tbuckley/cabot-search huggingface dataset:
Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis
Authors: Yuji Shiba, Masafumi Takahashi, Takeki Hata, Hideki Murayama, Hajime Morimoto, Hirohiko Ise, Takashi Nagasawa, Uichi Ikeda
Journal: Cardiovascular Research (2008)

AimsThe chemokine stromal cell-derived factor-1 (SDF-1) and its receptor (CXCR4, CXC chemokine receptor 4) play a critical role in the process of post-natal neovascularization. Here, we investigated the role of CXCR4+ bone marrow cells (BMCs) in neovascularization in a murine hindlimb ischaemia model.
Contribution of DNA polymerase η to immunoglobulin gene hypermutation in the mouse
Authors: Frédéric Delbos, Annie De Smet, Ahmad Faili, Said Aoufouchi, Jean-Claude Weill, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2005)

The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase η, a translesional polymerase whose inactivation is responsible for the xeroderma pigmentosum variant (XP-V) syndrome in humans. Mutations show an 85% G/C biased pattern, similar to that reported for XP-V patients. Breeding these mice with animals harboring the stop codon mutation of the 129/Olain background in their DNA polymerase ι gene did not alter this pattern further. Although this G/C biased mutation profile resembles that of mice deficient in the MSH2 or MSH6 components of the mismatch repair complex, the residual A/T mutagenesis of polη-deficient mice differs markedly. This suggests that, in the absence of polη, the MSH2–MSH6 complex is able to recruit another DNA polymerase that is more accurate at copying A/T bases, possibly polκ, to assume its function in hypermutation.
HUMAN AUTOIMMUNE NEUROPATHIES
Authors: T. W. Ho, G. M. McKhann, J. W. Griffin
Journal: Annual Review of Neuroscience (1998)

▪ Abstract Peripheral nerve diseases are among the most prevalent disorders of the nervous system. Because of the accessibility of the peripheral nervous system (PNS) to direct physiological and pathological study, neuropathies have traditionally played a unique role in developing our understanding of basic mechanism of nervous system injury and repair. At present they are providing new insight into the mechanisms of immune injury to the nervous system. A rapidly growing catalogue of PNS disorders are now suspected to be immune-mediated, and in the best understood of these disorders, the molecular and cellular targets of immune attack are known, and the pathophysiology follows directly from the specific immune injury. This review summarizes the immunologically relevant features of the PNS, then considers selected immune-mediated neuropathies, focusing on pathogenetic mechanisms. Finally, the PNS is providing a testing ground for new immunotherapies and approaches to protection and regeneration, including the use of trophic factors. The current status of treatment and implications for future approaches is reviewed.
Lack of association between HLA DRB1* alleles and RS3PE syndrome
Authors: E TOUSSIROT, S BERTHIER, D WENDLING, P TIBERGHIEN
Journal: Annals of the Rheumatic Diseases (1998)

In 1985, McCarty and colleagues reported a series of patients characterised by symmetrical and acute synovitis, marked pitting oedema, seronegativity resulting from the absence of rheumatoid factors (RF), increased acute phased reactants, lack of bony erosions on radiography, and benign and short course (RS3PE syndrome: remitting seronegative symmetrical synovitis with pitting oedema).1Most patients were older men. A pitting oedema was also observed in other conditions (polymyalgia rheumatica (PMR) and late onset peripheral spondylarthropathy (LOPS)).2 3 Whether the RS3PE syndrome represents a distinct clinical entity remains controversial.

This syndrome was initially reported to be associated with HLA-B (B7) rather than HLA-DR (DR4) antigens.1 4Recently, an association with HLA-A2 was reported.5 The association between RA and HLA-DRB1* alleles expressing the shared epitope (SE) (*0401, *0404, *0405, *0408, *0101, *0102, *1001, *1402) is well established. Older age onset RA and seronegative RA are known to be poorly or slightly related to DR4.6 7 Futhermore, an association was reported between the HLA-DR antigens that contain the SE and …
Putative Monosomy 5 In Myelodysplastic Syndromes (MDS) Is Probably Resulting From Chromothripsis
Authors: Zuzana Zemanova, Kyra Michalova, Halka Buryova, Jana Brezinova, Libuse Lizcova, Karla Kostylkova, Iveta Sarova, Silvia Izakova, Sarka Ransdorfova, Zdenek Krejcik, Michaela Dostalova Merkerova, Magda Siskova, Anna T Jonasova, Radana Neuwirtova, Jaroslav Cermak
Journal: Blood (2013)
Microvascular Function Relates to Insulin Sensitivity and Blood Pressure in Normal Subjects
Authors: Erik H. Serné, Coen D. A. Stehouwer, Jan C. ter Maaten, Piet M. ter Wee, Jan A. Rauwerda, Ab J. M. Donker, Reinold O. B. Gans
Journal: Circulation (1999)

Background —A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. Methods and Results —Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r =−0.50, P &lt;0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity ( r =0.84, P &lt;0.001; r =0.78, P &lt;0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP ( r =−0.53, P &lt;0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure ( R 2 =38%) and insulin sensitivity ( R 2 =71%) could be explained by microvascular function. Conclusions —Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.
Preferences for aspects of a dermatology consultation
Authors: J. Coast, C. Salisbury, D. De Berker, A. Noble, S. Horrocks, T.J. Peters, T.N. Flynn
Journal: British Journal of Dermatology (2006)

Background General practitioners with special interests (GPSIs) are increasingly being used to provide dermatology services in the U.K. Little is known about U.K. dermatology patient attitudes to proposed variations in secondary care service delivery or the values they attach to aspects of the care they receive. Objectives To quantify preferences for different attributes of care within dermatology secondary care services. Methods Attributes of care that are important to dermatology patients were derived using in‐depth qualitative interviews with 19 patients at different points in the care pathway. A discrete choice experiment using 'best–worst scaling' was sent by post to 119 patients referred to secondary care dermatology services and suitable for GPSI care who had agreed to participate in research. Results Four attributes were derived from the qualitative work: waiting, expertise, thorough care and convenience. For the discrete choice experiment, 99 patients returned questionnaires, 93 of which contained sufficient data for analysis. All attributes were found to be quantitatively important. The attribute of greatest importance was expertise of the doctor, while waiting time was of least importance. Respondents were willing to wait longer than the current 3 months maximum to receive care that was thorough, 2·1 months to see a team led by an expert and 1·3 months to attend a consultation that is easy to get to. Conclusions Although the need to reduce outpatient waiting times is a key policy driver behind the expansion of GPSI services, this does not appear to be the most important issue for patients. The thoroughness with which the consultation is provided and the expertise of the clinician seen are higher priorities.
Results of Annual Screening in Phase I of the United Kingdom Familial Ovarian Cancer Screening Study Highlight the Need for Strict Adherence to Screening Schedule
Authors: Adam N. Rosenthal, Lindsay Fraser, Ranjit Manchanda, Philip Badman, Susan Philpott, Jessica Mozersky, Richard Hadwin, Fay H. Cafferty, Elizabeth Benjamin, Naveena Singh, D. Gareth Evans, Diana M. Eccles, Steven J. Skates, James Mackay, Usha Menon, Ian J. Jacobs
Journal: Journal of Clinical Oncology (2012)

To establish the performance characteristics of annual transvaginal ultrasound and serum CA125 screening for women at high risk of ovarian/fallopian tube cancer (OC/FTC) and to investigate the impact of delayed screening interval and surgical intervention.Between May 6, 2002, and January 5, 2008, 3,563 women at an estimated ≥ 10% lifetime risk of OC/FTC were recruited and screened by 37 centers in the United Kingdom. Participants were observed prospectively by centers, questionnaire, and national cancer registries.Sensitivity for detection of incident OC/FTC at 1 year after last annual screen was 81.3% (95% CI, 54.3% to 96.0%) if occult cancers were classified as false negatives and 87.5% (95% CI, 61.7% to 98.5%) if they were classified as true positives. Positive and negative predictive values of incident screening were 25.5% (95% CI, 14.3 to 40.0) and 99.9% (95% CI, 99.8 to 100) respectively. Four (30.8%) of 13 incident screen-detected OC/FTCs were stage I or II. Compared with women screened in the year before diagnosis, those not screened in the year before diagnosis were more likely to have ≥ stage IIIc disease (85.7% v 26.1%; P = .009). Screening interval was delayed by a median of 88 days before detection of incident OC/FTC. Median interval from detection screen to surgical intervention was 79 days in prevalent and incident OC/FTC.These results in the high-risk population highlight the need for strict adherence to screening schedule. Screening more frequently than annually with prompt surgical intervention seems to offer a better chance of early-stage detection.
Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.
Authors: N Suzuki, T Sakane, E G Engleman
Journal: Journal of Clinical Investigation (1990)

Although the presence of anti-DNA antibody is a hallmark of systemic lupus erythematosus (SLE), neither the subsets of B cells that secrete anti-DNA antibody nor the stimuli responsible for the induction of anti-DNA secretion is known. In particular, the role of CD5+ B cells in human SLE, a distinct subpopulation of antibody-secreting cells shown previously to be a source of anti-DNA antibody in murine models of SLE, is unknown. To approach these questions, we developed a sensitive enzyme-linked immunospot (ELIspot) assay to measure spontaneous secretion of antibody to single-stranded (ss) DNA, double-stranded (ds) DNA, tetanus toxoid, and polyclonal immunoglobulin (Ig) by purified CD5+ and CD5- B cells of 15 SLE patients and 15 healthy control subjects. The B cells of only 1 of 15 healthy subjects secreted a significant level of anti-ssDNA antibody, and none secreted anti-dsDNA. By contrast, in the majority of SLE patients both CD5+ and CD5- B cells secreted IgG and/or IgM anti-ssDNA as well as anti-dsDNA antibody. Further analysis of the anti-ssDNA response revealed that the level of IgG and IgM anti-DNA antibody secretion by CD5- B cells correlated closely with the level of polyclonal Ig production by the same subpopulation (r = 0.81 and 0.70, respectively). In contrast, production of anti-DNA by CD5+ B cells occurred independently of polyclonal Ig production by both CD5+ and CD5- B cell subpopulations. These results suggest that in human SLE there exist two anti-DNA antibody-producing B cell subpopulations with distinct induction mechanisms: one (CD5+), which independently secretes anti-DNA, and another (CD5-), which produces anti-DNA as an apparent consequence of polyclonal B cell activation.
Intron Invasions Trace Algal Speciation and Reveal Nearly Identical Arctic and Antarctic<i>Micromonas</i>Populations
Authors: Melinda P. Simmons, Charles Bachy, Sebastian Sudek, Marijke J. van Baren, Lisa Sudek, Manuel Ares, Alexandra Z. Worden
Journal: Molecular Biology and Evolution (2015)

Spliceosomal introns are a hallmark of eukaryotic genes that are hypothesized to play important roles in genome evolution but have poorly understood origins. Although most introns lack sequence homology to each other, new families of spliceosomal introns that are repeated hundreds of times in individual genomes have recently been discovered in a few organisms. The prevalence and conservation of these introner elements (IEs) or introner-like elements in other taxa, as well as their evolutionary relationships to regular spliceosomal introns, are still unknown. Here, we systematically investigate introns in the widespread marine green alga Micromonas and report new families of IEs, numerous intron presence–absence polymorphisms, and potential intron insertion hot-spots. The new families enabled identification of conserved IE secondary structure features and establishment of a novel general model for repetitive intron proliferation across genomes. Despite shared secondary structure, the IE families from each Micromonas lineage bear no obvious sequence similarity to those in the other lineages, suggesting that their appearance is intimately linked with the process of speciation. Two of the new IE families come from an Arctic culture (Micromonas Clade E2) isolated from a polar region where abundance of this alga is increasing due to climate induced changes. The same two families were detected in metagenomic data from Antarctica—a system where Micromonas has never before been reported. Strikingly high identity between the Arctic isolate and Antarctic coding sequences that flank the IEs suggests connectivity between populations in the two polar systems that we postulate occurs through deep-sea currents. Recovery of Clade E2 sequences in North Atlantic Deep Waters beneath the Gulf Stream supports this hypothesis. Our research illuminates the dynamic relationships between an unusual class of repetitive introns, genome evolution, speciation, and global distribution of this sentinel marine alga.
Controlled expiration in mechanically-ventilated patients with chronic obstructive pulmonary disease (COPD)
Authors: JG Aerts, B van den Berg, JM Bogaard
Journal: European Respiratory Journal (1997)

In patients with severe chronic obstructive pulmonary disease (COPD), lung emptying may be affected by flow limitation. We tested the hypothesis that the airway compression leading to flow limitation can be counteracted by controlling the expiratory flow. The effects of an external resistor on lung emptying were studied in six patients with COPD, who were mechanically ventilated whilst sedated and paralysed. Respiratory mechanics were obtained during ventilatory support with and without the resistor. Airway compression was assessed using the interruptor method. For the study, a turbulent resistor was applied with the highest resistance level that did not increase the end-expiratory lung volume. At this resistance level, external positive end-expiratory pressure (PEEP) was generated in all patients. As total PEEP levels remained unchanged at both settings during the controlled expiration, the levels of intrinsic PEEP were significantly decreased from 0.96+/-0.30 to 0.53+/-0.19 kPa (mean+/-SD). Comparison of the expiratory flow-volume curves at both settings revealed that, during the controlled expiration, the flows were significantly decreased during the first 40% of the expired volume and significantly increased during the last 60%. As the end-expiratory lung volumes remained unchanged during both settings, these increments in flow indicated a decrease in effective resistance. Airway compression was observed during unimpeded expirations in all patients using the interruptor method. During the application of the resistor, airway compression was no longer detectable. In patients with chronic obstructive pulmonary disease receiving ventilatory support, the application of an external resistor could decrease effective expiratory resistance by counteracting airway compression, without increments in end-expiratory lung volume.
Enhancing immunogenicity by limiting susceptibility to lysosomal proteolysis
Authors: Lélia Delamarre, Rachael Couture, Ira Mellman, E. Sergio Trombetta
Journal: The Journal of Experimental Medicine (2006)

T cells recognize protein antigens as short peptides processed and displayed by antigen-presenting cells. However, the mechanism of peptide selection is incompletely understood, and, consequently, the differences in the immunogenicity of protein antigens remain largely unpredictable and difficult to manipulate. In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. We compared the immunogenicity of proteins with the same sequence (same T cell epitopes) and structure (same B cell epitopes) but with different susceptibilities to lysosomal proteolysis. After immunizing mice with each of the proteins adsorbed onto aluminum hydroxide as adjuvant, we measured serum IgG responses as a physiological measure of the antigen's ability to be presented on major histocompatibility complex class II molecules and to prime CD4+ T cells in vivo. For two unrelated model antigens (RNase and horseradish peroxidase), we found that only the less digestible forms were immunogenic, inducing far more efficient T cell priming and antibody responses. These findings suggest that stability to lysosomal proteolysis may be an important factor in determining immunogenicity, with potential implications for vaccine design.
The nursing position after operation and the work of breathing
Authors: R. Marshall
Journal: Thorax (1969)

Patients after operation are often nursed with the foot of the bed raised in order to facilitate drainage of blood from the legs and of secretions from the trachea. Measurements of the changes in lung volume, of the oxygen cost of breathing, and of the movements of the rib cage and abdomen in the sitting, supine, and 15 degree head-down positions have been made in three subjects. The subjects selected were one overweight, one of medium, and one of lean body build. The oxygen cost of breathing was considerably increased in the head-down position in the overweight subject, less so in the one of medium build, and not at all in the lean subject. The cause of the increased oxygen cost of breathing and of its influence on the position in which patients are nursed after operation is discussed.
Pulmonary Nuclear Medicine: Techniques in Diagnosis of Lung Disease
Journal: Thorax (1985)

Infection with one microorganism can influence secondary infections with other, unrelated pathogens by for example, breaching mucosal barriers or altering the host9s immune response. While this topic has been studied in detail for respiratory viral infections facilitating bacterial superinfections, the reverse order is less well understood. In order to investigate how the presence of bacteria affects a secondary viral infection, bronchial epithelial cells (BEAS-2B) were exposed to heat-inactivated (hi) suspensions of nontypeable H. influenzae (NTHI), Pseudomonas aeruginosa or Streptococcus pneumoniae and subsequently infected with Respiratory Syncytial Virus (RSV). Response to infection was measured by monitoring cytokine release and viral replication. Exposure to bacteria and viral infection independently caused the release of the inflammatory cytokines IL-6 and IL-8 by BEAS-2B cells. When cells were first exposed to hi-NTHI and then infected with RSV, release of both cytokines was synergistically enhanced. Seventy-two hours after viral infection, measured cytokine levels exceeded a purely additive effect of the individual pathogens by 120% (IL-6) and 150% (IL-8), respectively. This exaggerated response was not linked to viral replication and was to such extent only seen for hi-NTHI but none of the other pathogens. Our data suggest that bacteria can contribute to the severity of secondary viral infections in a pathogen-specific manner. Considering the substantial proportion of patients with chronic lung diseases whose lungs are colonized with bacteria, it seems likely that such colonization can affect their susceptibility and response to secondary viral infections.
Scaling Up the 2010 World Health Organization HIV Treatment Guidelines in Resource-Limited Settings: A Model-Based Analysis
Authors: Rochelle P. Walensky, Robin Wood, Andrea L. Ciaranello, A. David Paltiel, Sarah B. Lorenzana, Xavier Anglaret, Adam W. Stoler, Kenneth A. Freedberg
Journal: PLoS Medicine (2010)

Background The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4<350 cells/µl instead of CD4<200 cells/µl), multiple sequential ART regimens, and replacement of first-line stavudine with tenofovir. This paper considers what to do first in resource-limited settings where immediate implementation of all of the WHO recommendations is not feasible. Methods and Findings We use a mathematical model and local input data to project clinical and economic outcomes in a South African HIV-infected cohort (mean age = 32.8 y, mean CD4 = 375/µl). For the reference strategy, we assume that all patients initiate stavudine-based ART with WHO stage III/IV disease and receive one line of ART (stavudine/WHO/one-line). We rank—in survival, cost-effectiveness, and equity terms—all 12 possible combinations of the following: (1) stavudine replacement with tenofovir, (2) ART initiation (by WHO stage, CD4<200 cells/µl, or CD4<350 cells/µl), and (3) one or two regimens, or lines, of available ART. Projected life expectancy for the reference strategy is 99.0 mo. Considering each of the guideline components separately, 5-y survival is maximized with ART initiation at CD4<350 cells/µl (stavudine/<350/µl/one-line, 87% survival) compared with stavudine/WHO/two-lines (66%) and tenofovir/WHO/one-line (66%). The greatest life expectancies are achieved via the following stepwise programmatic additions: stavudine/<350/µl/one-line (124.3 mo), stavudine/<350/µl/two-lines (177.6 mo), and tenofovir/<350/µl/two-lines (193.6 mo). Three program combinations are economically efficient: stavudine/<350/µl/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS]), tenofovir/<350/µl/one-line (US$1,140/YLS), and tenofovir/<350/µl/two-lines (US$2,370/YLS). Conclusions In settings where immediate implementation of all of the new WHO treatment guidelines is not feasible, ART initiation at CD4<350 cells/µl provides the greatest short- and long-term survival advantage and is highly cost-effective. Please see later in the article for the Editors' Summary