tbuckley/cabot-search huggingface dataset:
Abstract 742: Development of novel naphthalimide derivatives as potential melanoma therapeutics
Authors: Ugir Hossain Sk, A.S. Prakasha Gowda, Melissa A. Gimbor, Raghavendra Gowda, Gavin P. Robertson, Thomas E. Spratt, Jong K. Yun, Shantu Amin, Arun K. Sharma
Journal: Cancer Research (2010)

Abstract Over the years, several naphthalimide analogs with varying efficacy have been reported as having promising anti-cancer properties. Some analogs such as mitonafide, a tolemerase inhibitor, have shown an interesting antitumor activity both preclinically and in phase I and phase II clinical trials. However, it suffers from severe toxicity issues, especially central nervous system (CNS) toxicity. Because of toxicity issues, mitonafide could only be delivered by i.v. infusion, and still CNS toxicity is a major issue. This problem was overcome by adapting a delivery strategy of 5 days continuous infusion, but this regimen was not effective in NSCLC or colorectal cancer patients, while still having severe myelotoxicity in the latter case. These observations warranted optimization of mitonafide structure by adding appropriate functional groups that could help reduce systemic toxicity, while keeping the key naphthalimide moiety intact. We hypothesized that incorporation of functional groups such as isothiocyanate group which is present various naturally occurring agents found in cruciferous vegetables would enhance the bioavailability and reduce systemic toxicity levels. By analogy, isoselenocyanate group which has recently been shown by us to follow a similar mechanism with enhanced potency was also introduced. Furthermore, we also synthesized a series of mitonafide analogs with functional alterations such as thiourea and selenourea in place of N,N-dimethyl functionality in mitonafide, with or without nitro substitution. Interestingly, all the sulfur analogs [IC50 (72 h): 2-9 uM] were more cytotoxic than their corresponding selenium derivatives [IC50 (72 h): 11-24 uM], as observed by the MTS assay in various human melanoma cell lines. This was in sharp contrast to our earlier studies, where isosteric selenium analogs were more effective in killing multiple cancer cells and about 3 times more effective in inhibiting melanoma tumor development. Furthermore, the sulfur analogs effectively induced apoptosis in UACC 903 human melanoma cells. Nitro substitution or increase in alkyl chain length did not seem to make any significant difference in the activity of these compounds. Though the IC50 values were 2-4 times lower for mitonafide [IC50 (72 h): 1-2 uM] compared to novel isothiocyante or thiourea derivatives, these new derivatives were well tolerated when injected i.p. in mice everyday for a month. The new naphthalimide derivatives thus hold solid promise as melanoma therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 742.
Pericardial Effusion
Authors: FRIEDA SILVA, LOURDES GARCÍA, CHARLIE FLORES, DAVID STORER, FRANCISCO AGUILÓ
Journal: Clinical Nuclear Medicine (1996)

A case in which a prolonged hypothyroid state resulted in development of a pericardial effusion is presented. The compensatory mechanism for protein homeostasis is lost in severe hypothyroidism. Iodine is transported to the pericardial space, which is filled with a high-protein content fluid and remains trapped. The mechanism for the accumulation of the fluid in the pericardial space is discussed. To prevent this unusual but dangerous complication, the authors recommend close monitoring of the patient's clinical status and serum thyroid stimulating hormone. The use of a short acting thyroxine substitute for at least 2 weeks can decrease occurrence of this complication and will shorten the time the patient needs to be hypothyroid.
Cardiovascular risk and attitudes to lifestyle: what do patients think?
Authors: C Silagy, J Muir, A Coulter, M Thorogood, L Roe
Journal: BMJ (1993)

OBJECTIVE--To examine the relation between subjects9 level of cardiovascular risk and their beliefs about the harmfulness of their smoking habit, current diet, and level of exercise, together with their stated desire to modify such behaviour. DESIGN--Self administered postal health and life-style questionnaire followed by a structured health check conducted by a nurse. SETTING--Five general practices in Luton and Dunstable, Bedfordshire. SUBJECTS--5803 people aged 35-64 years enrolled in the OXCHECK trial who attended for a health check before 1 March 1992. MAIN OUTCOME MEASURES--Perceived risk to health of lifestyle behaviours, desire to modify behaviour, and a reported serious attempt to modify behaviour in the preceding year. RESULTS--A high proportion of smokers and those who were physically inactive perceived their behaviour to be harmful (1020; (76%; 95% confidence interval 74% to 79%) and 350 (74%; 70% to 78%) respectively) and wished to modify it (1212 (79%; 77% to 81%) and 375 (74%; 71% to 78%) respectively). In contrast, only 289 (45%; 41% to 48%) of obese people and 188 (14%; 12% to 16%) of people with a high dietary fat intake perceived their current diet to be harmful. The more cardiovascular risk factors present, the more likely subjects were to perceive a health risk attached to their diet and lack of exercise (p &lt; 0.01 in both cases) and to want to improve their diet. CONCLUSION--Awareness of the health risk from smoking and motivation to stop is high. Further efforts are required, however, to educate the public about the risks associated with a high dietary fat intake. Although the health risks of inactivity were widely recognised, motivation to take more exercise needs to be increased.
The Spanish experience of public-private partnerships with the drinks and food industries
Authors: M. A. Royo-Bordonada
Journal: BMJ (2014)

Gornall shows how the drinks industry strongly influences public health policy.1 It seems that the public health responsibility deal favoured corporations by giving them privileged access to the health policy table and the opportunity to co-finance government health promotion campaigns. The Spanish government may be following a similar path.

On 19 December 2013 the Ministry of Health launched an underage drinking prevention campaign funded by the Spanish Spirits Federation. …
The kindness of strangers
Authors: Fiona Godlee
Journal: BMJ (2005)

On the fourth anniversary of 9/11, Americans find themselves once again counting the cost of an unimaginable catastrophe. This time though, the world has looked on not in awe at the human spirit arising from the ashes of the Twin Towers, but in shock and shame at the sight of the world's richest country doing so little so late for its poorest people. The fallout from Hurricane Katrina will be weighed in thousands of lives lost and many more thousands wrecked (pp 526, 531, 582), and in further damage to America's reputation around the world.

When the US …
Do Ganglion-Blocking Agents and Reserpine Affect Central Vasomotor Activity?
Authors: JAMES W. MCCUBBIN, IRVINE H. PAGE
Journal: Circulation Research (1958)

In a majority of experiments on both dogs and cats, hypotensive doses of tetraethylam-monium chloride or mecamylamine caused no change or moderate increase in efferent electric activity in the largely preganglionic thoracic portion of the splanchnic nerve, and caused complete and prolonged elimination of efferent activity in the postganglionic inferior cardiac and renal nerves. Both drugs failed to suppress changes in splanchnic nerve activity that were elicited refiexly. These results imply strongly that both ganglion-blocking drugs, in dosage used intravenously to induce hypotension, act mainly through their peripheral effects rather than through one on central vasomotor synapses. In both dogs and cats, reserpine caused slowly progressive and marked diminution in efferent splanchnic nerve activity, which supports the hypothesis that the central action of this agent contributes to its hypotensive effect.
Serum and Cerebrospinal-Fluid Transaminase Concentrations in Various Neurologic Disorders
Authors: Ralph M. Myerson, J. K. Hurwitz, Theodore Sall
Journal: New England Journal of Medicine (1957)

THE enzyme glutamic oxalacetic transaminase (GOT) is widely distributed in animal tissues but appears to be most concentrated in the myocardium, liver, skeletal muscle, brain and kidney.1 2 3 It has been repeatedly demonstrated that a rise in the serum level of GOT follows acute damage to the myocardium, liver and skeletal muscle. Relatively little work has been done on the effect of neurologic disorders on GOT levels. Wakim and Fleisher4 have demonstrated that experimental cerebral infarction in dogs leads to a marked increase in the activity of GOT in cerebrospinal fluid roughly proportional to the extent and severity of the infarct. . . .
When the heart sleeps... Is the vagus resetting the myocardial 'redox clock'?
Authors: C. Vecoli, N. Paolocci
Journal: Cardiovascular Research (2007)

> “…living in the very copper rigging and secular miracle of communication 
> 
> untroubled by the dumb voltages flickering their miles, the night long 
> 
> in the thousands of unheard messages” .
> 
> Thomas Pynchon, from The Crying of Lot 49 (1966) The Crying of Lot 49 
Reactive oxygen species (ROS) are main actors in the evolving drama of congestive heart failure (CHF),1 a neuroendocrine disorder in which excess ROS signalling contributes to sympathetic efferent fibre hyperactivation.2 Enhanced sympathetic outflow favours arrhythmias, myocardial remodelling/dysfunction and premature death ( Figure 1 ), thus having pathogenetic and prognostic meaning. However, the sympathetic ‘arm’ of the autonomic nervous system (ANS) acts not only as a ‘victim’ of ROS but also as an ‘executioner’ of further ROS-induced myocardial damage. Indeed, spill-over of catecholamines and other hypertrophic agents such as serotonin, angiotensin II, and endothelin-1 may amplify oxidative stress via their own enhanced catabolism and/or ROS-induced ROS release from mitochondria, triggering apoptosis and cell death. Yet, many unknowns still surround the ANS–ROS ‘bi-univocal’ relationship in CHF. One is the role of the parasympathetic (vagal) component. Vagal nerve stimulation (VNS) limits the frequency of lethal ventricular arrhythmias in dogs,3 and in rats it attenuates cardiac remodelling and improves survival.4 The mechanisms for the latter, however, remain elusive.



 Figure 1  
Schematic representation of the contribution of sympathetic efferent overflow, NO and reactive oxygen species (ROS) in the pathogenesis of congestive heart failure (CHF). Some of the possible sites for the intervention of vagal efferent/afferent fibres (and their mediators) to brake the effects of the ‘sympathetic-ROS axis’ on heart structure and function are also depicted.



In the current issue of Cardiovascular Research … 

*Corresponding author. Tel: +1 410 502 6165; fax: +1 410 502 2558. E-mail address : npaoloc1{at}jhmi.edu
Detection and distribution of hepatitis C—specific antigens in naturally infected liver
Authors: Keril Blight, Richard R. Lesniewski, Justin T. Labrooy, Eric J. Gowans
Journal: Hepatology (1994)

Hepatitis C virus antigen expression was examined using peptide antibodies in liver tissue taken at biopsy from four chronic carriers of hepatitis C virus. Hepatitis C virus antigens E2/NS1, NS3, NS4 and NS5 were widespread in unfixed frozen liver sections and were present as distinct granules or foci within the cytoplasm of hepatocytes and in infiltrating lymphocytes in portal tracts. Fixation of frozen sections with 1% formalin improved the histological appearance of the tissue section without reducing the sensitivity of antigen detection. However, in tissue sections fixed in acetone, chloroform, carbon tetrachloride or methyl carnoys, detection of all hepatocyte-specific hepatitis C virus antigens was significantly reduced. Dual immunostaining of liver sections for lymphocyte cluster of differentiation markers and hepatitis C virus antigens determined that a high proportion of cluster of differentiation 20-positive B cells and cluster of differentiation 4-and cluster of differentiation 8-positive T cells, predominant in lymphoid aggregates, were positive for hepatitis C virus antigens.
VARIABILITY OF FRACTIONAL FLOW RESERVE ACCORDING TO THE VARIOUS METHODS TO INDUCE HYPEREMIA
Authors: Woo-Hyun Lim, Bon Kwon Koo, Chang-Wook Nam, Joon Hyung Doh, Chee Hae Kim, Ji-Hyun Jung, Jin Joo Park, Jung-kyu Han, Han-Mo Yang, Kyung Woo Park, Hyo-Soo Kim, Hiroaki Takashima, Katsuhisa Waseda, Tetsuya Amano, Daiki Kato, Akiyoshi Kurita, Young-Bae Park
Journal: Journal of the American College of Cardiology (2014)
Use of Sniff Nasal-Inspiratory Force to Predict Survival in Amyotrophic Lateral Sclerosis
Authors: Ross K. Morgan, Stephen McNally, Michael Alexander, Ronan Conroy, Orla Hardiman, Richard W. Costello
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Respiratory muscle weakness is the usual cause of death in amyotrophic lateral sclerosis. The prognostic value of the forced vital capacity (FVC), mouth-inspiratory force, and sniff nasal-inspiratory force were established in a group of 98 patients with amyotrophic lateral sclerosis who were followed trimonthly for 3 years. Sniff nasal-inspiratory force correlated with the transdiaphragmatic pressure (r = 0.9, p < 0.01). Sniff nasal-inspiratory force was most likely to be recorded at the last visit (96% of cases), compared with either the FVC or mouth-inspiratory force (86% and 81%, respectively, p < 0.01). A sniff nasal-inspiratory force less than 40 cm H(2)O was significantly related with nocturnal hypoxemia. When sniff nasal-inspiratory force was less than 40 cm H(2)O, the hazard ratio for death was 9.1 (p = 0.001), and the median survival was 6 +/- 0.3 months. The sensitivity of FVC < 50% for predicting 6-month mortality was 58% with a specificity of 96%, whereas sniff nasal-inspiratory force less than 40 H(2)O had a sensitivity of 97% and a specificity of 79% for death within 6 months. Thus the sniff nasal-inspiratory force test is a good measure of respiratory muscle strength in amyotrophic lateral sclerosis, it can be performed by patients with advanced disease, and it gives prognostic information.
Neurone-specific enolase and S-100: new markers for delineating the innervation of the respiratory tract in man and other mammals.
Authors: M N Sheppard, S S Kurian, S C Henzen-Logmans, F Michetti, D Cocchia, P Cole, R A Rush, P J Marangos, S R Bloom, J M Polak
Journal: Thorax (1983)

Lung innervation has been studied in the past by methylene blue staining and silver impregnation and more recently by histochemical methods. These techniques give only a partial picture of the total innervation. We have delineated the innervation of the lung in man and three other mammalian species by immunostaining with antibodies to two new markers of nervous tissue. These markers are neurone-specific enolase (NSE), an enzyme present in nerve cells in both the central and the peripheral nervous systems, and S-100, a protein found in glial cells. Throughout the respiratory tract NSE was localised in ganglion cells and nerve fibres in all species examined, while S-100 was found in the supporting glial cells of ganglia and in Schwann cells of peripheral nerves. The distribution of NSE immunoreactivity in serial sections was compared with that of acetylcholinesterase-containing, noradrenergic, and peptide-containing nerves. In all areas NSE was found to be a specific marker for all three types of nerves. Thus these two antibodies provide an effective histological means of examining both the neuronal and the non-neuronal components of the lung innervation and should be of value in investigating this system in lung disease.
New Report Rejects Accrediting of Those Who Provide Ethics Consultation Services
Authors: Donald F. Phillips
Journal: JAMA (1999)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of amlodipine, atenolol and their combination on myocardial ischemia during treadmill exercise and ambulatory monitoring
Authors: Richard F. Davies, Habibullah Habibi, W. Peter Klinke, Pierre Dessain, Claude Nadeau, Denis C. Phaneuf, Serge Lepage, Sankaranarayanan Raman, Margaret Herbert, Kathy Foris, Wolfgang Linden, Jennifer A. Buttars
Journal: Journal of the American College of Cardiology (1995)
Cyproheptadine displays preclinical activity in myeloma and leukemia
Authors: Xinliang Mao, Sheng-ben Liang, Rose Hurren, Marcela Gronda, Sue Chow, G. Wei Xu, Xiaoming Wang, Reza Beheshti Zavareh, Nazir Jamal, Hans Messner, David W. Hedley, Alessandro Datti, Jeff L. Wrana, Yuanxiao Zhu, Chang-xin Shi, Kyle Lee, Rodger Tiedemann, Suzanne Trudel, A. Keith Stewart, Aaron D. Schimmer
Journal: Blood (2008)
The Literature of Medicine: Reviews, Notes, and Listings: Pulmonary Medicine: The Airway
Authors: Daniel F. Danzl
Journal: Annals of Internal Medicine (1993)

Corrections15 April 1993Correction: Page count for The Airway: Emergency ManagementFREEDaniel F. Danzl, MDDaniel F. Danzl, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-8-199304150-00034 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the 1 February 1993 issue of Annals, an incorrect page count was given for The Airway: Emergency Management by Robert H. Dailey, Barry Simon, Gary P. Young, and Ronald D. Stewart. The correct page count for this $64.00 book is 385.REFERENCE1. Danzl DF. The Airway: Emergency Management. Ann Intern Med. 1993; 118:239. Google Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 April 1993Volume 118, Issue 8Page: 653 ePublished: 15 August 2000 Issue Published: 15 April 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE NEGRI BODIES IN RABIES
Authors: Ernest M. Watson
Journal: The Journal of Experimental Medicine (1913)

1. The Negri bodies, as the etiological agent in rabies, present two general types or phases in morphology, in growth, and in reproduction. 2. These two phases are constantly cyclic in their development and correspond (1) to a multiplicative, or schizogonous, and (2) to a reproductive, or sporogonous, life cycle. 3. By the detailed study of these forms and their succeeding stages we are inclined to believe that the Negri bodies are definite protozoan parasites, and from a study of their life history we are led to place them in the suborder of Cryptocysts, or Microsporidia, of the Sporozoa, and more definitely among the Oligosporogenea of the Glugeidae family, which forms produce but one pansporoblast. With the recent advances in the growth of tissues outside the body, particularly the work of Carrel, Burrows, Harrison, Lewis and Lewis, and Rous upon the infectiousness of tumor extracts, with the results of Noguchi in cultivating pathogenic Treponema pallidum, important discoveries concerning the Negri bodies will undoubtedly be made in the near future.
GSK's head of finance in China is banned from leaving the country
Authors: J. Parry
Journal: BMJ (2013)

UK national Steve Nechelput, the head of finance for GlaxoSmithKline’s China operations, has been barred from leaving the country since the end of June as investigations into widespread bribery by GSK executives continue.

A GSK spokesperson said, “We have been aware of the travel restrictions on Steve since the end of June. At no point has he been questioned, arrested or detained. He …
Interchange of Licenses.
Authors: Chas. S. Stockton
Journal: JAMA (1903)

Newark, N. J., Nov. 20, 1903. <h3>To the Editor:</h3> —At the meeting of the National Board of Dental Examiners, held at Nashville, N. C., last August, the following resolution was unanimously adopted after full discussion: <i>Resolved</i>, That an interchange of license to practice dentistry be, and is hereby recommended to be. granted by the various state boards, on the following specific conditions: Any dentist who has been in legal practice for five years or more, and is a reputable dentist of good moral character, and who is desirous of making a change of residence into another state, may apply to the examining board of the state in which he resides, for a new certificate which shall attest to his moral character and professional attainments, and said certificate, if granted, shall be deposited with the examining board of the state in which he proposes to reside, and the said board, in
Right or Left Ventricular Pacing in Young Minipigs With Chronic Atrioventricular Block
Authors: Aida Salameh, Stefan Dhein, Katja Blanke, Ardawan Rastan, Bahi Hiyasat, Anna Dietze, Axel Sobiraij, Ingo Dähnert, Jan Janousek
Journal: Circulation (2012)

Left ventricular (LV) dyssynchrony may occur as a result of right ventricular (RV) pacing and is a known risk factor for the development of heart failure. In children with complete atrioventricular block, pacing-induced dyssynchrony lasting for decades might be especially deleterious for LV function. To determine the hemodynamic and ultrastructural remodeling after either RV free wall or LV apical pacing, we used a chronic minipig model.Fourteen piglets 8 weeks of age underwent atrioventricular node ablation and were paced from either the RV free wall or the LV apex at 120 bpm for 1 year (7 age-matched minipigs served as controls with spontaneous heart rates of 104 ± 5 bpm). Echocardiographic examinations, pressure-volume loops, patch-clamp investigations, and examinations of connexin43, calcium-handling proteins, and histomorphology were carried out. RV free wall-paced minipigs exhibited significantly more LV dyssynchrony than LV apex-paced animals, which was accompanied by worsening of LV function (maximum LV mechanical delay/LV ejection fraction: RV free wall pacing, 154 ± 36 ms/28 ± 3%, LV apical pacing, 52 ± 19 ms/45 ± 2%, control 47 ± 14 ms/62 ± 1%; P=0.0001). At the cellular level, both pacemaker groups exhibited a significant reduction in L-type calcium and peak sodium current, shortening of action potential duration and amplitude, increased cell capacity, and alterations in the calcium-handling proteins that were similar for RV free wall- and LV apex-paced animals.The observed molecular remodeling seemed to be more dependent on heart rate than on dyssynchrony. LV apical pacing is associated with less dyssynchrony, a more physiological LV contraction pattern, and preserved LV function as opposed to RV free wall pacing.