tbuckley/cabot-search huggingface dataset:
Capitalizing on the Immunogenicity of Dying Tumor Cells
Authors: Catia Fonseca, Glenn Dranoff
Journal: Clinical Cancer Research (2008)

Abstract Cancer cell death occurs continually during tumor development and progression, whereas the selective killing of surviving cancer cells remains the primary objective of antineoplastic treatments. Recent insights into the immunologic consequences of cancer cell death have begun to elucidate the ways in which host antitumor immunity is shaped during cancer pathogenesis and then modulated by therapeutic intervention. Dying tumor cells evoke a range of host responses, dependent in part upon the mode of cell death, which may either impede or foster additional immune-mediated cancer destruction. Within the tumor microenvironment, the capture of apoptotic tumor cells by macrophages and dendritic cells may trigger tolerance networks that contribute to immune suppression, whereas the uptake of necrotic cancer cells may engender inflammatory pathways that fuel antitumor cytotoxicity. Milk fat globule epidermal growth factor 8, a phosphatidylserine-binding protein, and MHC class I chain–related protein A, an NKG2D ligand, play key roles in these competing outcomes. A deeper understanding of the mechanisms underlying the immunogenicity of dying cells informs the crafting of strategies that exploit endogenous or treatment-induced cancer cell death as the basis for stimulating sustained host antitumor cytotoxic reactions.
The Mef/Elf4 Transcription Factor Fine Tunes the DNA Damage Response
Authors: Goro Sashida, Narae Bae, Silvana Di Giandomenico, Takashi Asai, Nadia Gurvich, Elena Bazzoli, Yan Liu, Gang Huang, Xinyang Zhao, Silvia Menendez, Stephen D. Nimer
Journal: Cancer Research (2011)

Abstract The ATM kinase plays a critical role in initiating the DNA damage response that is triggered by genotoxic stresses capable of inducing DNA double-strand breaks. Here, we show that ELF4/MEF, a member of the ETS family of transcription factors, contributes to the persistence of γH2AX DNA damage foci and promotes the DNA damage response leading to the induction of apoptosis. Conversely, the absence of ELF4 promotes the faster repair of damaged DNA and more rapid disappearance of γH2AX foci in response to γ-irradiation, leading to a radio-resistant phenotype despite normal ATM phosphorylation. Following γ-irradiation, ATM phosphorylates ELF4, leading to its degradation; a mutant form of ELF4 that cannot be phosphorylated by ATM persists following γ-irradiation, delaying the resolution of γH2AX foci and triggering an excessive DNA damage response. Thus, although ELF4 promotes the phosphorylation of H2AX by ATM, its activity must be dampened by ATM-dependent phosphorylation and degradation to avoid an excessive DNA damage response. Cancer Res; 71(14); 4857–65. ©2011 AACR.
Nutrition and respiratory health in adults: findings from the Health Survey for Scotland
Authors: Y. Kelly, A. Sacker, M. Marmot
Journal: European Respiratory Journal (2003)

There is a growing body of evidence to support the hypothesised links between consumption of antioxidant rich foods and the occurrence of obstructive airway disease. The main research question was to examine the relationships between two types of dietary exposure and two indicators of respiratory morbidity in Scottish adults. The relationships between dietary consumption of fruit, vegetables and fish, and plasma levels of vitamins A, C, E and β-carotene, and pulmonary function (forced expiratory volume in one second (FEV 1 )) and symptoms (phlegm production and shortness of breath with wheezing), were examined in a random population sample of adults. A dose/response relationship was found between fruit consumption and pulmonary function. In comparison with eating fruit rarely or never, eating fruit at least once per day, 1–6 times per week, and 1–3 times per month were associated with differences of 132, 100 and 63 mL in FEV 1 , after adjustment for known confounders and dietary intake of vegetables and fish (n=6186). An sd score change in plasma vitamin C was associated with a 49 mL difference in FEV 1 (n=930). Fruit and vitamin E were associated with a reduced prevalence of phlegm production for 3 months or more per year. The most beneficial combination of dietary components may be found in natural foodstuffs, particularly fresh fruit.
Mild to moderate influenza activity in Europe and the detection of novel A(H1N2) and B viruses during the winter of 2001-02
Authors: W J Paget, T J Meerhoff, N L Goddard
Journal: Eurosurveillance (2002)

Influenza activity in Europe during the 2001-02 influenza season was mild to moderate. Compared to historical data, the intensity was low in six countries, medium in eleven and high in one country (Spain). The dominant virus circulating in Europe was influenza A(H3N2). Two novel influenza virus strains were isolated during the 2001-02 season: influenza A(H1N2) viruses (mainly isolated in the United Kingdom and Ireland, but also in Belgium, France, Germany, the Netherlands, Portugal, Sweden, Switzerland and Romania), and influenza B viruses belonging to the B/Victoria/2/87 lineage (mainly isolated in Germany, but also sporadically in France, Italy, the Netherlands and Norway). With the exception of H1N2 virus detections in England, and Ireland and the influenza B viruses belonging to the B/Victoria/2/87 lineage in Germany, these two viruses did not circulate widely in Europe and did not play an important role in influenza activity during the 2001-02 season. An influenza B virus belonging to the B/Victoria/2/87 lineage will be included in the 2002-03 influenza vaccine. The new subtype influenza A(H1N2) is covered by the 2002-03 vaccine, as the haemagglutinin and neuraminidase components of the H1N2 viruses are antigenically similar to the vaccine components (H1N1 and H3N2).
Combined effect of IL‐10 and TGF‐β1 promoter polymorphisms as a risk factor for aspirin‐intolerant asthma and rhinosinusitis
Authors: S.‐H. Kim, E.‐M. Yang, H.‐N. Lee, B.‐Y. Cho, Y.‐M. Ye, H.‐S. Park
Journal: Allergy (2009)

It has been known that interleukin (IL)-10 promoter polymorphisms at -1082A/G, -819T/C and -592A/C, may influence IL-10 expression and associate with asthma. Interleukin-10 facilitates the regulatory function of transforming growth factor (TGF)-beta. The goal of this study was to investigate a gene-gene interaction between IL-10 and TGF-beta1 polymorphisms in Korean asthmatics with aspirin hypersensitivity.Single-nucleotide polymorphism genotyping of IL-10 and TGF-beta1 genes was performed and the functional effect of the IL-10 polymorphisms was analysed applying a luciferase reporter assay and an electrophoretic mobility shift assay.Among the patients with asthma, polymorphism at -1082A/G was significantly associated with the phenotype of aspirin-intolerant asthma, AIA (P = 0.007, P(c) = 0.021). Moreover, a synergistic effect between the TGF-beta1-509C/T and IL-10-1082A/G polymorphisms on the phenotype of AIA was noted; when stratified by the presence of rhinosinusitis, the frequency of rare alleles (the CT or TT genotype of TGF-beta1-509C/T and AG or GG genotype of IL-10-1082A/G) was significantly higher in the patients with AIA (15.2%) when compared with those with ATA (6.3%, P = 0.031; odds ratio 4.111; 95% confidence interval 1.504-11.235). In an in vitro functional assay, the -1082G reporter plasmid exhibited significantly greater promoter activity when compared with the -1082A construct in Jurkat T cells (P = 0.011). Moreover, we found that the transcription factor Myc-associated zinc-finger protein preferentially bound the -1082G allele.Our results suggest that IL-10 promoter polymorphisms contribute to the development of AIA and that rhinosinusitis may interact genetically with TGF-beta1.
Long-term Exposure to PM <sub>2.5</sub> and Incidence of Acute Myocardial Infarction
Authors: Jaime Madrigano, Itai Kloog, Robert Goldberg, Brent A. Coull, Murray A. Mittleman, Joel Schwartz
Journal: Environmental Health Perspectives (2012)

Background: A number of studies have shown associations between chronic exposure to particulate air pollution and increased mortality, particularly from cardiovascular disease, but fewer studies have examined the association between long-term exposure to fine particulate air pollution and specific cardiovascular events, such as acute myocardial infarction (AMI).Objective: We examined how long-term exposure to area particulate matter affects the onset of AMI, and we distinguished between area and local pollutants.Methods: Building on the Worcester Heart Attack Study, an ongoing community-wide investigation examining changes over time in myocardial infarction incidence in greater Worcester, Massachusetts, we conducted a case–control study of 4,467 confirmed cases of AMI diagnosed between 1995 and 2003 and 9,072 matched controls selected from Massachusetts resident lists. We used a prediction model based on satellite aerosol optical depth (AOD) measurements to generate both exposure to particulate matter ≤ 2.5 μm in diameter (PM2.5) at the area level (10 × 10 km) and the local level (100 m) based on local land use variables. We then examined the association between area and local particulate pollution and occurrence of AMI.Results: An interquartile range (IQR) increase in area PM2.5 (0.59 μg/m3) was associated with a 16% increase in the odds of AMI (95% CI: 1.04, 1.29). An IQR increase in total PM2.5 (area + local, 1.05 μg/m3) was weakly associated with a 4% increase in the odds of AMI (95% CI: 0.96, 1.11).Conclusions: Residential exposure to PM2.5 may best be represented by a combination of area and local PM2.5, and it is important to consider spatial gradients within a single metropolitan area when examining the relationship between particulate matter exposure and cardiovascular events.
Rebuilding a diseased lung: repair and regeneration
Authors: Melanie Königshoff, Sejal Saglani, Benjamin J. Marsland, Oliver Eickelberg
Journal: European Respiratory Journal (2013)

Chronic lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer and pulmonary fibrosis, are the second leading cause of death in the world. Currently, only limited therapeutic options exist for chronic lung diseases; in particular, causative therapeutic approaches are missing. Lung transplantation remains the only available therapy for many patients with end-stage lung disease; however, the number of patients listed for lung transplantation by far surpasses the number of suitable donor organs.

Beyond lung transplantation, several approaches to repair and regenerate lung tissue, with the aim of restoring lung function, have made substantial progress in recent years and hold great promise for future therapies. Importantly, advancement in our understanding of the underlying pathogenesis of distinct chronic lung diseases will be crucial for the development of novel, targeted therapeutic approaches.

The mission of the European Respiratory Society (ERS) is to alleviate suffering from respiratory disease and promote lung health through research, knowledge sharing, and medical and public education. In support of this mission, the ERS hosts the annual Lung Science Conference (LSC) in Estoril, Portugal, which brings together leading experts (basic scientists, physician scientists and clinicians alike) on distinct topics of relevance to respiratory medicine. In addition, the ERS is strongly committed to encourage, nurture and mentor future generations of world class respiratory scientists and clinicians. The LSC represents one of the main platforms to encourage debate and interaction between young doctoral and postdoctoral scientists with established investigators. In particular, this is facilitated by special mentoring sessions and the Young Investigator Competition, which enables younger delegates to present themselves and their work to established investigators.

In April 2012, an outstanding line-up of international experts met on the occasion of the 10th LSC in Estoril, Portugal, to present and discuss novel findings and exchange novel ideas and opportunities that promote our …
Use of health services by children and young people according to ethnicity and social class: secondary analysis of a national survey
Authors: H. Cooper, C. Smaje, S. Arber
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b> To assess whether equity is achieved in use of general practitioner, outpatient, and inpatient services by children and young people according to their ethnic group and socioeconomic background. <b>Design</b> Secondary analysis of the British general household survey, 1991-94. <b>Subjects</b> 20 473 children and young people aged between 0 and 19 years. <b>Main outcome measures</b> Consultations with a general practitioner within a two week period, outpatient attendances within a three month period, and inpatient stays during the past year. <b>Results</b> There were no significant class differences in the use of health services by children and young people, and there was little evidence of variation in use of health services according to housing tenure and parental work status. South Asian children and young people used general practitioner services more than any other ethnic group after controlling for socioeconomic background and perceived health status, but the use of hospital outpatient and inpatient services was significantly lower for children and young people from all minority ethnic groups compared with the white population. <b>Conclusions</b> Our results differ from previous studies, which have reported significant class differences in use of health services for other age groups. We found no evidence that children and young people9s use of health services varied according to their socioeconomic status, suggesting that equity has been achieved. A child or young person9s ethnic origin, however, was clearly associated with use of general practitioner and hospital services, which could imply that children and young people from minority ethnic groups receive a poorer quality of health care than other children and young people.
Psychological and neural responses to art embody viewer and artwork histories
Authors: Oshin Vartanian, James C. Kaufman
Journal: Behavioral and Brain Sciences (2013)

Abstract The research programs of empirical aesthetics and neuroaesthetics have reflected deep concerns about viewers' sensitivities to artworks' historical contexts by investigating the impact of two factors on art perception: viewers' developmental (and educational) histories and the contextual histories of artworks. These considerations are consistent with data demonstrating that art perception is underwritten by dynamically reconfigured and evolutionarily adapted neural and psychological mechanisms.
New insights into the role of endogenous opioids in the pathogenesis of gastrointestinal and liver disease
Authors: A. R Mani, K. P Moore
Journal: Gut (2009)

Opiates have been known for centuries for their role in the management of pain. In 1975, Hughes and Kosterlitz isolated two endogenous peptides (enkephalins) from pig brain with high affinity for opioid receptors.1 Later, other groups of endogenous opioids, the endorphins, dynorphins and endomorphins were discovered. These endogenous opioid peptides bind to multiple opioid receptors (mu, delta and kappa) which belong to the G protein-coupled super-family of receptors. Initially the function of these peptides was thought to be limited to analgesia and the modulation of gastrointestinal motility; however, recent data have elucidated that endogenous opioids can regulate cell growth, differentiation and survival in non-neuronal systems such as inflammatory cells and biliary epithelia, as well as hepatic stellate cells.2–5

The involvement of endogenous opioids in the pathophysiology of gastrointestinal and hepatobiliary disease has been widely studied in recent years. The most significant observations directing the interest toward this field have been: (1) endogenous opioids exhibit anti-inflammatory properties in the gut and this effect may have implication in the management of inflammatory bowel disease;6 (2) biliary injury is associated with increased production of endogenous opioids7 and opioid receptor antagonists have a beneficial effect on pruritus of cholestasis;8 (3) endogenous opioids modulate hepatic stellate cell activation and opioid receptor antagonists show an anti-fibrotic effect in experimental models of hepatic fibrosis;4 5 (4) a novel opioid receptor (opioid growth factor receptor) has recently been identified which plays an important role in the negative regulation of cell proliferation in pancreatic cancer.9

The purpose of this brief review is to examine the available data concerning the role of endogenous opioids in the pathophysiology of gastrointestinal and liver disease and to discuss new therapeutic possibilities of opioid manipulation in gastrointestinal diseases.

### Endogenous opioids and inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic, …
Essential Role(s) of the Intrarenal Renin-Angiotensin System in Transforming Growth Factor–β1 Gene Expression and Induction of Hypertrophy of Rat Kidney Proximal Tubular Cells in High Glucose
Authors: Shao-Ling Zhang, Catherine To, Xing Chen, Janos G. Filep, Shiow-Shih Tang, Julie R. Ingelfinger, John S. D. Chan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. These studies investigated the question of whether the intrarenal renin-angiotensin system (RAS) is essential for transforming growth factor–β1 (TGF-β1) gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose in vitro. Antisense and sense angiotensinogen (ANG) cDNAs were stably transfected into rat immortalized renal proximal tubular cells (IRPTC). ANG secretion from rat IRPTC was quantified by a specific RIA for rat ANG. Cellular ANG, TGF-β1, and collagen α1 (type IV) mRNA levels were determined by Northern blot analysis or by reverse transcriptase–PCR assay. Hypertrophy of IRPTC was analyzed by Western blotting of cellular p27Kip1 protein, flow cytometry, and cellular protein assay. The results showed that stable transfer of antisense ANG cDNA into IRPTC suppressed the basal TGF-β1 and collagen α1 (type IV) mRNA expression and blocked the stimulatory effect of high glucose (i.e., 25 mM) on TGF-β1 and collagen α1 (type IV) mRNA expression and induction of IRPTC hypertrophy. In contrast, stable transfer of sense ANG cDNA into IRPTC had no significant effect on these parameters. These data demonstrate that local intrarenal RAS activation is essential for TGF-β1 gene expression and induction of hypertrophy of renal proximal tubular cells in high glucose.
Function of Bone Marrow in Suppressing Thymic Lymphomas Induced by 7,12-Dimethylbenz[α]anthracene 2
Authors: P. O. Ottonen, J. K. Ball
Journal: JNCI Journal of the National Cancer Institute (1973)

The neonatal injection of 7,12-dimethylbenz[α]anthracene (DMBA) into the low leukemic strain of CFW mice resulted in a 100% incidence of thymic lymphomas. Injection of normal, syngeneic bone marrow cells 1–21 days post DMBA treatment markedly reduced the tumor incidence but did not affect the mean latent period. At 30 days post bone marrow injection there was evidence of extensive re-population (approximately 80%) of both thymus and bone marrow in DMBA-treated animals given normal bone marrow 5–21 days after DMBA. When normal bone marrow was given 1 or 35 days after DMBA treatment, the number of donor-derived cells at 30 days post bone marrow injection was less extensive (approximately 50%) in both bone marrow and thymus. Therefore, the establishment of a successful chimera depended on the interval between DMBA treatment and bone marrow injection. At tumor development (90 or more days post DMBA treatment) the cells of both thymus and bone marrow of mice given bone marrow 5–35 days post DMBA treatment (87–176 days post bone marrow injection) but showing no visible signs of thymic lymphoma were still predominantly of donor origin (approximately 90%). However, at 100–150 days post bone marrow injection, no donor cells were found in the thymus and bone marrow of mice given normal bone marrow 1 day post DMBA injection. Direct cytologic examination of the induced thymic lymphomas showed that all were derived from host cells, even though in the same mice (provided the tumor had not disseminated) the bone marrow was still donor in origin. The exception to this occurred in mice given normal bone marrow 1 day post DMBA treatment. In these mice the dividing cells in the bone marrow of tumor-bearing mice were all host in origin, even though the tumors were confined to the thymus. Since the injected bone marrow resulted in a 50% reduction in the tumor incidence, it would appear that the ability of normal bone marrow to reduce the incidence of thymic lymphomas is not related to its ability to establish a permanent chimera.
Prothrombotic State, Cardiovascular, and Metabolic Syndrome Risk Factors in Prepubertal Children Born Large for Gestational Age
Authors: Eleni N. Evagelidou, Vasileios I. Giapros, Anna S. Challa, Vasileios K. Cholevas, Georgios A. Vartholomatos, Ekaterini C. Siomou, Nikolaos I. Kolaitis, Eleni T. Bairaktari, Styliani K. Andronikou
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate metabolic syndrome and cardiovascular disease risk factors in prepubertal children born large for gestational age (LGA) to nondiabetic, nonobese mothers. RESEARCH DESIGN AND METHODS At 6–7 years of age, the comparison of various factors was made between 31 LGA and 34 appropriate-for-gestational-age (AGA) children: fibrinogen, antithrombin III, protein C and S, fasting insulin, glucose, homeostasis assessment model of insulin resistance (HOMA-IR) index, adiponectin, leptin, visfatin, IGF-1, IGF-binding protein (IGFBP)-1, IGFBP-3, lipids, and the genetic factors V Leiden G1691A mutation, prothrombin 20210A/G polymorphism, and mutation in the enzyme 5,10-methylenetetrahydrofolate-reductase gene (MTHFR-C677T). RESULTS LGA children had higher levels of leptin (P &amp;lt; 0.01), fasting insulin (P &amp;lt; 0.01), and HOMA-IR (P &amp;lt; 0.01), but lower IGFBP-3 (P = 0.0001), fibrinogen (P = 0.0001), and lipoprotein(a) (P &amp;lt; 0.001) than AGA children. Significantly more LGA children were homozygous for the MTHFR-C677T mutation (P = 0.0016). CONCLUSIONS Being born LGA to nondiabetic, nonobese mothers is associated with diverse effects on cardiometabolic risk factors at prepuberty.