Medical and Societal information from the Research Community	Number of Articles: 17,750,454 Number of Contributors: 57 Number of Queries: 12,899,077
	Save this page:  Send this page	Login  or Create a Free Account

GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Humans or Animals Humans Animals Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Results(1-25 of 74) Sort By: Publication Date Relevance Took: 0.995 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 3 1 2 3 > (74 articles found) Controlled, single-step, stratum corneum disruption as a pretreatment for immunization via a patch. May 23, 2008 David M Frerichs,Larry R Ellingsworth,Sarah A Frech,David C Flyer,Christina P Villar,Jianmei Yu,Gregory M Glenn A Skin Prep System (SPS) has been developed to provide a well-tolerated and controlled method of stratum corneum disruption using mild abrasion as part of transcutaneous immunization (TCI). In this study, four groups (n=10) of volunteers were pretreated with the SPS using three different lengths of... ( view more ) mild abrasive strips (13 mm, 25 mm and 38 mm), or a handheld applicator. They then received a vaccine patch containing 50 microg of the heat-labile enterotoxin from Escherichia coli (LT) at day 0 and day 21. Subsequent anti-LT IgG antibody responses were dependent on abrasive strip length, with highest immune responses seen after use of the longest strip. The development of a simple, single-use, disposable device that is well-tolerated and allows disruption to be modulated represents an important step forward in physical penetration enhancement for the skin. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Increased level of IL-32 during human immunodeficiency virus infection suppresses HIV replication. May 15, 2008 Sahibzada T Rasool,Heng Tang,Jianmei Wu,Wei Li,Muhammad Mahmood Mukhtar,Jingwen Zhang,Yongxin Mu,Huang Xioa Xing,Jianguo Wu,Ying Zhu Interleukin-32 was recently identified as a pro-inflammatory cytokine produced by T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes. IL-32 is induced by IFN-gamma in a time-dependent manner suggesting a role for IL-32 in innate and adaptive immune responses. In this study w... ( view more )e present evidence that Human immunodeficiency virus promotes interleukin-32 production at both mRNA and protein levels. Our results showed that there is a 74% increase in the serum levels of IL-32 among HIV patients as compared to healthy individuals. There was a three-fold increase in the promoter activity of the IL-32 in the present infections HIV clone. This increase in IL-32 promoter activity was substantiated by increased IL-32 mRNA and protein levels. We have also demonstrated that IL-32 suppresses HIV replication. Our results show that HIV LTR activity was increased by more than six-folds when endogenous IL-32 was knocked down by IL-32-specific siRNA whereas it decreased by one-fold when IL-32 was over expressed in the cells. Similarly a more than two-fold increase and a 50% decrease in HIV p24 values were noted when IL-32 was knocked down and when IL-32 was over expressed in the cells, respectively. Our present work shows that raised IL-32 levels in HIV infection may in turn hamper HIV replication; one of the protective mechanisms of nature. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Dual binding site inhibitors of B-RAF kinase. May 1, 2008 Ronald L Wolin,Scott D Bembenek,Jianmei Wei,Shelby Crawford,Katherine Lundeen,Anders Brunmark,Lars Karlsson,James P Edwards,Jonathan M Blevitt Computer aided modeling guided the design of a series of diarylimidazole compounds (11-22) intended to interact with both the ATP and adjacent allosteric binding domains of B-RAF kinase. Their ability to inhibit the function of B-RAF kinase and intracellular ERK1/2 phosphorylation were evaluated. View Full Abstract View Article Details View Coded Data Related Articles The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus). Apr 24, 2008 Ray Ming,Shaobin Hou,Yun Feng,Qingyi Yu,Alexandre Dionne-Laporte,Jimmy H Saw,Pavel Senin,Wei Wang,Benjamin V Ly,Kanako L T Lewis,Steven L Salzberg,Lu Feng,Meghan R Jones,Rachel L Skelton,Jan E Murray,Cuixia Chen,Wubin Qian,Junguo Shen,Peng Du,Moriah Eustice,Eric Tong,Haibao Tang,Eric Lyons,Robert E Paull,Todd P Michael,Kerr Wall,Danny W Rice,Henrik Albert,Ming-Li Wang,Yun J Zhu,Michael Schatz,Niranjan Nagarajan,Ricelle A Acob,Peizhu Guan,Andrea Blas,Ching Man Wai,Christine M Ackerman,Yan Ren,Chao Liu,Jianmei Wang,Jianping Wang,Jong-Kuk Na,Eugene V Shakirov,Brian Haas,Jyothi Thimmapuram,David Nelson,Xiyin Wang,John E Bowers,Andrea R Gschwend,Arthur L Delcher,Ratnesh Singh,Jon Y Suzuki,Savarni Tripathi,Kabi Neupane,Hairong Wei,Beth Irikura,Maya Paidi,Ning Jiang,Wenli Zhang,Gernot Presting,Aaron Windsor,Rafael Navajas-Pérez,Manuel J Torres,F Alex Feltus,Brad Porter,Yingjun Li,A Max Burroughs,Ming-Cheng Luo,Lei Liu,David A Christopher,Stephen M Mount,Paul H Moore,Tak Sugimura,Jiming Jiang,Mary A Schuler,Vikki Friedman,Thomas Mitchell-Olds,Dorothy E Shippen,Claude W dePamphilis,Jeffrey D Palmer,Michael Freeling,Andrew H Paterson,Dennis Gonsalves,Lei Wang,Maqsudul Alam Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three ... ( view more )times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Preparation and characterization of hydrophobic TiO(2) pillared clay: the effect of acid hydrolysis catalyst and doped Pt amount on photocatalytic activity. Apr 15, 2008 Xuejun Ding,Taicheng An,Guiying Li,Shanqing Zhang,Jiaxin Chen,Jianmei Yuan,Huijun Zhao,Hui Chen,Guoying Sheng,Jiamo Fu Titanium hydrate sols were prepared using different acid hydrolysis catalysts, i.e., acetic acid and hydrochloric acid. The platinum-doped TiO(2) sol-gels were also synthesized by adding K(2)PtCl(6) into the titanium hydrate sols. The hydrophobic montmorillonite clay, treated with organic cationic ... ( view more )surfactant, i.e., hexadecyltrimethylammonium bromide, was used as a template to prepare TiO(2) pillared photocatalyst with the above sols. Scanning electron microscopy (SEM), X-ray diffraction (XRD) and energy dispersive X-ray analysis (EDX) were employed to characterize the resulting photocatalysts. The adsorption performance and photoactivity of prepared pillared clays were studied by using methyl orange as a model organic pollutant. The preliminary results indicated that the hydrophobic TiO(2) pillared clay prepared with acetic acid as the acid hydrolysis catalysts possessed higher photocatalytic activity than that with hydrochloric acid. Due to the excellent sedimentation property of the clay, the resulting pillared photocatalyst is easily recovered and reused in the postrun treatment. Also the doping of platinum into the hydrophobic photocatalyst can increase the photocatalytic activity significantly. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors. Apr 1, 2008 Scott D Edmondson,Lan Wei,Jinyou Xu,Jackie Shang,Shiyao Xu,Jianmei Pang,Ashok Chaudhary,Dennis C Dean,Huaibing He,Barbara Leiting,Kathryn A Lyons,Reshma A Patel,Sangita B Patel,Giovanna Scapin,Joseph K Wu,Maria G Beconi,Nancy A Thornberry,Ann E Weber The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity to form reactive metabolites, thus revealing a potential liabilit... ( view more )y for this class of DPP-4 inhibitors. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of lysine 411 in substrate carboxyl group binding to the human reduced folate carrier, as determined by site-directed mutagenesis and affinity inhibition. Apr 2008 Yijun Deng,Zhanjun Hou,Lei Wang,Christina Cherian,Jianmei Wu,Aleem Gangjee,Larry H Matherly Reduced folate carrier (RFC) is the major membrane transporter for folates and antifolates in mammalian tissues. Recent studies used radioaffinity labeling with N-hydroxysuccinimide (NHS)-[(3)H]methotrexate (MTX) to localize substrate binding to residues in transmembrane domain (TMD) 11 of human RF... ( view more )C. To identify the modified residue(s), seven nucleophilic residues in TMD11 were mutated to Val or Ala and mutant constructs expressed in RFC-null HeLa cells. Only K411A RFC was not inhibited by NHS-MTX. By radioaffinity labeling with NHS-[(3)H]MTX, wild-type (wt) RFC was labeled; for K411A RFC, radiolabeling was abolished. When Lys411 was replaced with Ala, Arg, Gln, Glu, Leu, and Met, only K411E RFC showed substantially decreased transport. Nine classic diamino furo[2,3-d]pyrimidine antifolates with unsubstituted alpha- and gamma-carboxylates (1), hydrogen- or methyl-substituted alpha-(2,3) or gamma-(4,5) carboxylates, or substitutions of both alpha- and gamma-carboxylates (6-9) were used to inhibit [(3)H]MTX transport with RFC-null K562 cells expressing wt and K411A RFCs. For wt and K411A RFCs, inhibitory potencies were in the order 4 > 5 > 1 > 3 > 2; 6 to 9 were poor inhibitors. Inhibitions decreased in the presence of physiologic anions. When NHS esters of 1, 2, and 4 were used to covalently modify wt RFC, inhibitory potencies were in the order 2 > 1 > 4; inhibition was abolished for K411A RFC. These results establish that Lys411 participates in substrate binding via an ionic association with the substrate gamma-carboxylate; however, this is not essential for transport. An unmodified alpha-carboxylate is required for high-affinity substrate binding to RFC, whereas the gamma-carboxyl is not essential. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Synthesis of MCM-22 zeolite by an ultrasonic-assisted aging procedure. Apr 2008 Baoyu Wang,Jianmei Wu,Zhong-Yong Yuan,Niu Li,Shouhe Xiang The synthesis of MCM-22 zeolite under hydrothermal crystallization conditions has been performed by an ultrasonic-assisted aging procedure. The ultrasonic-assisted aging of the initial aluminosilicate gel can shorten the crystallization time of MCM-22, decrease the amount of hexamethyleneimine (HMI... ( view more )) used, and broaden the range of SiO(2)/Al(2)O(3) ratios. By using the ultrasonic aging, pure phase of high-silica MCM-22 products with SiO(2)/Al(2)O(3)>100 can be obtained. When SiO(2)/Al(2)O(3) ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Liposomal coencapsulated fludarabine and mitoxantrone for lymphoproliferative disorder treatment. Apr 2008 Xiaobin Zhao,Jianmei Wu,Natarajan Muthusamy,John C Byrd,Robert J Lee Fludarabine (FLU)-based combination therapies are commonly used to treat low-grade lymphoma and chronic lymphocytic leukemia (CLL) patients. In vitro and clinical studies have indicated advantages when FLU and mitoxantrone (MTO) are applied in combination. To further enhance this effect, these two ... ( view more )agents were coencapsulated in liposomes. FLU was passively encapsulated during liposome formation, and MTO was loaded with a transmembrane pH gradient. Entrapment efficiency, particle size, stability, and drug release kinetics were characterized. In vitro cytotoxicity study was carried out in two representative B-cell lines: Wac3CD5 and Raji. Synergism as measured by combination index (CI) was observed in cells treated with liposomes coencapsulating FLU and MTO. Annexin V/propidium iodide (PI) analysis further confirmed that coencapsulated FLU and MTO improved the percentage of apoptosis among primary CLL cells. These data suggest that adopting liposomes containing coencapsulated drug combinations constitutes a potential strategy to promote drug synergism and may have utility in the treatment of leukemia and lymphoma. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A novel B-RAF inhibitor blocks interleukin-8 (IL-8) synthesis in human melanoma xenografts, revealing IL-8 as a potential pharmacodynamic biomarker. Mar 2008 Shelby Crawford,Daniel Belajic,Jianmei Wei,Jason P Riley,Paul J Dunford,Scott Bembenek,Anne Fourie,James P Edwards,Lars Karlsson,Anders Brunmark,Ronald L Wolin,Jonathan M Blevitt B-RAF mutations have been identified in the majority of melanoma and a large fraction of colorectal and papillary thyroid carcinoma. Drug discovery efforts targeting mutated B-RAF have yielded several interesting molecules, and currently, three compounds are undergoing clinical evaluation. Inhibiti... ( view more )on of B-RAF in animal models leads to a slowing of tumor growth and, in some cases, tumor reduction. Described within is a novel series of diaryl imidazoles with potent, single-digit nanomolar, anti-B-RAF activity. One compound from this series has been detailed here and has been shown to block B-RAF(V600E)-dependent extracellular signal-regulated kinase 1/2 phosphorylation in SK-MEL-28 melanoma cells as well as soft agar colony formation and proliferation. Importantly, interleukin-8 (IL-8) was identified by quantitative real-time PCR and ELISA as a product of the elevated mitogen-activated protein kinase signaling in these cells. Plasma concentrations of IL-8 in mice bearing melanoma xenografts were significantly reduced following exposure to B-RAF inhibitors. Taken together, these data suggest that IL-8 could serve as a tractable clinical biomarker. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Immunostimulant adjuvant patch enhances humoral and cellular immune responses to DNA immunization. Jan 2008 Mikayel Mkrtichyan,Anahit Ghochikyan,Nina Movsesyan,Adrine Karapetyan,Gayane Begoyan,Jianmei Yu,Gregory M Glenn,Ted M Ross,Michael G Agadjanyan,David H Cribbs The focus of this report is on the development of an improved DNA immunization protocol, which takes advantage of the strengths of DNA immunization, as well as those associated with adjuvant delivered by transcutaneous immunostimulatory (IS) patches. Because transcutaneous delivery of adjuvants to ... ( view more )the skin at the vaccination site has been shown to amplify the immune response to protein antigens, we hypothesized that the same IS patch when placed on the skin at the site of DNA injection could further enhance the immune response to a DNA influenza vaccine. We have combined an influenza DNA vaccine, hemagglutinin fused with three copies of complement C3d, to enhance uptake and antigen presentation, with an IS patch containing heat-labile enterotoxin from Escherichia coli. Coadministration of a potent adjuvant in IS patches placed on the skin at the site of DNA vaccination dramatically amplifies anti-influenza antibody immune response. Supplementing DNA vaccines with IS patches may be a particularly valuable strategy because DNA vaccines can be rapidly modified in response to mutations in pathogens, and individuals with compromised immune systems such as transplant patients and the elderly will benefit from the enhanced antibody response induced by the IS patches. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Methane oxidation by an extremely acidophilic bacterium of the phylum Verrucomicrobia. Dec 6, 2007 Peter F Dunfield,Anton Yuryev,Pavel Senin,Angela V Smirnova,Matthew B Stott,Shaobin Hou,Binh Ly,Jimmy H Saw,Zhemin Zhou,Yan Ren,Jianmei Wang,Bruce W Mountain,Michelle A Crowe,Tina M Weatherby,Paul L E Bodelier,Werner Liesack,Lu Feng,Lei Wang,Maqsudul Alam Aerobic methanotrophic bacteria consume methane as it diffuses away from methanogenic zones of soil and sediment. They act as a biofilter to reduce methane emissions to the atmosphere, and they are therefore targets in strategies to combat global climate change. No cultured methanotroph grows optim... ( view more )ally below pH 5, but some environments with active methane cycles are very acidic. Here we describe an extremely acidophilic methanotroph that grows optimally at pH 2.0-2.5. Unlike the known methanotrophs, it does not belong to the phylum Proteobacteria but rather to the Verrucomicrobia, a widespread and diverse bacterial phylum that primarily comprises uncultivated species with unknown genotypes. Analysis of its draft genome detected genes encoding particulate methane monooxygenase that were homologous to genes found in methanotrophic proteobacteria. However, known genetic modules for methanol and formaldehyde oxidation were incomplete or missing, suggesting that the bacterium uses some novel methylotrophic pathways. Phylogenetic analysis of its three pmoA genes (encoding a subunit of particulate methane monooxygenase) placed them into a distinct cluster from proteobacterial homologues. This indicates an ancient divergence of Verrucomicrobia and Proteobacteria methanotrophs rather than a recent horizontal gene transfer of methanotrophic ability. The findings show that methanotrophy in the Bacteria is more taxonomically, ecologically and genetically diverse than previously thought, and that previous studies have failed to assess the full diversity of methanotrophs in acidic environments. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles In silico and in vitro pharmacogenetic analysis in mice. Nov 6, 2007 Yingying Guo,Peng Lu,Erin Farrell,Xun Zhang,Paul Weller,Mario Monshouwer,Jianmei Wang,Guochun Liao,Zhaomei Zhang,Steven Hu,John Allard,Steve Shafer,Jonathan Usuka,Gary Peltz Combining the experimental efficiency of a murine hepatic in vitro drug biotransformation system with in silico genetic analysis produces a model system that can rapidly analyze interindividual differences in drug metabolism. This model system was tested by using two clinically important drugs, tes... ( view more )tosterone and irinotecan, whose metabolism was previously well characterized. The metabolites produced after these drugs were incubated with hepatic in vitro biotransformation systems prepared from the 15 inbred mouse strains were measured. Strain-specific differences in the rate of 16 alpha-hydroxytestosterone generation and irinotecan glucuronidation correlated with the pattern of genetic variation within Cyp2b9 and Ugt1a loci, respectively. These computational predictions were experimentally confirmed using expressed recombinant enzymes. The genetic changes affecting irinotecan metabolism in mice mirrored those in humans that are known to affect the pharmacokinetics and incidence of adverse responses to this medication. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Pyrazole-based cathepsin S inhibitors with improved cellular potency. Oct 15, 2007 Jianmei Wei,Barbara A Pio,Hui Cai,Steven P Meduna,Siquan Sun,Yin Gu,Wen Jiang,Robin L Thurmond,Lars Karlsson,James P Edwards High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of CatS inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency,... ( view more ) dramatic effects on cellular activity were observed. Optimization afforded indole- and benzothiophene-derived analogues that were high affinity CatS inhibitors (IC(50)=20-40 nM) with good cellular potency (IC(50)=30-340 nM). ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Transcutaneous immunization with heat-labile enterotoxin: development of a needle-free vaccine patch. Oct 2007 Gregory M Glenn,David C Flyer,Larry R Ellingsworth,Sarah A Frech,David M Frerichs,Robert C Seid,Jianmei Yu The skin is an attractive target for vaccine delivery. Adjuvants and antigens delivered into the skin can result in potent immune responses and an unmatched safety profile. The heat-labile enterotoxin (LT) from Escherichia coli, which acts both as antigen and adjuvant, has been shown to be delivere... ( view more )d to human skin efficiently when used in a patch, resulting in strong immune responses. Iomai scientists have capitalized on these observations to develop late-stage products based on LT. This has encouraged commercial-level product development of a delivery system that is efficient, user-friendly and designed to address important medical needs. Over the past 2 years, extensive clinical testing and optimization has allowed the patch to evolve to a late-stage product. As a strategy for approval of a revolutionary vaccine-delivery system, the singular focus on optimization of LT delivery has enabled technical progress to extend patch-vaccine product development beyond LT. The field efficacy of the LT-based travelers' diarrhea vaccine has validated this approach. The discussion of transcutaneous immunization is unique, in that any consideration of the adjuvant must also include delivery, and the significant advances in a commercial patch application system are described. In this review, we integrate these concepts, update the clinical data and look to the future. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles c-Maf interacts with c-Myb to down-regulate Bcl-2 expression and increase apoptosis in peripheral CD4 cells. Oct 2007 Siying Peng,Saif Lalani,Jianmei W Leavenworth,I-Cheng Ho,Mary E Pauza The transcription factor c-Maf is critical for IL-4 production and the development of Th2 cells, which promote humoral immunity and protect against extracellular parasites. Yet, little else is known of c-Maf function in CD4 cells. Here, we identify a novel role for c-Maf in regulating susceptibilit... ( view more )y to apoptosis. Overexpression of c-Maf results in increased susceptibility of CD4 cells to apoptosis induced by multiple stimuli, including growth factor withdrawal, dexamethasone, irradiation, and TCR engagement. This effect is independent of Fas or p53; however, Bcl-2 expression is reduced in c-Maf Tg CD4 cells. Immunoprecipitation and Western blot analyses demonstrate that c-Maf-c-Myb complex formation is enhanced among T cells from c-Maf Tg mice compared to non-Tg littermates following TCR engagement. Unlike non-Tg T cells, c-Myb binding to the Bcl-2 promoter is not detectable in c-Maf Tg T cells by chromatin immunoprecipitation. In reporter assays, Bcl-2 promoter activity is reduced by c-Maf in a dose-dependent manner. Furthermore, transgene-mediated Bcl-2 expression corrects the apoptosis defect observed among c-Maf Tg CD4 cells. These data suggest that c-Maf can interact with c-Myb to reduce Bcl-2 expression, thereby limiting CD4 cell survival following TCR engagement. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles On the growth model of the capillaries in the porous silk fibroin films. Oct 2007 Bai Lun,Xu Jianmei,Sun Qilong,Di Chuanxia,Song Jiangchao,Wu Zhengyu This paper discussed the random growth model of the capillaries in its growing process, analyzed the relations between the growth of the capillaries, the metabolism of the organism tissue, and micro environmental condition and secretion of the growth factors. Furthermore, the paper discussed the gr... ( view more )owth law of the capillaries in the porous silk fibroin films (PSFF) in order to provide a theoretical basis for the designing and making of the new biomaterial of the PSFF more suitable for the growth of the cells and capillaries. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Anatomy of the posterior caudal lobe of the cerebellum and the eminentia granularis posterior in a mormyrid fish. Jun 10, 2007 Holly R Campbell,Johannes Meek,Jianmei Zhang,Curtis C Bell The cerebellum of mormyrid fish is of interest for its large size and unusual histology. The mormyrid cerebellum, as in all ray-finned fishes, has three subdivisions--valvula, corpus, and caudal lobe. The structures of the mormyrid valvula and corpus have been examined previously, but the structure... ( view more ) of the mormyrid caudal lobe has not been studied. The mormyrid caudal lobe includes a posterior caudal lobe associated with the electrosense and an anterior caudal lobe associated with lateral line and eighth nerve senses. In this article we describe cellular elements of the posterior caudal lobe and of the eminentia granularis posterior (EGp) in the mormyrid fish Gnathonemus petersii. The EGp gives rise to the parallel fibers of the posterior caudal lobe. We used intracellular injection of biocytin, extracellular injection of biotinylated dextran amine, and immunohistochemistry with antibodies to gamma-aminobutyric acid, inositol triphosphate receptor I, calretinin, and Zebrin II. The histological structure of the posterior caudal lobe is markedly irregular in comparison to that of the corpus and the valvula, and a tight modular organization of cerebellar elements is less apparent here. Most Purkinje cell bodies are in the middle of the molecular region. Their dendrites are only roughly oriented in the sagittal plane, extend both ventrally and dorsally, and branch irregularly. Climbing fibers terminate only on smooth dendrites near the soma. Most Purkinje cell axons terminate locally on eurydendroid cells that project outside the cortex. The results provide an additional variant to the already large set of different cerebellar and cerebellum-like structures. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity. May 15, 2007 Roger A Smith,Zahra Fathi,Furahi Achebe,Christiana Akuche,Su-Ellen Brown,Soongyu Choi,Jianmei Fan,Susan Jenkins,Harold C E Kluender,Anish Konkar,Rico Lavoie,Ronald Mays,Jennifer Natoli,Stephen J O'Connor,Astrid A Ortiz,Ning Su,Christy Taing,Susan Tomlinson,Theresa Tritto,Gan Wang,Stephan-Nicholas Wirtz,Wai Wong,Xiao-Fan Yang,Shihong Ying,Zhonghua Zhang Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Furthe... ( view more )r optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 K(i)=3.7nM, and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models. ( view less ) View Full Abstract View Article Details   Related Articles Understanding the degradation pathway of a poorly water-soluble drug formulated in PEG-400. Apr 11, 2007 Jianmei D Kochling,Hai Miao,Christopher R Young,Adam R Looker,Michael Shannon,Eda Ross Montgomery VX-497 is a poorly water-soluble compound. It is formulated in PEG-400 and encapsulated in softgel capsules. Although the drug product is stable at refrigerated conditions, many degradation peaks have been observed at accelerated storage conditions. An investigation utilizing high performance liqui... ( view more )d chromatography-mass spectrometry (HPLC-MS) was conducted to understand the degradation mechanism of the active pharmaceutical ingredient (VX-497) in PEG-400 formulation. Results revealed that the degradation was mainly caused by the reaction between VX-497 with moisture (hydrolysis) and PEG-400 (PEGylation). The numerous degradation peaks observed in the samples stored at accelerated conditions were PEG adducts covalently attached to portions of the VX-497 molecule, which were confirmed by comparison with synthetic markers. Investigation also found that an impurity, which was present in the VX-497 drug substance, reacted with PEG-400 following the same reaction mechanism, and generated additional impurities in the VX-497 drug product. By changing the process for drug substance synthesis, pure batches of VX-497 were obtained. Furthermore, it was found that the reaction between VX-497 and PEG-400 was temperature and time dependent. When the drug product was manufactured at 45 degrees C and the processing time was controlled, the PEG degradants and by-products were reduced to non-detectable levels, resulting in greatly improved drug product quality. This paper presents an integrated effort among analytical, process, and formulation scientists on how to develop a better drug product by understanding the fundamental issues of the drug product, namely the degradation mechanism. ( view less ) View Full Abstract View Article Details   Related Articles Granular cells of the mormyrid electrosensory lobe and postsynaptic control over presynaptic spike occurrence and amplitude through an electrical synapse. Mar 2007 Jianmei Zhang,Victor Z Han,Johannes Meek,Curtis C Bell Primary afferent fibers from the electroreceptors of mormyrid electric fish use a latency code to signal the intensity of electrical current evoked by the fish's own electric organ discharge (EOD). The afferent fibers terminate centrally in the deep and superficial granular layers of the electrosen... ( view more )sory lobe with morphologically mixed chemical-electrical synapses. The granular cells in these layers seem to decode afferent latency through an interaction between primary afferent input and a corollary discharge input associated with the EOD motor command. We studied the physiology of deep and superficial granular cells in a slice preparation with whole cell patch recording and electrical stimulation of afferent fibers. Afferent stimulation evoked large all-or-none electrical excitatory postsynaptic potentials (EPSPs) and large all or none GABAergic inhibitory postsynaptic potentials (IPSPs) in both superficial and deep granular cells. The amplitudes of the electrical EPSPs depended on postsynaptic membrane potential, with maximum amplitudes at membrane potentials between -65 and -110 mV. Hyperpolarization beyond this level resulted in either the abrupt disappearance of EPSPs, a step-like reduction to a smaller EPSP, or a graded reduction in EPSP amplitude. Depolarization to membrane potentials lower than that yielding a maximum caused a linear decrease in EPSP amplitude, with EPSP amplitude reaching 0 mV at potentials between -55 and -40 mV. We suggest that the dependence of EPSP size on postsynaptic membrane potential is caused by close linkage of pre- and postsynaptic membrane potentials through a high-conductance gap junction. We also suggest that this dependence may result in functionally important nonlinear interactions between synaptic inputs. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Constrained analogs of CB-1 antagonists: 1,5,6,7-Tetrahydro-4H-pyrrolo[3,2-c]pyridine-4-one derivatives. Feb 1, 2007 Roger A Smith,Zahra Fathi,Su-Ellen Brown,Soongyu Choi,Jianmei Fan,Susan Jenkins,Harold C E Kluender,Anish Konkar,Rico Lavoie,Ronald Mays,Jennifer Natoli,Stephen J O'Connor,Astrid A Ortiz,Brent Podlogar,Christy Taing,Susan Tomlinson,Theresa Tritto,Zhonghua Zhang A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazole CB-1 antagonist rimonabant. Certain examples exhibited very potent hCB-1 receptor binding affinity and functional antagonism with Ki and Kb values below 10 nM, and with high selectivity for CB-1 over ... ( view more )CB-2 (>100-fold). A representative analog was established to cause significant appetite suppression and reduction in body weight gain in industry-standard rat models used to develop new therapeutics for obesity. ( view less ) View Full Abstract View Article Details   Related Articles Induced expression of cathepsins and cystatin C in a murine model of demyelination. Feb 2007 Jianmei Ma,Kenji F Tanaka,Gen Yamada,Kazuhiro Ikenaka While proteolytic enzymes are involved in the pathogenesis of multiple sclerosis (MS), the involvement of cathepsins has not been characterized in detail. To better understand the role of cathepsins, cDNA microarray analysis was used to study the brains of proteolipid protein transgenic (plp ( tg )... ( view more ) /-) mice, an animal model that closely mimics the failure of remyelination in MS. Analysis revealed upregulated expression of cathepsins L, H and B and their inhibitor, cystatin C. By in situ hybridization, the induction of cathepsins was primarily limited to microglia/macrophages of the white matter, with continuous expression from 2 to 8 months of age. Elevated protein level of cathepsins was confirmed at 4 months of age. In contrast, elevated expression of cystatin C was found in astrocytes. The ratio of microglia/macrophages to astrocytes increased throughout the course of demyelination, suggesting that the ratio of secreted cathepsins to cystatin C increased during that period. We propose that in MS, remyelination may be impaired by increasing activity of cathepsins inadequately controlled by cystatin C. ( view less ) View Full Abstract View Article Details   Related Articles Fruit quality of transgenic tomatoes with suppressed expression of LeETR1 and LeETR2 genes. 2007 Bili Bao,Leqin Ke,Jianmei Jiang,Tiejin Ying Tomato fruit is renowned for its high concentration of phyto-nutrients such as lycopene and carotenoids, overall contribution to nutrition and human health. The effect of antisense suppression of ethylene receptor genes LeETR1 and LeETR2 over the quality of tomato fruit was investigated in this pap... ( view more )er. During the different stages of ripening, the fruit of antisense transgenic tomatoes of ale1 and ale2, compared to their wild type B1, showed higher total soluble solids, acidity and electrolytes accumulations and color development; lower fruit firmness, fruit viscosity and fruit elasticity. However, no significant difference of Vc content, total sugar, fruit pH value and fruit pigments between transgenic lines and B1 were noticed. ale1 and ale2 showed shortened shelf life. The data suggest that fruit with suppressed LeETR1 and LeETR2 genes expression have stronger ethylene response, which accelerate fruit ripening and greatly altered tomato variety characteristics. ( view less ) View Full Abstract View Article Details   Related Articles Antioxidant activities of various extracts of lotus (Nelumbo nuficera Gaertn) rhizome. 2007 Dongmei Yang,Qiushuang Wang,Leqin Ke,Jianmei Jiang,Tiejin Ying Lotus rhizome powder was extracted with solvents of different polarities. Antioxidant activities of the extracts were evaluated by a 2, 2'-diphenylpicrylhydrazyl (DPPH) assay and a beta-carotene bleaching assay, and compared with that of butylated hydroxyanisole (BHA) and ascorbic acid. Methanol sh... ( view more )owed the highest extract yield among all of solvents. Although acetone extract had the highest total phenolics content, methanol extract had the highest total phenolics recovery from lotus powder (20.1 mg catechin equivalents/100g lotus powder). Extract of either methanol or acetone demonstrated the highest DPPH scavenging activity at both 66.7 mg/L and 133.3 mg/L. All extracts exhibited higher antioxidant activity coefficient (AAC) than that of ascorbic acid, furthermore, dichloromethane and petroleum extracts had comparable AAC with BHA by the beta-carotene bleaching assay. The properties of the extracting solvents significantly affected the yield, total phenolics content and antioxidant activity of lotus rhizome extracts. ( view less ) View Full Abstract View Article Details   Related Articles Page 1 of 3 1 2 3 > (74 articles found)

      
 ESRNexus is provided as a service by TrialStat Corporation. ESRNexus is a registered trademark of TrialStat Corporation. Copyright 2008. View a list of all articles here