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Thomas Vogt

Publications and source records attributed to Thomas Vogt.

At least 55 records · Page 3Linked to original sources
PubMed2004

Cations modulate the substrate specificity of bifunctional class I O-methyltransferase from Ammi majus.

Caffeoyl-coenzyme A O-methyltransferase cDNA was cloned from dark-grown Ammi majus L. (Apiaceae) cells treated with a crude fungal elicitor and the open reading frame was expressed in Escherichia coli. The translated polypeptide of 27.1-kDa shared significant identity to other members of this highly conserved class of proteins and was 98.8% identical to the corresponding O-methyltransferase from parsley. For biochemical characterization, the recombinant enzyme could be purified to apparent homogeneity by metal-affinity chromatography, although the recombinant enzyme did not contain any affinity tag. Based on sequence analysis and substrate specificity, the enzyme classifies as a cation-dependent O-methyltransferase with pronounced preference for caffeoyl coenzyme A, when assayed in the presence of Mg2+-ions. Surprisingly, however, the substrate specificity changed dramatically, when Mg2+ was replaced by Mn2+ or Co2+ in the assays. This effect could point to yet unknown functions and substrate specificities in situ and suggests promiscuous roles for the lignin specific cluster of plant O-methyltransferases.

Acyl Coenzyme A↗
PubMed2004

Pioglitazone and rofecoxib combined with angiostatically scheduled trofosfamide in the treatment of far-advanced melanoma and soft tissue sarcoma.

BACKGROUND: Combined treatment approaches targeting tumor cells as well as stromal cells may control chemorefractory malignancies. In the current study, the authors sought to test one such combined approach in the treatment of chemorefractory melanoma and soft tissue sarcoma. METHODS: A Phase II trial was initiated to analyze the activity of a continuously administered molecularly targeted treatment regimen (daily pioglitazone [45 mg administered orally] and rofecoxib [25 mg administered orally]) combined with sequentially added angiostatic chemotherapy for patients with previously treated metastatic melanoma (n = 19) or soft tissue sarcoma (n = 21). Angiostatic chemotherapy consisted of trofosfamide (50 mg) administered orally 3 times daily beginning on the 15th day after the start of molecularly targeted therapy. RESULTS: Forty patients were evaluable for response and toxicity. Major side effects (World Health Organization Grade 3 or 4) were not observed. Objective responses and disease stabilization lasting longer than 6 months were noted in 11% and 11%, respectively, of all patients with melanoma and in 19% and 14%, respectively, of all patients with soft tissue sarcoma. Complete remission was noted in one patient with melanoma and in three patients with sarcoma. Both normal C-reactive protein (CRP) levels and CRP levels that decreased by > 30% during the 14-day biomodulator pretreatment period were found to be predictive of prolonged progression-free survival. CONCLUSIONS: To our knowledge, the current study is the first to demonstrate that a novel, completely orally administered combined biomodulator/metronomic chemotherapy regimen may be active and well tolerated in patients with chemorefractory malignancies.

Administration, Oral↗
PubMed2004

Synchrotron X-ray powder diffraction and computational investigation of purely siliceous zeolite Y under pressure.

High-pressure synchrotron X-ray powder diffraction measurements of a sample of purely siliceous zeolite Y (faujasite) were carried out up to 8.0 GPa at room temperature using a diamond anvil cell. Measurements using silicone oil as the pressure-transmitting medium show compression of the zeolite followed by a loss of long-range ordering at 2.2 GPa. The experimentally determined bulk modulus, 38(2) GPa, is, within experimental error, identical to that of quartz. When using a methanol:ethanol:water mixture (16:3:1) as the pressure-transmitting medium, two distinct compressibility regions are observed with a dramatic change in the compression mechanism at 4 GPa. Rietveld refinement analysis of the powder patterns provides a detailed description of the underlying chemistry, with sequential pore filling the main response up to 4 GPa and framework distortions at higher pressures.

Journal Article↗
PubMed2004

The dopamine D2 receptor ligand 18F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism.

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinson's disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D2 receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D2 receptor antagonist fluorine-18 desmethoxyfallypride (18F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180-200 MBq 18F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of 18F-DMFP PET. We found the striatal 18F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44+/-0.42) compared with the healthy control subjects (3.61+/-0.43) and the IPS patients (3.21+/-0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate 18F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider 18F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than 11C-labelled D2 radioligands.

Adult↗
PubMed2004

Regiospecificity and kinetic properties of a plant natural product O-methyltransferase are determined by its N-terminal domain.

A recently discovered, S-adenosyl-L-methionine and bivalent cation-dependent O-methyltransferase from the ice plant, Mesembryanthemum crystallinum, is involved in the methylation of various flavonoid and phenylpropanoid conjugates. Differences in regiospecificity as well as altered kinetic properties of the recombinant as compared to the native plant O-methyltransferase can be attributed to differences in the N-terminal part of the protein. Upon cleavage of the first 11 amino acids, the recombinant protein displays essentially the same substrate specificity as observed earlier for the native plant enzyme. Product formation of the newly designed, truncated recombinant enzyme is consistent with light-induced accumulation of methylated flavonoid conjugates in the ice plant. Therefore, substrate affinity and regiospecificity of an O-methyltransferase in vivo and in vitro can be controlled by cleavage of an N-terminal domain.

Flavonoids↗
PubMed2004

Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers.

BACKGROUND: Eph receptors and their ligands, the ephrins, represent a large class of cell-cell communication molecules with well-defined developmental functions. Their role in healthy adult tissues and in human disease is still largely unknown, although diverse roles in carcinogenesis have been postulated. METHODS: We established a set of fluorescent PCR probes and primers for the definition of individual gene expression profiles of 12 different Eph receptors and 8 ephrins in 13 different healthy tissues. The mRNA expression profiles were studied in human lung, colorectal, kidney, liver, and brain cancers. RESULTS: The family of Eph receptors/ephrins was widely expressed in adult tissues with organ-site-specific patterns: EphB6 was highest in the thymus, compatible with an involvement in T-cell maturation. Brain and testis shared a unique pattern with EphA6, EphA8, and EphB1 being the most prominent. EphA7 had a high abundance in the kidney vasculature. Ephrin-A3 was up-regulated 26-fold in lung cancer, and EphB2 was up-regulated 9-fold in hepatocellular carcinoma. EphA8 was down-regulated in colon cancer, and EphA1/EphA8 was down-regulated in glioblastomas. CONCLUSION: Eph/Ephrin genes are widely expressed in all adult organs with certain organ-site-specific patterns. Because their function in adult tissues remains unknown, further analysis of their role in disease may disclose new insights beyond their well-defined meaning in development.

Adult↗
PubMed2004

Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic kaposi sarcoma.

BACKGROUND: Kaposi sarcoma (KS) in patients who are seronegative and seropositive for human immunodeficiency virus is currently the most common malignant tumor in central Africa. It accounts for 50% of all tumors reported in central African countries. Owing to the rising number of patients and the limitations of current therapies, there is an urgent demand for new strategies to treat KS. OBSERVATION: We describe a 42-year-old dark-skinned patient from Mozambique with endemic KS. The tumor was first diagnosed 8 years earlier when an ulcerated nodule appeared at his right ankle joint. Subsequently, multiple reddish brown nodules appeared on both feet and the left thigh. Results of dermatohistopathological analysis confirmed the diagnosis of KS. Topical therapies including cryotherapy, carbon-dioxide laser, and photodynamic therapy could not prevent new recurrences and further cutaneous dissemination. Therefore, a novel antiangiogenic systemic therapy was started that was previously shown to be effective in angiosarcomas other than KS. The regimen consists of the biomodulators pioglitazone hydrochloride and rofecoxib combined with a metronomic (daily) low-dose chemotherapy with trofosfamide. We observed a partial remission, which has been stable for 18 months. No significant toxic effects were observed. CONCLUSION: The suggested antiangiogenic strategy has the potential to become a cheap, practical, feasible alternative treatment for endemic KS, particularly suitable for the outpatient setting.

Adult↗
PubMed2004

Discrimination of melanocytic tumors by cDNA array hybridization of tissues prepared by laser pressure catapulting.

Gene expression profiling by cDNA array analysis in melanoma is hampered by the need for large amounts of RNA to prepare reliable probes for array hybridization. On the other hand, for ex vivo analysis of malignant cells from melanocytic tumors laser pressure catapulting is an essential prerequisite to obtain noncontaminated melanocytic preparations; however, laser pressure catapulting prepared material provides only nanogram amounts of RNA. In this study we present an approach to overcome these limitations by combining laser pressure catapulting and real-time polymerase chain reaction based SMART cDNA amplification technology. Reproducible and reliable hybridization patterns from about 500 laser pressure catapulting prepared cell equivalents from 22 cases of melanocytic tumors were generated using array analysis. Univariate analysis revealed significant differences of the expression pattern of melanocytic nevi, melanomas, and melanoma metastases. Multivariate analysis with four genes being the best univariate discriminative features (tyrosinase related protein 2, translation initiation factor 2 gamma, ubiquitine conjugating enzyme E2I and one expressed sequence tag) allowed clustering of nevi, melanomas, and melanoma metastases with an accuracy of 82%. Data validation was performed by additional quantitative reverse transcription-polymerase chain reaction (TaqMan-reverse transcription-polymerase chain reaction). Taken together, this study shows, that (1) array analysis is feasible on tumors with rather low cell numbers, and (2) differences in expression profiles allow discrimination between benign and malignant lesions. Expression patterns of marker genes defined in unequivocal histopathologic entities may improve the diagnostic and prognostic assessment of difficult melanocytic lesions, which is still the hardest problem in dermatopathology.

Biopsy↗
PubMed2004

Progressive hyperpigmentation and generalized lentiginosis without associated systemic symptoms: a rare hereditary pigmentation disorder in south-east Germany.

Familial progressive hyperpigmentation is rarely described in the literature. We report on five patients from three different families presenting with a peculiar progressive pigmentary disorder. The patients show a progressive diffuse, partly blotchy, hyperpigmentation, intermixed with scattered small hypopigmented macules, a few large hypopigmented areas, occasional café-au-lait spots and, most remarkably, a generalized lentiginosis. Histology revealed different degrees of basal layer hyperpigmentation and pigment incontinence, also in the spots appearing hypopigmented. Ultrastructural analysis showed a normal mode of Caucasian-like melanogenesis with varying content of regular melanosome complexes within the keratinocytes. All families are clustered in a small area around the town of Teublitz in south-east Germany with about 20,000 inhabitants, suggesting a genetic founder effect. Pedigree analysis is compatible with an autosomal dominant mode of inheritance with variable penetrance. Only a few similar, but not identical, cases have been reported in the past. This cluster of cases may therefore represent a rare and perhaps novel variant of a familial progressive disorder of hyperpigmentation.

Adolescent↗
PubMed2004

Site-directed mutagenesis and protein 3D-homology modelling suggest a catalytic mechanism for UDP-glucose-dependent betanidin 5-O-glucosyltransferase from Dorotheanthus bellidiformis.

In livingstone daisy (Dorotheanthus bellidiformis), betanidin 5-O-glucosyltransferase (UGT73A5) is involved in the regiospecific glucosylation of betanidin and various flavonols. Based on sequence alignments several amino acid candidates which might be essential for catalysis were identified. The selected amino acids of the functionally expressed protein, suggested to be involved in substrate binding and turnover, were substituted via site-directed mutagenesis. The substitution of two highly conserved amino acids, Glu378, located in the proposed UDP-glucose binding site, and His22, located close to the N-terminus, led to the complete loss of enzyme activity. A 3D model of this regiospecific betanidin and flavonoid glucosyltransferase was constructed and the active site modelled. This model was based on the crystallographic structure of a bacterial UDP-glucose-dependent glucosyltransferase from Amycolatopsis orientalis used as a template and the generated null mutations. To explain the observed inversion in the configuration of the bound sugar, semiempirical calculations favour an SN-1 reaction, as one plausible alternative to the generally proposed SN-2 mechanism discussed for plant natural product glucosyltransferases. The calculated structural data do not only explain the abstraction of a proton from the acceptor betanidin, but further imply that the reaction mechanism might also involve a catalytic triad, with similarities described for the serine protease family.

Aizoaceae↗
PubMed2004

Lentigo maligna and lentigo maligna melanoma in young adults.

BACKGROUND: We observed two young women with skin types II to III according to Fitzpatrick's classification who developed pigmented macules in the face that were histologically diagnosed as lentigo maligna melanomas. OBJECTIVE: The objective of this study was to examine lentigo maligna melanoma in young adults. METHODS: According to private photographs of one of those patients a precursor lesion was clinically apparent as early as in her 26th year. Ten years later, the diagnosis of a lentigo maligna melanoma was made. The other patient was diagnosed with lentigo maligna at the age of 37. After excision, a relapse occurred in her 39th year. At this time histopathology revealed an early invasive lentigo maligna melanoma. RESULTS: These case reports demonstrate that the diagnosis of both lentigo maligna and lentigo maligna melanoma cannot be dismissed because of young age or well-tanning skin types. CONCLUSION: We conclude that owing to changes in social behavior and sporting activities with high short-term ultraviolet exposures, one must be aware of the possibility of an unusual early onset of lentigo maligna and lentigo maligna melanoma already in the third and fourth decade of life. Furthermore, our observations support the effectiveness of dermatoscopy in diagnosing ambiguous pigmented skin lesions in sun-exposed skin.

Adult↗
PubMed2004

Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis.

BACKGROUND: Pimecrolimus cream 1% is a non-steroid, selective inflammatory cytokine inhibitor indicated for atopic dermatitis (AD). OBJECTIVE: To compare the safety and efficacy of pimecrolimus cream 1%-based treatment versus conventional therapy in adults with moderate AD. METHODS: Patients were randomized to receive pimecrolimus cream 1% (n = 62) or vehicle (n = 68) at the first signs/symptoms of AD, for 24 weeks as required. A moderately potent topical corticosteroid (prednicarbate 0.25% cream) was allowed in both groups to treat flares. RESULTS: Corticosteroids were required on fewer days in the pimecrolimus group, compared with the vehicle group (9.7 vs. 37.8%, p < 0.001). Furthermore, 59.7% of pimecrolimus-treated patients experienced no flares during the study period, compared with 22.1% of vehicle-treated patients (p < 0.001). Pimecrolimus cream 1% was well tolerated throughout the study. CONCLUSION: For adults with moderate AD, pimecrolimus cream 1% is well tolerated, reduces the incidence of flares, reduces/eliminates corticosteroid use, improves long-term disease control and enhances the patients' quality of life.

Administration, Cutaneous↗
PubMed2003

Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors.

BACKGROUND: Systemic therapy options for patients with advanced angiosarcomas are limited, and their prognosis is poor. The idea of angiostatic therapy following the paradigm of metronomic dosed chemotherapeutics combined with proapoptotic biomodulators had not been considered previously in these patients. Therefore, in a pilot study, the efficacy of metronomically scheduled, low-dose trofosfamide in combination with the peroxisome proliferator-activated receptor gamma agonist, pioglitazone, and the selective cyclooxygenase-2 inhibitor, rofecoxib, was evaluated in patients with advanced vascular malignancies. METHODS: Six patients with advanced and pretreated but progressive, malignant vascular tumors (5 angiosarcomas and 1 hemangioendothelioma) received a combination of pioglitazone (45 mg per day orally) plus rofecoxib (25 mg per day orally) and, after 14 days, trofosfamide (3 x 50 mg per day orally). The therapy was administered continuously until progression was observed. If necessary, doses were modified according to side effects. RESULTS: Two patients responded with complete remission of disease, one patient responded with partial remission, and three patients achieved stabilization of disease (no change). The median progression-free survival was 7.7 months (range, 2-15 months). Side effects generally were mild (World Health Organization Grade 1-2). Hospitalization was not necessary. CONCLUSIONS: This new triple combination of low-dose metronomic trofosfamide, pioglitazone, and rofecoxib may represent a feasible new alternative in the palliative treatment of patients with advanced malignant vascular tumors.

Administration, Oral↗
PubMed2003

Doping gamma-Fe(2)O(3) nanoparticles with Mn(III) suppresses the transition to the alpha-Fe(2)O(3) structure.

Here we report on a mixed oxide system, gamma-Fe2O3 nanoparticles doped with Mn(III), where the transition from the cubic to the more stable hexagonal alpha-Fe2O3 structure is suppressed. When amorphous Fe2O3 is heated at 300 degrees C for 3 h, ferrimagnetic gamma-Fe2O3 is observed as the sole product. On the other hand, when the temperature is raised to 500 degrees C, one observes only antiferromagnetic alpha-Fe2O3 as the product. However, upon doping with 8.5 wt % Mn(III), the amorphous nanoparticles crystallized to mainly the gamma-Fe2O3 matrix after heating at 500 degrees C for 3 h, and need to be heated to >650 degrees C for the complete transition to the alpha-Fe2O3 structure to take place.

Journal Article↗
PubMed2003

A novel Mg(2+)-dependent O-methyltransferase in the phenylpropanoid metabolism of Mesembryanthemum crystallinum.

Upon irradiation with elevated light intensities, the ice plant (Mesembryanthemum crystallinum) accumulates a complex pattern of methylated and glycosylated flavonol conjugates in the upper epidermal layer. Identification of a flavonol methylating activity, partial purification of the enzyme, and sequencing of the corresponding peptide fragments revealed a novel S-adenosyl-l-methionine-dependent O-methyltransferase that was specific for flavonoids and caffeoyl-CoA. Cloning and functional expression of the corresponding cDNA verified that the new methyltransferase is a multifunctional 26.6-kDa Mg(2+)-dependent enzyme, which shows a significant sequence similarity to the cluster of caffeoyl coenzyme A-methylating enzymes. Functional analysis of highly homologous members from chickweed (Stellaria longipes), Arabidopsis thaliana, and tobacco (Nicotiana tabacum) demonstrated that the enzymes from the ice plant, chickweed, and A. thaliana possess a broader substrate specificity toward o-hydroquinone-like structures than previously anticipated for Mg(2+)-dependent O-methyltransferases, and are distinctly different from the tobacco enzyme. Besides caffeoyl-CoA and flavonols, a high specificity was also observed for caffeoylglucose, a compound never before reported to be methylated by any plant O-methyltransferase. Based on phylogenetic analysis of the amino acid sequence and differences in acceptor specificities among both animal and plant O-methyltransferases, we propose that the enzymes from the Centrospermae, along with the predicted gene product from A. thaliana, form a novel subclass within the caffeoyl coenzyme A-dependent O-methyltransferases, with potential divergent functions not restricted to lignin monomer biosynthesis.

Acyl Coenzyme A↗
PubMed2003

Pressure-induced cation migration and volume expansion in the defect pyrochlores ANbWO6 (A = NH4+, Rb+, H+, K+).

The structural and compositional evolution of four members of the ANbWO(6) (A = NH4+, Rb+, H+, K+) defect pyrochlore family have been studied as a function of pressure up to 7 GPa, using a diamond anvil cell and monochromatic synchrotron X-ray powder diffraction. In response to increasing hydrostatic pressure, NH(4)NbWO(6) and RbNbWO(6) both initially contract but then undergo a fairly abrupt increase in their unit cell volumes above a characteristic threshold pressure. NH(4)NbWO(6) exhibits a 5.8% increase in the cubic unit cell edge once the pressure exceeds approximately 3.4 GPa, while the RbNbWO(6) unit cell expansion is larger ( approximately 7.5%) but less abrupt, beginning near 3.0 GPa. Rietveld refinements reveal that the reversible expansion is driven by insertion of water into the structural channels that interpenetrate the NbWO(6)(-) octahedral corner sharing framework. The insertion of extra water is accompanied by displacement of the NH(4)(+) or Rb(+) ions to a smaller site in the channel structure, which triggers the pressure-induced expansion of the pyrochlore framework. This mechanism explains the counterintuitive expansion of the pyrochlore framework in response to application of external pressure. It should be noted that the expansion exhibited by the pyrochlore framework must coincide with a decrease in the volume of the hydrostatic fluid so that the net volume of the system decreases with increasing pressure. Similar behavior is not observed for KNbWO(6).H(2)O or HNbWO(6).H(2)O, both of which contract in response to increasing pressure. For these smaller monovalent cations, pressure-induced volume expansion does not occur because the hydrated state and subsequent cation shift are already stable at ambient conditions.

Journal Article↗