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排序方式: 共有227条查询结果,搜索用时 31 毫秒
191.
192.
Lei Wang Mary C. Casey Sanjeev Kumar V. Vernekar Rajkumar Lalji Sahani Karen A. Kirby Haijuan Du Huanchun Zhang Philip R. Tedbury Jiashu Xie Stefan G. Sarafianos Zhengqiang Wang 《药学学报(英文版)》2021,11(3):810-822
Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site. Specifically, we replaced the inter-domain-interacting, electron-rich indole ring of PF74 with less electron-rich isosteres, including imidazolidine-2,4-dione, pyrimidine-2,4-dione, and benzamide, and identified four potent antiviral compounds (10, 19, 20 and 26) with markedly improved metabolic stability. Compared to PF74, analog 20 exhibited similar submicromolar potency, and much longer (51-fold) half-life in human liver microsomes (HLMs). Molecular docking corroborated that 20 binds to the PF74 binding site, and revealed distinct binding interactions conferred by the benzamide moiety. Collectively, our data support compound 20 as a promising antiviral lead.KEY WORDS: HIV-1, Capsid protein, PF74, Microsomal stability 相似文献
193.
Subclassification of autoimmune pancreatitis: a histologic classification with clinical significance
Deshpande V Gupta R Sainani N Sahani DV Virk R Ferrone C Khosroshahi A Stone JH Lauwers GY 《The American journal of surgical pathology》2011,35(1):26-35
Autoimmune pancreatitis (AIP) is a chronic inflammatory disease of the pancreas. Examination of pancreatic resection specimens from patients with AIP has shown that there are 2 subclasses of this disease. However, there is no widely accepted pathologic classification scheme and the clinical significance of such a classification remains to be established. In this study, we revisited the subclassification of AIP and examine whether this provides clinically and prognostically meaningful information. We evaluated 29 pancreatic resection specimens from patients with AIP. Demographic, clinical, and imaging data were recorded, as was evidence of extrapancreatic manifestations. In addition to a detailed and semiquantitative histologic evaluation, immunohistochemistry for IgG4 was performed on pancreatic and extrapancreatic tissues. We also evaluated 48 consecutive cases of chronic pancreatitis, not otherwise specified. The resected specimens could readily be subclassified into 2 subtypes: type 1 (n=11) and type 2 (n=18). In comparison with patients with type 2 disease, patients with type 1 disease were significantly more likely to be males (P=0.09), older (P=0.02), and present with jaundice (P=0.01), and less likely to be associated with abdominal pain (P=0.04). On imaging, the pancreatic tail cut-off sign was exclusively seen in patients with type 2 disease (4 of 10 cases). Hypercellular inflamed interlobular stroma was unique to type 1 pattern (91%), whereas significant ductal injury in the form of microabscesses and ductal ulceration was almost exclusively seen in type 2 pattern (78%). Eight of 10 patients with a type 1 pattern had evidence of a systemic disease. Three patients with type 2 disease had recurrent episodes of pancreatitis after their pancreatic resection. In comparison with the cohort of chronic pancreatitis, not otherwise specified, type 2 AIP cases were less likely to be associated with a history of alcohol abuse, and showed significantly more foci of periductal inflammation and neutrophilic microabscesses. Our review of pancreatic resection specimens shows 2 histologically distinct forms of AIP. Our data support the concept that type 1 AIP is a systemic disease and is the pancreatic manifestation of IgG4-related systemic disease. Type 2 disease is confined to the pancreas. The intensity of the periductal inflammatory infiltrate and the presence of ductal neutrophilic abscesses are features that assist in distinguishing type 2 AIP from chronic pancreatitis, not otherwise specified. Although imperfect, clinical and imaging features may help distinguish the 2 subtypes of AIP. On the basis of these significant differences between the 2 types of AIP, we advocate the position that all subsequent studies attempt to substratify their patients into these 2 groups. 相似文献
194.
Michael M Maher Mannudeep K Kalra Brian C Lucey Kartik Jhaveri Dushyant V Sahani Peter F Hahn Mary Jane O'Neill Peter R Mueller 《Journal of Medical Imaging and Radiation Oncology》2004,48(1):64-68
We describe the imaging findings of the HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome in a gravid 36‐year‐old‐woman who presented at 19.5 weeks gestation with severe right upper quadrant pain. Ultrasound findings suggested a focal hyperechoic liver lesion suggesting pregnancy‐related hepatopathy prior to development of biochemical signs of HELLP syndrome. Within 3 days, the patient developed characteristic clinical and laboratory evidence of the HELLP syndrome. MR imaging at this time demonstrated localized hepatic ischaemia, further strengthening the diagnosis of HELLP syndrome. 相似文献
195.
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197.
Rapid advances in imaging technologies, such as multidetector CT, MRI, and positron emission tomography (PET) or PET-CT have
improved detection, characterization, and staging of colorectal liver metastases. Imaging provides important information in
detecting the stage of disease and formulating an appropriate treatment strategy. Response to novel targeted therapies can
also be assessed with newer imaging tools. Therefore, knowledge of the established and emerging imaging techniques is essential
for selecting an appropriate modality in the management of liver metastases from colorectal cancer. 相似文献
198.
199.
Electron contamination from a sealed 60Co radiation source has been investigated comprehensively using a CaSO4:Dy based TLD badge and LiF crystals. It has been found that due to electron contamination, the thermoluminescence (TL) detectors exhibit over response which can be corrected by applying a magnetic field. It has also been found that for a source-to-dosimeter distance of 50 cm, the ratio of the TL readouts of the third to first discs of the TLD badge reduces from ~1.5 to ~1.00 after applying a magnetic field. Hence detectors which are sensitive to electrons as well as photons, and are capable of distinguishing them, can lead to an erroneous measurement. This happens because the contribution due to electron contamination interferes with pure gamma calibration. The study is helpful in establishing accurate calibration and appropriate correction factors for personnel monitoring carried out using CaSO4:Dy based TLD badge. 相似文献
200.
Prabhakar PD Prabhakar AM Prabhakar HB Sahani D 《Magnetic Resonance Imaging Clinics of North America》2010,18(3):497-514, xi
Magnetic resonance cholangiopancreatography (MRCP) is an elegant MR technique for noninvasively delineating the biliary system. Technologic advances in MRCP acquisition and processing and the routine availability of three-dimensional sequences have facilitated detailed assessment of biliary anatomy and pathologic or congenital processes; therefore, invasive endoscopic retrograde cholangiopancreatography is rarely needed for establishing a diagnosis. MRCP can be combined with contrast-enhanced MR imaging to enable concurrent evaluation of organs such as the liver and pancreas in addition to functional biliary imaging. This review focuses on the current use of MRCP to evaluate nonmalignant processes affecting the biliary system. 相似文献