tbuckley/cabot-search huggingface dataset:
Water-clogging antibodies
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

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Antibodies from patients with neuromyelitis optica bind to the water channel aquaporin-4 (yellow) in brain tissue.Autoantibodies produced during a severe variant of multiple sclerosis (MS) latch on to water channels in the brain, according to Lennon and colleagues on 

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Incidence of <b> <i>BRAF</i> </b> Oncogene Mutation and Clinical Relevance for Primary Cutaneous Melanomas
Authors: Masaru Shinozaki, Akihide Fujimoto, Donald L. Morton, Dave S. B. Hoon
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of the study was to clarify the incidence of B-raf oncogene (BRAF) mutations in primary cutaneous melanomas, their relation to tumor progression, and effect on disease outcome. Somatic mutations of BRAF kinase, a component of the Ras-mitogen-activated protein/extracellular signal-regulated kinase kinase-mitogen-activated protein kinase pathway, are frequently reported (&amp;gt;65%) in nevi and malignant melanomas. Experimental Design: We assessed BRAF mutation frequency in exons 11 and 15 in primary (n = 59) and metastatic (n = 68) melanomas. Direct sequencing of PCR products was performed on DNA isolated and purified from microdissected tumors. Results: Eighteen mutations (31%) at exon 15 were detected in primary melanoma with a significantly (P = 0.001) higher frequency in patients &amp;lt; 60 years old. Incidence of BRAF mutation did not correlate with Breslow thickness. Presence of BRAF mutation of primary tumors did not effect overall disease-free survival. BRAF mutation frequency in metastatic lesions was 57% and significantly (P = 0.0024) higher than primary melanomas. Conclusions: The study suggests that BRAF mutation may be acquired during development of metastasis but is not a significant factor for primary tumor development and disease outcome.
Intravascular Photoacoustics for Image-Guidance and Temperature Monitoring During Plasmonic Photothermal Therapy of Atherosclerotic Plaques: A Feasibility Study
Authors: Doug Yeager, Yun-Sheng Chen, Silvio Litovsky, Stanislav Emelianov
Journal: Theranostics (2014)

Recently, combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging has been demonstrated as a novel imaging modality capable of visualizing both morphology (via IVUS) and cellular/molecular composition (via IVPA) of atherosclerotic plaques, using both endogenous tissue absorbers and exogenous contrast agents. Plasmonic gold nanoparticles were previously utilized as IVPA contrast agents which co-localize with atherosclerotic plaques, particularly phagocytically active macrophages. The present work demonstrates the use of IVUS/IVPA imaging as a tool for localized temperature monitoring during laser heating. The temperature dependent change in IVPA signal intensity of silica-coated gold nanorod contrast agents absorbing within the near-infrared optical wavelength range is evaluated and shown to have a linear relationship, with a slope greater than that of endogenous tissue. A continuous wave laser was subsequently incorporated into the IVUS/IVPA integrated catheter and utilized to selectively heat the nanoparticles with simultaneous IVPA temperature monitoring. IVUS/IVPA, therefore, provides a platform for detection and temperature monitoring of atherosclerotic plaques through the selective heating of plasmonic gold nanoparticle contrast agents.
Serial sputum cell counts in the management of chronic airflow limitation
Authors: K Parameswaran, MM Pizzichini, D Li, E Pizzichini, PK Jeffery, FE Hargreave
Journal: European Respiratory Journal (1998)

This case study illustrates the usefulness of serial induced sputum cell counts from cytospins to investigate the nature of airway inflammation in a patient presumed to have prednisone-dependent asthma for 30 yrs. She had bronchiectasis and chronic airflow limitation. Exacerbations of breathlessness were associated with an increase in chronic airflow limitation with little or no sputum. Induced sputum showed elevated total cell and neutrophil counts at each exacerbation with no increase in the proportion of eosinophils. Pathogenic bacteria were cultured at each flare-up. The dose of prednisone was reduced progressively and each exacerbation was treated with an appropriate antibiotic without increasing the dose of prednisone, as was the case previously. The infections were associated with bronchiectasis of the right upper lobe which was removed. Examination of the specimen confirmed neutrophilic infiltration and did not show the usual airway structural changes of asthma. These results provide further evidence of the value of sputum cell counts in practice, in this case to prevent overtreatment with prednisone in a patient with recurrent deteriorations in airflow which were due to recurrent infections.
Reflexive empathy: On predicting more than has ever been observed
Authors: Albert Bandura
Journal: Behavioral and Brain Sciences (2002)

A model positing that perception of another's affective state automatically generates matching emotional and instrumental responses predicts more than has ever been observed. Reflexive empathicness would produce emotional exhaustion, inhibitory strain, and debilitate everyday functioning. Self-regulation of empathic responses involves, not only reactive inhibition, but agentic proactive control. Pervasive inhumanities involve selective disengagement of empathic restraints through dissociative psychosocial mechanisms.
Effect of nitric oxide on oxygenation and mortality in acute lung injury: systematic review and meta-analysis
Authors: Neill K J Adhikari, Karen E A Burns, Jan O Friedrich, John T Granton, Deborah J Cook, Maureen O Meade
Journal: BMJ (2007)

To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS.Systematic review and meta-analysis.Medline, CINAHL, Embase, and CENTRAL (to October 2006), proceedings from four conferences, and additional information from authors of 10 trials.Two reviewers independently selected parallel group randomised controlled trials comparing nitric oxide with control and extracted data related to study methods, clinical and physiological outcomes, and adverse events.Mortality, duration of ventilation, oxygenation, pulmonary arterial pressure, adverse events.12 trials randomly assigning 1237 patients met inclusion criteria. Overall methodological quality was good. Using random effects models, we found no significant effect of nitric oxide on hospital mortality (risk ratio 1.10, 95% confidence interval 0.94 to 1.30), duration of ventilation, or ventilator-free days. On day one of treatment, nitric oxide increased the ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) (13%, 4% to 23%) and decreased the oxygenation index (14%, 2% to 25%). Some evidence suggested that improvements in oxygenation persisted until day four. There was no effect on mean pulmonary arterial pressure. Patients receiving nitric oxide had an increased risk of developing renal dysfunction (1.50, 1.11 to 2.02).Nitric oxide is associated with limited improvement in oxygenation in patients with ALI or ARDS but confers no mortality benefit and may cause harm. We do not recommend its routine use in these severely ill patients.
Relationship between bile acid malabsorption and pancreatic insufficiency in cystic fibrosis.
Authors: A M Weber, C C Roy, L Chartrand, G Lepage, O L Dufour, C L Morin, R Lasalle
Journal: Gut (1976)

Bile acid loss (mg/m2 24h) in the stools of 43 cystic fibrosis (CF) children with pancreatic insufficiency was 751-1 +/- 48-3, while that of six without clinical evidence of pancreatic disease (133-4 +/- 15-9) did not differ from values in 25 controls (109-8 +/- 9-8). There was a good correlation between the degree of bile acid (BA) and fat sequestration. Concomitant changes in bile acid and fat loss were observed in the one group of six patients studied on and off pancreatic enzymes as well as in a second group of seven children treated with pancreatic supplements and maintained on a normal diet followed by a low fat diet supplemented with medium chain triglycerides. Administration of NA bicarbonate led to a significant decrease in fat loss (15-8 +/- 2-7 leads to 10-3 +/- 1-9) without any simultaneous change in bile acid excretion (533-1 +/- 58-3 leads to 500-4 +/- 58-6). Qualitative bile acid patterns in controls, in infants after an ileal resection, and in patients with CF or with coeliac disease showed that the percentage of primary BA followed closely the total amount excreted except in situations where antibiotics were administered. The exact mechanism for the increased loss of BA in CF is unknown. It is found in all age groups and is related to the presence and degree of pancreatic insufficiency. The possibility that unhydrolysed triglycerides may interfere with the intestinal absorption of bile acid needs further confirmation.
Intrinsic Diurnal Variations in Cardiac Metabolism and Contractile Function
Authors: Martin E. Young, Peter Razeghi, Ari M. Cedars, Patrick H. Guthrie, Heinrich Taegtmeyer
Journal: Circulation Research (2001)

Diurnal variation of cardiac function in vivo has been attributed primarily to changes in factors such as sympathetic activity. No study has investigated previously the intrinsic properties of the heart throughout the day. We therefore investigated diurnal variations in metabolic flux and contractile function of the isolated working rat heart and how this related to circadian expression of metabolic genes. Contractile performance, carbohydrate oxidation, and oxygen consumption were greatest in the middle of the night, with little variation in fatty acid oxidation. The expression of all metabolic genes investigated (including regulators of carbohydrate utilization, fatty acid oxidation, and mitochondrial function) showed diurnal variation, with a general peak in the night. In contrast, pressure overload–induced cardiac hypertrophy completely abolished this diurnal variation of metabolic gene expression. Thus, over the course of the day, the normal heart anticipates, responds, and adapts to physiological alterations within its environment, a trait that is lost by the hypertrophied heart. We speculate that loss of plasticity of the hypertrophied heart may play a role in the subsequent development of contractile dysfunction.
Novel TOPK Inhibitor HI-TOPK-032 Effectively Suppresses Colon Cancer Growth
Authors: Dong Joon Kim, Yan Li, Kanamata Reddy, Mee-Hyun Lee, Myoung Ok Kim, Yong-Yeon Cho, Sung-Young Lee, Jong-Eun Kim, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2012)

The serine-threonine mitogen-activated protein kinase kinase family member T-LAK cell-originated protein kinase (TOPK/PBK) is heavily involved in tumor development, cancer growth, apoptosis, and inflammation. Despite the identification of TOPK as a promising novel therapeutic target, no inhibitor of TOPK has yet been reported. In this study, we screened 36 drug candidates using an in vitro kinase assay and identified the novel TOPK inhibitor HI-TOPK-032. In vitro, HI-TOPK-032 strongly suppressed TOPK kinase activity but had little effect on extracellular signal-regulated kinase 1 (ERK1), c-jun-NH2-kinase 1, or p38 kinase activities. HI-TOPK-032 also inhibited anchorage-dependent and -independent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer cell apoptosis through regulation of the abundance of p53, cleaved caspase-7, and cleaved PARP. In vivo, administration of HI-TOPK-032 suppressed tumor growth in a colon cancer xenograft model. Our findings therefore show that HI-TOPK-032 is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic against colorectal cancer.
Enhanced Ca <sup>2+</sup> -Activated Na <sup>+</sup> -Ca <sup>2+</sup> Exchange Activity in Canine Pacing-Induced Heart Failure
Authors: Ion A. Hobai, Brian O’Rourke
Journal: Circulation Research (2000)

Abstract —Defective excitation-contraction coupling in heart failure is generally associated with both a reduction in sarcoplasmic reticulum (SR) Ca 2+ uptake and a greater dependence on transsarcolemmal Na + -Ca 2+ exchange (NCX) for Ca 2+ removal. Although a relative increase in NCX is expected when SR function is impaired, few and contradictory studies have addressed whether there is an absolute increase in NCX activity. The present study examines in detail NCX density and function in left ventricular midmyocardial myocytes isolated from normal or tachycardic pacing–induced failing canine hearts. No change of NCX current density was evident in myocytes from failing hearts when intracellular Ca 2+ ([Ca 2+ ] i ) was buffered to 200 nmol/L. However, when [Ca 2+ ] i was minimally buffered with 50 μmol/L indo-1, Ca 2+ extrusion via NCX during caffeine application was doubled in failing versus normal cells. In other voltage-clamp experiments in which SR uptake was blocked with thapsigargin, both reverse-mode and forward-mode NCX currents and Ca 2+ transport were increased &gt;2-fold in failing cells. These results suggest that, in addition to a relative increase in NCX function as a consequence of defective SR Ca 2+ uptake, there is an absolute increase in NCX function that depends on [Ca 2+ ] i in the failing heart.
Iron in finger-nails and in the liver
Authors: L. L. CHANG, C. L. GOH, G. R. WADSWORTH
Journal: British Journal of Dermatology (1973)

The mean iron content of finger-nails of 113 apparently normal subjects was found to be 67.6 μg/g dry nail (±43.7). There was no age or sex variation. No relationship was found between the concentration of iron in finger-nails and that stored in the liver.
Keeping It Local: Evidence for Positive Selection in Swedish Arabidopsis thaliana
Authors: Christian D. Huber, Magnus Nordborg, Joachim Hermisson, Ines Hellmann
Journal: Molecular Biology and Evolution (2014)

Detecting positive selection in species with heterogeneous habitats and complex demography is notoriously difficult and prone to statistical biases. The model plant Arabidopsis thaliana exemplifies this problem: In spite of the large amounts of data, little evidence for classic selective sweeps has been found. Moreover, many aspects of the demography are unclear, which makes it hard to judge whether the few signals are indeed signs of selection, or false positives caused by demographic events. Here, we focus on Swedish A. thaliana and we find that the demography can be approximated as a two-population model. Careful analysis of the data shows that such a two island model is characterized by a very old split time that significantly predates the last glacial maximum followed by secondary contact with strong migration. We evaluate selection based on this demography and find that this secondary contact model strongly affects the power to detect sweeps. Moreover, it affects the power differently for northern Sweden (more false positives) as compared with southern Sweden (more false negatives). However, even when the demographic history is accounted for, sweep signals in northern Sweden are stronger than in southern Sweden, with little or no positional overlap. Further simulations including the complex demography and selection confirm that this is not compatible with global selection acting on both populations, and thus can be taken as evidence for local selection within subpopulations of Swedish A. thaliana. This study demonstrates the necessity of combining demographic analyses and sweep scans for the detection of selection, particularly when selection acts predominantly local.
P243 Duration and choice of antibiotics in hospital admitted community acquired pneumonia patients over a period of 5 years in NHS South East of Scotland
Authors: G. C. Choudhury, P. M. Mandal, A. A. Akram, A. S. Singanayagam, J. C. Chalmers, A. H. Hill
Journal: Thorax (2010)

<h3>Introduction</h3> <i>Clostridium difficile</i> infection is associated with class of antibiotics as well as the duration of treatment. The aim of this study was to ascertain if the rate of hospital related <i>Clostridium difficile</i> varied with the duration and choice of antibiotics in those admitted to hospital with Community Acquired Pneumonia (CAP) over a period of 5 years (2005–2009). <h3>Methods</h3> As a part of a prospective observational study of CAP in NHS Lothian, we investigated the duration and choice of antibiotics in hospital admitted CAP and the rate of <i>Clostridium difficile</i> infection in these patients over a period of 5 years (2005–2009). For multiple comparisons, we used the Kruskal–Wallis test for numerical data and Chi squared test for the categorical data. <h3>Results</h3> The duration and choice of antibiotics are tabulated in the Abstract P243 Table 1. The length of antibiotics used for severe CAP was therefore, longer than mild CAP. The duration of antibiotics for all severity of CAP, has not changed between 2005 and 2009. There has been a reducing usage of cephalosporins and macrolides with rising use of co-amoxiclav. The contribution of CAP as a cause for <i>Clostridium difficile</i>, however, remains unchanged. <h3>Conclusion</h3> In conclusion our study shows that the proportion of <i>Clostridium difficile</i> cases due to CAP has not changed in NHS Lothian between 2005 and 2009, despite significant reduction of cephalosporins and macrolide use. Randomised controlled trials are needed to assess whether reducing the length of treatment will influence <i>Clostridium difficile</i> rates.
The Effects of Work on the Pulmonary Circulation in Mitral Stenosis
Authors: HARALD ELIASCH, GEOFFREY WADE, LARS WERKÖ
Journal: Circulation (1952)

In an attempt to understand more fully the hemodynamic effects in mitral stenosis, the vascular response to effort was studied in 12 cases. It was found that pulmonary arterial pressures rose, but did not necessarily parallel changes in the pulmonary "capillary venous" pressure (pcv), suggesting that the response pattern may be modified by secondary pulmonary vascular change. Further, in some studies, pulmonary "capillary venous" pressures were found to rise initially and then fall despite continuing work, emphasizing the necessity to choose work of such a degree and duration that a steady state may be obtained.
Interleukin-15 and Its Receptor Augment Dendritic Cell Vaccination against the<i>neu</i>Oncogene through the Induction of Antibodies Partially Independent of CD4 Help
Authors: Jason C. Steel, Charmaine A. Ramlogan, Ping Yu, Yoshio Sakai, Guido Forni, Thomas A. Waldmann, John C. Morris
Journal: Cancer Research (2010)

Interleukin-15 (IL-15) stimulates the diffrentiation and proliferation of T, B, and natural killer cells; enhances CD8(+) cytolytic T-ceII activity; helps maintain CD44(hi)CD8(+) memory T cells; and stimulates immunoglobulin synthesis by B cells. IL-15 is trans-presented to effector cells by its receptor, IL-15Ralpha, expressed on dendritic cells (DC) and monocytes. We examined the antitumor effect of adenoviral-mediated gene transfer of IL-15 and IL-15Ralpha to augment a DC vaccine directed against the NEU (ErbB2) oncoprotein. Transgenic BALB-neuT mice vaccinated in late-stage tumor development with a DC vaccine expressing a truncated NEU antigen, IL-I5, and its receptor (DC(Ad.Neu+Ad_mIL-15+Ad.mlL-15Ralpha)) were protected from mammary carcinomas, with 70% of animals tumor-free at 30 weeks compared with none of the animals vaccinated with NEU alone (DC(Ad.Neu)). The combination of neu, IL-15, and IL-15Ralpha gene transfer leads to a significaintly greater anti-NEU antibody response compared with mice treated with DC(Ad.Neu) or DC(Ad.Neu) combined with either IL-15 (DC(Ad.Neu+Ad.mlL-15)) or lL-15Ralpha (DC(Ad.Neu+Ad.mlL-15Ralpha)). The antitumor effect was antibody mediated and involved modulation of NEU expression and signaIing. Depletion of CD4(+) cells did not abrogate the antitumor effect of the vaccine, nor did it inhibit the induction of anti-NEU aritibodies. Coexpression of IL-15 and IL-15Ralpha in an anticancer vaccine enhanced immune responses against the NEU antigen and may overcome impaired CD4(+) T-helper function.
Identification of a Crucial Energetic Footprint on the α1 Helix of Human Histocompatibility Leukocyte Antigen (Hla)-A2 That Provides Functional Interactions for Recognition by Tax Peptide/Hla-A2–Specific T Cell Receptors
Authors: Brian M. Baker, Richard V. Turner, Susan J. Gagnon, Don C. Wiley, William E. Biddison
Journal: The Journal of Experimental Medicine (2001)

Structural studies have shown that class I major histocompatibility complex (MHC)-restricted peptide-specific T cell receptor (TCR)-α/βs make multiple contacts with the α1 and α2 helices of the MHC, but it is unclear which or how many of these interactions contribute to functional binding. We have addressed this question by performing single amino acid mutagenesis of the 15 TCR contact sites on the human histocompatibility leukocyte antigen (HLA)-A2 molecule recognized by the A6 TCR specific for the Tax peptide presented by HLA-A2. The results demonstrate that mutagenesis of only three amino acids (R65, K66, and A69) that are clustered on the α1 helix affected T cell recognition of the Tax/HLA-A2 complex. At least one of these three mutants affected T cell recognition by every member of a large panel of Tax/HLA-A2–specific T cell lines. Biacore measurements showed that these three HLA-A2 mutations also altered A6 TCR binding kinetics, reducing binding affinity. These results show that for Tax/HLA-A2–specific TCRs, there is a location on the central portion of the α1 helix that provides interactions crucial to their function with the MHC molecule.
Loss of 14-3-3σ in Prostate Cancer and Its Precursors
Authors: Liang Cheng, Chong-Xian Pan, Jian-Ting Zhang, Shaobo Zhang, Michael S. Kinch, Lang Li, Lee Ann Baldridge, Christopher Wade, Zhiqiang Hu, Michael O. Koch, Thomas M. Ulbright, John N. Eble
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The 14-3-3 family proteins are highly conserved over many mammalian species. The σ isoform (also called HME-1 or stratifin) is expressed in epithelial cells. Loss of 14-3-3σ is associated with failure to arrest the cell cycle at the G2-M phase checkpoint after DNA damage that leads to increased G2-type chromosomal aberrations. The role of 14-3-3σ in prostatic carcinogenesis is uncertain. Experimental Design: We studied one hundred and eleven specimens of invasive prostate adenocarcinoma with paired, adjacent high-grade prostatic intraepithelial neoplasia and normal prostate epithelium. Immunohistochemistry was used to detect the expression of 14-3-3σ. The findings were correlated with various clinical pathological parameters. Results: 14-3-3σ is ubiquitously expressed at high levels in normal prostate epithelium. Its expression is significantly decreased in prostatic intraepithelial neoplasia and prostatic adenocarcinoma. Ninety percent of samples of prostatic intraepithelial neoplasia had no or low 14-3-3σ expression. Ninety-seven percent of invasive adenocarcinomas had no or low 14-3-3σ expression. In most specimens (90%), suppression of 14-3-3σ expression occurred during the development of prostatic intraepithelial neoplasia from normal epithelium. Conclusions: Our data suggest that loss of 14-3-3σ contributes to the development of prostate adenocarcinoma. 14-3-3σ expression is significantly decreased during the progression of normal prostatic epithelium to prostatic intraepithelial neoplasia and invasive cancer.