Fleming K

References (2)

Title : Brain metabolic and clinical effects of rivastigmine in Alzheimer's disease - Potkin_2001_Int.J.Neuropsychopharmacol_4_223
Author(s) : Potkin SG , Anand R , Fleming K , Alva G , Keator D , Carreon D , Messina J , Wu JC , Hartman R , Fallon JH
Ref : Int J Neuropsychopharmacol , 4 :223 , 2001
Abstract : In-vivo metabolic measures with positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET) have demonstrated hypometabolism in temporal, frontal, and hippocampal areas during the early stages of Alzheimer's disease (AD). Progression of the dementia in AD involves compromised cholinergic functioning. Cholinesterase inhibitors have demonstrated efficacy in improving cognition and behaviour in AD. In this study, we demonstrate the usefulness of FDG-PET in measuring the progression of untreated AD and its modification by treatment with rivastigmine (Exelon, Novartis Pharmaceuticals, East Hanover, New Jersey, USA), a centrally selective cholinesterase inhibitor of the carbamate type. Patients with mild to moderate probable AD (Mini-Mental Status Exam scores of 10-26, inclusive) were enrolled in a double-blind, placebo controlled comparison of three fixed daily doses of rivastigmine (3, 6, or 9 mg/d) or placebo for 26 wk. FDG-PET scans were obtained on 27 patients at baseline and following 26 wk of treatment using the Snodgrass Picture Naming activation task. A total of 71.4% of the patients treated with placebo deteriorated clinically compared to only 25.0% of the patients treated with rivastigmine (chi2 = 4.8; p & 0.03). Rivastigmine-responders (i.e. those who clinically improved or remained clinically stable as measured by the Clinicianaposs Interview-Based Impression of Change-plus) showed a marked increase in brain metabolism (p <0.01) involving, but not limited to, structures comprising the memory-related cortices and the prefrontal system. These metabolic changes were not observed in the placebo-treated patients or the rivastigmine non-responders. Of note is that responders increased hippocampal metabolism by 32.5% (p < 0.03) compared to a non-significant decrease in the non-responders (6.4%) and placebo-treated patients (4.1%). These results are consistent with the literature suggesting that FDG-PET can sensitively measure the progression of AD and its improvement with cholinesterase inhibitors. Rivastigmine prevented the expected deterioration in clinical status and dramatically increased brain metabolic activity in a majority of patients.
ESTHER : Potkin_2001_Int.J.Neuropsychopharmacol_4_223
PubMedSearch : Potkin_2001_Int.J.Neuropsychopharmacol_4_223
PubMedID: 11602028

Title : The DNA sequence of human chromosome 22 - Dunham_1999_Nature_402_489
Author(s) : Dunham I , Hunt AR , Collins JE , Bruskiewich R , Beare DM , Clamp M , Smink LJ , Ainscough R , Almeida JP , Babbage AK , Bagguley C , Bailey J , Barlow KF , Bates KN , Beasley OP , Bird CP , Blakey SE , Bridgeman AM , Buck D , Burgess J , Burrill WD , Burton J , Carder C , Carter NP , Chen Y , Clark G , Clegg SM , Cobley VE , Cole CG , Collier RE , Connor R , Conroy D , Corby NR , Coville GJ , Cox AV , Davis J , Dawson E , Dhami PD , Dockree C , Dodsworth SJ , Durbin RM , Ellington AG , Evans KL , Fey JM , Fleming K , French L , Garner AA , Gilbert JGR , Goward ME , Grafham DV , Griffiths MND , Hall C , Hall RE , Hall-Tamlyn G , Heathcott RW , Ho S , Holmes S , Hunt SE , Jones MC , Kershaw J , Kimberley AM , King A , Laird GK , Langford CF , Leversha MA , Lloyd C , Lloyd DM , Martyn ID , Mashreghi-Mohammadi M , Matthews LH , Mccann OT , Mcclay J , Mclaren S , McMurray AA , Milne SA , Mortimore BJ , Odell CN , Pavitt R , Pearce AV , Pearson D , Phillimore BJCT , Phillips SH , Plumb RW , Ramsay H , Ramsey Y , Rogers L , Ross MT , Scott CE , Sehra HK , Skuce CD , Smalley S , Smith ML , Soderlund C , Spragon L , Steward CA , Sulston JE , Swann RM , Vaudin M , Wall M , Wallis JM , Whiteley MN , Willey DL , Williams L , Williams SA , Williamson H , Wilmer TE , Wilming L , Wright CL , Hubbard T , Bentley DR , Beck S , Rogers J , Shimizu N , Minoshima S , Kawasaki K , Sasaki T , Asakawa S , Kudoh J , Shintani A , Shibuya K , Yoshizaki Y , Aoki N , Mitsuyama S , Roe BA , Chen F , Chu L , Crabtree J , Deschamps S , Do A , Do T , Dorman A , Fang F , Fu Y , Hu P , Hua A , Kenton S , Lai H , Lao HI , Lewis J , Lewis S , Lin S-P , Loh P , Malaj E , Nguyen T , Pan H , Phan S , Qi S , Qian Y , Ray L , Ren Q , Shaull S , Sloan D , Song L , Wang Q , Wang Y , Wang Z , White J , Willingham D , Wu H , Yao Z , Zhan M , Zhang G , Chissoe S , Murray J , Miller N , Minx P , Fulton R , Johnson D , Bemis G , Bentley D , Bradshaw H , Bourne S , Cordes M , Du Z , Fulton L , Goela D , Graves T , Hawkins J , Hinds K , Kemp K , Latreille P , Layman D , Ozersky P , Rohlfing T , Scheet P , Walker C , Wamsley A , Wohldmann P , Pepin K , Nelson J , Korf I , Bedell JA , Hillier L , Mardis E , Waterston R , Wilson R , Emanuel BS , Shaikh T , Kurahashi H , Saitta S , Budarf ML , McDermid HE , Johnson A , Wong ACC , Morrow BE , Edelmann L , Kim UJ , Shizuya H , Simon MI , Dumanski JP , Peyrard M , Kedra D , Seroussi E , Fransson I , Tapia I , Bruder CE , O'Brien KP
Ref : Nature , 402 :489 , 1999
Abstract : Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.
ESTHER : Dunham_1999_Nature_402_489
PubMedSearch : Dunham_1999_Nature_402_489
PubMedID: 10591208
Gene_locus related to this paper: human-CES5A , human-SERHL2