tbuckley/cabot-search huggingface dataset:
Severe upper gastrointestinal polyposis associated with sparse colonic polyposis in a familial adenomatous polyposis family with an APC mutation at codon 1520
Authors: B A Leggett, J P Young, K Biden, R L Buttenshaw, N Knight, A E Cowen
Journal: Gut (1997)

Background —Familial adenomatous polyposis usually results in colonic polyposis with hundreds to thousands of polyps, congenital hypertrophy of the retinal pigment epithelium (CHRPE), and variable extracolonic features. Recent reports indicate that patients with distal mutations between codons 1445 and 1578 do not express CHRPE and have a high incidence of desmoid tumours. Patients —The family studied has an unusual phenotype of sparse colonic polyposis but profuse upper gastrointestinal polyposis. Affected subjects do not have CHRPE. Methods —The protein truncation test followed by sequencing identified a 2 base pair deletion at codon 1520 in the APC gene. This results in a frameshift creating a stop codon 13 codons downstream. Results —This family demonstrates that sparse colonic polyposis but severe upper tract polyposis may be associated with mutations between codons 1445 and 1578. Conclusions —Study of duodenal and colonic polyps in further cases with mutations in this region is warranted. Such mutations may preferentially cause duodenal adenomas and desmoid tumours as somatic mutations in these tumours also occur in this region, unlike colorectal tumours where somatic mutations occur more proximally. This study emphasises the importance of screening the upper gastrointestinal tract even when the colonic disease is mild.
The Effects of Drugs on Membrane Fluidity
Authors: D B Goldstein
Journal: The Annual Review of Pharmacology and Toxicology (1984)

Anesthetics almost always disorder or "fluidize" membranes, i.e. the drugs increase the mobility of spin labels and reduce order parameters. This effect is universal at high concentrations above the clinical range, but in some kinds of membranes low concentrations of drugs have an ordering effect. Drugs that carry charges, including many local anesthetics, often stiffen membranes, as do long-chain alcohols or fatty acids that mimic natural membrane components. The potencies of short-chain alcohols correlate well with lipid solubility, but a cutoff is reached at 10-12 carbons, where pharmacological actions become weak or absent despite a progressive increase in lipid solubility. The cutoff is partly explained by the ordering action of the long chains and partly by the difficulty of administering such water-insoluble drugs in vivo. The idea of membrane disorder does not exclude some specificity. Closely related drugs may have different molecular shapes and may be capable of forming hydrogen bonds with different orientations, affecting their ability to make membrane more fluid. Perhaps for this reason, there is a remarkable stereospecificity in the disordering effect of anesthetic steroids, chloralose, and long-chain alkenols. Some specificity is mediated by different membrane environments. The drug action may actually reverse from order to disorder on addition of cholesterol, but in other experimental systems cholesterol blocks a disordering effect, and we cannot yet explain the action of drugs in different biomembranes. Further, drugs may have differential solubilities in membranes of different composition. This cannot always be predicted from octanol:water partition coefficients because branched molecules are differentially excluded from structured bilayers. Charged drugs react quite differently with charged and neutral phospholipids and may have differential actions on the two sides of the bilayer because of the asymmetry of the phospholipid distribution. The deeper reaches of the membrane seem particularly sensitive to disordering, even by drugs that presumably reside near the surface. Thus, proteins whose midregions are sensitive to disordering may be especially disrupted by drugs. This is a new field of pharmacology, currently applied only to a small group of drugs. But an understanding of the physiocochemical actions of drugs in hydrophobic regions of cells will clearly be needed for full understanding of membrane-bound drug receptors, enzymes, and transport systems. This is just a beginning.
Oncoproteomic profiling with antibody microarrays
Authors: Mohamed SS Alhamdani, Christoph Schröder, Jörg D Hoheisel
Journal: Genome Medicine (2009)

The incidence of cancer and its associated mortality are increasing globally, indicating an urgent need to develop even more effective and sensitive sets of biomarkers that could help in early diagnosis and consequent intervention. Given that many cellular processes are carried out by proteins, cancer research has recently shifted toward an exploration of the full proteome for such discovery. Among the advanced methodologies that are being developed for analyzing the proteome, antibody microarrays have become a prominent tool for gathering the information required for a better understanding of disease biology, early detection, discrimination of tumors and monitoring of disease progression. Here, we review the technical aspects and challenges in the development and use of antibody microarray assays and examine recently reported applications in oncoproteomics.
Uric acid clearance in patients with gout and normal subjects.
Authors: M L Snaith, J T Scott
Journal: Annals of the Rheumatic Diseases (1971)

The causes of hyperuricaemia in so-called primary gout remain undetermined.Only a proportion of patients has been shown by studies of isotope dilution (Seegmiller, Grayzel, Laster, and Liddle, 1961) or of urinary excretion (Gutman and Yu, 1957) to produce excessive quantities of uric acid, but it is generally thought that uric acid clearance in most patients with gout does not differ markedly from that found in normal subjects (Gutman and Yu, 1957).Opinions on this subject have not been unanimous, however, and we have therefore re- examined the uric acid clearance figures in a number of gouty subjects, comparing them with a control group.
Cost of a roller skating rink to the local accident and emergency department.
Authors: N Nayeem, S E Shires, J E Porter
Journal: British Journal of Sports Medicine (1990)

A 14 month retrospective study was undertaken to determine the cost implications of the opening of a roller skating rink to the local hospital accident and emergency department (A and E). A total of 398 patients attended following injury at the roller skating rink, of whom 384 were included in the study. The estimated cost of their injuries was determined by the hospital accounts department. The average cost per patient attending the A and E department following roller skating injury was about 100 pounds. The total cost to the A and E department of all injuries sustained at the rink over this period was 38,412 pounds. The cost implications of opening a roller skating rink for the A and E department are considerable. If proposals for self-budgeting are applied, A and E departments will have to seek additional funding if such leisure facilities are opened in their vicinity.
RISC RNA Sequencing for Context-Specific Identification of In Vivo MicroRNA Targets
Authors: Scot J. Matkovich, Derek J. Van Booven, William H. Eschenbacher, Gerald W. Dorn
Journal: Circulation Research (2010)

MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo.To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs).We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts.RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.
Id3 Is a Novel Atheroprotective Factor Containing a Functionally Significant Single-Nucleotide Polymorphism Associated With Intima–Media Thickness in Humans
Authors: Amanda C. Doran, Allison B. Lehtinen, Nahum Meller, Michael J. Lipinski, R. Parker Slayton, Stephanie N. Oldham, Marcus D. Skaflen, Joseph Yeboah, Stephen S. Rich, Donald W. Bowden, Coleen A. McNamara
Journal: Circulation Research (2010)

Rationale : The gene encoding the helix–loop–helix transcription factor Id3 (inhibitor of differentiation-3) is located within atherosclerosis susceptibility loci of both mice and humans, yet its influence on atherosclerosis is not known. Objective : The present study sought to determine whether polymorphisms in the ID3 gene were associated with indices of atherosclerosis in humans and if loss of Id3 function modulated atherogenesis in mice. Methods and Results : Six tagging single-nucleotide polymorphisms (SNPs) (tagSNPs) in the human ID3 gene were assessed in participants of the Diabetes Heart Study. One tagSNP, rs11574, was independently associated with carotid intima–media thickness (IMT). The human ID3 variant at rs11574 results in an alanine to threonine substitution in the C terminus. To determine the effect of this polymorphism on the basic function of Id3, site-directed mutagenesis of the human ID3 gene at rs11574 was performed. Results demonstrated a significant reduction in coimmunoprecipitation of the known E-protein partner, E12, with Id3 when it contains the sequence encoded by the risk allele (Id3105T). Further, Id3105T had an attenuated ability to modulate E12-mediated transcriptional activation compared to Id3 containing the ancestral allele (Id3105A). Microarray analysis of vascular smooth muscle cells from WT and Id3 −/− mice revealed significant modulation of multiple gene pathways implicated in atherogenesis. Moreover, Id3 −/− ApoE −/− mice developed significantly more atherosclerosis in response to 32 weeks of Chow or Western diet feeding than Id3 +/+ ApoE −/− mice. Conclusions : Taken together, results provide novel evidence that Id3 is an atheroprotective factor and link a common SNP in the human ID3 gene to loss of Id3 function and increased IMT.
Efficacy and safety of galantamine in patients with mild to moderate Alzheimer's disease: multicentre randomised controlled trial
Authors: G. K Wilcock, S. Lilienfeld, E. Gaens
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the efficacy and safety of galantamine in the treatment of Alzheimer9s disease. <b>Design:</b> Randomised, double blind, parallel group, placebo controlled trial. <b>Setting:</b> 86 outpatient clinics in Europe and Canada. <b>Participants:</b> 653 patients with mild to moderate Alzheimer9s disease. <b>Intervention:</b> Patients randomly assigned to galantamine had their daily dose escalated over three to four weeks to maintenance doses of 24 or 32 mg. <b>Main outcome measures:</b> Scores on the 11 item cognitive subscale of the Alzheimer9s disease assessment scale, the clinician9s interview based impression of change plus caregiver input, and the disability assessment for dementia scale. The effect of apolipoprotein E4 genotype on reponse to treatment was also assessed. <b>Results:</b> At six months, patients who received galantamine had a significantly better outcome on the 11 item cognitive subscale of the Alzheimer9s disease assessment scale than patients in the placebo group (mean treatment effect 2.9 points for lower dose and 3.1 for higher dose, intention to treat analysis, P&lt;0.001 for both doses). Galantamine was more effective than placebo on the clinician9s interview based impression of change plus caregiver input (P&lt;0.05 for both doses <i>v</i> placebo). At six months, patients in the higher dose galantamine group had significantly better scores on the disability assessment for dementia scale than patients in the placebo group (mean treatment effect 3.4 points, P&lt;0.05). Apolipoprotein E genotype had no effect on the efficacy of galantamine. 80% (525) of patients completed the study. <b>Conclusion:</b> Galantamine is effective and well tolerated in Alzheimer9s disease. As galantamine slowed the decline of functional ability as well as cognition, its effects are likely to be clinically relevant.
Religious Affiliation and Suicide Attempt
Authors: Kanita Dervic, Maria A. Oquendo, Michael F. Grunebaum, Steve Ellis, Ainsley K. Burke, J. John Mann
Journal: American Journal of Psychiatry (2004)

Few studies have investigated the association between religion and suicide either in terms of Durkheim's social integration hypothesis or the hypothesis of the regulative benefits of religion. The relationship between religion and suicide attempts has received even less attention.Depressed inpatients (N=371) who reported belonging to one specific religion or described themselves as having no religious affiliation were compared in terms of their demographic and clinical characteristics.Religiously unaffiliated subjects had significantly more lifetime suicide attempts and more first-degree relatives who committed suicide than subjects who endorsed a religious affiliation. Unaffiliated subjects were younger, less often married, less often had children, and had less contact with family members. Furthermore, subjects with no religious affiliation perceived fewer reasons for living, particularly fewer moral objections to suicide. In terms of clinical characteristics, religiously unaffiliated subjects had more lifetime impulsivity, aggression, and past substance use disorder. No differences in the level of subjective and objective depression, hopelessness, or stressful life events were found.Religious affiliation is associated with less suicidal behavior in depressed inpatients. After other factors were controlled, it was found that greater moral objections to suicide and lower aggression level in religiously affiliated subjects may function as protective factors against suicide attempts. Further study about the influence of religious affiliation on aggressive behavior and how moral objections can reduce the probability of acting on suicidal thoughts may offer new therapeutic strategies in suicide prevention.
The Insulin-Like Growth Factor Axis
Authors: Antoni Bayes-Genis, Cheryl A. Conover, Robert S. Schwartz
Journal: Circulation Research (2000)

Abstract —Insulin-like growth factors I and II (IGF-I and -II) and their regulatory proteins are secreted by cells of the cardiovascular system. They are growth promoters for arterial cells and mediators of cardiovascular disease. IGFs are bound to IGF binding proteins (IGFBPs), which modulate IGF ligand-receptor interaction and consequently to IGF action. IGFBPs are in turn posttranslationally modulated by specific proteases. This dynamic balance (IGFs, IGFBPs, and IGFBP proteases) constitutes the IGF axis and ultimately determines the extent of IGF-dependent cellular effects. Dysregulated actions of this axis influence coronary atherosclerosis through effects on vascular smooth muscle cell growth, migration, and extracellular matrix synthesis in the atherosclerotic plaque. IGF-I promotes macrophage chemotaxis, excess LDL cholesterol uptake, and release of proinflammatory cytokines. Endothelial cells also receive the effects of IGFs stimulating their migration and organization forming capillary networks. Neointimal hyperplasia of restenosis after coronary artery injury is also modulated by the IGF axis. IGFs stimulate vascular smooth muscle cell proliferation and migration to form the neointima and upregulate tropoelastin synthesis after disruption of the elastic layer. Understanding IGF axis regulation establishes a scientific basis for strategies directed to limit or reverse plaque growth and vulnerability in atherosclerosis and in the neointimal hyperplasia of restenosis.
Longitudinal Tethering of Arteries in Dogs
Authors: DALI J. PATEL, DONALD L. FRY, Joseph S. Janicki
Journal: Circulation Research (1966)

The magnitude and properties of longitudinal vascular tethering were studied in the thoracic aorta, abdominal aorta, and femoral artery of 23 dogs. The tethering was found to consist of a dominant viscoelastic restraining element that demonstrated a moderate degree of stress relaxation and a significant inertial component that was related to the mass of the vessel and its surrounding tissues (the "added mass"). Static and dynamic studies of these properties showed them to be surprisingly linear. The simplest linear model that could simulate these experimental data consisted of two elastic components, two frictional components and a lumped inertial component. Within the physiologic range of frequencies (1 to 20 cycles/sec), the two elastic components became dynamically coupled so that they appeared to act as a single spring, the stiffness of which could be characterized by a "dynamic spring constant." The mean value of the dynamic spring constant was 12 g/cm 3 for the thoracic aorta; it increased along the aorta toward the femoral artery to almost 70 times that value. Contrary to the simple tethering model assumed by Womersley, these data showed that the mechanical behavior of the system is strongly influenced by frictional components.
The Role of Autoantibodies in Autoimmune Disease
Authors: Yaakov Naparstek, Paul H. Plotz
Journal: Annual Review of Immunology (1993)

In autoimmune diseases, autoantibodies may be the actual pathogenetic agents of the disease, the secondary consequences of tissue damage, or the harmless footprints of an etiologic agent. Establishing a pathogenetic role for autoantibodies requires that they meet stringent criteria. It appears that the location of the presumptive target antigen most critically influences the pathogenetic potential of autoantibodies. Autoantibodies directed against cell surface targets, such as hormone receptors, are clearly pathogenetic; those directed against extracellular targets, such as circulating molecules or extracellular matrix, may or may not cause any damage. Those apparently directed against intracellular targets are usually not pathogenetic unless it can be clearly demonstrated (a) that the antigen is released from within the cell so that it can bind onto a cell surface receptor or other extracellular location, such as proteinase 3; (b) that the antigen moves to an aberrant site on the cell surface, such as, perhaps, the small ribonucleoprotein antigen Ro; or (c) that a cross-reactive molecule, the actual target, such as the membrane ribosomal P-like protein, is at an accessible location.
The Prevalence of Mental Disorders among the Homeless in Western Countries: Systematic Review and Meta-Regression Analysis
Authors: Seena Fazel, Vivek Khosla, Helen Doll, John Geddes
Journal: PLoS Medicine (2008)

Background There are well over a million homeless people in Western Europe and North America, but reliable estimates of the prevalence of major mental disorders among this population are lacking. We undertook a systematic review of surveys of such disorders in homeless people. Methods and Findings We searched for surveys of the prevalence of psychotic illness, major depression, alcohol and drug dependence, and personality disorder that were based on interviews of samples of unselected homeless people. We searched bibliographic indexes, scanned reference lists, and corresponded with authors. We explored potential sources of any observed heterogeneity in the estimates by meta-regression analysis, including geographical region, sample size, and diagnostic method. Twenty-nine eligible surveys provided estimates obtained from 5,684 homeless individuals from seven countries. Substantial heterogeneity was observed in prevalence estimates for mental disorders among the studies (all Cochran's χ2 significant at p < 0.001 and all I2 > 85%). The most common mental disorders were alcohol dependence, which ranged from 8.1% to 58.5%, and drug dependence, which ranged from 4.5% to 54.2%. For psychotic illness, the prevalence ranged from 2.8% to 42.3%, with similar findings for major depression. The prevalence of alcohol dependence was found to have increased over recent decades. Conclusions Homeless people in Western countries are substantially more likely to have alcohol and drug dependence than the age-matched general population in those countries, and the prevalences of psychotic illnesses and personality disorders are higher. Models of psychiatric and social care that can best meet these mental health needs requires further investigation.
Association Between Hospital Process Performance and Outcomes Among Patients With Acute Coronary Syndromes
Authors: Eric D. Peterson, Matthew T. Roe, Jyotsna Mulgund, Elizabeth R. DeLong, Barbara L. Lytle, Ralph G. Brindis, Sidney C. Smith, Charles V. Pollack, L. Kristin Newby, Robert A. Harrington, W. Brian Gibler, E. Magnus Ohman
Journal: JAMA (2006)

ContextSelected care processes are increasingly being used to measure hospital quality; however, data regarding the association between hospital process performance and outcomes are limited.ObjectivesTo evaluate contemporary care practices consistent with the American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations, to examine how hospital performance varied among centers, to identify characteristics predictive of higher guideline adherence, and to assess whether hospitals' overall composite guideline adherence was associated with observed and risk-adjusted in-hospital mortality rates.Design, Setting, and ParticipantsAn observational analysis of hospital care in 350 academic and nonacademic US centers of 64 775 patients enrolled in the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) National Quality Improvement Initiative between January 1, 2001, and September 30, 2003, presenting with chest pain and positive electrocardiographic changes or cardiac biomarkers consistent with non–ST-segment elevation acute coronary syndrome (ACS).Main Outcome MeasuresUse of 9 ACC/AHA class I guideline-recommended treatments and the correlation among hospitals' use of individual care processes as well as overall composite adherence rates.ResultsOverall, the 9 ACC/AHA guideline-recommended treatments were adhered to in 74% of eligible instances. There was modest correlation in hospital performance among the individual ACS process metrics. However, composite adherence performance varied widely (median [interquartile range] composite adherence scores from lowest to highest hospital quartiles, 63% [59%-66%] vs 82% [80%-84%]). Composite guideline adherence rate was significantly associated with in-hospital mortality, with observed mortality rates decreasing from 6.31% for the lowest adherence quartile to 4.15% for the highest adherence quartile (P<.001). After risk adjustment, every 10% increase in composite adherence at a hospital was associated with an analogous 10% decrease in its patients' likelihood of in-hospital mortality (adjusted odds ratio, 0.90; 95% confidence interval, 0.84-0.97; P<.001).ConclusionA significant association between care process and outcomes was found, supporting the use of broad, guideline-based performance metrics as a means of assessing and helping improve hospital quality.