tbuckley/cabot-search huggingface dataset:
In-vivo skin test.
Authors: U Ambanelli, G F Ferraccioli
Journal: Annals of the Rheumatic Diseases (1982)

Reactive arthritis associated with campylobacter enteritis Sm, Eastmond and his colleagues' really should not compare chalk with cheese.They studied patients infected in a single explosive outbreak of campylobacter enteritis, all presumably due to the same strain of Campylobacter jejuni.We studied cases occurring sporadically, diagnosed but not necessarily infected, within the Harrow Heath District, and probably
HIV-1 Upregulates VEGF in Podocytes
Authors: Sonal Navin Korgaonkar, Xiaobei Feng, Michael D. Ross, Ting-chi Lu, Vivette D'Agati, Ravi Iyengar, Paul E. Klotman, John Cijiang He
Journal: Journal of the American Society of Nephrology (2008)

HIV-associated nephropathy (HIVAN) is characterized by collapsing FSGS. Because transgenic mice with podocyte-specific overexpression of the vascular endothelial growth factor 164 (VEGF164) isoform also develop collapsing FSGS, we sought to determine whether VEGF plays a role in HIVAN. Compared with controls, immunohistochemistry revealed that kidneys from HIV-1-transgenic mice (Tg26) and from patients with HIVAN had greater expression of both VEGF and its transcriptional regulator, hypoxia-inducible factor 2alpha (HIF-2alpha). Similarly, mRNA and protein levels of VEGF and HIF-2alpha were increased in HIV-infected podocytes in vitro, and this transcriptional upregulation was found to be stimulated by the HIV viral protein Nef in a Src kinase-and Stat3-dependent manner. HIV-1 also upregulated VEGFR2 and its co-receptor neuropilin-1 and suppressed the expression of semaphorin 3a in the podocyte. Exogenous VEGF stimulated proliferation and de-differentiation of podocytes, which are features of collapsing FSGS, and VEGFR2 neutralizing antibodies reversed these features in podocytes infected with HIV-1 or isolated from Tg26 mice. In conclusion, HIV-1 induces VEGF and VEGFR2 expression in podocytes, and this may be a critical step in the pathogenesis of HIVAN.
Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing
Authors: Camilla I. Svensson, Michela Zattoni, Charles N. Serhan
Journal: The Journal of Experimental Medicine (2007)

Inflammatory conditions can lead to debilitating and persistent pain. This hyperalgesia reflects sensitization of peripheral terminals and facilitation of pain signaling at the spinal level. Studies of peripheral systems show that tissue injury triggers not only inflammation but also a well-orchestrated series of events that leads to reversal of the inflammatory state. In this regard, lipoxins represent a unique class of lipid mediators that promote resolution of inflammation. The antiinflammatory role of peripheral lipoxins raises the hypothesis that similar neuraxial systems may also down-regulate injury-induced spinal facilitation of pain processing. We report that the lipoxin A4 receptor is expressed on spinal astrocytes both in vivo and in vitro and that spinal delivery of lipoxin A4, as well as stable analogues, attenuates inflammation-induced pain. Furthermore, activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in astrocytes, which has been indicated to play an important role in spinal pain processing, was attenuated in the presence of lipoxins. This linkage opens the possibility that lipoxins regulate spinal nociceptive processing though their actions upon astrocytic activation. Targeting mechanisms that counterregulate the spinal consequences of persistent peripheral inflammation provide a novel endogenous mechanism by which chronic pain may be controlled.
Pulmonary Aspergilloma
Authors: Jose Ramirez-R.
Journal: New England Journal of Medicine (1964)

EXCEPT for pulmonary resection in selected cases, the therapy of pulmonary aspergillosis has been generally ineffective. Nevertheless, in isolated cases, cures have followed the administration of nystatin by mouth1 and by aerosol2 and the parenteral injection of stilbamidine.3 More recently, the administration of 24 to 30 gm. of potassium iodide by mouth in 2 cases4 and of amphotericin B intravenously in another5 was also thought to be therapeutically effective. However, the drug intolerance and electrolyte imbalance resulting from large doses of iodides taken by mouth4 and the systemic and renal toxic effects of intravenously administered amphotericin6 , 7 prevent a casual approach . . .
Oxidative effects of selenite on rat ventricular contractility and Ca movements
Authors: B Turan
Journal: Cardiovascular Research (1996)

Objective: The study aimed at characterizing the effects of selenite, known for its reactivity with thiols, on cardiac contractility and excitation-contraction coupling. Methods: The inotropic effects of selenite were studied on rat papillary muscles. Freshly isolated rat ventricular myocytes were used to determine the selenite-induced alterations in thiol contents, free Ca2+ levels (in fura-2 loaded cells), Ca2+ currents and contractile properties of skinned cells. Results: Selenite, at concentrations ≥ 0.1 mM, affected muscle contractions by inducing a transient positive inotropic effect (up to 120 ± 3% of control in 1 mM selenite) followed by a gradual decline of developed tension together with an increase in resting tension (respectively to 37 ± 3 and 166 ± 5% of their control values after 20 min exposure). These changes, irreversible on washout, could be reversed by the disulfide reducing agent dithiothreitol (DTT, 1 mM). Lowering temperature from 35 ° to 22 °C or preincubating the muscles with the disulfonic stilbene SITS (0.2 mM) completely prevented the selenite-induced transient positive inotropy and rise in resting tension. In isolated myocytes, 10 min exposure to 1 mM selenite induced a 40 ± 9% decrease of total sulfhydryl content. At this concentration, selenite rapidly caused a rise of basal [Ca2+]i together with a diminution of the Ca2+ spike amplitude (respectively to 165 ± 15 and 45 ± 9% of their control values after 5 min exposure). In addition, selenite significantly enhanced at each Ca2+ concentration the force generated by skinned myocytes. Ca2+ currents, measured at 22 °C, decreased by 28 ± 8% in the presence of 1 mM selenite. These effects were reversed by DTT. Conclusions: The results demonstrate that selenite, through alterations of cellular thiol redox status, induced a dual action on muscle contraction that can be imputed to a combined action on Ca2+ channels, Ca2+ transporters and contractile proteins. Extracellular negative effects of selenite are due to a partial reduction of Ca2+ current magnitude. Intracellular effects are mediated both by a diminution of Ca2+ handing by intracellular organelles and by a sensitization of the contractile to Ca2+ ions. The results further indicate that selenite uptake into the cardiac cells occurs mainly through the temperature-sensitive anion exchanger.
Superoxide generation by human monocytes and macrophages
Authors: Stephen J. Weiss, Gerald W. King, Albert F. Lobuglio
Journal: American Journal of Hematology (1978)

Abstract Intracellular and extracellular superoxide (O 2 .− ) generation by human monocytes and macrophages was quantitated by the nitroblue tetrazolium (NBT) reduction method. Human monocytes reduced 4.4 ± 0.9 nmoles/10 6 cells/15 minutes with an increase to 12.4 ± 1.3 during phagocytosis of zymosan. Based on inhibition by superoxide dismutase, superoxide generation of these cells was 1.8 ± 0.3 nmoles in the resting state and 16.8 ± 2.8 nmoles with zymosan phagocytosis. Human macrophages obtained by thoracentesis had comparable levels of NBT reduction and O 2 .− generation. Monocytes from a patient with chronic granulomatous disease demonstrated no increment in O 2 .− production during phagocytosis. Thus, human monocytes and macrophages appear capable of generating substantial amounts of O 2 .− during phagocytosis which may play an important role in bactericidal and other cell functions.
Modeling the impact on virus transmission of <i>Wolbachia</i> -mediated blocking of dengue virus infection of <i>Aedes aegypti</i>
Authors: Neil M. Ferguson, Duong Thi Hue Kien, Hannah Clapham, Ricardo Aguas, Vu Tuan Trung, Tran Nguyen Bich Chau, Jean Popovici, Peter A. Ryan, Scott L. O’Neill, Elizabeth A. McGraw, Vo Thi Long, Le Thi Dui, Hoa L. Nguyen, Nguyen Van Vinh Chau, Bridget Wills, Cameron P. Simmons
Journal: Science Translational Medicine (2015)

Experimental work and modeling studies reveal that Aedes aegypti infected with the Wolbachia bacterium have reduced vector competence for the transmission of dengue viruses.
Ryanodine Receptor Current Amplitude Controls Ca <sup>2+</sup> Sparks in Cardiac Muscle
Authors: Tao Guo, Dirk Gillespie, Michael Fill
Journal: Circulation Research (2012)

In cardiac muscle, Ca(2+)-induced Ca(2+) release (CICR) from the sarcoplasmic reticulum (SR) is mediated by ryanodine receptor (RyR) Ca(2+) release channels. The inherent positive feedback of CICR is normally well-controlled. Understanding this control mechanism is a priority because its malfunction has life-threatening consequences.We show that CICR local control is governed by SR Ca(2+) load, largely because load determines the single RyR current amplitude that drives inter-RyR CICR.We differentially manipulated single RyR Ca(2+) flux amplitude and SR Ca(2+) load in permeabilized ventricular myocytes as an endogenous cell biology model of the heart. Large RyR-permeable organic cations were used to interfere with Ca(2+) conductance through the open RyR pore. Single-channel studies show this attenuates current amplitude without altering other aspects of RyR function. In cells, the same experimental maneuver increased resting SR Ca(2+) load. Despite the increased load, Ca(2+) spark (inter-RyR CICR events) frequency decreased and sparks terminated earlier.Spark local control follows single RyR current amplitude, not simply SR Ca(2+) load. Spark frequency increases with load because spontaneous RyR openings at high loads produce larger currents (ie, a larger CICR trigger signal). Sparks terminate when load falls to the point at which single RyR current amplitude is no longer sufficient to sustain inter-RyR CICR. Thus, RyRs that spontaneously close no longer reopen and local Ca(2+) release ends.
The effects of age and skill level on knee musculature co-contraction during functional activities: A systematic review
Authors: Kevin R. Ford, Antonie J. van den Bogert, Gregory D Myer, Robert Shapiro, Timothy E. Hewett
Journal: British Journal of Sports Medicine (2008)

Objectives- To systematically review the current literature relating the effects of age and skill level to motor control patterns of knee musculature co-contraction during functional movements. Methods- A search of electronic databases was performed with the search terms specifying co-contraction (cocontract*, co-contract*, coactive* or co-activ*). The search was focused on the effects age and/or skill level and were limited by the keywords of age or skill level (skill*) or experience (experi*). Results- The search yielded a total of six peer reviewed manuscripts that met the search criteria and were included in the review. Conclusions- The relationship between adequate dynamic joint stability and efficient movement patterns are complex. Co-contraction related to age and skill development varies among studies due to technical and practical considerations. Adequate antagonistic co-contraction of hamstrings musculature appears to be a component of all functional movements to possibly maintain dynamic knee stability and protect against excessive joint loads. Future investigations that further delineate the appropriate lower extremity agonist and antagonist relationships during dynamic tasks may help elucidate injury risk mechanisms in specific populations.
Frameworks on shifting sands
Authors: R. lngvaldsen, H.T.A. Whiting
Journal: Behavioral and Brain Sciences (1995)

Abstract Feldman and Levin present a model for movement control in which the system is said to seek equilibrium points, active movement being produced by shifting frames of reference in space. It is argued that whatever merit this model might have is limited to an understanding of “the how” and not “the why” we move. In this way the authors seem to be forced into a dualistic position leaving the upper level of the proposed control hierarchy “floating.”
Expression in yeast of a Plasmodium vivax antigen of potential use in a human malaria vaccine.
Authors: P J Barr, H L Gibson, V Enea, D E Arnot, M R Hollingdale, V Nussenzweig
Journal: The Journal of Experimental Medicine (1987)

DNA coding for 234 amino acids of the circumsporozoite (CS) protein of Plasmodium vivax was incorporated into yeast expression vectors. The DNA encoded all the repeat domain and codons for a highly conserved sequence, KLKQP, found in CS proteins from all malaria parasites. Yeast cells transformed with these autonomously replicating plasmids expressed, upon induction, high levels of the CS polypeptide. The malaria antigen was purified in good yields from yeast extracts and was injected into mice using alum as adjuvant. The antibodies recognized the authentic CS protein, and at high dilutions, they inhibited the invasion of hepatocytes by sporozoites in vitro.
Relationship of Gene Expression and Chromosomal Abnormalities in Colorectal Cancer
Authors: Dafna Tsafrir, Manny Bacolod, Zachariah Selvanayagam, Ilan Tsafrir, Jinru Shia, Zhaoshi Zeng, Hao Liu, Curtis Krier, Robert F. Stengel, Francis Barany, William L. Gerald, Philip B. Paty, Eytan Domany, Daniel A. Notterman
Journal: Cancer Research (2006)

Abstract Several studies have verified the existence of multiple chromosomal abnormalities in colon cancer. However, the relationships between DNA copy number and gene expression have not been adequately explored nor globally monitored during the progression of the disease. In this work, three types of array-generated data (expression, single nucleotide polymorphism, and comparative genomic hybridization) were collected from a large set of colon cancer patients at various stages of the disease. Probes were annotated to specific chromosomal locations and coordinated alterations in DNA copy number and transcription levels were revealed at specific positions. We show that across many large regions of the genome, changes in expression level are correlated with alterations in DNA content. Often, large chromosomal segments, containing multiple genes, are transcriptionally affected in a coordinated way, and we show that the underlying mechanism is a corresponding change in DNA content. This implies that whereas specific chromosomal abnormalities may arise stochastically, the associated changes in expression of some or all of the affected genes are responsible for selecting cells bearing these abnormalities for clonal expansion. Indeed, particular chromosomal regions are frequently gained and overexpressed (e.g., 7p, 8q, 13q, and 20q) or lost and underexpressed (e.g., 1p, 4, 5q, 8p, 14q, 15q, and 18) in primary colon tumors, making it likely that these changes favor tumorigenicity. Furthermore, we show that these aberrations are absent in normal colon mucosa, appear in benign adenomas (albeit only in a small fraction of the samples), become more frequent as disease advances, and are found in the majority of metastatic samples. (Cancer Res 2006; 66(4): 2129-37)
The value of productivity: human-capital versus friction-cost method
Authors: W B van den Hout
Journal: Annals of the Rheumatic Diseases (2009)

Many cost-of-illness studies have investigated the impact of rheumatoid arthritis on productivity, invariably concluding that productivity costs are high. Different methods exist to value productivity. The human-capital method takes the patient's perspective and counts any hour not worked as an hour lost. By contrast, the friction-cost method takes the employer's perspective, and only counts as lost those hours not worked until another employee takes over the patient's work. Both methods can produce widely different results. Productivity costs have the potential to compensate for the costs of expensive biological agents, but only in early-onset disease when patients still have jobs and if productivity is given full weight by using the human-capital method. If productivity is given less weight by excluding productivity costs or by using the friction-cost method, then currently, biological agents are probably too expensive.
Measurement of nasal potential difference in young children with an equivocal sweat test following newborn screening for cystic fibrosis
Authors: I. Sermet-Gaudelus, E. Girodon, D. Roussel, E. Deneuville, S. Bui, F. Huet, M. Guillot, R. Aboutaam, M. Renouil, A. Munck, M. des Georges, A. Iron, C. Thauvin-Robinet, I. Fajac, G. Lenoir, M. Roussey, A. Edelman
Journal: Thorax (2010)

<h3>Background</h3> A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) with sweat chloride levels in the intermediate range and only one or no identified CF-causing mutations. <h3>Objectives</h3> To investigate the diagnostic value for CF of assessing CF transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference in children with HIRT. <h3>Methods</h3> A specially designed protocol was used to assess nasal potential difference (NPD) in 23 young children with HIRT (3 months–4 years) with inconclusive neonatal screening. Results were analysed with a composite score including CFTR-dependent sodium and chloride secretion. Results were correlated with genotype after extensive genetic screening and with clinical phenotype at follow-up 3 years later. <h3>Results</h3> NPD was interpretable for 21 children with HIRT: 13 had NPD composite scores in the CF range. All 13 were finally found to carry two <i>CFTR</i> mutations. At follow-up, nine had developed a chronic pulmonary disease consistent with a CF diagnosis. The sweat test could be repeated in nine children, and six had sweat chloride values ≥60 mmol/l. Of the eight children with normal NPD scores, only two had two CFTR mutations, both wide-spectrum mutations. None had developed a CF-like lung disease at follow-up. The sweat test could be reassessed in five of these eight children and all had sweat chloride values &lt;60 mmol/l. CF diagnosis was ruled out in six of these eight children. <h3>Conclusion</h3> Evaluation of CFTR function in the nasal epithelium of young children with inconclusive results at CF newborn screening is a useful diagnostic tool for CF.
Passage of Intratracheally Instilled Ultrafine Particles from the Lung into the Systemic Circulation in Hamster
Authors: A. NEMMAR, H. VANBILLOEN, M. F. HOYLAERTS, P. H. M. HOET, A. VERBRUGGEN, B. NEMERY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The mechanisms of particulate pollution-related cardiovascular morbidity and mortality are not well understood. We studied the passage of radioactively labeled ultrafine particles after their intratracheal instillation. Hamsters received a single intratracheal instillation of 100 μ g albumin nanocolloid particles (nominal diameter ⩽ 80 nm) labeled with 100 μ Ci technetium-99m and were killed after 5, 15, 30, and 60 min. In blood, radioactivity, expressed as percentage of total body radioactivity per gram blood, amounted to 2.88 ± 0.80%, 1.30 ± 0.17%, 1.52 ± 0.46%, and 0.21 ± 0.06% at 5, 15, 30, and 60 min, respectively. Thin-layer chromatography showed only one peak of radioactivity corresponding to unaltered 99mTc-albumin nanocolloid. In the liver, radioactivity, expressed as percentage of total radioactivity per organ, amounted to 0.10 ± 0.07%, 0.23 ± 0.06%, 1.24 ± 0.27%, and 0.06 ± 0.02% at 5, 15, 30, and 60 min, respectively. Lower values were observed in the heart, spleen, kidneys, and brain. Dose dependence was assessed at 30 min following instillation of 10 μ g and 1 μ g 99mTc-albumin per animal (n = 3 at each dose), and values of the same relative magnitudes as after instillation of 100 μ g were obtained. We conclude that a significant fraction of 99mTc-albumin, taken as a model of ultrafine particles, rapidly diffuses from the lungs into the systemic circulation.
What Happens Now? Psychosocial Care for Cancer Survivors After Medical Treatment Completion
Authors: Annette L. Stanton
Journal: Journal of Clinical Oncology (2012)

The growing population of adults living with a history of cancer in the United States mandates attention to quality of life and health in this group, as well as to the implementation of evidence-based interventions to address psychosocial and physical concerns at completion of medical treatments and beyond. The goals of this article are to document the need for attention to psychosocial domains during the re-entry and later phases of the cancer survivor trajectory, offer an overview of current evidence on efficacy of psychosocial interventions during those phases, and offer suggestions for application and research regarding post-treatment psychosocial care.
Dual regulation of IRF4 function in T and B cells is required for the coordination of T–B cell interactions and the prevention of autoimmunity
Authors: Partha S. Biswas, Sanjay Gupta, Roslynn A. Stirzaker, Varsha Kumar, Rolf Jessberger, Theresa T. Lu, Govind Bhagat, Alessandra B. Pernis
Journal: The Journal of Experimental Medicine (2012)

Effective humoral responses to protein antigens require the precise execution of carefully timed differentiation programs in both T and B cell compartments. Disturbances in this process underlie the pathogenesis of many autoimmune disorders, including systemic lupus erythematosus (SLE). Interferon regulatory factor 4 (IRF4) is induced upon the activation of T and B cells and serves critical functions. In CD4+ T helper cells, IRF4 plays an essential role in the regulation of IL-21 production, whereas in B cells it controls class switch recombination and plasma cell differentiation. IRF4 function in T helper cells can be modulated by its interaction with regulatory protein DEF6, a molecule that shares a high degree of homology with only one other protein, SWAP-70. Here, we demonstrate that on a C57BL/6 background the absence of both DEF6 and SWAP-70 leads to the development of a lupus-like disease in female mice, marked by simultaneous deregulation of CD4+ T cell IL-21 production and increased IL-21 B cell responsiveness. We furthermore show that DEF6 and SWAP-70 are differentially used at distinct stages of B cell differentiation to selectively control the ability of IRF4 to regulate IL-21 responsiveness in a stage-specific manner. Collectively, these data provide novel insights into the mechanisms that normally couple and coordinately regulate T and B cell responses to ensure tight control of productive T–B cell interactions.
Overview of PDEs and Their Regulation
Authors: Kenji Omori, Jun Kotera
Journal: Circulation Research (2007)

Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleotide concentrations, which are determined by a balance in production and degradation of cAMP and cGMP. Degradation of cyclic nucleotides is catalyzed by 3′,5′-cyclic nucleotide phosphodiesterases (PDEs), and therefore regulation of PDEs hydrolytic activity is important for modulation of cellular functions. Mammalian PDEs are composed of 21 genes and are categorized into 11 families based on sequence homology, enzymatic properties, and sensitivity to inhibitors. PDE families contain many splice variants that mostly are unique in tissue-expression patterns, gene regulation, enzymatic regulation by phosphorylation and regulatory proteins, subcellular localization, and interaction with association proteins. Each unique variant is closely related to the regulation of a specific cellular signaling. Thus, multiple PDEs function as a particular modulator of each cardiovascular function and regulate physiological homeostasis.