tbuckley/cabot-search huggingface dataset:
Community-Based Interventions to Promote Blood Pressure Control in a Developing Country
Authors: Tazeen H. Jafar, Juanita Hatcher, Neil Poulter, Muhammad Islam, Shiraz Hashmi, Zeeshan Qadri, Rasool Bux, Ayesha Khan, Fahim H. Jafary, Aamir Hameed, Ata Khan, Salma H. Badruddin, Nish Chaturvedi
Journal: Annals of Internal Medicine (2009)

Background: Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries. Objective: To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults. Design: Cluster randomized, 2 × 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574) Setting: 12 randomly selected communities in Karachi, Pakistan. Patients: 1341 patients 40 years or older with hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or already receiving treatment). Measurements: Reduction in systolic blood pressure from baseline to end of follow-up at 2 years. Intervention: Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management. Results: The age, sex, and baseline blood pressure–adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis). Limitations: Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure. Conclusion: Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries. Primary Funding Source: Wellcome Trust.
The animal variations: When mechanisms matter in accounting for function
Authors: Hugo Viciana, Nicolas Claidiere
Journal: Behavioral and Brain Sciences (2007)

Abstract We contend that Ramsey et al.'s definition of animal innovation sensu process may be partially misleading when investigating mechanisms underlying animal innovation. By excluding social learning from the “process” of innovation, they may be reproducing a dichotomous schema that does not accurately correspond to our knowledge of the acquisition of novel behavioral variants. This gives us some reason to doubt the functional specification of the defined process of innovation.
AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update
Authors: Sidney C. Smith, Jerilyn Allen, Steven N. Blair, Robert O. Bonow, Lawrence M. Brass, Gregg C. Fonarow, Scott M. Grundy, Loren Hiratzka, Daniel Jones, Harlan M. Krumholz, Lori Mosca, Richard C. Pasternak, Thomas Pearson, Marc A. Pfeffer, Kathryn A. Taubert
Journal: Circulation (2006)

HomeCirculationVol. 113, No. 19AHA/ACC Guidelines for Secondary Prevention for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2006 Update
Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis
Authors: M C Vonk, Z Marjanovic, F H J van den Hoogen, S Zohar, A V M B Schattenberg, W E Fibbe, J Larghero, E Gluckman, F W M B Preijers, A P J van Dijk, J J Bax, P Roblot, P L C M van Riel, J M van Laar, D Farge
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc. <h3>Patients and methods:</h3> A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 μg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used. <h3>Results:</h3> After a median follow-up of 5.3 (1–7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan–Meier estimated survival at 5 years was 96.2% (95% CI 89–100%) and at 7 years 84.8% (95% CI 70.2–100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9–86%) at 5 years and 57.1% (95% CI 39.3–83%) at 7 years. <h3>Conclusion:</h3> This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.
Functional Antifreeze Glycoprotein Genes in Temperate-Water New Zealand Nototheniid Fish Infer an Antarctic Evolutionary Origin
Authors: C.-H. C. Cheng
Journal: Molecular Biology and Evolution (2003)

The fish fauna of the Antarctic Ocean is dominated by five endemic families of the Perciform suborder Notothenioidei, thought to have arisen in situ within the Antarctic through adaptive radiation of an ancestral stock that evolved antifreeze glycoproteins (AFGPs) enabling survival as the ocean chilled to subzero temperatures. The endemism results from geographic confinement imposed by a massive oceanographic barrier, the Antarctic Circumpolar Current, which also thermally isolated Antarctica over geologic time, leading to its current frigid condition. Despite this voluminous barrier to fish dispersal, a number of species from the Antarctic family Nototheniidae now inhabit the nonfreezing cool temperate coasts of the southern continents. The origin of these temperate-water nototheniids is not completely understood. Since the AFGP gene apparently evolved only once, before the Antarctic notothenioid radiation, the presence of AFGP genes in extant temperate-water nototheniids can be used to infer an Antarctic evolutionary origin. Genomic Southern analysis, PCR amplification of AFGP genes, and sequencing showed that Notothenia angustata and Notothenia microlepidota endemic to southern New Zealand have two to three AFGP genes, structurally the same as those of the Antarctic nototheniids. At least one of these genes is still functional, as AFGP cDNAs were obtained and low levels of mature AFGPs were detected in the blood. A phylogenetic tree based on complete ND2 coding sequences showed monophyly of these two New Zealand nototheniids and their inclusion in the monophyletic Nototheniidae consisted of mostly AFGP-bearing taxa. These analyses support an Antarctic ancestry for the New Zealand nototheniids. A divergence time of approximately 11 Myr was estimated for the two New Zealand nototheniids, approximating the upper Miocene northern advance of the Antarctic Convergence over New Zealand, which might have served as the vicariant event that lead to the northward dispersal of their most recent common ancestor. Similar secondary northward dispersal likely applies to the South American nototheniid Paranotothenia magellanica, which has four AFGP genes in its DNA, but not to the sympatric nototheniid Patagonotothen tessellata, which does not appear to have any AFGP sequences in its genome at all.
T Cell Receptors in Murine Autoimmune Diseases
Authors: H Acha-Orbea, L Steinman, H O McDevitt
Journal: Annual Review of Immunology (1989)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Blockade of Nonhormonal Fibroblast Growth Factors by FP-1039 Inhibits Growth of Multiple Types of Cancer
Authors: Thomas C. Harding, Li Long, Servando Palencia, Hongbing Zhang, Ali Sadra, Kevin Hestir, Namrata Patil, Anita Levin, Amy W. Hsu, Deborah Charych, Thomas Brennan, James Zanghi, Robert Halenbeck, Shannon A. Marshall, Minmin Qin, Stephen K. Doberstein, Diane Hollenbaugh, W. Michael Kavanaugh, Lewis T. Williams, Kevin P. Baker
Journal: Science Translational Medicine (2013)

A soluble FGF receptor trap effectively inhibits tumor growth in the absence of toxicity.
Endogenous heparinoids in acute variceal bleeding
Authors: U Thalheimer
Journal: Gut (2005)

The risk of variceal bleeding in cirrhotics is associated with increasing liver dysfunction, larger varices, endoscopic red signs, and higher portal pressure. However, why bleeding occurs unpredictably and infrequently in individual patients is unknown.

Bacterial infections occur in 35–66% of cirrhotics presenting with gastrointestinal bleeding.1 We proposed a possible pathophysiological basis linking infection and variceal bleeding via endotoxin induced endothelin release and subsequent portal pressure rise, combined with impaired platelet aggregation due to endotoxin induced nitric oxide and prostacyclin.2 Infected cirrhotics demonstrate a heparin effect using heparinase I modified thromboelastography (TEG) and have anti-Xa activity.3,4 Now we show similar findings in two cirrhotics during the course of acute variceal bleeding.

Patient 1 was male, 66 years old (Child-Pugh grade C), and patient 2 was female, 42 years old …
Isolation of Patient‐Related Antigens from Allergen Extracts by Means of Protein A‐Sepharose‐Patient IgG<sub>1,2,4</sub> Bio‐Affinity Chromatography
Authors: I. Søndergaard, B. Weeke
Journal: Allergy (1984)

A method is described for bio‐affinity purification of patient‐specific IgG reactive antigens by using protein A‐sepharose allergic patient serum and the corresponding antigen/allergen extract. The optimal conditions for each step have been determined and it is shown that the non‐specific binding of both serum proteins and antigens can be kept at very low levels by a high ionic strength. The specificity of the reaction has been shown by biospecific elution of 125 I‐labelled antigens by non‐labelled antigens and also by comparison of the amount of antigen bound by sera from hyposensitized patients with that from non‐atopic individuals. It is suggested that the isolated antigen‐IgG‐immune complexes could be used for a specific and active immunotherapy.
Avidity-Mediated Enhancement of <i>In vivo</i> Tumor Targeting by Single-Chain Fv Dimers
Authors: Gregory P. Adams, Mei-Sheng Tai, John E. McCartney, James D. Marks, Walter F. Stafford, L.L. Houston, James S. Huston, Louis M. Weiner
Journal: Clinical Cancer Research (2006)

Abstract Radiolabeled single-chain Fv (sFv) molecules display highly specific tumor retention in the severe combined immunodeficient (SCID) mouse model; however, the absolute quantity of sFv retained in the tumors is diminished by the rapid renal elimination resulting from the small size of the sFv molecules (Mr 27,000) and by dissociation of the monovalent sFv from tumor-associated antigen. We previously reported significant improvement in tumor retention without a loss of targeting specificity on converting monovalent sFv into divalent [(sFv′)2] dimers, linked by a disulfide bond between COOH-terminal cysteinyl peptides engineered into the sFv′. However, our data for enhanced dimer localization in tumors could not distinguish between the contributions of enhanced avidity and increased systemic retention associated with the larger size of 54 kDa [(sFv′)2] dimers relative to 27-kDa sFv. In this investigation, we have compared tumor targeting of divalent anti-c-erbB-2/HER2/neu 741F8-1 (sFv′)2 homodimers with monovalent 741F8/26-10 (sFv′)2 heterodimers (Mr 54,000) and 741F8 sFv monomers (741F8 sFv has binding specificity for erbB-2/HER2/neu and 26-10 sFv specificity for digoxin and related cardiac glycosides). These studies allowed us to distinguish the dominant effect of valency over molecular weight in accounting for the superior tumor retention of 741F8-1 (sFv′)2 homodimers. Each of the radioiodinated species was administered i.v. to SCID mice bearing SK-OV-3 human tumor xenografts and tumor localization at 24 hours post i.v. injection was determined for 125I-741F8-1 (sFv′)2 (3.57 %ID/g), 125I-741F8/26-10 (sFv′)2 (1.13 %ID/g), and 125I-741F8-1 sFv (1.25 %ID/g). These findings substantiate that the improved tumor retention of (sFv′)2 homodimers over sFv monomers results from the availability of dual binding sites rather than from the slower systemic clearance of homodimers.
A Randomized Trial of Strategies for Assessing Eligibility for Long-Term Domiciliary Oxygen Therapy
Authors: Gordon H. Guyatt, Mika Nonoyama, Christina Lacchetti, Ron Goeree, Douglas McKim, Diane Heels-Ansdell, Roger Goldstein
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Restricting oxygen administration to those who benefit is desirable.To determine the impact of alternative strategies for assessing eligibility for domiciliary oxygen on funded oxygen use, quality of life, and costs.We randomized applicants for domiciliary oxygen therapy to an assessment system that relied on data collected by oxygen providers at the time of application and judgments by Home Oxygen Program personnel (conventional assessment) or to a system of data collection by a respiratory therapist that included, in patients unstable at the time of initial assessment, a repeat assessment after 2 months of stability (alternative assessment).A total of 276 applicants were allocated to the conventional arm and 270 to the alternative assessment. In the year after application, oxygen use was lower in the alternative arm with no between-group differences in mortality, quality of life, or resource use in the community. Although alternative assessment applicants had on average higher assessment costs by dollars Canadian 155 per applicant, these costs were more than offset by decreased Home Oxygen Program costs of dollars Canadian 596 per applicant using Canadian cost weights. The comparable U.S. dollar figures were dollars US 309 and dollars US 432, respectively, and the difference in cost between strategies was therefore smaller using U.S. cost weights.Reassessment of applicants for domiciliary oxygen after several months of stability identifies an appreciable portion of initially eligible patients who are no longer eligible, thus reducing program costs to public funders without adverse consequences on quality of life, mortality, or other resource use.
Molecular and Functional Identification of Cyclic AMP-Sensitive BK <sub>Ca</sub> Potassium Channels (ZERO Variant) and L-Type Voltage-Dependent Calcium Channels in Single Rat Juxtaglomerular Cells
Authors: Ulla G. Friis, Finn Jørgensen, Ditte Andreasen, Boye L. Jensen, Ole Skøtt
Journal: Circulation Research (2003)

This study aimed at identifying the type and functional significance of potassium channels and voltage-dependent calcium channels (Ca v ) in single rat JG cells using whole-cell patch clamp. Single JG cells displayed outward rectification at positive membrane potentials and limited net currents between −60 and −10 mV. Blockade of K + channels with TEA inhibited 83% of the current at +105 mV. Inhibition of K V channels with 4-AP inhibited 21% of the current. Blockade of calcium-sensitive voltage-gated K + channels (BK Ca ) with charybdotoxin or iberiotoxin inhibited 89% and 82% of the current, respectively. Double immunofluorescence confirmed the presence of BK Ca and renin in the same cell. cAMP increased the outward current by 1.6-fold, and this was inhibited by 74% with iberiotoxin. Expression of the cAMP-sensitive splice variant (ZERO) of BK Ca was confirmed in single-sampled JG cells by RT-PCR. The resting membrane potential of JG cells was −32 mV and activation of BK Ca with cAMP hyperpolarized cells on average 16 mV, and inhibition with TEA depolarized cells by 17 mV. The cells displayed typical high-voltage activated calcium currents sensitive to the L-type Ca v blocker calciseptine. RT-PCR analysis and double-immunofluorescence labeling showed coexpression of renin and L-type Ca v 1.2. The cAMP-mediated increase in exocytosis (measured as membrane capacitance) was inhibited by depolarization to +10 mV, and this inhibitory effect was blocked with calciseptine, whereas K + -blockers had no effect. We conclude that JG cells express functional cAMP-sensitive BK Ca channels (the ZERO splice variant) and voltage-dependent L-type Ca 2+ channels.
Superantigens: Just Like Peptides Only Different
Authors: Thomas Proft, John Fraser
Journal: The Journal of Experimental Medicine (1998)

The exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes are prototype molecules for the larger family of superantigens (SAGs). This family now includes many structurally unrelated molecules of disparate origins reflecting a wide evolutionary convergence towards the common goal of
Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens.
Authors: I Stroynowski, J Forman, R S Goodenow, S G Schiffer, M McMillan, S O Sharrow, D H Sachs, L Hood
Journal: The Journal of Experimental Medicine (1985)

Coding potential of the Q6 gene from the Qa-2a region of BALB/c Crgl mice was analyzed by a combination of hybrid class I gene construction and DNA-mediated gene transfer. Recombinant genes were created by exon shuffling of the 5' coding region of the Q6 gene and the 3' coding region of a gene encoding a transplantation antigen (Kd, Dd, or Ld), or the inverse. Some of these hybrid class I genes were expressed in the transfected mouse fibroblasts (L cells). The hybrid class I molecules encoded by the 5' end of the Q6 gene and the 3' end of the Ld gene precipitated as 45,000 mol wt molecules associated with beta 2-microglobulin. The expression of the hybrid proteins indicates that 926 basepairs of the 5' flanking region upstream of the structural Q6 gene contain a promoter that functions as a transcription initiation site in L cells. The 3' portion of the Q6 gene appears to be responsible for the lack of cell surface expression of the intact Q6 and the hybrid Ld/Q6 genes in mouse fibroblasts. Accordingly, this portion of the Q6 class I gene may play a regulatory role in tissue-specific expression. Serological analyses of hybrid Q6 proteins suggested that Q6 may be a structural gene for CR (H-2 crossreactive) antigen found normally on subpopulations of lymphocytes. If this identification is correct, Q6 gene will define a new category of class I genes encoding approximately 40,000 mol wt molecules and carrying a characteristic truncated cytoplasmic tail. Analysis of L cells transfected with Q6 hybrid genes demonstrated also that the cytotoxic T cells specific for Qa-2a region-coded antigens recognize the amino-terminal alpha 1-alpha 2 domain of Q6 fusion products. This recognition can be blocked by anti-Qa-2a alloantiserum and monoclonal antibodies reactive with the alpha 3-beta 2-microglobulin portion of the Q6 hybrids. We propose that the structural requirements for the anti-Qa-2a cytotoxic T lymphocyte-specific epitopes on target molecules are the same as for anti-H-2-alloreactive cytotoxic T lymphocyte determinants on transplantation antigens and that the mechanism of target recognition is similar in both cases. This interpretation is consistent with the following structural similarities found in both categories of class I molecules: (a) Kd and Q6 alpha 1-alpha 2 domains share serologically defined epitopes.(ABSTRACT TRUNCATED AT 400 WORDS)
Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease
Authors: Paolo A. Hernandez, Robert J. Gorlin, John N. Lukens, Shoichiro Taniuchi, Jože Bohinjec, Fleur Francois, Mary E. Klotman, George A. Diaz
Journal: Nature Genetics (2003)
Relationship between quantitative CT metrics and health status and BODE in chronic obstructive pulmonary disease
Authors: Carlos H Martinez, Ya-Hong Chen, Phillip M Westgate, Lyrica X Liu, Susan Murray, Jeffrey L Curtis, Barry J Make, Ella A Kazerooni, David A Lynch, Nathaniel Marchetti, George R Washko, Fernando J Martinez, MeiLan K Han
Journal: Thorax (2012)

<h3>Background</h3> The value of quantitative CT (QCT) to identify chronic obstructive pulmonary disease (COPD) phenotypes is increasingly appreciated. The authors hypothesised that QCT-defined emphysema and airway abnormalities relate to St George9s Respiratory Questionnaire (SGRQ) and Body-Mass Index, Airflow Obstruction, Dyspnea and Exercise Capacity Index (BODE). <h3>Methods</h3> 1200 COPDGene subjects meeting Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria for COPD with QCT analysis were included. Total lung emphysema was measured using the density mask technique with a −950 Hounsfield unit threshold. An automated programme measured mean wall thickness (WT), wall area percentage (WA%) and 10 mm lumenal perimeter (pi10) in six segmental bronchi. Separate multivariate analyses examined the relative influence of airway measures and emphysema on SGRQ and BODE. <h3>Results</h3> In separate models predicting SGRQ score, a 1 unit SD increase in each airway measure predicted higher SGRQ scores (for WT, 1.90 points higher, p=0.002; for WA%, 1.52 points higher, p=0.02; for pi10, 2.83 points higher p&lt;0.001). The comparable increase in SGRQ for a 1 unit SD increase in emphysema percentage in these models was relatively weaker, significant only in the pi10 model (for emphysema percentage, 1.45 points higher, p=0.01). In separate models predicting BODE, a 1 unit SD increase in each airway measure predicted higher BODE scores (for WT, 1.07-fold increase, p&lt;0.001; for WA%, 1.20-fold increase, p&lt;0.001; for pi10, 1.16-fold increase, p&lt;0.001). In these models, emphysema more strongly influenced BODE (range 1.24–1.26-fold increase, p&lt;0.001). <h3>Conclusion</h3> Emphysema and airway disease both relate to clinically important parameters. The relative influence of airway disease is greater for SGRQ; the relative influence of emphysema is greater for BODE.