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Biomedical subjects

R Stadler

Publications and source records attributed to R Stadler.

At least 19 recordsLinked to original sources

[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↗

[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↗

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↗

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↗

[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↗

[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↗

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↗

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↗

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↗

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↗

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↗

[Photodynamic therapy of cutaneous T-cell lymphoma at special sites].

Therapy of the heterogenous group of primary cutaneous B- and T-cell lymphomas is based upon type of lymphoma and its staging. Treatment, especially for rare forms, has not yet been standardised. Two patients with uncommon primary cutaneous T-cell lymphomas received both traditional therapy and topical photodynamic therapy (PDT) in areas that are difficult to reach with classic methods (ear, eyebrow, side of foot). The first patient had a rare type of medium/large cell pleomorphic, CD8-positive, CD30-negative, primary cutaneous T-cell lymphoma with primary involvement of the ear. As the tumor progressed during PUVA, interferon alpha and retinoid therapy, topical PDT was employed. A histologically confirmed partial remission was obtained. As the disease further evolved the patient received radiotherapy and has now been in complete remission for 10 months. The other patient preserted with the classical picture of mycosis fungoides in initial tumour stage. This patient received in addition to PUVA therapy and interferon alpha, topical PDT to the eyebrow and side of the foot. A complete remission was achieved and histologically confirmed. In the palliative treatment of cutaneous T-cell lymphoma, PDT is a new experimental method, especially for problem locations. It is tissue sparing, has few side effects, can be repeated as often as necessary and achieves good cosmetic results.

Aged↗

[Long-pulsed frequency-doubled neodymium:YAG laser in treatment of superficial varicose veins. Initial clinical experiences].

Many different therapeutic approaches are employed to treat small vessels on the leg. In recent years a variety of lasers (argon, Neodymium: YAG and dye lasers) have been used as well as sclerotherapy, cryosurgery and electrosurgery. None of these lasers are entirely satisfactory, and there are a number of side effects. Because of its special physical characteristics, the newly developed long-pulsed frequency-doubled neodymium: YAG laser has clear advantages in the treatment of vascular lesions compared to other laser systems. These include: no vessel rupture compared to dye laser, no epidermal lesions compared to argon laser. In clinical tests it shows a high rate of effectiveness with minimal side effects.

Adult↗

[Post-traumatic pyoderma gangrenosum: combination therapy with intravenous immunoglobulins and systemic corticosteroids].

Pyoderma gangraenosum is a rare, chronic type of skin ulceration of unknown aetiology. It occasionally appears following trauma. There are no set standards for the treatment of pyoderma gangraenosum. It is essential to consider acuteness of progression as well as underlying systemic diseases and possible drug side effects before initiating a therapy. Immunosuppressive as well as immunomodulating agents are most often used with varying degrees of success. We report a 45-year-old patient who suffered from an extensive posttraumatic pyoderma gangraenosum after cardiac bypass operation. With short-term combination therapy consisting of high dose intravenous immunoglobulins and systemic corticosteroids, the progression of the disease could be stopped within a few days.

Anti-Inflammatory Agents↗

[Differentiated local therapy of chronic wounds with modern wound dressings].

Differentiated local therapy of chronic wounds with modern wound dressings. The therapy of chronic wounds comprises besides treating the underlying disease, for instance compression therapy and phlebosurgery with venous ulcus cruris modern differentiated local therapy. Conventional wound therapy comprises primarily of colour solutions, various ointments, local antimicrobial agents, and sterile pressure bandages. Although it has been proven that conventional methods impede wound healing compared with modern wound dressings they are still widely used. In comparison the principle of moist wound healing is the basis of modern differentiated wound therapy. Therefore a vast number of modern wound dressings has been established in the last years. As not every wound dressing is suitable for every type of wound the knowledge of available modern wound dressings is essential in order to choose the wound dressing which is most suitable for the individual case. In the exudation/cleaning phase polyurethane foams, alginates and dressings containing activated charcoal are indicated. They can also be used in the granulation phase. The granulation phase is main indication for hydrokolloids and hydrogels. They are also used beside non-adhesive dressings and alginates in the epithelialisation phase. Besides the above synthetic wound dressings cytokines and biological skin equivalents are increasingly used in modern wound therapy. Biological skin equivalents comprise of epidermis equivalents, dermis substitutes and combined epidermis-dermis equivalents which are being developed at present. These will possibly be more effective on wound closure. Phase adapted use of modern wound dressings enables acute and chronic wounds to heal quickly and without complications. Present clinical studies are evaluating the importance of cytokines and new vital skin substitutes, which might offer interesting possibilities for further improvement in wound treatment.

Bandages↗

A male gametophyte-specific monosaccharide transporter in Arabidopsis.

The AtSTP2 gene (sugar transport protein 2) of Arabidopsis thaliana encodes a high affinity, low specificity monosaccharide carrier that can transport a number of hexoses and pentoses at similar rates. AtSTP2 has 12 putative transmembrane helices and a molecular mass of 55.0 kDa. AtSTP2 expression was localized in AtSTP2 promoter-beta-glucuronidase (GUS) Arabidopsis plants showing AtSTP2-driven GUS activity during pollen maturation and also in germinating pollen. Immunohistochemical studies with anti-AtSTP2 antiserum as well as RNA in situ hybridization analyses modified these results and showed that AtSTP2 expression is confined to the early stages of gametophyte development. Both AtSTP2 mRNA and AtSTP2 protein are first seen at the time of beginning callose degradation and microspore release from the tetrades. AtSTP2 mRNA and AtSTP2 protein are no longer detected after the mitotic divisions and the formation of the trinucleate gametophyte. No AtSTP2 mRNA or AtSTP2 protein is seen in fully developed or germinating pollen. The putative role of AtSTP2 in the uptake of glucose units resulting from callose degradation during pollen maturation is discussed.

Amino Acid Sequence↗

The AtSUC1 sucrose carrier may represent the osmotic driving force for anther dehiscence and pollen tube growth in Arabidopsis.

The Arabidopsis AtSUC1 protein has previously been characterized as a plasma membrane H+-sucrose symporter. This paper describes the sites of AtSUC1 gene expression and AtSUC1 protein localization and assigns specific functions to this sucrose transporter in anther development and pollen tube growth. RNase protection assays revealed AtSUC1 expression exclusively in floral tissue, which was confirmed by analyses of AtSUC1 promoter-beta-glucuronidase (GUS) plants. In situ hybridizations identified AtSUC1 expression in anther connective tissue, in funiculi and in fully developed pollen grains. Indirect immuno-fluorescence analyses with anti-AtSUC1 antiserum confirmed AtSUC1 protein localization in the connective tissue and funiculi. In mature pollen grains, however, despite high AtSUC1 mRNA levels no AtSUC1 protein was found. Only after pollination of stylar papillae was AtSUC1 protein detected inside the pollen and later inside the growing pollen tubes, suggesting a translation of pre-existing AtSUC1 mRNA after pollination. Pollen germination analyses underlined the important role of sucrose for pollen tube growth. The data presented suggest a role of AtSUC1 in the controlled dehiscence of Arabidopsis anthers. It is postulated that an important function of AtSUC1 is the cell-specific modulation of water potentials.

Amino Acid Sequence↗

Prospective randomized multicenter clinical trial on the use of interferon -2a plus acitretin versus interferon -2a plus PUVA in patients with cutaneous T-cell lymphoma stages I and II.

Cutaneous T-cell lymphoma (CTCL) constitutes a malignant proliferative disease involving mostly CD4(+) T cells arising in the skin. Because of the lack of curative treatment options, interferons (IFN) have been introduced into the therapy of CTCL. Although effective even in advanced disease, response rates were about 50% and the duration of response was short. To improve the results of interferon monotherapy, combinations of IFN with oral photochemotherapy (PUVA) or retinoids were investigated in nonrandomized trials showing higher response rates. We have therefore conducted this prospective randomized multicenter trial to compare these two combination therapies, ie, IFN plus PUVA and IFN plus acitretin. IFN -2a was administered at 9 MU three times weekly subcutaneously in both groups, with lower increasing doses during the first week. Photochemotherapy was applied after oral intake of 8-methoxypsoralen (0.6 mg/kg body weight) 5x weekly during the first 4 weeks, 3x weekly from weeks 5 through 23, and 2x weekly from weeks 24 through 48, with escalating doses beginning with 0.25 J/cm2. Twenty-five milligrams of acitretin was administered daily during the first week, and 50 mg was administered from weeks 2 through 48. Of 98 patients randomized in this study, 82 stage I and II patients were evaluable: 40 in the IFN+PUVA group and 42 in the IFN+acitretin group. With 70% complete remissions in the IFN+PUVA group, this treatment was significantly superior to the IFN+acitretin group with only 38.1% complete remissions. Time to response was significantly shorter in the IFN+PUVA group, with 18.6 weeks compared with 21.8 weeks in the IFN+acitretin group. Side effects were mostly mild to moderate and did not differ significantly in both treatment groups. However, there were more adverse events leading to study discontinuation in the IFN+acitretin group. Based on these findings, we conclude that IFN plus oral photochemotherapy is superior to IFN plus acitretin, inducing more complete remissions in patients with CTCL stages I and II.

Acitretin↗