tbuckley/cabot-search huggingface dataset:
CD19 is functionally and physically associated with surface immunoglobulin.
Authors: J M Pesando, L S Bouchard, B E McMaster
Journal: The Journal of Experimental Medicine (1989)

The pan-B and B cell-specific sIg and CD19 antigens are functionally and physically associated in the presence of anti-Ig mAb. Incubation of B cells with anti-Ig antibodies causes rapid, specific, reversible, concentration-dependent, and unidirectional comodulation of CD19 on every mature B cell studied. Comodulation is produced by mAbs specific for the gamma, mu, kappa, and lambda chains of Ig, and by at least one idiotype-specific mAb. Comodulation is observed using 15 CD19-specific mAbs that detect at least three different CD19 epitopes. Of 18 surface antigens studied, only CD19 is comodulated. Loss of sIg and CD19 occurs concurrently during anti-Ig modulation and demonstrates a comparable dependence on anti-Ig concentration, suggesting that these are parallel rather than serial events. Incubation with anti-Ig specifically cocaps and suggests internalization of anti-CD19 mAb. Comodulation of sIg and CD19 by anti-Ig but not anti-CD19 mAbs suggests that ligand binding enables sIg to then interact with CD19. We propose that CD19 is a component of the B cell antigen receptor and suggest that it could facilitate signal transduction by sIg-antigen complexes.
Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis
Authors: Jérôme Avouac, Dörte Huscher, Daniel E Furst, Christian F Opitz, Oliver Distler, Yannick Allanore
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To establish an expert consensus on which criteria are the most appropriate in clinical practice to refer patients with systemic sclerosis (SSc) for right heart catheterisation (RHC) when pulmonary hypertension (PH) is suspected. <h3>Methods</h3> A three stage internet based Delphi consensus exercise involving worldwide PH experts was designed. In the first stage, a comprehensive list of domains and items combining evidence based indications and expert opinions were obtained. In the second and third stages, experts were asked to rate each item selected in the list. After each of stages 2 and 3, the number of items and criteria were reduced according to a cluster analysis. <h3>Results</h3> A literature search and the opinions of 47 experts participating in Delphi stage 1 provided a list of seven domains containing 142 criteria. After stages 2 and 3, these domains and tools were reduced to three domains containing eight tools: clinical (progressive dyspnoea over the past 3 months, unexplained dyspnoea, worsening of WHO dyspnoea functional class, any finding on physical examination suggestive of elevated right heart pressures and any sign of right heart failure), echocardiography (systolic pulmonary artery pressure &gt;45 mm Hg and right ventricle dilation) and pulmonary function tests (diffusion lung capacity for carbon monoxide &lt;50% without pulmonary fibrosis). <h3>Conclusions</h3> Among experts in pulmonary arterial hypertension–SSc, a core set of criteria for clinical practice to refer SSc patients for RHC has been defined by Delphi consensus methods. Although these indications are recommended by this expert group to be used as an interim tool, it will be necessary to formally validate the present tools in further studies.
ON THE VALUE OF AN ABNORMAL RISE IN THE AVERAGE LEVEL OF THE DIAPHRAGM AS A GUIDE TO THE VOLUME OF THE BLOOD IN ACTIVE CIRCULATION.
Authors: T. S. Wilson
Journal: BMJ (1907)

THE object of this paper is to bring forward clinical evidence in favour of the following propositions:1. When, from any cause, the total volume of the blood in circulation is materially diminished, the.total bulk of the intrathoracic viscera is correspondingly diminished
Impact of DOTS compared with DOTS-plus on multidrug resistant tuberculosis and tuberculosis deaths: decision analysis
Authors: Timothy R Sterling, Harold P Lehmann, Thomas R Frieden
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> This study sought to determine the impact of the World Health Organization9s directly observed treatment strategy (DOTS) compared with that of DOTS-plus on tuberculosis deaths, mainly in the developing world. <b>Design:</b> Decision analysis with Monte Carlo simulation of a Markov decision tree. <b>Data sources:</b> People with smear positive pulmonary tuberculosis. <b>Data analysis:</b> Analyses modelled different levels of programme effectiveness of DOTS and DOTS-plus, and high (10%) and intermediate (3%) proportions of primary multidrug resistant tuberculosis, while accounting for exogenous reinfection. <b>Main outcome measure:</b> The cumulative number of tuberculosis deaths per 100 000 population over 10 years. <b>Results:</b> The model predicted that under DOTS, 276 people would die from tuberculosis (24 multidrug resistant and 252 not multidrug resistant) over 10 years under optimal implementation in an area with 3% primary multidrug resistant tuberculosis. Optimal implementation of DOTS-plus would result in four (1.5%) fewer deaths. If implementation of DOTS-plus were to result in a decrease of just 5% in the effectiveness of DOTS, 16% more people would die with tuberculosis than under DOTS alone. In an area with 10% primary multidrug resistant tuberculosis, 10% fewer deaths would occur under optimal DOTS-plus than under optimal DOTS, but 16% more deaths would occur if implementation of DOTS-plus were to result in a 5% decrease in the effectiveness of DOTS <b>Conclusions:</b> Under optimal implementation, fewer tuberculosis deaths would occur under DOTS-plus than under DOTS. If, however, implementation of DOTS-plus were associated with even minimal decreases in the effectiveness of treatment, substantially more patients would die than under DOTS. <h3>What is already known on this topic</h3> DOTS is an effective, albeit underused, strategy for treating tuberculosis DOTS may be insufficiently effective in treating multidrug resistant tuberculosis The use of toxic reserve drugs (DOTS-plus) is an effective but costly strategy for treating multidrug resistant tuberculosis The impact of the implementation of DOTS-plus on overall tuberculosis control is unknown <h3>What this study adds</h3> If implementation of DOTS-plus is associated with even minimal decreases in the effectiveness of DOTS, more patients would die with tuberculosis under DOTS-plus than under DOTS alone If DOTS-plus is implemented, it must not divert resources from and decrease the effectiveness of DOTS
Long‐term outcomes in paediatric asthma
Authors: S. Pedersen
Journal: Allergy (2002)

Over the years the aims of asthma management have changed markedly from effective prednisolone treatment of symptoms and exacerbations towards more use of continuous prophylactic treatment. With our new understanding of the disease and its management definition of the aims of treatment and assessment of optimal asthma control have become much more complex. Even in times of evidence‐based medicine our asthma management is based upon findings of effects on various outcomes in somewhat short‐term (&lt;1 year) controlled studies. However, assumptions about long‐term effects upon the basis of findings in such studies should be made with great caution. Good examples of this are studies which assess the risk of systemic effects and clinical adverse effects of inhaled corticosteroids. From such studies it has become clear that systemic effects detected in short‐term trials may have no predictive value of long‐term adverse effects. Thus steroid‐induced changes in lower leg growth rates assessed by knemometry do not predict long‐term statural growth. Moreover, steroid‐induced changes in statural growth over 1 year are not predictive of effects upon attained adult height. In contrast, reduced growth caused by uncontrolled asthma disease also seems to affect attained adult height adversely. These findings suggest that long‐term outcomes should play a larger role when future asthma management strategies are decided. Some important long‐term outcomes of asthma management in children include cure or remission of the disease, prevention of complications of the disease (airway remodelling, adverse effects upon growth/adult height, peak bone mineral density, physical impairment and psychosocial development) or its pharmacological management (adverse effects upon adult height, peak bone mineral density). More controlled long‐term studies (several years) are needed to provide a better understanding of how these outcomes are best achieved.
Association of incident obstructive sleep apnoea with outcomes in a large cohort of US veterans
Authors: Miklos Z Molnar, Istvan Mucsi, Marta Novak, Zoltan Szabo, Amado X Freire, Kim M Huch, Onyebuchi A Arah, Jennie Z Ma, Jun L Lu, John J Sim, Elani Streja, Kamyar Kalantar-Zadeh, Csaba P Kovesdy
Journal: Thorax (2015)

<h3>Rationale</h3> There is a paucity of large cohort studies examining the association of obstructive sleep apnoea (OSA) with clinical outcomes including all-cause mortality, coronary heart disease (CHD), strokes and chronic kidney disease (CKD). <h3>Objectives</h3> We hypothesised that a diagnosis of incident OSA is associated with higher risks of these adverse clinical outcomes. <h3>Methods, measurements</h3> In a nationally representative cohort of over 3 million (n=3 079 514) US veterans (93% male) with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m<sup>2</sup>, we examined the association between the diagnosis of incident OSA, treated and untreated with CPAP, and: (1) all-cause mortality, (2) incident CHD, (3) incident strokes, (4)incident CKD defined as eGFR&lt;60 mL/min/1.73 m<sup>2</sup>, and (5) slopes of eGFR. <h3>Main results</h3> Compared with OSA-negative patients, untreated and treated OSA was associated with 86% higher mortality risk, (adjusted HR and 95% CI 1.86 (1.81 to 1.91) and 35% (1.35 (1.21 to 1.51)), respectively. Similarly, untreated and treated OSA was associated with 3.5 times (3.54 (3.40 to 3.69)) and 3 times (3.06 (2.62 to 3.56)) higher risk of incident CHD; 3.5 times higher risk of incident strokes (3.48 (3.28 to 3.64) and 3.50 (2.92 to 4.19)) for untreated and treated OSA, respectively. The risk of incident CKD was also significantly higher in untreated (2.27 (2.19 to 2.36)) and treated (2.79 (2.48 to 3.13)) patients with OSA. The median (IQR) of the eGFR slope was −0.41 (−2.01 to 0.99), −0.61 (−2.69 to 0.93) and −0.87 (−3.00 to 0.70) mL/min/1.73 m<sup>2</sup> in OSA-negative patients, untreated OSA-positive patients and treated OSA-positive patients, respectively. <h3>Conclusions</h3> In this large and contemporary cohort of more than 3 million US veterans, a diagnosis of incident OSA was associated with higher mortality, incident CHD, stroke and CKD and with faster kidney function decline.
AqF026 Is a Pharmacologic Agonist of the Water Channel Aquaporin-1
Authors: Andrea J. Yool, Johann Morelle, Yvette Cnops, Jean-Marc Verbavatz, Ewan M. Campbell, Elizabeth A.H. Beckett, Grant W. Booker, Gary Flynn, Olivier Devuyst
Journal: Journal of the American Society of Nephrology (2013)

Aquaporin-1 (AQP1) facilitates the osmotic transport of water across the capillary endothelium, among other cell types, and thereby has a substantial role in ultrafiltration during peritoneal dialysis. At present, pharmacologic agents that enhance AQP1-mediated water transport, which would be expected to increase the efficiency of peritoneal dialysis, are not available. Here, we describe AqF026, an aquaporin agonist that is a chemical derivative of the arylsulfonamide compound furosemide. In the Xenopus laevis oocyte system, extracellular AqF026 potentiated the channel activity of human AQP1 by >20% but had no effect on channel activity of AQP4. We found that the intracellular binding site for AQP1 involves loop D, a region associated with channel gating. In a mouse model of peritoneal dialysis, AqF026 enhanced the osmotic transport of water across the peritoneal membrane but did not affect the osmotic gradient, the transport of small solutes, or the localization and expression of AQP1 on the plasma membrane. Furthermore, AqF026 did not potentiate water transport in Aqp1-null mice, suggesting that indirect mechanisms involving other channels or transporters were unlikely. Last, in a mouse gastric antrum preparation, AqF026 did not affect the Na-K-Cl cotransporter NKCC1. In summary, AqF026 directly and specifically potentiates AQP1-mediated water transport, suggesting that it deserves additional investigation for applications such as peritoneal dialysis or clinical situations associated with defective water handling.
Serum Prognostic Markers in Head and Neck Cancer
Authors: François Meyer, Élodie Samson, Pierre Douville, Thierry Duchesne, Geoffrey Liu, Isabelle Bairati
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Recognized prognostic factors do not adequately predict outcomes of head and neck cancer (HNC) patients after their initial treatment. We identified from the literature nine potential serum prognostic markers and assessed whether they improve outcome prediction. Experimental Design: A pretreatment serum sample was obtained from 527 of the 540 HNC patients who participated in a randomized controlled trial. During follow-up, 115 had a HNC recurrence, 110 had a second primary cancer (SPC), and 216 died. We measured nine potential serum prognostic markers: prolactin, soluble interleukin-2 (IL-2) receptor-α, vascular endothelial growth factor, IL-6, squamous cell carcinoma antigen, free β-human choriogonadotropin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, and soluble epidermal growth factor receptor. Cox regression was used to identify a reference predictive model for (a) HNC recurrence, (b) SPC incidence, and (c) overall mortality. Each serum marker was added in turn to these reference models to determine by the likelihood ratio test whether it significantly improved outcome prediction. We controlled for the false discovery rate that results from multiple testing. Results: IL-6 was the only serum marker that significantly improved outcome prediction. Higher levels of IL-6 were associated with a higher SPC incidence. The hazard ratio comparing the uppermost quartile to the lowest quartile of IL-6 was 2.68 (95% confidence interval, 1.49-4.08). IL-6 was also associated with SPC-specific mortality but not with mortality due to other causes. No marker improved outcome prediction for cancer recurrence or overall mortality. Conclusions: IL-6 significantly improves outcome prediction for SPC in HNC patients. Clin Cancer Res; 16(3); 1008–15
Respiratory syncytial virus in critically ill adult patients with community-acquired respiratory failure: a prospective observational study
Authors: D.S.Y. Ong, T.E. Faber, P.M.C. Klein Klouwenberg, O.L. Cremer, E. Christiaan Boerma, M. Sietses, A.M. van Loon, M.J.M. Bonten, L.J. Bont
Journal: Clinical Microbiology and Infection (2013)
Unique Hexosaminidase Reduces Metabolic Survival Signal and Sensitizes Cardiac Myocytes to Hypoxia/Reoxygenation Injury
Authors: Gladys A. Ngoh, Heberty T. Facundo, Tariq Hamid, Wolfgang Dillmann, Natasha E. Zachara, Steven P. Jones
Journal: Circulation Research (2008)

Metabolic signaling through the posttranslational linkage of N -acetylglucosamine ( O -GlcNAc) to cellular proteins represents a unique signaling paradigm operative during lethal cellular stress and a pathway that we and others have recently shown to exert cytoprotective effects in vitro and in vivo. Accordingly, the present work addresses the contribution of the hexosaminidase responsible for removing O -GlcNAc (ie, O -GlcNAcase) from proteins. We used pharmacological inhibition, viral overexpression, and RNA interference of O -GlcNAcase in isolated cardiac myocytes to establish its role during acute hypoxia/reoxygenation. Elevated O -GlcNAcase expression significantly reduced O -GlcNAc levels and augmented posthypoxic cell death. Conversely, short interfering RNA directed against, or pharmacological inhibition of, O -GlcNAcase significantly augmented O -GlcNAc levels and reduced posthypoxic cell death. On the mechanistic front, we evaluated posthypoxic mitochondrial membrane potential and found that repression of O -GlcNAcase activity improves, whereas augmentation impairs, mitochondrial membrane potential recovery. Similar beneficial effects on posthypoxic calcium overload were also evident. Such changes were evident without significant alteration in expression of the major putative components of the mitochondrial permeability transition pore (ie, voltage-dependent anion channel, adenine nucleotide translocase, cyclophilin D). The present results provide definitive evidence that O -GlcNAcase antagonizes posthypoxic cardiac myocyte survival. Moreover, such results support a renewed approach to the contribution of metabolism and metabolic signaling to the determination of cell fate.
Role of Anthracyclines in the Treatment of Early Breast Cancer
Authors: Luca Gianni, Larry Norton, Norman Wolmark, Thomas M. Suter, Gianni Bonadonna, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2009)

To review data relating to anthracyclines in the adjuvant treatment of early breast cancer.This is a report from a seminar in which the future of anthracyclines in the adjuvant treatment of breast cancer was considered. In particular, the question of whether anthracyclines should now be discarded and replaced by taxanes was addressed.Accumulating data from large randomized trials indicate that genetic markers may have a role in predicting sensitivity to cytotoxic drugs. However, no reliable, validated test is available for predicting sensitivity to anthracyclines in particular. Topoisomerase IIalpha amplification and/or deletion, especially in conjunction with human epidermal growth factor receptor-2 amplification, has been proposed to fulfill this role but more data are needed. Currently, only one published trial has shown that a taxane-based regimen may be superior to an anthracycline-based regimen, but several trials indicate that combinations including both anthracyclines and taxanes may be better still. Further studies aimed at optimizing anthracyclines and taxanes in combination, and integrating biologic agents, seem to be the way forward. There is no validated test that can determine whether anthracyclines can be of greater benefit than other agents for individual patients.Anthracyclines have been extensively tested in clinical trials spanning several decades; currently, there are insufficient data to recommend replacing them in the adjuvant treatment of breast cancer.
Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis.
Authors: D C Currie, C Lueck, H J Milburn, C Harvey, J L Longbottom, J H Darbyshire, A J Nunn, P J Cole
Journal: Thorax (1990)

Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2.25 mg, placebo 2.5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these) was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis.
MEN4901/T-0128, a New Camptothecin Derivative–Carboxymethyldextran Conjugate, Has Potent Antitumor Activities in a Panel of Human Tumor Xenografts in Nude Mice
Authors: Fumiko Fujita, Masako Koike, Masahide Fujita, Yasuo Sakamoto, Satoshi Okuno, Takayuki Kawaguchi, Shigeru Yano, Toshiro Yano, Satoko Kiuchi, Toshihisa Fujiwara, Shinzoh Kudoh, Masatoshi Kakushima
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The purpose of the present study was to evaluate the antitumor activity and pharmacokinetic profile of MEN4901/T-0128 in nude mice bearing human tumor xenografts in comparison with irinotecan (CPT-11) and T-2513. Experimental Design: We have determined the antitumor activity of MEN4901/T-0128, CPT-11, and T-2513 in BALB/cA Jcl nude mice bearing human gastric (H-81), colon (H-110), lung (Mqnu-1, H-74), esophageal (H-204), liver (H-181), and pancreatic (H-48) cancer lines, which had been serially transplanted s.c. and maintained in nude mice, and characterized the pharmacokinetic profile of MEN4901/T-0128 in nude mice bearing human gastric carcinoma St-4. Results: MEN4901/T-0128 administered i.v. showed a marked antitumor activity in each of these tumor models, producing tumor shrinkage in the models of H-204 and H-181 carcinomas at its maximum tolerated dose of 80 mg/kg (expressed as T-2513) weekly for 4 weeks (q7d × 4) and tumor-shrinking or marked growth-inhibitory effects in the models of H-81, H-110, Mqnu-1, H-74, and H-48 carcinomas at 1/3 of its maximum tolerated dose (q7d × 4). Pharmacokinetic analysis showed that MEN4901/T-0128 had an extended plasma half-life with sustained tumor levels of T-2513, which may explain the superior activity of MEN4901/T-0128 in vivo. Conclusions: Because the efficacies of some drugs in this human cancer-nude mouse panel correlated well with their clinical outcomes in patients with the same type of cancers, the findings provide direct support that MEN4901/T-0128 is more efficacious than CPT-11 and is an excellent candidate for clinical trials for the treatment of solid tumors.
A preliminary study of patient comfort associated with customised mouthguards.
Authors: C McClelland, M Kinirons, L Geary
Journal: British Journal of Sports Medicine (1999)

To compare patient perception of custom made mouthguards of ideal and less than ideal designs in terms of their comfort and "wearability".A mouthguard of ideal design (A) and one incorporating common design faults of underextension and unadjusted occlusion (B) were provided for 22 active sportsmen and women. They were not informed of the details of the design or the status of the protector. Half the participants were asked to wear mouthguard A first and the other half wore B first, each worn for one hour on two consecutive nights. Questionnaires were used to evaluate and rate the comfort and wearability of each mouthguard.Eighteen people completed the study. The ideal appliance was rated as significantly more retentive and comfortable overall and specifically was more comfortable to lips, gums, and tongue. It was also recognised as being less bulky, less likely to keep the teeth apart, or to cause pain in the jaw muscles.Comfort is likely to be increased if mouthguards are extended labially to within 2 mm of the vestibular reflection, adjusted to allow even occlusal contact, rounded at the buccal peripheries, and tapered at the palatal edges.