tbuckley/cabot-search huggingface dataset:
Induction of Melanoma Phenotypes in Human Skin by Growth Factors and Ultraviolet B
Authors: Carola Berking, Richelle Takemoto, Kapaettu Satyamoorthy, Takahashi Shirakawa, Malihe Eskandarpour, Johan Hansson, Patricia A. VanBelle, David E. Elder, Meenhard Herlyn
Journal: Cancer Research (2004)

Abstract Exposure to UV radiation likely plays a key role in melanoma development, whereas other etiologic agents remain unknown. Here we show that in normal human skin an increased expression of a combination of three growth factors, basic fibroblast growth factor, stem cell factor, and endothelin-3, along with exposure to UVB can transform normal melanocytes into a melanoma phenotype within 4 weeks. Invasion of melanoma lesions was found in skin from newborn donors, whereas melanomas in adult skin were of a noninvasive in situ type only. This suggests that susceptibility of skin to exogenous tumor promoters is dependent on age. This is the first report on human cancer initiation in vivo in which an imbalance of physiological factors combined with an environmental carcinogen can lead to transformation of normal tissue.
Living Without Creatine
Authors: Craig A. Lygate, Dunja Aksentijevic, Dana Dawson, Michiel ten Hove, Darci Phillips, Joseph P. de Bono, Debra J. Medway, Liam Sebag-Montefiore, Imre Hunyor, Keith M. Channon, Kieran Clarke, Sevasti Zervou, Hugh Watkins, Robert S. Balaban, Stefan Neubauer
Journal: Circulation Research (2013)

Creatine is thought to be involved in the spatial and temporal buffering of ATP in energetic organs such as heart and skeletal muscle. Creatine depletion affects force generation during maximal stimulation, while reduced levels of myocardial creatine are a hallmark of the failing heart, leading to the widely held view that creatine is important at high workloads and under conditions of pathological stress.We therefore hypothesised that the consequences of creatine-deficiency in mice would be impaired running capacity, and exacerbation of heart failure following myocardial infarction.Surprisingly, mice with whole-body creatine deficiency due to knockout of the biosynthetic enzyme (guanidinoacetate N-methyltransferase [GAMT]) voluntarily ran just as fast and as far as controls (>10 km/night) and performed the same level of work when tested to exhaustion on a treadmill. Furthermore, survival following myocardial infarction was not altered, nor was subsequent left ventricular (LV) remodelling and development of chronic heart failure exacerbated, as measured by 3D-echocardiography and invasive hemodynamics. These findings could not be accounted for by compensatory adaptations, with no differences detected between WT and GAMT(-/-) proteomes. Alternative phosphotransfer mechanisms were explored; adenylate kinase activity was unaltered, and although GAMT(-/-) hearts accumulated the creatine precursor guanidinoacetate, this had negligible energy-transfer activity, while mitochondria retained near normal function.Creatine-deficient mice show unaltered maximal exercise capacity and response to chronic myocardial infarction, and no obvious metabolic adaptations. Our results question the paradigm that creatine is essential for high workload and chronic stress responses in heart and skeletal muscle.
Detection and analysis of alternative splicing in Yarrowia lipolytica reveal structural constraints facilitating nonsense-mediated decay of intron-retaining transcripts
Authors: Meryem Mekouar, Isabelle Blanc-Lenfle, Christophe Ozanne, Corinne Da Silva, Corinne Cruaud, Patrick Wincker, Claude Gaillardin, Cécile Neuvéglise
Journal: Genome biology (2010)

Hemiascomycetous yeasts have intron-poor genomes with very few cases of alternative splicing. Most of the reported examples result from intron retention in Saccharomyces cerevisiae and some have been shown to be functionally significant. Here we used transcriptome-wide approaches to evaluate the mechanisms underlying the generation of alternative transcripts in Yarrowia lipolytica, a yeast highly divergent from S. cerevisiae. Experimental investigation of Y. lipolytica gene models identified several cases of alternative splicing, mostly generated by intron retention, principally affecting the first intron of the gene. The retention of introns almost invariably creates a premature termination codon, as a direct consequence of the structure of intron boundaries. An analysis of Y. lipolytica introns revealed that introns of multiples of three nucleotides in length, particularly those without stop codons, were underrepresented. In other organisms, premature termination codon-containing transcripts are targeted for degradation by the nonsense-mediated mRNA decay (NMD) machinery. In Y. lipolytica, homologs of S. cerevisiae UPF1 and UPF2 genes were identified, but not UPF3. The inactivation of Y. lipolytica UPF1 and UPF2 resulted in the accumulation of unspliced transcripts of a test set of genes. Y. lipolytica is the hemiascomycete with the most intron-rich genome sequenced to date, and it has several unusual genes with large introns or alternative transcription start sites, or introns in the 5' UTR. Our results suggest Y. lipolytica intron structure is subject to significant constraints, leading to the under-representation of stop-free introns. Consequently, intron-containing transcripts are degraded by a functional NMD pathway.
Significance of Hypoxia in Malignant Glioma. Re: Evans et al. Hypoxia is important in the biology and aggression of human glial brain tumors. Clin Cancer Res 2004;10:8177–84
Authors: Dirk Vordermark
Journal: Clinical Cancer Research (2005)

To the Editor: 

I read with great interest the article by Evans et al. ([1][1]), showing that with increasing WHO grade human glioma exhibits tumor hypoxia of increasing severity as determined by analysis of the injected hypoxia marker EF5 on immunistochemistry. At the same time, the intensity of
The Association of Framingham and Reynolds Risk Scores With Incidence and Progression of Coronary Artery Calcification in MESA (Multi-Ethnic Study of Atherosclerosis)
Authors: Andrew P. DeFilippis, Michael J. Blaha, Chiadi E. Ndumele, Matthew J. Budoff, Donald M. Lloyd-Jones, Robyn L. McClelland, Susan G. Lakoski, Mary Cushman, Nathan D. Wong, Roger S. Blumenthal, Joao Lima, Khurram Nasir
Journal: Journal of the American College of Cardiology (2011)
CADMIUM FUME INHALATION AND EMPHYSEMA
Authors: A.G. Davison, A.J. Newman Taylor, J. Darbyshire, D.R. Chettle, C.J.G. Guthrie, D. O'Malley, H.T. Mason, P.M. Fayers, K.M. Venables, C.A.C. Pickering, D. Franklin, M.C. Scott, H. Holden, A.L. Wright, D. Gompertz
Journal: The Lancet (1988)
Upper-Airway Stimulation for Obstructive Sleep Apnea
Authors: Patrick J. Strollo, Ryan J. Soose, Joachim T. Maurer, Nico de Vries, Jason Cornelius, Oleg Froymovich, Ronald D. Hanson, Tapan A. Padhya, David L. Steward, M. Boyd Gillespie, B. Tucker Woodson, Paul H. Van de Heyning, Mark G. Goetting, Olivier M. Vanderveken, Neil Feldman, Lennart Knaack, Kingman P. Strohl
Journal: New England Journal of Medicine (2014)

Obstructive sleep apnea is associated with considerable health risks. Although continuous positive airway pressure (CPAP) can mitigate these risks, effectiveness can be reduced by inadequate adherence to treatment. We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea. Using a multicenter, prospective, single-group, cohort design, we surgically implanted an upper-airway stimulation device in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea-hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ≥15 indicating moderate-to-severe apnea) and the oxygen desaturation index (ODI; the number of times per hour of sleep that the blood oxygen level drops by ≥4 percentage points from baseline). Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawal trial. The study included 126 participants; 83% were men. The mean age was 54.5 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68%, from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy-maintenance group (8.9 and 7.2 events per hour, respectively); the AHI score was significantly higher (indicating more severe apnea) among the 23 participants in the therapy-withdrawal group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure-related serious adverse events was less than 2%. In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea. (Funded by Inspire Medical Systems; STAR ClinicalTrials.gov number, NCT01161420.).
Role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin in guinea-pigs
Authors: C Kuroiwa, E Umeno, H Nogami, S Kano, T Hirose, S Nishima
Journal: European Respiratory Journal (1996)

To elucidate the role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin (Bk), we studied the effects of FK224, a neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonist, on the bronchoconstriction induced by intravenous (i.v.) administration of Bk (5-100 micrograms.kg-1) in guinea-pigs. Total pulmonary resistance -(RL) was measured using a pressure-volume sensitive body plethysmograph in anaesthetized artificially ventilated guinea-pigs pretreated with atropine (1 mg.kg-1) and propranolol (1 mg.kg-1). In the control group, i.v. administration of Bk produced a dose-dependent increase in RL. In animals pretreated with FK224, bronchoconstriction induced by higher doses of Bk (10, 50 and 100 micrograms.kg-1) was significantly reduced, whilst the bronchoconstriction caused by lower doses of Bk (5 and 7.5 micrograms.kg-1) was not. Pretreatment with a combination of FK224 and indomethacin markedly inhibited the bronchoconstriction induced by each dose of Bk compared with the groups pretreated with FK224 alone. Although pretreatment with indomethacin alone significantly reduced RL at a high dose of Bk (50 micrograms.kg-1), the reduction was significantly lower than that produced by a combination of FK224 and indomethacin. These results suggest that intravenous administration of a high dose of bradykinin causes bronchoconstriction both by cyclo-oxygenase products and by release of tachykinins.
Cancer Genetic Testing and Assisted Reproduction
Authors: Kenneth Offit, Kelly Kohut, Bartholt Clagett, Eve A. Wadsworth, Kelly J. Lafaro, Shelly Cummings, Melody White, Michal Sagi, Donna Bernstein, Jessica G. Davis
Journal: Journal of Clinical Oncology (2006)

Purpose Because of increasing uptake of cancer genetic testing and the improving survival of young patients with cancer, health care practitioners including oncologists will increasingly be asked about options for assisted reproduction by members of families affected by hereditary cancer syndromes. Among these reproductive options, preimplantation genetic diagnosis (PGD) offers the opportunity to select embryos without familial cancer-predisposing mutations. Methods A review of the published literature supplemented by a survey of PGD centers in the United States. Results Prenatal diagnosis and/or embryo selection after genetic testing has already been performed in the context of more than a dozen familial cancer syndromes, including the common syndromes of genetic predisposition to colon and breast cancer. Conclusion While constituting new reproductive options for families affected by cancer, the medical indications and ethical acceptance of assisted reproductive technologies for adult-onset cancer predisposition syndromes remain to be defined. Continued discussion of the role of PGD in the reproductive setting is needed to inform the responsible use of these technologies to decrease the burden of heritable cancers.
Perceived Stigma as a Predictor of Treatment Discontinuation in Young and Older Outpatients With Depression
Authors: Jo Anne Sirey, Martha L. Bruce, George S. Alexopoulos, Deborah A. Perlick, Patrick Raue, Steven J. Friedman, Barnett S. Meyers
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The authors’ goal was to examine the extent to which perceived stigma affected treatment discontinuation in young and older adults with major depression. METHOD: A two-stage sampling design identified 92 new admissions of outpatients with major depression. Perceived stigma was assessed at admission. Discontinuation of treatment was recorded at 3-month follow-up. RESULTS: Although younger patients reported perceiving more stigma than older patients, stigma predicted treatment discontinuation only among the older patients. CONCLUSIONS: Patients’ perceptions of stigma at the start of treatment influence their subsequent treatment behavior. Stigma is an appropriate target for intervention aimed at improving treatment adherence and outcomes.
Angiotensin-Converting Enzyme Genotype Modulates Pulmonary Function and Exercise Capacity in Treated Patients With Congestive Stable Heart Failure
Authors: M.Roselle Abraham, Lyle J. Olson, Michael J. Joyner, Stephen T. Turner, Ken C. Beck, Bruce D. Johnson
Journal: Circulation (2002)

The gene encoding ACE exhibits an insertion/deletion polymorphism resulting in 3 genotypes (DD, ID, and II), which affects serum and tissue ACE activity as well as other vasoactive substances. Pulmonary function is frequently abnormal in patients with congestive heart failure (CHF), the mechanism of which has not been completely characterized. ACE inhibition has been shown to improve diffusion across the alveolar-capillary membrane and to improve exercise capacity and gas exchange in CHF. The aim of the current study was to determine if ACE genotype is associated with altered pulmonary function and exercise intolerance in patients with treated CHF.Fifty-seven patients (stratified according to ACE genotype as 17 DD, 28 ID, 12 II) with ischemic and dilated cardiomyopathy, left ventricular ejection fraction (LVEF) <35%, and <10 pack-years of smoking history were studied. All patients were receiving standard therapy for left ventricular systolic dysfunction. Pulmonary function, LVEF, serum ACE, plasma angiotensin II, atrial natriuretic peptide, and brain natriuretic peptide were measured at baseline. Peak VO2 and gas exchange measurements were assessed with graded exercise. Resting LVEF was similar among the genotype groups (25% to 28%), and no differences were observed in diastolic function or pulmonary artery pressures (P>0.05). Mean peak VO2 and forced vital capacity (% Pred) were significantly reduced (P<0.05), whereas mean serum ACE activity and plasma angiotensin II concentration were highest in DD homozygotes. Subjects homozygous for the D-allele also demonstrated higher mean ventilatory equivalents for carbon dioxide (VE/VCO2) during exercise (P<0.05).ACE DD genotype is associated with decreased exercise tolerance in CHF, possibly mediated by altered pulmonary function. Pharmacological strategies effecting more complete inhibition of serum and tissue ACE and/or potentiation of bradykinin may improve exercise capacity in patients with CHF and ACE DD genotype.
New ways in which GLP-1 can regulate glucose homeostasis
Authors: D. A. D'Alessio
Journal: Journal of Clinical Investigation (2005)

Glucagon-like peptide–1 (GLP-1) has a diverse set of peripheral actions which all serve to promote enhanced glucose tolerance, and for this reason it has become the basis for new treatments for type 2 diabetes. In this issue of the JCI, Knauf et al. provide clear evidence that GLP-1 signaling in the CNS is also linked to the control of peripheral glucose homeostasis by inhibiting non–insulin-mediated glucose uptake by muscle and increasing insulin secretion from the pancreas. The authors’ work points to an important need to integrate diverse GLP-1 signaling actions and peripheral GLP-1 function in order to better understand both normal and abnormal glucose homeostasis.
Why glucocorticoids ought to be kept on the World Antidoping Agency's list of banned products
Authors: Bernard Montalvan, Martine Duclos
Journal: British Journal of Sports Medicine (2008)

Certain international sports federations are requesting that glucocorticoids (GCs) should be removed from the World Antidoping Agency (WADA)’s list of banned products. Their arguments are based on the fact that GCs are in widespread use in sports medicine and have no demonstrated ergogenic activity. We will show that, although their ergogenic activity may be difficult to detect, it is real and the use of corticosteroids poses a real danger to athletes’ health. We consider that this class of product should remain on the WADA’s list of banned products.

### Human data

There is nothing in the literature to support the hypothesis that there is any relationship between performance and corticosteroid use in humans, but this is explained by the fact that little work has been done on this question and that the work that has been done has been based on inappropriate tests. In consequence, the data available do not necessarily mean that GCs do not affect performance.

In the experiments cited, performance was evaluated in terms of effects either on maximal oxygen consumption (maximum duration 10–12 min)1 or a short series of submaximal exertions;2 in no case has a prolonged endurance test (to exhaustion) been conducted, nor any series of brief high-effort exercises in which GCs might attenuate impressions of fatigue and pain. In practice, certain of their known pharmacological properties suggest that GCs could indeed enhance performance, and this would explain why they are in such widespread use in the sporting world: neurostimulatory effects at cerebral GC receptors could attenuate central impressions of fatigue, and anti-inflammatory and analgesic effects could inhibit sensations of muscle pain on effort as well as raising the fatigue threshold. The metabolic effects of these compounds consolidate glycogen reserves in muscle tissue3 and accelerate lipolysis and glycolysis mechanisms induced by catecholamines and growth hormone, …
Role of the ceramide-signaling pathway in cytokine responses to P-fimbriated Escherichia coli.
Authors: M Hedlund, M Svensson, A Nilsson, R D Duan, C Svanborg
Journal: The Journal of Experimental Medicine (1996)

Escherichia coli express fimbriae-associated adhesins through which they attach to mucosal cells and activate a cytokine response. The receptors for E. coli P fimbriae are the globoseries of glycosphingolipids; Gal alpha 1--&amp;gt;4Gal beta-containing oligosaccharides bound to ceramide in the outer leaflet of the lipid bilayer. The receptors for type 1 fimbriae are mannosylated glycoproteins rather than glycolipids. This study tested the hypothesis that P-fimbriated E. coli elicit a cytokine response through the release of ceramide in the receptor-bearing cell. We used the A498 human kidney cell line, which expressed functional receptors for P and type 1 fimbriae and secreted higher levels of interleukin (IL)-6 when exposed to the fimbriated strains than to isogenic nonfimbriated controls. P-fimbriated E. coli caused the release of ceramide and increased the phosphorylation of ceramide to ceramide 1-phosphate. The IL-6 response to P-fimbriated E. coli was reduced by inhibitors of serine/threonine kinases but not by other protein kinase inhibitors. In contrast, ceramide levels were not influenced by type 1-fimbriated E. coli, and the IL-6 response was insensitive to the serine/threonine kinase inhibitors. These results demonstrate that the ceramide-signaling pathway is activated by P-fimbriated E. coli, and that the receptor specificity of the P fimbriae influences this process. We propose that this activation pathway contributes to the cytokine induction by P-fimbriated E. coli in epithelial cells.
Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value
Authors: W.Y. Au, A.K.W. Lie, R. Liang, Y.-L. Kwong, C.-C. Yau, M.M.C. Cheung, K.-C. Ngan, W.-H. Lau, K.-H. Wong, H.-Y. Yiu, H.-C. Cheng, K.-H. Au, J.K.C. Chan
Journal: Annals of Oncology (2003)
Comparing Mortality of Elderly Patients on Hemodialysis versus Peritoneal Dialysis
Authors: Wolfgang C. Winkelmayer, Robert J. Glynn, Murray A. Mittleman, Raisa Levin, Joseph S. Pliskin, Jerry Avorn
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. The objective of this study was to evaluate differences in mortality over the first year of renal replacement therapy (RRT) between elderly patients starting treatment on hemodialysis (HD) versus peritoneal dialysis (PD). For the period of 1991 to mid-1996, this study defined an inception cohort of all patients aged >65 yr with new-onset chronic RRT who were New Jersey Medicare and/or Medicaid beneficiaries in the year before RRT and who had been diagnosed with renal disease more than 1 yr before RRT. Propensity scores were calculated for first treatment assignment from a large number of baseline covariates. Mortality was then compared among patients initially assigned to HD versus PD using multivariate 90-d interval Cox models controlled for propensity scores and center stratification. Peritoneal dialysis starters had a 16% higher rate of death during the first 90 d of RRT compared with HD patients (hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.96 to 1.42)]. Mortality did not differ between day 91 and 180 (HR, 1.03; 95% CI, 0.71 to 1.51). Thereafter, PD starters again died at a higher rate (HR, 1.45; 95% CI, 1.07 to 1.98). These findings were more pronounced among patients with diabetes. Sensitivity analyses using more stringent criteria to ensure that first treatment choice reflected long-term treatment choice confirmed the presence of an association between PD and mortality. In conclusion, compared with HD, peritoneal dialysis appears to be associated with higher mortality among older patients, particularly among those with diabetes, even after controlling for a large number of risk factors for mortality, propensity scores to control for nonrandom treatment assignment, and center stratification.
VACCINE THERAPY IN DISEASES OF THE SKIN
Authors: ARTHUR WHITFIELD
Journal: British Journal of Dermatology (1919)

Journal Article VACCINE THERAPY IN DISEASES OF THE SKIN Get access ARTHUR WHITFIELD, M.D., F.R.C.P. ARTHUR WHITFIELD, M.D., F.R.C.P. Professor of Dermatology in King's College, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 31, Issue 2, 1 April 1919, Pages 79–83, https://doi.org/10.1111/j.1365-2133.1919.tb09695.x Published: 01 April 1919