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Biomedical subjects

Thomas Vogt

Publications and source records attributed to Thomas Vogt.

At least 37 records · Page 2Linked to original sources
PubMed2005

Clonidine induces nitric oxide- and prostaglandin-mediated vasodilation in healthy human skin.

Sustained sympathetic activation not only leads to vasoconstriction but also might induce paradox vasodilation. This study was performed to explore whether and how alpha(2)-receptor stimulation mediates this vasodilation. We investigated 11 healthy subjects in 33 dermal microdialysis (MD) sessions. After nerve trunk blockade, MD fibers were inserted and perfused with physiological saline until skin trauma-related vasodilation subsided. Thereafter, fibers were perfused with either clonidine solutions (10(-3), 5 x 10(-4), 10(-4) mol/l), N(G)-monomethyl-l-arginine (L-NMMA; nitric oxide synthase blocker), acetylsalicylic acid (ASA; cyclooxygenase blocker), or combinations of these. Laser-Doppler scanning of the investigated skin revealed that clonidine not only induces vasoconstriction but subsequently also vasodilation with higher concentrations (P < 0.001). In contrast, both L-NMMA and ASA induced vasoconstriction (P < 0.001). By coapplication of 10(-3) mol/l clonidine with L-NMMA or ASA, vasodilation was partially prevented (P < 0.001). Our results demonstrate that sustained alpha(2)-receptor stimulation induces vasodilation in a dose-dependent way, which is mediated by nitric oxide and prostaglandin mechanisms in human skin.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2005

Ephrin-B2 is differentially expressed in the intestinal epithelium in Crohn's disease and contributes to accelerated epithelial wound healing in vitro.

AIM: Eph receptor tyrosine kinases and their membrane bound receptor-like ligands, the ephrins, represent a bi-directional cell-cell contact signaling system that directs epithelial movements in development. The meaning of this system in the adult human gut is unknown. We investigated the Eph/ephrin mRNA expression in the intestinal epithelium of healthy controls and patients with inflammatory bowel disease (IBD). METHODS: mRNA expression profiles of all Eph/ephrin family members in normal small intestine and colon were established by real-time RT-PCR. In addition, differential expression in IBD was investigated by cDNA array technology, and validated by both real-time RT-PCR and immunohistochemistry. Potential effects of enhanced EphB/ephrin-B signaling were analyzed in an in vitro IEC-6 cell scratch wound model. RESULTS: Human adult intestinal mucosa exhibits a complex pattern of Eph receptors and ephrins. Beside the known prominent co-expression of EphA2 and ephrinA1, we found abundantly co-expressed EphB2 and ephrin-B1/2. Interestingly, cDNA array data, validated by real-time PCR and immunohistochemistry, showed upregulation of ephrin-B2 in both perilesional and lesional intestinal epithelial cells of IBD patients, suggesting a role in epithelial homeostasis. Stimulation of ephrin-B signaling in ephrin-B1/2 expressing rat IEC-6-cells with recombinant EphB1-Fc resulted in a significant dose-dependent acceleration of wound closure. Furthermore, fluorescence microscopy showed that EphB1-Fc induced coordinated migration of wound edge cells is associated with enhanced formation of lamellipodial protrusions into the wound, increased actin stress fiber assembly and production of laminin at the wound edge. CONCLUSION: EphB/ephrin-B signaling might represent a novel protective mechanism that promotes intestinal epithelial wound healing, with potential impact on epithelial restitution in IBD.

Crohn Disease↗
PubMed2005

One-step synthesis of core(Cr)/shell(gamma-Fe(2)O(3)) nanoparticles.

Core(Cr)/shell(gamma-Fe(2)O(3)) nanoparticles were synthesized by mixing Fe(CO)(5) and Cr(CO)(6) in the 9:1 ratio. These particles exhibit narrow size distribution with 13.5 nm as mean diameter and uniform spherical shape. The TEM image, which is in good agreement with the synchrotron powder XRD pattern, reveals the heterogeneous nature (core/shell structure). The analysis of the pattern reveals gamma-Fe(2)O(3) structure and a metal crystal structure. Mossbauer spectra, which support the superparamagnetic behavior determined by H-M measurement, do not show any traceable amount of Fe(0). This suggests that the metal component is Cr. EELS analysis and iron mapping suggest controlled stoichiometry and also confirm a core made of Cr and a shell made of gamma-Fe(2)O(3).

Journal Article↗
PubMed2005

Controlling the size of magnetic nanoparticles using pluronic block copolymer surfactants.

We have successfully controlled the size of magnetic nanoparticles by adjusting the surfactant/solvent ratio. Gamma-Fe(2)O(3) nanoparticles of 5.6 and 12.7, and Fe(0) nanoparticles of 22.3 nm in diameter were prepared, all having spherical shape and uniform size as confirmed by TEM. Mössbauer spectra confirmed Fe(3+) for the 5.6 and 12.7 nm particles and Fe(3+) and Fe(0) for 22.3 nm particles, in good agreement with synchrotron XRD patterns. Both room temperature and 5 K H-M measurements show that 22.3 nm particles have much higher magnetization than their oxide counterparts, in agreement with their being Fe(0). T-M measurements show superparamagnetism for 5.6 and 12.7 nm particles and ferromagnetism for 22.3 nm particles.

Ferric Compounds↗
PubMed2005

[Rheumatoid arthritis--clinical picture and important differential diagnoses].

Rheumatoid Arthritis is a chronic disease of unknown origin. It affects the joints, but also virtually every other organ. Its cause remains still unknown. The prevalence rate is approximately 1% worldwide, with some racial differences. Women are affected three times more often than men. Symmetric swelling of the joints and a substantial morning stiffness are the typical signs of the disease. Most often the wrists, MCP and PIP joints, and the ankle and MTP joints are affected. The arthritis is usually progressive, leading to destructive changes of the affected joints. Neurological symptoms can occur following destruction of the atlantoaxial joint. Diagnosis and classification of the disease follows the 1987 revised American Rheumatism Association criteria, but for practical purposes the approach described by Visser et al. seems more useful, calculating odds ratios for persisting and erosive disease. Effective treatment can start earlier with this approach. Conventional radiology and serum markers, especially the newer antibodies against CCP are important aids in diagnosing rheumatoid arthritis. Diseases to be separated from rheumatoid are other arthritides of autoimmune origin, the cristal arthropathies, vasculitides, septic and parainfectious arthritides, osteoarthritis, and paraneoplastic syndromes.

Arthritis, Rheumatoid↗
PubMed2005

Overexpression and hyperphosphorylation of retinoblastoma protein in the progression of malignant melanoma.

Mutation, absence or abnormal functioning of retinoblastoma protein are fundamental elements of uncontrolled growth in human cancer. In this study, we analyze the expression of retinoblastoma protein and phosphorylated retinoblastoma protein in melanocytic tumors in vivo. Real-time RT-PCR and immunohistochemistry (tissue microarrays and conventional histological sections) reveal that retinoblastoma protein is progressively upregulated in advanced and metastatic malignant melanomas in vivo. However, this increase is paralleled by increased retinoblastoma protein inactivation due to protein phosphorylation. Interestingly, retinoblastoma protein phosphorylation occurs not homogeneously, but with a 'growth zone'-related pattern. In superficial spreading melanomas a subepidermal-lateral maximum of phosphorylated retinoblastoma protein can be frequently observed. Accordingly, nodular vertically invasive melanomas are characterized by a strong staining of phosphorylated retinoblastoma protein in deep-dermal invading protrusions of the tumor. Furthermore, Kaplan-Meier analysis of 13 cases of advanced melanomas with long-time follow-up suggests a significant negative impact of retinoblastoma protein phosphorylation on survival of melanoma patients independent of tumor thickness. We conclude that the evaluation of phosphorylated retinoblastoma protein in melanocytic tumors could become a helpful adjunct in clinicopathological routine.

Disease Progression↗
PubMed2005

Retinoblastoma-binding protein 2-homolog 1: a retinoblastoma-binding protein downregulated in malignant melanomas.

In malignant melanomas, the loss of cell cycle control is thought to be due to a lack of retinoblastoma protein (pRb)-activity. Members of the previously described family of retinoblastoma-binding proteins (RBPs) are supposed to act as pRb-modulating factors. Based on RNA-fingerprinting of normal human melanocytes, we previously described a new family member with high sequence homology to the retinoblastoma-binding protein-2 (RBP-2), termed RBP2-Homolog 1 (RBP2-H1). Based on its UVB responsiveness, it was hypothesized that this gene may also play a role in melanocytic tumors. In the present study, we can confirm by real-time RT-PCR (six common melanocytic nevi, five advanced nodular melanomas and seven melanoma metastases) and immunohistochemistry (tissue microarrays: 52 melanocytic nevi, 60 melanomas, 60 metastases; and conventional sections: five common nevi, four advanced nodular melanomas, five melanoma metastases) that RBP2-H1 expression is progressively downregulated in advanced and metastatic melanomas in vivo with a certain intratumoral heterogeneity. Whereas benign melanocytic nevi are RBP2-H1 positive in about 70% of the cases, a lack of RBP2-H1 expression was found in 90% of the primary malignant melanomas and 70% of the melanoma metastases, respectively. Interestingly, a similar deficiency can be found in glioblastomas, but not epithelial cancers. In accordance to the in vivo data, established melanoma cell lines exhibit low but heterogeneous levels of RBP2-H1 expression. By co-immunoprecipitation, we provide the first evidence that a subfraction of total RBP2-H1 can bind to pRb, which makes this protein a true pRb-interacting factor. We conclude that loss of RBP2-H1 is a common finding in the progression of malignant melanomas. Since a direct interaction of RBP2-H1 and pRb seems possible, the loss of RBP2-H1 may possibly contribute to uncontrolled growth in malignant melanomas.

Base Sequence↗
PubMed2005

Relationship between tobacco control policies and the delivery of smoking cessation services in nonprofit HMOs.

BACKGROUND: This project examined tobacco policies and delivery of cessation services in nonprofit HMOs that collectively provide comprehensive medical care to more than 8 million members. METHODS: Three annual surveys with health plan managers showed that all of these health plans had written tobacco control guidelines that became more comprehensive over the span of this study. We also surveyed a random sample of 4207 current smokers who had attended a primary care visit in the past year (399-528 at each of nine health plans). RESULTS: Of these smokers, 71% reported advice to quit, 56% were asked about their willingness to quit, 49% were provided some assistance in quitting (mostly self-help material or information about classes or counseling), and 9% were offered some kind of follow-up. Smokers receiving assistance in quitting reported higher satisfaction with their care. CONCLUSIONS: In general, health plans with the most comprehensive policies also showed higher rates of implementing tobacco treatment programs in primary care. Compared with tobacco control efforts of a decade or more ago, considerable progress has been made. However, there is still room for improvement in the proportion of smokers who receive the most effective forms of assistance in quitting.

Adult↗
PubMed2005

Gene expression profile changes between melanoma metastases and their daughter cell lines: implication for vaccination protocols.

Vaccination protocols based on autologous tumor material often require in vitro culturing of tumor cells to obtain enough cellular material for the production of the vaccine. Cancer cells and particularily melanoma cells are known for their genomic instability. Therefore, it can be assumed that melanoma cells acquire genomic changes and thereby changes in the transcriptome during in vitro culturing. This may lead to a shift of epitopes expressed on the tumor cells. We analyzed the transcriptome of in vitro cultured melanoma cells prepared from melanoma metastases. Comparing the gene expression changes between the tumors and their offspring cell lines, we demonstrate that with increasing passage numbers, gene expression changes increase drastically.

Cancer Vaccines↗
PubMed2005

Severe contact urticaria to guar gum included as gelling agent in a local anaesthetic.

We report the first case of a life-threatening immediate-type hypersensitivity caused by Dynexan, a local anaesthetic gel. After mucosal application by his dentist, a 63-year-old man rapidly developed urticaria, dyspnea and, at last, he collapsed and remained unconscious for 2 hr despite emergency care. While the standard prick tests were negative to all local anaesthetics tested including lidocaine, a 1-fold positive reaction was detected to Meyprogat 60, an ingredient of Dynexan. As the gelling agent Meyprogat represents a derivative of guar (synonymous guar gum, guaran, E-412), we subsequently tested different guar products derived from Cyamopsis tetragonoloba beans and, as control, the closely related locust bean gum E-410. In the prick-to-prick tests, the guar-derived food additive Provigel NAG 905 provoked a 1-fold positive reaction. Native guar beans pounded and resuspended in water showed a 2-fold positive reaction, whereas no reaction was found to derivatives of locust bean gum. Specific immunoglobulin E were negative in all cases. Despite the common use of guar as versatile food additive or gelling agent, this is the first case of a severe immediate-type hypersensitivity after mucosal contact.

Anaphylaxis↗
PubMed2005

Congenital cartilaginous rests of the neck (wattles).

BACKGROUND: Congenital cartilaginous rests of the neck (wattles) are very rare, probably branchiogenic malformations. OBJECTIVE: To discuss the clinical and histologic features and the therapy of wattles. METHODS: We report a 4-year-old patient with symmetric exophytic nodules of the neck that had been present since birth. RESULTS: The two lesions, 0.5 3 0.5 cm, were removed. The histopathologic examination confirmed ectopic cartilaginous tissue. CONCLUSION: Wattles must be excised, including their cartilaginous core, after having sonographically excluded fistulae or sinuses.

Cartilage Diseases↗
PubMed2005

New indications for established drugs: combined tumor-stroma-targeted cancer therapy with PPARgamma agonists, COX-2 inhibitors, mTOR antagonists and metronomic chemotherapy.

In search of new strategies for the treatment of cancer, the interaction between tumor and stroma attracts more and more attention. Disruption of stroma functions, e.g. angiogenesis, has evolved into a promising target for cancer therapies. Since stromal cells are genetically stable, stroma-targeted therapies seem to be less susceptible to the development of drug resistance. Several well-established drugs, which had initially been developed for other indications, also exhibit antitumor activity. Among those, PPARgamma agonists, COX-2 inhibitors, and mTOR antagonists are the most remarkable examples. Current research data and clinical experience suggest that these drugs target stroma functions in cancer, in particular angiogenesis, but immunological mechanisms and direct antitumor effects seem to participate as well. In addition to these drugs, frequent administration of low-dose chemotherapeutics, referred to as metronomic chemotherapy, reveals profound anti-angiogenic effects. In the meantime, a multitude of preclinical and clinical studies have been undertaken, which demonstrate the efficacy of these drugs in cancer therapy. Combinatorial use of these agents has been suggested to be superior in terms of antitumor efficacy and prevention of drug resistance. The toxicity of these therapies is surprisingly low compared with conventional high-dose chemotherapy regimens. Patients with advanced disease, often heavily pretreated and presenting multiple drug resistance, could particularly profit from such tumor-stroma-targeted therapies. However, larger randomized clinical trials are required for further evaluation and optimization of this concept.

Animals↗
PubMed2005

Ephrin-B2 overexpression enhances integrin-mediated ECM-attachment and migration of B16 melanoma cells.

Eph-receptor tyrosine kinases (Eph-RTKs) and their membrane-bound receptor-like ligands, the ephrins, represent a cell-cell signaling system that directs cellular migration during development. Differential expression in cancer suggests similar roles in tumor progression. We have previously shown that ephrin-B2 mRNA is overexpressed in advanced malignant melanomas (MM). In this study, immunohistochemistry revealed a most prominent expression of ephrin-B2 in the invasive front of advanced MM. Therefore, we addressed the question of whether ephrin-B2 signaling modulates MM cell migration and matrix interaction. Using a wild-type ephrin-B2-negative B16 mouse MM subclone we show that overexpression of ephrin-B2 leads to the formation of multiple lamellipodia, enhanced polymerisation of actin fibers, and induction of focal adhesion complexes with constitutive activation of focal adhesion kinase. Consequently, ephrin-B2-overexpressing B16 cells display a significant increase of beta1-integrin-mediated attachment to matrix components, preferentially laminin and fibronectin. As a further effect of ephrin-B2 overexpression, we observed an accelerated migration in both Boyden chamber invasion experiments as well as in in vitro scratch-wound assays. We conclude that ephrin-B2 can act as a major modulator of cell migration and matrix interactions of MM cells, which possibly contributes to the expansion and metastatic spread of MM in vivo.

Animals↗
PubMed2005

Staphylococcus aureus in patients with rheumatoid arthritis under conventional and anti-tumor necrosis factor-alpha treatment.

OBJECTIVE: To compare the prevalence of nasal and oral Staphylococcus aureus in patients with rheumatoid arthritis (RA) with the prevalence in controls with other rheumatic diseases, and to determine predictors of S. aureus carriage and the influence of treatment with anti-tumor necrosis factor-a (anti-TNF-alpha) agents. METHODS: Eighty-one patients with RA and 83 other control patients of 2 outpatient rheumatology clinics were cultured for nasal and oral carriage of S. aureus. Quantitative nasal cultures for S. aureus were performed from swabs of the anterior nares, the posterior pharynx, and the soft palate. Information on medications, medical conditions, and risk factors for S. aureus carriage was collected from all participants by a questionnaire and confirmed by chart review. RESULTS: The S. aureus carriage rate (nasal and/or oral colonization) was 34.6% among RA patients and 32.5% among controls (p = 0.87). Being treated with an anti-TNF-alpha agent plus methotrexate (MTX) was the only independent predictor of S. aureus carriage (OR 3.24, 95% CI 1.16-9.05, p = 0.025). The S. aureus carriage rate among RA patients treated with an anti-TNF-alpha agent plus MTX was 60% (9/15) versus 23.1% (3/13) in RA patients treated with an anti-TNF-alpha agent only (p = 0.049). All S. aureus isolates were susceptible to oxacillin. CONCLUSION: The S. aureus carriage rate among patients with RA was not higher than among controls. Treatment with anti-TNF-alpha agents was not associated with an increased S. aureus carriage rate. However, treatment with an anti-TNF-alpha agent plus MTX may predispose patients to S. aureus carriage.

Adalimumab↗