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71.
Noriko Usui Kouji Matsushima Anne M. Pilaro Dan L. Longo Robert H. Wiltrout 《Biotherapy》1996,9(4):199-208
Recombinant human interleukin 1α (rh IL-1α) and etoposide (VP-16) synergize for direct growth inhibition of several human
tumor cell linesin vitro. Our previous studies demonstrated that VP-16 increased the number of membrane-associated IL-1 receptors (IL-1Rs) and also
enhanced the internalization of receptor-bound rh IL-1α. The purposes of this study were to test our hypothess that these
events were critical to the synergy between rhIL-1α and VP-16, to determine whether rhIL-1α and VP-16 synergize to increase
superoxide (SO) anion radical productionin vitro since SO anion has been implicated in the toxic effects of IL-1, and to investigate the antitumor efficacy of the combinaton
against tumors in vivo. A375/C6 melanoma cells and OVCAR-3 ovarian carcinoma cells were tested with IL-1 receptor antagonist
(IL-1ra) before exposure to rhIL-1α, VP-16 and rhIL-1α plus VP-16. The synergistic or antagonistic effects were assessed by
MTT assay. SO production was measured by reduction of cytochrome C. Athymic female mice bearing the A375/C6 melanoma were
treated by rhIL-1α, VP-16, and rhIL-1α+VP-16. The antitumor effects were evaluated by quantitating tumor growth and survival
time. Pretreatment with the IL-1ra abrogated the synergistic effects of rhIL-1α and VP-16. The production of SO radical by
A375/C6 cells was increased 2.5 fold by the combination of rhIL-1α and VP-16, and the addition of exogenous SOD blocked the
synergy between rhIL-1α and VP-16. However, when A375/S0D15 cells which over-expressed manganese superoxide dismutase (MnSOD)
after MnSOD cDNA transfecton were exposed to rhIL-1α and VP-16, in vitro antagonism was observed. In vivo studies demonstrated
that the combination of rhIL-1α and VP-16 delayed tumor growth better than either agent alone, although long-term survival
was not improved because of substantial toxicity. Our results suggest that the synergistic antitumor effects of IL-1α and
VP-16 may be due to IL-1R modulation and increased internalization of IL-1-IL-1R complex by VP-16 treatment, as well as to
a subsequent increase in SO anion radical production from the tumor cells exposed to both drugs. Thus, the combnation of IL-1α
and VP-16 might prove useful for the treatment of malignant diseasein vivo, if the increased toxicity can be reduced or managed.
The US Government’s right to retain a non-exclusive royalty-free license on and to any copyright is acknowledged. 相似文献
72.
The effects of prolonged emersion and submersion by tidal manipulation on marine macrobenthos 总被引:3,自引:3,他引:0
Hummel Herman Fortuin Anne W. Bogaards Roelof H. Meijboom Andre de Wolf Lein 《Hydrobiologia》1994,282(1):219-234
Effects of tidal manipulation, resulting in prolonged periods of emersion and submersion or in protracted tidal cycles, on estuarine benthic animals are reviewed.Prolonged submersion periods did not show effects on mortality of most benthic animals tested, with the exception of the crumb-of-bread sponge Halichondrea panicea, which, at low water-flow rates, was covered with a layer of bacteria and subsequently died.Protracted low-water periods of 18 hours during several weeks hardly caused any mortality. However, protracted low-water periods of 30 hours during some weeks or emersion during several days caused a strong increase in mortality, depending on: the duration of emersion, temperature, condition of the animals, species and age. At temperatures below –1 °C and above 24 °C mortality was generally high. Animals with a low glycogen content were more sensitive to emersion than those with a high content. Species with a shell and those that are relatively big were less sensitive than those without a shell or of small size.The reproductive cycle of benthic animals could be delayed or accelerated by both emersion and submersion. 相似文献
73.
Gary L. Johnson Anne M. Gardner Carol Lange-Carter Nan-Xin Qian Marijane Russell Sim Winitz 《Journal of cellular biochemistry》1994,54(4):415-422
Serpentine receptors coupled to the heterotrimeric G protein, Gi2, are capable of stimulating DNA synthesis in a variety of cell types. A common feature of the Gi2-coupled stimulation of DNA synthesis is the activation of the mitogen-activated protein kinases (MAPKs). The regulation of MAPK activation by the Gi2-coupled thrombin and acetylcholine muscarinic M2 receptors occurs by a sequential activation of a network of protein kinases. The MAPK kinase (MEK) which phosphorylates and activates MAPK is also activated by phosphorylation. MEK is phosphorylated and activated by either Raf or MEK kinase (MEKK). Thus, Raf and MEKK converge at MEK to regulate MAPK. Gi2-coupled receptors are capable of activating MEK and MAPK by Raf-dependent and Raf-independent mechanisms. Pertussis toxin catalyzed ADP-ribosylation of αi2 inhibits both the Raf-dependent and-independent pathways activated by Gi2-coupled receptors. The Raf-dependent pathway involves Ras activation, while the Raf-independent activation of MEK and MAPK does not involve Ras. The Raf-independent activation of MEK and MAPK most likely involves the activation of MEKK. The vertebrate MEKK is homologous to the Ste11 and Byr2 protein kinases in the yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, respectively. The yeast Ste11 and Byr2 protein kinases are involved in signal transduction cascades initiated by pheromone receptors having a 7 membrane spanning serpentine structure coupled to G proteins. MEKK appears to be conserved in the regulation of G protein-coupled signal pathways in yeast and vertebrates. Raf represents a divergence in vertebrates from the yeast pheromone-responsive protein kinase system. Defining MEKK and Raf as a divergence in the MAPK regulatory network provides a mechanism for differential regulation of this system by Gi2-coupled receptors as well as other receptor systems, including the tyrosine kinases. 相似文献
74.
THE POPULATION DYNAMICS OF NORTHERN SEA LIONS, 1975-1985 总被引:1,自引:1,他引:0
Abstract: Populations of northern sea lions ( Eumetopias jubatus ) in the vicinity of Marmot Island, Alaska declined during 1975–1985 at about 5% per year (Merrick et al. 1987). The cause of this decline is not known. A life table for the northern sea lion was calculated assuming that life spans follow a Weibull distribution. Samples of northern sea lions taken in the vicinity of Marmot Island, Alaska during 1975–1978 and 1985–1986 indicate that the average age of females older than 3 yr increased about 1.55 yr (SD = 0.35 yr) while the population was declining at about 5% per year. Fecundity rates decreased by 10% over the same period, but the decrease was not statistically significant (Calkins and Goodwin 1988). Possible causes of the population decline and the change in age structure were examined by writing the Leslie matrix population equation in terms of changes in juvenile and adult survival rates and fecundity, and examining the short–term behavior of the trajectories of the average age of adult females, total number of females, and total number of pups with respect to those changes in the vital parameters. From the observed rate of declines of adults and the changes in average age of adult females and fecundity, estimates of the changes in adult and juvenile survival were calculated; estimates of the standard deviations of these changes were estimated via a bootstrap procedure. One purpose of this exercise is to aid in setting priorities for research for determining the cause of the decline. An explanation for the observed declines in numbers of adult sea lions consistent with the observed fecundity rates, a rate of decrease of 5% in the number of adults, and the corresponding increase in average age (of females age 3 yr and older) was a 10%–20% decrease in the survival of juveniles (age 0-3 yr) coupled with an insignificant change in adult survival (0.03%, SD = 1%). 相似文献
75.
Per Putkonen Charlotta Nilsson Kerstin Hild Reinhold Benthin Martin Cranage Anne Marie Aubertin Gunnel Biberfeld 《Journal of medical primatology》1993,22(2-3):100-103
Several groups have reported protection against experimental SIV infection in macaques immunized with a whole inactivated virus vaccine. The aim of the current study was to investigate whether five macaques vaccinated with whole inactivated SIV and previously shown to be protected against challenge with two divergent strains of SIV grown on human cells could resist challenge with a subsequent homologous SIV grown on macaque cells. We show here that this same vaccine did not protect when the challenge virus was grown on primary cells of monkey origin. 相似文献
76.
Vertical structure of seed banks and the impact of depth of burial on recruitment in two temporary marshes 总被引:3,自引:0,他引:3
The structure of the seed bank (including Chara oospores), in relation to depth within the sediment and disturbance, was studied in two Rhône delta temporary marshes for two years. The seeds of all species were concentrated in the top 2 cm of sediment with very low numbers beeing found below 4 cm. When an exclosure eliminated disturbances of the sediment by animals, the vertical repartition of seeds at site 2 was more pronounced than outside the exclosure.In experiment 1, the emergence capacity of seeds from different depths and buried under layers of sterile equivalent to those in the field was measured. Depending of the species, 22 to 98% of the seeds germinated from unburied seeds in the top 2 cm. Only 1% of the oospores of Chara (from site 2) at 2 to 4 cm depth in the sediment emerged.In experiment 2, surface seed bank samples were placed under 0, 2 or 4 cm sterile sediment depth. The samples contained numerous recent seeds and the emergence percentage reached 41% (for Ruppia maritima). Only the seeds of Zannichellia spp failed to germinate from a depth of 2 cm or more. The emergence percentage from 2 cm depth or more was always lower than at the surface. These experiments showed that both burial and ageing of seeds decrease germination capacity.The majority of the active seeds located at the surface germinate when the marsh is flooded. Seeds located between 2 and 4 cm can be brought back to the surface by disturbances and play the role of a reserve involved in maintenance of populations that go without seed production for one or some years. 相似文献
77.
78.
Neil C. Talbot Vernon G. Pursel Caird E. Rexroad Jr. Thomas J. Caperna Anne M. Powell Roger T. Stone 《In vitro cellular & developmental biology. Animal》1994,30(12):851-858
Summary The secondary culture of non-transformed parenchymal hepatocytes has not been possible. STO feeder cell-dependent secondary
cultures of fetal pig hepatocytes were established by colony isolation from primary cultures of 26-d fetal livers. The liver
cells had the typical polygonal morphology of parenchymal hepatocytes. They also spontaneously differentiated to form small
biliary canaliculi between individual cells or progressed further to large multicellular duct-like structures or cells undergoing
gross lipid accumulation and secretion. The secondary hepatocyte cultures expressed alpha-fetoprotein (AFP), albumin, and
β-fibrinogen mRNA, and conditioned medium from the cells contained elevated levels of transferrin and albumin. STO feeder
cell co-culture may be useful for the sustainable culture of hepatocytes from other species. 相似文献
79.
Anne N. Murphy Edward J. Unsworth William G. Stetler-Stevenson 《Journal of cellular physiology》1993,157(2):351-358
Tissue inhibitor of metalloproteinase-2 (TIMP-2), a protease inhibitor that binds to the latent and active forms of 72 kDa type IV collagenase (gelatinase A), was found to inhibit the in vitro proliferation of human microvascular endothelial (HME) cells stimulated with bFGF and 5% serum. The maximal inhibitory effect of TIMP-2 on incorporation of 3H-thymidine was evident 24 hours after bFGF stimulation of these cells and ranged between 45 and 60%. The half-maximal effective concentration of TIMP-2 was 107 ± 12 nM (S.D.). In contrast, TIMP-1 was not found to slow the growth of HME cells. The inhibition of cell proliferation observed with TIMP-2 was not mimicked by addition to the culture medium of BB94, a general matrix metalloproteinase inhibitor, nor antibodies to the 72 kDa type IV collagenase. In addition to growth, two other cell functions associated with the angiogenic process were tested for sensitivity to TIMP-2. Cell adhesion to tissue culture platic was slightly stimulated by TIMP-2, and cell migration was inhibited with short-term exposure to TIMP-2, but neither process was affected by longer-term exposure. The ability of TIMP-2 to inhibit cultured endothelial cell proliferation independent of protease inhibitory activity suggests that TIMP-2 may have additional actions which may limit neovascularization associated with solid tumor growth and metastasis in vivo. © 1993 Wiley-Liss, Inc. 相似文献
80.