tbuckley/cabot-search huggingface dataset:
12(S)-HETE Enhancement of Prostate Tumor Cell Invasion: Selective Role of PKC 
Authors: B. Liu, R. J. Maher, Y. A. Hannun, A. T. Porter, K. V. Honn
Journal: JNCI Journal of the National Cancer Institute (1994)

Prostate carcinoma has become the second most fatal cancer in American men. In Dunning R3327 rat prostate adenocarcinoma cells, elevated invasiveness positively correlates with metastatic potential. However, the mechanism(s) responsible for regulation of tumor cell motility and invasion is poorly understood. We have reported that a lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], augments tumor cell metastatic potential through activation of protein kinase C (PKC).We proposed to determine the effect of 12(S)-HETE on the motility and invasion of low-metastatic rat prostate AT2.1 tumor cells and the effect of 12(S)-HETE activation of specific PKC isoform(s) in these processes.The motility of AT2.1 cells was determined by the colloidal gold phagokinetic track assay and the invasiveness measured as their ability to invade through basement membrane Matrigel-coated filters. Expression of PKC isoforms was determined by Western blotting of the whole cell lysate with isoform-specific anti-PKC antibodies. Cytosol and membrane fractions were prepared and the subcellular distribution of PKC was analyzed by Western blotting and activity assay. The effect of 12(S)-HETE on cell proliferation was examined. Data were analyzed for significance of difference with the two-sampled, two-sided Student's t test.12(S)-HETE increased the motility and invasion of AT2.1 cells, and this 12(S)-HETE-increased motility and invasion were inhibited by a selective PKC inhibitor, calphostin C, as well as a Ca2 chelator, bis-(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/tetra(acetoxy-methyl)ester. AT2.1 cells expressed the PKC isoforms alpha and delta, and 12(S)-HETE increased the membrane association of PKC alpha but not delta. Further, the motility and invasion of AT2.1 cells were increased by thymelea toxin, a selective activator of PKC alpha over PKC delta.12(S)-HETE augments the invasiveness of AT2.1 cells via selective activation of PKC alpha.12(S)-HETE modulation of PKC alpha invasiveness may be an important mechanism of action for the regulation of the invasive potential of rat prostate carcinoma cells, and the 12-lipoxygenase enzyme and/or PKC alpha may serve as key targets for the development of anti-invasive agents useful for combating the spread of prostate cancer.
Ergometer training volume and previous injury predict back pain in rowing; strategies for injury prevention and rehabilitation
Authors: Fiona Wilson, Conor Gissane, Alison McGregor
Journal: British Journal of Sports Medicine (2014)

The most commonly reported injury site in rowers is the lower back. Research in recent years has focused on epidemiology and biomechanical analyses to try and understand mechanisms that contribute to this injury's onset. Injury surveillance mainly comprises retrospective questionnaires and reviews of medical records with a lack of prospective data. Of studies that reported 12-month data, the incidence of low back pain ranged from 31.8 to 51% of the cohort. Of the limited studies that specifically examined low back pain in rowers, (1) history of lumbar spine injury and (2) volume of ergometer training were the most significant risk factors for injury onset. Studies of technique on the rowing ergometer have indicated the importance of lumbopelvic rotation during rowing. Greater pelvic rotation at either end of the stroke is ideal—as opposed to lumbar flexion and extension; this tends to be poorly demonstrated in novice rowers on ergometers. Furthermore, technique can deteriorate with the demands of rowing intensity and duration, which puts the rower returning from injury at additional risk.
Effects of intrinsic PEEP on pulmonary gas exchange in mechanically-ventilated patients
Authors: R Brandolese, C Broseghini, G Polese, M Bernasconi, G Brandi, J Milic-Emili, A Rossi
Journal: European Respiratory Journal (1993)

The aim of the study was to assess the impact of the intrinsic positive end-expiratory pressure (PEEPi) on pulmonary gas exchange in mechanically-ventilated patients, by comparing the effects of similar levels (0.8-0.9 kPa) of positive end-expiratory pressure (PEEP) and PEEPi. Ten patients with acute respiratory failure, without chronic airway disease, were studied with three ventilatory modes: 1) intermittent positive pressure ventilation with zero end-expiratory pressure (ZEEP mode); 2) continuous positive pressure ventilation with PEEP set by the ventilator (PEEP mode); and 3) intrinsic PEEP elicited by adequate shortening of the expiratory time (PEEPi mode). Cardiorespiratory variables (e.g. respiratory compliance and resistance, arterial and mixed venous blood gases, cardiac output, pulmonary capillary pressure, oxygen delivery) were measured during each ventilatory mode. Compared to ZEEP, both PEEP and PEEPi decreased cardiac output while increasing arterial oxygen tension (PaO2). However, the improvement of PaO2 was more consistent (8 out of 10 patients), and larger (+2.1 kPa, on average, p < 0.05) with PEEP than with PEEPi (5 out of 10 patients, and +1.4 kPa, on average, NS). Since the effects of PEEP and PEEPi on ventilation, lung volume, compliance, cardiac output (QT), mixed venous oxygen tension (PvO2) and oxygen consumption (VO2) were similar, we attributed the less favourable impact of PEEPi on PaO2 to a less homogeneous distribution of PEEPi between lung units with different time constant, and hence to a more uneven distribution of the inspired gas.
The Sequence Ontology: a tool for the unification of genome annotations
Authors: Karen Eilbeck, Suzanna E Lewis, Christopher J Mungall, Mark Yandell, Lincoln Stein, Richard Durbin, Michael Ashburner
Journal: Genome biology (2005)

The Sequence Ontology (SO) is a structured controlled vocabulary for the parts of a genomic annotation. SO provides a common set of terms and definitions that will facilitate the exchange, analysis and management of genomic data. Because SO treats part-whole relationships rigorously, data described with it can become substrates for automated reasoning, and instances of sequence features described by the SO can be subjected to a group of logical operations termed extensional mereology operators.
Selectivity of Dobutamine for Adrenergic Receptor Subtypes
Authors: R. Sanders Williams, Timothy Bishop
Journal: Journal of Clinical Investigation (1981)

The cardiovascular responses elicited by dobutamine are distinctly different from those produced by other adrenergic or dopaminergic agonists. To test the hypothesis that dobutamine could have differential affinities for adrenergic receptor subtypes, and that such subtype selectivity could be related to its relatively unique pharmacologic properties, we assessed the ability of dobutamine to displace adrenergic radioligands from membrane receptors in a number of tissues of previously characterized adrenergic receptor subtype. For beta adrenergic receptors identified by (-) [(3)H]dihydroalprenolol (DHA), dobutamine had significantly greater affinity for the beta(1) subtype (K(D) = 2.5 muM in rat heart and 2.6 muM in turkey erythrocyte) than for the beta(2) subtype (K(D) = 14.8 muM in frog heart and 25.4 muM in rat lung) (P < 0.001). For alpha adrenergic receptors, dobutamine had markedly greater affinity for the alpha(1)-subtype identified by [(3)H]prazosin (K(D) = 0.09 muM in rat heart and 0.14 muM in rabbit uterus) than for the alpha(2)-subtype identified by [(3)H]dihydroergocryptine (DHE) (K(D) = 9.3 muM in human platelet) or by [(3)H]yohimbine (K(D) = 5.7 muM in rabbit uterus) (P < 0.001). Like other beta(1)-agonists, in the absence of guanine nucleotide, dobutamine competition curves for DHA binding in rat heart demonstrated two classes of binding sites, with one site of significantly higher affinity (K(D) = 0.5 muM, P = 0.008) than the single class of binding sites (K(D) = 5.2 muM) identified in the presence of guanine nucleotide. However, unlike beta(2)- or alpha(2)-agonists, dobutamine displacement of DHA binding in rat lung or of DHE binding in human platelets demonstrated only a single class of binding sites, and guanine nucleotide had only minimal effects. We conclude that dobutamine is selective for beta(1) as opposed to beta(2), and for alpha(1) as opposed to alpha(2) adrenergic receptors. Furthermore, guanine nucleotide effects on dobutamine binding, and biochemical response data in vitro suggest that dobutamine is a beta(1)-agonist, but has little intrinsic activity at beta(2) and alpha(2)-receptors. This selectivity for adrenergic receptor subtypes may be part of the basis for dobutamine's distinctive pharmacologic properties in vivo.
Treatment and survival of patients with small-cell lung cancer: small steps forward, but not for patients &gt;80
Authors: M.L.G. Janssen-Heijnen, H.A.A.M. Maas, S Siesling, C.C.E. Koning, J.W.W. Coebergh, H.J.M. Groen
Journal: Annals of Oncology (2011)
Redesign of the Health Care Delivery System
Authors: Kevin Grumbach
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
An evidence based approach to reducing antibiotic use in children with acute otitis media: controlled before and after study
Authors: C. Cates
Journal: BMJ (1999)

Two recent reviews questioned the routine use of antibiotics in the initial management of acute otitis media. 1 2 My practice partners and I responded to the reviews by changing our policy, with the aim of reducing such prescribing in children. We measured the change one year after adopting the new policy.

From July 1997 my practice partners and I changed our policy on routine prescription of antibiotics in the initial management of acute otitis media in children. In children who were not particularly ill we gave the parents a handout that summarised the limited benefit of antibiotics on the basis of the data presented in the Cochrane review.1 We advised parents to give regular paracetamol suspension; we also offered an antibiotic prescription but asked the parents to keep it for a day or two. They could redeem it at a pharmacy if the child did not got better over this period.

A local practice acted as a concurrent control. Both practices use …
Randomized, Double-Blind, Placebo-Controlled, Phase II Trial of Sorafenib and Erlotinib or Erlotinib Alone in Previously Treated Advanced Non–Small-Cell Lung Cancer
Authors: David R. Spigel, Howard A. Burris, F. Anthony Greco, Dianna L. Shipley, Elke K. Friedman, David M. Waterhouse, Robert C. Whorf, R. Brian Mitchell, Davey B. Daniel, Jeffrey Zangmeister, J. David Bass, John D. Hainsworth
Journal: Journal of Clinical Oncology (2011)

Sorafenib, an oral multikinase inhibitor, has shown preliminary activity in non-small-cell lung cancer (NSCLC). Patients with advanced NSCLC were treated with erlotinib with or without sorafenib in this multicenter phase II trial.Key eligibility criteria included the following: stage IIIB or IV NSCLC; one to two prior regimens; Eastern Cooperative Oncology Group performance status of 0 to 2; and measurable disease. Patients were randomly assigned 2:1 to sorafenib (400 mg orally twice a day) plus erlotinib (150 mg orally daily) or placebo plus erlotinib and stratified by squamous/nonsquamous histology and prior bevacizumab. Treatment efficacy, measured by progression-free survival (PFS) and overall response rate (ORR), was compared. Treatment of 168 patients allowed detection of 40% improvement in the historical PFS of 2.2 months with single-agent erlotinib.One hundred sixty-eight patients enrolled from February 2008 to February 2009. Clinical characteristics of the two groups were similar. ORRs for sorafenib/erlotinib and placebo/erlotinib were 8% and 11%, respectively (P = .56); disease control rates were 54% and 38%, respectively (P = .056). Median PFS was 3.38 months for sorafenib/erlotinib versus 1.94 months for placebo/erlotinib (hazard ratio, 0.86; 95% CI, 0.60 to 1.22; P = .196). Seventy-two patients consented to analyses of tumor epidermal growth factor receptor (EGFR). In 67 patients with EGFR wild-type (WT) tumors, median PFS was 3.38 months for sorafenib/erlotinib versus 1.77 months for placebo/erlotinib (P = .018); median overall survival (OS) was 8 months for sorafenib/erlotinib versus 4.5 months for placebo/erlotinib (P = .019). An OS advantage for sorafenib/erlotinib was suggested among 43 patients with fluorescent in situ hybridization (FISH) EGFR-negative tumors (P = .064). Both regimens were tolerable, with modest toxicity increase with sorafenib.Although there was little difference in ORR or PFS, subset analyses in EGFR WT and EGFR FISH-negative patients suggest a benefit for the combination of erlotinib/sorafenib compared with single-agent erlotinib with respect to PFS and OS.
Reassessing the cardiac risk profile in chronic hemodialysis patients
Authors: B N Becker, J Himmelfarb, W L Henrich, R M Hakim
Journal: Journal of the American Society of Nephrology (1997)

Journal of the American Society of Nephrology : JASN 8(3):p 475-486, March 1997. | DOI: 10.1681/ASN.V83475
Development of inhibitors of the fibroblast growth factor receptor (FGFR) kinase using a fragment based approach
Authors: M Squires, G Saxty, C Murray, Berdini, G Ward, D Miller, S Rich, A Cleasby, Saalau, , Bethell, S, J Coyle, Van, Montfort, R, A Madin, M Carr, A OBrien, C GriffithsJones, E Vickerstaff, R Nijjar, B Graham, J Cosme, A Pike, J Lewis, M Batey, A Peasland, J Irving, J Lyons, D Newell, N Thompson
Journal: Cancer Research (2008)

1545  Recent data in a number of tumour types has implicated Fibroblast Growth Factor (FGF) and Fibroblast Growth Factor receptor (FGFR) signalling as being key to the molecular pathology of cancer. FGFR is a receptor tyrosine kinase which activates the extracellular signal-regulated kinase / mitogen-activated protein kinase and the protein kinase B / Akt pathways which promote cell growth and survival. Amplification, over-expression or activating mutations of fibroblast growth factor receptors have been associated with bladder tumours, multiple myeloma, hormone-refractory prostate cancer and breast cancer.  Multiple lead series of FGFR inhibitors were developed using Astex’s fragment based medicinal chemistry approach, Pyramid™, linked to high throughput X-ray Crystallography. We describe here the identification and characterisation of these lead molecules. In particular we detail the pharmacological profile of compounds from one of the lead series that demonstrate activity against FGFR 1-3 with an IC50
DNA methylation profiling of human chromosomes 6, 20 and 22
Authors: Florian Eckhardt, Joern Lewin, Rene Cortese, Vardhman K Rakyan, John Attwood, Matthias Burger, John Burton, Tony V Cox, Rob Davies, Thomas A Down, Carolina Haefliger, Roger Horton, Kevin Howe, David K Jackson, Jan Kunde, Christoph Koenig, Jennifer Liddle, David Niblett, Thomas Otto, Roger Pettett, Stefanie Seemann, Christian Thompson, Tony West, Jane Rogers, Alex Olek, Kurt Berlin, Stephan Beck
Journal: Nature Genetics (2006)
<i>Helicobacter pylori,</i> Lewis antigens, and inflammation
Authors: M A HENEGHAN, A P MORAN
Journal: Gut (2001)

Editor,—In a recent issue of Gut , Zheng et al reported that peptic ulcer disease was associated with increased expression of Lewis (Le) antigens but not cagA , iceA , or vacA in Chinese patients infected with Helicobacter pylori ((2000) Gut 47:18–22.[OpenUrl][1][Abstract/FREE Full Text][2]). These data raise as many questions as they answer and add further controversy to an intriguing area of microbiology and gastroenterology. Lex and/or Ley blood group determinants are commonly found on the lipopolysaccharide (LPS) of H pylori isolates. These determinants have been identified on approximately 80–90% of isolates from all patient series examined to date.1-3 In our own series, 74/84 (88%) isolates expressed either Lex or Ley, with 47/84 (56%) of isolates coexpressing both determinants.4 No difference was identified in the prevalence of Lex or Leyexpression on H pylori strains isolated from ulcer patients and those strains isolated from patients with chronic gastritis, nor was an association demonstrated between host and bacterial Lewis phenotype. Since the report of Zheng et al we have reviewed our raw data regarding the prevalence of strains expressing two or more Lewis antigens. We found that two or more … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BClinical%2BMicrobiology%26rft.stitle%253DJ.%2BClin.%2BMicrobiol.%26rft.aulast%253DSimoons-Smit%26rft.auinit1%253DI.%2BM.%26rft.volume%253D34%26rft.issue%253D9%26rft.spage%253D2196%26rft.epage%253D2200%26rft.atitle%253DTyping%2Bof%2BHelicobacter%2Bpylori%2Bwith%2Bmonoclonal%2Bantibodies%2Bagainst%2BLewis%2Bantigens%2Bin%2Blipopolysaccharide%26rft_id%253Dinfo%253Apmid%252F8862584%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=jcm&resid=34/9/2196&atom=%2Fgutjnl%2F48%2F6%2F869.1.atom
Gene Expression Patterns and Profile Changes Pre- and Post-Erlotinib Treatment in Patients with Metastatic Breast Cancer
Authors: Sherry X. Yang, Richard M. Simon, Antoinette R. Tan, Diana Nguyen, Sandra M. Swain
Journal: Clinical Cancer Research (2005)

Abstract Purpose: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. Experimental Design: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. Results: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 α 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor–linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor–linked signal transduction (74 genes, P = 0.007). Conclusions: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.
Analysis of Nuclear Copies of Mitochondrial Sequences in Honeybee (Apis mellifera) Genome
Authors: S. K. Behura
Journal: Molecular Biology and Evolution (2007)

At least 0.08% of the Apis mellifera nuclear genome contains sequences that originated from mitochondria. These nuclear copies of mitochondrial sequences (numts) are scattered all over the honeybee chromosomes and have originated by multiple independent insertions of mitochondrial DNA (mtDNA) as evident by phylogenetic analysis. Apart from original insertions, moderate duplications of numts also contributed to the present pattern and distribution of mitochondrial sequences in honeybee chromosomes. Assimilation of mitochondrial genes in the nuclear genome is mediated by extensive fragmentations of the original inserts. Replication slippage seems to be a major mechanism by which small sequences are inserted or deleted from mtDNA destined to nucleus. Most of the honeybee numts (84%) are located in the nongenic regions. The majority (94%) of the numts that are located in predicted nuclear genes have originated from mitochondrial genes coding for cytochrome oxidase and NADH dehydrogenase subunits. On the other hand, the mitochondrial rRNA or tRNA gene sequences are predominantly (88%) located in nongenic regions of the genome. Evidences also support for exertion of purifying selection on numts located in specific genes. Comparative analysis of numts of European, African, and Africanized honeybees suggests that numt evolution in A. mellifera is probably not demarked by speciation time frame but may be a continuous and dynamic process.
A phase 1 study of vinblastine in combination with carboplatin for children with low-grade gliomas: a Children's Oncology Group phase 1 consortium study
Authors: R. I. Jakacki, E. Bouffet, P. C. Adamson, I. F. Pollack, A. M. Ingle, S. D. Voss, S. M. Blaney
Journal: Neuro-Oncology (2011)

Both carboplatin and vinblastine have demonstrated single-agent activity in children with low-grade gliomas. A phase 1 trial evaluating 2 different schedules of these 2 agents in combination was performed: (1) Schedule A = carboplatin (140 mg/m(2)) weekly × 3 + vinblastine (4.5 or 3.5 mg/m(2)) weekly × 6, every 6 weeks; (2) Schedule B = carboplatin (300, 400, or 500 mg/m(2)) on day 1 + vinblastine (4.0 mg/m(2)) weekly × 3, every 4 weeks. Twenty-six patients, median (range) age 4.4 (0.7-14.8) years, were enrolled. Four of 9 patients enrolled on Schedule A had recurrent grade 4 neutropenia, suggesting that this schedule was not feasible. Seventeen patients were enrolled on Schedule B. At the 500 mg/m(2) carboplatin dose level, 2 of 3 patients developed dose-limiting toxicity (elevated alkaline phosphatase, neutropenia). At the 400 mg/m(2) carboplatin dose level, none of the 6 patients had dose-limiting toxicity. Ten of 16 patients who received treatment on Schedule B completed the prescribed 12 courses. Of the 21 patients evaluable for response, central review confirmed 1 partial response and 6 minor responses. Eleven patients had stable disease (>3 months) and 3 developed progressive disease. Seven of 9 patients with visual pathway tumors and acute visual changes prior to enrollment had documented improvement. The recommended phase 2 dose and schedule is carboplatin, 400 mg/m(2)/dose on day 1, and vinblastine, 4 mg/m(2)/dose, weekly × 3, repeated every 4 weeks. Further study of this regimen in patients with low-grade glioma is warranted.