Search Results - (Author, Cooperation:N. Cairns)
-
1Latest Papers from Table of Contents or Articles in PressC. Cruchaga ; C. M. Karch ; S. C. Jin ; B. A. Benitez ; Y. Cai ; R. Guerreiro ; O. Harari ; J. Norton ; J. Budde ; S. Bertelsen ; A. T. Jeng ; B. Cooper ; T. Skorupa ; D. Carrell ; D. Levitch ; S. Hsu ; J. Choi ; M. Ryten ; J. Hardy ; D. Trabzuni ; M. E. Weale ; A. Ramasamy ; C. Smith ; C. Sassi ; J. Bras ; J. R. Gibbs ; D. G. Hernandez ; M. K. Lupton ; J. Powell ; P. Forabosco ; P. G. Ridge ; C. D. Corcoran ; J. T. Tschanz ; M. C. Norton ; R. G. Munger ; C. Schmutz ; M. Leary ; F. Y. Demirci ; M. N. Bamne ; X. Wang ; O. L. Lopez ; M. Ganguli ; C. Medway ; J. Turton ; J. Lord ; A. Braae ; I. Barber ; K. Brown ; P. Passmore ; D. Craig ; J. Johnston ; B. McGuinness ; S. Todd ; R. Heun ; H. Kolsch ; P. G. Kehoe ; N. M. Hooper ; E. R. Vardy ; D. M. Mann ; S. Pickering-Brown ; N. Kalsheker ; J. Lowe ; K. Morgan ; A. David Smith ; G. Wilcock ; D. Warden ; C. Holmes ; P. Pastor ; O. Lorenzo-Betancor ; Z. Brkanac ; E. Scott ; E. Topol ; E. Rogaeva ; A. B. Singleton ; M. I. Kamboh ; P. St George-Hyslop ; N. Cairns ; J. C. Morris ; J. S. Kauwe ; A. M. Goate
Nature Publishing Group (NPG)
Published 2013Staff ViewPublication Date: 2013-12-18Publisher: Nature Publishing Group (NPG)Print ISSN: 0028-0836Electronic ISSN: 1476-4687Topics: BiologyChemistry and PharmacologyMedicineNatural Sciences in GeneralPhysicsKeywords: African Americans/genetics ; Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/*genetics/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Brain/metabolism ; Case-Control Studies ; Europe/ethnology ; Exome/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/*genetics ; Humans ; Male ; Peptide Fragments/metabolism ; Phospholipase D/deficiency/*genetics/metabolism ; Protein Processing, Post-Translational/genetics ; ProteolysisPublished by: -
2Articles: DFG German National LicensesAlam, Z. I. ; Jenner, A. ; Daniel, S. E. ; Lees, A. J. ; Cairns, N. ; Marsden, C. D. ; Jenner, P. ; Halliwell, B.
Oxford, UK : Blackwell Science Ltd
Published 1997Staff ViewISSN: 1471-4159Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: MedicineNotes: Abstract: Oxidative damage has been implicated in the pathology of Parkinson's disease (PD), e.g., rises in the level of the DNA damage product, 8-hydroxy-2′-deoxyguanosine, have been reported. However, many other products result from oxidative DNA damage, and the pattern of products can be diagnostic of the oxidizing species. Gas chromatography/mass spectrometry was used to examine products of oxidation and deamination of all four DNA bases in control and PD brains. Products were detected in all brain regions examined, both normal and PD. Analysis showed that levels of 8-hydroxyguanine (8-OHG) tended to be elevated and levels of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine) tended to be decreased in PD. The most striking difference was a rise in 8-OHG in PD substantia nigra (p = 0.0002); rises in other base oxidation/deamination products were not evident, showing that elevation in 8-OHG is unlikely to be due to peroxynitrite (ONOO−) or hydroxyl radicals (OH•), or to be a prooxidant effect of treatment with l-Dopa. However, some or all of the rise in 8-OHG could be due to a change in 8-OHG/FAPy guanine ratios rather than to an increase in total oxidative guanine damage.Type of Medium: Electronic ResourceURL: -
3Articles: DFG German National LicensesMUIR, P. ; NICHOLSON, F. ; SHARIEF, M. K. ; THOMPSON, E. J. ; CAIRNS, N. J. ; LANTOS, P. ; SPENCER, G. T. ; KAMINSKI, H. J. ; BANATVALA, J. E.
Oxford, UK : Blackwell Publishing Ltd
Published 1995Staff ViewISSN: 1749-6632Source: Blackwell Publishing Journal Backfiles 1879-2005Topics: Natural Sciences in GeneralType of Medium: Electronic ResourceURL: -
4Articles: DFG German National LicensesStaff View
ISSN: 0040-4020Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002Topics: Chemistry and PharmacologyType of Medium: Electronic ResourceURL: -
5Articles: DFG German National LicensesStaff View
ISSN: 1420-9071Keywords: Key words. Ubiquinol:cytochrome c oxidoreductase; ATP synthase; mitochondrial electron transport chain; Alzheimer’s disease; Down syndrome; neuronal cell death; neurodegenerative disease.Source: Springer Online Journal Archives 1860-2000Topics: BiologyMedicineNotes: Abstract. Ubiquinol:cytochrome c oxidoreductase (complex III) and ATP synthase (complex V) are important enzymes in the mitochondrial electron transport chain. Defects in mitochondrial respiratory enzymes have been reported for several neurodegenerative diseases. In this study, we applied the proteomic approach to investigate protein levels of complex III core protein 1 and complex V β chain in brain regions of Alzheimer’s disease (AD) and Down syndrome (DS) patients. Complex III core protein 1 was significantly reduced in the temporal cortex of AD patients. Complex V β chain was significantly reduced in the frontal cortex of DS patients. We conclude that decreased mitochondrial respiratory enzymes could contribute to the impairment of energy metabolism observed in DS. These decreases could also cause the generation of reactive oxygen species and neuronal cell death (apoptosis) in DS as well as AD.Type of Medium: Electronic ResourceURL: -
6Articles: DFG German National LicensesStaff View
ISSN: 1438-2199Keywords: Amino acids ; RT/PCR ; Protooncogene ; ets-2Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Summary Protooncogenes (PO) play a crucial role for brain biology and pathology. Only the concerted action of protooncogenes enables normal brain development. The reliable and sensitive quantification of brain PO is still holding centre stage in neurobiological research. The aim of our study was therefore the determination of PO in minute amounts of brain areas. For this purpose we decided to apply the most sensitive detection principle of competitive reverse transcriptase polymerase chain reaction using capillary electrophoresis and laser-induced fluorescence detection. We selected the PO ets-2 for our studies as this transcription factor was shown to be involved in neurodegenerative disease. As little as 10ng of total RNA each were extracted from 5 different regions of human postmortem brain and used in the assay system. Our results revealed that the ets-2 gene transcript was detectable at the atto-gram level in the brain (54.5 ± 17.7 ag/ 10 ng RNA in the occipital lobe, 34.2 ± 7.5 in temporal lobe, 40.2 ± 15.6 in the frontal lobe, 31.4 ± 15.7 in the cerebellum, and undetectably low in the parietal lobe). This is the first report at this sensitivity level providing neurobiology with a powerful analytical tool.Type of Medium: Electronic ResourceURL: -
7Articles: DFG German National LicensesStaff View
ISSN: 0040-4039Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002Topics: Chemistry and PharmacologyType of Medium: Electronic ResourceURL: -
8Articles: DFG German National LicensesStaff View
ISSN: 1432-0533Keywords: Key words Pick’s disease ; Pick bodies ; Frontal and temporal cortex ; Alzheimer’s disease ; Principal ; components analysisSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The densities of Pick bodies (PB), Pick cells (PC), senile plaques (SP) and neurofibrillary tangles (NFT) in the frontal and temporal lobe were determined in ten patients diagnosed with Pick’s disease (PD). The density of PB was significantly higher in the dentate gyrus granule cells compared with the cortex and the CA sectors of the hippocampus. Within the hippocampus, the highest densities of PB were observed in sector CA1. PC were absent in the dentate gyrus and no significant differences in PC density were observed in the remaining brain regions. With the exception of two patients, the densities of SP and NFT were low with no significant differences in mean densities between cortical regions. In the hippocampus, the density of NFT was greatest in sector CA1. PB and PC densities were positively correlated in the frontal cortex but no correlations were observed between the PD and AD lesions. A principal components analysis (PCA) of the neuropathological variables suggested that variations in the densities of SP in the frontal cortex, temporal cortex and hippocampus were the most important sources of heterogeneity within the patient group. Variations in the densities of PB and NFT in the temporal cortex and hippocampus were of secondary importance. In addition, the PCA suggested that two of the ten patients were atypical. One patient had a higher than average density of SP and one familial patient had a higher density of NFT but few SP.Type of Medium: Electronic ResourceURL: -
9Articles: DFG German National LicensesGattaz, W. F. ; Förstl, H. ; Braus, D. F. ; Maras, A. ; Cairns, N. J. ; Levy, R.
Springer
Published 1996Staff ViewISSN: 1433-8491Keywords: Alzheimer's disease ; phospholipase A2 ; Brain phospholipids ; Platelets ; Amyloid precursor protein ; β-amyloidSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Phospholipase A2 (PLA2) is a key enzyme in the metabolism of membrane phospholipids. PLA2 influences the processing and secretion of the amyloid precursor protein, which give rise to the β-amyloid peptide, the major component of the amyloid plaque in Alzheimer's disease (AD). We investigated the PLA2 activity in two samples: in post-mortem brains from 23 patients with AD and 20 non-demented elderly controls, and platelets from 16 patients with a diagnosis of probable AD, 13 healthy controls and 14 elderly patients with a major depression. In AD brains PLA2 activity was significantly decreased in the parietal, and to a lesser degree in the frontal, cortex. Lower PLA2 activity correlated significantly with an earlier onset of the disease, an earlier age at death and higher counts of neurofibrillary tangles and senile plaques. In platelets PLA2 activity was also significantly reduced in the AD group as compared with healthy and depressed controls. The reduction of the enzyme activity in platelets correlated with an early disease onset and with the severity of cognitive impairment, indicating a relationship between abnormally low PLA2 activity and a more severe form of the illness. The present results provide new evidence for a disordered phospholipid metabolism in AD brains and suggest that reduced PLA2 activity may contribute to the production of amyloidogenic peptides in the disease. Further studies are needed to examine whether PLA2 activity in platelets may be useful as a peripheral marker for a subgroup of patients with AD.Type of Medium: Electronic ResourceURL: -
10Articles: DFG German National LicensesStaff View
ISSN: 1435-1463Keywords: Keywords: Piracetam ; membrane ; human brain ; hippocampus ; Alzheimer's disease.Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Summary. The in vitro effects of piracetam treatment on the fluidity of membranes from the hippocampus of Alzheimer's Disease patients (AD) and non-demented controls were studied. Hippocampal membranes of AD patients showed a significant lower hydrocarbon core fluidity compared with membranes from elderly non-demented controls. Preincubation with piracetam enhanced the hydrocarbon core fluidity of hippocampal membranes from AD-patients as well as elderly controls in a concentration depending fashion, although the effect was more pronounced for the AD membranes. In the presence of piracetam, the difference of the membrane fluidity between AD and control membranes was not longer apparent.Type of Medium: Electronic ResourceURL: