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排序方式: 共有722条查询结果,搜索用时 31 毫秒
1.
Dr. Michael Gosland Pharm.D. Dr. Bert Lum Pharm.D. Dr. Julia Schimmelpfennig Pharm.D. Dr. James Baker Pharm.D. Dr Michael Doukas M.D. 《Pharmacotherapy》1996,16(1):16-39
Cisplatin in combination with other cytotoxic agents is the backbone for a potential cure of testicular germ cell neoplasms and is a critical factor in the substantial activity observed in the treatment of small cell lung cancer, bladder cancer, and ovarian germ cell tumors. Resistance to cisplatin at the onset of treatment or at relapse limits its curative potential, however. Laboratory studies using both cells selected for cisplatin resistance by exposure to sublethal concentrations and biopsy specimens from patients' tumors provide insights for the potential mechanisms of resistance. The mechanisms identified in vitro include a complex and wide array of related and unrelated pathways such as alterations in cellular drug transport, enhanced DNA repair dependent and independent of signal transduction pathways, and enhanced intracellular detoxification such as glutathione and metallothionein systems. Studies of these mechanisms have identified a number of agents with known potential for administration to humans and that reverse cisplatin resistance in vitro; for example, reversal of cellular accumulation defects by dipyridamole; inhibition of DNA repair by hydroxyurea, pentoxifylline, and novobiocin; inhibition of the glutathione system by ethacrynic acid and buthionine sulfoximine; and inhibition of signal transduction pathways by cyclosporine, tamoxifen, and calcium channel-blocking agents. Current phase I clinical trials are focusing on the most effective doses and schedules to administer these agents in combination with cisplatin. Initial uncontrolled trials in limited numbers of patients suggest that the addition of modulators of cisplatin has the potential to reverse resistance in patients previously failing therapy. Another promising avenue for circumventing cisplatin resistance is the development of noncross-resistant platinum analogs. 相似文献
2.
M L Cibull M E Thompson L Smith C D Jennings M A Doukas E J Pavlik D E Powell 《American journal of hematology》1987,24(3):293-299
The emergence of a near-haploid clone of cells in blast phase chronic myelogenous leukemia is an unusual event. We report such a case and review eight other cases described in the English literature. The significance of the substantial loss of genetic material is discussed as is the phenotypic and genotypic heterogeneity observed in this group of patients. 相似文献
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5.
Efstathios T Detorakis Konstantinos Ioannakis Doukas Dardabounis Vassilios P Kozobolis 《Ophthalmic surgery, lasers & imaging》2007,38(6):508-510
A 70-year-old woman had corneal ulcer and melting after complicated cataract surgery with polymethylmethacrylate lens implant insertion. A conjunctival flap was initially used to cover the defect with a plan to perform keratoplasty later. Fifteen months postoperatively, she presented with total absence of central corneal tissue and iris and exposure of the implant. The eye was not inflamed, painful, or hard on palpation and visual acuity was counting fingers at 3 m. The preservation of globe integrity despite exposure of the polymethylmethacrylate implant implies a stable adhesion between polymethylmethacrylate and residual corneal tissue and may prove useful in keratoprosthesis design. 相似文献
6.
Vasoactive amines and eicosanoids interactively regulate both polymorphonuclear leukocyte diapedesis and albumin permeability in vitro 总被引:2,自引:0,他引:2
Previously we reported that cultured endothelial cells (ECs) can promote or inhibit polymorphonuclear leukocyte (PMN) diapedesis and albumin permeability in vitro by altering monolayer intercellular integrity (an activity influenced by pretreatment with exogenous amines). Endothelial eicosanoid release was also seen to stimulate both PMN motility and diapedesis. We now demonstrate that these endothelial activities are related. Thromboxane (Tx) B2 pretreatment of ECs results in increased diapedesis and permeability across the monolayers whereas 6-keto-PGF1 alpha pretreatment has the opposite effects, demonstrating that these eicosanoids exert direct effects upon ECs, in addition to their direct effects upon PMNs as previously described. Norepinephrine (NE) or serotonin (5HT) pretreatment of ECs inhibits the release of TxB2 and 6-keto-PGF1 alpha, with the result that the stimulation of PMN motility by these EC metabolites is eliminated. In contrast, histamine increases the endothelial release of eicosanoids, resulting in a further increase in PMN motility. We conclude that histamine directly reduces EC monolayer integrity (by altering the endothelial cytoskeleton) and also increases eicosanoid release, actions which both enhance PMN motility and further reduce monolayer integrity. Conversely, NE and 5HT both increase intercellular integrity and decrease eicosanoid release, thereby decreasing PMN motility, diapedesis, and albumin permeability. 相似文献
7.
AG Nettetal 《MedR Medizinrecht》2007,25(11):664-666
Abstrakt 1. Nimmt ein Patient einen ihm von seinem (Zahn-)Arzt einger?umten Exklusiv-Termin nicht wahr, obwohl er auf dessen Eigenschaft
ausdrücklich hingewiesen wurde, so hat er dem (Zahn-)Arzt den Behandlungsausfall abzüglich eines angemessenen Eigenanteils
des (Zahn-)Arztes zu ersetzen.
2. Die Ersatzpflicht tritt auch dann ein, wenn der Patient den Termin nicht in der in dem Behandlungsvertrag vorgesehenen
Frist absagt. Eine hierfür seitens des (Zahn-)Arztes bestimmte Frist von zwei Tagen vor Behandlungsbeginn stellt sich für
den Patienten grunds?tzlich auch nicht als unangemessene Benachteiligung i.S. des § 307 BGB dar.
3. Ein Anspruch des Arztes entf?llt auch bei nur mündlicher Vereinbarung nicht unter dem Gesichtspunkt des § 4 Abs. 5b BMV-Z,
denn diese Vorschrift ist teleologisch dahin zu reduzieren, dass nur zahn?rztliche Honoraransprüche aus erfolgten Behandlungen
schriftlich vereinbart werden müssen. Soweit es jedoch um einen vertraglichen Anspruch wegen einer Leistungsst?rung geht,
vermag das Schriftformerfordernis des § 4 Abs. 5b BMV-Z grunds?tzlich nicht einzugreifen. (Leits?tze des Bearbeiters) 相似文献
8.
9.
Early during rat thymus ontogeny, an important proportion of thymocytes
expresses IL-2R and contains IL-2 mRNA. To investigate the role of the
IL-2-IL-2R complex in rat T cell maturation, we supplied either recombinant
rat IL-2 or blocking anti-CD25 mAb to rat fetal thymus organ cultures
(FTOC) under several experimental conditions. The IL-2 treatment initially
stimulated the growth of thymocytes and, as a result, induced T cell
differentiation, but the continuous addition of IL-2 to rat FTOC, as well
as the anti-CD25 administration, resulted in cell number decrease and
inhibition of thymocyte maturation. These results indicate that immature
rat thymocytes bear functional high- affinity IL-2R and that IL-2 promotes
T cell differentiation as a consequence of its capacity to stimulate cell
proliferation. Modifications in TCR alpha beta repertoire and increased
numbers of NKR- P1+ cells, largely NK cells, were also observed in
IL-2-treated FTOC. Furthermore, IL-2-responsiveness of different thymocyte
subsets changed throughout thymic ontogeny. Immature CD4-CD8-cells
responded to IL-2 in two stages, early in thymus development and around
birth, in correlation with the maturation of two distinct waves of thymic
cell progenitors. Mature CD8+ thymocytes maximally responded to IL-2 around
birth, supporting a role for IL-2 in the increased proliferation of mature
thymocytes observed in vivo in the perinatal period. Taken together, these
findings support a role for IL-2 in rat T cell development.
相似文献
10.
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