tbuckley/cabot-search huggingface dataset:
Abstract B1: Hypoxia inducible factor (HIF) promotes reductive carboxylation by regulating citrate levels and renders VHL-deficient and hypoxic cells sensitive to glutamine deprivation
Authors: Paulo Gameiro, Ana Metelo, Rojo Pérez-Carro, Arreola Alexandra, Zongwei Wang, Kimryn W. Rathmell, Aria Olumi, Pilar López-Larrubia, Gregory Stephanopoulos, Othon Iliopoulos
Journal: Cancer Research (2013)

Abstract Hypoxia is a hallmark of tumor microenvironment. We showed before that exposure of cells to hypoxia reprograms cell metabolism and directs an IDH1-mediated reductive carboxylation (RC) of glutamine-derived alpha-ketoglutarate (a-KG) for lipogenesis. In addition Von Hippel-Lindau (VHL)-deficient renal cell carcinoma cells use glutamine to generate citrate and lipids through RC of a-KG. To gain insights into the role of HIF and the molecular mechanisms underlying RC we took advantage of a panel of disease-associated VHL mutants and showed that HIF expression is necessary and sufficient for the induction of RC in human renal cell carcinoma (RCC) cells. HIF expression drastically reduces intracellular citrate levels. Feeding VHL-deficient RCC cells with acetate or citrate, or knocking-down PDK-1 and ACLY enzymes restored intracellular citrate levels and suppressed RC. These data suggest that HIF-induced low intracellular citrate levels promote the reductive flux by mass action, to maintain lipogenesis. Expression of HIF renders hypoxic and VHL-deficient cells addicted to glutamine in vitro. VHL-deficient cells displayed significantly less growth than their isogenic counterparts in media containing low glutamine concentration or in the presence of a glutaminase inhibitor. Systemic administration of a glutaminase inhibitor (BPTES) suppressed the growth of VHL-deficient human RCC cell lines as xenografts in nude mice. Lastly, we investigated whether RC occurs in vivo. We metabolically labeled mice bearing VHL-deficient tumors by infusing them with 13C-1-Glutamine for up to 6 hours and we detected the early formation of labeled citrate in the tumors; thus we showed for the first time RC in vivo. Our data provide mechanistic insights into the signaling events that mediate hypoxia-induced RC, strongly suggest that RC is an in vivo phenomenon in growing tumors and highlight potential novel therapeutic approaches for treatment of hypoxic and VHL-deficient tumors based on their metabolic signature. Citation Format: Paulo Gameiro, Ana Metelo, Rojo Pérez-Carro, Arreola Alexandra, Zongwei Wang, Kimryn W. Rathmell, Aria Olumi, Pilar López-Larrubia, Gregory Stephanopoulos, Othon Iliopoulos. Hypoxia inducible factor (HIF) promotes reductive carboxylation by regulating citrate levels and renders VHL-deficient and hypoxic cells sensitive to glutamine deprivation. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B1.
NON-RECOVERY OF HEMOGLOBIN LEVELS AFTER ACUTE MYOCARDIAL INFARCTION AND CORONARY INTERVENTION: A MARKER OF POOR PROGNOSIS
Authors: Eran Leshem Rubinow, Arie Steinvil, Ori Rogowski, Shlomo Berliner, Raanan Raz, Gabriel Chodick, Varda Shalev
Journal: Journal of the American College of Cardiology (2011)
Neuraminidase Antibodies and H5N1: Geographic-Dependent Influenza Epidemiology Could Determine Cross-Protection against Emerging Strains
Authors: Jesus F Bermejo-Martin, David J Kelvin, Yi Guan, Honglin Chen, Pilar Perez-Breña, Inmaculada Casas, Eduardo Arranz, Raul O de Lejarazu
Journal: PLoS Medicine (2007)

We have read with great
The Investigation of Dysphagia
Authors: David J. Curtis
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In the MEDICAL NEWS &amp; PERSPECTIVES article entitled "Dysphagia Management Means Diagnosis, Exercise, Reeducation,"<sup>1</sup>cineradiography's role in the diagnosis of dysphagia was stressed. There is no question that dynamic pictures are essential in the evaluation of this disorder; however, appropriate information can be obtained with considerably less radiation exposure for the patient by recording this information on videotape (videofluoroscopy) rather than 16- or 35-mm film (cineradiography).<sup>2-5</sup>The distinction is important, as the patient exposure per frame for cineradiography is approximately 6 mR (1.5×10-<sup>6</sup>C/kg),<sup>3</sup>while for videofluoroscopy it is approximately 0.1 mR (2.6×1.-<sup>8</sup>C/kg) per frame.<sup>3,4</sup>
New Treatment Option
Authors: Patrick M. Colletti
Journal: Clinical Nuclear Medicine (2013)

A 66-year-old man with prostate cancer presented with intractable pain associated with multifocal bone metastases. After receiving 180 µCi (1.35 µCi/kg) of 223Ra chloride, radiation survey measured 0.2 mR/h at 1 m, and the patient was discharged to home. He will return monthly for the next 5 months for repeat 223Ra chloride administrations. 223Ra chloride is the first Food and Drug Administration–approved unsealed α-emitting radiopharmaceutical.
Fulminant Hepatitis during Treatment with Propylthiouracil
Authors: Milton J. Eisen
Journal: New England Journal of Medicine (1953)

THE effectiveness and relative lack of toxicity of propylthiouracil have made it valuable in the treatment of thyrotoxicosis. Untoward reactions, especially granulocytopenia, rarely hepatic injury, were encountered frequently with its predecessor, thiouracil. However, hematologic changes with propylthiouracil have proved so unusual that some clinicians consider periodic blood counts an unnecessary precaution during therapy.1 Abandonment of such a safeguard is to be decried since other authors2 3 4 report as high as a 2 to 4 per cent incidence of toxic reactions with propylthiouracil. In 1651 treated cases granulocytopenia occurred in 19.4 The literature contains several reports of liver damage in patients receiving . . .
Prosthetic Mitral Valve with Partial Thrombosis
Authors: David T Schachter
Journal: New England Journal of Medicine (2009)

A 63-year-old woman presented with 2 weeks of progressive dyspnea. She had a history of dilated cardiomyopathy and a St. Jude prosthetic valve in the mitral position. The physical examination was notable for bibasilar crackles and a muffled S1 heart sound.
Imaging of Small Intestinal Tumours
Authors: C BARTRAM
Journal: Gut (1999)

Imaging of Small Intestinal Tumours . Edited by Gourtosyiannis NC, Nolan DJ. (Pp 414; illustrated; $284.50.) Elsevier Science, 1997. ISBN 0-444-89997-9.

I was interested to learn that the radiology of small bowel tumours was first described by Golden in 1928. Since then all the standard works on gastrointestinal radiology have contained sections on small bowel tumours, but to my knowledge no other single work on this subject matter has emerged. Small bowel tumours represent less than 2% of all primary gastrointestinal (GI) tract tumours, but change in endoscopic practice means that the small bowel is now of greater importance to the GI radiologist, making a book …
Distinct spatio-temporal Ca2+ signaling elicited by integrin α2β1 and glycoprotein VI under flow
Authors: Mario Mazzucato, Maria Rita Cozzi, Monica Battiston, Martine Jandrot-Perrus, Maurizio Mongiat, Patrizia Marchese, Thomas J. Kunicki, Zaverio M. Ruggeri, Luigi De Marco
Journal: Blood (2009)
Familial Hypertrophic Pyloric Stenosis
Authors: T. Fenwick
Journal: BMJ (1953)

BnDICAL JotmiIn 17 missed cases, group C, the patients suffered angina pectoris virtually confined to effort.The diagnosis depends, above all, on a careful case history.Fever, perhaps the most useful, is the most neglected physical sign; by contrast, excessive reliance is placed on the presence or absence of pericardial friction.There is evidence that disability was more prolonged in (even mild) missed cases than in those diagnosed and treated early.The significance of and reasons for delayed diagnosis, and the cardiographic changes, are discussed.
Bacterial DNA in patients with cirrhosis and noninfected ascites mimics the soluble immune response established in patients with spontaneous bacterial peritonitis
Authors: Rubén Francés, Pedro Zapater, José M. González-Navajas, Carlos Muñoz, Rocío Caño, Rocío Moreu, Sonia Pascual, Pablo Bellot, Miguel Pérez-Mateo, José Such
Journal: Hepatology (2008)

Bacterial infections and severity of associated inflammatory reaction influence prognosis in patients with advanced cirrhosis. We compared the innate immune response to bacterial DNA (bactDNA) translocation with that caused by viable bacteria translocation in patients with spontaneous bacterial peritonitis and the relationship between the cytokine response and serum levels of bactDNA. The bactDNA translocation was investigated in 226 patients with cirrhosis and noninfected ascites, 22 patients with spontaneous bacterial peritonitis, and 10 patients with ascites receiving continuous norfloxacin. Serum and ascitic fluid tumor necrosis factor α, interferon-γ, interleukin-12, and nitric oxide metabolites were measured via enzyme-linked immunosorbent assay. Bacterial genomic identifications were made via amplification and sequencing of the 16S ribosomal RNA gene and digital quantization with DNA Lab-on-chips. The bactDNA was present in 77 noninfected patients (34%) and in all cases of spontaneous bacterial peritonitis, even in those with culture-negative ascitic fluid. No patient receiving norfloxacin showed bactDNA translocation. Levels of all cytokines were similar in patients with bactDNA translocation or spontaneous bacterial peritonitis and significantly higher than in patients without bactDNA or in those receiving norfloxacin. Serum bactDNA concentration paralleled levels of all cytokines and nitric oxide in a series of patients with bactDNA translocation or spontaneous bacterial peritonitis followed during 72 hours. Antibiotic treatment in the series of patients with spontaneous bacterial peritonitis did not abrogate bactDNA translocation in the short term. Conclusion: bactDNA translocation-associated cytokine response is indistinguishable from that in patients with spontaneous bacterial peritonitis and is dependent on bactDNA concentration. Norfloxacin abrogates bactDNA translocation and cytokine response.
Dorothea Koffman (née Herrmann)
Authors: Andrew Koffmann
Journal: BMJ (2007)

The daughter of a well-known singing teacher, Dorothea Koffman grew up in Berlin between the world wars. She was determined to study medicine but was unable to secure admission to a German university as her mother was Jewish, so she began her studies in Prague in 1935. When the political situation worsened three years later, Dorothea transferred to the University of Berne and then a year after that to the University of Geneva. She was unable to return to Germany as her passport would have been confiscated, and she therefore holidayed in England, where she visited her childhood sweetheart, Jurij. A …
The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer
Authors: P. Venkatesan, Nagaprasad Puvvada, Rupesh Dash, B.N. Prashanth Kumar, Devanand Sarkar, Belal Azab, Amita Pathak, Subhas C. Kundu, Paul B. Fisher, Mahitosh Mandal
Journal: Biomaterials (2011)
Absence from school related to children's and parental smoking habits.
Authors: A. Charlton, V. Blair
Journal: BMJ (1989)

A sample of 2885 children aged 12 and 13 who completed a questionnaire survey in school in January 1987 were given a second questionnaire on a specified date in May 1987. The smoking habits, parental smoking habits, sex, and social background of the children who were present on both dates were compared with those of the children who were absent on the second occasion. Regular smoking was significantly more common among those absent for the second questionnaire: among boys 181/877 (21%) who never smoked, 109/486 (22%) who sometimes smoked, and 21/45 (47%) who regularly smoked were absent, and among girls the figures were 157/947 (17%), 117/487 (24%), and 17/43 (40%) respectively. Thus the odds ratio for those who sometimes smoked was 1.29 and for regular smokers 3.09 against those who never smoked. Whatever the children9s smoking habits, the proportion who were absent was higher when both parents or at least the mother smoked, the odds ratio being 1.39; the proportions absent were 203/1180 (17%) if neither parent or only the father smoked v 135/644 (21%) if both parents or only mother smoked for children who never smoked; 105/529 (20%) v 121/444 (27%) for those who sometimes smoked; and 10/27 (37%) v 28/61 (46%) for those who regularly smoked. Sex and social background had little effect, though there was an overall higher rate of absence among boys from industrial areas. The findings show a higher rate of minor ailments in children who smoke and in children whose mother smokes. If children are having frequent days off school for minor ailments possibly they or their parents would benefit from advice and help in stopping smoking.
Decreased Occipital Cortical Glutamate Levels in Response to Successful Cognitive-Behavioral Therapy and Pharmacotherapy for Major Depressive Disorder
Authors: Chadi G. Abdallah, Mark J. Niciu, Lisa R. Fenton, Madonna K. Fasula, Lihong Jiang, Anne Black, Douglas L. Rothman, Graeme F. Mason, Gerard Sanacora
Journal: Psychotherapy and Psychosomatics (2014)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Previous studies have demonstrated that antidepressant medication and electroconvulsive therapy increase occipital cortical &amp;#947;-aminobutyric acid (GABA) in major depressive disorder (MDD), but a small pilot study failed to show a similar effect of cognitive-behavioral therapy (CBT) on occipital GABA. In light of these findings we sought to determine if baseline GABA levels predict treatment response and to broaden the analysis to other metabolites and neurotransmitters in this larger study. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 40 MDD outpatients received baseline proton magnetic resonance spectroscopy (&lt;sup&gt;1&lt;/sup&gt;H-MRS), and 30 subjects completed both pre- and post-CBT &lt;sup&gt;1&lt;/sup&gt;H-MRS; 9 CBT nonresponders completed an open-label medication phase followed by an additional/3rd &lt;sup&gt;1&lt;/sup&gt;H-MRS. The magnitude of treatment response was correlated with occipital amino acid neurotransmitter levels. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Baseline GABA did not predict treatment outcome. Furthermore, there was no significant effect of CBT on GABA levels. However, we found a significant group × time interaction (F&lt;sub&gt;1, 28&lt;/sub&gt; = 6.30, p = 0.02), demonstrating reduced glutamate in CBT responders, with no significant glutamate change in CBT nonresponders. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; These findings corroborate the lack of effect of successful CBT on occipital cortical GABA levels in a larger sample. A reduction in glutamate levels following treatment, on the other hand, correlated with successful CBT and antidepressant medication response. Based on this finding and other reports, decreased occipital glutamate may be an antidepressant response biomarker. Healthy control comparator and nonintervention groups may shed light on the sensitivity and specificity of these results.
Independent and Incremental Prognostic Value of <sup>201</sup> Tl Lung Uptake at Rest in Patients With Severe Postischemic Left Ventricular Dysfunction
Authors: Claudio Marcassa, Michele Galli, Claudio Baroffio, Ermanno Eleuteri, Riccardo Campini, Pantaleo Giannuzzi
Journal: Circulation (2000)

Background —An elevated 201 Tl lung uptake after stress is related to an adverse prognosis. Methods and Results —The functional and prognostic significance of resting 201 Tl lung uptake was assessed in 124 consecutive patients with ischemic heart disease and ejection fraction ≤35% undergoing rest-redistribution tomography to evaluate myocardial viability. 201 Tl lung uptake significantly correlated with pulmonary wedge pressure ( r =0.66; P &lt;0.01) and with a restrictive physiology by Doppler echocardiography ( P &lt;0.001). During a 13±13-month follow-up, 13 patients died and 23 patients required hospitalization as the result of worsening heart failure or nonfatal myocardial infarction (cumulative events rate 29%). Patients with events had a significantly higher 201 Tl lung/heart ratio (L/H) ( P &lt;0.001). A L/H value &gt;0.61 best separated patients with and without events (ROC area under curve 0.82). Event-free survival was significantly lower in patients with L/H &gt;0.61 ( P &lt;0.001); L/H &gt;0.61 (χ 2 =10.8; P &lt;0.001) and a restrictive filling pattern (χ 2 =3.6; P &lt;0.05) were independent predictors of events. The prognostic value of L/H was incremental over that obtained by clinical, echographic and Doppler data (global χ 2 =20.8). Conclusions —In patients with severe postischemic left ventricular dysfunction undergoing rest-redistribution 201 Tl imaging, an increased lung tracer uptake showed incremental prognostic value over clinical and other imaging findings, providing clinically useful risk assessment.
English claims against Vioxx manufacturer are on brink of collapse
Authors: Clare Dyer
Journal: BMJ (2005)

A compensation claim in the English courts against Merck, the US manufacturer of the withdrawn painkiller rofecoxib (Vioxx), looks set to be abandoned because the 500 claimants cannot get funding.

An appeal against the refusal of legal aid was turned down this week, and hopes for a no win, no fee deal backed by insurance have been dashed.

If the case went ahead on a no win, no fee basis, insurance would be necessary to cover Merck's estimated costs of £5m ($8.6m; £7.3m) if the claimants lost. Insurers will sometimes agree to take a deferred premium—collecting a premium …
Pharmacogenomics of Cisplatin Sensitivity in Non-Small Cell Lung Cancer
Authors: Maimon C. Rose, Elina Kostyanovskaya, R. Stephanie Huang
Journal: Genomics Proteomics & Bioinformatics (2014)

Abstract Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer (NSCLC) as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomarkers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.
The Capsaicin-Sensitive Afferent Neuron in Skeletal Muscle Is Abnormal in Heart Failure
Authors: Scott A. Smith, Maurice A. Williams, Jere H. Mitchell, Pradeep P.A. Mammen, Mary G. Garry
Journal: Circulation (2005)

Background— In heart failure, the cardiovascular response to activation of the skeletal muscle exercise pressor reflex (EPR) is exaggerated. Group IV afferent neurons, primarily stimulated by the metabolic by-products of skeletal muscle work, contribute significantly to the EPR. Therefore, it was postulated that alterations in the activity of group IV neurons contribute to the EPR dysfunction manifest in heart failure. Methods and Results— Group IV afferent fibers were ablated in neonatal Sprague-Dawley rats by subcutaneous administration of capsaicin. In neonatal capsaicin-treated adult animals, selective activation of the EPR, by electrically induced static muscle contraction, recapitulated the exaggerated increases in heart rate and blood pressure observed in rats with dilated cardiomyopathy (DCM). Furthermore, compared with control animals, both neonatal capsaicin-treated and DCM rats displayed a decreased pressor response to the intra-arterial administration of capsaicin within the hindlimb, a maneuver that selectively excites group IV afferent neurons. Moreover, expression of mRNA for the capsaicin receptor TRPv1, a marker of group IV fibers, was downregulated in DCM animals compared with controls. Conclusions— These findings suggest that EPR dysfunction in heart failure results in part from functional and molecular alterations in group IV fibers. Furthermore, the responsiveness of these metabolically sensitive neurons appears to be blunted in DCM, indicating that their contribution to the EPR may be reduced. This occurs despite an overall exaggeration of the EPR in heart failure. These insights into the basic mechanisms of EPR dysfunction are essential to the development of effective therapeutic strategies aimed at improving exercise capacity in heart failure.
A Multicenter Study on the Prevalence of Diabetic Neuropathy in Italy
Authors: Domenico Fedele, Giancarlo Comi, Carlo Coscelli, Domenico Cucinotta, Eva L Feldman, Giovanni Ghirlanda, Douglas A Greene, Paolo Negrin, Fausto Santeusanio
Journal: Diabetes Care (1997)

OBJECTIVE The prevalence of neuropathy, a common complication of diabetes, was determined in diabetic patients recruited from 109 outpatient diabetes clinics in Italy. RESEARCH DESIGN AND METHODS Neuropathy was diagnosed using the Diabetic Neuropathy Index (DNI), a standardized examination developed for use in the outpatient setting. A total of 8,757 diabetic patients were studied, 51.2% men and 48.8% women, with average and median ages of 56 and 58 years, respectively. RESULTS Of the 8,757 patients, 32.3% had neuropathy, defined as a positive score of &amp;gt; 2 points on the DNI. A total of 2,033 (49.6% men and 50.4% women) were administered the Diabetic Neuropathy Score (DNS), the second component of the screening program, by a neurologist. This component consists of a quantitative neurological examination and nerve conduction studies that together provide a summated score. A total of 335 patients (16.5%) were not neuropathic, and 395 (19.4%) had borderline, 453 (22.3%) mild, 592 (29.1%) moderate, and 258 (12.7%) severe neuropathy. The concordance between a positive score on the DNI and a DNS indicating neuropathy was 83.5%. The severity of neuropathy increased with both age and disease duration. Of patients with neuropathy, 64.1% had an average age between 58 and 59 years with a disease duration between 12.4 ± 8.4 years (mild neuropathy) and 15.6 ± 9.7 years (severe neuropathy). CONCLUSIONS Neuropathy is a common complication of diabetes and, in this study, was present in 32.3% of all patients. An increased awareness of the high prevalence of neuropathy can lead to early therapeutic intervention and possible prevention of later neuropathic complications, such as infection and foot ulcers.
Euthanasia, Clinical Practice and the Law
Authors: J. Walton
Journal: BMJ (1994)

Ed Luke Gormally Linacre Centre, £ 12.75, pp 248 ISBN 0 906561 08 6

The editor of this unusual volume is director of the Linacre Centre, a national Catholic bioethics centre established in 1977 by the Roman Catholic archbishops of England and Wales, who are its trustees. I say unusual because the book effectively consists of two separate books, if not three. Tdhe first, of just over 100 pages, is a restatement of a working party report first published in 1982, entitled Euthanasia and Clinical Practice: Trends, Principles and Alternatives. Book two embraces a 56 page submission from the centre submitted in 1993 to the House of Lords Select Committee on Medical …
Testosterone regulates Arp2/3 expression by DNA methylation in hippocampus
Authors: Liang Zhou, Ximeng Zhang, Xuefei Wu, Huan Yang, Kaiyin Zhong, Hecheng Wang, Ting Zhou, Tianxiao Sheng, Yawei Tong, Dongsheng Fan, Dehua Chui
Journal: Molecular Neurodegeneration (2012)

Background The Arp2/3 complex is a seven-protein assembly that is critical for actin nucleation and branching in cells. Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence Arp2/3 complex DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the Arp2 within adult brain is dependent upon testosterone exposure.