tbuckley/cabot-search huggingface dataset:
Protection by antibiotics against myeloperoxidase-dependent cytotoxicity to lung epithelial cells in vitro.
Authors: A Cantin, D E Woods
Journal: Journal of Clinical Investigation (1993)

Myeloperoxidase, in the presence of noncytotoxic concentrations of H2O2, was used to induce cytotoxicity to the lung epithelial cell line, AKD. When the cationic aminoglycosides, tobramycin and gentamicin were added to the cells in the presence of myeloperoxidase and H2O2, cytotoxicity was completely inhibited. In addition, tobramycin prevented cytotoxicity induced by cystic fibrosis sputum and H2O2. Protection against myeloperoxidase and H2O2 was also observed with the thioether-containing antibiotics, ticarcillin and ceftazidime, but at higher concentrations than with the aminoglycosides. Analysis of spectral properties, dimethylsulfoxide-mediated reduction, and ethyl acetate/NaCl partitioning, demonstrated that aminoglycosides converted HOCl to hydrophilic noncytotoxic chloramines, but were unable to prevent the oxidation of sulfhydryls and methionine by HOCl. In contrast, ticarcillin and ceftazidime were highly effective inhibitors of HOCl-mediated sulfhydryl and methionine oxidation. These results suggest that aminoglycosides protect lung epithelial cells against myeloperoxidase-dependent oxidant injury by binding to anionic cell surfaces and converting HOCl to hydrophilic noncytotoxic chloramines, whereas penicillins and cephalosporins are potent HOCl scavengers capable of protecting critical extracellular molecules against oxidation.
Management of antiplatelet treatment in patients undergoing endoscopic procedures
Authors: A. Mancuso, L. Montalbano, G. D'Amico
Journal: Gut (2010)

We believe that the guidelines for the management of anticoagulant and antiplatelet treatment in patients undergoing endoscopic procedures, recently published in Gut , are an important tool for the correct management of such patients and are well balanced.1 However, we wish to make some comments about antiplatelet treatment. In the Introduction, the authors state that aspirin treatment can be continued for all endoscopic procedures (without reporting any reference), suggesting that this is an obvious and strongly evidence-based statement. In our opinion, although we broadly agree with this statement, evidence about it is weak. In fact, the “strongest” evidence about the low risk of bleeding after endoscopic biopsy or polipectomy in patients taking aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) comes from a prospective …
The role of HLA genes in familial spondyloarthropathy: a comprehensive study of 70 multiplex families
Authors: R Said-Nahal
Journal: Annals of the Rheumatic Diseases (2002)

Objectives: To investigate whether HLA alleles, other than HLA-B27, influence predisposition to spondyloarthropathy (SpA) in multiplex families. Methods: Seventy French families with at least two affected SpA members were recruited. Patients, and their first degree relatives were typed for HLA-A, B, C, and DR, and extended HLA haplotypes were determined. The distribution of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes in SpA families was compared with the distribution of these alleles among HLA-B27+ haplotypes in the French general population. Contribution to SpA susceptibility of HLA-A, B, C, and DR alleles, other than HLA-B27, was tested by transmission disequilibrium test. The contribution of HLA alleles to specific presentation features of SpA was examined. Results: Frequencies of HLA-A, C, and DR alleles carried on HLA-B27+ haplotypes from SpA families were comparable with those seen in the French population, except for DR13 which was overrepresented among patients (pcorr&lt;0.001). Most interestingly, the HLA-DR4 allele was transmitted in excess to patients with SpA, independently of linkage to HLA-B27 (pcorr=0.05), and in a direction opposite to that for HLA-B27+ unaffected siblings (pcorr=0.01). Finally, the distribution of HLA alleles was not related to the presentation feature of SpA. Conclusion: HLA predisposition to familial SpA appears not to be limited to HLA-B27, but some HLA-DR alleles also have a significant influence. In particular, HLA-DR4 contributes significantly to a genetic predisposition to SpA, which may have implications in our understanding of SpA pathogenesis.
Genetic Deletion of the A <sub>1</sub> Adenosine Receptor Limits Myocardial Ischemic Tolerance
Authors: Melissa E. Reichelt, Laura Willems, Jose G. Molina, Chun-Xiao Sun, Janci C. Noble, Kevin J. Ashton, Jurgen Schnermann, Michael R. Blackburn, John P. Headrick
Journal: Circulation Research (2005)

Adenosine receptors may be important determinants of intrinsic ischemic tolerance. Genetically modified mice were used to examine effects of global A 1 adenosine receptor (A 1 AR) knockout (KO) on function and ischemic tolerance in perfused mouse hearts. Baseline contractile function and heart rate were unaltered by A 1 AR KO, which was shown to abolish the negative chronotropic effects of 2-chloroadenosine (A 1 AR-mediated) without altering A 2 adenosine receptor–mediated coronary dilation. Tolerance to 25 minutes global normothermic ischemia (followed by 45 minutes reperfusion) was significantly limited by A 1 AR KO, with impaired contractile recovery (reduced by ≈25%) and enhanced lactate dehydrogenase (LDH) efflux (increased by ≈100%). Functional effects of A 1 AR KO involved worsened systolic pressure development with little to no change in diastolic dysfunction. In contrast, cardiac specific A 1 AR overexpression enhanced ischemic tolerance with a primary action on diastolic dysfunction. Nonselective receptor agonism (10 μmol/L 2-chloroadenosine) protected wild-type and also A 1 AR KO hearts (albeit to a lesser extent), implicating protection via subtypes additional to A 1 ARs. However, A 1 AR KO abrogated effects of 2-chloroadenosine on ischemic contracture and diastolic dysfunction. These data are the first demonstrating global deletion of the A 1 AR limits intrinsic myocardial resistance to ischemia. Data indicate the function of intrinsically activated A 1 ARs appears primarily to be enhancement of postischemic contractility and limitation of cell death.
Performance-based financing at the Global Fund to Fight AIDS, Tuberculosis and Malaria: an analysis of grant ratings and funding, 2003–12
Authors: Victoria Y Fan, Denizhan Duran, Rachel Silverman, Amanda Glassman
Journal: The Lancet Global Health (2013)

<h2>Summary</h2><h3>Background</h3> Performance-based financing can be used by global health funding agencies to improve programme performance and thus value for money. The Global Fund to Fight AIDS, Tuberculosis and Malaria was one of the first global-health funders to deploy a performance-based financing system. However, its complex, multistep system for calculating and paying on grant ratings has several components that are subjective and discretionary. We aimed to test the association between grant ratings and disbursements, an indication of the extent to which incentives for performance are transmitted to grant recipients. <h3>Methods</h3> We obtained publicly available data for 508 Global Fund grants from 2003 to 2012 with performance ratings and corresponding disbursements, merged with other datasets that contained data for relevant country characteristics. We used regression analysis to identify predictors of grant disbursements in phase 2 (typically the latter 3 of 5 years of a grant), using two dependent variables: whether a grant had any phase-2 disbursements, and the phase-2 disbursement amount. In a separate analysis, we also investigated the predictors of grant performance ratings. <h3>Findings</h3> Grant performance rating in phase 1 was positively associated with having any disbursements in phase 2, but no association was seen between phase-1 ratings and phase-2 disbursement amounts. Furthermore, performance ratings are not replicable by external observers, both because subjective and discretionary decisions are made in the generation of performance measures and because the underlying data are not available. <h3>Interpretation</h3> The Global Fund's present performance-based funding system does not adequately convey incentives for performance to recipients, and the organisation should redesign this system to explicitly link a portion of the funds to a simple performance measure in health coverage or outcomes, measured independently and robustly. <h3>Funding</h3> Bill & Melinda Gates Foundation.
Phenotypic Analysis of Peanut-Responsive T Cells at Baseline in Subjects Enrolled in CoFAR6, a Randomized Placebo-Controlled Epicutaneous Immunotherapy (EPIT) Trial for the Treatment of Peanut Allergy
Authors: David Chiang, A. Wesley Burks, Wendy Davidson, Peter Dawson, Alexander Grishin, Alice Henning, Stacie M. Jones, Donald Y.M. Leung, Robert W. Lindblad, Andrew H. Liu, Amy M. Scurlock, Scott H. Sicherer, Brian P. Vickery, Robert A. Wood, Hugh A. Sampson, Cecilia Berin
Journal: Journal of Allergy and Clinical Immunology (2015)
Changing Incident Diabetes Regimens
Authors: Mary Margaret Huizinga, Christianne L. Roumie, Tom A. Elasy, Harvey J. Murff, Robert Greevy, Xulei Liu, Theodore Speroff, Marie Griffin
Journal: Diabetes Care (2007)

Introduced in the mid-1950s, sulfonylureas have historically been the first line of treatment for type 2 diabetes (1). Metformin was introduced to the U.S. market in 1994 and has since experienced increasing market share (2). Metformin has many advantages over the sulfonylureas, including decreased weight gain and less risk of hypoglycemia (3). Despite some debate, the American Diabetes Association (ADA) recommended in 2006 that metformin be used as the first-line agent unless contraindicated (4). Whereas metformin use as a first-line agent was increasing before the ADA recommendations, no clear estimate of incident glycemic control regimens is available.

A retrospective cohort of patients …
Attracting AID to targets of somatic hypermutation
Authors: Atsushi Tanaka, Hong Ming Shen, Sarayu Ratnam, Prashant Kodgire, Ursula Storb
Journal: The Journal of Experimental Medicine (2010)

The process of somatic hypermutation (SHM) of immunoglobulin (Ig) genes requires activation-induced cytidine deaminase (AID). Although mistargeting of AID is detrimental to genome integrity, the mechanism and the cis-elements responsible for targeting of AID are largely unknown. We show that three CAGGTG cis-elements in the context of Ig enhancers are sufficient to target SHM to a nearby transcribed gene. The CAGGTG motif binds E47 in nuclear extracts of the mutating cells. Replacing CAGGTG with AAGGTG in the construct without any other E47 binding site eliminates SHM. The CA versus AA effect requires AID. CAGGTG does not enhance transcription, chromatin acetylation, or overall target gene activity. The other cis-elements of Ig enhancers alone cannot attract the SHM machinery. Collectively with other recent findings, we postulate that AID targets all genes expressed in mutating B cells that are associated with CAGGTG motifs in the appropriate context. Ig genes are the most highly mutated genes, presumably because of multiple CAGGTG motifs within the Ig genes, high transcription activity, and the presence of other cooperating elements in Ig enhancers.
Key contribution of CPEB4-mediated translational control to cancer progression
Authors: Elena Ortiz-Zapater, David Pineda, Neus Martínez-Bosch, Gonzalo Fernández-Miranda, Mar Iglesias, Francesc Alameda, Mireia Moreno, Carolina Eliscovich, Eduardo Eyras, Francisco X Real, Raúl Méndez, Pilar Navarro
Journal: Nature Medicine (2011)
Adiponectin: The Link Between Obesity and Asthma in Women?
Authors: Lisa G. Wood, Peter G. Gibson
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Abstract Supplemental oxygen improves exercise tolerance of normoxemic and hypoxemic COPD patients. We determined whether non-hypoxemic COPD patients undergoing exercise training while breathing supplemental oxygen achieve higher intensity and thereforeimprove exercise capacity more than patients breathing air. A double -blinded trial was performed involving 29 non-hypoxemic patients (67 years, exercise SaO 2 >88%) with COPD (FEV1 =36 % pred). All exercised on cycle ergometers for 45 minutes, 3 times/week for 7 weeks at high intensity targets. During exercise they received oxygen (3 L/minute)(n=14) or compressed air (3 L/minute)(n=15). Both groups had higher exercise tolerance after training and when breathing oxygen. However, the oxygen trained group incre ased training work rate more rapidly than the air trained group. Mean (±SD) work rate during the last week was 62±19 Watts (oxygen trained group) and 52±22 Watts (air trained group) (p < 0.01). After training, endurance in constant work rate tests increase d more in oxygen trained group (14.5 minutes) than in air trained group (10.5 minutes) (p<0.05). At isotime, breathing rate decreased 4 breaths/minute in oxygen trained group and 1 breath/minute in air trained group (p=0.001). We conclude that supplementa l oxygen provided during high -intensity training yields higher training intensity and evidence of gains in exercise tolerance in laboratory testing. Words in Abstract: 202Keywords: Chronic Obstructive Pulmonary Disease; Pulmonary Rehabilitation, Dyspnea
Cardiac atrial myosin adenosine triphosphatase of animals and humans: distinctive enzymatic properties compared with cardiac ventricular myosin.
Authors: Y Yazaki, S Ueda, R Nagai, K Shimada
Journal: Circulation Research (1979)

Cardiac myosin obtained from atria had a higher Ca2+-activated ATPase activity than did cardiac myosin from ventricles in various species of animals and in humans. The increased specific activity of Ca2+-activated adenosine triphosphatase (ATPase) of atrial myosin appeared to correlate with the level of the activity of ventricular myosin ATPase in the animal, since the same order in ATPase activity, as observed in ventricular myosins from various animals, was noted in atrial myosins. The enzymatic properties of atrial myosin also were characterized by no activation by N-ethylmaleimide, low activating energy, and a lower rate of inactivation at alkaline pH compared with the same properties of ventricular myosin. These findings suggest a difference in the myosin molecule at or near the active site, involving some sulfhydryl groups, between the two types of cardiac myosin. The Mg2+-activated ATPase activity, both in the presence and absence of actin (which is thought to be closely related to the basic contraction mechanism), also was enhanced in atrial myosin. Thus, the ATPase activities of atrial and ventricular myosins were different with special reference to the reaction pathway involving calcium and magnesium ions and appear to account for the difference in the velocity of contraction between the atria and the ventricles.
Carbonic Anhydrase Function and the Epithelial Organization of H+ Secretion in Turtle Urinary Bladder
Authors: John H. Schwartz, Seymour Rosen, Philip R. Steinmetz
Journal: Journal of Clinical Investigation (1972)

The function of carbonic anhydrase in H+ secretion by the turtle bladder was studied in vitro. Dose response curves were obtained for the carbonic anhydrase inhibitors, acetazolamide and ethoxzolamide, with and without addition of CO2 to the system. In addition, carbonic anhydrase was assayed in homogenates of mucosal cells. The activity in the homogenates was 155±16 U/g dry wt, of which only 11 U represented contamination from erythrocytes; after addition of 5 × 10−6m acetazolamide, no enzyme activity was detectable.
<i>EGFR</i> Fluorescence <i>In situ</i> Hybridization Pattern of Chromosome 7 Disomy Predicts Resistance to Cetuximab in KRAS Wild-type Metastatic Colorectal Cancer Patients
Authors: Yu-Hong Li, Fang Wang, Lin Shen, Yan-Ming Deng, Qiong Shao, Fen Feng, Xin An, Feng-Hua Wang, Zhi-Qiang Wang, Rui-Hua Xu, Jian-Yong Shao
Journal: Clinical Cancer Research (2010)

Metastatic colorectal cancer patients with low epidermal growth factor receptor (EGFR) gene copy number are unlikely to respond to anti-EGFR monoclonal antibody (mAb) treatment. The objective of this study was to investigate EGFR fluorescence in situ hybridization (FISH) patterns of chromosome 7 disomy with efficacy of cetuximab therapy in metastatic colorectal cancer patients.We detected the EGFR FISH patterns and KRAS status in 74 tumors from cetuximab-treated metastatic colorectal cancer patients and analyzed with response rate (RR) and progression-free survival (PFS).One of the 16 (6.25%) patients with chromosome 7 homogeneous disomy (defined as FISH negative) had objective response to cetuximab. A total of 53(76.8%) patients with chromosome 7 pattern of variable ratios of disomy versus polysomy (defined as FISH positive) had a significantly higher RR (37.7% versus 6.25%; P = 0.01), a trend towards longer PFS (4.5 versus 2.9 months; P = 0.07). Among 54 KRAS wild-type patients, EGFR FISH-positive patients had significantly higher RR (51.3% versus 9%; P = 0.01) and longer PFS (5.0 versus 2.3 months; P = 0.02) than EGFR FISH-negative patients. However, among 20 KRAS mutant-type patients, there was no difference in RR (0% versus 0%) and PFS (2.5 versus 3.8 months; P = 0.51) between EGFR FISH-positive and -negative patients.Our results show firstly that patients with EGFR FISH pattern of chromosome 7 disomy have a very low chance to benefit from cetuximab-based therapy. EGFR FISH pattern of chromosome 7 disomy may be as a negative predicative factor for cetuximab response in KRAS wild-type metastatic colorectal cancer patients.
A Comparison of On-Line Hemodiafiltration and High-Flux Hemodialysis
Authors: RICHARD A. WARD, BA[Combining Diaeresis]RBEL SCHMIDT, JEANNINE HULLIN, GU[Combining Diaeresis]NTHER F. HILLEBRAND, WALTER SAMTLEBEN
Journal: Journal of the American Society of Nephrology (2000)

Some of the morbidity associated with chronic hemodialysis is thought to result from retention of large molecular weight solutes that are poorly removed by diffusion in conventional hemodialysis. Hemodiafiltration combines convective and diffusive solute removal in a single therapy. The hypothesis that hemodiafiltration provides better solute removal than high-flux hemodialysis was tested in a prospective, randomized clinical trial. Patients were randomized to either on-line postdilution hemodiafiltration or high-flux hemodialysis. The groups did not differ in body size, treatment time, blood flow rate, or net fluid removal. The filtration volume in hemodiafiltration was 21 +/-1 L. Therapy prescriptions were unchanged for a 12-mo study period. Removal of both small (urea and creatinine) and large (ss(2)-microglobulin and complement factor D) solutes was significantly greater for hemodiafiltration than for high-flux hemodialysis. The increased urea and creatinine removal did not result in lower pretreatment serum concentrations in the hemodiafiltration group. Pretreatment plasma beta(2)-microglobulin concentrations decreased with time (P< 0.001); however, the decrease was similar for both therapies (P = 0.317). Pretreatment plasma complement factor D concentrations also decreased with time (P<0.001), and the decrease was significantly greater with hemodiafiltration than with high-flux hemodialysis (P = 0.010). The conclusion is that on-line hemodiafiltration provides superior solute removal to high-flux hemodialysis over a wide molecular weight range. The improved removal may not result in lower pretreatment plasma concentrations, however, possibly because of limitations in mass transfer rates within the body.
FURTHER STUDIES ON IMMUNITY IN EXPERIMENTAL CRYPTOCOCCOSIS
Authors: Donald B. Louria, Theresa Kaminski, Gerald Finkel
Journal: The Journal of Experimental Medicine (1963)

Following infection with 10(3) cells of Cryptococcus neoformans, progressive multiplication occurred in all tissues for 7 to 28 days. Thereafter, most mice gained control of the infection so that 3 to 6 months after inoculation, tissues were usually sterile or contained only small numbers of cryptococci. Survivors challenged 1 to 4 months after infection with 10(3) cells lived longer than controls and had an increased survival rate. Pretreatment with bacterial endotoxin also resulted in protection against cryptococcal challenge. Endotoxin-protected animals showed no ability to limit the infection until circulating antibody could be demonstrated. Histologic studies revealed an increased cellular infiltration in the brains of specifically protected and endotoxin-protected mice 1 to 2 weeks after challenge. However, control of cryptococcal multiplication could be correlated with the presence of antibody but could not be correlated with the enhanced cellular response. Although protection against cryptococcal challenge appears to be antibody-dependent, it is unclear whether protective antibody is to be found in plasma or is tissue-bound.
Multiple Roles of Chemokine (C-C Motif) Ligand 2 in Promoting Prostate Cancer Growth
Authors: J. Zhang, Y. Lu, K. J. Pienta
Journal: JNCI Journal of the National Cancer Institute (2010)

Prostate cancer continues to be the most common nonskin cancer diagnosed and the second leading cause of cancer death in men in the United States. Prostate cancer that has metastasized to bone remains incurable. The interactions between prostate cancer cells and the various cells of the host microenvironment result in enhanced growth of tumor cells and activation of host cells that together culminate in osteoblastic bone metastases. These dynamic tumor–host interactions are mediated by cancer and host-produced cytokines and chemokines. Among them, chemokine (C-C motif) ligand 2 (CCL2) has been identified as a prominent modulator of metastatic growth in the bone microenvironment. CCL2 is produced by bone marrow osteoblasts, endothelial cells, stromal cells, and prostate cancer cells. It has been demonstrated to modulate tumor-associated macrophage migration and promote osteoclast maturation. In addition, CCL2 functions through binding to its receptor CCR2 to induce prostate cell proliferation, migration, and invasion in both autocrine and paracrine manners. CCL2 protects prostate cancer cells from autophagic death by activating survivin through a PI3K/AKT (phosphatidylinositol 3-kinase/protein kinase B)–dependent mechanism. Inhibition of CCL2 substantially decreases macrophage infiltration, decreases osteoclast function, and inhibits prostate cancer growth in bone in preclinical animal models. The multiple roles of CCL2 in the tumor microenvironment make it an attractive therapeutic target in metastatic prostate cancer as well as in other cancers.
Contour of Electrically Induced Premature Ventricular Beats Before and After Experimental Myocardial Infarction in Dog
Authors: Emmons G. Paine, Michael McDonough, Louis A. Soloff
Journal: Circulation Research (1962)

Ventricular premature beats were produced by stimulating electrodes inserted into the anterolateral right ventricular and into the midlateral left ventricular wall of 13 openchest anesthetized dogs. In 9 of the 13, acute myocardial infarction deformed the final deflection of the experimentally induced ventricular extrasystoles so that they mimicked the diagnostic pattern present in the beats of sinus origin. In 4 of the 13, no changes occurred in either the extrasystoles or in the beats of sinus origin until the infarcted region was brought into contact with the thoracic wall, at which time diagnostic patterns of infarction appeared in both types of ventricular complexes. Reinfarction produced by ligating an additional coronary branch produced comparable changes in the final deflection of the premature and sinus-propagated beat. These findings suggest that the inscription of the terminal deflections of premature ventricular beats is dominated by events within the infarcted region. They support the clinical concept that the configuration of ventricular extrasystoles may be of value in the recognition of acute myocardial infarction. The findings do not explain, however, the occasional absence of diagnostic findings in ventricular premature beats in electrocardiograms otherwise diagnostic of human myocardial infarction.