tbuckley/cabot-search huggingface dataset:
Exposure to Ultrafine Particles from Ambient Air and Oxidative Stress–Induced DNA Damage
Authors: Elvira Vaclavik Bräuner, Lykke Forchhammer, Peter Møller, Jacob Simonsen, Marianne Glasius, Peter Wåhlin, Ole Raaschou-Nielsen, Steffen Loft
Journal: Environmental Health Perspectives (2007)

Particulate matter, especially ultrafine particles (UFPs), may cause health effects through generation of oxidative stress, with resulting damage to DNA and other macromolecules.We investigated oxidative damage to DNA and related repair capacity in peripheral blood mononuclear cells (PBMCs) during controlled exposure to urban air particles with assignment of number concentration (NC) to four size modes with average diameters of 12, 23, 57, and 212 nm.Twenty-nine healthy adults participated in a randomized, two-factor cross-over study with or without biking exercise for 180 min and with exposure to particles (NC 6169-15362/cm(3)) or filtered air (NC 91-542/cm(3)) for 24 hr.The levels of DNA strand breaks (SBs), oxidized purines as formamidopyrimidine DNA glycolase (FPG) sites, and activity of 7,8-dihydro-8-oxoguanine-DNA glycosylase (OGG1) in PBMCs were measured by the Comet assay. mRNA levels of OGG1, nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), and heme oxygenase-1 (HO1) were determined by real-time reverse transcriptase-polymerase chain reaction.Exposure to UFPs for 6 and 24 hr significantly increased the levels of SBs and FPG sites, with a further insignificant increase after physical exercise. The OGG1 activity and expression of OGG1, NUDT1, and HO1 were unaltered. There was a significant dose-response relationship between NC and DNA damage, with the 57-nm mode as the major contributor to effects. Concomitant exposure to ozone, nitrogen oxides, and carbon monoxide had no influence.Our results indicate that UFPs, especially the 57-nm soot fraction from vehicle emissions, causes systemic oxidative stress with damage to DNA and no apparent compensatory up-regulation of DNA repair within 24 hr.
928 Insulin-like growth factor-I (IGF-I) therapy in patients with advanced liver cirrhosis. Results of a randomized double-blind, controlled pilot study
Authors: M CONCHILLO, R DEKNEGT, M PAYERAS, J QUIROGA, B SANGRO, I HERRERO, C YOSHIZAWA, P JANSEN, B SCHARSCHMIDT, J PRIETO
Journal: Hepatology (2003)
Effects of Different Modes of Exercise Training on Glucose Control and Risk Factors for Complications in Type 2 Diabetic Patients
Authors: Neil J. Snowling, Will G. Hopkins
Journal: Diabetes Care (2006)

We sought to meta-analyze the effects of different modes of exercise training on measures of glucose control and other risk factors for complications of diabetes.The 27 qualifying studies were controlled trials providing, for each measure, 4-18 estimates for the effect of aerobic training, 2-7 for resistance training, and 1-5 for combined training, with 1,003 type 2 diabetic patients (age 55 +/- 7 years [mean +/- between-study SD]) over 5-104 weeks. The meta-analytic mixed model included main-effect covariates to control for between-study differences in disease severity, sex, total training time, training intensity, and dietary cointervention (13 studies). To interpret magnitudes, effects were standardized after meta-analysis using composite baseline between-subject SD.Differences among the effects of aerobic, resistance, and combined training on HbA(1c) (A1C) were trivial; for training lasting >/=12 weeks, the overall effect was a small beneficial reduction (A1C 0.8 +/- 0.3% [mean +/- 90% confidence limit]). There were generally small to moderate benefits for other measures of glucose control. For other risk factors, there were either small benefits or effects were trivial or unclear, although combined training was generally superior to aerobic and resistance training. Effects of covariates were generally trivial or unclear, but there were small additional benefits of exercise on glucose control with increased disease severity.All forms of exercise training produce small benefits in the main measure of glucose control: A1C. The effects are similar to those of dietary, drug, and insulin treatments. The clinical importance of combining these treatments needs further research.
Peroxisome proliferator-activated receptor alpha induction of uncoupling protein 2 protects against acetaminophen-induced liver toxicity
Authors: Andrew D. Patterson, Yatrik M. Shah, Tsutomu Matsubara, Kristopher W. Krausz, Frank J. Gonzalez
Journal: Hepatology (2012)

Acetaminophen (APAP) overdose causes acute liver failure in humans and rodents due in part to the destruction of mitochondria as a result of increased oxidative stress followed by hepatocellular necrosis. Activation of the peroxisome proliferator-activated receptor alpha (PPARα), a member of the nuclear receptor superfamily that controls the expression of genes encoding peroxisomal and mitochondrial fatty acid β-oxidation enzymes, with the experimental ligand Wy-14,643 or the clinically used fibrate drug fenofibrate, fully protects mice from APAP-induced hepatotoxicity. PPARα-humanized mice were also protected, whereas Ppara-null mice were not, thus indicating that the protection extends to human PPARα and is PPARα-dependent. This protection is due in part to induction of the PPARα target gene encoding mitochondrial uncoupling protein 2 (UCP2). Forced overexpression of UCP2 protected wildtype mice against APAP-induced hepatotoxicity in the absence of PPARα activation. Ucp2-null mice, however, were sensitive to APAP-induced hepatotoxicity despite activation of PPARα with Wy-14,643. Protection against hepatotoxicity by UCP2-induction through activation of PPARα is associated with decreased APAP-induced c-jun and c-fos expression, decreased phosphorylation of JNK and c-jun, lower mitochondrial H2O2 levels, increased mitochondrial glutathione in liver, and decreased levels of circulating fatty acyl-carnitines. These studies indicate that the PPARα target gene UCP2 protects against elevated reactive oxygen species generated during drug-induced hepatotoxicity and suggest that induction of UCP2 may also be a general mechanism for protection of mitochondria during fatty acid β-oxidation. (HEPATOLOGY 2012;56:281–290)
THE RENAL PATHOLOGY OF NUTRITIONAL HYPERTENSION IN RATS
Authors: Royall M. Calder
Journal: The Journal of Experimental Medicine (1944)

Rats subsisting on a diet partially deficient in the heat-stable fractions of the vitamin B complex are known to experience a rise in blood pressure. The present study shows that after prolonged administration of this dietary, abnormal structural changes occur in the kidneys. The surface of this organ becomes finely granular. The afferent arterioles show degenerative changes, consisting of irregular subendothelial hyaline deposits which encroach on the lumen. The interlobular arteries undergo the same change, plus degeneration of the media; the lumen of these vessels is likewise compromised. Resultant, small, streak-like areas of ischemic atrophy occur in both cortex and medulla, with necrosis of the epithelial lining of the uriniferous tubules. The glomeruli are reduced in size, the number of their component loops decreased, their pattern simplified, and the capillary basement membrane thickened. In addition to these changes, kidneys from animals on a more profoundly deficient diet display numerous areas of hemorrhagic infiltration in the cortical and subcapsular regions. The possible identity of these lesions with those seen in essential hypertension in man is discussed.
Cytokine Response Patterns, Exposure to Viruses, and Respiratory Infections in the First Year of Life
Authors: Christopher C. Copenhaver, James E. Gern, Zhanhai Li, Peter A. Shult, Louis A. Rosenthal, Lance D. Mikus, Carol J. Kirk, Kathy A. Roberg, Elizabeth L. Anderson, Christopher J. Tisler, Douglas F. DaSilva, Heidi J. Hiemke, Kevin Gentile, Ronald E. Gangnon, Robert F. Lemanske
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Daycare attendance and siblings are associated with viral-induced wheezing in children. Preexisting immunologic factors may influence the expression of viral infections in infancy, and in turn, recurrent infections may influence the development of immune responses. A total of 285 children were enrolled in the Childhood Origins of Asthma Project at birth and followed for at least 1 year. Cord blood and 1-year mononuclear cells were stimulated with phytohemagglutinin, and cytokine-response profiles were measured by enzyme-linked immunosorbent assay. Nasal lavage was performed for moderate to severe respiratory illnesses. Daycare attendance and/or siblings significantly increased the likelihood of contracting respiratory syncytial virus (1.5–1.6-fold increase) and rhinovirus (1.8–2.1-fold increase), and increased the risk of rhinovirus-induced wheezing (14–18% vs. 2%, p = 0.011). Cord blood IFN-γ responses were inversely related to the frequency of viral respiratory infections (rs = −0.11, p = 0.05), and more significant for subjects with high exposure to other children (rs = −0.27, p = 0.028). The interval change in infantile IFN-γ responses correlated positively with the frequency of viral infections in infancy (rs = 0.12, p = 0.047). These data suggest that neonatal IFN-γ responses may influence antiviral activity, or may represent a marker of antiviral immunity maturation. Conversely, the frequency of viral infections in infancy can influence IFN-γ responses.
RELEASE OF BETAMETHASONE DERIVATIVES FROM OINTMENTS—IN VIVO AND IN VITRO STUDIES
Authors: M. J. BUSSE, P. HUNT, K. A. LEES, P. N. D. MAGGS, T. M. McCARTHY
Journal: British Journal of Dermatology (1969)

SUMMARY.— The vasoconstrictor test of McKenzie and Stoughton (1962) has been adapted for studying the release of betamethasone 17‐valerate and 21‐desoxy betamethasone 17‐propionate from ointments. Vasoconstriction on the skin of volunteers was assessed quantally by noting presence or absence of vasoconstriction or quantitatively by measuring diameters of vasoconstricted areas. The quantitative method employs corticosteroid doses higher than those used in the quantal method of McKenzie and Stoughton. The vasoconstrictor potencies of 3 betamethasone derivatives have been compared using the quantitative method in order to confirm its validity. The quantitative method was used for comparing various ointment bases with betamethasone 17‐valerate or 21‐desoxy betamethasone 17‐propionate. High relative potencies were obtained by the inclusion of propylene glycol in the ointments. Ointments containing betamethasone 17‐valerate and varying amounts of hydrogenated lanolin were compared. The quantitative and quantal methods showed that relative vasoconstrictor potency increased or diminished respectively with increased concentration of hydrogenated lanolin. The effect of hydrogenated lanolin in vehicles on the release of betamethasone 17‐valerate was studied using two in vitro model systems and the results are discussed in relation to those of the in vivo experiments.
Omega-3 Fatty Acid Blood Levels
Authors: H. Robert Superko, Scott M. Superko, Khurram Nasir, Arthur Agatston, Brenda C. Garrett
Journal: Circulation (2013)

cardiac death or myocardial infarction rates (Table 3). 25,30,51etermination of blood omega-3 levels may help guide the appropriate use of dietary fish or omega-3 supplements in a personalized heart disease prevention strategy.
Perinatal Choline Effects on Neonatal Pathophysiology Related to Later Schizophrenia Risk
Authors: Randal G. Ross, Sharon K. Hunter, Lizbeth McCarthy, Julie Beuler, Amanda K. Hutchison, Brandie D. Wagner, Sherry Leonard, Karen E. Stevens, Robert Freedman
Journal: American Journal of Psychiatry (2013)

This is an exciting and highly important paper describing a novel perinatal treatment of a risk factor for schizophrenia. Deficient cerebral inhibition is a brain deficit related to poor sensory gating and attention in schizophrenia and other disorders. This inhibition develops perinatally, influenced by genetic and in utero factors. Amniotic choline activates fetal α7-nicotinic acetylcholine receptors and facilitates development of cerebral inhibition. Increasing this activation may protect infants from future illness by promoting normal brain development. That supplementation of the diet with choline improves P50 inhibition in infants represents a paradigm shifting approach to the prevention of psychiatric illness. It was a finding like this that led to the now routine regimen for pregnant women to take folic acid supplements.
Focal overexpression of CEACAM6 contributes to enhanced tumourigenesis in head and neck cancer via suppression of apoptosis
Authors: Sarina Cameron, Lilia Merida de Long, Mehlika Hazar-Rethinam, Eleni Topkas, Liliana Endo-Munoz, Andrew Cumming, Orla Gannon, Alexander Guminski, Nicholas Saunders
Journal: Molecular Cancer (2012)

Abstract Background Overexpression of CEACAM6 has been reported for a number of malignancies. However, the mechanism of how CEACAM6 contributes to cancer formation and its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. Therefore, we examined the role of CEACAM6 in head and neck squamous cell carcinoma (HNSCC). Methods CEACAM6 expression was examined in normal squamous epithelia as well as a number of patient HNSCC samples and tumours derived from HNSCC cell lines injected into NOD/SCID mice. CEACAM6 expression was manipulated in HNSCC cell lines by shRNA-mediated CEACAM6 knockdown or virally-delivered overexpression of CEACAM6. The role of CEACAM6 in tumour growth and chemotherapeutic sensitivity was then assessed in vivo and in vitro respectively. Results CEACAM6 expression was significantly increased in highly tumourigenic HNSCC cell lines when compared to poorly tumourigenic HNSCC cell lines. Moreover, HNSCC patient tumours demonstrated focal expression of CEACAM6. Functional investigation of CEACAM6, involving over-expression and knock down studies, demonstrated that CEACAM6 over-expression could enhance tumour initiating activity and tumour growth via activation of AKT and suppression of caspase-3 mediated cell death. Conclusion We report that CEACAM6 is focally overexpressed in a large fraction of human HNSCCs in situ. We also show that over-expression of CEACAM6 increases tumour growth and tumour initiating activity by suppressing PI3K/AKT-dependent apoptosis of HNSCC in a xenotransplant model of HNSCC. Finally, our studies indicate that foci of CEACAM6 expressing cells are selectively ablated by treatment of xenotransplant tumours with pharmacological inhibitors of PI3K/AKT in vivo .
Mediastinal mass in a healthy adolescent at The Children's Hospital at Westmead, Australia
Authors: Ameneh Khatami, Alex C Outhred, Philip N Britton, Emilie Huguon, David J E Lord, Melanie Wong, Amanda Charlton, Alison M Kesson, David Isaacs
Journal: Thorax (2014)

A previously well adolescent from the tropical South Pacific island of Futuna was transferred due to a 3-month to 4-month history of intermittent fevers, anorexia, weight loss, lethargy and haemoptysis.A Mantoux test was negative.CT scan demonstrated a large mediastinal mass and lymphadenopathy with broncho-vascular compression, and bilateral pleural and pericardial effusions, (figure 1A).At admission, he was persistently febrile with non-tender cervical lymphadenopathy and hepatomegaly, and had moderate respiratory distress.The presumptive diagnosis was lymphoma.Initial blood tests demonstrated haemoglobin 92 g/L; white cell count 16×10 9 /L (neutrophils 11×10 9 /L, lymphocytes 1.3×10 9 /L, eosinophils 1.2×10 9 /L); erythrocyte sedimentation rate 128 mm/h; C-reactive protein 313 mg/L; normal liver and renal function tests.After 1 week, he developed acute renal impairment with peak serum creatinine 368 mmol/L.Renal ultrasound scan (USS) demonstrated bilateral increased echogenicity.Cultures and cytology of the pleural effusion were non-diagnostic.Cervical lymph node biopsies demonstrated reactive histopathological changes and fibrosis, without evidence of malignancy.
Hematopoietic stem/progenitor cells, generation of induced pluripotent stem cells, and isolation of endothelial progenitors from 21- to 23.5-year cryopreserved cord blood
Authors: Hal E. Broxmeyer, Man-Ryul Lee, Giao Hangoc, Scott Cooper, Nutan Prasain, Young-June Kim, Coleen Mallett, Zhaohui Ye, Scott Witting, Kenneth Cornetta, Linzhao Cheng, Mervin C. Yoder
Journal: Blood (2011)
GIS and Disease
Authors: Ellen K. Cromley
Journal: Annual Review of Public Health (2003)

▪ Abstract Geographic information systems (GIS) and related technologies like remote sensing are increasingly used to analyze the geography of disease, specifically the relationships between pathological factors (causative agents, vectors and hosts, people) and their geographical environments. GIS applications in the United States have described the sources and geographical distributions of disease agents, identified regions in time and space where people may be exposed to environmental and biological agents, and mapped and analyzed spatial and temporal patterns in health outcomes. Although GIS show great promise in the study of disease, their full potential will not be realized until environmental and disease surveillance systems are developed that distribute data on the geography of environmental conditions, disease agents, and health outcomes over time based on user-defined queries for user-selected geographical areas.
Acute effect of pretreatment with single conventional dose of salmeterol on dose-response curve to oxitropium bromide in chronic obstructive pulmonary disease
Authors: M. Cazzola, F. Di Perna, S. Centanni, C. Califano, C. F. Donner, M. D'Amato, G. D'Amato
Journal: Thorax (1999)

<h3>BACKGROUND</h3> An earlier study documented that, in patients with chronic obstructive pulmonary disease (COPD), addition of ipratropium bromide at the clinically recommended dose (40 μg) does not produce any further bronchodilation than that achieved with salmeterol 50 μg alone. However, the dose of ipratropium bromide needed to produce near maximal bronchodilation is several times higher than the customary dosage. The full therapeutic potential of combined salmeterol plus an anticholinergic drug can therefore only be established using doses higher than those currently recommended in the marketing of these agents. A study was undertaken to examine the possible acute effects of higher than conventional doses of an anticholinergic agent on the single dose salmeterol induced bronchodilation in patients with stable and partially reversible COPD. <h3>METHODS</h3> Thirty two outpatients received 50 μg salmeterol or placebo. Two hours after inhalation a dose-response curve to inhaled oxitropium bromide (100 μg/puff) or placebo was constructed using one puff, one puff, two puffs, and two puffs—that is, a total cumulative dose of 600 μg oxitropium bromide. Dose increments were given at 20 minute intervals with measurements being made 15 minutes after each dose. On four separate days all patients received one of the following: (1) 50 μg salmeterol + 600 μg oxitropium bromide; (2) 50 μg salmeterol + placebo; (3) placebo + 600 μg oxitropium bromide; (4) placebo + placebo. <h3>RESULTS</h3> Salmeterol induced a good bronchodilation (mean increase 0.272 l; 95% CI 0.207 to 0.337) two hours after its inhalation. Oxitropium bromide elicited an evident dose-dependent increase in forced expiratory volume in one second (FEV<sub>1</sub>) and this occurred also after pretreatment with salmeterol with a further mean maximum increase of 0.152 l (95% CI of differences 0.124 to 0.180). <h3>CONCLUSIONS</h3> This study shows that acute pretreatment with 50 μg salmeterol does not block the possibility of inducing more bronchodilation with an anticholinergic agent when a higher than normal dosage of the muscarinic antagonist is used.
Studies on the Liver to Kidney Switch of Erythropoietin Production
Authors: Esmail D. Zanjani, Joao L. Ascensao, Philip B. McGlave, Mussa Banisadre, Robert C. Ash
Journal: Journal of Clinical Investigation (1981)

Although the liver is the major site of erythropoietin (Ep) production in the fetus, this function is assumed by kidneys in the adult. The mechanisms underlying the liver to kidney switch of Ep formation are not understood. We studied the natural progression of this transition in sheep by measuring Ep production in response to anemia in normal and bilaterally nephrectomized fetal and newborn sheep beginning at about 80 d gestation (normal gestation: 140 d). Removal of both kidneys before induction of anemia did not affect Ep formation up to about 120 d of gestation. A significant reduction (29%, P < 0.02) in Ep synthesis was first noted at about 130 d of gestation (initiation of switch). This level of nephrectomy-induced reduction of Ep formation persisted until about 15 d after birth. Thereafter, bilateral nephrectomy caused further significant decreases (P < 0.05) in Ep production, gradually resulting in near total absence of Ep production at about day 40 postpartum (completion of switch). Chronic administration of testosterone (12 mg/wk) or estradiole benzoate (1.5 mg/d, 5 d/wk) to the fetus/newborn beginning at 85-90 d of gestation enhanced or suppressed erythropoiesis, respectively, but failed to affect the time at which the liver to kidney switch was initiated and/or completed. By contrast, a significant delay (P < 0.001) in the onset, but not completion of the switch occurred in animals that were either thyroidectomized or rendered chronically anemic beginning in the second third of the gestation period. Administration of thyroxin (1.2 mg/d, 5 d/wk) to thyroidectomized fetus/newborns not only prevented the delay in the initiation of the switch, but also accelerated the rate at which the switch was completed. These results demonstrate that in sheep (a) the liver to kidney switch of Ep production is initiated in utero during the last third of the gestation period, but is completed after birth, (b) this transition occurs gradually; the assumption of Ep producing capacity by the kidney is not preceded by an abrupt loss of hepatic Ep formation; and (c) the switch is not affected by changes in sex hormone levels during the prenatal-postnatal growth periods, but is profoundly influenced by alterations in thyroid hormone and oxygen supply-demand levels.
Circulating tumor cells in small-cell lung cancer: a predictive and prognostic factor
Authors: T.J.N. Hiltermann, M.M. Pore, A. van den Berg, W. Timens, H.M. Boezen, J.J.W. Liesker, J.H. Schouwink, W.J.A. Wijnands, G.S.M.A. Kerner, F.A.E. Kruyt, H. Tissing, A.G.J. Tibbe, L.W.M.M. Terstappen, H.J.M. Groen
Journal: Annals of Oncology (2012)