Ziegler A

References (7)

Title : Safety and efficacy of mTOR inhibitor treatment in patients with tuberous sclerosis complex under 2 years of age - a multicenter retrospective study - Saffari_2019_Orphanet.J.Rare.Dis_14_96
Author(s) : Saffari A , Brosse I , Wiemer-Kruel A , Wilken B , Kreuzaler P , Hahn A , Bernhard MK , van Tilburg CM , Hoffmann GF , Gorenflo M , Hethey S , Kaiser O , Kolker S , Wagner R , Witt O , Merkenschlager A , Mockel A , Roser T , Schlump JU , Serfling A , Spiegler J , Milde T , Ziegler A , Syrbe S
Ref : Orphanet J Rare Dis , 14 :96 , 2019
Abstract : BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem disease with prominent neurologic manifestations such as epilepsy, cognitive impairment and autism spectrum disorder. mTOR inhibitors have successfully been used to treat TSC-related manifestations in older children and adults. However, data on their safety and efficacy in infants and young children are scarce. The objective of this study is to assess the utility and safety of mTOR inhibitor treatment in TSC patients under the age of 2 years. RESULTS: A total of 17 children (median age at study inclusion 2.4 years, range 0-6; 12 males, 5 females) with TSC who received early mTOR inhibitor therapy were studied. mTOR inhibitor treatment was started at a median age of 5 months (range 0-19 months). Reasons for initiation of treatment were cardiac rhabdomyomas (6 cases), subependymal giant cell astrocytomas (SEGA, 5 cases), combination of cardiac rhabdomyomas and SEGA (1 case), refractory epilepsy (4 cases) and disabling congenital focal lymphedema (1 case). In all cases everolimus was used. Everolimus therapy was overall well tolerated. Adverse events were classified according to the Common Terminology Criteria of Adverse Events (CTCAE, Version 5.0). Grade 1-2 adverse events occurred in 12 patients and included mild transient stomatitis (2 cases), worsening of infantile acne (1 case), increases of serum cholesterol and triglycerides (4 cases), changes in serum phosphate levels (2 cases), increase of cholinesterase (2 cases), transient neutropenia (2 cases), transient anemia (1 case), transient lymphopenia (1 case) and recurrent infections (7 cases). No grade 3-4 adverse events were reported. Treatment is currently continued in 13/17 patients. Benefits were reported in 14/17 patients and included decrease of cardiac rhabdomyoma size and improvement of arrhythmia, decrease of SEGA size, reduction of seizure frequency and regression of congenital focal lymphedema. Despite everolimus therapy, two patients treated for intractable epilepsy are still experiencing seizures and another one treated for SEGA showed no volume reduction. CONCLUSION: This retrospective multicenter study demonstrates that mTOR inhibitor treatment with everolimus is safe in TSC patients under the age of 2 years and shows beneficial effects on cardiac manifestations, SEGA size and early epilepsy.
ESTHER : Saffari_2019_Orphanet.J.Rare.Dis_14_96
PubMedSearch : Saffari_2019_Orphanet.J.Rare.Dis_14_96
PubMedID: 31053163

Title : A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease - Wild_2011_Circ.Cardiovasc.Genet_4_403
Author(s) : Wild PS , Zeller T , Schillert A , Szymczak S , Sinning CR , Deiseroth A , Schnabel RB , Lubos E , Keller T , Eleftheriadis MS , Bickel C , Rupprecht HJ , Wilde S , Rossmann H , Diemert P , Cupples LA , Perret C , Erdmann J , Stark K , Kleber ME , Epstein SE , Voight BF , Kuulasmaa K , Li M , Schafer AS , Klopp N , Braund PS , Sager HB , Demissie S , Proust C , Konig IR , Wichmann HE , Reinhard W , Hoffmann MM , Virtamo J , Burnett MS , Siscovick D , Wiklund PG , Qu L , El Mokthari NE , Thompson JR , Peters A , Smith AV , Yon E , Baumert J , Hengstenberg C , Marz W , Amouyel P , Devaney J , Schwartz SM , Saarela O , Mehta NN , Rubin D , Silander K , Hall AS , Ferrieres J , Harris TB , Melander O , Kee F , Hakonarson H , Schrezenmeir J , Gudnason V , Elosua R , Arveiler D , Evans A , Rader DJ , Illig T , Schreiber S , Bis JC , Altshuler D , Kavousi M , Witteman JC , Uitterlinden AG , Hofman A , Folsom AR , Barbalic M , Boerwinkle E , Kathiresan S , Reilly MP , O'Donnell CJ , Samani NJ , Schunkert H , Cambien F , Lackner KJ , Tiret L , Salomaa V , Munzel T , Ziegler A , Blankenberg S
Ref : Circ Cardiovasc Genet , 4 :403 , 2011
Abstract : BACKGROUND: eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). METHODS AND RESULTS: In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7x10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3x10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4x10(-3)). CONCLUSIONS: The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD.
ESTHER : Wild_2011_Circ.Cardiovasc.Genet_4_403
PubMedSearch : Wild_2011_Circ.Cardiovasc.Genet_4_403
PubMedID: 21606135
Gene_locus related to this paper: human-LIPA

Title : Evidence that mobile lipids detected in rat brain glioma by 1H nuclear magnetic resonance correspond to lipid droplets - Remy_1997_Cancer.Res_57_407
Author(s) : Remy C , Fouilhe N , Barba I , Sam-Lai E , Lahrech H , Cucurella MG , Izquierdo M , Moreno A , Ziegler A , Massarelli R , Decorps M , Arus C
Ref : Cancer Research , 57 :407 , 1997
Abstract : Mobile lipids have been detected by proton nuclear magnetic resonance (NMR) in animal and human tumors (cultured cells, biopsies, and in vivo), but their origin and subcellular location are still unclear. They have been associated with malignancy, metastatic ability, drug resistance, and necrosis. We wanted to determine whether these lipids are located within plasma membrane microdomains or in lipid droplets for a C6 cell-induced rat glioma. NMR-visible mobile lipids were found in all subcellular fractions isolated from the rat tumor, except in the cytosolic supernatants. Transmission electron microscopy showed that lipid droplets were present in all subcellular fractions containing NMR-visible lipids and in the necrotic and perinecrotic areas of the tumor. The mean diameter of droplets isolated by flotation in the subcellular fractionation protocol was 0.97 microm (n = 682; droplet profile diameter range between 0.2 and 5.0 microm). The apparent diffusion coefficient for these lipids (46 +/- 17 microm2 s(-1) measured in vivo by proton spectroscopy was four orders of magnitude higher than would be expected if mobile lipids were inside plasma membrane microdomains. The combined results demonstrated that mobile lipids detected in vivo by proton NMR in the C6 rat glioma are located in large lipid droplets, associated with the necrotic process.
ESTHER : Remy_1997_Cancer.Res_57_407
PubMedSearch : Remy_1997_Cancer.Res_57_407
PubMedID: 9012466

Title : Kinetic studies of co-operativity at atrial muscarinic M2 receptors with an infinite dilution procedure - Christopoulos_1997_Biochem.Pharmacol_53_795
Author(s) : Christopoulos A , Lanzafame A , Ziegler A , Mitchelson F
Ref : Biochemical Pharmacology , 53 :795 , 1997
Abstract : The effects of two competitive antagonists and two allosteric ligands on the rate of dissociation of [3H]N-methylscopolamine ([3H]NMS) were studied at atrial muscarinic acetylcholine M2 receptors by the technique of "infinite dilution." The dissociation rate for [3H]NMS, initiated by diluting the incubation mixture in a 100-fold volume of buffer, was 0.61 +/- 0.10 min-1. Addition of the competitive antagonists, atropine or NMS, to the dilution medium did not alter the observed [3H]NMS dissociation rate. In contrast, gallamine and the bisquaternary, heptane-1,7-bis-(dimethyl-3'-phthalimidopropyl-ammonium bromide) (C7/3'-phth), produced a concentration-dependent slowing of the dissociation rate of [3H]NMS, with IC50 values of 7.5 microM and 196 nM, respectively. Gallamine exhibited an increased modulatory potency when equilibration with the tissue was allowed prior to dilution. The findings showed that the influence of low concentrations of allosteric modulators on the [3H]NMS dissociation rate may be demonstrated separately from any effects on association rate, and that the contact time with the allosteric ligand may influence the extent of these effects.
ESTHER : Christopoulos_1997_Biochem.Pharmacol_53_795
PubMedSearch : Christopoulos_1997_Biochem.Pharmacol_53_795
PubMedID: 9113100

Title : The effect of gallamine, gallopamil and nifedipine on responses to acetylcholine and carbachol in the taenia of the guinea-pig caecum - Mitchelson_1984_Br.J.Pharmacol_83_145
Author(s) : Mitchelson F , Ziegler A
Ref : British Journal of Pharmacology , 83 :145 , 1984
Abstract : The effects of gallamine, gallopamil and nifedipine on isotonic contractions of the isolated taenia of the guinea-pig caecum produced by acetylcholine (ACh) or carbachol (CCh) were investigated. Gallamine (0.1 to 0.3 mM) inhibited contractions produced by CCh more than those produced by ACh. The difference was still present after pretreatment of the tissue with paraoxon (10 microM for 20 min) to inhibit cholinesterases or in experiments carried out in the presence of tetrodotoxin (0.3 microM) to exclude possible ganglionic stimulation by the agonists. Gallopamil or nifedipine selectively inhibited the tonic response to ACh in the absence or presence of paraoxon. The phasic response to ACh or the tonic response to CCh (0.1 or 1 microM) was much less affected. Reduction of the Ca2+ content of the bath medium reduced phasic and tonic responses to ACh more than the tonic response to CCh. These results suggest that there are differences in the interaction of ACh and CCh with muscarinic receptors in this muscle.
ESTHER : Mitchelson_1984_Br.J.Pharmacol_83_145
PubMedSearch : Mitchelson_1984_Br.J.Pharmacol_83_145
PubMedID: 6487885

Title : Proceedings: The slow action of atropine and the competitive nature of its anti-muscarinic action -
Author(s) : Carrier GO , Ziegler A
Ref : Naunyn Schmiedebergs Arch Pharmacol , 282 :suppl 282:R15 , 1974
PubMedID: 4276533

Title : [Relation between inhibition of acetylcholinesterase and binding of 3H-diisopropylphosphorofluoridate under the influence of alkane-bis-ammonium compounds] -
Author(s) : Ohnesorge FK , Stege R , Ziegler A
Ref : Naunyn Schmiedebergs Arch Pharmakol , 266 :417 , 1970
PubMedID: 4253843