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991.
WL Greer DC Riddell S Murty TL Gillan GS Girouard SM Sparrow C Tatlidil MJ Dobson PE Neumann 《Clinical genetics》1999,55(4):248-255
Niemann-Pick type D (NPD) disease is a severe degenerative disorder of the nervous system characterized by the accumulation of tissue cholesterol and sphingomyelin. Because of a founder effect, it is unusually common in southwestern Nova Scotia, Canada. We have confirmed that almost all patients from 20 affected sibships descended on both sides from a small group of Acadians who settled in this region in about the year 1767. Previously using classic linkage analysis of this large kindred, we defined the critical gene region to a 13-cM chromosome segment between D18S869 and D18S66. Seven ESTs have been positioned within this interval. Carstea et al. (Niemann Pick C disease gene: homology to mediators of cholesterol homeostasis. Science 1997: 277: 232-235) recently demonstrated that one of these ESTs is the Niemann-Pick type C (NPCI) gene, the gene disrupted in most patients with NPC disease, and we have shown that a G3097-->T mutation in the NPC1 gene is also responsible for NPD. Here we report the development of five new polymorphic microsatellite markers and the testing for complete linkage disequilibrium in our single large NPD kindred that allowed us to reduce the NPD critical region to a 1-cM (1.3-1.6 Mb) interval between D18S1398 and D18S1108. In contrast, Carstea et al., using classic linkage analysis, required more than 18 unrelated NPC families to reduce the NPC1 critical region to a 5-cM interval. Our work supports the finding that NPD is an allelic variant of NPC1, and illustrates the power of large kindreds, which are common in Atlantic Canada and other relatively isolated areas, for gene mapping and identification. 相似文献
992.
The hypothalamic paraventricular nucleus, representing cell bodies in which thyrotropin-releasing hormone is synthesized, and the median eminence, representing nerve terminals, were incubated in vitro. Various hypo- and hyperosmotic solutions were tested to determine osmotic sensitivity of thyrotropin-releasing hormone secretion. High KCl (56 mM) causing membrane depolarization was used as a non-specific control stimulus to induce thyrotropin-releasing hormone secretion. A 30% decrease of medium osmolarity (from 288 to 202 mOsmol/l) increased thyrotropin-releasing hormone secretion from both the paraventricular nucleus and median eminence. A 30% decrease of medium NaCl content by its replacement with choline chloride did not affect basal thyrotropin-releasing hormone secretion. Increasing medium osmolarity with biologically inactive L-glucose did not affect basal or KCl-induced thyrotropin-releasing hormone secretion from either structure. Medium made hyperosmotic (350-450 mOsmol/l) by increasing the NaCl concentration resulted in a dose-dependent decrease of basal thyrotropin-releasing hormone secretion and abolished KCl-induced thyrotropin-releasing hormone secretion. If an osmotically equivalent amount of choline chloride was substituted for NaCl, there was no effect on thyrotropin-releasing hormone secretion, indicating a specific action of Na+. This study indicates a specific sensitivity to high concentrations of Na+ ions of both thyrotropin-releasing hormone-producing parvocellular paraventricular neurons and thyrotropin-releasing hormone-containing nerve terminals in the median eminence. 相似文献
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994.
A. J. Shipman G. W. G. Guy I. Smith S. Ostlere W. Greer R. Smith 《Osteoporosis international》1999,9(5):420-426
The vertebral bone mineral density (BMD), bone mineral content (BMC) and bone area of the lumbar spine were measured using
a bone densitometer in 8789 women aged 33–73 years who had had no previous hormone replacement therapy (HRT). The overall
relationship between BMD and age was analyzed on a year-by-year basis, and comprised three separate regions that could each
be described by a straight line: 33–46 years (gradient = 0.00166 g cm−2/year), 47–63 years (gradient = 0.0121 g cm−2/year) and 64–73 years (gradient = 0.0045 g cm−2/year). Above the age of 50 years our results were higher than the BMD in most previous reports. In those 3198 women who knew
the time of their last menstrual period (mean age 49.25 years, SD 4.83) bone loss was most rapid in the first 10 menopausal
years. In the whole group, the relationship between BMC and age was found to be similar to that of BMD, with three distinct
regions, including a rapid drop between the ages of 47 and 63 years (gradient 0.781 g/year). Bone area showed a much more
gradual (though significant) decrease with age. Based on WHO definitions and using BMD as an indicator, the percentage of
women with osteoporosis varied from zero in the younger age group to about 30% of women aged over 70 years; in contrast, where
BMC was used, although the trend with age had a similar shape, the percentages at each year were about half those derived
from the corresponding BMD values. Osteopenia derived in the same way occurred in about 50% of women over 70 years using either
BMD or BMC. The results presented here provide a reliable local reference range for lumbar spine bone densitometry measurements.
They also show that for this site BMD and BMC cannot be used interchangeably to define osteoporosis.
Received: 13 March 1998 / Accepted: 23 September 1998 相似文献
995.
C C Meltzer P E Kinahan P J Greer T E Nichols C Comtat M N Cantwell M P Lin J C Price 《Journal of nuclear medicine》1999,40(12):2053-2065
Because of limitations of spatial resolution, quantitative PET measurements of cerebral blood flow, glucose metabolism and neuroreceptor binding are influenced by partial-volume averaging among neighboring tissues with differing tracer concentrations. METHODS: Two MR-based approaches to partial-volume correction of PET images were compared using simulations and a multicompartment phantom. The two-compartment method corrects PET data for the diluting effects of cerebrospinal fluid (CSF) spaces. The more complex three-compartment method also accounts for the effect of partial-volume averaging between gray and white matter. The effects of the most significant sources of error on MR-based partial-volume correction, including misregistration, resolution mismatch, segmentation errors and white matter heterogeneity, were evaluated. We also examined the relative usefulness of both approaches in PET studies of aging and neurodegenerative disease. RESULTS: Although the three-compartment method was highly accurate (with 100% gray matter recovery achieved in simulations), it was also more sensitive to all errors tested, particularly image segmentation and PET-MR registration. CONCLUSION: Based on these data, we conclude that the two-compartment approach is better suited for comparative PET studies, whereas the three-compartment algorithm is capable of greater accuracy for absolute quantitative measures. 相似文献
996.
Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction. 总被引:9,自引:0,他引:9
C C Meltzer M N Cantwell P J Greer D Ben-Eliezer G Smith G Frank W H Kaye P R Houck J C Price 《Journal of nuclear medicine》2000,41(11):1842-1848
It remains a matter of controversy as to whether cerebral perfusion declines with healthy aging. In vivo imaging with PET permits quantitative evaluation of brain physiology; however, previous PET studies have inconsistently reported aging reductions in cerebral blood flow (CBF), oxygen metabolism, and glucose metabolism. In part, this may be because of a lack of correction for the dilution effect of age-related cerebral volume loss on PET measurements. METHODS: CBF PET scans were obtained using [15O]H2O in 27 healthy individuals (age range, 19-76 y) and corrected for partial-volume effects from cerebral atrophy using an MR-based algorithm. RESULTS: There was a significant difference (P = 0.01) in mean cortical CBF between young/midlife (age range, 19-46 y; mean +/- SD, 56+/-10 mL/100 mL/min) and elderly (age range, 60-76 y; mean +/- SD, 49+/-2.6 mL/100 mL/min) subgroups before correcting for partial-volume effects. However, this group difference resolved after partial-volume correction (young/midlife: mean +/- SD, 62+/-10 mL/100 mL/min; elderly: mean +/- SD, 61+/-4.8 mL/100 mL/min; P = 0.66). When all subjects were considered, a mild but significant inverse correlation between age and cortical CBF measurements was present in the uncorrected but not the corrected data. CONCLUSION: This study suggests that CBF may not decline with age in healthy individuals and that failure to correct for the dilution effect of age-related cerebral atrophy may confound interpretation of previous PET studies that have shown aging reductions in physiologic measurements. 相似文献
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