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51.
52.
CT Baker FG Salituro JJ Court DD Deininger EE Kim B Li PM Novak BG Rao S Pazhanisamy WC Schairer RD Tung 《Canadian Metallurgical Quarterly》1998,8(24):3631-3636
A combination of structure-based design and both solution, and solid-phase synthesis were utilized to derive a potent (nM) series of HIV-1 protease inhibitors bearing a structurally novel backbone. Detailed structural analysis of several inhibitors prepared in this series has suggested that rigidification of the P1/P2 region of this class of molecules may result in compounds with improved potency. 相似文献
53.
MR Gillmore EA Wells EE Simpson DM Morrison MJ Hoppe A Wilsdon 《Canadian Metallurgical Quarterly》1998,24(1):131-151
This paper reports the results of a study in which age (grade level), racial/ethnic, and gender differences in beliefs and perceived norms about drinking were examined in a multi-ethnic urban sample of 4th through 7th grade children. Results showed that older children held beliefs and perceived norms that were more favorable toward drinking than younger children. The major difference between older and younger children lay in their differential estimates of the likelihood of certain consequences occurring and not in their evaluation of these consequences of drinking. Further, older children not only displayed less motivation to comply with their parents and greater motivation to comply with their peers, but they also perceived their parents, as well as their peers, as less disapproving of drinking than did younger children. There were few gender or race/ethnicity differences at these ages in children's beliefs and perceived norms about drinking. 相似文献
54.
The specificity of lymphocyte homing from the blood into a tissue is determined in part by complementary pairs of adhesion receptors on lymphocytes and endothelial cells termed homing receptors and vascular addressins, respectively. The mucosal vascular addressin involved in lymphocyte homing to Peyer's patches is a 66-kDa glycoprotein, MAdCAM-1. Investigation of the regulation and molecular genetics of MAdCAM-1 have been hampered by the lack of a murine cell line expressing this adhesion molecule. We show herein using indirect immunofluorescence studies that MAdCAM-1 can be induced on a murine endothelial cell line, bEnd.3, by cytokines and LPS. Western blot analysis of MAdCAM-1 purified by affinity column chromatography from TNF-alpha-treated bEnd.3 cells demonstrates a 66-kDa protein that comigrates in SDS-PAGE with the MAdCAM-1 constitutively found on high endothelial venules in murine mesenteric lymph nodes. Comparison of MAdCAM-1 expression on the bEnd.3 cells was made to the expression of adhesion molecules ICAM-1 and VCAM-1. MAdCAM-1 and VCAM-1 are not constitutively expressed on the bEND.3 surface but can be induced in a concentration-dependent manner by LPS, TNF-alpha, and IL-1. ICAM-1 is constitutively expressed on the endothelioma surface and expression is increased by TNF-alpha, IL-1, LPS, and IFN-gamma. Surface expression of MAdCAM-1 peaks 12 to 18 h after exposure to TNF-alpha and remains elevated at 48 h, whereas expression of VCAM-1 peaks at 4 h and inducible ICAM-1 peaks between 4 and 18 h. Interestingly, IFN-gamma has differential effects on expression of these three adhesion receptors. IFN-gamma alone induces VCAM-1 and enhances ICAM-1 expression, but does not induce MAdCAM-1. Furthermore, although, preincubation of bEND.3 cells with IFN-gamma modestly increases the induction of ICAM-1 and VCAM-1 in response to TNF-alpha and IL-1, it dramatically reduces the TNF-alpha, IL-1, and LPS-induced expression of MAdCAM-1. MAdCAM-1 on bEnd.3 cells is functional as the murine T lymphoma TK1, known to bind MAdCAM-1, also binds to TNF-alpha-stimulated endothelioma but not to unstimulated cells. This binding is blocked by the antibodies against MAdCAM-1 and against the alpha 4-chain of its integrin receptor, alpha 4 beta 7, on TK1 cells.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
55.
Since the inception of mobile coronary care units (MCCU), patients with sudden cardiac death (SCD) saved by advanced emergency medical technicians (EMT-A) can be studied retrospectively and prospectively. Forty-eight cases of SCD found in ventricular fibrillation (VF) were successfully resuscitated. Only 32% had a myocardial infarction. Most survivors were New York Heart Association (NYHA) class I or II. All class IV survivors with severe congestive heart failure died within 45 days. All class II survivors had angina as the limiting factor. Of all patients with VF, 23% survived. Eighty percent of survivors were class I or II and have resumed previous lifestyles. No clear cut symptom complex was identified. Rescue response time was generally less than five minutes. Intracardiac medications were administered without complications. Empirical administration of sodium bicarbonate correlated poorly with arterial blood gas determinations. 相似文献
56.
GA Masters AM Mauer PC Hoffman D Wyka BL Samuels SA Krauss S Watson H Golomb EE Vokes 《Canadian Metallurgical Quarterly》1998,9(6):677-680
PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents. 相似文献
57.
AIM: The study of quality of life and 24-h monitoring blood pressure data in elderly patients with isolated systolic hypertension (SH) on arifon monotherapy. MATERIALS AND METHODS: 22 patients over 65 (mean age 69.8 +/- 1.3 years) suffering from SH entered the open trial. 24-h monitoring of blood pressure was performed at least 2 weeks after discontinuation of the previous antihypertensive treatment and after 4 weeks of arifon monotherapy (2.5 mg once a day). Quality of life was evaluated according to the standard SIP questionnaire. RESULTS: Arifon 4-week treatment resulted in a significant fall of systolic pressure for 24 hours, day and night (by 16.2, 13.7 and 17.4%, respectively; p < 0.001). Variability of blood pressure did not change much. 24-h index for systolic and diastolic blood pressure increased 2-fold and by 46%, respectively. Moreover, the rate of the systolic pressure growth in the morning hours decreased by 36.7% (p < 0.05). Psychosomatic status by SIP questionnaire changed for the best. CONCLUSION: Arifon is an effective treatment of SH and improves quality of life. 相似文献
58.
Saionara V. Costa Nilsa T. Azana Pei Shieh Talita Mazon 《Ceramics International》2018,44(11):12174-12179
In this work, we demonstrated a novel and effective approach on the use of low-cost electrodes, an eco-friendly substrate and zinc oxide (ZnO) micro or nanorods (MRs or NRs, respectively) for building triboelectric devices (TENGs). The reported strategy focuses on using low-cost materials and fabrication processes. For the first time and without any pre-treatment, an aluminum recyclable paper from the milk carton (named ARP) was used as a substrate and TENG bottom electrode. A systematic study on the growing of ZnO structures on ARP by chemical bath deposition has been carried out. We found that the ZnO rods size, and resistivity of the TENG upper electrode considerably influence the power density of the device. Such sustainable, low-priced ZnO-based TENGs can produce up to 1.6μW/cm2 output power density when operated at 50?Hz. The fabrication of an eco-friendly nanogenerator demonstrates the possibility of manufacturing low-cost, flexible, and large-area energy harvesting devices for future applications. 相似文献
59.
Effects of insertions and deletions in a beta-bulge region of Escherichia coli dihydrofolate reductase 总被引:1,自引:0,他引:1
The role of a beta-bulge in Escherichia coli dihydrofolate reductase (DHFR)
has been explored by a series of insertion and deletion mutations.
Insertion of a seven amino acid sequence from a structurally equivalent
'beta-blowout' sequence from human DHFR destabilizes E. coli DHFR by 3.6
kcal/mol and decreases catalytic efficiency (kcat/K(m)) 34- fold. Deletion
of F137, delta 137, the looped out residue in the bulge, also destabilizes
E. coli DHFR by 2.8 kcal/mol but only decreases catalytic efficiency
threefold. Concurrent deletion of F137 and mutation of, V136 to proline to
try and maintain the strand twist associated with the beta-bulge decreases
protein stability by 3.4 kcal/mol and decreases catalytic efficiency
84-fold. These insertion/deletion mutations were also constructed in a D27S
DHFR background. The D27S mutation has been described previously and
proposed to remove the catalytic acid from the active site. The delta 137
mutation partially suppresses the effect of the D27S mutation as it
decreases the K(m) for substrate, dihydrofolate, twofold. Non-additive
effects are observed for the insertion/deletion mutations in wild-type
versus D27S DHFR backgrounds, consistent with structural changes.
相似文献
60.
EE Brooks NS Gray A Joly SS Kerwar R Lum RL Mackman TC Norman J Rosete M Rowe SR Schow PG Schultz X Wang MM Wick D Shiffman 《Canadian Metallurgical Quarterly》1997,272(46):29207-29211
The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 was required for half-maximal inhibition of the enzyme activity. In cells exposed to CVT-313, hyperphosphorylation of the retinoblastoma gene product was inhibited, and progression through the cell cycle was arrested at the G1/S boundary. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. To evaluate the effects of CVT-313 in vivo, we tested this agent in a rat carotid artery model of restenosis. A brief intraluminal exposure of CVT-313 to a denuded rat carotid artery resulted in more than 80% inhibition of neointima formation. These observations suggest that CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation. 相似文献