tbuckley/cabot-search huggingface dataset:
Expression of Inducible Nitric Oxide Synthase in Rat Experimental Autoimmune Myocarditis With Special Reference to Changes in Cardiac Hemodynamics
Authors: Satoru Hirono, M. Omedul Islam, Mikio Nakazawa, Yutaka Yoshida, Makoto Kodama, Akira Shibata, Tohru Izumi, Shoichi Imai
Journal: Circulation Research (1997)

Excessive NO produced by an inducible NO synthase (iNOS) has been implicated in many types of immune-associated disorders of the cardiovascular system, but it remains to be determined whether NO plays a role in myocarditis. Thus, the significance of iNOS expression in the development of experimental autoimmune myocarditis (EAM), an animal model of human giant cell myocarditis, was investigated. Lewis rats were immunized with cardiac myosin and were killed 7, 14, 21, 28, and 49 days after immunization. The development of severe myocarditis was observed on days 14, 21, and 28 in association with significant deterioration of hemodynamics determined by cardiac catheterization, which peaked on day 21. In parallel with histological severity of myocarditis and deterioration of cardiac performance, iNOS activity in the heart measured by [14C]L-citrulline formation was markedly increased on days 14, 21, and 28. The expression of iNOS was confirmed by immunoblotting and was localized to the infiltrating inflammatory cells found in the vicinity of necrotic myocytes by immunohistochemical analysis. Aminoguanidine, a selective inhibitor of iNOS, significantly decreased the iNOS activity (1.04 +/- 0.37 compared with 29.1 +/- 8.62 pmol.min-1.mg protein-1 in untreated myosin-immunized rats, P < .01) and effectively attenuated histopathological changes of EAM on day 21. Hemodynamic parameters were also improved from 64 +/- 3 to 89 +/- 3 mm Hg for mean blood pressure, from 80 +/- 2 to 113 +/- 4 mm Hg for left ventricular systolic pressure, from 7.8 +/- 0.3 to 3.2 +/- 0.3 mm Hg for left ventricular end-diastolic pressure, from 2867 +/- 137 to 4180 +/- 102 mm Hg/s for +dP/dt, and from 2717 +/- 132 to 4180 +/- 184 mm Hg/s for -dP/dt (P < .01). The values after aminoguanidine treatment were not significantly different from the control values. These results suggest an important role for NO in mediating pathophysiological changes in myocarditis of autoimmune origin.
Cardiotrophin-1 defends the liver against ischemia-reperfusion injury and mediates the protective effect of ischemic preconditioning
Authors: Maria Iñiguez, Carmen Berasain, Eduardo Martinez-Ansó, Matilde Bustos, Puri Fortes, Diane Pennica, Matias A. Avila, Jesús Prieto
Journal: The Journal of Experimental Medicine (2006)

Ischemia-reperfusion (I/R) liver injury occurs when blood flow is restored after prolonged ischemia. A short interruption of blood flow (ischemic preconditioning [IP]) induces tolerance to subsequent prolonged ischemia through ill-defined mechanisms. Cardiotrophin (CT)-1, a cytokine of the interleukin-6 family, exerts hepatoprotective effects and activates key survival pathways like JAK/STAT3. Here we show that administration of CT-1 to rats or mice protects against I/R liver injury and that CT-1–deficient mice are exceedingly sensitive to this type of damage. IP markedly reduced transaminase levels and abrogated caspase-3 and c-Jun–NH2-terminal kinase activation after I/R in normal mice but not in CT-1–null mice. Moreover, the protective effect afforded by IP was reduced by previous administration of neutralizing anti–CT-1 antibody. Prominent STAT3 phosphorylation in liver tissue was observed after IP plus I/R in normal mice but not in CT-1–null mice. Oxidative stress, a process involved in IP-induced hepatoprotection, was found to stimulate CT-1 release from isolated hepatocytes. Interestingly, brief ischemia followed by short reperfusion caused mild serum transaminase elevation and strong STAT3 activation in normal and IL-6–deficient mice, but failed to activate STAT3 and provoked marked hypertransaminasemia in CT-1–null animals. In conclusion, CT-1 is an essential endogenous defense of the liver against I/R and is a key mediator of the protective effect induced by IP.
Effect of eight months of inhaled beclomethasone dipropionate and budesonide on carbohydrate metabolism in adults with asthma.
Authors: K Kiviranta, M Turpeinen
Journal: Thorax (1993)

BACKGROUND--The safety of high dose inhaled steroids has been a subject of debate. The efficacy and safety of beclomethasone dipropionate and budesonide inhalations were evaluated by measuring their effects on pulmonary function, on the hypothalamic-pituitary-adrenocortical axis, and on carbohydrate metabolism in adults with unstable asthma. METHODS--Fifteen adults with unstable asthma and 15 healthy controls were studied. Eight patients were treated with beclomethasone dipropionate in initially high (2 mg/day for five months) and subsequently lower (1 mg/day for three months) doses. Seven patients were treated with budesonide at doses of 1.6 mg/day for five months followed by 0.8 mg/day for three months. Blood glucose and serum insulin were measured in an oral glucose tolerance test and plasma cortisol in an adrenocorticotrophic hormone test. The antiasthmatic effect of treatment was evaluated by measuring peak morning expiratory flow rates and forced expiratory volume in one second (FEV1). RESULTS--The FEV1 increased significantly after one month of treatment (medians 88% v 96%, p < 0.01), and nocturnal symptoms disappeared within two weeks of treatment in both groups. At one month, the high dose significantly decreased serum insulin concentrations as calculated from the areas under the incremental two hours curves in the glucose tolerance test. The decrease was 59% for beclomethasone dipropionate (medians 76 v 31 mU/l/h, p < 0.005) and 42% for budesonide (medians 79 v 46 mU/l/h, p < 0.01). The median areas at five and eight months were intermediate for both drugs. No significant differences were found when the five and eight month values were compared either with the baseline or with one month values. The difference between the baseline values of both groups and the respective values in healthy controls was significant (medians 79 v 49 mU/l/h, p < 0.01). The one month values for the patients and control subjects were similar. Paralleling the changes for insulin, the area under the incremental two hour blood glucose curve decreased significantly (medians 1.4 v 0.4 mmol/l/h, p < 0.05) during the first month of treatment. The five and eight month values were intermediate (medians 0.8 and 0.7 mmol/l/h, respectively). These changes were not significant compared with the baseline or the one month areas. Similar changes were seen in both treatment groups. Neither treatment had any significant effect on plasma cortisol in the one hour adrenocorticotrophic hormone test. CONCLUSIONS--In patients stressed by uncontrolled asthma, the antiasthmatic effect of high dose beclomethasone dipropionate and budesonide was accompanied by a significant initial decrease in insulin resistance with a parallel improvement in glucose tolerance. During prolonged treatment a small increase in insulin sensitivity was found. The overall effect of beclomethasone dipropionate and budesonide inhalations on carbohydrate metabolism may be beneficial in patients with uncontrolled asthma.
Pneumococcal infection in adults: burden of disease
Authors: J.J.C. Drijkoningen, G.G.U. Rohde
Journal: Clinical Microbiology and Infection (2013)

To overview the present global burden of pneumococcal disease is important because new preventive measures such as the pneumococcal conjugate vaccine 13 are currently being evaluated. Pneumococcal disease is roughly divided into non-invasive and invasive disease. The burden of non-invasive pneumococcal disease in adults is mainly determined by community-acquired pneumonia. Pneumococcal pneumonia has high incidence rates and carries a high mortality risk, especially in the elderly. Within the cluster of invasive pneumococcal diseases, pneumonia also represents the most common infectious source. Incidence and mortality rates of both non-invasive and invasive disease have changed as a result of pneumococcal vaccination in children. However, especially elderly patients with comorbidities remain vulnerable to morbidity and mortality caused by pneumococcal disease. The current review summarizes the current knowledge on the epidemiology including outcome of the main clinical forms of pneumococcal disease, with a special focus on elderly patients. Furthermore, the economic burden and future vaccine strategies are briefly discussed.
Sonic hedgehog expression correlates with fundic gland differentiation in the adult gastrointestinal tract
Authors: G R van den Brink
Journal: Gut (2002)

Sonic hedgehog (Shh) is an important endodermal morphogenetic signal during the development of the vertebrate gut. It controls gastrointestinal patterning in general, and gastric gland formation in particular. We have previously shown that Shh regulates gastric gland proliferation in the adult but detailed analysis of its expression along the adult gastrointestinal tract has never been undertaken. We therefore studied Shh expression along the normal human and rodent adult gastrointestinal tract as well as in intestinal metaplasia of the stomach, gastric and intestinal metaplasia of the oesophagus, and gastric heterotopia in Meckel's diverticulum.The studies were performed with in situ hybridisation and by immunohistochemistry using an antibody that recognises the Shh precursor form.We found that in the normal gastrointestinal tract, high levels of Shh were expressed in the fundic glands of the stomach. Shh expression was also found in fundic gland metaplasia and heterotopia. However, Shh expression was lost in intestinal metaplasia of the stomach.We found a strong correlation between Shh expression and fundic gland differentiation. Our current study therefore provides evidence that in addition to its role in gastric epithelial development, Shh plays a unique role in gastric epithelial differentiation in adults.
Reactivity of the Human Fetal Pulmonary Circulation to Maternal Hyperoxygenation Increases During the Second Half of Pregnancy
Authors: Juha Rasanen, Dennis C. Wood, Robert H. Debbs, Jose Cohen, Stuart Weiner, James C. Huhta
Journal: Circulation (1998)

The aims of the present study were to determine whether maternal hyperoxygenation affects human fetal pulmonary circulation and whether there is a gestational age-related response in the fetal pulmonary circulation to maternal hyperoxygenation during the second half of gestation.Twenty women between 20 and 26 weeks of gestation and 20 women between 31 and 36 weeks of gestation with normal singleton pregnancies were randomized to receive either 60% humidified oxygen or medical compressed air (room air) by a face mask. Fetal aortic and pulmonary valve; ductus arteriosus (DA); and right (RPA), left (LPA), and distal (DPA) pulmonary artery blood velocity waveforms were obtained by Doppler ultrasound before, during, and after maternal administration of either 60% oxygen or room air. Left and right ventricular cardiac outputs, DA volume blood flow, and RPA and LPA volume blood flows (Qp) were calculated. Foramen ovale volume blood flow (left ventricular cardiac output-Qp) was estimated. Pulsatility index (PI) values of DA, RPA, LPA, and DPA were calculated. Maternal hyperoxygenation did not change any of the measured fetal parameters between 20 and 26 weeks, whereas between 31 and 36 weeks, the PI values of RPA, LPA, and DPA decreased (P<.0001) and the PI of DA increased (P<.0001). In addition, Qp increased (P<.001), and DA volume blood flow (P<.01) and foramen ovale volume blood flow (P<.03) decreased. Left and right ventricular cardiac outputs were unchanged. All changes returned to baseline after maternal hyperoxygenation was discontinued.Reactivity of the human fetal pulmonary circulation to maternal hyperoxygenation increases with advancing gestation; this suggests that fetal pulmonary circulation is under acquired vasoconstriction at least after 31 to 36 weeks of gestation.
Wheat allergen exposure and the prevalence of work‐related sensitization and allergy in bakery workers
Authors: J. H. Jacobs, T. Meijster, E. Meijer, E. Suarthana, D. Heederik
Journal: Allergy (2008)

Occupational airway diseases are common among bakers. The present study describes the association between exposure to wheat allergen levels and sensitization to wheat allergens, work-related upper and lower respiratory symptoms and asthma in bakery workers.As part of a Health Surveillance System for early detection of (allergic) occupational airway diseases a so-called 'validation study' was performed among Dutch bakers for validation of a diagnostic model that predict the likelihood of sensitization to specific workplace allergens. The present study used serology and questionnaire results of a subgroup of 860 bakers participating in the validation study. An earlier developed job-exposure matrix was used to predict average and cumulative personal exposure to wheat allergens.The prevalence of wheat sensitization, work-related respiratory symptoms and asthma increased till average wheat exposure levels of approximately 25-30 microg/m3, leveled off and decreased at higher exposure concentrations. Exposure-response curves showed a stronger pronounced bell-shape with cumulative exposure. Associations were strongest for asthma and work-related lower respiratory symptoms (PR approximately 2 and PR approximately 3.5-4.5 for average and cumulative exposure, respectively). Associations were only found in atopics. Wheat sensitization was an important factor in the prevalence of respiratory symptoms.In accordance with earlier studies, the present study showed a bell-shaped exposure-response relationship especially for cumulative wheat allergen exposure with sensitization, allergic respiratory symptoms and asthma. The healthy worker effect may be the possible explanation for the bell-shaped relationship.
The Road We Must Take: Multidisciplinary Team Science
Authors: Mary L. Disis, John T. Slattery
Journal: Science Translational Medicine (2010)

Translational research is acknowledged to be complex and to require a diverse skill set. Many organizations, particularly academic institutions, have invested in educational programs, facilities, and enhanced resources to encourage translational research. Critically needed, however, is an emphasis on creating and sustaining multidisciplinary research teams. It is through the power of many and a diverse approach to our health care problems that we will realize lasting solutions.
Comparison of leukocyte counts in sputum, bronchial biopsies, and bronchoalveolar lavage.
Authors: P Maestrelli, M Saetta, A Di Stefano, P G Calcagni, G Turato, M P Ruggieri, A Roggeri, C E Mapp, L M Fabbri
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To determine the relationship between inflammatory cells in sputum, bronchoalveolar lavage (BAL), and bronchial mucosa, we counted the number of leukocytes in sputum, BAL, and bronchial biopsies obtained from subjects with asthma and with chronic bronchitis in stable condition or during exacerbations. Sputum was induced by inhalation of hypertonic saline in the asthma group. Spontaneous sputum was collected in the chronic bronchitis groups. Differential counts of leukocytes were performed on cytospin preparations of sputum and BAL. Eosinophils, macrophages, neutrophils, and lymphocytes were quantified in the submucosa of the bronchial biopsies. In asthma and in stable chronic bronchitis, the percentages of neutrophils were significantly higher in sputum than in BAL, whereas the opposite was true of the percentages of macrophages and lymphocytes. The lymphocyte was the predominant cell infiltrating the bronchial submucosa in all groups. BAL eosinophils correlated with submucosal and sputum eosinophils in the asthma and exacerbated chronic bronchitis groups. A similar trend was observed between submucosal and sputum eosinophils. In conclusion, the relative proportion of inflammatory cells was different in sputum, BAL, and bronchial mucosa. However, there was a fairly good agreement between the number of eosinophils counted with the three techniques in asthmatics and in exacerbated chronic bronchitics, suggesting that sputum cell analysis may be used for a noninvasive assessment of airway eosinophilia.
Contextual Influences on Visual Processing
Authors: Thomas D. Albright, Gene R. Stoner
Journal: Annual Review of Neuroscience (2002)

▪ Abstract The visual image formed on the retina represents an amalgam of visual scene properties, including the reflectances of surfaces, their relative positions, and the type of illumination. The challenge facing the visual system is to extract the “meaning” of the image by decomposing it into its environmental causes. For each local region of the image, that extraction of meaning is only possible if information from other regions is taken into account. Of particular importance is a set of image cues revealing surface occlusion and/or lighting conditions. These information-rich cues direct the perceptual interpretation of other more ambiguous image regions. This context-dependent transformation from image to perception has profound—but frequently under-appreciated—implications for neurophysiological studies of visual processing: To demonstrate that neuronal responses are correlated with perception of visual scene properties, rather than visual image features, neuronal sensitivity must be assessed in varied contexts that differentially influence perceptual interpretation. We review a number of recent studies that have used this context-based approach to explore the neuronal bases of visual scene perception.
Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies
Authors: Patrick Yu-Wai-Man, Philip G. Griffiths, Patrick F. Chinnery
Journal: Progress in Retinal and Eye Research (2010)

Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies.
Gastroenterology. 2nd edition.
Authors: R A HARRY
Journal: Gut (2000)

Gastroenterology. 2nd edition. Edited by Travis SPL, Taylor RH, Misiewicz JJ. (Pp 505; illustrated; £29.25.) UK: Blackwell Science, 1998. ISBN 0632048875.

The first edition of this handbook was a valuable resource to both junior hospital staff and family doctors for its practical coverage of basic gastroenterology. In the seven years since it was first published, there have been many advances in gastroenterology …
P219 Ten year mortality in a primary care COPD cohort: multidimensional index BOD more discriminant than GOLD staging
Authors: N. P. Keaney, K. Ansari, J. Munby, M. Price, A. Kay, I. K. Taylor
Journal: Thorax (2011)

<h3></h3> Of potential prognostic variables for COPD to use in a multidimensional staging tool, BMI, severity of airflow obstruction (FEV<sub>1</sub>% predicted) and the MRC Dyspnoea Score (BOD) have been shown to be useful for a more complete assessment of the impact of the disease.1 In 1999–2002 we identified 431 patients (208 women) with COPD in primary care surgeries and recorded their BOD scores (maximum 7). For men and women (mean±SD): age was 66±10 and 64±10; pack/years 34±19 and 34±18; BMI 27±5 and 25±6; FEV<sub>1</sub>% predicted 55±15 and 57±16; and MRC Dyspnoea Score 2.6±1.0 and 2.6±1.0; with BOD scores 1.9±1.5 and 2.0±1.6 respectively. The low mean BOD scores indicate the mainly moderate severity for this primary care cohort (only one subject had an MRC score of 5). Because of the similarities in these variables for men and women further analysis is of the whole cohort. Mortality was assessed in October 2010 and a Kaplan–Meier analysis for those with BOD scores 0 and 1 shows 80% and 75% probability of survival, whereas for a BOD score of &gt;4 the 10-year survival was &lt;20%. By way of contrast GOLD stages 1 and 2 had a 75% and 60% survival with Stage 4 showing a 60% survival. The Cox regression model (Abstract P219 table 1) demonstrated that BOD was a better predictor of survival than age and that smoking history was a significant covariate. Ten year survival was &lt;10% when smoking history (with age and co-morbidity score) was added to a BOD score of &gt;4 in a Kaplan–Meier plot. <h3>Conclusion</h3> BOD, a multidimensional index of the clinical impact of COPD is valid for a 10-year prognosis and outperforms GOLD staging over that period.
<i>Anatomical, Phylogenetical and Clinical Studies on the Central Nervous System.</i>By B. Brouwer, Professor of Clinical Neurology, University of Amsterdam. Lectures delivered on the Herter Foundation. Johns Hopkins University, 1926. I. Projection of the Retina in the Brain. II. Pathology of Sensibility. III. Significance of Phylogenetic Studies for the Neurologist. (<i>Baltimore: The Williams and Wilkins Company, 1927.</i>)
Authors: Leo M. Davidoff
Journal: American Journal of Psychiatry (1928)
Extracellular Matrix Molecules and their Receptors: Functions in Neural Development
Authors: L F Reichardt, K J Tomaselli
Journal: Annual Review of Neuroscience (1991)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More