tbuckley/cabot-search huggingface dataset:
Abstract A34: Nitric Oxide enhances inflammation, microRNA-21 expression and KRAS-induced lung carcinogenesis
Authors: Hirokazu Okayama, Motonobu Saito, Oue Naohide, Jonathan M. Weiss, Jimmy Stauffer, Seiichi Takanoshita, Robert H. Wiltrout, S. Perwez Hussain, Curtis C. Harris
Journal: Clinical Cancer Research (2012)

Abstract Mutant KRAS in lung cancers induce molecular pathways that regulate cellular proliferation, survival and inflammation, which enhance tumorigenesis. Inducible nitric oxide synthese (NOS2) up-regulation and sustained nitric oxide (NO•) generation are induced during the inflammatory response and correlate positively with lung tumorigenesis. To explore the mechanistic contribution of NOS2 to KRAS-induced lung tumorigenesis and inflammation, we used a genetic strategy of crossing NOS2 knockout (NOS2KO) C57BL6 inbred mice with a KRASG12D-driven mouse lung cancer model. KRASG12D/NOS2KO mice exhibited delayed lung tumorigenesis, resulting in a longer overall survival time compared with that of KRASG12D/NOS2WT (wildtype) controls. Correspondingly, tumors in KRASG12D/NOS2KO mice had reduced tumor cell proliferation in adenomas and carcinomas. NOS2-deficiency also led to dramatically suppressed inflammatory response by attenuation of macrophage recruitment into alveoli and within tumor foci. In contrast, FOXP3+ regulatory T cells were increased in tumors from KRASG12D/NOS2KO mice. We further analyzed the expression of microRNA-21 (miR-21), an oncogenic non-coding RNA involved in oncogenic Ras signaling, by quantitative reverse transcription PCR and in situ hybridization. Lung carcinomas dissected from KRASG12D/NOS2KO mice showed a significantly reduced miR-21 expression along with decreased tumor cell proliferation, suggesting that NOS2-deficiency could attenuate RAS signaling pathways that transactivate miR-21 expression. Therefore, deletion of NOS2 decreases lung tumor growth as well as inflammatory responses initiated by oncogenic KRAS, suggesting that both KRAS and NOS2 cooperate in driving lung tumorigenesis and inflammation. Inhibition of NOS2 may have a therapeutic value in lung cancers with oncogenic KRAS mutations.
Blood Cultures Drawn from Indwelling Central Venous Catheters
Authors: David R. Snydman, Robin Ruthazer
Journal: Annals of Internal Medicine (2000)

Letters6 June 2000Blood Cultures Drawn from Indwelling Central Venous CathetersDavid R. Snydman, MD and Robin Ruthazer, MPHDavid R. Snydman, MDNew England Medical Center; Boston, MA 02111 (Snydman)New England Medical Center; Boston, MA 02111 (Ruthazer)Search for more papers by this author and Robin Ruthazer, MPHNew England Medical Center; Boston, MA 02111 (Snydman)New England Medical Center; Boston, MA 02111 (Ruthazer)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-11-200006060-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Johnson's interest in our study. We agree that all positive blood cultures require clinical interpretation and concur that blood cultures drawn peripherally and those drawn from a catheter need such interpretation. We have provided a conservative interpretation based on the lower boundary of the 95% CI for the two methods.Dr. Johnson makes an interesting point about the omission of the predictive value for discordant results. In response to his request we provide these results, but we believe that these results do not indicate a need to obtain a peripheral sample after obtaining a catheter ... Author, Article, and Disclosure InformationAffiliations: New England Medical Center; Boston, MA 02111 (Snydman)New England Medical Center; Boston, MA 02111 (Ruthazer) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoClinical Utility of Blood Cultures Drawn from Indwelling Central Venous Catheters in Hospitalized Patients with Cancer Jeffrey A. DesJardin , Matthew E. Falagas , Robin Ruthazer , John Griffith , Dorothy Wawrose , David Schenkein , Kenneth Miller , and David R. Snydman Blood Cultures Drawn from Indwelling Central Venous Catheters James R. Johnson Metrics 6 June 2000Volume 132, Issue 11Page: 922KeywordsBloodCathetersNegative predictive valuePositive predictive value Issue Published: 6 June 2000 CopyrightCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Neuropeptide signaling and hydrocephalus: SCO with the flow
Authors: David J Picketts
Journal: Journal of Clinical Investigation (2006)

Congenital hydrocephalus affects 0.1–0.3% of live births, with a high mortality rate (~50%) in the absence of surgical intervention. Although the insertion of shunts alleviates the symptoms of the majority of congenital cases, the molecular basis of hydrocephalus and the mechanisms of cerebrospinal fluid (CSF) circulation remain largely unknown. Two important players are the subcommissural organ/Reissner's fiber (SCO/RF) complex and the ventricular ependymal (vel) cells that together facilitate the flow of the CSF through the narrow canals of the ventricular system. In this issue of the JCI, Lang et al. demonstrate that overexpression of the pituitary adenylate cyclase–activating polypeptide (PACAP) type I (PAC1) receptor gene results in abnormal development of the SCO and vel cells, leading to congenital hydrocephalus (see the related article beginning on page 1924). The ligand for the PAC1 receptor is the neuropeptide PACAP, which uncovers what the authors believe to be a novel role for this signaling cascade in the regulation of CSF circulation.
Effects of S-adenosylmethionine on lipid peroxidation and liver fibrogenesis in carbon tetrachloride-induced cirrhosis
Authors: Marta Gassó, Mireia Rubio, Gregorio Varela, María Cabré, Joan Caballería, Elena Alonso, Ramón Deulofem, Jordi Camps, América Giménez, María Pajares, Albert Parés, José M. Mato, Joan Rodés
Journal: Journal of Hepatology (1996)
Oral Contraceptive Use and Association With Glucose, Insulin, and Diabetes in Young Adult Women
Authors: Catherine Kim, David S. Siscovick, Stephen Sidney, Cora E. Lewis, Catarina I. Kiefe, Thomas D. Koepsell
Journal: Diabetes Care (2002)

OBJECTIVE— We studied the associations between 1) current use of oral contraceptives (OCs) and 2) glucose levels, insulin levels, and diabetes in young women. RESEARCH DESIGN AND METHODS—Subjects were women (n = 1,940) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective observational study of African-Americans and whites aged 18–30 years at enrollment in 1985–1986. We analyzed the cross-sectional associations between 1) current use of OCs and 2) fasting glucose, fasting insulin, and presence of diabetes using generalized estimating equations to adjust for repeated measures. We also examined the effect of current use of OCs on incident diabetes at year 10 of the study. RESULTS—In unadjusted analyses, current use was associated with lower fasting glucose levels [–3.1 mg/dl, 95% CI (−3.7, −2.5)] and reduction in the odds of diabetes [odds ratio 0.56 (0.32, 0.97)], but not lower fasting insulin levels [−0.01 μU/ml (−0.03, 0.02)], compared with nonuse in both African-American and white women. After adjustment for covariates, current use of OCs was still associated with lower fasting glucose levels [–1.8 mg/dl (−2.4, –1.3)] and lower odds of diabetes [odds ratio 0.56 (0.33, 0.95)], although the associations were attenuated. After adjustment, current use of OCs was associated with higher insulin levels [0.12 μU/ml (0.006, 0.23)]. No association existed between pattern of use of OCs and incident diabetes at year 10, although the total number of new persons with diabetes at year 10 was small (n = 17). CONCLUSIONS—Current use of OCs is associated with lower glucose levels in young African-American and white women and may be associated with lower odds of diabetes.
Sequencing of soy oil and soy lecithin allergens*1
Authors: Y. Errahali, G. Kanny, M. Morisset, C. Cren-Olive, C. Rolando, M. Metche, D.A. Moneret-Vautrin, J.P. Nicolas, S. Fremont
Journal: Journal of Allergy and Clinical Immunology (2004)
Management of the College Student with Homicidal Impulses—The "Whitman Syndrome"
Authors: JOHN L. KUEHN, JOHN BURTON
Journal: American Journal of Psychiatry (1969)

The authors discuss the management of globally hostile students who have the means to carry out their threats through the use of firearms. Three such students and their treatment are described. Management of the patients emphasized recognition, consultation, hospitalization, and use of drugs and brief psychotherapy.
A potential method of correcting intracavitary left ventricular filling pressures for the effects of positive end-expiratory airway pressure.
Authors: R V Ditchey, J Lindenfeld, E W Grogan, G O Zerbe
Journal: Circulation (1985)

Based on the observation that positive end-expiratory airway pressure (PEEP) causes comparable increments in intrapericardial and right-sided intracardiac pressures, we hypothesized that intracavitary left ventricular filling pressures measured in the presence of PEEP can be corrected for increased intrathoracic pressure by subtracting the effects of PEEP on intracavitary right ventricular filling pressures. Ventricular function curves (aortic blood flow vs intracavitary left ventricular end-diastolic pressure [LVEDP]) were generated with and without 15 cm of water of PEEP in eight dogs. All curves were shifted to the right by PEEP (i.e., intracavitary LVEDP was higher for any submaximal level of aortic blood flow). However, when pressures measured in the presence of PEEP were "corrected" by subtracting the corresponding increment in intracavitary right ventricular end-diastolic pressure caused by PEEP at each level of ventricular filling, control and corrected PEEP data points appeared to fall on the same curve in five dogs, and differed only slightly in three dogs. Mean control and corrected PEEP curves derived by averaging polynomial regression coefficients for each condition differed significantly from uncorrected PEEP curves (p less than .05), but not from each other. Analogous curves based on mean left atrial pressure were corrected equally well by subtracting the effects of PEEP on mean right atrial pressure. We conclude that the increments in intracavitary right heart filling pressures caused by PEEP can be used to correct intracavitary left heart filling pressures for the effects of PEEP on intrathoracic pressure.
Analysis of asynchronous wall motion by regional pressure-length loops in patients with coronary artery disease
Authors: Shigetake Sasayama, Hiroshi Nonogi, Masatoshi Fujita, Tsunetaro Sakurai, Akira Wakabayashi, Chuichi Kawai, Shigeru Eiho, Michiyoshi Kuwahara
Journal: Journal of the American College of Cardiology (1984)
Ten-year haematological follow-up: Mortality and haematological changes
Authors: W. E. Waters, J. L. Withey, G. S. Kilpatrick, P. H. N. Wood, M. Abernethy
Journal: BMJ (1969)

In a 10-year follow-up study of 543 men and 180 women seen in a community survey in 1958 mortality was examined in relation to the 1958 haematological data, and 91% of the survivors were re-examined. Analyses based on the 1958 haemoglobin and packed cell volume estimations suggested that those with values near the mean may subsequently have lower death rates. Higher death rates occurred in those having low serum iron levels. Comparisons of haemoglobin concentrations and of packed cell volumes in 1958 and 1968 show correlation coefficients (r) between 0.30 and 0.60 in various subgroups.
Isolated minimal change nephropathy associated with diclofenac.
Authors: G D Beun, K M Leunissen, P J Van Breda Vriesman, J P Van Hooff, W Grave
Journal: BMJ (1987)

Attendancefor smear test after initial letter and two reminders % Greater response shown by appoint-Letter only Appointment ment group (95% group group confidence interval) No (%) attending after initial letter 26/122 (21) 43/118 (36) 15 (4 to 27) Cumulative total (%) after first reminder 34/122 (28)* 52/118 (44) 16 (4 to 28) Cumulative total (%) after second reminder 39/122 (32)t 56/118 (47) 15 (3 to 28) Cumulative total (%) women aged 45-54-5 after second reminder 28/74 (38) 29/61 (48) 10 (-7 to 26) Cumulative total (%) women aged 54-5-65 years after second reminder 11/48 (23) 27/57 (47) 24 (6 to 43)* Included two women who attended a health authority clinic.t Included three women who attended a health authority clinic.
Pulmonary Alveolar Proteinosis
Authors: Zarir F Udwadia, Sushil Jain
Journal: New England Journal of Medicine (2007)

A 45-year-old male farmer presented with breathlessness, dry cough, and bilateral alveolar and interstitial opacities, leading to a diagnosis of pulmonary alveolar proteinosis. Bilateral lung lavage was performed with 12 liters of saline. The lavage fluid gradually cleared.
Race and Venous Thromboembolism
Authors: Samuel Z. Goldhaber
Journal: Circulation (2014)

C onventional teaching is that a racial gradient exists for the frequency of venous thromboembolism (VTE) in the United States.Asian Americans have the lowest risk, and blacks have the highest risk.Hispanic Americans and Americans of European ancestry have an intermediate risk, with Hispanic Americans having less frequent VTE than those of European but non-Hispanic heritage.The most apparent paradox is that blacks have the highest rate of VTE, even though they rarely carry the prothrombin gene mutation or factor V Leiden mutation, 2 genetic abnormalities that predispose to VTE.Based on genetic profiling (nature), one might have predicted that blacks would have a low rate of VTE.In 1 study, in comparison with individuals of European ancestry and adjusting for age and sex, blacks had a 30% to 60% higher incidence of VTE than European Americans. 1 This finding suggests that environmental and socioeconomic factors and perhaps healthcare disparities (nurture) play an important role in determining the risk of developing VTE.
Four Years' Experience With External Cardiac Resuscitation
Authors: C. Walton Lillehei
Journal: JAMA (1965)

Resuscitation of patients with cardiac asystole or ventricular fibrillation by thoracotomy for cardiac massage combined with artificial ventilation has rarely been successful in the authors' experience. In the ten-year period from 1950 through 1959, there was only one case of successful resuscitation outside of the operating room postanesthesia area, with emergency thoracotomy for massage. In contrast, with external methods, 33 patients were successfully resuscitated and were discharged from the hospital in the four-year period from 1959 through 1963. One successful case required more than three hours of external massage and ventilation, emphasizing the value of sustained efforts in certain cases. On the basis of this experience, external massage combined with artificial ventilation appears to be the method of choice for the management of cardiac arrest or ventricular fibrillation. Direct open cardiac massage would appear to be indicated where the chest is already open or where cardiac tamponade is suspected.
Economics notes: Handling uncertainty in economic evaluation
Authors: A. Briggs
Journal: BMJ (1999)

It is increasingly common to find the results of economic evaluations that report results in terms of cost per life year or cost per quality adjusted life year (QALY) grouped together for comparison in so called cost effectiveness league tables. It is worrying, however, that the rankings in such league tables are made on the basis of point estimates of cost effectiveness without any consideration for the inherent uncertainty involved in their calculation. Consider the figure, where the point estimates for seven different healthcare interventions are plotted in increasing order of magnitude. What is immediately apparent is that the range of uncertainty (shown by the size of the bars around the point estimates) is such that a completely different ranking than that obtained from the order of the point estimates is possible. If policymakers are to be fully informed …
Abstract 490: Investigation of telomere shortening caused by dyskeratosis congenita-associated heterozygous TIN2 mutations
Authors: Duy C. Tran, Amanda K. Frank, Lifeng Xu
Journal: Cancer Research (2014)

Abstract The ends of eukaryotic chromosomes are composed of repetitive telomere sequences bound by the shelterin protein complex. Telomerase, a reverse transcriptase complex, is known to express in highly proliferative tissues and cells in humans to maintain a constant telomere length and to sustain their proliferative potential. Heterozygous missense mutations within one of the shelterin proteins, TIN2, have been identified in patients with Dyskeratosis Congenita (DC), a multiple stem-cell failure syndrome characterized by extremely short telomeres in affected patients. Our study aims to elucidate the mechanism by which TIN2 mutations shorten telomeres in human cells. TIN2 is an essential protein that tethers the shelterin complex together. We generated HCT 116 colorectal cancer cell lines containing heterozygous TIN2 R282H mutation, one of the most common DC-related TIN2 mutations, by zinc-finger-nuclease facilitated gene editing. Clones with heterozygous TIN2 mutation showed progressive telomere shortening, while the wild-type (WT) clones showed no change in telomere length over extended cell proliferation. The progressive telomere shortening phenotype in TIN2 mutants can be rescued by exogenous expression of WT TIN2. However, TIN2 mutant clones do not contain elevated levels of deprotected telomeres, suggesting that the TIN2 mutation does not lead to overall telomere deprotection. We are currently investigating whether the DC-related TIN2 mutation induces telomere shortening by inhibiting telomerase or by accelerating telomere attrition through telomerase-independent mechanisms. Citation Format: Duy C. Tran, Amanda K. Frank, Lifeng Xu. Investigation of telomere shortening caused by dyskeratosis congenita-associated heterozygous TIN2 mutations. [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 490. doi:10.1158/1538-7445.AM2014-490
Recombinant versus natural human 111In-β2-microglobulin for scintigraphic detection of Aβ2m amyloid in dialysis patients
Authors: Jürgen Schäffer, Wolfgang Burchert, Jürgen Floege, Peter Gielow, Christine Kionka, Reinhold P. Linke, Elisabeth H. Weiss, Stanley Shaldon, Karl M. Koch
Journal: Kidney International (2000)
Effects of β-Adrenergic Blocking Therapy on Left Ventricular Diastolic Relaxation Properties in Patients With Dilated Cardiomyopathy
Authors: Michael H. Kim, William H. Devlin, Sunil K. Das, Janet Petrusha, Daniel Montgomery, Mark R. Starling
Journal: Circulation (1999)

Background —The hemodynamic mechanism for the improvement in left ventricle (LV) end-diastolic pressure in cardiomyopathy patients treated with β-adrenergic blocking agents is controversial. We hypothesized that the salutary effect of this kind of therapy on LV end-diastolic pressure would be indicative of an improvement in late, passive diastolic relaxation properties. Methods and Results —We studied 14 cardiomyopathy patients in normal sinus rhythm with no arteriographic evidence of coronary artery disease and an LV ejection fraction of ≤40% by radionuclide angiography both before and after 6 months of metoprolol therapy with simultaneous micromanometry and biplane cineventriculography. Four comparable patients who were not treated with metoprolol were studied in a similar fashion and served as control subjects. In those receiving metoprolol, LV end-diastolic pressure decreased ( P =0.001). The isovolumic relaxation index, τ ln , shortened ( P =0.03). In a similar fashion, the LV chamber stiffness constant, κ, decreased ( P =0.02), LV volume elastance improved ( P =0.04), and the myocardial stiffness constant, κ e , decreased ( P =0.02). A multiple regression analysis revealed that the decrease in LV end-diastolic pressure was indicative of significant improvements in τ ln and κ e with the relationship: LV end-diastolic pressure=−4.73+0.27 τ ln +0.54 κ e ( r =0.81, P &lt;0.0001). These LV diastolic relaxation properties did not change or worsened in the control cardiomyopathy patients. Conclusions —We conclude that the decrease in LV end-diastolic pressure in cardiomyopathy patients treated with metoprolol is an indicator of improvement in LV diastolic properties resulting from more complete myocardial relaxation.
Prioritizing Chemicals and Data Requirements for Screening-Level Exposure and Risk Assessment
Authors: Jon A. Arnot, Trevor N. Brown, Frank Wania, Knut Breivik, Michael S. McLachlan
Journal: Environmental Health Perspectives (2012)

Background: Scientists and regulatory agencies strive to identify chemicals that may cause harmful effects to humans and the environment; however, prioritization is challenging because of the large number of chemicals requiring evaluation and limited data and resources.Objectives: We aimed to prioritize chemicals for exposure and exposure potential and obtain a quantitative perspective on research needs to better address uncertainty in screening assessments.Methods: We used a multimedia mass balance model to prioritize > 12,000 organic chemicals using four far-field human exposure metrics. The propagation of variance (uncertainty) in key chemical information used as model input for calculating exposure metrics was quantified.Results: Modeled human concentrations and intake rates span approximately 17 and 15 orders of magnitude, respectively. Estimates of exposure potential using human concentrations and a unit emission rate span approximately 13 orders of magnitude, and intake fractions span 7 orders of magnitude. The actual chemical emission rate contributes the greatest variance (uncertainty) in exposure estimates. The human biotransformation half-life is the second greatest source of uncertainty in estimated concentrations. In general, biotransformation and biodegradation half-lives are greater sources of uncertainty in modeled exposure and exposure potential than chemical partition coefficients.Conclusions: Mechanistic exposure modeling is suitable for screening and prioritizing large numbers of chemicals. By including uncertainty analysis and uncertainty in chemical information in the exposure estimates, these methods can help identify and address the important sources of uncertainty in human exposure and risk assessment in a systematic manner.