tbuckley/cabot-search huggingface dataset:
Prediction of Clinical Outcome in Islet Allotransplantation
Authors: Federico Bertuzzi, Camillo Ricordi
Journal: Diabetes Care (2007)

Recent progresses in the pancreas’ enzymatic digestion process along with novel immunosuppression strategies have led to successful clinical trials of islet transplantation in humans. On the other hand, clinical outcome remains variable and unpredictable in centers with limited experience. The possibility of predicting in vivo islet graft function should allow the selection of preparations on the basis of their potential success, thus improving the overall results and making the processes more consistent and reproducible.

Graft function prediction is a work in progress. Initially, the best parameters representative of engrafted islet mass in recipients should be defined. Fasting C-peptide and exogenous insulin requirements are commonly used, although other methods for a more complete characterization of graft function (i.e., β-score) have recently been described but not validated in a large number of patients. In addition, some of these data were shown to predict long-term graft function and might be used to establish whether recipients require further islet infusions.

Many pretransplant parameters representative of islet preparations and predictive for in vivo function have been proposed. C-peptide values as well as the exogenous insulin requirements of recipients were shown to be directly correlated with the number of transplanted islets, but there are many exceptions to this association. Other methods to define the quality of an islet preparation include analyses of islet morphology, cell composition, response to glucose, and viability and production of proinflammatory molecules. The most promising appear to be those that simultaneously analyze more than one aspect of islet physiology.

Islet transplantation has great potential for the normalization of the main parameters of glucose metabolism in diabetic patients. A sufficient number of islets can now be obtained from good quality pancreata more frequently than in the past, and diabetes can generally be reversed, normalizing A1C levels and eliminating severe hypoglycemic episodes (1). Clinical …
Transient depolarization and spontaneous voltage fluctuations in isolated single cells from guinea pig ventricles. Calcium-mediated membrane potential fluctuations.
Authors: H Matsuda, A Noma, Y Kurachi, H Irisawa
Journal: Circulation Research (1982)

Under the influence of cardiotonic steroids, single ventricular cells exhibit transient depolarization after a train of driven action potentials or, in voltage clamp experiments, transient inward current after a depolarizing clamp pulse. Transient depolarization or transient inward current was abolished by an intracellular injection of ethyleneglycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) or by superfusion of 5 mM caffeine. Transient depolarization was elicited even in the control Tyrode's solution by an intracellular injection of CaCl2 or augmented by an injection of adenosine 3',5'-cyclic monophosphoric acid (cAMP). Along with transient depolarization or transient inward current, digitalis intoxication promoted spontaneous oscillatory fluctuations in membrane potential or in membrane current. Their power spectra showed peaks at frequencies ranging from 2 to 7 Hz, which coincided well with the frequency of repetitive transient depolarization or transient inward current. The fluctuations were eliminated by intracellular injections of EGTA and decreased in amplitude by 5 mM caffeine with a shift toward higher frequencies. Depolarization of the membrane caused a shift of the spectrum peak toward higher frequencies. These results suggest that an oscillatory release of Ca from intracellular storage sites is the common basis underlying both the transient events (depolarization or inward current) and the spontaneous miniature fluctuations in membrane potential or current.
The effects of membrane potential, extracellular potassium, and tetrodotoxin on the intracellular sodium ion activity of sheep cardiac muscle.
Authors: C T January, H A Fozzard
Journal: Circulation Research (1984)

The intracellular sodium ion activity was measured using liquid ion-exchange microelectrodes with rapid response times in sheep Purkinje fibers and ventricular muscle under voltage control. The mean sodium ion activity in quiescent Purkinje fibers was 8.5 mM at a holding potential of -80 mV. With maintained hyperpolarizing (-110 mV) or depolarizing (-40 and 0 mV) voltage steps, sodium ion activity increased or decreased, respectively. At 0 mV, the mean steady state value for the sodium ion activity was 3.8 mM. Following a voltage step to 0 mV, or back to -80 mV, the time course of the sodium ion activity change could be fitted by single exponentials, with similar half-times. Increasing the extracellular potassium ion concentration from 5.4 to 15 mM did not alter the steady state value of the sodium ion activity at clamped voltages of -80 or 0 mV, which suggests that the external potassium ion activating site of the Na-K pump was saturated. With the extracellular potassium concentration 0 mM (holding potential -80 mV), the sodium ion activity increased. When maintained depolarizing steps to 0 mV were applied, the sodium ion activity decreased by up to 20 mM. This large fall in sodium ion activity is assumed to represent partial reactivation of the Na-K pump due to potassium ion accumulation in clefts. We also studied the stimulation-dependent change in sodium ion activity. Trains of action potentials or short duration depolarizing voltage clamp steps caused a frequency dependent rise in sodium ion activity. The magnitude of the rise of sodium ion activity was not altered by lengthening the duration of each voltage clamp step, but was inhibited by tetrodotoxin or by holding the membrane potential at -50 mV between depolarizing steps. These results show that sodium ion activity is a complex function of membrane voltage, depolarization frequency, and time. The rise in sodium ion activity with stimulation appears to depend on sodium ion entry regulated by the sodium channel, and may be important in the modulation of intracellular calcium and tension through the Na+-Ca++ exchange mechanism.
Hypoxia-Selective Targeting by the Bioreductive Prodrug AQ4N in Patients with Solid Tumors: Results of a Phase I Study
Authors: Mark R. Albertella, Paul M. Loadman, Philip H. Jones, Roger M. Phillips, Roy Rampling, Neil Burnet, Chris Alcock, Alan Anthoney, Egils Vjaters, Chris R. Dunk, Peter A. Harris, Alvin Wong, Alshad S. Lalani, Chris J. Twelves
Journal: Clinical Cancer Research (2008)

Abstract Purpose: AQ4N is a novel bioreductive prodrug under clinical investigation. Preclinical evidence shows that AQ4N penetrates deeply within tumors and undergoes selective activation to form AQ4, a potent topoisomerase II inhibitor, in hypoxic regions of solid tumors. This proof-of-principle, phase I study evaluated the activation, hypoxic selectivity, and safety of AQ4N in patients with advanced solid tumors. Experimental Design: Thirty-two patients with cancer (8 glioblastoma, 9 bladder, 8 head and neck, 6 breast, and 1 cervix) received a single 200 mg/m2 dose of AQ4N before elective surgery. AQ4 and AQ4N levels in 95 tissues (tumor, healthy tissue) were assessed by liquid chromatography-tandem mass spectrometry. Tissue sections were also analyzed for AQ4 fluorescence using confocal microscopy, and for expression of the hypoxia-regulated glucose transporter, Glut-1. Results: Activated AQ4 was detected in all tumor samples with highest levels present in glioblastoma (mean 1.2 μg/g) and head and neck (mean 0.65 μg/g) tumors; 22 of 32 patients had tumor AQ4 concentrations ≥0.2 μg/g, levels previously shown to be active in preclinical studies. In 24 of 30 tumor samples, AQ4 was detected at higher concentrations than in adjacent normal tissue (tumor to normal ratio range 1.1-63.6); distant skin samples contained very low concentrations of AQ4 (mean 0.037 μg/g). Microscopic evaluation of tumor sections revealed that AQ4 colocalized within regions of Glut-1+ hypoxic cells. Conclusions: AQ4N was activated selectively in hypoxic regions in human solid tumors. Intratumoral concentrations of AQ4 exceeded those required for activity in animal models and support the evaluation of AQ4N as a novel tumor-targeting agent in future clinical studies.
Somatostatin does not reduce oesophageal variceal pressure in liver cirrhotics.
Authors: G Kleber, T Sauerbruch, G Fischer, G Paumgartner
Journal: Gut (1988)

Transmural oesophageal variceal pressure was determined by direct puncture of the varices in 27 patients with liver cirrhosis and oesophageal varices. Variceal pressure was not influenced three to six minutes after somatostatin bolus administration and slightly increased during somatostatin infusion. Thus, potential haemostatic benefits of somatostatin cannot be explained by pressure reductions in the varices.
Shopping Vouchers Sweeten Incentive for Pregnant Women to Quit Smoking
Authors: Anita Slomski
Journal: JAMA (2015)

The chance to earn shopping vouchers offered with a smoking cessation program was a bigger motivator for inner-city pregnant women to quit smoking than was the free quit-smoking program alone (Tappin D et al. BMJ. doi:10.1136/bmj.h134 [published online January 27, 2015]).
Low HDL Cholesterol Is Associated With the Risk of Stroke in Elderly Diabetic Individuals
Authors: Toshio Hayashi, Seinosuke Kawashima, Hideki Itoh, Nobuhiro Yamada, Hirohito Sone, Hiroshi Watanabe, Yoshiyuki Hattori, Takashi Ohrui, Koutaro Yokote, Hideki Nomura, Hiroyuki Umegaki, Akihisa Iguchi
Journal: Diabetes Care (2009)

To clarify the relationship between lipid levels and ischemic heart disease (IHD) and cerebrovascular disease (CVD) in diabetic individuals.
The gene encoding decay-accelerating factor (DAF) is located in the complement-regulatory locus on the long arm of chromosome 1.
Authors: D M Lublin, R S Lemons, M M Le Beau, V M Holers, M L Tykocinski, M E Medof, J P Atkinson
Journal: The Journal of Experimental Medicine (1987)

Delay-accelerating factor (DAF) protects host cells from complement-mediated damage by regulating the activation of C3 convertases on host cell surfaces. Using a panel of hamster-human somatic cell hybrids, the DAF gene was mapped to human chromosome 1. In situ hybridization studies using human metaphase cells further localized the gene to bands 1q31-41, with the largest cluster of grains at 1q32. This establishes the close linkage of the DAF gene to genes for four other proteins (C3b/C4b receptor or complement receptor 1, C3d receptor or complement receptor 2, factor H, and C4-binding protein) that share 60-amino-acid homologous repeats as well as complement-regulatory or -receptor activity, thereby enlarging the complement-regulatory gene family on the long arm of human chromosome 1.
Extreme Conservation and Non-Neutral Evolution of the cpmA Circadian Locus in a Globally Distributed Chroococcidiopsis sp. from Naturally Stressful Habitats
Authors: Volodymyr Dvornyk, Akhee Sabiha Jahan
Journal: Molecular Biology and Evolution (2012)

Cyanobacteria are among the most ancient organisms known to have circadian rhythms. The cpmA gene is involved in controlling the circadian output signal. We studied polymorphism and divergence of this gene in six populations of a stress-tolerant cyanobacterium, Chroococcidiopsis sp., sampled in extreme habitats across the globe. Despite high haplotype diversity (0.774), nucleotide diversity of cpmA is very low (π = 0.0034): the gene appears to be even more conserved than housekeeping genes. Even though the populations were sampled thousands kilometers apart, they manifested virtually no genetic differentiation at this locus (FST = 0.0228). Using various tests for neutrality, we determined that evolution of cpmA significantly departures from the neutral model and is governed by episodic positive selection.
Myocardial Perfusion Imaging for Evaluation and Triage of Patients With Suspected Acute Cardiac Ischemia
Authors: James E. Udelson, Joni R. Beshansky, Daniel S. Ballin, James A. Feldman, John L. Griffith, Gary V. Heller, Robert C. Hendel, J. Hector Pope, Robin Ruthazer, Ethan J. Spiegler, Robert H. Woolard, Jonathan Handler, Harry P. Selker
Journal: JAMA (2002)

ContextObservational studies of acute myocardial perfusion imaging in emergency department (ED) patients with chest pain have suggested high sensitivity and negative predictive value for acute cardiac ischemia, but use of this method has not been prospectively tested.ObjectiveTo assess whether incorporating acute resting perfusion imaging into an ED evaluation strategy for patients with suspected acute ischemia but no initial electrocardiogram (ECG) changes diagnostic of acute ischemia improves clinical decision making for initial ED triage.Design, Setting, and PatientsProspective, randomized controlled trial conducted at 7 academic medical centers and community hospitals between July 1997 and May 1999 among 2475 adult ED patients with chest pain or other symptoms suggestive of acute cardiac ischemia and with normal or nondiagnostic initial ECG results.InterventionPatients were randomly assigned to receive either the usual ED evaluation strategy (n = 1260) or the usual strategy supplemented with results from acute resting myocardial perfusion imaging using single-photon emission computed tomography with injection of 20 to 30 mCi of Tc-99m sestamibi (n = 1215), interpreted in real time by local staff physicians and with results provided to the ED physician for incorporation into clinical decision making.Main Outcome MeasureAppropriateness of triage decision either to admit to hospital/observation or to discharge directly home from the ED.ResultsAmong patients with acute cardiac ischemia (ie, acute myocardial infarction [MI] or unstable angina; n = 329), there were no differences in ED triage decisions between those receiving standard evaluation and those whose evaluation was supplemented by a sestamibi scan. Among patients with acute MI (n = 56), 97% vs 96% were hospitalized (relative risk [RR], 1.00; 95% confidence interval [CI], 0.89-1.12), and among those with unstable angina (n = 273), 83% vs 81% were hospitalized (RR, 0.98; 95% CI, 0.87-1.10). However, among patients without acute cardiac ischemia (n = 2146), hospitalization was 52% with usual care vs 42% with sestamibi imaging (RR, 0.84; 95% CI, 0.77-0.92).ConclusionsSestamibi perfusion imaging improves ED triage decision making for patients with symptoms suggestive of acute cardiac ischemia without obvious abnormalities on initial ECG. In this study, unnecessary hospitalizations were reduced among patients without acute ischemia, without reducing appropriate admission for patients with acute ischemia.
Pediatrics, Surfactant, and Cystic Fibrosis in <i>AJRCCM</i> 2002
Authors: Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Pediatrics (62) Pulmonary Function Testing and Diagnostic Techniques (13) Normative Values (1) Thoracoabdominal Compression (1) Spirometry (4) Forced Oscillation (3) Exhaled Nitric Oxide (1) Respiratory Muscles and Mechanics (3) Mechanical Ventilation (4) Respiratory Syncytial Virus Bronchiolitis (8) Sleep and Control of Breathing (5) Pediatric Asthma (23) Epidemiology (6) Risk Factors: Air Pollution (1) Risk Factors: Aeroallergens (2) Risk Factors: Parental Asthma and Exposure (1) Airway Inflammation (6) Airway Hyperreactivity (3) Clinical Issues (1) Treatment (3) Other Pediatric Issues (9) Passive Smoking (2) Lung Development (2) Bronchopulmonary Dysplasia (5) Surfactant Biology and Disorders (11) Pathophysiology (7) Treatment (3) Workshop (1) Cystic Fibrosis (12) Genetics (1) Lung Inflammation (2) Microbiology (1) Pathophysiology and Exercise Performance (3) Treatment (3) Gene Therapy (1) Lung Transplantation (2) Outcome (2)
Preferential nuclear accumulation of JAK2V617F in CD34+ but not in granulocytic, megakaryocytic, or erythroid cells of patients with Philadelphia-negative myeloproliferative neoplasia
Authors: Ciro R. Rinaldi, Paola Rinaldi, Adele Alagia, Marica Gemei, Nicola Esposito, Fabio Formiggini, Vincenzo Martinelli, Vitalyi Senyuk, Giuseppina Nucifora, Fabrizio Pane
Journal: Blood (2010)
Primary B Cell Immunodeficiencies: Comparisons and Contrasts
Authors: Mary Ellen Conley, A. Kerry Dobbs, Dana M. Farmer, Sebnem Kilic, Kenneth Paris, Sofia Grigoriadou, Elaine Coustan-Smith, Vanessa Howard, Dario Campana
Journal: Annual Review of Immunology (2009)

Sophisticated genetic tools have made possible the identification of the genes responsible for most well-described immunodeficiencies in the past 15 years. Mutations in Btk, components of the pre-B cell and B cell receptor (λ5, Igα, Igβ), or the scaffold protein BLNK account for approximately 90% of patients with defects in early B cell development. Hyper-IgM syndromes result from mutations in CD40 ligand, CD40, AID, or UNG in 70–80% of affected patients. Rare defects in ICOS or CD19 can result in a clinical picture that is consistent with common variable immunodeficiency, and as many as 10% of patients with this disorder have heterozygous amino acid substitutions in TACI. For all these disorders, there is considerable clinical heterogeneity in patients with the same mutation. Identifying the genetic and environmental factors that influence the clinical phenotype may enhance patient care and our understanding of normal B cell development.
Schnurri-3 is an essential regulator of osteoblast function and adult bone mass
Authors: D. C Jones, M. N Wein, L. H Glimcher
Journal: Annals of the Rheumatic Diseases (2007)

Skeletal remodelling is a cyclical process where under normal physiological conditions, bone formation occurs at sites where bone resorption has previously taken place. Homeostatic remodelling of the skeleton is mediated by osteoclasts, giant multinucleated cells of haematopoietic origin that are responsible for bone resorption and osteoblasts, which originate from mesenchymal stem cells, and synthesise the matrix constituents on bone-forming surfaces.1 Proliferation, differentiation and bone remodelling activities of these cells involve a complex temporal network of growth factors, signalling proteins and transcription factors. Dysregulation of any one component may disrupt the remodelling process and contribute to the pathogenesis of common skeletal disorders, like osteoporosis and Paget's disease. Rare single gene disorders resulting in elevated bone mass due to osteoclast defects are collectively termed osteopetrosis. Rarer still are single gene disorders, collectively termed osteosclerosis, in which elevated bone mass is due to intrinsically elevated osteoblast activity.2 While we have learned much about the molecular control of skeletal formation and remodelling from these mutations, additional genes that regulate bone mass have yet to be characterised.
Acetabular dysplasia and osteoarthritis of the hip in elderly white women
Authors: N. E Lane, M. C Nevitt, C. Cooper, A. Pressman, R. Gore, M. Hochberg
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To examine the association of acetabular dysplasia and osteoarthritis (OA) of the hip among elderly white women. <h3>METHODS</h3> Pelvic radiographs from a sample of 165 white women aged 65 and above with radiographic hip OA and 88 white women aged 65 and above without radiographic changes of hip OA were read for evidence of acetabular dysplasia by a single trained investigator. Acetabular dysplasia was assessed using measurements of the centre edge angle and the acetabular depth, which are both reduced in this condition. Odds ratios for the association between acetabular dysplasia and hip OA were estimated using logistic regression analysis. <h3>RESULTS</h3> Fourteen (3.4%) hips had a centre edge angle &lt; 25°, 46 (11.2%) hips had an acetabular depth of &lt; 9 mm, and 54 (13.2%) hips had acetabular dysplasia defined as either of the above. Hips with OA had a small, but not statistically significant, increased prevalence of abnormal centre edge angle (odds ratio: 1.43; 95% confidence intervals: 0.46, 4.46), abnormal acetabular depth (1.47; 0.78, 2.77) and acetabular dysplasia (1.33; 0.74, 2.40). <h3>CONCLUSION</h3> These results do not support the hypothesis that mild acetabular dysplasia accounts for a substantial proportion of hip OA in elderly white women. A study with a much larger sample size would be required to rule out a weak association between dysplasia and hip OA of the magnitude actually observed in our study.
Soluble CD86 protein in serum samples of patients with asthma
Authors: H-Z Shi
Journal: Thorax (2004)

<b>Background:</b> Previous studies have reported that soluble (s) CD86 is involved in the initiation of the immune response. A study was undertaken to investigate the concentrations of sCD86 in serum samples from patients with bronchial asthma and to determine the cell origin of sCD86. <b>Methods:</b> Serum sCD86 concentrations were measured in 52 asthmatic subjects and 25 non-atopic normal volunteers using an enzyme linked immunosorbent assay, and the relationship of serum sCD86 concentrations to asthma severity and to total and differential white cell counts was analysed. Each type of white blood cell was purified and cultured in vitro to determine the cell origin of serum sCD86. <b>Results:</b> Serum samples from patients with an acute asthma exacerbation had much higher levels of sCD86 (585.4 (20.5) IU/ml) than those from stable asthmatics (479.6 (15.7) IU/ml, p&lt;0.001) and healthy individuals (435.1 (13.8) IU/ml, p&lt;0.001), and there was no difference between the latter two groups (p = 0.079). In asthmatic subjects the serum sCD86 level was inversely correlated with airway responsiveness, forced expiratory volume in 1 second, and with arterial carbon dioxide tension. In addition, the serum sCD86 level was positively correlated with numbers of lymphocytes, eosinophils, monocytes, but not neutrophils. The in vitro experiments indicated that sCD86 was produced by monocytes. <b>Conclusions:</b> The serum sCD86 protein level was significantly increased in asthmatic subjects during an exacerbation and correlated with the severity of asthma. sCD86 is most probably derived from monocytes in the peripheral blood.