distinct forms of MF. Distinct subforms such as ichthyotic MF, adnexotropic (including syringotropic and folliculotropic) MF, MF with follicular mucinosis, granulomatous MF with granulomatous slack skin and papuloerythroderma of Ofuji are delineated in more detail.

Diagnosis, Differential↗
PubMed2006

[Cutaneous lymphomas: classification and stage-adjusted therapy].

Cutaneous lymphomas are a heterogeneous group of clonal proliferations of T and B lymphocytes with various clinical manifestations and prognosis. The new EORTC WHO classification of cutaneous T- and B-cell lymphomas provides a uniform nomenclature based on clinical, histologic, cytologic and molecular biological features. Accurate classification is a prerequisite for uniform therapeutic concepts. For office-based dermatologist, more than 50% of the therapies deal with classic forms of cutaneous T-cell lymphomas, type mycosis fungoides. In recent years the paradigm for the therapy of cutaneous T-cell lymphomas has changed. Since early aggressive treatment with cytostatic agents does not increase the response rate or overall survival, a commonly accepted stage-adapted therapy is recommended. In this review the current status of the therapy of cutaneous lymphoma is described in detail.

Antineoplastic Agents↗
PubMed2006

Multicentre, phase II trial on the safety and efficacy of topical tacrolimus ointment for the treatment of lichen sclerosus.

BACKGROUND: Lichen sclerosus is a chronic inflammatory autoimmune disease causing significant sclerosis, atrophy and pruritus. Treatment remains unsatisfactory, with potent corticosteroids being the most effective therapy. OBJECTIVES: To conduct a multicentre, phase II trial to assess the safety and efficacy of tacrolimus ointment 0.1% for the treatment of lichen sclerosus with a follow-up period of 18 months at 10 university and teaching hospitals in Germany and Austria. METHODS: Eighty-four patients (49 women, 32 men and three girls) aged between 5 and 85 years with long-standing, active lichen sclerosus (79 with anogenital and five with extragenital localization) were treated with topical tacrolimus ointment 0.1% twice daily for 16 weeks. Computerized analysis of the lesional area was performed. The primary endpoint was clearance of active lichen sclerosus. Secondary endpoints were time to optimal response, reduction of sclerosis and duration of remission. RESULTS: The primary endpoint (clearance of active lichen sclerosus) was reached by 43% of patients at 24 weeks of treatment. Partial resolution was reached in 34% of patients. Maximal effects occurred between week 10 and 24 of therapy. Treatment led to a significant reduction of the total lesional area (P < 0.01) and to a significant decline in the total symptom score (P < 0.005). Symptoms (e.g. itching) and findings (erythema, erosions and induration) showed significant improvement. No serious adverse events were observed. There were three (9%) recurrences during the follow-up period. CONCLUSIONS: Topical tacrolimus ointment 0.1% was safe and effective for the treatment of long-standing active lichen sclerosus.

Adolescent↗
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↗
PubMed2005

Drift studies--comparison of field and wind tunnel experiments.

Drift at pesticide application leads to a pollution of non-target crops, non-target species and surface water. Spray drift is influenced by many factors like environmental conditions, vegetation, technical conditions, and physical properties of the tank mixes and influenced by Chemicals. Field experiments to characterise spray drift effects with the risk of permanent changing weather conditions can be supported by wind tunnel experiments. Wind tunnel experiments do not lead to the same soil deposition curves like field experiments, but the ratio of drift reduction potential is comparable.

Agriculture↗
PubMed2003

Bexarotene--an alternative therapy for progressive cutaneous T-cell lymphoma? First experiences.

BACKGROUND: A standard therapy for advanced cutaneous T-cell lymphomas has not yet been defined. Bexarotene is a new retinoid x receptor-specific retinoid that has been approved for systemic second-line therapy for cutaneous T-cell lymphomas in the USA and Europe. In order to evaluate the efficacy of bexarotene in cutaneous T-cell lymphomas, a pilot trial was initiated. PATIENTS AND METHODS: In a pilot project 10 patients with advanced cutaneous T-cell lymphomas, who had received a variety of previous treatments, were treated with bexarotene at the departments of dermatology in Münster, Minden and Charité Berlin, Germany. The patients received bexarotene at a dose of 300 mg/m2 body surface daily. According to the percentage of tumour reduction and affected body surface, the response rates were divided in complete and partial remission, stable disease and progressive disease. Laboratory parameters i.e. cholesterol, triglycerides transaminases, T3, T4, and TSH were screened regularly. RESULTS: In 2 patients a short partial remission was achieved; however, after a few weeks progression followed. In 4 patients a lasting stabilisation was obtained. The other 4 patients showed a progressive disease during therapy. 6 patients developed hypertriglyceridemia with levels up to 2000 mg/dl; therapy had to be suspended in 3 patients because of these adverse drug events. CONCLUSION: Weighing benefits and risks, bexarotene can at present not be recommended as standard therapy in the treatment of patients with progressive cutaneous lymphomas.

Adult↗
PubMed2002

[Thalidomide therapy of cutaneous lupus erythematosus].

Immunosuppressive and immune-modulating substances such as corticosteroids, chloroquin, hydroxychloroquin, azathioprin, methotrexate, and others are standards in therapy of cutaneous lupus erythematosus. However, alternative substances are necessary when standard therapy regimens fail or are associated with side effects. Describing the course of disease in five female patients, we demonstrate alternative treatment of subacute cutaneous lupus erythematosus with thalidomide, showing good symptom response and possible side effects. By careful patient selection, we observed no polyneuropathy as it is most commonly described. In two cases, maculopapulous exanthema induced by medication was seen. The teratogeny of the substance must be taken into account in prescription. In selected cases, thalidomide can be a highly effective therapeutic option in the treatment of subacute cutaneous lupus erythematosus.

Adult↗
PubMed2002

[Scleredema adultorum in secondary hyperparathyroidism].

Scleredema adultorum, or Buschke's scleredema, belongs to the group of mucinoses. It is characterised by thickened and indurated skin. Histopathology shows thickened dermis with an infiltration of mucin between swollen collagen bundles. There are reports about many associations with scleredema adultorum, e.g., with diabetes mellitus and multiple myeloma. One case is known with associated primary hyperparathyroidism. For the first time we report a case of scleredema adultorum and secondary hyperparathyroidism, in a 46-year-old patient. Both forms of hyperparathyroidism have increased levels of parathormone. Therefore, these increased levels could have an influence on collagen metabolism.

Biopsy↗
PubMed2001

Ethylene hormone receptor action in Arabidopsis.

Small gaseous molecules play important roles in biological signaling in both animal and plant physiology. The hydrocarbon gas ethylene has long been known to regulate diverse aspects of plant growth and development, including fruit ripening, leaf senescence and flower abscission. Recent progress has been made toward identifying components involved in ethylene signal transduction in the plant Arabidopsis thaliana. Ethylene is perceived by five receptors that have similarity to two-component signaling proteins. The hydrophobic amino-terminus of the receptors binds ethylene, and mutations in this domain both prevent ethylene binding and confer ethylene insensitivity to the plant; the carboxyl-terminal portion of the receptors has similarity to bacterial his tidine protein kinases. Genetic data suggest a model in which ethylene binding inhibits receptor signaling, yet precisely how these receptors function is unclear. Two of the receptors have been found to associate with a negative regulator of ethylene responses called CTR1, which appears to be a mitogen-activated protein kinase (MAPK) kinase kinase.

Animals↗
PubMed2001

Tandem mass spectrometric accurate mass performance of time-of-flight and Fourier transform ion cyclotron resonance mass spectrometry: a case study with pyridine derivatives.

The interpretation of mass spectra is a key process during compound identification, and the combination of tandem mass spectrometry (MS/MS) with high-accuracy mass measurements may deliver crucial information on the identity of a compound. Obtaining accurate mass data of fragment ions in MS/MS reveals the particular problem of mass calibration when a lockmass, which is frequently used to obtain accurate masses in MS, is absent. An alternative technique is to recalibrate the MS/MS spectrum using a reference MS/MS spectrum acquired under the same conditions. We have tested and validated this approach using a hybrid quadrupole/orthogonal acceleration reflectron-type time-of-flight (TOF) mass spectrometer. The results were compared with those obtained under similar conditions on a Fourier transform ion cyclotron resonance (FT-ICR) instrument. We found that the mass accuracy observed with such an "external" recalibration on the TOF instrument in MS/MS is identical to what can be obtained on a similar instrument operating in one-dimensional MS mode using the lockmass technique. However, mass accuracy in both cases is one order of magnitude inferior to that obtained using FTMS, and also inferior to that observed using sector field MS when operated at comparable resolution. Nevertheless, for small (<200 Da) molecules, this mass accuracy was still sufficient to have the "true" elemental composition identified as the first hit in about 70% of all cases. It was possible to elucidate the fragmentation mechanism of eight azaheterocycles containing a pyridine moiety, where the accurate mass data from the TOF instrument allowed distinction between two alternative fragmentation pathways.

Cyclotrons↗
PubMed2001

[Association between UVA1 and PUVA bath therapy and development of malignant melanoma].

After 18 months of intensive UVA1- and bath PUVA therapy for urticaria pigmentosa, a female patient developed a malignant melanoma on the right thigh. This can be taken as further indication that intense UVA1 or PUVA therapy is capable of inducing malignant melanoma, even though this risk has not been completely proven. The total dose of UVA1 was 910 J/cm2, while the total dose of PUVA was 214.4 J/cm2. It is unclear to what extent modified UVA application of long-wave UVA light (UVA1) and modified PUVA therapy (bath PUVA) have a similar risk compared to known data.

Adult↗
PubMed2001

[Ulcerative esophagitis and colitis as rare manifestations of Adamantiades-Behcet disease].

We report the case of a 39-year-old German women who suffered from chronic inflammatory bowel disease which had not been exactly classified for 6 years. In the course of the disease she developed recurrent iritis, nodular skleritis, oral and genital ulcer, erythema nodosum and axillary folliculitis. For the first time retrosternal pain occurred. Endoscopy of the upper gastrointestinal tract showed mid esophageal ulcer formation. Colonoscopy demonstrated ulcerative colitis with no involvement of rectal mucosa. Histologically a cutaneous vasculitis in the lower limb was seen and diagnosis of Adamantiades-Behçet disease with marked gastrointestinal involvement and rare manifestation in the esophagus was established. A therapy with prednisolone, azathioprine and mesalazine was started. Under this regimen stomatitis, esophagitis and cutaneous vasculitis resolved, while the colitis showed partial remission now for up to one year.

Adult↗
PubMed2001

Diffuse melanosis arising from metastatic melanoma: pathogenetic function of elevated melanocyte peptide growth factors.

The origin of diffuse melanosis resulting from metastatic melanoma is unknown. We examined the light microscopic and ultrastructural changes in the skin of an affected 35-year-old woman and determined the peripheral blood levels of melanocyte growth factors. A total of 7 biopsy specimens were examined by light and electron microscopy and immunohistology (S-100, HMB45, MART1, CD68, MAC387). Serum/plasma levels of melanocyte growth factors of the patient were determined by enzyme-linked immunosorbent assays and compared with those of normal volunteers (n = 10) and amelanotic patients with metastatic melanoma (n = 10), matched to the UICC stage of the affected patient. Hyperpigmented but otherwise apparently normal skin of the patient displayed epidermal melanocyte hyperplasia, increased melanogenesis, and dermal pigment stored in histiocytes and other cells along with extracellular deposits. Blood levels of alpha-melanocyte stimulating hormone, hepatocyte growth factor, and endothelin-1 were significantly elevated in the affected patient. Aberrant production of these factors may not only be responsible for activation of the pigment system in diffuse melanosis of metastatic melanoma, but also for increased proliferation, motility, and pigment incontinence of normal and malignant melanocytes.

Adult↗
PubMed2000

Management of regional metastases.

Treatment of regional melanoma metastases aims not only at local remission of the primary tumour but also at prevention or delay of distant metastases. Regional metastases can occur as satellite, in-transit and regional lymph node metastases. This is an overview of the current therapeutic modalities for regional metastatic melanoma: surgical management of relapse, satellite and in-transit metastases; therapeutic lymphadenectomy; development from elective lymph node dissection to sentinel lymph node dissection (SLND); radiotherapy and isolated limb perfusion. Instead of elective lymph node dissection the new microstaging technique by means of SLND is gaining particular importance. For this method prognostic relevance is expected and thus it is supposed to be an important staging parameter for adjuvant treatment planning.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed2000

AtSUC3, a gene encoding a new Arabidopsis sucrose transporter, is expressed in cells adjacent to the vascular tissue and in a carpel cell layer.

The cDNA corresponding to the open reading frame T17M13.3 from Arabidopsis chromosome II was isolated and the encoded protein was characterized as a member of a subgroup of higher plant sucrose transporters. The AtSUC3 (Arabidopsis thaliana sucrose transporter 3) open reading frame encodes a protein with 594 amino acid residues, being 81 and 82 residues longer than the previously described Arabidopsis sucrose carriers AtSUC1 and AtSUC2. About 50 of these additional amino acids are part of an extended cytoplasmic loop separating the N-terminal from the C-terminal half of the protein. For functional characterization the AtSUC3 cDNA was expressed in baker's yeast. Substrate specificities, energy dependence and K(m) values of the recombinant protein were determined. Removal of the enlarged cytoplasmic loop and expression of the truncated cDNA caused no detectable change in the kinetic properties of the protein, suggesting a transport-independent function for this cytoplasmic domain. Immunolocalization with an AtSUC3-specific antiserum identified the protein in a cell layer separating the phloem from the mesophyll and in a single, subepidermal cell layer of the carpels that is important for pod dehiscence. These localizations suggest a possible role of AtSUC3 in the funnelling of sucrose from the mesophyll towards the phloem, and possibly in pod shatter.

Amino Acid Sequence↗
PubMed2000

Monosaccharide/proton symporter AtSTP1 plays a major role in uptake and response of Arabidopsis seeds and seedlings to sugars.

The aim of this study was to investigate the in vivo properties and function of the high-affinity monosaccharide/proton symporter AtSTP1 of Arabidopsis. We isolated an Atstp1 knock-out mutant and found that this plant grows and develops normally. The AtSTP1 gene is expressed in germinating seeds and seedlings, with AtSTP1 activity found mainly in the seedling root. The rate of uptake of [(14)C]-3-O-methylglucose and [(14)C]-D-glucose is 60% less in Atstp1 seedlings than in the wild type, showing that AtSTP1 is the major monosaccharide transporter in Arabidopsis seedlings. Transport of D-galactose and D-mannose is also up to 60% less in Atstp1 seedlings compared to wild type, but transport of D-fructose, L-arabinose and sucrose is not reduced. Germination of Atstp1 seed shows reduced sensitivity to D-mannose, demonstrating that AtSTP1 is active before germination. Atstp1 seedlings grow effectively on concentrations of D-galactose that inhibit wild-type growth, even at up to 100 mM D-galactose, indicating that active transport by AtSTP1 plays a major role at very high concentrations of exogenous sugar. These findings provide insight into the physiological function of AtSTP1 and clearly establish its importance in the uptake of extracellular sugars by the embryo and in seedlings.

Arabidopsis↗
PubMed1999

Structural analysis of a plant sucrose carrier using monoclonal antibodies and bacteriophage lambda surface display.

Monoclonal antibodies were raised and selected against recombinant Plantago major PmSUC2 sucrose carrier protein. Epitopes of two monoclonal antibodies (PS2-1A2 and PS2-4D4) were mapped using N-terminally truncated PmSUC2 proteins and a lambda library displaying random PmSUC2 peptides. PS2-1A2 recognizes an octapeptide close to the N-terminus of PmSUC2, PS2-4D4 binds to a decapeptide at the very C-terminus. Analyses of antibody binding to yeast protoplasts with functionally active, tagged PmSUC2 protein revealed that both epitopes are located in cytoplasmic domains of PmSUC2. These results support a model for plant sucrose transporters containing 12 transmembrane helices with the N-terminus and the C-terminus on the cytoplasmic side of the plasma membrane.

Amino Acid Sequence↗