tbuckley/cabot-search huggingface dataset:
Arsenic-Associated Oxidative Stress, Inflammation, and Immune Disruption in Human Placenta and Cord Blood
Authors: Sultan Ahmed, Sultana Mahabbat-e Khoda, Rokeya Sultana Rekha, Renee M. Gardner, Syeda Shegufta Ameer, Sophie Moore, Eva-Charlotte Ekström, Marie Vahter, Rubhana Raqib
Journal: Environmental Health Perspectives (2010)

BackgroundArsenic (As) exposure during pregnancy induces oxidative stress and increases the risk of fetal loss and low birth weight.ObjectivesIn this study we aimed to elucidate the effects of As exposure on immune markers in the placenta and cord blood, and the involvement of oxidative stress.MethodsPregnant women were enrolled around gestational week (GW) 8 in our longitudinal, population-based, mother–child cohort in Matlab, an area in rural Bangladesh with large variations in As concentrations in well water. Women (n = 130) delivering at local clinics were included in the present study. We collected maternal urine twice during pregnancy (GW8 and GW30) for measurements of As, and placenta and cord blood at delivery for assessment of immune and inflammatory markers. Placental markers were measured by immunohistochemistry, and cord blood cytokines by multiplex cytokine assay.ResultsIn multivariable adjusted models, maternal urinary As (U-As) exposure both at GW8 and at GW30 was significantly positively associated with placental markers of 8-oxoguanine (8-oxoG) and interleukin-1β (IL-1β); U-As at GW8, with tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); and U-As at GW30, with leptin; U-As at GW8 was inversely associated with CD3+ T cells in the placenta. Cord blood cytokines (IL-1β, IL-8, IFNγ, TNFα) showed a U-shaped association with U-As at GW30. Placental 8-oxoG was significantly positively associated with placental proinflammatory cytokines. Multivariable adjusted analyses suggested that enhanced placental cytokine expression (TNFα and IFNγ) was primarily influenced by oxidative stress, whereas leptin expression appeared to be mostly mediated by As, and IL-1β appeared to be influenced by both oxidative stress and As.ConclusionAs exposure during pregnancy appeared to enhance placental inflammatory responses (in part by increasing oxidative stress), reduce placental T cells, and alter cord blood cytokines. These findings suggest that effects of As on immune function may contribute to impaired fetal and infant health.
Model for Hypoxic Pulmonary Vasoconstriction Involving Mitochondrial Oxygen Sensing
Authors: Gregory B. Waypa, Navdeep S. Chandel, Paul T. Schumacker
Journal: Circulation Research (2001)

Abstract —We tested whether mitochondria function as the O 2 sensor underlying hypoxic pulmonary vasoconstriction (HPV). In buffer-perfused rat lungs, rotenone, myxothiazol, and diphenyleneiodonium, which inhibit mitochondria in the proximal region of the electron transport chain (ETC), abolished HPV without attenuating the response to U46619. Cyanide and antimycin A inhibit electron transfer in the distal region of the ETC, but they did not abolish HPV. Cultured pulmonary artery (PA) myocytes contract in response to hypoxia or to U46619. The hypoxic response was abolished while the response to U46619 was maintained in mutant (ρ 0 ) PA myocytes lacking a mitochondrial ETC. To test whether reactive oxygen species (ROS) derived from mitochondria act as signaling agents in HPV, the antioxidants pyrrolidinedithiocarbamate and ebselen and the Cu,Zn superoxide dismutase inhibitor diethyldithiocarbamate were used. These abolished HPV without affecting contraction to U46619, suggesting that ROS act as second messengers. In cultured PA myocytes, oxidation of intracellular 2′,7′-dichlorofluorescin diacetate (DCFH) dye increased under 2% O 2 , indicating that myocytes increase their generation of H 2 O 2 during hypoxia. This was attenuated by myxothiazol, implicating mitochondria as the source of increased ROS during HPV. These results indicate that mitochondrial ATP is not required for HPV, that mitochondria function as O 2 sensors during hypoxia, and that ROS generated in the proximal region of the ETC act as second messengers in the response.
Prevention of occupational asthma
Authors: KM Venables
Journal: European Respiratory Journal (1994)

This paper focuses on the prevention of asthma caused by exposure to sensitizing agents in the workplace. Control of exposure (primary prevention) is the most direct method of reducing the number of incident cases. Screening programmes are also necessary as a "safety net", and have value as secondary prevention, because early detection may improve long-term prognosis. It is recommended that regulatory or advisory bodies with responsibility for occupational asthma publish a guidance document on occupational asthma explaining their current concepts. Surveillance activities provide information on how common asthma is relative to other occupational lung diseases, and on the relative frequency of occurrence of asthma caused by different agents. Publication of a list of sensitizing agents would aid those with responsibility for control of exposure in the workplace. Epidemiological research on exposure-response relations is is necessary as a background to prevention. This paper recommends such studies. Immunotoxicological research also has a role in testing hypotheses that cannot be tested in human subjects. Some standardization of screening programmes in industry is desirable. A short symptoms questionnaire is economical and acceptable to workers, but there are other approaches. Finally, evaluative research on prevention measures gives information on their effectiveness and efficiency.
Attenuated GLP-1 secretion in obesity: cause or consequence?
Authors: L R Ranganath, J M Beety, L M Morgan, J W Wright, R Howland, V Marks
Journal: Gut (1996)

Hypersecretion of insulinotropic factors such as glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(7-36)amide (GLP-1) have been postulated to account for the hyperinsulinaemia of obesity.To examine the role of GLP-1 and GIP in obese women and matched controls.Six lean and six obese women subjects matched for age.The gut hormone, plasma glucose, and serum triglyceride responses were studied over 180 minutes after oral carbohydrate and fat meals. Heparin (10,000 units) was given intravenously at 120 minutes.There was pronounced attenuation of plasma GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but no such difference in response to oral fat load. There were no differences in the plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall in plasma GLP-1 values in all subjects after administration of heparin.Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects. The cause of this attenuation of GLP-1 secretion is not known although we suggest that both this fall and the overall reduction in GLP-1 values in obese subjects may be related to an increase in plasma non-esterified fatty acids.
Signatures of human regulatory T cells: an encounter with old friends and new players
Authors: Susanne Pfoertner, Andreas Jeron, Michael Probst-Kepper, Carlos A Guzman, Wiebke Hansen, Astrid M Westendorf, Tanja Toepfer, Andres J Schrader, Anke Franzke, Jan Buer, Robert Geffers
Journal: Genome biology (2006)

Abstract Background Naturally occurring CD4 + CD25 + regulatory T cells (T Reg ) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on T Reg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. Results To improve characterization of human T Reg cells, we compiled a unique microarray consisting of 350 T Reg cell associated genes (Human T Reg Chip) based on whole genome transcription data from human and mouse T Reg cells. T Reg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in T Reg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3 , CTLA4 , and CCR7 ) that are known to be involved in T Reg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human T Reg cells (including LGALS3 , TIAF1 , and TRAF1 ). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human T Reg cell function. Conclusion The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human T Reg cells. The Human T Reg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate T Reg cells under physiologic and diseased conditions.
Political infants? Developmental origins of the negativity bias
Authors: Katherine D Kinzler, Amrisha Vaish
Journal: Behavioral and Brain Sciences (2014)

Abstract The negativity bias in human cognition emerges in infancy and continues throughout childhood. To fully understand the relationship between differences in attention to negative stimuli and variance in political ideologies, it is critical to consider human development and the process by which early individual differences in negativity unfold and are shaped by both genes and environment.
Screening immigrants to Ireland from countries with a high prevalence of tuberculosis would be clinically beneficial and cost effective
Authors: Oscar Duffy, Dillon Annette, Terry O'Connor
Journal: European Respiratory Journal (2013)

The total amount TB cases in Ireland are increasing due to foreign-born patients residing in Ireland. Many countries use systematic screening programmes to identify and treat such cases but Ireland does not.  The aims of this research were to determine whether there is an increase in TB cases in Ireland due to foreign born cases that correlates with the recent rise in immigration; to find out whether foreign-born cases coming from countries where the incidence of TB is greater than 40/100,000 per year have the highest effect on TB rates in Ireland; to examine policies for TB screening in other industrialised countries and to estimate the potential clinical benefit and cost of introducing a screening programme for immigrants from countries with a high incidence of TB. Immigration data and Irish TB epidemiology were collected from the internet. Costs for the diagnoses and management of active and latent TB were obtained from Monthly Index of Medical Specialists (MIMS) handbook and TB specialists in Cork. The theoretical screening model applied to years 2008-2010 inclusive. Our results show that the cost of active case detection (screening) and treatment of subsequent positive cases from 2008-2010 costs €4,082,249. The cost of treating TB by passive case detection was estimated at €2,206,700. Therefore active case detection would have cost an additional €1,875,549 in this 3- year period or €625,183 each year.
SALMONELLOSIS: Host Immune Responses and Bacterial Virulence Determinants<sup>1</sup>
Authors: Bradley D. Jones, Stanley Falkow
Journal: Annual Review of Immunology (1996)

▪ Abstract The lifestyle of bacterial pathogens requires them to establish infection in the face of host immunity. Upon entering a potential host, a variety of interactions are initiated, the outcome of which depends upon a myriad of attributes of each of the participants. In this review we discuss the interactions that occur between pathogenic Salmonella species and the host immune systems, but when appropriate to broaden perspective, we have provided a general overview of the interactions between bacterial pathogens and animal hosts. Pathogenic Salmonella species possess an array of invasion genes that produce proteins secreted by a specialized type III secretion apparatus. These proteins are used by the bacteria to penetrate the intestinal mucosa by invading and destroying specialized epithelial M cells of the Peyer's patches. This manuever deposits the bacteria directly within the confines of the reticuloendothelial system. The host responds to these actions with nonspecific phagocytic cells and an imflammatory response as well as by activating specific cellular and humoral immune responses. Salmonella responds to this show of force directly. It appears that the bacteria invade and establish a niche within the very cells that have been sent to destroy them. Efforts are underway to characterize the factors that allow these intracellular bacteria to customize intracellular vacuoles for their own purposes. It is the constant play between these interactions that determines the outcome of the host infection, and clearly they will also shape the evolution of new survival strategies for both the bacterium and the host.
Efficacy of 5-day cefpodoxime proxetil for recurrent pharyngitis in adults. A comparative study with 10-day penicillin V or amoxycillin—clavulanate
Authors: Henri Portier, Pierre Gehanno, Philippe Weber, Henri Dabernat, Françoise Ichou, Antoine Clermont, Sylvie Fiessinger
Journal: Clinical Microbiology and Infection (1997)
Bronchus associated lymphoid tissue (BALT) in human lung: its distribution in smokers and non-smokers.
Authors: I Richmond, G E Pritchard, T Ashcroft, A Avery, P A Corris, E H Walters
Journal: Thorax (1993)

Bronchus associated lymphoid tissue (BALT) is a normal component of the lung's immune system in many animals and may be analogous to gut associated lymphoid tissue (GALT). This study aimed at assessing the nature and extent of BALT in human lung and determining whether its expression is induced within the human airway in response to smoking.Paraffin embedded, formalin fixed full thickness bronchial wall sections were examined from 31 whole lung specimens derived from both smokers and non-smokers. Samples were taken from throughout the bronchial tree to include main stem bronchi, lobar bronchi and segmental bronchi, as well as first to third generation carinae. Standard 4 microns step sections were stained by haematoxylin and eosin and immunocytochemical methods to show foci of BALT.Examination of 256 airway sites detected 46 foci of BALT. These differed from those described in other mammals in being distributed throughout the bronchial tree, in being found in relation to bronchial glandular epithelium as well as luminal bronchial epithelium, and in lacking any accompanying M cells. Analysis by smoking status showed that the expression of BALT was significantly more common in smokers than non-smokers (82% (14/17) v 14% (2/14) respectively).The findings support the view that BALT in humans is an integral feature in a comparatively small proportion of lungs from non-smokers while being significantly more prominent in lungs from smokers. The tissue shows several important differences from that described in other mammals.
Emerging allergies to cannabis
Authors: Virginie Doyen, Claire Ledent, Francis Corazza, Olivier Michel, Michel Mairesse
Journal: European Respiratory Journal (2014)

Cannabis (C) is a popular smoked drug deriving from  Cannabis sativa  (CS). We report 6 clinical cases of immediate hypersensitivity related to CS.  Subjects were young adults (27-41 years; 2M/4F) current or former C smokers. Symptoms were:plant food allergies due to cross-reactive lipid transfer proteins (LTP) (n= 5) (Metz-Favre C et al. Eur Ann Allergy Clin Immunol. 2011 Dec;43(6):193-5), rhinitis/asthma (n= 3), contact urticaria/eczema (n=3) and effort anaphylaxis (n=1). All had positive CS sIgE (median 8.05 (4.35-21.9) kU/L) (Ebo D et al. Int Arch Allergy Immunol. 2013;161:220-8). In 1 case, SPT with crude CS was made and strongly positive. All subjects were atopic.  Up to now, C consumption has been associated with respiratory side effects such pneumomediastin, pneumoconiosis and chronic bronchitis. The lung cancer risk is probable but not yet demonstrated and cases of IgE mediated hypersensitivity have increased. Interestingly, CS has been shown to have bronchodilator effects. Different route of exposure are possible: the skin and the respiratory tract during CS preparation and consumption but also through exposure to CS pollen that is anemophilous and transportable over long distances. To date, several causal allergens associated with CS allergy has been proposed: an oxygen-evolving enhancer protein, a ribulose-bisphosphate carboxylase and a LTP. Our cases were all sensitized to LTP but other CS potential allergens has not been tested.  CS smoking is able to induce different kinds of IgE mediated hypersensitivity: conjunctivitis, rhinitis, asthma, contact urticaria and anaphylaxis. Questioning about smoking habits should be part of every allergologic clinical history taking into account the high frequency of C smokers and its sensitizing potential.
Mammary Tumor Regression Elicited by Wnt Signaling Inhibitor Requires IGFBP5
Authors: Bob Y. Liu, Irina Soloviev, XiaoDong Huang, Peter Chang, James A. Ernst, Paul Polakis, Chie Sakanaka
Journal: Cancer Research (2012)

Wnt ligand-driven tumor growth is inhibited by the soluble Wnt inhibitor Fzd8CRD, but the mechanism through which this effect is mediated is unknown. In the MMTV-Wnt1 mouse model, regression of mammary tumors by Fzd8CRD treatment coincides with an acute and strong induction of insulin-like growth factor (IGF)-binding protein IGFBP5, an antagonist of IGF signaling that mediates involution of mammary gland in females after offspring are weaned. In this study, we show that repression of this IGF inhibitory pathway is crucial for Wnt-driven growth of mammary tumors. We found that IGFBP5 regulation was mediated by the β-catenin-dependent Wnt pathway. Wnt, in addition to IGF ligands, facilitated tumor growth by paracrine communication among tumor cells. In addition, Fzd8CRD caused precocious induction of IGFBP5 in normal mammary glands undergoing involution, implying an acceleration of the involution process by inhibition of Wnt signaling. The molecular and phenotypic parallel between tumor regression and mammary gland involution suggests that Wnt-driven mammary tumors use the same growth mechanism as proliferating normal mammary glands.
Combined enzyme defect of mitochondrial fatty acid oxidation.
Authors: S Jackson, R S Kler, K Bartlett, H Briggs, L A Bindoff, M Pourfarzam, D Gardner-Medwin, D M Turnbull
Journal: Journal of Clinical Investigation (1992)

A young girl presented with recurrent episodes of muscle weakness culminating in a severe attack of generalized muscle weakness. In the muscle mitochondria from the patient there was an abnormal pattern of intermediates of beta-oxidation with an accumulation of 3-hydroxyacyl- and 2-enoyl-CoA and carnitine esters, and 3-oxoacylcarnitines. There was low activity of long-chain 3-hydroxyacyl-CoA dehydrogenase in mitochondria from all tissues. The activity of long-chain 2-enoyl-CoA hydratase was low in muscle mitochondria and 3-oxoacyl-CoA thiolase activity measured with 3-oxohexadecanoyl-CoA as substrate was low in fibroblast, muscle, and cardiac mitochondria but only partial deficiency was present when the activity was measured with 3-oxooctanoyl-CoA. The activity of the long-chain 3-hydroxyacyl-CoA dehydrogenase and long-chain 3-oxoacyl-CoA thiolase in fibroblasts from the patient's parents was intermediate between those of controls and the patient. The patient has a combined defect of the long-chain 3-hydroxyacyl-CoA dehydrogenase, long-chain 3-oxoacyl-CoA thiolase, and long-chain 2-enoyl-CoA hydratase which appears to be inherited in an autosomal recessive manner. This suggests there is a multifunctional enzyme catalyzing these activities in human mitochondria and that this enzyme is deficient in our patient.
Association of an Educational Program in Mindful Communication With Burnout, Empathy, and Attitudes Among Primary Care Physicians
Authors: Michael S. Krasner
Journal: JAMA (2009)

Primary care physicians report high levels of distress, which is linked to burnout, attrition, and poorer quality of care. Programs to reduce burnout before it results in impairment are rare; data on these programs are scarce.To determine whether an intensive educational program in mindfulness, communication, and self-awareness is associated with improvement in primary care physicians' well-being, psychological distress, burnout, and capacity for relating to patients.Before-and-after study of 70 primary care physicians in Rochester, New York, in a continuing medical education (CME) course in 2007-2008. The course included mindfulness meditation, self-awareness exercises, narratives about meaningful clinical experiences, appreciative interviews, didactic material, and discussion. An 8-week intensive phase (2.5 h/wk, 7-hour retreat) was followed by a 10-month maintenance phase (2.5 h/mo).Mindfulness (2 subscales), burnout (3 subscales), empathy (3 subscales), psychosocial orientation, personality (5 factors), and mood (6 subscales) measured at baseline and at 2, 12, and 15 months.Over the course of the program and follow-up, participants demonstrated improvements in mindfulness (raw score, 45.2 to 54.1; raw score change [Delta], 8.9; 95% confidence interval [CI], 7.0 to 10.8); burnout (emotional exhaustion, 26.8 to 20.0; Delta = -6.8; 95% CI, -4.8 to -8.8; depersonalization, 8.4 to 5.9; Delta = -2.5; 95% CI, -1.4 to -3.6; and personal accomplishment, 40.2 to 42.6; Delta = 2.4; 95% CI, 1.2 to 3.6); empathy (116.6 to 121.2; Delta = 4.6; 95% CI, 2.2 to 7.0); physician belief scale (76.7 to 72.6; Delta = -4.1; 95% CI, -1.8 to -6.4); total mood disturbance (33.2 to 16.1; Delta = -17.1; 95% CI, -11 to -23.2), and personality (conscientiousness, 6.5 to 6.8; Delta = 0.3; 95% CI, 0.1 to 5 and emotional stability, 6.1 to 6.6; Delta = 0.5; 95% CI, 0.3 to 0.7). Improvements in mindfulness were correlated with improvements in total mood disturbance (r = -0.39, P < .001), perspective taking subscale of physician empathy (r = 0.31, P < .001), burnout (emotional exhaustion and personal accomplishment subscales, r = -0.32 and 0.33, respectively; P < .001), and personality factors (conscientiousness and emotional stability, r = 0.29 and 0.25, respectively; P < .001).Participation in a mindful communication program was associated with short-term and sustained improvements in well-being and attitudes associated with patient-centered care. Because before-and-after designs limit inferences about intervention effects, these findings warrant randomized trials involving a variety of practicing physicians.
The need for psychological needs: A role for social capital
Authors: John L. Locke, Catherine M. Flanagan
Journal: Behavioral and Brain Sciences (2013)

Abstract Van de Vliert embraces a “supply side” model of human needs, underplaying a “demand” model whereby individuals, motivated by psychological needs, develop coping strategies that help them meet their personal goals and collectively exert an influence on social and economic systems. Undesirable climates may inflate the value of financial capital, but they also boost the value of social capital.