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排序方式: 共有2713条查询结果,搜索用时 15 毫秒
1.
Dr. Yahu A. Liu Dr. Qihui Jin Qiang Ding Dr. Xueshi Hao Tingting Mo Shanshan Yan Dr. Yefen Zou Dr. Zhihong Huang Xiaoyue Zhang Wenqi Gao Dr. Tom Y.-H. Wu Chun Li Dr. Badry Bursalaya Dr. Michael Di Donato Dr. You-Qing Zhang Lisa Deaton Dr. Weijun Shen Dr. Brandon Taylor Anwesh Kamireddy Dr. George Harb Dr. Jing Li Dr. Yong Jia Dr. Andrew M. Schumacher Dr. Bryan Laffitte Dr. Richard Glynne Dr. Shifeng Pan Dr. Peter McNamara Dr. Valentina Molteni Dr. Jon Loren 《ChemMedChem》2020,15(16):1562-1570
Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control. GNF4877, a potent dual inhibitor of DYRK1A and glycogen synthase kinase 3β (GSK3β) was previously reported to induce primary human β-cell proliferation in vitro and in vivo. Herein, we describe the lead optimization that lead to the identification of GNF4877 from an aminopyrazine hit identified in a phenotypic high-throughput screening campaign measuring β-cell proliferation. 相似文献
2.
J. B. Quinn G. E. Schumacher L. W. Schultheis 《Journal of Failure Analysis and Prevention》2004,4(1):41-46
Several days after heart surgery, a patient discovered his upper right canine tooth had broken at the root. Such tooth damage,
recognized post-operatively, is usually assumed to be caused by blunt mechanical force from an instrument used by the anesthesiologist
during placement of a breathing tube at the start of surgery.
In this case, the patient had saved the crown portion of the broken tooth, and it was possible to examine the root fracture
characteristics. The curvature and direction of the crack path and natural tooth situation suggested that failure could be
described through a cantilever beam model. This was confirmed when a whole extracted sample tooth was embedded and broken
by a measured force in a manner consistent with the model. The resulting fracture surface matched that of the patient’s broken
canine tooth. However, the high load and force direction necessary to fracture the root was inconsistent with forces applied
during the anesthesia procedure. The failure analysis and further investigation indicated tooth clenching on the breathing
tube during recovery was the likely cause of fracture.
This paper presents an alternate explanation for intubation-related dental injury, demonstrates the practicality of fractographic
analysis of biological materials, and introduces a methodology for simulating in vitro tooth settings for mechanical testing. 相似文献
3.
A cost comparison of balloon angioplasty and stenting versus endarterectomy for the treatment of carotid artery stenosis 总被引:1,自引:0,他引:1
WD Jordan GD Roye WS Fisher D Redden HA McDowell 《Canadian Metallurgical Quarterly》1998,27(1):16-22; discussion 22-4
PURPOSE: Percutaneous transluminal angioplasty with stenting (PTAS) of the carotid artery has been advocated as an alternative treatment for high-grade stenosis. Rationale for this approach includes less morbidity, shorter recovery, and lower cost when compared with carotid endarterectomy (CEA). METHODS: The clinical results and hospital charges of patients who underwent elective treatment for carotid stenosis were reviewed. During a concurrent 14-month period, 218 patients were admitted 229 times for 234 procedures for the treatment of 239 carotid bifurcation stenoses, 109 by PTAS and 130 by CEA. Hospital charges were reviewed for each hospitalization and were categorized according to radiology, operating room, cardiac catheterization laboratory, and all other hospital charges. RESULTS: The combined incidence of postprocedure strokes and deaths were: PTAS, eight strokes (7.7%) and one death (0.9%); CEA, two strokes (1.5%) and two deaths (1.5%). Total hospital charges per admission for the two groups were $30,140 for PTAS and $21,670 for CEA. The average postprocedure length of stay for PTAS was 2.9 days (median, 2 days) and for CEA was 3.1 days (median, 3 days). Cardiac catheterization laboratory charges for the PTAS group were $12,968, whereas the operating room charges for the CEA group were $4263. When hospitalizations that were extended by complications were excluded, the average total charges for the PTAS group (n = 84) dropped to $24,848 (mean length of stay, 1.9 days) and for the CEA group (n = 111) to $19,247 (mean length of stay, 2.6 days). CONCLUSIONS: After evaluating hospital charges, PTAS for the treatment of carotid stenosis cannot currently be justified on the basis of reduced costs alone. With future cost-containing measures, total hospital charges can be reduced in both groups. 相似文献
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6.
Estrogen treatment affects the hepatic synthesis and/or secretion of several proteins involved in clinically important pathological processes such as atherosclerosis, hypertension, and thrombosis. The endocrine regulation of the estrogen receptor (ER) concentration in primary cultures of rat hepatocytes was studied. Human growth hormone (hGH) and dexamethasone (DEX) in combination increased ER concentration 6-fold and ER mRNA levels 2.5-fold. These effects were not significantly different from those observed after treatment with the purely somatogenic bovine growth hormone (GH) in combination with DEX. Treatment with the lactogen ovine prolactin in the presence or absence of DEX did not significantly affect ER or ER mRNA concentrations. Triiodothyronine treatment at the most effective concentration (50 nM) increased ER and ER mRNA levels twofold. Medium supplementation with estradiol (0.1 nM) throughout the experiment did not affect the response to treatment with hGH and DEX. Treatment with high concentrations of ethinylestradiol in combination with hGH and DEX, however, increased the ER level twice as much as hGH and DEX without addition of estradiol or ethinylestradiol, whereas the ER mRNA concentration was the same in both the GH+DEX group and GH+ DEX+ (estradiol or ethinylestradiol) groups. These data indicate the importance of GH in combination with glucocorticoids for the maintenance of ER concentrations in the rat liver. Thyroid hormones may be of some, although minor importance, whereas the data suggest that prolactin is not directly involved in hepatic ER regulation. 相似文献
7.
Comparison of two methods of surfactant administration and the effect on dosing-associated hypoxemia
M Nelson JJ Nicks MA Becker LA Vrlenich V Bhatt-Mehta RE Schumacher 《Canadian Metallurgical Quarterly》1997,17(6):450-454
OBJECTIVE: The purpose of our study was to test the hypothesis that surfactant dosing through a proximal sideport adapter on an endotracheal tube leads to more dosing-associated hypoxemia compared with a method of dosing that uses a double-lumen endotracheal tube. STUDY DESIGN: Using adequate sample size to compare significant changes in O2 saturation (power > 0.8, alpha < 0.05) we enrolled 36 infants with respiratory distress syndrome in this randomized trial. A 10% change in O2 saturation was considered clinically significant. Nineteen infants received 38 doses of surfactant through the sideport adapter. Seventeen infants received 31 doses of surfactant through the nonventilation lumen of a double-lumen endotracheal tube. Two main outcome measures were assessed: time-averaged O2 saturation values 30 minutes after dosing and the largest absolute fall in O2 saturation for each patient. RESULTS AND CONCLUSIONS: Time-averaged O2 saturation measures were higher in the proximal sideport group (p = 0.02), but the magnitude of difference was probably not clinically significant. No significant difference was detected between groups when we compared largest absolute drop in O2 saturation. Secondary analyses found no effect of birth weight or dose number (second vs third dose) on either outcome measure. 相似文献
8.
OBJECTIVE: The most common indication for electroconvulsive therapy (ECT) is major depression. It is less recognized that ECT is effective also in the treatment of acute mania. This article aims to provide a comprehensive and critical review of the literature on the use of ECT for manic patients. METHOD: All published papers in the English language on the use of ECT in acute mania that could be found were reviewed with regard to efficacy, frequency and number of treatments, bilateral versus unilateral electrode placement, predictors of antimanic response, stability of therapeutic response, cognitive consequences, and other relevant issues. RESULTS: The evidence indicates that ECT is associated with remission or marked clinical improvement in 80% of manic patients and that it is an effective treatment for patients whose manic episodes have responded poorly to pharmacotherapy. Manic patients do not require a high frequency or prolonged course of treatments to respond to ECT. The seizure threshold appears to be lower in manic patients than in depressed patients. The issues of relapse following response to ECT, cognitive consequences of ECT, and the relative merits of unilateral versus bilateral ECT in manic patients require further study. CONCLUSIONS: ECT is an effective and safe treatment for acute mania. Remission of mania following ECT reflects a primary therapeutic effect rather than a secondary consequence of an ECT-induced organic brain syndrome. 相似文献
9.
Diethylstilbestrol (DES), a synthetic estrogen, is known to be a carcinogen in human and in animals. This study was designed to examine the interaction of DES with yeast RNA in aqueous solution at physiological pH with drug/RNA-phosphate (P) molar ratios of 1/80, 1/40, 1/20, 1/10, 1/4, and 1/2. Fourier transform infrared (FTIR) difference spectroscopy was used to determine the drug binding mode, the binding constant, the sequence selectivity, and RNA secondary structure in the RNA.DES complexes. Spectroscopic evidence showed that at low drug concentration (1/80 and 1/40), DES is intercalating through both Gua-Cyt and Ade-Urd base pairs with minor interaction with the backbone PO2 group (external binding). The calculated binding constant of K approximately 8.5 x 10(4) M-1 at a drug concentration of 3.12 x 10(-4) M shows that DES is a weaker intercalator than those of the methylene blue, acridine orange, and ethidium bromide. At high drug content (r > 1/40, where r represents the DES/RNA-phosphate molar ratio), a partial helix destabilization occurs with no alteration of RNA conformation upon drug complexation. However, a comparison with DNA.DES complexes showed that drug intercalation causes major reduction of the B-DNA structure in favor of A-DNA with no participation of the backbone PO2 group in the DES. DNA complexation. 相似文献
10.
A new sub-class of binding protein-dependent transporter with specificity for a broad range of polar amino acids has been identified by sequence comparison, in Rhizobium leguminosarum, Rhodobacter capsulatus, Escherichia coli and Pseudomonas fluorescens. Southern blotting and PCR analysis has shown that transporters from this new sub-class are widely distributed in Gram-negative bacteria, including, in addition to the above, Citrobacter freundii, Erwinia carotovorum and Rhizobium meliloti. ABC transporters of polar amino acids can be divided into two groups: those with narrow solute specificity and the newly identified sub-class with broad solute specificity. The binding and inner membrane proteins from transporters with a broad solute specificity are larger by approximately 30% than those with a narrow solute specificity. Multiple alignment of the inner membrane proteins from all sequenced polar amino acid transporters indicates there is an N-terminal conserved region that may be involved in solute specificity. A conserved arginine or lysine at residue 30 of this region is changed to glutamate in arginine transporters. Residue 53 also has a strong correlation with the charge on the transported solute, with basic amino acid transporters replacing an aliphatic amino acid at this position with a negatively charged amino acid. The general amino acid permease from R. leguminosarum, which will transport aliphatic as well as basic and acidic amino acids, juxtaposes two prolines at residues 52 and 53 of the N-terminal conserved region. 相似文献