tbuckley/cabot-search huggingface dataset:
Trends in the Exposure of Nonsmokers in the U.S. Population to Secondhand Smoke: 1988–2002
Authors: James L. Pirkle, John T. Bernert, Samuel P. Caudill, Connie S. Sosnoff, Terry F. Pechacek
Journal: Environmental Health Perspectives (2006)

The objective of this study was to describe the exposure of nonsmokers in the U.S. population to secondhand smoke (SHS) using serum cotinine concentrations measured over a period of 14 years, from October 1988 through December 2002. This study consists of a series of National Health and Nutrition Examination Surveys (NHANES) measuring serum cotinine as an index of SHS exposure of participants. Study participants were individuals representative of the U.S. civilian, noninstitutionalized population, > or = 4 years of age. We analyzed serum cotinine and interview data from NHANES obtained during surveys conducted during four distinct time periods. Our results document a substantial decline of approximately 70% in serum cotinine concentrations in nonsmokers during this period. This decrease was reflected in all groups within the population regardless of age, sex, or race/ethnicity. The large decrease that we observed in serum cotinine concentrations suggests a substantial reduction in the exposure of the U.S. population to SHS during the 1990s. The exposure of nonsmokers to SHS represents an important public health concern. Our findings suggest that recent public health efforts to reduce such exposures have had an important effect, although children and non-Hispanic black nonsmokers show relatively higher levels of serum cotinine.
Induction of an Antigen Cascade by Diversified Subcutaneous/Intratumoral Vaccination Is Associated with Antitumor Responses
Authors: Chie Kudo-Saito, Jeffrey Schlom, James W. Hodge
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimulatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication-competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA+ tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEA+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA+ tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.
Improvement of Darier disease with diclofenac sodium 3% gel
Authors: Fernando Millán-Parrilla, Beatriz Rodrigo-Nicolás, Paula Molés-Poveda, Miquel Armengot-Carbó, Esther Quecedo-Estébanez, Enrique Gimeno-Carpio
Journal: Journal of the American Academy of Dermatology (2014)
New-feature learning: How common is it?
Authors: Robert M. French, Mark Weaver
Journal: Behavioral and Brain Sciences (1998)

The fixed-feature viewpoint Schyns et al. are opposing is not a widely held theoretical position but rather a working assumption of cognitive psychologists – and thus a straw man. We accept their demonstration of new-feature acquisition, but question its ubiquity in category learning. We suggest that new-feature learning (at least in adults) is rarer and more difficult than the authors suggest.
Calcium Plus Vitamin D Supplementation and the Risk of Breast Cancer
Authors: Rowan T. Chlebowski, Karen C. Johnson, Charles Kooperberg, Mary Pettinger, Jean Wactawski-Wende, Tom Rohan, Jacques Rossouw, Dorothy Lane, Mary Jo O’Sullivan, Shagufta Yasmeen, Robert A. Hiatt, James M. Shikany, Mara Vitolins, Janu Khandekar, F. Allan Hubbell
Journal: JNCI Journal of the National Cancer Institute (2008)

Although some observational studies have associated higher calcium intake and especially higher vitamin D intake and 25-hydroxyvitamin D levels with lower breast cancer risk, no randomized trial has evaluated these relationships.Postmenopausal women (N = 36 282) who were enrolled in a Women's Health Initiative clinical trial were randomly assigned to 1000 mg of elemental calcium with 400 IU of vitamin D(3) daily or placebo for a mean of 7.0 years to determine the effects of supplement use on incidence of hip fracture. Mammograms and breast exams were serially conducted. Invasive breast cancer was a secondary outcome. Baseline serum 25-hydroxyvitamin D levels were assessed in a nested case-control study of 1067 case patients and 1067 control subjects. A Cox proportional hazards model was used to estimate the risk of breast cancer associated with random assignment to calcium with vitamin D(3). Associations between 25-hydroxyvitamin D serum levels and total vitamin D intake, body mass index (BMI), recreational physical activity, and breast cancer risks were evaluated using logistic regression models. Statistical tests were two-sided.Invasive breast cancer incidence was similar in the two groups (528 supplement vs 546 placebo; hazard ratio = 0.96; 95% confidence interval = 0.85 to 1.09). In the nested case-control study, no effect of supplement group assignment on breast cancer risk was seen. Baseline 25-hydroxyvitamin D levels were modestly correlated with total vitamin D intake (diet and supplements) (r = 0.19, P < .001) and were higher among women with lower BMI and higher recreational physical activity (both P < .001). Baseline 25-hydroxyvitamin D levels were not associated with breast cancer risk in analyses that were adjusted for BMI and physical activity (P(trend) = .20).Calcium and vitamin D supplementation did not reduce invasive breast cancer incidence in postmenopausal women. In addition, 25-hydroxyvitamin D levels were not associated with subsequent breast cancer risk. These findings do not support a relationship between total vitamin D intake and 25-hydroxyvitamin D levels with breast cancer risk.
Studies on Specific Transplantation Resistance to Polyoma-Virus-Induced Tumors. III. Transplantation Resistance to Genetically Compatible Polyoma Tumors Induced by Polyoma Tumor Homografts&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Hans Olof Sjögren
Journal: JNCI Journal of the National Cancer Institute (1964)

Homografts of 16 different polyoma tumors induced resistance to subsequent isografting of 12 different polyoma tumors. No resistance was detected in animals similarly pretreated with 16 nonpolyoma tumors. One exceptional methylcholanthrene-induced sarcoma, previously shown to be susceptible to the polyoma-virus-induced resistance, was weakly susceptible also to the resistance induced by polyoma homografts and itself induced a weak resistance to polyoma tumor isografts. Seven other nonpolyoma tumors tested grew equally well in all recipient categories. Only a resistance demonstrated in mice developing no antiviral antibodies was regarded as an indication of immunity induced by the tumor cells. Polyoma tumor cells X-irradiated with 8000 r failed to induce the resistance. Eight polyoma tumor lines grew out in preirradiated recipients after inoculation of 2 to 50 times lower cell doses than in irradiated animals, while 3 spontaneous mammary carcinomas grew equally well in the 2 groups.
Risk of cutaneous malignant melanoma in patients with celiac disease: A population-based study
Authors: Benjamin Lebwohl, Hanna Eriksson, Johan Hansson, Peter H.R. Green, Jonas F. Ludvigsson
Journal: Journal of the American Academy of Dermatology (2014)

Celiac disease (CD) carries an increased risk of several malignancies, including cancers of the gastrointestinal tract and hematologic malignancies. The disease course of cutaneous malignant melanoma (CMM) is affected by the immune status of the host, and therefore may be associated with CD.We sought to test for an association between CD and CMM in a population-based setting.We queried all (n = 28) pathology departments in Sweden and identified patients with intestinal histology consistent with CD. Each patient was matched to up to 5 control subjects by age, gender, calendar period, and region. Using Cox proportional hazards, we tested for an association between CD and the subsequent diagnosis of CMM.Among patients with CD (n = 29,028), 78 subsequently developed CMM (0.3%). Compared with control subjects there was no significant association between CD and CMM (hazard ratio 0.94, 95% confidence interval 0.73-1.20). This null association was similar for men (hazard ratio 0.99, 95% confidence interval 0.68-1.44) and women (hazard ratio 0.89, 95% confidence interval 0.64-1.24), and in all age strata.Lack of data regarding undiagnosed CD is a limitation.In this population-based study we found no association between CD and the subsequent diagnosis of CMM. Prior studies showing a positive association between these 2 entities may have been a result of referral bias.
Characterisation of retinoblastomas without RB1 mutations: genomic, gene expression, and clinical studies
Authors: Diane E Rushlow, Berber M Mol, Jennifer Y Kennett, Stephanie Yee, Sanja Pajovic, Brigitte L Thériault, Nadia L Prigoda-Lee, Clarellen Spencer, Helen Dimaras, Timothy W Corson, Renée Pang, Christine Massey, Roseline Godbout, Zhe Jiang, Eldad Zacksenhaus, Katherine Paton, Annette C Moll, Claude Houdayer, Anthony Raizis, William Halliday, Wan L Lam, Paul C Boutros, Dietmar Lohmann, Josephine C Dorsman, Brenda L Gallie
Journal: The Lancet Oncology (2013)
Effect of changes in ventricular relaxation on early diastolic coronary blood flow in canine hearts.
Authors: L J Domalik-Wawrzynski, W J Powell, L Guerrero, I Palacios
Journal: Circulation Research (1987)

Since the gradient between aortic pressure and left ventricular diastolic pressure is a major determinant of coronary blood flow, a change in left ventricular relaxation by its effect on early diastole could diminish early diastolic coronary flow. Two interventions that resulted in impaired left ventricular relaxation, hypothermia, and reperfusion following a left anterior descending coronary artery occlusion were studied to evaluate whether there were associated changes in coronary blood flow. With both interventions, there was a significant prolongation of left ventricular relaxation (p less than 0.01) accompanied by a significant decrease in early diastolic coronary blood flow (p less than 0.01). Verapamil did not have a significant effect on these hemodynamic changes during hypothermia. However, verapamil significantly blunted the effects of reperfusion following ischemia on ventricular relaxation (p less than 0.002) and early diastolic coronary blood flow (p less than 0.01). Thus, impaired left ventricular relaxation has an adverse impact on early diastolic coronary blood flow, which, under the condition of reperfusion following regional myocardial ischemia, can be alleviated with calcium channel blockade.
Cellular profiles in asthmatic airways: a comparison of induced sputum, bronchial washings, and bronchoalveolar lavage fluid
Authors: V. M. Keatings, D. J. Evans, B. J. O'Connor, P. J. Barnes
Journal: Thorax (1997)

BACKGROUND: Analysis of bronchoalveolar lavage fluid has improved our understanding of the pathogenesis of asthma. Safety issues and access to expert resources limit this techniques as a research tool. Induced sputum is a non-invasive method of collecting airway fluid which is applicable to subjects with a range of severity of airflow obstruction. The method of sputum collection and processing differs between groups. A study was undertaken to compare induced sputum with bronchoscopically collected fluid. METHODS: Sixteen patients with mild stable asthma underwent both sputum induction and bronchoscopic examination with bronchial washings and bronchoalveolar lavage (BAL) in random order, with each procedure being separated by an interval of 12 days. Airway fluid was processed and stained for differential cell counting. RESULTS: Induced sputum was relatively rich in neutrophils and eosinophils compared with bronchial washings and BAL fluid (mean (SE) 1.3 (0.4)%, 5.0 (2.7)%, and 36.4 (3.7)% neutrophils and 0.6 (0.1)%, 1.6 (0.6)%, and 3.3 (1.1)% eosinophils in BAL fluid, bronchial washings, and induced sputum, respectively). The proportions of cells obtained at sputum induction correlated with those in bronchial washings but not BAL fluid (r = 0.6 and 0.7 for neutrophils and eosinophils, respectively, p &lt; 0.05). By contrast, induced sputum had a lower proportion of lymphocytes and macrophages than bronchial washings or BAL fluid, without any correlation. CONCLUSION: Induced sputum is rich in neutrophils and eosinophils and poor in lymphocytes, suggesting an origin in the larger airways. Induced sputum adequately reflects the findings in fluid collected by direct bronchoscopy.
Interleukin-6 receptor blockage ameliorates murine lupus nephritis.
Authors: B A Kiberd
Journal: Journal of the American Society of Nephrology (1993)

The therapeutic effects of a neutralizing monoclonal antibody (mAb) to the interleukin-6 receptor (IL-6R) were examined in the MRL-lpr/lpr murine lupus nephritis model. Animals (15 wk old) were treated with ip mAb IL-6R for 5 wk. GFR in these mice at the end of this treatment period were comparable to those of congenic strain disease-resistant MRL-(+)/+ controls treated with rat immunoglobulin G (IgG) (254 +/- 61 versus 285 +/- 26 microL/min; P = not significant). GFR was significantly (P < 0.05) lower in lpr/lpr mice receiving ip rat IgG (disease controls) at the same time (165 +/- 76 microL/min). The fractional mesangial volume (Mv) and surface density of open glomerular capillaries (Sv) in mAb II-6R-treated lpr/lpr and IgG-treated +/+ mice (Mv, 0.21 +/- 0.04 and 0.19 +/- 0.04 micron3/micron3; Sv, 0.18 +/- 0.01 and 0.20 +/- 0.01 micron/micron2, respectively) were similar. However, Mv (0.40 +/- 0.04) was significantly higher (P < 0.001) and Sv (0.13 +/- 0.04) was lower (P < 0.01) in IgG-treated lpr/lpr animals. Treatment with mAb IL-6R significantly reduced anti-dsDNA antibody levels after Week 2 of treatment, but these values rebounded at Week 4. The late development of neutralizing antibodies and the increased secretion of IL-6 at Week 4 were likely responsible. Despite these events, neutralizing mAb to the IL-6R proved to be effective therapeutically, as demonstrated by preserved glomerular function and structure.
Qualitative network models and genome-wide expression data define carbon/nitrogen-responsive molecular machines in Arabidopsis
Authors: Rodrigo A Gutiérrez, Laurence V Lejay, Alexis Dean, Francesca Chiaromonte, Dennis E Shasha, Gloria M Coruzzi
Journal: Genome biology (2007)

Carbon (C) and nitrogen (N) metabolites can regulate gene expression in Arabidopsis thaliana. Here, we use multi-network analysis of microarray data to identify molecular networks regulated by C and N in the Arabidopsis root system.We used the Arabidopsis whole genome Affymetrix gene chip to explore global gene expression responses in plants exposed transiently to a matrix of C and N treatments. We used ANOVA analysis to define quantitative models of regulation for all detected genes. Our results suggest that about half of the Arabidopsis transcriptome is regulated by C, N or CN interactions. We found ample evidence for interactions between C and N that include genes involved in metabolic pathways, protein degradation and auxin signaling. To provide a global, yet detailed, view of how the cell molecular network is adjusted in response to the CN treatments, we constructed a qualitative multi-network model of the Arabidopsis metabolic and regulatory molecular network, including 6,176 genes, 1,459 metabolites and 230,900 interactions among them. We integrated the quantitative models of CN gene regulation with the wiring diagram in the multi-network, and identified specific interacting genes in biological modules that respond to C, N or CN treatments.Our results indicate that CN regulation occurs at multiple levels, including potential post-transcriptional control by microRNAs. The network analysis of our systematic dataset of CN treatments indicates that CN sensing is a mechanism that coordinates the global and coordinated regulation of specific sets of molecular machines in the plant cell.
Systems medicine: the future of medical genomics and healthcare
Authors: Charles Auffray, Zhu Chen, Leroy Hood
Journal: Genome Medicine (2009)

High-throughput technologies for DNA sequencing and for analyses of transcriptomes, proteomes and metabolomes have provided the foundations for deciphering the structure, variation and function of the human genome and relating them to health and disease states. The increased efficiency of DNA sequencing opens up the possibility of analyzing a large number of individual genomes and transcriptomes, and complete reference proteomes and metabolomes are within reach using powerful analytical techniques based on chromatography, mass spectrometry and nuclear magnetic resonance. Computational and mathematical tools have enabled the development of systems approaches for deciphering the functional and regulatory networks underlying the behavior of complex biological systems. Further conceptual and methodological developments of these tools are needed for the integration of various data types across the multiple levels of organization and time frames that are characteristic of human development, physiology and disease. Medical genomics has attempted to overcome the initial limitations of genome-wide association studies and has identified a limited number of susceptibility loci for many complex and common diseases. Iterative systems approaches are starting to provide deeper insights into the mechanisms of human diseases, and to facilitate the development of better diagnostic and prognostic biomarkers for cancer and many other diseases. Systems approaches will transform the way drugs are developed through academy-industry partnerships that will target multiple components of networks and pathways perturbed in diseases. They will enable medicine to become predictive, personalized, preventive and participatory, and, in the process, concepts and methods from Western and oriental cultures can be combined. We recommend that systems medicine should be developed through an international network of systems biology and medicine centers dedicated to inter-disciplinary training and education, to help reduce the gap in healthcare between developed and developing countries.
Dysfunction of the longitudinal muscles of the oesophagus in eosinophilic oesophagitis
Authors: H. Korsapati, A. Babaei, V. Bhargava, R. Dohil, A. Quin, R. K. Mittal
Journal: Gut (2009)

<h3>Background:</h3> Oesophageal motility, as measured by manometry, is normal in the majority of patients with eosinophilic oesophagitis (EO). However, manometry measures only the circular muscle function of the oesophagus. The goal of the present study was to assess circular and longitudinal muscle function during peristalsis in patients with EO. <h3>Methods:</h3> Ultrasound imaging and manometry were simultaneously acquired during swallow-induced peristalsis in patients with EO and controls to measure the longitudinal muscle and circular muscle contraction, respectively. A probe with an ultrasound transducer was positioned 2 cm and then 10 cm above the lower oesophageal sphincter and five, 5 ml water swallows were recorded before and after edrophonium. <h3>Results:</h3> There is no difference in the incidence of swallow-induced peristalsis and manometric pressures (a marker of circular muscle contraction) between controls and patients with EO. However, changes in the muscle thickness (a marker of longitudinal muscle contraction) are markedly diminished in patients with EO, at both 2 and 10 cm above the lower oesophageal sphincter. The longitudinal muscle response to edrophonium is markedly blunted in patients with EO. Normal subjects demonstrate synchrony between the circular and longitudinal muscle contraction during peristalsis that is affected by edrophonium. On the other hand, patients with EO demonstrate mild asynchrony of circular and longitudinal muscle contraction during swallow-induced contractions that is not altered by edrophonium. <h3>Conclusions:</h3> In patients with EO, there is selective dysfunction of the longitudinal muscle contraction during peristalsis. It is proposed that the longitudinal muscle dysfunction in EO may contribute to dysphagia.
2-Chlorodeoxyadenosine Treatment in Hairy Cell Leukemia
Authors: Ajay Anand
Journal: Annals of Internal Medicine (1994)

Letters15 January 19942-Chlorodeoxyadenosine Treatment in Hairy Cell LeukemiaAjay Anand, MDAjay Anand, MDNew England Deaconess Hospital; Boston, MA 02215Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-120-2-199401150-00024 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Drs. Saven and Piro [1] describe complete remissions induced by 2-chlorodeoxyadenosine (2-CdA) in patients with hairy cell leukemia who had not responded to 2′-deoxycoformycin (DCF) therapy. I draw attention to further data on the subject.Another group of investigators treated two patients with hairy cell leukemia who were unresponsive to therapy with 2-DCF; one patient's marrow showed residual hairy cells, and the other had a residual bulky abdominal mass [2]. Both had a sustained, complete response to treatment with 2-CdA, thus supporting a lack of cross-resistance between these two purine analogs. The responses were achieved with a ...References1. Saven A, Piro LD. Complete remissions in hairy cell leukemia with 2-chlorodeoxyadenosine after failure with 2′-deoxycoformycin. Ann Intern Med. 1993; 119:278-83. Google Scholar2. Tallman MS, Hakimian D, Variakojis D, Koslow D, Sisney GA, Rademaker AW, et al. A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood. 1992; 80:2203-9. Google Scholar3. Kawasaki H, Carrera CJ, Piro LD, Saven A, Kipps TJ, Carson DA. Relationship of deoxycytidine kinase and cytoplasmic 5′-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood. 1993; 81:597-601. Google Scholar Author, Article, and Disclosure InformationAffiliations: New England Deaconess Hospital; Boston, MA 02215 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 January 1994Volume 120, Issue 2Page: 169KeywordsAdenosineBone marrowChronic lymphocytic leukemiaDNA damageDeoxycytidineDrugsLymphocytic leukemiaPurines Issue Published: 15 January 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...