tbuckley/cabot-search huggingface dataset:
Reversal of Paralysis and Reduced Inflammation from Peripheral Administration of β-Amyloid in T <sub>H</sub> 1 and T <sub>H</sub> 17 Versions of Experimental Autoimmune Encephalomyelitis
Authors: Jacqueline L. Grant, Eliver Eid Bou Ghosn, Robert C. Axtell, Katja Herges, Hedwich F. Kuipers, Nathan S. Woodling, Katrin Andreasson, Leonard A. Herzenberg, Leonore A. Herzenberg, Lawrence Steinman
Journal: Science Translational Medicine (2012)

β-Amyloid reduces inflammation and improves symptoms in a mouse model of multiple sclerosis.
Uterine adenomyosis in the infertility clinic
Authors: R. Devlieger
Journal: Human Reproduction Update (2003)

This review discusses uterine adenomyosis as a (co-)factor in female subfertility. The clinical presentation of adenomyosis uteri is reviewed as well as recent developments in non-invasive imaging modalities for the condition. Different treatment options are discussed, focusing on conservative management in patients who wish to maintain their childbearing capacity.
Lung function decline in relation to mould and dampness in the home: the longitudinal European Community Respiratory Health Survey ECRHS II
Authors: D. Norback, J.-P. Zock, E. Plana, J. Heinrich, C. Svanes, J. Sunyer, N. Kunzli, S. Villani, M. Olivieri, A. Soon, D. Jarvis
Journal: Thorax (2011)

<h3>Background</h3> There are few longitudinal studies that have examined the association of lung function decline with indoor mould and dampness. Lung function decline in relation to dampness and mould in the home has studied in adults over a 9 year period. <h3>Methods</h3> Spirometry was performed twice in participants in the European Respiratory Health Survey (ECRHS I and II) who were initially examined aged 20–45 years, in 1990–1995 and 9 years later (n=6443). Information on their current home was collected twice by interview. Dampness (water damage or damp spots) and indoor mould, ever and in the last 12 months, were assessed. A dampness score and a mould score were calculated. In addition, 3118 homes at 22 centres were inspected directly at follow-up for the presence of dampness and mould. <h3>Results</h3> Dampness and mould were common. Overall, 50.1% reported any dampness and 41.3% any indoor mould in either ECRHS I or ECRHS II. Women with dampness at home had an additional decline in forced expiratory volume in 1 s (FEV<sub>1</sub>) of −2.25 ml/year (95% CI −4.25 to −0.25), with a significant trend in increased lung function decline in relation to the dampness score (p=0.03). The association in women was significant when excluding those with asthma at baseline. Observed damp spots in the bedroom was associated with a significant additional decline in FEV<sub>1</sub> of −7.43 ml/year (95% CI −13.11 to 1.74) in women. <h3>Conclusion</h3> Dampness and indoor mould growth is common in dwellings, and the presence of damp is a risk factor for lung function decline, especially in women.
Human essential myosin light chain isoforms revealed distinct myosin binding, sarcomeric sorting, and inotropic activity
Authors: D. Petzhold, J. Lossie, S. Keller, S. Werner, H. Haase, I. Morano
Journal: Cardiovascular Research (2011)

In this paper, we tested the hypothesis that different binding affinities of the C-terminus of human cardiac alkali (essential) myosin light chain (A1) isoforms to the IQ1 motif of the myosin lever arm provide a molecular basis for distinct sarcomeric sorting and inotropic activity. We employed circular dichroism and surface plasmon resonance spectroscopy to investigate structural properties, secondary structures, and protein–protein interactions of a recombinant head-rod fragments of rat cardiac β-myosin heavy chain aa664–915 with alanine-mutated IQ2 domain (rβ-MYH664–915IQala4) and A1 isoforms [human atrial (hALC1) and human ventricular (hVLC-1) light chains]. Double epitope-tagging competition was used to monitor the intracellular localization of exogenously introduced hALC-1 and hVLC-1 constructs in neonatal rat cardiomyocytes. Contractile functions of A1 isoforms were investigated by monitoring shortening and intracellular-free Ca2+ (Fura-2) of adult rat cardiomyocytes infected with adenoviral (Ad) vectors using hALC-1 or β-galactosidase as expression cassettes. hALC-1 bound more strongly (greater than three-fold lower KD) to rβ-MYH664–915 than did hVLC-1. Sorting specificity of A1 isoforms to sarcomeres of cardiomyocytes rose in the order hVLC-1 to hALC-1. Replacement of endogenous VLC-1 by hALC-1 in adult rat cardiomyocytes increased contractility while the systolic Ca2+ signal remained unchanged. Intense myosin binding of hALC-1 provides a mechanism for preferential sarcomeric sorting and Ca2+-independent positive inotropic activity.
Cellular Radiation Dosimetry and Its Implications for Estimation of Radiation Risks
Authors: G. Mike Makrigiorgos
Journal: JAMA (1990)

Radiation absorbed doses at the cellular level were calculated for routine, human lung perfusion examinations after the intravenous injection of technetium 99m—labeled microspheres or macroaggregated albumin. In such studies, more than 90% of these particles are trapped in the precapillary arterioles of the lung, resulting in an extremely inhomogeneous distribution of radionuclide. We used a computer program that accounted for the inhomogeneity of radiopharmaceutical distribution and calculated the dose to individual lung cells. Absorbed doses to individual lung cells were found to vary by a factor of about 30 000. We believe that such findings call for a reevaluation of the justification for dosimetry at the organ level and an examination of the implications of absorbed doses calculated at the cellular level for the estimation of radiation risks. (<i>JAMA</i>. 1990;264:592-595)
Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients
Authors: Jan Balzer, Tienush Rassaf, Christian Heiss, Petra Kleinbongard, Thomas Lauer, Marc Merx, Nicole Heussen, Heidrun B. Gross, Carl L. Keen, Hagen Schroeter, Malte Kelm
Journal: Journal of the American College of Cardiology (2008)
More `salt' talks: diet and hypertension
Authors: Lanny Newman
Journal: JAMA (1982)

Conventional wisdom regarding the causes, prevalence, and treatment of hypertension was challenged by experts at a recent symposium on nutrition and BP control in Arlington, Va. The three-day meeting was jointly sponsored by the National Kidney Foundation, the Department of Health and Human Services, and the International Life Sciences Institute, Washington, DC. (The latter is an industry-supported organization that says it "provides for liaison between scientists from national regulatory agencies, concerned industries, research institutes, and universities" in establishing the safety of food, drug, and cosmetic ingredients and other chemicals.) Much attention was paid to the growing controversy over sodium intake and its relationship with high BP. John H. Laragh, MD, Hilda Altschul Professor of Medicine and director of the cardiovascular center and the hypertension center at New York Hospital-Cornell Medical Center, criticized the recent public health initiatives by the federal government to reduce sodium in the American diet, calling these
Plasma Homocysteine Predicts Mortality Independently of Traditional Risk Factors and C-Reactive Protein in Patients With Angiographically Defined Coronary Artery Disease
Authors: Jeffrey L. Anderson, Joseph B. Muhlestein, Benjamin D. Horne, John F. Carlquist, Tami L. Bair, Troy E. Madsen, Robert R. Pearson
Journal: Circulation (2000)

Background —Plasma homocysteine (tHCY) has been associated with coronary artery disease (CAD). We tested whether tHCY also increases secondary risk, after initial CAD diagnosis, and whether it is independent of traditional risk factors, C-reactive protein (CRP), and methylenetetrahydrofolate reductase ( MTHFR ) genotype. Methods and Results —Blood samples were collected from 1412 patients with severe angiographically defined CAD (stenosis ≥70%). Plasma tHCY was measured by fluorescence polarization immunoassay. The study cohort was evaluated for survival after a mean of 3.0±1.0 years of follow-up (minimum 1.5 years, maximum 5.0 years). The average age of the patients was 65±11 years, 77% were males, and 166 died during follow-up. Mortality was greater in patients with tHCY in tertile 3 than in tertiles 1 and 2 (mortality 15.7% versus 9.6%, P =0.001 [log-rank test], hazard ratio [HR] 1.63). The relative hazard increased 16% for each 5-μmol/L increase in tHCY ( P &lt;0.001). In multivariate Cox regression analysis, controlling for univariate clinical and laboratory predictors, elevated tHCY remained predictive of mortality (HR 1.64, P =0.009), together with age (HR 1.72 per 10-year increment, P &lt;0.0001), ejection fraction (HR 0.84 per 10% increment, P =0.0001), diabetes (HR 1.98, P =0.001), CRP (HR 1.42 per tertile, P =0.004), and hyperlipidemia. Homozygosity for the MTHFR variant was weakly predictive of tHCY levels but not mortality. Conclusions —In patients with angiographically defined CAD, tHCY is a significant predictor of mortality, independent of traditional risk factors, CRP, and MTHFR genotype. These findings increase interest in tHCY as a secondary risk marker and in secondary prevention trials (ie, with folate/B vitamins) to determine whether reduction in tHCY will reduce risk.
The role of intrathecal chemotherapy prophylaxis in patients with diffuse large B-cell lymphoma
Authors: H.-T. Arkenau, G. Chong, D. Cunningham, D. Watkins, R. Agarwal, B. Sirohi, M. Trumper, A. Norman, A. Wotherspoon, A. Horwich
Journal: Annals of Oncology (2006)
Endometriosis, retrograde menstruation and peritoneal inflammation in women and in baboons
Authors: T. M. D'Hooghe
Journal: Human Reproduction Update (2002)

The aim of this review was to assess critically the importance of the frequency, quantity and quality of retrograde menstruation and its relationship to peritoneal inflammation. The basis was the current evidence in women and in baboons supporting the Sampson hypothesis that retrograde menstruation is a key factor in the pathogenesis of endometriosis. It is not proven that retrograde menstruation is a universal phenomenon occurring similarly in women with and without endometriosis. A more thorough understanding of the physiological, cytological and immunological events in peritoneal fluid, peritoneum, endometrium and uterus during menstruation in women with and without endometriosis is critical in order to understand the pathogenesis of this enigmatic disease.
Prognostic value of CpG island methylator phenotype among colorectal cancer patients: a systematic review and meta-analysis
Authors: Y.Y. Juo, F.M. Johnston, D.Y. Zhang, H.H. Juo, H. Wang, E.P. Pappou, T. Yu, H. Easwaran, S. Baylin, M. van Engeland, N. Ahuja
Journal: Annals of Oncology (2014)
Peptides as antigens. Importance of orientation.
Authors: T Dyrberg, M B Oldstone
Journal: The Journal of Experimental Medicine (1986)

Factors known to be important in producing protein-reactive peptide antibodies include the accessibility of the region from which the peptide sequence is derived, the hydrophilic-phobic character of the sequence, and the length of the peptide. The data presented here indicate that the orientation of the peptide coupled to a carrier protein also influences the binding pattern of peptide antibodies. An octapeptide, representing a sequence from the alpha chain of the human acetylcholine receptor, was coupled either through an N- or C-terminal cysteine-glycine-glycine linker to a carrier protein and used to immunize rabbits. The resulting antisera reacted at comparable titers to the uncoupled immunizing peptides, but did not crossreact with the identical but opposite-linked peptide. Characterization of the binding to other homologous peptides showed that immunization with the N-terminal-linked peptide induced antibodies reactive specifically with the C-terminal amino acid(s). Immunization with the C-linked peptide resulted in antibodies reactive with a site of the peptide near the C-terminus.
Comparing On-Pump and Off-Pump Coronary Artery Bypass Grafting
Authors: Frank W. Sellke, J. Michael DiMaio, Louis R. Caplan, T. Bruce Ferguson, Timothy J. Gardner, Loren F. Hiratzka, Eric M. Isselbacher, Bruce W. Lytle, Michael J. Mack, John M. Murkin, Robert C. Robbins
Journal: Circulation (2005)

One of the most hotly debated and polarizing issues in cardiac surgery has been whether coronary artery bypass grafting (CABG) without the use of cardiopulmonary bypass or cardioplegia (off-pump CABG, or OPCAB) is superior to that performed with the heart-lung machine and the heart’s being chemically arrested (standard CABG). Various clinical trials are reviewed comparing the 2 surgical strategies, including several large retrospective analyses, meta-analyses, and the randomized trials that address different aspects of standard CABG and OPCAB. Although definitive conclusions about the relative merits of standard CABG and OPCAB are difficult to reach from these varied randomized and nonrandomized studies, several generalizations may be possible. Patients may achieve an excellent outcome with either type of procedure, and individuals’ outcomes likely depend more on factors other than whether they underwent standard CABG or OPCAB. Nevertheless, there appear to be trends in most studies. These trends include less blood loss and need for transfusion after OPCAB, less myocardial enzyme release after OPCAB up to 24 hours, less early neurocognitive dysfunction after OPCAB, and less renal insufficiency after OPCAB. Fewer grafts tend to be performed with OPCAB than with standard CABG. Length of hospital stay, mortality rate, and long-term neurological function and cardiac outcome appear to be similar in the 2 groups. To definitively answer the remaining questions of whether either strategy is superior and in which patients, a large-scale prospective randomized trial is required.
Efficacy and Safety of Opioid Agonists in the Treatment of Neuropathic Pain of Nonmalignant Origin
Authors: Elon Eisenberg, Ewan D. McNicol, Daniel B. Carr
Journal: JAMA (2005)

In the United States, an estimated 2 million persons have neuropathic pain that is often resistant to therapy. The use of opioids for neuropathic pain remains controversial, in part because studies have been small, have yielded equivocal results, and have not established the long-term risk-benefit ratio of this treatment.To assess the efficacy and safety of opioid agonists for the treatment of neuropathic pain based on published randomized controlled trials (RCTs).We searched MEDLINE (1966 to December 2004) and the Cochrane Central Register of Controlled Trials (fourth quarter, 2004) for articles in any language, along with reference lists of reviews and retrieved articles, using a combination of 9 search terms for RCTs with 32 terms for opioids and 15 terms for neuropathic pain.Trials were included in which opioid agonists were given to treat central or peripheral neuropathic pain of any etiology, pain was assessed using validated instruments, and adverse events were reported. Studies in which drugs other than opioid agonists were combined with opioids or opioids were administered epidurally or intrathecally were excluded.Data were extracted by 2 independent investigators and included demographic variables, diagnoses, interventions, efficacy, and adverse effects.Twenty-two articles met inclusion criteria and were classified as short-term (less than 24 hours; n = 14) or intermediate-term (median = 28 days; range = 8-56 days; n = 8) trials. The short-term trials had contradictory results. In contrast, all 8 intermediate-term trials demonstrated opioid efficacy for spontaneous neuropathic pain. A fixed-effects model meta-analysis of 6 intermediate-term studies showed mean posttreatment visual analog scale scores of pain intensity after opioids to be 14 units lower on a scale from 0 to 100 than after placebo (95% confidence interval [CI], -18 to -10; P<.001). According to number needed to harm (NNH), the most common adverse event was nausea (NNH, 3.6; 95% CI, 2.9-4.8), followed by constipation (NNH, 4.6; 95% CI, 3.4-7.1), drowsiness (NNH, 5.3; 95% CI, 3.7-8.3), vomiting (NNH, 6.2; 95% CI, 4.6-11.1), and dizziness (NNH, 6.7; 95% CI, 4.8-10.0).Short-term studies provide only equivocal evidence regarding the efficacy of opioids in reducing the intensity of neuropathic pain. Intermediate-term studies demonstrate significant efficacy of opioids over placebo for neuropathic pain, which is likely to be clinically important. Reported adverse events of opioids are common but not life-threatening. Further RCTs are needed to establish their long-term efficacy, safety (including addiction potential), and effects on quality of life.
Lymphadenopathy and Jaundice
Authors: Jennie Y. Law, Purva Gopal, Hsiao C. Li
Journal: JAMA Oncology (2015)

A man in his 20s had a large right supraclavicular lymph node, extensive mediastinal lymphadenopathy, a large extracardiac mass abutting the left atrium, hepatomegaly, and multiple splenic lesions. What is your diagnosis?
Maternal Hyperglycemia Improves Fetal Cardiac Function During Tachycardia-Induced Heart Failure in Pigs
Authors: M.R. Schmidt, M. Smerup, S.B. Kristiansen, H.E. Bøtker, O. Schmitz, V.E. Hjortdal, K.E. Sørensen, A.N. Redington
Journal: Circulation (2004)

Fetal tachycardia often leads to cardiac failure, which in experimental settings can be prevented by direct fetal glucose-insulin administration. In this study, we hypothesize that similar effects can be obtained indirectly by inducing maternal hyperglycemia.Systolic and diastolic indices (dP/dt(max) and tau) of left ventricular function were measured by use of high-fidelity catheters during 180 minutes of aggressive atrial pacing ( approximately 300 bpm) in 12 preterm porcine fetuses. In 6 fetuses, maternal hyperglycemia (15 mmol/L) was induced for the last 120 minutes of pacing. The remaining fetuses served as controls. Glucose, insulin, and free fatty acid levels were determined, as was fetal myocardial glycogen content. Maternal glucose infusion led to significant fetal hyperglycemia and hyperinsulinemia but did not change the inherently low fetal levels of free fatty acids. There were no differences between groups with regard to dP/dt(max) (1025+/-226 and 1037+/-207 mm Hg, P=NS) and tau (20.6+/-2.0 and 21.4+/-1.6 ms, P=NS) at baseline (100%). During the 180 minutes of pacing, systolic function (dP/dt(max)) and diastolic function (tau) deteriorated more in the control group than in the hyperglycemic group (P<0.001 for both). At 180 minutes, dP/dt(max) was 62+/-18% of baseline in controls and 85+/-11% in hyperglycemic fetuses (P=0.03), and tau was 117+/-12% and 98+/-4%, respectively (P=0.004).Induced maternal hyperglycemia improves fetal cardiac function during fetal tachycardia and suggests a possible additional therapeutic option to improve the function of the failing fetal heart before or during antiarrhythmic therapy. The findings may be relevant in fetal heart failure in general.
UK investments in global infectious disease research 1997–2010: a case study
Authors: Michael G Head, Joseph R Fitchett, Mary K Cooke, Fatima B Wurie, Andrew C Hayward, Rifat Atun
Journal: The Lancet Infectious Diseases (2012)

Infectious diseases account for 15 million deaths per year worldwide, and disproportionately affect young people, elderly people, and the poorest sections of society. We aimed to describe the investments awarded to UK institutions for infectious disease research.We systematically searched databases and websites for information on research studies from funding institutions and created a comprehensive database of infectious disease research projects for the period 1997-2010. We categorised studies and funding by disease, cross-cutting theme, and by a research and development value chain describing the type of science. Regression analyses were reported with Spearman's rank correlation coefficient to establish the relation between research investment, mortality, and disease burden as measured by disability-adjusted life years (DALYs).We identified 6170 funded studies, with a total research investment of UK£2·6 billion. Studies with a clear global health component represented 35·6% of all funding (£927 million). By disease, HIV received £461 million (17·7%), malaria £346 million (13·3%), tuberculosis £149 million (5·7%), influenza £80 million (3·1%), and hepatitis C £60 million (2·3%). We compared funding with disease burden (DALYs and mortality) to show low levels of investment relative to burden for gastrointestinal infections (£254 million, 9·7%), some neglected tropical diseases (£184 million, 7·1%), and antimicrobial resistance (£96 million, 3·7%). Virology was the highest funded category (£1 billion, 38·4%). Leading funding sources were the Wellcome Trust (£688 million, 26·4%) and the Medical Research Council (£673 million, 25·8%).Research funding has to be aligned with prevailing and projected global infectious disease burden. Funding agencies and industry need to openly document their research investments to redress any inequities in resource allocation.None.
Direct evidence from intraneural recordings for increased central sympathetic outflow in patients with heart failure.
Authors: W N Leimbach, B G Wallin, R G Victor, P E Aylward, G Sundlöf, A L Mark
Journal: Circulation (1986)

Patients with heart failure have increased vascular resistance and evidence for increased neurohumoral drive. High levels of circulating norepinephrine are found in patients with heart failure, but it is not known whether they reflect increased sympathetic neural activity or result from altered synthesis, release, or metabolism of norepinephrine. We used microneurography (peroneal nerve) to directly record sympathetic nerve activity to muscle (mSNA) and also measured plasma norepinephrine levels in patients with heart failure and in normal control subjects. Our goal was to determine whether sympathetic nerve activity is increased in patients with heart failure and whether plasma norepinephrine levels correlate with levels of mSNA in heart failure. Resting muscle sympathetic nerve activity in 16 patients with moderate to severe heart failure (54 +/- 5 bursts/min, mean +/- SE) was significantly higher (p less than .01) than the levels of activity in either nine age-matched normal control subjects (25 +/- 4 bursts/min) or 19 "young" normal control subjects (24 +/- 2 bursts/min). We found a significant correlation between plasma norepinephrine levels and mSNA (r = .73, p less than .05). Neither mSNA nor plasma norepinephrine levels correlated with total systemic vascular resistance, cardiac index, left ventricular ejection fraction, or heart rate. However, both mSNA and plasma norepinephrine levels showed significant positive correlations (p less than .05) with left ventricular filling pressures (r = .80, mSNA vs filling pressures; r = .82, norepinephrine levels vs filling pressures) and mean right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Identification of nine new susceptibility loci for testicular cancer, including variants near DAZL and PRDM14
Authors: Elise Ruark, Sheila Seal, Heather McDonald, Feng Zhang, Anna Elliot, KingWai Lau, Elizabeth Perdeaux, Elizabeth Rapley, Rosalind Eeles, Julian Peto, Zsofia Kote-Jarai, Kenneth Muir, Jeremie Nsengimana, Janet Shipley, D Timothy Bishop, Michael R Stratton, Douglas F Easton, Robert A Huddart, Nazneen Rahman, Clare Turnbull
Journal: Nature Genetics (2013)