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L Fr?yland DK Asiedu H Vaagenes A Garras O Lie GK Totland RK Berge 《Canadian Metallurgical Quarterly》1995,36(12):2529-2540
The mechanism behind the hypolipidemic effect of tetradecylthioacetic acid (CMTTD, a non-beta-oxidizable 3-thia fatty acid) was studied in hamsters fed a high cholesterol diet (2%), which resulted in hyperlipidemia. Treating hyperlipidemic hamsters with CMTTD resulted in a progressive hypocholesterolemic and hypotriacylglycerolemic effect. Decreased plasma cholesterol was followed by a 39% and 30% reduction in VLDL-cholesterol and LDL-cholesterol, respectively. In contrast, the HDL-cholesterol content was not affected, thus decreasing the VLDL-cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol ratios. 3-Hydroxy-3-methylglutaryl- (HMG) CoA reductase activity and its mRNA level were unchanged after CMTTD administration. Also, the LDL receptor and LDL receptor-related protein (LRP-4) mRNAs were unchanged. The decrease in plasma triacylglycerol was accompanied by a 45% and 56% reduction in VLDL-triacylglycerol and LDL-triacylglycerol, respectively. The hypolipidemic effect of CMTTD was followed by a 1.4-fold increase in mitochondrial fatty acid oxidation and a 2.3-fold increase in peroxisomal fatty acid oxidation. CMTTD treatment led to an accumulation of dihomo-gamma-linolenic acid (20:3n-6) in liver, plasma, very low density lipoprotein, and heart. Noteworthy, CMTTD accumulated more in the heart, plasma, and VLDL particles compared to the liver, and in the VLDL particle alpha-linolenic acid (18:3n-3) decreased whereas eicosatetraenoic acid (20:4n-3) increased. In addition, linoleic acid (18:2n-6) and the total amount of polyunsaturated fatty acids decreased, the latter mainly due to a decrease in n-6 fatty acids. The present data show that CMTTD was detected in plasma and incorporated into VLDL, liver, and heart. The relative incorporation (mol%) of CMTTD was heart > VLDL > liver. In conclusion, CMTTD causes both a hypocholesterolemic and hypotriacylglycerolemic effect in hyperlipidemic hamsters. 相似文献
3.
Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro 总被引:1,自引:0,他引:1
ME Bracke BM Vyncke EA Bruyneel SJ Vermeulen GK De Bruyne NA Van Larebeke K Vleminckx FM Van Roy MM Mareel 《Canadian Metallurgical Quarterly》1993,68(2):282-289
The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells. 相似文献
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Z Zhu J Yao T Johns K Fu I De Bie C Macmillan AP Cuthbert RF Newbold J Wang M Chevrette GK Brown RM Brown EA Shoubridge 《Canadian Metallurgical Quarterly》1998,20(4):337-343
A drug with cationic characteristics such as procaine can be conveyed in a Carbomer hydrogel in two different ways: (i) in the form of salt in solution in the aqueous phase, and (ii) in the base form salified with the same polymer. Introduction of the drug into the hydrogel with different concentrations of polymer produced, in both cases, a reduction in viscosity in relation to drug concentration. The gels with procaine salified with the polymer showed greater viscosity. The drug release rate, in general, diminished with the increase in polymer concentration. Nevertheless, when this concentration was maintained, there was no variation in release rate when the viscosity produced as a consequence of drug concentration was changed. Gels with procaine salified with the carboxyvinylic polymer had a faster release rate than those with procaine in the hydrochloride form dissolved in the aqueous phase. These results have also been confirmed by a simulated absorption test. 相似文献
6.
Point-to-point functional movements involve simultaneous shoulder and elbow joint rotations. In able-bodied subjects these movements are fully automatic, and feed-forward control ensures the synergistic activity of many muscles. Synergy between joint rotations was defined and described as a scaling between joint angular velocities [19]. Similarly, subjects who can control their shoulder movements may be assisted in reaching tasks by functional electrical stimulation (FES) of elbow extensor muscles. The synergistic control paradigm can be implemented in real-time by employing a hierarchically structured production-rules method. The use of production-rules necessitates the acquisition of knowledge and the assembly of a rule-base. A nonparametric technique was designed for the identification of the rules. The identification process was divided into two phases: determination of the scaling parameters, and determination of the stimulation parameters. The scaling parameters, needed for the coordination of movements, were determined in able-bodied subjects. Those depend exclusively on the initial and target positions of the hand. The number of scalings could be reduced by dividing the workspace into 12 zones. The stimulation parameters, needed for the execution of movements, were determined in subjects with paralyzed elbow extensor muscles by identifying triplets: elbow angular velocity, elbow angular acceleration (velocity increments), and the corresponding pulse durations for various classes of movements and loads attached to the hand. 相似文献
7.
C Bain R Keller GK Collington LR Trabulsi S Knutton 《Canadian Metallurgical Quarterly》1998,66(8):3900-3908
Elevated concentrations of intracellular calcium ([Ca]i) have been implicated as an important signalling event during attaching and effacing (A/E) lesion formation by enteropathogenic Escherichia coli (EPEC). The highly localized nature of the cytoskeletal and cell surface alterations occurring during A/E lesion formation suggests that there should be equally localized EPEC-induced signalling events. To analyze further the calcium responses to infection of HEp-2 cells by EPEC, we employed calcium-imaging fluorescence microscopy, which allows both temporal and spatial measurements of [Ca]i in live cells. Using this imaging technique, not only were we unable to detect any significant elevation in [Ca]i at sites of A/E EPEC adhesion, but, with several different classical EPEC and enterohemorrhagic E. coli (EHEC) strains and three different infection procedures, each of which resulted in extensive A/E bacterial adhesion, we were unable to detect any significant alterations in [Ca]i in infected cells compared to uninfected cells. In addition, chelation of intracellular free calcium with bis-(aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not, as previously reported, prevent A/E lesion formation. We conclude that increased [Ca]i are not required for A/E lesion formation by EPEC and EHEC. 相似文献
8.
TH Kim WC Bowen DB Stolz D Runge WM Mars GK Michalopoulos 《Canadian Metallurgical Quarterly》1998,244(1):93-104
The present study has examined the distribution of axons of differing sizes in the optic pathway of the ground squirrel. Axon diameters were measured from electron micrographs at various locations across sections of the optic nerve and tract, and total distributions and numbers were estimated. In both the nerve and tract, roughly 1.2 million optic axons were present. The population of optic axons had a unimodal size distribution, peaking at 0.9 microm in diameter and having an extended tail toward larger diameters. Local axon diameter distributions in the optic tract indicated distinct (though partially overlapping) axon diameter classes, including one of fine sizes peaking at 0.8-0.9 microm, a second of medium sizes peaking around 1.7-1.8 microm, and a third composed of the larger fibers with diameters up to 4.8 microm. The fine-caliber axons were found at all locations in the tract, and were the only axons present immediately adjacent to the pia, while the medium- and coarse-caliber axons were found at deeper locations. Curiously, the larger axons were found primarily in the medial parts of the tract, where axons from the dorsal retina normally course. A similarly restricted distribution of the larger axons was observed in the dorsotemporal parts of the optic nerve, suggesting that this difference in the tract may relate to an asymmetric distribution of ganglion cells on the retina giving rise to these axons. Measurements of axonal size taken within the optic fiber layer in dorsal and ventral parts of the retina confirmed this asymmetry, consistent with previous demonstrations of soma size differences in the dorsal versus ventral retina. The partial segregation of axons by size in the optic tract of the ground squirrel then reflects both the asymmetric distribution of retinal ganglion cell classes and the chronotopic reordering of optic axons that occurs within the chiasmatic region. 相似文献
9.
Anna Korzynska Wojciech Strojny Andreas Hoppe David Wertheim Pawel Hoser 《Pattern Analysis & Applications》2007,10(4):301-319
This paper describes a segmentation method combining a texture based technique with a contour based method. The technique
is designed to enable the study of cell behaviour over time by segmenting brightfield microscope image sequences. The technique
was tested on artificial images, based on images of living cells and on real sequences acquired from microscope observations
of neutrophils and lymphocytes as well as on a sequence of MRI images. The results of the segmentation are compared with the
results of the watershed and snake segmentation methods. The results show that the method is both effective and practical.
相似文献
Anna KorzynskaEmail: |
10.
GK Rivera D Pinkel JV Simone ML Hancock WM Crist 《Canadian Metallurgical Quarterly》1993,329(18):1289-1295
BACKGROUND: Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. METHODS: To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). RESULTS: The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. CONCLUSIONS: The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae. 相似文献