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1.
I A Cliffe E L Lien H L Mansell K E Steiner R S Todd A C White R M Black 《Journal of medicinal chemistry》1992,35(7):1169-1175
A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a standard dose of 100 mg/kg to fed rats. The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido[1,2-a]indoles was investigated. Relative potencies of a number of the most active compounds were defined by three-point dose-response studies. The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido[1,2-a]indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group. The most potent 10-amino derivatives were 57 and 58. 相似文献
2.
Locomotor strategies before independent walking: prospective study of 50 mentally retarded children.
To investigate the association between pre-walking locomotor strategies and psychomotor developments in children with mental retardation (MR), 50 children with non-specific MR were included in this study. There were 29 boys and 21 girls, 96% of whom had moderate to severe MR. They were followed from 4-53 months to 25-99 months of age, and their follow-up periods ranged from 10 to 48 months (mean 30 months). According to the pre-walking locomotor strategies, these children were categorized into three groups: the crawling group (n = 34) who used crawling or creeping as their main locomotion pattern before independent walking; the shuffling group (n = 9) who used shuffling prior to independent walking; and the direct-walking group (n = 7) who did not have any other locomotor strategies except rolling. In almost all motor developmental milestones, children in the direct-walking group developed earlier than those in the crawling and shuffling groups. Children in the crawling group had more advanced developments than those in the shuffling group. The difference in the mean ratio developmental quotients of the Bayley Mental Scale among the three groups was not significant. The present study showed that crawling may not be a necessary prerequisite for early ambulation or better cognitive function in MR children. 相似文献
3.
N. S. Stuart P. Philip A. L. Harris K. Tonkin S. Houlbrook J. Kirk E. A. Lien J. Carmichael 《British journal of cancer》1992,66(5):833-839
Twenty-six patients with relapsed or drug-resistant cancer were treated with a combination of oral etoposide (300 mg day-1 for 3 days) and high-dose oral tamoxifen as a potential modulator of drug resistance (480 or 720 mg day-1 for 6 days beginning 3 days before etoposide). One patient with relapsed high-grade lymphoma and one with adenocarcinoma of unknown primary site has a partial response. Toxicity consisting of nausea, vomiting and subjective dizziness, unsteadiness of gait and malaise occurred during tamoxifen treatment. Serum levels of tamoxifen averaged 3-3.5 microM on day 4 of all courses of treatment at both 480 and 720 mg day-1. N-desmethyltamoxifen levels were lower than tamoxifen during the first course (2 microM) but increased to equal tamoxifen levels during the second course. Didesmethyltamoxifen levels remained below 1 microM. In vitro, both tamoxifen and the standard modulator of multidrug resistance, verapamil, produced minor enhancement of etoposide cytotoxicity in the MCF-7 wt cell line but produced no enhancement with any other cell line. High, intermittent doses of tamoxifen can be given with acceptable toxicity and produce serum levels that have been shown to modulate drug resistance in vitro. In vitro, however, such levels have no significant effect on etoposide cytotoxicity towards a range of wild-type and MDR cell lines. 相似文献
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Sarah J Spence Rita M Cantor Lien Chung Sharon Kim Daniel H Geschwind Maricela Alarcón 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(6):591-598
The identification of autism susceptibility genes has been hampered by phenotypic heterogeneity of autism, among other factors. However, the use of endophenotypes has shown preliminary success in reducing heterogeneity and identifying potential autism-related susceptibility regions. To further explore the utility of using language-related endophenotypes, we performed linkage analysis on multiplex autism families stratified according to delayed expressive speech and also assessed the extent to which parental phenotype information would aid in identifying regions of linkage. A whole genome scan using a multipoint non-parametric linkage approach was performed in 133 families, stratifying the sample by phrase speech delay and word delay (WD). None of the regions reached suggested genome-wide or replication significance thresholds. However, several loci on chromosomes 1, 2, 4, 6, 7, 8, 9, 10, 12, 15, and 19 yielded nominally higher linkage signals in the delayed groups. The results did not support reported linkage findings for loci on chromosomes 7 or 13 that were a result of stratification based on the language delay endophenotype. In addition, inclusion of information on parental history of language delay did not appreciably affect the linkage results. The nominal increase in NPL scores across several regions using language delay endophenotypes for stratification suggests that this strategy may be useful in attenuating heterogeneity. However, the inconsistencies in regions identified across studies highlight the importance of increasing sample sizes to provide adequate power to test replications in independent samples. 相似文献
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BACKGROUND: Although soy formulas have been designed to meet the nutrient requirements of human infants, they also contain phytate, which may negatively affect trace element absorption. OBJECTIVE: We evaluated the effect of removing phytate on zinc and copper absorption and status in infant rhesus monkeys and suckling rat pups and evaluated differences between intact and partially hydrolyzed soy protein. DESIGN: In monkeys, regular and low-phytate soy formulas were fed exclusively for 4 mo and whole-body absorption and retention of 65Zn, 67Cu, 59Fe, 54Mn, and 47Ca were determined at different time points with a whole-body counter. Subsequently, zinc and copper absorption from several human infant formulas and the effect of phytate concentration were evaluated in suckling rat pups by using 65Zn and 64Cu. Finally, infant rhesus monkeys were fed low-phytate formulas with intact or hydrolyzed soy protein for 4 mo and plasma zinc and copper were measured monthly. RESULTS: In the first monkey study, zinc absorption at 1 mo was higher from low-phytate soy formula (36%) than from regular soy formula (22%), whereas there was no significant difference between groups in the absorption of other minerals. Plasma copper was significantly lower in monkeys fed low-phytate soy formula from 2 to 4 mo. In rat pups, zinc absorption was significantly higher from low-phytate soy formula (78%) than from regular soy formula (51%) and hydrolysis of the protein had no significant effect. Phytate content or protein hydrolysis did not significantly affect copper absorption. In the second monkey study, plasma copper concentrations were highest in monkeys fed the low-phytate, hydrolyzed-protein soy formula. CONCLUSION: Reducing the phytate content and partially hydrolyzing the protein in soy formula had a beneficial effect on zinc and copper absorption and status in infant rhesus monkeys. 相似文献
9.
Lien CA 《Current opinion in anaesthesiology》1999,12(4):467-471
As the quality of currently available relaxants has improved, the need to combine relaxants to minimize the incidence and severity of their side-effects has decreased. Little work has been done in the past year characterizing the effects of combining different non-depolarizing neuromuscular blocking agents. That which has been done sheds some light on the nature of their interactions. 相似文献
10.
Inhibition of herpes simplex virus type 1 and adenovirus type 5 by heterocyclic Schiff bases of aminohydroxyguanidine tosylate 总被引:3,自引:0,他引:3
Eleven heterocyclic Schiff bases of aminohydroxyguanidine tosylate (SB-AHGs), compounds I-XI, were tested for antiviral activity against herpes simplex virus type 1 (HSV-1) and adenovirus type 5 (Ad 5) via plaque reduction and virus yield reduction assays. This work was undertaken to test the hypothesis that low molecular weight SB-AHGs (MW < 235 for the free SB) make better antiviral agents than high MW SB-AHGs (MW > 300). The plaque reduction assay method demonstrated that three compounds, I, VII and IX, had moderate activity against HSV-1, with 50% inhibitory concentration (IC50) values of 38.0, 23.5 and 52.1 microM, respectively. Against Ad 5, compounds I, VIII and XI exhibited moderate activity, with IC50 values of 52.7, 19.3 and 5.1 microM, respectively. Among the compounds screened, compound I (1-[(3'-hydroxy-6'-methyl-2'-pyridyl)methylene]amino-3-hydroxyguanidi ne tosylate) was the most promising antiviral candidate, with selectivity indices (SI) of 10.2 (HSV-1) and 7.6 (Ad 5), respectively. Virus yield reduction assays indicated that compound I had less antiviral potency against HSV-1 than against Ad 5. The antiviral effects of compound I at a high input virus multiplicity of infection (MOI > 5) indicated that compound I had effective anti-adenoviral activity at 24 h post infection. This work demonstrated that some of SB-AHGs only have moderate antiviral activities against Ad 5 and HSV-1 viruses. In general, low MW SB-AHGs have low cytotoxicities to the host cells. 相似文献