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931.
In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were superior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. Compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested. 相似文献
932.
WJ Cho EK Kim MJ Park SU Choi CO Lee SH Cheon BG Choi BH Chung 《Canadian Metallurgical Quarterly》1998,6(12):2449-2458
In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA. 相似文献
933.
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
934.
We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae. 相似文献
935.
Watson M.E. Chilla J.L.A. Rocca J.J. Kim J.-W. Lile D.L. Vogt T.J. Robinson G.Y. 《Quantum Electronics, IEEE Journal of》1995,31(2):254-260
We report modulation saturation and time response measurements on InGaAs-InGaP MQW modulators. The measurements yield a saturation intensity of (3.7±0.1) kW/cm2 for a 0-10 V swing and switching times between 10 and 90 ns, depending on the bias voltage and incident light intensity. The observed dependence indicates that field screening due to carrier build-up is the dominant physical mechanism determining both the speed and the saturation intensity. This conclusion is supported by results of theoretical calculations 相似文献
936.
P Eiselt BS Kim B Chacko B Isenberg MC Peters KG Greene WD Roland AB Loebsack KJ Burg C Culberson CR Halberstadt WD Holder DJ Mooney 《Canadian Metallurgical Quarterly》1998,14(1):134-140
Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors. 相似文献
937.
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
938.
Although the lung is almost always involved in sarcoidosis and respiratory failure is not uncommonly caused by intrinsic lung disease, chronic alveolar hypoventilation on the basis of neurosarcoidosis has not been previously described. This report describes the case of a 42-year-old woman with sarcoidosis and documented involvement of the lungs, muscle, peripheral nerves, and skin. She presented with ventilatory failure and a vital capacity of 700mL and required hospitalization for intubation and mechanical ventilation. After failing ventilator weaning attempts and requiring continuous ventilatory assistance, she was extubated to continuous use of noninvasive intermittent positive pressure ventilation (IPPV). She eventually weaned to nocturnal-only use of noninvasive IPPV. However, her PaCO2 remained elevated during daytime hours despite the fact that her vital capacity had returned to 3,600mL. She was not obese, and her oxyhemoglobin saturation (SaO2) was normal on room air. Subsequent attempts to discontinue nocturnal nasal IPPV resulted in marked nocturnal decreases in SaO2 and return of symptoms. This case illustrates successful noninvasive management of an apparently unique occurrence of central alveolar hypoventilation caused by neurosarcoidosis. 相似文献
939.
940.
We report the use of magnetic resonance imaging (MRI) for in situ tumor growth rate studies of experimental intracranial 9L tumors. T2-weighted spin-echo coronal magnetic resonance images of rat brains with 9L tumors were obtained every 2 days beginning at 8-11 days postimplantation using a 7 tesla MRI system. Tumors were clearly delineated in the images as a hyperintense region with a relatively well-demarcated border and minimal peritumoral edema. Tumor volumes from individual slices were summed together to yield the total tumor volume. The accuracy of this methodology for volumetric determination was verified by MRI phantom studies. Tumor growth rates determined from sequential MRI measurements of tumor volumes were quantitated in terms of volumetric doubling time. Tumor doubling times were found to range from 50 to 81 h, with an average of 66 +/- 8 h (n = 10). Intracranial 9L tumors were found to grow exponentially over the entire life span of the animal, allowing treated animals to serve as their own controls since the volumetric doubling time could be determined from three to four MRI scans before treatment administration. The intracerebral tumor growth delay following a single injection of 1, 3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg i.p.) allowed for noninvasive determination of in vivo log cell kill. A 2.0 +/- 0.2 (n = 3) log cell kill from 1,3-bis(2-chloroethyl)-1-nitrosourea treatment was found from post-treatment MRI volume measurements. These results demonstrate that MRI provides a powerful and sensitive method for assessing the growth and treatment response of intracranial 9L tumors in the rat. 相似文献