tbuckley/cabot-search huggingface dataset:
Patients with COPD: do we fail them from beginning to end?
Authors: M R Partridge
Journal: Thorax (2003)

Respiratory physicians should take some responsibility for what could be regarded as the neglect of patients with COPD and need to raise the profile of the disease with governments and funding bodies. The aim is to prevent its cause, modify its natural history, focus research and ensure the implementation of all measures that may reduce the suffering.

In the UK 17 500 men and 14 500 women die every year from chronic obstructive pulmonary disease (COPD). Work reported in this issue of Thorax suggests that these figures are likely to be falsely low.1 The published death rate compares with 13 000 women dying of breast cancer and 9500 men dying of prostate cancer every year. Both of the latter two diseases now attract much publicity, considerable research expenditure and, for breast cancer at least, a very expensive health service screening programme, the value of which is continually debated. Globally, COPD is the fourth or fifth leading cause of death and both morbidity and mortality are predicted to rise. The World Health Organisation (WHO) is one of the few organisations to have recognised the impending burden of this disease to both the individual and to society, publishing both a consultation document on the development of a comprehensive approach for the prevention and control of respiratory disease2 and also an implementation strategy.3 At a national level few countries have health initiatives to help those with COPD, and perhaps the respiratory fraternity should take some responsibility for what could be regarded as the neglect of this group of patients—neglect not necessarily at the level of personal care, but neglect in terms of failure to ensure that governments and health departments resource the necessary care, and resource research into better management.

In what areas might we have failed these patients? “I …
POTENTIATION OF PRESSOR EFFECTS OF NOR-EPINEPHRINE AND EPINEPHRINE IN MAN BY DESOXYCORTICOSTERONE ACETATE 1
Authors: W. Raab, R. J. Humphreys, E. Lepeschkin
Journal: Journal of Clinical Investigation (1950)

In connection with the problem of the possible role played by the sympathomimetic neurohormones (nor-epinephrine and epinephrine) in the pathogenesis of essential hypertension, interest has been focused lately on substances which are capable of abnormally intensifying the vasoconstrictor power of epinephrine in the mesentery of the rat and the perfused rabbit's ear, such as the chemically undefined agent  which originates in the kidney (1) and protein fractions, extracted from the kidneys and other tissues, as well as hypertensin and tyrosin (2). A participation of adrenal cortical steroids in such sensitizing mechanisms is suggested by the restoration of the impaired VEM formation in the
Tumour necrosis factor‐α induced CD70 and interleukin‐7R mRNA expression in BEAS‐2B cells
Authors: K. Wolf, C. Schulz, G.A.J. Riegger, M. Pfeifer
Journal: European Respiratory Journal (2002)

Over the past few years, evidence has emerged for the potential role of the human bronchial epithelial cell in the initiation and progress of inflammation of the airway. Thus, the aim of this study was to investigate the expression pattern of cytokines and immunomodulatory factors in the human bronchial epithelial cell. To elucidate this highly complex expression and regulation pattern, the simian virus‐40 transformed human bronchial-epithelial cell line BEAS‐2B was stimulated with human recombinant tumour necrosis factor (hrTNF)‐α (10 ng·mL −1 (specific activity, 2.86×10 7 U·mg −1 )) and messenger ribonucleic acid (mRNA) expression pattern was analysed by complementary deoxyribonucleic acid (cDNA) array analysis. Among 375 arrayed cDNA clones, 173 (46%) were detected in BEAS‐2B cells. The levels of expression of 17 genes, including those of monocyte chemoattractant protein (MCP)‐1, intercellular adhesion molecule (ICAM)‐1, growth-related oncogene (GRO) α, β, γ, interleukin (IL)‐7 receptor, CD70, IL‐6, IL‐8, granulocyte-macrophage colony-stimulating factor (GM‐CSF) and regulated in activation, normal T‐cell expressed and secreted (RANTES) were elevated after TNF‐α stimulation. The differential character of 12 clones was further characterised and verified by real time polymerase chain reaction (PCR) analysis of total ribonucleic acid (RNA) isolated from BEAS‐2B cells after 4 or 16 h incubation with increasing TNF‐α concentrations (1 pg–10 ng·mL −1 ). The authors semiquantified concentration-dependent mRNA upregulation of cytokines and immunology factors identified in the array and could determine threshold values of mRNA increases at 10 pg·mL −1 –1 ng·mL −1 TNF‐α by real-time PCR. For CD70 (CD27 ligand) and interleukin‐7 receptor, which to the best of the author's knowledge have not yet been described in the human bronchial epithelial cell, a rapid and continuous messenger ribonucleic acid increase induced by 100 pg·mL −1 tumour necrosis factor‐α after only 60–90 min was shown. A potential role for these genes in the inflammatory process in the human bronchial epithelial cell is proposed.
The Epidemiology of Firearm Violence in the Twenty-First Century United States
Authors: Garen J. Wintemute
Journal: Annual Review of Public Health (2014)

This brief review summarizes the basic epidemiology of firearm violence, a large and costly public health problem in the United States for which the mortality rate has remained unchanged for more than a decade. It presents findings for the present in light of recent trends. Risk for firearm violence varies substantially across demographic subsets of the population and between states in patterns that are quite different for suicide and homicide. Suicide is far more common than homicide and its rate is increasing; the homicide rate is decreasing. As with other important health problems, most cases of fatal firearm violence arise from large but low-risk subsets of the population; risk and burden of illness are not distributed symmetrically. Compared with other industrialized nations, the United States has uniquely high mortality rates from firearm violence.
Delivering affordable cancer care in high-income countries
Authors: Richard Sullivan, Jeffrey Peppercorn, Karol Sikora, John Zalcberg, Neal J Meropol, Eitan Amir, David Khayat, Peter Boyle, Philippe Autier, Ian F Tannock, Tito Fojo, Jim Siderov, Steve Williamson, Silvia Camporesi, J Gordon McVie, Arnie D Purushotham, Peter Naredi, Alexander Eggermont, Murray F Brennan, Michael L Steinberg, Mark De Ridder, Susan A McCloskey, Dirk Verellen, Terence Roberts, Guy Storme, Rodney J Hicks, Peter J Ell, Bradford R Hirsch, David P Carbone, Kevin A Schulman, Paul Catchpole, David Taylor, Jan Geissler, Nancy G Brinker, David Meltzer, David Kerr, Matti Aapro
Journal: The Lancet Oncology (2011)
MOTOR CARS FOR MEDICAL MEN: FINAL IMPRESSIONS OF THE MOTOR SHOW
Authors: H. M. Buist
Journal: BMJ (1925)

gE~~~~~~~~~~~~~~)tDIC*L JOU*NA beginning with the forms of life witlh which the student is most familiar and worlks out from this in both directions.It appears thiat this method of presentationlhas been appreciated by the students the authoir teaches, judging from his remarksIn the preface to this edition.Dr. RICHIARD HI.HUNTER'S Short History of Anatomy,9 which is intended for inedical stu(lents enteringy on their anatomical course, fulfills its purpose well.It gives a concise and read- able account of the subject fromn the time of Hippocrates to the passing of the Anatomy Act in 1832.The student will not only learn from this boolk something about Herophilus, Galen, Sylvius, Vesalius, Fallopius, the Hunters, and the Monros, to nmention only those who have given their name to some anatomical structure, but will also gain a clear idea of the difficulties with which the early anatomists had to contend.The workli is to be warmly recommended to the student who
Risk HLA-DQA1 and PLA<sub>2</sub>R1 Alleles in Idiopathic Membranous Nephropathy
Authors: H.C. Stanescu, M. Arcos-Burgos, A. Medlar, D. Bockenhauer, A. Kottgen, L. Dragomirescu, C. Voinescu, N. Patel, K. Pearce, M. Hubank, H.A.F. Stephens, V. Laundy, S. Padmanabhan, A. Zawadzka, J.M. Hofstra, M.J.H. Coenen, M. den Heijer, L.A.L.M. Kiemeney, D. Bacq-Daian, B. Stengel, S.H. Powis, P. Brenchley, J. Feehally, A.J. Rees, H. Debiec, J.F.M. Wetzels, P. Ronco, P.W. Mathieson, R. Kleta
Journal: New England Journal of Medicine (2011)

Idiopathic membranous nephropathy is a major cause of the nephrotic syndrome in adults, but its etiologic basis is not fully understood. We investigated the genetic basis of biopsy-proven cases of idiopathic membranous nephropathy in a white population.We performed independent genomewide association studies of single-nucleotide polymorphisms (SNPs) in patients with idiopathic membranous nephropathy from three populations of white ancestry (75 French, 146 Dutch, and 335 British patients). The patients were compared with racially matched control subjects; population stratification and quality controls were carried out according to standard criteria. Associations were calculated by means of a chi-square basic allele test; the threshold for significance was adjusted for multiple comparisons (with the Bonferroni method).In a joint analysis of data from the 556 patients studied (398 men), we identified significant alleles at two genomic loci associated with idiopathic membranous nephropathy. Chromosome 2q24 contains the gene encoding M-type phospholipase A(2) receptor (PLA(2)R1) (SNP rs4664308, P=8.6×10(-29)), previously shown to be the target of an autoimmune response. Chromosome 6p21 contains the gene encoding HLA complex class II HLA-DQ alpha chain 1 (HLA-DQA1) (SNP rs2187668, P=8.0×10(-93)). The association with HLA-DQA1 was significant in all three populations (P=1.8×10(-9), P=5.6×10(-27), and P=5.2×10(-36) in the French, Dutch, and British groups, respectively). The odds ratio for idiopathic membranous nephropathy with homozygosity for both risk alleles was 78.5 (95% confidence interval, 34.6 to 178.2).An HLA-DQA1 allele on chromosome 6p21 is most closely associated with idiopathic membranous nephropathy in persons of white ancestry. This allele may facilitate an autoimmune response against targets such as variants of PLA2R1. Our findings suggest a basis for understanding this disease and illuminate how adaptive immunity is regulated by HLA.
Acute myeloid leukemia and lung cancer occurring in a chronic lymphocytic leukemia patient treated with fludarabine and autologous peripheral blood stem-cell transplantation
Authors: G. Meloni, A. Proia, V. Guerrisi, I. Cordone, R. De Cuia, S. Fenu, F.R. Mauro, E. Pescarmona, G. Reato, F. Mandelli
Journal: Annals of Oncology (2000)
Stimulation of primary in vitro IgE antibody responses in culture of human peripheral mononuclear cells.
Authors: M Nonaka, B L Zuraw, C H O'Hair, D H Katz
Journal: The Journal of Experimental Medicine (1981)

Experiments are presented herein that demonstrate the capacity to stimulate human peripheral mononuclear cells to synthesize and secrete significant quantities of IgE molecules in vitro by exposure to appropriate concentrations of 2,4-dinitrophenyl (DNP)-protein conjugates, pokeweed mitogen (PWM), or a combination of DNP-proteins and PWM. Cultures stimulated in this fashion synthesize increased quantities of both total IgE and DNP-specific IgE antibody molecules. This in vitro human IgE antibody system should provide a useful tool for further exploration of regulatory control of IgE responses in both normal humans and those manifesting various forms of IgE-mediated allergic disorders.
Pathology of Melanoma
Authors: David E. Elder
Journal: Clinical Cancer Research (2006)

Abstract The purposes of pathologic examination of a lesion suspected of being a malignant melanoma are to provide an accurate diagnosis of melanoma (or not), and to provide prognostic information useful in the clinical management of the patient. In the near future, pathologic attributes will also likely be used to predict responses to therapy, as a guide to the selection of specific therapeutic agents such as “small molecule” inhibitors of signaling pathways.
The role of uncoupling protein 3 in human physiology
Authors: W. Timothy Garvey
Journal: Journal of Clinical Investigation (2003)

Obesity is simply understood as an imbalance between energy intake and expenditure in favor of weight accretion.However, the human biological interface between food consumption and energy dissipation results in broad individual differences in eating behavior, physical activity, and efficiency of fuel storage and metabolism.In particular, the basal metabolic rate, which accounts for the greatest portion of overall energy expenditure, can vary almost twofold among individuals.Classically, three major biochemical systems are believed to contribute to basal thermogenesis: futile cycles, Na + /K + ATPase activity, and mitochondrial proton leak.The latter is the most important quantitative contributor and can explain up to 50% of the basal metabolic rate (1).The molecular basis of mitochondrial proton leak is unclear, despite its importance in the understanding of energy balance and its potential as a therapeutic target for obesity treatment.The article by Hesselink and colleagues in this issue of the JCI (2) addresses whether uncoupling protein 3 contributes to mitochondrial proton leak in human skeletal muscle.
Current misunderstandings in the management of ulcerative colitis
Authors: T. Ochsenkuhn, G. D'Haens
Journal: Gut (2011)

Past and ongoing therapeutic concepts for ulcerative colitis have only been moderately successful. A significant proportion of patients with ulcerative colitis will still have to undergo colectomy and overall half of the patients do not achieve sustained remission, leading to impairment of physical and mental health, social life, employment issues and sexual activity. Reluctance to treat patients early on with sufficiently potent drug regimens is obvious. Several popular misconceptions might have led to this situation. First, ulcerative colitis is still considered a more 'benign' disease than Crohn9s disease. Furthermore, the general assumption is often that colectomy can 'cure' the disease. Mucosal healing as a therapeutic target has not been widely accepted. Finally, the use of antitumour necrosis factor antibodies in ulcerative colitis has been low because this treatment is considered to be less effective than in Crohn9s disease. In the current review we try to disprove these misunderstandings by discussing relevant studies showing how harmful this disease can be and explaining why future studies targeting sustained suppression of inflammation could have an enormous impact on the natural course of the disease. Until these studies are available, we encourage physicians to intensify and maintain treatment until sustained remission and mucosal healing has been reached.
Hormone therapy and cognitive function
Authors: P. M. Maki, E. Sundermann
Journal: Human Reproduction Update (2009)

Clinical trials yield discrepant information about the impact of hormone therapy on verbal memory and executive function. This issue is clinically relevant because declines in verbal memory are the earliest predictor of Alzheimer's disease and declines in executive function are central to some theories of normal, age-related changes in cognition. We conducted a systematic review of randomized clinical trials of hormone therapy (i.e. oral, transdermal, i.m.) and verbal memory, distinguishing studies in younger (i.e. ≤65 years of age; n = 9) versus older (i.e. >65 years; n = 7) women and studies involving estrogen alone versus estrogen plus progestogen. Out of 32 placebo-controlled trials, 17 were included (13 had no verbal memory measures and 2 involved cholinergic manipulations). We also provide a narrative review of 25 studies of executive function (two trials), since there are insufficient clinical trial data for systematic review. There is some evidence for a beneficial effect of estrogen alone on verbal memory in younger naturally post-menopausal women and more consistent evidence from small-n studies of surgically post-menopausal women. There is stronger evidence of a detrimental effect of conjugated equine estrogen plus medroxyprogesterone acetate on verbal memory in younger and older post-menopausal women. Observational studies and pharmacological models of menopause provide initial evidence of improvements in executive function with hormone therapy. Future studies should include measures of executive function and should address pressing clinical questions; including what formulation of combination hormone therapy is cognitively neutral/beneficial, yet effective in treating hot flashes in the early post-menopause.
MHC Class II Expression Restricted to CD8α+ and CD11b+ Dendritic Cells Is Sufficient for Control of <i>Leishmania major </i>
Authors: Maria P. Lemos, Fatima Esquivel, Phillip Scott, Terri M. Laufer
Journal: The Journal of Experimental Medicine (2004)

Control of the intracellular protozoan, Leishmania major, requires major histocompatibility complex class II (MHC II)–dependent antigen presentation and CD4+ T cell T helper cell 1 (Th1) differentiation. MHC II–positive macrophages are a primary target of infection and a crucial effector cell controlling parasite growth, yet their function as antigen-presenting cells remains controversial. Similarly, infected Langerhans cells (LCs) can prime interferon (IFN)γ–producing Th1 CD4+ T cells, but whether they are required for Th1 responses is unknown. We explored the antigen-presenting cell requirement during primary L. major infection using a mouse model in which MHC II, I-Aβb, expression is restricted to CD11b+ and CD8α+ dendritic cells (DCs). Importantly, B cells, macrophages, and LCs are all MHC II–negative in these mice. We demonstrate that antigen presentation by these DC subsets is sufficient to control a subcutaneous L. major infection. CD4+ T cells undergo complete Th1 differentiation with parasite-specific secretion of IFNγ. Macrophages produce inducible nitric oxide synthase, accumulate at infected sites, and control parasite numbers in the absence of MHC II expression. Therefore, CD11b+ and CD8α+ DCs are not only key initiators of the primary response but also provide all the necessary cognate interactions for CD4+ T cell Th1 effectors to control this protozoan infection.
After the accident, after the ambulance, what kind of care?
Authors: Beverly J. Montgomeryg
Journal: JAMA (1980)

In the past decade and a half, a network of more than 300 trauma care centers has developed as part of the national Emergency Medical Services system. The result is that standards for such care are becoming more uniform. Mortality for accidents that maim has dropped, and highway accidents and burn injuries in general have received much special attention. At the recent American College of Surgeons meeting in Chicago, a multi-day symposium on trauma care attracted much of the membership. Chairman of the symposium was Robert J. Freeark, MD, of Loyola University of Chicago's Stritch School of Medicine. Among other topics, the aftermath of high-speed collision injuries was discussed. <h3>The Contused Lung and Fluid Resuscitation</h3> "One of the big issues in trauma care is whether to use albumin for fluid resuscitation," Freeark told<i>JAMA</i>MEDICAL NEWS. "Neurosurgeons keep telling us we need albumin. But the issue is controversial. Albumin is
In vivo measurement of apolipoprotein E from the brain interstitial fluid using microdialysis
Authors: Jason D Ulrich, Jack M Burchett, Jessica L Restivo, Dorothy R Schuler, Philip B Verghese, Thomas E Mahan, Gary E Landreth, Joseph M Castellano, Hong Jiang, John R Cirrito, David M Holtzman
Journal: Molecular Neurodegeneration (2013)

Abstract Background The APOE4 allele variant is the strongest known genetic risk factor for developing late-onset Alzheimer’s disease. The link between apolipoprotein E (apoE) and Alzheimer’s disease is likely due in large part to the impact of apoE on the metabolism of amyloid β (Aβ) within the brain. Manipulation of apoE levels and lipidation within the brain has been proposed as a therapeutic target for the treatment of Alzheimer’s disease. However, we know little about the dynamic regulation of apoE levels and lipidation within the central nervous system. We have developed an assay to measure apoE levels in the brain interstitial fluid of awake and freely moving mice using large molecular weight cut-off microdialysis probes. Results We were able to recover apoE using microdialysis from human cerebrospinal fluid (CSF) in vitro and mouse brain parenchyma in vivo . Microdialysis probes were inserted into the hippocampus of wild-type mice and interstitial fluid was collected for 36 hours. Levels of apoE within the microdialysis samples were determined by ELISA. The levels of apoE were found to be relatively stable over 36 hours. No apoE was detected in microdialysis samples from apoE KO mice. Administration of the RXR agonist bexarotene increased ISF apoE levels while ISF Aβ levels were decreased. Extrapolation to zero-flow analysis allowed us to determine the absolute recoverable concentration of apoE3 in the brain ISF of apoE3 KI mice. Furthermore, analysis of microdialysis samples by non-denaturing gel electrophoresis determined lipidated apoE particles in microdialysis samples were consistent in size with apoE particles from CSF. Finally, we found that the concentration of apoE in the brain ISF was dependent upon apoE isoform in human apoE KI mice, following the pattern apoE2&gt;apoE3&gt;apoE4. Conclusions We are able to collect lipidated apoE from the brain of awake and freely moving mice and monitor apoE levels over the course of several hours from a single mouse. Our technique enables assessment of brain apoE dynamics under physiological and pathophysiological conditions and in response to therapeutic interventions designed to affect apoE levels and lipidation within the brain.
Affect and non-uniform characteristics of predictive processing in musical behaviour
Authors: Rebecca S. Schaefer, Katie Overy, Peter Nelson
Journal: Behavioral and Brain Sciences (2013)

Abstract The important roles of prediction and prior experience are well established in music research and fit well with Clark's concept of unified perception, cognition, and action arising from hierarchical, bidirectional predictive processing. However, in order to fully account for human musical intelligence, Clark needs to further consider the powerful and variable role of affect in relation to prediction error.
The New Public Health Litigation
Authors: W. E. Parmet, R. A. Daynard
Journal: Annual Review of Public Health (2000)

▪ Abstract In recent years there has been an increasing use of litigation as a public health tool. Litigation has been brought to advance policies concerning such matters as tobacco, gun violence, and lead paint. This article discusses this development and the criticism that can be leveled at using litigation to develop public health policy. The article concludes that, although litigation may not always be successful, it can deter dangerous activities and play an important role in advancing the political and social struggle for public health.
Effects of advanced selection methods on sperm quality and ART outcome: a systematic review
Authors: Tamer M. Said, Jolande A. Land
Journal: Human Reproduction Update (2011)

BACKGROUNDCurrent routine semen preparation techniques do not inclusively target all intrinsic sperm characteristics that may impact the fertilization potential. In order to address these characteristics, several methods have been recently developed and applied to sperm selection. The objective of this study was to systematically review the literature describing these advanced sperm selection methods focusing on their anticipated benefits on sperm quality and assisted reproductive technique (ART) outcome.
Telomere shortening is correlated with the DNA damage response and telomeric protein down-regulation in colorectal preneoplastic lesions
Authors: C.M. Raynaud, S.J. Jang, P. Nuciforo, S. Lantuejoul, E. Brambilla, N. Mounier, K.A. Olaussen, F. André, L. Morat, L. Sabatier, J.-C. Soria
Journal: Annals of Oncology (2008)