tbuckley/cabot-search huggingface dataset:
Lymphokine enhances oxygen-independent activity against intracellular pathogens.
Authors: H W Murray, G I Byrne, C D Rothermel, D M Cartelli
Journal: The Journal of Experimental Medicine (1983)

To determine if mechanisms other than the generation of toxic oxygen intermediates are active against intracellular pathogens, oxidatively deficient mouse L cells and monocyte-derived macrophages from patients with chronic granulomatous disease were stimulated with soluble lymphocyte products. Despite no enhancement in oxidative activity, these cells displayed effective microbistatic activity against both T. gondii and C. psittaci. These results suggest a potential role for nonoxidative mechanisms in the mononuclear phagocyte's activity against intracellular pathogens, and indicate that lymphokines can regulate both oxygen-dependent and oxygen-independent antimicrobial responses.
Acquired digital arteriovenous malformation: a report of three cases and study with epiluminescence microscopy
Authors: C-H. Yang, K. Ohara
Journal: British Journal of Dermatology (2002)

Summary Acquired digital arteriovenous malformation is an abnormal connection between the arteriole and venule in the finger, fed by the digital vessels. Lesions are characterized by small, slightly raised dark-red macules on the distal part of the fingers. In the past, similar cases had been described using the terms 'cutaneous keratotic haemangioma' and 'periungual and subungual arteriovenous tumours'. In this article, we would like to discuss three additional cases that were studied using epiluminescence microscopy. Pathological findings and the possible pathogenesis are also presented.
Tuberculosis of the oesophagus
Authors: A. R. Fahmy, R. Guindi, A. Farid
Journal: Thorax (1969)

A case of primary tuberculosis of the oesophagus is presented; the patient was successfully treated by oesophagectomy. The condition, being rare, has stimulated the authors to review the literature concerning primary and secondary oesophageal tuberculosis. The history, modes of infection, the pathology, clinical picture, diagnosis, investigations, and methods of treatment are discussed. In contradistinction to the secondary disease, which is terminal, primary tuberculosis of the oesophagus is a curable disease with a fairly good prognosis. The case report shows that the surgeon should pay careful attention to the site of the anastomosis; otherwise post-operative stricture can develop. Even this responds well to dilatations and the patient can regain normal health.
Greenfield on language, tools, and brain
Authors: Philip Swann
Journal: Behavioral and Brain Sciences (1998)

Greenfield (1991t) fails in an attempt to defend her own original synthesis of cognitivist and nativist accounts of language development. The proposed synchronous stages of object and phoneme combination are not supported by the empirical data she presents. The functional specification of hypothetical neural circuits is almost entirely speculative. Nor is it likely that new data could save her model, since it is formulated in a simplistic information processing framework that is now of little more than historical interest.
Increased Frequency of De Novo Copy Number Variants in Congenital Heart Disease by Integrative Analysis of Single Nucleotide Polymorphism Array and Exome Sequence Data
Authors: Joseph T. Glessner, Alexander G. Bick, Kaoru Ito, Jason G. Homsy, Laura Rodriguez-Murillo, Menachem Fromer, Erica Mazaika, Badri Vardarajan, Michael Italia, Jeremy Leipzig, Steven R. DePalma, Ryan Golhar, Stephan J. Sanders, Boris Yamrom, Michael Ronemus, Ivan Iossifov, A. Jeremy Willsey, Matthew W. State, Jonathan R. Kaltman, Peter S. White, Yufeng Shen, Dorothy Warburton, Martina Brueckner, Christine Seidman, Elizabeth Goldmuntz, Bruce D. Gelb, Richard Lifton, Jonathan Seidman, Hakon Hakonarson, Wendy K. Chung
Journal: Circulation Research (2014)

Rationale : Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. Objective : To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. Methods and Results : We studied 538 CHD trios using genome-wide dense single nucleotide polymorphism arrays and whole exome sequencing. Results were experimentally validated using digital droplet polymerase chain reaction. We compared validated CNVs in CHD cases with CNVs in 1301 healthy control trios. The 2 complementary high-resolution technologies identified 63 validated de novo CNVs in 51 CHD cases. A significant increase in CNV burden was observed when comparing CHD trios with healthy trios, using either single nucleotide polymorphism array ( P =7×10 −5 ; odds ratio, 4.6) or whole exome sequencing data ( P =6×10 −4 ; odds ratio, 3.5) and remained after removing 16% of de novo CNV loci previously reported as pathogenic ( P =0.02; odds ratio, 2.7). We observed recurrent de novo CNVs on 15q11.2 encompassing CYFIP1, NIPA1 , and NIPA2 and single de novo CNVs encompassing DUSP1, JUN, JUP, MED15, MED9, PTPRE SREBF1, TOP2A , and ZEB2 , genes that interact with established CHD proteins NKX2-5 and GATA4 . Integrating de novo variants in whole exome sequencing and CNV data suggests that ETS1 is the pathogenic gene altered by 11q24.2-q25 deletions in Jacobsen syndrome and that CTBP2 is the pathogenic gene in 10q subtelomeric deletions. Conclusions : We demonstrate a significantly increased frequency of rare de novo CNVs in CHD patients compared with healthy controls and suggest several novel genetic loci for CHD.
Emergency Suprapubic Catheterization
Authors: J. M. Buchanan
Journal: BMJ (1963)

BOURNr L drug she noted a marked increase in libido, which she could only relieve by masturba- tion.She stopped taking the tablets and the effect dwindled within a day or two, but the whole episode led to a great deal of guilt and self-reproach in subsequent depressive phases (the patient being a devout Roman Catholic).At the time, however, it was considered that this might have been a purely manic symptom and not due to chlorprothixene.Her " manic" phases were later partially controlled with prothipendyl hydrochloride (" tolnate ") 40 mg.t.d.s.In July, 1963, chlorprothixene 30 mg. t.d.s. was again prescribed and within a few days she noticed increased libido and she again resorted to masturbation.The effect dwindled rapidly once she stopped taking the drug, even though her manic phase continued for another week, hence one must conclude that it was an effect of the drug.I am, etc.,
Meeting Report: Exploiting the Tumor Microenvironment for Therapeutics
Authors: Giovanni Melillo, Gregg L. Semenza
Journal: Cancer Research (2006)

Abstract Recent progress in understanding the role of the tumor microenvironment in cancer progression was the subject of the 2nd International Tumor Metabolism Summit entitled “Exploiting the Tumor Microenvironment for Therapeutics,” a meeting held at Palazzo Ducale in Genoa, Italy, October 7 to 8, 2005. One of the major conceptual advances in oncology over the last decade has been the appreciation that all major aspects of cancer biology are influenced by the tumor microenvironment. Two important means by which cancer cells adapt to their microenvironment are by reprogramming cellular glucose/energy metabolism to use pathways that generate ATP in the absence of O2 and by stimulating angiogenesis to increase O2 delivery. These responses are principally mediated at the transcriptional level by hypoxia-inducible factor-1. This meeting emphasized the complexity of the tumor microenvironment and opportunities for therapeutic intervention by targeting transcriptional and metabolic pathways that are activated during cancer progression. A better understanding of the crosstalk between signaling pathways and metabolic alterations that contribute to the cancer phenotype may provide insights leading to the development of novel therapeutic strategies. (Cancer Res 2006; 66(9): 4558-60)
Eponym's 's
Authors: Victor C. Vaughan
Journal: JAMA (1986)

<h3>To the Editor.—</h3> In 1976, the<i>Manual for Authors &amp; Editors</i>of the American Medical Association (AMA) adopted as editorial style the removal of the 's from most eponymic designations and, in the opinion of some of us, achieved a very desirable simplification and uniformity of style. In the 1981 revision of the same manual the AMA restored the 's, presumably in response to the criticism of readers who found the loss of the 's jarring to the ear or clumsy on the tongue. The National Board of Medical Examiners has for most of its examinations in recent years left the 's off eponyms. We have been guided by the inconsistency that has been prevalent in such use. Consider that hyphenated eponyms, such as Niemann-Pick or Tay-Sachs, have not had apostrophes for years. Nor have Argyll Robinson, Pierre Robin, Treacher Collins, Bence Jones, Louis-Bar, nor Albers-Schönberg had apostrophes, despite the
Fatal Myocardial Sarcoidosis
Authors: G. Forbes, A. Usher
Journal: BMJ (1962)

Treatment resulted in a diminution of symptoms, but had no effect on the renal function or the radiographic appearance of the bones, and she died a year later in oliguric renal failure.The post-mortem findings are described.We wish to thank the many persons who assisted in the accumulation of the data about this patient, particularly
Measurement of responsiveness to inhaled histamine using FEV1: comparison of PC20 and threshold.
Authors: D W Cockcroft, B A Berscheid, K Y Murdock
Journal: Thorax (1983)

Two methods of interpreting histamine inhalation dose-response curves were compared in 27 normal and 41 asthmatic subjects. The histamine provocation concentration producing a 20% fall (PC20) in forced expiratory volume in one second (FEV1) was calculated on the basis of the lowest FEV1 after inhalation of saline and the lowest value after inhalation of histamine. The histamine threshold was determined as the first histamine concentration causing the FEV1 to fall more than 2 SD below the mean of five pre-histamine (three pre-saline, two post-saline) FEV1 determinations. The PC20 was on average one doubling concentration larger than the threshold. The PC20 provided better discrimination between asthmatic and normal subjects than did the histamine threshold and was significantly more reproducible. These findings suggest that the histamine threshold may prove useful for studies on populations, particularly those with a low degree of responsiveness to histamine, because of the possibility of measuring a response at a lower histamine concentration. On the other hand, the PC20 is preferable for clinical use in individuals because of its better discriminating power and better reproducibility.
Angiopoietin-2 Confers Atheroprotection in apoE <sup>−/−</sup> Mice by Inhibiting LDL Oxidation via Nitric Oxide
Authors: Asif Ahmed, Takeshi Fujisawa, Xi-Lin Niu, Shakil Ahmad, Bahjat Al-Ani, Kunal Chudasama, Allyah Abbas, Rahul Potluri, Vineet Bhandari, Clarence M. Findley, Gregory K.W. Lam, Jianhua Huang, Peter W. Hewett, Melissa Cudmore, Christopher D. Kontos
Journal: Circulation Research (2009)

Atherosclerosis is promoted by a combination of hypercholesterolemia and vascular inflammation. The function of Angiopoietin (Ang)-2, a key regulator of angiogenesis, in the maintenance of large vessels is unknown. A single systemic administration of Ang-2 adenovirus (AdAng-2) to apoE(-/-) mice fed a Western diet significantly reduced atherosclerotic lesion size ( approximately 40%) and oxidized LDL and macrophage content of the plaques. These beneficial effects were abolished by the inhibition of nitric oxide synthase (NOS). In endothelial cells, endothelial NOS activation per se inhibited LDL oxidation and Ang-2 stimulated NO release in a Tie2-dependent manner to decrease LDL oxidation. These findings demonstrate a novel atheroprotective role for Ang-2 when endothelial cell function is compromised and suggest that growth factors, which stimulate NO release without inducing inflammation, could offer atheroprotection.
Long term mortality after severe starvation during the siege of Leningrad: prospective cohort study
Authors: P. Sparen
Journal: BMJ (2004)

To determine whether starvation during periods of increased growth after birth have long term health consequences.Analysis of cardiovascular risk factors and mortality in a longitudinal follow up after the 1941-4 siege of Leningrad. Mortality measured from 1975 up to the end of 1999.St Petersburg, Russia (formerly Leningrad).5000 men born 1916-35 who lived in Leningrad, randomly selected to take part in health examinations in 1975-7. Of the 3905 men who participated, a third had experienced the siege.Relative risk of ischaemic heart disease and mortality from stroke by siege exposure. Odds ratios and means for several cardiovascular risk factors.Three to six decades after the siege, in men who experienced the siege around the age of puberty blood pressure was raised (mean difference in systolic 3.3 mm Hg, in diastolic 1.3 mm Hg) as was mortality from ischaemic heart disease (relative risk 1.39, 95% confidence interval 1.07 to 1.79) and stroke (1.67, 1.15 to 2.43), including haemorrhagic stroke (1.71, 0.90 to 3.22). The effect on mortality was partly mediated via blood pressure but not by any other measured biological, behavioural, or social factor.Starvation, or accompanying chronic stress, particularly at the onset of or during puberty, may increase vulnerability to later cardiovascular disease.
Relation between body weight and the gastric and intestinal handling of an oral caloric load.
Authors: C Johansson, K Ekelund
Journal: Gut (1976)

The gastric and intestinal handling of a standard liquid 300-ml meal (0.89 kcal/ml) was examined in 10 healthy, non-obese subjects by a quantitative multiple-indicator dilution technique. Such a meal contains about one-tenth of the daily energy requirements. The heavier the subject the more energy was transferred from the stomach to the intestine during the first 80 minutes after taking the meal. A high body weight was also associated with a rapid transit through the proximal 70 cm of intestine and the passing of a substantial part of the meal calories to the lower intestine. These circumstances favour a fast incorporation of fed calories. In subjects with lower body weights eneryg was delivered more slowly from the stomach. The absorbed an equal amount of energy in the proximal intestine as did the heavier subjects, but during the longer transit times. The percentage absorption in the investigated segment was therefore higher.
Experiments with human papilloma virus in cell culture
Authors: HEATHER A. CUBIE
Journal: British Journal of Dermatology (1974)

Monolayer cell cultures infected in the usual way with human papilloma virus produced no significant changes. However, when a nucleic acid extract of the virus was used and the cultures were incubated at a lower temperature (33°C), perinuclear fluorescence was observed 6 weeks after inoculation.
Stomatin-like Protein 2 Is Overexpressed in Cancer and Involved in Regulating Cell Growth and Cell Adhesion in Human Esophageal Squamous Cell Carcinoma
Authors: Liyong Zhang, Fang Ding, Wenfeng Cao, Zhongmin Liu, Wei Liu, Zaicheng Yu, Yu Wu, Wendong Li, Yanda Li, Zhihua Liu
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It has been implicated in interaction with erythrocyte cytoskeleton and presumably other integral membrane proteins, but not directly with the membrane bilayer. We show here the involvement of SLP-2 in human esophageal squamous cell carcinoma (ESCC), lung cancer, laryngeal cancer, and endometrial adenocarcinoma and the effects of SLP-2 on ESCC cells. Experimental Design: Previous work of cDNA microarray in our laboratory revealed that SLP-2 was significantly up-regulated in ESCC. The expression of SLP-2 was further evaluated in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma by semiquantitative reverse transcription-PCR, Western blot, and immunohistochemistry. Mutation detection of SLP-2 exons was done by PCR and automated sequencing. Antisense SLP-2 eukaryotic expression plasmids were constructed and transfected into human ESCC cell line KYSE450. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, clonogenecity assay, flow cytometry assay, nude mice tumorigenetic assay, and cell attachment assay were done to investigate the roles of SLP-2 gene. Results: All tumor types we tested showed overexpression of SLP-2 compared with their normal counterparts (P ≤ 0.05). Moreover, immunohistochemistry analysis of mild dysplasia, severe dysplasia, and ESCC showed that overexpression of SLP-2 occurred in premalignant lesions. Mutation analysis indicated that no mutation was found in SLP-2 exons. KYSE450 cells transfected with antisense SLP-2 showed decreased cell growth, proliferation, tumorigenecity, and cell adhesion. Conclusions: SLP-2 was first identified as a novel cancer-related gene overexpressed in human ESCC, lung cancer, laryngeal cancer, and endometrial adenocarcinoma. Decreased cell growth, cell adhesion, and tumorigenesis in the antisense transfectants revealed that SLP-2 may be important in tumorigenesis.
Central role of RAGE-dependent neointimal expansion in arterial restenosis
Authors: Taichi Sakaguchi, Shi Fang Yan, Shi Du Yan, Dmitri Belov, Ling Ling Rong, Monica Sousa, Martin Andrassy, Steven P. Marso, Stephan Duda, Bernd Arnold, Birgit Liliensiek, Peter P. Nawroth, David M. Stern, Ann Marie Schmidt, Yoshifumi Naka
Journal: Journal of Clinical Investigation (2003)

Cellular proliferation, migration, and expression of extracellular matrix proteins and MMPs contribute to neointimal formation upon vascular injury. Wild-type mice undergoing arterial endothelial denudation displayed striking upregulation of receptor for advanced glycation end products (RAGE) in the injured vessel, particularly in activated smooth muscle cells of the expanding neointima. In parallel, two of RAGE’s signal transducing ligands, advanced glycation end products (AGEs) and S100/calgranulins, demonstrated increased deposition/expression in the injured vessel wall. Blockade of RAGE, employing soluble truncated receptor or antibodies, or in homozygous RAGE null mice, resulted in significantly decreased neointimal expansion after arterial injury and decreased smooth muscle cell proliferation, migration, and expression of extracellular matrix proteins. A critical role for smooth muscle cell RAGE signaling was demonstrated in mice bearing a transgene encoding a RAGE cytosolic tail-deletion mutant, specifically in smooth muscle cells, driven by the SM22α promoter. Upon arterial injury, neointimal expansion was strikingly suppressed compared with that observed in wild-type littermates. Taken together, these data highlight key roles for RAGE in modulating smooth muscle cell properties after injury and suggest that RAGE is a logical target for suppression of untoward neointimal expansion consequent to arterial injury.
A phase I study of intravenous TZT-1027 administered on day 1 and day 8 of a three-weekly cycle in combination with carboplatin given on day 1 alone in patients with advanced solid tumours
Authors: A. Greystoke, S. Blagden, A.L. Thomas, E. Scott, G. Attard, R. Molife, L. Vidal, S. Pacey, D. Sarkar, A. Jenner, J.S. De-Bono, W. Steward
Journal: Annals of Oncology (2006)
Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix.
Authors: S Eisenberg, E Sehayek, T Olivecrona, I Vlodavsky
Journal: Journal of Clinical Investigation (1992)

Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase-treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors.
New Strategies in Glioblastoma: Exploiting the New Biology
Authors: Howard A. Fine
Journal: Clinical Cancer Research (2015)

Glioblastoma is one of the deadliest human cancers. There have been few significant therapeutic advances in the field over the past two decades, with median survival of only about 15 months despite aggressive neurosurgery, radiotherapy, and chemotherapy. Nevertheless, the past 5 years has seen an explosion in our understanding of the genetic and molecular underpinnings of these tumors, leading to renewed optimism about potential new therapeutic approaches. Several of the most promising new approaches include oncogenic signal transduction inhibition, angiogenesis inhibition, targeting canonical stem cell pathways in glioblastoma stem cells, and immunotherapy. As promising as many of these approaches appear, they have not had an impact yet on the natural history of the disease or on patient long-term outcomes. Nevertheless, it is hoped that with time such approaches will lead to more effective treatments, but issues such as the unique biology and anatomy of the central nervous system, impaired drug delivery, poor preclinical models with resultant nonpredictive preclinical screening, and poor clinical trial design potentially impede the rapid development of such new therapies. In this article, we review the excitement and challenges that face the development of effective new treatments that exploit this new biology.
Use of tuberculin skin test, IFN-γ release assays and IFN-γ-induced protein-10 to identify children with TB infection
Authors: Mohammed A. Yassin, Roberta Petrucci, Kefyalew T. Garie, Greg Harper, Aklilo Teshome, Isabel Arbide, Girum Asnake, Habiba J. Ahmed, Tadesse Mammo, Kedir Yesuf, Luis E. Cuevas
Journal: European Respiratory Journal (2012)

Current tests of tuberculosis (TB) infection (tuberculin skin test (TST), interferon (IFN)-γ-release assays (IGRAs) and IFN-γ-induced protein (IP)-10) have limitations and their value when used consecutively to identify infected children has not been explored. This study describes TST, IGRA and IP-10 responses in children in contact with adults with TB, the agreement of the tests and whether using multiple tests indentifies more infected children. 330 children (aged 1-15 yrs) in contact with adults with pulmonary TB and 156 controls were studied in Ethiopia. Children exposed to adults with high bacilli grades in sputum were more likely to have positive TST, IFN-γ and IP-10 than controls. The agreement of positive tests was directly associated with the sputum bacilli grades (p<0.001 for all). The agreement of negative tests was higher in control children. The consecutive use of the tests increased the number of children classified as having at least one positive test. Using three tests increases the number of children classified as infected. This increase is associated with the bacilli load of the adults. Using only one test may underestimate the proportion of infected children, but the interpretation of the data is difficult due to the lack of reference standards.