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排序方式: 共有680条查询结果,搜索用时 0 毫秒
1.
G H Mickisch G T Merlino P M Aiken M M Gottesman I Pastan 《The Journal of urology》1991,146(2):447-453
Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials. 相似文献
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Access to medical care for black and white Americans. A matter of continuing concern 总被引:28,自引:2,他引:26
A 1986 national survey of use of health services shows a significant deficit in access to health care among black compared with white Americans. This gap was experienced by all income levels of black Americans. In addition, the study points to significant underuse by blacks of needed medical care. Moreover, blacks compared with whites are less likely to be satisfied with the qualitative ways their physicians treat them when they are ill, more dissatisfied with the care they receive when hospitalized, and more likely to believe that the duration of their hospitalizations is too short. 相似文献
6.
Richard W. Bowtell Andrew Peters Jonathan C. Sharp Peter Mansfield Edward W. Hsu Nanci Aiken Anthony Horsman Stephen J. Blackband 《Magnetic resonance in medicine》1995,33(6):790-794
NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T2 relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T2 difference between the nucleus and cytoplasm in these cells represents primarily a true T2 relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo. 相似文献
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Ghosh D; Stewart DR; Nayak NR; Lasley BL; Overstreet JW; Hendrickx AG; Sengupta J 《Human reproduction (Oxford, England)》1997,12(5):914-920
The present study was undertaken to assess the temporal association between
the profiles of serum concentrations of oestradiol-17beta, progesterone,
chorionic gonadotrophin (CG) and relaxin in pregnancies established
naturally, and after embryo transfer, as well as in failed pregnancies in
rhesus monkeys. In naturally mated cycles (group 1) a conception rate of
75% was obtained. In group 1, the mean day of CG detection in serum was
11.5 +/- 1.9 day post-ovulation, and for relaxin, 9.0 +/- 2.5 day
post-ovulation. In group 2, embryo transfer to synchronous, non-mated
surrogate recipients was performed; seven embryo transfer cycles yielded
three pregnancies which were allowed to continue to term and normal infants
were delivered. In embryo transfer cycles the mean day of CG detection was
14.8 +/- 1.8 day post- ovulation, and for relaxin, 11.4 +/- 2.6 day
post-ovulation. A delay of about 3 days was observed in the appearance in
circulation of CG (P < 0.05) and also of relaxin (P < 0.05) between
natural mated and embryo transfer conception cycles. Significant
differences (P < 0.05 for progesterone and P < 0.03 for oestradiol)
were obtained for the areas under the curves for progesterone and
oestradiol between days 12 and 16 in conception cycles compared with failed
pregnancies. These data provide the first observation of the normal
hormonal signals associated with maternal recognition of transferred
embryos during the peri- implantation period, and suggest that the use of
such an experimental primate embryo transfer model may help to elucidate
components of maternal and embryonic signal-response mechanisms during
embryo implantation.
相似文献
9.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
10.
The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production. 相似文献