tbuckley/cabot-search huggingface dataset:
Norepinephrine increases the pathogenic potential of Campylobacter jejuni
Authors: T A Cogan, A O Thomas, L E N Rees, A H Taylor, M A Jepson, P H Williams, J Ketley, T J Humphrey
Journal: Gut (2006)

<b>Background:</b><i>Campylobacter jejuni</i> can cause a spectrum of diseases in humans, ranging from enteritis and diarrhoea to severe inflammation, profuse bloody diarrhoea and chronic relapsing infection. Norepinephrine (NE) levels in the intestine increase under conditions of stress and trauma, and are thought to result in spill over of NE into the intestinal lumen. NE is known to stimulate the growth of a range of bacterial species, and to increase the pathogenicity of <i>Escherichia coli</i>. <b>Aim:</b> To determine the effects of NE on the pathogenic potential of <i>C jejuni</i> in a model system. <b>Methods:</b><i>C jejuni</i> was grown in iron-replete and iron-limited media in the presence and absence of 100 μM NE. Several virulence-associated characteristics, including motility and cell invasion, were measured. <b>Results:</b> When <i>C jejuni</i> was grown in iron-limited media in the presence of NE, growth rate, motility and invasion of cultured epithelial cells were increased compared with cultures grown in the absence of NE. Bacteria exposed to NE during growth also caused greater subsequent disruption of cultured epithelial cell monolayers, inducing widespread breakdown of tight junctions. <b>Conclusion:</b> Exposure to NE causes an increase in the virulence-associated properties of <i>Campylobacter</i>. Stress and concomitant infection could therefore be contributory factors to the variable presentation of this disease.
Nonneutral Evolution of the Transcribed Pseudogene Makorin1-p1 in Mice
Authors: O. Podlaha
Journal: Molecular Biology and Evolution (2004)

Pseudogenes are nonfunctional relics of formerly functional genes and are thought to evolve neutrally. In some pseudogenes, however, the molecular evolutionary patterns are atypical of neutrally evolving sequences, exhibiting sequence conservation, codon-usage bias, and other features associated with functional genes. Makorin1-p1 is a transcribed pseudogene first identified in the mouse Mus musculus. The transcript of Makorin1-p1 can regulate the stability of the transcript of its paralogous functional gene Makorin1. Specifically, the half-life of Makorin1 mRNA increases significantly in the presence of Makorin1-p1 transcript, and targeted deletion of Makorin1-p1 is lethal in mice. Here, we show that Makorin1-p1 originated after the separation of Mus and Rattus but before the divergence of M. musculus and M. pahari. The transcribed region of Makorin1-p1 exhibits rates of point and indel substitutions that are two to four times lower than those in the untranscribed region, suggesting that the transcribed region is under functional constraint and is not evolving neutrally. Although the transcript of Makorin1-p1 likely functions by its sequence similarity to Makorin1, we find no evidence of gene conversion between them, indicating that functional conservation alone is sufficient to maintain their coordinated evolution. A duplication-degeneration model is proposed to explain how Makorin1-p1 was co-opted into the regulatory system of Makorin1. There are over 10,000 pseudogenes in a typical mammalian genome, and it is plausible that many functional but untranslatable pseudogenes exist. Our results illustrate the potential of using evolutionary analysis to identify such pseudogenes from genome sequences.
Night shift decreases cognitive performance of ICU physicians
Authors: François Maltese, Mélanie Adda, Amandine Bablon, Sami Hraeich, Christophe Guervilly, Samuel Lehingue, Sandrine Wiramus, Marc Leone, Claude Martin, Renaud Vialet, Xavier Thirion, Antoine Roch, Jean-Marie Forel, Laurent Papazian
Journal: Intensive Care Medicine (2015)
Perioperative Maintenance of Normothermia Reduces the Incidence of Morbid Cardiac Events
Authors: Steven M. Frank, Lee A. Fleisher, Michael J. Breslow, Michael S. Higgins, Krista F. Olson, Susan Kelly, Charles Beattie
Journal: JAMA (1997)

To assess the relationship between body temperature and cardiac morbidity during the perioperative period.Randomized controlled trial comparing routine thermal care (hypothermic group) to additional supplemental warming care (normothermic group).Operating rooms and surgical intensive care unit at an academic medical center.Three hundred patients undergoing abdominal, thoracic, or vascular surgical procedures who either had documented coronary artery disease or were at high risk for coronary disease.The relative risk of a morbid cardiac event (unstable angina/ischemia, cardiac arrest, or myocardial infarction) according to thermal treatment. Cardiac outcomes were assessed in a double-blind fashion.Mean core temperature after surgery was lower in the hypothermic group (35.4+/-0.1 degrees C) than in the normothermic group (36.7+/-0.1 degrees C) (P<.001) and remained lower during the early postoperative period. Perioperative morbid cardiac events occurred less frequently in the normothermic group than in the hypothermic group (1.4% vs 6.3%; P=.02). Hypothermia was an independent predictor of morbid cardiac events by multivariate analysis (relative risk, 2.2; 95% confidence interval, 1.1-4.7; P=.04), indicating a 55% reduction in risk when normothermia was maintained. Postoperative ventricular tachycardia also occurred less frequently in the normothermic group than in the hypothermic group (2.4% vs 7.9%; P=.04).In patients with cardiac risk factors who are undergoing noncardiac surgery, the perioperative maintenance of normothermia is associated with a reduced incidence of morbid cardiac events and ventricular tachycardia.
Screening for Postmenopausal Osteoporosis: A Review of the Evidence for the U.S. Preventive Services Task Force
Authors: Heidi D. Nelson, Mark Helfand, Steven H. Woolf, Janet D. Allan
Journal: Annals of Internal Medicine (2002)

Background: Although osteoporotic fractures present an enormous health burden, it is not clear whether screening to identify high-risk persons is appropriate. Purpose: To examine evidence on the benefits and harms of screening postmenopausal women for osteoporosis. Data Sources: MEDLINE (1966 to May 2001), HealthSTAR (1975 to May 2001), and Cochrane databases; reference lists; and experts. Study Selection: English-language abstracts that included original data about postmenopausal women and osteoporosis and addressed the effectiveness of risk factor assessment, bone density tests, or treatment were included. Data Extraction: Selected information about patient population, interventions, clinical end points, and study design were extracted, and a set of criteria was applied to evaluate study quality. Data Synthesis: No trials of the effectiveness of screening have been published. Instruments developed to assess clinical risk factors for low bone density or fractures have moderate to high sensitivity and low specificity. Among different bone density tests measured at various sites, bone density measured at the femoral neck by dual-energy x-ray absorptiometry is the best predictor of hip fracture. Women with low bone density have approximately a 40% to 50% reduction in fracture risk when treated with bisphosphonates. Conclusions: Population screening would be based on evidence that the risk for osteoporosis and fractures increases with age, that the short-term risk for fracture can be estimated by bone density tests and risk factors, and that fracture risk can be reduced with treatment. The role of risk factor assessment and different bone density techniques, frequency of screening, and identification of subgroups for which screening is most effective remain unclear.
Mortality and survival in rheumatoid arthritis: a 25 year prospective study of 100 patients.
Authors: P A Reilly, J A Cosh, P J Maddison, J J Rasker, A J Silman
Journal: Annals of the Rheumatic Diseases (1990)

One hundred patients with classical (52) or definite (48) rheumatoid arthritis (RA) at one year after onset were followed up for 25 years. By then 63 had died, in one third of whom RA had either directly caused or contributed to death. These patients, at one year after onset of arthritis, had a higher proportion with classical RA and more functional impairment than the rest. Thirty five of the surviving 37 patients were seen for review. Eleven were well with no functional impairment. At one year after onset they had a lower erythrocyte sedimentation rate (ESR) and higher haemoglobin than the others, in whom a poorer outcome was associated with a persistently raised ESR and lower haemoglobin. The initial Rose-Waaler titre was a poor prognostic guide, but a better functional outcome was associated with conversion to seronegativity or a marked fall in rheumatoid factor level.
Ampakines Enhance Weak Endogenous Respiratory Drive and Alleviate Apnea in Perinatal Rats
Authors: Jun Ren, Xiuqing Ding, John J. Greer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Apnea of prematurity, which is prevalent among infants born at less than 34 weeks gestation, is treated with caffeine, theophylline, or aminophylline. However, not all newborns respond adequately to, or tolerate, methylxanthine administration, and thus alternative pharmacological therapies are required.Rodent models are used to test the hypothesis that the ampakine CX1739, a positive allosteric modulator of amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors, strengthens perinatal respiratory drive and reduces apneas. We also provide a systematic study of the effects of caffeine for comparison.Respiratory neural activity was recorded from brainstem-spinal cord in vitro perinatal rat preparations, and [Formula: see text]e was recorded in newborn rat pups using whole-body plethysmography under normoxic and hypoxic conditions.Using in vitro brainstem-spinal cord preparations, we found that CX1739 (10-100 μM) dose-dependently increases the frequency of respiratory activity generated by fetal and newborn rat preparations under normoxic and hypoxic conditions. Plethysmographic recordings in vivo from Postnatal Day 0 rats demonstrated that CX1739 (10 mg/kg) increases the frequency and regularity of ventilation, reduces apneas, and protects against hypoxia-induced respiratory depression.The net effect of ampakine enhancement of respiratory drive in perinatal rodents is a marked increase in ventilation and the regularity of respiratory patterns in perinatal rat preparations. Importantly, from the perspective of clinical applications, CX1739 readily crosses the blood-brain barrier, is metabolically stable, and has passed through phase I and II clinical trials in adults.
A1C Between 5.7 and 6.4% as a Marker for Identifying Pre-Diabetes, Insulin Sensitivity and Secretion, and Cardiovascular Risk Factors
Authors: Carlos Lorenzo, Lynne E. Wagenknecht, Anthony J.G. Hanley, Marian J. Rewers, Andrew J. Karter, Steven M. Haffner
Journal: Diabetes Care (2010)

OBJECTIVE A1C is an optional method for diagnosing diabetes and also for detecting individuals at increased risk of the disease. However, how A1C compares with fasting (FPG) and 2-h plasma glucose for detecting at-risk individuals is not well known. RESEARCH DESIGN AND METHODS A 2-h glucose tolerance test, frequently sampled intravenous glucose tolerance test, and A1C were obtained at the follow-up examination in 855 participants in the Insulin Resistance Atherosclerosis Study (IRAS). For this report, 385 individuals were at increased risk of diabetes as defined by A1C between 5.7 and 6.4%, impaired glucose tolerance (IGT), and/or impaired fasting glucose (IFG). RESULTS IFG and IGT identified 69.1 and 59.5% of all individuals at increased risk of diabetes, respectively. A1C 5.7–6.4% detected 23.6% of all at-risk individuals, although more African Americans (31.4%) and Hispanics (35.2%) than non-Hispanic whites (9.9%). Relative to A1C, FPG was more strongly related to fasting insulin (r = 0.38 vs. 0.26; P &amp;lt; 0.01), acute insulin response (r = – 0.20 vs. – 0.09; P &amp;lt; 0.01), and waist circumference (r = 0.43 vs. 0.25; P &amp;lt; 0.001) by the Spearman correlation test. Similarly, 2-h plasma glucose was more strongly related to Si (r = – 0.40 vs. – 0.27; P &amp;lt; 0.01) and triglycerides (r = 0.30 vs. 0.08; P &amp;lt; 0.001). CONCLUSIONS A1C 5.7–6.4% is less sensitive for detecting at-risk individuals than IFG and IGT, particularly among non-Hispanic whites. Single determinations of FPG and 2-h plasma glucose seem to be more precise correlates of insulin resistance and secretion than A1C and, in general, better for other metabolic disorders.
Antiestrogens and Their Therapeutic Applications in Breast Cancer and Other Diseases
Authors: Simak Ali, Laki Buluwela, R. Charles Coombes
Journal: Annual Review of Medicine (2010)

The identification of the link between breast cancer and estrogens has led to the development of antiestrogens, in particular tamoxifen, to inhibit the activities of estrogen receptors (ERs) in breast cancer cells. The clinical use of tamoxifen has played a major part in decreasing breast cancer mortality over the past 30 years. Though antiestrogenic in the breast, some antiestrogens have estrogen-like actions in other tissues, acting to promote bone density and protect against cardiovascular disease, thus raising the possibility of their use in counteracting the effects of estrogen loss following menopause. Moreover, antiestrogens show efficacy as chemopreventive agents in women at high risk of developing breast cancer. Thus, antiestrogens define an important and well-understood class of cancer drug, which continue to be a mainstay in breast cancer treatment.
Challenging behaviour and learning disabilities: summary of NICE guidance
Authors: S. Pilling, E. Marcus, C. Whittington, G. Murphy
Journal: BMJ (2015)

This is one of a series of BMJ summaries of new guidelines based on the best available evidence; they highlight important recommendations for clinical practice, especially where uncertainty or controversy exists.It is relatively common for people with a learning disability to develop behaviour that challenges.In educational, health, and social care settings, prevalence rates of challenging behaviour in people with learning disabilities vary from 10% to 15%, 1 2 with rates peaking between the ages of 20 and 49 years.Rates are higher in people with more severe disabilities and within inpatient settings. 1Behaviour that challenges includes aggression, self injury, stereotypic behaviour, and withdrawal, which often result from the interaction of personal and environmental factors.Such behaviour can have detrimental consequences for the person, including lower quality of life, restrictive practices, physical abuse, and out of area placements. 1 This article summarises the most recent recommendations from the National Institute for Health and Care Excellence (NICE) on challenging behaviour and learning disabilities in adults, children, and young people. 3 RecommendationsNICE recommendations are based on systematic reviews of the best available evidence and explicit consideration of cost effectiveness.When minimal evidence is available, recommendations are based on the Guideline Development Group's experience and opinion of what constitutes good practice.Evidence levels for the recommendations are given in italic in square brackets.
The endothelin system and its role in pulmonary arterial hypertension (PAH)
Authors: J Pepke-Zaba
Journal: Thorax (2005)

Endothelin receptor antagonists represent a major advance in the treatment of PAH but much remains to be learned of their effectiveness in specific forms of pulmonary hypertension

The endothelin system is emerging as an important mediator in pulmonary arterial hypertension (PAH) and the endothelin receptor antagonists represent a major advance in the treatment of this condition. PAH results from a massive proliferation of myofibroblast cells in the intima of small pulmonary arteries. Thickening of the media is also observed and abnormal proliferation of endothelial cells may result in plexiform lesions.

The endothelin system has been extensively studied over the 15 years since its initial discovery by Yanagisawa and co-workers in 1988. It is clear that endothelin 1 (ET-1) is a key mediator of pulmonary vascular biology and pathophysiology. It is a powerful vasoconstrictor and proliferative cytokine. In the early 1990s ET-1 was identified as an important mediator of PAH. Plasma ET-1 levels were found to be elevated in patients with pulmonary hypertension and correlated with the raised pulmonary vascular resistance.1 Furthermore, expression of ET-1 mRNA and protein was increased in endothelial cells comprising vascular lesions in primary pulmonary hypertension.2

The availability of ET-1 receptor antagonists allowed testing of these compounds in experimental models. In rat models of experimental pulmonary hypertension—including pulmonary hypertension induced by chronic (2–3 weeks) hypoxia3 and by the alkaloid monocrotaline—ET-1 antagonists prevent the development of PAH. More compelling is the finding that ET-1 antagonists can partly reverse established PAH in experimental models.4 These observations suggest that ET-1 antagonists can potentially reverse established pulmonary vascular remodelling rather than simply prevent vasoconstriction.5 In clinical PAH the main component of the increased pulmonary vascular resistance is remodelling rather than vasoconstriction. However, in animal models the predominant lesion is medial hypertrophy rather than intimal thickening, and …
TYPE-SPECIFIC ANTIGENS, M AND T, OF MATT AND GLOSSY VARIANTS OF GROUP A HEMOLYTIC STREPTOCOCCI
Authors: Rebecca C. Lancefield
Journal: The Journal of Experimental Medicine (1940)

1. Two qualitatively different type-specific antigens, designated M and T, have been found present in matt variants of group A hemolytic streptococci, but only one of these, the T antigen, occurs in the degraded glossy variant. 2. The protein nature of the M antigen, present in matt variants only, has been demonstrated in previous work, but the chemical characteristics of the newly recognized antigenic factor, T, present in both variants, have not been determined. This T factor is identified only by its immunological reactions. It is unknown whether the two type-specific antigenic factors, M and T, occur as separate chemical entities in the matt variant or in conjugation. 3. Antibody to the type-specific protein, M, appears responsible for the M precipitin reaction, for type-specific protection, and, as a rule, for part of the type-specific agglutination of matt variants, but in type 1 it does not cause agglutination. 4. Antibody to the second type-specific antigen, T, seems to be solely responsible for type-specific agglutination of the glossy form and to play a large rôle in type-specific agglutination of the matt form, but apparently it is not involved in protection. This T antibody causes all of the type-specific agglutination of type 1. Consequently, type 1 matt and glossy variants agglutinate and absorb agglutinin alike, and antisera to both are identical in content of type-specific agglutinin though they differ in respect to M antibody. 5. Recognition of the principle underlying type-specific agglutination of glossy variants makes it possible to suggest, with certain reservations, the use of glossy variants for type classification by agglutination. These variants are suitable for preparing type-specific agglutinating antisera, and they form stable suspensions for use in the reaction. Improved methods are needed for deriving glossy from matt variants.
Transcriptome analysis of human cancer reveals a functional role of Heme Oxygenase-1 in tumor cell adhesion
Authors: Stefanie Tauber, Alexander Jais, Markus Jeitler, Sandra Haider, Julia Husa, Josefine Lindroos, Martin Knöfler, Matthias Mayerhofer, Hubert Pehamberger, Oswald Wagner, Martin Bilban
Journal: Molecular Cancer (2010)

Abstract Background Heme Oxygenase-1 (HO-1) is expressed in many cancers and promotes growth and survival of neoplastic cells. Recently, HO-1 has been implicated in tumor cell invasion and metastasis. However, the molecular mechanisms underlying these biologic effects of HO-1 remain largely unknown. To identify a common mechanism of action of HO-1 in cancer, we determined the global effect of HO-1 on the transcriptome of multiple tumor entities and identified a universal HO-1-associated gene expression signature. Results Genome-wide expression profiling of Heme Oxygenase-1 expressing versus HO-1 silenced BeWo choriocarcinoma cells as well as a comparative meta-profiling of the preexisting expression database of 190 human tumors of 14 independent cancer types led to the identification of 14 genes, the expression of which correlated strongly and universally with that of HO-1 (P = 0.00002). These genes included regulators of cell plasticity and extracellular matrix (ECM) remodeling (MMP2, ADAM8, TGFB1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30), and phosphorylation (ALPPL2). We selected PXDN, an adhesion molecule involved in ECM formation, for further analysis and functional characterization. Immunofluorescence and Western blotting confirmed the positive correlation of expression of PXDN and HO-1 in BeWo cancer cells as well as co-localization of these two proteins in invasive extravillous trophoblast cells. Modulation of HO-1 expression in both loss-of and gain-of function cell models (BeWo and 607B melanoma cells, respectively) demonstrated a direct relationship of HO-1 expression with cell adhesion to Fibronectin and Laminin coated wells. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo and 607B cells led to reduced cell attachment to Laminin and Fibronectin coated wells. Conclusions Collectively, our results show that HO-1 expression determines a distinct 'molecular signature' in cancer cells, which is enriched in genes associated with tumorigenesis. The protein network downstream of HO-1 modulates adhesion, signaling, transport, and other critical cellular functions of neoplastic cells and thus promotes tumor cell growth and dissemination.
IFN-γ production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo
Authors: Birgit Sawitzki, Cherry I. Kingsley, Vanessa Oliveira, Mahzuz Karim, Manuela Herber, Kathryn J. Wood
Journal: The Journal of Experimental Medicine (2005)

The significance of cytokine production by CD4+ regulatory T (T reg) cells after antigen exposure in vivo and its impact on their regulatory activity remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4 therapy generates alloantigen reactive T reg cells that can prevent rejection of donor-specific skin grafts that are mediated by naive CD45RBhighCD4+ T cells. To examine the kinetics and importance of cytokine gene transcription by such alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor alloantigen in vivo. CD25+CD4+ T cells, but not CD25−CD4+ T cells, showed a fivefold increase in IFN-γ mRNA expression within 24 h of reencountering alloantigen in vivo. This expression kinetic was highly antigen-specific and was of functional significance. Neutralizing IFN-γ at the time of cotransfer of alloantigen reactive T reg cells, together with CD45RBhighCD4+ effector T cells into Rag−/− skin graft recipients, resulted in skin graft necrosis in all recipients; the generation and function of alloantigen-reactive T reg cells was impaired dramatically in IFN-γ–deficient mice. These data support a unique role for IFN-γ in the functional activity of alloantigen-reactive T reg cells during the development of operational tolerance to donor alloantigens in vivo.