tbuckley/cabot-search huggingface dataset:
Inhibition of indium-111 platelet accretion onto venous thrombi in dogs by prostacyclin.
Authors: G Czer, K M Moser, R Konopka, M T Hartman
Journal: Circulation Research (1983)

The known platelet anti-aggregant effects of prostacyclin (epoprostenol) suggest that it may have therapeutic potential in conditions in which the platelet plays a pathophysiological role. The growth of venous thrombi is one such condition. We have attempted to determine, in a canine model of fresh venous thrombosis, whether prostacyclin infusion inhibits platelet accretion in vivo and how this in vivo event related to hemodynamic and in vitro platelet anti-aggregant effects. Gamma camera imaging over thrombi for accretion of indium-111-labeled platelets disclosed that prostacyclin, at an infusion rate of 50 ng/kg per min, inhibited platelet accretion in vivo and resulted in a 95 +/- 4% decrease in in vitro adenosine diphosphate-induced platelet aggregation, and a decrease in mean arterial pressure to 86 +/- 4% of pre-infusion values. Step-wise decrements of prostacyclin infusion demonstrated that platelet accretion occurred in vivo at infusion rates of approximately 10-20 ng/kg per min and correlated with an in vitro adenosine diphosphate-induced aggregation of 54 +/- 13% of control values. Thus, prostacyclin, in a dose that causes only a mild decrease in systemic pressure, can completely inhibit platelet uptake onto fresh venous thrombi in the dog, and this inhibition correlates closely with in vitro adenosine diphosphate-induced platelet aggregation. The potential therapeutic implications of these findings are discussed.
Improvement of pressurised aerosol deposition with Nebuhaler spacer device.
Authors: S P Newman, A B Millar, T R Lennard-Jones, F Moren, S W Clarke
Journal: Thorax (1984)

The effect on aerosol deposition from a pressurised metered dose inhaler of a 750 cm3 spacer device with a one way inhalation valve (Nebuhaler, Astra Pharmaceuticals) was assessed by means of an in vivo radiotracer technique. Nine patients with obstructive lung disease took part in the study. The pattern of deposition associated with use of a metered dose inhaler alone was compared with that achieved with the spacer used both for inhalation of single puffs of aerosol and for inhalation of four puffs actuated in rapid succession and then inhaled simultaneously. On each occasion there was a delay of 1 s between aerosol release and inhalation, simulating poor inhaler technique. With the metered dose inhaler alone, a mean (SEM) 8.7 (1.8)% of the dose reached the lungs and 80.9 (1.9)% was deposited in the oropharynx. With single puffs from the spacer 20.9 (1.6)% of the dose (p less than 0.01) reached the lungs, only 16.5 (2.3)% (p less than 0.01) was deposited in the oropharynx, and 55.8 (3.1)% was retained within the spacer itself. With four puffs from the spacer 15.2 (1.5)% reached the lungs (p = 0.02 compared with the metered dose inhaler alone, p less than 0.01 compared with single puffs from the spacer), 11.4 (1.2)% was deposited in the oropharynx, and 67.5 (1.8)% in the device itself. It is concluded that the spacer device gives lung deposition of metered dose aerosols comparable to or greater than a correctly used inhaler and oropharyngeal deposition is greatly reduced. The spacer should be used preferably for the inhalation of single puffs of aerosol but may also be used for the inhalation of up to four puffs actuated in rapid succession and then inhaled simultaneously.
Levofloxacin in first-line eradication regimens for Helicobacter pylori: better test antibiotic susceptibility before treating
Authors: J. Molina-Infante, J. P. Gisbert
Journal: Gut (2010)

We sincerely congratulate Romano et al 1 for their recent manuscript in Gut showing that levofloxacin-containing sequential therapy can overcome suboptimal cure rates of clarithromycin-containing sequential therapy (≤80% in the intention-to-treat analysis), in a setting with a high clarithromycin resistance rate (20%) but a low levofloxacin resistance rate (3%). Interestingly, we failed to replicate their results in a prior trial with quite a similar design, …
Comparison of fluorescence in situ hybridisation using peptide nucleic acid probes, Gram stain/acridine orange leukocyte cytospin and differential time to positivity methods for detection of catheter-related bloodstream infection in patients after haematopoietic stem cell transplantation
Authors: R. Krause, H.F. Salzer, M. Hönigl, T. Valentin, H.W Auner, I. Zollner-Schwetz
Journal: Clinical Microbiology and Infection (2010)
Macrolide Antibiotics and the Risk of Cardiac Arrhythmias
Authors: Richard K. Albert, Joseph L. Schuller
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Section:ChooseTop of pageAbstract <<DefinitionsElectrophysiology and Gen...Dose–Response IssuesCardiac Events after Macr...RR and Incidence of Arrhy...Reducing the Risk of Arrh...ConclusionsReferencesCITING ARTICLES
Adenosine and renal sodium handling
Authors: R Fransen, H A Koomans
Journal: Journal of the American Society of Nephrology (1995)

Adenosine infusion is associated with natriuresis as well as antinatriuresis. The physiologic significance of these opposite effects is unknown but may have to do with different conditions of ischemia, in which adenosine accumulates. These effects were characterized in the rat. First, intrarenal and systemic infusions within one animal were performed. Infusing 10 micrograms/min into the left renal artery increased sodium by approximately 50%; however, the subsequent infusion of 50 micrograms/min into the thoracic aorta decreased sodium excretion by approximately 60%, in association with a small reduction of blood pressure. Second, to explore the effect of intrarenal adenosine in tubular sodium handling, free-flow micropuncture experiments were performed. The intrarenal infusion of 10 micrograms/min again caused sodium excretion, but no change in GFR, volume, and sodium deliveries up to the early distal tubule was found. Apparently, the direct effect of adenosine in the kidney is sodium excretion, by a tubular action beyond the early distal tubule. Third, to further characterize the indirect effect, which apparently is sodium retention, adenosine was infused systemically at low rates, in order to avoid a decrease in blood pressure. A 25 micrograms/min infusion again caused sodium retention, in the absence of a fall in blood pressure. After acute left renal denervation, the antinatriuretic effect disappeared in the denervated kidney but remained in the right kidney. These data suggest that increased intrarenal adenosine suppresses sodium reabsorption at some distal nephron site, appropriately decreasing the workload of the kidney. On the other hand, systemic adenosine stimulates sodium reabsorption, an effect that is appropriate to improve systemic circulation and depends on the renal nerves.
Mobility and Localization of Proteins in Excitable Membranes
Authors: M M Poo
Journal: Annual Review of Neuroscience (1985)

Studies of the cell membrane in the past two decades have led to the realization of the dynamic nature of membrane organization. Under favorable conditions, membrane components are capable of rotational and translational motions as well as extensive lateral interactions within the membrane matrix. This dynamic property of the cell membrane bears important consequences regarding the cellular mechanisms responsible for development and maintenance of mem­ brane organization . For example, it is well known that mature nerve and muscle cells usually have a specific pattern of protein distribution in their plasma membranes: Transmitter receptors and ionic channels are frequently segregated or localized in specific regions of the membrane. If the proteins are laterally mobile in the membrane, how does a nonrandom protein topog­ raphy develop? How is it maintained in the face of metabolic turnover of the proteins? Is protein topography modifiable in the mature membrane? The answers to these questions are directly relevant for understanding the function and the plasticity of excitable membranes. The main subjects to be covered in the present review are (a) The lateral mobility of membrane proteins in the developing and mature excitable cells; (b) the nonrandom distribution of proteins in excitable membranes and possible mechanisms responsible for the development and maintenance of such distri­ bution; (c) the implications of protein mobility in the functions of developing and mature excitable cells. For other aspects of the structure and organization of excitable membranes, a number of recent reviews may be consulted (Stri­ chartz 1977, Patrick et al 1978, Pfenninger 1978, Rogart 1981).
Universal Design of Research: Inclusion of Persons with Disabilities in Mainstream Biomedical Studies
Authors: Ann S. Williams, Shirley M. Moore
Journal: Science Translational Medicine (2011)

Although persons with disabilities of all kinds have as wide a range of health conditions as the general population, they are profoundly underrepresented in mainstream health research. Such underrepresentation might contribute to the health disparities in this population. We propose the concept of Universal Design of Research (UDR), which would promote routine inclusion of persons with disabilities in mainstream biomedical and psychosocial studies, without the need for adaptation or specialized design. Elements of UDR include the use of multisensory formats for recruiting participants, presenting research instruments and interventions, and data gathering from participants and should promote the inclusion of participants with a wide range of abilities, thus enhancing the generalizability of results.
Reduced uptake of apoptotic cells by macrophages in systemic lupus erythematosus: correlates with decreased serum levels of complement
Authors: M Bijl
Journal: Annals of the Rheumatic Diseases (2005)

Defects in phagocytosis of apoptotic cells have a role in the pathogenesis of autoimmune diseases. Decrease of phagocytosis of apoptotic cells occurs in systemic lupus erythematosus (SLE). Factors underlying this decrease are, presently, unknown.To analyse the expression of relevant membrane receptors of monocyte derived macrophages (MDM) from patients with SLE and assess their ability to phagocytose apoptotic cells in comparison with MDM from healthy controls. Additionally, to compare phagocytosis in the presence of SLE sera with that in normal human serum (NHS).Human peripheral blood monocytes were isolated from patients and controls, and cultured for 7 days to obtain MDM. Membrane expression of CD14, CD18, CD36, and CD51/61 was measured. MDM were incubated with apoptotic Jurkat cells in the presence of NHS or serum from patients with active or inactive disease.No differences in phagocytosis capacity were found between MDM from patients and controls. Membrane expression of the respective receptors was comparable in patients and controls. However, when MDM from controls were incubated with apoptotic cells in patient serum, phagocytosis was significantly decreased in comparison with incubation in NHS. This effect depended on the patients' disease activity and could be reversed by addition of NHS. Reduced uptake of apoptotic cells was associated with decreased levels of complement C1q, C4, and C3, but not with levels of complement factor B.Reduced uptake of apoptotic cells by MDM from patients with SLE is not an intrinsic defect but is serum dependent and associated with decreased levels of C1q, C4, and C3.
Molecular Characterization of a Superoxide-Generating NAD(P)H Oxidase in the Ventilatory Muscles
Authors: DANESH JAVESGHANI, SHELDON A. MAGDER, ESTHER BARREIRO, MARK T. QUINN, SABAH N. A. HUSSAIN
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The molecular sources of reactive oxygen species (ROS) in skeletal muscles are not well understood. We hypothesized that nonphagocyte NAD(P)H oxidase could be a source of ROS in muscle fibers. We thus investigated the existence, structure, and contribution of nonphagocyte NAD(P)H oxidase to ROS production in rat skeletal muscles. ROS production and NAD(P)H oxidase activity were evaluated by lucigenin-enhanced chemiluminescence and NADH consumption rate, whereas enzyme composition was monitored by reverse transcription-polymerase chain reaction and immunoblotting. Basal O2 − production in muscle strips from normal rats averaged 1.4 nmol/mg per 10 min and increased to ∼ 18 nmol/mg per 10 min in the presence of NADH. Muscle O2 − production and NADH consumption were inhibited by Tiron, superoxide dismutase, apocynin, and diphenyleneiodonium but not by inhibitors of cyclo-oxygenases, xanthine oxidase, nitric oxide synthases (NOS), and mitochondrial enzymes. We detected mRNA and proteins of p22 phox , gp91 phox , p47 phox , and p67 phox subunits in normal rat muscles. These subunits were localized in close proximity to the sarcolemma. Induction of sepsis in rats doubled muscle O2 − production with no major changes in muscle NADPH oxide subunit expression. In lipopolysaccharide-treated but not in control muscles, O2 − production was increased significantly by NOS inhibition. We conclude that a constitutively active NAD(P)H oxidase enzyme complex exists in normal skeletal muscle fibers and contributes to ROS production. In septic rats, this production is increased but measurable O2 − is reduced by enhanced NO production.
Influence of progesterone on membrane potential and peak tension of myocardial fibres
Authors: J. MENDOZA, W. C. D. MELLO
Journal: Cardiovascular Research (1974)

The effect of progesterone on membrane potential and peak tension of mammalian myocardial fibres was investigated in vitro. It was found that the hormone decreases the mechanical responses and reduces action potential duration concomitantly. On the other hand, the hormone reduces 45Ca uptake, an effect which is probably related to the shortening of the action potential. An increased 22Na efflux was also found on muscles treated by progesterone.
Myxoma Virus Virotherapy for Glioma in Immunocompetent Animal Models: Optimizing Administration Routes and Synergy with Rapamycin
Authors: XueQing Lun, Tommy Alain, Franz J. Zemp, Hongyuan Zhou, Masmudur M. Rahman, Mark G. Hamilton, Grant McFadden, John Bell, Donna L. Senger, Peter A. Forsyth
Journal: Cancer Research (2010)

Abstract Oncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of MYXV in immunocompetent racine glioma models. Here, we report that MYXV infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. Intratumoral administration of MYXV with rapamycin improved viral replication in the tumor and significantly prolonged host survival. Similarly, coadministration via a method of convection-enhanced delivery (CED) enhanced viral replication and efficacy in vivo. Mechanisms by which rapamycin improved MYXV oncolysis included an inhibition of type I IFN production in vitro and a reduction of intratumoral infiltration of CD68+ microglia/macrophages and CD163+ macrophages in vivo. Our findings define a method to improve MYXV efficacy against gliomas by rapamycin coadministration, which acts to promote immune responses engaged by viral delivery. Cancer Res; 70(2); 598–608
TOX Provides a Link Between Calcineurin Activation and CD8 Lineage Commitment
Authors: Parinaz Aliahmad, Emmett O'Flaherty, Peggy Han, Olivia D. Goularte, Beverley Wilkinson, Masanobu Satake, Jeffery D. Molkentin, Jonathan Kaye
Journal: The Journal of Experimental Medicine (2004)

T cell development is dependent on the integration of multiple signaling pathways, although few links between signaling cascades and downstream nuclear factors that play a role in thymocyte differentiation have been identified. We show here that expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation. TOX expression is also sufficient to initiate positive selection to the CD8 lineage in the absence of MHC-TCR interactions. TOX-mediated positive selection is associated with up-regulation of Runx3, implicating CD4 silencing in the process. Interestingly, a strong T cell receptor-mediated signal can modify this cell fate. We further demonstrate that up-regulation of TOX in double positive thymocytes is calcineurin dependent, linking this critical signaling pathway to nuclear changes during positive selection.
Development of a Model of Early-Onset IgA Nephropathy
Authors: Keiko Okazaki, Yusuke Suzuki, Mareki Otsuji, Hitoshi Suzuki, Masao Kihara, Tadahiro Kajiyama, Azusa Hashimoto, Hiroyuki Nishimura, Rhubell Brown, Stacy Hall, Jan Novak, Shozo Izui, Sachiko Hirose, Yasuhiko Tomino
Journal: Journal of the American Society of Nephrology (2012)

ddY mice spontaneously develop IgA nephropathy (IgAN) with a variable age of disease onset. Establishing a model with early-onset IgAN could aid the investigation of mechanisms that underlie the pathogenesis of this disease. On the basis of histologic grading in serial biopsies, we previously classified ddY mice into early-onset, late-onset, and quiescent groups. Here, we selectively mated mice with the early-onset phenotype for >20 generations and established “grouped ddY” mice that develop IgAN within 8 weeks of age. Similar to human IgAN, the prognosis was worse for male mice than females. These mice homogeneously retained genotypes of four marker loci previously associated with the early-onset phenotype, confirming a close association of these loci with early-onset IgAN in ddY mice. Grouped ddY mice comprised two sublines, however, which had distinct genotypes at a susceptibility locus for high serum IgA levels, which maps within the Ig heavy-chain gene complex. The subline bearing the Igh-2a IgA allotype had a more rapid course of fatal disease and lower oligosaccharide content, suggesting that aberrant IgA glycosylation may promote the progression of murine IgAN. Taken together, these data indicate that grouped ddY mice may be a useful model for the identification of susceptibility genes and the underlying molecular mechanisms involved in the pathogenesis of human IgAN.
Restoring Natural Sensory Feedback in Real-Time Bidirectional Hand Prostheses
Authors: Stanisa Raspopovic, Marco Capogrosso, Francesco Maria Petrini, Marco Bonizzato, Jacopo Rigosa, Giovanni Di Pino, Jacopo Carpaneto, Marco Controzzi, Tim Boretius, Eduardo Fernandez, Giuseppe Granata, Calogero Maria Oddo, Luca Citi, Anna Lisa Ciancio, Christian Cipriani, Maria Chiara Carrozza, Winnie Jensen, Eugenio Guglielmelli, Thomas Stieglitz, Paolo Maria Rossini, Silvestro Micera
Journal: Science Translational Medicine (2014)

A multigrasp, bidirectional hand prosthesis delivers dynamic sensory feedback, allowing a user with a hand amputation to achieve fine grasping force control and realistic object sensing.
Macrophage-dependent Apoptosis of CD4+ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor
Authors: Andrew D. Badley, David Dockrell, Margaret Simpson, Ron Schut, David H. Lynch, Paul Leibson, Carlos V. Paya
Journal: The Journal of Experimental Medicine (1997)

Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.
Intestinal pseudo-obstruction in systemic amyloidosis
Authors: D. A. Legge, E. E. Wollaeger, H. C. Carlson
Journal: Gut (1970)

The occurrence of clinical manifestations of mechanical intestinal obstruction in eight cases of systemic amyloidosis is reported. Seven similar cases have been recorded in the literature and are briefly reviewed. Correct diagnosis is important in these cases if useless surgical treatment or prolonged diagnostic investigations are to be avoided. Gastrointestinal involvement by systemic amyloidosis should be considered in a patient presenting with clinical manifestations of mechanical obstruction but paralytic ileus seen on plain films. In these cases an attempt should be made, by means of a barium enema, to exclude an obstructing lesion of the colon or distal small bowel. Once amyloidosis is considered, it can be confirmed easily and safely by biopsy of the rectal or small-intestinal mucosa.
Angiogenic Factors and the Risk of Adverse Outcomes in Women With Suspected Preeclampsia
Authors: Sarosh Rana, Camille E. Powe, Saira Salahuddin, Stefan Verlohren, Frank H. Perschel, Richard J. Levine, Kee-Hak Lim, Julia B. Wenger, Ravi Thadhani, S. Ananth Karumanchi
Journal: Circulation (2012)

Background— An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia. Methods and Results— We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th–75th percentile, 15.5–112.2] versus 10.8 [25th–75th percentile, 4.1–28.6]; P &lt;0.0001). Among those presenting at &lt;34 weeks (n=167), the results were more striking (226.6 [25th–75th percentile, 50.4–547.3] versus 4.5 [25th–75th percentile, 2.0–13.5]; P &lt;0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6–156.6). Among participants presenting at &lt;34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P =0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ≥85 compared with 15.8% of women with an sFlt1/PlGF ratio &lt;85 (hazard ratio, 15.2; 95% confidence interval, 8.0–28.7). Conclusions— In women with suspected preeclampsia presenting at &lt;34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.