tbuckley/cabot-search huggingface dataset:
Higher dosage nicotine patches increase one‐year smoking cessation rates: results from the European CEASE trial
Authors: P Tønnesen, P Paoletti, G Gustavsson, M.a Russell, R Saracci, A Gulsvik, B Rijcken, U Sawe, None members of the Steering Committee of Cease on behalf of the European Respiratory Society
Journal: European Respiratory Journal (1999)

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study. The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six chest clinics enrolled a total of 3,575 smokers. Subjects were allocated to one of five treatment arms: placebo and either standard or higher dose nicotine patches (15 mg and 25 mg daily) each given for 8 or 22 weeks with adjunctive moderately intensive support. The 12 month sustained success rates were: 25 mg patch for 22 weeks (L-25), 15.4%; 25 mg patch for 8 weeks (S-25), 15.9%; 15 mg patch for 22 weeks (L-15), 13.7%; 15 mg patch for 8 weeks (S-15), 11.7%; and placebo (P-0) 9.9% (placebo versus 15 mg, p&lt;0.05; 25 mg versus 15 mg, p&lt;0.03; 25 mg versus placebo, p&lt;0.001, Chi-squared test). There was no significant difference in success rate between the two active treatment durations. Of the first week abstainers (n=1,698), 25.1% achieved success at 12 months as opposed to first week smokers, 2.7% of 1,877 subjects (p&lt; 0.001). In summary, a higher than standard dose of nicotine patch was associated with an increase in the long-term success in smoking cessation but continuation of treatment beyond 8-12 weeks did not increase the success rates.
Androgen deprivation therapy increases the sensitivity of human prostate carcinoma cells to T cell-mediated lysis through an androgen receptor dependent mechanism
Authors: Sofia Gameiro, Andressa Ardiani, Anna R Kwilas, Renee N Donahue, James W Hodge
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Despite recent advances in diagnosis and therapy, prostate cancer remains the most frequently diagnosed non-skin cancer in the United States and the third leading cause of cancer deaths. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in
Misuse of Inhaled Bronchodilator Agents
Authors: K. B. Saunders
Journal: BMJ (1965)

In the course of doing simple lung-function tests on patients with chronic bronchitis, asthma, or emphysema it became clear that many of those using bronchodilator aerosols were not using them correctly.Since it seemed possible that such patients might not be gaining maximum benefit, and since the recently developed pressurized aerosols are expensive, it was thought reasonable to examine in more detail the use and effect of inhaled bronchodilators in out-patients routinely attending a chest department. ProcedureForty-six subjects were studied.They were a consecutive series of patients who had used sprays for periods varying from twelve years to one month, seen personally in the course of routine out-patient sessions.Each answered a standard questionary, the main purpose of which was to elicit the total amount of bronchodilator used by the patients and its subjective effect.Dyspnoea was graded by the same questions as those used in the M.R.C.
β-Catenin Promotes Survival of Renal Epithelial Cells by Inhibiting Bax
Authors: Zhiyong Wang, Andrea Havasi, Jonathan M. Gall, Haiping Mao, John H. Schwartz, Steven C. Borkan
Journal: Journal of the American Society of Nephrology (2009)

Ischemia activates Bax, a proapoptotic BCL2 protein, as well as the prosurvival beta-catenin/Wnt signaling pathway. To test the hypothesis that beta-catenin/Wnt signaling regulates Bax-mediated apoptosis after induction of metabolic stress, which occurs during renal ischemia, we infected immortalized and primary proximal tubular epithelial cells with adenovirus to express either constitutively active or dominant negative beta-catenin constructs. Constitutively active beta-catenin significantly decreased apoptosis and improved cell survival after metabolic stress. Furthermore, active beta-catenin decreased Bax activation, oligomerization, and translocation to mitochondria, and reduced both organelle membrane injury and apoptosis. Dominant negative beta-catenin had the opposite effects. Because Akt regulates Bax, we examined the effects of the beta-catenin mutants on Akt expression and activation. Constitutively active beta-catenin increased Akt-1 expression and activation before and after stress, and treatment with a phosphatidylinositol-3 kinase inhibitor antagonized the protective effects of beta-catenin on Akt activation, Bax inhibition, and cell survival. In addition, beta-catenin significantly increased the rate of phosphorylation at Bax serine(184), an Akt-specific target. Taken together, these results suggest that beta-catenin/Wnt signaling promotes survival of renal epithelial cells after metabolic stress, in part by inhibiting Bax in a phosphatidylinositol-3 kinase/Akt-dependent manner.
Improved survival in COPD: reasons for hope
Authors: D. W Mapel
Journal: Thorax (2010)

Not long ago treatment of chronic obstructive pulmonary disease (COPD) was viewed with a sense of nihilism.1 Patients were chronically and irreversibly debilitated. Treatments brought only brief palliative relief, and most had serious side effects. Worst of all, many patients were hopelessly addicted to nicotine, and the frustration of watching patient after patient continue to destroy their lungs in spite of their warnings caused many doctors to give up on even diagnosing the disease. Sceptics could point to the relative lack of efficacy of inhaled steroids in COPD. Cynics could question the motives of those who want to help persons who have destroyed their own health.

The last decade has seen the introduction of new treatments for COPD, which in turn have brought a new perspective and sense of energy.1 It is not uncommon in medicine that the discovery of new treatments results in a surge of new interest in a disease. Many examples of this phenomenon are notable in recent history: sleep apnoea, pulmonary hypertension and erectile dysfunction are but a few. The release of the long-acting anticholinergic drug tiotropium, the approval of combined long-acting β2 agonist/corticosteroid inhalers for COPD, development of new nebulised agents and release of innovative medications for nicotine addiction have provided us with new effective tools for COPD. Advocacy groups for COPD have multiplied and grown worldwide. In countries where it is allowed, …
'Refusing treatment--please see': an analysis of capacity assessments carried out by a liaison psychiatry service
Authors: G. Ranjith, M. Hotopf
Journal: Journal of the Royal Society of Medicine (2004)

The assessment of capacity to consent to a healthcare decision is an important part of day-to-day work in general hospitals.The role of liaison psychiatric services in assessment of capacity has not been well studied in British practice.We looked at all such referrals (35) to a liaison psychiatric service in a teaching hospital in the course of one year.The commonest referrals were regarding capacity to consent to a therapeutic procedure, followed by postdischarge placement and ability to self-discharge.Organic mental disorders were the most frequent cause of incapacity.20 (57%) of the referrals were for patients who had refused the intervention in question, and in 12 of these the contentious issue was resolved.Liaison psychiatric services can be useful not only in offering a second opinion or clarifying the influence of psychopathology on decision-making ability but also mediating between the patient and the clinical team.
BACE1 gene variants do not influence BACE1 activity, levels of APP or Aβ isoforms in CSF in Alzheimer's disease
Authors: Annica Sjölander, Henrik Zetterberg, Ulf Andreasson, Lennart Minthon, Kaj Blennow
Journal: Molecular Neurodegeneration (2010)

The BACE1 gene encodes the beta-site APP-cleaving enzyme 1 and has been associated with Alzheimer's disease (AD). BACE1 is the most important β-secretase responsible for the generation of Alzheimer-associated amyloid β-proteins (Aβ) and may play a role in the amyloidogenic process in AD. We hypothesized that BACE1 gene variants might influence BACE1 activity or other markers for APP metabolism in the cerebrospinal fluid (CSF) and thereby contribute to the development of AD. We genotyped a Swedish sample of 269 AD patients for the rs638405 single nucleotide polymorphism (SNP) in the BACE1 gene and correlated genotype data to a broad range of amyloid-related biomarkers in CSF, including BACE1 activity, levels of Aβ40, Aβ42, α- and β-cleaved soluble APP (α-sAPP and β-sAPP), as well as markers for Alzheimer-type axonal degeneration, i.e., total-tau and phospho-tau181. Gene variants of BACE1 were neither associated with amyloid-related biomarkers, nor with markers for axonal degeneration in AD.
Effect of Sunscreens on UV Radiation-Induced Enhancement of Melanoma Growth in Mice
Authors: P. Wolf, C. K. Donawho, M. L. Kripke
Journal: JNCI Journal of the National Cancer Institute (1994)

Background : Epidemiologic evidence suggests that exposure to UV radiation plays a significant role in the development of melanoma skin cancers. As early surgical removal of the melanoma is the only effective therapy, current strategies for reducing mortality from melanoma focus on prevention of the disease. Chemical sunscreens protect mice from development of skin cancers that resemble sunlight-induced human squamous cell cancers, but there appears to be a complex relationship between UV radiation exposure and development of melanoma. Purpose: We asked whether common sunscreens would protect mice against UV radiation-induced enhancement of melanoma incidence. Methods: C3H mice were exposed to 4.8 kJ/m 2 UVB from FS40 sunlamps twice a week for 3 weeks. Sunscreens containing 7.5% 2 -ethylhexyl-p- methoxycinnamate, 8% octyl-N-dimethyl-p- aminobenzoate, 6% benzophenone-3, or the oil-in-water vehicle alone were applied to the ears and tails of the mice 20 minutes before irradiation. At various times during and after exposure, we determined UV radiation-induced inflamation by measuring ear swelling. We also examined the ears histologically for UV radiation-induced alterations. One day after the final irradiation, 2.5 ×10 4 syngeneic K1735 melanoma cells were injected into the external ears. Mice were examined weekly for tumor growth for 5–8 weeks after tumor cell injection. Control mice were treated in the identical way except for exposure to UV radiation. Results : The incidence of melanomas was significantly higher in the UV-irradiated mice. All three sunscreens protected against UV radiation-induced ear swelling and clearly diminished histopathologic alterations, including sunburn cell formation, epidermal hyperplasia, and mono-nuclear cell infiltrate in the dermis. However, the sunscreens failed to protect against UV radiation-induced increase in melanoma incidence. The sunscreens or vehicle alone did not significantly alter tumor growth. Conclusions: Protection against sunburn does not necessarily imply protection against other possible UV radiation effects, such as enhanced melanoma growth. Implications: Sunscreen protection against UV radiation-induced inflammation may encourage prolonged exposure to UV radiation and thus may actually increase the risk of melanoma development. These findings suggest that further research on the ability of sunscreens to prevent melanoma is urgently needed. [J Natl Cancer Inst 86: 99−105, 1994].
The Arrest of Growth in Four Cases of Cancer by a Powerful Interrupted Voltaic Current
Authors: J. I. Parsons
Journal: BMJ (1889)

kindly sent to me by Dr. Potter, of Kensington Infirmary).Family: five children, no miscarriages; last child 14 years.Past History: Two years ago she had a lump taken out of the upper part of the right breast at the Cancer Hospital.It recurred in twelve months' time, and has continued to grow since.She suffered no pain, or very little, from it.Present Condition: At the upper part of the right breast there is a small, hard, nodular mass, about 2 inches long and 1 inclh broad.The skin over it is movable, but not freely so; it is attached to the pectoralis major and surrounding tissues, but it is not adherent to the ribs.There is no enlargement of the axillary or other glands.January 18th, 1889.Interrupted voltaic current was applied to the growth, strength 600 milliamperes.January 20th.Patient has experienced no pain or other ill effect from the current, and can go home.March 12th.The growth appears to have shrunk, and she has no pain and no enlarged glands.
A phenotypic screening platform to identify small molecule modulators of Chlamydomonas reinhardtii growth, motility and photosynthesis
Authors: Simon E Alfred, Anuradha Surendra, Chris Le, Ken Lin, Alexander Mok, Iain M Wallace, Michael Proctor, Malene L Urbanus, Guri Giaever, Corey Nislow
Journal: Genome biology (2012)

Chemical biology, the interfacial discipline of using small molecules as probes to investigate biology, is a powerful approach of developing specific, rapidly acting tools that can be applied across organisms. The single-celled alga Chlamydomonas reinhardtii is an excellent model system because of its photosynthetic ability, cilia-related motility and simple genetics. We report the results of an automated fitness screen of 5,445 small molecules and subsequent assays on motility/phototaxis and photosynthesis. Cheminformatic analysis revealed active core structures and was used to construct a naïve Bayes model that successfully predicts algal bioactive compounds.
Molecular Pathways: Multimodal Cancer-Killing Mechanisms Employed by Oncolytic Vesiculoviruses
Authors: Douglas J. Mahoney, David F. Stojdl
Journal: Clinical Cancer Research (2012)

Cancer is a heterogeneous disease that, for the most part, is not effectively managed with existing therapies. Oncolytic viruses are an attractive class of experimental cancer medicine because, unlike conventional chemotherapeutic and molecularly targeted drugs, they orchestrate tumor cell death in multiple ways simultaneously. In this review, we discuss the numerous cancer-killing "pathways" marshalled by oncolytic vesiculoviruses. From directly infecting and lysing malignant cells, to engaging the host's innate and adaptive anticancer immune responses, to inducing vascular collapse within a tumor, oncolytic vesiculovirus therapy commandeers a coordinated, multipronged assault on cancer that is curative in numerous preclinical models. And as our appreciation of these mechanisms has progressed, so has our capacity to engineer improved outcomes. Notably, efforts to polarize the host's immune system toward the tumor and away from the virus have been particularly effective in immunocompetent murine models, and hold tremendous therapeutic promise for human patients. With a first-in-man phase I trial recently initiated in the United States, the clinical significance of oncolytic vesiculorivus therapy, after nearly 15 years of development, may soon come into focus.
Progressive familial intrahepatic cholestasis types 1, 2, and 3
Authors: P L M JANSEN, M M MÜLLER
Journal: Gut (1998)

Progressive familial intrahepatic cholestasis (PFIC) is a group of diseases characterised by cholestasis and biliary cirrhosis. Byler disease, the best known member of this group, is now also known as PFIC type 1. Byler disease is named after Jacob Byler, a farmer of Amish ancestry, who settled in Pennsylvania in the late 18th century. Patients have recurrent and later persistent cholestasis.1The recurrent disease pattern is reminiscent of benign recurrent intrahepatic cholestasis (BRIC). In contrast to BRIC, Byler disease eventually evolves into biliary cirrhosis. Clinically the disease is characterised by jaundice, steatorrhoea, reduced growth, and a relatively low to normal serum γ-glutamyltranspeptidase (γGT) activity despite an elevated alkaline phosphatase. Positional cloning studies in a large Byler kindred revealed a mutation in a locus at chromosome 18q21-q22, the FIC1 locus.2-4 In their recent paper in Nature Genetics Bull et al suggest that this mutation affects a member of a subfamily of P-type ATPases; other members of this subfamily seem to be involved in ATP dependent aminophospholipid transport. FIC1 is expressed in several epithelial tissues and more strongly in the intestine than in the liver. Patients with this disease have high serum bile salt concentrations. Disturbed hepatobiliary (and perhaps intestinal) transport of bile salts is the most likely cause. How this relates to a P-type ATPase, possibly mediating aminophospholipid transport, is currently unknown. As expected, BRIC is genetically related to Byler disease as FIC1 is also mutated in BRIC patients, confirming earlier reports.4-6 

Another form of …
Treponema pallidum receptor binding proteins interact with fibronectin.
Authors: K M Peterson, J B Baseman, J F Alderete
Journal: The Journal of Experimental Medicine (1983)

Analysis of plasma proteins avidly bound to T. pallidum surfaces revealed the ability of T. pallidum to acquire numerous host macromolecules. No acquisition was evident by the avirulent spirochete, T. phagedenis biotype Reiter. Western blotting technology using hyperimmune antifibronectin serum as a probe revealed the ability of virulent treponemes to avidly bind fibronectin from a complex medium such as plasma. The specificity of the tiplike adherence of motile T. pallidum to fibronectin-coated glass surfaces and to fibronectin on HEp-2 cells was reinforced by the observation that pretreatment of coverslips or cell monolayers with monospecific antiserum against fibronectin substantially reduced T. pallidum attachment. The stoichiometric binding of T. pallidum to fibronectin-coated coverslips and the inability of unlabeled or 35S-radiolabeled treponemes to interact with glass surfaces treated with other plasma proteins further established the specific nature of the interaction between virulent T. pallidum and fibronectin. The avid association between three outer envelope proteins of T. pallidum and fibronectin was also demonstrated. These treponemal surface proteins have been previously identified as putative receptor-binding proteins responsible for T. pallidum parasitism of host cells. The data suggest that surface fibronectin mediates tip-oriented attachment of T. pallidum to host cells via a receptor-ligand mechanism of recognition.
Genome-Wide Associations and Functional Genomic Studies of Musculoskeletal Adverse Events in Women Receiving Aromatase Inhibitors
Authors: James N. Ingle, Daniel J. Schaid, Paul E. Goss, Mohan Liu, Taisei Mushiroda, Judy-Anne W. Chapman, Michiaki Kubo, Gregory D. Jenkins, Anthony Batzler, Lois Shepherd, Joseph Pater, Liewei Wang, Matthew J. Ellis, Vered Stearns, Daniel C. Rohrer, Matthew P. Goetz, Kathleen I. Pritchard, David A. Flockhart, Yusuke Nakamura, Richard M. Weinshilboum
Journal: Journal of Clinical Oncology (2010)

We performed a case-control genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) associated with musculoskeletal adverse events (MS-AEs) in women treated with aromatase inhibitors (AIs) for early breast cancer.A nested case-control design was used to select patients enrolled onto the MA.27 phase III trial comparing anastrozole with exemestane. Cases were matched to two controls and were defined as patients with grade 3 or 4 MS-AEs (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v3.0) or those who discontinued treatment for any grade of MS-AE within the first 2 years. Genotyping was performed with the Illumina Human610-Quad BeadChip.The GWAS included 293 cases and 585 controls. A total of 551,358 SNPs were analyzed, followed by imputation and fine mapping of a region of interest on chromosome 14. Four SNPs on chromosome 14 had the lowest P values (2.23E-06 to 6.67E-07). T-cell leukemia 1A (TCL1A) was the gene closest (926-7000 bp) to the four SNPs. Functional genomic studies revealed that one of these SNPs (rs11849538) created an estrogen response element and that TCL1A expression was estrogen dependent, was associated with the variant SNP genotypes in estradiol-treated lymphoblastoid cells transfected with estrogen receptor alpha and was directly related to interleukin 17 receptor A (IL17RA) expression.This GWAS identified SNPs associated with MS-AEs in women treated with AIs and with a gene (TCL1A) which, in turn, was related to a cytokine (IL17). These findings provide a focus for further research to identify patients at risk for MS-AEs and to explore the mechanisms for these adverse events.
Claudin-1 expression in airway smooth muscle exacerbates airway remodeling in asthmatic subjects
Authors: Hiroyuki Fujita, Maciej Chalubinski, Claudio Rhyner, Philippe Indermitte, Norbert Meyer, Ruth Ferstl, Angela Treis, Enrique Gomez, Ahmet Akkaya, Liam O’Mahony, Mübeccel Akdis, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2011)
Lung cancer screening feasibility in Australia
Authors: Henry M. Marshall, Rayleen V. Bowman, John Ayres, Jane Crossin, Melanie Lau, Richard E. Slaughter, Stanley Redmond, Linda Passmore, Elizabeth McCaul, Deborah Courtney, Steven C. Leong, Morgan Windsor, Paul V. Zimmerman, Ian A. Yang, Kwun M. Fong
Journal: European Respiratory Journal (2015)

The National Lung Screening Trial (NLST) reported a 20% relative reduction in lung cancer-specific mortality using low-dose computed tomography (LDCT) screening [1]. US Preventative Services Task Force modelling [2] illustrates the potentially large benefits of screening, yet nationwide population-based screening has not been adopted. Controversial issues include high false positivity, and uncertain cost-effectiveness and relative applicability to different settings and countries [3–6]. The Queensland Lung Cancer Screening Study (QLCSS) is the first study to assess NLST screening protocol feasibility in Australia. Low-dose CT screening using the NLST protocol appears feasible in the Australian health setting <http://ow.ly/JwtU2>
2B4 Acts As a Non–Major Histocompatibility Complex Binding Inhibitory Receptor on Mouse Natural Killer Cells
Authors: Kyung-Mi Lee, Megan E. McNerney, Susan E. Stepp, Porunelloor A. Mathew, John D. Schatzle, Michael Bennett, Vinay Kumar
Journal: The Journal of Experimental Medicine (2004)

Natural killer (NK) cells are critical in the immune response to tumor cells, virally infected cells, and bone marrow allografts. 2B4 (CD244) is expressed on all NK cells and the ligand for 2B4, CD48, is expressed on hematopoietic cells. Cross-linking 2B4 on NK cells with anti-2B4 monoclonal antibody leads to NK cell activation in vitro. Therefore, 2B4 is considered to be an activating receptor. Surprisingly, we have found, using antibody-blocking and 2B4-deficient NK cells, that NK lysis of CD48+ tumor and allogeneic targets is inhibited by 2B4 ligation. Interferon γ production by NK cells is also inhibited. Using a peritoneal tumor clearance assay, it was found that 2B4−/− mice have increased clearance of CD48+ tumor cells in vivo. Retroviral transduction of 2B4 was sufficient to restore inhibition in 2B4−/− primary NK cells. It was found that although mature NK cells express SH2D1A, in vitro–derived NK cells do not. However, both populations are inhibited by 2B4 ligation. This indicates that 2B4 inhibitory signaling occurs regardless of the presence of SH2D1A. These findings reveal a novel role for 2B4 as a non–major histocompatibility complex binding negative regulator of NK cells.
882-2 Effects of avasimibe on coronary atherosclerosis assessed by intravascular ultrasound
Authors: Jean-Claude Tardif, Jean Gregoire, Jacques Lesperance, Josep Rodes, Todd Anderson, Eric Cohen, Olivier Bertrand, Michel Lemay, Fernando Alfonso, Francois Reeves, Lawrence Title, Alita Hassan, Richard McLain, Milton Pressler, Philippe L L'Allier
Journal: Journal of the American College of Cardiology (2004)