tbuckley/cabot-search huggingface dataset:
Serum and synovial fluid adenosine deaminase activity in patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis.
Authors: H Yuksel, T F Akoglu
Journal: Annals of the Rheumatic Diseases (1988)

Adenosine deaminase activity was determined in paired samples of serum and synovial fluid taken from patients with rheumatoid arthritis (n = 12), reactive arthritis (n = 13), and osteoarthritis (n = 7), and the value of this investigation in the diagnosis of synovial swellings was assessed. Increased activity was found in the synovial fluid taken from patients with rheumatoid disease and reactive arthritis, though values were less raised in the latter. Synovial fluid taken from patients with osteoarthritis did not show significantly raised adenosine deaminase activity as compared with that of normal controls (n = 3).
Safety and effectiveness of immunotherapy in patients with indolent systemic mastocytosis presenting with Hymenoptera venom anaphylaxis
Authors: David González de Olano, Iván Álvarez-Twose, María I. Esteban-López, Laura Sánchez-Muñoz, María D. Alonso Díaz de Durana, Arantza Vega, Andres García-Montero, Eloina González-Mancebo, Teresa Belver, María D. Herrero-Gil, Montserrat Fernández-Rivas, Alberto Orfao, Belén de la Hoz, Mariana C. Castells, Luis Escribano
Journal: Journal of Allergy and Clinical Immunology (2008)
ABC of nutrition. Nutritional advice for other chronic diseases.
Authors: A S Truswell
Journal: BMJ (1985)

CHRONIC DISEASES CrownDental caries affects people predominantly in the first 25 years of life.Dental enamel is the hardest material in the body.Its weakness is that, name because it is basically calcium phosphate, it is dissolved by acid.Three factors together contribute to caries. StreptococciInfection-A specific species of viridans streptococci, Streptococcus W \\ Dentine\ X g inside mutans, metabolises sugars to lactic acid and polymerises sugars to a layer of covering polysaccharide in which the bacteria are shielded from saliva and the tongue.Some people harbour more of these bacteria than others.Substrate-Most sugars serve as substrate-sucrose, glucose, fructose, and lactose (apparently not sorbitol or xylitol).Starches too, if they stay in a\\ pulp X the mouth are split to sugars by salivary amylase.Consumption of sugary foods between meals, especially if they are sticky and consumption is Cavity inside repeated, favours the development of caries.Brushing the teeth and enamel rinsing the mouth after meals reduces the likelihood of caries.5.4 5 ar without fluoride 10 Age5 L_ 4 <,, 3 |No fluoride El E 8 Fluoride R Resistance oftlie teeth-Caries is more likely in 22 c6 fissures.In older people the "mature" enamel is 2-Area w4thfluoridel more resistant.An intake of 1-3 mg/day of LA 1~~~~~~~~~~~~~4 . 1 > , : 2 g * * gfluoride-as occurs, for example, if drinking water is fluoridated at a concentration of 1 mg/l-1976
Myeloid-related protein 8/14 levels in children with obstructive sleep apnoea
Authors: J. Kim, R. Bhattacharjee, A. B. Snow, O. S. Capdevila, L. Kheirandish-Gozal, D. Gozal
Journal: European Respiratory Journal (2009)

Obstructive sleep apnoea (OSA) is common in children and leads to multiple end-organ morbidities. Myeloid-related protein (MRP) 8/14 plays an important pathophysiological role in atherosclerosis, and plasma levels correlate with endothelial cell dysfunction. We hypothesised that MRP8/14 levels would be altered in children with OSA. 255 children (aged 7.6±1.5 yrs) were included after a sleep study and a morning blood sample. MRP8/14 and interleukin-6 plasma levels were assayed using ELISA and C-reactive protein by immunoturbidometry. Endothelial function was assessed as the hyperaemic response after occlusion of the brachial artery. Plasma log MRP8/14 levels showed apnoea/hypopnoea index (AHI) dose-dependent increases regardless of obesity. Moreover, log MRP8/14 levels correlated with log AHI (r = 0.340, p&lt;0.001) after controlling for age and body mass index Z-score, and with endothelial function. Children with the highest MRP levels (&gt;1.34 ug·mL<sup>−1</sup>) had 2.4- and 5.4-fold increased odds of mild OSA and moderate-to-severe OSA, respectively, after adjusting for confounding variables. Plasma MRP8/14 levels are associated with paediatric OSA and may reflect increased risk for cardiovascular morbidity. The short- and long-term consequences of elevated MRP8/14 on cardiovascular function in the context of paediatric OSA remain to be defined.
Algal Genes in the Closest Relatives of Animals
Authors: G. Sun, Z. Yang, A. Ishwar, J. Huang
Journal: Molecular Biology and Evolution (2010)

The spread of photosynthesis is one of the most important but controversial topics in eukaryotic evolution. Because of massive gene transfer from plastids to the nucleus and because of the possibility that plastids have been lost in evolution, algal genes in aplastidic organisms often are interpreted as footprints of photosynthetic ancestors. These putative plastid losses, in turn, have been cited as support for scenarios involving the spread of plastids in broadscale eukaryotic evolution. Phylogenomic analyses identified more than 100 genes of possible algal origin in Monosiga, a unicellular species from choanoflagellates, a group considered to be the closest protozoan relatives of animals and to be primitively heterotrophic. The vast majority of these algal genes appear to be derived from haptophytes, diatoms, or green plants. Furthermore, more than 25% of these algal genes are ultimately of prokaryotic origin and were spread secondarily to Monosiga. Our results show that the presence of algal genes may be expected in many phagotrophs or taxa of phagotrophic ancestry and therefore does not necessarily represent evidence of plastid losses. The ultimate prokaryotic origin of some algal genes and their simultaneous presence in both primary and secondary photosynthetic eukaryotes either suggest recurrent gene transfer events under specific environments or support a more ancient origin of primary plastids.
Contribution of in vitro culture methods for respiratory epithelial cells to the study of the physiology of the respiratory tract
Authors: M Jorissen, B Van der Schueren, H Van den Berghe, JJ Cassiman
Journal: European Respiratory Journal (1991)

Different techniques for culturing respiratory epithelial cells have been developed to overcome the limitations of studies on in vivo and on bioptic material. However, each culture technique has its limitations, specifically concerning the expression of differentiated properties. These methods and limitations are described and discussed. Special attention is given to recent developments, which may resolve some of the current problems.
CD155/PVR Enhances Glioma Cell Dispersal by Regulating Adhesion Signaling and Focal Adhesion Dynamics
Authors: Kevin E. Sloan, Jean K. Stewart, Allison F. Treloar, Russell T. Matthews, Daniel G. Jay
Journal: Cancer Research (2005)

We recently identified the immunoglobulin-CAM CD155/PVR (the poliovirus receptor) as a regulator of cancer invasiveness and glioma migration, but the mechanism through which CD155/PVR controls these processes is unknown. Here, we show that expression of CD155/PVR in rat glioma cells that normally lack this protein enhances their dispersal both in vitro and on primary brain tissue. CD155/PVR expression also reduced substrate adhesion, cell spreading, focal adhesion density, and the number of actin stress fibers in a substrate-dependent manner. Furthermore, we found that expression of CD155/PVR increased Src/focal adhesion kinase signaling in a substrate-dependent manner, enhancing the adhesion-induced activation of paxillin and p130Cas in cells adhering to vitronectin. Conversely, depletion of endogenous CD155/PVR from human glioma cells inhibited their migration, increased cell spreading, and down-regulated the same signaling pathway. These findings implicate CD155/PVR as a regulator of adhesion signaling and suggest a pathway through which glioma and other cancer cells may acquire a dispersive phenotype.
Effect of N-acetylcysteine on sympathetic hyperinnervation in post-infarcted rat hearts
Authors: T.-M. Lee, P.-Y. Lai, N.-C. Chang
Journal: Cardiovascular Research (2009)

The purpose of this study was to determine whether N-acetylcysteine (NAC) attenuates cardiac sympathetic hyperinnervation through replenishment of glutathione in infarcted rats.After ligation of the coronary artery, male Wistar rats were randomized to either vehicle, NAC, or vitamins C + E groups for 4 weeks. Post-infarction was associated with increased oxidant release, as measured by tissue isoprostane and myocardial glutathione. Measurement of myocardial norepinephrine levels revealed a significant elevation in vehicle-treated infarcted rats compared with sham-operated rats. Sympathetic hyperinnervation was blunted after administering NAC, as assessed by immunofluorescent analysis of tyrosine hydroxylase and western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in the vehicle-treated infarcted rats were significantly higher than those in animals treated with NAC. Although NAC and vitamins showed similar effects on ventricular remodelling, only NAC demonstrated beneficial effects on sympathetic hyperinnervation. Furthermore, the effects of NAC on nerve growth factor were abolished by administering l-buthionine sulfoximinem, an inhibitor of gamma-glutamylcysteine ligase.Chronic use of NAC, but not vitamins, after infarction is associated with down-regulation of nerve growth factor proteins, probably through a glutathione-dependent pathway, and thus plays a critical role in the beneficial effect on the arrhythmogenic response to programmed electrical stimulation.
Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1
Authors: Xiaoyu Li, Fotini Gounari, Alexei Protopopov, Khashayarsha Khazaie, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2008)

Mutations resulting in overexpression of intracellular Notch1 (ICN1) are frequently observed in human T cell acute lymphoblastic leukemia (T-ALL). We have determined the consequences of ICN1 overexpression from retroviral vectors introduced into bone marrow cells. Early consequences are the generation of polyclonal nontumorigenic CD4+8+ T cell receptor (TCR)-αβ+ cells that do not qualify as tumor precursors despite the observation that they overexpress Notch 1 and c-Myc and degrade the tumor suppressor E2A by posttranslational modification. The first tumorigenic cells are detected among more immature CD4−8+TCR-αβ− cells that give rise to monoclonal tumors with a single, unique TCR-β chain and diverse TCR-α chains, pinpointing malignant transformation to a stage after pre-TCR signaling and before completion of TCR-α rearrangement. In T-ALL, E2A deficiency is accompanied by further transcriptional up-regulation of c-Myc and concomitant dysregulation of the c-Myc-p53 axis at the transcriptional level. Even though the tumors consist of phenotypically heterogeneous cells, no evidence for tumor stem cells was found. As judged by array-based comparative genomic hybridization (array CGH) and spectral karyotype (SKY) analysis, none of the tumors arise because of genomic instability.
Effectiveness of Antimalarial Drugs
Authors: J. Kevin Baird
Journal: New England Journal of Medicine (2005)

A global resurgence of malaria has taken place as a result of a lapse in preventive efforts and the emergence of resistance to standard antimalarial drugs. New therapies are available, but because of social, economic, and clinical factors, the use of older drugs persists. This review considers current approaches to the prevention and treatment of malaria.
Remarks on Sayre's Treatment of Spinal Disease
Authors: C. H. Golding-Bird
Journal: BMJ (1878)

feore ofLyedanc , I" s .aee to wh'k he a lie his method of: tha brc,That is tt sa, tht he, by sheer rce, and without any tenotomy or other operation, broke WE the lower femoral epiphysis and tore some of the ligamentous tissue on the outer side of the joint, and improved the deformity.I tried this method,-now mrore than three years ago, when the Children's Hospital was at Ratcliff Cross, and partially succeeded, after using considerable force, in which I was aided by a colleague.The other day, I tried it again in a mila case of genu vaJgum; but I, and several other gentlemen, who used considerable force, failed to make any, impression on the deformity.
The Progress and Promise of Molecular Imaging Probes in Oncologic Drug Development
Authors: Gary J. Kelloff, Kenneth A. Krohn, Steven M. Larson, Ralph Weissleder, David A. Mankoff, John M. Hoffman, Jeanne M. Link, Kathryn Z. Guyton, William C. Eckelman, Howard I. Scher, Joyce O'Shaughnessy, Bruce D. Cheson, Caroline C. Sigman, James L. Tatum, George Q. Mills, Daniel C. Sullivan, Janet Woodcock
Journal: Clinical Cancer Research (2005)

Abstract As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency, and cost-effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have great potential as oncologic drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmacokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analyses may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. This article outlines the scientific basis of oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes.
BGC 945, a Novel Tumor-Selective Thymidylate Synthase Inhibitor Targeted to α-Folate Receptor–Overexpressing Tumors
Authors: David D. Gibbs, Davinder S. Theti, Nadya Wood, Matthew Green, Florence Raynaud, Melanie Valenti, Martin D. Forster, Fraser Mitchell, Vassilios Bavetsias, Elisa Henderson, Ann L. Jackman
Journal: Cancer Research (2005)

Abstract BGC 945 is a cyclopenta[g]quinazoline–based, thymidylate synthase inhibitor specifically transported into α-folate receptor (α-FR)–overexpressing tumors. Affinity of BGC 945 for the α-FR is 70% of the high-affinity ligand folic acid. In contrast to conventional antifolates, BGC 945 has low affinity for the widely expressed reduced-folate carrier (RFC). The Ki for isolated thymidylate synthase is 1.2 nmol/L and the IC50 for inhibition of the growth of α-FR-negative mouse L1210 or human A431 cells is ∼7 μmol/L. In contrast, BGC 945 is highly potent in a range of α-FR-overexpressing human tumor cell lines (IC50 ∼1-300 nmol/L). Pharmacokinetic variables measured following i.v. injection of 100 mg/kg BGC 945 to KB tumor–bearing mice showed rapid plasma clearance (0.021 L/h) and tissue distribution. The terminal half-lives in plasma, liver, kidney, spleen, and tumor were 2, 0.6, 5, 21, and 28 hours, respectively. Tumor BGC 945 concentration at 24 hours was ∼1 nmol/g tissue, at least 10-fold higher than that in plasma or normal tissues. Inhibition of thymidylate synthase in tissues leads to increased incorporation of 5-[125I]-iodo-2′-deoxyuridine ([125I]dUrd) into DNA. Forty-eight hours after injection of 100 mg/kg 6RS-BGC 945 ([125I]dUrd injected at 24 hours), tumor was the only tissue with incorporation above control level (6-fold). The RFC-mediated thymidylate synthase inhibitor plevitrexed also increased uptake of [125I]dUrd in tumor (10-fold) but, in contrast, also caused increased incorporation in other normal tissues such as spleen and small bowel (4.5- and 4.6-fold, respectively). These data suggest that BGC 945 selectively inhibits thymidylate synthase in α-FR-overexpressing tumors and should cause minimal toxicity to humans at therapeutic doses. (Cancer Res 2005; 65(24): 11721-8)
OP27 * ETOPOSIDE PHARMACOKINETICS FOLLOWING INTRA-CEREBROSPINAL FLUID ADMINISTRATION IN PATIENTS WITH LEPTOMENINGEAL METASTASES
Authors: L. Meijer, G. Veal, D. Walker, R. Grundy
Journal: Neuro-Oncology (2014)

INTRODUCTION: Daily intra-cerebrospinal fluid (CSF) etoposide administration regimens are in use, by-passing the blood-brain-barrier and offering higher CSF drug concentrations at 1/30th to 1/340th the dose in conventional systemically administered standard and high dose etoposide regimens, respectively. METHOD: 42 pharmacokinetic samples were obtained from a paediatric (36) and adult patient (6). Etoposide 0.75 mg was administered over 1-2 minutes via the intra-ventricular (IVT) or lumbar route (LR), on 5 consecutive days for 1-3 weeks. CSF sampling at 4h (IVT: 3, LR: 3), 8h (IVT: 3, LR: 2), 18h (IVT: 1, LR: 1), 24h (IVT: 11, LR: 9), and 72h (IVT: 5, LR: 4). Etoposide concentrations were determined by LC/MS analysis, with a detection limit of 0.1 µg/ml. RESULTS: No acute neurotoxicity was observed. Single IVT administration with LR sampling yielded higher concentrations than LR administration with IVT sampling at 4h and 8h (1.73 and 0.93 µg/ml, vs. 1.42 and 0.76 µg/ml, respectively), also observed with simultaneous LR and IVT administration (median LR concentration 5.11 and 1.77 µg/ml at 4h and 8h; median IVT concentration 3.64 and 1.48 µg/ml at 4h and 8h). Concentrations at 24h were <0.2 (median 0.15, 14 samples) and at 72h <0.1 µg/ml (8 samples), irrespective of routes and sample sites. CONCLUSION: Intra-CSF etoposide administration at this dose level is safe, with almost complete clearence at 24h, and good distribution throughout the CSF compartment, irrespective of delivery route. Higher LR compared to IVT concentrations are probably related to CSF stasis. The rapid clearance characteristic warrants investigation of continuous drug infusion to sustain targeted CSF steady state etoposide concentrations.
Platelet activation in patients with thrombotic thrombocytopenic purpura
Authors: Maureane Hoffman, Dougald M. Monroe, Harold R. Roberts
Journal: American Journal of Hematology (1993)

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome of unknown etiology. It is characterized by platelet microthrombi in small vessels, which results in tissue dysfunction and a microangiopathic hemolytic anemia. Activation of coagulation is not a prominent feature of TTP. It is not known whether the process which results in platelet aggregate formation might also activate platelets. Using GMP-140 as a marker of activation, we examined the activation state of circulating platelets in seven TTP patients and three normal controls, as well as the ability of purified platelets from three TTP patients and three controls to be activated in vitro. There was no statistically significant difference in the percentage of activated platelets circulating in patients and controls (4% vs. 2%). Both TTP and control platelets increased GMP-140 expression and procoagulant activity after stimulation with thrombin or the calcium ionophore A23187. Thus, we conclude that TTP patients do not have a significantly increased proportion of circulating activated platelets, and their platelets can be activated normally by thrombin or a calcium ionophore.
Tumor necrosis factor ? induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin
Authors: K PORTER, N TURNER, D OREGAN, S BALL
Journal: Cardiovascular Research (2004)

Objective: Tumor necrosis factor α (TNFα) is implicated in myocardial remodeling, a process in which activated cardiac fibroblasts (myofibroblasts) secrete matrix-degrading metalloproteinases (MMPs) and undergo increased proliferation and invasion. Statins are cholesterol-lowering drugs that also have direct cellular effects, which may underlie their ability to reduce myocardial remodeling. This study investigated the effect of TNFα on human cardiac myofibroblast proliferation, invasion and MMP-9 secretion, and determined whether these properties were modulated by simvastatin. Methods: Human cardiac myofibroblasts were cultured from right atrial appendage. TNF receptor expression was quantified by immunoblotting. Cell proliferation, invasion, MMP-9 secretion and MMP-9 mRNA expression were determined by cell counting, Matrigel-coated modified Boyden chamber assays, gelatin zymography and RT-PCR, respectively. Results: Human atrial myofibroblasts expressed the TNF-RI and TNF-RII receptor subtypes. TNFα (1 ng/ml) induced a 23.1±3.9% increase in cell number after 4 days (P<0.001). Additionally, TNFα (1–10 ng/ml) significantly (P<0.01) increased myofibroblast invasion, with a concomitant increase in MMP-9 secretion, that was due to increased MMP-9 mRNA levels. Using TNF-R-specific neutralizing antibodies, we determined that these cellular effects of TNFα were predominantly TNF-RI-mediated. Simvastatin (0.1–10 μmol/l) concentration dependently inhibited TNFα-induced myofibroblast proliferation, invasion and MMP-9 secretion. Conclusions: TNFα, acting predominantly via the TNF-R1 receptor, increased human atrial myofibroblast proliferation, invasion and MMP-9 secretion, all of which were inhibited by simvastatin. Inhibition of cytokine-induced cardiac myofibroblast activation by statins provides a rationale for their use in patients with cardiac pathologies characterized by adverse myocardial remodeling.
Impact of chemotherapy regimen and hematopoietic growth factor on mobilization and collection of peripheral blood stem cells in cancer patients
Authors: M.R. Nowrousian, S. Waschke, P. Bojko, A. Welt, P. Schuett, P. Ebeling, M. Flasshove, T. Moritz, J. Schuette, S. Seeber
Journal: Annals of Oncology (2003)