tbuckley/cabot-search huggingface dataset:
THE EFFECT OF <i>BORDETELLA PERTUSSIS</i> ON LYMPHOCYTE CYCLIC AMP METABOLISM
Authors: Charles W. Parker, Stephen I. Morse
Journal: The Journal of Experimental Medicine (1973)

Bordetella pertussis culture fractions produce decreased metabolic responses to isoproterenol and epinephrine in mice and rats, suggesting the possibility of systemic beta adrenergic blockade. The present study was undertaken to elucidate the mechanism of the alteration in adrenergic responsiveness and to clarify its relationship to other biological effects of the organism. Lymphocytes were selected as a suitable tissue because of the marked alteration in lymphocyte distribution in pertussis-treated mice and rats, suggesting a change in the surface properties of these cells. Human peripheral blood lymphocytes, purified by nylon fiber chromatography, were studied. In short incubation experiments (20 min or less) B. pertussis did not alter the cyclic AMP response to isoproterenol, prostaglandin E (PGE(1)), or methacholine. However, when cells were preincubated with B. pertussis for 90 min at 37 degrees C, the responses to all three agents were markedly inhibited. Although these observations provide direct confirmation of the ability of B. pertussis to inhibit catecholamine responsiveness, the fact that PGE(1) and methacholine responses were also inhibited suggests that blockade at the level of the beta adrenergic receptor is doubtful. The inhibitory activity was localized in a nondialyzable, protein-rich fraction that is precipitated from B. pertussis culture fluid by ammonium sulfate at 90% of saturation. The bulk of the activity was obtained in the load volume after 50,000 g centrifugation in a cesium chloride gradient, density 1.2-1.5 (fraction 4). Fraction 4 produced a change in lymphocyte hormonal responsiveness at concentrations as low as 5 ng/ml. The relationship between cyclic AMP inhibitory activity in isolated human cells and leukocytosis-producing activity in intact mice was studied. The two activities seemed to parallel one another quite closely until the final Sephadex G-150 fractionation step, in which the two activities were obtained in the same column fraction, but a greater recovery of the leukocytosis-producing activity was obtained. Additional purification will be required to establish conclusively whether the same macromolecule is responsible for both activities. The availability of a bacterial product that markedly inhibits cyclic AMP accumulation in purified lymphocytes may help to clarify the role of cyclic AMP in lymphocyte activation by antigen and nonspecific mitogens.
Observations of isolated enterocytes and of their subcellular components using transmission and scanning electron microscopy
Authors: M. N. Marsh, T. J. Peters, A. C. Brown
Journal: Gut (1971)

Isolated epithelial cells and their subcellular organelles were examined both by transmission and by scanning electron microscopy. It was shown that scanning electron microscopy is particularly useful for displaying the three-dimensional structure of the brush border. Furthermore, it has been possible to observe the basal aspect of separated epithelium for the first time. Studies on the scanning electron microscopic appearance of isolated nuclei, mitochondria, and lysosomes did not reveal any evidence of surface structure.
Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial
Authors: Paul D Griffiths, Anna Stanton, Erin McCarrell, Colette Smith, Mohamed Osman, Mark Harber, Andrew Davenport, Gareth Jones, David C Wheeler, James O'Beirne, Douglas Thorburn, David Patch, Claire E Atkinson, Sylvie Pichon, Paul Sweny, Marisa Lanzman, Elizabeth Woodford, Emily Rothwell, Natasha Old, Ruth Kinyanjui, Tanzina Haque, Sowsan Atabani, Suzanne Luck, Steven Prideaux, Richard SB Milne, Vincent C Emery, Andrew K Burroughs
Journal: The Lancet (2011)
Tamoxifen and ICI 182,780 negatively influenced cardiac cell growth via an estrogen receptor-independent mechanism
Authors: I Mercier
Journal: Cardiovascular Research (2003)

Recent studies have demonstrated that selective estrogen receptor modulators (SERMs) reduced identifiable risk factors implicated in cardiovascular disease. Despite this observation, the direct effect of SERMs on cardiac cell growth remains unexplored.Neonatal rat cardiac myocytes (CM) and fibroblasts (CF) were exposed to either the partial estrogen receptor agonist/antagonist 4-OH tamoxifen (e.g., SERM) or the pure estrogen receptor antagonist ICI 182,780 and the effect on DNA synthesis, cell cycle protein expression and extracellular signal-regulated kinase (ERK1/2) phosphorylation were assessed.The treatment of CM and CF with either 4-OH tamoxifen or ICI 182,780 decreased DNA synthesis in the absence of apoptosis via an estrogen receptor-independent pathway. In CM and CF, 4-OH tamoxifen and ICI 182,780 treatment reduced proliferating cell nuclear antigen protein expression and concomitantly increased p27Kip1. 4-OH Tamoxifen and ICI 182,780 treatment increased ERK1/2 phosphorylation in CM and CF, and ERK1/2 kinase (MEK)-dependent inhibition of ERK1/2 activation attenuated ICI 182,780-mediated suppression of DNA synthesis.These data are the first to describe cardiac cells as novel targets of SERMs and ICI 182,780, and highlight the role of the ERK1/2 pathway in the suppression of DNA synthesis.
Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial
Authors: Edward J Gane, Stuart K Roberts, Catherine AM Stedman, Peter W Angus, Brett Ritchie, Rob Elston, David Ipe, Peter N Morcos, Linda Baher, Isabel Najera, Tom Chu, Uri Lopatin, M Michelle Berrey, William Bradford, Mark Laughlin, Nancy S Shulman, Patrick F Smith
Journal: The Lancet (2010)
Constitutive intestinal NF-κB does not trigger destructive inflammation unless accompanied by MAPK activation
Authors: Monica Guma, Dariusz Stepniak, Helena Shaked, Martina E. Spehlmann, Steve Shenouda, Hilde Cheroutre, Ildelfonso Vicente-Suarez, Lars Eckmann, Martin F. Kagnoff, Michael Karin
Journal: The Journal of Experimental Medicine (2011)

Nuclear factor (NF)-κB, activated by IκB kinase (IKK), is a key regulator of inflammation, innate immunity, and tissue integrity. NF-κB and one of its main activators and transcriptional targets, tumor necrosis factor (TNF), are up-regulated in many inflammatory diseases that are accompanied by tissue destruction. The etiology of many inflammatory diseases is poorly understood, but often depends on genetic factors and environmental triggers that affect NF-κB and related pathways. It is unknown, however, whether persistent NF-κB activation is sufficient for driving symptomatic chronic inflammation and tissue damage. To address this question, we generated IKKβ(EE)IEC mice, which express a constitutively active form of IKKβ in intestinal epithelial cell (IECs). IKKβ(EE)IEC mice exhibit NF-κB activation in IECs and express copious amounts of inflammatory chemokines, but only small amounts of TNF. Although IKKβ(EE)IEC mice exhibit inflammatory cell infiltration in the lamina propria (LP) of their small intestine, they do not manifest tissue damage. Yet, upon challenge with relatively mild immune and microbial stimuli, IKKβ(EE)IEC mice succumb to destructive acute inflammation accompanied by enterocyte apoptosis, intestinal barrier disruption, and bacterial translocation. Inflammation is driven by massive TNF production, which requires additional activation of p38 and extracellular-signal–regulated kinase mitogen-activated protein kinases (MAPKs).
VEGF receptor signaling links inflammation and tumorigenesis in colitis-associated cancer
Authors: Maximilian J. Waldner, Stefan Wirtz, André Jefremow, Moritz Warntjen, Clemens Neufert, Raja Atreya, Christoph Becker, Benno Weigmann, Michael Vieth, Stefan Rose-John, Markus F. Neurath
Journal: The Journal of Experimental Medicine (2010)

Whereas the inhibition of vascular endothelial growth factor (VEGF) has shown promising results in sporadic colon cancer, the role of VEGF signaling in colitis-associated cancer (CAC) has not been addressed. We found that, unlike sporadic colorectal cancer and control patients, patients with CAC show activated VEGFR2 on intestinal epithelial cells (IECs). We then explored the function of VEGFR2 in a murine model of colitis-associated colon cancer characterized by increased VEGFR2 expression. Epithelial cells in tumor tissue expressed VEGFR2 and responded to VEGF stimulation with augmented VEGFR2-mediated proliferation. Blockade of VEGF function via soluble decoy receptors suppressed tumor development, inhibited tumor angiogenesis, and blocked tumor cell proliferation. Functional studies revealed that chronic inflammation leads to an up-regulation of VEGFR2 on IECs. Studies in conditional STAT3 mutant mice showed that VEGFR signaling requires STAT3 to promote epithelial cell proliferation and tumor growth in vivo. Thus, VEGFR-signaling acts as a direct growth factor for tumor cells in CAC, providing a molecular link between inflammation and the development of colon cancer.
Hyperbilirubinemia of Fasting
Authors: Peter V. D. Barrett
Journal: JAMA (1971)

The effect of a 44- to 48-hour fast on the serum bilirubin concentration was studied in five normal subjects and in five patients with hepatic dysfunction. The total serum bilirubin (TSB) concentration increased progressively during the fasting period in all patients; expressed as a percent of the control value, it averaged 240% for the normal subjects and 194% for the patients with hepatic dysfunction at the completion of the fast (<i>P</i>&gt;0.05). One normal subject fasted for 110 hours; the TSB increased to 326% of the control value at 63 hours and then fell to approximately twice the control value for the remainder of the fast. A diurnal rhythm of the TSB was demonstrated in one patient, but was suppressed by nocturnal feedings. It was concluded that an increase in bilirubin concentration occurs as a function of fasting.
Impact of Automated Calls With Nurse Follow-Up on Diabetes Treatment Outcomes in a Department of Veterans Affairs Health Care System: A randomized controlled trial
Authors: J D Piette, M Weinberger, F B Kraemer, S J McPhee
Journal: Diabetes Care (2001)

We evaluated automated telephone disease management (ATDM) with telephone nurse follow-up as a strategy for improving diabetes treatment processes and outcomes in Department of Veterans Affairs (VA) clinics. We also compared the results with those of a prior ATDM trial conducted in a county health care system.A total of 272 VA patients with diabetes using hypoglycemic medications were randomized. During the 1-year study period, intervention patients received biweekly ATDM health assessment and self-care education calls, and a nurse educator followed up with patients based on their ATDM assessment reports. Telephone surveys were used to measure patients' self-care, symptoms, and satisfaction with care. Outpatient service use was evaluated using electronic databases and self-reports, and glycemic control was measured by HbA1c and serum glucose testing.At 12 months, intervention patients reported more frequent glucose self-monitoring and foot inspections than patients receiving usual care and were more likely to be seen in podiatry and diabetes specialty clinics. Intervention patients also were more likely than control patients to have had a cholesterol test. Among patients with baseline HbA1c levels > or =8%, mean end-point values were lower among intervention patients than control patients (8.7 vs. 9.2%, respectively; P = 0.04). Among intervention and control patients with baseline values > or =9%, mean end-point values were 9.1 and 10.2%, respectively (P = 0.04). At follow-up, intervention patients reported fewer symptoms of poor glycemic control than control patients and greater satisfaction with their health care.This intervention improved the quality of VA diabetes care. Intervention effects for most end points replicated findings from the prior county clinic trial, although intervention-control differences in the current study were smaller because of the relatively good self-care and health status among the current study's enrollees.
Myocardial Infarct–Sparing Effect of Adenosine A <sub>2A</sub> Receptor Activation Is due to Its Action on CD4 <sup>+</sup> T Lymphocytes
Authors: Zequan Yang, Yuan-Ji Day, Marie-Claire Toufektsian, Yaqin Xu, Susan I. Ramos, Melissa A. Marshall, Brent A. French, Joel Linden
Journal: Circulation (2006)

Background— We previously used adenosine A 2A receptor (A2AR) knockout (KO) mice and bone marrow transplantation to show that the infarct-sparing effect of A2AR activation at reperfusion is primarily due to effects on bone marrow–derived cells. In this study we show that CD4 + but not CD8 + T lymphocytes contribute to myocardial ischemia/reperfusion injury. Method and Results— After a 45-minute occlusion of the left anterior descending coronary artery and reperfusion, T cells accumulate in the infarct zone within 2 minutes. Addition of 10 μg/kg of the A2AR agonist ATL146e 5 minutes before reperfusion produces a significant reduction in T-cell accumulation and a significant reduction in infarct size (percentage of risk area) measured at 24 hours. In Rag1 KO mice lacking mature lymphocytes, infarct size is significantly smaller than in C57BL/6 mice. Infarct size in Rag1 KO mice is increased to the level of B6 mice by adoptive transfer of 50 million CD4 + T lymphocytes derived from C57BL/6 or A2AR KO but not interferon-γ KO mice. ATL146e completely blocked the increase in infarct size in Rag1 KO mice reconstituted with B6 but not A2AR KO CD4 + T cells. The number of neutrophils in the reperfused heart at 24 hours after infarction correlated well with the number of lymphocytes and infarct size. Conclusions— These results strongly suggest that the infarct-sparing effect of A2AR activation is primarily due to inhibition of CD4 + T-cell accumulation and activation in the reperfused heart.
A Tale of Two Retinal Domains: Near-Optimal Sampling of Achromatic Contrasts in Natural Scenes through Asymmetric Photoreceptor Distribution
Authors: Tom Baden, Timm Schubert, Le Chang, Tao Wei, Mariana Zaichuk, Bernd Wissinger, Thomas Euler
Journal: Neuron (2013)

Highlights•Mouse retina samples visual scenes above the horizon using >90% functional S cones•Functional S cones preferentially encode dark over light contrasts•Dark bias of functional S cones matches the predominance of dark contrasts in the sky•Ventral S opsin dominance as adaptation to achromatic differences in sky versus groundSummaryFor efficient coding, sensory systems need to adapt to the distribution of signals to which they are exposed. In vision, natural scenes above and below the horizon differ in the distribution of chromatic and achromatic features. Consequently, many species differentially sample light in the sky and on the ground using an asymmetric retinal arrangement of short- (S, "blue") and medium- (M, "green") wavelength-sensitive photoreceptor types. Here, we show that in mice this photoreceptor arrangement provides for near-optimal sampling of natural achromatic contrasts. Two-photon population imaging of light-driven calcium signals in the synaptic terminals of cone-photoreceptors expressing a calcium biosensor revealed that S, but not M cones, preferred dark over bright stimuli, in agreement with the predominance of dark contrasts in the sky but not on the ground. Therefore, the different cone types do not only form the basis of "color vision," but in addition represent distinct (achromatic) contrast-selective channels.
The Uses and Limitations of Ultra-Violet Radiation in Dermatology: The Evolution of Actinotherapy
Authors: S. E. Dore
Journal: BMJ (1927)

mCALJ U 55 clinic in connexion with her ante-natal department, and only found it necessary to induce abortion in the rare cases when every other treatment had failed.She was agreeably surprised at ths6 small number of Caesarean sections Pro- fessor Kerrhad men-tioned.She .hadabandoned steriliza- tion for lheart cases to a great extent, and strongly dis- approved of hysterectomy as the miieans to this end.Future pregnancy mig,ht be prevented by z rays or radium, or a conitraceptive pessary might be used when further preg- nancy w%as not advisable for a year or two.She thought that many patients with tuberculosis becanmle worse through being discharged too soon from a sanatoriulmi to bad home conditions for fear that labour nlight occur in the saiiatorium.Dr. MARY MACNICOL (Edinburgh) thought that the out- look in syphilis with pregnancy was very good, but with gonorrhoea the reverse was the case.She urged that once a patient was known to bave had syphilis the treatrnent should be giveen ini every subsequent pregnancy, even if the Wassermanii reaction was niegative.A history of repeated miscarriages was sufficient to justify a course of anti- syphilitic treatment.With more attention to cervical and vaginal discharges less would be heard of the occurrence of autogenetic puerperal sepsis.Dr. E. K. MACKENZIE (Tain) gave his experiences as a rural practitioner far away from specialist advice and help.Cases of mitral stenosis and aortic incompetence had caused him the greatest amount of worry.He thought that digitalis should be r-estricted to cases of fibrillation.The menital state of cardiac patienits, especially in aortic disease, was sometimes particularly distressing.Mr. R. H. PARAMORE (Rugby) explained the absence of higher blood pressure in normal pregnanicy as being due to the rise of intra-abdominial pressure, wlhich increased the blood supply of the brain and extremities.It was the rise in pressuire within the abdomen which led to an increased strain on the right side of the heart, and hence, in disease, to failure of compensation.In cases where Caesarean section was called for on account of cardiac distress he suggested that hysterectomy would be advan- tageous by removing the products of involution, which otherwise might seriously affect the already embarrassed heart muscle.
Investigating the genetic association between<i>ERAP1</i>and spondyloarthritis
Authors: Amir Kadi, Brigitte Izac, Roula Said-Nahal, Ariane Leboime, Liesbet Van Praet, Kurt de Vlam, Dirk Elewaut, Gilles Chiocchia, Maxime Breban
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> A robust association between polymorphisms in the non-major histocompatibility complex gene <i>ERAP1</i> and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of <i>ERAP1</i> polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype–phenotype correlations. <h3>Methods</h3> We studied 734 independent SpA cases and 632 controls from two European cohorts. Five single-nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30187 and rs2287987 were genotyped, and case-control association analyses were carried using PLINK 1.07 software. Linkage disequilibrium and haplotypes were estimated with Haploview. Analysis was first carried out in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients. <h3>Results</h3> Consistent with previous studies conducted in AS, rs30187 was the most significantly associated SNP with SpA (p=0.008 in the French, and p=6.46×10<sup>−4</sup> in the Belgian cohorts). In the combined cohorts, this SNP was associated with both AS and non-AS (P<sub>combined</sub><i></i>= 3.9×10<sup>−5</sup> and P<sub>combined</sub><i></i>= 0.005, respectively). A similar trend was observed with other SNPs. The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P<sub>combined</sub><i></i>= 9.08×10<sup>−4</sup>), including AS and non-AS (P<sub>combined</sub>=6.16×10<sup>−4</sup> and P<sub>combined</sub>=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P<sub>combined</sub>=2.36×10<sup>−7</sup>, P<sub>combined</sub><i></i>= 5.69×10<sup>−6</sup> and P<sub>combined</sub><i></i>= 2.13×10<sup>−4</sup>, respectively). <h3>Conclusions</h3> This is the first study to show an association between several polymorphisms located in ERAP1 and SpA as a whole. Our findings demonstrate consistent association of the same SNPs and haplotypes with both AS and non-AS subtypes of SpA.
Serum procalcitonin level: clinical significance
Authors: D. Aggarwal, P.R. Mohapatra, P. Aggarwal
Journal: European Respiratory Journal (2011)

Serum procalcitonin level: clinical significanceTo the Editors:The study by UGAJIN et al. [1] nicely evaluates the role of procalcitonin in differentiating community-acquired pneumonia (CAP) from pulmonary tuberculosis (PTB).They have further highlighted its prognostic value in PTB.Few aspects regarding this promising biomarker need to be discussed to understand its clinical significance.Procalcitonin, a propeptide of calcitonin, is an important host response biomarker indicative of infection.In particular, it aids in assessing the severity of infection and its prognosis [2,3].Using this severity marker to differentiate two infectious diseases seems unjustified.Both the diseases can have varying degrees of severity and may also be confounded by factors such as immunocompromised status and presence of comorbidities, such as post surgery [4], trauma [5], acute exacerbations of chronic obstructive pulmonary disease and acute coronary syndrome, which can alter procalcitonin levels.Clinical presentations, pattern of radiological involvement and sputum examination still remain the gold standard, as well as cost-effective measures to differentiate PTB and CAP.Serum procalcitonin, although an important prognostic marker, may not be useful in the presence of the aforementioned comorbidities.Extensive radiological involvement, multiorgan infection, high sputum positivity and drug resistance are more reliable markers for severity of tuberculosis and poor prognosis.Serum procalcitonin measurement should be performed in selected cases of PTB where its positivity should alert the clinician to search for tubercular foci in other organs of the body.
Impact of Diabetes and Its Treatment on Cognitive Function Among Adolescents Who Participated in the Diabetes Control and Complications Trial
Authors: Gail Musen, Alan M. Jacobson, Christopher M. Ryan, Patricia A. Cleary, Barbara H. Waberski, Katie Weinger, William Dahms, Meg Bayless, Nancy Silvers, Judith Harth, Neil White
Journal: Diabetes Care (2008)

The purpose of this study was to evaluate whether severe hypoglycemia or intensive therapy affects cognitive performance over time in a subgroup of patients who were aged 13-19 years at entry in the Diabetes Control and Complications Trial (DCCT).This was a longitudinal study involving 249 patients with type 1 diabetes who were between 13 and 19 years old when they were randomly assigned in the DCCT. Scores on a comprehensive battery of cognitive tests obtained during the Epidemiology of Diabetes Interventions and Complications follow-up study, approximately 18 years later, were compared with baseline performance. We assessed the effects of the original DCCT treatment group assignment, mean A1C values, and frequency of severe hypoglycemic events on eight domains of cognition.There were a total of 294 reported episodes of coma or seizure. Neither frequency of hypoglycemia nor previous treatment group was associated with decline on any cognitive domain. As in a previous analysis of the entire study cohort, higher A1C values were associated with declines in the psychomotor and mental efficiency domain (P < 0.01); however, the previous finding of improved motor speed with lower A1C values was not replicated in this subgroup analysis.Despite relatively high rates of severe hypoglycemia, cognitive function did not decline over an extended period of time in the youngest cohort of patients with type 1 diabetes.