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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
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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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Relative carriage rates of nuclear dehydrogenating clostridia in two populations of different colorectal cancer risk
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Carriage of nuclear dehydrogenating clostridia has been associated with colon cancer and implicated in its aetiology. This study has compared the carriage of these organisms in a British population at high risk for the development of colon cancer with a low risk Nigerian population. Clostridia were found in all of the stools from both populations. Nuclear dehydrogenating clostridia were only found in the stools of the British subjects (32%). These results support the suggestion that the carriage rate of nuclear dehydrogenating clostridia in a population is related to the risk of colon cancer. 相似文献
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Development of hatching blastocysts from immature human oocytes following in-vitro maturation and fertilization using a co-culture system 总被引:8,自引:0,他引:8
Hwu YM; Lee RK; Chen CP; Su JT; Chen YW; Lin SP 《Human reproduction (Oxford, England)》1998,13(7):1916-1921
Recently, in-vitro maturation (IVM) of immature human oocytes recovered
from non-stimulated follicles has been applied in the treatment of
infertility. However, in previous reports, very few embryos cultured in
conventional medium have reached the expanded blastocyst stage following
in-vitro maturation and fertilization (IVM/IVF). The objective of this
study was to investigate whether the developmental competence of human
embryos following IVM/IVF could be enhanced by the use of a human ampullary
cell co-culture system. Immature human oocytes were aspirated from small
follicles at Caesarean section and then cultured in medium containing human
menopausal gonadotrophin for 36 to 48 h, followed by insemination. Zygotes
were randomly cultured either in conventional culture medium alone or in
the co-culture system. Of 48 embryos cultured in conventional medium alone,
all arrested at the 2-16- cell stage on day 3 after insemination. Of 46
embryos cultured in the co-culture system, 26 embryos (56.5%) arrested at
the 2-16-cell stage. Six embryos (13%) developed to the morula stage.
Fourteen embryos (30.4%) developed to expanded blastocysts and two
blastocysts were hatching on day 7 after insemination. We conclude that
co-culture significantly enhances the development of blastocysts in embryos
resulting from IVM/IVF.
相似文献
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Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization 总被引:11,自引:0,他引:11
The development and application of fluorescence in-situ hybridization
(FISH) has opened the way for comprehensive studies on numerical chromosome
abnormalities in human spermatozoa. FISH can be rapidly applied to large
numbers of spermatozoa and thus overcomes the major limitation of
karyotyping spermatozoa after penetration of zona-free hamster oocytes. The
simultaneous hybridization of two or more chromosome-specific probes to
spermatozoa and subsequent detection of the bound probes using different
fluorescent detection systems enables two or more chromosomes to be
localized simultaneously in the same spermatozoon and provides a technique
for undertaking reasonable estimates of aneuploidy. The most commonly used
probes are those which bind to the centromeric region of specific
chromosomes. Most studies to date have concentrated on estimating
aneuploidy in spermatozoa from normospermic men, although reports are
beginning to appear on aneuploidy in spermatozoa from subfertile and
infertile men. Multi- probe FISH studies have generally reported disomy
(hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary
evidence that some chromosomes such as X, Y and 21 are predisposed towards
higher rates of non-disjunction during spermatogenesis. There are also
suggestions of inter-donor variability in aneuploidy frequencies for
specific chromosomes, although this requires confirmation in larger
studies. While FISH is clearly a powerful technique that has many
applications in reproductive medicine, it must also be realized that it
does have limitations and the technology itself is still evolving and has
yet to be fully validated on spermatozoa.
相似文献