tbuckley/cabot-search huggingface dataset:
Altered Fibrin Clot Structure in the Healthy Relatives of Patients With Premature Coronary Artery Disease
Authors: Joseph D. Mills, Robert A.S. Ariëns, Michael W. Mansfield, Peter J. Grant
Journal: Circulation (2002)

A family history of premature coronary artery disease (CAD) is an independent cardiovascular risk factor. Fibrin clots composed of dense fiber networks are found in young CAD patients and may occur in the relatives of such individuals.The ex vivo fibrin structure of 100 healthy male relatives of patients with premature CAD and 100 age-matched control subjects was assessed by measurement of permeability (K(s)), fiber mass-length ratio ( micro ), and turbidity (lag phase and maximum absorbency [max DeltaAbs]). Scanning electron microscopy was performed on selected samples. Relatives and controls shared similar levels of conventional cardiovascular risk factors. K(s) was lower in relatives than in controls, 12.2 (11.1 to 13.3) versus 15.2 (14.0 to 16.5) x10(-9) cm(2) (P<0.001), associated with a smaller decrease in micro, 8.5 (7.7 to 9.2) versus 9.7 (8.9 to 10.5) x 10(13) Da/cm (P<0.05), respectively. Lag phase was shorter in relatives than in controls, 39 (37 to 41) versus 47 (44 to 50) seconds (P<0.001), and max DeltaAbs was higher in relatives, 0.78 (0.74 to 0.82) versus 0.71 (0.67 to 0.74) in controls (P=0.02), which indicates the presence of thicker fibers in relatives. After adjustment for fibrinogen levels, lag phase and K(s) remained significantly different between relatives and control subjects. Scanning electron microscopy images confirmed increased fiber diameter in relatives, possibly of reduced density. Factor XIII Val34Leu and fibrinogen Aalpha Thr312Ala and Bbeta -455 G/A showed no association with clot structure.The male relatives of patients with premature CAD form fibrin clots that begin polymerization more quickly, have thicker fibers, and are less permeable than those of control subjects.
Effect of tidal volume on the output and particle size distribution of hypertonic saline from an ultrasonic nebulizer
Authors: J Riedler, CF Robertson
Journal: European Respiratory Journal (1994)

The purpose of the present study was to measure the output and particle size distribution of hypertonic saline from an ultrasonic nebulizer over the range of tidal volumes (VT) used in an epidemiological survey of asthma in children. A Starling pump was used to generate different VTs from 250 to 500 ml, at different respiratory rates of 12 and 20 breaths.min-1, to cover the normal range of respiratory pattern of children aged 7-14 yrs. The Starling pump was connected to a Timeter Compuneb Ultrasonic Nebulizer Model MP 500 with 24 cm of corrugated aerosol tubing, ID 2.2 cm, and a two-way non-rebreathing valve. Nebulizer output was measured by weighing the nebulizer chamber plus tubing and valve before and after each nebulization. To measure particle size distribution, a Malvern Particle Sizer M 3.0 (laser diffraction) was used, with a special adapter attached between valve and Starling pump. Nebulizer output increased linearly from 1.6 to 2.5 ml.min-1 for VT 250 to 500 ml, with little influence by the respiratory frequency. Furthermore, we found that in the range of VT = 300-500 ml the mass median aerodynamic diameter (MMAD) was 2.61 microns, with 100% of the particles less than 5 microns, whereas at VT = 150-250 ml the MMAD was 8.89 microns, with 90% larger than 5 microns. As output from this ultrasonic nebulizer correlates linearly with tidal volumes, size correction may not be necessary in hypertonic saline challenge tests in children. Above a VT of 300 ml, the MMAD is in the respirable range, with 100% of particles less than 5 microns.(ABSTRACT TRUNCATED AT 250 WORDS)
The Relationship between DNA Replication and Human Genome Organization
Authors: A. Necsulea, C. Guillet, J.-C. Cadoret, M.-N. Prioleau, L. Duret
Journal: Molecular Biology and Evolution (2009)

Assessment of the impact of DNA replication on genome architecture in Eukaryotes has long been hampered by the scarcity of experimental data. Recent work, relying on computational predictions of origins of replication, suggested that replication might be a major determinant of gene organization in human (Huvet et al. 2007. Human gene organization driven by the coordination of replication and transcription. Genome Res. 17:1278–1285). Here, we address this question by analyzing the first large-scale data set of experimentally determined origins of replication in human: 283 origins identified in HeLa cells, in 1% of the genome covered by ENCODE regions (Cadoret et al. 2008. Genome-wide studies highlight indirect links between human replication origins and gene regulation. Proc Natl Acad Sci USA. 105:15837–15842). We show that origins of replication are not randomly distributed as they display significant overlap with promoter regions and CpG islands. The hypothesis of a selective pressure to avoid frontal collisions between replication and transcription polymerases is not supported by experimental data as we find no evidence for gene orientation bias in the proximity of origins of replication. The lack of a significant orientation bias remains manifest even when considering only genes expressed at a high rate, or in a wide number of tissues, and is not affected by the regional replication timing. Gene expression breadth does not appear to be correlated with the distance from the origins of replication. We conclude that the impact of DNA replication on human genome organization is considerably weaker than previously proposed.
THE EFFECT OF CYTOTOXIC AGENTS ON THE PASSIVE TRANSFER OF CELL-MEDIATED IMMUNITY
Authors: S. P. Tripathy, G. B. Mackaness
Journal: The Journal of Experimental Medicine (1969)

A system involving the passive transfer of committed lymphoid cells from Listeria-immune donors has been used to study the phases of the immune response which are sensitive to the immunosuppressive action of various cytotoxic agents. The agents investigated included cyclophosphamide, vinblastine, methotrexate, azathioprine, and X-irradiation. Complete suppression of passive immunization was obtained by the administration of cyclophosphamide or vinblastine to recipients at the time of cell transfer or by prior X-irradiation of recipients a day before cell transfer. Methotrexate was only partially suppressive, whereas azathioprine had no effect at all. The donor cell responsible for the transfer of immunity to recipients was shown to be a resting cell which is sensitive to the action of cyclophosphamide but not to vinblastine. The results of this investigation suggest that the donor cells undergo multiplication in the tissues of the recipient, presumably in response to specific stimulation by Listeria antigens. This in turn results in the activation of host macrophages. The immunosuppressive action of cyclophosphamide, vinblastine, and irradiation in the cell-transfer system has been discussed in relation to a direct cytotoxic action on the immune lymphoid cells of the donor and specific interference with their proliferation in the recipient, as well as impairment of macrophage production on the part of the recipient itself.
Series on education: Impact on medical students of incorporating GALS screen teaching into the medical school curriculum
Authors: Fox Ra, Dacre Je, Clark Cl, Scotland Ad
Journal: Annals of the Rheumatic Diseases (2000)

To assess the impact of GALS locomotor screen teaching to all 3rd year medical students, at a British medical school.In 1998, during their 3rd year, all students were taught the GALS screen in a one hour small group session. At the end of this year, 242 medical students undertook a 16 station Objective Structured Clinical Examination (OSCE). One station assessed the locomotor screening examination, while six stations assessed the examination of other systems. The students completed a five point likert scale, self rating their confidence in each of the skills assessed at this time. Pre-registration house officers (PRHOs) at two London hospitals were invited to undertake the same OSCE and self rating.The students performed the locomotor screen well (mean station score 80%). Three body systems were examined better and one significantly worse (p<0.05). 22/40 PRHOs undertook the assessment. Compared with the students they examined the locomotor system (mean score 20%, p<0.001), but not other systems, less well. The PRHOs felt less confident (p<0.05) examining the locomotor system (mean rating 3.6/5) than the other systems (mean rating 4.6/5), while no significant difference in confidence ratings was seen for the students.Students who are taught the GALS screen as part of the curriculum, perform it well in an end of year OSCE, as confidently as other systems, and to a higher standard than PRHOs. Further study is required to determine whether this benefit persists, overcoming the poor skills and confidence in locomotor examination of existing PRHOs, not previously taught a GALS screen.
Positive Selection within a Diatom Species Acts on Putative Protein Interactions and Transcriptional Regulation
Authors: J. A. Koester, W. J. Swanson, E. V. Armbrust
Journal: Molecular Biology and Evolution (2012)

Diatoms are the most species-rich group of microalgae, and their contribution to marine primary production is important on a global scale. Diatoms can form dense blooms through rapid asexual reproduction; mutations acquired and propagated during blooms likely provide the genetic, and thus phenotypic, variability upon which natural selection may act. Positive selection was tested using genome and transcriptome-wide pair-wise comparisons of homologs in three genera of diatoms (Pseudo-nitzschia, Ditylum, and Thalassiosira) that represent decreasing phylogenetic distances. The signal of positive selection was greatest between two strains of Thalassiosira pseudonana. Further testing among seven strains of T. pseudonana yielded 809 candidate genes of positive selection, which are 7% of the protein-coding genes. Orphan genes and genes encoding protein-binding domains and transcriptional regulators were enriched within the set of positively selected genes relative to the genome as a whole. Positively selected genes were linked to the potential selective pressures of nutrient limitation and sea surface temperature based on analysis of gene expression profiles and identification of positively selected genes in subsets of strains from locations with similar environmental conditions. The identification of positively selected genes presents an opportunity to test new hypotheses in natural populations and the laboratory that integrate selected genotypes in T. pseudonana with their associated phenotypes and selective forces.
A2B Adenosine Receptor Induces Protective Antihelminth Type 2 Immune Responses
Authors: Nirav Patel, Wenhui Wu, Pankaj K. Mishra, Fei Chen, Ariel Millman, Balázs Csóka, Balázs Koscsó, Holger K. Eltzschig, György Haskó, William C. Gause
Journal: Cell Host & Microbe (2014)
Bosentan in inoperable chronic thromboembolic pulmonary hypertension
Authors: R Hughes
Journal: Thorax (2005)

Comorbidity in elderly NSCLC patientsWe read with interest the report by Janssen-Heijnen and associates on the effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer (NSCLC). 1 The authors concluded that the number of comorbid conditions had no significant influence on the treatment chosen for patients with non-localised disease.We share the authors' opinion that ''comorbidity had no independent prognostic effect''.In their report, the authors used the Charlson comorbidity index and analysed the number of comorbid conditions. 1 However, they did not examine the scoring system of the index.We would like to know why the authors did not use the scoring of the index, and whether the conclusion would be changed if the scoring system was used.In the original article by Charlson et al and other related studies, 2-5 ''angina pectoris'' was not evaluated as one of the cardiovascular comorbid diseases.However, Janssen-Heijnen et al 1 included ''angina pectoris'' as a comorbid disease although they did not describe it precisely.We consider this inclusion is reasonable, and we would appreciate hearing from the authors whether ''angina pectoris'' would be evaluated as one of the cardiovascular comorbid diseases in future studies to evaluate the effect on mortality, and what score it should be assigned.
Pharmacogenetics and Cardiovascular Disease—Implications for Personalized Medicine
Authors: Julie A. Johnson, Larisa H. Cavallari
Journal: Pharmacological Reviews (2013)

The past decade has seen tremendous advances in our understanding of the genetic factors influencing response to a variety of drugs, including those targeted at treatment of cardiovascular diseases. In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies, and some health centers are using this information in the care of their patients. There are many challenges in moving from research data to translation to practice; we discuss some of these barriers and the approaches some health systems are taking to overcome them. The body of literature that has led to the clinical implementation of <i>CYP2C19</i> genotyping for clopidogrel, <i>VKORC1, CYP2C9;</i> and <i>CYP4F2</i> for warfarin; and <i>SLCO1B1</i> for statins is comprehensively described. We also provide clarity for other genes that have been extensively studied relative to these drugs, but for which the data are conflicting. Finally, we comment briefly on pharmacogenetics of other cardiovascular drugs and highlight <i>β</i>-blockers as the drug class with strong data that has not yet seen clinical implementation. It is anticipated that genetic information will increasingly be available on patients, and it is important to identify those examples where the evidence is sufficiently robust and predictive to use genetic information to guide clinical decisions. The review herein provides several examples of the accumulation of evidence and eventual clinical translation in cardiovascular pharmacogenetics.
Osmotic error in erythrocyte volume determinations
Authors: William Beautyman, Terry Bills
Journal: American Journal of Hematology (1982)

Because of osmotic effects erythrocytes suspended in their native plasma do not have the same volume as the same erythrocytes suspended in Isoton. The discrepancy varies depending upon the osmolality and composition of the native plasma and the length of time the cells have been suspended in Isoton. consequently, the MCV recorded in an electronic particle counter (Coulter in this case) may differ markedly from the true in vivo MCV. A similar error affects the Coulter hematocrit, which is calculated from the MCV and the erythrocyte count. This matrix effect should be taken into account in any laboratory quality assurance program.
Circulating cell-free DNA levels in Portuguese patients with psoriasis vulgaris according to severity and therapy
Authors: S. Coimbra, C. Catarino, E. Costa, H. Oliveira, A. Figueiredo, P. Rocha-Pereira, A. Santos-Silva
Journal: British Journal of Dermatology (2013)

Inflammation has a key role in the pathogenesis of psoriasis. Circulating cell-free DNA (CFD) is a marker of tissue cell damage closely associated with inflammation.We aimed to understand the relation of CFD levels with psoriasis severity, defined by the Psoriasis Area and Severity Index (PASI), with inflammation and with psoriasis therapy.Forty-six patients with psoriasis vulgaris were evaluated before (T0) and after 12 weeks (T12) of treatment with narrowband ultraviolet light B (NB-UVB; n = 17), psoralen plus UVA (PUVA; n = 20) or topical therapy (n = 9). We evaluated interleukin (IL)-6 and circulating CFD levels.Compared with controls, at T0, patients presented significantly higher levels of circulating CFD. CFD presented a significant positive correlation with IL-6 and a trend towards a positive correlation with PASI. Multiple linear regression analysis identified IL-6 as an independent variable associated with CFD circulating levels. As shown by the PASI score, a trend towards higher values of CFD was observed in the severe psoriasis forms; moderate and severe psoriasis presented also significantly higher CFD values, compared with control. Both NB-UVB and PUVA treatments significantly decreased the levels of CFD.Patients with psoriasis, at the active stage of the disease, presented an increased inflammation associated with raised circulating CFD levels, which seem to be linked to psoriasis severity. Both NB-UVB and PUVA, anti-inflammatory therapies, were effective in decreasing CFD values. We propose that the evaluation of circulating CFD may provide a new biomarker to monitor psoriasis, its severity and its treatment.
Why the dynamical hypothesis cannot qualify as a law of qualitative structure
Authors: Nick Braisby, Richard Cooper, Bradley Franks
Journal: Behavioral and Brain Sciences (1998)

Van Gelder presents the dynamical hypothesis as a novel law of qualitative structure to compete with Newell and Simon's (1976) physical symbol systems hypothesis. Unlike Newell and Simon's hypothesis, the dynamical hypothesis fails to provide necessary and sufficient conditions for cognition. Furthermore, imprecision in the statement of the dynamical hypothesis renders it unfalsifiable.
FUNDAMENTAL EFFECTS OF EPILEPTOGENOUS AGENTS UPON THE CENTRAL NERVOUS SYSTEM
Authors: E. A. Spiegel, M. Spiegel-Adolf
Journal: American Journal of Psychiatry (1936)

1. The permeability of the cell surfaces for electrolytes was studied in vitro and in vivo by measuring the polarizability of the brain tissue. 2. Agents that produce swelling of the brain by increasing the state of hydration of the brain tissue (e. g., distilled water, alkali) increase the permeability, as shown by the decrease in polarizibility. This is a reversible process, as indicated by the effect of some acids and of hypertonic salt solutions after previous swelling of the brain. 3. These experiments support the view that pathologic processes which call forth swelling of the brain produce an impairment of the cell surfaces in that their density is lowered. The transitory increase in permeability of the cell surfaces that is, according to the modern theories of excitation, an essential part of the excitation process is thus facilitated, and the threshold of the cells for metabolic or other stimuli is lowered. This explains the mechanism by which swelling of the brain increases the convulsive reactivity. Investigations are under way to ascertain as to whether other epileptogenous agents have similar basic effects.
A Multicenter, Randomized, Double-Blind, Controlled Trial of Nebulized Epinephrine in Infants with Acute Bronchiolitis
Authors: Claire Wainwright, Luis Altamirano, Marise Cheney, Joyce Cheney, Scott Barber, Darrell Price, Sue Moloney, Ann Kimberley, Nick Woolfield, Susan Cadzow, Frank Fiumara, Peter Wilson, Steve Mego, Dianne VandeVelde, Sharon Sanders, Peter O'Rourke, Paul Francis
Journal: New England Journal of Medicine (2003)

The treatment of infants with bronchiolitis is largely supportive. The role of bronchodilators is controversial. Most studies of the use of bronchodilators have enrolled small numbers of subjects and have examined only short-term outcomes, such as clinical scores.
Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediated by reciprocal secretion of adenosine and IL-6
Authors: Shanthi V. Sitaraman, Didier Merlin, Lixin Wang, Michelle Wong, Andrew T. Gewirtz, Mustapha Si-Tahar, James L. Madara
Journal: Journal of Clinical Investigation (2001)

Adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5′ AMP. Using intestinal epithelial cell line T84, we studied the effect of adenosine on the secretion of IL-6, a proinflammatory cytokine involved in neutrophil degranulation and lymphocyte differentiation. Stimulation of T84 monolayers with either apical or basolateral adenosine induces A2b receptor–mediated increase in IL-6 secretion, which is polarized to the apical (luminal) compartment. In addition, Salmonella typhimurium, TNF-α, and forskolin, known inducers of IL-6 secretion in intestinal epithelial cells, also stimulate IL-6 secretion into the apical compartment. We show that IL6 promoter induction by adenosine occurs through cAMP-mediated activation of nuclear cAMP-responsive element-binding protein (CREB). We also show that IL-6 released in the luminal (apical) compartment achieves a sufficient concentration to activate neutrophils (from which the adenosine signal originates), since such IL-6 is found to induce an intracellular [Ca++] flux in neutrophils. We conclude that adenosine released in the intestinal lumen during active inflammation may induce IL-6 secretion, which is mediated by cAMP/CREB activation and occurs in an apically polarized fashion. This would allow sequential activation of neutrophil degranulation in the lumen — a flow of events that would, in an epithelium-dependent fashion, enhance microbicidal activity of neutrophils as they arrive in the intestinal lumen.
Impact of Achieved Blood Pressure on Cardiovascular Outcomes in the Irbesartan Diabetic Nephropathy Trial
Authors: Tomas Berl, Lawrence G. Hunsicker, Julia B. Lewis, Marc A. Pfeffer, Jerome G. Porush, Jean-Lucien Rouleau, Paul L. Drury, Enric Esmatjes, Donald Hricik, Marc Pohl, Itamar Raz, Philippe Vanhille, Thomas B. Wiegmann, Bernard M. Wolfe, Francesco Locatelli, Samuel Z. Goldhaber, Edmund J. Lewis
Journal: Journal of the American Society of Nephrology (2005)

Elevated arterial pressure enhances the risk for cardiovascular (CV) events in patients with diabetic nephropathy. The optimal BP and the component of the elevated BP that affect the risk have not been defined. A post hoc analysis was performed to assess the impact of achieved systolic, diastolic, and pulse pressures on CV outcomes in 1590 adults who had overt diabetic nephropathy and were enrolled in the Irbesartan Diabetic Nephropathy Trial (IDNT) and had a baseline serum creatinine above the normal range, up to 266 micromol/L (3.0 mg/dL), 24-h urine protein >900 mg/d, and at least 6 mo of follow-up. Patients were randomized to irbesartan, amlodipine, or placebo, with other antihypertensive agents to a BP goal of < or =135/85 mmHg. Progressively lower achieved systolic BP (SBP) to 120 mmHg predicted a decrease in CV mortality and congestive heart failure (CHF) but not myocardial infarctions (MI). A SBP below this threshold was associated with increased risk for CV deaths and CHF events. Achieved diastolic BP <85 mmHg was associated with a trend to increase in all-cause mortality, significant increase in MI, but decreased risk for strokes. Increased pulse pressure predicted increased all-cause mortality, CV mortality, MI, and CHF. It is concluded that achieved SBP approaching 120 mmHg and diastolic BP of 85 mmHg are associated with the best protection against CV events in these patients. BP < or =120/85 may be associated with an increase in CV events.
AMPK and SNF1: Snuffing Out Stress
Authors: D. Grahame Hardie
Journal: Cell Metabolism (2007)

AMP-activated protein kinase (AMPK) has attracted much attention for its key role in energy homeostasis. Three new papers providing structural information on mammalian and yeast AMPK homologs give insights into the binding of the regulatory nucleotides AMP and ATP and how mutations are associated with cardiac glycogen storage disorders.