tbuckley/cabot-search huggingface dataset:
Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep
Authors: KYLE C. ELROD, WILLIAM R. MOORE, WILLIAM M. ABRAHAM, RICHARD D. TANAKA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. Lactoferrin, a cationic protein released from activated neutrophils, binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor of tryptase and found that it is both a potent (Ki' is 24 nM) and selective inhibitor. Size exclusion chromatography studies revealed that lactoferrin disrupted the quaternary structure of active tryptase. Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.
Overexpression of heat shock protein 27 protects against ischaemia/reperfusion-induced cardiac dysfunction via stabilization of troponin I and T
Authors: Xi-Yuan Lu, Le Chen, Xiao-Long Cai, Huang-Tian Yang
Journal: Cardiovascular Research (2008)

Heat shock protein 27 (Hsp27) renders cardioprotection from ischaemia/reperfusion (I/R) injury, but little is known about its role in myofilaments. We proposed that increased expression of Hsp27 may improve post-ischaemic contractile dysfunction by preventing I/R-induced cardiac troponin I (cTnI) and troponin T (cTnT) degradation. Adenovirus-mediated Hsp27 overexpression improved contractile function in perfused rat hearts subjected to global no-flow I/R (30-min/30-min). Such improvement was further confirmed in Hsp27-overexpressing cardiomyocytes subjected to simulated I/R (20-min/30-min). Moreover, these cells showed restored myofilament response to Ca2+ but not intracellular Ca2+ transients. The protection correlated with attenuation of I/R-induced cTnI and cTnT degradation. Confocal microscopy revealed co-localization of Hsp27 with these proteins. Co-immunoprecipitation and pull-down assays further confirmed that Hsp27 interacted with the COOH-terminus of cTnI and the NH2-terminus of cTnT and that Hsp27 overexpression decreased the interaction between μ-calpain (a protease mediating proteolysis of cTnI and cTnT) and cTnI or cTnT under I/R. The findings reveal a novel role of Hsp27 in the protection of cTnI and cTnT from I/R-induced degradation by preventing their proteolytic cleavage via interacting with these proteins. Such protection may result in restored post-ischaemic myofilament response to Ca2+ and improved post-ischaemic contractile function.
Prospective Study of the Accuracy of <i>EGFR</i> Mutational Analysis by High-Resolution Melting Analysis in Small Samples Obtained from Patients with Non–Small Cell Lung Cancer
Authors: Tomoya Fukui, Yuichiro Ohe, Koji Tsuta, Koh Furuta, Hiromi Sakamoto, Toshimi Takano, Hiroshi Nokihara, Noboru Yamamoto, Ikuo Sekine, Hideo Kunitoh, Hisao Asamura, Takaaki Tsuchida, Masahiro Kaneko, Masahiko Kusumoto, Seiichiro Yamamoto, Teruhiko Yoshida, Tomohide Tamura
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Epidermal growth factor receptor (EGFR) mutations, especially in-frame deletions in exon 19 (DEL) and a point mutation in exon 21 (L858R), predict gefitinib sensitivity in patients with non–small cell lung cancer (NSCLC). In this study, we verified the accuracy of EGFR mutation analysis in small samples by high-resolution melting analysis (HRMA), which is a rapid method using PCR amplification with a dye to analyze the melting curves in NSCLC. Experimental Design: We designed a prospective study to compare the sensitivity and specificity of HRMA and DNA sequencing with laser capture microdissection. Eligible patients with lung lesions were screened by bronchoscopy or percutaneous needle biopsy to histologically confirm the diagnosis, followed by surgical resection of the NSCLC. Small diagnostic specimens were analyzed for EGFR mutations by HRMA, and the surgically resected specimens were examined for mutations by HRMA and DNA sequencing. Results: The analyses for EGFR mutations were conducted in 52 eligible cases of the 92 enrolled patients. EGFR mutations were detected in 18 (34.6%) patients. The results of HRMA from surgically resected specimens as well as DNA sequencing revealed 100% sensitivity and specificity. On the other hand, the sensitivity and specificity of HRMA from the small diagnostic specimens were 83.3% and 100%, respectively. Conclusions: In this study, we showed that HRMA is a highly accurate method for detecting DEL and L858R mutations in patients with NSCLC, although it is necessary to consider the identification of patients with a false-negative result when the analysis is conducted using small samples.
Neural Substrates of Treatment Response to Cognitive-Behavioral Therapy in Panic Disorder With Agoraphobia
Authors: Ulrike Lueken, Benjamin Straube, Carsten Konrad, Hans-Ulrich Wittchen, Andreas Ströhle, André Wittmann, Bettina Pfleiderer, Christina Uhlmann, Volker Arolt, Andreas Jansen, Tilo Kircher
Journal: American Journal of Psychiatry (2013)

Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia.Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores.At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time.This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.
Prognostic impact of tumor-specific HMG-CoA reductase expression in primary breast cancer.
Authors: S Borgquist, A Jögi, F Pontén, L Ryden, D Brennan, K Jirström
Journal: Cancer Research (2009)

Abstract Abstract #5071 Background&amp;#x2028; We have previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up.&amp;#x2028; Methods &amp;#x2028; The expression of HMG-CoAR was assessed by immunohistochemistry (IHC) on tissue microarrays with tumour specimens from 498 consecutive breast cancer cases with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free and breast cancer specific survival.&amp;#x2028; Results &amp;#x2028; In line with our previous findings, tumour-specific HMG-CoAR expression was associated with, low grade (p &amp;lt;0.001), small (p = 0.007), ERα positive (p =0.01), Ki-67 negative (p =0.02) tumors. Patients with tumours expressing HMG-CoAR, had a significantly prolonged disease-free-survival, also when adjusted for established prognostic factors; RR= 0.60, 95% CI (0.40-0.92); p=0.02. In estrogen receptor negative tumours, however, there was a trend, however non-significant, towards a shorter DFS in HMG-CoAR expressing tumours.&amp;#x2028; Conclusion&amp;#x2028; HMG-CoAR expression is an independent predictor of a prolonged disease-free-survival in primary breast cancer. This may, however, not be true for ERα negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5071.
Cocaine use rises markedly among 16-29 year olds
Authors: R. Watson
Journal: BMJ (2002)

Cocaine use among young adults in Britain is expanding faster than anywhere else in Europe, according to a new report.

The annual report from the Lisbon based European Monitoring Centre for Drugs and Drug Addiction, giving figures for 2000, shows that 5% of people in England and Wales between the ages of 16 and 29 took the drug at some point during the previous 12 months—compared with 1% in 1996.

“Overall, the drug situation in the United Kingdom is very stable, but we have seen a sharp increase in the use of cocaine as it becomes more acceptable on the recreational scene,” said Mike Trace, the United Kingdom's former deputy drugs “tsar” who now chairs the …
Calcium-Mediated Mechanisms in Chemically Induced Cell Death
Authors: Pierluigi Nicotera, Giorgio Bellomo, Sten Orrenius
Journal: The Annual Review of Pharmacology and Toxicology (1992)

Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, ...Read More
Stereophotogrammetry and relief photography in the assessment of foot disorders.
Authors: A D Craxford, A Rutherford, M S Evans, C Park
Journal: Annals of the Rheumatic Diseases (1981)

Expanded polyethylene foam (Plastazote) is used in the treatment of rheumatoid, diabetic, and leprotic foot disorders. This paper describes a diagnostic use for this material. Two photographic techniques combine to give vivid and quantitative representations of foot deformities which are easily applicable to clinical use. Relief photography uses illumination to create an illusion of solidity in a 2-dimensional photography. Stereophotogrammetry produces contour plots from stereopairs of photographs of the Plastazote footprint. After use the impressions are trimmed and slipped into the patient's shoes in the same way as any other foam insole.
Fetal hemoglobin reactivation in baboon and man: A short perspective
Authors: Donald Lavelle, Joseph Desimone, Paul Heller
Journal: American Journal of Hematology (1993)

Abstract Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5‐azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating γ‐chain synthesis. © 1993 Wiley‐Liss, Inc.
Smooth muscle cell phenotypic switching in atherosclerosis
Authors: D. Gomez, G. K. Owens
Journal: Cardiovascular Research (2012)

Smooth muscle cells (SMCs) possess remarkable phenotypic plasticity that allows rapid adaptation to fluctuating environmental cues, including during development and progression of vascular diseases such as atherosclerosis. Although much is known regarding factors and mechanisms that control SMC phenotypic plasticity in cultured cells, our knowledge of the mechanisms controlling SMC phenotypic switching in vivo is far from complete. Indeed, the lack of definitive SMC lineage-tracing studies in the context of atherosclerosis, and difficulties in identifying phenotypically modulated SMCs within lesions that have down-regulated typical SMC marker genes, and/or activated expression of markers of alternative cell types including macrophages, raise major questions regarding the contributions of SMCs at all stages of atherogenesis. The goal of this review is to rigorously evaluate the current state of our knowledge regarding possible phenotypes exhibited by SMCs within atherosclerotic lesions and the factors and mechanisms that may control these phenotypic transitions.
THE TREATMENT OF UTERINE FIBROIDS BY X RAYS
Authors: J. D. Harris
Journal: BMJ (1919)

TREATMENT -F UY t 14Ef FIIOIDS BY X' RAYS- Local bulging was present in nine aes) and--when present was a valuable-qign.Whenz the bulging is lateral it is seen best by arranging the patient strsaht in his bed in a good light, and observing from the foot of the bed.In a few cases the bulging was forwards.Epigastric varicosity was not present in any case.Lung complications were present in 13 cases.In 12 they were confined to the right -base and afforaed a dia- gnostic sign of value.The signs observed were: Basal crepitations in 7 cases; basal pneumonia in 4 cases; pleuritic friction sound in 3 cases.In one case from which 5 oz. of pus had been withdrawn, an abscess (probably a second one) burst into the base of the right lung five days later.Ten ounces of brownish pus were coughed up in twenty-four hours, the expectoration became bile-stained on the third day, gradually diminished, and the patient made a good recovery.Decubitus.-Nocharacteristic position was observed.Leucocytosis.-Infourteen of these cases a white blood count was made, and a polymorphonuclear leucocytosis was found in every case.The average white count was 18,600.Rigidity of the right rectus abdominis was observed in about half the cases.From the above analysis it will be seen that there were seven outstanding diagnostic signs present in this series:
Addressing overdiagnosis and overtreatment in cancer: a prescription for change
Authors: Laura J Esserman, Ian M Thompson, Brian Reid, Peter Nelson, David F Ransohoff, H Gilbert Welch, Shelley Hwang, Donald A Berry, Kenneth W Kinzler, William C Black, Mina Bissell, Howard Parnes, Sudhir Srivastava
Journal: The Lancet Oncology (2014)
Do fish oils prevent restenosis after coronary angioplasty?
Authors: A Leaf, M B Jorgensen, A K Jacobs, G Cote, D A Schoenfeld, J Scheer, B H Weiner, J D Slack, M A Kellett, A E Raizner
Journal: Circulation (1994)

BACKGROUND The omega-3 polyunsaturated fatty acids derived from fish oils have been shown to modulate many factors believed to affect the pathogenesis of atherosclerosis. Because certain features of restenosis following angioplasty mimic some of the early changes of atherogenesis, some researchers have suggested that fish oil might prevent restenosis following angioplasty. We report the effects of omega-3 fatty acids on the rate of restenosis following percutaneous intraluminal coronary angioplasty (PTCA). METHODS AND RESULTS From August 1989 through September 1992, 551 patients were randomized to start receiving a daily dietary supplement of ten 1.0-g capsules containing 80.6% ethyl esters of omega-3 fatty acids providing 4.1 g eicosapentaenoic acid (EPA) and 2.8 g docosahexaenoic acid (DHA) for 6 months or an equal amount of an ethyl ester of corn oil. Four hundred seventy subjects who were well matched for risk factors completed successful angioplasty of one or multiple lesions in native coronary vessels and constituted the study cohort, of whom 447 were evaluable at 6 months after PTCA. The criteria for restenosis were that the quantitative coronary angiography at 6 months show a &gt; 30% increase in narrowing at the stenosis site or loss of at least half of the gain achieved at the time of PTCA and final restenosis with &lt; 50% luminal diameter remaining. In 93% of the patients, the end point was determined by angiography and in all except 1% of these by quantitative coronary angiography. Compliance with the fish oil supplement was good as judged by incorporation of EPA and DHA in plasma and red blood cell phospholipids. The restenosis rate among analyzable patients was 46% for corn oil and 52% for fish oil (P = .37). The addition of 200 mg alpha-tocopherol for all subjects during the study had no effect on restenosis rates. CONCLUSIONS This was the largest of such trials to date, and a supplement of 8 g/d of omega-3 fatty acids failed to prevent the usual high rate of restenosis after PTCA. No adverse effects were attributable to this large daily supplement of omega-3 fatty acids.
Recognition of the Class Ib Molecule Qa-1b by Putative Activating Receptors Cd94/Nkg2c and Cd94/Nkg2e on Mouse Natural Killer Cells
Authors: Russell E. Vance, Amanda M. Jamieson, David H. Raulet
Journal: The Journal of Experimental Medicine (1999)

The heterodimeric CD94/NKG2A receptor, expressed by mouse natural killer (NK) cells, transduces inhibitory signals upon recognition of its ligand, Qa-1b, a nonclassical major histocompatibility complex class Ib molecule. Here we clone and express two additional receptors, CD94/NKG2C and CD94/NKG2E, which we show also bind to Qa-1b. Within their extracellular carbohydrate recognition domains, NKG2C and NKG2E share extensive homology with NKG2A (93–95% amino acid similarity); however, NKG2C/E receptors differ from NKG2A in their cytoplasmic domains (only 33% similarity) and contain features that suggest that CD94/NKG2C and CD94/NKG2E may be activating receptors. We employ a novel blocking anti-NKG2 monoclonal antibody to provide the first direct evidence that CD94/NKG2 molecules are the only Qa-1b receptors on NK cells. Molecular analysis reveals that NKG2C and NKG2E messages are extensively alternatively spliced and ∼20-fold less abundant than NKG2A message in NK cells. The organization of the mouse Cd94/Nkg2 gene cluster, presented here, shows striking similarity with that of the human, arguing that the entire CD94/NKG2 receptor system is relatively primitive in origin. Analysis of synonymous substitution frequencies suggests that within a species, NKG2 genes may maintain similarities with each other by concerted evolution, possibly involving gene conversion–like events. These findings have implications for understanding NK cells and also raise new possibilities for the role of Qa-1 in immune responses.
Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease
Authors: David A van Heel, Subrata Ghosh, Matt Butler, Karen A Hunt, Anna MC Lundberg, Tariq Ahmad, Dermot PB McGovern, Clive Onnie, Kenichi Negoro, Sue Goldthorpe, Brian MJ Foxwell, Christopher G Mathew, Alastair Forbes, Derek P Jewell, Raymond J Playford
Journal: The Lancet (2005)
Feeding the inflamed pancreas
Authors: C R PENNINGTON
Journal: Gut (1998)

See article on page 431 

There is a renewed awareness of the detrimental impact of undernutrition on organ function and clinical outcome. There is also evidence that in some clinical circumstances nutritional support will reverse nutritional depletion and improve recovery.1Nutritional recovery may not be achieved in the metabolically stressed patient.2 The effects of nutritional depletion occur early,3 and subsequent recovery may be prolonged in the severely depleted patient.4 Thus, there is emphasis on early nutritional intervention to prevent or retard the development of malnutrition in patients who are unable to eat or absorb an adequate oral diet. The British Society of Gastroenterology guidelines suggest that such patients should not be deprived of nutrition for more than seven days, and that nutritional support should be considered earlier in patients who are already malnourished or who are metabolically stressed.5 The conventional management of patients with acute pancreatitis includes parenteral nutrition, which is instituted early in the course of the illness, partly because of the frequently associated ileus, and partly for fear of the consequences of stimulating pancreatic function by oral …
Memantine for patients with Parkinson's disease dementia or dementia with Lewy bodies: a randomised, double-blind, placebo-controlled trial
Authors: Murat Emre, Magda Tsolaki, Ubaldo Bonuccelli, Alain Destée, Eduardo Tolosa, Alexandra Kutzelnigg, Andrés Ceballos-Baumann, Slobodan Zdravkovic, Anna Bladström, Roy Jones
Journal: The Lancet Neurology (2010)