tbuckley/cabot-search huggingface dataset:
Endothelin(B) receptor activates NHE-3 by a Ca2+-dependent pathway in OKP cells.
Authors: T S Chu, Y Peng, A Cano, M Yanagisawa, R J Alpern
Journal: Journal of Clinical Investigation (1996)

To examine the mechanisms by which endothelin (ET) regulates the Na/H antiporter isoform, NHE-3, OKP cells were stably transfected with ET(A) and ET(B) receptor cDNA. In cells overexpressing ET(B), but not ET(A) receptors, ET-1 increased Na/H antiporter activity (JNa/H). This effect was inhibited by a nonselective endothelin receptor blocker and by a selective ET(B) receptor blocker but was not inhibited by an ET(A) selective receptor blocker. In ET(B)-overexpressing cells, 10(-8) M ET-1 inhibited adenylyl cyclase, but protein kinase A inhibition and pertussis toxin pretreatment did not affect Na/H antiporter activation by ET-1. ET-1 caused a transient increase in cell [Ca2+], followed by a sustained increase. Increases in cell [Ca2+] were partially inhibited by pertussis toxin. ET-1-induced increases in J(Na/H) were 50% inhibited by clamping cell [Ca2+] low with BAPTA, and by KN62, a Ca-calmodulin kinase inhibitor. Inhibitors of protein kinase C, cyclooxygenase, lipoxygenase, and cytochrome P450 and cyclic GMP were without effect. In ET(A)-overexpressing cells, ET-1 increased cell [Ca2+] but did not increase JNa/H. In summary, binding of ET-1 to ET(B) receptors increases Na/H antiporter activity in OKP cells, an effect mediated in part by increases in cell [Ca2+] and Ca-calmodulin kinase. Increases in cell [Ca2+] are not sufficient for Na/H antiporter activation.
A specific DAMP profile identifies susceptibility to smoke-induced airway inflammation
Authors: S. D. Pouwels, I. H. Heijink, A. J. M. van Oosterhout, M. C. Nawijn
Journal: European Respiratory Journal (2013)

To the Editor: 

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, with a worldwide prevalence of 9–10% [1]. COPD is associated with chronic, neutrophilic inflammation in the lungs, causing destruction of lung parenchyma (emphysema) and/or remodelling of the airways with mucus hypersecretion (bronchitis) [2]. Chronic exposure to noxious particles and gases, such as cigarette smoke, is the major risk factor for COPD, while susceptibility to the disease has a strong genetic component [2]. While the activity of the innate immune system increases with disease progression during early stages of COPD, the precise nature of the factors that trigger innate immune responses in COPD is currently unknown. Cell damage and death upon exposure to cigarette smoke in COPD may induce the release of damage associated molecular patterns (DAMPs) [3]. Elevated levels of several prototypic DAMPs, including high-mobility group box (HMGB)1, heat shock proteins (HSPs) and S100A8, have been observed in bronchoalveolar lavage (BAL) fluid, serum and epithelial lining fluid of COPD patients [4–6]. DAMPs activate cells of the innate immune system upon binding to pattern recognition receptors, such as toll-like receptors (TLRs) and receptor for advanced glycation end-products (RAGE). Importantly, the AGER gene, which encodes the RAGE receptor, is a genome-wide association study susceptibility gene for COPD [7].

To date, studies investigating the role of DAMPs in COPD have focused on the analysis of a single DAMP. However, while each individual DAMP triggers …
Anaerobic Infection of the Brain.
Authors: H. S. Heineman
Journal: Annals of Internal Medicine (1963)

s1 April 1963Anaerobic Infection of the Brain.H. S. Heineman, M.D., A. I. Braude, M.D., F.A.C.P.H. S. Heineman, M.D.Search for more papers by this author, A. I. Braude, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-736_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe mortality and morbidity from brain abscess remain forbiddingly high despite the advent of antibiotics, which are given generally on the basis of incomplete bacteriologic data. Since the literature places little emphasis on the accurate identifications of infecting organisms in brain abscess, a careful bacteriologic study was made of all brain abscesses of nontraumatic origin at this hospital. These cases have consistently yielded a group of bacteria hitherto given only sporadic mention.In a series of 17 consecutive cases during a 5-year period, 15 yielded a heavy growth of anaerobic bacteria, and 2 were sterile. Anaerobes alone were isolated from... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Pittsburgh, Pa. (CS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 736-736KeywordsAbscessesAnaerobic bacteriaAntibioticsBacteriaBrainMorbidityMortality Issue Published: 1 April 1963 PDF downloadLoading ...
Abstract 68: Nampt regulates fatty acid synthesis, ER homeostasis, and survival in prostate cancer
Authors: Sarah Ryan, Steven Kridel
Journal: Cancer Research (2010)

Abstract Nicotinamide adenine dinucleotide (NAD) is crucial for the survival of living organisms. This coenzyme functions in both redox metabolism and as a substrate for several proteins, notably Sirtuin deacetylases and poly-(ADP ribose) polymerases, which control stress response and apoptosis in cancer. The rate limiting step of NAD biosynthesis is catalyzed by Nicotinamide phosphoribosyl transferase (Nampt). Recent evidence suggests Nampt may play a role in cancer by regulating survival. The Nampt inhibitor FK866 is in phase II clinical trials against a variety of solid malignancies, however no studies have focused on the role of NAD in prostate cancer (PCa). Because tumor cells have a high requirement for NAD and PCa has increased fatty acid synthesis, we hypothesized that Nampt is important for PCa cell survival and metabolism. Our studies demonstrate that Nampt activity is required for the survival of prostate tumor cells (PC-3, LNCaP, and DU145), but not normal prostate epithelial cells, as determined by treatment with FK866. Exogenous NAD rescued cell death, indicating FK866 is a specific inhibitor of Nampt. To test whether PCa cells can rely on de novo NAD synthesis, we treated cell lines with FK866 and added back nicotinic acid, the substrate for the de novo pathway. Only DU145 cell survival was rescued by nicotinic acid demonstrating that NAD biosynthesis pathways are heterogeneous in PCa. Furthermore, expression of Nicotinic acid phosphoribosyl transferase (Naprt1), the rate-limiting step of the de novo pathway, correlated with the rescue by nicotinic acid in DU145 cells. Additionally, Nampt inhibition activated endoplasmic reticulum (ER) stress and autophagy in a pro-survival manner in all cell lines. Interestingly, FK866 also dramatically reduced fatty acid synthesis in PC-3 and DU145 cells, independent of fatty acid synthase levels. However, LNCaP cells showed no decrease in 14C-acetate incorporation. Robust phosphorylation of ACC occured in DU145 and PC-3 cells upon treatment with FK866, and this effect was rescued by adding back NAD. This correlated with reduced ATP levels and activation (phosphorylation) of AMPK at T172. LNCaP cells had a less dramatic depletion of ATP and no changes in AMPK or ACC phosphorylation, indicating a potential mechanism of fatty acid synthesis shutdown. However, lipid synthesis (as measured by incorporation of 14C-choline) was reduced in all 3 cell lines, albeit to a lesser extent in LNCaP cells. Overall, these findings demonstrate a novel role for Nampt in PCa, and highlight the contribution of NAD to ER homeostasis, fatty acid synthesis, and survival. Targeting NAD biosynthesis could be a novel approach to disrupting PCa cell survival and lipid synthesis. 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 68.
Use of bone biochemical markers with dual-energy x-ray absorptiometry for early determination of bone loss in persons with spinal cord injury
Authors: Laurent Ma[iuml ]moun, Isabelle Couret, Jean-Paul Micallef, Edouard Peruchon, Denis Mariano-Goulart, Michel Rossi, Jean-Louis Leroux, Freddy Ohanna
Journal: Metabolism (2002)
Exercise-Induced Improvement in Insulin Sensitivity Is Not Mediated by Change in Cardiorespiratory Fitness
Authors: Andrea M. Brennan, Miu Lam, Paula Stotz, Robert Hudson, Robert Ross
Journal: Diabetes Care (2014)

Although exercise-induced improvement in cardiorespiratory fitness (CRF) and reduction in abdominal obesity are putative mechanisms by which chronic exercise attenuates insulin resistance (1), the independent contribution of each is unknown. We therefore investigated whether improvement in abdominal obesity and/or CRF mediates the effect of exercise on insulin sensitivity in abdominally obese adults.

Participants included sedentary, abdominally obese men and women who participated in two previously published exercise interventions (2,3). Participants were randomized to control ( n = 18) or supervised aerobic exercise ( n = 59) for 3 (women) or 4 (men) months. CRF (VO2peak) was measured using a maximal treadmill test, abdominal obesity by magnetic resonance imaging and waist circumference (WC), and insulin sensitivity by the hyperinsulinemic-euglycemic clamp.

Simple mediation analysis (Table 1) revealed that with the exception of …
Accidental Discovery of Lung Metastases From Differentiated Thyroid Cancer by 99mTc Sodium Pertechnetate Scan in a Patient With Secondary Hyperparathyroidism
Authors: Alfredo Campennì, Rosaria M. Ruggeri, Domenico Santoro, Mariapaola Cucinotta, Stefania Conti, Alessandro Sindoni, Guido Bellinghieri, Sergio Baldari
Journal: Clinical Nuclear Medicine (2012)

We present a 75-year-old-man affected by chronic renal failure in whom metastases from differentiated thyroid cancer (DTC) were incidentally discovered at TcO4 neck-thorax scan in the setting of a diagnosis of secondary hyperparathyroidism. Ten years before, he had undergone near-total thyroidectomy for a multinodular goiter. Result of the pathological examination was negative for DTC. At our observation, serum thyroglobulin was high in the absence of Tg-Ab, consistent with metastatic disease. Neck ultrasonographynography was negative. The patient underwent I therapy (3700 MBq) after stimulation with recombinant human thyroid-stimulating hormone. Postdose whole-body scan confirmed the metastases already demonstrated by TcO4.
Improved Functional Status and Quality of Life in Prohibitive Surgical Risk Patients With Degenerative Mitral Regurgitation After Transcatheter Mitral Valve Repair
Authors: D. Scott Lim, Matthew R. Reynolds, Ted Feldman, Saibal Kar, Howard C. Herrmann, Andrew Wang, Patrick L. Whitlow, William A. Gray, Paul Grayburn, Michael J. Mack, Donald D. Glower
Journal: Journal of the American College of Cardiology (2013)
Spreading research in primary care safely
Authors: A. E. Livingstone
Journal: BMJ (2001)

EDITOR—The contributions by Green and Dovey and Thomas et al discuss general practice research networks. They highlight how crucial research based in primary health care is to the effective delivery of this care and the understanding of population health. 1 2 The news section of the same issue, however, reports the suspension of an east London general practitioner for entering patients in a trial without consent and forging signatures.3

I am concerned about how the potential of general practices to contribute to research, whether it be experimental …
Screening for lung cancer using low dose computed tomography
Authors: M. C. Tammemagi, S. Lam
Journal: BMJ (2014)

Screening for lung cancer with low dose computed tomography can reduce mortality from the disease by 20% in high risk smokers. This review covers the state of the art knowledge on several aspects of implementing a screening program. The most important are to identify people who are at high enough risk to warrant screening and the appropriate management of lung nodules found at screening. An accurate risk prediction model is more efficient than age and pack years of smoking alone at identifying those who will develop lung cancer and die from the disease. Algorithms are available for assessing people who screen positive to determine who needs additional imaging or invasive investigations. Concerns about low dose computed tomography screening include false positive results, overdiagnosis, radiation exposure, and costs. Further work is needed to define the frequency and duration of screening and to refine risk prediction models so that they can be used to assess the risk of lung cancer in special populations. Another important area is the use of computer vision software tools to facilitate high throughput interpretation of low dose computed tomography images so that costs can be reduced and the consistency of scan interpretation can be improved. Sufficient data are available to support the implementation of screening programs at the population level in stages that can be expanded when found to perform well to improve the outcome of patients with lung cancer.
Terrorism in familiar places
Authors: Douglas Kamerow
Journal: BMJ (2005)

One of the more pleasant aspects of my job as BMJ USA 's editor is traveling to London regularly to work with my BMJ colleagues. BMJ Publishing Group offices are located in an imposing neoclassical building in a leafy part of Bloomsbury opposite Tavistock Square that has served as the headquarters of the British Medical Association since 1925. As the world now knows, one of the July 7 terrorist bombs exploded just outside BMA House in a double-decker bus, spattering blood and body …
Environmental exposure and sensitization to cockroach, dust mite, and cat allergen: Correlation with asthma symptoms in a population of disadvantaged, inner-city children in the san francisco bay area
Authors: Katherine L Taylor, Elizabeth G Hoyte, Stewart N Taylor, Michelle L Mayer, Kathleen T Biederman, Paul J Sharek, Tom N Robinson, David A Bergman, Richard S Shames, Dale T Umetsu
Journal: Journal of Allergy and Clinical Immunology (2002)
Differences in Selection Drive Olfactory Receptor Genes in Different Directions in Dogs and Wolf
Authors: Rui Chen, David M. Irwin, Ya-Ping Zhang
Journal: Molecular Biology and Evolution (2012)

The olfactory receptor (OR) gene family is the largest gene family found in mammalian genomes. It is known to evolve through a birth-and-death process. Here, we characterized the sequences of 16 segregating OR pseudogenes in the samples of the wolf and the Chinese village dog (CVD) and compared them with the sequences from dogs of different breeds. Our results show that the segregating OR pseudogenes in breed dogs are under strong purifying selection, while evolving neutrally in the CVD, and show a more complicated pattern in the wolf. In the wolf, we found a trend to remove deleterious polymorphisms and accumulate nondeleterious polymorphisms. On the basis of protein structure of the ORs, we found that the distribution of different types of polymorphisms (synonymous, nonsynonymous, tolerated, and untolerated) varied greatly between the wolf and the breed dogs. In summary, our results suggest that different forms of selection have acted on the segregating OR pseudogenes in the CVD since domestication, breed dogs after breed formation, and ancestral wolf population, which has driven the evolution of these genes in different directions.
Weil's Disease in an Army Camp
Authors: S. Varadi
Journal: BMJ (1943)

In the last few years numerous articles on leptospirosis icterohaemorrhagica have been published in this country.The cases were either sporadic or occurred in endemics in certain occupations (sewer labourers, fish-workers, coalminers, etc.).The first authentic record was that of Manson-Bahr et al. (1922).In 1923 an epidemic of jaundice in coal-pits in East Lothian was described by Gulland and Buchanan (1924).In 1934 Hamilton Fairley reported cases of leptospirosis among sewer labourers in London.Swan and McKeon in 1935 recorded 12 cases among coal-miners in Northumberland and Durham, to which they added 17 others in 1938.Davidson and Smith in 1936, describing Weil's disease in fish-workers, gave a detailed account of its clinical manifestations.
Composition of extracts of airborne grain dusts: lectins and lymphocyte mitogens.
Authors: S A Olenchock, D M Lewis, J C Mull
Journal: Environmental Health Perspectives (1986)

Airborne grain dusts are heterogeneous materials that can elicit acute and chronic respiratory pathophysiology in exposed workers. Previous characterizations of the dusts include the identification of viable microbial contaminants, mycotoxins, and endotoxins. We provide information on the lectin-like activity of grain dust extracts and its possible biological relationship. Hemagglutination of erythrocytes and immunochemical modulation by antibody to specific lectins showed the presence of these substances in extracts of airborne dusts from barley, corn, and rye. Proliferation of normal rat splenic lymphocytes in vitro provided evidence for direct biological effects on the cells of the immune system. These data expand the knowledge of the composition of grain dusts (extracts), and suggest possible mechanisms that may contribute to respiratory disease in grain workers.
It's Over, Debbie
Authors: Susan D. Wilson
Journal: JAMA (1988)

<h3>To the Editor.</h3> —I read with a great deal of interest the article entitled "It's Over, Debbie."<sup>1</sup> My father, age 85 years, has been in a nursing home for more than a year. He is incontinent, has lost his memory and ability to comprehend and reason, and is hospitalized periodically for pneumonia, urinary tract infection, dehydration, and so on. He has now lost his ability to swallow, and since Christmas he has been fed through a tube inserted in his nose. Because he tries to remove the tube, his hands are tied at all times to the bed rails. He is not comatose but he does not recognize his family and he has no understanding of why he is being forced to lie in bed under these circumstances. I believe that if I were asked to make a list of ways in which to torture people, this would have
Abstract P4-12-03: Role of primary tumor molecular characteristics in identifying relapses in HER2-positive breast carcinomas adjuvantly treated with trastuzumab
Authors: T Triulzi, L De Cecco, M Giussani, S Canevari, ML Carcangiu, S Menard, M Campiglio, E Tagliabue
Journal: Cancer Research (2013)

Abstract Trastuzumab, a recombinant humanized monoclonal antibody directed to the HER2 protein, has shown survival benefits in women with HER2-positive breast cancer, and treatment is now FDA-approved in combination with chemotherapy. Nonetheless, some patients relapse after treatment, underscoring the need to identify patients for whom chemotherapy + trastuzumab is adequate versus patients requiring additional drugs. To search for factors predictive of relapse in HER2-positive breast carcinoma patients treated adjuvantly with trastuzumab, we conducted gene expression profiling analysis in 53 cases selected among a cohort of 243 patients (32 of whom relapsed) treated in the clinic with chemotherapy + trastuzumab in our institute during 2006-2009, with median follow-up of 32 months; the 53 cases comprised 23 of the relapsed and 30 of the non-relapsed patients with similar clinico-pathological characteristics (size, lymph node involvement and estrogen receptor positivity) for whom sufficient material was available. RNA extracted from formalin-fixed, paraffin-embedded (FFPE) was profiled using HumanHT12_v4 wgDASL expression BeadChips (Illumina). A Cox's proportional hazard model was used to estimate the association between gene expression and relapse-free survival (RFS), and a multivariate permutation test was used to check the proportion of false discoveries. Analysis identified 330 probes corresponding to 308 unique genes as significantly associated to RFS (a&amp;lt;0.005; permutation test p&amp;lt;0.01), showing an enrichment for gene ontology biological processes such as cell cycle regulation of immune cell proliferation and activation, cytoskeleton organization, ER pathway and ion transport. We also tested the feasibility of developing a predictive model including the gene expression data. Based on 10-fold cross-validation, our model was able to stratify patients into two groups (high and low risk), with a 4-year RFS probability of 14.5% in high-risk versus 87% in low-risk tumors (HR = 8.33, 95% CI = 3.53-18.18, p&amp;lt;0.0001). To test whether this signature identifies patients with intrinsic poor prognosis independent of trastuzumab treatment, we conducted in silico analysis on a dataset containing 144 HER2-positive breast carcinomas treated with chemotherapy alone; results revealed an inverse association between risk groups and prognosis, with an overall survival probability of 83% in our high-risk group and 63% in the low-risk group (HR = 0.60, 95% CI = 0.37-0.94, p = 0.0249). Together, our results suggest the usefulness of molecular characteristics of primary tumors as indicators of early relapse in patients treated adjuvantly with trastuzumab and as tools to identify patients for whom additional treatments are required. Supported by AIRC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-03.
From sporadic atypical nevi to familial melanoma: Risk analysis for melanoma in sporadic atypical nevus patients
Authors: Femke A. de Snoo, Marije W. Kroon, Wilma Bergman, Jeanet A.C. ter Huurne, Jeanine J. Houwing-Duistermaat, Leny van Mourik, Dyon G.C.T.M. Snels, Martijn H. Breuning, Rein Willemze, Rune R. Frants, Nelleke A. Gruis
Journal: Journal of the American Academy of Dermatology (2007)