tbuckley/cabot-search huggingface dataset:
P90 Cyclin-dependent kinases 7 and 9 specifically regulate neutrophil transcription and their inhibition drives apoptosis to promote resolution of inflammation
Authors: A. G. Rossi, R. Duffin, C. Haslett, A. E. Leitch
Journal: Thorax (2011)

<h3>Introduction and Objectives</h3> Terminally-differentiated neutrophils are short-lived but key effector cells of the innate immune response and play a prominent role in the pathogenesis and propagation of many inflammatory diseases including interstitial lung disease. BAL neutrophilia has been correlated with poor outcome in idiopathic pulmonary fibrosis (IPF) and neutrophils are the dominant cell type in acute exacerbations of IPF as well as in diffuse alveolar damage. Non-specific cyclin-dependent kinase inhibitor drugs have previously been shown to resolve neutrophil-dominant inflammation in the murine bleomycin lung injury model an established model of IPF. Here we elucidate the mechanism by which CDK inhibitor drugs mediate neutrophil apoptosis and hence promote resolution of inflammation. <h3>Methods</h3> We isolated peripheral blood neutrophils from healthy human donors and performed a variety of experiments including microarray, confocal microscopy and apoptosis assays (flow cytometry, fluorometric assay, DNA ladders and mitochondrial integrity assay and western blotting) to show that specific effects on neutrophil transcriptional capacity are responsible for CDK-inhibitor driven neutrophil apoptosis. Finally we show that specific CDK inhibitors drive resolution of neutrophil-dominant inflammation in the murine bleomycin lung injury model (Histology, BAL analysis). <h3>Results</h3> CDK inhibitors drive neutrophil apoptosis. Neutrophil apoptosis is dependent on a critical balance of pro- and anti-apoptotic proteins. Functional transcriptional machinery is present in human peripheral blood neutrophils. CDKs are present in neutrophils and their activity is both demonstrated and modulated with the use of specific CDK inhibitors. Specific CDK inhibition is a successful strategy for the resolution of murine bleomycin lung injury. <h3>Conclusion</h3> We highlight a novel mechanism that controls both neutrophil transcription and apoptosis that could be targeted by selective CDK inhibitor drugs to resolve established neutrophil-dominant inflammation.
Clinical patterns of hepatocellular carcinoma in nonalcoholic fatty liver disease: A multicenter prospective study
Authors: Fabio Piscaglia, Gianluca Svegliati‐Baroni, Andrea Barchetti, Anna Pecorelli, Sara Marinelli, Claudio Tiribelli, Stefano Bellentani
Journal: Hepatology (2015)

Nonalcoholic fatty liver disease (NAFLD) represents the hepatic manifestation of metabolic syndrome and may evolve into hepatocellular carcinoma (HCC). Only scanty clinical information is available on HCC in NAFLD. The aim of this multicenter observational prospective study was to assess the clinical features of patients with NAFLD-related HCC (NAFLD-HCC) and to compare them to those of hepatitis C virus (HCV)-related HCC. A total of 756 patients with either NAFLD (145) or HCV-related chronic liver disease (611) were enrolled in secondary care Italian centers. Survival was modeled according to clinical parameters, lead-time bias, and propensity analysis. Compared to HCV, HCC in NAFLD patients had a larger volume, showed more often an infiltrative pattern, and was detected outside specific surveillance. Cirrhosis was present in only about 50% of NAFLD-HCC patients, in contrast to the near totality of HCV-HCC. Regardless of tumor stage, survival was significantly shorter (P = 0.017) in patients with NAFLD-HCC, 25.5 months (95% confidence interval 21.9-29.1), than in those with HCV-HCC, 33.7 months (95% confidence interval 31.9-35.4). To eliminate possible confounders, a propensity score analysis was performed, which showed no more significant difference between the two groups. Additionally, analysis of patients within Milan criteria submitted to curative treatments did not show any difference in survival between NAFLD-HCC and HCV-HCC (respectively, 38.6 versus 41.0 months, P = nonsignificant)NAFLD-HCC is more often detected at a later tumor stage and could arise also in the absence of cirrhosis, but after patient matching, it has a similar survival rate compared to HCV infection; a future challenge will be to identify patients with NAFLD who require more stringent surveillance in order to offer the most timely and effective treatment.
In AF requiring warfarin interruption, no bridging was noninferior to anticoagulation bridging for thromboembolism
Authors: Anthony Donato
Journal: Annals of Internal Medicine (2015)

ACP Journal Club17 November 2015In AF requiring warfarin interruption, no bridging was noninferior to anticoagulation bridging for thromboembolismAnthony Donato, MD, MHPEAnthony Donato, MD, MHPEReading Health System, Reading, Pennsylvania, USA (A.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-163-10-005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationDouketis JD, Spyropoulos AC, Kaatz S, et al; BRIDGE Investigators. Perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med. 2015;373:823-33. https://pubmed.ncbi.nlm.nih.gov/26095867Clinical Impact RatingsHospitalists: Cardiology: Hematology: References1. Douketis JD, Spyropoulos AC, Spencer FA, et al; American College of Chest Physicians. Perioperative management of antithrombotic therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141:e326S-50S. [PMID: 22315266] Google Scholar2. PERIOP 2—A safety and effectiveness study of LMWH bridging therapy versus placebo bridging therapy for patients on long term warfarin and require temporary interruption of their warfarin. www.clinicaltrials.gov/ct2/show/NCT00432796 (accessed 18 Aug 2015). Google Scholar Author, Article, and Disclosure InformationAffiliations: Reading Health System, Reading, Pennsylvania, USA (A.D.)This article was published at Annals.org on 3 November 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 17 November 2015Volume 163, Issue 10Page: JC5KeywordsAtrial fibrillationCardiac surgeryHemorrhageInternational normalized ratioIschemic strokeLow molecular weight heparinOrthopedic surgerySurgeryThromboembolismTransient ischemic attacks ePublished: 17 November 2015 Issue Published: 17 November 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial
Authors: Yu Wei, Xue-bin Ji, Ya-wen Wang, Jing-xia Wang, En-qin Yang, Zheng-cheng Wang, Yu-qi Sang, Zuo-mu Bi, Cui-ai Ren, Fang Zhou, Guo-qiang Liu, Jun Peng, Ming Hou
Journal: Blood (2015)
Diagnostic criteria for complicated grief disorder
Authors: M J Horowitz, B Siegel, A Holen, G A Bonanno, C Milbrath, C H Stinson
Journal: American Journal of Psychiatry (1997)

Some prolonged and turbulent grief reactions include symptoms that differ from the DSM-IV criteria for major depressive disorder. The authors investigated a new diagnosis that would include these symptoms.They developed observer-based definitions of 30 symptoms noted clinically in previous longitudinal interviews of bereaved persons and then designed a plan to investigate whether any combination of these would serve as criteria for a possible new diagnosis of complicated grief disorder. Using a structured diagnostic interview, they assessed 70 subjects whose spouses had died. Latent class model analyses and signal detection procedures were used to calibrate the data against global clinical ratings and self-report measures of grief-specific distress.Complicated grief disorder was found to be characterized by a smaller set of the assessed symptoms. Subjects elected by an algorithm for these symptoms patterns did not significantly overlap with subjects who received a diagnosis of major depressive disorder.A new diagnosis of complicated grief disorder may be indicated. Its criteria would include the current experience (more than a year after a loss) of intense intrusive thoughts, pangs of severe emotion, distressing yearnings, feeling excessively alone and empty, excessively avoiding tasks reminiscent of the deceased, unusual sleep disturbances, and maladaptive levels of loss of interest in personal activities.
WITHDRAWN: Preparation and optimization of fenofibrate loaded self-microemulsifying drug delivery system (SMEDDS) by application of Box–Behnken design
Authors: Jin Wook Tak, Bijay Kumar Poudel, Pathak Shiva, Toe Kyung Go, Kyu Bong Woo, Dong Shik Kim, Han-Gon Choi, Jee-Heon Jeong, Chul Soon Yong, Jong Oh Kim
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
A Vision for Global Cancer Medicine: Pursuing the Equity of Chance
Authors: Agnes Binagwaho, Claire M. Wagner, Paul E. Farmer
Journal: Journal of Clinical Oncology (2015)

At the turn of the century, some claimed that HIV/AIDS was a disease that could not be managed in low-income settings. It was argued that "poor people would not comply with treatment," and that treatment was too expensive and too complicated to deliver. But over the past two decades, data on outcomes have thoroughly disproved this myth. Similar arguments have more recently been made about cancer treatment: chemotherapy was said to be too toxic and too costly and that it required administration expertise beyond that available in low-income settings. We argue that these claims are similarly rooted in ideology rather than evidence. Fortunately, such claims are starting to be refuted by a diverse set of global cancer partnerships around the world that are documenting progress and positive results. In this review article, we provide examples of programs that can give us reason to hope that the treatment playing field is being leveled such that birthplace does not determine survival prognosis. We believe that through strong collaborative efforts and solidarity, the equity of chance can be achieved for patients with cancer worldwide.
Biology of Opioid Peptides
Authors: A Beaumont, J Hughes
Journal: The Annual Review of Pharmacology and Toxicology (1979)

Opioid peptides are endogenous or synthetic peptides, with a spectrum of pharmacological activity similar to that of morphine and other narcotic agonist drugs. The designation opioid peptide can be made if (a) it produces morphine-like, naloxone reversible effects in several in vitro bioassay sys­ tems such as the guinea pig ileum (1), the cat nictitating membrane (2), the mouse vas deferens (3), and the neuroblastoma X glioma tissue culture preparation (4), and (b) if the peptide competes at low concentrations with opiate ligands for binding at opiate receptor binding sites (5-7). An addi­ tional, although not essential, criterion might include the production of naloxone reversible analgesia. These criteria exclude substance P which does have analgesic activity (8, 9), fragments of adrenocorticotropic hor­ mone which have very weak opiate receptor binding activity (10), and the morphine-like factor identified on the basis of morphine antibody recog­ nition (11). At present only three endogenous opiate peptides have been identified that have any claim to a physiological function. These are leucine5-enkepha­ lin (12), methionine5-enkephalin (12), and ,a-endorphin (13-16). Other frag­ ments of ,B-lipotropin such as LPH 61-69, LPH 61-76, LPH 61-77, and LPH 61-87 have opioid peptide activity (17-19) but current evidence sug­ gests that these may be artifacts of extraction or degradation products of ,B-endorphin (20). Other unidentified opioid peptides undoubtedly exist (21-24), but in the absence of structural and chemical identification it is impossible to assess their significance or biological function. The term endorphin as a generic name for opioid peptides has little to recommend
Genetic Control of Autoimmune Diabetes in the Nod Mouse
Authors: L S Wicker, J A Todd, L B Peterson
Journal: Annual Review of Immunology (1995)

The nonobese diabetic (NOD) mouse is a model of human autoimmune insulin-dependent diabetes mellitus. The NOD mouse also serves as a model for studying complex polygenic diseases because at least fourteen different loci are linked to disease development. The first Idd locus recognized, Idd1, is linked to the major histocompatibility complex (MHC), and its inheritance and expression are a paradigm for the other non-MHC Idd genes. The NOD allele at Idd1 does not behave as a recessive diabetes susceptibility gene, as it was originally thought to be, but instead it acts as a dominant gene with varying degrees of penetrance for the phenotypes of insulitis, a prediabetic inflammatory lesion, and spontaneous diabetes. MHC congenic strains of mice have shown that the NOD MHC is essential but, by itself, not sufficient for developing diabetes. The contributions of non-MHC Idd loci have also been assessed with NOD congenic strains derived by replacing NOD-specific chromosomal segments with those from diabetes-resistant strains of mice. While only partial protection from disease is provided by resistance alleles at single non-MHC Idd loci, epistatic interaction between two of the loci, Idd3 and Idd10, produced nearly complete protection from diabetes. Identifying Idd genes and defining their biologic functions should further our understanding of autoimmune disease pathogenesis and facilitate development of new treatments for diabetes.
Coordinated use of sequentially escalated cyclophosphamide and cell-cycle-specific chemotherapy (N4SE protocol) for advanced neuroblastoma: experience with 100 patients.
Authors: B H Kushner, L Helson
Journal: Journal of Clinical Oncology (1987)

A rationally devised induction regimen of vincristine, Adriamycin (Adria Laboratories, Columbus, OH), and sequentially-escalated cyclophosphamide (CPM), followed by S-phase-specific agents (5-fluorouracil [5-FU]/cytosine arabinoside [ara-C]/hydroxyurea), was used in 100 patients with neuroblastoma. Of 17 patients under 1 year of age at diagnosis, complete (CR)/good partial (GPR) responses with long-term disease-free survival were achieved in 11 (85%) of 13 new patients and in two of four previously treated patients; six of the GPRs also received myeloablative therapy with autologous bone marrow rescue to consolidate remission status. The 83 patients over 1 year of age at diagnosis included three groups: (1) 36 new patients whose N4SE included maximal-dose CPM (ie, up to 140 to 160 mg/kg/course); (2) an earlier group of 18 new patients whose N4SE included moderate-dose CPM (ie, up to 80 mg/kg/course); and (3) 29 previously treated patients who all received the maximal-dose N4SE regimen. For new patients, CR/GPR rates were 72% in the maximal-dose group v 39% in the earlier moderate-dose group (P = .029). A CR/GPR rate of 41% and a partial response rate of 17% were observed for the 29 previously treated patients, all but two of whom had large tumor burdens after therapy that included moderate doses of CPM. Despite consolidation with myeloablative therapy, many responders in the three groups ultimately relapsed. The N4SE was strongly myelosuppressive, but only two patients died from associated infection. Extramedullary toxicity was limited to hemorrhagic cystitis in four of 33 CPM previously treated patients; this problem did not occur in the 67 new patients. The data indicate that the maximal-dose N4SE is an effective induction regimen for neuroblastoma, can achieve marked regressions of disease resistant to less intensive therapy, and is sparing of major body organs. This high rate of remission induction must be coupled with improvements in consolidation therapy to assure long-term disease-free survival of poor-risk patients.
Synthesis, characterization, antioxidant and anticancer evaluation of some novel flavone-4-oximes
Authors: B.S. Jayashree, Sri Gurushyam, Aravinda Pai
Journal: Asian Journal of Pharmaceutical Sciences (2015)

A series of novel flavone-4-oximes were synthesized by the oximation of substituted flavones. The synthesized compounds were characterized by various spectrochemical methods including IR, MS and NMR spectroscopy. Out of the 14 test compounds screened for their antioxidant activity, compounds such as JGS-VI (a N,N dimethyl benzaldehyde derivative) and JGS-VII (a 3,4 dimethoxy benzaldehyde derivative) exhibited antioxidant activity comparable to that of ascorbic acid and quercetin as standards following DPPH method. Compounds such as JGS-II (a p-fluoro benzaldehyde derivative), JGS-IV (a p-methyl benzaldehyde derivative) and JGS-V (a thiophene-2-aldehyde derivative) exhibited antioxidant activity among all the test compounds screened against ABTS. However, none of them showed any significant scavenging activity against nitric oxide scavenging assay in the concentration range of 200 μM-25μM. Further, anti-cancer potency for all the test compounds were evaluated by MTT assay against two different cell lines namely MCF-7 and Hep-G2. Compounds such as JGS-I (a p-chloro benzaldehyde derivative), JGS-II (a p-fluoro benzaldehyde derivative), JGS-IV, JGS-V (a thiophene -2-aldehyde derivative), JGS-VI and JGS-IX (a 3,4 chloro benzaldehyde derivative) exhibited activity better than the rest of the test compounds tested against MCF-7 cell lines. Compounds such as JGS-VI, JGS-VII, JGS-VIII (a p-bromo benzaldehyde derivative) and JGS-IX exhibited anti-cancer activity better than other test compounds tested against Hep-G2 cell lines. Thus, a few of the synthesized test compounds could become promising anti-cancer agents.
MLL5 Orchestrates a Cancer Self-Renewal State by Repressing the Histone Variant H3.3 and Globally Reorganizing Chromatin
Authors: Marco Gallo, Fiona J. Coutinho, Robert J. Vanner, Tenzin Gayden, Stephen C. Mack, Alex Murison, Marc Remke, Ren Li, Naoya Takayama, Kinjal Desai, Lilian Lee, Xiaoyang Lan, Nicole I. Park, Dalia Barsyte-Lovejoy, David Smil, Dominik Sturm, Michelle M. Kushida, Renee Head, Michael D. Cusimano, Mark Bernstein, Ian D. Clarke, John E. Dick, Stefan M. Pfister, Jeremy N. Rich, Cheryl H. Arrowsmith, Michael D. Taylor, Nada Jabado, David P. Bazett-Jones, Mathieu Lupien, Peter B. Dirks
Journal: Cancer Cell (2015)
Systemic Delivery of Polypeptide Drugs Through Ocular Route
Authors: G C Chiou
Journal: The Annual Review of Pharmacology and Toxicology (1991)

Heme oxygenases (HO) catabolize free heme, that is, iron (Fe) protoporphyrin (IX), into equimolar amounts of Fe2+, carbon monoxide (CO), and biliverdin. The stress-responsive HO-1 isoenzyme affords protection against programmed cell death. The mechanism ...Read More
Physiologic Basis for the Control of Body Fat Distribution in Humans
Authors: R L Leibel, N K Edens, S K Fried
Journal: Annual Review of Nutrition (1989)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Single assessment may be dangerous
Authors: R. J MacFadyen, T. M Macdonald, P. Clarkson, N. M Wheeldon
Journal: BMJ (1995)

EDITOR,--Both the paper by C M Francis and colleagues1 and the accompanying editorial2 regarding open access echocardiography for heart failure might be interpreted as suggesting that a key role of such a service is the withdrawal of “inappropriate” drug treatment. It is suggested that this decision should be based on one echocardiographic examination per subject, with what might be regarded as a higher than average rate of non-quantitative study (42% quoted). If it is assumed, as is implied, that there was no corroborative history nor examination performed to assess patients further, …
Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity
Authors: Niklas K. Finnberg, Prashanth Gokare, Arunasalam Navaraj, Krystle A. Lang Kuhs, George Cerniglia, Hideo Yagita, Kazuyoshi Takeda, Noboru Motoyama, Wafik S. El-Deiry
Journal: Cancer Research (2015)

The combination of TRAIL death receptor agonists and radiochemotherapy to treat advanced cancers continues to be investigated in clinical trials. We previously showed that normal cells with a functional DNA damage response (DDR) upregulate the expression of death-inducing receptor DR5/TRAILR2/TNFRSF10B in a p53-dependent manner that sensitizes them to treatment with DR5 agonists. However, it is unclear if targeting DR5 selectively sensitizes cancer cells to agonist treatment following exposure to DNA-damaging chemotherapy, and to what extent normal tissues are targeted. Here, we show that the combined administration of the DR5 agonistic monoclonal antibody (mAb) and chemotherapy to wild-type mice triggered synergistic gastrointestinal toxicities (GIT) that were associated with the death of Lgr5(+) crypt base columnar stem cells in a p53- and DR5-dependent manner. Furthermore, we confirmed that normal human epithelial cells treated with the human DR5-agonistic mAb and chemotherapeutic agents were also greatly sensitized to cell death. Interestingly, our data also indicated that genetic or pharmacologic targeting of Chk2 may counteract GIT without negatively affecting the antitumor responses of combined DR5 agonist/chemotherapy treatment, further linking the DDR to TRAIL death receptor signaling in normal cells. In conclusion, the combination of DR5-targeting agonistic mAbs with DNA damaging chemotherapy may pose a risk of developing toxicity-induced conditions, and the effects of mAb-based strategies on the dose-limiting toxicity of chemotherapy must be considered when establishing new combination therapies.
Persistent occurrence of serogroup Y/sequence type (ST)-23 complex invasive meningococcal disease among patients aged five to 14 years, Italy, 2007 to 2013
Authors: Cecilia Fazio, Arianna Neri, Giovanna Renna, Paola Vacca, Raffaele Antonetti, Anna Maria Barbui, Laura Daprai, Paolo Lanzafame, Lucia Rossi, Iolanda Santino, Carlo Tascini, Caterina Vocale, Paola Stefanelli
Journal: Eurosurveillance (2015)

In Italy, the incidence of invasive meningococcal disease (IMD) has remained stable since 2007 (around 0.3 cases/100,000 inhabitants). However, as reported for other European countries, an increase of serogroup Y Neisseria meningitidis has been observed. In this study we report IMD cases from 2007 to 2013 in Italy and investigate the clinical and epidemiological features of cases affected by serogroup Y. Molecular characteristics of serogroup Y strains are also described. During the study period, the proportion of IMD cases due to serogroup Y increased, ranging from 2% in 2007 to 17% in 2013 (odds ratio (OR): 8.8), whereby the five to 14 years age group was mostly affected (p &lt; 0.001). Overall 81 serogroup Y IMD cases were identified, with a median age of 18 years, ranging from three months to 84 years. Of the 81 respective patient samples, 56 were further subject to molecular typing. The sequence type (ST)-23 complex (clonal complex (cc)23) was predominant among serogroup Y meningococci (54/56 samples), and included nine different STs. Presumably, ST-23 was the founding genotype, with all the other STs presenting as single-locus variants. All cc23 isolates analysed harboured mutations in the lpxL1 gene; however, no associations among lpxL1 mutations, ST and age group were identified. Overall, these findings generate scientific evidence for the use of the quadrivalent meningococcal conjugate vaccine in the five to 14 years age group.