tbuckley/cabot-search huggingface dataset:
1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and Polychlorinated Biphenyls and Breast Cancer: Combined Analysis of Five U.S. Studies
Authors: F. Laden, G. Collman, K. Iwamoto, A. J. Alberg, G. S. Berkowitz, J. L. Freudenheim, S. E. Hankinson, K. J. Helzlsouer, T. R. Holford, H.-Y. Huang, K. B. Moysich, J. D. Tessari, M. S. Wolff, T. Zheng, D. J. Hunter
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Environmental exposure to organochlorines has been examined as a potential risk factor for breast cancer. In 1993, five large U.S. studies of women located mainly in the northeastern United States were funded to evaluate the association of levels of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) and polychlorinated biphenyls (PCBs) in blood plasma or serum with breast cancer risk. We present a combined analysis of these results to increase precision and to maximize statistical power to detect effect modification by other breast cancer risk factors. Methods: We reanalyzed the data from these five studies, consisting of 1400 case patients with breast cancer and 1642 control subjects, by use of a standardized approach to control for confounding and assess effect modification. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) by use of the random-effects model. All statistical tests were two-sided. Results: When we compared women in the fifth quintile of lipid-adjusted values with those in the first quintile, the multivariate pooled OR for breast cancer associated with PCBs was 0.94 (95% CI = 0.73 to 1.21), and that associated with DDE was 0.99 (95% CI = 0.77 to 1.27). Although in the original studies there were suggestions of elevated breast cancer risk associated with PCBs in certain groups of women stratified by parity and lactation, these observations were not evident in the pooled analysis. No statistically significant associations were observed in any other stratified analyses, except for an increased risk with higher levels of PCBs among women in the middle tertile of body mass index (25–29.9 kg/m2); however, the risk was statistically nonsignificantly decreased among heavier women. Conclusions: Combined evidence does not support an association of breast cancer risk with plasma/serum concentrations of PCBs or DDE. Exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer experienced in the northeastern United States.
Verticillin A Overcomes Apoptosis Resistance in Human Colon Carcinoma through DNA Methylation-Dependent Upregulation of BNIP3
Authors: Feiyan Liu, Qianqian Liu, Dafeng Yang, Wendy B. Bollag, Keith Robertson, Ping Wu, Kebin Liu
Journal: Cancer Research (2011)

Drug resistance is a major cause of failure in cancer chemotherapy. Therefore, identification and combined use of adjuvant compounds that can overcome drug resistance may improve the efficacy of cancer therapy. We screened extracts of Verticillium species-infected mushrooms for antitumor compounds and identified the compound Verticillin A as an inducer of hepatoma cell apoptosis in vitro and an inhibitor of tumor xenograft growth in vivo. Verticillin A exhibited a potent apoptosis-sensitizing activity in human colon carcinoma cells exposed to TRAIL or Fas in vitro. Furthermore, Verticillin A effectively sensitized metastatic human colon carcinoma xenograft to TRAIL-mediated growth inhibition in vivo. At the molecular level, we observed that Verticillin A induces cell-cycle arrest in the G₂ phase of the cell cycle in human colon carcinoma cells, markedly upregulating BNIP3 in both hepatoma and colon carcinoma cells. Notably, silencing BNIP3 decreased the sensitivity of tumor cells to Verticillin A-induced apoptosis in the absence or presence of TRAIL. We found that the BNIP3 promoter is methylated in both human hepatoma and colon carcinoma cells and tumor specimens. Verticillin A upregulated the expression of a panel of genes known to be regulated at the level of DNA methylation, in support of the concept that Verticillin A may act by demethylating the BNIP3 promoter to upregulate BNIP3 expression. Taken together, our findings identify Verticillin A as a potent apoptosis sensitizer with great promise for further development as an adjuvant agent to overcome drug resistance in human cancer therapy.
Newly Diagnosed and Previously Known Diabetes Mellitus and 1-Year Outcomes of Acute Myocardial Infarction
Authors: David Aguilar, Scott D. Solomon, Lars Køber, Jean-Lucien Rouleau, Hicham Skali, John J.V. McMurray, Gary S. Francis, Marc Henis, Christopher M. O’Connor, Rafael Diaz, Yuri N. Belenkov, Sergei Varshavsky, Jeffrey D. Leimberger, Eric J. Velazquez, Robert M. Califf, Marc A. Pfeffer
Journal: Circulation (2004)

Background— A prior diagnosis of diabetes mellitus is associated with adverse outcomes after acute myocardial infarction (MI), but the risk associated with a new diagnosis of diabetes in this setting has not been well defined. Methods and Results— We assessed the risk of death and major cardiovascular events associated with previously known and newly diagnosed diabetes by studying 14 703 patients with acute MI enrolled in the VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Patients were grouped by diabetic status: previously known diabetes (insulin use or diagnosis of diabetes before MI, n=3400, 23%); newly diagnosed diabetes (use of diabetic therapy or diabetes diagnosed at randomization [median 4.9 d after infarction], but no known diabetes at presentation, n=580, 4%); or no diabetes (n=10 719). Patients with newly diagnosed diabetes were younger and had fewer comorbid conditions than did patients with previously known diabetes. At 1 year after enrollment, patients with previously known and newly diagnosed diabetes had similarly increased adjusted risks of mortality (hazard ratio [HR] 1.43; 95% confidence interval [CI], 1.29 to 1.59 and HR, 1.50; 95% CI, 1.21 to 1.85, respectively) and cardiovascular events (HR, 1.37; 95% CI, 1.27 to 1.48 and HR, 1.34; 95% CI, 1.14 to 1.56). Conclusions— Diabetes mellitus, whether newly diagnosed or previously known, is associated with poorer long-term outcomes after MI in high-risk patients. The poor prognosis of patients with newly diagnosed diabetes, despite having baseline characteristics similar to those of patients without diabetes, supports the idea that metabolic abnormalities contribute to their adverse outcomes.
Researches on the Mechanical Dilatation of the Cervix Uteri, and the Appliances Used for the Purpose
Authors: J. M. Duncan
Journal: BMJ (1872)

THE investigations, the results of which are given in the following paper, were begun simply with a view to greater exactness of knowledge of the powers and uses of the various means employed to dilate the cervix uteri in obstetrics and gynaecology.As the inquiry advanced, numerous physiological and therapeutical points arose in my nmind, which ap- peared to throw light on it, or to be themselves illustrated; and to some of them reference will be made.For the dilatation of the cervix uteri, cutting instruments are occa- sionally used, but no account of their action is here attempted, as it is of the simplest kind, and its power is practically unlimited.The means to which attention will be directed are:I. The bougie.2. The tangle-tent.3. The sponge-tent.4. The India-rubber bag, commonly made fiddle-shaped, and named after Barnes.
Adenosine mediates IL-13–induced inflammation and remodeling in the lung and interacts in an IL-13–adenosine amplification pathway
Authors: Michael R. Blackburn, Chun G. Lee, Hays W.J. Young, Zhou Zhu, Janci L. Chunn, Min Jong Kang, Suman K. Banerjee, Jack A. Elias
Journal: Journal of Clinical Investigation (2003)

IL-13 is an important mediator of inflammation and remodeling. We hypothesized that adenosine accumulation, alterations in adenosine receptors, and adenosine-IL-13 autoinduction are critical events in IL-13-induced pathologies. To test this, we characterized the effects of IL-13 overexpression on the levels of adenosine, adenosine deaminase (ADA) activity, and adenosine receptors in the murine lung. We also determined whether adenosine induced IL-13 in lungs from ADA-null mice. IL-13 induced an inflammatory and remodeling response that caused respiratory failure and death. During this response, IL-13 caused a progressive increase in adenosine accumulation, inhibited ADA activity and mRNA accumulation, and augmented the expression of the A1, A2B, and A3 but not the A2A adenosine receptors. ADA enzyme therapy diminished the IL-13-induced increase in adenosine, inhibited IL-13-induced inflammation, chemokine elaboration, fibrosis, and alveolar destruction, and prolonged the survival of IL-13-transgenic animals. In addition, IL-13 was strongly induced by adenosine in ADA-null mice. These findings demonstrate that adenosine and adenosine signaling contribute to and influence the severity of IL-13-induced tissue responses. They also demonstrate that IL-13 and adenosine stimulate one another in an amplification pathway that may contribute to the nature, severity, progression, and/or chronicity of IL-13 and/or Th2-mediated disorders.
Regulation of Gene Expression by Cyclic GMP
Authors: Renate B. Pilz, Darren E. Casteel
Journal: Circulation Research (2003)

Cyclic GMP, produced in response to nitric oxide and natriuretic peptides, is a key regulator of vascular smooth muscle cell contractility, growth, and differentiation, and is implicated in opposing the pathophysiology of hypertension, cardiac hypertrophy, atherosclerosis, and vascular injury/restenosis. cGMP regulates gene expression both positively and negatively at transcriptional as well as at posttranscriptional levels. cGMP-regulated transcription factors include the cAMP-response element binding protein CREB, the serum response factor SRF, and the nuclear factor of activated T cells NF/AT. cGMP can regulate CREB directly, through phosphorylation by cGMP-dependent protein kinase, or indirectly, through activation of mitogen-activated protein kinase pathways; regulation of SRF and NF/AT by cGMP is indirect, through modulation of RhoA and calcineurin signaling, respectively. Downregulation of the RNA-binding protein HuR by cGMP leads to destabilization of guanylate cyclase mRNA, but this posttranscriptional mechanism may affect many more cGMP-regulated genes. In this review, we discuss the role of cGMP-regulated gene expression in (patho)physiological processes most relevant to the cardiovascular system, such as regulation of vascular tone, cardiac hypertrophy, phenotypic modulation of vascular smooth muscle cells, and regulation of cell proliferation and apoptosis.
Molecular Evolution of Bat Color Vision Genes
Authors: D. Wang
Journal: Molecular Biology and Evolution (2003)

The two suborders of bats, Megachiroptera (megabats) and Microchiroptera (microbats), use different sensory modalities for perceiving their environment. Megabats are crepuscular and rely on a well-developed eyes and visual pathway, whereas microbats occupy a nocturnal niche and use acoustic orientation or echolocation more than vision as the major means of perceiving their environment. In view of the differences associated with their sensory systems, we decided to investigate the function and evolution of color vision (opsin genes) in these two suborders of bats. The middle/long wavelength (M/L) and short wavelength (S) opsin genes were sequenced from two frugivorous species of megabats, Haplonycteris fischeri and Pteropus dasymallus formosus, and one insectivorous species of microbat, Myotis velifer. Contrary to the situation in primates, where many nocturnal species have lost the functional S opsin gene, both crepuscular and strictly nocturnal species of bats that we examined have functional M/L and S opsin genes. Surprisingly, the S opsin in these bats may be sensitive to UV light, which is relatively more abundant at dawn and at dusk. The M/L opsin in these bats appears to be the L type, which is sensitive to red and may be helpful for identifying fruits among leaves or for other purposes. Most interestingly, H. fischeri has a recent duplication of the M/L opsin gene, representing to date the only known case of opsin gene duplication in non-primate mammals. Some of these observations are unexpected and may provide insights into the effect of nocturnal life on the evolution of opsin genes in mammals and the evolution of the life history traits of bats in general.
Epithelial NAIPs protect against colonic tumorigenesis
Authors: Ramanjaneyulu Allam, Michel H. Maillard, Aubry Tardivel, Vijaykumar Chennupati, Hristina Bega, Chi Wang Yu, Dominique Velin, Pascal Schneider, Kendle M. Maslowski
Journal: The Journal of Experimental Medicine (2015)

NLR family apoptosis inhibitory proteins (NAIPs) belong to both the Nod-like receptor (NLR) and the inhibitor of apoptosis (IAP) families. NAIPs are known to form an inflammasome with NLRC4, but other in vivo functions remain unexplored. Using mice deficient for all NAIP paralogs (Naip1-6Δ/Δ), we show that NAIPs are key regulators of colorectal tumorigenesis. Naip1-6Δ/Δ mice developed increased colorectal tumors, in an epithelial-intrinsic manner, in a model of colitis-associated cancer. Increased tumorigenesis, however, was not driven by an exacerbated inflammatory response. Instead, Naip1-6Δ/Δ mice were protected from severe colitis and displayed increased antiapoptotic and proliferation-related gene expression. Naip1-6Δ/Δ mice also displayed increased tumorigenesis in an inflammation-independent model of colorectal cancer. Moreover, Naip1-6Δ/Δ mice, but not Nlrc4-null mice, displayed hyper-activation of STAT3 and failed to activate p53 18 h after carcinogen exposure. This suggests that NAIPs protect against tumor initiation in the colon by promoting the removal of carcinogen-elicited epithelium, likely in a NLRC4 inflammasome-independent manner. Collectively, we demonstrate a novel epithelial-intrinsic function of NAIPs in protecting the colonic epithelium against tumorigenesis.
The health benefits of vegetables and fruit rise with consumption, finds study
Authors: J. Wise
Journal: BMJ (2014)

People who eat seven or more portions of fruit and vegetables a day have the lowest risk of mortality from any cause, say researchers. And vegetables have significantly higher health benefits than fruit, says the study published in the Journal of Epidemiology and Community Health .1

Researchers from University College London used the 2001-08 Health Survey for England to look at the eating habits of a random sample of 65 226 participants aged 35 and older. This was linked to UK mortality data up to the first quarter of 2013.

After excluding deaths within a year …
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Authors: A. C. Howlett
Journal: Pharmacological Reviews (2002)

Two types of cannabinoid receptor have been discovered so far, CB<sub>1</sub> (2.1: CBD:1:CB1:), cloned in 1990, and CB<sub>2</sub>(2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB<sub>1</sub> and CB<sub>2</sub> exhibit 48% amino acid sequence identity. Both receptor types are coupled through G proteins to adenylyl cyclase and mitogen-activated protein kinase. CB<sub>1</sub> receptors are also coupled through G proteins to several types of calcium and potassium channels. These receptors exist primarily on central and peripheral neurons, one of their functions being to inhibit neurotransmitter release. Indeed, endogenous CB<sub>1</sub> agonists probably serve as retrograde synaptic messengers. CB<sub>2</sub> receptors are present mainly on immune cells. Such cells also express CB<sub>1</sub>receptors, albeit to a lesser extent, with both receptor types exerting a broad spectrum of immune effects that includes modulation of cytokine release. Of several endogenous agonists for cannabinoid receptors identified thus far, the most notable are arachidonoylethanolamide, 2-arachidonoylglycerol, and 2-arachidonylglyceryl ether. It is unclear whether these eicosanoid molecules are the only, or primary, endogenous agonists. Hence, we consider it premature to rename cannabinoid receptors after an endogenous agonist as is recommended by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. Although pharmacological evidence for the existence of additional types of cannabinoid receptor is emerging, other kinds of supporting evidence are still lacking.
Antibiotic prophylaxis of experimental endocarditis after dental extractions.
Authors: R Malinverni, C D Overholser, J Bille, M P Glauser
Journal: Circulation (1988)

In rats with catheter-induced sterile aortic valve vegetations we studied the efficacy of single-dose amoxicillin and single-dose erythromycin prophylaxis for the prevention of bacterial endocarditis after extractions of periodontally diseased teeth. Endocarditis after extractions occurred in 89% of control animals and was due to group G streptococci, to Staphylococcus aureus, or to both organisms. A single-dose of amoxicillin or erythromycin successfully prevented endocarditis due to these bacterial species. The analysis of the bacteremia (by culturing blood drawn 1 min after extraction on penicillinase-containing blood agar plates) indicated that amoxicillin did not influence the incidence or the magnitude of circulating group G streptococci and S. aureus, while erythromycin apparently suppressed them. However, when care was taken to eliminate blood erythromycin by a lysis-centrifugation process, the incidence and magnitude of bacteremia after erythromycin prophylaxis was similar to that in control rats. We conclude that single doses of amoxicillin and erythromycin successfully prevent experimental endocarditis after dental extractions. Since this prophylaxis was operative by mechanisms other than the prevention of the circulation of bacteria before seeding the valvular vegetations, it suggests that recommendations for prevention of bacterial endocarditis should not be aimed only at providing adequate antibiotic blood levels to suppress the bacteremia produced by the invasive procedure.
Foam cell-forming J774 macrophages have markedly elevated acyl coenzyme A:cholesterol acyl transferase activity compared with mouse peritoneal macrophages in the presence of low density lipoprotein (LDL) despite similar LDL receptor activity.
Authors: I Tabas, G C Boykow, A R Tall
Journal: Journal of Clinical Investigation (1987)

Cholesteryl ester (CE) accumulation in arterial wall macrophages (foam cells) is a prominent feature of atherosclerotic lesions. We have previously shown that murine J774 macrophages, unlike mouse peritoneal macrophages, accumulate large amounts of CE from unmodified low density lipoprotein (LDL). We now report a direct comparison of acyl coenzyme A:cholesterol acyl transferase (ACAT) activity in J774 and mouse peritoneal macrophages. Despite similar chloroquine-inhibitable 125I-LDL degradation in the two macrophages, ACAT activity in LDL-treated J774 macrophages was 10-30-fold higher than that in LDL-treated mouse peritoneal macrophages. In contrast, acetyl-LDL (matched for degradation with LDL) caused marked stimulation of ACAT activity in mouse peritoneal macrophages. From these data we conclude that in the presence of LDL, J774 macrophages have a highly active ACAT cholesterol esterification pathway compared with mouse peritoneal macrophages; and in mouse peritoneal macrophages, there is a marked difference in the ability of acetyl-LDL vs. LDL to stimulate ACAT even when the lipoproteins are matched for degradation.
Muscle activity in cycling: the double burst
Authors: M Arkesteijn, S A Jobson, J Hopker, L Passfield
Journal: British Journal of Sports Medicine (2011)

The period of a muscle's activity during cycling can be described by the onset and offset of electrical activity. Certain muscles can exhibit two distinct periods of activity (a ‘double burst'), reflecting different muscular functions during a pedal revolution. Our aims were to determine (1) the consistency of the double burst pattern in the Gastrocnemius Lateralis (GL) muscle during cycling and (2) by how much the reliability of the offset of GL is improved by taking the double burst into account. 11 cyclists volunteered to participate. Participants cycled for 6 min at 265 W and 90 rev.min -1 on three separate days. Using surface electromyography, an ensemble-average of GL was constructed from a 30 s segment. Onset and offset threshold was set at 25% of the peak activity of the ensemble-averaged pattern to determine the crank angle of onset/offset. Two onsets/offsets were recorded for double bursts. Reliability of the primary offset was determined using the Standard Method (SM), that is, the offset of the final activity; and an Alternative Method (AM), which incorporated the muscular function, with the most frequent offset across days being regarded as the ‘primary' offset. A double burst was consistently detected for only 7 of the 11 cyclists. AM showed better reliability for the offset than SM (Standard Error of Measurement: 6.8° vs 21.3°, Intra Class Correlation: 0.82 vs 0.47). The double burst pattern is commonly observed in GL while cycling in trained cyclists. However, detection across several days is more difficult and could lead to erroneous conclusions about the (double) burst pattern. When analysing muscles with a possible double burst pattern, researchers could incorporate the muscle's function. This decreases the impact of an inconsistent double burst pattern across measurements.
Absence of Striatal Volume Differences Between Depressed Subjects With No Comorbid Medical Illness and Matched Comparison Subjects
Authors: Eric J. Lenze, Yvette I. Sheline
Journal: American Journal of Psychiatry (1999)

The striatum (caudate and putamen) appears to be important in the pathogenesis of depression. Some studies show smaller than normal striatal structure volumes in depressed subjects. This study compared striatal volumes in depressed and nondepressed women, screened to exclude major cerebrovascular disease risk factors and comorbid medical illness.Caudate and putamen volumes were measured from magnetic resonance imaging scans of 24 depressed women and 24 matched nondepressed comparison subjects.Caudate and putamen volumes were not significantly different between depressed and nondepressed groups.These findings differ from those of previous studies, possibly because of the exclusion of subjects with cerebrovascular risk factors in this study.