tbuckley/cabot-search huggingface dataset:
Inner London general practice
Authors: J C. Murdoch
Journal: BMJ (1981)

<h3>Background</h3> Scleral cross-linking is a potential method to inhibit axial elongation of the eye, preventing the progression of pathological myopia. Formaldehyde releasers, which are common preservatives found in cosmetics and ophthalmic solutions, have been shown to be not only effective in cross-linking corneal collagen in vitro and in vivo, but also have minimal toxicity effects on the eye. The present study aims to evaluate the efficacy of scleral cross-linking using sodium hydroxymethylglycinate (SMG) to inhibit eye growth using an in vivo rabbit model. <h3>Methods</h3> A cross-linking solution containing 40 mM SMG was delivered to the sub-Tenon’s space behind the equator. The application regimen included a two-quadrant injection performed five times over 2 weeks on New Zealand White rabbits (n=5, group 1), and one-time injection followed for up to 5 days on Dutch-Belted rabbits (n=6, group 2). Group 1 was monitored serially for axial length changes using B-scan ultrasound for 5–6 weeks. Group 2 was injected with a higher viscosity solution formulation. Both groups were evaluated for thermal denaturation temperature changes of the sclera postmortem. <h3>Results</h3> Axial growth was limited by 10%–20% following SMG treatment as compared with the untreated eye. Thermal denaturation analysis showed increased heat resistance of the treated eyes in the areas of injection. Overall, the SMG treatment inhibited eye growth with few side effects from the injections. <h3>Conclusions</h3> Cross-linking solutions delivered via sub-Tenon injection provide a potential method for limiting axial length growth in progressive myopia and could be used as a potential treatment for myopia.
Self-management of fatigue in rheumatoid arthritis: a randomised controlled trial of group cognitive-behavioural therapy
Authors: S. Hewlett, N. Ambler, C. Almeida, A. Cliss, A. Hammond, K. Kitchen, B. Knops, D. Pope, M. Spears, A. Swinkels, J. Pollock
Journal: Annals of the Rheumatic Diseases (2011)

Objectives To investigate the effect of group cognitive behavioural therapy (CBT) for fatigue self-management, compared with groups receiving fatigue information alone, on fatigue impact among people with rheumatoid arthritis (RA). Methods Two-arm, parallel randomised controlled trial in adults with RA, fatigue ≥6/10 (Visual Analogue Scale (VAS) 0–10, high bad) and no recent change in RA medication. Group CBT for fatigue self-management comprised six (weekly) 2 h sessions, and consolidation session (week 14). Control participants received fatigue self-management information in a 1 h didactic group session. Primary outcome at 18 weeks was the impact of fatigue measured using two methods (Multi-dimensional Assessment of Fatigue (MAF) 0–50; VAS 0–10), analysed using intention-to-treat analysis of covariance with multivariable regression models. Results Of 168 participants randomised, 41 withdrew before entry and 127 participated. There were no major baseline differences between the 65 CBT and 62 control participants. At 18 weeks CBT participants reported better scores than control participants for fatigue impact: MAF 28.99 versus 23.99 (adjusted difference −5.48, 95% CI −9.50 to −1.46, p=0.008); VAS 5.99 versus 4.26 (adjusted difference −1.95, 95% CI −2.99 to −0.90, p<0.001). Standardised effect sizes for fatigue impact were MAF 0.59 (95% CI 0.15 to 1.03) and VAS 0.77 (95% CI 0.33 to 1.21), both in favour of CBT. Secondary outcomes of perceived fatigue severity, coping, disability, depression, helplessness, self-efficacy and sleep were also better in CBT participants. Conclusions Group CBT for fatigue self-management in RA improves fatigue impact, coping and perceived severity, and well-being. Trial registration: ISRCTN 32195100
Simultaneous Targeting of Toll- and Nod-Like Receptors Induces Effective Tumor-Specific Immune Responses
Authors: Johan Garaude, Andrew Kent, Nico van Rooijen, J. Magarian Blander
Journal: Science Translational Medicine (2012)

A cancer vaccine of irradiated tumor cells expressing flagellin primes effective NLRC4/NAIP5- and TLR5-dependent antitumor immune responses.
Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase
Authors: Satori A. Marchitti, Richard A. Deitrich, Vasilis Vasiliou
Journal: Pharmacological Reviews (2007)

Aldehydes are highly reactive molecules formed during the biotransformation of numerous endogenous and exogenous compounds, including biogenic amines. 3,4-Dihydroxyphenylacetaldehyde is the aldehyde metabolite of dopamine, and 3,4-dihydroxyphenylglycolaldehyde is the aldehyde metabolite of both norepinephrine and epinephrine. There is an increasing body of evidence suggesting that these compounds are neurotoxic, and it has been recently hypothesized that neurodegenerative disorders may be associated with increased levels of these biogenic aldehydes. Aldehyde dehydrogenases are a group of NAD(P)<sup>+</sup>-dependent enzymes that catalyze the oxidation of aldehydes, such as those derived from catecholamines, to their corresponding carboxylic acids. To date, 19 aldehyde dehydrogenase genes have been identified in the human genome. Mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, γ-hydroxybutyric aciduria, and pyridoxine-dependent seizures, most of which are characterized by neurological abnormalities. Several pharmaceutical agents and environmental toxins are also known to disrupt or inhibit aldehyde dehydrogenase function. It is, therefore, possible to speculate that reduced detoxification of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde from impaired or deficient aldehyde dehydrogenase function may be a contributing factor in the suggested neurotoxicity of these compounds. This article presents a comprehensive review of what is currently known of both the neurotoxicity and respective metabolism pathways of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde with an emphasis on the role that aldehyde dehydrogenase enzymes play in the detoxification of these two aldehydes.
Connective Tissue Growth Factor–Specific Monoclonal Antibody Therapy Inhibits Pancreatic Tumor Growth and Metastasis
Authors: Nadja Dornhöfer, Suzanne Spong, Kevin Bennewith, Ali Salim, Stephen Klaus, Neeraja Kambham, Carol Wong, Fiona Kaper, Patrick Sutphin, Rendall Nacalumi, Michael Höckel, Quynh Le, Michael Longaker, George Yang, Albert Koong, Amato Giaccia
Journal: Cancer Research (2006)

Abstract Pancreatic cancer is highly aggressive and refractory to most existing therapies. Past studies have shown that connective tissue growth factor (CTGF) expression is elevated in human pancreatic adenocarcinomas and some pancreatic cancer cell lines. To address whether and how CTGF influences tumor growth, we generated pancreatic tumor cell lines that overexpress different levels of human CTGF. The effect of CTGF overexpression on cell proliferation was measured in vitro in monolayer culture, suspension culture, or soft agar, and in vivo in tumor xenografts. Although there was no effect of CTGF expression on proliferation in two-dimensional cultures, anchorage-independent growth (AIG) was enhanced. The capacity of CTGF to enhance AIG in vitro was linked to enhanced pancreatic tumor growth in vivo when these cells were implanted s.c. in nude mice. Administration of a neutralizing CTGF-specific monoclonal antibody, FG-3019, had no effect on monolayer cell proliferation, but blocked AIG in soft agar. Consistent with this observation, anti-CTGF treatment of mice bearing established CTGF-expressing tumors abrogated CTGF-dependent tumor growth and inhibited lymph node metastases without any toxicity observed in normal tissue. Together, these studies implicate CTGF as a new target in pancreatic cancer and suggest that inhibition of CTGF with a human monoclonal antibody may control primary and metastatic tumor growth. (Cancer Res 2006; 66(11): 5816-27)
Assessing nutritional state in inflammatory bowel disease.
Authors: R V Heatley
Journal: Gut (1986)

Nutrient depletion is a common complication of inflammatory bowel disease, and some of the consequences can be severe. Although it is often easy to recognise the most severely undernourished subjects, those with lesser degrees of malnutrition may prove more difficult to detect. Measurements of many nutritional variables will be abnormal in patients with inflammatory bowel disease, especially in those with Crohn9s disease, but are not always relevant to the clinical management of patients. Anthropometric means of assessment, in particular, measurement of mid arm circumference, can act as a simple, reproducible method of detecting those most at risk of appreciable undernutrition.
Essential role of Jun family transcription factors in PU.1 knockdown–induced leukemic stem cells
Authors: Ulrich Steidl, Frank Rosenbauer, Roel G W Verhaak, Xuesong Gu, Alexander Ebralidze, Hasan H Otu, Steffen Klippel, Christian Steidl, Ingmar Bruns, Daniel B Costa, Katharina Wagner, Manuel Aivado, Guido Kobbe, Peter J M Valk, Emmanuelle Passegué, Towia A Libermann, Ruud Delwel, Daniel G Tenen
Journal: Nature Genetics (2006)
α-E-Catenin Inactivation Disrupts the Cardiomyocyte Adherens Junction, Resulting in Cardiomyopathy and Susceptibility to Wall Rupture
Authors: Farah Sheikh, Yinhong Chen, Xingqun Liang, Alain Hirschy, Antine E. Stenbit, Yusu Gu, Nancy D. Dalton, Toshitaka Yajima, Yingchun Lu, Kirk U. Knowlton, Kirk L. Peterson, Jean-Claude Perriard, Ju Chen
Journal: Circulation (2006)

Background— α-E-catenin is a cell adhesion protein, located within the adherens junction, thought to be essential in directly linking the cadherin-based adhesion complex to the actin cytoskeleton. Although α-E-catenin is expressed in the adherens junction of the cardiomyocyte intercalated disc, and perturbations in its expression are observed in models of dilated cardiomyopathy, its role in the myocardium remains unknown. Methods and Results— To determine the effects of α-E-catenin on cardiomyocyte ultrastructure and disease, we generated cardiac-specific α-E-catenin conditional knockout mice (α-E-cat cKO). α-E-cat cKO mice displayed progressive dilated cardiomyopathy and unique defects in the right ventricle. The effects on cardiac morphology/function in α-E-cat cKO mice were preceded by ultrastructural defects in the intercalated disc and complete loss of vinculin at the intercalated disc. α-E-cat cKO mice also revealed a striking susceptibility of the ventricular free wall to rupture after myocardial infarction. Conclusions— These results demonstrate a clear functional role for α-E-catenin in the cadherin/catenin/vinculin complex in the myocardium in vivo. Ablation of α-E-catenin within this complex leads to defects in cardiomyocyte structural integrity that result in unique forms of cardiomyopathy and predisposed susceptibility to death after myocardial stress. These studies further highlight the importance of studying the role of α-E-catenin in human cardiac injury and cardiomyopathy in the future.
Injectable, Pore‐Forming Hydrogels for In Vivo Enrichment of Immature Dendritic Cells
Authors: Catia S. Verbeke, David J. Mooney
Journal: Advanced Healthcare Materials (2015)

Biomaterials‐based vaccines have emerged as a powerful method to evoke potent immune responses directly in vivo, without the need for ex vivo cell manipulation, and modulating dendritic cell (DC) responses in a noninflammatory context could enable the development of tolerogenic vaccines to treat autoimmunity. This study describes the development of a noninflammatory, injectable hydrogel system to locally enrich DCs in vivo without inducing their maturation or activation, as a first step toward this goal. Alginate hydrogels that form pores in situ are characterized and used as a physical scaffold for cell infiltration. These gels are also adapted to control the release of granulocyte–macrophage colony stimulating factor (GM‐CSF), a potent inducer of DC recruitment and proliferation. In vivo, sustained release of GM‐CSF from the pore‐forming gels leads to the accumulation of millions of cells in the material. These cells are highly enriched in CD11b + CD11c + DCs, and further analysis of cell surface marker expression indicates these DCs are immature. This study demonstrates that a polymeric delivery system can mediate the accumulation of a high number and percentage of immature DCs, and may provide the basis for further development of materials‐based, therapeutic vaccines.
Airway responsiveness: associated features in infants with recurrent respiratory symptoms
Authors: A. Kotaniemi-Syrjanen, L. P. Malmberg, A. S. Pelkonen, K. Malmstrom, M. J. Makela
Journal: European Respiratory Journal (2007)

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of ≤0.90 mg producing a 40% fall (PD<sub>40</sub>) in the maximal flow at functional residual capacity (<i>V</i>′<sub>max,FRC</sub>), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3–13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5–428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1–22.5), functional residual capacity z-score ≥2 (OR 36.8; 95% CI 2.9–472.6), and <i>V</i>′<sub>max,FRC</sub> z-score (OR 0.5; 95% CI 0.2–0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD<sub>40</sub><i>V</i>′<sub>max,FRC</sub> &gt;0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.
The role of the reviewer in editorial decision-making
Authors: R Coronel
Journal: Cardiovascular Research (1999)

Scientific journals are confronted with increasing numbers of submitted manuscripts. Because of page limitations, these journals have to revert to a high rejection rate. The standard form accompanying manuscripts submitted to Cardiovascular Research was changed in order to entice reviewers in an advisory behaviour more suited to the editorial rejection rate. All original manuscripts submitted to Cardiovascular Research during the previous four years were analyzed. The recommended rejection rate of individual reviewers was 23% and, with increasing experience, reviewers become more critical. The reviewer’s recommendations and indication of scientific priority did not match the journal’s rejection rate. An effort to lure the reviewers into a more critical advisory behaviour was effective. However, unanimity between reviewers is rare. The reviewer’s recommendations do not justify high rejection rates and a wider dissemination of scientific information in the biomedical field is called for.
Accumulation of 5-hydroxytryptamine leads to dysfunction of adrenergic nerves in canine coronary artery following intimal damage in vivo.
Authors: R A Cohen, K M Zitnay, R M Weisbrod
Journal: Circulation Research (1987)

Previous in vitro studies have demonstrated that coronary artery adrenergic nerves are a principal site of accumulation of 5-hydroxytryptamine released from aggregating platelets. The purpose of this study was to determine whether 5-hydroxytryptamine is accumulated by adrenergic nerves at sites of endothelial damage and platelet aggregation in vivo. Coronary artery 5-hydroxytryptamine content and response to in vitro adrenergic nerve stimulation were studied in dogs 24 hours following balloon catheter-induced intimal injury. 5-Hydroxytryptamine content was significantly increased in the catheter-damaged arteries, and there was a coincident decrease in the content of norepinephrine. The relaxation caused by acetylcholine was abolished in the catheter-injured arteries, indicating loss of this endothelial cell-mediated function. The normal beta-adrenergic relaxation caused by nerve stimulation was inhibited, and in some cases, contractions resulted; these effects were prevented by serotonergic receptor antagonists. The sensitivity to exogenously added norepinephrine was unchanged, indicating that the changes in the response to nerve stimulation were not due to an altered smooth muscle response to the native neurotransmitter. These observations indicate that following intimal damage, which produces platelet aggregation on the luminal surface of the blood vessel, 5-hydroxytryptamine can assume a transmitter role in coronary artery adrenergic nerves and thereby cause their dysfunction.
Inhaled Bronchodilator Therapy in Mechanically Ventilated Patients
Authors: RAJIV DHAND, MARTIN J. TOBIN
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Therapeutic aerosols are commonly used in mechanically ventilated patients, mainly to deliver bronchodilator drugs. Because ventilator-supported patients often receive several different classes of medications parenterally, the inhaled route of administration is particularly useful as an alternate route for drug delivery. Both nebulizers and metered-dose inhalers (MDIs) can be adapted for use in ventilator circuits. Traditionally, nebulizers have been used to deliver bronchodilators, antibiotics, and surfactant in mechanically ventilated patients, whereas MDIs chiefly have been used to deliver beta-adrenergic and anticholinergic bronchodilators (1). In the past, the combination of an MDI with an elbow adapter was considered to be ineffective (2) due to aerosol impaction in the ventilator circuit and endotracheal tube (3). However, recent studies (4‐6) have clearly established the efficacy of MDIs for delivering bronchodilators in mechanically ventilated patients, with the caveat that the technique needs to be carefully executed. With a better understanding of the many factors influencing aerosol delivery and deposition in mechanically ventilated patients, it is possible to provide a scientific basis for inhaled bronchodilator therapy in these patients. FACTORS INFLUENCING LOWER RESPIRATORY TRACT DEPOSITION OF AEROSOL In mechanically ventilated patients, the efficiency of aerosol delivery to the lower respiratory tract depends on several factors that are not concerns in ambulatory patients (7). Important determinants of aerosol deposition in ventilator-supported patients include the delivery system, particle size, characteristics of the ventilator circuit, ventilator mode, and patient-related factors. The effect of each factor on aerosol delivery is difficult to elucidate because of the large number of variables involved. Therefore, several investigators have conducted in vitro studies to define each variable’s influence on aerosol delivery with mechanical ventilators.
In Vivo Assessment of the Risk Profile of Evolving Individual Coronary Plaques
Authors: Peter H. Stone, Charles L. Feldman
Journal: Circulation (2011)

T he natural history of coronary plaques within an individ- ual patient with coronary disease is highly heterogeneous.Over time, each plaque may exhibit a different temporal pattern of progression, quiescence, or regression, as well as a variable rate of change.The trajectory of the natural history of a particular plaque depends on the level of systemic risk factors and patient-specific genetics, as well as local phenomena, such as the detailed local blood flow patterns, arterial wall characteristics, including plaque size and shape, and arterial remodeling characteristics.Local endothelial shear stress (ESS) is one of the most fundamental factors influencing endothelial structure and function, and it is the central factor responsible for the localization of coronary atherosclerotic plaque formation and progression. 1Recent methodological innovations allow detailed in vivo characterization of local ESS and remodeling behavior of the artery based on biplane angiography, intravascular ultrasound (IVUS), reconstruction of the artery in 3-dimensional space, and computational fluid dynamics calculations. 2,3Analysis of the radiofrequency patterns from the IVUS signal has also been used to estimate plaque composition. 4These methodologies not only allow detailed characterization of plaque at a single point in time but, if studied in a serial manner, now allow prognostic insight into how plaques change over time and what antecedent features predict the future behavior of that plaque.
Impaired Fasting Glucose and Impaired Glucose Tolerance in Women With Prior Gestational Diabetes Are Associated With a Different Cardiovascular Profile
Authors: Luis Felipe Pallardo, Lucrecia Herranz, Pilar Martin-Vaquero, Teresa Garcia-Ingelmo, Cristina Grande, Mercedes Jañez
Journal: Diabetes Care (2003)

OBJECTIVE—The purpose of this study was to investigate the association of cardiovascular risk factors to impaired glucose tolerance (IGT) and to impaired fasting glucose (IFG) in women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—We studied 838 women with prior GDM. Postpartum glucose tolerance status was classified as normal, IFG, IGT, IFG plus IGT, and diabetes according to the World Health Organization criteria. Postpartum BMI, waist circumference, blood pressure, triglyceride, cholesterol, and HDL cholesterol were assessed. RESULTS—BMI and blood pressure were significantly higher in women with IFG than in women with normal glucose status. BMI and waist circumference were significantly higher in women with IFG plus IGT than in women with normal glucose status. No differences were observed between women with IGT and normal glucose status. The prevalence of hypertension and obesity was significantly increased in IFG compared with normal glucose status. The prevalence of obesity and abnormal lipids was significantly increased in IFG plus IGT compared with normal glucose status. IGT showed no increased prevalence of cardiovascular risk factors. CONCLUSIONS—Traditional cardiovascular risk factors have a stronger association with isolated IFG than with isolated IGT in women with prior GDM.
CHANGE IN THE STRUCTURE OF SHOPE PAPILLOMA VIRUS-INDUCED ARGINASE ASSOCIATED WITH MUTATION OF THE VIRUS
Authors: Stanfield Rogers
Journal: The Journal of Experimental Medicine (1971)

The change in the state of the virus-induced enzyme associated with a mutation in the virus provides additional evidence that the enzyme is synthesized from virus rather than rabbit genetic information. This change in structure results in differences in stability of polymerization, degree of optical rotary dispersion (ORD) specific rotation, change in elution characteristics from carboxymethyl cellulose, and a reduction in specific activity of the arginase. Liver arginase differs markedly in ORD characteristics from the virus-induced enzyme. In contrast to the virus-induced enzyme, it showed no negative Cotton effect at 233 nm until it was activated with manganese. Manganese had no influence on the ORD spectrum of virus-induced arginase. In addition, liver arginase is denatured by 4 M urea, while the virus-induced enzyme requires 10 M urea for denaturation.