tbuckley/cabot-search huggingface dataset:
Fluorescence imaging of reactive oxygen metabolites generated in single macrophage cells (NR8383) upon phagocytosis of natural zeolite (erionite) fibers.
Authors: J F Long, P K Dutta, B D Hogg
Journal: Environmental Health Perspectives (1997)

In this paper we address the phenomenon of reactive oxygen metabolite generation subsequent to phagocytosis of mineral fibers by macrophages. Natural erionite fibers were chosen because of their established toxicity. Macrophages (cell line NR8383) were loaded with the dye 5-(and 6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate and exposed to erionite particles by centrifuging cells and fibers together to effect adherence. Reactive oxygen metabolite generation was examined by monitoring the fluorescence of oxidized dye formed via the reaction with oxygen species produced during phagocytosis. Individual cells were repeatedly scanned for up to 2 hr to monitor the evolution of this fluorescence. It was found that erionite-exposed cells had a mean total fluorescence of three times that of controls during the first 35 min, declining to two times that of controls at 35-60 min and about the same level as that of controls at 60-80 min. Ultrastructural studies of similarly treated aliquots of cells showed marked variation in size and numbers of the phagocytized particles. This study demonstrates that intracellular oxidation can be monitored on a single cell basis over a period of time. Quantitative studies are in progress to establish the relationship between the phagocytized particulate load and the extent of fluorescence.
Deficit of tRNALys modification by Cdkal1 causes the development of type 2 diabetes in mice
Authors: Fan-Yan Wei, Takeo Suzuki, Sayaka Watanabe, Satoshi Kimura, Taku Kaitsuka, Atsushi Fujimura, Hideki Matsui, Mohamed Atta, Hiroyuki Michiue, Marc Fontecave, Kazuya Yamagata, Tsutomu Suzuki, Kazuhito Tomizawa
Journal: Journal of Clinical Investigation (2011)

The worldwide prevalence of type 2 diabetes (T2D), which is caused by a combination of environmental and genetic factors, is increasing. With regard to genetic factors, variations in the gene encoding Cdk5 regulatory associated protein 1-like 1 (Cdkal1) have been associated with an impaired insulin response and increased risk of T2D across different ethnic populations, but the molecular function of this protein has not been characterized. Here, we show that Cdkal1 is a mammalian methylthiotransferase that biosynthesizes 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) in tRNA(Lys)(UUU) and that it is required for the accurate translation of AAA and AAG codons. Mice with pancreatic β cell-specific KO of Cdkal1 (referred to herein as β cell KO mice) showed pancreatic islet hypertrophy, a decrease in insulin secretion, and impaired blood glucose control. In Cdkal1-deficient β cells, misreading of Lys codon in proinsulin occurred, resulting in a reduction of glucose-stimulated proinsulin synthesis. Moreover, expression of ER stress-related genes was upregulated in these cells, and abnormally structured ER was observed. Further, the β cell KO mice were hypersensitive to high fat diet-induced ER stress. These findings suggest that glucose-stimulated translation of proinsulin may require fully modified tRNA(Lys)(UUU), which could potentially explain the molecular pathogenesis of T2D in patients carrying cdkal1 risk alleles.
Interactions of oxygen radicals with airway epithelium.
Authors: D T Wright, L A Cohn, H Li, B Fischer, C M Li, K B Adler
Journal: Environmental Health Perspectives (1994)

Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS.
Chaos and neural coding: Is the binding problem a pseudo-problem?
Authors: Antonino Raffone, Cees van Leeuwen
Journal: Behavioral and Brain Sciences (2001)

Tsuda's article suggests several plausible concepts of neurodynamic representation and processing, with a thoughtful discussion of their neurobiological grounding and formal properties. However, Tsuda's theory leads to a holistic view of brain functions and to the controversial conclusion that the “binding problem” is a pseudo-problem. By contrast, we stress the role of chaotic patterns in solving the binding problem, in terms of flexible temporal coding of visual scenes through graded and intermittent synchrony.
1090-218 Randomized comparison of anatomical versus voltage-guided ablation of the cavotricuspid isthmus for atrial flutter
Authors: Burr W Hall, Srikar Veerareddy, Peter Cheung, Kamala Tamirisa, Jihn Han, Kristina Lemola, Aman Chugh, Frank Pelosi, Fred Morady, Hakan Oral
Journal: Journal of the American College of Cardiology (2004)
Abstract 2471: Immunosuppressive effect of elevated epidermal ornithine decarboxylase activity
Authors: Martin P. Keough, Karen DeFeo, Candace S. Hayes, Susan K. Gilmour
Journal: Cancer Research (2010)

Abstract Tumor promoting agents, such as phorbol esters, promote tumorigenesis via induction of inflammation and hyperplasia. However, the immunosuppressive/immunomodulating properties of tumor promoting agents may play a relevant role in tumor promotion as well. Because elevated polyamine biosynthesis is sufficient to promote skin tumorigenesis, we hypothesized that increased activity of epidermal ornithine decarboxylase (ODC), a key regulatory enzyme in polyamine biosynthesis, may suppress the cutaneous immune response in addition to stimulating proliferation. To investigate the role of ODC in the control of cutaneous inflammation, a well-known model of T cell mediated inflammation was used. A contact hypersensitivity (CHS) response was elicited in the ears of both ODC transgenic mice, in which ODC is targeted to the epidermis, and their normal littermates by topical sensitization and challenge with oxazolone. Unlike in normal littermate mice, ear swelling was dramatically reduced in ODC transgenic mice after elicitation of CHS. Flow cytometric and immunohistochemical analyses of the infiltrating immune cells revealed fewer infiltrating immune cells, especially neutrophils, in the elicited ears of ODC transgenic mice. The specific ODC inhibitor, α-difluoromethylornithine, abrogated the suppressive effects of ODC in CHS reactions. Adoptive transfer of sensitized lymphocytes from either ODC transgenic or normal littermate mice to naïve ODC transgenic or wild-type mice indicated that elevated epidermal ODC activity suppress both the sensitization and elicitation phases of CHS. Cytokines are central mediators of immune functions associated with inflammatory reactions. The cytokine profile of ex vivo stimulated lymphocytes isolated from draining lymph nodes showed reduced levels of IL-6 and IL-10 in sensitized and challenged ODC transgenic mice. In vivo labeling of dendritic cells by topical application of fluorescein isothiocyanate (FITC) showed fewer FITC-labeled dendritic cells in the draining lymph nodes of ODC transgenic mice compared to normal littermates. Vascular permeability was assessed using Evans blue extravasation assays during the elicitation phase of CHS. At 24 hours after induction of CHS, there was 45% less plasma extravasation of Evans blue dye into the ear skin of ODC transgenic mice compared to normal littermates. Collectively these data indicate elevated epidermal ODC activity can suppress a number of functions associated with cutaneous inflammatory reactions. In addition to promoting cellular proliferation, the immune suppression mediated by increased epidermal ODC activity may provide an environment conducive to tumor growth. This work was supported by NIH grant CA070739. 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 2471.
ETIOLOGY OF THE 1933 EPIDEMIC OF ENCEPHALITIS
Authors: RALPH S. MUCKENFUSS
Journal: JAMA (1934)

The epidemic of encephalitis occurring in St. Louis and Kansas City during the summer of 1933 differed in a number of clinical and epidemiologic characteristics from the majority of previously reported epidemics. Since it is probable that these differences may be the result of different causative agents, no attempt will be made to review the voluminous and conflicting literature on the etiology of encephalitis, and this paper will be limited strictly to studies on the disease occurring in epidemic form in the recent outbreak. Investigations into the etiology of the 1933 outbreak of encephalitis may be said to have begun before the nature of the disease was recognized or the onset of an epidemic was suspected. When the first few cases were admitted to the St. Louis County Hospital, the nature of the febrile illness was not immediately appreciated, and many cultures of blood and spinal fluid were made, as
The closed eyes sign: an aid to diagnosing non-specific abdominal pain.
Authors: D. W. Gray, J. M. Dixon, J. Collin
Journal: BMJ (1988)

<h3>Background</h3> Behcet9s Syndrome Activity Scale (BSAS), a patient reported outcome measure for Behcet9s syndrome, has been validated for routine clincial care and have been shown to differentiate active treatment from placebo in clinical trials. Currently, there are no identified thresholds for disease activity levels for BSAS. <h3>Objectives</h3> To determine resmission, low, moderate and high disease activity level threshold scores for BSAS. <h3>Methods</h3> Behcet9s patients seen at the NYU Behcet9s Center had their demographic, clinical features and outcomes data abstracted. Confirmed Behcet9s diagnosis was determined if ISG criteria were met at any time during the course of observation. Concordance correlation was estimated between the BSAS and the RAPID3; both outcomes were scaled to [0-100]. Proposed BSAS severity categories are as: Near-Remission = [0-10), Low = [10-30), Moderate=[30-60), and High = [60-100]. Weighted Kappa statistics were estimated between BSAS and RAPID3 severity categories. RAPID3 categories were based upon published<sup>1</sup> as well as matching the proposed BSAS severity categories. <h3>Results</h3> First observation data on 832 subjects were abstracted for this analysis. 504 (63%) met ISG criteria for Behcet9s, 616 (74%) were female with an average age of 35 years (±13.8). Concordance between BSAS and RAPID3 was moderate (CCC =0.518). BSAS severity categories classified 7% Near-Remission, 24% Low, 48% Moderate, and 21% of the study population as High disease severity (Table). Published RAPID3 categories classified 44% of subjects as High, while matching RAPID3 categories only classified 20%. Agreement between categories was moderate for both RAPID3 classifications. <h3>Conclusions</h3> BSAS, a patient reported outcome measure for Behcet9s syndrome, correlates well with other composite indices of disease activity. Proposed cut off points for near-remission, low, moderate and high activity for BSAS may be used in clinical care for a “treat-to-target” approach to Behcet9s treatment. <h3>References</h3> Pincus T, Swearingen CJ, Bergman M, Yazici Y. J Rheumatol 2008 Nov;35(11):2136-47. <h3>Disclosure of Interest</h3> Y. Yazici Grant/research support from: BMS, Celgene, Genentech, Consultant for: BMS, Celgene, H. Bernstein: None declared, C. Swearingen: None declared
ON THE POSSIBILITY OF RESTORING MOVEMENT TO A PARALYSED VOCAL CORD BY NERVE ANASTOMOSIS: (An Experimental Inquiry.)
Authors: L. Colledge
Journal: BMJ (1925)

4. It follows direct trauma of the chest wall or lung, and surgical operations on the abdomiien, even remote from the diaplhragm.5. It gives definite physical signs, whlicll may simulate pneeumlionia or pleural effusion.6.The differential diagnosis depends on determiniing the position of the apex beat and the diaphragm.7. It may, in cases of injury, affect the lung on the side remote fromii the trauma.8. Its occutrrence, whilst of itself not necessarily of grave import, yet places another burden on a patient already struggling with injury or disease.9. Treatmiient should be preventive.
Physicians and Health Policy-Reply
Authors: Don E. Detmer
Journal: JAMA (1980)

<h3>In Reply.—</h3> Dr Menken raises an important point that was not fully addressed in my editorial. Physicians are needed in civic affairs both as concerned amateurs and as professionals. The clinician seriously interested in becoming a policy professional is indeed wise to prepare himself adequately in the "basic sciences" of policy. An educational model for such basic training is the Kellogg Fellowship Program in Administrative Medicine at the University of Wisconsin. Both types of fellowship programs, eg, Johnson and Kellogg, have unique value, and those physicians with a mix of both types of preparation are, with other things being equal, likely to make the greatest contributions.
Good News for Gene Therapy
Authors: Anton Berns
Journal: New England Journal of Medicine (2004)

The promise of gene therapy has been dimmed in the past few years by a number of setbacks, including the development of T-cell leukemia in infants treated for severe combined immunodeficiency. A recent study suggests that these cases do not augur ill for the field as a whole and that specific changes to gene-therapy protocols may reduce the chances that such therapy will inadvertently trigger cancer.
P3-16-10: The Efficacy of Zoledronic Acid in Breast Cancer Adjuvant Therapy: A Meta-Analysis of Randomized Controlled Trials.
Authors: J Lu, T Yan, W Yin, Q Zhou, L Zhou, Y Jiang, Y Du, Z Shao
Journal: Cancer Research (2011)

Abstract Background: The effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomized controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy. Methods: We searched Pubmed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992–2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004–2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study endpoints were the DFS. Secondary endpoints were OS, distant or loco-regional recurrence free survival and bone metastasis free survival. Results: Compared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival (OS), disease free survival (DFS), bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (RR=0.763, 95%CI 0.658−0.884, p&amp;lt;0.001) and reduce the risk of distant (RR=0.744, 95% CI 0.611−0.906, p=0.003) and locoregional recurrence (RR=0.508, 95% CI 0.340−0.760, p=0.001). Discussion: Adjuvant zoledronic acid may potentially improve the prognosis of postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal couterparts, differing disease stages, and various pathological types of breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-10.
Low frequency of detectable human cytomegalovirus DNA in coronary atherosclerotic lesions obtained by coronary endatherectomy
Authors: P.W. Radke, S. Merkelbach, H. Dörge, F. Schöndube, M. Voß, P.K. Haager, H.G. Klues, B.J. Messmer, S. Handt, P. Hanrath
Journal: Journal of the American College of Cardiology (1998)
The Unasked Question
Authors: Jeffrey L. Brown
Journal: JAMA (2012)

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Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production
Authors: Meihui Pan, Arthur I. Cederbaum, Yuan-Li Zhang, Henry N. Ginsberg, Kevin Jon Williams, Edward A. Fisher
Journal: Journal of Clinical Investigation (2004)

How ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) lower plasma lipid levels is incompletely understood. We previously showed that marine ω-3 PUFAs (docosahexaenoic acid [DHA] and eicosapentaenoic acid) stimulate a novel pathway, post-ER presecretory proteolysis (PERPP), that degrades apolipoprotein B100 (ApoB100), thereby reducing lipoprotein secretion from liver cells. To identify signals stimulating PERPP, we examined known actions of ω-3 PUFA. In rat hepatoma or primary rodent hepatocytes incubated with ω-3 PUFA, cotreatment with the iron chelator desferrioxamine, an inhibitor of iron-dependent lipid peroxidation, or vitamin E, a lipid antioxidant, suppressed increases in thiobarbituric acid–reactive substances (TBARSs; a measure of lipid peroxidation products) and restored ApoB100 recovery and VLDL secretion. Moreover, ω-6 and nonmarine ω-3 PUFA, also prone to peroxidation, increased ApoB100 degradation via intracellular induction of TBARSs. Even without added fatty acids, degradation of ApoB100 in primary hepatocytes was blocked by desferrioxamine or antioxidant cotreatment. To extend these results in vivo, mice were infused with DHA, which increased hepatic TBARSs and reduced VLDL-ApoB100 secretion. These results establish a novel link between lipid peroxidation and oxidant stress with ApoB100 degradation via PERPP, and may be relevant to the hypolipidemic actions of dietary PUFAs, the basal regulation of ApoB100 secretion, and hyperlipidemias arising from ApoB100 overproduction.
Drug companies to declare all payments made to doctors from 2012
Authors: J. Carlowe
Journal: BMJ (2010)

Doctors have welcomed changes to the drug industry’s code of practice, which 

requires companies to make an annual declaration of how much money they have paid to doctors for use of their services.

The ruling is part of several amendments to the Association of the British Pharmaceutical Industry (ABPI) code of practice.

The changes will see each drug company declare the amount and the number of times payments were made to doctors, including speaker fees, advisory boards and consultancy and sponsorship for attendance at meetings. 

The first declaration will be made in 2013 for payments made in 2012. The code, however, does not require individual doctors to be named, …
The Death Receptor 3–TNF-like protein 1A pathway drives adverse bone pathology in inflammatory arthritis
Authors: Melanie Jane Bull, Anwen Siân Williams, Zarabeth Mecklenburgh, Claudia Jane Calder, Jason Peter Twohig, Carole Elford, Bronwen Alice James Evans, Tania F. Rowley, Tomasz J. Slebioda, Vadim Y. Taraban, Aymen Al-Shamkhani, Eddie Chung Yern Wang
Journal: The Journal of Experimental Medicine (2008)

Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints that is associated with cartilage and bone destruction. Death Receptor 3 (DR3), a tumor necrosis factor (TNF) receptor superfamily member, has recently been associated with the pathogenesis of RA. We demonstrate that absence of DR3 confers resistance to the development of adverse bone pathology in experimental antigen-induced arthritis (AIA). DR3ko mice exhibited a reduction in all histopathological hallmarks of AIA but, in particular, failed to develop subchondral bone erosions and were completely protected from this characteristic of AIA. In contrast, TNF-like protein 1A (TL1A), the ligand for DR3, exacerbated disease in a dose- and DR3-dependent fashion. Analysis of osteoclast number within AIA joint revealed a reduction in areas susceptible to bone erosion in DR3ko mice, whereas in vitro osteoclastogenesis assays showed that TL1A could directly promote osteoclastogenesis in mouse and man. Treatment with antagonistic anti-TL1A mAb protected animals in a systemic model of RA disease collagen-induced arthritis. We therefore conclude that the DR3–TL1A pathway regulates joint destruction in two murine models of arthritis and represents a potential novel target for therapeutic intervention in inflammatory joint disease.
974-40 Ventricular and Myocardial Function Following Regression of Hypertensive Left Ventricular Hypertrophy
Authors: Gerard P. Aurigemma, John S. Gottdiener, William H. Gaasch, David Williams, Zahid Jamal, Domenic J. Reda, Barry J. Materson
Journal: Journal of the American College of Cardiology (1995)