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11.
高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数 总被引:1,自引:0,他引:1
本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4~5.6%,血浓69.6~1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。 相似文献
12.
Edward T Mannix Melanie Roberts Daniel P Fagin Brandie Reid Mark O Farber 《The Journal of asthma》2003,40(4):349-355
Athletes have a high prevalence (11-50%) of exercise-induced asthma, which may be caused by the hyperventilation accompanying repetitive bouts of strenuous exercise. We hypothesized that recreational exercisers would display a similar trend. Eucapnic voluntary hyperventilation (EVH) bronchoprovocation (breathing 21% O2, 5% CO2, and 74% N2 at 60% of MVV for 5 minutes) was performed to determine the prevalence of airways hyperresponsiveness (AHR) in adults (n=212, 146 males, mean +/- standard deviation, age 32 +/- 10 years) who exercised regularly (10 +/- 10 years, 31 +/- 28% of their lives): none had a previous diagnosis of asthma. AHR was defined by at least a 10%, 20%, or 25% decline in FEV1, FEF(25-75), or PEFR, respectively, by spirometry at 1, 5, 10, and 15 minutes post-EVH. Forty-one of 212 (19%) tested positive for AHR: 20 of 41 (49%) were positive by FEV1, 28 of 41 (68%) by FEF(25-75), and 27 of 41 (66%) by PEFR. Comparing responders with nonresponders: pre-EVH lung function was equivalent, except for FEV1, which was reduced (p<0.05) in responders (96 +/- 13 vs. 102 +/- 12% predicted). Mean maximal negative deflections for responders were: for FEV1, -17 +/- 7%; FEF(25-75), -31 +/- 10%; PEFR, -38 +/- 11%. Ranges of decline for responders were: FEV1, -10 to -33%; FEF(25-75), -20 to -59%; PEFR, -25- to -70%. We conclude that in these regular exercisers, the prevalence of AHR is high and comparable with some athletic populations. 相似文献
13.
Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress 总被引:3,自引:0,他引:3
Pretreatment of cultured hepatocytes with the ferric iron chelator deferoxamine prevents the killing of the cells by tert-butyl hydroperoxide (TBHP). Incubation of the deferoxamine-pretreated hepatocytes in a serum-free medium containing only 0.25 nM iron restored the sensitivity of the cells to TBHP within 4 to 6 hr. An amino acid-free medium accelerated the restoration of sensitivity in parallel with an enhanced rate of degradation of 14C-prelabeled protein. By contrast, inhibitors of the autophagic degradation of protein, including chymostatin, 3-methyladenine, benzyl alcohol, colchicine, oligomycin, and methylamine, inhibited the restoration of sensitivity of deferoxamine-treated hepatocytes to TBHP in parallel with their inhibition of protein degradation. With chymostatin, 3-methyladenine, benzyl alcohol, and colchicine, there was a parallel dose dependency of both the inhibition of protein turnover and the inhibition of the restoration of sensitivity to TBHP. Ascorbic acid, known to specifically retard the autophagic degradation of ferritin, inhibited the restoration of sensitivity to TBHP without effect on the general rate of protein turnover. None of the agents studied had any protective effect on the toxicity of TBHP for hepatocytes that were not pretreated with deferoxamine. These data indicate that the autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by TBHP. 相似文献
14.
石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成 总被引:4,自引:1,他引:3
石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。 相似文献
15.
16.
Mosaicism for an FMR1 gene deletion in a fragile X female 总被引:2,自引:0,他引:2
Fan H Booker JK McCandless SE Shashi V Fleming A Farber RA 《American journal of medical genetics. Part A》2005,136(2):214-217
Most cases of fragile X syndrome result from expansion of CGG repeats in the FMR1 gene; deletions and point mutations of FMR1 are much less common. Mosaicism for an FMR1 full mutation with a deletion or with a normal allele has been reported in fragile X males. Here we report on a fragile X female who is mosaic for an FMR1 full mutation and an intragenic deletion. The patient is a 4-year-old girl with developmental delay, autistic-like behaviors, and significant speech and language abnormalities. Southern blotting demonstrated the presence of a methylated full mutation, a normal allele in methylated and unmethylated forms, and an additional fragment smaller than the normal methylated allele. This result indicates that the patient is mosaic for a full mutation and a deletion, in the presence of a normal allele. By DNA sequence analysis, we mapped the 5' breakpoint 63/65 bp upstream from the CGG repeat region and the 3' breakpoint 86/88 bp downstream of the CGG repeats within the FMR1 gene. The deletion removed 210 bp, including the entire CGG repeat region. The full mutation was inherited from a premutation in the patient's mother. The deletion, which remained methylated at the Eag I and Nru I sites, was probably derived from the full mutation allele. Mosaicism of this type is rare in females with a fragile X mutation but should be kept in mind in the interpretation of Southern blots. 相似文献
17.
Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy 总被引:3,自引:0,他引:3
Kelsell RE; Gregory-Evans K; Payne AM; Perrault I; Kaplan J; Yang RB; Garbers DL; Bird AC; Moore AT; Hunt DM 《Human molecular genetics》1998,7(7):1179-1184
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to
within an 8 cM interval on chromosome 17p12-p13. The retinal- specific
guanylate cyclase gene (RETGC-1), which maps to within this genetic
interval and previously was implicated in Leber's congenital amaurosis, was
screened for mutations within this family and in a panel of small families
and individuals with various cone and cone- rod dystrophy phenotypes. A
missense mutation (E837D) was identified in affected members of the CORD6
family, as well as a second missense mutation (R838C) in three other
families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene
to be implicated in cone-rod dystrophy and this is the first report of
dominant mutations in this gene.
相似文献
18.
Studies on Acute Methionine Toxicity: I. Nucleolar Disaggregation in Guinea Pig Hepatic Cells with Methionine or Ethionine and Its Reversal with Adenine 下载免费PDF全文
Hisashi Shinozuka Larry W. Estes Emmanuel Farber 《The American journal of pathology》1971,64(2):241-256
The effects of methionine and ethionine on the fine structure of hepatic cell nucleoli of guinea pigs and rats were investigated. A single intraperitoneal injection of methionine into guinea pigs results in the disruption of nucleolonema as early as 2 hours after the injection. By 4 hours, nucleoli show complete fragmentation consisting of many small fragments and small remnants of nucleoli. Large aggregates of interchromatinic granules and condensation of chromatin appear in the nucleoplasm. These changes are remarkably similar to the lesions induced by ethionine in the liver of the rat or the guinea pig. The methionine-induced nuclear and nucleolar lesions persist up to 10 hours after the injection. The administration of adenine 4 hours after the methionine injection reverses the nucleolar lesions by 8 hours. The appearance of incompletely reconstructed nucleoli with twisted ropelike structures suggests a pattern of recovery very similar to the adenine-induced nucleolar reformation in ethionine-treated rats. Injecting methionine into rats induced no nucleolar abnormalities. It is suggested that the mechanism of nucleolar fragmentation induced by methionine or ethionine is related to the accumulation of S-adenosyl compounds with concomitant ATP deficiency in the liver. 相似文献
19.
B R Broxup V E Valli G L Losos D H Percy E Farber I McMillan 《Toxicologic pathology》1988,16(4):401-417
Classification of rat hepatocellular proliferative lesions can vary between pathologists as the many qualitative histologic criteria have not been satisfactorily evaluated and ranked for prognostic value. Computer-assisted morphometry offers an objective method to evaluate certain cellular features. The Solt-Farber resistant hepatocyte model was used in this study to produce populations of rats with a full range of hepatocellular proliferative lesions. Cellular features within the lesions were then measured morphometrically and the data were analyzed by animal age and by subjective lesion diagnosis. The nuclear/cytoplasmic ratio followed by the cell area and nuclear area were found to be the most important parameters for separating microscopic foci and islands of cellular alteration, an early hyperplastic lesion, from other hepatocellular proliferative lesions. The coefficient of variation, as a relative measure of heterogeneity, increased in a linear manner for cell, nuclear and nucleolar areas as the animals aged and was significantly higher for cell and nuclear area in hepatocellular carcinoma compared to other hepatocellular proliferative lesions. Hepatocyte nodules (representing primarily late hyperplastic lesions) and persistent hepatocyte nodules (lesions with similarities to hepatocellular adenoma) could not be satisfactorily separated within the limits of this study. As these borderline lesions show a continuum of cytologic change, other features, such as architectural change, are necessary to satisfactorily classify them on a subjective basis. An alternative approach is to use discriminant functions derived from morphometric studies. 相似文献
20.
Dissecting the complexity of the memory T cell response 总被引:2,自引:0,他引:2
Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that
persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature
of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory
T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have
applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell
pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing
receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems.
These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses
and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to
deciphering the complex nature of the memory immune response. 相似文献