tbuckley/cabot-search huggingface dataset:
Sex Differences in Evaluation and Outcome of Unstable Angina
Authors: Véronique L. Roger
Journal: JAMA (2000)

ContextThe existence of sex bias in the delivery of cardiac care is controversial, and little is known about the association between sex and delivery of care and outcomes at an early point in the diagnostic sequence, such as when patients present for the evaluation of chest pain.ObjectiveTo test the hypothesis that female sex is negatively associated with care delivered to and outcomes of persons diagnosed as having unstable angina.DesignInception population-based cohort study with an average of 6 years of follow-up.SettingEmergency departments (EDs) in Olmsted County, Minnesota.PatientsA total of 2271 Olmsted County residents (1306 men and 965 women) who presented to the ED for the first time with symptoms meeting criteria for unstable angina between 1985 and 1992.Main Outcome MeasuresUse of cardiac procedures within 90 days of ED visit, overall mortality, and cardiac events (cardiac death, nonfatal myocardial infarction, nonfatal cardiac arrest, and congestive heart failure), compared by sex and Agency for Health Care Policy and Research cardiovascular risk category (low, intermediate, or high).ResultsWomen were older (P&lt;.001), more likely to have a history of hypertension (P = .001), and less likely to present with typical angina (P = .004) than men. Men were more likely than women to undergo noninvasive cardiac tests (relative risk [RR], 1.27; 95% confidence interval [CI], 1.14-1.40) as well as invasive cardiac procedures (RR, 1.72; 95% CI, 1.51-1.97). After adjustment, male sex was associated with a 24% increase in the use of cardiac procedures. Survival of both men and women in the high and intermediate risk categories was significantly lower than expected per the general population (P&lt;.001). Women had a worse outcome than men, but after multivariate adjustment, male sex was associated with a trend toward an increase in the risk of death (RR, 1.23; 95% CI, 0.99-1.54) and significantly associated with increased risk of cardiac events (RR, 1.21; 95% CI, 1.03-1.42).ConclusionsOur population-based data indicate that after an ED visit for symptoms of unstable angina, the use of cardiac procedures was lower in women, but after taking into account baseline characteristics, men experienced worse outcomes.
Dietary Fat and Meat Intake in Relation to Risk of Type 2 Diabetes in Men
Authors: Rob M. van Dam, Walter C. Willett, Eric B. Rimm, Meir J. Stampfer, Frank B. Hu
Journal: Diabetes Care (2002)

OBJECTIVE—To examine dietary fat and meat intake in relation to risk of type 2 diabetes. RESEARCH DESIGN AND METHODS—We prospectively followed 42,504 male participants of the Health Professionals Follow-Up Study who were aged 40–75 years and free of diagnosed diabetes, cardiovascular disease, and cancer in 1986. Diet was assessed by a validated food frequency questionnaire and updated in 1990 and 1994. During 12 years of follow-up, we ascertained 1,321 incident cases of type 2 diabetes. RESULTS—Intakes of total fat (multivariate RR for extreme quintiles 1.27, CI 1.04–1.55, P for trend=0.02) and saturated fat (1.34, 1.09–1.66, P for trend=0.01) were associated with a higher risk of type 2 diabetes. However, these associations disappeared after additional adjustment for BMI (total fat RR 0.97, CI 0.79–1.18; saturated fat 0.97, 0.79–1.20). Intakes of oleic acid, trans-fat, long-chain n-3 fat, and α-linolenic acid were not associated with diabetes risk after multivariate adjustment. Linoleic acid was associated with a lower risk of type 2 diabetes in men &amp;lt;65 years of age (RR 0.74, CI 0.60–0.92, P for trend=0.01) and in men with a BMI &amp;lt;25 kg/m2 (0.53, 0.33–0.85, P for trend=0.006) but not in older and obese men. Frequent consumption of processed meat was associated with a higher risk for type 2 diabetes (RR 1.46, CI 1.14–1.86 for ≥5/week vs. &amp;lt;1/month, P for trend &amp;lt;0.0001). CONCLUSIONS—Total and saturated fat intake were associated with a higher risk of type 2 diabetes, but these associations were not independent of BMI. Frequent consumption of processed meats may increase risk of type 2 diabetes.
Prevention of venous thromboembolism after major abdominal surgery
Authors: M.A. Mcnally, W.G. Kernohan, J.G. Brown, M.D. Laverick, R.A.B. Mollan, Henri Bounameaux, Olivier Huber, V.V. Kakkar, A.T. Cohen, R.A. Edmonson, S.K. Das, D.J. Cooper, H. Lévesque, D. Vasse, B. Legallicier, N. Cailleux, N. Moore, J.Y. Borg, H. Courtois
Journal: The Lancet (1993)
Networking of differentially expressed genes in human cancer cells resistant to methotrexate
Authors: Elisabet Selga, Carlota Oleaga, Sara Ramírez, M Cristina de Almagro, Véronique Noé, Carlos J Ciudad
Journal: Genome Medicine (2009)

The need for an integrated view of data obtained from high-throughput technologies gave rise to network analyses. These are especially useful to rationalize how external perturbations propagate through the expression of genes. To address this issue in the case of drug resistance, we constructed biological association networks of genes differentially expressed in cell lines resistant to methotrexate (MTX).Seven cell lines representative of different types of cancer, including colon cancer (HT29 and Caco2), breast cancer (MCF-7 and MDA-MB-468), pancreatic cancer (MIA PaCa-2), erythroblastic leukemia (K562) and osteosarcoma (Saos-2), were used. The differential expression pattern between sensitive and MTX-resistant cells was determined by whole human genome microarrays and analyzed with the GeneSpring GX software package. Genes deregulated in common between the different cancer cell lines served to generate biological association networks using the Pathway Architect software.Dikkopf homolog-1 (DKK1) is a highly interconnected node in the network generated with genes in common between the two colon cancer cell lines, and functional validations of this target using small interfering RNAs (siRNAs) showed a chemosensitization toward MTX. Members of the UDP-glucuronosyltransferase 1A (UGT1A) family formed a network of genes differentially expressed in the two breast cancer cell lines. siRNA treatment against UGT1A also showed an increase in MTX sensitivity. Eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) was overexpressed among the pancreatic cancer, leukemia and osteosarcoma cell lines, and siRNA treatment against EEF1A1 produced a chemosensitization toward MTX.Biological association networks identified DKK1, UGT1As and EEF1A1 as important gene nodes in MTX-resistance. Treatments using siRNA technology against these three genes showed chemosensitization toward MTX.
Two keratins MW 50,000 and 56,000 are synthesized by psoriatic epidermis
Authors: J. McGUIRE, M. OSBER, LUANN LIGHTFOOT
Journal: British Journal of Dermatology (1984)

Journal Article Two keratins MW 50,000 and 56,000 are synthesized by psoriatic epidermis Get access J. McGUIRE, J. McGUIRE Department of Dermatology, Yale University, School of Medicine, New Haven, Connecticut 06510, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar M. OSBER, M. OSBER Department of Dermatology, Yale University, School of Medicine, New Haven, Connecticut 06510, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar LUANN LIGHTFOOT LUANN LIGHTFOOT Department of Dermatology, Yale University, School of Medicine, New Haven, Connecticut 06510, U. S. A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s27, 1 July 1984, Pages 27–37, https://doi.org/10.1111/j.1365-2133.1984.tb15579.x Published: 01 July 1984
Telemedicine: Emerging e-medicine
Authors: Seong K. Mun, Jeanine W. Turner
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract This paper reviews the emergence of telemedicine and its recent expansion and use within the healthcare industry. Through this review, several examples of telemedicine within a variety of applications provide a broad context to discuss the challenges and opportunities facing the emergence of e-medicine. These examples provide snapshots of a teleradiology system used by the military, teleconsultations used in neurosurgery and hemodialysis, and home telemedicine used in diabetes care. Based on the discussion of telemedicine's history and expansion and the examples provided, a framework is offered for understanding the evolution of telemedicine applications through four stages. These stages include: (a) development of basic technological capabilities, (b) development of relevant applications, (c) the integration of technical applications within a complex environment, and (d) transformation of the operating environment. Implications for this framework are discussed.
Targeted Chemotherapy for Head and Neck Cancer with a Chimeric Oncolytic Adenovirus Coding for Bifunctional Suicide Protein FCU1
Authors: João D. Dias, Ilkka Liikanen, Kilian Guse, Johann Foloppe, Marta Sloniecka, Iulia Diaconu, Ville Rantanen, Minna Eriksson, Tanja Hakkarainen, Monika Lusky, Philippe Erbs, Sophie Escutenaire, Anna Kanerva, Sari Pesonen, Vincenzo Cerullo, Akseli Hemminki
Journal: Clinical Cancer Research (2010)

Transfer of prodrug activation systems into tumors by using replication-deficient viruses has been suggested to be an effective method for achieving high local and low systemic anticancer drug concentrations. However, most current suicide gene therapy strategies are still hindered by poor efficiency of in vivo gene transfer, inefficient tumor penetration, limited bystander cell killing effect, and need of large prodrug doses. We hypothesized that local amplification provided by a replication competent platform would help overcome these limitations.We generated a transductionally and transcriptionally targeted oncolytic adenovirus Ad5/3-Delta24FCU1 expressing the fusion suicide gene FCU1. FCU1 encodes a bifunctional fusion protein that efficiently catalyzes the direct conversion of 5-FC, a relatively nontoxic antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine monophosphate, bypassing the natural resistance of certain human tumor cells to 5-fluorouracil.We examined the efficacy of Ad5/3-Delta24FCU1 and the replication-defective control Ad5/3-FCU1 with and without 5-FC. FCU1 expression was confirmed by Western blot, whereas enzymatic conversion levels in vitro and in vivo were determined by high-performance liquid chromatography separation. Significant antitumor effect was observed in vitro and in vivo in a murine model of head and neck squamous cell carcinoma. Although we observed a decrease in viral DNA copy number in vitro and in tumors treated with Ad5/3-Delta24FCU1 and 5-FC, suggesting an effect on virus replication, the highest antitumor effect was observed for this combination.It seems feasible and efficacious to combine adenovirus replication to the FCU1 prodrug activation system.
Varenicline and risk of psychiatric conditions, suicidal behaviour, criminal offending, and transport accidents and offences: population based cohort study
Authors: Yasmina Molero, Paul Lichtenstein, Johan Zetterqvist, Clara Hellner Gumpert, Seena Fazel
Journal: BMJ (2015)

<b>Objective</b> To examine associations between varenicline and the incidence of a range of adverse outcomes. <b>Design</b> Population based cohort study using within person analyses to control for confounding by indication. <b>Setting</b> Whole population of Sweden. <b>Participants</b> 7 917 436 people aged 15 and over, of whom 69 757 were treated with varenicline between 2006 and 2009. <b>Main outcome measures</b> Incidence of new psychiatric conditions, suicidal behaviour, suspected and convicted criminal offending, transport accidents, and suspected and convicted traffic offences. <b>Results</b> In the whole population, 337 393 new psychiatric conditions were diagnosed during follow-up. In addition, 507 823 suspected and 338 608 convicted crimes, 40 595 suicidal events, 124 445 transport accidents, and 99 895 suspected and 57 068 convicted traffic crimes were recorded. Within person analyses showed that varenicline was not associated with significant hazards of suicidal behaviour, criminal offending, transport accidents, traffic offences, or psychoses. However, varenicline was associated with a small increase in the risk of anxiety conditions (hazard ratio 1.23, 95% confidence interval 1.01 to 1.51) and mood conditions (1.31, 1.06 to 1.63), which was only seen in people with pre-existing psychiatric disorders. <b>Conclusions</b> Concerns that varenicline is associated with an increased risk of many adverse outcomes, including suicidality and accidents, are not supported in this observational study. The small increase in risk of two psychiatric conditions in people with pre-existing psychiatric disorders needs to be confirmed using other research designs.
Histology of Developing Plasma Cell Neoplasia Induced By Mineral Oil in BALB/c Mice
Authors: Michael Potter, Ross C. MacCardle
Journal: JNCI Journal of the National Cancer Institute (1964)

Early stages of the histogenesis of plasma cell neoplasia were observed in BALB/c mice given intraperitoneal injections of mineral oil. These changes were found exclusively in the mesenteric oil granulomas, and consisted of focal collections of proliferating plasma cells. It could not be determined from the histologic evidence whether the plasma cells of the oil granuloma differentiated in situ from a tissue cell such as the perivascular adventitial cell of capillaries, or from a cell of distant origin that migrated into the oil granuloma, e.g., a lymphocyte.
Effect of salt depletion and propranolol on blood pressure and plasma renin activity in various forms of hypertension.
Authors: G G Geyskes, P Boer, J Vos, F H Leenen, E J Mees
Journal: Circulation Research (1975)

The effect of propranolol therapy on the mean arterial pressure (MAP) and plasma renin activity (PRA) was studied in three groups of hypertensive patients who were also treated with saliuretics. Group A: In 14 patients with essential hypertension on chlorthalidone treatment, an additional daily dose of 640 mg propranolol for two months led to a significant reduction of the MAP (from 124 to 105 mm Hg) and PRA (from 5.3 to 2.0 ng AI/ml/hr standing). There was no correlation between MAP reduction and either the original levels or change in PRA. Group B: In 14 patients with essential hypertension and 5 with renal artery stenosis studied on a fixed salt intake, the plasma and extracellular volumes, PRA, and blood pressures were recorded before and after three days of diuretic induced salt depletion and, with maintenance of the depleted state, after three days of propranolol. Salt depletion resulted in a decrease in MAP from 132 to 128 mm Hg (NS), and PRA increased from 3.4 to 22.3 ng AI/ml/hr (P less than 0.01). There was no correlation between change in MAP and PRA control values, PRA change, or any of the volume parameters. Addition of propranolol was followed by a rapid MAP decrease to 111 mm Hg (P less than 0.01), and the PRA dropped to a mean of 8.5 (P less than 0.01). No correlation was found between change in MAP and change in PRA. The patients with renal artery stenosis did not differ in their reactions from those with essential hypertension. Group C: In five patients with moderate renal failure and normal to expanded 82-Br distribution volume, propranolol lowered MAP by 10% and lowered the PRA in all five. Salt depletion by furosemide to 82-Br volumes below normal resulted in a 10% decrease of MAP and a marked rise in PRA. In this state propranolol was followed by a further MAP reduction of 18% and a decrease in PRA. There was no quantitative relationship between MAP and PRA change during either of the treatment regimes. It is concluded that in various forms of hypertension, the blood pressure can be effectively lowered by combining diuretics and propranolol regardless of the pretreatment PRA level.
Accumulation of Multipotent Progenitors with a Basal Differentiation Bias during Aging of Human Mammary Epithelia
Authors: James C. Garbe, Francois Pepin, Fanny A. Pelissier, Klara Sputova, Agla J. Fridriksdottir, Diana E. Guo, Rene Villadsen, Morag Park, Ole W. Petersen, Alexander D. Borowsky, Martha R. Stampfer, Mark A. LaBarge
Journal: Cancer Research (2012)

Abstract Women older than 50 years account for 75% of new breast cancer diagnoses, and the majority of these tumors are of a luminal subtype. Although age-associated changes, including endocrine profiles and alterations within the breast microenvironment, increase cancer risk, an understanding of the cellular and molecular mechanisms that underlies these observations is lacking. In this study, we generated a large collection of normal human mammary epithelial cell strains from women ages 16 to 91 years, derived from primary tissues, to investigate the molecular changes that occur in aging breast cells. We found that in finite lifespan cultured and uncultured epithelial cells, aging is associated with a reduction of myoepithelial cells and an increase in luminal cells that express keratin 14 and integrin-α6, a phenotype that is usually expressed exclusively in myoepithelial cells in women younger than 30 years. Changes to the luminal lineage resulted from age-dependent expansion of defective multipotent progenitors that gave rise to incompletely differentiated luminal or myoepithelial cells. The aging process therefore results in both a shift in the balance of luminal/myoepithelial lineages and to changes in the functional spectrum of multipotent progenitors, which together increase the potential for malignant transformation. Together, our findings provide a cellular basis to explain the observed vulnerability to breast cancer that increases with age. Cancer Res; 72(14); 3687–701. ©2012 AACR.
Reconstitution of Caspase-3 Confers Low Glucose-Enhanced Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Cytotoxicity and Akt Cleavage
Authors: Yong J. Lee, Christopher J. Froelich, Naoya Fujita, Takashi Tsuruo, Jin H. Kim
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: We have previously observed that glucose deprivation enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic death as well as caspase activation (caspase-3, -9, and -8) in human prostate adenocarcinoma DU-145 cells. In this study, we used caspase-3-deficient MCF-7 breast cancer cells to examine the possible role of caspase-3 in glucose deprivation-enhanced TRAIL cytotoxicity. Results: Combined glucose deprivation and 200 ng/ml TRAIL treatment markedly induced cytotoxicity in caspase-3 cDNA transfected cells (MCF-7/casp-3) but not in control vector transfected cells (MCF-7/vector). We also observed that the level of Akt, an antiapoptotic protein, was reduced by treatment with TRAIL in MCF-7/casp-3 cells but not in MCF-7/vector cells. The reduction of Akt by TRAIL was promoted in the absence of glucose in MCF-7/casp-3 cells. However, pretreatment with 20 μm Z-LEHD-FMK, a caspase-9 inhibitor, protected MCF-7/casp-3 cells from the combinatorial treatment of TRAIL and glucose deprivation-induced cytotoxicity. This compound also prevented the reduction of Akt level during the combinatorial treatment. Moreover, this Akt reduction was not inhibited by treatment with MG-132, a proteosome inhibitor. Data from site-directed mutagenesis show that Akt was cleaved at amino acid 108, but not 119, during treatment with TRAIL and glucose deprivation. Conclusions: Our results suggest that caspase-3 is involved in the reduction of Akt level, and its involvement is mediated through caspase-9 activation. The reduction of Akt level is also due to cleavage of Akt rather than degradation of Akt.
Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes
Authors: Bryan Williams, Peter S. Lacy, Simon M. Thom, Kennedy Cruickshank, Alice Stanton, David Collier, Alun D. Hughes, H. Thurston, Michael O’Rourke
Journal: Circulation (2006)

Background— Different blood pressure (BP)–lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol±thiazide-based versus amlodipine±perindopril-based therapy) on derived central aortic pressures and hemodynamics. Methods and Results— The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Δ0.7 mm Hg; 95% CI, −0.4 to 1.7; P =0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Δ4.3 mm Hg; 95% CI, 3.3 to 5.4; P &lt;0.0001; central aortic pulse pressure, Δ3.0 mm Hg; 95% CI, 2.1 to 3.9; P &lt;0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc–defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P &lt;0.0001; adjusted for baseline variables, P &lt;0.05). Conclusions— BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.
Aptamers: Active Targeting Ligands for Cancer Diagnosis and Therapy
Authors: Xu Wu, Jiao Chen, Min Wu, Julia Xiaojun Zhao
Journal: Theranostics (2015)

Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells.Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required.They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment).In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics.The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer.Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy.Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment.