tbuckley/cabot-search huggingface dataset:
Oil Refinery Effluents: Evidence of Cocarcinogenic Activity in the Trout Embryo Microinjection Assay&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C D Metcalfe, R A Sonstegard
Journal: JNCI Journal of the National Cancer Institute (1985)

Extracts prepared from oil refinery effluents (soxhlet and XAD-2) were tested for carcinogenic potential by means of the rainbow trout (Salmo gairdneri) embryo-injection bioassay. No neoplasms were detected in fish given injections of refinery extracts alone (with and without exogenous rat S-9 activation). Refinery extracts coinjected with aflatoxin B1 induced elevated frequencies of hepatic neoplasms. This cocarcinogenic effect was most pronounced when aflatoxin B1 was preincubated with rat S-9 prior to injection. Effluent extracts coinjected with a direct-acting carcinogen [N-methyl-N'-nitro-N-nitrosoguanidine (CAS: 56-57-5)] did not increase the incidence of hepatic neoplasms (with and without exogenous S-9 activation).
Abstract 3192: The environmental estrogen bisphenol A (BPA) regulates mammary gland stem cells
Authors: Cydney Nichols, Xiangming Ding, Gustavo Miranda-Carboni, Susan Amy Krum
Journal: Cancer Research (2014)

Abstract A study by the Centers for Disease Control revealed detectable levels of the environmental toxin Bisphenol A (BPA) in urine samples from over 92% of people in the NHANES (National Health and Nutrition Examination Survey) study. BPA is a small molecule used in the polymerization of polycarbonate plastics. These plastics are widely used in food containers, water bottles, dental fillings and toys, among many other products. BPA is similar to the synthetic estrogen diethylstilbesterol (DES) and can bind to estrogen receptor alpha (ERα) or estrogen receptor beta (ERβ). Because BPA is lipophilic and has been detected in mammary gland fat in humans, we hypothesize that BPA is an estrogen mimic in the stromal adipocytes in the breast and can induce stem cell proliferation and survival, leading to breast tumor formation. Indeed, BPA increases the size and number of mammospheres from normal mouse mammary gland and from human MCF7 breast cancer cells. Adipocytes co-cultured with mammospheres increased the size of the spheres, and BPA further increased the size of adipocyte co-cultured mammospheres. BPA upregulates the stem cell markers Nanog, OCT4 and SOX2 in mammospheres. ERα and pCREB were shown to bind to an enhancer downstream of the SOX2 gene after BPA treatment. Finally, BPA increased the size of tumor xenografts in NUDE mice. Together these experiments demonstrate that BPA may induce breast cancer via ERα and pCREB regulation of breast cancer stem cells. Citation Format: Cydney Nichols, Xiangming Ding, Gustavo Miranda-Carboni, Susan Amy Krum. The environmental estrogen bisphenol A (BPA) regulates mammary gland stem cells. [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 3192. doi:10.1158/1538-7445.AM2014-3192
Statewide Study of Diagnostic Agreement in Breast Pathology
Authors: W A Wells, P A Carney, M S Eliassen, A N Tosteson, E R Greenberg
Journal: JNCI Journal of the National Cancer Institute (1998)

This study assessed the degree of diagnostic agreement among community-based general pathologists reading slides of representative breast tissue specimens and tested whether diagnostic variability is associated with type of breast specimen (e.g., core needle or excisional biopsy) or slide quality.Twenty-six of the 44 eligible pathologists working at community-based pathology practices in New Hampshire participated. Each pathologist evaluated slides of breast tissue obtained from 30 case subjects randomly selected from a statewide breast pathology database. The diagnostic categories used were benign, benign with atypia, noninvasive malignant, and invasive malignant. The levels of agreement (i.e., kappa coefficients) for the diagnoses were assessed.Agreement was high among pathologists for assignment of diagnostic category (kappa coefficient = 0.71) and was nearly perfect for their selection of benign versus malignant categories (kappa coefficient = 0.95). There was less agreement for the categories of noninvasive malignant and benign with atypia (kappa coefficients of 0.59 and 0.22, respectively). There was no apparent relationship between levels of diagnostic agreement and specimen type or perceived slide quality.Diagnostic agreement for breast tissue specimens is high overall among community-based pathologists, but clinically relevant disagreements may occur in the assessment of noninvasive malignant diagnoses. The establishment of reread policies for certain diagnostic categories may reduce the possibility that diagnostic misclassification will lead to overtreatment or undertreatment. The high degree of diagnostic reproducibility for invasive cancerous lesions of the breast suggests that it is unnecessary for a central review of these lesions in national cancer trials.
Advances in Understanding Benzene Health Effects and Susceptibility
Authors: Martyn T. Smith
Journal: Annual Review of Public Health (2010)

Benzene is a ubiquitous chemical in our environment that causes acute leukemia and probably other hematological cancers. Evidence for an association with childhood leukemia is growing. Exposure to benzene can lead to multiple alterations that contribute to the leukemogenic process, indicating a multimodal mechanism of action. Research is needed to elucidate the different roles of multiple metabolites in benzene toxicity and the pathways that lead to their formation. Studies to date have identified a number of polymorphisms in candidate genes that confer susceptibility to benzene hematotoxicity. However, a genome-wide study is needed to truly assess the role of genetic variation in susceptibility. Benzene affects the blood-forming system at low levels of occupational exposure, and there is no evidence of a threshold. There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.
Pesticide Spraying for West Nile Virus Control and Emergency Department Asthma Visits in New York City, 2000
Authors: Adam M. Karpati, Mary C. Perrin, Tom Matte, Jessica Leighton, Joel Schwartz, R. Graham Barr
Journal: Environmental Health Perspectives (2004)

Pyrethroid pesticides were applied via ground spraying to residential neighborhoods in New York City during July-September 2000 to control mosquito vectors of West Nile virus (WNV). Case reports link pyrethroid exposure to asthma exacerbations, but population-level effects on asthma from large-scale mosquito control programs have not been assessed. We conducted this analysis to determine whether widespread urban pyrethroid pesticide use was associated with increased rates of emergency department (ED) visits for asthma. We recorded the dates and locations of pyrethroid spraying during the 2000 WNV season in New York City and tabulated all ED visits for asthma to public hospitals from October 1999 through November 2000 by date and ZIP code of patients' residences. The association between pesticide application and asthma-related emergency visits was evaluated across date and ZIP code, adjusting for season, day of week, and daily temperature, precipitation, particulate, and ozone levels. There were 62,827 ED visits for asthma during the 14-month study period, across 162 ZIP codes. The number of asthma visits was similar in the 3-day periods before and after spraying (510 vs. 501, p = 0.78). In multivariate analyses, daily rates of asthma visits were not associated with pesticide spraying (rate ratio = 0.92; 95% confidence interval, 0.80-1.07). Secondary analyses among children and for chronic obstructive pulmonary disease yielded similar null results. This analysis shows that spraying pyrethroids for WNV control in New York City was not followed by population-level increases in public hospital ED visit rates for asthma.
Deregulation of the telomerase reverse transcriptase (TERT) gene by chromosomal translocations in B-cell malignancies
Authors: Inga Nagel, Monika Szczepanowski, José I. Martín-Subero, Lana Harder, Takashi Akasaka, Ole Ammerpohl, Evelyne Callet-Bauchu, Randy D. Gascoyne, Stefan Gesk, Doug Horsman, Wolfram Klapper, Aneela Majid, José A. Martinez-Climent, Stephan Stilgenbauer, Holger Tönnies, Martin J. S. Dyer, Reiner Siebert
Journal: Blood (2010)
Alternatively activated macrophage-derived RELM-α is a negative regulator of type 2 inflammation in the lung
Authors: Meera G. Nair, Yurong Du, Jacqueline G. Perrigoue, Colby Zaph, Justin J. Taylor, Michael Goldschmidt, Gary P. Swain, George D. Yancopoulos, David M. Valenzuela, Andrew Murphy, Margaret Karow, Sean Stevens, Edward J. Pearce, David Artis
Journal: The Journal of Experimental Medicine (2009)

Differentiation and recruitment of alternatively activated macrophages (AAMacs) are hallmarks of several inflammatory conditions associated with infection, allergy, diabetes, and cancer. AAMacs are defined by the expression of Arginase 1, chitinase-like molecules, and resistin-like molecule (RELM) α/FIZZ1; however, the influence of these molecules on the development, progression, or resolution of inflammatory diseases is unknown. We describe the generation of RELM-α–deficient (Retnla−/−) mice and use a model of T helper type 2 (Th2) cytokine-dependent lung inflammation to identify an immunoregulatory role for RELM-α. After challenge with Schistosoma mansoni (Sm) eggs, Retnla−/− mice developed exacerbated lung inflammation compared with their wild-type counterparts, characterized by excessive pulmonary vascularization, increased size of egg-induced granulomas, and elevated fibrosis. Associated with increased disease severity, Sm egg–challenged Retnla−/− mice exhibited elevated expression of pathogen-specific CD4+ T cell–derived Th2 cytokines. Consistent with immunoregulatory properties, recombinant RELM-α could bind to macrophages and effector CD4+ Th2 cells and inhibited Th2 cytokine production in a Bruton's tyrosine kinase–dependent manner. Additionally, Retnla−/− AAMacs promoted exaggerated antigen-specific Th2 cell differentiation. Collectively, these data identify a previously unrecognized role for AAMac-derived RELM-α in limiting the pathogenesis of Th2 cytokine-mediated pulmonary inflammation, in part through the regulation of CD4+ T cell responses.
Effects of Hematin in Hepatic Porphyria
Authors: G. JEELANI DHAR
Journal: Annals of Internal Medicine (1975)

The present study was carried out in five cases of hepatic porphyria, including three of acute intermittent porphyria, one of variegate porphyria, and one of porphyria cutanea tarda in clinical remission. In two cases of acute intermittent porphyria (in relapse), a marked lowering effect on serum and urine porphobilinogen and delta-aminolevulinic acic was observed, together with prompt and gratifying clinical improvement. In a third case, in chemical remission but with longstanding psychoneurosis, no significant effects were noted, nor were any observed in the case of porphyria cutanea tarda. Although clinical improvements occurred in the case of variegate porphyria, the results were inconclusive for reasons given. Hematin was generally well tolerated. Preliminary reference is made to a transitory renal injury, without sequelae, where an excess of hematin was given in relation to time. Limits of tolerance are proposed. In the light of these observations the basic mechanism of the acute attack is diccussed.
Inflammatory links between obesity and metabolic disease
Authors: Carey N. Lumeng, Alan R. Saltiel
Journal: Journal of Clinical Investigation (2011)

The obesity epidemic has forced us to evaluate the role of inflammation in the health complications of obesity. This has led to a convergence of the fields of immunology and nutrient physiology and the understanding that they are inextricably linked. The reframing of obesity as an inflammatory condition has had a wide impact on our conceptualization of obesity-associated diseases. In this Review, we highlight the cellular and molecular mechanisms at play in the generation of obesity-induced inflammation. We also emphasize how defining the immune regulation in metabolic tissues has broadened the understanding of the diversity of inflammatory responses.
Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy
Journal: New England Journal of Medicine (2011)

In patients with established cardiovascular disease, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein (LDL) cholesterol levels with statin therapy. It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein (HDL) cholesterol is superior to simvastatin alone in reducing such residual risk.
Circulating osteoprotegerin levels are associated with age, waist-to-hip ratio, serum total cholesterol, and low-density lipoprotein cholesterol levels in healthy Korean women
Authors: Eun Sook Oh, Eun-Jung Rhee, Ki Won Oh, Won Young Lee, Ki Hyun Baek, Kun Ho Yoon, Moo Il Kang, Eun Joo Yun, Cheol Young Park, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park
Journal: Metabolism (2004)
Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis
Authors: Teh-ia Huo, Jaw-ching Wu, Pui-ching Lee, Gar-yang Chau, Wing-yu Lui, Shyh-haw Tsay, Ling-tan Ting, Full-young Chang, Shou-dong Lee
Journal: Hepatology (1998)

The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the natural history of chronic hepatitis B virus (HBV)-infected patients was low. Previous studies regarding the prognosis in such patients were controversial. Among 1,355 chronic carriers from 1985 to 1997, spontaneous HBsAg clearance was observed in 55 patients. During a mean follow-up period of 23 months, 18 (32.7%; all were male subjects) developed serious complications, including 11 with hepatocellular carcinoma (HCC) (9 of them underwent surgical resection), 6 with cirrhosis, and 1 with subfulminant liver failure. The overall cumulative probability of complications was 29.8% at 4 years, and it was higher in males ( P = .044) and patients aged 45 years or more ( P = .006); the latter carried an 8.6-fold increased risk (95% CI: 1.2-64.6; P = .037) of adverse events. Histories of acute or chronic infection by hepatitis A virus, C virus (HCV), or D virus (HDV) were present in 42% of patients. Patients seropositive for antibodies against HCV (anti-HCV) or HDV (anti-HDV) had higher alanine transaminase (ALT) levels (&gt;40 U/L; P = .008) after sero-clearance. HBV DNA was detectable in 31% of 51 subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV or anti-HDV, and also in an HCC patient’s serum and tumor. Staining of liver HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results demonstrated that hepatitis B viremia may persist, and adverse complications were not rare in HBsAg-clearance patients. All such patients should be closely monitored, which may allow for earlier detection of HCC.
Hypoxia-Inducible Factor-1α Obstructs a Wnt Signaling Pathway by Inhibiting the hARD1-Mediated Activation of β-Catenin
Authors: Ji-Hong Lim, Yang-Sook Chun, Jong-Wan Park
Journal: Cancer Research (2008)

Although a splice variant of mouse mARD1s was found to acetylate and destabilize hypoxia-inducible factor-1alpha (HIF-1alpha), human hARD1 has no such activities. Nonetheless, hARD1 has been reported to bind directly with HIF-1alpha. Here, we addressed the functional significance of the hARD1-HIF-1alpha interaction. Because hARD1 acetylates and activates beta-catenin, we examined whether HIF-1alpha regulates the hARD1-mediated activation of Wnt signaling. It was found that HIF-1alpha binds hARD1 through the oxygen-dependent degradation domain and, in so doing, dissociates hARD1 from beta-catenin, which prevents beta-catenin acetylation. In LiCl-stimulated HEK293 or cancer cell lines with active Wnt signaling, beta-catenin acetylation and activity were suppressed in hypoxia, and these suppressions were mediated by HIF-1alpha. Moreover, HIF-1alpha disruption of hARD1/beta-catenin repressed TCF4 activity, resulting in c-Myc suppression and p21(cip1) induction. In addition, we confirmed that the HIF-1alpha NH(2) terminal inactivates TCF4 by directly binding beta-catenin. In conclusion, HIF-1alpha was found to inactivate the Wnt signaling by binding to hARD1 or beta-catenin, which may contribute to the hypoxia-induced growth arrest of tumor cells.
Cardiac Ischemia Activates Vascular Endothelial Cadherin Promoter in Both Preexisting Vascular Cells and Bone Marrow Cells Involved in Neovascularization
Authors: Naoko Kogata, Yuji Arai, James T. Pearson, Kazuaki Hashimoto, Kyoko Hidaka, Tatsuya Koyama, Satoshi Somekawa, Yoshikazu Nakaoka, Minetaro Ogawa, Ralf H. Adams, Masato Okada, Naoki Mochizuki
Journal: Circulation Research (2006)

Vascular endothelial cadherin (VE-cadherin) is expressed on vascular endothelial cells, which are involved in developmental vessel formation. However, it remains elusive how VE-cadherin–expressing cells function in postnatal neovascularization. To trace VE-cadherin–expressing cells, we developed mice expressing either green fluorescent protein or LacZ driven by VE-cadherin promoter using Cre-loxP system. Although VE-cadherin promoter is less active after birth than during embryogenesis in blood vessels, it is reactivated on cardiac ischemia. Both types of reporter-positive cells are found in the vasculature and in the infarcted myocardium. Those found in the vasculature were pre-existing endothelial cells and incorporated endothelial progenitor cells derived from extracardiac tissue. In addition to the vasculature, VE-cadherin promoter-activated cells were positive for CD45 in the bone marrow cells of the infarcted mice. VE-cadherin promoter–reactivated CD45-positive leukocytes were also found in the infarcted area. In addition, VE-cadherin promoter was activated in the bone marrow vessels of the infarcted mice. Collectively, our findings reveal a new ischemia-induced neovascularization mechanism involving VE-cadherin; the re-expressed VE-cadherin–mediated cell adhesion between cells may be involved not only in homing of bone marrow–derived cells to ischemic area but also mobilization from bone marrow.
Sequencing of Docetaxel (D) and Abiraterone Acetate (Aa) for Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
Authors: Z. Zafeiriou, R. Ferraldeschi, A. Omlin, C. Pezaro, D. Mukherji, D. Lorente, A. Altavilla, S. Sideris, P. Rescigno, J. Mateo, D. Bianchini, A. Smith, R. Perez Lopez, N. Mehra, P. Ravi, E. Grist, N. Tunariu, G. Attard, J.S. de Bono
Journal: Annals of Oncology (2014)
Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts
Authors: Hans F A Vasen, Ignacio Blanco, Katja Aktan-Collan, Jessica P Gopie, Angel Alonso, Stefan Aretz, Inge Bernstein, Lucio Bertario, John Burn, Gabriel Capella, Chrystelle Colas, Christoph Engel, Ian M Frayling, Maurizio Genuardi, Karl Heinimann, Frederik J Hes, Shirley V Hodgson, John A Karagiannis, Fiona Lalloo, Annika Lindblom, Jukka-Pekka Mecklin, Pal Møller, Torben Myrhoj, Fokko M Nagengast, Yann Parc, Maurizio Ponz de Leon, Laura Renkonen-Sinisalo, Julian R Sampson, Astrid Stormorken, Rolf H Sijmons, Sabine Tejpar, Huw J W Thomas, Nils Rahner, Juul T Wijnen, Heikki Juhani Järvinen, Gabriela Möslein
Journal: Gut (2013)

<h3>Background</h3> The UK introduced financial incentives for management of atrial fibrillation (AF) in 2006, after which there was an increase in the proportion of AF patients diagnosed as resolved. Removal of incentives in Scotland provides a natural experiment to investigate the effects of withdrawal of an incentive on diagnosis of resolved AF. <h3>Aim</h3> Investigate effects of introduction and withdrawal of financial incentives on the diagnosis of resolved AF. <h3>Design &amp; setting</h3> Cohort study in a large database of UK primary care records, before and after introduction of incentives in April 2006 in Scotland, England and Northern Ireland, and their withdrawal in April 2016 in Scotland. <h3>Method</h3> Interrupted time-series analysis of monthly rates of resolved AF. from January 2000 to September 2019. <h3>Results</h3> We included 251,526 adult patients with AF, of whom 14,674 were diagnosed as resolved AF. In April 2006 there were similar shift-changes in rates of resolved AF per 1,000 in England 1.55 (95% CI: 1.11–2.00) and Northern Ireland 1.54 (95% CI: 0.91–2.18) and a smaller increase in Scotland 0.79 (95% CI: 0.04–1.53). There were modest downward post-introduction trends in all countries. After Scotland’s withdrawal of the incentive in April 2016 there was a small, statistically non-significant, downward shift in rate of resolved AF per 1000–0.39 (95% CI: −3.21–2.42) and no change in post-removal trend. <h3>Conclusions</h3> Introduction of a financial incentive coincided with an increase in resolved AF but we found no evidence its withdrawal led to a reduction.
Effect of mobile phone reminders on follow-up medical care of children exposed to or infected with HIV in Cameroon (MORE CARE): a multicentre, single-blind, factorial, randomised controlled trial
Authors: Jean Joel R Bigna, Jean Jacques N Noubiap, Charles Kouanfack, Claudia S Plottel, Sinata Koulla-Shiro
Journal: The Lancet Infectious Diseases (2014)
The regulation of intracellular pH in the diabetic myocardium
Authors: D Feuvray
Journal: Cardiovascular Research (1997)

Time for primary review 25 days.

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In myocardial cells, as in any given cell, steady-state intracellular pH (pHi) is strictly maintained within a narrow range at relatively alkaline values. Resting pHi (7.1–7.2) is determined by the algebraic sum of acid-loading and acid-extruding processes. Whenever acid-loading exceeds acid extrusion, pHi falls. The degree to which pHi changes is inversely related to the intracellular buffering power (βi). The role of intracellular buffering power, which is the first line of defence of a cardiac cell against an intracellular acid–base disturbance, is to moderate pHi changes produced by acute acid (or alkali) load [1]. However, buffering mechanisms cannot prevent a change in pHi, but only reduce its amplitude. The regulation of pHi then largely depends upon the activity of plasma membrane carrier-mediated transport of acid/base equivalents [2, 3]. Intracellular pH is important for the activity of a number of enzymes with optimal pH within the physiological pH range, as well as for the conductivity of ion channels [4], calcium homeostasis, and the efficiency of contractile elements [5, 6].

Despite a vast literature demonstrating myocardial metabolic changes associated with diabetes (for reviews, see Refs. [7, 8]), until recent years relatively few studies have addressed the effects of diabetes on intracellular pH. Yet, disturbances in intracellular pH or in the processes regulating intracellular pH may be expected to occur in diabetic hearts as a result of either altered cellular metabolism and/or cellular and subcellular membrane changes. This review provides a summary of the data obtained with both multicellular and single cell preparations, as well as with isolated hearts from chemically-induced diabetic rats.

The first study that allowed direct measurement of intracellular pH in cardiac cells of streptozotocin (STZ)-induced diabetic rat hearts was … 

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