tbuckley/cabot-search huggingface dataset:
THE IMMUNE RESPONSE AGAINST HAPTEN-AUTOLOGOUS PROTEIN CONJUGATES IN THE MOUSE
Authors: Bent Rubin, Hans Wigzell
Journal: The Journal of Experimental Medicine (1973)

Mice immunized with hapten-autologous serum albumin conjugates (DNP-mouse serum albumin) were shown to contain immune B and T cells with specificity for the conjugate. Fractionation on antigen-coated Sepharose beads showed that B cells could be subdivided in two major groups: those reacting against the haptenic group (DNP) and those reactive against the new antigenic determinants (NADs) introduced into the protein carrier by the hapten coupling. It was shown previously that humoral antibodies formed against hapten-mouse serum albumin conjugates also were directed against these two groups of antigenic determinants and that the immune response to the NADs does not follow the genetic rules of high or low response against the hapten used. All together these findings support the distinct nature of the NADs over the haptenic groups, as recognized both at the humoral and cellular level. Absorption of mouse cells immune to hapten-autologous serum albumin conjugates on antigen-coated Sepharose beads using a variety of incubation conditions resulted in no specific retention of T cells. Therefore we had to resort to specificity studies of T cells in relation to T cell function. Relatively pure immune T cell suspensions were obtained using fractionation on anti-immunoglobulin-coated columns. DNP-MSA-specific T cells were shown to be very specific for the DNP-MSA conjugate with only one exception: they cross-reacted with antigenic determinants on DNP-rat serum albumin. As DNP-specific help was excluded in the present transfer system (as shown by the inability of cells from DNP-skin-painted mice and DNP-heterologous protein conjugate specific T cells [anti-immunoglobulin column purified] to help a DNP-MSA response), these results demonstrate the NAD specificity of the DNP-MSA-reactive T cells. The cross-reactivity pattern of DNP-MSA-specific T cells was similar to that found for humoral anti-NAD antibodies produced against the same immunogen. Whether B and T cells are activated by the same antigenic determinants is discussed.
Effect of three animal models of inflammation on nerve fibres in the synovium.
Authors: P I Mapp, D A Walsh, N E Garrett, B L Kidd, S C Cruwys, J M Polak, D R Blake
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--Both sensory and sympathetic nerve fibres are depleted in the synovium in rheumatoid arthritis (RA). The hypothesis that the induction of an inflammatory response in the synovium is capable of causing depletion of nerve fibres was tested. METHODS--To investigate this phenomenon experimental arthritis in the rat was induced by three different methods and the synovium was examined for evidence of nerve depletion by immunocytochemistry. RESULTS--In a synovitis induced by latex spheres, a mainly macrophage foreign body type reaction, no nerve depletion was seen. In contrast both in an antigen-induced and a hydrogen peroxide-induced model of arthritis nerve fibre depletion was observed. This appeared to affect sensory and sympathetic nerve fibres equally. Nerve fibre depletion was only seen in areas of inflammatory cell infiltration indicating that a mixed lymphocyte and macrophage population of cells may be necessary for this effect. CONCLUSIONS--An inflammatory response, containing lymphocytes and macrophages, in the synovium is capable of the depletion of the finely myelinated and unmyelinated neuropeptide-containing nerves.
Distinguishing phenotypes of childhood wheeze and cough using latent class analysis
Authors: B. D. Spycher, M. Silverman, A. M. Brooke, C. E. Minder, C. E. Kuehni
Journal: European Respiratory Journal (2008)

Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions. From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age. The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels. This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.
Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development.
Authors: A Bartolazzi, R Peach, A Aruffo, I Stamenkovic
Journal: The Journal of Experimental Medicine (1994)

CD44 is implicated in the regulation of tumor growth and metastasis but the mechanism by which expression of different CD44 isoforms determines the rate of primary and secondary tumor growth remains unclear. In the present study we use a human melanoma transfected with wild-type and mutant forms of CD44 to determine which functional property of the CD44 molecule is critical in influencing tumor behavior. We show that expression of a wild-type CD44 isoform that binds hyaluronic acid augments the rapidity of tumor formation by melanoma cells in vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment to hyaluronate, fails to do so. The importance of CD44-hyaluronate interaction in tumor development is underscored by the differential inhibitory effect of soluble wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44-Ig is shown to block tumor development. Taken together, these observations suggest that the tumor growth promoting property of CD44 is largely dependent on its ability to mediate cell attachment to hyaluronate.
Expression of the human c-fms proto-oncogene product (colony-stimulating factor-1 receptor) on peripheral blood mononuclear cells and choriocarcinoma cell lines.
Authors: C W Rettenmier, R Sacca, W L Furman, M F Roussel, J T Holt, A W Nienhuis, E R Stanley, C J Sherr
Journal: Journal of Clinical Investigation (1986)

The c-fms gene product is related, and possibly identical, to the receptor for the mononuclear phagocyte colony stimulating factor, CSF-1. Using antisera to a recombinant v-fms--coded polypeptide, glycoproteins encoded by the human c-fms locus were detected in mononuclear cells from normal peripheral blood and in promyelocytic HL-60 cells 24 h after induction of monocytic differentiation with phorbol ester. The 150-kD human c-fms--coded glycoprotein was expressed at the cell surface, was active as a tyrosine-specific protein kinase in vitro, and shared primary structural features with the product of the feline retroviral v-fms oncogene. A biochemically indistinguishable glycoprotein was detected in human choriocarcinoma cell lines. Like peripheral blood mononuclear cells and phorbol ester-treated HL-60 cells, the choriocarcinoma cells expressed high affinity binding sites for human CSF-1. In addition to serving as a lineage specific growth factor in hematopoiesis, CSF-1 may play a role in normal trophoblast development.
Ischemic Postconditioning in Pigs
Authors: Andreas Skyschally, Patrick van Caster, Kerstin Boengler, Petra Gres, Judith Musiolik, Dustin Schilawa, Rainer Schulz, Gerd Heusch
Journal: Circulation Research (2008)

Ischemic postconditioning (IPoC) reduces infarct size following ischemia/reperfusion. Whether or not phosphorylation of RISK (reperfusion injury salvage kinases) (AKT, ERK1/2, P70S6K, GSK3β) is causal for protection by IPoC is controversial. We therefore studied the impact of RISK on IPoC in anesthetized pigs subjected to 90 minutes of left anterior descending coronary artery hypoperfusion and 120 minutes of reperfusion. In protocol 1, IPoC, by 6 cycles of 20/20 seconds of reperfusion/reocclusion (n=13), was compared with immediate full reperfusion (IFR) (n=15). In protocol 2, IPoC (n=4) or IFR (n=4) was performed with pharmacological RISK blockade by IC coinfusion of Wortmannin and U0126. Infarct size was determined by TTC staining, and the expression of phosphorylated RISK proteins by Western blot analysis in biopsies. In protocol 1, infarct size was 20±3% (percentage of area at risk; mean±SEM) with IPoC and 33±4% ( P &lt;0.05) with IFR. RISK phosphorylation increased with reperfusion but was not different between IPoC and IFR. In protocol 2, Wortmannin and U0126 blocked the increases in RISK phosphorylation during reperfusion, but infarct size was still smaller with IPoC (15±7%) than with IFR (35±6%; P &lt;0.05).
Differential Diagnosis of Pulmonary Carcinoma Following Head and Neck Cancer by Genetic Analysis
Authors: T.W. Geurts, M.L.F van Velthuysen, F. Broekman, T. Hooft van Huysduynen, M.W.M. van den Brekel, N. van Zandwijk, H. van Tinteren, P. Nederlof, A.J.M. Balm, R.H. Brakenhoff
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Patients with head and neck cancer often develop a lung tumor that can be diagnosed as distant metastasis (DM) or second primary tumor (SPT). In this study, we use TP53 mutation analysis for validation of an allelic loss marker panel and a decision algorithm for distinguishing between DM and SPT. Experimental Design: Tumor pairs of 39 patients were analyzed for TP53 mutations, for patterns of allelic loss and immunohistochemical analysis of p53 expression. Results of these three analyses were compared, using mutation analysis as gold standard. Results: Loss of heterozygosity (LOH) analysis indicated DM in 15 and SPT in 23 cases (one inconclusive). TP53 mutation analysis was informative in 15 cases. Based on the p53 mutation status alone, nine tumors were diagnosed as SPT and six as DM. In all 15 cases the LOH analysis was in concordance with the TP53 mutation analysis. Immunostaining for p53 showed promise as a first scan to diagnose lung tumors as SPT but cannot be used to diagnose DM. Conclusion: The TP53 mutation data validate the suitability of the LOH marker panel and decision algorithm for differential diagnosis of DM and SPT in the lung. LOH analysis can theoretically be exploited in almost all cases and is less laborious than TP53 mutation analysis.
Chromatin-based Mechanisms of Renal Epithelial Differentiation
Authors: Kameswaran Surendran, Raphael Kopan
Journal: Journal of the American Society of Nephrology (2011)

Successful regenerative renal medicine depends on understanding the molecular mechanisms by which diverse phenotypes of epithelial cells differentiate from metanephric mesenchyme to populate nephrons. Whereas many genes are maintained in a poised state within the population of pluripotent progenitors, specialized epithelial functions reflect the selective expression of a subset of genes and the repression of all others. Here we highlight some common mechanisms of cell differentiation and epigenetic regulation to discuss their implications for renal epithelial development, repair, and disease.
Chronic Bronchitis and Chronic Obstructive Pulmonary Disease
Authors: Victor Kim, Gerard J. Criner
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can develop CB, and small airway pathology has been linked to worse clinical outcomes, such as increased mortality and lesser improvement in lung function after lung volume reduction surgery. However, in recent years, a greater understanding of the importance of CB as a phenotype to identify patients with a beneficial response to therapy has been described. Herein we review the epidemiology of CB, the evidence behind its clinical consequences, the current understanding of the pathophysiology of goblet cell hyperplasia in COPD, and current therapies for CB.
Functional Sympatholysis During Exercise in Patients With Type 2 Diabetes With Intact Response to Acetylcholine
Authors: Pia Thaning, Laurids T. Bune, Morten Zaar, Bengt Saltin, Jaya B. Rosenmeier
Journal: Diabetes Care (2011)

Sympathetic vasoconstriction is blunted in contracting human skeletal muscles (functional sympatholysis). In young subjects, infusion of adenosine and ATP increases blood flow, and the latter compound also attenuates α-adrenergic vasoconstriction. In patients with type 2 diabetes and age-matched healthy subjects, we tested 1) the sympatholytic capacity during one-legged exercise, 2) the vasodilatory capacity of adenosine and ATP, and 3) the ability to blunt α-adrenergic vasoconstriction during ATP infusion.In 10 control subjects and 10 patients with diabetes and normal endothelial function, determined by leg blood flow (LBF) response to acetylcholine infusion, we measured LBF and venous NA, with and without tyramine-induced sympathetic vasoconstriction, during adenosine-, ATP-, and exercise-induced hyperemia.LBF during acetylcholine did not differ significantly. LBF increased ninefold during exercise and during adenosine- and ATP-induced hyperemia. Infusion of tyramine during exercise did not reduce LBF in either the control or the patient group. During combined ATP and tyramine infusions, LBF decreased by 30% in both groups. Adenosine had no sympatholytic effect.In patients with type 2 diabetes and normal endothelial function, functional sympatholysis was intact during moderate exercise. The vasodilatory response for adenosine and ATP did not differ between the patients with diabetes and the control subjects; however, the vasodilatory effect of adenosine and ATP and the sympatholytic effect of ATP seem to decline with age.
Conformity under uncertainty: Reliance on gender stereotypes in online hiring decisions
Authors: Eric Luis Uhlmann, Raphael Silberzahn
Journal: Behavioral and Brain Sciences (2014)

Abstract We apply Bentley et al.’s theoretical framework to better understand gender discrimination in online labor markets. Although such settings are designed to encourage employer behavior in the northwest corner of Homo economicus , actual online hiring decisions tend to drift southeast into a “confirmation bias plus weak feedback loops” pattern of discrimination based on inaccurate social stereotypes.
Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial
Authors: Gregg W Stone, Harvey D White, E Magnus Ohman, Michel E Bertrand, A Michael Lincoff, Brent T McLaurin, David A Cox, Stuart J Pocock, James H Ware, Frederick Feit, Antonio Colombo, Steven V Manoukian, Alexandra J Lansky, Roxana Mehran, Jeffrey W Moses
Journal: The Lancet (2007)
Association between air pollution and general practitioner visits for respiratory diseases in Hong Kong
Authors: T W Wong
Journal: Thorax (2006)

<h3>Introduction</h3> The Northern Ontario School of Medicine (NOSM) has a social accountability mandate to serve the healthcare needs of the people of Northern Ontario, Canada. A multiyear, multimethod tracking study of medical students and postgraduate residents is being conducted by the Centre for Rural and Northern Health Research (CRaNHR) in conjunction with NOSM starting in 2005 when NOSM first enrolled students. The objective is to understand how NOSM9s selection criteria and medical education programmes set in rural and northern communities affect early career decision-making by physicians with respect to their choice of medical discipline, practice location, medical services and procedures, inclusion of medically underserved patient populations and practice structure. <h3>Methods and analysis</h3> This prospective comparative longitudinal study follows multiple cohorts from entry into medical education programmes at the undergraduate (UG) level (56–64 students per year at NOSM) or postgraduate (PG) level (40–60 residents per year at NOSM, including UGs from other medical schools and 30–40 NOSM UGs who go to other schools for their residency training) and continues at least 5 years into independent practice. The study compares learners who experience NOSM UG and NOSM PG education with those who experience NOSM UG education alone or NOSM PG education alone. Within these groups, the study also compares learners in family medicine with those in other specialties. Data will be analysed using descriptive statistics, χ<sup>2</sup> tests, logistic regression, and hierarchical log-linear models. <h3>Ethics and dissemination</h3> Ethical approval was granted by the Research Ethics Boards of Laurentian University (REB #2010-08-03 and #2012-01-09) and Lakehead University (REB #031 11-12 Romeo File #1462056). Results will be published in peer-reviewed scientific journals, presented at one or more scientific conferences, and shared with policymakers and decision-makers and the public through 4-page research summaries and social media such as Twitter (@CRaNHR, @NOSM) or Facebook.
Immune Mechanisms in Leukemia: Suppression of Cellular Immunity by Starvation 2
Authors: Douglas Martinez, Susan Cox, Omelan A. Lukasewycz, William H. Murphy
Journal: JNCI Journal of the National Cancer Institute (1975)

The effects of starvation on the cellular immune response of C58/Wm mice to syngeneic malignant lymphoid cells (1b cells) were studied. Mice were starved 1-3 days before or after immunization. The capacity of starved animals to survive immunization was used to quantify immunosuppression. When starvation bracketed immunization by -1 to +1 days, only 2 of 23 mice survived primary immunization, compared with 100% survival for nonstarved controls. A 2-day period of starvation +1 to +7 days after primary immunization reduced survival about 30%. For a test of the effect of starvation on the secondary immune response, mice were immunized, starved 2 days, and then challenged with viable lb cells. When mice were starved from -3 to +1 days before or after challenge, there was a 25-45% decrease in survival. Starvation caused a disproportionate depletion of lymphoid tissue elements. The proportional loss in the weight of the spleen and thymus was essentially twice as great as the loss in total body weight. The peripheral blood leukocyte count was reduced by about 20% when mice were starved 1 day and by approximately 50% when they were starved 2 days. When mice were starved 1-2 days, the differential leukocyte count did not shift and there was no significant change in the number of blood erythrocytes or in the hematocrit. Starvation for 2 days caused a 65-70% reduction in the number of viable mononuclear spleen cells. Starvation for 3 days caused about 90% reduction. Adoptive cell transfer experiments showed that the immunocompetence of individual spleen immunocytes was not reduced by starvation.
Cardiac 1-adrenergic drive in pathological remodelling
Authors: E. A. Woodcock, X.-J. Du, M. E. Reichelt, R. M. Graham
Journal: Cardiovascular Research (2007)

The heart is richly innervated by sympathetic nerves, and both acute and chronic regulation of cardiac function via sympathetically released catecholamines acting on cardiomyocyte adrenergic receptors (ARs), is critical for circulatory homeostasis. Cardiomyocytes express α1A- and α1B-, and β1- and β2-AR subtypes, which are all members of the G-protein-coupled receptor superfamily that signal via interaction with heterotrimeric G-proteins. Cardiac function – both inotropy and chronotropy – is regulated predominantly by β1-AR. Activation of α1-ARs also results in increased contractility, as well as changes in the electrophysiological properties and metabolic responses of the heart. Nonetheless, there is little evidence that cardiac α1-ARs play a major functional role under normal physiological conditions. In pathological settings, α1-ARs may function in a compensatory fashion to maintain cardiac inotropy when the β-AR system is downregulated and uncoupled from G-proteins and effectors. In addition, as we consider here, recent evidence from clinical studies and from genetically engineered animal models indicates that α1-ARs are importantly involved in both developmental cardiomyocyte growth, as well as pathological hypertrophy. In the presence of pressure overload or with myocardial infarction, activation of α1-ARs, particularly the α1A-subtype, also appears to produce important pro-survival effects at the level of the cardiomyocyte, and to protect against maladaptive cardiac remodelling and decompensation to heart failure.
Randomized comparison of progenitor-cell mobilization using chemotherapy, stem-cell factor, and filgrastim or chemotherapy plus filgrastim alone in patients with ovarian cancer.
Authors: A Weaver, J Chang, E Wrigley, E de Wynter, P J Woll, M Lind, B Jenkins, C Gill, P M Wilkinson, R Pettengell, J A Radford, C D Collins, T M Dexter, N G Testa, D Crowther
Journal: Journal of Clinical Oncology (1998)

PURPOSE This was the first randomized study to investigate the efficacy of peripheral-blood progenitor cell (PBPC) mobilization using stem-cell factor (SCF) in combination with filgrastim (G-CSF) following chemotherapy compared with filgrastim alone following chemotherapy. PATIENTS AND METHODS Forty-eight patients with ovarian cancer were treated with cyclophosphamide and randomized to receive filgrastim 5 microg/kg alone or filgrastim 5 microg/kg plus SCF. The dose of SCF was cohort-dependent (5, 10, 15, and 20 microg/kg), with 12 patients in each cohort, nine of whom received SCF plus filgrastim and the remaining three patients who received filgrastim alone. On recovery from the WBC nadir, patients underwent a single apheresis. RESULTS SCF in combination with filgrastim following chemotherapy enhanced the mobilization of progenitor cells compared with that produced by filgrastim alone following chemotherapy. This enhancement was dose-dependent for colony-forming unit-granulocyte-macrophage (CFU-GM), burst-forming unit-erythrocyte (BFU-E), and CD34+ cells in both the peripheral blood and apheresis product. In the apheresis product, threefold to fivefold increases in median CD34+ and progenitor cell yields were obtained in patients treated with SCF 20 microg/kg plus filgrastim compared with yields obtained in patients treated with filgrastim alone. Peripheral blood values of CFU-GM, BFU-E, and CD34+ cells per milliliter remained above defined threshold levels longer with higher doses of SCF. The higher doses of SCF offer a greater window of opportunity in which to perform the apheresis to achieve high yields. CONCLUSION SCF (15 or 20 microg/kg) in combination with filgrastim following chemotherapy is an effective way of increasing progenitor cell yields compared with filgrastim alone following chemotherapy.