tbuckley/cabot-search huggingface dataset:
High Dietary Inorganic Phosphate Increases Lung Tumorigenesis and Alters Akt Signaling
Authors: Hua Jin, Cheng-Xiong Xu, Hwang-Tae Lim, Sung-Jin Park, Ji-Young Shin, Youn-Sun Chung, Se-Chang Park, Seung-Hee Chang, Hee-Jeong Youn, Kee-Ho Lee, Yeon-Sook Lee, Yoon-Cheol Ha, Chan-Hee Chae, George R. Beck, Myung-Haing Cho
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis.The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development.Experiments were performed on 5-week-old male K-ras(LA1) lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods.A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras(LA1) mice.Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.
Arrhythmic Cardiac Arrest Due to Isolated Coronary Artery Spasm: Long-Term Outcome of Seven Resuscitated Patients
Authors: Philippe Chevalier, Antoine Dacosta, Pascal Defaye, Thierry Chalvidan, Eric Bonnefoy, Gilbert Kirkorian, Karl Isaaz, Bernard Denis, Paul Touboul
Journal: Journal of the American College of Cardiology (1998)
Fetal Heart Rate Predictors of Long QT Syndrome
Authors: Jason L. Mitchell, Bettina F. Cuneo, Susan P. Etheridge, Hitoshi Horigome, Hsin-Yi Weng, D. Woodrow Benson
Journal: Circulation (2012)

Fetal long QT syndrome (LQTS) is associated with complex arrhythmias including torsades de pointes and 2° atrioventricular block. Sinus bradycardia has also been associated with fetal LQTS, but little is known of this rhythm manifestation. Our purpose was to characterize the fetal heart rate (FHR)/gestational age (GA) profile of fetal LQTS.We ascertained fetal LQTS subjects by family history (Group 1) or fetal arrhythmia referral (Group 2). We compared FHR in LQTS subjects versus normal fetuses. To identify FHR predictors of LQTS, we calculated a bradycardia index as % of LQTS FHR recordings either ≤110 beats per minute (obstetric standard) or ≤3(rd) percentile for GA. Among 42 LQTS subjects, 26 were in Group 1 and 16 in Group 2. There were 536 normal fetuses. The bradycardia index was only 15% for FHR ≤110 beats per minute, but 66% for FHR ≤3rd percentile for GA. Ten fetuses with complex arrhythmias also had severe and sustained sinus bradycardia throughout gestation. Identifying a fetal proband in Group 2 resulted in LQTS diagnosis in 9 unsuspected members of 6 families.FHR varies by GA in both normal and LQTS fetuses. Postnatal evaluation of neonates with FHR ≤3(rd) percentile for GA may improve ascertainment of LQTS in fetuses, neonates, and undiagnosed family members.
Illustrations of the Value of the Microscope in the Treatment of the Sterile Condition
Authors: J. M. Sims
Journal: BMJ (1868)

campaign in J864, in which Professor Langenbeck performed a sub- periosteal resection of a large portion of the diaphysis of both tibia and fibula, and which was brought to a successful termination, with com- plete re-formation of bone.Time would not permit me to discuss some other points connected with this subject, which I consider of the utmost importance.I shall content myself, therefore, with stating the following propositions, which are based on the physiological experiments and clinical experiences of M. Ollier especially, Langenbeck, Lucke, Aloon, Wood, my own, and others who are interested in this subject.These are:i. That, in subperiosteal resections, the reproduction of bone is more complete, and effected with greater rapidity, than after total removal of both bone and periosteum.2. That the osseous reproductive properties of the membrane vary ac- cording as it is taken from the long or short bones, being greater in the former than in the latter.(Ollier.)3. That the normal form of the joint is better preserved than when the precaution of leaving the periosteal covering is taken.4. That the subperiosteal resection involves less danger than when conducted on the old principle.This proposition is grounded chiefly on the results of Ollier's experiments on the lower animals; the number of unfavourable results which followed when the membrane was re- moved being much greater than when it was left.
Activation of AMP-Activated Protein Kinase by Metformin Improves Left Ventricular Function and Survival in Heart Failure
Authors: Susheel Gundewar, John W. Calvert, Saurabh Jha, Iris Toedt-Pingel, Sang Yong Ji, Denise Nunez, Arun Ramachandran, Mauricio Anaya-Cisneros, Rong Tian, David J. Lefer
Journal: Circulation Research (2008)

Clinical studies have reported that the widely used antihyperglycemic drug metformin significantly reduces cardiac risk factors and improves clinical outcomes in patients with heart failure. The mechanisms by which metformin exerts these cardioprotective effects remain unclear and may be independent of antihyperglycemic effects. We tested the hypothesis that chronic activation of AMP-activated protein kinase (AMPK) with low-dose metformin exerts beneficial effects on cardiac function and survival in in vivo murine models of heart failure. Mice were subjected to permanent left coronary artery occlusion or to 60 minutes left coronary artery occlusion followed by reperfusion for 4 weeks. High-resolution, 2D echocardiography was performed at baseline and 4 weeks after myocardial infarction to assess left ventricular dimensions and function. Metformin (125 μg/kg) administered to mice at ischemia and then daily improved survival by 47% ( P &lt;0.05 versus vehicle) at 4 weeks following permanent left coronary artery occlusion. Additionally, metformin given at reperfusion and then daily preserved left ventricular dimensions and left ventricular ejection fraction ( P &lt;0.01 versus vehicle) at 4 weeks. The improvement in cardiac structure and function was associated with increases in AMPK and endothelial nitric oxide synthase (eNOS) phosphorylation, as well as increased peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α expression in cardiac myocytes. Furthermore, metformin significantly improved myocardial cell mitochondrial respiration and ATP synthesis compared to vehicle. The cardioprotective effects of metformin were ablated in mice lacking functional AMPK or eNOS. This study demonstrates that metformin significantly improves left ventricular function and survival via activation of AMPK and its downstream mediators, eNOS and PGC-1α, in a murine model of heart failure.
ROLE OF THE MENTAL HEALTH WORKER AS A MEDIUM OF INTERACTION
Authors: WINTHROP ROCKEFELLER
Journal: American Journal of Psychiatry (1966)

In summary, for its part as an agency of interaction the mental health association accepts a responsibility for the recruitment and screening of suitable candidates for appropriate volunteer assignments in hospital, clinic and community mental health center as determined and defined by the psychiatric profession. The mental health association acknowledges its mandate for continuing self-education and the assumption of community leadership as motivator and interpreter to the public of the needs of the mentally ill. We recognize the limitations we have in the shortage of business and industry leaders in our ranks and we have pledged ourselves to correct this weakness. We understand the importance of our responsibility in the critical area of legislative action and we promise to intensify our effort toward this citizen obligation. With guidance and support, the mental health association can truly become the "voice of the people of America" in matters pertaining to mental illness.
A search for a transmissible agent in Crohn's disease.
Authors: R V Heatley, P M Bolton, E Owen, W J Williams, L E Hughes
Journal: Gut (1975)

Controversy exists as to whether a transmissible agent is responsible for Crohn9s disease. Previous reports have suggested that sarcoid-like granulomas can develop in animals following inoculation of homogenates derived from bowel affected by Crohn9s disease. This study involved the injection of Crohn9s tissue homogenates into experimental animals under a variety of conditions which might be expected to favour the demonstration of such an agent. Homogenates have been inoculated into the ileum of rats, mice, and rabbits and also given inoculated into ileum and footpads of rats which have previously been rendered lymphoedematous by surgical interruption of the draining lymphatics. Bowel homogenates from a total of 17 patients with Crohn9s disease have been injected into 91 experimental animals. No macroscopic or microscopic changes indicative of Crohn9s disease were detected. Thus study does not support the suggestion that a transmissible agent is present in Crohn9s disease.
497 APPLICATION OF MELD SCORE IN ARGENTINA HAS DEMONSTRATED A NEGATIVE IMPACT ON WAITING LIST MORTALITY AND HAS BEEN ASSOCIATED WITH LOWER EARLY POST TRANSPLANT SURVIVAL
Authors: A. Villamil, J.C. Bandi, P. Casciato, S. Marciano, M. Bonacci, O. Galdame, E. de Santibañnes, A.C. Gadano
Journal: Journal of Hepatology (2010)
A Novel <b> <i>Ex vivo</i> </b> Model System for Evaluation of Conditionally Replicative Adenoviruses Therapeutic Efficacy and Toxicity
Authors: Tyler O. Kirby, Angel Rivera, Daniel Rein, Minghui Wang, Ilya Ulasov, Martina Breidenbach, Manjula Kataram, Juan L. Contreras, Carlos Krumdieck, Masato Yamamoto, Marianne G. Rots, Hidde J. Haisma, Ronald D. Alvarez, Parameshwar J. Mahasreshti, David T. Curiel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Current animal tumor models are inadequate for the evaluation of toxicity and efficacy of conditionally replicative adenoviruses. A novel model system is needed that will provide insight into the anticipated therapeutic index of conditionally replicative adenoviruses preclinically. We endeavored to show a novel model system, which involves ex vivo evaluation of conditionally replicative adenovirus toxicity and therapeutic efficacy in thin, precision-cut slices of human primary tumor and liver. Experimental Design: The Krumdieck thin-slice tissue culture system was used to obtain and culture slices of tumor xenografts of ovarian cancer cell lines, human primary ovarian tumors, and human liver. We determined the viability of slices in culture over a period of 36 to 48 hours by ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxphenyl-2-(4-sulfophenyl)-2H-tetrazolium, inner salt)]) (MTS) assay. In vitro Hey cells, slices of Hey xenografts, and human ovarian tumor or human liver slices were infected with 500vp/cell of either replication competent wild-type adenovirus (Ad5/3wt), conditionally replicative adenovirus (Ad5/3cox-2), or the replication deficient adenovirus (Ad5/3luc1). At 12-, 24-, and 36-hour intervals, the replication of adenoviruses in these slices was determined by quantitative reverse transcription-PCR of adenoviral E4 copy number. Results: Primary tumor slices were able to maintain viability for up to 48 hours after infection with nonreplicative virus (Ad5luc1). Infection of Hey xenografts with Ad5/3cox-2 showed replication consistent with that seen in Hey cells infected in an in vitro setting. Primary tumor slices showed replication of both Ad5/3wt and Ad5/3cox over a 36-hour time period. Human liver slices showed replication of Ad5/3wt but a relative reduction in replication of Ad5/3cox-2 indicative of conditional replication “liver off” phenotype, thus predicting lower toxicity. Conclusions: The thin-slice model system represents a stringent method of ex vivo evaluation of novel replicative adenoviral vectors and allows assessment of human liver replication relative to human tumor replication. This is the first study to incorporate this system for evaluation of therapeutic efficacy and replicative specificity of conditionally replicative adenoviruses. Also, the study is the first to provide a valid means for preclinical assay of potential conditionally replicative adenovirus-based hepatotoxicities, thus providing a powerful tool to determine therapeutic index for clinical translation of conditionally replicative adenoviruses.
Twisting tails exposed
Authors: Susan E. Levin, Arthur Weiss
Journal: The Journal of Experimental Medicine (2005)

The mechanism by which the ligand occupancy state of the T cell receptor complex is converted into intracellular signaling information has been a controversial topic. Although the majority of structural studies argue against a conformational change, recent studies support the possibility for such a change within the CD3 components of the TCR complex. In this commentary, the evidence for TCR conformational change is reviewed and potential mechanisms for its initiation are explored.
Aminoguanidine inhibits advanced glycation end products formation on beta2-microglobulin.
Authors: F F Hou, J Boyce, G M Chertow, J Kay, W F Owen
Journal: Journal of the American Society of Nephrology (1998)

Because advanced glycation end products (AGE)-modified beta2-microglobulin (AGE-beta2M) is a dominant constituent of amyloid in dialysis-related amyloidosis (DRA), AGE-beta2M may be directly involved in the pathobiology of DRA. In experimental diabetes mellitus, blocking the formation of AGE prevents AGE-mediated tissue damage. In this study, it is postulated that similar pharmacologic intervention may be beneficial in DRA. Aminoguanidine, a nucleophilic hydrazine compound that prevents AGE formation on collagen, may have a similar effect on the advanced glycation of beta2M. To test this hypothesis, beta2M was incubated in vitro with 50 or 100 mM D-glucose for 3 wk in the presence and absence of incremental concentrations of aminoguanidine. On the basis of enzyme-linked immunosorbent assay and immunoblots using anti-AGE-keyhole limpet hemocyanin antibody, aminoguanidine inhibited glucose-induced N(epsilon)-(carboxymethyl)lysine formation on beta2M. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, 26 to 53% inhibition occurred. Fluorospectrometry examination showed that aminoguanidine also inhibited the formation of fluorescent AGE on beta2M in a dose-dependent manner. At aminoguanidine-glucose molar ratios of 1:8 to 1:1, fluorescent product generation was inhibited by 30 to 70%. Furthermore, aminoguanidine suppressed the AGE formation on beta2M bound to AGE-modified collagen. If aminoguanidine is similarly active in vivo, this compound may be of clinical utility for treating DRA in patients on maintenance dialysis.
Plasma amino-terminal pro-brain natriuretic peptide and accuracy of heart-failure diagnosis in primary care
Authors: Susan P. Wright, Robert N. Doughty, Ann Pearl, Greg D. Gamble, Gillian A. Whalley, Helen J. Walsh, Gary Gordon, Warwick Bagg, Helen Oxenham, Tim Yandle, Mark Richards, Norman Sharpe
Journal: Journal of the American College of Cardiology (2003)
P98 Cervical TB lymphadenitis: A predominantly right-sided phenomenon due to ascending infection from the thorax
Authors: FV Cresswell, B Vijayakumar, L John, RN Davidson
Journal: Thorax (2013)

<h3>Introduction</h3> Cervical Tuberculous (TB) Lymphadenitis is the commonest presentation of extrapulmonary TB. There is however little evidence about its aetiology; consensus is divided as to whether it arises from infection via the pharyngeal lymphoid ring or from thoracic infection. Our clinical suspicions were that it is most frequently a right-sided phenomenon as a result of <i>Mycobacterium Tuberculosis</i> ascending the right paratracheal chain following pulmonary inoculation. <h3>Methods</h3> We explored this hypothesis by retrospectively reviewing 211 cases of cervical TB lymphadenitis diagnosed at Northwick Park Hospital in London. We assessed clinical findings, neck ultrasound findings, chest radiograph findings and explored the literature to see what other evidence exists to support or refute this hypothesis. <h3>Results</h3> Clinical assessment found that 62.1% (P &lt; 0.0001) cases had right-sided disease, 28.9% left-sided and 9.0% bilateral. Of the 153 ultrasound scans available, 62% showed supraclavicular lymphadenitis (levels IV&amp;V nodes) and only 9.5% submental/submandibular lymphadenitis (level I nodes). 205 chest x-rays were studied, the most frequent abnormality was lymphadenopathy (40/205), including 25 paratracheal lymphadenopathy (23/25 right-sided). Notably, 22/23 patients with right paratracheal lymphadenopathy had right-sided cervical lymphadenitis. <h3>Discussions</h3> Our findings suggest that ascending infection from the thorax via the paratracheal chain following pulmonary inoculation plays the greatest role in the aetiology of cervical lymphadenitis. We explain this using anatomical studies. Infection via the pharynx may be implicated in those exhibiting upper cervical lymphadenitis. In some low-resource setting where TB may be diagnosed on clinical grounds alone, knowledge that right-sided supraclavicular nodes are the most frequently affected may add confidence to clinical decision-making.
Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.
Authors: M Santos, M W Schilham, L H Rademakers, J J Marx, M de Sousa, H Clevers
Journal: The Journal of Experimental Medicine (1996)

Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.
A3 Adenosine Receptor Ligands: History and Perspectives
Authors: Pier Giovanni Baraldi, Barbara Cacciari, Romeo Romagnoli, Stefania Merighi, Katia Varani, Pier Andrea Borea, Giampiero Spalluto
Journal: Medicinal Research Reviews (2000)

Adenosine regulates many physiological functions through specific cell membrane receptors. On the basis of pharmacological studies and molecular cloning, four different adenosine receptors have been identified and classified as A1, A2A, A2B, and A3. These adenosine receptors are members of the G-protein-coupled receptor family. While adenosine A1 and A2A receptor subtypes have been pharmacologically characterized through the use of selective ligands, the A3 adenosine receptor subtype is presently under study in order to better understand its physio-pathological functions. Activation of adenosine A3 receptors has been shown to stimulate phospholipase C and D and to inhibit adenylate cyclase. Activation of A3 adenosine receptors also causes the release of inflammatory mediators such as histamine from mast cells. These mediators are responsible for processes such as inflammation and hypotension. It has also been suggested that the A3 receptor plays an important role in brain ischemia, immunosuppression, and bronchospasm in several animal models. Based on these results, highly selective A3 adenosine receptor agonists and/or antagonists have been indicated as potential drugs for the treatment of asthma and inflammation, while highly selective agonists have been shown to possess cardioprotective effects. The updated material related to this field of research has been rationalized and arranged in order to offer an overview of the topic. © 2000 John Wiley & Sons, Inc. Med Res Rev, 20, No. 2, 103–128, 2000
QT interval variability and spontaneous ventricular tachycardia or fibrillation in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients
Authors: Mark C. Haigney, Wojciech Zareba, Philip J. Gentlesk, Robert E. Goldstein, Michael Illovsky, Scott McNitt, Mark L. Andrews, Arthur J. Moss
Journal: Journal of the American College of Cardiology (2004)
Being Mindful of Later-Life Sleep Quality and Its Potential Role in Prevention
Authors: Adam P. Spira
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal