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排序方式: 共有464条查询结果,搜索用时 62 毫秒
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W L Sibbitt Jr L J Haseler R R Griffey S D Friedman W M Brooks 《AJNR. American journal of neuroradiology》1997,18(7):1271
PURPOSETo determine the neurometabolism of patients with active neuropsychiatric systemic lupus erythematosus (NPSLE) by using proton MR spectroscopy.METHODSThirty-six patients with SLE and eight control subjects were studied with proton MR spectroscopy to measure brain metabolites. Peaks from N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and at 1.3 parts per million (ppm) lipid, macromolecules, and lactate were measured. Patients were classified as having major NPSLE (seizures, psychosis, major cognitive dysfunction, delirium, stroke, or coma) (n = 15) or minor NPSLE (headache, minor affective disorder, or minor cognitive disorder) (n = 21). Patients with major NPSLE were severely ill and hospitalized.RESULTSSLE patients had lower NAA and increased metabolites at 1.3 ppm than did control subjects (NAA/Cr(SLE) = 1.90 +/- 0.35, NAA/Cr(Control) = 2.16 +/- 0.26; 1.3 ppm/Cr(SLE) = 0.49 +/- 0.41, 1.3 ppm/Cr(Control) = 0.27 +/- 0.05). NAA/Cr in patients with current or prior major NPSLE was lower than in patients without major NPSLE. Increased peaks at 1.3 ppm were present in all SLE subgroups, but particularly in patients with major NPSLE. These resonances were not evident at an echo time of 136, indicating that these signals were not lactate.CONCLUSIONMajor NPSLE, past or present, is associated with decreased levels of NAA. Elevated peaks around 1.3 ppm do not represent lactate even in severely ill patients, indicating that global ischemia is not characteristic of NPSLE. Neurochemical markers determined by MR spectroscopy may be useful for determining activity and degree of brain injury in NPSLE. 相似文献
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These investigations test the hypothesis developed previously, that there are biomolecules which control and integrate cellular differentiation. Our specific interest in cellular differentiation lies in the area of what we refer to as basal or primitive cellular differentiation mechanisms. These mechanisms are common to all cells, and are required for simple recognition and growth regulation. We have investigated two models, the IMR-90 human fetal lung fibroblast model as a representative of normal growth control, and the CG model, canine glioma cells, a transplantable growth transformed cell line. These two models represent normal, and aberrant cellular differentiation control. In previous studies we have shown that the arrangement of the cell surface oligosaccharide structure on these cell types are predictive of phenotypic transition. We have developed, and partially characterized a series of BIOMODULATORS (BM) which delay the onset of display of neoplastic cells. Three classes of BIOMODULATOR have been explored; (1) a large molecular weight natural product (25-35 kDa), PokeWeed Mitogen (PWM); (2) a small molecular weight natural product (500 Da) Cellular Activator and Differentiator (CAD) and a number of natural and synthetic analogs; and (3) an indolizidine alkaloid natural product, Swainsonine (Sw) which has a known cellular target (oligosaccharide biosynthesis). Preliminary data is presented which structurally links some of these BIOMODULATORS in terms of their effective stereochemistry. These BIOMODULATORS, when used before PDL 38, prevent the cell surface oligosaccharide display changes typical of morphological senescence and delay their onset to PDL 100 or more. These BIOMODULATORS also appear to have regulatory effects on the neoplastic cell models. This re-regulation results in increases in generation time and an increase in the ability of these cells to be recognized by cytotoxic lymphocytes. Proton NMR linewidth measurements of the fraction of 'bound' water associated with the cellular surface of treated and untreated cell populations showed induced physical changes in the cell surface related to the use of the BIOMODULATOR and correlated to the oligosaccharide display changes. These data were interpreted as indicating an increase in the organizational level of these cells. The data for normal and neoplastic cell populations are compared and contrasted in an effort to form the basis for an analytical approach to the control and integration of differentiation mechanisms. 相似文献
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Noninvasive metabolic magnetic resonance (MR) imaging reflecting glucose metabolism in the aldose-reductase-sorbitol (ARS) pathway was performed in the rabbit head; after administration of the fluorinated glucose analogue 3-fluoro-3-deoxy-D-glucose (3FD-glucose), fluorine-19 images were generated. Images of 3FD-glucose showed significant 3FD-glucose uptake by adipose tissue, indicating its buffering effects in case of excess loads of glucose. Images of 3-fluoro-3-deoxy-D-sorbitol (3FD-sorbitol) demonstrated the spatial distribution of aldose reductase activities and significant sorbitol accumulation in the lens. Images of 3-fluoro-3-deoxy-D-fructose (3FD-fructose) showed preferential uptake of fructose by muscle tissue. The extremely low toxicity of 3FD-glucose indicates promise for its clinical application in metabolic imaging. 相似文献
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Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
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In a child with some features of Turner's syndrome, gonosomal mosaicism with an isodicentric nonfluorescent (idic)Y chromosome was detected (mos 45,X/47,X,idic(Y)(q11),idic(Y)(11)/46,X,idic(Y)(q11)). Histopathological examination showed streak gonads with some evidence of ovarian stroma and no sign of gonadoblastoma. Polymerase chain reaction (PCR) analysis in blood lymphocytes and gonadal tissues using primers of seven loci along the Y chromosome, including the sex determined region (SRY), azoospermia factor region (AZF) and the deleted in azoospermia ( DAZ ) gene was positive for all loci tested, confirming the isodicentric character of the Y chromosome and indicating the presence of the AZF region. It is remarkable that the existence of spermatogenesis controlling genes does not play an important role in gonadal development and differentiation in a phenotypic female with some Turner stigmata. The data presented here are briefly discussed with previously-described patients. 相似文献
10.
Galactose neuropathy. Structural changes evaluated by nuclear magnetic resonance spectroscopy 总被引:1,自引:0,他引:1
We examined the hypothesis that the polyol accumulation resulting from chronic galactose supplementation in the diet produces endoneurial edema that can be prevented by inhibition of aldose reductase. We explored the potential of nuclear magnetic resonance (NMR) spectroscopy to quantitate and characterize the water accumulation in the sciatic nerve in this "galactose neuropathy." The data demonstrate a 16% increase in gravimetrically determined total water content of nerve in the galactose-fed rat after 8 mo of this diet and a 50% increase in the T1 relaxation time for nerve water as determined by NMR spectroscopy. Prolongation of the T1 relaxation time reflects increased rotation of water in a magnetic field, consistent with an extracellular site of the additional water. Simultaneous feeding of sorbinil to inhibit aldose reductase resulted in normalization of both total nerve water and of the prolongation of T1 relaxation time. These data define the NMR-spectroscopic state of endoneurial edema in the galactose-fed rat and suggest specific application to the investigation of the role of aldose reductase in human diabetic neuropathy. 相似文献