tbuckley/cabot-search huggingface dataset:
Abstract P042: Association of Long-Term Coffee Consumption with Total and Cause-Specific Mortality
Authors: Ming Ding, Ambika Satija, Shilpa Bhupathiraju, Qi Sun, Jiali Han, Walter Willett, Rob van Dam, Frank Hu
Journal: Circulation (2015)

BACKGROUND: Coffee is one of the most popular beverages worldwide; however, the association between coffee consumption and risk of mortality remains inconclusive. METHOD: We examined the associations of consumption of total, caffeinated, and decaffeinated coffee with risk of subsequent total and cause-specific mortality among 121,704 women in the Nurses’ Health Study (1984 - 2013), 116,683 women in the Nurses’ Health Study 2 (1991 - 2013), and 51,530 men in the Health Professionals Follow-up Study (1986 - 2013). Participants with a history of cancer, heart disease, or stroke at baseline were excluded. Coffee consumption was assessed at baseline using a semi-quantitative food frequency questionnaire. RESULTS: During 5,048,976 person-years of follow-up, 20,025 women and 13,391 men died. Consumption of total, caffeinated, and decaffeinated coffee were non-linearly associated with total mortality (P for non-linear trend &lt; 0.001). The pooled hazard ratios (HRs) for death among participants who drank coffee, as compared with those who did not, were 0.96 (95% CI: 0.92 - 1.00) for coffee consumption less than one cup/d, 0.89 (95% CI: 0.86 - 0.92) for coffee consumption one to three cups/d, 0.91 (95% CI: 0.87 - 0.95) for coffee consumption three to five cups/d, and 1.01 (95% CI: 0.96 - 1.06) for coffee consumption more than five cups/d (p for non-linearity &lt; 0.001; p for non-linear trend &lt; 0.001). When restricting to never smokers, compared to non-drinkers, the multivariate adjusted HRs of total mortality across categories of total coffee consumption were 0.93 (0.86-1.02) for 1 cup/d, 0.87 (0.82-0.96) for 1-3 cups/d, 0.85 (0.77-0.94) for 3-5 cups/d, and 0.83 (0.71-0.97) for &gt;5 cups/d (p for non-linearity = 0.15; p for linear trend &lt;0.001). A significant inverse association was observed for both caffeinated coffee (p for trend &lt; 0.001) and decaffeinated coffee (p for trend = 0.03). CONCLUSION: These data indicate higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was associated with lower risk of total mortality.
A founder ectodysplasin A receptor (EDAR) mutation results in a high frequency of the autosomal recessive form of hypohidrotic ectodermal dysplasia in India
Authors: M.D. Bashyam, A.K. Chaudhary, E.C. Reddy, V. Reddy, V. Acharya, H.A. Nagarajaram, A.R.R. Devi, L. Bashyam, A.B. Dalal, N. Gupta, M. Kabra, M. Agarwal, S.R. Phadke, R. Tainwala, R. Kumar, S.V. Hariharan
Journal: British Journal of Dermatology (2011)

Background Hypohidrotic/anhidrotic ectodermal dysplasia (HED) is a rare Mendelian disorder affecting ectodermal tissues. The disease is primarily caused by inactivation of any one of three genes, namely ectodysplasin A1 (EDA-A1), which encodes a ligand belonging to the tumour necrosis factor (TNF) superfamily; ectodysplasin A receptor (EDAR), encoding the EDA-A1 receptor and ectodysplasin A receptor-associated death domain (EDARADD), encoding an adaptor protein. X-linked recessive (EDA-A1), the predominant form of HED, as well as autosomal recessive and dominant (EDAR and EDARADD) inheritance patterns have been identified in affected families. Objectives To determine the common genes causing HED in India. Methods We performed mutation analysis on 26 HED families from India (including 30 patients). In addition, we carried out sequence and structural analysis of missense/nonsense and insertion/deletion mutations. Results Among the 26 families analysed, disease-causing EDAR mutations were identified in 12 (46%) while EDA-A1 mutations were detected in 11 (42%). Four novel mutations in EDAR and five in EDA-A1 were identified. More importantly, a possible founder EDAR mutation, namely c.1144G>A, was identified in five independent families, thus accounting for about one-fifth of affected families in whom mutation was detected. A majority of EDA-A1 mutations localized to the TNF-like domain while the location of EDAR mutations was more widespread. Conclusions This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.
Characterization of ARC-111 as a TOP 1/HIF 1α inhibitor.
Authors: Fanying Meng, Xuan-Thao Nguyen, Xiaohong Cai, Jian-Xin Duan, Mark Matteucci, Charles Hart
Journal: Cancer Research (2006)

5540  The hypoxia-inducible factor-1 (HIF-1) transcription factor is an essential regulator of tumorigenesis and an attractive molecular target for cancer therapy. In the current study, we demonstrate that ARC-111 specifically inhibits hypoxia-induced accumulation of HIF-1α in multiple human cancer cell lines (H460, PC3, CCRF). ARC-111 inhibits specifically HIF-1α protein synthesis but not global protein synthesis. We demonstrate that inhibition of HIF-1α accumulation by ARC-111 is independent of proteasomal degradation. In addition, we demonstrate that Topoisomerase I (Top 1) is required for HIF-1α inhibition by ARC-111 by using Top I mutant cell lines (CEM/C1, CEM/C2). Experiments performed with nocodazole indicate that ARC-111 inhibits HIF-1α accumulation in a cell-cycle independent manner. Our findings provide support for the clinical application of ARC-111 to target hypoxic tumors.
Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase
Authors: Boris M. Hogema, Maneesh Gupta, Henry Senephansiri, Terry G. Burlingame, Melissa Taylor, Cornelis Jakobs, Ruud B. H. Schutgens, Wolfgang Froestl, O. Carter Snead, Ramon Diaz-Arrastia, Teodoro Bottiglieri, Markus Grompe, K. Michael Gibson
Journal: Nature Genetics (2001)
Abstract P089: Adiposity and risk of stroke: body shape matters more than body weight
Authors: Suzanne E Judd, Virginia J Howard, George Howard, Susan Lakoski, Mary Cushman, Brett M Kissela
Journal: Circulation (2014)

Background: Higher body mass index (BMI) and larger waist circumference (WC), characteristics of increased adiposity, are associated with greater risk of cardiovascular disease (CVD). However, an obesity paradox (improved survival in those with history of stroke) has been observed in some populations. We hypothesized that BMI would be associated with decreased risk of stroke but that this association would be attenuated after accounting for WC. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS) study recruited 30,239 black and white participants age 45 years and older from across the United States between 2003 and 2007. WC, height and weight were measured during a baseline in home visit and participants were followed every 6 months. Strokes were adjudicated by physicians after review of medical records. Cox proportional hazards models were used to assess stroke risk. BMI and WC were modeled in quintiles. Results: We observed 1047 incident and recurrent strokes over a mean of 6.3 years. Higher BMI and lower WC were associated with decreased risk of stroke after adjustment for demographic and medical risk factors (Table). Having both BMI and WC in the model dramatically increased the strength of association for the other variable. Collinearity was not present. The observed association was consistent across race, sex, age, WC, and history of stroke (all p for interaction &gt;0.20). Conclusion: Increased BMI, the main measure used to define obesity, was not a stroke risk factor. Increased risk of stroke was observed in WC less than the current recommendations of 88 cm for women and 102 cm for men. Smaller waist sizes and maintenance of lean mass are important targets for stroke prevention.&lt;br
In Vitro Cellular Drug Resistance and Prognosis in Newly Diagnosed Childhood Acute Lymphoblastic Leukemia
Authors: G.J.L. Kaspers, A.J.P. Veerman, R. Pieters, C.H. Van Zantwijk, L.A. Smets, E.R. Van Wering, A. Van Der Does-Van Den Berg
Journal: Blood (1997)
CONTROL OF THE TOBACCO HABIT
Authors: John L. Dorsey
Journal: Annals of Internal Medicine (1936)

Article1 November 1936CONTROL OF THE TOBACCO HABITJOHN L. DORSEY, M.D., F.A.C.P.JOHN L. DORSEY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-5-628 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe physician is frequently called upon to plan a regimen for the patient under his care where it is more or less apparent that some restriction in the use of tobacco is desirable. The indications for such limitation are not clear-cut because the effects of nicotine as a chronic poison to those who habitually smoke to excess are by no means obvious, and are certainly subject to considerable individual variation. Whether nicotine plays a definite part in various forms of vascular disturbance may be open to some discussion, but it is within the practitioner's routine experience to observe that appetite... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland*Received for publication April 30, 1936. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFrom the Birth of the Smokers' Clinic to the Invention of Nicorette: Problematizing Smoking as Addiction in Sweden 1955-1971Current and Emerging Pharmacotherapeutic Options for Smoking CessationLobeline for smoking cessationHistory, chemistry and biology of alkaloids from Lobelia inflataEstado actual y futuras terapias farmacológicas en la deshabituación tabáquicaTratamiento farmacológico del tabaquismoNon-Nicotine Pharmacotherapy for Smoking CessationAdvances in Non-Nicotine Pharmacotherapy for Smoking CessationLobeline for smoking cessationCommunity-based Programs for Smoking CessationCigarette smoking: The clinician's role in cessation, prevention, and public healthProgress in understanding the relationship between the pharmacological effects of nicotine and human tobacco dependenceThe nature and treatment of cigarette dependenceThe Treatment of Cigarette DependenceThe Problem of Cigarette Smoking and Its ControlLobeline and Reduction of Cigarette SmokingMedikamentöse Behandlung des RauchersClinical factors in smoking withdrawal: preliminary report.THE TREATMENT OF ADDICTIVE SMOKERSBUFFERED LOBELINE AS A SMOKING DETERRENTRADIOGRAPHY OF THE EARLOBELINE AND NICOTINEL 1 November 1936Volume 10, Issue 5Page: 628-631KeywordsHabitsNicotinePatientsTobacco control ePublished: 1 December 2008 Issue Published: 1 November 1936 PDF downloadLoading ...
Incidence of Mammary and Pituitary Tumors in Hybrid Mice Treated with Stilbestrol for Varying Periods&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Flavia L. Richardson
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Incidence of Mammary and Pituitary Tumors in Hybrid Mice Treated with Stilbestrol for Varying Periods Get access Flavia L. Richardson Flavia L. Richardson Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 6, June 1957, Pages 813–829, https://doi.org/10.1093/jnci/18.6.813 Published: 01 June 1957 Article history Received: 17 February 1957 Published: 01 June 1957
Abstract P266: Change in the Association Between Serum Lipids and Coronary Heart Disease among Middle-Aged Adults: Observational Data from the Pre- and Post-Statin Era.
Authors: Lisandro D Colantonio, Vera Bittner, Emily B Levitan, Shia Kent, Monika M Safford, Paul Muntner
Journal: Circulation (2014)

Dyslipidemia is a major risk factor for coronary heart disease (CHD) and is usually treated with statins. Few observational studies have examined associations between lipids and CHD in the era of widespread statin use. The objective of the current analysis was to contrast the association between serum lipids and incident coronary heart disease (CHD) among middle-aged adults before and after statin use became widespread. Methods: We analyzed data from 14,590 Atherosclerosis Risk In Communities (ARIC) study participants who were recruited in 1987-1989 (pre-statins), and 13,196 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants (9,578 not taking statins) who were recruited in 2003-2007 (post-statins). Our analysis was restricted to participants 45 to 64 years of age without a history of CHD at baseline. Total and HDL cholesterol (HDL-C) and fasting triglycerides (TG) were measured at baseline and used to calculate LDL-C, non-HDL-C, total-to-HDL-C ratio and total-to-TG ratio. Each lipid parameter was categorized into four levels based on REGARDS quartile cut-points. Results: In ARIC, participants with higher LDL-C were more likely to have diabetes and use antihypertensive medication, whereas these CHD risk factors were progressively less common at higher LDL-C in REGARDS participants not taking statins. Over a maximum 7 years of follow up, 513 and 278 incident CHD events occurred among ARIC and REGARDS participants, respectively. After multivariable adjustment, higher categories of each lipid marker (lower categories of HDL-C) were associated with a higher hazard ratio (HR) for CHD among ARIC participants, but not among REGARDS participants not taking statins (figure). No association between lipid markers and CHD was observed among REGARDS participants taking statins. DISCUSION: The current analysis suggests that the widespread preferential use of statins among high risk individuals may have obscured the association between lipids and incident CHD.
Benzyl Alcohol: A novel treatment for acetaminophen overdose?
Authors: Hartmut Jaeschke, Kuo Du
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: We read with interest the recent article by Cai et al. suggesting that "benzyl alcohol (BA) may prove to be a useful adjunct in the treatment of APAP and other forms of sterile liver injury."1 We would like to point out a few reasons why BA will not likely be a clinically useful therapeutic option for APAP overdose patients. First, as the authors discussed themselves,1 BA can inhibit mitochondrial respiration and is toxic at higher doses. Second, 100 μM of BA was shown to inhibit the enzyme activities of Cyp1A2, Cyp2E1, and Cyp3A4 by 20%‐50%.2 Because the authors used approximately 9 mM of BA for the in vitro experiments and exposed the liver to mM concentrations in vivo,1 the protective effect was most likely caused by P450 inhibition. This conclusion is supported by the almost 100% protection in vivo and the fact that BA was most effective when given during a narrow window around the time of APAP treatment, which confirms that BA only protects when present during the metabolism phase of APAP. However, the established clinical antidote, N‐acetylcysteine, is most effective during the metabolism phase and beyond with lower risk. Third, the authors argue about an inhibitory effect of BA on the inflammasome.1 Interestingly, all studies that investigated a role of the Nalp3 inflammasome and interleukin‐1β (IL‐1β) in APAP hepatotoxicity are in agreement that damage‐associated‐molecular patterns released from necrotic cells activate macrophages to generate cytokines, including pro‐IL‐1β.1 All groups also agree that inhibition or deficiency of caspase‐1 eliminates processing of pro‐IL‐1β to the active cytokine.1 Most important, all agree that only a few pg/mL of IL‐1β are actually produced during APAP hepatotoxicity.1 However, the fact that mice treated with 10,000‐fold more recombinant IL‐1β had no effect on APAP‐induced liver injury clearly indicates that minor quantities of endogenously generated IL‐1β have no impact on APAP hepatotoxicity.4 Thus, there is little chance that the inflammasome and IL‐1β will be clinically relevant targets. Case in point, in APAP overdose patients, there is no significant IL‐1β formation (Control: 3.8 ± 0.5 pg/mL [n = 3]; APAP: 5.5 ± 1.7 pg/mL [n = 10]) and neutrophils do not contribute to the injury.5
Normalizing Myocardial Carbohydrate Metabolism Reverses Energetic Impairment and Diastolic Dysfunction in a Rodent Model of Obesity
Authors: Andrew J Lewis, MIchael S Dodd, Joevin Sourdon, Kieran Clarke, Stefan Neubauer, Damian J Tyler
Journal: Circulation (2014)

Background:  The role of abnormal cardiac substrate metabolism in the development of obesity cardiomyopathy and the therapeutic potential of interventions targeting substrate metabolism are unknown. We hypothesised; (1) that obesity would impair both myocardial carbohydrate metabolism and energetics resulting in diastolic dysfunction and (2) that normalisation of carbohydrate metabolism would reverse these changes.   Methods:  Obese (n=36, 471±45g) and normal weight Long Evans rats (n=12, 383±34g) were diet standardized (67% carbohydrate, ≥5 days). We then performed in vivo hyperpolarized [1-13C] and [2-13C] magnetic resonance spectroscopy (MRS), echocardiography and perfused heart 31P MRS to evaluate myocardial metabolism, structure and function. Two obese groups were subsequently treated with either Liraglutide (a GLP-1 analogue, 0.2mg/kg twice daily, 7 days, n=12) or calorie restriction (70% usual intake, 28 days, n=12) and then restudied.   Results:  Obesity caused left ventricular (LV) hypertrophy (2.1 vs 1.8mm, P   Conclusions:  Treatment with either Liraglutide (weight-neutral) or calorie restriction normalized myocardial carbohydrate metabolism, energetics and diastolic function. These findings suggest a key role for myocardial metabolism in the development of obesity cardiomyopathy and identify PDH as a potential clinical therapeutic target.
Retention of 4-hydroxytamoxifen and levels of estradiol in the breast of high-risk women.
Authors: Robert T. Chatterton, Michael J. Avram, Villian S. Naeem, Rachel H. Cohn, Seema A. Khan
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5431 

Objective: Evaluate the formation and retention of 4-hydroxytamoxifen (4-HT) in the breast and determine the relation to estradiol and tamoxifen levels in serum and breast fluid. Background: Tamoxifen is an orally effective estrogen receptor (ER) modulator, reducing the incidence of ER+ breast cancer by approximately 70%; however 30% of ER+ cancers and essentially no ER- cancers are not prevented. There are no published data on variability of formation and retention of the active metabolite of tamoxifen in ductal lavage fluid (DLF) or the concomitant levels of estradiol that may compete for the ER. Methods: Twenty patients with Gail scores of >1.7 were offered tamoxifen for prophylaxis, 20 mg/day. Both women who accepted tamoxifen, and those who declined, were recruited to the study. DLF was collected before treatment and after approximately 6 mo. Blood was collected at the time of ductal lavage. DLF was lyophilized and reconstituted to 4 ml and total protein concentration was measured. Estradiol was measured by ELISA in serum and DLF; tamoxifen and 4-hydroxytamoxifen were measured by HPLC-mass spectrometry. Results: 13 women accepted TAM therapy. The concentrations of 4-HT in DLF varied from undetectable to 0.81 ng/ml with a CV of 53.6%; those of tamoxifen varied from undetectable to 9.4 ng/ml with a CV of 42.8%. The ratio of 4-HT to tamoxifen in serum was 0.048, and in DLF was 0.124. The correlation of DLF TAM with DLF 4-HT was 0.90, whereas that between serum tamoxifen and DLF 4-HT was 0.49.. The correlation of serum and DLF 4-HT was 0.42. DLF estradiol concentrations were negatively correlated with DLF 4-HT, r = -0.50, but DLF androstenedione and DHEA were not correlated with DLF 4-HT, -0.09 and -0.07, respectively. Tamoxifen treatment increased estradiol levels in the DLF from 20.9 to 77.6 pg/mg protein (p = 0.03 by Wilcoxon’s test) over 6 mo. Conclusions: The concentrations of 4-HT and tamoxifen in DLF are highly variable with undetectable levels in some samples. The higher correlation of DLF 4-HT with DLF tamoxifen and the higher ratio of 4-HT to tamoxifen imply that DLF 4-HT is primarily formed from tamoxifen in the breast. The increase in estradiol in DLF is consistent with previous data on serum levels but the negative correlation of DLF 4-HT with DLF estradiol suggests that, to some degree, 4-HT is competing with estradiol for binding sites in the breast. These data are consistent with the hypothesis that ineffective prophylactic treatment may be related to inadequate inhibition of estrogen action at the level of the breast in some women.
Abstract 707: Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate
Authors: Min Sang Lee, Jung Eun Lee, Eunkyoung Byun, Nak Won Kim, Haeshin Lee, Ji Hoon Jeong
Journal: Cancer Research (2014)

Abstract Purpose : Low cytotoxicity and high cellular gene delivery capability are among the most important prerequisites for the selection of a non-viral carrier. In this study, we report the development of calcium phosphate (CAP) nanoparticles stabilized by a conjugate of the biological adhesive molecule, 3,4-dihydroxy-L-phenylalanine (dopa), and a nontoxic hydrophilic natural polymer, hyaluronic acid (HA), for targeted siRNA delivery to cancer cells. Methods : Dopa-conjugated HA (dopa-HA) was synthesized by EDC/NHS chemistry and analyzed by spectrometry and 1H-NMR. Stabilized calcium phosphate nanoparticles containing siRNA (CAP/siRNA/dopa-HA) was prepared by simply mixing CaCl2 solution containing siRNA with a HEPES buffer containing Na2HPO4 and subsequent addition of a solution containing dopa-HA. The particles were characterized by using light scattering method and transmission electron microscope (TEM). The gene silencing and cancer cell-targeting ability of CAP/siRNA/dopa-HA was evaluated by monitoring cellular reporter activity (luciferase) in human colon carcinoma cells permanently expressing firefly luciferase. Confocal microscopy and FACS analysis were performed to assess CD44-specific cellular delivery. Bio-distribution and in vivo gene silencing of CAP/siRNA/dopa-HA nanoparticles were studied in an animal model bearing tumor xenograft. Results : CAP/siRNA/dopa-HA can form compact nanoparticles that effectively protect siRNA from enzymatic degradation despite the structural drawbacks of siRNA, such as low charge density and short and rigid structure. In addition, stabilized CAP nanoparticles were able to maintain their colloidal stability in a physiological salt condition for over a week. The superior ability of CAP/siRNA/dopa-HA to maintain the integrity of encapsulated siRNA and the stability in solution of the nanoparticles allow this formulation to achieve improved intratumoral accumulation of siRNA and a high level of target gene silencing in solid tumors after systemic administration. Conclusion Considering its biocompatibility, transfection efficacy, and tumor targeting capability, this stabilized organic-inorganic hybrid gene delivery platform should be considered a promising candidate carrier for systemic siRNA delivery and targeted cancer therapy. Citation Format: Min Sang Lee, Jung Eun Lee, Eunkyoung Byun, Nak Won Kim, Haeshin Lee, Ji Hoon Jeong. Tumor-targeted delivery of siRNA using stabilized calcium phosphate nanoparticles based on bio-inspired hyaluronic acid conjugate. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 707. doi:10.1158/1538-7445.AM2014-707