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81.
CD14 is not involved in Rhodobacter sphaeroides diphosphoryl lipid A inhibition of tumor necrosis factor alpha and nitric oxide induction by taxol in murine macrophages. 总被引:3,自引:3,他引:0
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F Kirikae T Kirikae N Qureshi K Takayama D C Morrison M Nakano 《Infection and immunity》1995,63(2):486-497
Taxol, a microtubule stabilizer with anticancer activity, mimics the actions of lipopolysaccharide (LPS) on murine macrophages in vitro. Recently, it was shown that taxol-induced macrophage activation was inhibited by the LPS antagonist Rhodobacter sphaeroides diphosphoryl lipid A (RsDPLA). To investigate the mechanisms of taxol-induced macrophage activation, the present study focused on the interaction of LPS, RsDPLA, and taxol in the activation of and binding to macrophages. Taxol alone induced murine C3H/He macrophages to secrete tumor necrosis factor alpha (TNF) and to produce nitric oxide (NO) with kinetics similar to that of LPS. Macrophages from LPS-hyporesponsive C3H/HeJ mice, in contrast, did not yield any detectable TNF and NO production in response to LPS or taxol. RsDPLA inhibited taxol-induced TNF and NO production from C3H/He macrophages in a dose-dependent manner. The inhibition by RsDPLA was specific for LPS and taxol in that RsDPLA did not inhibit heat-killed Listeria monocytogenes- or zymosan-induced TNF production. Polymyxin B blocked the inhibitory effect of RsDPLA on taxol-induced TNF production. The inhibitory activity of RsDPLA appeared to be reversible since macrophages still responded to taxol in inducing TNF production after the RsDPLA was washed out with phosphate-buffered saline prior to the addition of taxol. Taxol-induced TNF production was not inhibited by colchicine, vinblastine, or 10-deacetylbaccatine III. A mutant cell line, J7.DEF3, defective in expression of a CD14 antigen, responded equally well to taxol by producing TNF as did the parent J774.1 cells. This suggested that the activation of macrophages by taxol does not require CD14. Taxol-induced TNF production by the mutant cells was also inhibited by RsDPLA. 125I-labeled LPS and 3H-labeled taxol was reported to bind to J774.1 cells predominantly via CD14 and microtubules, respectively. The binding of 125I-labeled LPS to J7.DEF3 cells was about 30 to 40% of that to J774.1 cells. The binding of 125I-LPS to J774.1 cells was inhibited by unlabeled LPS and RsDPLA but not by taxol. On the other hand, 3H-labeled taxol bound to both J774.1 cells and J7.DEF3 cells in similar time- and dose-dependent manners. The binding of [3H]taxol to these cells was inhibited by taxol but not by LPS or RsDPLA. Although the binding studies failed to examine cross competition for binding to macrophages, a possible explanation of these results is that LPS, RsDPLA, and taxol share the same molecule(s) on murine macrophages for their functional receptor(s), which is neither CD14 nor tubulin. 相似文献
82.
Are cytokines possible mediators of cancer cachexia? 总被引:1,自引:0,他引:1
Yoshikazu Noguchi Takaki Yoshikawa Akihiko Matsumoto Gösta Svaninger Johan Gelin 《Surgery today》1996,26(7):467-475
The possible role of cytokines in the development of cancer cachexia was reviewed from the literature. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, interferon (IFN)-gamma and leukemia inhibitory factor (LIF) can elicit many but not all host changes seen in cancer cachexia, including loss of appetite, loss of body weight, and the induction of acute-phase protein synthesis. However, these cytokines are not always demonstrated in the circulation of the cancer patients. The inability to detect circulating cytokines may be due to their low rate of production, their short half-life and rapid clearance from plasma, or their mode of action (autocrine or paracrine). Different cytokines are induced to stimulate the same response. This is very different from hormonal regulation, where a hormone acts on a cell directly through a specific receptor without depending on other mediators. Specific antibodies including anti-IFN-gamma, anti-TNF and anti-IL-6 antibodies, as well as the cyclooxygenase inhibitor indomethacin, have been used to reverse cancer cachexia. Overlapping physiologic activities make it unlikely that a single substance is the sole cause of cancer cachexia. It is hoped that further investigation on other cytokines and their possible relationships with hormones will help to clarify the mechanisms of cancer cachexia in the near future.This work was supported by a grant from the Japan-Sweden Foundation in 1991. 相似文献
83.
84.
隔离饲养及给药时刻对小鼠阿米卡星药物动力学的影响 总被引:1,自引:0,他引:1
目的:研究社会环境及给药时刻对小鼠阿米卡星代谢的影响。方法:小鼠按饲养环境;隔离饲养(I)或集体饲养(A)及给药时间:日中(D)及午液(N)随机分为:I-D,I-N,A-D,A-N4组,饲养4周后于D(13:00)或N(01:00)sc阿米卡星15mg.kg^-1测定给药后血浆浓度,以开放一室模型拟合计算有关药代动力学参数,结果:A-N组阿米卡星清除较率A-D及I-N组增大,血浆半衰期变短,0-1 相似文献
85.
Hiroshi Shimada Masao Nanko Shoichi Fujii Hidenobu Masui Shinji Togo Hideyuki Ike Akira Nakano Shigeo Ohki 《Journal of Hepato-Biliary-Pancreatic Surgery》1995,2(2):116-121
Hepatic micrometastases of the parenchyma adjacent to a macroscopic lesion were detected in 17 of 31 resected liver metastases.
Fifty-nine micrometastatic lesions were detected in total; 26 lesions were situated in the portal vein (PV), 22 in the central
vein (CV), 5 in the bile duct (BD), and 6 in the sinusoid (SS). A histological study confirmed the direct invasion of the
macrometastatic cancer cells into the adjacent PV, CV, BD, and SS. According to the tumor doubling time, the mean diameter
of the macrometastases in 19 remnant livers was calculated to have been 0.57±0.87 cm at the time of the primary resection.
The calculated diameter of 3 of these 19 macrometastases was found to be less than 0.01 cm, the minimum implantable size,
indicating that the cancer recurrence in these specimens may have developed from macroscopic metastatic lesions as a satellite,
and not from the primary tumor. In 13 patients who received doses of 5250 mg or more of 5 fluorouracil (FU) via the hepatic
artery, the cumulative disease-free rate 2 years postoperatively was 100%; this value was 47.6% in 11 patients who received
less than 5250 mg of 5 FU via the hepatic artery, and 0% in 39 patients who received no chemotherapy (P<0.005). These results suggest that anatomical hepatic resection for satellite lesions, combined with prophylactic hepatic
arterial chemotherapy for micrometastases, decreases the recurrence rate of hepatic metastases in the remnant liver. 相似文献
86.
Keigo Kohara Tomio Ono Keiko Tominaga-Yoshino Tomokazu Shimonaga Seiichi Kawashima Akihiko Ogura 《Brain research》1998,809(2):285
Neurons survive when their activity is maintained. An influential hypothesis on the cellular mechanism underlying this phenomenon is that there is an appropriate range of intracellular Ca2+ concentration ([Ca2+]i) for survival. The rat cerebellar granule neuron in culture serves as the most often used model system for the analysis of activity-dependent survival, since it does not survive unless an excitant (KCl or glutamate) is added to the culture medium. Against the above-mentioned hypothesis, we found in our previous examination no difference between steady-state [Ca2+]i in granule neurons cultured under high KCl (i.e., survival) and low KCl (i.e., death) conditions. In this report, we present the quantitative background of unchanged [Ca2+]i between the two culture conditions. Influx of Ca2+ due predominantly to L-type voltage-dependent calcium channels was higher in high KCl cultures than in low KCl cultures. At the same time, efflux of Ca2+ due to the activity of Ca2+/Na+ antiport was also higher in high KCl cultures. Additionally, we found that the endocytotic activity was greater in high KCl cultures than in low KCl cultures, as monitored by the rate of uptake of horseradish peroxidase added to medium. Since the uptake was blocked by an internal Ca2+ chelator, the increased endocytotic activity in high KCl cultures might be a consequence of the enhanced Ca2+ turnover. 相似文献
87.
M. Kamberi T. Kotegawa K. Tsutsumi K. Nakamura S. Nakano 《European journal of clinical pharmacology》1998,54(8):633-637
Objective: To investigate the effect of acidification and alkalinization on the pharmacokinetics of sparfloxacin in healthy subjects.
Methods: A single 200-mg oral dose of sparfloxacin was given to nine healthy Japanese volunteers on three separate occasions under
different conditions of urinary pH. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride
and sodium bicarbonate, respectively. The concentrations of sparfloxacin and its metabolite in plasma and urine were determined
by high-performance liquid chromatography assays.
Results: The difference between treatments for Cmax, AUC∞, and CL · f−1 were found to be significant. The relative bioavailability of sparfloxacin was 84.4% and 122.3% after ammonium chloride and
sodium bicarbonate treatments, respectively. The amount of unchanged sparfloxacin in urine samples collected 0–48 h after
sparfloxacin administration represented 10.1% of the dose in the control, 14.3% of the dose in urine acidification and 8.4%
of the dose with alkalinization of urine. Renal clearance was found to depend on urinary pH. However, the plasma elimination
and the metabolism of sparfloxacin were not significantly altered by acidification or alkalinization of the urine.
Conclusion: The urinary pH dependence of the renal clearance of sparfloxacin will be of minor clinical importance with regard to the
low contribution of renal excretion to the overall elimination of sparfloxacin. On the other hand, the alteration in the environmental
pH in the gastrointestinal tract, produced by the concomitant ingestion of ammonium chloride or sodium bicarbonate, influences
the absorption and bioavailability of sparfloxacin. This effect is likely to be clinically significant.
Received: 18 March 1998 / Accepted in revised form: 1 July 1998 相似文献
88.
To investigate possible effects of implantation on apoptosis, we examined
the cleavage of DNA in human chorionic villi and decidua in intrauterine
and ectopic pregnancy. Very limited but detectable cleavage of DNA was
recognized in the chorionic villi and decidua in normal pregnancy. A ladder
pattern, characteristic of the apoptotic breakdown of DNA, was present in
the villi in tubal pregnancy. High molecular weight DNA was predominant in
the decidua in tubal pregnancy. Quantitative analysis of low molecular
weight fragments of DNA revealed a significant increase in the villous
tissue, together with a significant decrease in the decidual tissue, in
tubal pregnancy as compared to those in normal pregnancy. An analysis in
situ revealed that apoptotic cells were predominant in the
syncytiotrophoblast in tubal pregnancy. In decidual tissue, labelled cells
were occasionally seen in normal pregnancy, and their numbers decreased in
tubal pregnancy. The present study demonstrates that apoptosis occurs in
the villi, but not in the decidua in tubal pregnancy, unlike the situation
in normal pregnancy. Our results suggest that the implantation site might
affect the occurrence of apoptotic changes in early pregnancy of humans.
相似文献
89.
A 17-year-old girl developed vomiting of sudden onset, followed by a state of confusion that progressed rapidly to coma within one day. Laboratory tests indicated iron deficiency anemia and reactive thrombocytosis, but there was no evidence of coagulopathy. There was no history of medication including the contraceptive pill, either. Emergency CT scan without contrast enhancement showed increased density along the course of the vein of Galen and internal cerebral veins. A repeated CT scan without contrast enhancement carried out 24 hours after the onset of the illness confirmed extensive bilateral hypodensity of the thalami, basal ganglia and adjacent white matter. There was also a prominent spontaneous increase in the density of the deep cerebral venous system. MRI was performed 3 days after the onset of the illness, which showed absence of a flow void in the region of the internal cerebral veins and septal veins on T1-weighed images. T2-weighted images showed low intensity in these veins. At autopsy, the bilateral internal cerebral veins were occluded by fresh thrombosis and hemorrhagic infarction was seen in the bilateral thalami. 相似文献
90.
Most gonadotropes in the pituitary of male Suncus murinus L. are immunostained with both LH beta and FSH antisera, whereas only a few gonadotropes are positive only for LH beta. The former gonadotropes consist of polygonal or polyhedral cells of medium size, and can be identified by the presence of two types of secretory granules of low density: smaller ones (about 150-250 nm in diameter) which are spherical in shape, and larger ones of irregular form with a maximum diameter of about 1,500 nm. The endoplasmic reticulum is not prominent, while the Golgi apparatus is distinct. Mitochondria are found throughout the cytoplasm but are often concentrated in and around the region of the Golgi apparatus. These fine structural features are somewhat similar to those of the classical Barnes "FSH cells" and Kurosumi-Oota "FSH cells". 相似文献