tbuckley/cabot-search huggingface dataset:
Abstract 1261: A preneoplastic switch to glycolytic metabolism driven by a PI3K-induced transcriptional program
Authors: Valeria G. Antico Arciuch, Antonio Di Cristofano
Journal: Cancer Research (2011)

Abstract Most cancer cells exhibit a peculiar metabolic behavior, producing energy by aerobic glycolysis instead of oxidative phosphorylation (Warburg effect). Several oncogenes directly drive this switch modulating the levels and activity of, among others, Hexokinase II, Lactate Dehydrogenase A, Pyruvate Kinase M2, and Pyruvate Dehydrogenase Kinase 1. We have generated a Pten-/- mouse model in which the PI3K pathway is selectively activated in the thyroid epithelial cells, leading to hyperplasia which later progresses to follicular carcinoma. Using proteomics to identify proteins differentially expressed in early hyperplastic lesions, we have found that the levels of many tricarboxylic acid cycle proteins are down-regulated in mutant thyroids. Down-regulation of these proteins is due to reduced mRNA expression, and results in reduced oxidative phosphorylation and enhanced glycolysis (over 3-fold increase in lactate production in mutants vs. wt). Furthermore, although mutant thyroids cells have a normal number of mitochondria, the expression of most mitochondrially-encoded genes is heavily down-regulated. Strikingly, none of the genes and proteins classically associated with the Warburg effect is found deregulated in the mutant thyroid cells. Analysis of the expression of transcription factors and co-activators involved in cellular metabolism revealed that the decrease in TCA cycle and OXPHOS genes is due to a reduction in ERRα, ERRγ, PPARα and PPARγ levels. Conversely, none of the co-activators analyzed (PRC1, PGC-1α, and PGC-1β) exhibited changes in mRNA expression. Pharmacological and genetic PI3K inhibition in mouse tumor-derived thyroid cancer cell lines increased the expression levels of both TCA cycle OXPHOS genes. Moreover, it also increased mtDNA amount, suggesting that the transition from hyperplasia to cancer involves additional alterations of the metabolic machinery. Likewise, PI3K inhibition induced a marked decrease in lactate secretion. Finally, these thyroid cancer cell lines exhibited high sensitivity to glycolysis inhibitors such as 3-bromopyruvate. Based on these compelling data, we propose a novel mechanism leading to the Warburg effect in preneoplastic lesions: PI3K activation initiates a coordinated rearrangement of the expression of metabolic genes, which favors aerobic glycolysis at the expense of TCA/OXPHOS. The elucidation of this process will lead to innovative targeted approaches to selectively disrupt tumor progression, while preserving normal metabolism in non mutated cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1261. doi:10.1158/1538-7445.AM2011-1261
BMA calls for ban on smoking images that "keep the habit cool" among children
Authors: Z. Kmietowicz
Journal: BMJ (2008)

The BMA has called on the UK governments to introduce a raft of tough measures to protect young people from the positive images of smoking seen regularly in films and magazines and on television.

Film censors should have to take account of a movie’s pro-smoking content when deciding on its classification, the BMA recommends. And it should be a legal requirement that all films and television programmes that portray positive images of smoking be preceded by an advertisement against smoking.

The BMA believes that these and other policies could help to make …
Identification of the JNK Signaling Pathway as a Functional Target of the Tumor Suppressor PTEN
Authors: Igor Vivanco, Nicolaos Palaskas, Chris Tran, Stephen P. Finn, Gad Getz, Norman J. Kennedy, Jing Jiao, Joshua Rose, Wanling Xie, Massimo Loda, Todd Golub, Ingo K. Mellinghoff, Roger J. Davis, Hong Wu, Charles L. Sawyers
Journal: Cancer Cell (2007)
A4.4 Zoledronate efficacy and safety in active paget’s disease- long-term follow-up and retreatment in clinical practice
Authors: E Vieira-Sousa, A Rodrigues, J Caetano Lopes, S Capela, F Ramos, R Figueira, J Polido-Pereira, C Ponte, R Campanilho-Marques, R Barros, J C Romeu, J A Pereira da Silva
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Bisphosphonates are first line therapy in the treatment Paget's Disease (PD). The objective of this observational study was to assess short and long-term efficacy and safety of zoledronate in the treatment of active PD. <h3>Methods</h3> Patients with active PD treated with zoledronate 5 mg were consecutively recruited and followed prospectively. Clinical and laboratory parameters (alkaline phosphatase (ALP), bone specific alkaline phosphatase (BSALP), procollagen type 1 N-terminal propeptide (P1NP), collagen type 1 beta C-terminal telopeptide (b-CTX), seric and urinary calcium and phosphorus and parathormone levels) were determined before, at 3 and every 6 months after treatment. Remission was defined as normalization of ALP. Retreatement was considered when ALP levels increased more than 25% of the upper limit of normal or of the nadir achieve in cases of non normalization of ALP. Adverse events were registered according to clinical protocol. <h3>Results</h3> 60 patients (60% males), with a mean age of 68 ± 11 years and a mean disease duration of 11 ± 9 years were included. 69% had polyostotic disease and a mean percentage of skeletal involvement of 10.8 ± 7.6%. 68% were symptomatic: 71% of those referring bone and 54% joint pain attributed to PD. 48.3% had been previously treated with pamidronate (cumulative dose 234 ± 209 mg). The mean follow-up period after zoledronate infusion was of 37 ± 13 months. Only 4 patients (6.6%) required retreatment, on average 30 months after the first zoledronate infusion. A marked reduction of ALP) was observed at 3 (70%) and 6 months (74%) being maximal at 12 months (75%) (p &lt; 0.001). At 3 and 6 months, 95% and 96% of patients respectively, achieved remission. Maximum effect was obtained at 12 months after treatment with 98% of patients being in remission. Significant reductions of the mean levels of BSALP, P1NP, and b-CTX (p &lt; 0.001) were also verified at 3, 6 and 12 months after treatment. 47% of patients reported pain improvement: 89% at 3 months, 7% at 6 months and 4% at 12 months. Transitory side effects were registered in 15 patients, 18% referred flu-like symptoms, 10% showed asymptomatic hypocalcaemia and 30% asymptomatic hypophosphoremia. <h3>Conclusions</h3> This study confirms the efficacy and safety of zoledronate in a Portuguese population of patients with active Paget's disease. Biochemical remission was achieved in 98% of patients at 12 months and improvement of pain in 47%, the majority 3 months after treatment. Furthermore these benefits were long-term sustained with only 6.6% of patients requiring retreatment during an average follow-up of 37 months.
Somatic gene therapy
Authors: J. Dorin
Journal: BMJ (1996)

Treating diseases by putting recombinant genes into somatic cells has been heralded as a brave new way forward for molecular medicine. The appeal of this strategy for inherited gene disorders is its simplistic rationale—that introducing a normal copy of the defective gene into mutant cells will ameliorate the disease phenotype. This means in theory that correcting the fundamental abnormality will treat both immediate and later symptoms even when the underlying biology of the disease may not be completely understood. It is thus understandable that gene therapy has been regarded with huge optimism. However, the absence of sensational cures now puts such optimism in question. Has there been any real progress towards clinical application, and is it realistic to expect single gene disorders such as cystic fibrosis, familial hypercholesterolaemia, and adenosine deaminase deficiency to be cured?

Diseases that offer the best prospects for gene therapy are those caused by single recessive gene defects. Of these, perhaps the highest priority for research should go to those that are fatal and in which the gene responsible is cloned, the target organ is relatively accessible, current treatments are inadequate, and there is some evidence from laboratory and animal studies that the suggested approach will be safe and effective. Scientific kudos and venture capital are certainly driving the move into clinical trials using first generation vectors and protocols; and the first …
Violent Behavior in Mental Illness: The Role of Substance Abuse
Authors: Jan Volavka, Jeffrey Swanson
Journal: JAMA (2010)

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
Deliberate self harm is common reason for emergency medical admission
Authors: O M Bennewith
Journal: BMJ (2001)

EDITOR—Isacson and Rich offer practical guidelines for the management of deliberate self harm while highlighting the extremely weak evidence base in this area.1 They suggest that a brief hospital admission should be considered to establish a good therapeutic relationship. Yet even for an issue as fundamental as whether or not to admit these people to hospital, the benefits are uncertain and the only relevant randomised trial was too small to detect clinically important effects.2 Cost effectiveness is likely to be even …
THE IMPORTANCE OF EARLY OPERATION IN GALL-STONES.
Authors: MAURICE H. RICHARDSON
Journal: JAMA (1900)

It is well established that there is no more valuable life and health conserving operation than the removal of an offending appendix in the period of health. The analogy between the appendix and the gall-bladder is in many ways striking, but it is not perfect. The appendix always contains within itself elements of sepsis, which by their escape into the peritoneal cavity threaten life; the gall-bladder does not; its contents threaten life only when, after prolonged irritation, it has yielded to infections brought from more or less remote areas. The appendix often becomes completely infected without warning; the gall-bladder seldom does. The appendix often contains one or more fecal stones which, septic in themselves, cause ulceration of the mucous lining and give opportunity for direct infection from bacteria right at hand; the gall-bladder may also contain stones, but it is questionable whether they have within themselves bacteria capable of causing
Soil Abatement and Lead Levels in Children
Authors: Thomas L. Schlenker
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The study by Weitzman et al<sup>1</sup>quantifying changes in children's blood lead levels in response to three different environmental interventions used in and around their homes is a valuable contribution to a field thirsting for quantitative data. Their data, combined with data generated from intervention studies in other locales, may be well used by thoughtful people to construct a cost-benefit analysis of household lead abatement that will guide US health and housing policy in the years to come. Weitzman et al deserve credit for a well-organized and scientifically sound study that in many ways will serve as a model for others. One apparent shortcoming, however, is the lack of a "no abatement" control group. (Because the study was confined to children with low levels of lead exposure [0.34 to 1.16 μmol/L (7 to 24 μg/dL)] in which abatement is of unproven value, one would not be
Airway hyperresponsiveness and cough-receptor sensitivity in children with recurrent cough.
Authors: A B Chang, P D Phelan, S M Sawyer, C F Robertson
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

In children, recurrent cough is a common presenting symptom that may represent asthma. We tested the hypotheses that children with recurrent cough have increased cough-receptor sensitivity (CRS) or airway hyperresponsiveness (AHR). Skin prick testing, the capsaicin CRS test, and hypertonic saline (HS) challenge were performed in 44 children (median age: 8.9 yr) with recurrent dry cough (> or = 2 episodes of cough, each lasting > or = 2 wk, within a period of 12 mo) and 44 controls. Measures of CRS were the concentration of capsaicin required to stimulate > or = 2 coughs (Cth) and > or = 5 coughs (C5). During the coughing period, Cth (mean log: 0.62 [95% CI: 0.43 to 0.81]) and C5 (mean log: 1.15 [95% CI: 0.86 to 1.44]) of the subjects without AHR were significantly lower (p = 0.0026, 0.027, respectively) than Cth (mean log: 1.27 [95% CI: 0.88 to 1.66]) and C5 (mean log: 1.79 [95% CI: 1.21 to 2.37]) of the subjects with AHR and those of the controls (p = 0.0002 and 0.0001). During the cough-free period, there was no difference in CRS among the groups. In subjects who demonstrated AHR, the provocation dose causing a > or = 15% fall in FEV1 (PD15) during the cough period was significantly lower (p = 0.005) than that during the cough-free period. We conclude that AHR or increased CRS is present during the coughing phase in children with recurrent cough.
Age of autonomy
Authors: K. Hemming
Journal: BMJ (2010)

Does 7 being the age of autonomy always benefit the child?1 Not all children will demonstrate this capability so young, and so the person who decides whether a child is autonomous is important. Usually it is the consulting doctor, who may have never met the child before the consultation.

In a recent episode of Embarrassing Bodies (Channel 4, 7 April 2010), a child …
CD36 deficiency predisposing young children to fasting hypoglycemia
Authors: Hironori Nagasaka, Tohru Yorifuji, Tomozumi Takatani, Yoshiyuki Okano, Hirokazu Tsukahara, Hidekatsu Yanai, Ken-ichi Hirano, Shu-Ping Hui, Satoshi Hirayama, Tetsuya Ito, Hitoshi Chiba, Takashi Miida
Journal: Metabolism (2010)
Six year survey of screening for Down's syndrome by maternal age and mid-trimester ultrasound scans
Authors: D. T Howe
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess the effectiveness of antenatal screening for Down9s syndrome by maternal age and routine mid-pregnancy ultrasound scanning. <b>Design:</b> Retrospective six year survey. <b>Setting:</b> Maternity units of a district general hospital. <b>Subjects:</b> Pregnant women booked for delivery in hospital between 1 January 1993 and 31 December 1998. <b>Main outcome measures:</b> All cases of Down9s syndrome occurring in district identified from regional congenital anomaly register and cytogenetic laboratory records. Women9s case notes were examined to identify indication for karyotyping, gestation at diagnosis, and outcome of pregnancy. <b>Results:</b> 31 259 deliveries occurred during study period, and 57 cases of Down9s syndrome were identified, four in failed pregnancies and 53 in ongoing pregnancies or in neonates. The analysis was confined to ongoing pregnancies or liveborn children. Invasive antenatal tests were performed in 6.6% (2053/31 259), and 68% (95% confidence interval 56% to 80%) of cases of Down9s syndrome were detected antenatally, giving a positive predictive value of 1.8%. There were 17 undetected cases, and in seven of these the women had declined an offer of invasive testing. In women aged less than 35 years the detection rate was 53% (30% to 76%). Most of the cases detected in younger women followed identification of ultrasound anomalies. <b>Conclusions:</b> The overall detection rate was considerably higher than assumed in demonstration projects for serum screening. As a result, the benefits of serum screening are much less than supposed. Before any new methods to identify Down9s syndrome are introduced, such as nuchal translucency or first trimester serum screening, the techniques should be tested in properly controlled trials. <h3>Key messages</h3> Serum screening for Down9s syndrome has never been compared with screening by maternal age in a controlled trial This study examined the effectiveness of screening by maternal age in combination with mid-trimester ultrasound scanning The overall detection rate was 68%, considerably more effective than assumed in demonstration projects of serum screening The benefits of serum screening, compared with screening by maternal age in conjunction with routine fetal anomaly scanning, may be much less than supposed A higher standard of evidence should be demanded before proposed new screening methods are adopted
Estimates of Physician Joint Ventures
Authors: Jean M. Mitchell
Journal: JAMA (1992)

In Reply.  —We thank the authors of the OIG study on physician joint ventures 1 for their interest, their pioneering research, and for clarifying the criteria used to identify independent physiological laboratories. In our article on the prevalence and scope of physician joint ventures in Florida, 2 we defined diagnostic imaging services to encompass all radiology Current Procedural Terminology (CPT) codes. We compared the CPT codes used in the OIG study with our criteria to ascertain the differences between the two approaches. This comparison revealed that more than 85% of the 82 HCPCS codes used in the OIG definition were radiology procedures. 1 The codes in the OIG definition not captured by our criteria included procedures such as electronic pacemaker analysis and cardiac events recording, which are typically performed in physicians' offices and not in freestanding facilities. Moreover, the OIG definition, like our criteria, did not include any radiation therapy
Cancer Pain: Assessment and Management
Authors: Charles F. von Gunten
Journal: Annals of Internal Medicine (2003)

Medical Writings: Book Notes4 November 2003Cancer Pain: Assessment and ManagementCharles F. von Gunten, MD, PhDCharles F. von Gunten, MD, PhDFrom San Diego Hospice Palliative Care San Diego California.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-139-9-200311040-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Bruera ED and Portenoy RK, eds. 485 pages. New York: Cambridge Univ Pr; 2003. $160. ISBN 0521773326. Order at uk.cambridge.org.Field of medicine: Cancer pain.Format: Hardcover book.Audience: Physicians who specialize in pain and palliative medicine and researchers in cancer pain management.Purpose: To provide a comprehensive, clinically oriented, and scholarly review of all aspects of the complex and multidimensional problem of cancer pain.Content: This textbook comprises contributions from 46 international experts. Edited by 2 of the most prominent physicianresearchers in pain and palliative medicine, the book is organized into 8 sections: 1) mechanisms and epidemiology, 2) assessment ... Author, Article, and Disclosure InformationAffiliations: From San Diego Hospice Palliative Care San Diego California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 November 2003Volume 139, Issue 9Page: 794KeywordsCancer treatmentEpidemiologyLibrariesPain managementPalliative carePopulation statisticsSoftware tools ePublished: 4 November 2003 Issue Published: 4 November 2003 Copyright & PermissionsCopyright © 2003 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The Hemodynamic Response to Medical Treatment of Portal Hypertension as a Predictor of Clinical Effectiveness in the Primary Prophylaxis of Variceal Bleeding in Cirrhosis
Authors: Carlo Merkel, Massimo Bolognesi, David Sacerdoti, Giancarlo Bombonato, Barbara Bellini, Raffaella Bighin, Angelo Gatta
Journal: Hepatology (2000)

In the prevention of variceal rebleeding, it is already established that hemodynamic response to drug treatment (decrease in hepatic venous pressure gradient [HVPG] to 12 mm Hg or by &gt;20%) is predictive of clinical effectiveness. In primary prophylaxis very few clinical data are available. We assessed the role of the hemodynamic response to beta–blockers or beta–blockers plus nitrates in predicting clinical efficacy of prophylaxis. A total of 49 cirrhotic patients with varices at risk of bleeding, without prior variceal bleeding, were investigated by hepatic vein catheterization before and after 1 to 3 months of chronic treatment with nadolol or nadolol plus isosorbide mononitrate, and were followed during treatment for up to 5 years. A total of 30 patients (61%) were good hemodynamic responders, and among them in 12 (24%) HVPG was ≤12 mm Hg during treatment. During treatment 9 patients had variceal bleeding: 7 were poor responders and 2 were good responders. The probability of bleeding at 3 years of follow–up was significantly higher in poor responders (41%) than in good responders (7%; P = .0008). No patient reaching an HVPG of 12 mm Hg or less during treatment had variceal bleeding during follow–up. Cox's regression analysis showed that poor hemodynamic response was the main factor predicting bleeding (β = 1.91; SE(β) = 0.80; P = .01). During follow–up 11 patients died of hepatic causes. Survival was related to Child–Pugh class and to initial value of HVPG, according to Cox's analysis. In conclusion, the assessment of hemodynamic response to drugs in terms of HVPG is the best predictor of efficacy of prophylaxis of variceal bleeding in patients treated with beta–blockers or beta–blockers plus nitrates.
ISTC programme is an expensive option
Authors: Simon P Kelly, Brenda Billington, Richard Smith, Rhod Daniel
Journal: BMJ (2007)

The improvement report in relation to cataract surgery1 is further evidence that the independent sector treatment centre (ISTC) programme was an expensive over-reaction to the need to increase rates of cataract surgery.2 Many ophthalmology departments had improved cataract surgery pathways, as part of Action on Cataract, an NHS initiative supported by the college,3 before the ISTC …
DENTITION, AND SOME OF ITS DISEASES.Read in the Section on Diseases of Children, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: MARION THRASHER
Journal: JAMA (1893)

Normal dentition is comparatively harmless. The teething in wild animals and barbarous nations is usually attended with no danger, and with but little inconvenience. The young, however, of beasts confined in cages, rarely live during the period of teething. In our age of civilized refinement, abnormal dentition is the rule. So deadly has it become, that one-third of the human family die before the twenty deciduous teeth have fully appeared. Its danger is constantly increasing. A few decades ago, when the practice of mothers nursing their children was more in vogue, the fatality was not nearly so great. Latterly it has become unfashionable, and children are fed on artificial food, and the result is an alarming mortality. Dentition in these children develops incidentally many diseases. The commonest are irritative fever, indigestion—with its attendant evils, flatulency, constipation and diarrhea—cerebral convulsions, stomatitis, capillary bronchitis and pneumonia. Practically, it is almost impossible to,