tbuckley/cabot-search huggingface dataset:
Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation
Authors: E Combet, S Paterson, K Iijima, J Winter, W Mullen, A Crozier, T Preston, K E L McColl
Journal: Gut (2007)

<h3>Background:</h3> The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and <i>N-</i>nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. <h3>Aims:</h3> To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. <h3>Methods:</h3> The nitrosative chemistry was modelled <i>in vitro</i> by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The <i>N-</i>nitrosamines formed were measured by gas chromatography–ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically. <h3>Results:</h3> In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of <i>N-</i>nitrosodimethylamine formed by fivefold, <i>N-</i>nitrosomorpholine by &gt;1000-fold, and totally prevented the formation of <i>N-</i>nitrosodiethylamine and <i>N-</i>nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of <i>N-</i>nitrosodimethylamine, <i>N-</i>nitrosodiethylamine and <i>N-</i>nitrosopiperidine formed by approximately 8-, 60- and 140-fold, respectively, compared with absence of ascorbic acid. <h3>Conclusion:</h3> The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with oxygen in the lipid phase.
Identification of Chronic Obstructive Pulmonary Disease in Lung Cancer Screening Computed Tomographic Scans
Authors: Onno M. Mets, Constantinus F. M. Buckens, Pieter Zanen, Ivana Isgum, Bram van Ginneken, Mathias Prokop, Hester A. Gietema, Jan-Willem J. Lammers, Rozemarijn Vliegenthart, Matthijs Oudkerk, Rob J. van Klaveren, Harry J. de Koning, Willem P. Th. M. Mali, Pim A. de Jong
Journal: JAMA (2011)

Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage.To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD.Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV(1)/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation.Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard.Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms.Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%.
Natural History of Ischemic Heart Disease in Relation to Arteriographic Findings
Authors: J. O'NEAL HUMPHRIES, LEWIS KULLER, RICHARD S. ROSS, GOTTLIEB C. FRIESINGER, E. EUGENE PAGE
Journal: Circulation (1974)

The severity of the atherosclerotic disease of the coronary arteries is demonstrated to be an important predictor of survival in a group of 224 patients followed from 5 to 12 years after coronary arteriography. The group consisted of young patients (average age 41.8 years) without hypertension or congestive heart failure, who were studied during the stable phase of their disease. The current status of 218 or 97% of this group of patients is known.
Subcutaneous fat necrosis of the newborn: a systematic evaluation of risk factors, clinical manifestations, complications and outcome of 16 children
Authors: E. Mahé, N. Girszyn, S. Hadj-Rabia, C. Bodemer, D. Hamel-Teillac, Y. De Prost
Journal: British Journal of Dermatology (2007)

Subcutaneous fat necrosis (SFN) of the newborn is a rare acute transient hypodermatitis that develops within the first weeks of life in term infants. It often follows a difficult delivery. Prognosis is generally good except for the development of hypercalcaemia in severe cases. Only several case reports or small patients series have been published.To evaluate risk factors, complications and outcomes of SFN in 16 consecutive patients seen from 1996 to 2002 in our Department of Paediatric Dermatology.On a case-report form created for the study, we recorded putative risk factors concerning the mother, pregnancy and delivery, clinical aspects of SFN, and early and late outcomes. The study was conducted in two stages: the first was a retrospective analysis of the observations and the second analysed data collected on children and their parents during a new consultation (n=10).All the children were born at term. Lesions appeared a mean of 4 days after delivery. Three-quarters of the children had diffuse SFN. Risk factors identified were newborn failure to thrive (12/16), forceps delivery (7/16), maternal high blood pressure (3/10) and/or diabetes (2/10), and newborn cardiac surgery (1/16). Putative novel risk factors were macrosomia (7/16), exposure to active (4/10) or passive (3/10) smoking during pregnancy, putative or known maternal, paternal or newborn risk factors for thrombosis (5/10), and dyslipidaemia (2/10). Complications were hypercalcaemia (9/16), pain (4/16), dyslipidaemia (1/16), renal insufficiency (1/16) and late subcutaneous atrophy (6/6).This study on 16 newborns with SFN provides new information. Familial or newborn risk factors for thrombosis are frequent. Macrosomia, familial dyslipidaemia and smoking should be evaluated. The main complications identified were severe pain, hypercalcaemia and subcutaneous atrophy.
Universal sex-specific instantiations of obsessive-compulsive disorder
Authors: Gad Saad
Journal: Behavioral and Brain Sciences (2006)

Numerous sex differences in obsessive-compulsive disorder (OCD) instantiations are likely universal, as the associated evolutionary threats and concerns onto which they map were differentially important to the two sexes. Hence, although some ritualized behaviors or thoughts are indeed culture-specific, others are both culturally and temporally invariant as they are rooted in universal Darwinian etiologies (e.g., the sex differences in OCD symptomatology posited here).
Measurement of Serum Uric Acid in Great Britain in 1963
Authors: E. G. L. Bywaters, V. P. Holloway
Journal: Annals of the Rheumatic Diseases (1964)

Serum uric acid measurement is often an essential step in the diagnosis of gouty arthritis, and its results may form the basis of treatment for pro- longed periods.Hyperuricaemia is known of course to occur without gout, either preceding it or arising from some of the other possible causes (Cohen and Bywaters, 1964) which include:1. Nitrogen retention 2. Increased purine turnover (as in leukaemia) or breakdown 3. The action of drugs such as chlorothiazide or pyrazinamide 4. Starvation, ketosis, or lactacidaemia (as in acute alcoholic excess) 5. Other metabolic faults such as glycogen disease or hypercalcaemia 6.Some unknown reason, when it is called "idiopathic".8-Mean 3-5 Range C2 3-4-2) 6-S.D. 0-46 4-n 2-1 i 2 -Mean 3-8 w Range C2-1-4-6) zL 6-S.D. 0-55 CZ
Probiotic/prebiotic supplementation of antiretrovirals improves gastrointestinal immunity in SIV-infected macaques
Authors: Nichole R. Klatt, Lauren A. Canary, Xiaoyong Sun, Carol L. Vinton, Nicholas T. Funderburg, David R. Morcock, Mariam Quiñones, Clayton B. Deming, Molly Perkins, Daria J. Hazuda, Michael D. Miller, Michael M. Lederman, Julie A. Segre, Jeffrey D. Lifson, Elias K. Haddad, Jacob D. Estes, Jason M. Brenchley
Journal: Journal of Clinical Investigation (2013)

HIV infection results in gastrointestinal (GI) tract damage, microbial translocation, and immune activation, which are not completely ameliorated with suppression of viremia by antiretroviral (ARV) therapy. Furthermore, increased morbidity and mortality of ARV-treated HIV-infected individuals is associated with these dysfunctions. Thus, to enhance GI tract physiology, we treated SIV-infected pigtail macaques with ARVs, probiotics, and prebiotics or with ARVs alone. This synbiotic treatment resulted in increased frequency and functionality of GI tract APCs, enhanced reconstitution and functionality of CD4+ T cells, and reduced fibrosis of lymphoid follicles in the colon. Thus, ARV synbiotic supplementation in HIV-infected individuals may improve GI tract immunity and thereby mitigate inflammatory sequelae, ultimately improving prognosis.
Rapid detection of BRCA1 mutations by the protein truncation test
Authors: Frans B.L. Hogervorst, Renée S. Cornelis, Mattie Bout, Margreethe van Vliet, Jan C. Oosterwijk, Renske Olmer, Bert Bakker, Jan G.M. Klijn, Hans F.A. Vasen, Hanna Meijers-Heijboer, Fred H. Menko, Cees J. Cornelisse, Johan T. den Dunnen, Peter Devilee, Gert-Jan B. van Ommen
Journal: Nature Genetics (1995)
In Utero Exposure to Chemotherapy: Effect on Cardiac and Neurologic Outcome
Authors: Kristel Van Calsteren, Patrick Berteloot, Myriam Hanssens, Ignace Vergote, Frederic Amant, Javier Ganame, Piet Claus, Luc Mertens, Lieven Lagae, Michel Delforge, Robert Paridaens, Lucien Noens, Yves Humblet, Bruno Vandermeersch, Xavier De Muylder
Journal: Journal of Clinical Oncology (2006)

This study consisted of two parts. Firstly, in a multicenter retrospective study women who received chemotherapy during pregnancy were recruited from four different Belgian centers. Clinical data were obtained through a questionnaire. Obstetric and perinatal data did not differ from earlier reported larger series and suggest morbidity after intrauterine exposure to cytotoxic drugs mainly appears to be related to (induced) prematurity. Nine pregnant women, 25 years to 39 years of age (median, 31 years), of whom one was having a twin pregnancy, had been treated with chemotherapy for different malignant disorders (four breast cancer, two acute myeloid, one lymphoblastic leukemia, one cervical cancer, and one undifferentiated oropharyngeal tumor). Cancer was diagnosed between 12 weeks and 24 weeks (median, 17 weeks) of pregnancy. Thirty-three cycles of antineoplastic drugs were administered between 15 weeks and 35 weeks (median, 25 weeks). Different types of chemotherapeutic regimens were administered. In seven cases, anthracyclines were used with a mean total cumulative dose of 240 mg/m*2. In the second and prospective part of the study, all children were invited for a full neurologic and cardiologic assessment. This assessment consisted of neurologic clinical evaluations by the same pediatric neurologist (L.L.). Standard echocardiographic data acquisition consisted of a standard transthoracic echocardiogram (to measure ventricular dimensions, mass, wall thickness, and fractional shortening) and blood pool Doppler (to assess diastolic function). Color Doppler myocardial imaging was performed from the inferolateral wall, interventricular septum, the left ventricular lateral, and the right ventricular free wall as previously explained to calculate myocardial deformation (peak systolic strain and strain rate). The examinations were performed by the same pediatric cardiologist (L.M.). Echocardiographic data were compared with those of an age- and sex-matched control group consisting of 10 healthy children.
Assessing Clinical Characteristics of the Manic State
Authors: ALLAN BEIGEL, DENNIS L. MURPHY
Journal: American Journal of Psychiatry (1971)

The authors found that 11 of the 26 items of the Manic-State Rating Scale characterized common elements of mania in 12 manic-depressive patients and that these items were highly correlated with independent ratings of change in the severity of mania. Eight other items provided a basis for dividing the patients into two groups: one showing elation and grandiosity but little paranoid or destructive symptomatology, and the other with minimal euphoria and grandiosity but more marked paranoid and destructive behavior. The authors also found ratable depression in 11 of these 12 patients.
A randomised placebo controlled 12 week trial of budesonide and prednisolone in rheumatoid arthritis
Authors: J. R. Kirwan, R. Hallgren, H. Mielants, F. Wollheim, E. Bjorck, T. Persson, C. Book, S. Bowman, M. Byron, N. Cox, M. Field, L. Kanerud, M. Leirisalo-Repo, Michel Malaise, A. Mohammad, R. Palmer, I. F. Petersson, B. Ringertz, P. Sheldon, M. Simonsson, N. Snowden, F. Van den Bosch
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To compare budesonide, a locally acting glucocorticoid with minimal systemic exposure, with conventional glucocorticoid treatment and placebo in rheumatoid arthritis. <b>Methods:</b> A double blind, randomised, controlled trial over 12 weeks in 143 patients with active rheumatoid arthritis, comparing budesonide 3 mg daily, budesonide 9 mg daily, prednisolone 7.5 mg daily, and placebo. Particular attention was paid to the pattern of clinical response and to changes in the four week period following discontinuation of treatment. <b>Results:</b> There were improvements in tender joint count and swollen joint count on budesonide 9 mg compared with placebo (28% for tender and 34% for swollen joint counts, p&lt;0.05). Prednisolone 7.5 mg gave similar results, while budesonide 3 mg was less effective. ACR20 response criteria were met by 25% of patients on placebo, 22% on budesonide 3 mg, 42% on budesonide 9 mg, and 56% on prednisolone 7.5 mg. A rapid and significant reduction in symptoms and signs in response to budesonide 9 mg and prednisolone 7.5 mg was evident by two weeks and maximal at eight weeks. There was no evidence that budesonide provided a different pattern of symptom control from prednisolone, or that symptoms became worse than placebo treatment levels after discontinuation of glucocorticoid treatment. Adverse effects attributable to glucocorticoids were equally common in all groups. <b>Conclusions:</b> The symptomatic benefits of budesonide 9 mg and prednisolone 7.5 mg are achieved within a short time of initiating treatment, are maintained for three months, and are not associated with any rebound in symptoms after stopping treatment.
Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women
Authors: J Paavonen, P Naud, J Salmerón, CM Wheeler, S-N Chow, D Apter, H Kitchener, X Castellsague, JC Teixeira, SR Skinner, J Hedrick, U Jaisamrarn, G Limson, S Garland, A Szarewski, B Romanowski, FY Aoki, TF Schwarz, WAJ Poppe, FX Bosch, D Jenkins, K Hardt, T Zahaf, D Descamps, F Struyf, M Lehtinen, G Dubin
Journal: The Lancet (2009)
Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer
Authors: G. Spitaleri, D.V. Matei, G. Curigliano, S. Detti, F. Verweij, S. Zambito, E. Scardino, B. Rocco, F. Nolè, L. Ariu, T. De Pas, F. de Braud, O. De Cobelli
Journal: Annals of Oncology (2009)
Decreased plasma isoleucine concentrations after upper gastrointestinal haemorrhage in humans.
Authors: C H Dejong, W J Meijerink, C L van Berlo, N E Deutz, P B Soeters
Journal: Gut (1996)

A decrease in arterial isoleucine values after intragastric blood administration in pigs has been observed. This contrasted with increased values of most other amino acids, ammonia, and urea. After an isonitrogenous control meal in these pigs all amino acids including isoleucine increased, and urea increased to a lesser extent, suggesting a relation between the arterial isoleucine decrease and uraemia after gastrointestinal haemorrhage.To extend these findings to humans, plasma amino acids were determined after gastrointestinal haemorrhage in patients with peptic ulcers (n = 9) or oesophageal varices induced by liver cirrhosis (n = 4) and compared with preoperative patients (n = 106).After gastrointestinal haemorrhage, isoleucine decreased in all patients by more than 60% and normalised within 48 hours. Most other amino acids increased and also normalised within 48 hours. Uraemia occurred in both groups, hyperammonaemia was seen in patients with liver cirrhosis.These results confirm previous findings in animals and healthy volunteers that plasma isoleucine decreases after simulated upper gastrointestinal haemorrhage. This supports the hypothesis that the absence of isoleucine in blood protein causes decreased plasma isoleucine values after gastrointestinal haemorrhage, and may be a contributory factor to uraemia and hyperammonaemia in patients with normal and impaired liver function, respectively. Intravenous isoleucine administration after gastrointestinal haemorrhage could be beneficial and will be the subject of further research.
Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by Differential Inhibition of EGFR Signaling Pathways in Non–Small Cell Lung Cancer
Authors: Viviana De Rosa, Francesca Iommelli, Marcello Monti, Rosa Fonti, Giuseppina Votta, Maria Patrizia Stoppelli, Silvana Del Vecchio
Journal: Clinical Cancer Research (2015)

One of the hallmarks of cancer cells is the excessive conversion of glucose to lactate under normoxic conditions, also known as the Warburg effect. Here, we tested whether the targeted inhibition of EGFR may revert this effect and reactivate mitochondrial oxidative phosphorylation in non-small cell lung cancer (NSCLC).Sensitive (HCC827) and resistant (H1975 and H1993) NSCLC cells were treated with a panel of EGFR or MET inhibitors, and then tested for changes of EGFR signaling, glycolytic cascade, and mitochondrial function. Silencing of key glycolytic enzymes was then performed with targeted siRNAs. Furthermore, tumor-bearing nude mice treated with EGFR inhibitors were evaluated with (18)F-FDG PET/CT and tumors were analyzed for glycolytic and mitochondrial proteins.Effective inhibition of EGFR signaling in NSCLC cells induced a dramatic reduction of hexokinase II (HKII) and phospho-pyruvate kinase M2 (p-PKM2, Tyr105) levels as well as an upregulation of mitochondrial complexes subunits (OXPHOS). Accordingly, a decreased lactate secretion and increased intracellular ATP levels were also observed in response to EGFR inhibitors. Downregulation of HKII and PKM2 by targeted siRNA transfection did not cause upregulation of OXPHOS but enhanced the effects of EGFR TKIs. Conversely, selective inhibition of AKT and ERK1/2 caused OXPHOS upregulation and glycolysis inhibition, respectively. Similar findings were obtained in tumors from animals treated with appropriate EGFR inhibitors.Our findings indicate that EGFR inhibitors may reactivate oxidative phosphorylation of cancer cells and provide a mechanistic clue for the rational combination of agents targeting EGFR-dependent proliferation and glucose metabolism in cancer therapy.
Cardiovascular development. Prospects for a genetic approach.
Authors: M C Fishman, D Y Stainier
Journal: Circulation Research (1994)

Genetics is a powerful tool, especially when used in combination with embryology, in the seeking of genes necessary for assembly of the cardiovasculature. The first questions must address the types of cellular decisions that are made during development. As for simpler systems in C elegans and D melanogaster, the lineage and cell-fate decisions of the cardiovascular progenitors need to be assessed. In addition it is likely that new paradigms will emerge for multicellular assembly. The study of cardiovascular mutations will define individual genetic steps that define organotypic decisions. A genetic approach is a natural extension of embryology, physiology, and anatomy, fields of great sophistication with regard to the cardiovasculature, because, like them, it focuses on integrative biology and on the intact organism. The zebrafish is particularly well suited to a combination genetic-embryologic study of the fashioning of the cardiovasculature.
Identification of the gene altered in Berardinelli–Seip congenital lipodystrophy on chromosome 11q13
Authors: Jocelyne Magré, Marc Delépine, Eliane Khallouf, Tobias Gedde-Dahl, Lionel Van Maldergem, Eric Sobel, Jeanette Papp, Muriel Meier, André Mégarbané, A. Bachy, A. Verloes, F. H. D'Abronzo, E. Seemanova, R. Assan, N. Baudic, C. Bourut, P. Czernichow, F. Huet, F. Grigorescu, M. De Kerdanet, D. Lacombe, P. Labrune, M. Lanza, H. Loret, Fumihiko Matsuda, J. Navarro, A. Nivelon-Chevalier, M. Polak, J. J. Robert, P. Tric, N. Tubiana-Rufi, C. Vigouroux, J. Weissenbach, S. Savasta, J. A. Maassen, O. Trygstad, P. Bogalho, P. Freitas, J. L. Medina, F. Bonnicci, B. I. Joffe, G. Loyson, V. R. Panz, F. J. Raal, S. O'Rahilly, T. Stephenson, C. R. Kahn, Mark Lathrop, Jacqueline Capeau
Journal: Nature Genetics (2001)
Induction of sleep apnoea with negative pressure ventilation in patients with chronic obstructive lung disease.
Authors: R D Levy, M G Cosio, L Gibbons, P T Macklem, J G Martin
Journal: Thorax (1992)

Negative pressure ventilation provides intermittent non-invasive ventilatory assistance for patients with advanced chronic obstructive lung disease. Upper airway obstruction during sleep, a reported complication of the technique, may, however, limit its clinical applicability.The effects of nocturnal negative pressure ventilation on ventilation and on indices of sleep quality were investigated in five patients with severe chronic obstructive lung disease (mean (SE) FEV1 31% (3%) predicted) who had completed three months of nightly negative pressure ventilation. Subjects underwent overnight polysomnography on consecutive nights, the first night serving as a control and negative pressure ventilation being provided on the second night. Ventilators were adjusted to result in maximum suppression of the peak phasic electromyogram signal from the diaphragm.Negative pressure ventilation resulted in substantial increases in episodes of obstructive apnoea and hypopnoea (mean (SE)/h 59.3 (19.8) v 3.2 (1.3) on control nights). Most obstructive events, however, were associated with under 3% oxygen desaturation, and the lowest recorded values for overnight oxygen saturation were similar on the two study nights. Negative pressure ventilation was also associated with significant increases in the frequencies of movement arousals and changes in sleep stage.Negative pressure ventilation applied during sleep to patients with advanced chronic obstructive lung disease may result in the development of recurrent episodes of apnoea and hypopnoea as well as altered sleep quality, which could limit its clinical applicability.