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741.
742.
Noboru Oriuchi Naoyuki Watanabe Hidetoshi Kanda Makoto Hashimoto Sumio Sugiyama Seiichi Takenoshita Kyouichi Imai Ryuzou Ueda K. Endo 《Cancer immunology, immunotherapy : CII》1998,46(6):311-317
The study was designed to clarify the difference in pharmacokinetics of monoclonal antibodies (mAb) in animal models and
humans, and to elucidate the applicability of animal models. 99mTc-labeled murine mAb – against carcinoembryonic antigen (designated BW431/26), and neural cell adhesion molecule (NE150)
– and one chimeric mouse/human mAb against nonspecific cross-reacting antigen (chNCA) were administered i.v. to normal mice
and athymic mice (370 kBq, 400 ng) xenografted with human cancer cells expressing antigens, and into patients with tumor (925
MBq, 1 mg). The biodistribution of two of the three mAb (not 99mTc-BW431/26) differed clearly in mice and patients. 99mTc-NE150 showed specific uptake in xenografted tumor and otherwise a normal biodistribution; however, clinical examination
showed increased uptake in the liver with rapid blood clearance (mean α half-life = 31.1 min) compared with 99mTc-BW431/26 (28.4 h). 99mTc-chNCA demonstrated increased blood clearance and renal excretion in both normal and athymic mice, with accumulation in
tumors. Clinical examination showed rapid blood clearance (mean α half-life = 6.4 min) and increased uptake in the liver.
High-performance liquid chromatographic analysis of 99mTc-chNCA revealed the immune complex in blood, suggesting uptake of the complex by the reticuloendothelial cells. The biodistribution
of radiolabeled mAb in animal and human models was variable and specific for each of the three mAb. The results of animal
studies with mAb should be evaluated carefully before being extrapolated to humans, on the basis of the nature of the mAb
and interacting substances.
Received: 9 April 1997 / Accepted 3 March 1998 相似文献
743.
New beta-lactamase-resistant cephem treatment of guinea pigs infected with Legionella pneumophila 总被引:4,自引:0,他引:4
The in vivo antimicrobial effect of seven new beta-lactamase-resistant cephems (cefotaxime, latamoxef, ceftazidime, ceftriaxone, cefotiam, cefbuperazone, and MT-141) on Legionella pneumophila (strain 81-066, serogroup IV) in guinea pigs was compared with that of erythromycin. As the minimal LD100 within one week was about 4.0 X 10(9) CFU/ml by intraperitoneal injection of the strain, the animals were inoculated with 2.0 ml of twofold dilutions of a suspension of this bacterium. The animals developed purulent peritonitis and systemic involvement demonstrated by the development of periangitis, pneumonia and pleuritis in the lungs. Three different doses of antibiotics were administered intraperitoneally immediately after the rectal temperature reached more than 40 C. Erythromycin had a significant therapeutic effect but none of the new cephems tested death of the infected guinea pigs. 相似文献
744.
Towako Hiraki Akio Takeuchi Takayasu Tsumaki Buntaro Zempo Shinji Kanda Yoshitaka Oka Yoshitaka Nagahama Kataaki Okubo 《Proceedings. Biological sciences / The Royal Society》2012,279(1749):5014-5023
To dissect the molecular and cellular basis of sexual differentiation of the teleost brain, which maintains marked sexual plasticity throughout life, we examined sex differences in neural expression of all subtypes of nuclear oestrogen and androgen receptors (ER and AR) in medaka. All receptors were differentially expressed between the sexes in specific nuclei in the forebrain. The most pronounced sex differences were found in several nuclei in the ventral telencephalic and preoptic areas, where ER and AR expression were prominent in females but almost completely absent in males, indicating that these nuclei represent female-specific target sites for both oestrogen and androgen in the brain. Subsequent analyses revealed that the female-specific expression of ER and AR is not under the direct control of sex-linked genes but is instead regulated positively by oestrogen and negatively by androgen in a transient and reversible manner. Taken together, the present study demonstrates that sex-specific target sites for both oestrogen and androgen occur in the brain as a result of the activational effects of gonadal steroids. The consequent sex-specific but reversible steroid sensitivity of the adult brain probably contributes substantially to the process of sexual differentiation and the persistent sexual plasticity of the teleost brain. 相似文献