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Jorg Kotzerke - One of the best experts on this subject based on the ideXlab platform.
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synthesis of a new hynic dapi derivative for labelling with 99mtechnetium and its in vitro evaluation in an frtl5 Cell line
MedChemComm, 2015Co-Authors: Sandra Ferl, Gerd Wunderlich, Rene Smits, Alexander Hoepping, Anne Naumann, Jorg KotzerkeAbstract:4′,6-Diamidine-2-phenylindole (DAPI) is a common fluorochrome that is able to bind to deoxyribonucleic acid (DNA) with distinct, sequence-dependent enhancement of fluorescence. This work presents the synthesis of a new multifunctional compound that includes the fluorescent dye as a 99mTechnetium (99mTc) carrier. A new technique for the bioconjugation of DAPI with 6-hydrazinonicotinic acid (HYNIC) through an amide linkage was developed. The radiolabelling was performed with HYNIC as a chelator and N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) as a coligand. Furthermore, experimental evidence showed that 99mTc complexes with DAPI as DNA-binding moieties are detectable in living Fischer rat thyroid follicular Cell line 5 (FRTL5) and their nuclei. The investigations indicated further that the new HYNIC-DAPI derivative is able to interact with double-stranded DNA. This establishes the possibility of locating 99mTc in close proximity to biological structures of living Cells, of which especially the genetic information-Carrying Cell compartments are at the centre of interest. In this context, further investigations are related to the radiotoxic effects of DNA-bound 99mTc-HYNIC-DAPI derivatives and dosimetric calculations.
Michael L. Cleary - One of the best experts on this subject based on the ideXlab platform.
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Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
Cell, 1992Co-Authors: Douglas C. Tkachuk, Sabine Kohler, Michael L. ClearyAbstract:Abstract We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino-terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 transloctions disrupt the HRX gene between these two motifs, and in a t(11;19)-Carrying Cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation.
Sandra Ferl - One of the best experts on this subject based on the ideXlab platform.
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synthesis of a new hynic dapi derivative for labelling with 99mtechnetium and its in vitro evaluation in an frtl5 Cell line
MedChemComm, 2015Co-Authors: Sandra Ferl, Gerd Wunderlich, Rene Smits, Alexander Hoepping, Anne Naumann, Jorg KotzerkeAbstract:4′,6-Diamidine-2-phenylindole (DAPI) is a common fluorochrome that is able to bind to deoxyribonucleic acid (DNA) with distinct, sequence-dependent enhancement of fluorescence. This work presents the synthesis of a new multifunctional compound that includes the fluorescent dye as a 99mTechnetium (99mTc) carrier. A new technique for the bioconjugation of DAPI with 6-hydrazinonicotinic acid (HYNIC) through an amide linkage was developed. The radiolabelling was performed with HYNIC as a chelator and N-(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)glycine (tricine) as a coligand. Furthermore, experimental evidence showed that 99mTc complexes with DAPI as DNA-binding moieties are detectable in living Fischer rat thyroid follicular Cell line 5 (FRTL5) and their nuclei. The investigations indicated further that the new HYNIC-DAPI derivative is able to interact with double-stranded DNA. This establishes the possibility of locating 99mTc in close proximity to biological structures of living Cells, of which especially the genetic information-Carrying Cell compartments are at the centre of interest. In this context, further investigations are related to the radiotoxic effects of DNA-bound 99mTc-HYNIC-DAPI derivatives and dosimetric calculations.
Lars Lannfelt - One of the best experts on this subject based on the ideXlab platform.
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microtubule associated protein tau in human fibroblasts with the swedish alzheimer mutation
Neuroscience Letters, 1996Co-Authors: Martin Ingelson, Eugeen Vanmechelen, Lars LannfeltAbstract:Abstract The principal neuropathological hallmarks of Alzheimer's disease (AD) are plaques containing amyloid β peptide (Aβ) and tangles with hyperphosphorylated tau. Tau is predominantly found in the nervous system but has been reported in fibroblasts from individuals with and without AD. Aβ is also found outside the nervous system and is released three times more from cultured fibroblasts Carrying the Swedish Alzheimer mutation in the amyloid precursor protein (APP) gene. In the present study, we determined tau levels in fibroblasts from carriers of the Swedish Alzheimer mutation and controls. We also characterized the expression of tau in these Cells. Primary fibroblast Cell lines from six individuals with and six without the mutation were investigated. ELISA measurements showed no statistically significant difference in tau levels between mutation-Carrying Cell lines and controls. On Western blot, four bands in the range of 47–67 kDa, corresponding to traditional tau isoforms, were detected with the Tau-1 and AT 120 antibodies. Furthermore, four bands between 110–125 kDa were detected. We thus conclude that increased levels of A/3 do not seem to increase the levels of tau in human fibroblasts. We also suggest that several of the traditional tau isoforms as well as isoforms of higher molecular weights, big tau, are expressed in this Cell type.
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characterization of muscarinic acetylcholine receptors in cultured adult skin fibroblasts effects of the swedish alzheimer s disease app 670 671 mutation on binding levels
Journal of Neural Transmission - Parkinson's Disease and Dementia Section, 1995Co-Authors: M Vestling, Lars Lannfelt, Richard F Cowburn, Nikolaos Venizelos, Bengt Winblad, Abdu AdemAbstract:We have characterised the muscarinic receptor subtypes found in human skin fibroblasts and compared binding levels in Cell lines from members of the Alzheimer's disease family with the Swedish amyloid precursor protein (APP) 670/671 mutation. Binding studies with [3H] quinuclidinyl benzilate ([3H]QNB) and the M2/M4 selective antagonist [3H](±)-5,11-dihydro-11-{[(2-[(di-propylamino)methyl]-1-piperidinyl}ethyl)amino]carbonyl}-6H-pyrido(2,3-b)(1,4) benzodiazepine-6-one ([3H]AF-DX 384) revealed the presence of a single population of muscarinic receptors on lysed fibroblast membranes. [3H]QNB binding was displaced by a number of selective muscarinic ligands with a rank order of potency: atropine>himbacine>methoctramine>(±)-p-fluoro-hexahydro-sila-difenidol hydrochloride>pirenzepine>muscarinic-toxin-3. APP 670/671 mutation Carrying Cell lines showed 25–35% lower levels of muscarinic receptors labelled with [3H]QNB, [3H]N-methyl scopolamine and [3H]AF-DX 384, compared to controls. This difference was not statistically significant due to large individual variation. It is concluded that muscarinic receptors on adult skin fibroblasts are predominantly of the M2 subtype. Since these Cells do not possess M1 and M3 receptor subtypes, they are unlikely to provide a good model for studying muscarinic receptor regulation of APP processing.
Douglas C. Tkachuk - One of the best experts on this subject based on the ideXlab platform.
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Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias.
Cell, 1992Co-Authors: Douglas C. Tkachuk, Sabine Kohler, Michael L. ClearyAbstract:Abstract We have identified a human homolog of the Drosophila trithorax protein that is structurally altered by 11q23 translocations in acute leukemias. Human trithorax (HRX) is a predicted 431 kd protein containing two potential DNA-binding motifs consisting of zinc fingers conserved with the fly protein and nonconserved amino-terminal "AT hook" motifs related to the DNA-binding motifs in HMG proteins. 11q23 transloctions disrupt the HRX gene between these two motifs, and in a t(11;19)-Carrying Cell line fusion transcripts are expressed from both derivative chromosomes. The more abundant derivative 11 transcript codes for a chimeric protein containing the AT hook motifs fused to a previously undescribed protein (ENL) from chromosome 19. These data suggest a novel role for a trithorax-homologous protein in multilineage human leukemias that may be mediated by DNA binding within the minor groove at AT-rich sites, implicated to play an important role in bacterial IHF-, yeast datin-, and mammalian HMG-mediated gene activation.