tbuckley/cabot-search huggingface dataset:
811. The Hotspots of Integration Targeted by the Site-Specific Integrase PhiC31 May Be Cell Line Dependent
Authors: Anja Ehrhardt, Jeffrey A. Engler, Michele P. Calos, Mark A. Kay
Journal: Molecular Therapy (2004)

Recent reports on insertional mutagenesis due to integration of gene therapy vectors into the host genome have raised concerns about the genetic manipulation of somatic cells. Previously, it was demonstrated that the phage integrase phiC31 derived from a Streptomyces phage mediates site-specific integration into the host genome of mammalian cells in vitro and in vivo by recombining the attB recognition site in an episomal plasmid and one or more pseudo attP sites in the host chromosome. However, a study which carefully analyzes the consequences of phage integrase mediated integration for each independent integration event has yet to be performed. In the present study we characterized the chromosomal integration sites after phiC31 mediated integration from extrachromosomal plasmids in the two liver derived cell lines Huh7 (human hepatoma cell line) and Hep1A (mouse hepatoma cell line) and the human embryonic kidney cell line 293. The number of cell clones selected in a colony forming assay from all three cell lines revealed a 6.0 fold, 17.2 fold and 4.5 fold increase in the number of colonies in Huh7 cells, Hep1A cells and 293 cells compared to the mutant integrase control group, respectively. Single cell clones from all three cell lines were amplified and the insertion sites were identified and characterized based on a plasmid rescue protocol. We found frequent smaller deletions of up to 26 bp in the chromosomal target sites (13 of 32 integrations) and deletions of up to 10 bp in the phage integrase attachment site attB (8 of 32 integrations) in both, Huh-7 and 293 cells. Surprisingly, we also detected insertions of up to 177 bp (7 of 32 integrants); most of the insertions were < 4 bp. The origin of these inserted DNA sequences remains to be determined. Out of the 32 independent integration events analyzed so far, three integrated into human chromosome 19 (19q13.31), a site not previously reported. Because these initial results do not yet have a statistically significant number of independent observations, further analyses of additional clones from all three cell lines are ongoing. In summary, these results suggest that hotspots in the host genome targeted by the site-specific integrase phiC31 may depend on the cell line and perhaps on the tissue from which the cell line is derived. These findings will have important implications on improving the safety of ex vivo and in vivo gene therapy approaches in which stable and long-term transgene expression levels are required.
The NHS: possibilities for the endgame
Authors: R. Smith
Journal: BMJ (1999)

<h3>Key points</h3> Not all patients with “difficult-to-control” asthma have “severe asthma”. Many of them have either an incorrect diagnosis, or mild-moderate asthma with unrecognised aggravating factors, or are non-compliant with prescribed therapy. For a diagnosis of severe asthma, it is necessary to confirm the diagnosis of asthma, to evaluate and treat endogenous and exogenous aggravating factors, and to closely follow the patient for ≥6 months. Severe asthma is a heterogeneous condition with different phenotypes. Defining clinical phenotypes is necessary to improve understanding of underlying mechanisms, to help guide current treatment and to provide clues for novel therapeutic interventions. Despite intensive multi-drug treatment with high-dose inhaled and oral corticosteroids, many patients with severe asthma remain uncontrolled. There is an urgent need for new, more-effective treatments. <h3>Educational aims</h3> To help the reader distinguish between “difficult-to-control”, “refractory” and “severe” asthma. To discuss the initial approach to and assessment of a patient with difficult-to-control asthma. To inform the reader how to recognise different clinical phenotypes of severe asthma. To outline management strategies and discuss treatment modalities. <h3>Summary</h3> “Severe asthma” refers to asthma that remains difficult to control despite intensive multidrug therapy, extensive assessment and management of comorbidity, and long-term observation by an asthma specialist. The three main clinical phenotypes of severe asthma include asthma with frequent severe exacerbations, asthma with chronic airflow limitation, and steroid-resistant asthma. Many patients with severe asthma are oral-steroid dependent. Classical steroid-sparing drugs (gold, methotrexate, cyclosporin) are only weakly effective and have unacceptable side-effects. Monoclonal antibodies against immunoglobulin (Ig)E and tumour necrosis factor (TNF)-α have shown clinical benefit in subgroups of patients with severe asthma, and large studies are under way to confirm these promising findings.
Experimental Arterial Thromboembolism in Baboons
Authors: Laurence A. Harker, Stephen R. Hanson, Thomas R. Kirkman
Journal: Journal of Clinical Investigation (1979)

A quantitative primate model of arterial thromboembolism has been characterized with respect to mechanism and usefulness in evaluating modifying variables. The model involved the kinetic measurements of 51Cr-platelets and 125I-fibrinogen consumption by femoral arteriovenous cannulae in chaired baboons.
PSA Screening and Elderly Men—Reply
Authors: Peter C. Albertsen
Journal: JAMA (2007)

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
Abstract 5610: Bivalirudin in Patients with Acute Coronary Syndromes Undergoing Saphenous Vein Graft Percutaneous Coronary Intervention: A Subgroup Analysis from the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Trial
Authors: Somjot S Brar, McLaurin T Brent, David A Cox, Frededck Feit, Antonio Colombo, Philip E Aylward, Angel R Cequier, Harald Darius, Walter Desmet, Lars H Rasmussen, Hans-Juergen Rupprecht, James Hoekstra, Roxana Mehran, Ajay Kirtane, Alexandra Lansky, Helen Parise, Gregg W Stone
Journal: Circulation (2008)
Anatomical Texts of the Earlier Middle Ages. A Study in the Transmission of Culture with a Revised Latin Text of Anatomia Cophonis and Translations of Four Texts.
Authors: George Washington Corner
Journal: JAMA (1927)

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
Systematic reviews of sublingual immunotherapy (SLIT)
Authors: S. Radulovic, D. Wilson, M. Calderon, S. Durham
Journal: Allergy (2011)

To cite this article: Radulovic S, Wilson D, Calderon M, Durham S. Systematic reviews of sublingual immunotherapy (SLIT). Allergy 2011; 66: 740–752. Abstract Allergic rhinitis is common worldwide, with significant morbidity and impact on quality of life. In patients who don't respond adequately to anti-allergic drugs. Subcutaneous allergen immunotherapy is effective although requires specialist administration. Sublingual immunotherapy may represent an effective and safer alternative. This Cochrane systematic review is an update of one published in 2003. We searched Cochrane ENT Group Trials Register, Central, PubMed, EMBASE, CINAHL, Web of Science, Biosis Previews, Cambridge Scientific Abstarcts, mRCT and additional sources. We included randomised, double-blind, placebo- controlled trials of sublingual immunotherapy in adults and children. Two authors selected studies and assessed them for quality. Data were put into RevMan 5.0 for a statistical analysis. We used standardised mean difference (SMD), with a random effect model to combine data. Sixty studies were included, with 49 suitable for meta-analysis. We found significant reductions in symptoms (SMD −0.49; 95%CI (−0.64 to −0.34, P < 0.00001)) and medication requirements (SMD −0.32; 95%CI (−0.43 to −0.21, P < 0.00001)) compared with placebo. None of the trials reported severe systemic reactions, anaphylaxis or use of Adrenaline. This updated review reinforces the conclusion of the original 2003 Cochrane Review that sublingual immunotherapy is effective for allergic rhinitis and appears a safe route of administration.
Allo-Major Histocompatibility Complex–Restricted Cytotoxic T Lymphocytes Engraft in Bone Marrow Transplant Recipients Without Causing Graft-Versus-Host Disease
Authors: Liquan Gao, Tian-Hui Yang, Sophie Tourdot, Elena Sadovnikova, Robert Hasserjian, Hans J. Stauss
Journal: Blood (1999)
Abstract P4-15-13: CDK8 inhibition potentiates anti-ER and anti-HER2 therapies in breast cancer
Authors: Martina S McDermott, Chang-uk Lim, Mengqian Chen, Alexander Chumanevich, James F Catroppo, Balazs Gyorffy, David Oliver, Igor B Roninson, Eugenia V Broude
Journal: Cancer Research (2015)

Abstract CDK8, along with its paralog CDK19, is a cyclin dependent kinase which, in contrast to other members of the CDK family does not regulate cell cycle progression. CDK8 acts as a pleiotropic transcription regulator potentiating the induction of transcription by several transcription factors. Immunohistochemical staining of breast tissue arrays and bioinformatics analysis of gene expression microarray data of breast cancer patients revealed that CDK8 is overexpressed in breast cancer and that higher CDK8 expression correlates with the failure of systemic therapy. Small-molecule selective inhibitors of CDK8 and CDK19 (Senexin A and Senexin B) inhibited the mitogenic effects of estrogen and estrogen-dependent transcription in estrogen receptor (ER)+ breast cancer cell lines. CDK8/19 inhibitors had a cytostatic effect on different ER+ cell lines, and this growth inhibition was synergistic with the effect of the anti-estrogen fulvestrant, particularly in ER+ cell lines resistant to estrogen deprivation. Some of the ER+ cell lines sensitive to CDK8/19 inhibition also express HER2, and therefore we tested CDK8/19 inhibitors in combination with the HER2 and EGFR tyrosine kinase inhibitor lapatinib and an anti-HER2 monoclonal antibody, a biosimilar of trastuzumab. CDK8/19 inhibition produced a synergistic decrease in cell growth with both HER2 inhibitors; this effect was especially pronounced with a trastuzumab biosimilar. Surprisingly, the synergistic effect with HER2 inhibitors was observed in both ER+ HER2+ and ER-HER2+ cell lines, suggesting an effect on a HER2-complementing molecular target other than ER. Interestingly, CDK8/19 inhibition also synergized with trastuzumab biosimilar in a breast cancer cell line that exhibits innate resistance to trastuzumab, suggesting that CDK8/19 inhibition can overcome trastuzumab resistance in breast cancer. These results suggest that combining anti-estrogen and anti-CDK8 therapy may be more effective than conventional hormone therapy for ER positive breast cancer and that combining anti-HER2 and anti-CDK8 therapy is a rational potential treatment for HER2+ breast cancer, regardless of ER status or sensitivity to trastuzumab. Citation Format: Martina S McDermott, Chang-uk Lim, Mengqian Chen, Alexander Chumanevich, James F Catroppo, Balazs Gyorffy, David Oliver, Igor B Roninson, Eugenia V Broude. CDK8 inhibition potentiates anti-ER and anti-HER2 therapies in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-15-13.
Abstract 14875: Evaluation Of Coronary Arteries Using Mutli-detector X-ray Computed Tomography In Pediaric and Young Adult Patients With Giant Coronary Aneurysms Caused By Kawasaki Disease
Authors: Yoshiyuki Kudo, Kenji Suda, Motofumi Iemura, Hironaga Yoshimoto, Yozo Teramachi, Hiroshi Nishino, Toyojiro Matsuishi
Journal: Circulation (2011)

[AIM] To determine usefulness of multi-detector x-ray computed tomography (MDCT) in the evaluation of coronary arteries in patients with giant coronary aneurysms (GAA) caused by Kawasaki disease (K...
The Hospitalization Burden and Post-Hospitalization Mortality Risk in Heart Failure With Preserved Ejection Fraction
Authors: Peter E. Carson, Inder S. Anand, Sithu Win, Thomas Rector, Markus Haass, Jose Lopez-Sendon, Alan Miller, John R. Teerlink, Michel White, Robert S. McKelvie, Michel Komajda, Michael R. Zile, John J. McMurray, Barry Massie
Journal: JACC Heart Failure (2015)
Therapeutic Ratio of Inhaled Corticosteroids in Adult Asthma
Authors: LARS P. NIELSEN, RONALD DAHL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Inhaled corticosteroids have become the mainstay treatment of bronchial asthma. However, simultaneous evaluations of efficacy and side effects are few. This study aimed to compare the relative effect of fluticasone propionate (FP) and budesonide (BUD) on bronchial responsiveness and endogenous cortisol secretion in adults with asthma. The study was double-blind and included 66 adults with asthma, who were randomized to FP (n = 33) or BUD (n = 33). Prestudy, all participants were clinically stable, using inhaled corticosteroids and hyperresponsive to methacholine. Eligible patients were randomized to three consecutive 2-wk periods with either FP 250 μ g twice daily, FP 500 μ g twice daily, and FP 1,000 μ g twice daily, or BUD 400 μ g twice daily, BUD 800 μ g twice daily, and BUD 1,600 μ g twice daily, delivered by Diskhaler and Turbuhaler, respectively. Before randomization and at the end of each treatment, bronchial methacholine PD20, 24-h urinary cortisol excretion (24-h UC), plasma cortisol, serum osteocalcin, and blood eosinophils were determined. The relative PD20 potency between FP and BUD was 2.51 (95% CI, 1.05–5.99; p < 0.05), while the relative 24-h UC potency was 0.60 (95% CI, 0.44–0.83; p < 0.01). The differential therapeutic ratio (FP/BUD) based on PD20 potency and 24-h UC was 4.18 (95% CI, 1.16–15.03; p < 0.05). The difference in systemic potency was also seen for plasma cortisol, serum osteocalcin, and blood eosinophils. Therapeutic ratio over a wide dose range, determined by impact on bronchial responsiveness and endogenous corticosteroid production, seems to favor FP.
Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system
Authors: Peiran Yang, Janet J Maguire, Anthony P Davenport
Journal: Trends in Pharmacological Sciences (2015)

•A biased apelin receptor agonist shows proof-of-concept for utility in the clinic.•Elabela/Toddler is a new apelin receptor ligand in the human cardiovascular system.•Enhancing apelin signalling is beneficial in pulmonary arterial hypertension. Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists. Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists.
Mouse model of pulmonary disease after aerosol infection with mycobacterium xenopi
Authors: Claire Andrejak, Sandeep Tyagi, Eric Nuermberger, Jacques Grosset
Journal: European Respiratory Journal (2011)

Rationale:  Opportunistic respiratory infections due to  M. xenopi  are on the rise in industrialized countries and current therapies are inadequate. Only two experimental studies with the beige and Swiss mouse models iv-infected have been performed so far. As aerosol inhalation is the probable route of infection in humans, we hypothesized that aerosol infection of mice would better recapitulate human infection and permit better assessment of the response to antibiotic treatment. Our first objective was to determine which strain of mice was the most susceptible to aerosol infection.   Methods:  Four strains of mice were tested: BALB/c, C57Bl/6, Beige, and athymic nu/nu (Nude). For each strain, thirty 6-week-old females were simultaneously aerosol infected with 4.7 log10 of  M. xenopi  ATCC # 19971. At 1, 2, 3, 4, 8, 12 and 23 weeks post-infection, three mice per group were sacrificed for gross lung lesions, spleen weight, and lung and spleen CFU counts. From week 4 to 12, 9 mice of each group were treated with clarithromycin 100 mg/kg/d 5 days a week. Three treated mice per group were sacrificed at week 8 and 12.   Results:  In BALB/c, C57Bl/6, Beige and Nude mice infected with  M. xenopi , the lung CFU counts steadily increased to reach 5.57, 5.92, 5.99, and 5.75 log10, respectively at week 4; 6.35, 6.72, 6.60 and 6.93 log10, respectively at week 8; 6.51, 6.43, 7.69, and 6.63 log10, respectively at week 12; and 6.59, 6.72, 8.16, 7.32 log10, respectively at week 2. In all mice,  M. xenopi  disseminated to the spleen. Clarithromycin treatment reduced significantly, by 2 log10, the lung CFU counts in all strains of mice.   Conclusion:  Nude mice were the most susceptible to aerosolized  M.xenopi  infection.
Abstract 9569: Circulating Plasma Brain Natriuretic Peptide Predicts Longitudinal Change in Blood Pressure: The Jackson Heart Study
Authors: Solomon K Musani, Ramachandran S Vasan, Preeti Singh, Aurelian Bidulescu, Tandaw E Samdarshi, Michael Steffes, Herman A Taylor, Ervin R Fox
Journal: Circulation (2011)

INTRODUCTION: Elevation in circulating brain natriuretic peptide (BNP) concentrations has been associated with hypertension in studies of non-Hispanic whites. However, the relation of plasma BNP concentration to progression in blood pressure (BP) category and to incident hypertension in African Americans is unknown. HYPOTHESIS: We assessed the hypothesis that higher circulating BNP concentrations in non-hypertensive African Americans will be associated with change in BP category and incident hypertension. METHODS: Our study population consisted of non-hypertensive participants of the Jackson Heart Study with BP, anthropometry and phlebotomy measures in both exam 1 (2000-04) and exam 2 (2005-08), and plasma measures of BNP in exam 1 only. We examined the relation of circulating BNP concentrations (categorical measures by quartile) to BP progression and to incident hypertension using multivariable logistic regression. The model adjusted for age, sex, BP categories (optimal; normal and high normal), systolic and diastolic BP, smoking, diabetes, body mass index, echo LV mass (all measured at baseline) and change in age between the two exam cycles. RESULTS: The study population consisted of 1,158 participants (mean age 49±12 years, 59% women). The median follow-up period was 5.0± 0.8 years. We observed 38.1% of the participants progressed to a higher BP stage and 20.1% of the participants developed incident hypertension. In the multivariable regression model, elevated plasma BNP concentrations (based on highest quartile) were significantly and positively associated with BP progression [p=0.006; OR, 1.8; 95% CI (1.2, 2.6)] and marginally and positively associated with incident hypertension [p=0.06; OR, 1.3; 95% CI (0.8, 2.1)]. Categorical BNP was significantly and positively associated with both BP progression (p=0.006) and incident hypertension (p = 0.04). CONCLUSION: In our community-based sample of middle-aged and elderly African Americans, higher plasma BNP concentrations were associated with increased risk of BP progression and incident hypertension in all participants.