tbuckley/cabot-search huggingface dataset:
Closed-Loop Control of Respiratory Drive Using Pressure-Support Ventilation
Authors: Jadranka Spahija, Jennifer Beck, Michel de Marchie, Alain Comtois, Christer Sinderby
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

By using diaphragm electrical activity (multiple-array esophageal electrode) as an index of respiratory drive, and allowing such activity above or below a preset target range to indicate an increased or reduced demand for ventilatory assistance (target drive ventilation), we evaluated whether the level of pressure-support ventilation can be automatically adjusted in response to exercise-induced changes in ventilatory demand. Eleven healthy individuals breathed through a circuit (18 cm H2O/L/second inspiratory resistance at 1 L/second flow; 0.5-1.0 L/second expiratory flow limitation) connected to a modified ventilator. Subjects breathed for 6-minute periods at rest and during 20 and 40 W of bicycle exercise, with and without target drive ventilation (the target was set to 60% of the increase in diaphragm electrical activity observed between rest and 20 W of unassisted exercise). With target drive ventilation during exercise, the level of pressure-support ventilation was automatically increased, reaching 13.3 +/- 4.0 and 20.3 +/- 2.8 cm H2O during 20- and 40-W exercise, respectively, whereas diaphragm electrical activity was reduced to a level within the target range. Both diaphragmatic pressure-time product and end-tidal CO2 were significantly reduced with target drive ventilation at the end of the 20- (p < 0.01) and 40-W (p < 0.001) exercise periods. Minute ventilation was not altered. These results demonstrate that target drive ventilation can automatically adjust pressure-support ventilation, maintaining a constant neural drive and compensating for changes in respiratory demand.
Association of Varying Number of Doses of Quadrivalent Human Papillomavirus Vaccine With Incidence of Condyloma
Authors: Eva Herweijer, Amy Leval, Alexander Ploner, Sandra Eloranta, Julia Fridman Simard, Joakim Dillner, Eva Netterlid, Pär Sparén, Lisen Arnheim-Dahlström
Journal: JAMA (2014)

Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine.To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting.An open cohort of all females aged 10 to 24 years living in Sweden (n = 1,045,165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers.Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting.A total of 20,383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100,000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100,000 person-years.Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.
A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer
Authors: S.M. Tolaney, J. Najita, J. Sperinde, W. Huang, W.Y. Chen, J. Savoie, M. Fornier, E.P. Winer, C. Bunnell, I.E. Krop
Journal: Annals of Oncology (2013)
New therapeutic avenues in ulcerative colitis: thinking out of the box
Authors: Joana Torres, Silvio Danese, Jean-Frédéric Colombel
Journal: Gut (2013)

<h3>BACKGROUND AND PURPOSE:</h3> There is growing evidence of leakage of gadolinium in an impaired blood-retina barrier. We investigated gadolinium enhancement in different eye compartments and correlated the enhancement with specific ophthalmologic diseases. <h3>MATERIALS AND METHODS:</h3> In a prospective clinical study (ClinicalTrials.gov Identifier: NCT05035251), 95 patients (63 with and 32 without ophthalmologic disease) were examined before and after gadolinium administration (20 and 120 minutes) with heavily T2-weighted FLAIR. The cohort was divided according to the location of pathology into anterior and posterior eye compartment groups. Relative signal intensity increase in the anterior eye chamber, vitreous body with retina, optic nerve sheath, and the Meckel cave was analyzed and correlated with the final clinical diagnosis. <h3>RESULTS:</h3> In patients with a disorder in the anterior eye compartment, significant signal intensity increases were found in the central anterior eye chamber (<i>P</i> 20 minutes = .000, <i>P</i> 120 minutes = .000), lateral anterior eye chamber (<i>P</i> 20 minutes = .001, <i>P</i> 120 minutes = .005), and vitreous body with retina (<i>P</i> 20 minutes = .02) compared with the control group. Patients with pathologies in the posterior eye compartment showed higher signal intensity levels in the central anterior eye compartment (<i>P</i> 20 minutes = .041) and vitreous body with retina (<i>P</i> 120 minutes = .006). <h3>CONCLUSIONS:</h3> Increased gadolinium enhancement was found in the central and lateral anterior eye compartments and the vitreous body with retina in patients with anterior eye compartment disorders 20 and 120 minutes after contrast application, suggesting impairment of the blood-aqueous barrier. In patients with a disorder in the posterior eye compartment, pathologic enhancement indicated disruption of the blood-retinal barrier that allows gadolinium to diffuse into the vitreous body with retina from posterior to anterior, opposite to the known physiologic glymphatic pathway.
Elevated Levels of Plasma C-Reactive Protein Are Associated With Decreased Graft Survival in Cardiac Transplant Recipients
Authors: Marc S. Eisenberg, Hong Jun Chen, Mark K. Warshofsky, Robert R. Sciacca, Hal S. Wasserman, Allan Schwartz, LeRoy E. Rabbani
Journal: Circulation (2000)

Inflammation may be involved in the origin of transplant coronary artery disease. We hypothesized that plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6), markers for systemic inflammation, would correlate with cardiac transplant graft survival.We studied 99 consecutive cardiac transplant recipients who were referred for routine endomyocardial biopsy and/or surveillance coronary angiography. Plasma levels of CRP and IL-6 were measured by their respective ELISAs. Patients were divided into 2 groups: those who died or required retransplantation and those who survived without the need for retransplantation. During the follow-up period of 5.0+/-2.7 years (range, 0.2 to 15.1 years) after transplant, 20 patients died and 9 required retransplantation. There was no significant difference in age, race, sex, cause of native myopathy, presence of diabetes, or use of aspirin, statins, or calcium channel blockers between the 2 groups. Although IL-6 did not relate to graft failure, CRP level was predictive of allograft failure (P:=0.003). The risk of allograft failure increased 36% for every 2-fold increase in CRP level. Moreover, CRP levels also correlated significantly with the frequency of grade 3 rejection (P:=0.02). In multivariate analysis, when combined with other significant predictors such as donor age and sex mismatching of the graft, CRP still significantly predicted graft failure (P:=0.025) with a 32% increase in the risk of graft failure for every 2-fold increase in CRP level.These findings suggest that elevated plasma levels of CRP are associated with subsequent allograft failure in cardiac transplant recipients.
Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay.
Authors: M J Bevan
Journal: The Journal of Experimental Medicine (1976)

Cytotoxic effector T cells of F1 (BALB/c X BALB.B) (H-2d/b) mice immunized against the minor histocompatibility differences of C57BL/10 (H-2b) can lyse targets from C57BL/10, but cannot lyse B10.D2 (H-2d) targets. Despite this lack of cross-reaction in the cytotoxic assay, C57BL/10 cells do prime F1 (BALB/c X BALB.B) mice for a secondary cytotoxic response to B10.D2. C57BL/10-primed, B10.D2-boosted cytotoxic cells lyse B10.D2 targets but not C57BL/10 targets. DBA/2 (H-2d) spleen cells or thymocytes prime F1 mice for a secondary response to DBA/2, B10.D2, and C57BL/10 cells, but DBA/2 mastocytes, P815, do not prime for a response to C57BL/10. Whether H-2 congenic lymphoid cells express minor histocompatibility determinants which cross-react at the cytotoxic T-cell level or the helper T-cell level is discussed.
Reperfusion-Induced Translocation of δPKC to Cardiac Mitochondria Prevents Pyruvate Dehydrogenase Reactivation
Authors: Eric N. Churchill, Christopher L. Murriel, Che-Hong Chen, Daria Mochly-Rosen, Luke I. Szweda
Journal: Circulation Research (2005)

Cardiac ischemia and reperfusion are associated with loss in the activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH). Pharmacological stimulation of PDH activity improves recovery in contractile function during reperfusion. Signaling mechanisms that control inhibition and reactivation of PDH during reperfusion were therefore investigated. Using an isolated rat heart model, we observed ischemia-induced PDH inhibition with only partial recovery evident on reperfusion. Translocation of the redox-sensitive δ-isoform of protein kinase C (PKC) to the mitochondria occurred during reperfusion. Inhibition of this process resulted in full recovery of PDH activity. Infusion of the δPKC activator H 2 O 2 during normoxic perfusion, to mimic one aspect of cardiac reperfusion, resulted in loss in PDH activity that was largely attributable to translocation of δPKC to the mitochondria. Evidence indicates that reperfusion-induced translocation of δPKC is associated with phosphorylation of the αE1 subunit of PDH. A potential mechanism is provided by in vitro data demonstrating that δPKC specifically interacts with and phosphorylates pyruvate dehydrogenase kinase (PDK)2. Importantly, this results in activation of PDK2, an enzyme capable of phosphorylating and inhibiting PDH. Thus, translocation of δPKC to the mitochondria during reperfusion likely results in activation of PDK2 and phosphorylation-dependent inhibition of PDH.
Proinflammatory S100A12 Can Activate Human Monocytes via Toll-like Receptor 4
Authors: Dirk Foell, Helmut Wittkowski, Christoph Kessel, Aloys Lüken, Toni Weinhage, Georg Varga, Thomas Vogl, Timo Wirth, Dorothee Viemann, Per Björk, Marieke A. D. van Zoelen, Faekah Gohar, Geetha Srikrishna, Matthias Kraft, Johannes Roth
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

S100A12 is overexpressed during inflammation and is a marker of inflammatory disease. Furthermore, it has been ascribed to the group of damage-associated molecular pattern molecules that promote inflammation. However, the exact role of human S100A12 during early steps of immune activation and sepsis is only partially described thus far.We analyzed the activation of human monocytes by granulocyte-derived S100A12 as a key function of early inflammatory processes and the development of sepsis.Circulating S100A12 was determined in patients with sepsis and in healthy subjects with experimental endotoxemia. The release of human S100A12 from granulocytes as well as the promotion of inflammation by activation of human monocytes after specific receptor interaction was investigated by a series of in vitro experiments.S100A12 rises during sepsis, and its expression and release from granulocytes is rapidly induced in vitro and in vivo by inflammatory challenge. A global gene expression analysis of S100A12-activated monocytes revealed that human S100A12 induces inflammatory gene expression. These effects are triggered by an interaction of S100A12 with Toll-like receptor 4 (TLR4). Blocking S100A12 binding to TLR4 on monocytes or TLR4 expressing cell lines (HEK-TCM) abrogates the respective inflammatory signal. On the contrary, blocking S100A12 binding to its second proposed receptor (receptor for advanced glycation end products [RAGE]) has no significant effect on inflammatory signaling in monocytes and RAGE-expressing HEK293 cells.Human S100A12 is an endogenous TLR4 ligand that induces monocyte activation, thereby acting as an amplifier of innate immunity during early inflammation and the development of sepsis.
LONG CHAIN FORMATION BY STRAINS OF GROUP A STREPTOCOCCI IN THE PRESENCE OF HOMOLOGOUS ANTISERUM: A TYPE-SPECIFIC REACTION
Authors: Gene H. Stollerman, Richard Ekstedt
Journal: The Journal of Experimental Medicine (1957)

Strains of group A streptococci, types 30 and 12, were observed to grow in extremely long chains in liquid media to which homologous antiserum was added. Addition to the media of antisera to heterologous types of streptococci failed to produce long chain growth. The long chain effect was destroyed by absorption of the antiserum with organisms of homologous type but was unaffected by absorption with organisms of heterologous types. The reaction disappeared at concentrations of antisera smaller than 0.25 per cent and was independent of complement or other heat-labile serum factors. Addition of trypsin to the culture to remove M protein from cells prevented long chain formation. The long chain effect depended upon the constant presence of antibody to the media. In its absence, the organisms promptly reverted to short chain growth. The phenomenon appears to have general applicability to those strains rich in M protein with only an occasional strain not responding as described. Further studies are in progress to determine the cause of this atypical response. The applicability of this phenomenon in detecting type-specific antibody using indicator strains of a variety of streptococcal types is discussed.
Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens
Authors: Sarah L. Jongbloed, Andrew J. Kassianos, Kylie J. McDonald, Georgina J. Clark, Xinsheng Ju, Catherine E. Angel, Chun-Jen J. Chen, P. Rod Dunbar, Robert B. Wadley, Varinder Jeet, Annelie J.E. Vulink, Derek N.J. Hart, Kristen J. Radford
Journal: The Journal of Experimental Medicine (2010)

The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-β, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)–activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C–activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8α+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
Evaluation of the National Comprehensive Cancer Network and American Urological Association Renal Cell Carcinoma Surveillance Guidelines
Authors: Suzanne B. Stewart, R. Houston Thompson, Sarah P. Psutka, John C. Cheville, Christine M. Lohse, Stephen A. Boorjian, Bradley C. Leibovich
Journal: Journal of Clinical Oncology (2014)

Purpose The National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) provide guidelines for surveillance after surgery for renal cell carcinoma (RCC). Herein, we assess the ability of the guidelines to capture RCC recurrences and determine the duration of surveillance required to capture 90%, 95%, and 100% of recurrences. Patients and Methods We evaluated 3,651 patients who underwent surgery for M0 RCC between 1970 and 2008. Patients were stratified as AUA low risk (pT1Nx-0) after partial (LR-partial) or radical nephrectomy (LR-radical) or as moderate/high risk (M/HR; pT2-4Nx-0/pTanyN1). Guidelines were assessed by calculating the percentage of recurrences detected when following the 2013 and 2014 NCCN and AUA recommendations, and associated Medicare costs were compared. Results At a median follow-up of 9.0 years (interquartile range, 5.7 to 14.4 years), a total of 1,088 patients (29.8%) experienced a recurrence. Of these, 390 recurrences (35.9%) were detected using 2013 NCCN recommendations, 742 recurrences (68.2%) were detected using 2014 NCCN recommendations, and 728 recurrences (66.9%) were detected using AUA recommendations. All protocols missed the greatest amount of recurrences in the abdomen and among pT1Nx-0 patients. To capture 95% of recurrences, surveillance was required for 15 years for LR-partial, 21 years for LR-radical, and 14 years for M/HR patients. Medicare surveillance costs for one LR-partial patient were $1,228.79 using 2013 NCCN, $2,131.52 using 2014 NCCN, and $1,738.31 using AUA guidelines. However, if 95% of LR-partial recurrences were captured, costs would total $9,856.82. Conclusion If strictly followed, the 2014 NCCN and AUA guidelines will miss approximately one third of RCC recurrences. Improved surveillance algorithms, which balance patient benefits and health care costs, are needed.
Haplotype Structure and Divergence at Human and Chimpanzee Serotonin Transporter and Receptor Genes: Implications for Behavioral Disorder Association Analyses
Authors: K. G. Claw, R. Y. Tito, A. C. Stone, B. C. Verrelli
Journal: Molecular Biology and Evolution (2010)

Genetic variation in the human serotonin system has long-been studied because of its functional consequences and links to various behavior-related disorders and it being routinely targeted in research and development for drug therapy. However, aside from clinical studies, little is known about this genetic diversity and how it differs within and between human populations with respect to haplotype structure, which can greatly impact phenotype association studies. In addition, no evolutionary approach among humans and other primates has examined how long- and short-term selective pressures explain existing serotonin variation. Here, we examine DNA sequence variation in natural population samples of 192 human and 40 chimpanzee chromosome sequences for the most commonly implicated ∼38-kb serotonin transporter (SLC6A4) and ∼63-kb serotonin 2A receptor (HTR2A) genes. Our comparative population genetic analyses find significant linkage disequilibrium associated with functionally relevant variants in humans, as well as geographic variation for these haplotypes, at both loci. In addition, although amino acid divergence is consistent with purifying selection, promoter and untranslated regions exhibit significantly high divergence in both species lineages. These evolutionary analyses imply that the serotonin system may have accumulated significant regulatory variation over both recent and ancient periods of time in both humans and chimpanzees. We discuss the implications of this variation for disease association studies and for the evolution of behavior-related phenotypes during the divergence of humans and our closest primate relatives.
Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum.
Authors: L L Thomsen, J B Gavin, C Tasman-Jones
Journal: Gut (1990)

The spatial relations between bacteria and the affected tissues can indicate pathogenic mechanisms. This study was undertaken to define the spatial relation of Helicobacter pylori to the human gastric mucosa. Antibodies against gastric mucus and ruthenium red were used to stabilise the glycoprotein structure of the mucus and glycocalyces in antral biopsy specimens from eight patients infected with H pylori. The location of organisms and ultrastructural features were assessed using systematic scanning and transmission electron microscopy: 92 (2)% (mean (SE] of H pylori were in the pit mucus, and 7 (3)% were in the surface mucus; 60 (12)% of H pylori were close to epithelial cells, with only 5 (2)% located near the epithelial intercellular junctions. Fine filamentous strands extended between organisms and nearby epithelial cells, with few organisms in membrane to membrane contact. H pylori were not observed between, beneath, or within cells of the gastric mucosa. The preferred location of H pylori in the gastric antrum is within the pit mucus close to the epithelial cell surface, with no evidence that they have a direct toxic effect on the mucosa.