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Thomas Vogt

Publications and source records attributed to Thomas Vogt.

At least 19 recordsLinked to original sources
PubMed2006

Chiral three-dimensional microporous nickel aspartate with extended Ni-O-Ni bonding.

In the course of our investigation aimed at the preparation of homochiral coordination polymers using readily available in optically pure form ligands and building blocks of condensed metal polyhedra, we recently reported a one-dimensional nickel aspartate compound [Ni(2)O(l-Asp)(H(2)O)(2)].4H(2)O (1) based on helical chains with extended Ni-O-Ni bonding. Here we report a new nickel aspartate [Ni(2.5)(OH)(l-Asp)(2)].6.55H(2)O (2) with a three-dimensional Ni-O-Ni connectivity that forms at a higher pH and is based on the same helices as in 1 which are connected by additional nickel octahedra to generate a chiral open framework with one-dimensional channels with minimum van der Waals dimensions of 8 x 5 A. The crystal structure of 2 was determined by synchrotron single-crystal X-ray diffraction on a 10 x 10 x 240 microm crystal.

Journal Article↗
PubMed2006

Cloning and functional characterisation of two regioselective flavonoid glucosyltransferases from Beta vulgaris.

Two full-length cDNAs encoding flavonoid-specific glucosyltransferases, UGT73A4 and UGT71F1, were isolated from a cDNA library of Beta vulgaris (Amaranthaceae) cell suspension cultures. They displayed high identity to position-specific betanidin and flavonoid glucosyltransferases from Dorotheanthus bellidiformis (Aizoaceae) and to enzymes with similar substrate specificities from various plant families. The open reading frame of the sequences encode proteins of 476 (UGT73A4) and 492 (UGT71F1) amino acids with calculated molecular masses of 54.07kDa and 54.39kDa, and isoelectric points of 5.8 and 5.6, respectively. Both enzymes were functionally expressed in Escherichia coli as His- and GST-tagged proteins, respectively. They exhibited a broad substrate specificity, but a distinct regioselectivity, glucosylating a variety of flavonols, flavones, flavanones, and coumarins. UGT73A4 showed a preference for the 4'- and 7-OH position in the flavonoids, whereas UGT71F1 preferentially glucosylated the 3- or the 7-OH position. Glucosylation of betanidin, the aglycone of the major betacyanin, betanin, in B. vulgaris was also observed to a low extent by both enzymes. Several O-glycosylated vitexin derivatives isolated from leaves of young B. vulgaris plants and rutin obtained from B. vulgaris tissue culture are discussed as potential endogenous products of UGT73A4 and UGT71F1. The results are analyzed with regard to evolution and specificity of plant natural product glucosyltransferases.

Base Sequence↗
PubMed2006

Expression profile of Eph receptors and ephrin ligands in human skin and downregulation of EphA1 in nonmelanoma skin cancer.

Eph receptors and ephrin ligands represent the largest family of receptor tyrosine kinases. Beyond their well-defined meaning in developmental processes, these molecules also have important functions in adult human tissues and cancer. However, the Eph/ephrin expression profile in human skin is only marginally studied. We therefore investigated the mRNA expression of 21 Eph receptors and ephrin ligands in adult human skin in comparison to 13 other adult human tissues using quantitative real-time RT-PCR. In addition, immunohistochemistry was established for some members (EphA1, EphA2 and EphA7) to confirm the results of the RT-PCR and to identify the expressing cells in the skin. We found all investigated family members expressed in human skin, but at highly varying levels. EphA1, EphB3 and ephrin-A3 turned out to be most prominently expressed in skin compared to other adult human tissues. EphA1 was exclusively expressed in the epidermis. We therefore investigated the expression of EphA1 in nonmelanoma skin cancers derived from the epidermis (56 basal cell carcinomas and 32 squamous cell carcinomas). As demonstrated by immunohistochemistry, both skin cancers displayed a significant downregulation of EphA1 compared to the normal epidermis. In squamous cell carcinoma, the EphA1 downregulation was associated with increased tumor thickness, although this was not significant. Our results indicate that Eph receptors and ephrin ligands are widely expressed in the adult human skin, particularly in the epidermis, and may play an important role in skin homeostasis. EphA1 seems to be a marker of the differentiated normal epidermis and its downregulation in nonmelanoma skin cancer may contribute to carcinogenesis of these very frequent human tumors. EphA1 represents a new potential prognostic marker and therapeutic target in nonmelanoma skin cancer.

Adult↗
PubMed2006

Loss of dipeptidyl peptidase IV immunostaining discriminates malignant melanomas from deep penetrating nevi.

The deep penetrating nevus is a rare variant of benign melanocytic nevus with histologic features mimicking vertical growth phase, nodular malignant melanoma. In this study, we expand on the search for new complementary discriminating markers by analyzing a selection of both cell cycle-related factors, such as retinoblastoma protein and phospho-retinoblastoma protein Ser795 as indicators for retinoblastoma protein activation/inactivation status, and invasion-related factors, such as matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3. MIB-1/Ki-67 was analyzed as an example for a common proliferation marker. Dipeptidyl peptidase IV/CD26 was analyzed as a marker affecting both proliferation and invasion of malignant melanocytic tumors. Semiquantitative assessment of both immunolocalization and immunoreactivity of retinoblastoma protein and phospho-retinoblastoma protein Ser795, MIB-1/Ki-67, matrix metalloproteinase-1, matrix metalloproteinase-2, membrane-type matrix metalloproteinase-1 and integrin beta3 revealed no consistent differences between deep penetrating nevi (n=14) and matched cases of nodular malignant melanomas (n=10). Matrix metalloproteinase-1 and matrix metalloproteinase-2 immunostaining of some deep penetrating nevi even exceeded that of nodular malignant melanomas. Membrane-type matrix metalloproteinase-1 expression scores of nodular malignant melanomas were higher than those of deep penetrating nevi, which was, however, not significantly discriminative. In contrast, immunostaining of dipeptidyl peptidase IV was significantly discriminative due to a consistent lack of dipeptidyl peptidase IV-expression in nodular malignant melanomas. These results add evidence that among the selected markers supposed to be relevant for melanoma progression the presence of dipeptidyl peptidase IV can be used to support diagnosis of deep penetrating nevi in doubtful cases. As loss of dipeptidyl peptidase IV may also be causally linked to the transition of invasive to metastatic phenotypes, the molecular mechanisms downstream of dipeptidyl peptidase IV deserve to be studied in more detail in future investigations.

Adenosine Deaminase↗
PubMed2006

High frequency of FGFR3 mutations in adenoid seborrheic keratoses.

FGFR3 germline mutations cause autosomal dominant skeletal disorders including achondroplasia, thanatophoric dysplasia, severe achondroplasia with developmental delay and acanthosis nigricans, and Crouzon syndrome. Somatic mutations of FGFR3 have been identified in bladder cancer, multiple myeloma, and other neoplasms. FGFR3 mutations have also been detected in 40% of seborrheic keratoses (SKs) of the hyperkeratotic and acanthotic subtype, which are very common benign skin tumors. Using a multiplex SNaPshot assay that covers 11 activating FGFR3 mutations, we investigated a series of 27 SKs of the adenoid subtype. Mutations were detected in 23 of 27 (85%) adenoid SKs. R248C mutations were the most frequent mutation type. In two SKs, the A393E mutation was found, which has not been described in acanthotic and hyperkeratotic SKs so far. Three adenoid SKs displayed two simultaneous FGFR3 mutations. Adenoid SKs seem to be characterized by a higher frequency of FGFR3 mutations than hyperkeratotic and acanthotic SKs. The mechanism for the high rate of somatic FGFR3 mutations in these benign skin tumors remains elusive, but UV light exposure may play a potential role, especially in the R248C mutations.

Aged↗
PubMed2006

Synthesis and structure of the bilayer hydrate Na0.3NiO2.1.3D2O.

The metal oxide bilayer deuterate (hydrate) Na(0.3)NiO2.1.3D2O (Na(0.3)NiO2.1.3H2O) were prepared from NaxNiO2 by extracting Na+ cations and simultaneously intercalating fully and nondeuterated water. High-resolution neutron powder diffraction, thermogravimetric analysis, and inductively coupled plasma atomic emission spectroscopy were used to show that a Na(0.3)(D2O)(1.3) network separates layers of edge-sharing NiO6 octahedra.

Journal Article↗
PubMed2006

Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells.

The loss of cell cycle control in malignant melanomas is thought to be due to a lack of retinoblastoma protein (pRb) activity. We have recently reported a progressive deficiency of the retinoblastoma-binding protein 2-homolog 1 (RBP2-H1) in advanced and metastatic melanomas in vivo, suggesting a role of RBP2-H1 in loss of pRb-mediated control. Therefore, in this study, we re-established the pRb-modulating function of RBP2-H1 in highly metastatic A375-SM melanoma cells by re-expressing its C-term (cRBP2-H1). As previously shown, the corresponding domains comprise the pRb-binding region of the RBP2-H1 protein (non-T/E1A-pRb-binding domain (NTE1A)). As a result, we detected pRb-hypophosphorylation selectively at Ser795, but not at Ser780 and Ser807/811 throughout the G1 phase of the cell cycle. As a further consequence, a block in G1/S transition was observed accompanied by a significant decrease of DNA replication and cellular proliferation. As demonstrated by cDNA microarrays of cRBP2-H1-transduced cells and confirmed by quantitative TaqMan reverse transcriptase-PCR, differential expression of melanoma-progression-related genes was observed, among them bone morphogenetic protein 2, follistatin, transforming growth factor alpha, hepatocyte growth factor, transcription factor 4 and microphthalmia-associated transcription factor. Conclusively, these data suggest that RBP2-H1 exerts a broad tumor-suppressive function partially mediated by pRb modulation. Therefore, re-establishing of RBP2-H1 could evolve as an interesting novel approach in developing experimental treatments for metastatic melanomas.

Cell Division↗
PubMed2006

Tissue microarray analysis of methylthioadenosine phosphorylase protein expression in melanocytic skin tumors.

BACKGROUND: Using tissue microarrays, we investigated whether methylthioadenosine phosphorylase (MTAP) protein expression is associated with clinicopathologic variables in benign and malignant melanocytic skin tumors. OBSERVATIONS: Cytoplasmic MTAP expression was detected in 227 (72.1%) of 315 informative cases. Expression was significantly reduced in primary malignant melanomas and in melanoma metastases compared with benign nevi (P<.001 for both). No difference was noted in MTAP expression between primary malignant melanomas and melanoma metastases. In primary malignant melanomas, a Ki67-labeling index less than 5% was associated with MTAP expression (P = .04), suggesting that loss of MTAP expression is associated with proliferation. No other variables had significant associations with MTAP expression. Lymph node metastases demonstrated significantly higher MTAP expression compared with skin metastases (P = .01). In the overall cohort, MTAP expression was not associated with prognosis. Among 26 patients with MTAP-positive melanomas and tumor recurrence, 18 patients who received interferon therapy had a significant benefit compared with 8 patients who did not receive interferon therapy (P = .009). This was not seen in the patients with MTAP-negative tumors. Conclusion Methylthioadenosine phosphorylase protein expression may be a predictive marker of interferon therapy resistance in patients with melanoma and disease progression.

Antineoplastic Agents↗
PubMed2006

[Stroma-targeted palliative tumor therapy with biomodulators].

In search of new strategies for the therapy of advanced tumors stroma-targeted approaches have been discussed recently, especially antiangiogenic therapies. It has turned out that some biomodulating drugs exhibit also effects against tumors beyond their original non-oncologic indication. Among these drugs are for example thalidomide,COX-2 inhibitors, PPARgamma agonists (thiazolidindiones) and mTOR antagonists (rapamycin). The antitumor efficacy of these therapeutics is fundamentally based on indirect effects on the stroma of the tumors. Combination therapies of these therapeutics seem to be superior to the use of single agents. These new biomodulating therapy approaches represent an interesting option for the palliative treatment of advanced tumors, especially as a supplement or extension of established chemo- and immunotherapeutic therapies, since they can be performed in an outpatient setting, the observed side effects are usually mild, and the therapies are therefore well accepted by the patients.

Animals↗
PubMed2006

Targeting T cells to hit B cells: successful treatment of cutaneous plasmacytosis with topical pimecrolimus.

Cutaneous plasmacytosis is a rare disease predominantly found in Japanese patients. We describe the case of a 75-year-old white female with cutaneous plasmacytosis of the face and involvement of the bone marrow. In contrast to other cases of cutaneous plasmacytosis, the patient revealed hypogammaglobulinemia and elevated levels of free light chains in the urine. Treatment with topical pimecrolimus 1%, which primarily targets T cells, led to almost complete clinical and histological remission of the skin lesions. Our report indicates that the therapeutically induced disappearance of the plasma cells was due to indirect T-cell-mediated effects.

Aged↗
PubMed2006

Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi.

Epidermal nevi are common congenital skin lesions with an incidence of 1 in 1,000 people; however, their genetic basis remains elusive. Germline mutations of the FGF receptor 3 (FGFR3) cause autosomal dominant skeletal disorders such as achondroplasia and thanatophoric dysplasia, which can be associated with acanthosis nigricans of the skin. Acanthosis nigricans and common epidermal nevi of the nonorganoid, nonepidermolytic type share some clinical and histological features. We used a SNaPshot multiplex assay to screen 39 epidermal nevi of this type of 33 patients for 11 activating FGFR3 point mutations. In addition, exon 19 of FGFR3 was directly sequenced. We identified activating FGFR3 mutations, almost exclusively at codon 248 (R248C), in 11 of 33 (33%) patients with nonorganoid, nonepidermolytic epidermal nevi. In 4 of these cases, samples from adjacent histologically normal skin could be analyzed, and FGFR3 mutations were found to be absent. Our results suggest that a large proportion of epidermal nevi are caused by a mosaicism of activating FGFR3 mutations in the human epidermis, secondary to a postzygotic mutation in early embryonic development. The R248C mutation appears to be a hot spot for FGFR3 mutations in epidermal nevi.

Adolescent↗
PubMed2006

Generation and characterization of a humanized bradykinin B1 receptor mouse.

Antagonists of the B1 bradykinin receptor (B1R), encoded by the BDKRB1 gene, offer the promise of novel therapeutic agents for inflammatory and neuropathic pain. However, the in vivo characterization of the pharmacodynamics of B1R antagonists is hindered by the low level of B1R expression in healthy tissue and the profound species selectivity exhibited by many compounds for the B1R. To circumvent these issues we generated two genetically engineered rodent models. The first is a transgenic rat over-expressing the human B1R under the control of the neuronal-specific enolase promoter; we previously reported the utility of this model in assessing human B1R receptor occupancy in the central nervous system of the rat. The second model, reported here, utilized gene-targeting by homologous recombination to replace the genomic coding sequence for the endogenous mouse B1R with that of the human B1R. The mRNA expression profile of the humanized Bdkrb1 (hBkdrb1) allele is similar to that of the mouse Bdkrb1 (mBkdrb1) in the wild-type animal. Furthermore, in vitro assays indicate that tissues isolated from the humanized mouse possess pharmacological properties characteristic of the human B1R. Therefore, we have generated a humanized B1R mouse model that is suitable for testing the efficacy of human B1R-selective compounds.

Acetamides↗
PubMed2005

Pressure induced octahedral tilting distortion in Ba2YTaO6.

Herein we communicate the first example of a pressure induced octahedral tilting distortion in a double perovskite phase, which was observed during the structural characterization of Ba2YTaO6 using high-pressure synchrotron X-ray powder diffraction.

Journal Article↗
PubMed2005

Temozolomide in combination with interferon-alfa versus temozolomide alone in patients with advanced metastatic melanoma: a randomized, phase III, multicenter study from the Dermatologic Cooperative Oncology Group.

PURPOSE: Temozolomide (TMZ) has shown efficacy in metastatic melanoma equal to that of dacarbazine (DTIC), the standard chemotherapeutic agent for melanoma. As the combination with interferon-alfa (IFN-alpha) appears superior to single-agent DTIC regarding response rates, the purpose of this study was to compare TMZ alone and TMZ plus IFN-alpha in terms of objective response (OR), overall survival, and safety in a prospective, randomized, multicenter trial. PATIENTS AND METHODS: Two hundred ninety-four patients with untreated stage IV metastatic melanoma (American Joint Committee on Cancer staging system) were randomly assigned to receive either oral TMZ alone (200 mg/m2/day; days 1 through 5 every 28 days) or in combination with subcutaneous IFN-alpha (5 MU/m2; days 1, 3, and 5 every week). RESULTS: Two hundred eighty-two patients were eligible for an intent-to-treat analysis, 271 patients were treated per protocol. In the TMZ + IFN-alpha arm, 33 (24.1%) of 137 patients responded to therapy (partial or complete remission) whereas in the monotherapy arm, in 18 (13.4%) of 134 patients, a response was evident. Thus, the response rate was significantly higher in the combination arm (P = .036). Median survival time was 8.4 months for patients treated with TMZ (95% CI, 7.07 to 9.27) and 9.7 months for those treated with the combination (95% CI, 8.26 to 11.18; P = .16). Dose modifications and interval prolongations due to hematologic toxicity were significantly more frequent in the TMZ + IFN-alpha arm (P < .001). CONCLUSION: In metastatic melanoma treatment with TMZ + IFN-alpha leads to a significantly superior OR rate compared to treatment with TMZ alone, which did not translate into prolonged survival in our study population.

Adult↗
PubMed2005

High-pressure neutron diffraction study of superhydrated natrolite.

Neutron powder diffraction data were collected on a sample of natrolite and a 1:1 (v/v) mixture of perdeuterated methanol and water at a pressure of 1.87(11) GPa. The natrolite sample was superhydrated, with a water content double that observed at ambient pressure. All of the water deuterium atoms were located and the nature and extent of the hydrogen bonding elucidated for the first time. This has allowed the calculation of bond valence sums for the water oxygen atoms, and from this, it can be deduced that the key energetic factor leading to loss of the additional water molecule upon pressure release is the poor coordination to sodium cations within the pores.

Journal Article↗
PubMed2005

Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells.

AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS: Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix(R) rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair-related genes is also accompanied by activation of the ERK1/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

Animals↗
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↗