tbuckley/cabot-search huggingface dataset:
Low Concentration of Oxidized Low-Density Lipoprotein and Lysophosphatidylcholine Upregulate Constitutive Nitric Oxide Synthase mRNA Expression in Bovine Aortic Endothelial Cells
Authors: Ken-ichi Hirata, Nobuhiko Miki, Yuichi Kuroda, Tsuyoshi Sakoda, Seinosuke Kawashima, Mitsuhiro Yokoyama
Journal: Circulation Research (1995)

Abstract Endothelium-dependent relaxation is markedly reduced in atherosclerotic arteries. Recently, the endothelium-dependent relaxing factor has been identified as nitric oxide (NO). We used RNase protection assay and immunoblotting to elucidate the effect of atherogenic lipoprotein on the expression of constitutive NO synthase (cNOS) mRNA and protein levels in bovine aortic endothelial cells. Twenty-four-hour exposure to a low concentration of oxidized low-density lipoprotein (10 μg protein/mL) upregulated cNOS mRNA levels (2.4±0.4-fold, P &lt;.01). However, native low-density lipoprotein and high-density lipoprotein did not have any effect on cNOS mRNA levels. Furthermore, 5 μg/mL of lysophosphatidylcholine (LPC) also upregulated cNOS mRNA levels (2.6±0.5-fold, P &lt;.01) at 8 hours. This action of LPC was abolished with cycloheximide but not with staurosporine. We concluded that atherogenic lipoproteins upregulate cNOS mRNA and protein levels in bovine aortic endothelial cells. This observation supports the hypothesis that an impairment of endothelium-dependent vasodilatation in atherosclerotic vessels may not be due to a decrease in cNOS expression. Moreover, the LPC action on cNOS mRNA levels requires new protein synthesis.
Metachromatic cells in nasal mucosa after allergen challenge
Authors: M. P. Borres, K. Irander, B. Björksten
Journal: Allergy (1990)

Metachromatic cells in the nasal mucosa were studied in relation to symptoms in 16 schoolchildren and 11 adults with hay fever who were challenged with pollen outside the pollen season, using either a gentle scraping‐cytocentrifugation method for collection of mucosal specimens or biopsies. There was a temporary redistribution of metachromatic cells towards the mucosal surface appearing 5–24 h after challenge, with a correlation between the quantity of metachromatic cells and symptom scores. Thus, a single exposure to high doses of allergen may contribute to priming in susceptible individuals.
Restriction Site Tiling Analysis: accurate discovery and quantitative genotyping of genome-wide polymorphisms using nucleotide arrays
Authors: Melissa H Pespeni, Thomas A Oliver, Mollie K Manier, Stephen R Palumbi
Journal: Genome biology (2010)

High-throughput genotype data can be used to identify genes important for local adaptation in wild populations, phenotypes in lab stocks, or disease-related traits in human medicine. Here we advance microarray-based genotyping for population genomics with Restriction Site Tiling Analysis. The approach simultaneously discovers polymorphisms and provides quantitative genotype data at 10,000s of loci. It is highly accurate and free from ascertainment bias. We apply the approach to uncover genomic differentiation in the purple sea urchin.
Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice
Authors: Lisheng Zhang, Yan-Dong Wang, Wei-Dong Chen, Xichun Wang, Guiyu Lou, Nian Liu, Min Lin, Barry M. Forman, Wendong Huang
Journal: Hepatology (2012)

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is the primary bile acid receptor. We previously showed that FXR was required for the promotion of liver regeneration/repair after physical resection or liver injury. However, the mechanism by which FXR promotes liver regeneration/repair is still unclear. Here we show that both hepatic-FXR and intestine-FXR contributed to promote liver regeneration/repair after either 70% partial hepatectomy or carbon tetrachloride-induced liver injury. Hepatic FXR, but not intestine FXR, is required for the induction of Foxm1b gene expression in liver during liver regeneration/repair. In contrast, intestine FXR is activated to induce FGF15 expression in intestine after liver damage. Ectopic expression of FGF15 was able to rescue the defective liver regeneration/repair in intestine-specific FXR null mice.These results demonstrate that, in addition to the cell-autonomous effect of hepatic FXR, the endocrine FGF15 pathway activated by FXR in intestine also participates in the promotion of liver regeneration/repair.
Action is needed to tackle UK's "astonishing" abundance of food, MPs are told
Authors: A. O'Dowd
Journal: BMJ (2015)

People are exposed to an “astonishing” amount of easily accessible and available food in the United Kingdom that is helping to raise obesity levels, experts have told MPs.

The sheer scale of the availability, accessibility, and affordability of food was an issue that the government was not tackling, MPs on the parliamentary health committee were told during an evidence session on 3 February for its inquiry into the health effects of physical activity and diet. MPs asked what the most effective measures should be for politicians to tackle obesity and to encourage physical activity.

Susan Jebb, professor of diet and population health at the University of Oxford, giving evidence, said, “Where I think we are absolutely not taking any action at the moment, and which is crucial, …
Use of Spinal Injections for Low Back Pain—Reply
Authors: J. Bart Staal, Patty J. Nelemans, Rob A. De Bie
Journal: JAMA (2013)

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
Type I interferon signaling is required for activation of the inflammasome during <i>Francisella</i> infection
Authors: Thomas Henry, Anna Brotcke, David S. Weiss, Lucinda J. Thompson, Denise M. Monack
Journal: The Journal of Experimental Medicine (2007)

Francisella tularensis is a pathogenic bacterium whose virulence is linked to its ability to replicate within the host cell cytosol. Entry into the macrophage cytosol activates a host-protective multimolecular complex called the inflammasome to release the proinflammatory cytokines interleukin (IL)-1β and -18 and trigger caspase-1–dependent cell death. In this study, we show that cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I interferon (IFN) response that is essential for caspase-1 activation, inflammasome-mediated cell death, and release of IL-1β and -18. Extensive type I IFN–dependent cell death resulting in macrophage depletion occurs in vivo during F. novicida infection. Type I IFN is also necessary for inflammasome activation in response to cytosolic Listeria monocytogenes but not vacuole-localized Salmonella enterica serovar Typhimurium or extracellular adenosine triphosphate. These results show the specific connection between type I IFN signaling and inflammasome activation, which are two sequential events triggered by the recognition of cytosolic bacteria. To our knowledge, this is the first example of the positive regulation of inflammasome activation. This connection underscores the importance of the cytosolic recognition of pathogens and highlights how multiple innate immunity pathways interact before commitment to critical host responses.
Human Papillomavirus-16 Is the Predominant Type Etiologically Involved in Penile Squamous Cell Carcinoma
Authors: Daniëlle A.M. Heideman, Tim Waterboer, Michael Pawlita, Pien Delis-van Diemen, Ingo Nindl, Joost A. Leijte, Johannes M.G. Bonfrer, Simon Horenblas, Chris J.L.M. Meijer, Peter J.F. Snijders
Journal: Journal of Clinical Oncology (2007)

Human papillomavirus (HPV) infections are suggested to be involved in the development of penile squamous cell carcinoma (SCC), but comprehensive studies to define the association are limited. Therefore, we performed molecular and serologic analyses for a broad spectrum of HPV types on a large series of 83 penile SCCs, and we compared serological findings to those of age-matched male controls (N = 83).Penile SCCs were subjected to detection and typing assays for mucosal and cutaneous HPVs and to subsequent, type-specific viral load and viral gene expression assays. Sera of patients and of controls were analyzed for type-specific mucosal and cutaneous HPV L1, E6, and/or E7 antibodies using bead-based, multiplex serology.HPV DNA of mucosal and/or cutaneous types was found in 46 of 83 (55%) penile SCCs. HPV16 was the predominant type, appearing in 24 (52%) of 46 of penile SCCs. The majority of HPV16 DNA-positive SCCs (18 of 24; 75%) demonstrated E6 transcriptional activity and a high viral load. Additionally, HPV16 molecular findings were strongly associated with HPV16 L1-, E6-, and E7-antibody seropositivity. Furthermore, serologic case-control analyses demonstrated that, in addition to the association of HPV16 with penile SCC, seropositivity against any HPV type was significantly more common in patients compared with in controls. HPV18 and HPV6 seropositivity were associated with HPV16-negative SCCs but were not correlated to molecular findings.HPV16 is the main HPV type etiologically involved in the development of penile SCC. Although individuals who develop penile SCC show a greater prior exposure to a broad spectrum of HPV types, insufficient evidence was found to claim a role for HPV types other than HPV16 in penile carcinogenesis.
Protection against methacholine-induced bronchospasm: salbutamol pMDI<i>versus</i>Clickhaler® DPI
Authors: M.T. Newhouse, P. Patel, M. Parry-Billings
Journal: European Respiratory Journal (2003)

Passive dry-powder inhalers (DPIs) have been developed as an alternative to pressurised metered-dose inhalers (pMDIs) to improve aerosol delivery on inhalation and eliminate the need for propellants. However, new DPI formulations of generic drugs must be rigorously compared with conventional pMDI therapy. This randomised, double-blind, double-dummy, placebo-controlled, seven-way crossover study evaluated bronchoprotection from methacholine challenge in order to compare a novel salbutamol DPI (Clickhaler®) with a reference salbutamol pMDI (Ventolin®). Adult asthma patients with airway hyperresponsiveness to methacholine (provocative concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (PC 20 ) &lt;4 mg·mL −1 ) were treated on separate days with 0, 100, 200 or 400 µg of salbutamol via the DPI or pMDI. Methacholine challenge was performed before and after salbutamol treatment and the PC 20 ratios analysed by Finney's bioassay to test for therapeutic equivalence of the inhalers. Eighteen patients completed the study and showed significant dose-related responses to salbutamol. The relative potency of DPI:pMDI was 1.29 (90% confidence interval 1.04–1.63). There were no treatment differences in safety (cardiac frequency, blood pressure, adverse events). Methacholine-challenge methodology provides a sensitive bioassay and has demonstrated therapeutic equivalence of the salbutamol Clickhaler® dry-powder inhaler with the conventional salbutamol pressurised metered-dose inhaler.
Mucoid impaction of the bronchi in relation to asthma and plastic bronchitis
Authors: A. D. Morgan, W. Bogomoletz
Journal: Thorax (1968)

Mucoid impaction of the bronchi is a condition which deserves wider recognition in this country. It should be considered in any asthmatic subject who may be suspected on clinical or radiological grounds to be suffering from pulmonary tuberculosis or neoplasm. Although 120 cases have been reported since 1951, there are no reports from this country in the British literature. As we have seen three cases in one hospital, we believe that mucoid impaction is being diagnosed under other headings, for example plastic bronchitis. Most of the changes in lungs removed for mucoid impaction are those of asthma, although other factors may play a part. We have compared the pathologies of mucoid impaction, asthma, and plastic bronchitis, and conclude that, while they overlap considerably, they are not identical. Mucoid impaction is an uncommon complication of asthma and certain forms of bronchitis; plastic bronchitis has a much wider aetiological background and is not a pathological entity.
Physical activity counselling in sports medicine: a call to action
Authors: Elizabeth (Liz) Joy, Steven N Blair, Patrick McBride, Robert Sallis
Journal: British Journal of Sports Medicine (2012)

Physical activity (PA) is a key component of healthy lifestyle and disease prevention. In contrast, physical inactivity accounts for a significant proportion of premature deaths worldwide. Physicians are in a critical position to help patients develop healthy lifestyles by actively counseling on PA. Sports medicine physicians, with their focus on sports and exercise medicine are uniquely trained to provide such expertise to patients, learners and colleagues. To succeed, physicians need clinical tools and processes that support PA assessment and counseling. Linking patients to community resources, and specifically to health and fitness professionals is a key strategy. Efforts should be made to expand provider education during medical school, residency and fellowship training, and continuing medical education. Lastly, physically active physicians are more likely to counsel patients to be active. A key message for the sports medicine community is the importance of serving as a positive PA role model.
Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205
Authors: Hiroshi Hirata, Yuji Hinoda, Varahram Shahryari, Guoren Deng, Koichi Nakajima, Z. Laura Tabatabai, Nobuhisa Ishii, Rajvir Dahiya
Journal: Cancer Research (2015)

Recently, long noncoding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues, where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased, whereas β-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchymal transition via E-cadherin recovery and β-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease.
Temporal variability is a personalized feature of the human microbiome
Authors: Gilberto E Flores, J Gregory Caporaso, Jessica B Henley, Jai Ram Rideout, Daniel Domogala, John Chase, Jonathan W Leff, Yoshiki Vázquez-Baeza, Antonio Gonzalez, Rob Knight, Robert R Dunn, Noah Fierer
Journal: Genome biology (2014)

Abstract Background It is now apparent that the complex microbial communities found on and in the human body vary across individuals. What has largely been missing from previous studies is an understanding of how these communities vary over time within individuals. To the extent to which it has been considered, it is often assumed that temporal variability is negligible for healthy adults. Here we address this gap in understanding by profiling the forehead, gut (fecal), palm, and tongue microbial communities in 85 adults, weekly over 3 months. Results We found that skin (forehead and palm) varied most in the number of taxa present, whereas gut and tongue communities varied more in the relative abundances of taxa. Within each body habitat, there was a wide range of temporal variability across the study population, with some individuals harboring more variable communities than others. The best predictor of these differences in variability across individuals was microbial diversity; individuals with more diverse gut or tongue communities were more stable in composition than individuals with less diverse communities. Conclusions Longitudinal sampling of a relatively large number of individuals allowed us to observe high levels of temporal variability in both diversity and community structure in all body habitats studied. These findings suggest that temporal dynamics may need to be considered when attempting to link changes in microbiome structure to changes in health status. Furthermore, our findings show that, not only is the composition of an individual’s microbiome highly personalized, but their degree of temporal variability is also a personalized feature.
Reporting of Serious Adverse Drug Reactions of Targeted Anticancer Agents in Pivotal Phase III Clinical Trials
Authors: Bostjan Seruga, Lynn Sterling, Lisa Wang, Ian F. Tannock
Journal: Journal of Clinical Oncology (2010)

Purpose Oncologists prescribe anticancer drugs based on results of phase III randomized clinical trials (RCTs), but some safety concerns appear only later in updated drug labels. Here, we analyze adverse drug reactions (ADRs) of targeted anticancer agents from updated drug labels and their reporting in corresponding pivotal RCTs. Methods We searched the US Food and Drug Administration (FDA) Web site for approved targeted anticancer drugs with updates of their labels related to safety in 2008 and 2009 and at least one RCT referenced in the updated drug label. For each drug, serious ADRs, including potentially fatal ADRs, were identified from the updated label. Published reports of RCTs referenced in the label were searched to determine whether they described these ADRs. Results We identified 12 eligible targeted anticancer agents with 36 corresponding RCTs referenced in updated drug labels. There were 76 serious ADRs reported in updated drug labels, and 50% (n = 38) were potentially fatal. Of these, 39% (n = 30) of all serious ADRs and 39% (n = 15) of potentially fatal ADRs were not described in any published report of RCTs, whereas 49% and 58%, respectively, were not described in initial drug labels. After a median 4.3 years between initial approval and update of drug labels, 42% (n = 5) of targeted cancer agents acquired one or more boxed warnings (the highest level of FDA alert). Conclusion Published reports of pivotal RCTs and initial drug labels contain limited information about serious ADRs of targeted anticancer agents. Rare but serious ADRs may be important causes of morbidity and mortality in general oncologic practice.
Issues for DSM-V: DSM-V Should Include a Conceptual Issues Work Group
Authors: Kenneth S. Kendler, Paul S. Appelbaum, Carl C. BELL, K. W.M. Fulford, S. Nassir Ghaemi, Kenneth F. Schaffner, G. Scott Waterman, Michael B. First, John Z. Sadler
Journal: American Journal of Psychiatry (2008)
Tumor Necrosis Factor- α Negatively Regulates Airway Hyperresponsiveness through γδ T Cells
Authors: ARIHIKO KANEHIRO, MICHAEL LAHN, MIKA J. MÄKELÄ, AZZEDDINE DAKHAMA, MASAKI FUJITA, ANTHONY JOETHAM, ROBERT J. MASON, WILLI BORN, ERWIN W. GELFAND
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Tumor necrosis factor (TNF)- α is a potent cytokine with immunomodulatory, proinflammatory, and pathobiologic activities. Although TNF- α is thought to play a role in mediating airway inflammation and airway hyperresponsiveness (AHR), its function is not well defined. TNF- α –deficient mice and mice expressing TNF- α in their lungs because of a TNF- α transgene placed under the control of the surfactant protein (SP)-C promoter (SP-C/TNF- α –transgenic mice) were sensitized to ovalbumin (OVA) and subsequently challenged with OVA via the airways; airway function in response to inhaled methacholine was monitored. In the TNF- α –deficient mice, AHR was significantly increased over that in controls. In contrast, the transgenic mice failed to develop AHR. In addition, sensitized/ challenged TNF- α –deficient mice had significantly increased numbers of eosinophils and higher levels of interleukin (IL)-5 and IL-10 in their bronchoalveolar lavage fluid than were found for control mice. However, in SP-C/TNF- α –transgenic mice, both the numbers of eosinophils and levels of IL-5 and IL-10 were significantly lower than in sensitized/challenged transgene-negative mice. γδ T cells have been shown to be activated by TNF- α and to negatively regulate AHR. Depletion of γδ T cells in the TNF- α –transgenic mice in the present study increased AHR, whereas depletion of these cells had no significant effect in TNF- α –deficient mice. These data indicate that TNF- α can negatively modulate airway responsiveness, controlling airway function in allergen-induced AHR through the activation of γδ T cells.
Isolation and preliminary biochemical characterization of the gonococcal H.8 antigen.
Authors: W Strittmatter, P J Hitchcock
Journal: The Journal of Experimental Medicine (1986)

We have presented a method for the extraction and isolation of the gonococcal H.8 antigen. There was no evidence of contamination by other gonococcal proteins, phospholipids, or LPS. The purified H.8 antigen was subjected to preliminary analysis and appeared to be a proteolipid consisting of both protein and lipid components. The amino acid composition was unusual; the peptide portion of the antigen was an alanine and proline-rich molecule that lacked aromatic and sulfur-containing amino acids. The overall amino acid composition is hydrophobic. A lipid constituent was also identified; it was made up of at least two lipid components, which were unique to the H.8 molecule. The chemical nature of the association of the protein and lipid is presently unknown, but it is clearly a tenacious one.
CD40 and adenosine A2 receptor agonist–cyclic adenosine monophosphate rescue B-cell antigen receptor–induced apoptosis through independent pathways and converge to prevent caspase activation
Authors: Naoki Sakata, Hideki Kawasome, Naohiro Terada, Gary L. Johnson, Erwin W. Gelfand
Journal: Journal of Allergy and Clinical Immunology (2000)