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排序方式: 共有443条查询结果,搜索用时 187 毫秒
1.
Leonidas JC; Berdon WE; Valderrama E; Neveling U; Schuval S; Weiss SJ; Hilfer C; Godine L 《Radiology》1996,198(2):377
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N-acetyl-L-aspartate and other amino acid metabolites in Alzheimer's disease brain: a preliminary proton nuclear magnetic resonance study. 总被引:1,自引:0,他引:1
We used proton nuclear magnetic resonance spectroscopy in this preliminary study of perchloric acid extracts of 12 Alzheimer's disease (AD) and five control brain samples to measure the relative levels of taurine, aspartate, glutamine, glutamate, gamma-aminobutyric acid (GABA), and the putative neuronal marker, N-acetyl-L-aspartate (NAA). We found no significant changes in taurine, aspartate, or glutamine. NAA was lower in AD compared with control, and this decrease correlated with the number of senile plaques and neurofibrillary tangles in adjacent tissue sections. GABA levels also were lower in AD brain. Glutamate levels were greater in AD than control and showed a close, inverse correlation with NAA levels. These findings suggest that the decrease in NAA reflects neuronal loss and that remaining neurons could be exposed to a relative excess of glutamate and a relative lack of GABA. If present in the neurotransmitter pool, this imbalance could result in neurotoxic cell damage. This hypothesis is further supported by in vitro and in vivo phosphorus 31 nuclear magnetic resonance findings. 相似文献
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Normal and diseased isolated lungs: high-resolution CT 总被引:8,自引:0,他引:8
6.
Donglu Zhang Marc Ogan Richard Gedamke Vikram Roongta Renke Dai Mingshe Zhu J Kent Rinehart Lewis Klunk James Mitroka 《Drug metabolism and disposition》2003,31(7):837-845
(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct. 相似文献
7.
Coakley G; Mok CC; Hajeer AH; Ollier WE; Turner D; Sinnott PJ; Hutchinson IV; Panayi GS; Lanchbury JS 《Rheumatology (Oxford, England)》1998,37(9):988-991
OBJECTIVE: To examine whether promoter polymorphisms associated with
variation in interleukin-10 (IL-10) production are relevant to the
development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS:
DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The
promoter region between -533 and - 1120 was amplified by polymerase chain
reaction, and polymorphisms detected by restriction enzyme digest or
sequence-specific oligonucleotide probing. RESULTS: We found no significant
difference in allele or haplotype frequencies between the groups.
CONCLUSION: There is no association between FS or RA and these recently
identified IL-10 promoter polymorphisms. Other genetic or environmental
factors could explain the alterations in IL-10 levels seen in these
conditions.
相似文献
8.
Anne M Fagan Rachel L Henson Yan Li Anna H Boerwinkle Chengjie Xiong Randall J Bateman Alison Goate Beau M Ances Eric Doran Bradley T Christian Florence Lai H Diana Rosas Nicole Schupf Sharon Krinsky-McHale Wayne Silverman Joseph H Lee William E Klunk Benjamin L Handen Ira T Lott 《Lancet neurology》2021,20(8):615-626
9.
Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro. 相似文献
10.
David M Wagner Jennifer Klunk Michaela Harbeck Alison Devault Nicholas Waglechner Jason W Sahl Jacob Enk Dawn N Birdsell Melanie Kuch Candice Lumibao Debi Poinar Talima Pearson Mathieu Fourment Brian Golding Julia M Riehm David J D Earn Sharon DeWitte Jean-Marie Rouillard Hendrik Poinar 《The Lancet infectious diseases》2014,14(4):319-326