tbuckley/cabot-search huggingface dataset:
Abstract LB-139: IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism
Authors: Alexandra R. Grassian, Seth Parker, Shawn Davidson, Ajit Divakaruni, Courtney Green, Xiamei Zhang, Kelly Slocum, Minying Pu, Fallon Lin, Chad Vickers, Carol Joud-Caldwell, Franklin Chung, Hong Yin, Erika Handly, Christopher Straub, Joseph D. Growney, Matt Vander Heiden, Anne Murphy, Raymond Pagliarini, Christian Metallo
Journal: Cancer Research (2014)

Abstract Mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a variety of tumor types, resulting in production of the proposed oncometabolite, 2-hydroxyglutarate (2-HG). How mutant IDH alters central carbon metabolism, though, remains unclear. To address this question, we performed 13C metabolic flux analysis (MFA) on an isogenic cell panel containing heterozygous IDH1/2 mutations. We observe a dramatic and consistent decrease in the ability of IDH1, but not IDH2, mutant cell lines to utilize reductive glutamine metabolism via the carboxylation of α-ketoglutarate to isocitrate. Additionally we find that cells with IDH1 mutations exhibit increased oxidative tricarboxylic acid (TCA) metabolism. Similar metabolic trends were observed in vivo as well, and also in endogenous, non-engineered IDH1/2 mutant cell lines. Interestingly, IDH1-mutant specific inhibitors were unable to reverse the decrease in reductive metabolism, suggesting that this metabolic phenotype is independent of 2-HG. Furthermore, this metabolic reprogramming increases the sensitivity of IDH1 mutant cells to hypoxia or electron transport chain (ETC) inhibition in vitro. IDH1 mutant cells also grow poorly as subcutaneous xenografts within hypoxic in vivo microenvironments. These results suggest that exploiting metabolic defects specific to IDH1 mutant cells could be an interesting avenue to explore therapeutically. Citation Format: Alexandra R. Grassian, Seth Parker, Shawn Davidson, Ajit Divakaruni, Courtney Green, Xiamei Zhang, Kelly Slocum, Minying Pu, Fallon Lin, Chad Vickers, Carol Joud-Caldwell, Franklin Chung, Hong Yin, Erika Handly, Christopher Straub, Joseph D. Growney, Matt Vander Heiden, Anne Murphy, Raymond Pagliarini, Christian Metallo. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-139. doi:10.1158/1538-7445.AM2014-LB-139
On the role of platelets in the pathogenesis of viral hepatitis
Authors: Matteo Iannacone, Giovanni Sitia, Luca G. Guidotti
Journal: Journal of Hepatology (2009)

We read with interest the commentary by Ulrich Spengler [1] where he evaluated a recent manuscript by Lang et al. [2] on the role of platelet-derived serotonin in the pathogenesis of viral hepatitis. We were somewhat surprised to see that work constituting the foundation of the above-mentioned study was not cited. A few years ago our group started investigating the role of platelets in the pathogenesis of viral hepatitis, using different mouse models that include transgenic mice replicating hepatitis B virus (HBV) at high levels in the hepatocyte and mice infected with hepatotropic adenoviruses and arenaviruses (i.e.
AVOIDANCE OF DEGENERATIVE LESIONS IN DIABETES MELLITUS
Authors: JULIAN D. BOYD
Journal: JAMA (1942)

Maintenance of life is not sufficient in itself as a goal in the treatment of diabetes mellitus. Insulin has made it easy for the patient with diabetes to survive. Therapy with insulin has such a broad zone of safety that its use tends to encourage a policy of laissez faire on the part of the patient and of the physician. Degenerative changes frequently develop in the diabetic patient who has been led to think that the management of his disease has been adequate. Because of this fact, confusion has arisen as to the essential cause of the sequelae of diabetes mellitus; are they inherent in the disease itself or do they reflect inadequacies in the level of control maintained throughout short or long intervals of the diabetic patient's life? To make an adequate appraisal of the part played by the disease itself as distinguished from conditions imposed by its noncontrol,
Abstract 1906: IL-6-mediated activation of STAT3 inhibits APC and T cell function in metastatic breast cancer
Authors: Karen S. Anderson, Tetsuro Sasada, Erik Nelson, Khash Khazaie, Gang Feng, Simon Lin, David A. Frank
Journal: Cancer Research (2010)

Abstract Background: The transcription factor STAT3 is a negative regulator of myeloid inflammatory immune responses, leading to profound suppression of dendritic cell (DC) and T cell function, and anti-tumor immunity. Blockade of STAT3 signaling in tumor models results in activation of innate immune cells, DCs, and tumor infiltration of T cells. We hypothesized that tumor associated macrophages (TAMs) from breast cancer patients were dysfunctional, due to IL-6-mediated activation of STAT3. Methods: To isolate sufficient numbers of CD14+ TAMs and CD3+ tumor infiltrating lymphocytes (TILs) for functional assays, 10 malignant effusions were obtained from breast cancer patients and peripheral blood was obtained from 8 healthy controls. Levels of up to 22 cytokines in the effusions and the blood were determined by Luminex cytokine assay. CD14+ TAMs and CD3+ TILs were magnetically sorted, and functional mixed lymphocyte reaction (MLR) assays were performed. Quantitation of STAT3 and tyrosine-phosphorylated STAT3 (pSTAT3) were determined by immunoblotting. RNA expression analysis of TILs and healthy donor CD3+ cells was performed using Affymetrix U133 microarrays. Results: Malignant effusions from breast cancer patients have high levels of IL-6 (mean 3188 pg/ml; range 966-5235), compared with serum from healthy donors (mean 88 pg/ml; p&amp;lt;0.0001). TAMs isolated from malignant effusions, but not peripheral blood, poorly stimulated healthy T cells in MLR, and showed increased expression of pSTAT3 and total STAT3 on immunoblot. A 30 minute exposure to a malignant effusion containing high levels of IL-6 markedly induced STAT3 activation in healthy donor CD14+ monocytes. Compared with CD3 cells from healthy donors (n=3), RNA microarray analysis of CD3+ TILs (n=3) showed downregulation in TCR signalling (Zap70, fyn, PI3K), NK/CTLs (CD160, KLRF1), and chemokines for T cell trafficking (CXCR4). Immunosuppressive factors (IL10, PDIA4, IL13R, STAT1, and VEGF) were upregulated (p&amp;lt;0.05). Conclusions: High levels of IL-6 in breast cancer malignant effusions are associated with both antigen presenting cell and T cell dysfunction. Inhibition of STAT3 is a potential target to enhance immune activation. 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 1906.
Low-salt Diet in Treatment of Hypertension
Authors: H. O. Bang, P. Bechgaard, A. L. Nielsen
Journal: BMJ (1949)

JOURNALipsilateral side was fixed or its excursion very much reduced, while on the contralateral side movement was free; yet the only case in his series to develop pulmonary complica- tions produced a lower-lobe atelectasis on the contralateral side.SummaryThe incidence of pulmonary complications following upper abdominal operations remains high.After an upper abdominal operation the vital capacity is regularly decreased to the region of 35% of its pre-operative volume.Intravenous drip procaine is an excellent method of relieving post-operative pain in cases in which it is important not to decrease pulmonary ventilation.There is evidence that some increase of vital capacity follows the relief of post-operative pain by this method in abdominal cases.This increase, however, is so small that it is suggested that other theoretical causes for the lowered vital capacity need investigation.
Transtracheal aspiration using rigid bronchoscopy and a rigid needle for investigating mediastinal masses.
Authors: M. L. Wilsher, A. M. Gurley
Journal: Thorax (1996)

Use of the flexible needle via the fibreoptic bronchoscope to aspirate mediastinal nodes or masses has largely superseded the use of the rigid needle via the rigid bronchoscope. However, the yield at fibreoptic bronchoscopy is relatively low, although this improves with the use of a wider gauge needle. In this study the sensitivity and the safety of rigid needle sampling of the mediastinum in the diagnosis of lung cancer is evaluated.Transtracheal needle aspiration (TTNA) was performed with the rigid bronchoscope and a rigid aspiration needle under general anaesthesia using a previous computed tomographic (CT) scan as a guide to the sample site. A cytopathologist immediately examined the specimens for adequacy and preliminary diagnosis, thus determining the number of aspirations.Twenty four patients were evaluated. The diagnostic sensitivity of TTNA was 88%. This led to a management decision in 21 patients. There were no false positives and no complications.TTNA using the rigid bronchoscope with CT scanning and a cytopathologist present is a sensitive and safe way of diagnosing lung cancer in patients with a mediastinal mass or enlarged mediastinal nodes.
Medical Management of Older Patients
Authors: Wingate M. Johnson
Journal: JAMA (1961)

The long-term management of the older patient is to be distinguished from the treatment of acute illness. The first interview must help to establish a satisfactory long-term relationship between patient and physician. The physical examination must be systematic and complete, but thoroughness is not incompatible with gentleness and tact. Methods of treatment should take into account the patient's life-long habits, and in cases where treatment is only palliative a careful choice of words often brings about acceptance of the situation. Prophylactic geriatrics seeks to prevent, postpone, or prepare for the infirmities of old age. The family doctor can help both his youngest and his oldest patients by leading the family to appreciate their need of a recognized place in the community.
A Medical Bibliography (Garrison and Morton): An Annotated Check-list of Texts Illustrating the History of Medicine
Authors: William K. Beatty
Journal: JAMA (1985)

Every specialty has its basic reference work. Garrison and Morton has served as the basic historical reference work for all facets of medicine for 40 years. For each major medical subject this invaluable book lists the important contributions (books and journal articles) in a chronological arrangement. Most entries also have an annotation that describes the clinical or research work reported in that publication. The new edition contains 7,830 entries.  A sample entry, the eighth under Thyroid Gland, will clarify the picture:  3812 COINDET, Jean Francois. 1774-1834. Decouverte d'un nouveau remede contre le goitre. Bibliotheque universelle , 1820, 14, 190-98; also in Ann Chim Phys , 1820, 15, 49-59. Coindet is usually regarded as the first to administer iodine in cases of goiter, with beneficial results. It had previously been prepared from seaweed by B. Courtois in 1812 ( Ann Chim (Paris) , 1813, 88, 304-10), and both Ampere and Humphry Davy were interested in
Angiogenic Markers Show High Prognostic Impact on Survival in Marginally Operable Non-small Cell Lung Cancer Patients Treated with Adjuvant Radiotherapy
Authors: Sigve Andersen, Tom Donnem, Samer Al-Saad, Khalid Al-Shibli, Lill-Tove Busund, Roy M. Bremnes
Journal: Journal of Thoracic Oncology (2009)
Pains are in the head, not the spine
Authors: Valerie Gray Hardcastle
Journal: Behavioral and Brain Sciences (1997)

The authors presume that activity in the dorsal horn or nociceptors is well correlated with pain sensations and behavior. This overlooks the myriad of interactions between cortex and our spinothalamic tract. It is better to think of our nociceptors, the dorsal horn, and the pain centers in our brain as all components in one larger and complex pain sensory system. [berkley; blumberg et al.; coderre &amp; katz; dickenson; mcmahon; wiesenfeld-hallin et al.]
Airway Wall Thickness Assessed Using Computed Tomography and Optical Coherence Tomography
Authors: Harvey O. Coxson, Brendan Quiney, Don D. Sin, Li Xing, Annette M. McWilliams, John R. Mayo, Stephen Lam
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Computed tomography (CT) has been shown to reliably measure the airway wall dimensions of medium to large airways. Optical coherence tomography (OCT) is a promising new micron-scale resolution imaging technique that can image small airways 2 mm in diameter or less.To correlate OCT measurements of airway dimensions with measurements assessed using CT scans and lung function.Forty-four current and former smokers received spirometry, CT scans, and OCT imaging at the time of bronchoscopy. Specific bronchial segments were identified and measured using the OCT images and three-dimensional reconstructions of the bronchial tree using CT.There was a strong correlation between CT and OCT measurements of lumen and wall area (r = 0.84, P < 0.001, and r = 0.89, P < 0.001, respectively). Compared with CT, OCT measurements were lower for both lumen and wall area by 31 and 66%, respectively. The correlation between FEV(1)% predicted and CT and OCT measured wall area (as percentage of the total area) of fifth-generation airways was very strong (r = -0.79, r = -0.75), but the slope of the relationship was much steeper using OCT than using CT (y = -0.33x + 82, y = -0.1x + 78), indicating greater sensitivity of OCT in detecting changes in wall measurements that relate to FEV(1).OCT can be used to measure airway wall dimensions. OCT may be more sensitive at detecting small airway wall changes that lead to FEV(1) changes in individuals with obstructive airway disease.
Comparison of Human Ventricular Activation with a Canine Model in Chronic Myocardial Infarction
Authors: THOMAS M. DANIEL, JOHN P. BOINEAU, DAVID C. SABISTON
Journal: Circulation (1971)

Ventricular activation was studied in 20 patients with ischemic heart disease at the time of surgery for myocardial revascularization. Because most of the activation studies in man were limited to recording of epicardial potentials, a canine model of chronic infarction was also studied. Pre- and postinfarction data were recorded in dogs and correlated with the anatomy of the lesions. Epicardial Q waves, when associated with delayed epicardial activation, were diagnostic of underlying infarctions in areas of the heart that did not normally exhibit Q waves. In areas normally containing Q waves, underlying infarction was associated with Q waves greater in duration than the normal range determined for those areas of the epicardium. The experimental model of chronic infarction showed epicardial delay to be due to slowed intramyocardial activation rather than to delay in Purkinje conduction. Correlations between electrical and anatomic data in two patients suggested that, within limits, the detailed relationships between infarction and activation established with the canine model could be applied to human infarction to understand the genesis of the epicardial potentials and the ECG. The technique was also felt to have a practical clinical application in selection of areas of myocardium for vascular implants or infarctectomy.
Scintigraphic Demonstration of Acute Gastrointestinal Bleeding Caused by Gallbladder Carcinoma Eroding the Colon
Authors: ABRAHAM CZERNIAK, S. TZILA ZWAS, MICHA Y. RABAU, ITAMAR AVIGAD, BENJAMINA BORAG, ISIDOR WOLFSTEIN
Journal: Clinical Nuclear Medicine (1985)

Massive lower gastrointestinal (Gl) bleeding caused by gallbladder carcinoma eroding into the colonic wall was demonstrated accurately by Tc-99m RBCs. In addition, retrograde bleeding into the gallbladder was also identified while arteriography did not show contrast extravasation. This case supports the use of Tc-99m RBCs over Tc-99m sulfur colloid for more accurate localization of lower Gl bleeding.
806 EVALUATION OF TOLERANCE AND OUTCOME OF PATIENTS WITH HEPATOCELLULAR CARCINOMA TREATED BY SORAFENIB (AFTER THE SHARP STUDY)
Authors: V. Ozenne, S. Pernot, M.-P. Vullierme, V. Paradis, T. Serste, C. Castelnau, D. Valla, T. Boulet, F. Degos
Journal: Journal of Hepatology (2009)
Risk Factors for Chronic Obstructive Pulmonary Disease in a European Cohort of Young Adults
Authors: Roberto de Marco, Simone Accordini, Alessandro Marcon, Isa Cerveri, Josep M. Antó, Thorarinn Gislason, Joachim Heinrich, Christer Janson, Deborah Jarvis, Nino Kuenzli, Bénédicte Leynaert, Jordi Sunyer, Cecilie Svanes, Matthias Wjst, Peter Burney
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: Few studies have investigated the factors associated with the early inception of chronic obstructive pulmonary disease (COPD).Objectives: We investigated COPD risk factors in an international cohort of young adults using different spirometric definitions of the disease.Methods: We studied 4,636 subjects without asthma who had prebronchodilator FEV1/FVC measured in the European Community Respiratory Health Survey both in 1991 to 1993 (when they were 20–44 yr old) and in 1999 to 2002. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease fixed cut-off criterion (FEV1/FVC < 0.70), and two criteria based on the Quanjer and LuftiBus reference equations (FEV1/FVC less than lower limit of normal). COPD determinants were studied using two-level Poisson regression models.Measurements and Main Results: COPD incidence ranged from 1.85 (lower limit of normal [Quanjer]) to 2.88 (Global Initiative for Chronic Obstructive Lung Disease) cases/1,000/yr. Although about half of the cases had smoked less than 20 pack-years, smoking was the main risk factor for COPD, and it accounted for 29 to 39% of the new cases during the follow-up. Airway hyperresponsiveness was the second strongest risk factor (15–17% of new cases). Other determinants were respiratory infections in childhood and a family history of asthma, whereas the role of sex, age, and of being underweight largely depended on the definition of COPD used.Conclusions: COPD may start early in life. Smoking prevention should be given the highest priority to reduce COPD occurrence. Airway hyperresponsiveness, a family history of asthma, and respiratory infections in childhood are other important determinants of COPD. We suggest the need for a definition of COPD that is not exclusively based on spirometry.
Gelatin–fibrinogen cryogel dermal matrices for wound repair: Preparation, optimisation and in vitro study
Authors: Maria B. Dainiak, Iain U. Allan, Irina N. Savina, Lisa Cornelio, Elizabeth S. James, Stuart L. James, Sergey V. Mikhalovsky, Hans Jungvid, Igor Yu. Galaev
Journal: Biomaterials (2009)
Platelet-derived soluble factors induce human extravillous trophoblast migration and differentiation: platelets are a possible regulator of trophoblast infiltration into maternal spiral arteries
Authors: Yukiyasu Sato, Hiroshi Fujiwara, Bin-Xiang Zeng, Toshihiro Higuchi, Shinya Yoshioka, Shingo Fujii
Journal: Blood (2005)
Risk levels for mite allergens. Are they meaningful?
Authors: A. Custovic, M. Chapman
Journal: Allergy (1998)

Allergens found in house dust are among the most common environmental antigens to which man is naturally exposed. Standardized methods for measuring allergen exposure are essential for assessing the relationship between exposure, sensitization, and the severity of asthma. Monoclonal antibody-based assays are the most widely used method for assessing allergen exposure. In the effort to define the best "index of exposure" to mite allergens, several factors need to be investigated, including: 1) whether allergen should be measured in reservoir dust or airborne 2) whether the results of reservoir measurement should be expressed as recovered allergen per unit weight or per unit area. As yet, airborne sampling is insufficiently sensitive to produce reliable and repeatable results. Therefore, measurement of house-dust-mite allergen concentration in reservoir dust should be regarded as the best-validated index of exposure. The results should be expressed and reported both per unit weight (concentration) and per unit area. The strongest predictor of chronic symptoms and acute exacerbation of asthma is sensitization to indoor allergens. A simple dose-response relationship between IgE-mediated hypersensitivity and allergen exposure has been established. For example, exposure to more than 2 μg Group 1 mite allergen/g dust should be regarded as a risk factor for the development of IgE antibody and asthma in susceptible children. The quantitative relationship between exposure and symptoms in patients already sensitized is complex due to a number of possible confounding factors (e.g., other allergens, viruses, asthma medication). A simple threshold level for provocation of asthmatic symptoms has not been clearly defined.
Which colour space(s) is Shepard talking about?
Authors: Lieven Decock, Jaap van Brakel
Journal: Behavioral and Brain Sciences (2001)

Contra Shepard we argue, first, that his presentation of a three-dimensional representational (psychological or phenomenal) colour space is at odds with many results in colour science, and, second, that there is insufficient evidence for Shepard's stronger claim that the three-dimensionality of colour perception has resulted from natural selection, moulded by the particulars of the solar spectrum and its variations. [Shepard]
Pseudomonas cepacia in cystic fibrosis.
Authors: D E Stableforth, D L Smith
Journal: Thorax (1994)

Abstract Background: Differences have shown to exist in some echocardiographic measurements that were attributed to racial, ethnic and gender. This study determined echocardiographic baseline data of normal adult left ventricular (LV) geometry in our locality. Methods: The study was performed on 1,192 apparently healthy adults. Participants below the age of 18 years or those with congenital or acquired cardiac abnormalities and history of long-term regular physical training were excluded. Trans-thoracic echocardiography was performed with Vivid T8 GE dedicated echocardiography machine with probe frequency of 1.7 to 3.2 MHz with integrated electrocardiography (ECG) recording electrodes. The study determined normal dimensions of interventricular diamensions. All measurements were indexed to body surface area (BSA) to obtain echocardiographic baseline normal reference values. Results: The mean + SD values of LV parameters for male and female participants were: LVIDd (44.80 ± 5.71 mm vs 42.75 ± 5.21 mm), LVIDs (33.54 ± 5.37 mm vs 30.38 ± 4.81 mm), and LVPWd (8.32 ± 1.26 mm vs 7.51 ± 1.22 mm). Females had more statistically significant interventricular septum in diastole (IVSd) (8.20 ± 1.38 mm vs 7.05 ± 1.27 mm) and interventricular septum in systole (IVSs) (9.08 ± 1.42 mm vs 8.99 ± 1.33 mm) (P &lt; 0.05). Conclusion: This research established echocardiographic baseline normal adult left ventricular geometry in the study population because in order to detect abnormalities, accurate definition of normal values of echocardiographic measurements is of utmost importance for a reliable clinical decision making. KEYWORDS: Echocardiography, normal values, ventricular geometry, Nnewi Nigeria
Prostaglandins and carcinoid tumours.
Authors: J Delmont, P Rampal
Journal: BMJ (1975)

correlationi between the vaginal lhormoinal state and the hody wcigl-t.l)uring treatentcit (which was nutritive, not hiormonal) irn all but one case thcre was a signiticanit alteration in the vaginal hormnonal cytological pattern in that appearance ot a cyclic character coul(d bc demonstrated ailthoughi menstruation had not vct returned.'Wc ftind this method very uscful, particularly as it can be repeated frcquently.