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51.
Qingju Wang Markku Alén Arja Lyytikäinen Leiting Xu Fran A Tylavsky Urho M Kujala Heikki Kröger Ego Seeman Sulin Cheng 《Journal of bone and mineral research》2010,25(7):1512-1520
Familial resemblance and diversity in bone structure and strength in adulthood are determined in part during growth. Whether these characteristics are established during gestation or shortly after birth is not known. Total‐body, lumbar spine, and femoral neck size and mass and indices of tibial bending strength and distal radial compressive strength were measured using bone densitometry and quantitative computed tomography in 236 girls at 18.5 years of age. Among them, 219, 141, and 105 girls had crown‐heel length (CHL) and weight recorded at birth and at 6 and 12 months of age, and then height and weight were recorded at 3, 5, 10, 13, and 15 years of age in 181, 176, 127, 111, and 228 girls, respectively. Of these girls, 101 and 93 girls also had bone structure assessed at 11 and 13 years of age, respectively. Similar bone measurements were made once in 78 mother‐father pairs. CHL and weight at birth did not correlate or did so weakly with bone traits in girls at 18 years of age. By contrast, CHL at 6 months correlated with the height, bone traits, and strength at puberty and at 18 years of age (r = 0.24–0.56, p < .001) in girls and with their parents' height and bone traits (r = 0.15–0.37, p < .05). When the girls' CHL at 6 months was stratified into quartiles, the absolute and relative differences in bone traits observed at puberty (~11.5 years) were maintained as these traits tracked during the ensuing 7 years. Similarly, weight at 6 months correlated with the girls' bone traits at puberty and 18 years of age (r = 0.22–0.55, p < .05). During puberty and at 18 years of age, the girls' bone traits correlated with the corresponding traits in their parents (r = 0.32–0.43, p < .01). It is concluded that familial resemblance in bone structural strength and the position of an individual's bone traits relative to others in adulthood are likely to be established during the first year of life. Thus susceptibility to bone fragility late in life has its antecedents established early in life. © 2010 American Society for Bone and Mineral Research 相似文献
52.
Babul Borah Tom Dufresne Joe Nurre Roger Phipps Paula Chmielewski Leigh Wagner Mark Lundy Mary Bouxsein Roger Zebaze Ego Seeman 《Journal of bone and mineral research》2010,25(1):41-47
Nonvertebral fractures account for 80% of all fractures and their accompanying morbidity and mortality. Despite this, the effect of drug therapy on cortical morphology has received limited attention, partly because cortical bone is believed to remodel less and decrease less with age than trabecular bone. However, the haversian canals traversing the cortex provide a surface for remodeling that produces bone loss, porosity, and cortical fragility. We developed a new method of 3D micro‐computed tomography (µCT) to quantify intracortical porosity and the effects of treatment. Women with osteoporosis randomized to risedronate (5 mg/day, n = 28) or placebo (n = 21) had paired transiliac biopsies at baseline and 5 years imaged using 3D µCT. Pores determined from 8 to 12 slices were stratified by their minor axis length into those 25 to 100 µm (closing cone of haversian canals), 100 to 300 µm (cutting cone of haversian canals), and >300 µm (coalescent cavities). Porosity was analyzed as pore area (percent bone area) and pore density (pore number/mm2). Medians are reported. Risedronate reduced pore area in the 25 to 100, 100 to 300, and 300 to 500 µm ranges over 5 years (p = .0008, .04, NS, respectively) corresponding to an 18% to 25% reduction. In the placebo group, pore area was unchanged. At 5 years, pore area and pore number/mm2 in the 25 to 100 µm range were each 17% lower in the risedronate group than in the placebo group (p = .02 and .04, respectively). Risedronate is likely to maintain bone strength and reduce nonvertebral fracture risk in part by reducing remodeling and therefore the number and size of intracortical cavities. © 2010 American Society for Bone and Mineral Research 相似文献
53.
I. Borgulová R. Mazanec I. Sakmaryová M. Havlová D. Šafka Brožková P. Seeman 《Neurogenetics》2013,14(3-4):189-195
Charcot-Marie-Tooth (CMT) disease is a heterogeneous disorder of the peripheral nervous system that collectively affects approximately 1 in 2,500 individuals, thus making it the most common inherited neurologic disorder. X-linked inheritance may account for 10–20 % of CMT neuropathy. We report a Czech family with a 30-year-old woman affected by CMT since the age of 10 years, originally as an isolated case. Nerve conduction study (NCS) showed demyelinating neuropathy, and DNA testing revealed a novel heterozygous gap junction beta-1 protein (GJB1) mutation c.784_786delTA. The same mutation, but surprisingly in heterozygous state, was subsequently found in her subjectively healthy father and later also in one of her sisters but not in her two other sisters. NCS showed intermediate type of motor and sensory neuropathy in these two females manifesting heterozygotes and normal results in the other healthy sisters and one brother, all without the c.784_786delTA mutation. The father has a phenotype milder than his daughter and has only subclinical signs of CMT. The index female patient had normal karyotype 46, XX, and normal FISH for centromeric X chromosome. We concluded that the proband’s father is a heterozygote due to the somatic mosaicism for the GJB1 mutation in his leukocytes (detected by DNA sequencing) and also in his germ cells as confirmed by the unexpectedly different genotypes in his four daughters. Quantitative analysis revealed a mutated signal in 25:75 allele proportion of mutated to healthy allele in the mosaic father. This study has important consequences for genetic counseling and prognosis in CMTX1 families. 相似文献
54.
Parkinson's disease treatment may cause impulse–control disorder via dopamine D3 receptors 下载免费PDF全文
Philip Seeman 《Synapse (New York, N.Y.)》2015,69(4):183-189
In treating Parkinson's disease with dopaminergic agonists, such as pramipexole, ropinirole, pergolide, rotigotine, apomorphine, or bromocriptine, it has been observed that a significant number of patients develop impulse–control disorders, such as compulsive shopping, pathological gambling, or hypersexuality. Because the dopamine agonists have high affinities for the dopamine D2 and D3 receptors, the drug dissociation constants of these drugs at the functional high‐affinity states of these receptors, namely D2High and D3High, were compared. The data show that, compared to the other dopamine agonist drugs, pramipexole has a relatively high selectivity for the dopamine D3 receptor, as compared to D2, suggesting that the D3 receptor may be a primary target for pramipexole. There is a trend showing that the proportion of impulse–control disorders is related to the selectivity for D3 receptors over D2 receptors, with pramipexole having the highest association with, or frequency of, impulse–control disorders. While the number of studies are limited, the proportion of patients with impulse–control disorder in Parkinson patients treated with an add‐on agonist were 32% for pramipexole, 25% for ropinirole, 16% for pergolide, 22% for rotigotine, 10% for apomorphine, and 6.8% for bromocriptine. Clinically, temporary replacement of pramipexole by bromocriptine may provide relief or reversal of the impulsive behavior associated with selective D3 stimulation by either pramipexole or ropinirole, while maintaining D2 stimulation needed for the anti‐Parkinson action. Synapse, 69:183–189, 2015 . © 2015 Wiley Periodicals, Inc. 相似文献
55.
Shelley E Taylor Barbara J Lehman Catarina I Kiefe Teresa E Seeman 《Neuropsychopharmacology》2006,60(8):819-824
BACKGROUND: Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset. METHODS: Participants (n = 3248) in the CARDIA study, age 32 to 47 years, completed measures of childhood SES (CSES), early family environment (risky families [RF]), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein. RESULTS: Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRP, all p < .05), with good overall model fit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both p < .05). CONCLUSIONS: Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index. 相似文献
56.
Vasdev N Natesan S Galineau L Garcia A Stableford WT McCormick P Seeman P Houle S Wilson AA 《Synapse (New York, N.Y.)》2006,60(4):314-318
Dopamine D2 partial agonists have been successfully used as schizophrenia therapeutics. Radiolabeled D2 partial agonists may have application in elucidating dopaminergic transmission. It was the goal of this work to radiolabel (S)-(-)propyl-3-(3-hydroxyphenyl)piperidine (preclamol; (-)3-PPP), a partial dopamine D2 agonist with carbon-11 (half-life=20.4 min) and to evaluate this novel radiopharmaceutical for dopaminergic imaging in rodent models. [11C]Preclamol was synthesized by acylation of (S)-3-(3-hydroxyphenyl)piperidine hydrochloride with [11C]propionyl chloride, followed by LiAlH4 reduction, and HPLC purification. Male Sprague-Dawley rats were injected in the tail vein with a saline solution of [11C]preclamol (1.1 mug/kg) and sacrificed at 5, 15, 30 and 60 min postinjection. Brain regions were excised, weighed, and measured for radioactivity. In vivo binding kinetics of [11C]preclamol were determined with beta-sensitive microprobes implanted into the striatum and cerebellum of an anesthetized rat. A full production of [11C]preclamol resulted in 34 mCi ready for injection (corresponding to 4% uncorrected radiochemical yield, based on starting [11C]CO2) with specific activity of 535 mCi/micromol. The total synthesis time was 45 min and resulted in chemically and radiochemically pure [11C]preclamol (>99%; n=3). High levels of radioactivity were observed in rat brain indicating good blood-brain barrier penetration of [11C]preclamol, with 0.5 to 0.7% injected dose per gram of wet tissue present in all brain regions at 5 minutes postinjection. Unfortunately, [11C]preclamol displayed minimal preferential uptake in dopaminergic brain regions. A low striatal specific binding (SB) ratio of 0.32 was determined ex vivo at 60 min postinjection and was in close agreement with the microprobe study over 60 min (peaked at 27 min postinjection; SB ratio=0.6). The binding potential value was only 0.34 over a 1 hour time course, suggesting that [11C]preclamol is not suitable for cerebral PET studies. 相似文献
58.
59.
S H Kim J L Sussman F L Suddath G J Quigley A McPherson A H Wang N C Seeman A RICH 《Proceedings of the National Academy of Sciences of the United States of America》1974,71(12):4970-4974
The three-dimensional structure of yeast phenylalanine tRNA serves as a useful basis for understanding the tertiary structure of all tRNAs. A large number of tRNA sequences have been surveyed and some general conclusions are drawn. There are only a few regions in the molecule in which there are differences in the number of nucleotides; and the structure of yeast phenylalanine tRNA can accommodate these differences by forming or enlarging protuberances on the surface of the basic framework molecule. The nature and distribution of the differences in number of nucleotides are surveyed and possible hydrogen bonding interactions are discussed for a number of tRNA classes. The two most significant features of the molecule are the large number of stacking interactions which are seen to include most of the nucleotides in the molecule and the system of specific hydrogen bonding interactions. It is likely that these stabilizing elements are preserved in all tRNA structures. 相似文献
60.
Dopamine partial agonist actions of the glutamate receptor agonists LY 354,740 and LY 379,268 总被引:1,自引:0,他引:1
Because glutamate compounds alter the release of dopamine and prolactin, the present study examined whether group II metabotropic receptor agonists, LY 354,740 and LY 379,268, had any direct in vitro action on dopamine D2 receptors on rat striatal tissue, cloned D2Long receptors, and prolactin release from anterior pituitary cells. In competition versus the D2-specific ligand [(3)H]domperidone, LY 354,740 had a dissociation constant of 24 nM at D2(High) (the functional high-affinity state of dopamine D2 receptors), while the value for LY 379,268 was 21 nM. LY 354,740 also stimulated by 50% the incorporation of [(35)S]-GTP-gamma-S at a concentration of 120 nM, but its maximal stimulation was only 22% of the maximum elicited by dopamine. LY 379,268 stimulated by 50% the incorporation of [(35)S]-GTP-gamma-S at 280 nM, but its maximal stimulation was also only 22% of the maximum elicited by dopamine. However, both LY 354,740 and LY 379,268 potently inhibited the dopamine-induced incorporation of [(35)S]-GTP-gamma-S with inhibitory Ki values of 43 nM and 30 nM, respectively. The release of prolactin from rat isolated anterior pituitary cells in culture was 50% inhibited by 20 nM LY 379,268 and by 100 nM LY 354,740. These Ki values are similar to those known for the mGluR II receptor, suggesting that these compounds may have both glutamate and dopamine actions in vivo. The dopamine agonist and antagonist actions of these compounds indicate that these drugs have properties of a dopamine partial agonist, and may, therefore, have antipsychotic action. 相似文献