tbuckley/cabot-search huggingface dataset:
Ras Induces Chromosome Instability and Abrogation of the DNA Damage Response
Authors: Adili Abulaiti, Aphrothiti J. Fikaris, Oxana M. Tsygankova, Judy L. Meinkoth
Journal: Cancer Research (2006)

Abstract Ras mutations are frequent in thyroid tumors, the most common endocrine malignancy. The ability of Ras to transform thyroid cells is thought to rely on its mitogenic activity. Unexpectedly, acute expression of activated Ras in normal rat thyroid cells induced a DNA damage response, followed by apoptosis. Notably, a subpopulation of cells evaded apoptosis and emerged with features of transformation, including the loss of epithelial morphology, dedifferentiation, and the acquisition of hormone- and anchorage-independent proliferation. Strikingly, the surviving cells showed marked chromosomal instability. Acutely, Ras stimulated replication stress as evidenced by the induction of ataxia telangiectasia mutated and Rad3-related protein kinase (ATR) activity (Chk1 phosphorylation) and of γH2A.X, a marker of DNA damage. Despite the activation of a checkpoint, cells continued through mitosis in the face of DNA damage, resulting in an increase in cells harboring micronuclei, an indication of defects in chromosome segregation and other forms of chromosome damage. Cells that survived exposure to Ras continued to exhibit replication stress (ATR activation) but no longer exhibited γH2A.X or full activation of p53. When rechallenged with Ras or DNA-damaging agents, the surviving cells were more resistant to apoptosis than parental cells. These data show that acute expression of activated Ras is sufficient to induce chromosomal instability in the absence of other signals, and suggest that Ras-induced chromosomal instability arises as a consequence of defects in the processing of DNA damage. Hence, abrogation of the DNA damage response may constitute a novel mechanism for Ras transformation. (Cancer Res 2006; 66(21): 10505-12)
EAACI Food Allergy and Anaphylaxis Guidelines. Protecting consumers with food allergies: understanding food consumption, meeting regulations and identifying unmet needs
Authors: A. Muraro, K. Hoffmann-Sommergruber, T. Holzhauser, L. K. Poulsen, M. H. Gowland, C. A. Akdis, E. N. C. Mills, N. Papadopoulos, G. Roberts, S. Schnadt, R. van Ree, A. Sheikh, S. Vieths
Journal: Allergy (2014)

Individuals suffering from IgE-mediated food allergy usually have to practise life-long food allergen avoidance. This document aims to provide an overview of recent evidence-based recommendations for allergen risk assessment and management in the food industry and discusses unmet needs and expectations of the food allergic consumer in that context. There is a general duty of care on the food industry and obligations in European Union legislation to reduce and manage the presence of allergens alongside other food hazards. Current evidence enables quantification of allergen reference doses used to set-up reliable food safety management plans for some foods. However, further work is required to include a wider variety of foods and to understand the impact of the food matrix as well as additional factors which affect the progression and severity of symptoms as a function of dose. Major concerns have been raised by patients, carers and patient groups about the use of precautionary 'may contain' labelling to address the issue of unintended presence of allergens; these therefore need to be reconsidered. New and improved allergen detection methods should be evaluated for their application in food production. There is an urgent requirement for effective communication between healthcare professionals, patient organizations, food industry representatives and regulators to develop a better approach to protecting consumers with food allergies.
Differential Signaling Pathways Are Activated in the Epstein-Barr Virus-Associated Malignancies Nasopharyngeal Carcinoma and Hodgkin Lymphoma
Authors: Jennifer A. Morrison, Margaret L. Gulley, Rajadurai Pathmanathan, Nancy Raab-Traub
Journal: Cancer Research (2004)

Abstract EBV is associated with the epithelial cancer, nasopharyngeal carcinoma (NPC), and the lymphoid malignancy, Hodgkin lymphoma (HL). The EBV latent membrane proteins 1 and 2A are expressed in these tumors. These proteins activate the phosphatidylinositol 3′-OH kinase (PI3K)/Akt pathway, which is commonly activated inappropriately in malignancy. In this study, the status of Akt activation and its targets, glycogen synthase kinase-3β (GSK-3β) and β-catenin, was investigated in NPC and HL clinical specimens. In the majority of HL and NPC specimens, Akt was activated, indicating an important role for this kinase in the development and/or progression of these tumors. Akt phosphorylates and inactivates GSK-3β, a negative regulator of the proto-oncoprotein β-catenin that is aberrantly activated in many cancers. GSK-3β was phosphorylated and inactivated with concomitant nuclear β-catenin accumulation in the majority of NPC specimens. The malignant cells of the majority of HL cases, however, did not have inactivated GSK-3β and lacked nuclear β-catenin expression. These data indicate that this signaling arm of PI3K/Akt is universal and important in NPC pathogenesis but is apparently not affected in HL. These findings point to a divergence in pathways activated by EBV in different cellular contexts.
Histamine and hypoxic pulmonary hypertension A quantitative study
Authors: F. RENGO, B. TRIMARCO, M. CHIARIELLO, B. RICCIARDELLI, M. VOLPE, R. VIOLINI, G. RASETTI
Journal: Cardiovascular Research (1978)

Hypoxia is the most effective and consistent stimulus to pulmonary hypertension in all species; however, the genesis of this phenomenon is still unclear. Histamine has been proposed as the possible mediator of this response and extensively studied. However, there remain doubts as to its behaviour in the different vascular districts during hypoxia. Accordingly, in seven dogs, histamine content was measured in the distal vena cava, hepatic vein, pulmonary artery and aorta; pulmonary artery pressure and systemic arterial pressure were also recorded. All measurements were repeated after 5 min of breathing a mixture containing 8% oxygen. Histamine content in the pulmonary artery blood was significantly increased during hypoxia (from 29 ± 3 to 36 ± 3 ng·cm−3 P<0.05) while it was unchanged in the aorta. Therefore, the difference between histamine content in the pulmonary artery and aorta increased. Moreover, the inferior vena cava content of this substance rose from 24 ± 4 to 32 ± 4 ng·cm−3 (P <0.05) and it did not change in the hepatic vein. Simultaneously pulmonary artery pressure rose from 1.6 ± 0.1 to 2.4 ± 0.1 kPa (12 ± 1 to 18 ± 1 mmHg) (P <0.01) and systemic arterial pressure changed only slightly. These experiments seem to demonstrate that histamine is released by the muscle during hypoxia, since it is increased in the distal vena cava and uptake by the lungs, as shown by the increase in the pulmonary artery and aorta. The role, if there is any, of the muscle-released histamine in the hypoxic pulmonary hypertension is still to be elucidated.
Paradoxical evolution of arterial blood gases during exercise in patients with chronic obstructive bronchitis
Authors: A Frans, E Lampert, N Tuo, T Clerbaux, W Nullens, J Lonsdorfer
Journal: European Respiratory Journal (1990)

In more than a thousand chronic obstructive lung disease (COLD) patients we have observed in six cases, that exercise-induced hypercapnia was accompanied by a concomitant improvement in arterial oxygen tension (PaO2) and a decrease in the alveolo-arterial O2. This behaviour was not due to technical errors. We explained the increase in PaO2 during exercise by three nonmutually exclusive mechanisms: 1) an increase in the respiratory quotient; 2) the exercise induced increase in alveolar ventilation, although inadequate to match the increase in CO2 production, would be redistributed to previously poorly ventilated regions of the lung, these regions therefore receiving enough oxygen to arterialize the blood flowing through the alveolar capillaries; 3) alternatively, perfusion would be redistributed in a more efficient way during exercise, so that even in the presence of hypoventilation, oxygenation would be improved.
On the influence of extracellular fluid volume expansion on bicarbonate reabsorption in the rat
Authors: Mabel L. Purkerson, Herbert Lubowitz, Rose W. White, Neal S. Bricker
Journal: Journal of Clinical Investigation (1969)

Bicarbonate reabsorption is classically regarded as a rate-limited process characterized by saturation kinetics. The tubular maximum (Tm), however, varies with glomerular filtration rate. Thus bicarbonate reabsorption, in common with sodium reabsorption, is characterized by glomerulo-tubular balance. The examination of bicarbonate reabsorption is accomplished using the bicarbonate titration technique; however, this method in its traditional form leads to marked expansion of extracellular fluid (ECF) volume. The possibility exists, therefore, that glomerulo-tubular balance for bicarbonate is altered by the volume expansion and thus that the classic pattern of reabsorption may actually reflect inhibited bicarbonate reabsorptive capacity. The present studies were performed in rats to examine this possibility. Bicarbonate titration studies were performed in two groups of animals: (a) those in which ECF volume expansion was minimized; and (b) those in which ECF volume expansion was exaggerated. In the first group, no Tm for bicarbonate was observed either in the majority of individual rats studied or in a group plot for all rats studied despite the fact that plasma bicarbonate concentrations were increased to values in excess of 60 mEq/liter. In the second group, a clear Tm was demonstrated both in individual animals and in group data and there was a lowered threshold for the excretion of bicarbonate. The data thus lend support to the view that the "normal" Tm for bicarbonate may actually represent an inhibited level of bicarbonate reabsorption induced by ECF volume expansion.
Factors that Affect Postdialysis Rebound in Serum Urea Concentration, Including the Rate of Dialysis
Authors: John T. Daugirdas, Tom Greene, Thomas A. Depner, John Leypoldt, Frank Gotch, Gerald Schulman
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V − B × (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h−1) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be predicted with acceptable accuracy from a postdialysis sample using a zero-intercept, K/V-based rate equation. Several patient or treatment-specific factors predict enhanced or reduced rebound. Rate equation slope coefficients for K/V of 0.39 (AV access) and 0.22 (venous access) are proposed when a 15- to 20-s slow-flow method is used to draw the postdialysis blood. Slightly higher K/V slope coefficients (0.46 and 0.29, respectively) should be used if a shorter (e.g., 10 s) slow-flow period is used. E-mail: [email protected]
Raised granzyme B levels are associated with erosions in patients with early rheumatoid factor positive rheumatoid arthritis
Authors: R Goldbach-Mansky
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Raised granzyme B in serum and synovium of patients with rheumatoid arthritis suggests a role for cytotoxic T cells and natural killer cells in the pathogenesis of this disease. <b>Objective:</b> To evaluate serum granzyme B in patients with early arthritis and correlate it with specific diagnosis and clinical indices of disease severity. <b>Methods:</b> 257 patients with inflammatory arthritis for less than one year (46% rheumatoid arthritis, 17% spondyloarthropathy, 37% undifferentiated arthritis) had a prospective clinical, serological, and radiographic evaluation. Granzyme B was measured in initial sera by ELISA. Patients were HLA typed for DR alleles using sequence specific primers. A logistic regression model was used to evaluate the potential prognostic value of serum granzyme B in predicting radiographic erosions after one year of follow up. <b>Results:</b> Granzyme B values were similar in rheumatoid arthritis, spondyloarthropathy, and undifferentiated arthritis. Concentrations were higher in rheumatoid factor (RF) positive patients than in RF negative patients (mean (SD): 3.15 (0.92) <i>v</i> 2.89 (0.71) pg/ml; p&lt;0.05). After one year, erosions were present in 30% of patients in the overall cohort, and in 44% of patients with rheumatoid arthritis. In the entire cohort, serum granzyme B did not predict erosions independently. However, high granzyme B was an independent predictor of early erosions in patients with RF positive rheumatoid arthritis (odds ratio = 4.83 (95% confidence interval, 1.13 to 20.59)) (p&lt;0.05). <b>Conclusions:</b> Granzyme B may be a useful prognostic marker in early rheumatoid arthritis and may provide important clues to the pathogenesis of this disease.
Interpretative strategies for lung function tests
Authors: R. Pellegrino, G. Viegi, V. Brusasco, R. O. Crapo, F. Burgos, R. Casaburi, A. Coates, C. P. M. van der Grinten, P. Gustafsson, J. Hankinson, R. Jensen, D. C. Johnson, N. MacIntyre, R. McKay, M. R. Miller, D. Navajas, O. F. Pedersen, J. Wanger
Journal: European Respiratory Journal (2005)

This section is written to provide guidance in interpreting pulmonary function tests (PFTs) to medical directors of hospital-based laboratories that perform PFTs, and physicians who are responsible for interpreting the results of PFTs most commonly ordered for clinical purposes.Specifically, this section addresses the interpretation of spirometry, bronchodilator response, carbon monoxide diffusing capacity (DL,CO) and lung volumes.The sources of variation in lung function testing and technical aspects of spirometry, lung volume measurements and DL,CO measurement have been considered in other documents published in this series of Task Force reports [1-4] and in the American Thoracic Society (ATS) interpretative strategies document [5].An interpretation begins with a review and comment on test quality.Tests that are less than optimal may still contain useful information, but interpreters should identify the problems and the
Preclinical Results of Camptothecin-Polymer Conjugate (IT-101) in Multiple Human Lymphoma Xenograft Models
Authors: Tontanai Numbenjapon, Jianyi Wang, David Colcher, Thomas Schluep, Mark E. Davis, Julienne Duringer, Leo Kretzner, Yun Yen, Stephen J. Forman, Andrew Raubitschek
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Camptothecin (CPT) has potent broad-spectrum antitumor activity by inhibiting type I DNA topoisomerase (DNA topo I). It has not been used clinically because it is water-insoluble and highly toxic. As a result, irinotecan (CPT-11), a water-soluble analogue of CPT, has been developed and used as salvage chemotherapy in patients with relapsed/refractory lymphoma, but with only modest activity. Recently, we have developed a cyclodextrin-based polymer conjugate of 20-(S)-CPT (IT-101). In this study, we evaluated the preclinical antilymphoma efficacy of IT-101 as compared with CPT-11. Experimental Design: We determined an in vitro cytotoxicity of IT-101, CPT-11, and their metabolites against multiple human lymphoma cell lines. In human lymphoma xenografts, the pharmacokinetics, inhibitions of tumor DNA topo I catalytic activity, and antilymphoma activities of these compounds were evaluated. Results: IT-101 and CPT had very high in vitro cytotoxicity against all lymphoma cell lines tested. As compared with CPT-11 and SN-38, IT-101 and CPT had longer release kinetics and significantly inhibit higher tumor DNA topo I catalytic activities. Furthermore, IT-101 showed significantly prolonged the survival of animals bearing s.c. and disseminated human xenografts when compared with CPT-11 at its maximum tolerated dose in mice. Conclusions: The promising present results provide the basis for a phase I clinical trial in patients with relapsed/refractory lymphoma.
Purification and partial primary sequence of a chemotactic protein for polymorphonuclear leukocytes derived from human lung giant cell carcinoma LU65C cells.
Authors: K Suzuki, H Miyasaka, H Ota, Y Yamakawa, M Tagawa, A Kuramoto, S Mizuno
Journal: The Journal of Experimental Medicine (1989)

A chemotactic protein for polymorphonuclear leukocytes (lung carcinoma-derived chemotaxin [LUCT]) was purified from culture fluid of the human lung giant cell carcinoma LU65C cells to electrophoretically homogeneous form through five sequential purification steps: DEAE-Sepharose, CM-Sepharose, HPLC on carboxyl-methylated-polyvinylalcohol resin, hydrophobic, and reversed-phase. The molecular mass was determined as approximately 10 kD by SDS-PAGE and isoelectric point was 10.7. The chemotactic activity (ED50 0.75 x 10(-9) M) was sevenfold more potent than that of FMLP (5 X 10(-9) M) and comparable with that of C5a (10(-9) M). NH2-terminal amino acid sequence and amino acid composition of LUCT strongly suggest that it may be closely related to the putative protein encoded by the cDNA clone (3-10C) and almost identical with a part of sequence of the chemotactic factor derived from stimulated human leukocytes in the 6th to 32nd, but not the NH2-terminal 5 amino acids. These results indicate that the carcinoma cells produce LUCT without any added stimulant and suggest that the previously isolated chemotactic monokines may correspond to des(1-5) of LUCT in the NH2-terminal region.
Reviews, Notes, and Listings: Diet, Demography, and Disease: Changing Perspectives on Anemia
Authors: David A. Sears
Journal: Annals of Internal Medicine (1993)

Literature of Medicine1 October 1993Reviews, Notes, and Listings: Diet, Demography, and Disease: Changing Perspectives on AnemiaDavid A. Sears, MDDavid A. Sears, MDBaylor College of Medicine, Houston, TX 77030.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-7_Part_1-199310010-00036 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Diet, Demography, and Disease: Changing Perspectives on AnemiaPatricia Stuart-Macadam and Susan Kent; eds. 285 pages. New York: Aldine de Gruyter; 1992. $59.95.It is hazardous to cross the boundary of one's discipline (hematology) to review work in another (anthropology). But when the subject is anemia and iron deficiency, and the editor of this group of reviews claims a comprehensive and holistic view, the risk is justifiable. A hypothesis woven into several of the essays in this book is that anemia caused by dietary iron deficiency may not have been as common in ancient populations as assumed; rather, the other hypoferremic anemia, ... Author, Article, and Disclosure InformationAffiliations: Baylor College of Medicine, Houston, TX 77030. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1993Volume 119, Issue 7_Part_1Page: 639KeywordsAnemiaBlood cellsDietHemoglobinInfectious diseasesIron deficiencyIron deficiency anemiaPernicious anemiaPopulation statisticsThalassemia ePublished: 15 August 2000 Issue Published: 1 October 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Security, Insecurity, and Health Workers
Authors: Heidi J. Larson, Zulfiqar A. Bhutta
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
1077 NRF2, A TRANSCRIPTION FACTOR MAINLY INVOLVED IN ANTIOXIDANT DEFENSE, REGULATES THE EXPRESSION OF ALR AUGMENTER OF LIVER REGENERATION
Authors: R. Dayoub, J. Lamle, A. Vogel, S. Werner, H.-J. Schlitt, M. Melter, T. Weiss
Journal: Journal of Hepatology (2011)