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Andreas Schmidt

Publications and source records attributed to Andreas Schmidt.

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

Bone morphogenetic protein 2 (BMP-2) induces in vitro invasion and in vivo hormone independent growth of breast carcinoma cells.

Breast cancer cell lines migrated towards a BMP-2 source depending on BMP-2 concentration. After a short exposure to BMP-2, the cells were able to migrate through matrigel. MCF-7 cells transfected with the BMP-2 gene also showed enhanced migratory properties and high expression of the metastasis-related gene BCSG1. In a xenograft model without estrogen supplementation MCF-7/BMP-2 cells formed tumors. These tumors were characterised by an enhanced vasculature and the formation of chondroid and osseous structures. In conclusion elevated levels of BMP-2 enhance the tumorigenic properties of breast carcinoma cells and drive the cells towards a more aggressive phenotype with estrogen independent growth.

Animals↗
PubMed2004

A short autonomous repression motif is located within the N-terminal domain of CTCF.

The vertebrate transcription factor CTCF is not only involved in transcriptional activation, insulation and genomic imprinting, but also in transcriptional repression. Sequence motifs mediating these activities have not been identified so far. We have mapped a short repression motif to residues 150-170 within the N-terminal domain of CTCF. This motif is active in HeLa, HEK293 and COS-7 cell lines where it is both sufficient and necessary for silencing either an SV40-, or a CMV-enhancer. It also represses the basal activity of an SV40 core promoter. Since this autonomous repression motif displays no sequence similarity to any other regulatory protein, it represents a yet unknown co-repressor recruiting motif.

Animals↗
PubMed2004

Transactivator mutants with altered effector specificity allow selective regulation of two genes by tetracycline variants.

A set of Tet repressor (TetR) based eukaryotic transactivators that respond to 4-de(dimethylamino)-6-deoxy-6-demethyl-tetracycline (cmt3) but no longer to tetracycline (tc) is presented. The novel transactivators exhibit high activation in absence of an effector and a 200-fold reduction of reporter gene activity in the presence of cmt3. The most cmt3-sensitive mutant was coexpressed with a tc-responsive Tet transregulator harbouring an altered DNA recognition specificity. Use of cmt3 and tc yields independent control of expression of two genes in the same cell without crosstalk.

Cell Division↗
PubMed2004

Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency.

We generated a knockout mouse model for guanidinoacetate N-methyltransferase (GAMT) deficiency (MIM 601240), the first discovered human creatine deficiency syndrome, by gene targeting in embryonic stem cells. Disruption of the open reading frame of the murine GAMT gene in the first exon resulted in the elimination of 210 of the 237 amino acids present in mGAMT. The creation of an mGAMT null allele was verified at the genetic, RNA and protein levels. GAMT knockout mice have markedly increased guanidinoacetate (GAA) and reduced creatine and creatinine levels in brain, serum and urine, which are key findings in human GAMT patients. In vivo (31)P magnetic resonance spectroscopy showed high levels of PGAA and reduced levels of creatine phosphate in heart, skeletal muscle and brain. These biochemical alterations were comparable to those found in human GAMT patients and can be attributed to the very similar GAMT expression patterns found by us in human and mouse tissues. We provide evidence that GAMT deficiency in mice causes biochemical adaptations in brain and skeletal muscle. It is associated with increased neonatal mortality, muscular hypotonia, decreased male fertility and a non-leptin-mediated life-long reduction in body weight due to reduced body fat mass. Therefore, GAMT knockout mice are a valuable creatine deficiency model for studying the effects of high-energy phosphate depletion in brain, heart, skeletal muscle and other organs.

Animals↗
PubMed2004

An approach toward azacycles using photochemical and radical cyclizations of N-alkenyl substituted 5-thioxopyrrolidin-2-ones.

The photochemical reactions of a series of cyclic N-alkenyl-substituted thioimides have been examined. Irradiation of N-3-methylbut-3-enyl-5-thioxo-pyrrolidin-2-one (16) results in intramolecular [2 + 2] cycloaddition to give the highly strained thietane 17, whose structure was confirmed on the basis of its X-ray analysis. Treatment of cycloadduct 17 with dimethyl(methylthio)sulfonium tetrafluoroborate gave 2,5,6,7-tetrahydropyrrolizin-3-one (20) in good yield. Further reduction of 20 with Raney-Ni afforded 5,5-dimethylhexahydro-pyrrolizin-1-one (21). This sequence of reactions demonstrates the facility with which the 2 + 2 photoadduct can be converted into the pyrrolizidine alkaloid core skeleton. The photochemistry of the closely related N-butenyl thioxopyrrolidin-one (22) proceeded in a slightly different fashion and produced 7-mercaptomethyl tetrahydropyrrolizin-3-one (24) in 68% yield. In contrast to the above results, irradiation of the thioxaphthalimido system containing an N-cycloalkenyl group in the side chain gave rise to products derived by gamma-hydrogen abstraction from the n-pi triplet excited state. The photobehavior of the related N-3-alkenyl pyrrolidine-2,5-dithione system (62) was also studied and found to give products derived from both a 2 + 2 cycloaddition (63) and hydrogen atom transfer (64). Finally, the reaction of several N-alkenyl substituted thioimides (71-73) with tributylstannane in the presence of AIBN gave cyclized products derived from transient radical intermediates.

Journal Article↗
PubMed2004

A digital reference model of the human bronchial tree.

In-vitro preparations of the human lung combined with high-resolution tomography can be used to derive precise models of the human lung. To develop an abstract graph representation, specially adapted image processing algorithms were applied to segment and delineate the bronchi. The graph thus obtained contains topological information about spatial coordinates, connectivities, diameters and branching angles of 1453 bronchi up to the 17th Horsfield order. The graph was analyzed for statistical and fractal properties and was compared with current models. Results indicate a model that exhibits asymmetry and multifractal properties. This newly established reference model is an important step forward in geometrical accuracy of the bronchial tree representation that will improve both analysis of lung images in clinical imaging and the realism of functional simulations.

Adult↗
PubMed2003

On benzo[b][1,4]diazepinium-olates, -thiolates and -carboxylates as anti-Hückel mesomeric betaines.

2,3-Diaminophenol 4, 3,4-diaminophenol 5, 4-methoxy-1,2-diaminobenzene 6, 3,4-diaminobenzenethiol 7, 2,3-diaminobenzoic acid 8, and 3,4-diaminobenzoic acid 9 were reacted with 2,4-pentanedione to yield the corresponding benzo[b][1,4]diazepinium salts, respectively. The hydroxy-benzo[b][1,4]diazepinium salts 17 and 18 do not form mesomeric betaines (MB) on deprotonation. Instead, they are converted into the diimines 24 and 25. By contrast, the 7-mercaptobenzo[b][1,4]diazepinium salt 20 yields the corresponding thiolate on increasing the pH of the solution. This MB, which possesses 4n pi-electrons, does not fit into the classification system of heterocyclic mesomeric betaines accepted today. Deprotonation of the betaine results in the formation of an instable anionic thiolate 31 which oxidizes immediately to the disulfide 32. The carboxy derivatives 21 and 22 readily form cross-conjugated mesomeric betaines. Whereas the diimine 34 proved to be instable, the sodium salt of the diimine 36 was unambiguously characterized. An X-ray single crystal analysis of 22 as its picrate is presented in order to gain additional insights into these 4n pi-electron systems.

Journal Article↗
PubMed2003

New pyrazolium-carboxylates as structural analogues of the pseudo-cross-conjugated betainic alkaloid nigellicine.

Pyrazolium-3-carboxylates were examined as relatives of the betainic alkaloid Nigellicine and as new examples of the sparsely populated class 16 of heterocyclic pseudo-cross-conjugated mesomeric betaines (PCCMB). The title compounds were prepared in a 4-step procedure starting from beta-diketo compounds 8 which were cyclized with substituted hydrazines. The resulting isomeric pyrazole esters 9 and 10 were separated and subsequently quaternized with dimethyl sulfate in the presence of nitrobenzene to pyrazolium esters 11 and 12. Saponification was best accomplished in diluted sulfuric acid, which resulted in the formation of the pseudo-cross-conjugated mesomeric betaines 13 and 14 in one step. Protonation to the corresponding carboxylic acids required the treatment of the betaines with tetrafluoroboric acid in dichloromethane. The effect of negative solvatochromism proves the charge separation in the ground state of the molecules. X-ray crystallographic analyses, semiempirical calculations, and ESI mass spectrometric measurements were performed to gain knowledge about the phenomenon of pseudo-cross-conjugation.

Alkaloids↗
PubMed2003

Single-chain Tet transregulators.

We demonstrate here that the Tet repressor (TetR), a dimeric allosterical regulatory protein, can be converted to a fully functional monomer when connected by a 29 amino acid linker. TetR-based transregulators are widely used to regulate gene expression in eukaryotes. They can be fused to form single-chain (sc) Tet transregulators with two TetR moieties and one eukaryotic regulatory domain. Sc variants of transactivator and transsilencer exhibit the same regulatory properties as their respective dimeric counterparts in human cell lines. In particular, the reverse 'tet-on' phenotype of rtTA variants is also present in the sc variants. Coexpression of a reverse transactivator and sc transsilencer leads to reduced background expression and shows full activation upon induction. The data demonstrate that sc Tet transregulators exhibit the phenotype of their respective dimers and lack functional interference when coexpressed in the same cell.

Cell Line↗
PubMed2003

Simultaneous determination of leflunomide and its active metabolite, A77 1726, in human plasma by high-performance liquid chromatography.

The isoxazol derivative leflunomide [N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide] is an inhibitor of de novo pyrimidine synthesis used for the treatment of rheumatoid artrithis. In the present study, a liquid-liquid extraction-based reversed-phase HPLC method with UV detection was validated and applied for the analysis of leflunomide and its active metabolite, A77 1726, in human plasma. The analytes were separated using a mobile phase, consisting of acetonitrile, water and formic acid (40/59.8/0.2, v/v), at a flow rate of 0.5 mL/min, and UV detection at 261 nm. The retention times for A77 1726, leflunomide and warfarin (internal standard) were 8.2, 16.2 and 12.2 min, respectively. The validated quantification range of the method was 0.05-100 micro g/mL for leflunomide and 0.1-100 micro g/mL for A77 1726. The developed procedure was applied to assess steady-state plasma concentrations of A77 1726 in patients with rheumatoid arthritis treated with 10 or 20 mg leflunomide per day.

Aniline Compounds↗
PubMed2003

MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)-deficient mice: validation of an animal model to study creatine deficiency.

As a model for guanidinoacetate methyltransferase (GAMT) deficiency in humans, a gene knockout mouse model was generated. Here we report on several metabolic abnormalities in these mice, observed by in vivo and in vitro MR spectroscopy. In (1)H MR spectra of brain and hindleg muscle a clearly reduced signal of creatine (Cr) was observed in GAMT-deficient (GAMT-/-) animals. Analysis of the (1)H MR spectra of GAMT-/- brain indicated little or no increase of a signal for guanidinoacetate (Gua). In proton MR spectra of muscle, a broad signal of low intensity was observed for Gua. However, substantial Gua accumulation in intact muscle tissue was unequivocally confirmed in high-resolution magic angle spinning spectra, in which the Gua signal was resolved as one clear sharp singlet. In (31)P MR analysis of brain and hindleg muscle a strongly reduced phosphocreatine (PCr) content was shown. In addition, a signal of phosphorylated Gua at 0.5 ppm upfield of PCr was observed, with much higher intensity in muscle than in brain. This signal decreased when ischemia was applied to the muscle and recovered after ischemia was released. Overall, the in vivo (31)P and (1)H MR spectroscopy of GAMT-/- mice is similar to that of human GAMT deficiency. This opens up new avenues for the fundamental study of tissue-type dependence of creatine synthesis and transport and for diagnostic and therapeutic aspects of creatine deficiencies in humans.

Animals↗
PubMed2003

An estimation of the incidence of noma in north-west Nigeria.

Noma (cancrum oris, stomatitis gangrenosa) is a quickly spreading orofacial gangrene in children, caused by a combination of malnutrition, debilitation because of concomitant diseases (measles) and intraoral infections. The global incidence of noma in the world is uncertain. By comparing large numbers of noma patients and cleft lip patients in a large referral hospital for these disorders in Sokoto, Nigeria, we calculated the incidence of noma in north-west Nigeria as 6.4 per 1000 children. Extrapolation of this incidence to the developing countries bordering the Sahara Desert (the noma belt of the world) gives an incidence of 25,600 for that region and a global incidence of 30,000-40,000. Noma is a good biological parameter of extreme poverty, and hence a global monitoring system for noma can be justified. Though economic progress is the most effective preventive measure against noma, medical prevention by vaccination programmes against measles should be enhanced as well.

Adolescent↗
PubMed2003

Differential expression and regulation of bone morphogenetic protein 7 in breast cancer.

Bone morphogenetic protein 7 (BMP-7) is an important regulator of cell development and differentiation of various organs. Tumorigenesis and tumor progression are also strongly associated with changes of the fate of cells which are highly differentiated in healthy tissues. Therefore, we studied the role of BMP-7 in breast cancer cell lines and in breast tumor tissue samples. BMP-7 is expressed in various cell lines, but in a cell line specific manner. The breast cancer cell lines MCF-7 and SK-BR-3 showed BMP-7 expression on the mRNA level. In T-47D we were not able to detect BMP-7 on the mRNA but on the protein level. Additionally, epidermal growth factor (EGF), a stimulator of proliferation, was not able to enhance BMP-7 expression on the transcriptional level. These findings are in contrast to the EGF-dependent regulation of BMP-6, indicating a differential regulation of these closely related TGF-beta members. In order to confirm the data obtained from cell cultures, we analyzed normal breast tissue and tumor tissue samples from 170 invasive ductal carcinomas of the breast by immunohistochemistry. We found BMP-7 expression in normal breast tissue in the end buds, but not in the ductus lactiferus. BMP-7 protein was detected in all 170 tumor samples. Comparing BMP-7 levels with histopathological parameters, we could not show a correlation of BMP-7 and the proliferation index nor with erbB receptors. But the expression of BMP-7 was highly correlated with estrogen receptor levels (p< or=0.01) and progesterone receptor levels (p< or =0.01) which are important markers for breast cancer prognosis and therapy.

Blotting, Western↗
PubMed2002

Synthesis of new pyridines with oligocations and oxygen nucleophiles.

Nucleophilic substitution of 4-(dimethylamino)pyridine on pentachloropyridine yielded pentakis(pyridine-2,3,4,5,6-pentayl)pyridinium, tris-(3,5-dichloropyridine-2,4,6-triyl)pyridinium, or (tetrachloropyridin-4-yl)pyridinium depending on the reaction conditions. Nucleophilic substitution with water, hydroxides, and alcoholates resulted in new betaines and highly substituted pyridines. [structure: see text]

Cations↗
PubMed2002

Prostate-specific antigen dynamics predict risk of progression in advanced prostate cancer treated with bicalutamide plus castration.

OBJECTIVE: The aim of this study was to investigate the prognostic value of prostate-specific antigen (PSA) dynamics in patients treated with combined androgen blockade (CAB). METHODS: Patients with locally advanced or metastatic prostate cancer (n = 317) received bicalutamide (50 mg once daily) plus either goserelin acetate or surgical castration for 48 weeks. Cox's proportional hazard analysis was used to determine whether the decline of PSA following the use of this combination is predictive of a delay in progression. RESULTS: PSA levels at weeks 4 and 12 were statistically significant prognostic markers in predicting disease progression. The PSA rate of change to week 12 was also a statistically significant prognostic marker, although the PSA rate of change at week 4 did not reach statistical significance. These results were statistically less robust than those for PSA levels. Bicalutamide plus castration was well tolerated and effective in advanced prostate cancer. CONCLUSION: These results suggest that PSA dynamics at weeks 4 and 12 may predict time to progression in advanced prostate cancer treated with CAB.

Aged↗
PubMed1997

Synthesis, Structure, and Magnetic Properties of Low-Valent Triangulo Cobalt-Hydride Clusters [XCo(3)(&mgr;-CO)(3)(PMe(3))(6)].

Syntheses and properties of low-valent clusters [X{Co(&mgr;-CO)(PMe(3))(2)}(3)], X = none (1), H (2), and H(3) (3), are reported. All solids are isostructural as explicitly shown by single-crystal structure data. The molecular structures of C(21)H(54)Co(3)O(3)P(6) (1) and C(21)H(57)Co(3)O(3)P(6) (3) contain central Co(3) units which form perfect equilateral triangles with Co-Co distances of 2.4055(5) and 2.432(1) Å, respectively. Both compounds crystallize in trigonal space group R&thremacr;c, with Z = 6: 1, a = 10.678(1) Å, c = 52.298(11) Å; 3, a = 10.679(2) Å, c = 52.729(12) Å. Compounds 1 and 2 form a continuous range of solid solutions. Powder samples exhibit molecular paramagnetism of different extent: At 298 K the effective magnetic moments for 1-3 are &mgr;(eff)/&mgr;(B) = 1.9, 3.1, and 2.7, respectively. The magnetic behavior could be rationalized in terms of the Curie-Weiss law for a one electron system (1) and two electron system (2). The two electron approximation has been discussed as well for 3 above 6.2 K. A description of the scope of exchange coupling is presented for 1.

Journal Article↗