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31.
JL Lagrange JL Fischel S Galliani P Formento T Guillot M Bardon G Milano 《Canadian Metallurgical Quarterly》1993,(11):1531-1535
The objective of the present in vitro study was to determine an optimal timing of the irradiation in the combination cisplatin (CDDP) and 5-fluorouracil-folinic-acid (5-FU-FA) allowing a maximal cytotoxic effect on a human cell line derived from a head and neck carcinoma (CAL 27 cells). The various tested chemoradiotherapy sequences were applied in parallel to human keratinocytes in culture (SVK 14 cells). This was done in order to define the best sequence allowing the achievement of an optimal selectivity of the cytotoxic effects. The drug sequence was: CDDP over 2 h then fresh medium was added including the tandem 5-FU-d,I FA applied 6 h after CDDP, for 5 days. Irradiation was applied only once and at various times within the drug sequence. The cytotoxicity effects of the different chemoradiotherapy combinations were assessed by the MTT semi-automated test. The part taken by the 5-FU-FA combinations in the overall cytotoxicity was examined; an effect was apparent on CAL 27 cells only. The evolution of the radiation effect (RE = cell survival after drugs/cell survival after drugs plus irradiation) was analysed as a function of the different times of irradiation within the given drug sequence. Clearly, the RE values were dependent upon time at which the radiation dose in the chemoradiotherapy regimen was administered. For CAL 27 cells, irradiation effects were maximal at the first irradiation time tested after the end of the CDDP exposure (i.e. t = 3.5 h). In contrast, this optimal chemoradiotherapy timing for better cytotoxicity on CAL 27 cells did not correspond to that of SVK 14 cells. Consequently, it was possible to establish that the best time for the selectivity index was located shortly after the CDDP exposure. 相似文献
32.
Using neutral/neutral and neutral/alkaline two-dimensional (2-D) gel techniques, we previously obtained evidence that initiation can occur at any of a large number of sites distributed throughout a broad initiation zone in the dihydrofolate reductase (DHFR) domain of Chinese hamster ovary (CHO) cells. However, other techniques have suggested a much more circumscribed mode of initiation in this locus. This dichotomy has raised the issue whether the patterns of replicating DNA on 2-D gels have been misinterpreted and, in some cases, may represent such noncanonical replication intermediates as broken bubbles or microbubbles. In an accompanying study (R. F. Kalejta and J. L. Hamlin, Mol. Cell. Biol. 16:4915-4922, 1996), we have shown that broken bubbles migrate to unique positions in three different gel systems and therefore are not likely to be confused with classic replication intermediates. Here, we have applied a broken bubble assay developed from that study to an analysis of the amplified DHFR locus in CHO cells. This assay gives information about the number and positions of initiation sites within a fragment. In addition, we have analyzed the DHFR locus by a novel stop-and-go-alkaline gel technique that measures the size of nascent strands at all positions along each arc in a neutral/neutral 2-D gel. Results of these analyses support the view that the 2-D gel patterns previously assigned to classic, intact replication bubbles and single-forked structures indeed correspond to these entities. Furthermore, potential nascent-strand start sites appear to be distributed at very frequent intervals along the template in the intergenic region in the DHFR domain. 相似文献
33.
34.
Perez A.T. Vazquez P.A. Castellanos A. 《Industry Applications, IEEE Transactions on》1995,31(4):761-767
The physical system to be considered is a blade-plane configuration in a dielectric liquid. For high electric fields, injection from the blade takes place with ions of the same polarity. The Coulomb force acting upon the injected charges originates an electrohydrodynamic (EHD) flow, referred in what follows as the charged jet. A laminar solution of this EHD jet is obtained using similarity analysis. If transport of charge is dominated by convection, i.e., neglecting molecular diffusion and ion drift, and the electric field is assumed constant, the problem is mathematically equivalent to the bidimensional thermal plume in the limit of large Prandtl numbers. The authors examine the stability of this EHD jet using linear theory and parallel-flow approximations. Neutral stability curves are computed numerically in terms of a nondimensional parameter which is the electrical analogous to the Grashof number. Finally, some experimental observations are presented, followed by a short discussion. The role played by the viscosity correlates reasonable well with the theoretical analysis 相似文献
35.
JL Banyer S Goldwurm L Cullen B van der Griend A Zournazi DJ Smit LW Powell EC Jazwinska 《Canadian Metallurgical Quarterly》1998,9(3):235-239
We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy. 相似文献
36.
BH Jhun JL Meinkoth JW Leitner B Draznin JM Olefsky 《Canadian Metallurgical Quarterly》1994,269(8):5699-5704
We have investigated the role of cellular p21ras protein in insulin and insulin-like growth factor-I (IGF-I) signaling pathways. Insulin stimulation increased Ras-GTP formation in Rat-1 fibroblasts overexpressing normal human insulin receptors (HIRc-B), far greater than in parental Rat-1 fibroblasts, indicating that competent insulin receptors mediate this response. Cellular microinjection of a dominant-negative mutant p21ras protein (N17 ras) or anti-p21ras monoclonal antibody (Y13-259) into HIRc-B cells reduced insulin- and IGF-I-stimulated DNA synthesis by 75-90%. Insulin-induced c-fos protein expression was also inhibited by 74%. Microinjection of oncogenic p21ras (T-24 ras) into HIRc-B cells activated the mitogenic pathway, and coinjection of N17 ras and T-24 ras showed that oncogenic p21ras rescued the cells from the N17 ras blockade. This later finding indicates that T-24 ras acts downstream of N17 ras. In conclusion, 1) microinjection of a dominant interferring ras mutant into quiescent cells abrogated subsequent insulin and IGF-I mitogenic signaling; 2) oncogenic ras protein rescued cells from the N17 ras blockade, indicating that T24 ras action is downstream of the site of N17 inhibition; and 3) p21ras is an intermediate signaling molecule in the insulin/IGF-I signal transduction pathway and is required for gene expression and DNA synthesis. 相似文献
37.
A Burger D Voges P Demange CR Perez R Huber R Berendes 《Canadian Metallurgical Quarterly》1994,237(4):479-499
Annexin V binds to phospholipids in a calcium-dependent manner and exhibits calcium channel activity in vitro. We prepared a variety of mutants yielding information about the structure-function relationship of the ion channel activity. All mutants were characterized by X-ray crystallography, electron microscopy and electrophysiological measurements. Their structures are insignificantly changed whereas their electrophysiological properties are drastically different. Glu95, located in the central hydrophilic pore of the molecule, is crucial for the ion selectivity filter as its exchange leads to reduced calcium and increased sodium conductance. The removal of Glu17, located on the protein surface and far from the ion conduction pathway, leads to the appearance of a second conductance level of 9 pS in addition to the conductance level of about 30 pS in the wild-type molecule. This was also the case for Glu78, which is part of a weak calcium binding site. The exchange of Glu17 and Glu78 produced a mutant retaining only the smaller conductance level. We conclude that these two residues influence the angle between the two halves of the molecule, which determines the diameter of the ion conduction pathway, thereby leading to the occurrence of a second conductance level. 相似文献
38.
A complete and effective rehabilitation program begins with a thorough subjective and objective evaluation of the problem and injury presented. Biomechanical changes, whether they are anatomically induced or as a result of a form of compensation, must be identified and properly addressed. During the initial phase of rehabilitation, the issues of pain and swelling often must be resolved before full range of motion and return to normal strength can be achieved successfully during the more advanced stages. It is important to incorporate the entire lower quadrant in exercises that are designed to improve proprioception and function, using both in open and closed kinetic chain exercises. Finally, the demands to which the patient is returning to must be recognized to successfully complete the recovery phase. 相似文献
39.
K Stelwagen DG Grieve JS Walton JL Ball BW McBride 《Canadian Metallurgical Quarterly》1993,76(4):992-1001
Twenty-five primigravid ewes were used to investigate the effect of bST, between 97 and 124 d of gestation, on mammogenesis and subsequent milk production. Five ewes (reference group) were slaughtered at 96 d of gestation, and the remaining ewes were injected daily with saline (control group: n = 10) or .1 mg/kg of BW of bST (bST group: n = 10). Following bST treatment, 5 control and 5 bST group ewes were slaughtered (slaughter group). The remaining ewes were slaughtered after lambing and being milked for 8 wk (production group). Weekly blood samples were obtained from both slaughter and production group ewes. Slaughter group ewes were also subjected to 8-h serial blood sampling at 98 d (period 1) and 123 d (period 2) of gestation. Milk production was 42% higher in ewes treated prepartum with bST than in those treated with saline. Results suggest that the increase in milk was due to an increase in mammary parenchymal cell number rather than to an increase in cellular activity. The high rate of [3H]thymidine incorporation into parenchymal tissue in reference group ewes suggests that the increase in parenchyma during the second trimester of gestation is due to cellular hyperplasia but that cellular hypertrophy may be more important during the last trimester. Plasma IGF-I concentrations were significantly higher during bST treatment and remained elevated between daily injections; the increase was greatest in period 2. 相似文献
40.
EH Jeffery K Abreo E Burgess J Cannata JL Greger 《Canadian Metallurgical Quarterly》1996,48(6):649-665
Although the full mechanisms are not yet elucidated, research into the mechanism of toxicity of aluminum (Al) on bone formation and remodeling and on hematopoietic tissue is ongoing. In contrast little information exists on the interactive effects of systemic Al and the kidney. In bone, both clinically and experimentally, high doses of Al inhibit remodeling, slowing both osteoblast and osteoclast activities and producing osteomalacia and adynamic bone disease. In contrast, while very low levels of Al are mitogenic in bones of experimental animals, the effect of low levels of Al in humans is unknown. Aluminum has been shown to have its mitogenic action at the osteoblast, but whether the effect on resorption is viz osteoblast-directed changes in osteoclast activity has not yet been determined. Parathyroid hormone (PTH) levels are disrupted by Al in humans and animals. Whether altered PTH levels play a major or even a minor role in Al-dependent osteotoxicity requires clarification. In hematopoietic tissue, Al causes a microcytic anemia, not reversible by iron. Friend leukemia cells treated with Al have been reported to accumulate excess iron, without incorporating it into ferritin or heme. It is not yet known which steps in iron metabolism are disrupted by Al, if they involve a single mechanism of action, or even if this disruption in iron metabolism accounts for the anemia seen in Al toxicosis. In kidney, research is needed to evaluate Al nephrotoxicity; there are almost no studies in this area. Furthermore, research is needed to evaluate mechanisms of renal Al excretion, presently shown by one study to occur at the distal tubule. Such studies might well throw light on whether Al plays a role in aggravating renal insufficiency, or whether the role of the kidney in Al toxicosis is limited to the causative effect of renal compromise on Al accumulation. In summary, while a number of mechanisms have been proposed for the toxic action of Al, no single mechanism emerges to explain these diverse effects of systemic Al. Recommendations for future research are presented and summarized in Table 1. 相似文献