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131.
132.
RL Hudkins M Iqbal CH Park J Goldstein JL Herman E Shek C Murakata JP Mallamo 《Canadian Metallurgical Quarterly》1998,8(14):1873-1876
Prodrug esters of the indolocarbazole CEP-751 (KT-6587) were prepared with the goal of identifying water soluble, stable but cleavable forms for intravenous dosing. A dipeptide proform Lys-beta-Ala (16, CEP-2563/KT-8391) was identified for advancement to clinical trials. 相似文献
133.
L Catoire M Pierron C Morvan CH du Penhoat R Goldberg 《Canadian Metallurgical Quarterly》1998,273(50):33150-33156
Well characterized pectin samples were incubated with cell wall-bound and -solubilized pure isoforms of pectinmethylesterase from mung bean hypocotyls (Vigna radiata). Both enzyme activity and average product structure were determined at intervals along the deesterification pathway at pH 5.6 and 7.6. The latter analyses were performed by 13C NMR spectroscopy, and the degree of esterification was probed by both 13C NMR and potentiometric measurements. A dichotomy was observed in the behavior of the alpha and gamma isoforms when compared with that of the beta isoenzyme. Ideal blockwise deesterification mechanisms reproduced the experimental average structures (methylester distribution) throughout the course of the reaction. In the case of the alpha and gamma isoforms, a single chain mechanism associated with a free carboxyl group at the second nearest neighbor position could be postulated at pH 5.6, whereas some multiple attack character was required to reproduce the data at pH 7.6. Several mechanisms that differed from the preceding ones were compatible with the data for the beta isoform at the two pH values. Both the nature of the polysaccharides produced in these reactions and the role of pectinmethylesterase in the cell wall-stiffening process along the growth gradient are discussed. 相似文献
134.
CP Cannon CM Gibson CH McCabe AA Adgey MJ Schweiger RF Sequeira G Grollier RP Giugliano M Frey HS Mueller RM Steingart WD Weaver F Van de Werf E Braunwald 《Canadian Metallurgical Quarterly》1998,98(25):2805-2814
BACKGROUND: Bolus thrombolytic therapy is a simplified means of administering thrombolysis that facilitates rapid time to treatment. TNK-tissue plasminogen activator (TNK-tPA) is a highly fibrin-specific single-bolus thrombolytic agent. METHODS AND RESULTS: In TIMI 10B, 886 patients with acute ST-elevation myocardial infarction presenting within 12 hours were randomized to receive either a single bolus of 30 or 50 mg TNK-tPA or front-loaded tPA and underwent immediate coronary angiography. The 50-mg dose was discontinued early because of increased intracranial hemorrhage and was replaced by a 40-mg dose, and heparin doses were decreased. TNK-tPA 40 mg and tPA produced similar rates of TIMI grade 3 flow at 90 minutes (62.8% versus 62.7%, respectively, P=NS); the rate for the 30-mg dose was significantly lower (54.3%, P=0.035) and was 65. 8% for the 50-mg dose (P=NS). A prespecified analysis of weight-based TNK-tPA dosing using median TIMI frame count demonstrated a dose response (P=0.001). Similar dose responses were observed for serious bleeding and intracranial hemorrhage, but significantly lower rates were observed for both TNK-tPA and tPA after the heparin doses were lowered and titration of the heparin was started at 6 hours. CONCLUSIONS: TNK-tPA, given as a single 40-mg bolus, achieved rates of TIMI grade 3 flow similar to those of the 90-minute bolus and infusion of tPA. Weight-adjusting TNK-tPA appears to be important in achieving optimal reperfusion; reduced heparin dosing appears to improve safety for both agents. Together with the safety results from the parallel Assessment of the Safety of a New Thrombolytic: TNK-tPA (ASSENT I) trial, an appropriate dose of this single-bolus thrombolytic agent has been identified for phase III testing. 相似文献
135.
JE Manson JM Gaziano A Spelsberg PM Ridker NR Cook JE Buring WC Willett CH Hennekens 《Canadian Metallurgical Quarterly》1995,5(4):261-269
The evidence for a potential benefit of antioxidant vitamins in the prevention and therapy of atherosclerotic disease is derived from laboratory, clinical, and observational epidemiologic studies but remains inconclusive. Data from randomized clinical trials are sparse, particularly for women. Therefore, it is both timely and important to conduct large-scale primary and secondary prevention trials of antioxidants and cardiovascular disease (CVD). The Women's Antioxidant and Cardiovascular Study (WACS) is a randomized, double-blind, placebo-controlled secondary prevention trial of the balance of benefits and risks of antioxidant vitamins (vitamins E and C, and beta-carotene) among 8000 women with preexisting CVD. This secondary prevention trial will be conducted as a companion to the recently started Women's Health Study, a primary prevention trial of vitamin E and beta-carotene, as well as aspirin. In the WACS, US female health professionals aged 40 years and older with a history of myocardial infarction, angina pectoris, coronary revascularization, stroke, transient cerebral ischemia, carotid endarterectomy, or peripheral artery surgery will be randomly assigned, utilizing a 2 x 2 x 2 factorial design, to receive vitamin E, vitamin C, beta-carotene, and/or placebo. Cardiovascular end points include nonfatal myocardial infarction, nonfatal stroke, coronary revascularization procedures, and total CVD mortality. The present article describes the rationale, design, and methods of the trial. 相似文献
136.
137.
This article illustrates a case of an aberrant cervical thymus presented as a neck mass. This is a case of a 4-month-old boy presenting with a right submandibular mass whose preoperative diagnosis was lymphangioma or neoplastic lesion. The mass was successfully removed and the histopathological examination showed normal thymic tissue with no diagnostic abnormality. This paper reviews the embryological background of aberrant cervical thymus, the varying clinical presentations with an emphasis on differential diagnosis, clinical work-up, and surgical treatment. 相似文献
138.
Patterned surfaces with alternating regions of amino silanes [N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS)] and alkyl silanes [dimethyldichlorosilane (DMS)] have been used to alter the kinetics of spatial distribution of cells in vitro. In particular, we have previously observed the preferential spatial distribution of bone cells on the EDS regions of EDS/ DMS patterned surfaces (10). In this study, we examined whether the mechanism of spatial distribution of cells on the EDS regions was adhesion mediated. Homogeneous layers of EDS and DMS were immobilized on quartz substrates and characterized by contact angle. X-ray photoelectron spectroscopy, and spectroscopic ellipsometry. The strength of bone cell attachment to the modified substrates was examined using a radial flow apparatus, within either 20 min or 2 hr of cell incubation in the presence of serum. A Weibull distribution was chosen to characterize the strength of cell-substratum adhesion. Within 20 min of cell exposure, the strength of adhesion was significantly larger on EDS and clean surfaces, compared with DMS surfaces (p < 0.001). Within 2 hr of cell incubation, there was no statistical difference between the strength of cell adhesion to EDS, DMS, and clean surfaces. The results of this study suggest that the surface chemistry mediates adhesion-based spatial cell arrangement through a layer of adsorbed serum proteins. 相似文献
139.
JT Sandlund T Fonseca T Leimig L Verissimo R Ribeiro V Lira CW Berard J Sixbey WM Crist L Mao G Chen CH Pui M Heim F Pedrosa 《Canadian Metallurgical Quarterly》1997,11(5):743-746
The purpose of this paper was to define the histologic distribution, clinical features, and treatment response of childhood non-Hodgkin lymphoma (NHL) in northeastern Brazil. We reviewed medical records and histopathologic studies of 98 children treated for NHL from 1980 to 1987 at a major pediatric cancer center in Recife, Brazil. Treatment outcome was evaluated in relation to tumor burden (stage and serum LDH) and type of therapy (LSA2L2 vs other multiagent chemotherapy). There was a striking predominance of the small noncleaved cell (Burkitt) subtype, which occurred in 92 of the 98 children and adolescents diagnosed with NHL. Subsequent analyses focused on these patients. The majority (n = 84) had advanced (stage III/IV) disease at diagnosis. The abdomen was the most common site of disease (84 cases); jaw involvement was rare (three cases). Five-year event-free survival (excluding treatment refusals) was significantly better for patients with limited vs advanced stage disease (75 +/- 14% vs 42 +/- 6%; P < 0.04). Elevated serum LDH (>500 U/l) was associated with a poorer outcome (P = 0.008). The type of chemotherapy did not affect EFS (P = 0.95). Only 39% of patients are long-term survivors, reflecting the high rate of septic deaths (25% of patients) and parental refusal/abandonment of therapy (10%). Epstein-Barr virus (EBV) was detected in tumor cells from eight of the 11 cases studied. In clinical presentation, these cases resemble sporadic Burkitt lymphoma, yet in their apparent responsiveness to LSA2L2 therapy and association with EBV, they do not. Childhood NHL in northeastern Brazil is predominantly of the Burkitt subtype, and is associated with clinical features that appear to distinguish it from the endemic and sporadic forms of this tumor. These cases may represent a third or intermediate subtype of Burkitt lymphoma. 相似文献
140.
WP Lin DD Ji CY Shiau TC Yang YW Yang TL Tsou ST Tang CH Chen YT Liu 《Canadian Metallurgical Quarterly》2003,142(3):158-165
Compounds N-(6,7-difluoroquinolonyl)-ampicillin (AU-1) and N-(6-fluoroquinolonyl)-ampicillin (FQ-1), synthesized by coupling of the carboxyl group of 6,7-difluoroquinolone (FP-3) and 6-fluoroquinolone (FP4), respectively, with the alpha-amino-group of ampicillin side chain, exhibit antipseudomonal activity similar to and lower acute toxicity than that of norfloxacin, whereas neither ampicillin nor the fluoroquinolone moieties, compound FP-3 or FP4, alone have such activity. Also, AU-1 and FQ-1 are active against tested clinical isolates of Pseudomonas aeruginosa that are highly resistant to norfloxacin, gentamicin, or both. The therapeutic efficacies of FQ-1 and norfloxacin were assessed and compared in neutropenic mice infected with a 90% lethal dose of P aeruginosa. Mice intraperitoneally administered FQ-1 (10 mg/kg) 4, 8, 24, and 48 hours after infection had survival rates as high as 80%, comparable to those of mice treated with norfloxacin at the same dosage and dosing schedule. The study of protoplast formation revealed that FQ-1 did not inhibit cell-wall biosynthesis but did induce cell filamentation of Bacillus subtilis at a level close to its minimal inhibition concentration. Both AU-1 and FQ-1 were able to intercalate into the double-stranded DNA. However, that FQ-1 lost such activity after it was treated with penicillinase suggests that the lactam-ring structure in ampicillin moiety of FQ-1 was hydrolyzed by penicillinase and that the hydrolyzed structure of FQ-1 does not own DNA-intercalation activity. 相似文献