tbuckley/cabot-search huggingface dataset:
RE: Exposure to Indoor Tanning Without Burning and Melanoma Risk by Sunburn History
Authors: M. Boniol, J.-F. Dore, R. Greinert, S. Gandini, J.-P. Cesarini
Journal: JNCI Journal of the National Cancer Institute (2015)

Re: Exposure to indoor tanning without burning and melanoma risk by sunburn historyVogel et al 1 provide another demonstration that the risk from sunbed use is not limited to skinsensitive populations and shows increased risk even in those not having experienced sunburns in their lifetimes.It counters the argument frequently put forward by the indoor tanning industry that indoor tanning prevents sunburn and adds further evidence of the carcinogenicity of indoor tanning.We are, however, concerned that those who consider vitamin D as a protective agent for cancer and thus defend sunbed use, might misinterpret the decline in odds ratio (OR) for increasing burns and consider that the increasing burns diminished the effect of sunbed use, hence providing "protection".Our interpretation is that the declining trend of OR from sunbed use by increasing number of burns is a marker of an additive effect of sunbed use.Indeed, the modeling approach used in most publications on this subject, including that of Vogel et al.( 1), relied on an implicit multiplicative effect of risk factors.The declining trend of association with sunbed use in the stratified analysis indicates a failure in the multiplicative effect assumption.In Table 1, we derive a crude calculation of ORs for sunburns (using 0 as reference), assuming a background risk of 10 per 100,000 person years, and model incidence in sunbed users and in non-users (Table 1).We also computed the difference in incidence between the two groups and apart from the first category based on small numbers, the risk difference remained constant.This suggests that sunbed use has an effect on melanoma risk independently from the effect of sunburns.This hypothesis is in line with a study in Iceland showing rapid decrease in incidence of melanoma after strong regulation of sunbeds, since a change in sunbed use would result in change in incidence independently of other factors. 2 Thus the additive effect of sunbed use could have been hidden by the multiplicative assumption used in past research.Consequently, the overall population impact of sunbed use could be even greater than anticipated.Sunbed exposure is by far the most easily preventable skin cancer risk factor.This is an important public health issue since the risk is high, especially in youth.The prevalence of sunbed use is very high in adolescents and young adults. 3A growing number of countries have introduced regulations to reduce the public's exposure.Such public health actions may result in a decrease in risk, as shown by the example in Iceland. 2,
Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity.
Authors: Pamela Reed Gibson, Amy Nicole-Marie Elms, Lisa Ann Ruding
Journal: Environmental Health Perspectives (2003)

Multiple chemical sensitivity (MCS) is a condition in which persons experience negative health effects in multiple organ systems from exposure to low levels of common chemicals. Although symptoms experienced from particular chemicals vary across persons, they are generally stable within persons. The sensitivities often spread over time, first to related chemicals and then to other classes of chemicals. This study examined self-reported perceived treatment efficacy of 101 treatments used by 917 persons with self-reported MCS. Treatments examined included environmental medicine techniques, holistic therapies, individual nutritional supplements, detoxification techniques, body therapies, Eastern-origin techniques, newer therapies, prescription items, and others. The three most highly rated treatments were creating a chemical-free living space, chemical avoidance, and prayer. Both creating a chemical-free living space and chemical avoidance were rated by 95% of respondents as helpful. Results for most therapies were mixed. Participants had consulted a mean of 12 health care providers and spent over one-third of their annual income on health care costs. We discuss this drain on personal resources and describe respondents' attitudes toward the possibility of healing from MCS.
Human T lymphocyte virus 1 from a leukemogenic cell line mediates in vivo and in vitro lymphocyte apoptosis.
Authors: M Leno, R M Simpson, F S Bowers, T J Kindt
Journal: The Journal of Experimental Medicine (1995)

HTLV-1 is implicated in the development of diverse diseases. However, most HTLV-1-infected individuals remain asymptomatic. How HTLV-1 infection leads to disparate consequences remains a mystery, despite extensive investigation of HTLV-1 isolates from infected individuals. As in human infection, experimental HTLV-1 infection in rabbits is generally benign, although HTLV-1-infected rabbit T cell lines that mediate lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal leukemia-like disease have been reported. We report here that thymuses from mature outbred rabbits inoculated with a lethal HTLV-1 T cell line (RH/K34) showed morphological and biochemical evidence of apoptosis, whereas thymuses from rabbits inoculated with nonlethal HTLV-1 T cell lines showed no signs of apoptosis. Exposure of rabbit or human lymphocytes to purified virus from RH/K34 caused rapid induction of apoptosis, providing an in vitro correlate to the pathogenic effects. By contrast, virus isolated from a nonlethal cell line mediated dose-dependent lymphocyte proliferation. These data implicate lymphocyte apoptosis as a potential mechanism by which the lethal HTLV-1 cell line causes fulminant disease and provide a means to identify factors contributing to HTLV-1 disease. Results from this HTLV-1 infection model can provide insight into variations in HTLV-1 pathogenicity in human infection.
Application of cDNA Microarrays in Determining Molecular Phenotype in Cardiac Growth, Development, and Response to Injury
Authors: Patricia D. Sehl, Julie T. N. Tai, Kenneth J. Hillan, Lesley A. Brown, Audrey Goddard, Renhui Yang, Hongkui Jin, David G. Lowe
Journal: Circulation (2000)

Normal myocardial development and the tissue response to cardiac stress are accompanied by marked changes in gene expression; however, the extent of these changes and their significance remain to be fully explored. We used cDNA microarrays for gene expression profiling in rat cardiac tissue samples to study developmental transitions and the response to myocardial infarction (MI).Microarrays with rat cDNAs for 86 known genes and 989 anonymous cDNAs obtained by molecular subtraction (representational difference analysis) of mRNA from sham-operated and 6-week post-MI samples were used in 2-color hybridization experiments. Twelve known genes previously associated with myocardial development were identified together with 10 uncharacterized expressed sequence tags and 36 genes not previously associated with cardiac development. After MI, genes associated with myocardial stress and wound healing exhibited differences in magnitude and expression kinetics, and 14 genes not previously associated with MI were identified. In situ hybridization revealed mRNA localization characteristic of wound healing and vascular and cardiomyocyte reactivity.Tissue analysis of gene expression with cDNA microarrays provides a measure of transcriptional or posttranscriptional regulation and cellular recruitment. Our results demonstrate the complexity of gene regulation in the developing myocardium and show that cDNA microarrays can be used to monitor the evolution of the cardiac stress-inducible phenotype.
Quality of life measurement in gastrointestinal and liver disorders
Authors: M R BORGAONKAR
Journal: Gut (2000)

Modern medicine has had a considerable impact on mortality rates for serious illness. Many chronic diseases which have previously been associated with an increased mortality now have survival rates approaching those of the background population. However, chronic diseases such as cancer, chronic pain syndromes, and chronic inflammatory conditions impose a considerable burden on families, the health care system, and society. Health related quality of life (HRQOL) is a concept that has developed from the need to estimate the impact of such chronic diseases. HRQOL measurement is a conceptual framework which attempts to predict daily function and well being based on subjective attitudes and experiences of physical, social, and emotional health. It has been evaluated predominantly from the patient9s viewpoint as proxy respondents appear to underestimate the full effect of chronic illness on functional status. Measuring HRQOL in clinical research is most frequently undertaken using multi-item questionnaires to estimate daily function. Factors which affect HRQOL can be broadly classed as disease related and disease independent. The use of different assessment techniques permits comparisons between and within disorders. Generic and disease specific instruments used together enhance the ability to direct treatment for individuals and patient populations. Psychometrically sound questionnaires must be used. However, the type of instrument and research methods adopted depend on the question of interest. We have attempted to catalogue and critically assess the disease specific instruments used in the assessment of chronic gastrointestinal disease.
Osteoporosis in patients undergoing lung transplantation
Authors: SL Ferrari, LP Nicod, J Hamacher, A Spiliopoulos, DO Slosman, T Rochat, JP Bonjour, R Rizzoli
Journal: European Respiratory Journal (1996)

The occurrence of osteoporotic fractures may seriously compromise the quality of life of lung transplant recipients. However, at present, the true risk of osteoporosis in such patients is unknown. We therefore prospectively evaluated bone mass changes in patients undergoing pulmonary transplantation. Bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and femoral shaft (FS), as well as whole body bone mineral content (WB-BMC) were measured in 21 consecutive candidates for lung transplantation (9 males and 12 females; mean+/-SD age 47+/-11 yrs). Twelve of the patients had their BMD remeasured within 6 months after surgery, and nine again after 1 year. Before transplantation, BMD at all sites as well as WB-BMC were significantly decreased as compared to the values in young healthy adults, FN being the most affected (FN -25+/-2%; LS, -12+/-4%; FS -9+/-2%, WB-BMC -15+/-4% (mean+/-SEM)). Seven out of 20 adult patients (35%) fulfilled World Health Organization (WHO) criteria for osteoporosis, i.e. BMD more than 2.5 SD below peak bone mass, whereas three had previously been diagnosed as having osteoporotic fractures of the spine or femoral neck. Within 6 months after transplantation, significant bone loss occurred, mostly at the LS level (-4.0+/-1.7%; p=0.04), despite calcium and vitamin D supplementation. Furthermore, two patients had new osteoporotic vertebral fractures. After 1 year, no further bone loss or new osteoporotic fractures were observed. In conclusion, evaluation of bone mass and prevention of bone loss should be considered early before lung transplantation. Further studies are needed to determine the efficacy of antiresorptive drugs on the prevention of accelerated bone loss and vertebral fractures after transplantation.
Inhibition of succinate dehydrogenase dysregulates histone modification in mammalian cells
Authors: Ana M Cervera, Jean-Pierre Bayley, Peter Devilee, Kenneth J McCreath
Journal: Molecular Cancer (2009)

Abstract Remodelling of mitochondrial metabolism is a hallmark of cancer. Mutations in the genes encoding succinate dehydrogenase (SDH), a key Krebs cycle component, are associated with hereditary predisposition to pheochromocytoma and paraganglioma, through mechanisms which are largely unknown. Recently, the jumonji-domain histone demethylases have emerged as a novel family of 2-oxoglutarate-dependent chromatin modifiers with credible functions in tumourigenesis. Using pharmacological and siRNA methodologies we show that increased methylation of histone H3 is a general consequence of SDH loss-of-function in cultured mammalian cells and can be reversed by overexpression of the JMJD3 histone demethylase. ChIP analysis revealed that the core promoter of IGFBP7 , which encodes a secreted protein upregulated after loss of SDHB , showed decreased occupancy by H3K27me3 in the absence of SDH . Finally, we provide the first evidence that the chief (type I) cell is the major methylated histone-immunoreactive constituent of paraganglioma. These results support the notion that loss of mitochondrial function alters epigenetic processes and might provide a signature methylation mark for paraganglioma.
JUMP HEIGHT IS THE CRITICAL FACTOR AFFECTING BETWEEN-SEX DIFFERENCES IN PATELLAR TENDON LOADING DURING LANDING IN VOLLEYBALL
Authors: I Janssen, J Steele, B Munro, N Brown
Journal: British Journal of Sports Medicine (2014)

Background Patellar tendinopathy is the most common overuse knee injury in volleyball, with men reporting more than twice the injury prevalence than women. However, whether between-sex variations in landing technique account for differences in patellar tendon loading is unknown. Objective Our objective was to compare the landing technique and patellar tendon loading in male and female volleyball players. We hypothesised that males would display differences in landing technique and generate higher patellar tendon loading due to having a higher jump height than the females. Design Controlled laboratory study. Setting A regulation height volleyball net and mounted volleyball were used to simulate volleyball court conditions. Participants Forty male and female volleyball players volunteered for this study. Participants were excluded if they were injured at the time of testing, had a history of lower limb surgery, equilibrium disorders, or orthopaedic or neurologic conditions that could influence their landing biomechanics. Risk factor assessment Independent t -tests were used to identify whether there were any between-sex differences in all 20 males and 20 females, or 13 males and 13 females matched for jump height. Main outcome measurements Three-dimensional lower limb kinematics were calculated to characterise landing technique. Patellar tendon loading was characterised by peak patellar tendon force and patellar tendon force loading rate. Results Males landed from a higher height (P&lt;.001), displayed differences in landing kinematics (P&lt;.05), and experienced higher patellar tendon loading (P=.002), than female players. These differences, however, dissipated when the participants were matched for jump height. Conclusions Jump height is the critical factor affecting patellar tendon loading, whereby a higher jump height is associated with higher patellar tendon loading, irrespective of sex. The between-sex disparity in patellar tendinopathy may, therefore, be due to males landing from greater heights causing higher patellar tendon loading, rather than being sex-related differences in landing technique.
Surfactant alterations in severe pneumonia, acute respiratory distress syndrome, and cardiogenic lung edema.
Authors: A Günther, C Siebert, R Schmidt, S Ziegler, F Grimminger, M Yabut, B Temmesfeld, D Walmrath, H Morr, W Seeger
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Bronchoalveolar lavage fluids (BALF) were analyzed for surfactant abnormalities in 153 patients with acute respiratory failure necessitating mechanical ventilation. Diagnoses were acute respiratory distress syndrome (ARDS) in the absence of lung infection (n = 16), severe pneumonia (PNEU; n = 88), ARDS and PNEU (n = 36), and cardiogenic lung edema (CLE; n = 13). The PNEU group was subdivided into groups with alveolar PNEU (n = 35), bronchial PNEU (n = 16), interstitial PNEU (n = 18) and nonclassified PNEU (n = 19). Comparison with healthy controls (n = 20) was undertaken. Total phospholipids (PL), proteins, PL classes (HPTLC) and surfactant apoproteins SP-A and SP-B (ELISA) were quantified in the original BALF. The 48,000 x g pellet from centrifugation of the BAL was used to assess the percentage of large surfactant aggregates (LSA) and the biophysical properties of the surfactant (pulsating bubble surfactometer). All groups with inflammatory lung injury (PNEU and/or ARDS) showed some decrease in the lavageable PL pool, a reduced LSA content in BALF, and a manifold increase in alveolar protein load. Marked changes in the PL profile were noted throughout the groups (a decrease in phosphatidylcholine (PC) and phosphatidylglycerol (PG) and an increase in phosphatidylinositol [PI] and sphingomyelin [SPH]). Concentrations of SP-A but not of SP-B in BALF were reduced. Minimum surface-tension values approached 0 mN/m in controls, and ranged from 10 to 25 mN/m in the absence of supernatant protein and from 20 to 35 mN/m in recombination with leaked protein in the groups with ARDS and/or PNEU. Abnormalities in alveolar PNEU surpassed those in bronchial PNEU, and interstitial PNEU presented a distinct pattern with extensive metabolic changes. All surfactant changes were absent in CLE except for a slight inhibition of surface activity by proteins. We conclude that pronounced surfactant abnormalities, comparable to those in ARDS in the absence of lung infection, occur in different entities of severe PNEU, but not in CLE.
Predictive Factors of Oxaliplatin Neurotoxicity: The Involvement of the Oxalate Outcome Pathway
Authors: Laurence Gamelin, Olivier Capitain, Alain Morel, Agnes Dumont, Sory Traore, Le Bouil Anne, Simard Gilles, Michele Boisdron-Celle, Erick Gamelin
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Oxaliplatin displays a frequent dose-limiting neurotoxicity due to its interference with neuron voltage-gated sodium channels through one of its metabolites, oxalate, a calcium chelator. Different clinical approaches failed in neurotoxicity prevention, except calcium-magnesium infusions. We characterized oxalate outcome following oxaliplatin administration and its interference with cations and amino acids. We then looked for genetic predictive factors of oxaliplatin-induced neurotoxicity. Experimental Design: We first tested patients for cations and oxalate levels and did amino acid chromatograms in urine following oxaliplatin infusion. In the second stage, before treatment with FOLFOX regimen, we prospectively looked for variants in genes coding for the enzymes involved (a) in the oxalate metabolism, especially glyoxylate aminotransferase (AGXT), and (b) in the detoxification glutathione cycle, glutathione S-transferase π, and for genes coding for membrane efflux proteins (ABCC2). Results: In the first 10 patients, urinary excretions of oxalate and cations increased significantly within hours following oxaliplatin infusion, accompanied by increased excretions of four amino acids (glycine, alanine, serine, and taurine) linked to oxalate metabolism. In a further 135 patients, a minor haplotype of AGXT was found significantly predictive of both acute and chronic neurotoxicity. Neither glutathione S-transferase π nor ABCC2 single nucleotide polymorphisms we looked for were linked to neurotoxicity. Conclusion: These data confirm the involvement of oxalate in oxaliplatin neurotoxicity and support the future use of AGXT genotyping as a pretherapeutic screening test to predict individual susceptibility to neurotoxicity.
Autophagy as a Stress-Response and Quality-Control Mechanism: Implications for Cell Injury and Human Disease
Authors: Lyndsay Murrow, Jayanta Debnath
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, is an essential cytoprotective response to pathologic stresses that occur during diseases such as cancer, ischemia, and infection. In addition to its role as a stress-response pathway, autophagy plays an essential quality-control function in the cell by promoting basal turnover of long-lived proteins and organelles, as well as by selectively degrading damaged cellular components. This homeostatic function protects against a wide variety of diseases, including neurodegeneration, myopathy, liver disease, and diabetes. This review discusses our current understanding of these two principal functions of autophagy and describes in detail how alterations in autophagy promote human disease.
CC Chemokine I-309 Is the Principal Monocyte Chemoattractant Induced by Apolipoprotein(a) in Human Vascular Endothelial Cells
Authors: Nasreen S. Haque, Xiaoxia Zhang, Deborah L. French, Jihong Li, Michael Poon, John T. Fallon, Brent R. Gabel, Mark B. Taubman, Marlys Koschinsky, Peter C. Harpel
Journal: Circulation (2000)

Background —Lipoprotein(a) [Lp(a)] is a risk factor for atherosclerosis; however, the mechanisms are unclear. We previously reported that Lp(a) stimulated human vascular endothelial cells to produce monocyte chemotactic activity. The apolipoprotein(a) [apo(a)] portion of Lp(a) was the active moiety. Methods and Results —We now describe the identification of the chemotactic activity as being due to the CC chemokine I-309. The carboxy-terminal domain of apo(a) containing 6 type-4 kringles (types 5 to 10), kringle V, and the protease domain was demonstrated to contain the I-309–inducing portion. Polyclonal and monoclonal anti–I-309 antibodies as well as an antibody against a portion of the extracellular domain of CCR8, the I-309 receptor, inhibited the increase in monocyte chemotactic activity induced by apo(a). I-309 antisense oligonucleotides also inhibited the induction of endothelial monocyte chemotactic activity by apo(a). I-309 mRNA was identified in human umbilical vein endothelial cells. Apo(a) induced an increase in I-309 protein in the endothelial cytoplasm and in the conditioned medium. Immunohistochemical studies have identified I-309 in endothelium, macrophages, and extracellular areas of human atherosclerotic plaques and have found that I-309 colocalized with apo(a). Conclusions —These data establish that I-309 is responsible for the monocyte chemotactic activity induced in human umbilical vein endothelial cells by Lp(a). The identification of the endothelial cell as a source for I-309 suggests that this chemokine may participate in vessel wall biology. Our data also suggest that I-309 may play a role in mediating the effects of Lp(a) in atherosclerosis.
Gadd45 is a novel mediator of cardiomyocyte apoptosis induced by ischaemia/hypoxia
Authors: M.-Y. Kim, E. J. Seo, D. H. Lee, E. J. Kim, H. S. Kim, H.-Y. Cho, E. Y. Chung, S. H. Lee, E. J. Baik, C.-H. Moon, Y.-S. Jung
Journal: Cardiovascular Research (2010)

Because apoptotic death plays a critical role in cardiomyocyte loss during ischaemic heart injury, a detailed understanding of the mechanisms involved is likely to have a substantial impact on the optimization and development of treatment strategies. The goal of this study was to assess gene profiling during ischaemia/hypoxia and to evaluate the functions of ischaemia/hypoxia-responsive genes in in vivo and in vitro ischaemia/hypoxia-induced cardiomyocyte apoptosis models. DNA microarray analysis and real-time polymerase chain reaction were performed on hearts obtained from an in vivo rat transient ischaemia model and on neonatal rat cardiomyocytes from an in vitro hypoxia model. Three genes, namely Ddit4, Gadd45β and Atf3, were found to be up-regulated in vivo and in vitro. Using loss-of-function and gain-of-function techniques, the functions of these ischaemia/hypoxia-responsive genes were evaluated. Ischaemia/hypoxia-induced cardiomyocyte apoptosis was remarkably attenuated by the small interfering RNA-mediated down-regulation of Gadd45β in vivo and in vitro, whereas ectopic Gadd45β expression significantly aggravated hypoxia-induced apoptosis in vitro. These results suggest that Gadd45β is a key player in ischaemia/hypoxia-induced apoptotic cardiomyocyte death, and that strategies based on its inhibition might be of benefit in the treatment of acute ischaemic heart disease.