tbuckley/cabot-search huggingface dataset:
Glycosphingolipids of Subcellular Fractions From Normal Rat Liver and Morris Hepatoma 5123TC&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: A M Dnistrian, V P Skipski, M Barclay, C C Stock
Journal: JNCI Journal of the National Cancer Institute (1979)

Neutral glycosphingolipids and gangliosides were quantified in lipid extracts from plasma membranes, mitochondria, microsomes, and nuclei isolated from normal rat liver and Morris hepatoma 5123TC. Results showed a higher content of glycosphingolipids, especially gangliosides, in hepatomas and differences in the distribution of glycosphingolipids among subcellular fractions. Differences in the glycosphingolipid composition of the hepatoma, namely, the absence of trisialogangliosides and an increase in the lower molecular weight gangliosides, reflected an altered metabolism of glycosphingolipids in this tumor. The results indicated that changes in membrane glycosphingolipids were not restricted to the cell surfaces of malignant cells, inasmuch as intracellular membrane fractions also exhibited altered glycosphingolipid profiles.
THE EYESIGHT OF THE POORER CITY CHILDREN
Authors: H. W. Thomson
Journal: BMJ (1907)

ufrine, but the albumose was again detected in it.The diar- rhoea stopped, but the patient sank and died in the early morning of July 6th.The relatives refused to allow anypo8t- mortem examination, declining to permit even the iemoval of one of the affected ribs.Examination of the Urine.On the day of this examination (July 2nd) the amount of urine passed was 70oz, and the albuminometer registered 2 parts per 1000.In reaction it was distinctly alkaline, and in appearance very turbid: On standing a heavy white deposit settled, which on microscopic examination showed abundance of triple phosphats, like the earlier specimen, embedded in a putty-like material.fo Identify the Bence-Jones albumose I proceeded as follows: 8cz. of the urine were filtered to remove the pbos- phatic deposit.The filtrate, which was still turbld, was care- fully neutralizsd and heated.A dense, sticky white precipitate rapidly appeared, which floated to the top; on further heating his largely disappeared.To separate any coagulable proteid this s)lution was now filtered while boiling.This second filtrate was allowed to cool, and then treated wlth nitric acid.An immediate precipitate occurred at the line of junction of the acid with the urine, which disappeared on heating and reappeared on cooling.In this it corresponds to the reaction of proto-albumose (or, as it is usually called now, primary proteose).After removal of this, nitric acid with sodium chloride produced afurther precipitate, which also disappeared on heating and reappeared on cooling.This correEponds to the reaction of secondary proteose.Millor's reagent gave a white precipitate with this filtrate, which became reddish-brown on boiling.To separate the Bence-Jones body some of the albumen-free solution was saturated with crystals of ammonium sulphate.The resulting precipitate was filtered off and redissolved by the aidition of water.With the bluret test it gave a violet
International Union of Basic and Clinical Pharmacology. LXXIV. Apelin Receptor Nomenclature, Distribution, Pharmacology, and Function
Authors: Sarah L. Pitkin, Janet. J. Maguire, Tom I. Bonner, Anthony P. Davenport
Journal: Pharmacological Reviews (2010)

A gene encoding a novel class a G-protein-coupled receptor was discovered in 1993 by homology cloning and was called APJ. It was designated an "orphan" receptor until 1998, when its endogenous ligand was identified and named apelin (for APJ endogenous ligand). Since this pairing, both apelin and its receptor have been found to have a widespread distribution in both the central nervous system and the periphery. A number of physiological and pathophysiological roles for the receptor have emerged, including regulation of cardiovascular function, fluid homeostasis, and the adipoinsular axis. This review outlines the official International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification nomenclature, designating the receptor protein as the apelin receptor, together with current knowledge of its pharmacology, distribution, and functions.
Factors associated with physicians' decisions to withdraw mechanical ventilation in anticipation of death
Authors: A R L Medford
Journal: Thorax (2003)

▴ Cook D, Rocker G, Marshall J, et al . Withdrawal of mechanical ventilation in anticipation of death in the intensive care unit. N Engl J Med2003;349:1123–32 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Eight hundred and fifty one consecutive patients mechanically ventilated for at least 72 hours in intensive care units in 15 different centres were prospectively followed. The relation between various factors and withdrawal of mechanical ventilation was assessed using … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DCook%26rft.auinit1%253DD.%26rft.volume%253D349%26rft.issue%253D12%26rft.spage%253D1123%26rft.epage%253D1132%26rft.atitle%253DWithdrawal%2Bof%2BMechanical%2BVentilation%2Bin%2BAnticipation%2Bof%2BDeath%2Bin%2Bthe%2BIntensive%2BCare%2BUnit%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa030083%26rft_id%253Dinfo%253Apmid%252F13679526%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa030083&link_type=DOI [3]: /lookup/external-ref?access_num=13679526&link_type=MED&atom=%2Fthoraxjnl%2F58%2F12%2F1041.atom [4]: /lookup/external-ref?access_num=000185369700005&link_type=ISI
Short- and Long-Term recovery of left ventricular function predicted at the time of primary percutaneous coronary intervention in anterior myocardial infarction
Authors: Matthijs Bax, Robbert J de Winter, Carl E Schotborgh, Karel T Koch, Martijn Meuwissen, Michiel Voskuil, Rob Adams, Karla J.J Mulder, Jan G.P Tijssen, Jan J Piek
Journal: Journal of the American College of Cardiology (2004)
P78 Impact of severe allergic asthma in children: highlighting a role for understanding the family perspective
Authors: K. G. Staley, R. Herzallah, H. Pandya, E. Humphreys, E. Gaillard
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Current understanding of paediatric severe allergic asthma tends to focus on the impact of the disease on the child in isolation from the impact on the wider family. We aimed to characterise a paediatric severe asthma population and assess the practical, financial and emotional burden on the family. <h3>Methods</h3> Case-note review of children (6–18 years) with severe, allergic asthma (BTS treatment step 4–5) was performed; identifying treatments, disease characteristics and practical limitations (e.g. missed schooldays, impingement on activities). Interviews with the primary care-giver of a child with severe allergic asthma were conducted and aimed to explore the impact of severe asthma on the overall family (e.g. missed workdays, time dedicated to care). Family profiles and cost-modelling will be performed to assess the emotional and economic impact on families of having a child with severe allergic asthma. <h3>Results</h3> 35 children from a severe asthma clinic between 2007 and 2010 were identified. Despite being on maximum or near-maximum treatment, nearly 50% of children reported symptoms that impacted on daily activities, or were troublesome at night. Furthermore, 40% reported poor school attendance due to asthma symptoms. When performed, the Asthma UK Asthma Control Test identified a mean score of 15 (range 10–25); with 5/6 patients reporting a score below 20 (very poor control). Data also suggests that the unpredictable nature of severe asthma has an impact on the child and family unit. For example, it was documented how a child felt ‘constantly…frightened of these episodes of shortness of breath’. Parents used the words ‘catastrophic’ and described how they were simply ‘fed-up with poor asthma control’, highlighting the perceived impact and frustration at caring for a child with severe asthma. Further work on family profiles and cost-modelling is being undertaken to assess the emotional and economic impact on a family of having a child with severe asthma. <h3>Conclusion</h3> These preliminary findings suggest that caring for a child with severe asthma has a considerable impact on the functioning of the family unit. A better understanding of the family perspective on the impact of severe allergic asthma in children may help improve outcomes by enabling the development of specific strategies.
PIK3CA alterations in Middle Eastern ovarian cancers
Authors: Jehad Abubaker, Prashant Bavi, Wael Al-Haqawi, Zeenath Jehan, Adnan Munkarah, Shahab Uddin, Khawla S Al-Kuraya
Journal: Molecular Cancer (2009)

PI3K/AKTsignaling pathway plays an important role in cell growth, proliferation, and tumorgenesis of various malignancies. This signaling pathway has been shown to be frequently altered in several human cancers including ovarian cancers. However the role of this oncogenic signaling pathway has not been explored in the Middle Eastern epithelial ovarian cancer (EOC). Therefore, we investigated PI3K/AKT genetic alterations such as PIK3CA amplification, PIK3CA mutation, PTEN protein loss and their relationships with various clinicopathological characteristics in 156 EOCs.Fluorescence in situ hybridization (FISH) technique and DNA sequencing were used to analyze PIK3CA amplification and mutation respectively. Expression of PIK3CA protein expression (p110 alpha), PTEN, p-AKT and Ki-67 was analyzed by immunohistochemistry. PIK3CA amplification was seen in 54 of 152 (35.5%) EOC cases analyzed; PIK3CA gene mutations in 6/153 EOC (3.9%); KRAS mutations in 3/154 EOC (1.9%), BRAF mutations in 3/156 EOC (1.9%), p53 mutation in 50/154 EOC (32.5%), and loss of PTEN protein expression in 33/144 EOC (22.9%). p110 alpha overexpression was associated with increased phosphorylation of AKT-Ser 473 and with the proliferation marker Ki-67.Our data showed mutual exclusivity between the molecular event of PIK3CA amplification and mutations in PIK3CA, KRAS, BRAF genes, which suggests that each of these alterations may individually be sufficient to drive ovarian tumor pathogenesis independently. High prevalence of genetic alterations in PI3K/AKT pathway in a Middle Eastern ovarian carcinoma provides genetic evidence supporting the notion that dysregulated PI3K/AKT pathways play an important role in the pathogenesis of ovarian cancers.
Postoperative Radiotherapy in Non—Small-Cell Lung Cancer Warrants Further Exploration in the Era of Adjuvant Chemotherapy and Conformal Radiotherapy
Authors: James A. Bonner, Sharon A. Spencer
Journal: Journal of Clinical Oncology (2006)

that PORT was not associated with an overall improvement in survival and was associated with a detrimental effect on survival for the subgroup of patients with stage I and II disease. Numerous authors have examined the trials that were included in the metaanalysis. These analyses have concluded that many trials lacked appropriate methodology for randomized trials or appropriate treatment regarding recent standards for care. 2,5,7-11 The PORT meta-analysis included trials in which a majority of patients received treatment with cobalt machines, and some groups of patients were treated with just one radiotherapy field each day (an anterior field one day and a posterior field the next). It has been shown that these treatments result in suboptimal dose distributions, which may potentially increase toxicity. 2,4,7 Additionally, a large proportion of the patients who were included in the meta-analysis (more than 30%) were participants in one randomized trial of Dautzenberg et al. 12 This trial allowed physicians to treat patients with daily fractions of 2.50 Gy and total doses of 60 Gy. These doses exceed the doses that have been considered the standard of care in North America for many years. 5,8-10 These high doses do not comply with recent practices because physicians have had concerns about dose-related toxicity and the potential for treatment-related deaths. Both of these suboptimal outcomes were augmented by PORT in the study of Dautzenberg et al. Additionally, a majority of patients who were entered onto the randomized trial of Dautzenberg et al were part of an effort to increase accrual by relaxing the protocol requirements (simplified protocol). It is possible that this simplification detracted from the balance that was sought with the randomization procedure. The analysis of the Surveillance, Epidemiology, and End Results (SEER) database, as highlighted in this issue, demonstrated several similar findings compared with the meta-analysis, with the striking exception of the results for patients with involvement of N2 lymph nodes (N2 disease). Overall, PORT did not have a significant effect on survival and was associated with a survival decrement for patients with N0 or N1 disease. However, PORT was associated with an improvement in survival for patients with N2 disease, unlike the metaanalysis. Therefore, how does the clinician assess the available literature regarding PORT in resected NSCLC and make rational treatment recommendations for patients?
A Phase I Study of Ultra Low Dose Interleukin-2 and Stem Cell Factor in Patients with HIV Infection or HIV and Cancer
Authors: Manisha H. Shah, Aharon G. Freud, Don M. Benson, Amy K. Ferkitich, Bruce J. Dezube, Zale P. Bernstein, Michael A. Caligiuri
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Ultra low doses of interleukin-2 (IL-2) can activate the high-affinity IL-2 receptor constitutively expressed on CD56bright natural killer (NK) cells, the CD34+ NK cell precursor, and CD4+CD25+ regulatory T cells (Tregs) in vivo. We have previously shown synergy between IL-2 and stem cell factor (SCF) in the generation of CD56bright NK cells from CD34+ hemopoietic progenitor cells in vitro and showed synergistic NK cell expansion in an in vivo preclinical model. To determine the safety, toxicity, and immune modulation of this combination of cytokines in vivo, we conducted a first-in-man phase I study. Experimental Design: A phase I dose escalation study was conducted using IL-2 at 900,000 or 650,000 IU/m2/d for 8 weeks with 5 or 10 μg/kg/d of SCF given thrice a week for 8 weeks in patients with HIV infection and/or cancer. Results: Ten of 13 patients completed therapy; four experienced the dose-limiting toxicities of grade 3 fatigue or urticaria. The maximum tolerated doses of IL-2 and SCF in combination is 650,000 IU/m2/d of IL-2 and 5 μg/kg/d thrice a week of SCF. NK cells were expanded over 2-fold on therapy; Tregs were expanded nearly 6-fold from baseline. Conclusions: Administration of IL-2 with SCF is safe and well tolerated and leads to expansion of lymphocyte subsets in patients with HIV or HIV and cancer; however, the changes in NK cell and Treg expansion seen with this cytokine combination were no different than those seen with a similar dose of IL-2 alone.
Targeting the heparin-binding domain of fibroblast growth factor receptor 1 as a potential cancer therapy
Authors: Ling Ling, Si Kee Tan, Ting Hwee Goh, Edwin Cheung, Victor Nurcombe, Andre J. van Wijnen, Simon M. Cool
Journal: Molecular Cancer (2015)

Aberrant activation of fibroblast growth factor receptors (FGFRs) deregulates cell proliferation and promotes cell survival, and may predispose to tumorigenesis. Therefore, selective inactivation of FGFRs is an important strategy for cancer therapy. Here as a proof-of-concept study, we developed a FGFR1 neutralizing antisera, IMB-R1, employing a novel strategy aimed at preventing the access of essential heparan sulfate (HS) co-receptors to the heparin-binding domain on FGFR1. The mRNA and protein expression level of FGFR1 and other FGFRs were examined in several lines of breast cancer and osteosarcoma cells and corresponding normal cells using Taqman real-time quantitative PCR and Western blot analysis. The specificity of IMB-R1 against FGFR1 was assessed with various ELISA-based approaches and Receptor Tyrosine Kinase array. Proliferation assay and apoptosis analysis were performed to assess the effect of IMB-R1 on cancer cell growth and apoptosis, respectively, in comparison with known FGFR1 inhibitors. The IMB-R1 induced alteration of intracellular signaling and gene expression were analysed using Western blot and microarray approaches. Immunohistochemical staining of FGFR1 using IMB-R1 were carried out in different cancer tissues from clinical patients. Throughout the study, statistical differences were determined by Student's t test where appropriate and reported when a p value was less than 0.05. We demonstrate that IMB-R1 is minimally cross-reactive for other FGFRs, and that it potently and specifically inhibits binding of heparin to FGFR1. Furthermore, IMB-R1 blocks the interaction of FGF2 with FGFR1, the kinase activity of FGFR1 and activation of intracellular FGFR signaling. Cancer cells treated with IMB-R1 displayed impaired FGF2 signaling, were unable to grow and instead underwent apoptosis. IMB-R1-induced cell death correlated with a disruption of antioxidative defense networks and increased expression of several tumor suppressors and apoptotic proteins, including p53. Immunostaining with IMB-R1 was stronger in human cancer tissues in which the FGFR1 gene is amplified. Our study suggests that blocking HS interaction with the heparin-binding domains of FGFR1 inhibited cancer cell growth, which can be an attractive strategy to inactivate cancer-related heparin-binding proteins.
MENINGITIS IN CHILDREN
Authors: W. M. Smith
Journal: BMJ (1914)

yTUDNxT!uu 1 MENINGITIS IN CHILDREN.2I94 uagnification of 450 diamneters, in normial fluid not more than two or three lymiplhocytes will be seen in each field, and not a single polymorph.In certain morbid affections of the central nervous system and its meninges there is a great increase in the cell cotunt.In acute inflammatory conditions, suchl as m-eningococcal or streptococcal m-eninigitis, polyniorplhs are present in enormiious numibers, producing turbidity as a rule.It must be reienmebered, however, tllat a con- siderable number of polymolorplhs may -be present with a perfectly clear fluid.The lymphocytes are increased in the more chronic
Blood-brain barrier invasion by group B Streptococcus depends upon proper cell-surface anchoring of lipoteichoic acid
Authors: Kelly S. Doran, Erin J. Engelson, Arya Khosravi, Heather C. Maisey, Iris Fedtke, Ozlem Equils, Kathrin S. Michelsen, Moshe Arditi, Andreas Peschel, Victor Nizet
Journal: Journal of Clinical Investigation (2005)

Group B streptococci (GBSs) are the leading cause of neonatal meningitis. GBSs enter the CNS by penetrating the blood-brain barrier (BBB), which consists of specialized human brain microvascular endothelial cells (hBMECs). To identify GBS factors required for BBB penetration, we generated random mutant libraries of a virulent strain and screened for loss of hBMEC invasion in vitro. Two independent hypo-invasive mutants possessed disruptions in the same gene, invasion associated gene (iagA), which encodes a glycosyltransferase homolog. Allelic replacement of iagA in the GBS chromosome produced a 4-fold decrease in hBMEC invasiveness. Mice challenged with the GBS DeltaiagA mutant developed bacteremia comparably to WT mice, yet mortality was significantly lower (20% vs. 90%), as was the incidence of meningitis. The glycolipid diglucosyldiacylglycerol, a cell membrane anchor for lipoteichoic acid (LTA) and predicted product of the IagA glycosyltransferase, was absent in the DeltaiagA mutant, which consequently shed LTA into the media. Attenuation of virulence of the DeltaiagA mutant was found to be independent of TLR2-mediated signaling, but bacterial supernatants from the DeltaiagA mutant containing released LTA inhibited hBMEC invasion by WT GBS. Our data suggest that LTA expression on the GBS surface plays a role in bacterial interaction with BBB endothelium and the pathogenesis of neonatal meningitis.
Delta-Like 4 Induces Notch Signaling in Macrophages
Authors: Erik Fung, Sai-Man Timothy Tang, James P. Canner, Kunio Morishige, Joseph F. Arboleda-Velasquez, Angelo A. Cardoso, Nadia Carlesso, Jon C. Aster, Masanori Aikawa
Journal: Circulation (2007)

Background— Activated macrophages contribute to the pathogenesis of inflammatory diseases such as atherosclerosis. Although Notch signaling participates in various aspects of immunity, its role in macrophage activation remains undetermined. Methods and Results— To explore the role of Notch signaling in inflammation, we examined the expression and activity of Notch pathway components in human primary macrophages in vitro and in atherosclerotic plaques. Macrophages in culture express various Notch pathway components including all 4 receptors (Notch1 to Notch4). Notch3 selectively increased during macrophage differentiation; however, silencing by RNA interference demonstrated that all receptors are functional. The ligand Delta-like 4 (Dll4) increased in macrophages exposed to proinflammatory stimuli such as lipopolysaccharide, interleukin-1β, or minimally-modified low-density lipoprotein in a Toll-like receptor 4– and nuclear factor-κB–dependent fashion. Soluble Dll4 bound to human macrophages. Coincubation of macrophages with cells that expressed Dll4 triggered Notch proteolysis and activation; increased the transcription of proinflammatory genes such as inducible nitric oxide synthase, pentraxin 3 and Id1; resulted in activation of mitogen-activated protein kinase, Akt, and nuclear factor-κB pathways; and increased the expression of Dll4 in macrophages. Notch3 knockdown during macrophage differentiation decreased the transcription of genes that promote inflammation, such as inducible nitric oxide synthase, pentraxin 3, Id1, and scavenger receptor-A. These in vitro findings correlate with results of quantitative immunohistochemistry, which demonstrated the presence of Dll4 and other Notch components within macrophages in atherosclerotic plaques. Conclusion— Dll4-triggered Notch signaling may mediate inflammatory responses in macrophages and promote inflammation.
The Appropriateness of Performing Coronary Angiography and Coronary Artery Revascularization in a Swedish Population
Authors: Ann Bengtson
Journal: JAMA (1994)

To evaluate the appropriateness of performing coronary angiography and revascularization in a Swedish population.Prospective population study of questionnaires and medical records.All the hospitals in southwestern Sweden that perform coronary angiography and revascularization.Random sample of 831 patients (with chronic stable angina) on the waiting list for coronary angiography or revascularization in southwestern Sweden in September 1990.Percentage of patients referred for coronary angiography or revascularization for appropriate, uncertain, or inappropriate indications.Of the patients referred for angiography, 89% were classified as appropriate, 9% as uncertain, and 2% as inappropriate. The percentages are similar for patients referred for coronary artery bypass graft surgery and for angioplasty (91% and 86%, respectively, classified as appropriate). The majority of patients had chest pain rated as Canadian Cardiovascular Society classes II through IV (93%), despite maximum anti-ischemic therapy in 90% of these patients.Few patients were referred for coronary angiography or revascularization for inappropriate or uncertain indications. The percentage of these patients who are from southwestern Sweden is similar to the percentage recently reported from New York State.