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931.
JL Wiley DR Compton PM Gordon C Siegel M Singer A Dutta AH Lichtman RL Balster RK Razdan BR Martin 《Canadian Metallurgical Quarterly》1996,35(12):1793-1804
delta 8-Tetrahydrocannabinol (delta 8-THC) is a naturally occurring cannabinoid with a characteristic pharmacological profile of in vivo effects. Previous studies have shown that modification of the structure of delta 8-THC by inclusion of a nitrogen-containing functional group alters this profile and may alkylate the cannabinoid receptor, similar to the manner in which beta-funaltrexamine (beta-FNA) alkylates the micro-opioid receptor. Two novel analogs of delta 8-THC were synthesized: a nitrogen mustard analog with a dimethylheptyl side chain (NM-delta 8-THC) and a cyano analog with a dimethylpentyl side chain (CY-delta 8-THC). Both analogs showed high affinity for brain cannabinoid receptors and when administered acutely, produced characteristic delta 9-THC-like effects in mice, including locomotor suppression, hypothermia, antinociception and catalepsy. CY-delta 8-THC shared discriminative stimulus effects with CP 55,940; for NM-delta 8-THC, these effects also occurred, but were delayed. Although both compounds attenuated the effects of delta 9-THC in the mouse behavioral tests, evaluation of potential antagonist effects of these compounds was complicated by the fact that two injections of delta 9-THC produced similar results, suggesting that acute tolerance or desensitization might account for the observations. NM-delta 8-THC, but not CY-delta 8-THC, attenuated the discriminative stimulus effects of CP 55,940 in rats several days following injection. Hence, addition of a nitrogen-containing functional group to a traditional cannabinoid structure does not eliminate agonist effects and may produce delayed attenuation of cannabinoid-induced pharmacological effects. 相似文献
932.
933.
DR Sain 《Canadian Metallurgical Quarterly》1994,105(3):25A-26A; author reply 39A
934.
935.
Self-determination theory (Deci & Ryan, 1985) posits that (a) people are inherently motivated to internalize the regulation of uninteresting though important activities; (b) there are two different processes through which such internalization can occur, resulting in qualitatively different styles of self-regulation; and (c) the social context influences which internalization process and regulatory style occur. The two types of internalization are introjection, which entails taking in a value or regulatory process but not accepting it as one's own, and integration, through which the regulation is assimilated with one's core sense of self. Introjection results in internally controlling regulation, whereas integration results in self-determination. An experiment supported our hypothesis that three facilitating contextual factors--namely, providing a meaningful rationale, acknowledging the behaver's feelings, and conveying choice--promote internalization, as evidenced by the subsequent self-regulation of behavior. This experiment also supported our expectation that when the social context supports self-determination, integration tends to occur, whereas when the context does not support self-determination, introjection tends to occur. 相似文献
936.
937.
DM Zimmerman BE Cantrell EC Smith JA Nixon RF Bruns B Gitter PA Hipskind PL Ornstein H Zarrinmayeh TC Britton DA Schober DR Gehlert 《Canadian Metallurgical Quarterly》1998,8(5):473-476
A 50-year-old male is described who presented with Fournier's gangrene as what is probably the first manifestation of a newly diagnosed acute myelogenous leukemia (AML), promyelocytic type or variant type M3 according to the FAB classification. Despite aggressive fluid resuscitation, tuned infusion of vasoactive drugs, appropriate antibiotics and extensive surgical debridement, the patient died within 24 h as a result of irreversible septic shock. 相似文献
938.
G Apseloff B Girten M Walker DR Shepard ME Krecic LS Stern N Gerber 《Canadian Metallurgical Quarterly》1993,264(3):1071-1078
Hind-limb unloading by tail suspension of rats, an established model of simulated microgravity, was used to examine the efficacy of aminohydroxybutane bisphosphonate (AHBuBP) and clenbuterol in preventing bone loss and muscle atrophy, respectively. Male Sprague-Dawley rats (299-372 g) were randomized into six groups of six: 1) unsuspended, saline, 2) unsuspended, saline, pair fed with group 3, 3) suspended, saline, 4) suspended, 0.03 mg/kg/day x 2 of AHBuBP, 5) suspended, 0.3 mg/kg/day x 2 of AHBuBP and 6) suspended, 0.3 mg/kg/day x 2 of AHBuBP + clenbuterol (0.5 mg/kg/day i.p. x 6, then 1 mg/kg/day i.p. x 6). Animals in groups 3 to 6 were tail suspended for 14 days from a system of double pulleys and allowed free mobility with their hind limbs unloaded. On days -2 and -1, before suspension on day 0, all rats received a single s.c. injection of either 2 ml/kg of normal saline (vehicle) or AHBuBP. All rats were tested for exercise tolerance before day -2 and on day 10, and grip strength before day -2 and on day 13. On day 14, the rats were euthanized and their humeri, tibias and femurs analyzed in vitro for bone density (by single-photon absorptiometry), strength and stiffness (by 3-point bending). Muscles were analyzed for weight, protein concentration and enzyme activity. Pair feeding had no effect other than on food consumption and body weight. AHBuBP caused a dose-dependent increase in bone density in humeri, tibias and femurs, even in tail-suspended rats, relative to control unsuspended animals, with no significant difference in bone strength or stiffness between AHBuBP groups and unsuspended animals.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
939.
AL McDonald RJ Fielder GE Diggle DR Tennant CE Fisher 《Canadian Metallurgical Quarterly》1996,15(9):739-746
A pragmatic possible approach to the prioritization of chemical carcinogens occurring as food contaminants is described, based on the carcinogenic risk to the population. This should be of value in ensuring that resources for assessment and management of carcinogens in food are directed to the most important areas with regard to carcinogenic risk to the population. Key components of this approach are an assessment of the carcinogenic hazard to humans combined with estimations of intakes per person and of the proportion of the population exposed. These are used to derive an index referred to as the Population Carcinogenic Index. Concerning the hazard assessment expert judgement is used to place the chemical in one of five categories. The highest category is for chemical carcinogens that are believed to act by a genotoxic mechanism. It is recognised that such compounds may vary enormously with respect to their potency and various approaches to ranking carcinogens on the basis of potency are reviewed. The approach adopted is to subdivide the genotoxic carcinogens category into high, medium and low potency based on the TD50 value. Methods of estimating intakes and exposed populations are considered and an approach which groups these into broad categories is developed. The hazard and exposure assessments are then combined to derive the Population Carcinogenicity Index. 相似文献
940.
O Takamiya G Kemball-Cook DM Martin DN Cooper A von Felten E Meili I Hann DR Prangnell H Lumley EG Tuddenham 《Canadian Metallurgical Quarterly》1993,2(9):1355-1359
Five unrelated subjects with dysfunctional coagulation factor VII (FVII) were studied in order to identify missense mutations affecting function. Exons 2 to 8 and the intron-exon junctions of their FVII genes were amplified from peripheral white blood cell DNA by PCR and screened by SSCP analysis. DNA fragments showing aberrant mobility were sequenced. The following mutations were identified: in case 1 (FVII:C < 1%, FVII:Ag 18%) a heterozygous A to G transition at nucleotide 8915 in exon 6 results in the amino acid substitution Lys-137 to Glu near the C-terminus of the FVIIa light chain; in case 2 (FVII:C 7%, FVII:Ag 47%) a heterozygous A to G transition at nucleotide 7834 in exon 5 results in the substitution of Gln-100 by Arg in the second EGF-like domain; in case 3 (FVII:C 20%, FVII:Ag 76%) a homozygous G to A transition at nucleotide position 6055 in exon 4 was detected resulting in substitution of Arg-79 by Gln in the first EGF-like domain; in case 5 (FVII:C 10%, FVII:Ag 52%) a heterozygous C to T transition at nucleotide position 6054 in exon 4 also results in the substitution of Arg79, but in this case it is replaced by Trp; case 4 (FVII:C < 1%, FVII:Ag 100%) was homozygous for a previously reported mutation (G to A) at nucleotide position 10715 in exon 8, substituting Gln for Arg at position 304 in the protease domain. Cases 1, 2 and 5 evidently have additional undetected mutations. 相似文献