tbuckley/cabot-search huggingface dataset:
T2 Vitamin D Enhances Bronchial Epithelial Cell Antioxidant Responses And Reduces Their Pro-inflammatory Cytokine Response To Stimulation By Urban Particulate Matter
Authors: P. Pfeffer, F. Kelly, C. Hawrylowicz
Journal: Thorax (2014)

<h3>Background</h3> Particulate matter (PM) air pollution and vitamin D deficiency are environmental factors associated with asthma exacerbations and severe asthma. PM stimulates cellular inflammatory pathways through oxidative stress and vitamin D has been shown in other organ systems to protect against oxidative stress. We therefore investigated whether vitamin D might protect against PM-induced pro-inflammatory responses. <h3>Methods</h3> Primary human bronchial epithelial cells (HBECs) were cultured with ambient PM and/or physiological concentrations of vitamin D. Production of pro-inflammatory cytokines was measured by multiplex bead array, gene transcription by microarray and oxidative stress with appropriate assays. <h3>Results</h3> Addition of vitamin D significantly decreased production of IL-6 by PM-stimulated HBECs (p = 0.011), however, the reduction was greater in HBECs from healthy (n = 8) than from asthmatic (n = 7) donors (48.7% vs 28.0% reduction, p = 0.048). Gene transcription microarray identified a subset of pro-inflammatory cytokine genes all down-regulated by vitamin D including <i>IL6</i>, <i>IL24</i>, <i>CXCL10</i> and <i>CCL20</i>. Microarray also identified effects of vitamin D on antioxidant genes including <i>G6PD</i> (3.1 fold-induction with 1,25(OH)D3, p &lt; 0.001). <i>G6PD </i>encodes glucose-6 phosphate dehydrogenase, which is vital for production of reducing equivalents for antioxidant responses. Vitamin D significantly increased the cellular ratio of reduced to oxidised glutathione (1.6 fold-increase with 25(OH)D3, p = 0.042), enhancing the ability of cellular antioxidant pathways to protectively respond to oxidative stress. Furthermore, addition of vitamin D reduced levels of PM-stimulated 8-isoprostane (19.8% reduction, p = 0.045), a marker of oxidative stress damage. Inhibition of G6PD reduced the beneficial effect of vitamin D on PM-stimulated HBEC responses. <h3>Conclusion</h3> Vitamin D beneficially modulates the response of human bronchial epithelial cells to pathological stimulation by PM, in part through enhancing antioxidant pathway responses. A reduction in PM-stimulated IL-6 is likely important given the association between PM, systemic inflammation and an IL-6 dependent coagulopathy in animal models. Furthermore, many of the vitamin D regulated mediators in the array have profound actions on the adaptive immune system. However, our research has also revealed the novel finding that cells from healthy and asthmatic individuals may respond differently to vitamin D.
Role of Parenting Style in Achieving Metabolic Control in Adolescents With Type 1 Diabetes
Authors: Maayan Shorer, Ravit David, Michal Schoenberg-Taz, Ifat Levavi-Lavi, Moshe Phillip, Joseph Meyerovitch
Journal: Diabetes Care (2011)

To examine the role of parenting style in achieving metabolic control and treatment adherence in adolescents with type 1 diabetes.Parents of 100 adolescents with type 1 diabetes completed assessments of their parenting style and sense of helplessness. Parents and patients rated patient adherence to the treatment regimen. Glycemic control was evaluated by HbA(1c) values.An authoritative paternal parenting style predicted better glycemic control and adherence in the child; a permissive maternal parenting style predicted poor adherence. A higher sense of helplessness in both parents predicted worse glycemic control and lesser adherence to treatment. Parental sense of helplessness was a significant predictor of diabetes control after correcting for other confounders (patient age, sex, and treatment method).An authoritative nonhelpless parenting style is associated with better diabetes control in adolescents. Paternal involvement is important in adolescent diabetes management. These results have implications for psychological interventions.
Expression of Inducible Nitric Oxide Synthase Inhibits Platelet Adhesion and Restores Blood Flow in the Injured Artery
Authors: Zhong-qun Yan, Tasuku Yokota, Weiguo Zhang, Go¨ran K. Hansson
Journal: Circulation Research (1996)

NO generated by endothelial cells is vasoprotective by antagonizing platelet adhesion and smooth muscle contraction. Since vascular smooth muscle cells (VSMCs) produce NO in response to cytokine stimulation and after arterial injury, we speculated that NO produced by VSMCs could compensate for the loss of endothelium. Using balloon catheter denudation of the rat carotid artery as a model for arterial injury and restenosis, we have evaluated the time course of expression of inducible NO synthase (iNOS) by in situ hybridization and immunohistochemistry and studied the effect of iNOS on platelet adhesion and blood flow of the injured vessel. iNOS mRNA and protein were expressed in the innermost layer of the media from day 1 and were subsequently detected in the neointima, whereas no expression was detectable in the uninjured artery. Systemic administration of N omega-nitro-L-arginine methyl ester (L-NAME) resulted in a twofold to threefold increase in the adhesion of 111In-labeled platelets to the injured vessel wall. Platelet adhesion was also enhanced threefold by local delivery of L-NAME from a gel surrounding the injured vessel, whereas the stereoisomer, D-NAME, had no effect. Finally, inhibition of NO synthase led to a 24% reduction of the blood flow in the injured carotid artery. These results demonstrate that arterial injury triggers the expression of iNOS in the lesion and that NO produced by iNOS inhibits platelet adhesion and restores blood flow. This could explain the disappearance of platelet thrombi from deendothelialized arterial surfaces within a few days after injury and indicates the importance of NO generated by iNOS for the maintenance of vascular tone. Thus, expression of iNOS in lesions may represent a protective mechanism that compensates for the loss of endothelium.
How SLPI soothes
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Organs such as the lung that are continuously exposed to inhaled microbes must be carefully guarded against excessive inflammation. A new study by Taggart and colleagues on page 1659 shows that a protease inhibitor that is produced in the airways helps subdue lung inflammation by shutting down the pro-inflammatory transcription factor NF-κB, both in the cytoplasm and the nucleus.One way the lung avoids inflammation-induced collateral damage is by producing protease inhibitors, such as SLPI (secretory leukocyte protease inhibitor). SLPI is produced by mucosal epithelial cells and inactivates potentially damaging enzymes, such as neutrophil elastase, that are produced by immune cells to help kill invading microbes.






Figure 

SLPI (green) enters the nucleus (red) of monocytes and competes with NF-κB for binding to gene promoters.




But SLPI's protective function is not limited to defusing dangerous proteases. SLPI is also a potent antimicrobial peptide (akin to defensins) and an antiinflammatory agent. This group and others have shown that SLPI's antiinflammatory activity stems in part from its ability to inhibit the degradation of IκBβ—an inhibitor protein that binds to cytoplasmic NF-κB. The importance of SLPI in limiting inflammation is evident in SLPI-deficient mice, which succumb to endotoxic shock in response to normally sublethal doses of bacterial lipopolysaccharide.

Here, Taggart and colleagues show that SLPI also targets NF-κB in the nucleus, where SLPI binds to κB binding sites on gene promoters, displacing the NF-κB protein p65. This competition inhibits the production of inflammatory cytokines such as interleukin (IL)-8 and TNF. Thus, any NF-κB protein that circumvents SLPI's roadblock in the cytoplasm would likely encounter a second wave of SLPI-mediated resistance in the nucleus.

The preferential production of this multifunctional protein at mucosal surfaces probably reflects the importance of preventing excessive immune activation in tissues barraged by environmental pathogens. Whether SLPI-mediated inhibition is defective in individuals prone to chronic inflammatory diseases of the mucosa, such as asthma or inflammatory bowel disease, remains to be tested.
Bronchial stenosis and sclerosing mediastinitis: an uncommon complication of external thoracic radiotherapy
Authors: S Dechambre, J Dorzee, J Fastrez, C Hanzen, P Van Houtte, JP d'Odemont
Journal: European Respiratory Journal (1998)

The side-effects of radiation therapy on the bronchial tree or on the mediastinum are seldom reported. In this setting, we report a case of sclerosing mediastinitis with bronchial stenosis discovered 1 yr after external radiotherapy for lung cancer. The patient was treated with a Dumont stent and has so far had an uneventful further course for up to 42 months. Bronchial stenosis related to mediastinal fibrosis after radiotherapy has not been reported previously.
Pediatrics. The Hygienic and Medical Treatment of Children
Authors: Charles Hunter Dunn
Journal: JAMA (1901)

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
Spontaneous Development of Liver Tumors in the Absence of the Bile Acid Receptor Farnesoid X Receptor
Authors: Fan Yang, Xiongfei Huang, Tangsheng Yi, Yun Yen, David D. Moore, Wendong Huang
Journal: Cancer Research (2007)

Abstract Farnesoid X receptor (FXR, NR1H4) is a member of the nuclear hormone receptor superfamily, which plays an essential role in regulating bile acid, lipid, and glucose homeostasis. Both male and female FXR−/− mice spontaneously developed liver tumors; however, no other tumors were developed after 15 months of age. In contrast, no liver tumors were observed in wild-type mice of the same age. Histologic analyses confirm that tumors were hepatocellular adenoma and carcinoma. Although there was no obvious tumor at ages 9 to 12 months, FXR−/− livers displayed prominent liver injury and inflammation. Strong labeling of apoptotic hepatocytes and liver damage–induced compensatory regeneration were observed. Deregulation of genes involved in bile acid homeostasis in FXR−/− mice was consistent with abnormal levels of bile acids presented in serum and liver. Genes involved in inflammation and cell cycle were up-regulated in aging FXR−/− mice but not in wild-type controls. Increasing the bile acid levels by feeding mice with a 0.2% cholic acid diet strongly promoted N-nitrosodiethylamine–initiated liver tumorigenesis, whereas lowering bile acid pool in FXR−/− mice by a 2% cholestyramine feeding significantly reduced the malignant lesions. Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis. [Cancer Res 2007;67(3):863–7]
Evaluation of Sympathetic Nerve Terminals With [ <sup>11</sup> C]Epinephrine and [ <sup>11</sup> C]Hydroxyephedrine and Positron Emission Tomography
Authors: Götz Münch, Ngoc T. B. Nguyen, Stephan Nekolla, Sibylle Ziegler, Otto Muzik, Pulak Chakraborty, Donald M. Wieland, Markus Schwaiger
Journal: Circulation (2000)

Background —The goal of the present study was to directly compare the new radiopharmaceutical agent [ 11 C]epinephrine (EPI) with [ 11 C]hydroxyephedrine (HED) through the use of PET. Methods and Results —Seven healthy volunteers and 10 patients were investigated after heart transplantation. PET images of both tracers were of excellent quality in the volunteers. Values for radiolabeled metabolites (measured in percent of blood activity) at 5, 20, and 60 minutes after injection were ≈35%, ≈82%, and ≈86% for EPI and ≈13%, ≈47%, and ≈78% for HED, respectively. At 35 minutes, metabolite-corrected mean myocardial retention fraction of EPI (0.235±0.022 min −1 ) was significantly greater ( P &lt;0.01) than that of HED (0.142±0.012 min −1 ). Corrected tracer retention fractions of both EPI and HED were significantly reduced in transplant recipients (0.055±0.004 min −1 , P &lt;0.0001; and 0.050±0.006 min −1 , P &lt;0.0001, respectively) compared with volunteers. Normalization of retention fractions of patients with transplantation within 1 year to volunteers resulted in a value (ratio expressed in percent) of 20.6±1.8% for EPI, significantly ( P &lt;0.03) smaller than 27.8±0.8% for HED. In patients with transplantation later than 1 year, the values were 26.0±2.9% for EPI compared with 44.2±5.6% for HED ( P &lt;0.014). Conclusions —Both tracers showed high selectivity for neuronal uptake in the heart, with a significant reduction in tracer retention in transplant recipients compared with volunteers. Compared with HED, EPI showed greater retention in volunteers and a lower retention ratio in transplant recipients, suggesting that EPI may be the superior tracer with higher sensitivity to neuronal abnormalities. Because EPI reflects neuronal uptake, metabolism, and storage, it may be more suitable for the study of neuronal integrity than HED, which primarily traces uptake-1 capacity.
Cigarette Smoking and Colorectal Cancer Risk in the European Prospective Investigation Into Cancer and Nutrition Study
Authors: Anke M. Leufkens, Fränzel J.B. Van Duijnhoven, Peter D. Siersema, Hendriek C. Boshuizen, Alina Vrieling, Antonio Agudo, Inger T. Gram, Elisabete Weiderpass, Christina Dahm, Kim Overvad, Anne Tjønneland, Anja Olsen, Marie–Christine Boutron–Ruault, Françoise Clavel–Chapelon, Sophie Morois, Domenico Palli, Sara Grioni, Rosario Tumino, Charlotta Sacerdote, Amalia Mattiello, Silke Herman, Rudolf Kaaks, Annika Steffen, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Dimitrios Trichopoulos, Petra H. Peeters, Carla H. van Gils, Henk van Kranen, Eliv Lund, Vanessa Dumeaux, Dagrun Engeset, Laudina Rodríguez, Maria–José Sánchez, Maria–Dolores Chirlaque, Aurelio Barricarte, Jonas Manjer, Martin Almquist, Bethany van Guelpen, Göran Hallmans, Kay–Tee Khaw, Nick Wareham, Konstantinos K. Tsilidis, Kurt Straif, Maria Leon–Roux, Paul Vineis, Teresa Norat, Elio Riboli, H. Bas Bueno–de–Mesquita
Journal: Clinical Gastroenterology and Hepatology (2010)
Causes of enuresis.
Authors: J. V. Braithwaite
Journal: BMJ (1969)

MEDICALJOURNAIto the latter means much.These units could also be used-for teaching purposes.At the general-practitioner hospital at which I attend students accompany me regularly.At the outpatients there they see more everyday cases than they would ever see at their teach- ing hospital, where referred cases tend to be of a highly specialized nature.
RE: Mortality After Radical Prostatectomy or External Beam Radiotherapy for Localized Prostate Cancer
Authors: D. A. Hamstra, R. C. Chen
Journal: JNCI Journal of the National Cancer Institute (2014)

We read with interest the report from Hoffman et al. (1) and its accompanying editorial (2) comparing mortality in men treated in the mid-1990s with radical prostatectomy or external beam radiotherapy (RT) for prostate cancer. This study highlights the difficulty of comparing mortality among treatments in prostate cancer using observational studies. As the authors discuss, RT evolved substantially since 1994, with more than 15 randomized trials performed, the most of any treatment modality in localized prostate cancer. The two most notable findings were the addition of androgen deprivation therapy (ADT) to RT and dose escalation. Randomized trials including more than 6000 patients demonstrated an overall mortality reduction when ADT is added to RT for patients with intermediate- and high-risk prostate cancer, with a relative reduction of approximately 50% (3). This alone would make up the mor tality difference between RT and prostatectomy the authors observed. Additional trials also demonstrated that long-term ADT further reduces mortality compared with short-term ADT (45). Unfortunately, in the mid-1990s, ADT use with RT was uncommon and long-term ADT was rare; this study included only 56 patients who received ADT, with unclear timing and duration. Although subgroup analysis was performed, the results are unreliable because of the small sample size and unknown treatment details. Further, five additional randomized trials published after 2000 consistently demonstrated a 15% to 20% reduction in prostate cancer recurrence with dose escalation (6 ). Together, these trials demonstrated that modern RT, compared with that used in this study, reduces prostate cancer recur rence and overall mortality, which must be a central consideration when interpreting the authors’ results. Although radical prostatectomy has also evolved, evidence clearly supporting improved survival with modern prostatectomy compared with older techniques is lacking. Another notable challenge is the ability of sophisticated analytic methods to fully control for confounding among patients who received radical prostatectomy vs RT—an especially relevant concern when mortality is the outcome of interest. The authors should be applauded for applying several propensity score methods to analyze the data; however, as they admit, residual confounding is likely. It would have been helpful to provide the adjusted overall mortality and cancer-specific mor
Understanding the Mechanisms of Sustained Signaling and T Cell Activation
Authors: Antonio Lanzavecchia
Journal: The Journal of Experimental Medicine (1997)

A Dynamic View of T Cell Behavior . For many years it has been known that T lymphocytes engage APCs in a long-lasting interaction that results in the generation of a rapid and sustained signal in T cells. Lasting almost 1 h, this sustained signal is required by T cells to maintain the transcription
Sherlock Holmes and a biological weapon
Authors: S. K Vora
Journal: Journal of the Royal Society of Medicine (2002)

Sir Arthur Conan Doyle created Sherlock Holmes during exciting times. He graduated from Edinburgh University Medical College in 1881, and Sherlock Holmes made his appearance (in The Study in Scarlet) in 1886. This was the golden age of microbiology, with landmark discoveries by Koch, Ehrlich and Pasteur amongst others, and the British Empire was at its height. It is not surprising that the Sherlock Holmes stories contain numerous references to infectious diseases, either local or imported from the farflung colonies. In the course of his adventures Sherlock Holmes became acquainted with bioterrorism.
Bexarotene and Erlotinib for Aerodigestive Tract Cancer
Authors: Konstantin H. Dragnev, W. Jeffrey Petty, Sumit Shah, Adrian Biddle, Neil B. Desai, Vincent Memoli, James R. Rigas, Ethan Dmitrovsky
Journal: Journal of Clinical Oncology (2005)

Purpose The epidermal growth factor receptor (EGFR) and cyclin D1 are overexpressed in lung carcinogenesis. The rexinoid, bexarotene, represses cyclin D1 and EGFR expression in vitro. It was hypothesized that combining bexarotene with the EGFR inhibitor, erlotinib, would augment clinical activity. Patients and Methods In vitro studies and a phase I clinical trial were performed. Twenty-four patients with advanced aerodigestive tract cancers were enrolled; 79% had non–small-cell lung cancer (NSCLC). The primary objective was to determine the maximum-tolerated dose. Clinical activity was a secondary objective. Results Combining erlotinib with bexarotene enhanced growth suppression in vitro compared with each single-agent treatment. This cooperatively repressed cyclin D1 expression. Clinically, the most frequent toxicities were mild hypertriglyceridemia and skin rash. Two serious treatment-related adverse events occurred (creatine phosphokinase elevation attributed to antilipid therapy and a case of generalized pain). Five objective responses (four partial and one minor) were observed in NSCLC patients. Responses were observed in males and smokers. EGFR sequence analyses did not reveal activating mutations in tumors from assessable responding patients. Median time to progression was 2.0 months; overall survival time was 14.1 months; and 1-year survival rate was 73.8%. Conclusion The recommended phase II doses are erlotinib 150 mg/d and bexarotene 400 mg/m 2 /d orally. These agents can be administered in combination at the recommended single-agent doses without added toxicity. Overall survival and clinical features of responding patients differ from prior reports of single-agent erlotinib treatment. These findings are encouraging and warrant further investigation of this regimen.
A Genomewide Association Study of Response to Lithium for Prevention of Recurrence in Bipolar Disorder
Authors: Roy H. Perlis, Jordan W. Smoller, Manuel A.R. Ferreira, Andrew McQuillin, Nick Bass, Jacob Lawrence, Gary S. Sachs, Vishwajit Nimgaonkar, Edward M. Scolnick, Hugh Gurling, Pamela Sklar, Shaun Purcell
Journal: American Journal of Psychiatry (2009)

Objective: Lithium remains a first-line treatment for bipolar disorder, but the mechanisms by which it prevents the recurrence of mood episodes are not known. The authors utilized data from a genomewide association study to examine associations between single nucleotide polymorphisms (SNPs) and the outcome of lithium treatment in two cohorts of patients with bipolar I disorder or bipolar II disorder. Method: The hazard for mood episode recurrence was examined among 1,177 patients with bipolar I disorder or bipolar II disorder, including 458 individuals treated with lithium carbonate or citrate, who were participants in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) cohort. SNPs showing the greatest evidence of association in Cox regression models were then examined for association with positive lithium response among 359 bipolar I or II disorder patients treated with lithium carbonate or citrate in a second cohort from the University College London. Results: The strongest association in the STEP-BD cohort (minimum p=5.5×10 –7 ) was identified for a region on chromosome 10p15 (rs10795189). Of the regions showing suggestive evidence (p<5× 10 –4 ) of association with lithium response, five were further associated with positive lithium response in the University College London cohort, including SNPs in a region on chromosome 4q32 spanning a gene coding for the glutamate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionate (AMPA) receptor GRIA2 . Conclusions: Multiple novel loci merit further examination for association with lithium response in bipolar disorder patients, including one region that spans the GRIA2 gene, for which expression has been shown to be regulated by lithium treatment.