tbuckley/cabot-search huggingface dataset:
OP06 Maternal obesity programs offspring innate immune dysregulation in non-alcoholic fatty liver disease
Authors: A. Mouralidarane, J. Soeda, A.-M. Samuelsson, P. Taylor, L. Poston, J. A. Oben
Journal: Gut (2011)

<h3>Introduction</h3> Obesity induced, non-alcoholic fatty liver disease (NAFLD), is the major cause of chronic liver dysfunction. In tandem, obesity and NAFLD rates in reproductive age women are rising. We have previously reported increased susceptibility to NAFLD in offspring exposed to maternal obesity via programming. <h3>Aim</h3> Our aim is to investigate the effects of maternal obesity on hepatic innate immune function in a more physiologically relevant model of NAFLD. <h3>Method</h3> Female mice were fed standard or obesogenic chow, before, throughout pregnancy and in lactation. Offspring were then weaned onto either standard or obesogenic chow and studied at 3, 6 and 12 months. Read-outs included biochemical and histological indicators of NAFLD and fibrosis, hepatic triglycerides, gene expression analysis of pro-fibrotic pathways, FACS analysis of liver innate immune cells and flow cytometric detection of ROS. <h3>Results</h3> Offspring only exposed to a post-weaning hyper-calorific diet (Group 2) exhibited raised leptin, ALT and hepatic triglyceride content compared to controls (Group 1) (p&lt;0.001). Moreover, hepatic gene expression of injury and fibrogenic markers were increased (Abstract OP06 table 1, p&lt;0.01). As expected, a more robust phenotype was observed at 12 compared to 3 months. Additionally, offspring exposed to maternal obesity plus a post-weaning hyper-calorific diet (Group 3), displayed a more profound NAFLD phenotype with development of fibrosis and a NAFLD Activity Score &gt;5. Mechanistically, we observed increased Kupffer cell numbers with impaired phagocytic function and raised ROS production, alongside reduced NKT cell numbers, in Group 3 compared to Group 1 (p&lt;0.01). <h3>Conclusion</h3> Maternal obesity programs development of offspring NAFLD with progression to fibrosis in the context of a post-weaning hyper-calorific diet. Innate immune dysfunction may be responsible for the observed programmed phenotype.
The dependence of myocardial ultrasonic integrated backscatter on contractile performance.
Authors: S A Wickline, L J Thomas, J G Miller, B E Sobel, J E Pérez
Journal: Circulation (1985)

We have recently shown that the cardiac cycle-dependent variation in myocardial ultrasonic integrated backscatter is blunted with regional ischemia in dogs. To determine if global and intramural regional myocardial contractile performance can be quantified by integrated backscatter, we analyzed ultrasonic responses after induction of increased and decreased contractility in five dogs. A recently developed analog data-acquisition system for measuring integrated backscatter in real time was used to sample radiofrequency signals gated from subepicardial or subendocardial regions. Base-line recordings of integrated backscatter, left ventricular pressure, left ventricular dP/dt, and wall thickness were made at 12 left ventricular sites for both intramural regions. Contractility was modified subsequently by either paired pacing or propranolol to produce significantly elevated or depressed values for maximum left ventricular dP/dt compared with baseline (1083 +/- 289 to 3001 +/- 570 mm Hg/sec; p less than .01 for all). The amplitude of the cyclic variation of integrated backscatter was 50% greater (arithmetically) in subendocardial than in subepicardial regions for all treatments (7.6 +/- 0.3 vs 6.0 +/- 0.5 dB, p less than .001). The maximum rate of change in integrated backscatter waveforms during isovolumetric contraction was faster with paired pacing and slower with propranolol than at baseline for all regions (56 +/- 6 to 74 +/- 6 to 82 +/- 5 dB/sec, p less than .005). The maximum rate of change in integrated backscatter also was greater in subendocardial than subepicardial regions (p less than .001). Thus, both regional and global differences in myocardial contractile performance are manifest quantitatively in integrated backscatter waveforms. We propose that the physiologic determinants of these differences may depend on regional and global variations in myofibril elastic characteristics.
A template for defining a causal relation between acute intrapartum events and cerebral palsy: international consensus statement
Authors: A. MacLennan
Journal: BMJ (1999)

encourage wrong assumptions or inappropriate management.The task force acknowledges that some cases of cerebral palsy probably originate in labour.By defining these cases it should also help to focus research on the many antenatal causes of cerebral palsy and their prevention as well as the prevention of intrapartum asphyxia, which has been the major clinical goal to date.
LYMPHOCYTES IN THE PSYCHONEUROSES
Authors: HARLEY C. SHANDS, JACOB E. FINESINGER
Journal: American Journal of Psychiatry (1948)

We have studied variations in absolute numbers of lymphocytes under conditions of daily living in small groups of normal controls and psychoneurotic patients. There CIRCULATING LYMPHOCYTES DURING STRESS AND NON-STRESS INTERVIEWS (MEAN VALUES) [See Source Pdf for Fig. 8] seems to be little difference between the controls and patients with anxiety neuroses in either males or females. In the female patients, a considerable group had diagnoses of hysteria, and in these the level of lymphocyte numbers during the day seemed appreciably lower than in the other groups. In a series of 13 pairs of stress and non-stress interviews, in 8 of the 13 there was evidence that the discussion of disturbing topics produced a mild alarm reaction.
Reciprocal regulation of pulmonary and cardiac angiotensin-converting enzyme in rats with severe left ventricular hypertrophy
Authors: M Pfeifer
Journal: Cardiovascular Research (1998)

Objective: Numerous studies support the concept that cardiac angiotensin-converting enzyme (ACE) is involved in the pathophysiology of left ventricular hypertrophy. However, the pulmonary vasculature is considered to be the most prominent site of ACE expression. We thus examined the tissue specificity of ACE regulation in rats with severe cardiac pressure overload hypertrophy in transition to cardiac failure with secondary pulmonary hypertension. Methods and Results: Rats were studied 12 weeks after banding of the ascending aorta (LVH, n=20) that resulted in a 1.7-fold increase in left ventricular (LV) to body weight ratio. In addition, as compared to sham-operated rats (n=20), we observed in LVH rats a 1.6-fold increase in right ventricular (RV) to body weight ratio, the development of pulmonary hypertension, and elevated plasma renin activities. Moreover, ACE mRNA and activity levels were more than 2-fold higher in both hypertrophied ventricles (P<0.01, each). In contrast, pulmonary ACE mRNA and activity levels were markedly decreased in animals with LVH (more than 30%, respectively, P<0.05 vs. sham). Interestingly, LV and RV ACE activity, as well as systolic pulmonary artery pressure and plasma renin activity, were all inversely related to pulmonary ACE activity. In order to differentiate the potential role of elevated renin in the down-regulation of pulmonary ACE, additional rats (n=12) were treated with furosemide that resulted in a 8-fold rise in plasma renin activity, but only in a marginal decrease of pulmonary ACE mRNA levels and activity (−10% vs. sham (n=8), P-value n.s.). Conclusions: The data indicate tissue specific reciprocal regulation of pulmonary and cardiac ACE in rats with cardiac pressure overload hypertrophy and pulmonary hypertension, a phenomenon that may potentially result in a partial shift of angiotensin II formation from the pulmonary to the cardiac circulation.
Evolution of Hox Post-Transcriptional Regulation by Alternative Polyadenylation and MicroRNA Modulation Within 12 Drosophila Genomes
Authors: Pedro Patraquim, Maria Warnefors, Claudio R. Alonso
Journal: Molecular Biology and Evolution (2011)

Hox genes encode a family of transcriptional regulators that operate differential developmental programs along the anteroposterior axis of bilateral animals. Regulatory changes affecting Hox gene expression are believed to have been crucial for the evolution of animal body plans. In Drosophila melanogaster, Hox expression is post-transcriptionally regulated by microRNAs (miRNAs) acting on target sites located in the 3′ untranslated regions (3′UTRs) of Hox mRNAs. Notably, recent work has shown that during D. melanogaster development Hox genes produce mRNAs with variable 3′UTRs (short and long forms) in different sets of tissues as a result of alternative polyadenylation; importantly, Hox short and long 3′UTRs contain very different target sites for miRNAs. Here, we use a computational approach to explore the evolution of Hox 3′UTRs treated with especial regard to miRNA regulation. Our work is focused on the 12 Drosophila species for which genomic sequences are available and shows, first, that alternative polyadenylation of Hox transcripts is a feature shared by all drosophilids tested in the study. Second, that the regulatory impact of miRNAs is evolving very fast within the Drosophila group. Third, that in contrast to the low degree of primary sequence conservation, Hox 3′UTR regions within the group show very similar RNA topology indicating that RNA structure is under strong selective pressure. Finally, we also demonstrate that Hox alternative polyadenylation can remodel the control regions seen by miRNAs by at least two mechanisms: via adding new cis-regulatory sequences—in the form of miRNA target sites—to short 3'UTR forms as well as by modifying the regulatory impact of miRNA target sites in short 3′UTR forms through changes in RNA secondary structure caused by the use of distal polyadenylation signals.
Randomized Trial of Radiation Therapy Plus Procarbazine, Lomustine, and Vincristine Chemotherapy for Supratentorial Adult Low-Grade Glioma: Initial Results of RTOG 9802
Authors: Edward G. Shaw, Meihua Wang, Stephen W. Coons, David G. Brachman, Jan C. Buckner, Keith J. Stelzer, Geoffrey R. Barger, Paul D. Brown, Mark R. Gilbert, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2012)

A prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).Eligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests.In all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02).PFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.
Effect of quinidine and temperature on sodium uptake and contraction frequency of cultured rat myocardial cells.
Authors: D McCall
Journal: Circulation Research (1976)

The effects of quinidine and temperature on Na influx and contraction frequency of synchronously contracting rat myocardial cells in monolayer cultures were studied. Quinidine (10(-6) M to 10(-1) M) produced a prompt reduction in Na influx, maximum after 30 seconds of exposure, and dose-dependent along a sigmoid log dose-response curve. At 37 degrees C, Na influx (mumol/10(11) cells per sec) decreased from 30.19 to 24.70 (P less than 0.001) and 10.49 (P less than 0.001) on exposure to quinidine, 10(-6) and 10(-2) M, respectively. Simultaneously the contraction frequency decreased from a control of 120/min to 105/min and 48/min with 10(-6) M and 5 X 10(-4) M quinidine. At higher concentrations spontaneous contractions ceased. The effects on Na influx and contraction were reversible by washing the cells free of the drug (30 seconds). A temperature-dependent decrease in the Na influx between 37 degrees C and 22 degrees C also induced a decrease in contraction frequency. Between 25 degrees C and 35 degrees C the Q10 values for Na influx and contraction frequency were 2.41 and 2.44 respectively. Under all conditions tested there was a constant linear relationship (r = 0.98) between Na influx and contraction frequency for all values of Na influx greater than 11.82 mumol/10(11) cells per sec. Na influx and contraction frequency were insensitive to tetrodotoxin (10(-5) g/ml) but very sensitive to verapamil and to changes in extracellular Na. Quinidine affected only the verapamil-sensitive Na influx. The results indicate a close relationship between verapamil-sensitive inward Na movement and automaticity in these cells and demonstrate that the quinidine-induced changes in automaticity are closely linked to the effect on Na influx.
Are All Chimeric Antigen Receptors Created Equal?
Authors: Jae H. Park, Renier J. Brentjens
Journal: Journal of Clinical Oncology (2015)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2014.57.5472 Journal of Clinical Oncology - published online before print January 20, 2015 PMID: 25605860 Are All Chimeric Antigen Receptors Created Equal? Jae H. ParkxJae H. ParkSearch for articles by this author , Renier J. BrentjensxRenier J. BrentjensSearch for articles by this author Show More Memorial Sloan Kettering Cancer Center, New York, NY https://doi.org/10.1200/JCO.2014.57.5472 First Page Full Text PDF Figures and Tables © 2015 by American Society of Clinical Oncology
Aromatherapy for sports and fitness
Authors: Preeti Sharma, Tilak R Meena
Journal: British Journal of Sports Medicine (2010)

The article describes the use of aromatherapy for achieving excellence in sports and fitness. Aromatherapy is the science of holistic approach for taking care of the body and mind using pleasant smelling of botanical oils. It has been extensively studied and found to be one of the fastest growing areas of alternative medicine. There have been numerous studies showing different plant oils' synergistic effects on body and mind energy facilitating excellence in sports and fitness. Most of the findings of these studies have found their way into various aromatherapy products and services. There are well over a hundred different natural essential oils having antiseptic, anti-inflammatory, pain relieving, antidepressant and even expectorant properties. The application of these oils not only helps to prevent and cure sports injuries but also to stimulate and relax the mind and body leading to higher fitness levels. Because of these inherent properties of essential oils, there is a growing interest in using them in toning up the body and mind in a variety of ways, viz. muscle preparation, musculo-skeletal, injury prevention, as sports medicine and an agent for uplifting sports psychology for achieving highest success rate in sports and fitness. Therefore, essential oils have a role in preparing the body and mind for optimum sports performance as well as postexertion recovery. They can be used as an aid to make the recovery faster by reducing the effect of fatigue and uplifting mind and body energy level. That is why essential oil therapy is now being recognised as a valuable therapy to enhance performance in sports and fitness.
Combined Transepithelial Phototherapeutic Keratectomy and Corneal Collagen Cross-Linking for Progressive Keratoconus
Authors: George D. Kymionis, Michael A. Grentzelos, George A. Kounis, Vasilios F. Diakonis, Aliki N. Limnopoulou, Sophia I. Panagopoulou
Journal: Ophthalmology (2012)
Many US medical associations and disease awareness groups depend heavily on funding by drug manufacturers
Authors: J. Lenzer
Journal: BMJ (2011)

Many medical societies and non-profit disease awareness organisations in the United States receive much of their funding from drug and device manufacturers, show documents recently released to the US senator Charles Grassley.

Senator Grassley, a Republican of Iowa, asked for financial information in December 2009 from 33 professional associations and groups that conduct research or promote disease awareness.

Among the organisations responding to Senator Grassley’s request was the American Medical Association, which reported that 16 drug, device, and communications companies donated nearly $5m (£3.1m; €3.5m) in 2007 for “continuing medical education” programmes and “communications conferences.”

Large donations to the association …
Attention Deficit/Hyperactivity Disorder: A Focused Overview for Children’s Environmental Health Researchers
Authors: Andréa Aguiar, Paul A. Eubig, Susan L. Schantz
Journal: Environmental Health Perspectives (2010)

Attention deficit/hyperactivity disorder (ADHD) is the most frequently diagnosed childhood neurobehavioral disorder. Much research has been done to identify genetic, environmental, and social risk factors for ADHD; however, we are still far from fully understanding its etiology. In this review we provide an overview of diagnostic criteria for ADHD and what is known about its biological basis. We also review the neuropsychological functions that are affected in ADHD. The goal is to familiarize the reader with the behavioral deficits that are hallmarks of ADHD and to facilitate comparisons with neurobehavioral deficits associated with environmental chemical exposures.Relevant literature on ADHD is reviewed, focusing in particular on meta-analyses conducted between 2004 and the present that evaluated associations between measures of neuropsychological function and ADHD in children. Meta-analyses were obtained through searches of the PubMed electronic database using the terms "ADHD," "meta-analysis," "attention," "executive," and "neuropsychological functions." Although meta-analyses are emphasized, nonquantitative reviews are included for particular neuropsychological functions where no meta-analyses were available.The meta-analyses indicate that vigilance (sustained attention), response inhibition, and working memory are impaired in children diagnosed with ADHD. Similar but somewhat less consistent meta-analytic findings have been reported for impairments in alertness, cognitive flexibility, and planning. Additionally, the literature suggests deficits in temporal information processing and altered responses to reinforcement in children diagnosed with ADHD. Findings from brain imagining and neurochemistry studies support the behavioral findings.Behavioral, neuroanatomical, and neurochemical data indicate substantial differences in attention and executive functions between children diagnosed with ADHD and non-ADHD controls. Comparisons of the neurobehavioral deficits associated with ADHD and those associated with exposures to environmental chemicals may help to identify possible environmental risk factors for ADHD and/or reveal common underlying biological mechanisms.
Establishment of reference values for differential cell counts in nasal lavage of healthy young adults
Authors: Yanqing Xie, Jiaxing Xie, Kefang Lai, Nanshan Zhong
Journal: European Respiratory Journal (2011)

Background:  Upper airway inflammation could be reflected by nasal lavage cytology test, which is characterized by advantages of non-invasive, simple, objective and costless. However, reference values nasal lavage cytology was not established.   Objectives:  To establish reference values and positive standard for nasal lavage cytology through screening normal healthy subjects and patients with allergic rhinitis according to strict inclusion criteria.   Methods:  143 normal healthy volunteers (control) and 166 subjects with allergic rhinitis (AR) were enrolled after detailed history inquiry, physical examination and allergen skin prick test. Nasal lavage cytology tests were performed, and the standard for judgment was defined as the average count of different inflammatory cells per 20 fields under 200× microscopic vision.   Results:  There was no statistical significance in gender constitutional proportion, age, height and weight among each group. 95% CI of neutrophils, eosinophils was (0∼12.61)/×200 and (0∼1.70)/×200, respectively. The median (interquartile range) of neutrophils were 0 (0.65)/×200 in AR group, which showed no statistical difference ( P >0.05) with that of normal group [0(0)/×200]. A significant difference was found in the median (interquartile range) of eosinophils [6.90(22.40)/×200] in AR group as compared with that of normal control group [0(0.10)/×200,  P    Conclusions:  Establishment of reference values of nasal lavage cytology test is helpful to discriminate normal individuals and patients with allergic rhinitis, but also a non-invasive tool for objective reflection on upper airway inflammation, which is of great value for scientific and clinical purposes.
ALS spinal neurons show varied and reduced mtDNA gene copy numbers and increased mtDNA gene deletions
Authors: Paula M Keeney, James P Bennett
Journal: Molecular Neurodegeneration (2010)

Spinal cord neurons of ALS patients demonstrate reduced cytochrome oxidase histochemical activity, and ALS spinal cord tissues have increased mitochondrial DNA (mtDNA) point mutations and depleted mtDNA levels. It is presently unknown whether mtDNA abnormalities are present in single human ALS neurons.Using laser capture microdissection (LCM) we isolated several hundred individual anterior spinal neurons from unfixed, frozen sections of 10 ALS and 7 age-matched CTL cervical spinal cords. DNA from each individual neuron was analyzed with multiplex qPCR for ND2, CO3, and ND4, three mitochondrial DNA genes encoding respiratory proteins. Scatterplots of individual spinal neuron results showed extensive heterogeneity of mtDNA gene levels across 4-5 orders of magnitude that were much more clustered in single Purkinje neurons isolated from CTL cerebella. Plots of ratios of ND4/ND2 and CO3/ND2 showed that many but not all ALS neurons from individuals contained low ratios of these mtDNA genes, implying greater abundances of mtDNA deletions in the major arc. Single CTL cerebellar Purkinje neurons did not contain high levels of apparent mtDNA deletions observed in anterior spinal neurons.At the time of ALS subjects' deaths, many but not all surviving anterior neurons in their cervical spinal cords have reduced mtDNA gene levels and increased mtDNA deletion abundances that arise for unclear reasons. If these anterior spinal neuron mtDNA gene deficiencies contribute to bioenergetic impairments, reduced synaptic function and increased risk of degeneration, then introduction into mitochondria and expression of intact mtDNA, now available through use of recently developed recombinant human TFAM, may reverse the course of ALS.