tbuckley/cabot-search huggingface dataset:
Abstract 4497: NVP-BKM120, a novel inhibitor of phosphoinosotide 3-kinase in Phase I/II clinical trials, shows significant antitumor activity in xenograft and primary tumor models
Authors: Michel Maira, Daniel Menezes, Sabina Pecchi, Kevin Shoemaker, Matthew Burger, christian Schnell, christine Fritsch, Saskia Brachmann, Tobi Nagel, William R. Sellers, Carlos Garcia-Echeverria, Marion Wiesmann, charles F. Voliva
Journal: Cancer Research (2010)

Abstract A substantial number of epidemiological and experimental studies support an important role for PI3K in the biology of human cancer. The activation of PI3K, and its downstream effectors, has been clearly validated as an essential step for the initiation and maintenance of the tumorigenic phenotype. Parallel to the clinical development of our dual pan-PI3K/mTOR modulators (e.g., NVP-BEZ235), we continued our drug discovery activities to identify PI3K inhibitors with distinct biological and pharmacological profiles. Following a structure-based design strategy, we have identified a new clinical candidate, NVP-BKM120. This 2,6-dimorpholino pyrimidine derivative is a potent pan-PI3K (e.g., IC50= 35 nM, p110α) that does not significantly inhibit other protein or lipid kinases (e.g., IC50= 4.6 μM, mTOR). The compound exhibits potent antiproliferative activity against a broad panel of tumour cell lines by specifically blocking the biological function of PI3K signaling components (e.g. IC50 = 93 nM S473P-Akt in Rat1-p110α cells). The activity of this pan-PI3K inhibitor in cellular settings translates well in in vivo models of human cancer. NVP-BKM120 shows good oral bioavailability in preclinical species and demonstrated significant antitumor activity (growth inhibition or regression) at tolerated doses in xenografts of diverse cancer lineage in mice and rat models. Consistent with its mechanism of action, transient increases in plasma insulin and glucose levels are observed in these studies. Analyses of tumor tissues after acute dosing or at the end of efficacy studies showed a good correlation between compound exposure, PI3K pathway blockade (reduction in P-Akt levels) and antitumor activity. Dose dependent tumor growth delay or regression is also observed in primary tumor models, and, as demonstrated previously with our dual pan-PI3K/mTOR inhibitor NVP-BEZ235, in vivo synergistic activity is observed when NVP-BKM120 is combined with a MEK inhibitor in K-Ras human cancer models. NVP-BKM120 is currently undergoing Phase I/II human clinical trials for the treatment of solid tumors and hematological malignancies. 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 4497.
Cigarette Smoking and Increased Central Adiposity
Authors: Elizabeth Barrett-Connor
Journal: Annals of Internal Medicine (1989)

Study Objective: To determine whether cigarette smoking is associated with central obesity in men and women. Design: A cross-sectional survey. Setting: A geographically defined population of older white adults. Participants: Men (836) and women (1112) ages 50 to 79. Interventions: None. Measurements and Main Results: Waist-hip circumference ratio and body mass index (weight in kg/height in m2) were measured in participants wearing light clothing without shoes. Past and current cigarette smoking habits were ascertained by a standard self-administered questionnaire. Cigarette smokers had higher waist-hip ratios than nonsmokers. We observed a dose-response relation of increasing waist-hip ratio with increasing number of cigarettes smoked. Although smokers were leaner than nonsmokers, the increased waist-hip ratio in smokers was independent of body mass index and was consistent within body-mass index tertiles. The associations, seen in both sexes, were stronger in women. Conclusions: Cigarette smokers have more central obesity than nonsmokers. These results suggest that body fat distribution can be modified by behavioral factors such as smoking.
Biomarkers in COPD: time for a deep breath
Authors: R A Stockley
Journal: Thorax (2007)

PCD are slowly being unravelled, owing to the multiple phenotypes of the disease and more than 200 different proteins used to construct the ciliary axoneme, it is likely to be some time before such tests are widely used in the diagnostic examination of patients with PCD.The diagnostic service is able to accept appropriate referrals from hospital consultants.However, the service does not extend to providing care for patients diagnosed with PCD.As experience of care for patients with PCD is limited, we would suggest a model similar to that for CF where patients should have access to a specialist paediatric respiratory consultant or thoracic physician with an interest in CF or non-CF bronchiectasis and be followed up regularly for life.The diagnostic service will allow a national database of patients with PCD to be established, facilitating clinical trials to help provide an evidence base for management.An active PCD patient and parent support group has been established which we encourage newly diagnosed patients to contact (www.pcdsupport.org.uk).
2',5'-oligoadenylate synthetase induction in lymphocytes of patients with connective tissue diseases.
Authors: W Hylton, J Cayley, C Dore, A.M Denman
Journal: Annals of the Rheumatic Diseases (1986)

Spontaneous production of the interferon induced enzyme 2',5'-oligoadenylate synthetase (2',5'-A synthetase) was significantly greater in blood lymphocytes of patients with systemic lupus erythematosus (SLE), Behçet's syndrome, and rheumatoid arthritis than in control lymphocytes. Alpha interferon (IFN-alpha) induced comparable production of enzyme in normal, rheumatoid, and Behçet's lymphocytes, and reduced, but still appreciable amounts in SLE lymphocytes. Phytohaemagglutinin (PHA) did not induce enzyme. Thus spontaneous production of 2',5'-A synthetase is encountered in several connective tissue diseases and seems likely to be induced by in-vivo exposure to interferons.
Atrioventricular conduction disturbances during hypoxia. Possible role of adenosine in rabbit and guinea pig heart.
Authors: L Belardinelli, F L Belloni, R Rubio, R M Berne
Journal: Circulation Research (1980)

Adenosine and related compounds can produce atrioventricular (A-V) conduction block. Similar conduction disturbances are observed in myocardial hypoxia. To investigate the possibility that adenosine might be causally involved in hypoxic conduction disturbances, we measured A-V conduction times, subdivided into atrial-to-His bundle (A-H) and His bundle-to-ventricular (H-V) intervals, with extracellular electrodes in isolated rabbit and guinea pig hearts perfused with modified Krebs-Henseleit solution. Adenosine produced dose-dependent prolongation of A-V conduction time in both species, although guinea pig hearts responded to lower doses (10(-7) M) and showed a steeper dose-response relationship than rabbit hearts. Higher adenosine doses produced second-degree heart block in both species. Conduction delay was confined to the A-H interval, implicating action on A-V node cells. Further investigation of guinea pig hearts revealed a specific antagonism towards adenosine's effects by 10(-5) M aminophylline. Conduction disturbances produced by acetylcholine or MnCl2 were unaffected by aminophylline as were adenosine's effects by atropine. Perfusion with hypoxic perfusate caused A-V conduction delays and second-degree block in guinea pigs hearts. This effect was dramatically attenuated by aminophylline. We conclude that endogenously released adenosine may cause at least some of the A-V conduction disturbances associated with acute myocardial hypoxia. Furthermore, methylxanthines may prove to be of therapeutic value in combatting such disturbances in a clinical setting.
Ethics: Kennedy Institute of Ethics Journal and CQ: Cambridge Quarterly of Healthcare Ethics: The International Journal for Healthcare Ethics Committees
Authors: G. D. Byrd
Journal: JAMA (1993)

<b>CQ: Cambridge Quarterly of Healthcare Ethics: The International Journal for Healthcare Ethics Committees</b>, David C. Thomasma, Thomasine Kushner, and Steve Heilig, editors, quarterly, $42 (personal), $84 (institutional), New York, NY, Cambridge University Press, winter 1992-. The field of bioethics and health care ethics, like most other biomedical disciplines, has grown rapidly over the past 15 to 20 years. This is clearly evidenced by the rapid growth of the literature. The most recent Kennedy Institute Scope Note on "Basic Resources in Bioethics" (published in the first issue of the<i>Kennedy Institute of Ethics Journal</i>) lists 14 core bioethics journals, not including the two reviewed here. These titles include well-established and highly respected journals like the<i>Hastings Center Report, American Journal of Law and Medicine, Journal of Clinical Ethics, and Linacre Quarterly</i>. Reviews of two other excellent new journals in this field appeared in<i>JAMA</i>during the past year.<sup>1,2</sup> Thus, with
Effectiveness of functional ankle taping for judo athletes: a comparison between judo bandaging and taping.
Authors: T Yamamoto, A Kigawa, T Xu
Journal: British Journal of Sports Medicine (1993)

This study was conducted to compare the effectiveness of the traditional method of ankle bandaging and the new method of ankle taping for judo athletes in Japan, and to introduce a functionally effective taping method for judo players. Four university judo athletes with ankle instability were selected to undertake radiography of the ankles before and after exercise, with bandaging at one time and taping at the other. Talar tilt (TT) angles were measured in order to compare the ankle-supporting effects. The results showed that the old ankle bandaging method had no role in eliminating the talar tilt during judo practice. In contrast, the new taping method was more effective in eliminating the talar tilt and supporting the involved ankles both mechanically and functionally.
Acid reflux event detection using the Bravo wireless versus the Slimline catheter pH systems: why are the numbers so different?
Authors: John Pandolfino, Qing Zhang, Mitchal Schreiner, Sudip Ghosh, Michael Roth, Peter J Kahrilas
Journal: Gut (2005)

<b>Objective:</b> This study analysed the relative accuracy of the Bravo wireless and the Slimline catheter-Mark III Digitrapper pH systems in the detection of acid reflux events. <b>Methods:</b> Twenty five asymptomatic subjects were studied. A Bravo capsule was placed 6 cm above the squamocolumnar junction (SCJ), marked by an endoclip, and a Slimline pH catheter was placed 5 cm above the manometrically localised lower oesophageal sphincter. The distance between the SCJ and each pH electrode was measured fluoroscopically. An in vivo pH reference was established using swallows of orange juice (pH 3.88). Concurrent pH data from the two systems were analysed in Excel spreadsheets. <b>Results:</b> Significantly more acid reflux events were reported by the Digitrapper system than the Bravo system (117.0 <i>v</i> 41.8). This was not explained by electrode position as there was no difference in median distance between the SCJ and either pH electrode (7.25 cm <i>v</i> 7.08 cm). The dominant source of discrepancy between systems was inaccuracy in electrode calibration and, after adjustment using the in vivo orange juice pH measurement, the discrepancy improved by 40%. However, discrepancy still existed and was most pronounced with short reflux events (1–15 s for the catheter, 1–17 s for the Bravo) associated with minimal intraoesophageal acidity and poor concordance between systems. <b>Conclusion:</b> Substantially more reflux events were reported by the Digitrapper system compared with the Bravo system; 40% of excess events were attributable to a flawed software scheme for electrode thermal calibration while most of the remainder were brief events with poor reproducibility between systems.
Hypnotism, Mesmerism and the New Witchcraft.
Authors: Ernest Abraham Hart
Journal: JAMA (1893)

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
Photosensitivity due to the ‘sunburn’ ultraviolet content of white fluorescent lamps
Authors: A. KOBZA, C.A. RAMSAY, I.A. MAGNUS
Journal: British Journal of Dermatology (2006)

Six photosensitive patients are described, who also showed skin sensitivity to white fluorescent lamps. The results of tests with monochromatic irradiation showed that all patients were very sensitive to the ‘sunburn’ part of the spectrum (300–320 nm) with a lowered minimal erythema dose and a delayed papular-type reaction. Tests with a number of cut-off glass filters demonstrated that the fluorescent lamp sensitivity in these patients was due to the small amount of ‘sunburn’ UVR emitted. Spectral power analysis of the lamps showed that, with the exposures used in our tests, sufficient 300–320 nm UVR is emitted to produce skin reactions in very sensitive persons.
Decreasing Mortality From Acute Biliary Diseases That Require Endoscopic Retrograde Cholangiopancreatography: A Nationwide Cohort Study
Authors: Paul D James, Gilaad G Kaplan, Robert P Myers, James Hubbard, Abdel Aziz Shaheen, Jill Tinmouth, Elaine Yong, Jonathan Love, Steven J Heitman
Journal: Clinical Gastroenterology and Hepatology (2013)
Progress in Medical Genetics, Vol. 1
Authors: C. Nash Herndon
Journal: JAMA (1961)

This volume is the first in a projected series, of which additional volumes are promised "as advances seem to require them." This series was undertaken with the purpose of providing a group of up-to-date summary papers, each covering a limited aspect of recent research. In it, the editor has assembled 8 summary papers, each written by recognized authorities in the field. The chapter on the hemoglobinopathies, by Donald L. Rucknagel and James V. Neel, is an outstanding summary of the voluminous literature concerned with the biochemistry, physiology, and genetics of sickle cell anemia, thalassemia, and other states associated with abnormal types of hemoglobin. The discussion of both environmental and genetic factors in the etiology of congenital malformations, by F. Clarke Fraser, should also be of particular interest to physicians. The fascinating associations that have been discovered in the ABO blood group and secretor factor with certain disease processes, particularly duodenal
Implantable Cardioverter-Defibrillators
Authors: Zachary Goldberger, Rachel Lampert
Journal: JAMA (2006)

Sudden cardiac death (SCD) is a major challenge facing contemporary cardiology. For an increasing number of patients, the current standard of care for the treatment and prevention of SCD is the implantable cardioverter-defibrillator (ICD). Since its introduction, there have been numerous advances in ICD technology, and indications for its use have expanded greatly in the past year.To highlight the evolving indications for and the numerous advances in ICD technology, with emphasis on primary and secondary prophylaxis of SCD.Electronic literature search of the Pubmed and MEDLINE databases from January 1996 to July 2005, using the Medical Subject Heading implantable defibrillator. Abstracts and titles were reviewed to identify English-language randomized controlled trials that included an ICD group and a non-ICD group and that had end points of all-cause mortality, cardiac death, and/or arrhythmic mortality as the main outcome. A further MEDLINE search was conducted to identify randomized controlled trials of cardiac resynchronization therapy (CRT) with a CRT and a non-CRT group (including both mortality and other end points). Other studies were included that clarify aspects of device function and other relevant issues. A total of 22 trials were identified.ICD implantation improves survival in patients with a history of life-threatening ventricular arrhythmia. More recent evidence shows that ICD implantation also improves survival as primary prophylaxis against SCD in patients at high risk for ventricular arrhythmias, including those with left ventricular ejection fraction (LVEF) of 35% or less and New York Heart Association class II or III heart failure and those with a history of myocardial infarction and LVEF of 30% or less. Cardiac resynchronization improves symptoms, quality of life, and survival for patients with advanced heart failure and intraventricular conduction delays and ventricular dyssynchrony.ICDs have been shown to improve survival as both primary and secondary prophylaxis in an expanding population of patients. Ongoing ICD research may continue to delineate groups with survival benefit from ICDs, and the use and indications of these devices in clinical practice will continue to expand.
Dynamic mammalian cardiogenesis investigated by high-resolution ultrasound in guinea pigs.
Authors: C Loeber, S J Goldberg, M J Hendrix, D J Sahn
Journal: Circulation (1983)

Ultrasonic cardiac imaging of human fetuses has been feasible only after 12 to 14 weeks gestation when the heart is completely formed.Our purpose was to develop a method of examining dynamic mammalian cardiogenesis with a high-resolution 9 MHz ultrasound scanner.Fetal guinea pig hearts were imaged in utero over the course of 10 days.All images were obtained after blastocyst implantation estimated to occur 8 days after fertilization with cardiogenesis occurring over the next 14 days.After laparotomies were performed on the gravid guinea pigs, sterile transducers were placed on their uterine horns and ultrasonic images were obtained.Further optical magnification of videotaped images was required to visualize cardiac details.Ten gravid guinea pigs were examined and three of 10 underwent serial imaging.The earliest cardiac images, recorded approximately 10 days after implanta- tion, demonstrated a partially fused heart tube, ventricle, bulbus cordis, and first aortic arch.During the next 24 hr looping of the heart, a primitive atrium and an unfused endocardial cushion structure were observed.Midway through the first week of cardiac development, ventricular and atrial septation and development of primitive atrioventricular valve tissue were imaged.At the end of the first week of cardiac development, more distinct endocardial cushion structure and atrial and ventricular septation were noted.Additionally, a functioning foraminal flap was observed.Midway through the second week of cardiac development, spiraling and division of the bulbus cordis were complete.Scanning electron microscopic examination verified the size and configuration of ultrasonically imaged struc- tures.The high-frequency imaging allowed dynamic recording of events in mammalian cardiogenesis.
Psychodynamic Aspects of Oral Contraception
Authors: Edward E. Wallach
Journal: JAMA (1968)

Emotional response to use of oral contraceptives results from numerous factors, basic among them are the attitudes of patient and husband towards (1) contraception, (2) pregnancy, and (3) sexuality. Concerns over potential side effects, subsequent fertility, and use of any medication are significant, as well as information received from the patient's physician, peers, and news media. The estrogenic and progestogenic components of oral contraceptives have been implicated in emotional alterations. Varied cyclic changes occurring throughout the menstrual cycle depend greatly upon metabolic effects and fluctuating levels of estrogens and progesterone. Therapeutic value has been attributed to oral contraceptives in management of psychiatric conditions, although depression has also been described in association with their use. Libido does not appear to be affected by these drugs.
Osteoporosis in Men with Hyperprolactinemic Hypogonadism
Authors: SUSAN L. GREENSPAN
Journal: Annals of Internal Medicine (1986)

To ascertain the effects of chronic hyperprolactinemia and testosterone deficiency on skeletal integrity in men, we measured forearm bone density and hormone concentrations in 18 men aged 30 to 79 who had prolactin-secreting pituitary tumors. We also measured vertebral bone density in 12 of the men. Patients with hyperprolactinemia had significant decreases in both forearm (p < 0.001) and vertebral bone density (p = 0.003) compared with age-matched controls. Cortical osteopenia was significantly related to the duration of hyperprolactinemia (p < 0.01) but not to the absolute levels of prolactin or androgens. Seven patients had longitudinal follow-up measurements of forearm bone density. Normalization of serum levels of prolactin or testosterone was associated with an increase in forearm bone density (p < 0.05). These data show that chronic hyperprolactinemia and testosterone deficiency in men have deleterious and previously unrecognized extragonadal effects that may be alleviated after normalization of hormone concentrations.
Liver transplantation in chronic viral B and C hepatitis
Authors: E. Moreno González, C. Loinaz, I. García, C. Lumbreras, R. Gómez, G. Moraleda, I. G-Pinto, F. Colina, C. Jiménez, V. Carreño, J. Bercedo, J. Ibáñez, N. Alberti, V. Maffettone
Journal: Journal of Hepatology (1993)
Neutrophil-mediated changes in vascular permeability are inhibited by topical application of aspirin-triggered 15-epi-lipoxin A4 and novel lipoxin B4 stable analogues.
Authors: T Takano, C B Clish, K Gronert, N Petasis, C N Serhan
Journal: Journal of Clinical Investigation (1998)

Neutrophil (PMN) activation is critical in inflammation and reperfusion injury, suggesting that PMN-directed therapies may be of clinical use. Here, leukotriene B4 (LTB4)-induced PMN influx in ear skin was equivalent between 5-lipoxygenase knockout and wild-type mice. To explore actions of lipoxin (LX) in PMN-mediated tissue injury, we prepared several novel LX stable analogues, including analogues of LXA4 and aspirin-triggered 15-epi-LXA4 as well as LXB4, and examined their impact in PMN infiltration and vascular permeability. Each applied topically to mouse ears inhibited dramatically PMN-mediated increases in vascular permeability (IC50 range of 13-26 nmol) with a rank order of 15(R/S)-methyl-LXA4 > 16-para-fluoro-phenoxy-LXA4 approximately 5(S)-methyl-LXB4 >/= 16-phenoxy-LXA4 > 5(R)-methyl-LXB4. These LX mimetics were as potent as an LTB4 receptor antagonist, yet results from microphysiometry with mouse leukocytes indicated that they do not act as LTB4 receptor level antagonists. In addition, within 24 h of delivery, > 90% were cleared from ear biopsies. Neither IL-8, FMLP, C5a, LTD4, nor platelet-activating factor act topically to promote PMN influx. When applied with LTB4, PGE2 enhanced sharply both infiltration and vascular permeability, which were inhibited by a fluorinated stable analogue of aspirin-triggered LX. These results indicate that mimetics of LXs and aspirin-triggered 15-epi-LXA4 are topically active in this model and are potent inhibitors of both PMN infiltration and PMN-mediated vascular injury.