tbuckley/cabot-search huggingface dataset:
Role of Cytochrome P-450 in Alveolar Hypoxic Pulmonary Vasoconstriction in Dogs
Authors: Matthew A. Miller, Charles A. Hales
Journal: Journal of Clinical Investigation (1979)

Alveolar hypoxia induces pulmonary vasoconstriction by an unknown mechanism. Cytochrome P-450 (C-P450) is found in the lung and may modify pulmonary vascular tone via its sensitivity to changes in oxygen tension or by affecting metabolism of a chemical mediator. Metyrapone and carbon monoxide are both inhibitors of C-P450. We tested alveolar hypoxic pulmonary vasoconstriction (AHPV) in 20 dogs before, during, and after separate administration of each inhibitor. Anesthetized dogs were ventilated through a double lumen endotracheal tube allowing ventilation of one lung with N(2) or CO as a hypoxic challenge and ventilation of the other lung with O(2) to maintain adequate systemic oxygenation. Distribution of lung perfusion was determined with intravenous (133)Xenon and external chest detectors. Before infusion of metyrapone, mean perfusion to the test lung decreased 30% with alveolar hypoxic challenge, but decreased only 10% during metyrapone infusion and returned to a base-line mean decrease of 31% after completion of metyrapone infusion. Prostaglandin F(2) alpha and angiotensin II infusions produced equivalent increases in pulmonary vascular resistance before and during metyrapone infusion. Before CO, mean test lung perfusion decreased 31% with alveolar hypoxia but was reduced only 10% from control when unilateral end-tidal CO% was >75%. Washout of alveolar CO with unilateral N(2) ventilation restored AHPV, with perfusion decreasing 29% from control. Thus, both metyrapone and carbon monoxide can reversibly inhibit AHPV. C-P450 may, therefore, be involved in the transduction process of the vasoconstrictor response to alveolar hypoxia.
Abstract 2015: Lysophosphatidylcholine induces apoptosis via suppressing STAT3 and HDAC3 activities and binding to the Bcl-xL promoter in K562 chronic myelogenous leukemia cells
Authors: Ji hoon Jung, Soo-Jin Jeong, Ji-Hyun Kim, Hyo-Jung Lee, Hyo-Jeong Lee, Eun-Ok Lee, Junghyo Kim, Sung-Hoon Kim
Journal: Cancer Research (2012)

Abstract Lysophosphatidylcholine (LPC) is a class of chemical compound which are derived from phosphatidylcholines usually isolated from the surface of wheat starch granules. In the present study, we investigated the molecular mechanisms responsible for LPC-induced apoptosis in chronic myeloid leukemia K562 cells. LPC exerted the inhibitory effect on the viability of K562 cells as well as other leukemic cell lines HL-60 and U937. Nonetheless, LPC significantly increased the acetylation of histone H3 at K18, 9 and 23 in K562 cells, but not in HL-60 and U937 cells. Consistently, LPC reduced histone deacetylase (HDAC) transcriptional activity and the expression of HDAC3 at protein level. LPC suppressed phosphorylation of mTOR and AKT, the upstream kinases of HDACs and induced p27 expression. We also found that LPC mediated inactivation of signal transducer and activator of transcription 3 (STAT3)-related signaling pathway in K562 cells, but not HL-60 and U937. LPC significantly inhibited phosphorylation and the DNA binding activity of STAT3, phosphorylation of Src and Janus activated kinase 2 (JAK2) as well as the expression of STAT3 target genes Cyclin D1, Cyclin E, Bcl-xL, Bcl-2, and Survivin at both protein and mRNA levels. LPC stimulated protein tyrosin phosphatases Src homology 2 domain-containing phosphatase 1 (SHP-1), but not SHP-2, SOCS-1 and PTEN. Blocking SHP-1 using sodium pervanadate or SHP-1 specific siRNA reversed LPC-mediated inactivation of STAT3 and HDAC and induction of apoptosis. Of importance, LPC blocked the nuclear translocation and interaction of HDAC3 and STAT3 as well as their binding onto the Bcl-xL promoter. Overall, our findings demonstrate that LPC has a potent anti-cancer activity through inducing apoptosis by suppressing HDAC3/STAT3 activation and binding to the Bcl-xL promoter in K562 cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2015. doi:1538-7445.AM2012-2015
Preexposure prophylaxis reduced HIV-1 spread in serodiscordant heterosexual couples
Authors: Michael A. Polis
Journal: Annals of Internal Medicine (2012)

ACP Journal Club20 November 2012Preexposure prophylaxis reduced HIV-1 spread in serodiscordant heterosexual couplesMichael A. Polis, MD, MPHMichael A. Polis, MD, MPHNational Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA (M.A.P.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-10-201211200-02003 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBaeten JM, Donnell D, Ndase P, et al; Partners PrEP Study Team. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med. 2012;367:399-410. https://pubmed.ncbi.nlm.nih.gov/22784037Clinical Impact RatingsGIM/FP/GP: Infectious Disease: References1 Grant RM, Lama JR, Anderson PL, et al; iPrEx Study Team. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010;363:2587-99. [PMID: 21091279] Google Scholar2 US Food and Drug Administration. 16 July 2012. FDA approves first drug for reducing the risk of sexually acquired HIV infection www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm (accessed 7 Sept 2012). Google Scholar Author, Article, and Disclosure InformationAffiliations: National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA (M.A.P.)This article was published at Annals.org on 6 November 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDeveloping Regulatory Strategy for Microbicides 20 November 2012Volume 157, Issue 10Page: JC5-3KeywordsCreatinineDrugsHIV infectionsHIV preventionHIV-1HeterosexualsProphylaxis ePublished: 20 November 2012 Issue Published: 20 November 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
D3-02: Updated Paclitaxel-Carboplatin Pharmacogenomic (PG) Analysis of Japan-SWOG Common Arm Study in Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: David R. Gandara, Tomoya Kawaguchi, John Crowley, Kiyoyuki Furuse, Masaaki Kawahara, Satoshi Teramukai, Steven Williamson, James Moon, Howard McLeod, Philip C. Mack
Journal: Journal of Thoracic Oncology (2007)
Abstract 3135: Pre-treatment p-EGFR levels in tumors from a genetically engineered mouse model of BRAFV600E colorectal cancer predict response to combined BRAF/EGFR inhibition
Authors: Erin M. Coffee, Ryan B. Corcoran, Jeffrey A. Engelman
Journal: Cancer Research (2014)

Abstract BRAFV600E colorectal cancer (CRC) patients do not exhibit responses to single-agent BRAF inhibition due to activation of EGFR. While combined BRAF and EGFR inhibition has shown some success in early clinical trials, there are still a subset of patients who do not respond to this combination. The purpose of this study is to identify which BRAFV600E tumors would be expected to respond to combined BRAF/EGFR inhibition based on the pre-treatment levels of pEGFR. A genetically engineered mouse model (GEMM) for Apc-/- BrafV600E/+ p53-/- CRC was used for the study. Tumors were induced in the colons using adenovirus expressing Cre recombinase. Tumors were visualized by optical colonoscopy and pre-treatment tissue biopsy samples were obtained. BRAF mutant mice were randomized to a combination treatment with a BRAF inhibitor (Dabrafenib), combined with either an EGFR inhibitor (Erlotinib) or a MEK inhibitor (Trametinib). Tumor growth or regression was followed for 21 days by colonoscopy. A retrospective analysis indicated that those tumors with high pre-treatment phosphorylated EGFR (p-EGFR) levels had significant responses to combined BRAF/EGFR therapy, while those tumors with little to no response to combined BRAF/EGFR therapy had low levels of p-EGFR prior to treatment. Furthermore, the majority of tumors that had a significant response to the combined BRAF/MEK therapy had the lowest levels of pre-treatment p-EGFR. These pre-clinical data suggest that BRAFV600E CRC patients could benefit from being stratified by p-EGFR levels prior to treatment. Those patients with high p-EGFR levels would be expected to respond best to combined BRAF/EGFR treatment, while those patients with low p-EGFR levels might benefit from a different combination therapy, such as combined BRAF/MEK inhibition. Citation Format: Erin M. Coffee, Ryan B. Corcoran, Jeffrey A. Engelman. Pre-treatment p-EGFR levels in tumors from a genetically engineered mouse model of BRAFV600E colorectal cancer predict response to combined BRAF/EGFR inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3135. doi:10.1158/1538-7445.AM2014-3135
THE ASSOCIATION OF LEFT VENTRICULAR EJECTION FRACTION WITH 1-YEAR MORTALITY AFTER MYOCARDIAL INFARCTION: FINDINGS FROM THE ACTION REGISTRY-GWTG MEDICARE LINKED DATABASE
Authors: Nadia Sutton, Shuang Li, Tracy Wang, James de Lemos, Jonathan Enriquez, Rashmee Shah, Laine Thomas, Gregg Fonarow
Journal: Journal of the American College of Cardiology (2015)
761. Dominant-Negative FGF Receptor Expression by Oncolytic HSV Vector for the Treatment of Malignant Peripheral Nerve Sheath Tumors
Authors: Ta-Chiang Liu, Tingguo Zhang, Hiroshi Fukuhara, Toshi Kuroda, Robert L. Martuza, Andreas Kurtz, Samuel D. Rabkin
Journal: Molecular Therapy (2005)

Top of pageAbstract
Oncolytic herpes simplex viruses (HSV) have emerged as a promising platform for cancer therapy. Their large size permits insertion of therapeutic transgenes to augment the cytotoxicity of the backbone vector. Here we examine the activity of a dominant-negative FGF receptor (dnFGFR). Fibroblast growth factor (FGF) has been shown to stimulate the proliferation of Schwann cells in vitro, in addition to its mitogenic activity in endothelial cells, indicating its importance in malignant peripheral nerve sheath tumors (MPNST). We established MPNST cell lines transformed with dnFGFR or the control plasmid and showed that dnFGFR decreased cell proliferation and migration in vitro and reduced vascularity and delayed tumor growth in vivo. The dnFGFR transgene was inserted into oncolytic HSV G47|[Delta]| (deleted in |[aacute]|47/Us11 promotor, |[gamma]|34.5, and a LacZ insertion inactivating ICP6), using the G47|[Delta]|-BAC (bacterial artificial chromosome) system. G47|[Delta]|-dnFGFR showed enhanced killing of both tumor and proliferating endothelial cells in vitro compared to the G47|[Delta]|-empty control vector. In vivo, G47|[Delta]|-dnFGFR was more efficacious than it's non-expressing parent G47|[Delta]|-empty at inhibiting MPNST growth. Therefore oncolytic HSV encoding antiangiogenic dominant-negative FGFR transgene is a new strategy for tumor treatment.
The BMA and trade union democracy: new style council elections
Authors: M. Lowe
Journal: BMJ (1986)

Trade  leaders must be answerable to their membership just as members of parliament are to their constituents. So the government decreed in the 1984 Trade Union Act that no member of a principal executive  of a   may vote in that body unless elected by members of the  by secret ballot.1 This means that the BMA will have to make some constitutional changes if it is to continue to represent doctors and to do so within the law. Ironically it was an Act of parliament 150 years ago?the Poor Law Amendment Act?that launched the BMA on the road to  unionism. In 1835 the three year old Provincial and Medical and Surgical Association?precursor of the BMA?set up the poor law committee with the aim of improving the intolerable working conditions of doctors employed under the amended poor law legislation. From that start through Lloyd George's national insurance legislation of 1911 and the introduction in 1948 of the National Health Service to the complexities of the 1984 Griffiths management reforms the BMA's trade union activities have steadily expanded. Today the BMA is a unique combination of professional organisation,  union, and limited company. The association almost lost its   functions in the early 1970s when a Conservative administration introduced legis? lation to control  activities. The BMA did not fulfil the requirements for being included in the statutory register of unions that was to be set up. After unsuccessfully arguing that professional negotiating bodies such as the BMA and the Royal College of Nursing should not be excluded from the scope of the Act an initiative by the association persuaded the government to include such organisations in a special section of the proposed register.2 Thus the BMA was able to continue with its   activities
Lowering Vaccine Costs
Authors: Rebecca Voelker
Journal: JAMA (1998)

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 Publications 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
Glomerulonephritis Associated with Antibody to Glomerular Basement Membrane
Authors: J. G. P. Sissons, D. J. Evans, D. K. Peters, A. J. Eisinger, J. M. Boulton-Jones, I. J. Simpson, M. Macanovic
Journal: BMJ (1974)

Glomerulonephritis associated with antibody to glomerular basement membrane, shown by linear staining of the glomerular basement membrane with fluoresceinated anti-IgG antisera, was found in only 10 out of 400 (2.5%) renal biopsy specimens studied by immunofluorescence. Seven of these cases had rapidly progressive glomerulonephritis, five with lung haemorrhage (Goodpasture's syndrome) and two without, and three had less severe nephritis without lung haemorrhage. Circulating antibody to glomerular basement membrane, measured by a passive haemagglutination technique and by indirect immunofluorescence, was detected in the serum of all patients with rapidly progressive glomerulonephritis by both techniques but only by the passive haemagglutination method in two of the other three patients. Two patients died of their lung haemorrhage, one despite bilateral nephrectomy, and lung haemorrhage and circulating antibody to glomerular basement membrane persisted after bilateral nephrectomy in another patient.
Progression of hypertrophic cardiomyopathy to dilated cardiomyopathy: Three new mutations in genes encoding sarcomeric proteins with two cases of double heterozygosity
Authors: Luisa Nanni, Maurizio Pieroni, Barbara Simionati, Rosanna Zimbello, Cristina Chimenti, Gerolamo Lanfranchi, Attilio Maseri, Andrea Frustaci
Journal: Journal of the American College of Cardiology (2003)
Feasibility of making nursery ductus and echo rounds with a hand-held ultrasound system equipped with a high-frequency probe
Authors: Xiaokui Li, Grant H. Burch, Ron G. Ilg, De-Ann M. Pillers, Joseph T. Gilhooly, Sue Ann Smith, Linda D. Wallen, Cynthia T. McEvoy, David J. Sahn
Journal: Journal of the American College of Cardiology (2003)
Screening for Cholesterol
Authors: E. Reiss
Journal: JAMA (1988)

<h3>To the Editor.</h3> —The results of the national cholesterol surveys reported by Schucker et al<sup>1</sup>show that efforts made to educate the public about the importance of knowing one's cholesterol level are making strides in the prevention of coronary disease. In a cholesterol screening coordinated by the American Health Foundation in Atlanta in November 1986, 10.2% of the 9913 people screened reported that they knew their cholesterol level. This finding is similar to the 7% reported by Schucker et al. The demographic data of the population screened in Atlanta were fairly representative for the area; those screened were preponderantly white, over 31 years of age, and married. Slightly more women than men participated in this screening. Over half of the sample had attended college for at least some period. Comparing this sample with the census data of the area, there were similar distributions in all categories, except the sample
Serum Vitamin B12 Levels and Vitamin B12 Binding Capacity in Pregnant and Non-pregnant Europeans and West Indians
Authors: T. S. Low-Beer, C. F. McCarthy, W. I. Austad, A. Brzechwa-Ajdukiewicz, A. E. Read
Journal: BMJ (1968)

The vitamin B(12) level and the capacity of serum to bind B(12) are higher in the West Indian population living in Great Britain than in Europeans. The B(12) level fell during pregnancy in both groups but remained higher in the West Indians. West Indians had higher levels of IgG.
897. Recombinant AAV2/8 Vector-Mediated Gene Therapy Corrects Hyperphenylalaninemia in Murine PKU
Authors: Cary O. Harding, Melanie B. Gillingham, Kelly Hamman, Andrew Bird, Dwight Koeberl
Journal: Molecular Therapy (2005)

Top of pageAbstract
Novel recombinant adeno-associated virus vectors pseudotyped with serotype 8 capsid (rAAV2/8) have recently shown exciting promise as effective liver-directed gene transfer reagents. We have designed and produced an rAAV2/8 vector containing the mouse phenylalanine hydroxylase (PAH) cDNA under the transcriptional control of a strong liver promoter (LSP) and have administered this vector to hyperphenylalaninemic Pahenu2 mice, a model of human PKU. Our hypothesis was that this vector would produce sufficient hepatocyte transduction frequency and PAH activity to correct blood phenylalanine (Phe) levels in murine PKU. Recombinant AAV2/8 vector was injected via the portal vein into five adult (four male and one female) hyperphenylalaninemic Pahenu2 homozygous mice (preinjection Phe = 2108 |[plusmn]| 102 |[mu]|M, normal = 145 |[plusmn]| 45 |[mu]|M) and evaluated the effect upon serum Phe levels weekly. Each animal received 2.5 X 1011 rAAV2/8 vector genomes via portal vein injection. A sixth Pahenu2 mouse (female, preinjection Phe = 3579 |[mu]|M) received only saline as a control, and serum Phe levels remained elevated in this animal (4174 |[mu]|M ten weeks following injection). Administration of rAAV2/8 yielded a dramatic and stable reduction in serum Phe to normal levels by 1-2 weeks following injection. At ten weeks following injection, serum Phe levels remained normal (157 |[plusmn]| 32 |[mu]|M) and were significantly reduced in comparison to pretreatment levels (p < 0.001). Phenylalanine clearance measured after parenteral Phe challenge significantly increased following rAAV2/8 treatment. Hyperphenylalaninemia-associated hypopigmentation was also completely corrected. Liver PAH activity was 6-10% of wild type levels in three mice that underwent liver biopsy at 8-10 weeks postinjection. Vector copy number, integration status of the vector genome, biodistribution, and long-term stability of expression will be evaluated. Recombinant AAV2/8-mediated, liver-directed gene therapy is a promising novel treatment approach for PKU and allied inborn errors of metabolism.
The profession, not the media, should assess where Kasai portoenterostomy should be performed
Authors: S Davison, V Miller, A Thomas, J Bowen, J Bruce
Journal: BMJ (1999)

EDITOR—The Children's Liver Disease Foundation recently published its report into the treatment of infants with biliary atresia by Kasai portoenterostomy.1This was covered in the BBC's news programme Northwest Tonight and in Trust Me, I'm a Doctor on 26 February. The report advocates that Kasai portoenterostomy should be performed only in centres that can produce outcome figures equivalent to those produced by group C in the table. Furthermore, the …
118. In Vivo Tracking of Long Term Gene Expression of AAV1 Using Fluorescence Imaging System
Authors: Ryuichi Yoneyama, Julieta Palomeque, Kozo Hoshino, Alec M. De Grand, John V. Frangioni, Roger Joseph Hajjar
Journal: Molecular Therapy (2006)

Top of pageAbstract
Introduction:

The kinetics of long term transgene expression of viral vectors is important as it directly influences the efficacy of the gene therapy. Conventional kinetic measurements require sacrificing animals at each data point and assessing the amount of transgene product in the tissue. This type of analysis is extremely laborious and contains inherent inaccuracy since it does not follow the time course of a single animal. In this study, in vivo tracking of transgene expression from adeno-aasociated virus type 1 (AAV-1) was performed using a green fluorescence protein (GFP) reporter and an specially designed optical imaging system.. Our results reveal the exact kinetics of AAV-1 expression and validate fluorescence imaging for kinetic measurements of long term expression of virally expressed genes.

Materials and Method:

Animals and Virus

40-day-old male hairless SKH1 mice were divided into 3 groups, each containing 3 mice. The right leg of Groups 1 and 2 were injected with 1012 and 1010 plaque forming unit (pfu) of adeno-associated virus type 1 encoding green fluorescent protain (AAV-1.GFP). respectively, in 50 ul normal saline. The left legs were injected with 50 ul normal saline as an internal control. Group 3 (control group) was injected with 50 ul normal saline into the both legs. The mice were anesthetized by intraperitoneal injection of 80 mg/kg body weight ketamine at the time of each measurement, and imaged over 13 weeks.

Imaging System

Selective excitation of GFP was produced by 475 nm light emission diode through a excitation filter HQ470/40x. Emitted fluorescence was collected through an emission filter HQ525/50m (Chroma Technology Corp, Rockingham, VT) on a Hamamatsu C8484 charge-coupled device camera (Hamamatsu Photonics Systems, Bridgewater, NJ). The strength of the transgene expression was measured as the ratio of the mean of fluorescence intensity of 0.5 cm2 ROI set on the right and left leg.

Results and Conclusions

The kinetics of GFP expression was clearly measured by assessing the fluorescence intensity of each animal. The images and graphs of representative animals are shown in the Figure. In Group 1, injected with 1012 pfu AAV-1.GFP, GFP expression reached a plateau at approximately 7 weeks, which was maintained until at least 13 weeks. In Group 2, injected with 1010 pfu AAV-1.GFP, GFP expression, reached its plateau at approximately 11 weeks. These results demonstrate the relationship between injected dose and transgene expression level, as well as the kinetics of expression.