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101.
对4’-去甲表鬼臼毒素的C_4位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C_4位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。  相似文献   
102.
PD 138312 and PD 140248 are novel broad-spectrum 7-pyrrolidinyl fluoronaphthyridines with a cyclopropyl or a difluorophenyl substitution at the 1 positions, respectively. They have been demonstrated to have excellent in vitro activity against gram-positive organisms. These compounds were evaluated for their in vivo potencies against acute systemic infections in mice and in a mouse pneumococcal pneumonia model. They were very effective by both the oral and subcutaneous routes of administration. Most remarkable were their comparative median protective values against methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes. In general, these compounds were 28- to 100-fold more active than ciprofloxacin against these clinically significant organisms when the drugs were given orally and 10- to 38-fold more active when the drugs were given parenterally. Average ratios of drug concentrations in mice after drug administration by the oral route to that after administration by the subcutaneous route indicate 34 to 44% greater bioavailabilities of PD 138312 and PD 140248 compared with that of ciprofloxacin. In a multidose pneumococcal mouse pneumonia model these new quinolones were extremely effective, with median curative doses of 2 to 2.8 mg/kg of body weight per dose. Ciprofloxacin was ineffective (median curative dose, >100 mg/kg per dose) in this model. Comparative pharmacokinetic studies in mice revealed a relative superiority of PD 140248. Peak levels of PD 140248 in blood after the administration of a single oral 50-mg/kg dose were twice those of PD 138312 and ciprofloxacin, with PD 140248 having a substantially longer half-life. These results indicate that PD 138312 and PD 140248 have excellent therapeutic potential against clinically important gram-positive pathogens when the drugs are administered both orally and parenterally.  相似文献   
103.
基于在4′-去甲基表鬼臼毒素母核C4位上联结含有杂原子的芳香环取代基,以此考察其结构与活性关系的设想,设计并合成了10个标题化合物。体外L1210白血病细胞与KB细胞生长抑制试验结果表明,这类化合物有较强的抗肿瘤活性。其中化合物SIPI-92-1772,1774,1775,1776,1777与1779的活性超过临床用药依托泊甙。其余化合物活性与依托泊甙相当或略低。  相似文献   
104.
Berger  CN; Sturm  KS 《Blood》1996,88(7):2502-2509
Differentiation of hematopoietic precursor cells results in the formation of clonally related descendent cells. Using the mosaic expression of beta-galactosidase in female mouse fetuses heterozygous for an X-linked lacZ transgene, we analyzed the clonal relationship of the hematopoietic progeny. The proportion of beta-galactosidase positive cells for different T- and B-lymphoid and myeloid cell populations was determined at different stages of fetal development. We found excellent correlations of the proportion of beta-galactosidase expressing cells for all hematopoietic lineages confirming that they share a common ancestry. Therefore, it was possible to estimate the number of common precursor cells (PC) based on binomial distribution and covariance analysis of pairs of different hematopoietic cell populations. Our results obtained from hematopoietic cells at 15.5 to 18.5 days of gestation indicated the presence of 15 to 18 lymphoid and 18 to 22 myeloid/lymphoid specific precursor cells. Statistical analysis of the precursor cell numbers showed a trend of increasing numbers that was highly significant. The precursor cell number was inversely related to maturity of the cell populations analyzed; ie, the lowest number of lymphoid and lymphoid/myeloid precursors was calculated when the most mature CD3+ T-cell population was used for comparison. Determination of PC numbers can therefore be used to assess the relative maturity and developmental potential of individual cell populations.  相似文献   
105.
Narcolepsy is a chronic condition that usually afflicts the patient for decades. It is more common than is generally appreciated. However, it is likely to be misdiagnosed because doctors are unfamiliar with some of the symptoms. Its significant socioeconomic impact on the patient's quality of life warrants prompt medical attention.  相似文献   
106.
Tears of the triangular fibrocartilage of the wrist: MR imaging   总被引:2,自引:0,他引:2  
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107.
The 3-aminoquinzolinediones represent a new series of antibacterial agents structurally related to the fluoroquinolones. They are inhibitors of bacterial gyrase and topoisomerase IV and demonstrate clinically useful antibacterial activity against fastidious Gram-negative and Gram-positive organisms, including multidrug- and fluoroquinolone-resistant organisms. These agents also demonstrate in vivo efficacy in murine systemic infection models.  相似文献   
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110.
Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid beta-galactosidase (beta-gal). The disease manifests itself either as an infantile, juvenile or adult form and is primarily a neurological disorder with progressive brain dysfunction. A mouse model lacking a functional beta-gal gene has been generated by homologous recombination and embryonic stem cell technology. Tissues from affected mice are devoid of beta-gal mRNA and totally deficient in GM1-ganglioside- hydrolyzing capacity. Storage material was already conspicuous in the brain at 3 weeks. By 5 weeks, extensive storage of periodic acid Schiff- positive material was observed in neurons throughout the brain and spinal cord. Consistent with the neuropathology, abnormal accumulation of GM1-ganglioside in the brain progressed from twice to almost five times the normal amount during the period from 3 weeks to 3.5 months. Despite the accumulation of brain GM1-ganglioside at the level equal to or exceeding that seen in gravely ill human patients, these mice show no overt clinical phenotype up to 4-5 months. However, tremor, ataxia and abnormal gait become apparent in older mice. Thus, the beta-gal- deficient mice appear to mimic closely the pathological, biochemical and clinical abnormalities of the human disease.   相似文献   
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