tbuckley/cabot-search huggingface dataset:
HPLC-Detected Albuminuria Predicts Mortality
Authors: Dianna J. Magliano, Kevan R. Polkinghorne, Elizabeth L.M. Barr, Qing Su, Steven J. Chadban, Paul Z. Zimmet, Jonathan E. Shaw, Robert C. Atkins
Journal: Journal of the American Society of Nephrology (2007)

Albuminuria is a risk factor for all-cause mortality. Urinary albumin is traditionally measured with an immunochemical method such as immunonephelometry (IN). High-performance liquid chromatography (HPLC) detects additional albumin that is missed by IN, but it is unknown if HPLC-detected albuminuria also predicts mortality in the general population. We measured urinary albumin at baseline with both IN and HPLC in 10,175 participants in the longitudinal Australian Diabetes, Obesity, and Lifestyle (AusDiab) study. Over 5.2 yr of follow-up, 319 participants died. In a Cox proportional hazards regression model, participants with albuminuria measured by IN or HPLC were approximately twice as likely to die as participants who were normoalbuminuric on both assays. Receiver-operator characteristic curve analyses suggest that each test has a similar ability to predict mortality. However, the HPLC assay provided information on mortality risk that the IN assay did not capture. We conclude that albuminuria, detected by either IN or HPLC, independently predicts mortality in a community-based sample. HPLC identifies some people at increased risk of mortality that IN would not detect.
Increases in Central Aortic Impedance Precede Alterations in Arterial Stiffness Measures in Type 1 Diabetes
Authors: Nancy K. Sweitzer, Mohan Shenoy, James H. Stein, Sunduz Keles, Mari Palta, Tamara LeCaire, Gary F. Mitchell
Journal: Diabetes Care (2007)

Increased pulse pressure has been associated with increased cardiovascular risk in individuals with diabetes. Changes in central aortic properties can increase central pulse pressure and may adversely affect microvascular perfusion and cardiac performance. This study was performed to define early changes in central arterial properties in a group of young individuals with type 1 diabetes.Seventeen individuals with type 1 diabetes and their nondiabetic control subjects who were participating in the Cardio-Diab Study had arterial stiffness and pulsatile hemodynamics measured with calibrated tonometry and pulsed Doppler. Aortic characteristic impedance (Z(c)) was calculated from the ratio of change in carotid pressure and aortic flow in early systole. Pulse wave velocity (PWV) was assessed from tonometry and body surface measurements.Duration of type 1 diabetes was 15.3 +/- 0.7 (mean +/- SD) years. In type 1 diabetic subjects, central pulse pressure was elevated (45 +/- 11 vs. 36 +/- 10 mmHg in control subjects, P = 0.02), as was peripheral pulse pressure (54 +/- 13 vs. 43 +/- 10 mmHg, P = 0.002). Z(c) was elevated in type 1 diabetes (179 +/- 57 vs. 136 +/- 42 dynes x s/cm5 in control subjects, P = 0.004), whereas PWV was not different (5.9 +/- 0.9 vs. 5.9 +/- 0.7 m/s in type 1 diabetic vs. control subjects, respectively; NS). There was a moderate correlation between Z(c) and urinary albumin excretion (coefficient 0.39, P = 0.02).Z(c) appears to be increased early in type 1 diabetes, before elevation of PWV and is associated with higher pulse pressure, which may contribute to renal microvascular damage in diabetes.
Genotype-Renal Function Correlation in Type 2 Autosomal Dominant Polycystic Kidney Disease
Authors: Riccardo Magistroni, Ning He, Kairong Wang, Robin Andrew, Ann Johnson, Patricia Gabow, Elizabeth Dicks, Patrick Parfrey, Roser Torra, Jose L. San-Millan, Eliecer Coto, Marjan van Dijk, Martijn Breuning, Dorien Peters, Nadja Bogdanova, Giulia Ligabue, Alberto Albertazzi, Nick Hateboer, Kyproula Demetriou, Alkis Pierides, Constantinos Deltas, Peter St. George-Hyslop, David Ravine, York Pei
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 1000 live births. Mutations of two genes, PKD1 and PKD2, account for the disease in approximately 80 to 85% and 10 to 15% of the cases, respectively. Significant interfamilial and intrafamilial renal disease variability in ADPKD has been well documented. Locus heterogeneity is a major determinant for interfamilial disease variability (i.e., patients from PKD1-linked families have a significantly earlier onset of ESRD compared with patients from PKD2-linked families). More recently, two studies have suggested that allelic heterogeneity might influence renal disease severity. The current study examined the genotype-renal function correlation in 461 affected individuals from 71 ADPKD families with known PKD2 mutations. Fifty different mutations were identified in these families, spanning between exon 1 and 14 of PKD2. Most (94%) of these mutations were predicted to be inactivating. The renal outcomes of these patients, including the age of onset of end-stage renal disease (ESRD) and chronic renal failure (CRF; defined as creatinine clearance ≤ 50 ml/min, calculated using the Cockroft and Gault formula), were analyzed. Of all the affected individuals clinically assessed, 117 (25.4%) had ESRD, 47 (10.2%) died without ESRD, 65 (14.0%) had CRF, and 232 (50.3%) had neither CRF nor ESRD at the last follow-up. Female patients, compared with male patients, had a later mean age of onset of ESRD (76.0 [95% CI, 73.8 to 78.1] versus 68.1 [95% CI, 66.0 to 70.2] yr) and CRF (72.5 [95% CI, 70.1 to 74.9] versus 63.7 [95% CI, 61.4 to 66.0] yr). Linear regression and renal survival analyses revealed that the location of PKD2 mutations did not influence the age of onset of ESRD. However, patients with splice site mutations appeared to have milder renal disease compared with patients with other mutation types (P < 0.04 by log rank test; adjusted for the gender effect). Considerable renal disease variability was also found among affected individuals with the same PKD2 mutations. This variability can confound the determination of allelic effects and supports the notion that additional genetic and/or environmental factors may modulate the renal disease severity in ADPKD. E-mail: [email protected]
Proteomics
Authors: Marianna Prokopi, Manuel Mayr
Journal: Circulation Research (2011)

The concept of using stem cells for cardiovascular repair holds great potential, but uncertainties in preclinical experiments must be addressed before their therapeutic application. Contemporary proteomic techniques can help to characterize cell preparations more thoroughly and identify some of the potential causes that may lead to a high failure rate in clinical trials. The first part of this review discusses the broader application of proteomics to stem cell research by providing an overview of the main proteomic technologies and how they might help the translation of stem cell therapy. The second part focuses on the controversy about endothelial progenitor cells (EPCs) and raises cautionary flags for marker assignment and assessment of cell purity. A proteomics-led approach in early outgrowth EPCs has already raised the awareness that markers used to define their endothelial potential may arise from an uptake of platelet proteins. A platelet microparticle-related transfer of endothelial characteristics to mononuclear cells can result in a misinterpretation of the assay. The necessity to perform counterstaining for platelet markers in this setting is not fully appreciated. Similarly, the presence of platelets and platelet microparticles is not taken into consideration when functional improvements are directly attributed to EPCs, whereas saline solutions or plain medium serve as controls. Thus, proteomics shed new light on the caveats of a common stem cell assay in cardiovascular research, which might explain some of the inconsistencies in the field.
TNF-α and TLR agonists increase susceptibility to HIV-1 transmission by human Langerhans cells ex vivo
Authors: Marein A.W.P. de Jong, Lot de Witte, Menno J. Oudhoff, Sonja I. Gringhuis, Philippe Gallay, Teunis B.H. Geijtenbeek
Journal: Journal of Clinical Investigation (2008)

Genital coinfections increase an individual's risk of becoming infected with HIV-1 by sexual contact. Several mechanisms have been proposed to explain this, such as the presence of ulceration and bleeding caused by the coinfecting pathogen. Here we demonstrate that Langerhans cells (LCs) are involved in the increased susceptibility to HIV-1 in the presence of genital coinfections. Although LCs are a target for HIV-1 infection in genital tissues, we found that immature LCs did not efficiently mediate HIV-1 transmission in an ex vivo human skin explant model. However, the inflammatory stimuli TNF-alpha and Pam3CysSerLys4 (Pam3CSK4), the ligand for the TLR1/TLR2 heterodimer, strongly increased HIV-1 transmission by LCs through distinct mechanisms. TNF-alpha enhanced transmission by increasing HIV-1 replication in LCs, whereas Pam3CSK4 acted by increasing LC capture of HIV-1 and subsequent trans-infection of T cells. Genital infections such as Candida albicans and Neisseria gonorrhea not only triggered TLRs but also induced TNF-alpha production in vaginal and skin explants. Thus, during coinfection, LCs could be directly activated by pathogenic structures and indirectly activated by inflammatory factors, thereby increasing the risk of acquiring HIV-1. Our data demonstrate a decisive role for LCs in HIV-1 transmission during genital coinfections and suggest antiinflammatory therapies as potential strategies to prevent HIV-1 transmission.
MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) Software Version 4.0
Authors: K. Tamura, J. Dudley, M. Nei, S. Kumar
Journal: Molecular Biology and Evolution (2007)

We announce the release of the fourth version of MEGA software, which expands on the existing facilities for editing DNA sequence data from autosequencers, mining Web-databases, performing automatic and manual sequence alignment, analyzing sequence alignments to estimate evolutionary distances, inferring phylogenetic trees, and testing evolutionary hypotheses. Version 4 includes a unique facility to generate captions, written in figure legend format, in order to provide natural language descriptions of the models and methods used in the analyses. This facility aims to promote a better understanding of the underlying assumptions used in analyses, and of the results generated. Another new feature is the Maximum Composite Likelihood (MCL) method for estimating evolutionary distances between all pairs of sequences simultaneously, with and without incorporating rate variation among sites and substitution pattern heterogeneities among lineages. This MCL method also can be used to estimate transition/transversion bias and nucleotide substitution pattern without knowledge of the phylogenetic tree. This new version is a native 32-bit Windows application with multi-threading and multi-user supports, and it is also available to run in a Linux desktop environment (via the Wine compatibility layer) and on Intel-based Macintosh computers under the Parallels program. The current version of MEGA is available free of charge at http://www.megasoftware.net.
Pathological Changes in Aortocoronary Bypass Grafts
Authors: G M Hutchins
Journal: Annual Review of Medicine (1980)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Intracellular cargo delivery using tat peptide and derivatives
Authors: Ming Zhao, Ralph Weissleder
Journal: Medicinal Research Reviews (2003)

Abstract Efficient delivery of therapeutic and diagnostic agents across the plasma membrane is crucial in developing novel therapies. Membrane permeating peptides, in particular HIV‐1 tat peptide and its derivatives, have enabled the intracellular delivery of cargos of various sizes and physicochemical properties. This review summarizes the current knowledge of tat‐derived cell permeating peptides in the transduction of exogenous molecules/complexes. © 2003 Wiley Periodicals, Inc. Med Res Rev, 24, No. 1, 1–12, 2004
Homocysteine and Marginal Vitamin Deficiency
Authors: Meir J. Stampfer
Journal: JAMA (1993)

Apart from calcium and iron requirements, nutrition in general (and vitamins in particular) has traditionally rated only a passing nod in medical school. Physicians in training are typically taught that a "balanced" diet is sufficient and that hardly anyone really needs vitamin supplements. Although frank vitamin deficiency is now uncommon in the United States, many investigators have long suspected that large segments of the US population are consuming suboptimal levels of several micronutrients; in recent years, compelling evidence has emerged that supports this contention. In national surveys, a substantial proportion of the US population consumes levels of several vitamins that are well below recommended intakes,<sup>1</sup>and recent evidence strongly indicates that such low intakes are associated with serious health consequences. The most striking recent example is the finding that folic acid supplements can reduce the risk of neural tube defects by approximately 70%. That relationship See also p 2693.
Dietary fish oil and airways obstruction.
Authors: J Britton
Journal: Thorax (1995)

Background.Fish contain n-3 polyunsaturated fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, which are known to interfere with the body's inflammatory response and may be of benefit in chronic inflammatory conditions.Methods.We studied the relation between the dietary intake of n-3 fatty acids and chronic obstructive pulmonary disease (COPD) in 8960 current or former smokers participating in a population-based study of atherosclerosis.Intake of fatty acids was estimated with a dietary questionnaire.The presence of COPD was assessed by a questionnaire on respiratory symptoms and by spirometry.Three case definitions of COPD were used: symptoms of chronic bronchitis (667subjects), physician-diagnosed emphysema reported by the subject (185subjects), andspirometrically detected COPD (197 subjects).Results.After control for pack-years of smoking, age, sex, race, height, weight, energy intake, and educational level, the combined intake of eicosapentaenoic acid and docosahexaenoic acid was inversely related to the risk of COPD in a quantity-dependent fashion.The adjusted odds ratio for the highest quartile of intake as compared with the lowest quartile was 066 for chronic bronchitis (95 percent confidence interval, 0*52 to 0*85; P<0 001 for linear trend across the range of intake values), 0.31 for physician-diagnosed emphysema (95 percent confidence interval, 0*18 to 0-52; P for linear trend, 0.003), and 0.50 for spirometrically detected COPD (95 percent confidence interval, 0.32 to 0-79; P for linear trend, 0.007).Conclusions.A high dietary intake of n-3 fatty acids may protect cigarette smokers against COPD.
Clinical arithmetic
Authors: C. Currie
Journal: BMJ (2003)

“On the 20th of May 1747, I took twelve patients in the scurvy, on board the Salisbury at sea. Their cases were as similar as I could have them. They all in general had putrid gums, the spots and lassitude, with weakness of their knees.” So begins James Lind's brief 1753 account of how he identified “the surest preservative, the most efficacious remedy” for a disease that in his time could kill sailors in their hundreds every year. In a comparison of six treatments—cider, elixir vitriol, vinegar, sea water, a laxative, and citrus fruit—the last produced “the most sudden and good effects,” despite a shortage of oranges and lemons that limited treatment to only six days.1 Thus a naval surgeon and a dozen seamen in six groups of two entered medical history, with both a cure for scurvy and an enduringly powerful method, the controlled clinical trial.
Does sulphasalazine cause drug induced systemic lupus erythematosus? No effect evident in a prospective randomised trial of 200 rheumatoid patients treated with sulphasalazine or auranofin over five years
Authors: M.-M. Gordon, D. R Porter, H. A Capell
Journal: Annals of the Rheumatic Diseases (1999)

<h3>BACKGROUND</h3> Sulphasalazine (SSZ) has been reported to cause drug induced systemic lupus erythematosus (SLE), but diagnosis of this complication in the context of rheumatoid arthritis (RA) is difficult. <h3>OBJECTIVE</h3> To determine prospectively: (1) if patients become seropositive for antinuclear antibodies (ANA) during prolonged treatment with SSZ without clinical evidence of SLE; (2) if ANA positive patients develop more adverse reactions than ANA negative patients; (3) if drug induced SLE was identified in this cohort. <h3>METHODS</h3> 200 patients enrolled in a randomised prospective trial of SSZ and auranofin (AUR) were followed up for five years. Baseline and annual ANA results were collected along with information on drug toxicity and reasons for discontinuation of treatment. <h3>RESULTS</h3> Over five years 24 patients stopped taking SSZ and 49 AUR because of side effects. Of the features common to SLE, rash developed in nine SSZ patients and 11 AUR treated patients and mouth ulcers in three and four patients respectively. Six SSZ treated patients and three treated with AUR developed leucopenia, which promptly resolved with drug withdrawal. No adverse event was ascribed to drug induced SLE. Of the 72 SSZ treated patients who were ANA negative or weakly positive at outset, 14 (19%) became strongly ANA positive compared with 11 (14%) of 80 AUR patients. Patients ANA positive at baseline or who became ANA positive were not more likely to develop drug toxicity or to withdraw from treatment than those ANA negative throughout. <h3>CONCLUSION</h3> ANA positivity is common in patients with RA, but the presence or development of ANA did not increase the likelihood of withdrawing from treatment. No case of drug induced SLE was seen over five years in this study.
396 STUDY OF HBV (RE)INFECTION IN THE COURSE OF LIVER TRANSPLANTATION IN HBV, HBV/HDV AND OCCULT HBV INFECTED PATIENTS
Authors: T. Pollicino, L. Caccamo, M.F. Donato, G. Raffa, G. Rossi, G. Raimondo
Journal: Journal of Hepatology (2013)
Antidisialoganglioside/granulocyte macrophage–colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcγRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis
Authors: Leonid S. Metelitsa, Stephen D. Gillies, Michael Super, Hiroyuki Shimada, C. Patrick Reynolds, Robert C. Seeger
Journal: Blood (2002)

Polymorphonuclear leukocytes (PMNs) mediate antibody-dependent cellular cytotoxicity (ADCC), which is increased by the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF). We sought to determine whether PMN ADCC also would be increased by the addition of an antibody/GM-CSF fusion protein and whether this would be associated with the up-regulation and activation of Mac-1 (CD11b/CD18) and with azurophil granule exocytosis. ADCC against LA-N-1 human neuroblastoma cells was evaluated with 4-hour calcein acetoxymethyl ester (calcein-AM) microcytotoxicity assay, electron microscopy, and multi-parameter flow cytometry. With the calcein-AM assay, LA-N-1 cell survival was 10%, 55%, and 75% when PMN ADCC was mediated by the antidisialoganglioside (anti-GD2) immunocytokine hu14.18/GM-CSF, by monoclonal antibody (mAb) hu14.18 mixed with GM-CSF, and by hu14.18 alone. Function-blocking mAbs demonstrated that FcγRII and FcγRIII were required for ADCC with hu14.18 alone or mixed with GM-CSF, but that only FcγRII was required for ADCC with hu14.18/GM-CSF. ADCC mediated by hu14.18 and hu14.18/GM-CSF was Mac-1 dependent. Electron microscopy demonstrated the greatest PMN adhesion, spreading, and lysis of targets with hu14.18/GM-CSF. Monoclonal antibodies blocking Mac-1 function allowed the tethering of PMN to targets with hu14.18/GM-CSF but prevented adhesion, spreading, and cytolysis. Flow cytometry showed that hu14.18 with or without GM-CSF and hu14.18/GM-CSF all mediated Mac-1–dependent PMN–target cell conjugate formation but that GM-CSF was required for the highest expression and activation of Mac-1, as evidenced by the mAb24-defined β2-integrin activation epitope. Hu14.18/GM-CSF induced the highest sustained azurophil granule exocytosis, almost exclusively in PMNs with activated Mac-1. Thus, hu14.18/GM-CSF facilitates PMN ADCC against neuroblastoma cells associated with FcγRII and Mac-1–dependent enhanced adhesion and degranulation.
Characteristics of the Cholesterol-Esterifying Activity in Normal and Atherosclerotic Rabbit Aortas
Authors: SAM HASHIMOTO, SEYMOUR DAYTON, ROSLYN B. ALFIN-SLATER, PHIET T. BUI, NOME BAKER, LEON WILSON
Journal: Circulation Research (1974)

Esterification of cholesterol with [1- 14 C]palmityl-CoA by an atherosclerotic cell-free homogenate was approximately 16-50-fold greater than that by a normal cell-free homogenate for a given amount of protein in the homogenate. This difference was due to hyperactivity of the cholesterol-esterifying system in the atherosclerotic cell-free homogenate rather than to depletion of radioactive palmityl-CoA in the reaction mixture containing normal homogenate. Neither an activator of cholesterol esterification in the soluble fraction of the atherosclerotic aortic homogenate nor an inhibitor in the soluble fraction of the normal aortic homogenate could be demonstrated. The pH optimum within the pH range covered for esterification and the apparent K m values were approximately the same in normal and atherosclerotic microsomes, suggesting that the enzymes were probably the same. The results suggested a higher concentration or a higher activity of the enzyme in or on atherosclerotic microsomes. An alternative possibility is that high concentrations of free cholesterol in the atherosclerotic microsomes were responsible for the augmented cholesterol esterification. This possibility seems unlikely, because the observed 2.3-fold increase in the free cholesterol concentration should not produce a 25-fold increase in cholesterol esterification. The rate of cholesterol esterification by atherosclerotic microsomes varied with the substrate: oleyl-CoA &gt; palmityl-CoA &gt; linoleyl-CoA.