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41.
42.
RJ Bergeron WR Weimar Q Wu Y Feng JS McManis 《Canadian Metallurgical Quarterly》1996,39(26):5257-5266
A series of analogues and homologues of spermine were synthesized, and their impact on MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor was evaluated. These tetraamines encompass both linear and cyclic compounds. The linear molecules include norspermine, N1, N11-diethylnorspermine, N1,N12-bis(2,2,2-trifluoroethyl)spermine, homospermine, and N1,N14-diethylhomospermine. The cyclic tetraamines consist of the piperidine analogues N1,N3-bis(4-piperidinyl)-1,3-diaminopropane, N1,N4-bis(4-piperidinyl)-1,4-diaminobutane, N1,N4-bis(4-piperidinylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-piperidinyl)ethyl]-1,4-diaminobutane and the pyridine analogues N1,N3-bis(4-pyridyl)-1,3-diaminopropane, N1,N4-bis(4-pyridyl)-1,4-diaminobutane, N1,N4-bis(4-pyridylmethyl)-1,4-diaminobutane, and N1,N4-bis[2-(4-pyridyl)-ethyl]-1,4-diaminobutane. This structure-activity set makes it possible to establish the importance of charge, intercharge distance, and terminal nitrogen substitution on polyamine-regulated MK-801 binding in the NMDA channel. Four families of tetraamines are included in this set: norspermines, spermines, homospermines, and tetraazaoctadecanes. Calculations employing a SYBYL modeling program revealed that the distance between terminal nitrogens ranges between 12.62 and 19.61 A. The tetraamines are constructed such that within families cyclics and acyclics have similar lengths but different nitrogen pKa's and thus different protonation, or charge, states at physiological pH. The pKa values for all nitrogens of each molecule and its protonation state at physiological pH are described. The modifications at the terminal nitrogens include introduction of ethyl and beta,beta,beta-trifluoroethyl groups and incorporation into piperidinyl or pyridyl systems. The studies clearly indicate that polyamine length, charge, and terminal nitrogen substitution have a significant effect on how the tetraamine regulates MK-801 binding to the NMDA receptor. Thus a structure-activity basis set on which future design of MK-801 agonists and antagonists can be based is now available. 相似文献
43.
All terrain vehicles (ATVs) have been associated with death and serious injury since their introduction into the marketplace. Fifteen cases of ATV-related brain and spinal cord injury reported to the Louisiana Central Nervous System Registry during 1995 were evaluated for severity, etiology, and outcome. Eleven (73%) of these injuries were sustained by persons under 18 years of age. Despite US Consumer Product Safety Commission and ATV manufacturer recommendations for age restrictions, ATVs continue to be popular recreational devices for children. 相似文献
44.
We have investigated the effects of the neutral endopeptidase inhibitor, SCH 42354, on the vasoreactivity of atrial natriuretic peptide (ANP) in rat isolated pulmonary resistance vessels (PRV) and isolated perfused lungs (IPL). PRV (n = 37) were mounted onto the jaws of a myograph and precontracted with PGF2alpha (100 mu M). Concentration-responses to ANP (0.17 to 340 nM) were determined before and after the addition of SCH 42354 (10, 30 and 100 nM). Each concentration of SCH 42354 caused a significant increase in potency (- log EC50) of ANP in isolated PRV. Lungs from normoxic rats (n = 13) were isolated and perfused with whole blood. An increase in pulmonary artery pressure was achieved by ventilating with an hypoxic gas mixture and concentration-responses obtained by incremental additions of ANP (40 nM to 12 mu M), before and after the addition of SCH 42354 (100 nM). SCH 42354 significantly increased the potency (- log EC50) of ANP in the rat IPL. ANP is partly metabolized by NEP. That an inhibitor of NEP increased the potency of ANP in isolated pulmonary vessels, and in isolated perfused whole lungs, suggested that SCH 42354 may be having a local action within the pulmonary vasculature. 相似文献
45.
Document image analysis: A primer 总被引:1,自引:0,他引:1
46.
47.
RP Whitehead J Jacobson TD Brown SA Taylor GR Weiss JS Macdonald 《Canadian Metallurgical Quarterly》1997,15(6):2414-2419
PURPOSE: Pancreatic cancer is difficult to treat, with most patients surgically unresectable at the time of diagnosis. Radiotherapy and chemotherapy can offer palliation, but more effective therapy is needed. This trial evaluated the effects of an aggressive schedule of paclitaxel given with granulocyte colony-stimulating factor (G-CSF) to patients with advanced pancreatic cancer. PATIENTS AND METHODS: All patients were required to have a histologic diagnosis of pancreatic adenocarcinoma with measurable disease and no prior chemotherapy or radiation therapy. Patients had to have performance status of 0 to 2, pretreatment absolute granulocyte count > or = 1,500/microL, and platelet count greater than or equal to the institutional lower limit of normal. Following pretreatment with dexamethasone, diphenhydramine, and cimetidine, patients received paclitaxel at a dose of 250 mg/m2 by 24-hour infusion on day 1, repeated every 21 days. G-CSF was given at a dose of 5 microg/kg/d on days 3 to 18 or until two consecutive absolute neutrophil counts (ANCs) > or = 10,000/microL were obtained. Doses of paclitaxel were modified depending on nadir counts. RESULTS: Forty-five patients were entered onto this study, with six ineligible. For the 39 eligible patients, there was one complete response (CR) and two partial responses (PRs), five stable/no responses, 23 increasing disease, two early deaths, and six patients whose assessment was inadequate to determine response. The response rate was therefore three of 39 or 8% (95% confidence interval [CI], 2% to 21%). The median survival time for the 39 eligible patients was 5 months. The most common toxicities were anemia, leukopenia/granulocytopenia, malaise/fatigue, nausea/vomiting, alopecia, thrombocytopenia, paresthesias, and liver function abnormalities. There was one death due to sepsis. CONCLUSION: Single-agent paclitaxel in this dose and schedule has minimal activity in pancreatic adenocarcinoma patients. 相似文献
48.
Assessed the retention of memory units for word-like strings of letters using the perceptions of 120 undergraduates in 2 experiments in determining how frequently various letters appeared. A series of strings was presented at 1 of 3 exposure durations. Within the series, the frequencies of occurrence of different strings and of the letters composing the strings were varied orthogonally. Results indicate that, at relatively long exposure durations, Ss could discriminate the frequency of occurrence for both strings and their constituent letters. The formation of global-level (string) memory units was indicated by judgments of string frequency being unaffected by either the frequencies of their component letters or experimental conditions (brief exposures) that prohibited accurate judgment of letter frequency. Although judgments of letter frequency were sometimes biased by the frequency of the strings containing the letters, the success with which the judgments discriminated different levels of letter frequency did not depend on the activation of string-level memory units. Furthermore, Ss' frequency judgments for letters were not predictable from their recall of the strings containing the letters. Results provide evidence for the formation of element-level (letter) memory units. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
49.
Kikushima K. Whitley T. Cooke R. Stalley K. Fake M. Lawrence E. 《Electronics letters》1994,30(17):1431-1432
The authors report the first use of a praseodymium-doped fluoride fibre amplifier (PDFFA) in a 24 TV channel FM-SCM transmission experiment. Twenty-four analogue FM-SCM-TV channels were amplified by a PDFFA without any observable degradation in picture quality. By using a single PDFFA as a post-amplifier, transmission over 104 km of `standard' 1.3 μm optimised fibre was demonstrated with a total loss budget of 45 dB. By using the same PDFFA as an inline amplifier, a loss budget of 53 dB was achieved 相似文献
50.
SF Ding JD Delhanty JS Dooley L Bowles CB Wood NA Habib 《Canadian Metallurgical Quarterly》1993,17(3):405-409
We have previously shown that the tumor suppressor gene for hepatocellular carcinoma (HCC) without cirrhosis may be located on chromosome 5q35-qter. In this study, we analyzed nine cases of primary HCC without cirrhosis using probes from the MCC and APC genes, which are in the region 5q21-22. None of the informative cases had allele loss detected by these probes, whereas the probe lambda MS8 for the region 5q35-qter showed allele loss in six out of six informative cases. The results confirm that the putative tumor suppressor gene for HCC without cirrhosis on chromosome 5q is distinct from the MCC and APC genes. 相似文献