tbuckley/cabot-search huggingface dataset:
DNA Adducts and Lung Cancer Risk: A Prospective Study
Authors: Marco Peluso, Armelle Munnia, Gerard Hoek, Michal Krzyzanowski, Fabrizio Veglia, Luisa Airoldi, Herman Autrup, Alison Dunning, Seymour Garte, Pierre Hainaut, Christian Malaveille, Emmanuelle Gormally, Giuseppe Matullo, Kim Overvad, Ole Raaschou-Nielsen, Francoise Clavel-Chapelon, Jacob Linseisen, Heiner Boeing, Antonia Trichopoulou, Dimitrios Trichopoulos, Anna Kaladidi, Domenico Palli, Vittorio Krogh, Rosario Tumino, Salvatore Panico, H. Bas Bueno-De-Mesquita, Petra H. Peeters, Merethe Kumle, Carlos A. Gonzalez, Carmen Martinez, Miren Dorronsoro, Aurelio Barricarte, Carmen Navarro, J. Ramón Quiros, Goran Berglund, Lars Janzon, Bengt Jarvholm, Nicholas E. Day, Tim J. Key, Rodolfo Saracci, Rudolf Kaaks, Elio Riboli, Paolo Vineis
Journal: Cancer Research (2005)

Abstract Objectives were to investigate prospectively the ability of DNA adducts to predict cancer and to study the determinants of adducts, especially air pollutants. DNA adducts were measured in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) investigation. Cases included newly diagnosed lung cancer (n = 115), upper respiratory cancers (pharynx and larynx; n = 82), bladder cancer (n = 124), leukemia (n = 166), and chronic obstructive pulmonary disease or emphysema deaths (n = 77) accrued after a median follow-up of 7 years among the EPIC former smokers and never-smokers. Three controls per case were matched for questionnaire analyses and two controls per case for laboratory analyses. Matching criteria were gender, age, smoking status, country of recruitment, and follow-up time. Individual exposure to air pollution was assessed using concentration data from monitoring stations in routine air quality monitoring networks. Leukocyte DNA adducts were analyzed blindly using 32P postlabeling technique. Adducts were associated with the subsequent risk of lung cancer, with an odds ratio (OR) of 1.86 [95% confidence interval (95% CI), 0.88-3.93] when comparing detectable versus nondetectable adducts. The association with lung cancer was stronger in never-smokers (OR, 4.04; 95% CI, 1.06-15.42) and among the younger age groups. After exclusion of the cancers occurring in the first 36 months of follow-up, the OR was 4.16 (95% CI, 1.24-13.88). A positive association was found between DNA adducts and ozone (O3) concentration. Our prospective study suggests that leukocyte DNA adducts may predict lung cancer risk of never-smokers. Besides, the association of DNA adduct levels with O3 indicates a possible role for photochemical smog in determining DNA damage.
Risk factors for sleep-disordered breathing in pregnancy
Authors: Grace W Pien, Allan I Pack, Nicholas Jackson, Greg Maislin, George A Macones, Richard J Schwab
Journal: Thorax (2013)

Symptoms of sleep-disordered breathing (SDB) are common among pregnant women, and several studies link SDB symptoms with gestational hypertension and preeclampsia. However, few prospective studies objectively measuring SDB during pregnancy have been performed.We performed a prospective cohort study examining risk factors for third trimester SDB in pregnant women.105 pregnant women from the Hospital of the University of Pennsylvania obstetrics practices completed first and third trimester overnight polysomnography studies. We examined whether the number of SDB events per hour of sleep increased during pregnancy. We performed unadjusted and multivariable logistic regression analyses to estimate the effects of usual and pregnancy-specific characteristics on development of third trimester obstructive sleep apnoea (OSA). In secondary analyses, we examined the relationship between objectively measured SDB, hypertensive disorders of pregnancy, and other adverse maternal-fetal outcomes.Mean Apnoea-Hypopnoea Index increased from 2.07 (SD 3.01) events/h at baseline (first trimester) to 3.74 (SD 5.97) in the third trimester (p=0.009). 10.5% of women had OSA in the first trimester. By the third trimester, 26.7% of women had OSA. In multivariable analyses, first trimester body mass index (BMI) and maternal age were significantly associated with third trimester OSA.Third trimester OSA is common. Risk factors for third trimester OSA among women without baseline SDB include higher baseline BMI and maternal age.
Habitual snoring as a risk factor for acute vascular disease
Authors: S Smirne, S Palazzi, M Zucconi, S Chierchia, L Ferini-Strambi
Journal: European Respiratory Journal (1993)

We wanted to assess habitual snoring as a credible risk factor for acute vascular disease, mainly stroke and myocardial infarction. The patients selected for the study had been admitted to the hospital through the emergency department, and were evaluated by means of multidimensional interviews and clinical records: 164 had acute cerebrovascular disease, and 136 cardiovascular disease; 330 patients with nonvascular disease were the controls. The evaluation showed 48% of vascular disease patients to be habitual snorers, but only 30% of the controls; the difference was statistically significant. Compared with the controls, in the cerebrovascular patients the risk (odds ratio) associated with habitual snoring was significantly increased, and of the same order as the risk associated with age over 65 yrs, male gender, diabetes mellitus, and dyslipidaemia; whilst the risk associated with hypertension was higher. In the cardiovascular patients, the risk associated with habitual snoring was again significantly increased and of the same order as the risk associated with male gender, body mass index > 29 (kg.m-2), dyslipidaemia, heavy smoking, excessive alcohol intake and hypertension. A logistic regression analysis, entering the variables in the following order: age, gender, body mass index, diabetes, dyslipidaemia, smoking, alcohol, hypertension, and habitual snoring, showed that habitual snoring carries a significant risk factor for stroke and myocardial infarction, even after adjusting for other factors. Since habitual snoring carries a definite risk for acute vascular disease, we conclude that inquiring about it should become routine practice.
Incidence of Coronary Heart Disease in Type 2 Diabetic Men and Women
Authors: Angelo Avogaro, Carlo Giorda, Marina Maggini, Edoardo Mannucci, Roberto Raschetti, Flavia Lombardo, Stefania Spila-Alegiani, Salvatore Turco, Mario Velussi, Ele Ferrannini
Journal: Diabetes Care (2007)

Cardiovascular disease (CVD) is the main cause of morbidity/mortality in diabetes. We set forth to determine incidence and identify predictors (including microvascular complications and treatment) of first coronary heart disease (CHD) event in CVD-free type 2 diabetic patients.A cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics, was followed up for 4 years. Baseline assessment included retinopathy, nephropathy, and foot ulcers. First CHD events (myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, and electrocardiogram-proven angina) were analyzed for 29,069 person-years.The age-standardized incidence rate (per 1,000 person-years) of first CHD event (n = 881) was 28.8 (95% CI 5.4-32.2) in men and 23.3 (20.2-26.4) in women. Major CHD (myocardial infarction, coronary artery bypass grafting, and percutaneous transluminal coronary angioplasty) was less frequent in women (5.8 [4.3-7.2]) than in men (13.1 [10.9-15.4]; a sex ratio of 0.5 [0.4-0.6]). Incidence rates of all outcomes were higher in patients with microvascular complications (for major CHD, age-adjusted rate ratios were 1.6 [1.2-2.21] in men and 1.5 [1.0-2.2] in women). By multivariate Cox analysis, age and diabetes duration were risk predictors common in both sexes. In men, glycemic control and treated hypertension were additional independent risk factors, but residing in the south was associated with a significant 29% risk reduction. In women, higher triglycerides/lower HDL cholesterol and microvascular complications were independent risk factors.In CVD-free patients with type 2 diabetes, risk of first CHD event depends on sex, geographic location, and presence of microvascular disease. Hyperglycemia and hypertension, particularly in men, and diabetic dyslipidemia, especially in women, are risk factors amenable to more aggressive treatment.
Peroxisome Proliferator-Activated Receptors and Atherogenesis
Authors: Nikolaus Marx, Hélène Duez, Jean-Charles Fruchart, Bart Staels
Journal: Circulation Research (2004)

A large body of data gathered over the past couple of years has identified the peroxisome proliferator-activated receptors (PPAR) α, γ, and β/δ as transcription factors exerting modulatory actions in vascular cells. PPARs, which belong to the nuclear receptor family of ligand-activated transcription factors, were originally described as gene regulators of various metabolic pathways. Although the PPARα, γ, and β/δ subtypes are ≈60% to 80% homologous in their ligand- and DNA-binding domains, significant differences in ligand and target gene specificities are observed. PPARα is activated by polyunsaturated fatty acids and oxidized derivatives and by lipid-modifying drugs of the fibrate family, including fenofibrate or gemfibrozil. PPARα controls expression of genes implicated in lipid metabolism. PPARγ, in contrast, is a key regulator of glucose homeostasis and adipogenesis. Ligands of PPARγ include naturally occurring FA derivatives, such as hydroxyoctadecadienoic acids (HODEs), prostaglandin derivatives such as 15-deoxyΔ 12,14 -prostaglandin J 2 , and glitazones, insulin-sensitizing drugs presently used to treat patients with type 2 diabetes. Ligands for PPARβ/δ are polyunsaturated fatty acids, prostaglandins, and synthetic compounds, some of which are presently in clinical development. PPARβ/δ stimulates fatty acid oxidation predominantly acting in muscle. All PPARs are expressed in vascular cells, where they exhibit antiinflammatory and antiatherogenic properties. In addition, studies in various animal models as well as clinical data suggest that PPARα and PPARγ activators can modulate atherogenesis in vivo. At present, no data are available relating to possible effects of PPARβ/δ agonists on atherogenesis. Given the widespread use of PPARα and PPARγ agonists in patients at high risk for cardiovascular disease, the understanding of their function in the vasculature is not only of basic interest but also has important clinical implications. This review will focus on the role of PPARs in the vasculature and summarize the present understanding of their effects on atherogenesis and its cardiovascular complications.
Interstitial cells of Cajal in the human fetal small bowel as shown by c-kit immunohistochemistry
Authors: T Wester, L Eriksson, Y Olsson, L Olsen
Journal: Gut (1999)

Background Interstitial cells of Cajal (ICCs) express the tyrosine kinase receptor c-kit, which is required for their development and spontaneous pacemaker activity in the bowel. From murine models it has been proposed that ICCs do not develop until after birth, but more recent findings indicate that c-kit is expressed early in the embryonic period. The temporal development of ICCs in the human gut remains unknown. Aim To investigate ICCs in the human fetal small bowel using c-kit immunohistochemistry. Subjects Small bowel specimens were obtained at post mortem examination of 16 fetuses and nine neonates, eight of whom were premature, born at gestational ages of 13 to 41 weeks, without gastrointestinal disorders. Methods Immunohistochemical analysis was performed on material fixed in formalin and embedded in paraffin. The specimens were exposed to antibodies raised against c-kit (an ICC marker) and neurone specific enolase (a general neuronal marker). The ABC complex method was used to visualise binding of antibodies to the corresponding antigens. Results c-kit immunoreactive cells were visualised from 13 weeks of gestation. The immunoreactivity was mainly localised in association with the myenteric plexus. From about 17–18 weeks of gestation, the ICCs formed a layer along the myenteric plexus, whereas this layer appeared to be disrupted at 13–16 weeks of gestation. Conclusions ICCs are c-kit immunoreactive at least from a gestational age of 13 weeks in the human fetal small intestine. From 17–18 weeks of gestation until birth, they form a continuous layer around the myenteric ganglia.
Topical Application of a Mucoadhesive Freeze-Dried Black Raspberry Gel Induces Clinical and Histologic Regression and Reduces Loss of Heterozygosity Events in Premalignant Oral Intraepithelial Lesions: Results from a Multicentered, Placebo-Controlled Clinical Trial
Authors: Susan R. Mallery, Meng Tong, Brian S. Shumway, Alice E. Curran, Peter E. Larsen, Gregory M. Ness, Kelly S. Kennedy, George H. Blakey, George M. Kushner, Aaron M. Vickers, Brian Han, Ping Pei, Gary D. Stoner
Journal: Clinical Cancer Research (2014)

Approximately 30% higher grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. Although surgery is the OIN treatment mainstay, many OIN lesions recur, which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural product-based bioadhesive gel on OIN lesions.This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze-dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 g × q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n = 22) and placebo (n = 18) gel cohorts. Evaluative parameters were: histologic grade, clinical size, and LOH.Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades, and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients, as demonstrated by high therapeutic efficacy, was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency.Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.
2009 World Congress on the Insulin Resistance Syndrome: Cardiovascular Disease Concepts
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2010)

This is the first of four articles summarizing presentations at the seventh World Congress on the Insulin Resistance Syndrome, held in San Francisco, California, on 5–7 November 2009. This article pertains to cardiovascular disease (CVD) concepts.

Yehuda Handelsman (Tarzania, CA), chair of the International Committee for Insulin Resistance, “revisited” the treatment of insulin resistance, discussing aspects of the metabolic findings of BARI-2D's insulin-sensitizing versus insulin-providing strategy comparison (1). “When it came to the control of glucose,” he said, “the group that was on sensitizers had a 0.5% improvement in A1C,” similar to that seen in PROactive (2). “We've seen [in RECORD (3) and ADOPT (4)],” he continued, “that if you are on sulfonylurea or metformin you lose control” whether on combination or single-agent treatment in comparison to the stability of glycemia with rosiglitazone. Furthermore, Handelsman pointed out that in BARI-2D, those undergoing CABG had better outcome with the insulin-sensitizing strategy.

Reviewing the concept of metabolic syndrome, which has been defined and redefined many times since first proposed as Syndrome X by Reaven (5), Handelsman emphasized the potential benefit of thiazolidinediones, but suggested that the flawed Nissen metaanalysis of rosiglitazone (6) has led to the misperception that insulin resistance treatment is not of benefit. He asked, “Should we treat insulin resistance pharmacologically?” If there is little evidence that treatment of the syndrome is effective beyond the benefit of treatment of the components, then we may need more data to justify insulin sensitizer administration outside of diabetes treatment. It may, however, be the case that insulin levels per se can be used in guiding pharmacologic treatment, and Handelsman reviewed the evidence that pioglitazone did reduce CV event rates in subset analyses of PROactive. Insulin resistance treatment appears of benefit in the polycystic ovary syndrome (PCOS), and in nonalcoholic fatty liver disease (NAFLD), …
Reliability and validity of a brief physical activity assessment for use by family doctors
Authors: A L Marshall, B J Smith, A E Bauman, S Kaur
Journal: British Journal of Sports Medicine (2005)

Objective: To evaluate the reliability and validity of a brief physical activity assessment tool suitable for doctors to use to identify inactive patients in the primary care setting. Methods: Volunteer family doctors (n = 8) screened consenting patients (n = 75) for physical activity participation using a brief physical activity assessment tool. Inter-rater reliability was assessed within one week (n = 71). Validity was assessed against an objective physical activity monitor (computer science and applications accelerometer; n = 42). Results: The brief physical activity assessment tool produced repeatable estimates of “sufficient total physical activity”, correctly classifying over 76% of cases (κ 0.53, 95% confidence interval (CI) 0.33 to 0.72). The validity coefficient was reasonable (κ 0.40, 95% CI 0.12 to 0.69), with good percentage agreement (71%). Conclusions: The brief physical activity assessment tool is a reliable instrument, with validity similar to that of more detailed self report measures of physical activity. It is a tool that can be used efficiently in routine primary healthcare services to identify insufficiently active patients who may need physical activity advice.
Cancers of the Kidney and Urinary Tract in Patients on Dialysis for End-Stage Renal Disease
Authors: John H. Stewart, Gherardo Buccianti, Lawrence Agodoa, Ryszard Gellert, Margaret R.E. McCredie, Albert B. Lowenfels, Alex P.S. Disney, Robert A. Wolfe, Peter Boyle, Patrick Maisonneuve
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Patients on maintenance dialysis have increased risk for cancer, especially in the kidney and urinary tract. In a retrospective cohort of 831,804 patients starting dialysis during 1980 to 1994 in the United States, Europe, or Australia and New Zealand, standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated for kidney and bladder cancers. Risks for cancers of the kidney (SIR 3.6; CI 3.5 to 3.8) and bladder (SIR 1.5; CI 1.4 to 1.6) were increased, relatively more in younger than older patients and more in female patients (kidney: SIR 4.6, CI 4.3 to 4.9; bladder: SIR 2.7, CI 2.4 to 2.9) than male patients (kidney: SIR 3.2, CI 3.0 to 3.4; bladder: SIR 1.3, CI 1.2 to 1.3). SIR for kidney cancer were raised in all categories of primary renal disease, and for bladder cancer in all but diabetes and familial, hereditary diseases. Notably high SIR occurred in toxic nephropathies (chiefly analgesic nephropathy) and miscellaneous conditions (a category that includes Balkan nephropathy), the excess of kidney cancer in these conditions being urothelial in origin. SIR for kidney cancer rose significantly, and those for bladder cancer fell (not reaching significance) with time on dialysis. There was no association with type of dialysis. The pattern of increased risk for renal parenchymal cancer in dialysis patients is consistent with causation through acquired renal cystic disease and of urothelial cancers of the kidney and bladder with the carcinogenic effects of certain primary renal diseases. E-mail: patrick.maisonneuve@ieo.it
Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA–N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy
Authors: N. Li, Z.-F. Zeng, S.-Y. Wang, W. Ou, X. Ye, J. Li, X.-H. He, B.-B. Zhang, H. Yang, H.-B. Sun, Q. Fang, B.-X. Wang
Journal: Annals of Oncology (2014)
Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome
Authors: Zhao-Hui Xu, Qi Yang, Bin Feng, Shui-bing Liu, Nan Zhang, Jiang-hao Xing, Xiao-Qiang Li, Yu-mei Wu, Guo-Dong Gao, Ming-Gao Zhao
Journal: Molecular Neurodegeneration (2012)

Abstract Background Fragile X syndrome (FXS) is caused by the absence of the mRNA-binding protein Fragile X mental retardation protein (FMRP), encoded by the Fmr1 gene. Overactive signaling by group 1 metabotropic glutamate receptor (Grp1 mGluR) could contribute to slowed synaptic development and other symptoms of FXS. Our previous study has identified that facilitation of synaptic long-term potentiation (LTP) by D1 receptor is impaired in Fmr1 knockout (KO) mice. However, the contribution of Grp1 mGluR to the facilitation of synaptic plasticity by D1 receptor stimulation in the prefrontal cortex has been less extensively studied. Results Here we demonstrated that DL-AP3, a Grp1 mGluR antagonist, rescued LTP facilitation by D1 receptor agonist SKF81297 in Fmr1 KO mice. Grp1 mGluR inhibition restored the GluR1-subtype AMPA receptors surface insertion by D1 activation in the cultured Fmr1 KO neurons. Simultaneous treatment of Grp1 mGluR antagonist with D1 agonist recovered the D1 receptor signaling by reversing the subcellular redistribution of G protein-coupled receptor kinase 2 (GRK2) in the Fmr1 KO neurons. Treatment of SKF81297 alone failed to increase the phosphorylation of NR2B-containing N-methyl D-aspartate receptors (NMDARs) at Tyr-1472 (p-NR2B-Tyr1472) in the cultures from KO mice. However, simultaneous treatment of DL-AP3 could rescue the level of p-NR2B-Tyr1472 by SKF81297 in the cultures from KO mice. Furthermore, behavioral tests indicated that simultaneous treatment of Grp1 mGluR antagonist with D1 agonist inhibited hyperactivity and improved the learning ability in the Fmr1 KO mice. Conclusion The findings demonstrate that mGluR1 inhibition is a useful strategy to recover D1 receptor signaling in the Fmr1 KO mice, and combination of Grp1 mGluR antagonist and D1 agonist is a potential drug therapy for the FXS.