tbuckley/cabot-search huggingface dataset:
Receptor-like specificity of a Plasmodium knowlesi malarial protein that binds to Duffy antigen ligands on erythrocytes.
Authors: J D Haynes, J P Dalton, F W Klotz, M H McGinniss, T J Hadley, D E Hudson, L H Miller
Journal: The Journal of Experimental Medicine (1988)

A 135-kD parasite protein, a minor component of the Plasmodium knowlesi malaria radiolabeled proteins released into culture supernatant at the time of merozoite release and reinvasion, specifically bound to human erythrocytes that are invaded and carry a Duffy blood group determinant (Fya or Fyb), but did not bind to human erythrocytes that are not invaded and do not carry a Duffy determinant (FyFy). Specific anti-Duffy antibodies blocked the binding of the 135-kD protein to erythrocytes carrying that specific Duffy determinant. Purified 135-kD protein bound specifically to the 35-45-kD Duffy glycoprotein on a blot of electrophoretically separated membrane proteins from Fya and Fyb erythrocytes but not from FyFy erythrocytes. Binding of the 135-kD protein was consistently greater to Fyb than to Fya both on the blot and on intact erythrocytes. The 135-kD protein also bound to rhesus erythrocytes that are Fyb and are invaded, but not to rabbit or guinea pig erythrocytes that are Duffy-negative and are not invaded. Cleavage of the Duffy determinant by pretreating Fyb human erythrocytes with chymotrypsin greatly reduced both invasion and binding of the 135-kD protein, whereas pretreating Fyb erythrocytes with trypsin had little effect on the Duffy antigen, the 135-kD protein binding, or on invasion. However, instances of invasion of other enzyme-treated erythrocytes that are Duffy-negative and do not bind the 135-kD protein suggest that alternative pathways for invasion do exist.
Anabolic steroid use among students at a British college of technology.
Authors: D J Williamson
Journal: British Journal of Sports Medicine (1993)

To determine the rate of current or previous use of anabolic steroids by students at a UK college of technology, a questionnaire survey of 687 day students was conducted. The questionnaire began with a general section for all of the students, which ended with the question 'Have you ever used anabolic steroids?'. A further section specifically for anabolic steroid users examined patterns of use, and how certain circumstances might affect the individual's decision to use anabolic steroids. The response rate to the questionnaire was 92%. The overall rate of current or previous use of anabolic steroids was 2.8% (4.4% in males, 1.0% in females). Of these, 56% had first used anabolic steroids at age 15 or less. Anabolic steroid users were more likely to be male, under 17 years of age, and participating in bodybuilding, weight-lifting or rugby. The results of this survey, if confirmed in other groups of young people, would suggest that use of anabolic steroids may be widespread in the UK.
Treatment of experimental pulmonary embolism by main pulmonary arterial infusion of a fibrinolytic agent
Authors: D. I. Magtira, M. Wells, R. Llamas, R. Clark, G. L. Baum
Journal: Thorax (1969)

The continuous instillation of plasmin (Thrombolysin) directly into the main pulmonary artery of greyhounds, using one half of the systemic doses, was found to be more effective in accelerating or enhancing <i>in vivo</i> lysis of artificially produced pulmonary emboli than systemic intravenous infusion. Animals which received direct pulmonary arterial instillations of Thrombolysin showed remarkably few macroemboli. By light microscopy, these clots showed zones of lysis mainly in the central portions of the clots. We suggest that the flow-guided catheterization of the main pulmonary artery used in this study on greyhounds can be applied to critically ill human subjects, as shown by earlier studies (Magtira, Winkler, Duprey, and Baum, 1966). Continuous infusions of thrombolytic agents directly into the main pulmonary artery might then offer an effective therapy for human pulmonary embolism, especially during that critical period following a massive or submassive embolic episode.
Comparative Analysis of Prothrombin Activators from the Venom of Australian Elapids
Authors: Liam St. Pierre, Paul P. Masci, Igor Filippovich, Natasha Sorokina, Neville Marsh, David J. Miller, Martin F. Lavin
Journal: Molecular Biology and Evolution (2005)

A key component of the venom of many Australian snakes belonging to the elapid family is a toxin that is structurally and functionally similar to that of the mammalian prothrombinase complex. In mammals, this complex is responsible for the cleavage of prothrombin to thrombin and is composed of factor Xa in association with its cofactors calcium, phospholipids, and factor Va. The snake prothrombin activators have been classified on the basis of their requirement for cofactors for activity. The two major subgroups described in Australian elapid snakes, groups C and D, are differentiated by their requirement for mammalian coagulation factor Va. In this study, we describe the cloning, characterization, and comparative analysis of the factor X– and factor V–like components of the prothrombin activators from the venom glands of snakes possessing either group C or D prothrombin activators. The overall domain arrangement in these proteins was highly conserved between all elapids and with the corresponding mammalian clotting factors. The deduced protein sequence for the factor X–like protease precursor, identified in elapids containing either group C or D prothrombin activators, demonstrated a remarkable degree of relatedness to each other (80%–97%). The factor V–like component of the prothrombin activator, present only in snakes containing group C complexes, also showed a very high degree of homology (96%–98%). Expression of both the factor X– and factor V–like proteins determined by immunoblotting provided an additional means of separating these two groups at the molecular level. The molecular phylogenetic analysis described here represents a new approach for distinguishing group C and D snake prothrombin activators and correlates well with previous classifications.
Cdc2-Like Kinases and DNA Topoisomerase I Regulate Alternative Splicing of Tissue Factor in Human Endothelial Cells
Authors: Andreas Eisenreich, Vladimir Y. Bogdanov, Andreas Zakrzewicz, Axel Pries, Silvio Antoniak, Wolfgang Poller, Heinz-Peter Schultheiss, Ursula Rauch
Journal: Circulation Research (2009)

Tumor necrosis factor (TNF)-α–stimulated human umbilical vein endothelial cells express 2 naturally occurring forms of tissue factor (TF), the primary initiator of blood coagulation: the soluble alternatively spliced isoform and the full-length TF isoform. The regulatory pathways enabling this phenomenon are completely unknown. Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing via phosphorylation of serine/arginine-rich proteins. In this study, we examined effects of serine/arginine-rich protein kinases on TF splicing following stimulation with TNF-α. Human endothelial cells were pretreated with specific inhibitors or small interfering RNAs against Cdc2-like kinases and DNA topoisomerase I before stimulation with TNF-α. TF levels were determined by semiquantitative RT-PCR, real-time PCR, and Western blotting. Cellular procoagulant activity was analyzed in a chromogenic TF activity assay. All 4 known Cdc2-like kinases forms were expressed in human endothelial cells. Selective inhibition of Cdc2-like kinases and DNA topoisomerase I elicited distinct changes in TF biosynthesis in TNF-α–stimulated endothelial cells, which impacted endothelial procoagulant activity. This study is the first to demonstrate that serine/arginine-rich protein kinases modulate splicing of TF pre-mRNA in human endothelial cells and, consequently, endothelial procoagulant activity under inflammatory conditions.
Feasibility of neuromuscular electrical stimulation (NMES) on the intensive care unit (ICU): Preliminary results
Authors: Johan Segers, Greet Hermans, Frans Bruyninckx, Geert Meyfroidt, Daniel Langer, Rik Gosselink
Journal: European Respiratory Journal (2012)

Background: Survivors of critical illness often have a prolonged ICU stay. To attenuate their reduction in muscle mass and muscle strength, NMES might be useful. Aim was to study feasibility and safety of NMES in ICU.

Methods: Patients with expected prolonged stay in ICU of 5 additional days (judged on day 3) without neurological disease were included. They received daily bilateral quadriceps NMES sessions of 25 minutes. Main outcome was to produce contraction of quadriceps. Patients with contraction in 75-100% of sessions were considered responders. Patient characteristics and stimulation parameters were compared between responders and non-responders. Safety was judged by cardiovascular and respiratory responses.

Results: 

View this table:

Table 1: Feasibility of NMES





View this table:

Table 2: Safety of NMES





Conclusion: In this small sample a trend is observed for age, APACHE II and edema to influence efficacy of NMES. NMES is a safe intervention in ICU.
THE EFFECT OF EXPOSURE TO THE FIFA 11+ WARM-UP PROGRAM ON INJURY RISK KNOWLEDGE AND PREVENTION BELIEFS IN ELITE FEMALE YOUTH SOCCER
Authors: CD McKay, K Steffen, M Romiti, CF Finch, CA Emery
Journal: British Journal of Sports Medicine (2014)

Background Injury knowledge and beliefs influence uptake of injury prevention programs. The effect of exposure to prevention programs on knowledge and beliefs is not well understood. Objective To explore the effect of exposure to the FIFA 11+ program on the injury knowledge and beliefs of female youth soccer coaches and players. Design A sub-cohort analysis from a cluster-randomized controlled trial. Setting Youth soccer league venues in Alberta, Canada. Participants 31 female teams [coaches n=29, players (ages 13–18) n=258]. Risk factor assessment Teams recorded FIFA 11+ adherence during the season. Main outcome measurements Coaches and players completed pre-season and post-season questionnaires to assess changes in injury knowledge and prevention beliefs after FIFA 11+ exposure. Results At baseline, 62.8% (95% CI: 48.4–77.3) of coaches and 75.8% (95% CI: 71.5–80.1) of players considered "inadequate warm-up" a risk factor for injury. There was no effect of 11+ adherence on this belief (odds ratio=1.0; 95% CI: 0.9–1.1), although more players (78.7%; 95% CI: 73.77–83.7) than coaches (51.7%; 95% CI: 33.55–69.9) considered "inadequate warm-up" a risk factor at post-season. At baseline, 13.8% (95% CI: 1.3–26.4) of coaches believed a warm-up could prevent muscle injuries, but none believed it could prevent knee and ankle injuries. For players, 9.7% (95% CI: 6.1–13.3), 4.7% (95% CI: 2.1–7.3), and 4.7% (95% CI: 2.1–7.3) believed a warm-up would prevent muscle, knee, and ankle injuies, respectively. There was no effect of adherence on post-season beliefs that a warm-up could prevent an injury, for coaches or players. Conclusions Exposure to the FIFA 11+ appears insufficient for changing injury risk or prevention beliefs over a single season. This could have implications for program delivery strategies and may influence sustained program use.
Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth
Authors: Evanthia Diamanti-Kandarakis, Christina Piperi
Journal: Human Reproduction Update (2005)

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. It is the most common endocrine disorder of women in reproductive age, a multifaceted reproductive, cosmetic and metabolic problem, with an enigmatic pathophysiological and molecular basis. Although the familial segregation has been noticed very early in the description of the syndrome and family studies in first-degree relatives of women diagnosed with PCOS reveal clustering of the disease, the genetic studies have not as yet determine the pattern of heredity. Part of the problem in genetic studies has been the lack of uniform criteria for diagnosis, heterogeneity of phenotypic features and the fact that the disorder is only expressed clinically in women during their reproductive years. Even within affected families and between sisters with polycystic ovaries, there is heterogeneity in presentation. However, regardless of diagnostic criteria used to identify profanes and to determine affected status in the kindred, the foundation of genetic studies suggests a strong familial component. Currently, PCOS is considered a polygenic trait that might result from the interaction of susceptible and protective genomic variants under the influence of environmental factors, whose role is under intensive investigation. Candidate genes cover a broad spectrum of an endless list of molecules which participate on every step of reproductive and metabolic pathways of this syndrome. Focused research in identification of these genes may provide valuable information and shed some light on the way out of the genomic labyrinth, elucidating the underlying pathophysiology and aiming at a more efficient therapeutic approach of this complicated endocrine disorder.
Components of verbal working memory
Authors: Aaro Toomela, J&uuml;ri Allik
Journal: Behavioral and Brain Sciences (1999)

The target article differentiates a new, syntactic component in verbal working memory. We suggest that several more components could be differentiated to make a model of working memory complete. Next, syntax is not always separable from the subject's verbal memory capacity as measured by standard working memory tasks. Finally, interference between different processes cannot be taken as evidence for the processes sharing the same resources. Interference might be a result of active mutual inhibition.
The neo-adjuvant, surgical and adjuvant treatment of gastric adenocarcinoma. Current expert opinion derived from the Seventh World Congress on Gastrointestinal Cancer, Barcelona, 2005
Authors: E. Van Cutsem, M. Dicato, N. Arber, A. Benson, D. Cunningham, E. Diaz-Rubio, B. Glimelius, R. Goldberg, D. Haller, K. Haustermans, Y. Koo-Kang, R. Labianca, I. Lang, B. Minsky, B. Nordlinger, A. Roth, P. Rougier, H.-J. Schmoll, A. Sobrero, J. Tabernero, A. Szawlowski, C. van de Velde
Journal: Annals of Oncology (2006)
Cerebrospinal Fever treated by M &amp; B 693
Authors: W. H. Osborn
Journal: BMJ (1939)

day of illness, well-marked signs of meningitis were present.Lumbar puncture on four successive days yielded respectively 30 c.cm., 33 c.cm., 30 c.cm., and 35 c.cm. of cerebrospinal fluid.The first two specimens were turbid and contained meningococci.The last specimen was clear, and the cell count was normal.Treatment.-On the day of admission 80 c.cm. of M.A.T. was given intraperitoneally, and on the following morning 30 c.cm. of M.A.T. intravenously.M & B 693 0.5 gramme was given four-hourly for the first three days, followed by 0.25 gramme four-hourly for one day.On April 12 she was sitting up playing with her toys.She was discharged, looking perfectly normal, on the twelfth day of her stay in hospital.
Activation of the Integrin Effector Kinase Focal Adhesion Kinase in Cancer Cells Is Regulated by Crosstalk between Protein Kinase Cα and the PDZ Adapter Protein mda-9/Syntenin
Authors: Cheol Hwangbo, Jaekyung Kim, Jung Joon Lee, Jeong-Hyung Lee
Journal: Cancer Research (2010)

Abstract Aberrant adhesion signaling pathways in cancer cells underlie their deadly invasive capabilities. The adhesion-related PDZ adapter protein mda-9/syntenin is a positive regulator of cancer cell progression in breast cancer, melanoma, and other human cancers. In this study, we report that mda-9/syntenin mediates adhesion-mediated activation of protein kinase Cα (PKCα) and focal adhesion kinase (FAK) by fibronectin (FN) in human breast cancer and melanoma cells. FN rapidly stimulated the expression of mda-9/syntenin and the activation of PKCα prior to activation of FAK. Inhibiting PKCα suppressed basal or FN-induced expression of mda-9/syntenin, as well as cell migration and invasion toward FN stimulated by mda-9/syntenin. Several lines of evidence suggested that activation of PKCα and expression of mda-9/syntenin were interdependent. First, mda-9/syntenin inhibition suppressed basal or FN-induced phosphorylation of PKCα at Thr638/641, whereas PKCα inhibition suppressed basal or FN-induced expression of mda-9/syntenin. Second, inhibiting either mda-9/syntenin or PKCα suppressed FN-induced formation of integrin-β1/FAK/c-Src signaling complexes. Third, inhibiting either mda-9/syntenin or PKCα suppressed FN-induced phosphorylation of FAK Tyr397 and c-Src Tyr416 and the induction of downstream effector signals to p38 and mitogen-activated protein kinase, Cdc42, and NF-κB. In summary, our findings offer evidence that mda-9/syntenin acts as a molecular adaptor linking PKCα and FAK activation in a pathway of FN adhesion by human breast cancer and melanoma cells. Cancer Res; 70(4); 1645–55
Ascorbic acid and tetrahydrobiopterin: looking beyond nitric oxide bioavailability
Authors: J. M. Muller-Delp
Journal: Cardiovascular Research (2009)

Endothelial dysfunction, manifested as reduced vasodilatory capacity, occurs in arteries exposed chronically to cardiovascular risk factors.1 Hyperglycaemia, hypercholesterolaemia, hypertension, ageing, and smoking have all been associated with endothelial dysfunction.2–4 Although the molecular basis of endothelial dysfunction remains incompletely understood, numerous studies support a loss of bioavailable nitric oxide (NO) as a key mechanism underlying the dysfunction.1,4 Both tetrahydrobiopterin (BH4) and ascorbic acid play a role in sustaining NO bioavailabilty,5–7 and supplementation with either BH4 or ascorbic acid has been shown to improve endothelial function in humans and in animal models.6,8,9 As a result, investigations of the cardiovascular implications of treatment with exogenous BH4 and ascorbic acid have focused on the endothelial effects of these compounds and their contribution to chemical stabilization of the enzyme endothelial nitric oxide synthase (eNOS) and protection of NO from scavenging by free radicals, respectively. Both BH4 and ascorbic acid may contribute to promoting NO-dependent vasodilation; however, both compounds possess redox capabilities that may alter vascular reactivity independent of their effects on the bioavailability of NO.10

In a study in this issue of Cardiovascular Research , Garry et al. investigated the possibility that pro-oxidant effects of BH4 and ascorbic acid potentiate NO-independent … 

*Corresponding author. Tel: +1 352 392 3791; fax: +1 352 846 0270. E-mail address : jdelp{at}ufl.edu
Particle Radiation Therapy Using Proton and Heavier Ion Beams
Authors: Daniela Schulz-Ertner, Hirohiko Tsujii
Journal: Journal of Clinical Oncology (2007)

Particle beams like protons and heavier ions offer improved dose distributions compared with photon (also called x-ray) beams and thus enable dose escalation within the tumor while sparing normal tissues. Although protons have a biologic effectiveness comparable to photons, ions, because they are heavier than protons, provide a higher biologic effectiveness. Recent technologic developments in the fields of accelerator engineering, treatment planning, beam delivery, and tumor visualization have stimulated the process of transferring particle radiation therapy (RT) from physics laboratories to the clinic. This review describes the physical, biologic, and technologic aspects of particle beam therapy. Clinical trials investigating proton and carbon ion RT will be summarized and discussed in the context of their relevance to recent concepts of treatment with RT.
Perception and action planning: Getting it together
Authors: David A. Westwood, Melvyn A. Goodale
Journal: Behavioral and Brain Sciences (2001)

Hommel et al. propose that high-level perception and action planning share a common representational domain, which facilitates the control of intentional actions. On the surface, this point of view appears quite different from an alternative account that suggests that “action” and “perception” are functionally and neurologically dissociable processes. But it is difficult to reconcile these apparently different perspectives, because Hommel et al. do not clearly specify what they mean by “perception” and “action planning.” With respect to the visual control of action, a distinction must be made between conscious visual perception and unconscious visuomotor processing. Hommel et al. must also distinguish between the what and how aspects of action planning, that is, planning what to do versus planning how to do it.
Expression of Interleukin-18 in Human Atherosclerotic Plaques and Relation to Plaque Instability
Authors: Ziad Mallat, Anne Corbaz, Alexandra Scoazec, Sandrine Besnard, Guy Lesèche, Yolande Chvatchko, Alain Tedgui
Journal: Circulation (2001)

Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown.In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) plaques (P<0.01).These results suggest, for the first time, a major role for IL-18 in atherosclerotic plaque destabilization leading to acute ischemic syndromes.
Rapid Rates of Lineage-Specific Gene Duplication and Deletion in the α-Globin Gene Family
Authors: Federico G. Hoffmann, Juan C. Opazo, Jay F. Storz
Journal: Molecular Biology and Evolution (2008)

Phylogeny reconstructions of the globin gene families have revealed that paralogous genes within species are often more similar to one another than they are to their orthologous counterparts in closely related species. This pattern has been previously attributed to mechanisms of concerted evolution such as interparalog gene conversion that homogenize sequence variation between tandemly duplicated genes and therefore create the appearance of recent common ancestry. Here we report a comparative genomic analysis of the alpha-globin gene family in mammals that reveal a surprisingly high rate of lineage-specific gene duplication and deletion via unequal crossing-over. Results of our analysis reveal that patterns of sequence similarity between paralogous alpha-like globin genes from the same species are only partly explained by concerted evolution between preexisting gene duplicates. In a number of cases, sequence similarity between paralogous sequences from the same species is attributable to recent ancestry between the products of de novo gene duplications. As a result of this surprisingly rapid rate of gene gain and loss, many mammals possess alpha-like globin genes that have no orthologous counterparts in closely related species. The resultant variation in gene copy number among species may represent an important source of regulatory variation that affects physiologically important aspects of blood oxygen transport and aerobic energy metabolism.