tbuckley/cabot-search huggingface dataset:
Dietary fat and asthma: is there a connection?
Authors: PN Black, S Sharpe
Journal: European Respiratory Journal (1997)

The last two decades have seen an increase in the prevalence of asthma, eczema, and allergic rhinitis in developed countries. This increase has been paralleled by a fall in the consumption of saturated fat and an increase in the amount of polyunsaturated fat in the diet. This is due to a reduction in the consumption of animal fat and an increase in the use of margarine and vegetable oils containing omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid. There is also evidence for a decrease in the consumption of oily fish which contain omega-3 PUFAs, such as eicosapentaenoic acid. In a number of countries, there are social class and regional differences in the prevalence of allergic disease, which are associated with differences in the consumption of PUFAs. Linoleic acid is a precursor of arachidonic acid, which can be converted to prostaglandin E2 (PGE2), whereas eicosapentaenoic acid inhibits the formation of PGE2. PGE2 acts on T-lymphocytes to reduce the formation of interferon-gamma (IFN-gamma) without affecting the formation of interleukin-4 (IL-4). This may lead to the development of allergic sensitization, since IL-4 promotes the synthesis of immunoglobulin E (IgE), whereas IFN-gamma has the opposite effect. Changes in the diet may explain the increase in the prevalence of asthma, eczema and allergic rhinitis. The effects of diet may be mediated through an increase in the synthesis of prostaglandin E2 which in turn can promote the formation of immunoglobulin E.
Social and Community Psychiatry
Authors: PETER SAINSBURY
Journal: American Journal of Psychiatry (1969)

The National Health Service was established at a time when psychiatry as a specialty was undergoing a period of rapid development and change. This coincidence, the author feels, has helped to determine not only the type of psychiatry practiced and the kinds of services established in Britain but the theoretical development of the field as well. He examines some of these effects in detail and concludes by describing a recent project to evaluate the social effects of a community psychiatric service.
Preventing injuries in water polo: have we scored?
Authors: M Mountjoy, A Junge
Journal: British Journal of Sports Medicine (2011)

Background Injury surveillance over time is the basis for the identification of injury trends and the development of injury prevention programs. Objective To analyse the injury trends in water polo over a 5 year period and evaluate injury prevention programs. Setting 2004 and 2008 Olympic Games and 2009 FINA World Championships. Participants All male and female water polo players participating in the tournaments. Methods New onset injuries were reported by the team physicians. Main outcome measurements Trends in injury incidence. Results The overall injury incidence in water polo has remained constant throughout the study period (OG 2004 20.1 per 1000 player matches; OG 2008 20.1 per 1000 player matches; and FINA 2009 19.3 per 1000 player matches). However, there have been significant differences in gender related injury incidence trends. Men's injury incidence has steadily decreased over the study period from a total of 27.6/1000 player matches in 2004 to 16.2/1000 player matches in 2008 and 14.9/1000 player matches in 2009. Women's injury incidence has shown an opposite trend over the study period (2004: 3.57/1000 player matches; 2008: 28.6/1000 player matches; and 2009: 23.8/1000 player matches). Conclusion The decrease in injury incidence in the men's game can possibly be attributed to the institution of an injury prevention program instituted in 2005 following the identification of a high incidence of head injuries and injuries caused by foul play in 2004. In contrast, the injury prevalence in women's water polo has increased over the study period. The cause of this is unknown although may be attributed an increase in aggression in the women's style of play as they try to emulate the men's game. The rising injury incidence in women's water polo and the lack of decrease in overall combined injury rates underscores the need for further injury surveillance and implementation of injury prevention programs.
Gold Nanoparticle‐Loaded Neural Stem Cells for Photothermal Ablation of Cancer
Authors: Kenna Schnarr, Rachael Mooney, Yiming Weng, Donghong Zhao, Elizabeth Garcia, Brian Armstrong, Alexander J. Annala, Seung U. Kim, Karen S. Aboody, Jacob M. Berlin
Journal: Advanced Healthcare Materials (2013)

Neural stem cells maintain their tumor tropism after internalizing gold nanorods. When exposed to a laser, the loaded cells heat up, destroying surrounding tumor cells. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Peptides Derived from the Histidine-Proline Domain of the Histidine-Proline-Rich Glycoprotein Bind to Tropomyosin and Have Antiangiogenic and Antitumor Activities
Authors: Fernando Doñate, Jose C. Juarez, Xiaojun Guan, Natalya V. Shipulina, Marian L. Plunkett, Ziva Tel-Tsur, David E. Shaw, William T. Morgan, Andrew P. Mazar
Journal: Cancer Research (2004)

Abstract The antiangiogenic activity of the multidomain plasma protein histidine-proline-rich glycoprotein (HPRG) is localized to its histidine-proline–rich (H/P) domain and has recently been shown to be mediated, at least partially, through binding to cell-surface tropomyosin in fibroblast growth factor-2-activated endothelial cells (X. Guan et al., Thromb Haemost, in press). HPRG and its H/P domain, but not the other domains of HPRG, bind specifically and with high affinity to tropomyosin. In this study, we characterize the interaction of the H/P domain with tropomyosin and delineate the region within the H/P domain responsible for that interaction. The H/P domain of HPRG consists mostly of repetitions of the consensus sequence [H/P][H/P]PHG. Applying an in vitro tropomyosin binding assay, we demonstrate that the synthetic peptide HHPHG binds to tropomyosin in vitro and inhibits angiogenesis and tumor growth in vivo. The affinity for tropomyosin increases exponentially upon multimerization of the HHPHG sequence, with a concurrent increase in antiangiogenic activity. Specifically, the tetramer (HHPHG)4 has significant antiangiogenic activity in the Matrigel plug model (IC50 ∼600 nm) and antitumor effects in two syngeneic mouse tumor models. Thus, we show that a 16-mer peptide analogue mimics the antiangiogenic activity of intact HPRG and is also able to inhibit tumor growth, suggesting that cell surface tropomyosin may represent a novel antiangiogenic target for the treatment of cancer.
Integrity of the alveolar-capillary barrier and alveolar surfactant system in smokers.
Authors: B Schmekel, J A Bos, A R Khan, B Wohlfart, B Lachmann, P Wollmer
Journal: Thorax (1992)

The permeability of the alveolar-capillary barrier to technetium-99m labelled diethylenetriamine pentaacetate (99mTc DTPA) is known to be greatly increased in smokers, but the underlying mechanism is poorly understood. Abnormal permeability of the alveolar epithelium as well as impaired surfactant function has been suggested. The purpose of this study was to examine transudation of urea and albumin into the alveoli and alveolar surfactant function in smokers and non-smokers and to relate these variables to the rate of alveolar-capillary transfer of 99mTc DTPA.Standardised bronchoalveolar lavage was performed and the yield of urea and albumin measured in the lavage fluid. The integrity of the alveolar surfactant system was assessed by measurement of the surface activity and of the yield of phospholipids in alveolar lavage fluid.The mean decay constant for the pulmonary clearance of 99mTc DTPA was 0.028/min in the smokers and 0.009/min in the non-smokers. The recovery of albumin and urea in alveolar lavage fluid was very similar in the two groups. The surface activity of alveolar lavage fluid was lower in smokers than in non-smokers (minimum surface tension 37.9 versus 28.6 mN/m) and the yield of phospholipids was reduced (2.08 versus 3.86 mg). The rate constant for the pulmonary clearance of 99mTc DTPA correlated with the yield of phospholipids at bronchoalveolar lavage.The study shows that increased alveolar-capillary transfer of 99mTc DTPA in smokers is not accompanied by increased transudation of small or large molecules into the alveoli. The findings support the hypothesis that increased clearance of 99mTc DTPA in smokers is related to surfactant dysfunction.
Randomized Phase II Trial of Sunitinib on an Intermittent Versus Continuous Dosing Schedule As First-Line Therapy for Advanced Renal Cell Carcinoma
Authors: Robert J. Motzer, Thomas E. Hutson, Mark R. Olsen, Gary R. Hudes, John M. Burke, William J. Edenfield, George Wilding, Neeraj Agarwal, John A. Thompson, David Cella, Akintunde Bello, Beata Korytowsky, Jinyu Yuan, Olga Valota, Bridget Martell, Subramanian Hariharan, Robert A. Figlin
Journal: Journal of Clinical Oncology (2012)

Sunitinib has shown antitumor activity with a manageable safety profile as metastatic renal cell carcinoma (RCC) treatment, when given by the standard intermittent schedule as well as a continuous daily dosing (CDD) schedule. A trial was conducted to compare the schedules.Patients with treatment-naive, clear cell advanced RCC were randomly assigned 1:1 to receive sunitinib 50 mg/d for 4 weeks followed by 2 weeks off treatment (schedule 4/2; n = 146) or 37.5 mg/d on the CDD schedule (n = 146) for up to 2 years. The primary end point was time to tumor progression.Median time to tumor progression was 9.9 months for schedule 4/2 and 7.1 months for the CDD schedule (hazard ratio, 0.77; 95% CI, 0.57 to 1.04; P = .090). No significant difference was observed in overall survival (23.1 v 23.5 months; P = .615), commonly reported adverse events, or patient-reported kidney cancer symptoms. Schedule 4/2 was statistically superior to CDD in time to deterioration, a composite end point of death, progression, and disease-related symptoms (P = .034). CONCLUSION; There was no benefit in efficacy or safety for continuous dosing of sunitinib compared with the approved 50 mg/d dose on schedule 4/2. Given the numerically longer time to tumor progression with the approved 50 mg/d dose on schedule 4/2, adherence to this dose and schedule remains the treatment goal for patients with advanced RCC.
Fever-induced QTc prolongation and ventricular arrhythmias in individuals with type 2 congenital long QT syndrome
Authors: Ahmad S. Amin, Lucas J. Herfst, Brian P. Delisle, Christine A. Klemens, Martin B. Rook, Connie R. Bezzina, Heather A.S. Underkofler, Katherine M. Holzem, Jan M. Ruijter, Hanno L. Tan, Craig T. January, Arthur A.M. Wilde
Journal: Journal of Clinical Investigation (2008)

Type 2 congenital long QT syndrome (LQT-2) is linked to mutations in the human ether a-go-go-related gene (HERG) and is characterized by rate-corrected QT interval (QTc) prolongation, ventricular arrhythmias, syncope, and sudden death. Recognized triggers of these cardiac events include emotional and acoustic stimuli. Here we investigated the repeated occurrence of fever-induced polymorphic ventricular tachycardia and ventricular fibrillation in 2 LQT-2 patients with A558P missense mutation in HERG. ECG analysis showed increased QTc with fever in both patients. WT, A558P, and WT+A558P HERG were expressed heterologously in HEK293 cells and were studied using biochemical and electrophysiological techniques. A558P proteins showed a trafficking-deficient phenotype. WT+A558P coexpression caused a dominant-negative effect, selectively accelerated the rate of channel inactivation, and reduced the temperature-dependent increase in the WT current. Thus, the WT+A558P current did not increase to the same extent as the WT current, leading to larger current density differences at higher temperatures. A similar temperature-dependent phenotype was seen for coexpression of the trafficking-deficient LQT-2 F640V mutation. We postulate that the weak increase in the HERG current density in WT-mutant coassembled channels contributes to the development of QTc prolongation and arrhythmias at febrile temperatures and suggest that fever is a potential trigger of life-threatening arrhythmias in LQT-2 patients.
Connecting Genomic Alterations to Cancer Biology with Proteomics: The NCI Clinical Proteomic Tumor Analysis Consortium
Authors: Matthew J. Ellis, Michael Gillette, Steven A. Carr, Amanda G. Paulovich, Richard D. Smith, Karin K. Rodland, R. Reid Townsend, Christopher Kinsinger, Mehdi Mesri, Henry Rodriguez, Daniel C. Liebler
Journal: Cancer Discovery (2013)

The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium is applying the latest generation of proteomic technologies to genomically annotated tumors from The Cancer Genome Atlas (TCGA) program, a joint initiative of the NCI and the National Human Genome Research Institute. By providing a fully integrated accounting of DNA, RNA, and protein abnormalities in individual tumors, these datasets will illuminate the complex relationship between genomic abnormalities and cancer phenotypes, thus producing biologic insights as well as a wave of novel candidate biomarkers and therapeutic targets amenable to verification using targeted mass spectrometry methods.
Heads or Tails: A Simple Reliability Check for Multiple Sequence Alignments
Authors: G. Landan, D. Graur
Journal: Molecular Biology and Evolution (2007)

The question of multiple sequence alignment quality has received much attention from developers of alignment methods. Less forthcoming, however, are practical measures for addressing alignment quality issues in real life settings. Here, we present a simple methodology to help identify and quantify the uncertainties in multiple sequence alignments and their effects on subsequent analyses. The proposed methodology is based upon the a priori expectation that sequence alignment results should be independent of the orientation of the input sequences. Thus, for totally unambiguous cases, reversing residue order prior to alignment should yield an exact reversed alignment of that obtained by using the unreversed sequences. Such "ideal" alignments, however, are the exception in real life settings, and the two alignments, which we term the heads and tails alignments, are usually different to a greater or lesser degree. The degree of agreement or discrepancy between these two alignments may be used to assess the reliability of the sequence alignment. Furthermore, any alignment dependent sequence analysis protocol can be carried out separately for each of the two alignments, and the two sets of results may be compared with each other, providing us with valuable information regarding the robustness of the whole analytical process. The heads-or-tails (HoT) methodology can be easily implemented for any choice of alignment method and for any subsequent analytical protocol. We demonstrate the utility of HoT for phylogenetic reconstruction for the case of 130 sequences belonging to the chemoreceptor superfamily in Drosophila melanogaster, and by analysis of the BaliBASE alignment database. Surprisingly, Neighbor-Joining methods of phylogenetic reconstruction turned out to be less affected by alignment errors than maximum likelihood and Bayesian methods.
The Role of Oxidative Stress–Altered Lipoprotein Structure and Function and Microinflammation on Cardiovascular Risk in Patients with Minor Renal Dysfunction
Authors: George A. Kaysen, Jason P. Eiserich
Journal: Journal of the American Society of Nephrology (2004)

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.
Growth‐differentiation factor 15 and osteoprotegerin in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the <scp>IABP‐SHOCK II</scp>‐trial
Authors: Georg Fuernau, Christian Poenisch, Ingo Eitel, Suzanne de Waha, Steffen Desch, Gerhard Schuler, Volker Adams, Karl Werdan, Uwe Zeymer, Holger Thiele
Journal: European Journal of Heart Failure (2014)
Value of renal biopsy in acute intrinsic renal failure.
Authors: D M Wilson, D R Turner, J S Cameron, C S Ogg, C B Brown, C Chantler
Journal: BMJ (1976)

Eighty-four patients presented with acute renal failure and features suggesting a diagnosis of intrinsic renal disease other than "acute reversible renal failure." Renal biopsy proved valuable in establishing the diagnosis, in indicating the reversibility of the lesion, and in helping to decide on treatment.
In Vitro Generation of Human Cytotoxic T Lymphocytes Specific for Peptides Derived From Prostate-Specific Antigen
Authors: P. Correale, C. Nieroda, S. Zaremba, M. Zhu, J. Schlom, K. Y. Tsang, W. Konstantin
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Protein antigens are presented to cytotoxic T lymphocytes as small peptides (approximately 9–10 amino acids long) bound to class I molecules of the major histocompatibility complex. The identification of tumor-associated antigens and specific peptide epitopes (i.e., antigenic determinants) may be useful in the development of anticancer vaccines. The generation of a cytotoxic T-cell response to one peptide epitope (amino acids 146–154) of human prostatespecific antigen (PSA) has been reported. Purpose: Our aim was to identify novel PSA peptides capable of eliciting specific cytotoxic T-cell responses. Methods: Candidate peptides were identified on the basis of the following criteria: 1) they contained consensus amino acid motifs for binding to HLAA2, which is the most common type of class I molecule; 2) they lacked strong homology with PSA-related kallikrein proteins; and 3) they were capable of stabilizing HLA-A2 class I molecules on the surface of human T2 (transport deletion mutant) cells, which are defective in antigen presentation. T-cell lines capable of killing (i.e., lysing) T2 target cells that had been pulsed with specific PSA peptides were generated from three different males (two disease-free individuals and one patient with prostate cancer) by incubating peripheral blood mononuclear cells with the peptides and interleukin 2. Specific cell lysis was monitored by the release of radioactivity from target cells that had been labeled with [ 111 In]oxyquinoline. Results: Two novel PSA peptides capable of eliciting cytotoxic T-cell responses were identified; these peptides were designated PSA-1 (amino acids 141–150) and PSA-3 (amino acids 154–163). Four different cytotoxic T-cell lines were generated in response to these peptides—three against PSA-3 and one against PSA-1. Specific lysis of peptide-pulsed T2 cells by the T-cell lines was blocked by the addition of a monoclonal antibody directed against class I molecules. The T-cell lines were also capable of lysing PSA-positive, HLA-A2-positive LNCaP cells (human prostate carcinoma cells). The specificity of LNCaP cell lysis was shown by the following: 1) the inability of added human K562 (chronic myelogenous leukemia) cells to inhibit it, 2) the ability of added anti-HLA-A2 antibodies to block it, and 3) the inability of the T-cell lines to induce substantial lysis of PSA-negative, HLA-A2-positive human cancer cells. Implications: Our studies form a rational basis for the use of PSA peptides or recombinant vectors encoding PSA in the development of anticancer vaccine immunotherapy protocols for patients with prostate cancer.
Adenomyoma in the pylorus.
Authors: I Janota, P G Smith
Journal: Gut (1966)

EDITORIAL SYNOPSIS Two cases of adenomyoma, composed chiefly of Brunner's glands, ducts, and smooth muscle, involving the submucosa and muscle of the pylorus, are described and discussed.Gland structures in the submucosa and muscle other than carcinoma are amongst the infrequent lesions of the pyloric region of the stomach.While pancreatic tissue accounts for a majority, adenomyoma is rare.Two further examples were recently encountered in partial gastrectomy specimens, and the cases are presented. CASE REPORTSCASE 1 A 27-year-old man had epigastric pain, relieved by antacids, occurring two hours after meals, for three years.A clinical diagnosis of peptic ulcer was made.At laparotomy a hard white thickening of the pylorus was found.Partial gastrectomy with closure of the duodenal stump and anastomosis of the stomach and jejunum was performed.Naked-eye examination revealed a localized thickening up to 1 5 cm., involving the muscle and submucosa of the anterior wall and lesser curve of the pyloric canal for 2 cm., extending into the pyloric sphincter, with minute spaces scattered through the submucosa and muscle.