Sample records for abolishes transepithelial leukocyte

  1. Phosphatidylcholine Reverses Ethanol-Induced Increase in Transepithelial Endotoxin Permeability and Abolishes Transepithelial Leukocyte Activation

    Mitzscherling, Katja; Volynets, Valentina; Parlesak, Alexandr


    Chronic alcohol abuse increases both intestinal bacterial overgrowth and intestinal permeability to macromolecules. Intestinal permeability of endotoxin, a component of the outer cell membrane of Gram-negative bacteria, plays a crucial role in the development of alcohol-induced liver disease (ALD......). As impaired bile flow leads to endotoxemia and the bile component phosphatidylcholine (PC) is therapeutically active in ALD, we tested the hypothesis that conjugated primary bile salts (CPBS) and PC inhibit ethanol-enhanced transepithelial permeability of endotoxin and the subsequent transepithelial...

  2. Transepithelial activation of human leukocytes by probiotics and commensal bacteria: role of Enterobacteriaceae-type endotoxin

    Bäuerlein, A.; Ackermann, S.; Parlesak, Alexandr


    (polymyxin, colistin) completely abrogated transepithelial activation of leukocytes. Enterobacteriaceae-type endotoxin is a crucial factor in transepithelial stimulation of leukocytes, regardless of whether it is produced by probiotics or other bacteria. Hence, transepithelial stimulation ofleukocytes...

  3. Transepithelial activation of human leukocytes by probiotics and commensal bacteria: Role of Enterobacteriaceae-type endotoxin

    Baeuerlein, Annette; Ackermann, Stefanie; Parlesak, Alexandr


    The goal of the current study was to clarify whether commercially available probiotics induce greater trans-epithelial activation of human leukocytes than do commensal, food-derived and pathogenic bacteria and to identify the compounds responsible for this activation. Eleven different bacterial s...

  4. Tre1, a G protein-coupled receptor, directs transepithelial migration of Drosophila germ cells.

    Prabhat S Kunwar


    Full Text Available In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR, Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

  5. Tre1, a G Protein-Coupled Receptor, Directs Transepithelial Migration of Drosophila Germ Cells

    Kunwar Prabhat S


    Full Text Available In most organisms, germ cells are formed distant from the somatic part of the gonad and thus have to migrate along and through a variety of tissues to reach the gonad. Transepithelial migration through the posterior midgut (PMG is the first active step during Drosophila germ cell migration. Here we report the identification of a novel G protein-coupled receptor (GPCR, Tre1, that is essential for this migration step. Maternal tre1 RNA is localized to germ cells, and tre1 is required cell autonomously in germ cells. In tre1 mutant embryos, most germ cells do not exit the PMG. The few germ cells that do leave the midgut early migrate normally to the gonad, suggesting that this gene is specifically required for transepithelial migration and that mutant germ cells are still able to recognize other guidance cues. Additionally, inhibiting small Rho GTPases in germ cells affects transepithelial migration, suggesting that Tre1 signals through Rho1. We propose that Tre1 acts in a manner similar to chemokine receptors required during transepithelial migration of leukocytes, implying an evolutionarily conserved mechanism of transepithelial migration. Recently, the chemokine receptor CXCR4 was shown to direct migration in vertebrate germ cells. Thus, germ cells may more generally use GPCR signaling to navigate the embryo toward their target.

  6. Neutrophil transepithelial migration: role of toll-like receptors in mucosal inflammation

    Titus A Reaves


    Full Text Available The symptomatic phases of many inflammatory diseases are characterized by migration of large numbers of neutrophils (PMN across a polarized epithelium and accumulation within a lumen. For example, acute PMN influx is common in diseases of the gastrointestinal system (ulcerative colitis, Crohn's disease, bacterial enterocolitis, gastritis, hepatobiliary system (cholangitis, acute cholecystitis, respiratory tract (bronchial pneumonia, bronchitis, cystic fibrosis, bronchiectasis, and urinary tract (pyelonephritis, cystitis. Despite these observations, the molecular basis of leukocyte interactions with epithelial cells is incompletely understood. In vitro models of PMN transepithelial migration typically use N-formylated bacterial peptides such as fMLP in isolation to drive human PMNs across epithelial monolayers. However, other microbial products such as lipopolysaccharide (LPS are major constituents of the intestinal lumen and have potent effects on the immune system. In the absence of LPS, we have shown that transepithelial migration requires sequential adhesive interactions between the PMN beta2 integrin CD11b/CD18 and JAM protein family members. Other epithelial ligands appear to be abundantly represented as fucosylated proteoglycans. Further studies indicate that the rate of PMN migration across mucosal surfaces can be regulated by the ubiquitously expressed transmembrane protein CD47 and microbial-derived factors, although many of the details remain unclear. Current data suggests that Toll-like receptors (TLR, which recognize specific pathogen-associated molecular patterns (PAMPs, are differentially expressed on both leukocytes and mucosal epithelial cells while serving to modulate leukocyte-epithelial interactions. Exposure of epithelial TLRs to microbial ligands has been shown to result in transcriptional upregulation of inflammatory mediators whereas ligation of leukocyte TLRs modulate specific antimicrobial responses. A better

  7. Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps.

    Vu Tran

    Full Text Available Transepithelial potential (TEP is the voltage across a polarized epithelium. In epithelia that have active transport functions, the force for transmembrane flux of an ion is dictated by the electrochemical gradient in which TEP plays an essential role. In epithelial injury, disruption of the epithelial barrier collapses the TEP at the wound edge, resulting in the establishment of an endogenous wound electric field (∼100 mV/mm that is directed towards the center of the wound. This endogenous electric field is implicated to enhance wound healing by guiding cell migration. We thus seek techniques to enhance the TEP, which may increase the wound electric fields and enhance wound healing. We report a novel technique, termed synchronization modulation (SM using a train of electric pulses to synchronize the Na/K pump activity, and then modulating the pumping cycles to increase the efficiency of the Na/K pumps. Kidney epithelial monolayers (MDCK cells maintain a stable TEP and transepithelial resistance (TER. SM significantly increased TEP over four fold. Either ouabain or digoxin, which block Na/K pump, abolished SM-induced TEP increases. In addition to the pump activity, basolateral distribution of Na/K pumps is essential for an increase in TEP. Our study for the first time developed an electrical approach to significantly increase the TEP. This technique targeting the Na/K pump may be used to modulate TEP, and may have implication in wound healing and in diseases where TEP needs to be modulated.

  8. Freshwater sponges have functional, sealing epithelia with high transepithelial resistance and negative transepithelial potential.

    Emily D M Adams

    Full Text Available Epithelial tissue - the sealed and polarized layer of cells that regulates transport of ions and solutes between the environment and the internal milieu - is a defining characteristic of the Eumetazoa. Sponges, the most ancient metazoan phylum, are generally believed to lack true epithelia, but their ability to occlude passage of ions has never been tested. Here we show that freshwater sponges (Demospongiae, Haplosclerida have functional epithelia with high transepithelial electrical resistance (TER, a transepithelial potential (TEP, and low permeability to small-molecule diffusion. Curiously, the Amphimedon queenslandica sponge genome lacks the classical occluding genes [5] considered necessary to regulate sealing and control of ion transport. The fact that freshwater sponge epithelia can seal suggests that either occluding molecules have been lost in some sponge lineages, or demosponges use novel molecular complexes for epithelial occlusion; if the latter, it raises the possibility that mechanisms for occlusion used by sponges may exist in other metazoa. Importantly, our results imply that functional epithelia evolved either several times, or once, in the ancestor of the Metazoa.

  9. Carrier peptide-mediated transepithelial permeation of biopharmaceuticals

    Kristensen, Mie; Nielsen, Hanne Mørck


    -penetrating peptides (CPPs). Two approaches for the carrier peptide-mediated transepithelial permeation of biopharmaceuticals are generally explored: Co-administration1 or covalent conjugation2. Co-administration is often the method of choice due to e.g. ease in sample preparation and flexibility in adjustment of the......-34)) and the widely studied CPP penetratin were employed as therapeutic cargo and carrier peptide, respectively....

  10. Transepithelial Na+ transport and the intracellular fluids: a computer study.

    Civan, M M; Bookman, R J


    Computer simulations of tight epithelia under three experimental conditions have been carried out, using the rheogenic nonlinear model of Lew, Ferreira and Moura (Proc. Roy. Soc. London. B 206:53-83, 1979) based largely on the formulation of Koefoed-Johnsen and Ussing (Acta Physiol. Scand. 42: 298-308. 1958). First, analysis of the transition between the short-circuited and open-circuited states has indicated that (i) apical Cl- permeability is a critical parameter requiring experimental definition in order to analyze cell volume regulation, and (ii) contrary to certain experimental reports, intracellular Na+ concentration (ccNa) is expected to be a strong function of transepithelial clamping voltage. Second, analysis of the effects of lowering serosal K+ concentration (csK) indicates that the basic model cannot simulate several well-documented observations; these defects can be overcome, at least qualitatively, by modifying the model to take account of the negative feedback interaction likely to exist between the apical Na+ permeability and ccNa. Third, analysis of the strongly supports the concept that osmotically induced permeability changes in the apical intercellular junctions play a physiological role in conserving the body's stores of NaCl. The analyses also demonstrate that the importance of Na+ entry across the basolateral membrane is strongly dependent upon transepithelial potential, cmNa and csK; under certain conditions, net Na+ entry could be appreciably greater across the basolateral than across the apical membrane. PMID:7057462

  11. A Clinical and Confocal Microscopic Comparison of Transepithelial PRK and LASEK for Myopia

    Safak Korkmaz


    Full Text Available Purpose. To compare the clinical and confocal microscopic results of transepithelial PRK versus LASEK for correction of myopia. Materials and Methods. Twelve patients with myopia received transepithelial PRK in one eye and LASEK in the other. In transepithelial PRK-treated eyes, the corneal epithelium was removed with 40 microns of excimer laser ablation and in LASEK-treated eyes with 25-second application of 18% ethanol. Time to epithelial healing, ocular discomfort, uncorrected and best corrected visual acuities, manifest refraction, haze, greyscale value, and keratocyte apoptosis in confocal microscopy were recorded. Results. The mean time to epithelial healing was significantly longer after LASEK (4.00 ± 0.43 versus 3.17 ± 0.6 days. On day 1, ocular discomfort was significantly higher after transepithelial PRK. The grade of haze, keratocyte apoptosis, and greyscale value in confocal microscopy were significantly higher in transepithelial PRK-treated eyes at 1 month. All transepithelial PRK- and LASEK-treated eyes achieved 20/25 or better UCVA and were within ±1.00 D of emmetropia at final visits. Conclusions. Both transepithelial PRK and LASEK offer effective correction of myopia at 1 year. However, LASEK appeared to induce less discomfort and less intense wound healing in the early postoperative period.

  12. Leukocyte Adhesion Deficiency (LAD)

    ... Content Marketing Share this: Main Content Area Leukocyte Adhesion Deficiency (LAD) LAD is an immune deficiency in ... are slow to heal also may have LAD. Treatment and Research Doctors prescribe antibiotics to prevent and ...

  13. Testosterone abolishes implicit subordination in social anxiety.

    Terburg, David; Syal, Supriya; Rosenberger, Lisa A; Heany, Sarah J; Stein, Dan J; Honk, Jack van


    Neuro-evolutionary theories describe social anxiety as habitual subordinate tendencies acquired through a recursive cycle of social defeat and submissive reactions. If so, the steroid hormone testosterone might be of therapeutic value, as testosterone is a main force behind implicit dominance drive in many species including humans. We combined these two theories to investigate whether the tendency to submit to the dominance of others is an implicit mechanism in social anxiety (Study-1), and whether this can be relieved through testosterone administration (Study-2). Using interactive eye-tracking we demonstrate that socially anxious humans more rapidly avert gaze from subliminal angry eye contact (Study-1). We replicate this effect of implicit subordination in social anxiety in an independent sample, which is subsequently completely abolished after a single placebo-controlled sublingual testosterone administration (Study-2). These findings provide crucial evidence for hormonal and behavioral treatment strategies that specifically target mechanisms of dominance and subordination in social anxiety. PMID:27448713

  14. Effect of proteolytic enzymes on transepithelial solute transport

    The effects of proteases on air-space clearance (AC) of small ([14C]sucrose, 342 daltons) and large (125I-neutral dextran, 70,000 daltons) solutes were studied in isolated, fluid-filled hamster lungs that were perfused in a nonrecirculating system. When instilled into the air spaces, porcine pancreatic elastase (0.1-0.4 mg/ml) and bovine pancreatic trypsin (BPT) (0.5-2.0 mg/ml), but neither Clostridium histolyticum collagenase (5.0 mg/ml) nor phenylmethylsulfonyl fluoride-inactivated BPT caused large increases in the AC of both tracer molecules. BPT-induced solute clearance was further characterized functionally and morphologically. The functional characteristics of solute AC under steady-state conditions did not indicate that transepithelial transport was diffusion-limited. Inhibition by millimolar concentrations of Zn2+ and by lung cooling, along with electron microscopic studies employing horseradish peroxidase as a macromolecule tracer, were consistent with epithelial solute transport by a vesicular mechanism (transcytosis). Solute transport from the interstitial compartment to the lung exterior was shown to occur via two pathways. By unknown mechanisms BPT caused small amounts of water to flow through an incompletely identified, extravascular pathway. In BPT-exposed lungs efflux of 125I-dextran 70 occurred almost exclusively through this pathway, whereas [14C]sucrose was transported to the lung exterior partly through this same pathway and partly through the vasculature. The large differences in the diffusion coefficients of the two tracers may have accounted for these observed patterns of solute efflux from the lung. The possible significance of our findings to the pathogenesis of experimental emphysema are discussed

  15. Beyond Ussing's chambers: contemporary thoughts on integration of transepithelial transport.

    Herrmann, Jeremy R; Turner, Jerrold R


    In the mid-20th century, Hans Ussing developed a chamber that allowed for the simultaneous measurement of current and labeled probe flux across epithelia. Using frog skin as a model, Ussing used his results to propose mechanisms of transcellular Na(+) and K(+) transport across apical (exterior/luminal) and basolateral (interior) membranes that is essentially unchanged today. Others took advantage of Ussing's chambers to study mucosal tissues, including bladder and intestines. It quickly became clear that, in some tissues, passive paracellular flux, i.e., across the tight junction, was an important component of overall transepithelial transport. Subsequent work demonstrated that activation of the apical Na(+)-glucose cotransporter SGLT1 regulated paracellular permeability such that intestinal paracellular transport could coordinate with and amplify transcellular transport. Intermediates in this process include activation of p38 MAPK, the apical Na(+)/H(+) exchanger NHE3, and myosin light chain kinase (MLCK). Investigators then focused on these processes in disease. They found that TNF induces barrier dysfunction via MLCK activation and downstream caveolin-1-dependent endocytosis of the tight junction protein occludin. TNF also inhibited NHE3, and both barrier loss and PKCα-dependent NHE3 inhibition were required for TNF-induced acute diarrhea, emphasizing the interplay between transcellular and paracellular transport. Finally, studies using immune-mediated inflammatory bowel disease models showed that mice lacking epithelial MLCK were initially protected, but became ill as epithelial damage progressed and provided a tight junction-independent means of barrier loss. None of these advances would have been possible without the insights provided by Ussing and others using Ussing's ingenious, and still useful, chambers. PMID:26702131

  16. Transepithelial resistance and claudin expression in trout RTgill-W1 cell line

    T. Trubitt, Rebecca; Rabeneck, D. Brett; Bujak, Joanna;


    In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1–2 days (20–80 Ω⋅cm2), which was then mai...

  17. Evaluation of Epithelial Integrity with Various Transepithelial Corneal Cross-Linking Protocols for Treatment of Keratoconus

    Suphi Taneri


    Full Text Available Purpose. Corneal collagen cross-linking (CXL has been demonstrated to stiffen cornea and halt progression of ectasia. The original protocol requires debridement of central corneal epithelium to facilitate diffusion of a riboflavin solution to stroma. Recently, transepithelial CXL has been proposed to reduce risk of complications associated with epithelial removal. Aim of the study is to evaluate the impact of various transepithelial riboflavin delivery protocols on corneal epithelium in regard to pain and epithelial integrity in the early postoperative period. Methods. One hundred and sixty six eyes of 104 subjects affected by progressive keratoconus underwent transepithelial CXL using 6 different riboflavin application protocols. Postoperatively, epithelial integrity was evaluated at slit lamp and patients were queried regarding their ocular pain level. Results. One eye had a corneal infection associated with an epithelial defect. No other adverse event including endothelial decompensation or endothelial damage was observed, except for epithelial damages. Incidence of epithelial defects varied from 0 to 63%. Incidence of reported pain varied from 0 to 83%. Conclusion. Different transepithelial cross-linking protocols have varying impacts on epithelial integrity. At present, it seems impossible to have sufficient riboflavin penetration without any epithelial disruption. A compromise between efficacy and epithelial integrity has to be found.

  18. Superoxide production by phagocytic leukocytes.

    Drath, D B; Karnovsky, M L


    Mononuclear phagocytic leukocytes, as well as polymorphonuclear leukocytes, produce and release superoxide at rest, and this is stimulated by phagocytosis. Of the mouse monocytic cells studied, alveolar macrophages released the largest amounts of superoxide during phagocytosis, followed by normal peritoneal macrophages. Casein-elicited and "activated" macrophages released smaller quantities. In the guinea pig, polymorphonuclear leukocytes and casein-elicited macrophages were shown to release superoxide during phagocytosis whereas alveolar macrophages did not. Superoxide release accounted for only a small fraction of the respiratory burst of phagocytosis in all but the normal mouse peritoneal macrophage, the guinea pig polymorphonuclear leukocyte, and probably the mouse alveolar macrophage. There are obviously considerable species differences in O2-release by various leukocytes that might reflect both the production and/or destruction (e.g. by dismutase) of that substance. PMID:804030

  19. Leukocyte biophysics. An invited review.

    Schmid-Schönbein, G W


    The biophysical properties of leukocytes in the passive and active state are discussed. In the passive unstressed state, leukocytes are spherical with numerous membrane folds. Passive leukocytes exhibit viscoelastic properties, and the stress is carried largely by the cell cytoplasm and the nucleus. The membrane is highly deformable in shearing and bending, but resists area expansion. Membrane tension can usually be neglected but plays a role in cases of large deformation when the membrane becomes unfolded. The constant membrane area constraint is a determinant of phagocytic capacity, spreading of cells, and passage through narrow pores. In the active state, leukocytes undergo large internal cytoplasmic deformation, pseudopod projection, and granule redistribution. Several different measurements for assessment of biophysical properties and the internal cytoplasmic deformation in form of strain and strain rate tensors are presented. The current theoretical models for active cytoplasmic motion in leukocytes are discussed in terms of specific macromolecular reactions. PMID:1705479

  20. Metallothionein mediates leukocyte chemotaxis

    Lynes Michael A


    Full Text Available Abstract Background Metallothionein (MT is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. Results In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis. Conclusion These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure.

  1. Effects of ouabain and furosemide on transepithelial electrical parameters of the isolated shark ciliary epithelium.

    Wiederholt, M; Zadunaisky, J A


    Sections of the ciliary epithelium of adult sharks (Squalus acanthias) were mounted in Ussing-type chambers (area 0.2 cm2) for measurements of transepithelial potential difference (PD), short circuit current (SCC) and calculation of transepithelial resistance (R). In 15 preparations PD was aqueous side negative (-0.51 +/- 0.12 mV; SCC 18.3 +/- 2.5 microA cm-2; R 30.7 +/- 3.1 Ohm cm2). However, in 15 other preparations incubated in identical Ringer's solution PD was aqueous side positive (0.53 +/- 0.09 mV; SCC -19.6 +/- 2.3 microA cm-2; R 27.9 +/- 2.8 Ohm cm2). 10(-5) M ouabain or 10(-4) M furosemide were applied either to the aqueous or blood side of the isolated ciliary epithelium at transepithelial negative or positive PD. When the transepithelial PD was positive on the aqueous side ouabain decreased PD and SCC within 15 to 45 min. When the spontaneous PD was negative both PD and SCC decreased when ouabain was applied to the blood side. When the drug was given to the aqueous side a biphasic response (first stimulation, then inhibition) of PD and SCC was observed. Furosemide when given to the blood side (with aqueous side PD positive) or to the aqueous side (with aqueous side PD negative) decreased PD and SCC. However, a transient stimulation of both electrical parameters was observed when furosemide was applied to either the blood side (with aqueous side PD negative) or to the aqueous side (with aqueous side PD positive). The polarity and magnitude of PD and SCC probably depend on the relative activity of sodium and chloride pumps across the cell membranes of the non-pigmented and/or pigmented cell layer. However, additional transport mechanisms cannot be excluded. PMID:3038770

  2. Pseudo-streaming potentials in Necturus gallbladder epithelium. I. Paracellular origin of the transepithelial voltage changes


    Apparent streaming potentials were elicited across Necturus gallbladder epithelium by addition or removal of sucrose from the apical bathing solution. In NaCl Ringer's solution, the transepithelial voltage (Vms) change (reference, basolateral solution) was positive with sucrose addition and negative with sucrose removal. Bilateral Cl- removal (cyclamate replacement) had no effect on the polarity or magnitude of the Vms change elicited by addition of 100 mM sucrose. In contrast, bilateral Na+ ...

  3. Synchronization Modulation Increases Transepithelial Potentials in MDCK Monolayers through Na/K Pumps

    Tran, Vu; Zhang, Xiaodong; Cao, Lin; Li, Hanqing; Lee, Benjamin; So, Michelle; Sun, Yaohui; Chen, Wei; Zhao, Min


    Transepithelial potential (TEP) is the voltage across a polarized epithelium. In epithelia that have active transport functions, the force for transmembrane flux of an ion is dictated by the electrochemical gradient in which TEP plays an essential role. In epithelial injury, disruption of the epithelial barrier collapses the TEP at the wound edge, resulting in the establishment of an endogenous wound electric field (∼100 mV/mm) that is directed towards the center of the wound. This endogenous...

  4. Transepithelial transport of the fluoroquinolone ciprofloxacin by human airway epithelial Calu-3 cells.

    Cavet, M E; West, M.; Simmons, N L


    Although fluoroquinolone antibiotics such as ciprofloxacin are able to gain access to lung tissue and both pleural and bronchial secretions, the characteristics of transport and cellular uptake of ciprofloxacin in human epithelial lung tissue remain obscure. We have chosen human airway epithelial (Calu-3) cells, reconstituted as functional epithelial layers grown on permeable filter supports, as a model with which to assess both transepithelial transport and cellular uptake of ciprofloxacin. ...

  5. Characterization of branchial transepithelial calcium fluxes in freshwater trout, Salmo gairdneri

    Experiments were performed to determine whether gill transepithelial calcium fluxes in the freshwater trout (Salmo gairdneri) are passive or require active transport and to characterize the mechanism involved. A comparison of the in vivo unidirectional flux ratios with the flux ratios calculated according to the transepithelial electrochemical gradients revealed that calcium uptake from the water requires active transport of Ca2+. The inhibition of calcium uptake by external lanthanum, the specific deposition of lanthanum on the apical surface of chloride cells, and the favorable electrochemical gradient for calcium across the apical membrane suggest that the initial step in branchial calcium uptake is the passive entry of calcium into the cytosol of chloride cells through apical channels that are permeable to calcium. The study of gill basolateral plasma membrane vesicles demonstrated the existence of a high-affinity calmodulin-dependent calcium-transporting system. This system actively transports calcium from the cytosol of chloride cells into the plasma against a sizeable electrochemical gradient, thereby completing the transepithelial uptake of calcium. Calcium efflux occurs passively through paracellular pathways between chloride cells and adjacent pavement cells or between neighboring pavement cells

  6. TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers

    Morton, Penny E.; Hicks, Alexander; Ortiz-Zapater, Elena; Raghavan, Swetavalli; Pike, Rosemary; Noble, Alistair; Woodfin, Abigail; Jenkins, Gisli; Rayner, Emma; Santis, George; Parsons, Maddy


    Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFα acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCδ pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings. PMID:27193388

  7. TNFα promotes CAR-dependent migration of leukocytes across epithelial monolayers.

    Morton, Penny E; Hicks, Alexander; Ortiz-Zapater, Elena; Raghavan, Swetavalli; Pike, Rosemary; Noble, Alistair; Woodfin, Abigail; Jenkins, Gisli; Rayner, Emma; Santis, George; Parsons, Maddy


    Trans-epithelial migration (TEpM) of leukocytes during inflammation requires engagement with receptors expressed on the basolateral surface of the epithelium. One such receptor is Coxsackie and Adenovirus Receptor (CAR) that binds to Junctional Adhesion Molecule-like (JAM-L) expressed on leukocytes. Here we provide the first evidence that efficient TEpM of monocyte-derived THP-1 cells requires and is controlled by phosphorylation of CAR. We show that TNFα acts in a paracrine manner on epithelial cells via a TNFR1-PI3K-PKCδ pathway leading to CAR phosphorylation and subsequent transmigration across cell junctions. Moreover, we show that CAR is hyper-phosphorylated in vivo in acute and chronic lung inflammation models and this response is required to facilitate immune cell recruitment. This represents a novel mechanism of feedback between leukocytes and epithelial cells during TEpM and may be important in controlling responses to pro-inflammatory cytokines in pathological settings. PMID:27193388

  8. Prolonged inhibition of bacterial protein synthesis abolishes Salmonella invasion.

    MacBeth, K J; Lee, C. A.


    We have found that prolonged inhibition of bacterial protein synthesis abolishes the ability of Salmonella typhimurium to enter HEp-2 cells. Our results suggest that an essential invasion factor has a functional half-life that is seen as a gradual loss of invasiveness in the absence of protein synthesis. Therefore, Salmonella invasiveness appears to be a transient phenotype that is lost unless protein synthesis is maintained. This finding may explain why salmonellae grown to stationary phase ...

  9. Barriers to entry : abolishing the barriers to understanding

    Keppler, Jan Horst


    BARRIERS TO ENTRY: ABOLISHING THE BARRIERS TO UNDERSTANDING by Jan-Horst Keppler Professor of economics Université Paris – Dauphine, LEDa, and Université Paris I Panthéon-Sorbonne, PHARE Port.: (+33 6) 77 81 37 46; Email: . Abstract The concept of a barrier to entry has been discussed least since Bain (1956) with important contributions by Spence (1977), Dixit (1980) or Milgrom and Roberts (1982). The more recent discussion is synth...

  10. Does Abolishing Fees Reduce School Quality? Evidence from Kenya

    Tessa Bold; Mwangi Kimenyi; Germano Mwabu; Justin Sandefur


    In 2003 Kenya abolished user fees in all government primary schools. We find that this Free Primary Education (FPE) policy resulted in a decline in public school quality and increased demand for private schooling. However, the former did not reflect a decline in value added by public schools - as anticipated if fees contribute to local accountability - but rather the selection of weaker pupils into free education. In contrast, affluent children who exited to the private sector in response to ...

  11. A scintiscan study using leukocytes

    A method of labelling leukocytes with 111-In-oxine is described that is easy to handle, reproducible and requires no sophisticated hardware. It is based on a leukocyte concentrate prepared from whole blood, which has an average cell content of 64.8%. Seventy-two patients selected from among those undergoing nephrologico-urological and neurological procedures or accident surgery were subjected to preliminary wholebody scintiscanning as well as a scintiscan study using leukocytes. It was calculated that the method is able to reveal the presence of an abscess with a sensitivity of 77%, a specificity of 98% and an accuracy of 89%. This examination may prove equally useful to follow up a confirmed inflammation, to determine its exact type and extent and to make a clear diagnostic distinction between an inflammatory process and a tumour. (TRV)

  12. Oestrogen-related receptor α is required for transepithelial H+ secretion in zebrafish.

    Guh, Ying-Jey; Yang, Chao-Yew; Liu, Sian-Tai; Huang, Chang-Jen; Hwang, Pung-Pung


    Oestrogen-related receptor α (ERRα) is an orphan nuclear receptor which is important for adaptive metabolic responses under conditions of increased energy demand, such as cold, exercise and fasting. Importantly, metabolism under these conditions is usually accompanied by elevated production of organic acids, which may threaten the body acid-base status. Although ERRα is known to help regulate ion transport by the renal epithelia, its role in the transport of acid-base equivalents remains unknown. Here, we tested the hypothesis that ERRα is involved in acid-base regulation mechanisms by using zebrafish as the model to examine the effects of ERRα on transepithelial H(+) secretion. ERRα is abundantly expressed in H(+)-pump-rich cells (HR cells), a group of ionocytes responsible for H(+) secretion in the skin of developing embryos, and its expression is stimulated by acidic (pH 4) environments. Knockdown of ERRα impairs both basal and low pH-induced H(+) secretion in the yolk-sac skin, which is accompanied by decreased expression of H(+)-secreting-related transporters. The effect of ERRα on H(+) secretion is achieved through regulating both the total number of HR cells and the function of individual HR cells. These results demonstrate, for the first time, that ERRα is required for transepithelial H(+) secretion for systemic acid-base homeostasis. PMID:26911965

  13. Should the Catholic Church abolish the rule of Celibacy?

    Men-Andri Benz; Reto Foellmi; Egon Franck; Urs Meister


    Since the Middle Ages, celibacy has been a requirement for those becoming priests in the Roman Catholic Church. In the ongoing discussions about reforms, a wide range of church members have asked for the abolishment of the celibacy requirement in order to meet the changed social and moral standards of believers and to increase the quality and quantity of priests. However, this paper shows that from a strategic point of view, there are good reasons for the Catholic Church to keep, or even to i...

  14. Identification of Polymorphonuclear Leukocyte and HL-60 Cell Receptors for Adhesins of Streptococcus gordonii and Actinomyces naeslundii

    Ruhl, Stefan; Cisar, John O.; Sandberg, Ann L.


    Interactions of oral streptococci and actinomyces with polymorphonuclear leukocytes (PMNs), mediated by sialic acid- and Gal/GalNAc-reactive adhesins, respectively, result in activation of the PMNs and thereby may contribute to the initiation of oral inflammation. Sialidase treatment of PMNs or HL-60 cells abolished adhesion of Streptococcus gordonii but was required for adhesion of Actinomyces naeslundii. The same effects of sialidase were noted for adhesion of these bacteria to a major 150-...

  15. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress

    Pedersen, Peter Steen; Braunstein, Thomas Hartig; Jørgensen, Anders;


    Osmotic water permeability (P(f )) was measured in spheroid-shaped human nasal airway epithelial explants pre-exposed to increasing levels of hyperosmotic stress. The fluid-filled spheroids, derived from nasal polyps, were lined by a single cell layer with the ciliated apical cell membrane facing......-CF spheroids and were not significantly influenced by hyperosmotic stress. The results suggest that hyperosmotic stress is an important activator of AQP-5 in human airway epithelium, leading to significantly increased transepithelial water permeability....... of aquaporin-5 (AQP5), studied by immunofluorescence and confocal microscopy, showed an increase in parallel with the increase in P(f ) following hyperosmotic stress. The AQP5 was localized both in cytoplasmic vesicles and in apical cell membranes. Spontaneous fluid absorption rates were equal in CF and non...

  16. Prolonged inhibition of bacterial protein synthesis abolishes Salmonella invasion.

    MacBeth, K J; Lee, C A


    We have found that prolonged inhibition of bacterial protein synthesis abolishes the ability of Salmonella typhimurium to enter HEp-2 cells. Our results suggest that an essential invasion factor has a functional half-life that is seen as a gradual loss of invasiveness in the absence of protein synthesis. Therefore, Salmonella invasiveness appears to be a transient phenotype that is lost unless protein synthesis is maintained. This finding may explain why salmonellae grown to stationary phase lose their ability to enter cultured cells. In addition, a short-lived capacity to enter cells may be important during infection so that bacterial invasiveness is limited to certain times and host sites during pathogenesis. PMID:8454361

  17. Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation

    Kvist, Malin; Hancock, Viktoria; Klemm, Per


    Bacterial biofilms cause numerous problems in health care and industry; notably, biofilms are associated with a large number of infections. Biofilm-dwelling bacteria are particularly resistant to antibiotics, making it hard to eradicate biofilm-associated infections. Bacteria rely on efflux pumps...... to get rid of toxic substances. We discovered that efflux pumps are highly active in bacterial biofilms, thus making efflux pumps attractive targets for antibiofilm measures. A number of efflux pump inhibitors (EPIs) are known. EPIs were shown to reduce biofilm formation, and in combination they...... could abolish biofilm formation completely. Also, EPIs were able to block the antibiotic tolerance of biofilms. The results of this feasibility study might pave the way for new treatments for biofilm-related infections and may be exploited for prevention of biofilms in general....

  18. Femoral venous reflux abolished by greater saphenous vein stripping.

    Walsh, J C; Bergan, J J; Beeman, S; Comer, T P


    Preoperative venous duplex scanning has revealed unexpected deep venous incompetence in patients with apparently only varicose veins. Acting on the hypothesis that the deep vein reflux was secondary to deep vein dilation caused by reflux volume, the following was done. Between July 1990 and April 1993, 29 limbs in 21 patients (16 females) were examined by color-flow duplex imaging to determine valve closure by the method of van Bemmelen. Instrumentation included high-resolution ATL-9 venous interrogation using a pneumatic cuff deflation stimulus of reflux in the standing, nonweight-bearing limb. All limbs showed greater saphenous vein reflux. Twenty-nine showed superficial femoral vein reflux and of these three showed popliteal vein reflux. Duplex testing was performed by a certified vascular technologist whose interpretation was blinded as to the results of clinical examination and grading of the severity of venous insufficiency. Surgery was performed on an outpatient basis under general anesthesia using groin-to-knee removal of the greater saphenous vein by the vein inversion technique of Van Der Strict. Stab avulsion of varicose tributary veins was accomplished during the same period of anesthesia. In 27 of 29 limbs with preoperative femoral reflux, that reflux was abolished by greater saphenous stripping. In patients with popliteal reflux both femoral and popliteal reflux was abolished. Improvement of deep venous hemodynamics by ablation of superficial reflux supports the reflux circuit theory of venous overload. Furthermore, preoperative evaluation of venous hemodynamics by duplex scanning appears to provide useful pre- and postoperative information regarding venous insufficiency in individual patients. PMID:7865395

  19. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P


    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. PMID:26831193

  20. Modification of leukocyte adherence inhibition (LAI) assay with 51Cr-labelled leukocytes

    Leukocyte adherence inhibition was measured by a new modified radioisotopic technique. Peripheral blood leukocytes were isolated and labelled with 51Cr. These leukocytes were incubated with medium or buffer alone and with medium or buffer containing tumor antigen or gluten. The glass surface for the adherence was prepared carefully. In all samples the adherence of leukocytes occured under the same conditions. The results of the LAI assay with gluten and stomach cancer antigen are reported and discussed. (author)

  1. Short communication: Pasteurization of milk abolishes bovine herpesvirus 4 infectivity.

    Bona, C; Dewals, B; Wiggers, L; Coudijzer, K; Vanderplasschen, A; Gillet, L


    Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus highly prevalent in the cattle population that has been isolated from the milk and the serum of healthy infected cows. Several studies reported the sensitivity and the permissiveness of some human cells to BoHV-4 infection. Moreover, our recent study demonstrated that some human cells sensitive but not permissive to BoHV-4 support a persistent infection protecting them from tumor necrosis factor-alpha-induced apoptosis. Together, these observations suggested that BoHV-4 could represent a danger for public health. To evaluate the risk of human infection by BoHV-4 through milk or serum derivatives, we investigated the resistance of BoHV-4 to the mildest thermal treatments usually applied to these products. The results demonstrated that milk pasteurization and thermal decomplementation of serum abolish BoHV-4 infectivity by inactivation of its property to enter permissive cells. Consequently, our results demonstrate that these treatments drastically reduce the risk of human infection by BoHV-4 through treated milk or serum derivatives. PMID:16107396

  2. Endothelial signalling events during leukocyte transmigration

    P.L. Hordijk


    The notion that it takes two to tango is certainly true for leukocyte transendothelial migration. A growing pallet of leukocyte adhesion-induced signaling events in endothelial cells have been identified, mediating both short-term (i.e. permeability) as well as long-term (i.e. regulation of transcri

  3. Conjugation of a cell-penetrating peptide to parathyroid hormone affects its structure, potency, and transepithelial permeation

    Kristensen, Mie; de Groot, Anne Marit; Berthelsen, Jens;


    Delivery of therapeutic peptides and proteins by the use of cell-penetrating peptides (CPPs) as carriers has been suggested as a feasible strategy. The aim of the present study was to investigate the effect of conjugating a series of well-known CPPs to the biologically active part of parathyroid...... hormone, i.e. PTH(1-34), and to evaluate the effect with regards to secondary structure, potency in Saos-2 cells, immunogenicity, safety as well as the transepithelial permeation across monolayers by using the Caco-2 cell culture model. Further, co-administration of CPP and PTH(1-34) as an alternative to...... covalent conjugation was compared with regards to the transepithelial permeation. CPP-conjugated PTH(1-34) fusion peptides were successfully expressed in Escherichia coli and purified from inclusion bodies. No clear correlation between the degree of secondary structure of the CPP-conjugated PTH(1...


    Rasgado-flores, H.; Mandava, V.; Siman, H.; Piennette, P.; Ngansop, T.; Rodriguez, A.; Chiwocha, T.; Pena-rasgado, C.; Bridges, R.


    Hyperosmotic challenge (HC) saline inhalation benefits Cystic Fibrosis (CF) patients. Surprisingly, these benefits are long-lasting and amiloride diminishes them. Our aim was to explain these effects. Human bronchial epithelial (HBE) cells from CF donors were grown in inserts and were used to measure amiloride-sensitive short circuit currents (I Na), and transepithelial conductance (G T) and capacitance (C T). HC solutions were prepared by either adding additional NaCl or mannitol to the isos...

  5. Absence of transepithelial anion exchange by rabbit OMCD: Evidence against reversal of cell polarity

    In the rabbit cortical collecting duct (CCD), Cl tracer crosses the epithelium predominantly via an anion exchange system that operates in either a Cl-Cl or Cl-HCO3 exchange mode. In the present study, the authors used the 36Cl lumen-to-bath rate coefficient (KCl, nm/s), a sensitive measurement of CCD transepithelial anion transport, to investigate the nature of Cl transport in the medullary collecting duct dissected from inner stripe, outer medulla (OMCD). The KCl in OMCD perfused and bathed in HCO3-Ringer solution was low and similar to that value observed in the CCD when anion exchange is inhibited and Cl permeates the epithelium by diffusion. To test the hypothesis that metabolic alkalosis could reverse the polarity of intercalated cells and thus induce an apical Cl-HCO3 exchanger in H+-secreting OMCD cells, they measured KCl in OMCD from rabbits make alkalotic by deoxycorticosterone and furosemide. Although the base-line KCl was slightly higher than in OMCD from control rabbits, the value was still far lower than the KCl under comparable conditions in CCD. They conclude (1) Cl transport across the MCD by anion exchange is immeasurably low or nonexistent; (2) unlike the CCD, Cl transport in OMCD is not responsive to cAMP; and (3) metabolic alkalosis does not induce an apical anion exchanger in OMCD, i.e., does not cause epithelial polarity reversal

  6. Leukocyte nucleus segmentation and nucleus lobe counting

    Zheng Zong-Han


    Full Text Available Abstract Background Leukocytes play an important role in the human immune system. The family of leukocytes is comprised of lymphocytes, monocytes, eosinophils, basophils, and neutrophils. Any infection or acute stress may increase or decrease the number of leukocytes. An increased percentage of neutrophils may be caused by an acute infection, while an increased percentage of lymphocytes can be caused by a chronic bacterial infection. It is important to realize an abnormal variation in the leukocytes. The five types of leukocytes can be distinguished by their cytoplasmic granules, staining properties of the granules, size of cell, the proportion of the nuclear to the cytoplasmic material, and the type of nucleolar lobes. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency.Biomedical technologists can currently recognize abnormal leukocytes using human eyes. However, the quality and efficiency of diagnosis may be compromised due to the limitations of the biomedical technologists' eyesight, strength, and medical knowledge. Therefore, the development of an automatic leukocyte recognition system is feasible and necessary. It is essential to extract the leukocyte region from a blood smear image in order to develop an automatic leukocyte recognition system. The number of lobes increased when leukemia, chronic nephritis, liver disease, cancer, sepsis, and vitamin B12 or folate deficiency occurred. Clinical neutrophil hypersegmentation has been widely used as an indicator of B12 or folate deficiency. Results The purpose of this paper is to contribute an automatic leukocyte nuclei image segmentation method for such recognition technology. The other goal of this paper is to develop the method of counting the number of lobes in a cell nucleus. The experimental results

  7. Leukocyte telomere dynamics in the elderly

    Steenstrup, Troels; Hjelmborg, Jacob V B; Mortensen, Laust Hvas;


    Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants of the...... years, assuming a 340 bp attrition during this period. This was not significantly different from the empirical observation of 7.5 % of individuals showing LTL elongation. We conclude that accumulation of ultra-short telomeres in leukocytes of the elderly reflects a shift toward shorter telomeres in the...

  8. Interactions Between Stably Rolling Leukocytes In Vivo

    King, M R; Kim, M B; Sarelius, I H; King, Michael R.; Ruscio, Aimee D.; Kim, Michael B.; Sarelius, Ingrid H.


    We have characterized the two-dimensional spatial dependence of the hydrodynamic interactions between two adhesively rolling leukocytes in a live venule in the mouse cremaster muscle. Two rolling leukocytes were observed to slow each other down when rolling together in close proximity, due to mutual sheltering from the external blood flow in the vessel lumen. These results are in agreement with a previous study of leukocyte rolling interactions using carbohydrate-coated beads in a parallel-plate flow chamber and a detailed computer model of adhesion in a multicellular environment.

  9. Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.

    Karaki, Shin-Ichiro; Ishikawa, Junji; Tomizawa, Yuka; Kuwahara, Atsukazu


    ε-Viniferin is a dehydrodimer of resveratrol, a polyphenol synthesized in many plants, including grapevine. The present study investigated the effects of ε-viniferin and resveratrol on epithelial secretory and barrier functions in isolated rat small and large intestinal mucosa. Mucosa-submucosa tissue preparations of various segments of the rat large and small intestines were mounted on Ussing chambers, and short-circuit current (Isc) and tissue conductance (Gt) were continuously measured. The mucosal addition of ε-viniferin (>10(-5) mol/L) and resveratrol (>10(-4) mol/L) to the cecal mucosa, which was the most sensitive region, induced an increase in Isc and a rapid phase decrease (P-1) followed by rapid (P-2) and broad (P-3) peak increases in Gt in concentration-dependent manners. Mucosal ε-viniferin (10(-4) mol/L), but not resveratrol (10(-4) mol/L), increased the permeability of FITC-conjugated dextran (4 kDa). The mucosal ε-viniferin-evoked changes in Isc (Cl(-) secretion), but not in Gt, were attenuated by a selective cyclooxygenase (COX)-1 inhibitor and a selective EP4 prostaglandin receptor. The mucosal ε-viniferin-evoked increase in Isc was partially attenuated, and P-2, but not P-1 or P-3, change in Gt was abolished by a transient receptor potential cation channel, subfamily A, member 1 (TRPA1) inhibitor. Moreover, the mucosal ε-viniferin concentration-dependently attenuated the mucosal propionate (1 mmol/L)-evoked increases in Isc and Gt Immunohistochemical studies revealed COX-1-immunoreactive epithelial cells in the cecal crypt. The present study showed that mucosal ε-viniferin modulated transepithelial ion transport and permeability, possibly by activating sensory epithelial cells expressing COX-1 and TRPA1. Moreover, mucosal ε-viniferin decreased mucosal sensitivity to other luminal molecules such as short-chain fatty acids. In conclusion, these results suggest that ε-viniferin modifies intestinal mucosal transport and barrier

  10. Leukocyte Activation in Obese Patients

    Minervino, Daniele; Gumiero, Daniela; Nicolazzi, Maria Anna; Carnicelli, Annamaria; Fuorlo, Mariella; Guidone, Caterina; Di Gennaro, Leonardo; Fattorossi, Andrea; Mingrone, Geltrude; Landolfi, Raffaele


    Abstract The rising prevalence of obesity is a major global health problem. In severe obesity, bariatric surgery (BS) allows to obtain a significant weight loss and comorbidities improvement, among them one of the factors is the thrombotic risk. In this observational study, we measured indices of leukocyte activation in severely obese patients as markers of increased thrombotic risk in relation with serum markers of inflammation before and after BS. Frequency of polymorphonuclear neutrophil-platelet (PLT) and monocyte (MONO)-PLT aggregates as well as of tissue factor (TF) expressing MONOs was measured in the peripheral blood of 58 consecutive obese patients and 30 healthy controls. In 31 of the 58 obese patients, data obtained at the enrollment were compared with those obtained at 3, 6, and 12 months after BS. Compared with healthy controls, obese patients showed a higher frequency of polymorphonuclear leukocyte (PMNL)-PLT aggregates (7.47 ± 2.45 [6.82–8.11]% vs 5.85 ± 1.89 [5.14–6.55]%, P = 0.001), MONO-PLT aggregates (12.31 ± 7.33 [10.38–14.24]% vs 8.14 ± 2.22 [7.31–8.97]%, P < 0.001), and TF expressing MONOs (4.01 ± 2.11 [3.45–4.56]% vs 2.64 ± 1.65 [2.02–3.25]%, P = 0.002). PMNL-PLT and MONO-PLT aggregate frequency was positively correlated with TF expressing MONOs (R2 = 0.260, P = 0.049 and R2 = 0.318, P = 0.015, respectively). BS was performed in 31 patients and induced a significant reduction of the body mass index, and waist and hip circumferences. These effects were associated with a significant decrease of PMNL-PLT aggregates at 12 months (7.58 ± 2.27 [6.75–8.42]% vs 4.47 ± 1.11 [3.93–5.01]%, P < 0.001), and a reduction of TF expressing MONOs at 6 (3.82 ± 2.04 [3.07–4.57]% vs 1.60 ± 1.69 [0.30–2.90]%, P = 0.008) and 12 months (3.82 ± 2.04 [3.07–4.57]% vs 1.71 ± 0.54 [1.45–1.97]%, P = 0.001) after BS. These data suggest that leukocyte

  11. Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers

    Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37 degrees C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by [14C]CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the unstirred boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier

  12. Transepithelial transport of aliphatic carboxylic acids studied in Madin Darby canine kidney (MDCK) cell monolayers

    Cho, M.J.; Adson, A.; Kezdy, F.J. (Upjohn Company, Kalamazoo, MI (USA))


    Transport of 14C-labeled acetic, propionic (PA), butyric, valeric, heptanoic (HA), and octanoic (OA) acids across the Madin Darby canine kidney (MDCK) epithelial cell monolayer grown on a porous polycarbonate membrane was studied in Hanks' balanced salt solution (HBSS) at 37{degrees}C in both apical-to-basolateral and basolateral-to-apical directions. At micromolar concentrations of solutes, metabolic decomposition was significant as evidenced by (14C)CO2 production during the OA transport. The apparent permeability (Pe) indicates that as lipophilicity increases, diffusion across the unstirred boundary layer becomes rate limiting. In support of this notion, transport of OA and HA was enhanced by agitation, showed an activation energy of 3.7 kcal/mol for OA, and resulted in identical Pe values for both transport directions. Analysis of Pe changes with varying alkyl chain length resulted in a delta G of -0.68 +/- 0.09 kcal/mol for -CH2-group transfer from an aqueous phase to the MDCK cells. When the intercellular tight junctions were opened by the divalent chelator EGTA in Ca2+/Mg2(+)-free HBSS, transport of the fluid-phase marker Lucifer yellow greatly increased because of paracellular leakage. PA transport also showed a significant increase, but OA transport was independent of EGTA. Although albumin also undergoes paracellular transport in the presence of EGTA and OA binds strongly to albumin, OA transport in EGTA solution was unchanged by albumin. These observations indicate that transmembrane transport is the major mechanism for lipophilic substances. The present study, together with earlier work on the transport of polar substances, shows that the MDCK cell monolayer is an excellent model of the transepithelial transport barrier.

  13. 21 CFR 864.7660 - Leukocyte alkaline phosphatase test.


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Leukocyte alkaline phosphatase test. 864.7660... Leukocyte alkaline phosphatase test. (a) Identification. A leukocyte alkaline phosphatase test is a device used to identify the enzyme leukocyte alkaline phosphatase in neutrophilic granulocytes...

  14. Indium-111 autologous leukocyte imaging in pancreatitis

    Anderson, J.R.; Spence, R.A.; Laird, J.D.; Ferguson, W.R.; Kennedy, T.L.


    Thirty-nine patients with acute pancreatitis have been assessed using a prognostic factor grading system, abdominal ultrasound, and autologous leukocyte imaging. Both prognostic factor grading and leukocyte imaging can accurately assess the severity of the disease early in its course. All patients with a negative indium-labeled leukocyte image recovered without sequelae, whereas five of the 12 patients with a positive image developed complications, including two deaths. Abdominal ultrasound is of no value in assessing severity, but is a useful method of detecting those patients with gallstone-associated disease. In patients with suspected abscess formation following acute pancreatitis, indium leukocyte imaging does not differentiate between fat necrosis and abscess formation. In this situation, computerized tomography should be carried out before laparotomy is undertaken.

  15. Effects of ochratoxin a on broiler leukocytes

    MA Moura


    Full Text Available This study evaluated alterations in the qualitative cellular profile of leukocytes caused by the administration of low doses of ochratoxin-A (OTA in poultry. Sixty chicks were separated in three experimental groups: control, PBS-treated and OTA-treated. Blood smears from all birds were analyzed three and six hours post-treatment. Differential leukocyte counting demonstrated that OTA reduced the percentage of lymphocytes and eosinophils and significantly increased the number of heterophils and monocytes.

  16. Engineering on abolishment measure of nuclear fuel facilities. Application of 3D-CAD to abolishment measure of nuclear fuel facilities

    The Japan Nuclear Cycle Development Institute (JNC) progresses some advancing R and Ds required for establishment of the nuclear fuel cycle under considering on safety, economical efficiency, environmental compatibility, and so on. An important item among them is a technology on safe abolishment of a nuclear energy facility ended its role, which is called the abolishment measure technique. Here was introduced at a center of viewpoint called on use of three dimensional CAD (3D-CAD), on outlines of engineering system for abolishment measure (subdivision engineering system) under an object of nuclear fuel facilities, constructed through subdivision and removal of refinement conversion facilities, by the Ningyo-toge Environmental Engineering Center of JNC. (G.K.)

  17. Penetratin-Mediated Transepithelial Insulin Permeation: Importance of Cationic Residues and pH for Complexation and Permeation

    Kristensen, Mie; Franzyk, Henrik; Klausen, M. T.;


    Penetratin is a widely used carrier peptide showing promising potential for mucosal delivery of therapeutic proteins. In the present study, the importance of specific penetratin residues and pH was investigated with respect to complexation with insulin and subsequent transepithelial insulin...... permeation. Besides penetratin, three analogues were studied. The carrier peptide-insulin complexes were characterized in terms of size and morphology at pH 5, 6.5, and 7.4 by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. At pH 7.4 mainly very large complexes were...

  18. A pharmacological modification of pain and epithelial healing in contemporary transepithelial all-surface laser ablation (ASLA

    Aslanides IM


    Full Text Available Ioannis M Aslanides, Vasilis D Selimis, Nikolaos V Bessis, Panagiotis N Georgoudis Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece Purpose: We report our experience with the use of the matrix regenerating agent (RGTA Cacicol® after reverse transepithelial all-surface laser ablation (ASLA-SCHWIND to assess the safety, efficacy, pain, and epithelial healing.Methods: Forty eyes of 20 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent transepithelial ASLA in both eyes, with one of the eyes randomly assigned to the use of the RGTA Cacicol. Postoperative pain and vision were subjectively assessed with the use of a questionnaire on the operative day, at 24 hours, 48 hours and 72 hours. Epithelial defect area size was measured at 24 hours, 48 hours, and 72 hours. Uncorrected distance visual acuity (UDVA and corrected distance visual acuity (CDVA were assessed at 1 month.Results: Mean UDVA at 1 month was LogMAR 0.028. The epithelial defect area was 10.91 mm2 and 13.28 mm2 at 24 hours and 1.39 mm2 and 1.24 mm2 at 48 hours for treated and nontreated eyes, respectively. Overall, 50% and 65% of treated and nontreated eyes healed by 48 hours. There was no statistically significant difference in the subjective vision between the groups, although vision of patients in the RGTA group was reported to be better. Pain scores were better at 24 hours and 48 hours in the RGTA group but with no statistically significant difference.Conclusion: The use of RGTA Cacicol shows faster epithelial recovery after transepithelial ASLA for myopia. Subjectively reported scores of pain and subjective vision were better in the RGTA group, although the difference was not statistically significant. There seems to be a consensual acceleration of epithelial healing even in eyes that did not receive treatment. There were no adverse events and no incidents of inflammation, delayed healing, or haze. Keywords: matrix

  19. Osteomyelitis: diagnosis with In-111-labeled leukocytes

    In a retrospective review, 485 patients with suspected osteomyelitis were studied. Of these, 453 patients were studied with both bone and indium-111 leukocyte scanning (173 sequentially and 280 simultaneously). The ability to determine that the infection was in bone rather than in adjacent soft tissue was greater with simultaneous bone scan and In-111 leukocyte studies than with sequential studies. The locations of suspected osteomyelitis were divided into central (containing active bone marrow), peripheral (hands and feet), and middle (between central and peripheral). Specificity remained high (about 90%) regardless of the location. Overall sensitivity was significantly lower in the central location than in the peripheral or middle location. Determination of whether the In-111 leukocyte activity was in bone or adjacent soft tissue was also more difficult when the infection was in the central location. For acute osteomyelitis, sensitivity was high regardless of the location. For chronic osteomyelitis, sensitivity was lower in the central location

  20. Corneal Biomechanical and Anterior Chamber Parameters Variations after 1-year of Transepithelial Corneal Collagen Cross-linking in Eyes of Children with Keratoconus

    Salman, Abdelrahman Gaber


    Aim: To assess the changes in corneal hysteresis (CH) and corneal resistance factor (CRF) 1-year following transepithelial corneal collagen cross-linking (CXL) treatment in eyes of children with keratoconus. Methods: This case series was conducted in 22 eyes of 22 children. Children aged 0.05). Conclusion: Transepithelial CXL in keratoconus in pediatric age group seems to have good stability in corneal biomechanical parameters after 1-year. Further studies with a larger sample and better study design are recommended to confirm our findings. PMID:26957852

  1. Effect of Apple, Baobab, Red-Chicory, and Pear Extracts on Cellular Energy Expenditure and Morphology of Caco-2 Cells using Transepithelial Electrical Resistance (TEER) and Scanning Electron Microscopy (SEM)

    The present study investigated the effects of four food extracts on the Caco-2 intestinal cell line using a new transepithelial electrical resistance method (TEER) concurrent with electron microscopy (SEM). Caco-2 cells are widely used in transepithelial studies because they can be cultured to creat...

  2. Clinical Observation of Transepithelial Corneal Collagen Cross-linking by Iontophoresis of Riboflavin in Treatment of Keratoconus

    Na Li; Zhengjun Fan; Xiujun Peng; Xu Pang; Chunyu Tian


    Purpose: To evaluate the efficacy and safety of transepithelial collagen cross-linking by iontophoretic delivery of riboflavin in treatment of progressive keratoconus.Methods:.Eleven patients (15 eyes) with progressive kerato-conus were enrolled. After 0.1% riboflavin-distilled water so-lution was deliveried via transepithelial iontophpresis for 5 min with 1 mA current, and ultraviolet radiation (370 nm,.3 mW /cm2) was performed at a 1.5 cm distance for 30 min. The fol-low up were 6 months in all eyes. The uncorrected visual acu-ity, corrected visual acuity,endothelial cell counting, corneal thickness,.intraocular pressure, corneal curvature, corneal to-pography,.OCT and corneal opacity before and 6-month after surgery were analyzed.Results: At 6 month postoperatively, mean uncorrected visual acuity and corrected visual acuity changed from 0.36 to 0.30 and from 0.42 to 0.57 without statistical significance..The mean value of each index of corneal curvature declined with-out statistical significance.Kmax value dereased from 60.91 to 59.91, and the astigmatism declined from 3.86 to 3.19. Cen-tral corneal thickness decreased from 460.93 μm to 455.40μm,.and thinnest corneal thickness declined from 450.87 μm to 440.60 μm with no statistical significance..Intraocular pres-sure was significantly elevated from 10.85 mmHg to 12.62 mmHg. Endothelial cell count did not change significantly. No corneal haze occurred. Mean depth of corneal demarcation line was 288.46 μm at 1 month postoperatively..Conclusion:.Transepithelial corneal collagen cross-linking by iontophoresis is effective and safe in the treatment of progres-sive keratoconus, and yields stable clinical outcomes during 6-month follow up..However,.long-term follow up is urgently required. (Eye Science 2014; 29:160-164)

  3. Comparison of single-step reverse transepithelial all-surface laser ablation (ASLA to alcohol-assisted photorefractive keratectomy

    Aslanides IM


    Full Text Available Ioannis M Aslanides,1 Sara Padroni,1 Samuel Arba Mosquera,2 Antonis Ioannides,1 Achyut Mukherjee11Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece; 2Schwind eye-tech-solutions GmbH, Kleinostheim, GermanyPurpose: To evaluate postoperative pain, corneal epithelial healing, development of corneal haze, refractive outcomes, and corneal aberrations in a novel one-step, modified transepithelial photorefractive keratectomy (PRK, termed All-surface laser ablation (ASLA, compared to conventional, alcohol-assisted PRK.Materials and methods: Sixty eyes of 30 myopic patients were prospectively recruited to a randomized fellow eye study. Patients underwent conventional alcohol-assisted PRK in one eye (control group and ASLA-modified transepithelial PRK in the other (30 eyes in each treatment arm. Primary endpoints were postoperative pain and haze scores at 1 day, 3 days, 1 week, and 1, 3, 6, and 12 months. Secondary endpoints included visual acuity at 1, 3, 6, and 12 months, corneal aberrations at 3, 6, and 12 months, and early and late onset haze. Refractive predictability, safety, and efficacy of the two methods were considered.Results: The average age of the cohort was 29 years (standard deviation [SD]: 9; range: 18–46, and the average spherical equivalent refractive error was -4.18 diopters (SD: 1.9. At 3 days after surgery, the average pain score was 64% lower in the ASLA group (P < 0.0005. At this point, 96% of ASLA eyes had no epithelial defect, whereas 43% in the alcohol-assisted group did not achieve complete epithelial healing, and required replacement of bandage contact lens. The haze level was consistently lower in the ASLA group at all time points from 1 to 6 months.Conclusion: This study shows that the ASLA technique may have a future role in refractive surgery, due to the fact that it offers faster epithelial healing, lower pain scores, and significantly less haze formation.Keywords: cornea, ASLA, PRK, alcohol

  4. Palmitoylated transmembrane adaptor proteins in leukocyte signaling

    Štěpánek, Ondřej; Dráber, Peter; Hořejší, Václav


    Roč. 26, č. 5 (2014), s. 895-902. ISSN 0898-6568 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Leukocyte * Adaptor * Palmitoylation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.315, year: 2014

  5. Abolishing Harrassment.

    Bates, Percy; And Others


    Although society is more aware of sexual harassment than it was in the past, the problem is not disappearing. Many school children are afraid to talk about it for fear of reprisal and humiliation. The articles in this issue focus on harassment and the schools in the following papers: (1) "Harassment Revisited" (Percy Bates); (2) "Sexual…

  6. Abolishing GDP

    Bergh, van den, H.


    Expectations and information about the growth of GDP per capita have a large influence on decisions made by private and public economic agents. It will be argued here that GDP (per capita) is far from a robust indicator of social welfare, and that its use as such must be regarded as a serious form of market and government failure. This article presents an update on the most important criticisms of GDP as an indicator of social welfare and economic progress. It further examines the nature and ...

  7. Abolishing GDP

    Bergh, van den Jeroen C.J.M.


    Expectations and information about the growth of GDP per capita have a large influence on decisions made by private and public economic agents. It will be argued here that GDP (per capita) is far from a robust indicator of social welfare, and that its use as such must be regarded as a serious form o

  8. Transepithelial resistance and claudin expression in trout RTgill-W1 cell line: effects of osmoregulatory hormones.

    Trubitt, Rebecca T; Rabeneck, D Brett; Bujak, Joanna K; Bossus, Maryline C; Madsen, Steffen S; Tipsmark, Christian K


    In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1-2 days (20-80Ω⋅cm(2)), which was then maintained for more than 6 days. Tetrabromocinnamic acid, a known stimulator of TER via casein kinase II inhibition, elevated TER in the cell line to 125% of control values after 2 and 6h. Treatment with ethylenediaminetetraacetic acid induced a decrease in TER to molecular weight in samples from rainbow trout gills but not from RTgill-W1 cultures, possibly due to low expression levels. Collectively, these results show that the RTgill-W1 cell layers have tight junctions between cells, are sensitive to hormone treatments, and may provide a useful model for in vitro study of some in vivo gill phenomena. PMID:25490293

  9. K+ channel openers restore verapamil-inhibited lung fluid resolution and transepithelial ion transport

    Su Xue-Feng


    Full Text Available Abstract Background Lung epithelial Na+ channels (ENaC are regulated by cell Ca2+ signal, which may contribute to calcium antagonist-induced noncardiogenic lung edema. Although K+ channel modulators regulate ENaC activity in normal lungs, the therapeutical relevance and the underlying mechanisms have not been completely explored. We hypothesized that K+ channel openers may restore calcium channel blocker-inhibited alveolar fluid clearance (AFC by up-regulating both apical and basolateral ion transport. Methods Verapamil-induced depression of heterologously expressed human αβγ ENaC in Xenopus oocytes, apical and basolateral ion transport in monolayers of human lung epithelial cells (H441, and in vivo alveolar fluid clearance were measured, respectively, using the two-electrode voltage clamp, Ussing chamber, and BSA protein assays. Ca2+ signal in H441 cells was analyzed using Fluo 4AM. Results The rate of in vivo AFC was reduced significantly (40.6 ± 6.3% of control, P Ca3.1 (1-EBIO and KATP (minoxidil channel openers significantly recovered AFC. In addition to short-circuit current (Isc in intact H441 monolayers, both apical and basolateral Isc levels were reduced by verapamil in permeabilized monolayers. Moreover, verapamil significantly altered Ca2+ signal evoked by ionomycin in H441 cells. Depletion of cytosolic Ca2+ in αβγ ENaC-expressing oocytes completely abolished verapamil-induced inhibition. Intriguingly, KV (pyrithione-Na, K Ca3.1 (1-EBIO, and KATP (minoxidil channel openers almost completely restored the verapamil-induced decrease in Isc levels by diversely up-regulating apical and basolateral Na+ and K+ transport pathways. Conclusions Our observations demonstrate that K+ channel openers are capable of rescuing reduced vectorial Na+ transport across lung epithelial cells with impaired Ca2+ signal.

  10. Preparation of 111In leukocytes after hemolytic removal of erythrocytes

    An optimized procedure is described for isolation and high-efficiency radiolabeling of leukocytes using 111In-oxine. The chief advantages over conventional methods include virtually no loss of leukocytes during washing and separation steps; a significant reduction in the time required to prepare leukocytes for radiolabeling compared to non-hemolytic preparations; a 28% increase in the average labeling efficiency obtained using 111In-oxine; > 95% cell viability as measured by the trypan blue exclusion test; elimination of contaminating red blood cells from the leukocyte pellet prior to labeling; and 80% survivability at 15 min post injection (measured as per cent of blood activity on leukocyte fraction). (author)

  11. Nicotinamide phosphoribosyltransferase leukocyte overexpression in Graves' opthalmopathy.

    Sawicka-Gutaj, Nadia; Budny, Bartłomiej; Zybek-Kocik, Ariadna; Sowiński, Jerzy; Ziemnicka, Katarzyna; Waligórska-Stachura, Joanna; Ruchała, Marek


    To investigate the role of NAMPT/visfatin in euthyroid patients with Graves' disease without (GD) and with Graves' ophthalmopathy (GO), we analyzed NAMPT leukocyte expression and its serum concentration. This was a single-center, cross-sectional study with consecutive enrollment. In total, 149 patients diagnosed with Graves' disease were enrolled in the study. We excluded subjects with hyper- or hypothyroidism, diabetes mellitus, other autoimmune disorders, active neoplastic disease, and infection. The control group was recruited among healthy volunteers adjusted for age, sex, and BMI with normal thyroid function and negative thyroid antibodies. Serum levels of visfatin, TSH, FT4, FT3, antibodies against TSH receptor (TRAb), antithyroperoxidase antibodies, antithyroglobulin antibodies, fasting glucose, and insulin were measured. NAMPT mRNA leukocyte expression was assessed using RT-qPCR. NAMPT/visfatin serum concentration was higher in GD (n = 44) and GO (n = 49) patients than in the control group (n = 40) (p = 0.0275). NAMPT leukocyte expression was higher in patients with GO (n = 30) than in GD patients (n = 27) and the control group (n = 29) (p < 0.0001). Simple linear regression analysis revealed that NAMPT/visfatin serum concentration was significantly associated with GD (β = 1.5723; p = 0.021). When NAMPT leukocyte expression was used as a dependent variable, simple regression analysis found association with TRAb, fasting insulin level, HOMA-IR, GD, and GO. In the stepwise multiple regression analysis, we confirmed the association between higher serum NAMPT/visfatin level and GD (coefficient = 1.5723; p = 0.0212), and between NAMPT leukocyte expression and GO (coefficient = 2.4619; p = 0.0001) and TRAb (coefficient = 0.08742; p = 0.006). Increased NAMPT leukocyte expression in patients with GO might suggest a presently undefined role in the pathogenesis of GO. PMID:26767650

  12. Chemokines in the corpus luteum: Implications of leukocyte chemotaxis

    Liptak Amy R


    Full Text Available Abstract Chemokines are small molecular weight peptides responsible for adhesion, activation, and recruitment of leukocytes into tissues. Leukocytes are thought to influence follicular atresia, ovulation, and luteal function. Many studies in recent years have focused attention on the characterization of leukocyte populations within the ovary, the importance of leukocyte-ovarian cell interactions, and more recently, the mechanisms of ovarian leukocyte recruitment. Information about the role of chemokines and leukocyte trafficking (chemotaxis during ovarian function is important to understanding paracrine-autocrine relationships shared between reproductive and immune systems. Recent advances regarding chemokine expression and leukocyte accumulation within the ovulatory follicle and the corpus luteum are the subject of this mini-review.

  13. Leukocyte migration in experimental inflammatory bowel disease

    E. P. Van Rees


    Full Text Available Emigration of leukocytes from the circulation into tissue by transendothelial migration, is mediated subsequently by adhesion molecules such as selectins, chemokines and integrins. This multistep paradigm, with multiple molecular choices at each step, provides a diversity in signals. The influx of neutrophils, monocytes and lymphocytes into inflamed tissue is important in the pathogenesis of chronic inflammatory bowel disease. The importance of each of these groups of adhesion molecules in chronic inflammatory bowel disease, either in human disease or in animal models, will be discussed below. Furthermore, the possibilities of blocking these different steps in the process of leukocyte extravasation in an attempt to prevent further tissue damage, will be taken into account.

  14. Indium-111 leukocyte scanning and fracture healing

    This study was undertaken to determine the specificity of indium-111 leukocyte scans for osteomyelitis when fractures are present. Midshaft tibial osteotomies were performed in 14 New Zealand white rabbits, seven of which were infected postoperatively with Staphylococcus aureus per Norden's protocol. All 14 rabbits were scanned following injection with 75 microCi of indium 111 at 72 h after osteotomy and at weekly intervals for 4 weeks. Before the rabbits were killed, the fracture sites were cultured to document the presence or absence of infection. The results of all infected osteotomy sites were positive, whereas no positive scans were found in the noninfected osteotomies. We concluded from this study that uncomplicated fracture healing does not result in a positive indium-111 leukocyte scan

  15. Effect of leukocyte hydrolases on bacteria

    Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites

  16. Comparison of technetium-99m-HM-PAO leukocytes with indium-111-oxine leukocytes for localizing intraabdominal sepsis

    Technetium-99m-HM-PAO [(99mTc]HM-PAO) leukocyte and indium-111-oxine (111In-oxine) leukocyte scanning were carried out simultaneously in 41 patients at 4 hr and 24 hr after reinjection to determine whether the 4-hr 99mTc scan could replace the 24-hr 111In scan for detecting intraabdominal sepsis. Abdominal infection was confirmed in 12 cases. The 4-hr 99Tc-leukocyte scan, the 4-hr 111In-leukocyte scan, and the 24-hr 111In-leukocyte scan yielded a sensitivity of 100%, 67%, and 100%, respectively, and a specificity of 62%, 90%, and 86%, respectively. The 24-hr 99mTc-leukocyte scan also produced a sensitivity of 100%, but it was falsely positive in all 29 cases without infection due to physiologic bowel uptake. False-positive 4-hr 99mTc-leukocyte scans were also produced by physiologic bowel uptake in seven cases all of whom had true-negative 4-hr and 24-hr 111In-leukocyte scans. Because of the high incidence of false-positive 4-hr [99mTc]HM-PAO leukocyte scans, it was concluded that they could not replace 24-hr 111In-leukocyte scans for detecting intraabdominal sepsis, and that serial 99mTc leukocyte scans starting earlier than 4 hr after reinjection must be evaluated

  17. Passive mechanical properties of human leukocytes.

    Schmid-Schönbein, G W; Sung, K L; Tözeren, H; Skalak, R; Chien, S


    Micropipette experiments are used to determine the rheological properties of human leukocytes. Individual cells in EDTA are subjected to a known aspiration pressure via a micropipette, and their surface deformation from the undeformed spherical shape is recorded on a television monitor. The cells are mathematically modeled as homogeneous spheres, and a standard solid viscoelastic model is found to describe accurately the deformation of the cell for small strains. These experimental and theore...

  18. Leukocyte trafficking in alveoli and airway passages

    Doerschuk Claire M


    Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circula...

  19. Rabbit cationic protein enhances leukocyte adhesiveness.

    Oseas, R S; Allen, J; Yang, H. H.; Baehner, R. L.; Boxer, L A


    Cationic protein purified from rabbit peritoneal polymorphonuclear leukocytes (PMN) was demonstrated to incite autoaggregation of the rabbit PMN and promote adhesiveness of human PMN to endothelial cells. PMN aggregation induced by supernatants derived from secretory PMN was blocked by a specific anticationic protein antibody. These studies reveal that a positively charged protein derived from the PMN can alter surface properties of the PMN itself and imply a role for this protein in PMN immo...

  20. Alginate microsphere compositions dictate different mechanisms of complement activation with consequences for cytokine release and leukocyte activation.

    Ørning, Pontus; Hoem, Kine Samset; Coron, Abba Elizabeth; Skjåk-Bræk, Gudmund; Mollnes, Tom Eirik; Brekke, Ole-Lars; Espevik, Terje; Rokstad, Anne Mari


    The inflammatory potential of 12 types of alginate-based microspheres was assessed in a human whole blood model. The inflammatory potential could be categorized from low to high based on the four main alginate microsphere types; alginate microbeads, liquefied core poly-l-ornithine (PLO)-containing microcapsules, liquefied core poly-l-lysine (PLL)-containing microcapsules, and solid core PLL-containing microcapsules. No complement or inflammatory cytokine activation was detected for the Ca/Ba alginate microbeads. Liquefied core PLO- and PLL-containing microcapsules induced significant fluid phase complement activation (TCC), but with low complement surface deposition (anti-C3c), and a low proinflammatory cytokine secretion, with exception of an elevated MCP-1(CCL2) secretion. The solid core PLL-containing microcapsules generated lower TCC but a marked complement surface deposition and significant induction of the proinflammatory cytokines interleukin (IL-1)β, TNF, IL-6, the chemokines IL-8 (CXCL8), and MIP-1α (CCL3) and MCP-1(CCL2). Inhibition with compstatin (C3 inhibitor) completely abolished complement surface deposition, leukocyte adhesion and the proinflammatory cytokines. The C5 inhibitions partly lead to a reduction of the proinflammatory cytokines. The leukocyte adhesion was abolished by inhibitory antibodies against CD18 and partly reduced by CD11b, but not by CD11c. Anti-CD18 significantly reduced the (IL-1)β, TNF, IL-6 and MIP-1α and anti-CD11b significantly reduced the IL-6 and VEGF secretion. MCP-1 was strongly activated by anti-CD18 and anti-CD11b. In conclusion the initial proinflammatory cytokine responses are driven by the microspheres potential to trigger complement C3 (C3b/iC3b) deposition, leukocyte activation and binding through complement receptor CR3 (CD11b/CD18). MCP-1 is one exception dependent on the fluid phase complement activation mediated through CR3. PMID:26993426

  1. The Effects of an Abolishing Operation Intervention Component on Play Skills, Challenging Behavior, and Stereotypy

    Lang, Russell; O'Reilly, Mark; Sigafoos, Jeff; Machalicek, Wendy; Rispoli, Mandy; Lancioni, Giulio E.; Aguilar, Jeannie; Fragale, Christina


    The purpose of this study was to reduce stereotypy and challenging behavior during play skills instruction by adding an abolishing operation component (AOC) to the intervention strategy. An alternating treatments design compared one condition in which participants were allowed to engage in stereotypy freely before beginning the play skills…

  2. Computational modeling of leukocyte adhesion cascade (LAC)

    Sarkar, Kausik


    In response to an inflammation in the body, leukocytes (white blood cell) interact with the endothelium (interior wall of blood vessel) through a series of steps--capture, rolling, adhesion and transmigration--critical for proper functioning of the immune system. We are numerically simulating this process using a Front-tracking finite-difference method. The viscoelastcity of the cell membrane, cytoplasm and nucleus are incorporated and allowed to change with time in response to the cell surface molecular chemistry. The molecular level forces due to specific ligand-receptor interactions are accounted for by stochastic spring-peeling model. Even though leukocyte rolling has been investigated through various models, the transitioning through subsequent steps, specifically firm adhesion and transmigration through endothelial layer, has not been modeled. The change of viscoelastic properties due to the leukocyte activation is observed to play a critical role in mediating the transition from rolling to transmigration. We will provide details of our approach and discuss preliminary results.

  3. Single-step transepithelial ASLA (SCHWIND) with mitomycin-C for the correction of high myopia: long term follow-up

    Aslanides IM; Georgoudis PN; Selimis VD; Mukherjee AN


    Ioannis M Aslanides, Panagiotis N Georgoudis, Vasilis D Selimis, Achyut N Mukherjee Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece Purpose: We wanted to compare the outcomes of single-step modified transepithelial photorefractive keratectomy (tPRK) termed a SCHWIND all surface laser ablation (ASLA) versus conventional alcohol-assisted photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) for the correction of higher myopia of 6.00 diopters (D)...

  4. Importance of the Direct Contact of Amorphous Solid Particles with the Surface of Monolayers for the Transepithelial Permeation of Curcumin.

    Kimura, Shunsuke; Kasatani, Sachiha; Tanaka, Megumi; Araki, Kaeko; Enomura, Masakazu; Moriyama, Kei; Inoue, Daisuke; Furubayashi, Tomoyuki; Tanaka, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira


    The amorphization has been generally known to improve the absorption and permeation of poorly water-soluble drugs through the enhancement of the solubility. The present study focused on the direct contact of amorphous solid particles with the surface of the membrane using curcumin as a model for water-insoluble drugs. Amorphous nanoparticles of curcumin (ANC) were prepared with antisolvent crystallization method using a microreactor. The solubility of curcumin from ANC was two orders of magnitude higher than that of crystalline curcumin (CC). However, the permeation of curcumin from the saturated solution of ANC was negligible. The transepithelial permeation of curcumin from ANC suspension was significantly increased as compared to CC suspension, while the permeation was unlikely correlated with the solubility, and the increase in the permeation was dependent on the total concentration of curcumin in ANC suspension. The absorptive transport of curcumin (from apical to basal, A to B) from ANC suspension was much higher than the secretory transport (from basal to apical, B to A). In vitro transport of curcumin through air-interface monolayers is large from ANC but negligible from CC particles. These findings suggest that the direct contact of ANC with the absorptive membrane can play an important role in the transport of curcumin from ANC suspension. The results of the study suggest that amorphous particles may be directly involved in the transepithlial permeation of curcumin. PMID:26656401

  5. Correlation between chloride flux via the mitochondria-rich cells and transepithelial water movement in isolated frog skin (Rana esculenta).

    Nielsen, R


    The coupling between net transepithelial Cl- influx and net water flow was investigated. Experiments were performed on isolated frog skin bathed in isotonic Cl- Ringer's solution in the presence of the Na+ channel blocking agent amiloride in the mucosal solution. The skins were voltage-clamped at -80 or -100 mV (with the serosal solution as reference). Under these conditions the current across the skin is carried by an influx of Cl-. In the absence of antidiuretic hormone the correlation between current and net water flow was low, but in the presence of the antidiuretic hormone, arginine vasotocin, there was a highly significant correlation between current and net water flow. The data presented here indicate that under steady state conditions about 70 molecules of water follow each Cl- ion across the skin. If the water influx is driven by electroosmosis one would expect that a change in current should result in an immediate change in the water flow. There was, however, a considerable time delay between the change in current and water flow. This indicates that the observed coupling between Cl- flux and water flow is caused by current-induced local osmosis and not electroosmosis. PMID:8719255

  6. Transepithelial electrical resistance (TEER): a functional parameter to monitor the quality of oviduct epithelial cells cultured on filter supports.

    Chen, Shuai; Einspanier, Ralf; Schoen, Jennifer


    Cultivation of oviduct epithelial cells on porous filters fosters in vivo-like morphology and functionality. However, due to the optical properties of the filter materials and the cells' columnar shape, cell quality is hard to assess via light microscopy. In this study, we aim to evaluate transepithelial electrical resistance (TEER) measurement as a prognostic quality indicator for the cultivation of porcine oviduct epithelial cells (POEC). POEC were maintained in four different types of media for 3 and 6 w to achieve diverse culture qualities, and TEER was measured before processing samples for histology. Culture quality was scored using morphological criteria (presence of cilia, confluence and cell polarity). We furthermore analyzed the correlation between cellular height (as a measure of apical-basal polarization) and TEER in fully differentiated routine cultures (biological variation) and in cultures with altered cellular height due to hormonal stimulation. Fully differentiated cultures possessed a moderate TEER between 500 and 1100 Ω*cm(2). Only 5% of cultures which exhibited TEER values in this defined range had poor quality. Sub-differentiated cultures showed either very low or excessively high TEER. We unveiled a highly significant (P monitor the differentiation status of oviduct epithelial cells in vitro. PMID:26223877

  7. Leukocyte trafficking in alveoli and airway passages

    Doerschuk Claire M


    Full Text Available Abstract Many pulmonary diseases preferentially affect the large airways or the alveoli. Although the mechanisms are often particular to each disease process, site-specific differences in leukocyte trafficking and the regulation of inflammation also occur. Differences in the process of margination, sequestration, adhesion, and migration occur that can be attributed to differences in anatomy, hemodynamics, and the expression of proteins. The large airways are nourished by the bronchial circulation, whereas the pulmonary circulation feeds the distal lung parenchyma. The presence of different cell types in large airways from those in alveoli might contribute to site-specific differences in the molecular regulation of the inflammatory process.

  8. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    Seifert, Thomas; Fisher, James P; Young, Colin N;


    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebr...... abolished by glycopyrrolate (P <0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen....

  9. Why we must abolish nuclear weapons after the end of the Cold War

    The end of the Cold War has offered a great opportunity to reduce or even abolish nuclear weapons, but the international community seemed to lose interest in nuclear weapons issues. Today, however, there are a lot of other major menaces to the survival of the mankind: pollution, hunger, poverty, ethnic conflicts. So the nuclear weapons issue is merely one of the most pressing threats to survival

  10. Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5'-oligoadenylate synthetase activity

    Nielsen, B; Hokland, M; Justesen, J;


    A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression of...... treatment these effects were gradually abolished, indicating an increasing effect of IFN-alpha in vivo with time. These results shows that the different PBMNC subpopulations and important immunological functions normalize with treatment. This normalization is, however, not seen until at least after 1 year...

  11. Allosuppressor T lymphocytes abolish migration inhibition factor production in autoimmune thyroid disease: evidence from radiosensitivity experiments

    The ability of normal T lymphocytes to abolish the production of migration inhibition factor by antigen-sensitized T lymphocytes of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in response to thyroid antigen has been studied by a modified migration inhibition factor test using isolated T lymphocytes alone. The production of migration inhibition factor was consistently abolished when normal T lymphocytes were mixed with GD or HT T lymphocytes in various ratios (1:9, 2:8, 5:5) as reported previously (Okita et al., 1980b). However, prior in-vitro irradiation (1000 rad) of the normal T lymphocytes resulted in loss of their ability to abolish migration inhibition factor production by the antigen-sensitized T lymphocytes of GD and HT. The effect is consistent with the radiosensitivity of suppressor T lymphocytes and indicates that the effect of normal T lymphocytes on GD and HT T lymphocytes is one of allosuppression. The results support the view that there is a defect in suppressor T cell function in GD and HT. (author)

  12. Indium-111 leukocyte imaging in appendicitis

    Indium-111-labeled leukocyte scintigraphy was applied to the diagnosis of acute appendicitis. Thirty-two patients observed in the hospital for possible appendicitis were prospectively studied. Scanning was done 2 hr after radiopharmaceutical injection. Thirteen scans were positive for acute appendicitis, and all but one were confirmed at laparotomy. In addition, two cases of colitis and two cases of peritonitis were detected. Of 15 negative studies, 11 had a benign course. Four patients with negative studies had laparotomy; two were found to have appendicitis and two had a normal appendix. Of 14 proven cases of appendicitis, 12 scans were positive for appendicitis with one false-positive scan, providing a sensitivity of 86%. Specificity was 93%: all negative cases except one had negative scans. Overall accuracy was 91% (29 of 32), comparing favorably with the accepted false-positive laparotomy rate of 25%. Use of In-111-labeled leukocyte scintigraphy serves to reduce the false-positive laparotomy rate and to shorten the clinical observation time in patients with acute appendicitis

  13. Photon Counts Statistics in Leukocyte Cell Dynamics

    In the present experiment ultra-weak photon emission/chemiluminescence from isolated neutrophils was recorded. It is associated with the production of reactive oxygen species (ROS) in the 'respiratory burst' process which can be activated by PMA (Phorbol 12-Myristate 13-Acetate). Commonly, the reaction is demonstrated utilizing the enhancer luminol. However, with the use of highly sensitive photomultiplier equipment it is also recorded without enhancer. In that case, it can be hypothesized that photon count statistics may assist in understanding the underlying metabolic activity and cooperation of these cells. To study this hypothesis leukocytes were stimulated with PMA and increased photon signals were recorded in the quasi stable period utilizing Fano factor analysis at different window sizes. The Fano factor is defined by the variance over the mean of the number of photon within the observation time. The analysis demonstrated that the Fano factor of true signal and not of the surrogate signals obtained by random shuffling increases when the window size increased. It is concluded that photon count statistics, in particular Fano factor analysis, provides information regarding leukocyte interactions. It opens the perspective to utilize this analytical procedure in (in vivo) inflammation research. However, this needs further validation.

  14. Effect of fatty acids on leukocyte function

    Pompéia C.


    Full Text Available Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

  15. Factors affecting leukocyte count in healthy adults.

    Carel, R S; Eviatar, J


    The relationships between white blood cell (WBC) count, smoking, and other health variables were determined among 35,000 apparently healthy men and women. The effect of smoking on the WBC count was greater than that of all other variables. The leukocyte level and the variance in WBC count values increased with increased smoking intensity. The relationship between smoking intensity and leukocyte level is expressed quantitatively by the following regression equation: WBC (10(3)/mm3) = 7.1 + 0.05(SM), where SM has seven values according to the smoking level. Multiple regression analysis with additional variables other than smoking did not much improve the predictive value of the equation. The effect of smoking on WBC count could be only partially explained by an inflammatory process, e.g., chronic bronchitis. Relationships of statistical significance (but mostly with r values of less than 0.10) were found between WBC count and the following variables: hemoglobin, heart rate, weight (or Quetelet index), cholesterol, uric acid, creatinine, sex, ethnic origin, systolic blood pressure, height, blood sugar, and diastolic blood pressure. The normal WBC count range for smokers differs from that of nonsmokers and is shifted to the right according to the smoking level. This may have both a diagnostic and prognostic significance in different clinical settings. PMID:4070192

  16. File list: Pol.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Pol.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 RNA polymerase Blood Polymorphonuclear... leukocytes ...

  17. File list: His.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available His.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 Histone Blood Polymorphonuclear ...leukocytes ...

  18. File list: Unc.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Unc.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 Unclassified Blood Polymorphonuclear... leukocytes ...

  19. File list: His.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available His.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 Histone Blood Polymorphonuclear ...leukocytes ...

  20. File list: Pol.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Pol.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 RNA polymerase Blood Polymorphonuclear... leukocytes ...

  1. File list: DNS.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available DNS.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 DNase-seq Blood Polymorphonuclear... leukocytes ...

  2. File list: His.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available His.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 Histone Blood Polymorphonuclear ...leukocytes ...

  3. File list: DNS.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available DNS.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 DNase-seq Blood Polymorphonuclear... leukocytes ...

  4. File list: Pol.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Pol.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 RNA polymerase Blood Polymorphonuclear... leukocytes ...

  5. File list: Oth.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Oth.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 TFs and others Blood Polymorphonuclear... leukocytes ...

  6. File list: DNS.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available DNS.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 DNase-seq Blood Polymorphonuclear... leukocytes ...

  7. File list: Unc.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Unc.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 Unclassified Blood Polymorphonuclear... leukocytes ...

  8. File list: DNS.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available DNS.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 DNase-seq Blood Polymorphonuclear... leukocytes ...

  9. File list: Oth.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Oth.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 TFs and others Blood Polymorphonuclear... leukocytes ...

  10. File list: Unc.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Unc.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 Unclassified Blood Polymorphonuclear... leukocytes ...

  11. File list: Oth.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Oth.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 TFs and others Blood Polymorphonuclear... leukocytes ...

  12. File list: Unc.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available Unc.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 Unclassified Blood Polymorphonuclear... leukocytes ...

  13. File list: His.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available His.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 Histone Blood Polymorphonuclear ...leukocytes ...

  14. Positive indium-111 leukocyte scintigraphy in a skeletal metastasis

    Sfakianakis, G.N.; Mnaymneh, W.; Ghandur-Mnaymneh, L.; Al-Sheikh, W.; Hourani, M.; Heal, A.


    Indium-111 scintigraphy is a method proposed for specific diagnosis and localization of focal infection. It has been found that, in general, cancers did not visualize with leukocyte scintigraphy. In this article, a case of positive indium-111 leukocyte scintigrams of a foot metstasis from a mucoepidermoid carcinoma of the lung is reported. (JMT)

  15. Multiple efflux pumps are involved in the transepithelial transport of colchicine: combined effect of p-glycoprotein and multidrug resistance-associated protein 2 leads to decreased intestinal absorption throughout the entire small intestine.

    Dahan, Arik; Sabit, Hairat; Amidon, Gordon L


    The purpose of this study was to thoroughly characterize the efflux transporters involved in the intestinal permeability of the oral microtubule polymerization inhibitor colchicine and to evaluate the role of these transporters in limiting its oral absorption. The effects of P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2), and breast cancer resistance protein (BCRP) inhibitors on colchicine bidirectional permeability were studied across Caco-2 cell monolayers, inhibiting one versus multiple transporters simultaneously. Colchicine permeability was then investigated in different regions of the rat small intestine by in situ single-pass perfusion. Correlation with the P-gp/MRP2 expression level throughout different intestinal segments was investigated by immunoblotting. P-gp inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), verapamil, and quinidine], and MRP2 inhibitors [3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), indomethacin, and p-aminohippuric acid (p-AH)] significantly increased apical (AP)-basolateral (BL) and decreased BL-AP Caco-2 transport in a concentration-dependent manner. No effect was obtained by the BCRP inhibitors fumitremorgin C (FTC) and pantoprazole. P-gp/MRP2 inhibitors combinations greatly reduced colchicine mucosal secretion, including complete abolishment of efflux (GF120918/MK571). Colchicine displayed low (versus metoprolol) and constant permeability along the rat small-intestine. GF120918 significantly increased colchicine permeability in the ileum with no effect in the jejunum, whereas MK571 augmented jejunal permeability without changing the ileal transport. The GF120918/MK571 combination caused an effect similar to that of MK571 alone in the jejunum and to that of GF120918 alone in the ileum. P-gp expression followed a gradient increasing from

  16. [Polar coordinates representation based leukocyte segmentation of microscopic cell images].

    Gu, Guanghua; Cui, Dong; Hao, Lianwang


    We propose an algorithm for segmentation of the overlapped leukocyte in the microscopic cell image. The histogram of the saturation channel in the cell image is smoothed to obtain the meaningful global valley point by the fingerprint smoothing method, and then the nucleus can be segmented. A circular region, containing the entire regions of the leukocyte, is marked off according to the equivalent sectional radius of the nucleus. Then, the edge of the overlapped leukocyte is represented by polar coordinates. The overlapped region by the change of the polar angle of the edge pixels is determined, and the closed edge of the leukocyte integrating the gradient information of the overlapped region is reconstructed. Finally, the leukocyte is exactly extracted. The experimental results show that our method has good performance in terms of recall ratio, precision ratio and pixel error ratio. PMID:21374971

  17. Visualization of transepithelial passage of the immunogenic 33-residue peptide from alpha-2 gliadin in gluten-sensitive macaques.

    Kaushiki Mazumdar

    Full Text Available BACKGROUND: Based on clinical, histopathological and serological similarities to human celiac disease (CD, we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2 antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from alpha(2-gliadin in the distal duodenum of gluten-sensitive macaques. METHODOLOGY/PRINCIPAL FINDINGS: Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal's distal duodenum following administration of a gluten-containing diet (GD and again after remission by gluten-free diet (GFD. Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with "leaky" duodenum, the peptide penetrated beneath the epithelium into the lamina propria. CONCLUSIONS/SIGNIFICANCE: The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.

  18. Cannabinoid-receptor expression in human leukocytes.

    Bouaboula, M; Rinaldi, M; Carayon, P; Carillon, C; Delpech, B; Shire, D; Le Fur, G; Casellas, P


    Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS), probably through the cannabinoid receptor, which has recently been cloned in rat and human. While numerous reports have also described effects of cannabinoids on the immune system, the observation of both mRNA and cannabinoid receptor has hitherto been exclusively confined to the brain, a reported detection in the testis being the sole example of its presence at the periphery. Here we report the expression of the cannabinoid receptor on human immune tissues using a highly sensitive polymerase-chain-reaction-based method for mRNA quantification. We show that, although present in a much lower abundance than in brain, cannabinoid receptor transcripts are found in human spleen, tonsils and peripheral blood leukocytes. The distribution pattern displays important variations of the mRNA level for the cannabinoid receptor among the main human blood cell subpopulations. The rank order of mRNA levels in these cells is B cells > natural killer cells > or = polymorphonuclear neutrophils > or = T8 cells > monocytes > T4 cells. Cannabinoid-receptor mRNA, which is also found in monocytic, as well as T and B leukemia cell lines but not in Jurkat cells, presents a great diversity of expression on these cells as well, B-cell lines expressing a much higher level than T-cell lines. The cannabinoid receptor PCR products from leukocytes and brain are identical both in size and sequence suggesting a strong similarity between central and peripheral cannabinoid receptors. The expression of this receptor was demonstrated on membranes of the myelomonocytic U937 cells using the synthetic cannabinoid [3H]CP-55940 as ligand. The Kd determined from Scatchard analysis was 0.1 nM and the Bmax for membranes was 525 fmol/mg protein. The demonstration of cannabinoid-receptor expression at both mRNA and protein levels on human leukocytes provides a molecular basis for cannabinoid action on these cells. PMID

  19. Margination of leukocytes in blood flow through small tubes.

    Goldsmith, H L; Spain, S


    Leukocyte margination in the vessels of the microcirculation has been attributed to a flow-dependent interaction with red cells. To determine the extent of this effect, experiments with human blood were done in 100- to 180-micron tubes to detect changes in cell distribution as a function of hematocrit and flow rate. Using a flow visualization technique, the leukocyte concentration distribution was determined in 45% ghost cell suspensions. Migration of cells toward the wall was observed at centerline velocities greater than 1 mm sec-1 and increased with increasing flow rate. The effect was probably due to a more rapid inward migration of ghosts than leukocytes because of fluid inertia and cell density differences. Experiments were therefore carried out in whole blood at hematocrits from 20 to 60%, measuring the number concentration of leukocytes and erythrocytes within the tube, nt, and comparing it to that in the infusing reservoir, no, (Fahraeus effect). At mean tube shear rates G less than 100 sec-1, nt/no less than 1 for both leukocytes and erythrocytes showing net migration of cells away from the wall, although at nearly all hematocrits there was an enrichment of leukocytes relative to erythrocytes in the tubes. At G less than 50 sec-1, nt/no remained less than 1 for erythrocytes but increased to greater than 1 for leukocytes showing migration toward the wall, the increase being greatest at 20% hematocrit in the 100-micron tubes. The nature of the effect was revealed by cine films which showed that, as the flow rate decreased, erythrocytes formed rouleaux which migrated inward creating a core and displacing leukocytes to the periphery. In control experiments using washed blood cells in phosphate buffer-albumin, nt/no less than 1 for both leukocytes and erythrocytes at all G and hematocrits, and leukocytes were now distributed. Cine films of washed blood confirmed that, in the absence of rouleaux, no significant inward migration of erythrocytes occurred. PMID

  20. Classification of human leukocyte antigen (HLA) supertypes

    Wang, Mingjun; Claesson, Mogens H


    Identification of new antigenic peptides, derived from infectious agents or cancer cells, which bind to human leukocyte antigen (HLA) class I and II molecules, is of importance for the development of new effective vaccines capable of activating the cellular arm of the immune response. However, the...... barrier to the development of peptide-based vaccines with maximum population coverage is that the restricting HLA genes are extremely polymorphic resulting in a vast diversity of peptide-binding HLA specificities and a low population coverage for any given peptide-HLA specificity. One way to reduce this...... complexity is to group thousands of different HLA molecules into several so-called HLA supertypes: a classification that refers to a group of HLA alleles with largely overlapping peptide binding specificities. In this chapter, we focus on the state-of-the-art classification of HLA supertypes including HLA...

  1. Mill, Gender Ideal and Gender Oppression: Do Feminists Need to Abolish Gender Roles?

    Popa, Bogdan


    While feminist scholarship generally looks at Mill’s ambiguities as confusions or flaws, I suggest that Mill’s ambivalence has to be taken at face value by feminist theory.Many feminists – and particularly liberal feminists- feel that human beings cannot develop their true potential until they would live in a society where men and women have complete equality. One solution to this problem is to abolish gender roles, or to value social and legal norms because they promote gender neutrality. Be...

  2. Serine substitution for cysteine residues in levansucrase selectively abolishes levan forming activity.

    Senthilkumar, Velusamy; Busby, Stephen J W; Gunasekaran, Paramasamy; Senthikumar, Velusamy; Bushby, Stephen J W


    Levansucrase is responsible for levan formation during sucrose fermentation of Zymomonas mobilis, and this decreases the efficiency of ethanol production. As thiol modifying agents decrease levan formation, a role for cysteine residues in levansucrase activity has been examined using derivatives of Z. mobilis levansucrase that carry serine substitutions of cysteine at positions 121, 151 or 244. These substitutions abolished the levan forming activity of levansucrase whilst only halving its activity in sucrose hydrolysis. Thus, polymerase and hydrolase activities of Z. mobilis levansucrase are separate and have different requirements for the enzyme's cysteine residues. PMID:14584923

  3. Abolished synthesis of cholic acid reduces atherosclerotic development in apolipoprotein E knockout mice[S

    Slätis, Katharina; Gåfvels, Mats; Kannisto, Kristina; Ovchinnikova, Olga; Paulsson-Berne, Gabrielle; Parini, Paolo; Jiang, Zhao-Yan; Eggertsen, Gösta


    To investigate the effects of abolished cholic acid (CA) synthesis in the ApoE knockout model [apolipoprotein E (apoE) KO],a double-knockout (DKO) mouse model was created by crossbreeding Cyp8b1 knockout mice (Cyp8b1 KO), unable to synthesize the primary bile acid CA, with apoE KO mice. After 5 months of cholesterol feeding, the development of atherosclerotic plaques in the proximal aorta was 50% less in the DKO mice compared with the apoE KO mice. This effect was associated with reduced inte...

  4. Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

    The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-α level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the systemic

  5. Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

    Minor, B G; Persson, M L; Post, C; Jonsson, G; Archer, T


    Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia. PMID:3133452

  6. Allogeneic leukocytes in cardiac surgery: Good or bad?

    Anneke Brand


    Full Text Available Worldwide, cardiac surgery is a common procedure requiring a large quantity of allogeneic blood products, which are associated with postoperative complications. Leukocytes present in blood products may play a role in these complications, which are referred to as transfusion-related immunomodulation (TRIM. Several randomized controlled trials (RCTs in different settings investigated the effects of allogeneic leukocytes in red blood cells (RBCs. Cardiac surgery studies reported a reduction in postoperative infections and mortality in patients that received leukocyte-reduced RBCs compared with leukocyte-containing RBCs; this was mainly due to more deaths due to infections and multiple organ dysfunction syndrome (MODS in the group that received leukocyte-containing RBCs. Patients with postoperative complications had higher concentrations of inflammatory mediators. These findings suggest that leukocyte-containing transfusion during cardiac surgery induces a second insult to the systemic inflammatory response. In the present review we discuss the possible role of blood transfusions in cardiac surgery. Especially, we focus on the possible role of allogeneic leukocytes associated with postoperative complications after cardiac surgery.

  7. Electrophoretic detection of protein p53 in human leukocytes

    The authors have found an acid-soluble protein with mol. wt. of about 53 kD in peripheral blood leukocytes of persons with Down's syndrome. It was present in different quantities in all 20 patients tested, but was virtually not discovered in 12 healthy blood donors. This paper determines the possible identity of this protein with protein p53 from mouse ascites carcinoma by comparing their electrophoretic mobilities, because the accuracy of electrophoretic determination of the molecular weight of proteins is not sufficient to identify them. The paper also describes experiments to detect a protein with electrophoretic mobility identical with that of a protein in the leukocytes of patients with Down's syndrome in leukocytes of patients with leukemia. To discover if protein p53 is involved in cell proliferation, the protein composition of leukocytes from healthy blood donors, cultured in the presence and absence of phytohemagglutinin (PHA), was compared. Increased incorporation of H 3-thymidine by leukocytes of patients with Down's syndrome is explained by the presence of a population of immature leukocytes actively synthesizing DNA in the peripheral blood of these patients, and this can also explain the presence of protein p53 in the leukocytes of these patients

  8. Imaging with FDG labelled leukocytes: is it clinically useful?

    In vivo and in vitro labeled leukocytes have been shown to be very effective in detecting different infectious and inflammatory conditions. The model of labeled leukocyte imaging is based on the powerful mechanisms of chemotaxis exerted on activated leukocytes by chemo-attractants. The avidity of inflammatory cells for fluorodeoxyglucose (FDG) has led to the concept of labeling leukocytes with [18 F]FDG ex vivo. This concept combines cell-bound radionuclide trafficking from the blood pool compartment to the lesion with the high resolution of positron emission tomography (PET) imaging. The further benefits of having a correlated anatomical map by implementing the acquisition on a hybrid PET/computed tomography (CT) device are obvious. The feasibility and the potential value of leukocyte PET(/CT) imaging in infection have been demonstrated. The available data suggest a high accuracy of the method. Still, leukocyte PET/CT should not be considered as the endpoint of infection imaging, since it only meets a part of the criteria of the ideal infection imaging agent. However, the common clinical need for specific detection of infection with anatomical precision, the availability of the components necessary for performing leukocyte PET/CT, their lack of toxicity or adverse effects and the absence of more superior tracers on the commercial market make it worthwhile to further investigate leukocyte PET/CT imaging in larger prospective series. The advantages of leukocyte PET/CT over the more conventional nuclear medicine and radiological methods makes this imaging tool likely to be useful in certain subsets of infected patients.

  9. Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice

    Mustroph, M.L.; Merritt, J R; Holloway, A.L.; Pinardo, H.; Miller, D S; Kilby, C.N.; Bucko, P.; Wyer, A.; Rhodes, J S


    Recent evidence suggests wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesized to enhance plasticity and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without ...

  10. Osteomyelitis complicating fracture: pitfalls of 111In leukocyte scintigraphy

    111In-labeled leukocyte imaging has shown greater accuracy and specificity than alternative noninvasive methods in the detection of uncomplicated osteomyelitis. Forty patients with suspected osteomyelitis complicating fractures (with and without surgical intervention) were evaluated with 111In-labeled leukocytes. All five patients with intense focal uptake, but only one of 13 with no uptake, had active osteomyelitis. However, mild to moderate 111In leukocyte uptake, observed in 22 cases, indicated the presence of osteomyelitis in only four of these; the other false-positive results were observed in noninfected callus formation, heterotopic bone formation, myositis ossificans, and sickle-cell disease. These results suggest that 111In-labeled leukocyte imaging is useful for the evaluation of suspected osteomyelitis complicating fracture but must be used in conjunction with clinical and radiographic correlation to avoid false-positive results

  11. Abolished ventilation and perfusion of lung caused by blood clot in the left main bronchus

    Afzelius, P; Bergmann, A; Henriksen, J H


    It is generally assumed that the lungs possess arterial autoregulation associated with bronchial obstruction. A patient with pneumonia and congestive heart failure unexpectedly developed frequent haemoptysis. High-resolution CT and diagnostic CT were performed as well as ventilation/perfusion (V....../Q) scintigraphy with single-photon emission CT (SPECT)/CT. V/Q SPECT/CT demonstrated abolished ventilation due to obstruction of the left main bronchus and markedly reduced perfusion of the entire left lung, a condition that was completely reversed after removal of a blood clot. We present the first pictorially...... documented case of hypoxia-induced pulmonary vasoconstriction and flow shift in a main pulmonary artery due to a complete intrinsic obstruction of the ipsilateral main bronchus. The condition is reversible, contingent on being relieved within a few days....

  12. Indonesia’s Regional Anti-Corruption Courts: Should They Be Abolished?

    Simon Butt


    Full Text Available Indonesia’s regional anti-corruption courts have been criticised in recent times for perceived impropriety and for acquitting defendants. Senior jurists and politicians have called for these courts to be abolished or recentralised. This article suggests that neither abolition nor recentralisation is prudent and that these criticisms might not be supported by available case statistics. In any event, this article argues, acquittal rates are very poor indicators of judicial performance. Indeed, acquittals might be legally correct, or even necessary, in some cases. More resources should be allocated to these courts, and to the Corruption Eradication Commission so that it can investigate and prosecute more cases in Indonesia’s regions.

  13. Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans

    Seifert, Thomas; Fisher, James P; Young, Colin N; Hartwich, Doreen; Ogoh, Shigehiko; Raven, Peter B; Fadel, Paul J; Secher, Niels H


    Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral......) (P <0.01) and cardiac output by approximately 40% (P <0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate...... abolished by glycopyrrolate (P <0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen....

  14. Production of monoclonal antibodies against canine leukocytes.

    Aguiar, Paulo Henrique Palis; Borges dos Santos, Roberto Robson; Lima, Carla Andrade; Rios de Sousa Gomes, Hilton; Larangeira, Daniela Farias; Santos, Patrícia Meira; Barrouin-Melo, Stella Maria; Conrado dos-Santos, Washington Luis; Pontes-de-Carvalho, Lain


    A panel of anti-canine leukocyte monoclonal antibodies (MAbs) was produced by immunizing BALB/c mice with canine peripheral blood mononuclear cells (PBMC), either resting or stimulated with concanavalin A (ConA). Three out of 28 clones-IH1, AB6, and HG6-screened by ELISA and producing antibody with the highest specificity for canine cell immunostaining, were subjected to three subsequent subcloning steps by limiting dilution, and selected for further characterization. These MAbs belonged to IgG1 (HG6 and IH1) and IgG2a (AB6) isotypes. The distribution of cell populations expressing the antigen recognized by the antibodies was identified by indirect immunoflorescence on canine PBMC and on tissue sections of lymph node, spleen, liver and skin. The possible crossreactivity with human PBMC was also examined in immunocytochemistry. One of the antibodies specifically recognized macrophages. The MAbs presented here can be foreseen as possible valuable diagnostic and research tools to study immune functions in dogs. PMID:15165486

  15. Labeled polymorphonuclear leukocytes: a comparison of methodology

    Polymorphonuclear neutrophilic granulocytes were separated from anti-coagulated whole blood using three techniques. The methods employed included volex sedimentation (VS), volex sedimentation with hypotonic lysis (VSHL), and Ficoll-Hypaque gradient separation (FH). The cells were labeled with 111In-oxine and 111In-tropolone. Studies were done with both blood from normal human volunteers and with canine blood. From the cell counts and differential, the harvested granulocytes, platelets, and red blood cells per milliliter of whole blood were calculated. Using the granulocyte chemotactic response to E. coli in agarose plates, the ratio of chemotactic migration to random migration (c./r.m.) was determined. Survival time for 111In labeled granulocytes were also determined in a canine model. The studies demonstrated that all procedures yielded 100% viability by the Trypan blue exclusion test. Chemotactic migration and leukocyte survival times were similar amongst all techniques. With the VSHL technique, there were significantly fewer red blood cells and platelets in the final preparation approaching the results of FH separation. The results suggest that, for a relatively pure granulocyte preparation, VSHL is an acceptable alternative to FH. (author)

  16. Leukocytic acetylcholine in chronic rejection of renal allografts

    Wilczynska, Joanna


    Leukocytes, which accumulate in graft blood vessels during fatal acute rejection of experimental renal allografts, synthesise and release acetylcholine (ACh). In this study, I tested the hypothesis that ACh produced by leukocytes accumulating in graft blood vessels contributes to the pathogenesis of chronic renal allograft vasculopathy (CAV). Kidneys were transplanted in the allogeneic Fischer 344 to Lewis rat strain combination. Isogeneic transplantations were performed in Lew...

  17. Association between diabetes complications and leukocyte counts in Iranian patients

    Moradi S


    Full Text Available Sedigheh Moradi1, Scott Reza Jafarian Kerman2, Farzaneh Rohani1, Fereshteh Salari21Endocrine and Metabolism Research Center (Firouzgar, Hemmat Campus, Tehran University of Medical Sciences, Tehran, Iran, 2Scientific Students Research Committee, Tehran University of Medical Sciences, Tehran, IranBackground: The long term complications of diabetes can be fatal. They are also renowned for being an economic burden. Previous studies have demonstrated a relationship between inflammatory markers and complications of diabetes. The objective of this study was to evaluate the relationship between leukocyte counts and these complications.Methods: The study included 184 patients diagnosed with type 2 diabetes. The study was carried out in Iran during 2007 and 2008. Data collected on the subjects were as follows: age, gender, weight, height, blood pressure, smoking history, lipid profile including low density lipoprotein (LDL, high density lipoprotein (HDL, total cholesterol, triglycerides, and leukocyte count, albuminuria, and retinopathy. Furthermore, information on cardiac history for 100 patients was collected. The subjects were split into two groups according to their leukocyte levels: low (≤7000/mm³ and high (>7000/mm³; and then analyzed by Student's t-test or Mann–Whitney U-test as appropriate.Results: The average leukocyte count in these patients was 7594 ± 1965/mm³. Leukocyte count was significantly different in patients with and without retinopathy and albuminuria (P < 0.0001. According to this analysis, a leukocyte count of 6750/mm³ with a sensitivity of 80.2% and a specificity of 56.4%, and a count of 7550/mm³ with a sensitivity of 63.2% and a specificity of 74.6% indicated at least one diabetes complication.Conclusion: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes.Keywords: leukocytes, diabetes complications, inflammation

  18. Leukocytes Detection, Classification and Counting in Smears of Peripheral Blood

    Martínez-Castro, J.; Reyes-Cadena, S.; E. Felipe-Riverón


    Using the k -NN classifier in combination with the first Minkowski metric, in addition to techniques of digital image processing, we developed a computational system platform-independent, which is able to identify, to classify and to count five normal types of leukocytes: neutrophils, eosinophils, basophils, monocytes and lymphocytes. It is important to emphasize that this work does not attempt to differentiate between smears of leukocytes coming from healthy and sick people; this is because ...

  19. Labeled leukocyte imaging: current status and future directions

    The ability to radiolabel inflammatory cells that migrate to foci of infection was a significant milestone in the evolution of infection imaging. More than 20 years after being approved for clinical use in the United States, labeled leukocyte imaging using cells labeled with 99m Tc exametazime or 111 Inoxine remains the radionuclide procedure of choice for diagnosing most infections in the immunocompetent population. In the central nervous system, labeled leukocyte imaging is useful for differentiating infection from tumor; in the postoperative setting, this test facilitates the differentiation of infection from normal postoperative changes. Labeled leukocyte imaging accurately diagnoses mycotic aneurysms and infected prosthetic vascular grafts. In patients with fever of unknown origin, a negative study excludes, with a high degree of certainty, infection as the source of fever. Labeled leukocyte imaging accurately diagnoses pedal osteomyelitis and is useful for distinguishing infection from the neuropathic joint in this population. Together with bone marrow imaging, the labeled leukocyte study is the imaging procedure of choice for diagnosing prosthetic joint infection. There are limitations to the test. Most of the leukocytes labeled are neutrophils, and the procedure is most useful for detecting neutrophil-mediated inflammatory processes, i.e., bacterial infections. It is less useful for illnesses in which the predominant cellular response is other than neutrophilic, such as most opportunistic infections and spinal osteomyelitis. The in vitro labeling procedure is time consuming and is not routinely available. Results of in vivo leukocyte labeling methods have been variable; none are available in the United States. Labeled leukocyte imaging suffers from inherently poor quality images. Single photon emission compute tomography/computed tomography improves lesion localization, and will undoubtedly improve the accuracy of the test. Efforts to develop methods of

  20. Poloxamer bioadhesive hydrogel for buccal drug delivery: Cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line.

    Zeng, Ni; Mignet, Nathalie; Dumortier, Gilles; Olivier, Elodie; Seguin, Johanne; Maury, Marc; Scherman, Daniel; Rat, Patrice; Boudy, Vincent


    A salbutamol sulfate (SS)-Poloxamer bioadhesive hydrogel specially developed for buccal administration was investigated by studying interactions with TR146 human buccal epithelium cells (i.e. cellular toxicity (i) and trans-epithelial SS diffusion (ii)). The assessment of cell viability (MTT, Alamar Blue), membrane integrity (Neutral Red), and apoptosis assay (Hoechst 33342), were performed and associated to Digital Holographic Microscopy analysis. After the treatment of 2h, SS solution induced drastic cellular alterations that were prevented by hydrogels in relation with the concentrations of poloxamer and xanthan gum. The formulation containing P407 19%/P188 1%/Satiaxane 0.1% showed the best tolerance after single and multiple administrations and significantly reduced the trans-epithelial permeability from 5.00±0.29 (×10(3)) (SS solution) to 1.83±0.22 cm/h. Digital Holographic Microscopy images in good agreement with the viability data confirmed the great interest of this direct technique. In conclusion, the proposed hydrogels represent a safe and efficient buccal drug delivery platform. PMID:26403384

  1. β2-Adrenergic Receptor-Dependent Sexual Dimorphism For Murine Leukocyte Migration

    de Coupade, Catherine; Brown, Adrienne S.; Dazin, Paul F; Levine, Jon D.; Green, Paul G.


    In wild-type FVB mice, leukocyte recruitment to lipopolysaccharide was sexually dimorphic, with a greater number of leukocytes recruited in females. In male β2-adrenergic receptor knock out mice (bred on a congenic FVB background) the number leukocytes recruited was increased ~4-fold, while in females there was no change, eliminating sexual dimorphism in leukocyte migration. While there were significantly fewer recruited CD62L+ and CD11a+ leukocytes in wild-type males, only in male β2-adrener...

  2. Expression of β2-integrin on leukocytes in liver cirrhosis

    Anatol Panasiuk; Janusz Zak; Elzbieta Maciorkowska; Bozena Panasiuk; Danuta Prokopowicz


    AIM: To analyze β2-integrin expression on blood leukocytes in liver cirrhosis.METHODS: In 40 patients with liver cirrhosis and 20healthy individuals, the evaluation of expression of CD11a (LFA-1α), CD11b (Mac-1α), CD11c (αX) and CD49d (VLA-4α) on peripheral blood leukocytes was performed using flow cytometry. The analysis was carried out in groups of patients divided into B and C according to Child-Pugh's classification.RESULTS: An increased CD11a, CD11b, CD11c and CD49d integrin expression was observed on peripheral blood leukocytes in liver cirrhosis. The integrin levels were elevated as the advancement of liver failure progressed. The highest expression of integrins occurred predominantly on monocytes. A slight expression of VLA-4 was found on lymphocytes and granulocytes and it increased together with liver failure. A positive correlation was noted between median intensity of fluorescence (MIF) expression on polymorphonuclear cells of CD11a and CD11c and CD49d (r = 0.42, P < 0.01; r = 053, P < 0.01, respectively) in liver cirrhosis stage C. However,no correlation was observed between integrin expression on leukocytes. The concentrations of sICAM-1, sVCAM-1,and TNFα, were significantly elevated in liver cirrhosis.CONCLUSION: β2-integrin expression on leukocytes increases in liver cirrhosis decompensated as the stage of liver failure increases, which is a result of permanent activation of leukocytes circulating through the inflamed liver environment. β2-integrin expression on circulating leukocytes can intensify liver cirrhosis.

  3. Improvement of cellulose catabolism in Clostridium cellulolyticum by sporulation abolishment and carbon alleviation

    Li, Yongchao [ORNL; Xu, Tao [University of Oklahoma, Norman; Tschaplinski, Timothy J [ORNL; Engle, Nancy L [ORNL; Graham, David E [ORNL; He, Zhili [University of Oklahoma, Norman; Zhou, Jizhong [University of Oklahoma, Norman


    Background Clostridium cellulolyticum can degrade lignocellulosic biomass, and ferment the soluble sugars to produce valuable chemicals such as lactate, acetate, ethanol and hydrogen. However, the cellulose utilization efficiency of C. cellulolyticum still remains very low, impeding its application in consolidated bioprocessing for biofuels production. In this study, two metabolic engineering strategies were exploited to improve cellulose utilization efficiency, including sporulation abolishment and carbon overload alleviation. Results The spo0A gene at locus Ccel_1894, which encodes a master sporulation regulator was inactivated. The spo0A mutant abolished the sporulation ability. In a high concentration of cellulose (50 g/l), the performance of the spo0A mutant increased dramatically in terms of maximum growth, final concentrations of three major metabolic products, and cellulose catabolism. The microarray and gas chromatography mass spectrometry (GC-MS) analyses showed that the valine, leucine and isoleucine biosynthesis pathways were up-regulated in the spo0A mutant. Based on this information, a partial isobutanol producing pathway modified from valine biosynthesis was introduced into C. cellulolyticum strains to further increase cellulose consumption by alleviating excessive carbon load. The introduction of this synthetic pathway to the wild-type strain improved cellulose consumption from 17.6 g/l to 28.7 g/l with a production of 0.42 g/l isobutanol in the 50 g/l cellulose medium. However, the spo0A mutant strain did not appreciably benefit from introduction of this synthetic pathway and the cellulose utilization efficiency did not further increase. A technical highlight in this study was that an in vivo promoter strength evaluation protocol was developed using anaerobic fluorescent protein and flow cytometry for C. cellulolyticum. Conclusions In this study, we inactivated the spo0A gene and introduced a heterologous synthetic pathway to manipulate the stress

  4. Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation

    Michael Schnoor


    Full Text Available Leukocyte extravasation is one of the essential and first steps during the initiation of inflammation. Therefore, a better understanding of the key molecules that regulate this process may help to develop novel therapeutics for treatment of inflammation-based diseases such as atherosclerosis or rheumatoid arthritis. The endothelial adhesion molecules ICAM-1 and VCAM-1 are known as the central mediators of leukocyte adhesion to and transmigration across the endothelium. Engagement of these molecules by their leukocyte integrin receptors initiates the activation of several signaling pathways within both leukocytes and endothelium. Several of such events have been described to occur during transendothelial migration of all leukocyte subsets, whereas other mechanisms are known only for a single leukocyte subset. Here, we summarize current knowledge on regulatory mechanisms of leukocyte extravasation from a leukocyte and endothelial point of view, respectively. Specifically, we will focus on highlighting common and unique mechanisms that specific leukocyte subsets exploit to succeed in crossing endothelial monolayers.

  5. A mutation abolishing the ZMPSTE24 cleavage site in prelamin A causes a progeroid disorder.

    Wang, Yuexia; Lichter-Konecki, Uta; Anyane-Yeboa, Kwame; Shaw, Jessica E; Lu, Jonathan T; Östlund, Cecilia; Shin, Ji-Yeon; Clark, Lorraine N; Gundersen, Gregg G; Nagy, Peter L; Worman, Howard J


    In 1994 in the Journal of Cell Science, Hennekes and Nigg reported that changing valine to arginine at the endoproteolytic cleavage site in chicken prelamin A abolishes its conversion to lamin A. The consequences of this mutation in an organism have remained unknown. We now report that the corresponding mutation in a human subject leads to accumulation of prelamin A and causes a progeroid disorder. Next generation sequencing of the subject and her parents' exomes identified a de novo mutation in the lamin A/C gene (LMNA) that resulted in a leucine to arginine amino acid substitution at residue 647 in prelamin A. The subject's fibroblasts accumulated prelamin A, a farnesylated protein, which led to an increased percentage of cultured cells with morphologically abnormal nuclei. Treatment with a protein farnesyltransferase inhibitor improved abnormal nuclear morphology. This case demonstrates that accumulation of prelamin A, independent of the loss of function of ZMPSTE24 metallopeptidase that catalyzes processing of prelamin A, can cause a progeroid disorder and that a cell biology assay could be used in precision medicine to identify a potential therapy. PMID:27034136

  6. Adrenergic blockade does not abolish elevated glucose turnover during bacterial infection

    Infusions of adrenergic antagonists were used to investigate the role of catecholamines in infection-induced elevations of glucose kinetics. Infection was produced in conscious catheterized rats by repeated subcutaneous injections of live Escherichia coli over 24 h. Glucose kinetics were measured by the constant intravenous infusion of [6-3H]- and [U-14C]glucose. Compared with noninfected rats, infected animals were hyperthermic and showed increased rates of glucose appearance, clearance, and recycling as well as mild hyperlacticacidemia. Plasma catecholamine concentrations were increased by 50-70% in the infected rats, but there were no differences in plasma glucagon, corticosterone, and insulin levels. Adrenergic blockade was produced by primed constant infusion of both propranolol (β-blocker) and phentolamine (α-blocker). A 2-h administration of adrenergic antagonists did not attenuate the elevated glucose kinetics or plasma lactate concentration in the infected rats, although it abolished the hyperthermia. In a second experiment, animals were infused with propranolol and phentolamine beginning 1 h before the first injection of E. coli and throughout the course of infection. Continuous adrenergic blockade failed to attenuate infection-induced elevations in glucose kinetics and plasma lactate. These results indicate that the adrenergic system does not mediate the elevated glucose metabolism observed in this mild model of infection

  7. Virtual lesions of the IFG abolish response facilitation for biological and non-biological cues

    Roger D Newman-Norlund


    Full Text Available Humans are faster to perform a given action following observation of that same action. Converging evidence suggests that the human mirror neuron system (MNS plays an important role in this phenomenon. However, the specificity of the neural mechanisms governing this effect remain controversial. Specialist theories of imitation suggest that biological cues are maximally capable of eliciting imitative facilitation. Generalist models, on the other hand, posit a broader role for the MNS in linking visual stimuli with appropriate responses. In the present study, we investigated the validity of these two theoretical approaches by disrupting the left and right inferior frontal gyrus (IFG during the preparation of congruent (imitative and incongruent (complementary actions cued by either biological (hand or non-biological (static dot stimuli. Delivery of TMS over IFG abolished imitative response facilitation. Critically, this effect was identical whether actions were cued by biological or non-biological stimuli. This finding argues against theories of imitation in which biological stimuli are treated preferentially and stresses the notion of the IFG as a vital center of general perception-action coupling in the human brain.

  8. Improving diagnosis of appendicitis. Early autologous leukocyte scanning

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of appendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging In 111 oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis

  9. Selective suppression of leukocyte recruitment in allergic inflammation

    CL Weller


    Full Text Available Allergic diseases result in a considerable socioeconomic burden. The incidence of allergic diseases, notably allergic asthma, has risen to high levels for reasons that are not entirely understood. With an increasing knowledge of underlying mechanisms, there is now more potential to target the inflammatory process rather than the overt symptoms. This focuses attention on the role of leukocytes especially Th2 lymphocytes that regulate allergic inflammation and effector cells where eosinophils have received much attention. Eosinophils are thought to be important based on the high numbers that are recruited to sites of allergic inflammation and the potential of these cells to effect both tissue injury and remodelling. It is hoped that future therapy will be directed towards specific leukocyte types, without overtly compromising essential host defence responses. One obvious target is leukocyte recruitment. This necessitates a detailed understanding of underlying mechanisms, particularly those involving soluble che-moattractants signals and cell-cell adhesion molecules.

  10. Kinetics of leukocyte sequestration in the lungs of acutely septic primates: A study using 111In-labeled autologous leukocytes

    To further clarify the role of leukocytes in the pathogenesis of ARDS, we studied the localization and kinetics of leukocyte migration using 111In-labeled autologous white cell scans (111In wbc scans) in four primates made acutely septic with infusions of Escherichia coli. Whole body images were obtained with a gamma camera and were acquired on computer every 15 min beginning immediately after the E. coli infusion. Simultaneous measurements of C5a and peripheral blood leukocyte count were also obtained. Within 5 min of initiating sepsis, three major events occurred: complement activation as measured by the production of C5a, a profound fall in peripheral leukocyte count, and a significant increase in the sequestration of leukocytes in the lungs. The pulmonary sequestration reached a peak at 15 min with a mean of 152% of baseline activity. This sequestration consisted of a population that was predominantly neutrophils. Damage to the pulmonary capillary endothelium was demonstrated by an increase in extravascular lung water. The results support a role for neutrophils and complement as mediators in the pathogenesis of ARDS

  11. Imaging Mass Spectrometry by Matrix-Assisted Laser Desorption/Ionization and Stress-Strain Measurements in Iontophoresis Transepithelial Corneal Collagen Cross-Linking

    Paolo Vinciguerra


    Full Text Available Purpose. To compare biomechanical effect, riboflavin penetration and distribution in transepithelial corneal collagen cross-linking with iontophoresis (I-CXL, with standard cross linking (S-CXL and current transepithelial protocol (TE-CXL. Materials and Methods. The study was divided into two different sections, considering, respectively, rabbit and human cadaver corneas. In both sections corneas were divided according to imbibition protocols and irradiation power. Imaging mass spectrometry by matrix-assisted laser desorption/ionization (MALDI-IMS and stress-strain measurements were used. Forty-eight rabbit and twelve human cadaver corneas were evaluated. Results. MALDI-IMS showed a deep riboflavin penetration throughout the corneal layers with I-CXL, with a roughly lower concentration in the deepest layers when compared to S-CXL, whereas with TE-CXL penetration was considerably less. In rabbits, there was a significant increase (by 71.9% and P=0.05 in corneal rigidity after I-CXL, when compared to controls. In humans, corneal rigidity increase was not significantly different among the subgroups. Conclusions. In rabbits, I-CXL induced a significant increase in corneal stiffness as well as better riboflavin penetration when compared to controls and TE-CXL but not to S-CXL. Stress-strain in human corneas did not show significant differences among techniques, possibly because of the small sample size of groups. In conclusion, I-CXL could be a valid alternative to S-CXL for riboflavin delivery in CXL, preserving the epithelium.

  12. Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice.

    Mustroph, M L; Merritt, J R; Holloway, A L; Pinardo, H; Miller, D S; Kilby, C N; Bucko, P; Wyer, A; Rhodes, J S


    Recent evidence suggests that wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesised to enhance plasticity and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin-thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without running wheels for 32 days. Half of the mice were fed chow containing valganciclovir to induce apoptosis in newly divided neurons, and the other half were fed standard chow. For the first 10 days, mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. On the last 4 days, mice were tested for CPP, and then euthanized for measurement of adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in the dentate gyrus. Levels of running were similar in mice fed valganciclovir-containing chow and normal chow. Valganciclovir significantly reduced the numbers of neurons (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary mice and runner mice. Valganciclovir-fed runner mice showed similar levels of neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed runner mice showed the same abolishment of CPP as runner mice with intact neurogenesis. The results demonstrate that elevated adult hippocampal neurogenesis resulting from running is not necessary for running to abolish cocaine CPP in mice. PMID:25393660

  13. Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells

    Kouichi Yamada


    Full Text Available When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V cells, UV-TLS was inhibited by caffeine or proteasome inhibitors. However, in normal human cells, the process was insensitive to these reagents. Reportedly, in yeast or mammalian cells, REV3 protein (a catalytic subunit of DNA polymerase ζ is predominantly involved in the former type of TLS. Here, we studied UV-TLS in fibroblasts derived from the Rev3-knockout mouse embryo (Rev3KO-MEF. In the wild-type MEF, UV-TLS was slow (similar to that of human cancer cells or XP-V cells, and was abolished by caffeine or MG-262. In 2 cell lines of Rev3KO-MEF (Rev3−/− p53−/−, UV-TLS was not observed. In p53KO-MEF, which is a strict control for Rev3KO-MEF, the UV-TLS response was similar to that of the wild-type. Introduction of the Rev3 expression plasmid into Rev3KO-MEF restored the UV-TLS response in selected stable transformants. In some transformants, viability to UV was the same as that in the wild-type, and the death rate was increased by caffeine. Our findings indicate that REV3 is predominantly involved in UV-TLS in mouse cells, and that the REV3 translesion pathway is suppressed by caffeine or proteasome inhibitors.

  14. Glycogen overload by postexercise insulin administration abolished the exercise-induced increase in GLUT4 protein.

    Chou, Chia-Hau; Tsai, Yin-Lan; Hou, Chien-Wen; Lee, Hsing-Hao; Chang, Wei-Hsiang; Lin, Tzi-Wen; Hsu, Tung-Hsiung; Huang, Yi-Jen; Kuo, Chia-Hua


    To elucidate the role of muscle glycogen storage on regulation of GLUT4 protein expression and whole-body glucose tolerance, muscle glycogen level was manipulated by exercise and insulin administration. Sixty Sprague-Dawley rats were evenly separated into three groups: control (CON), immediately after exercise (EX0), and 16 h after exercise (EX16). Rats from each group were further divided into two groups: saline- and insulin-injected. The 2-day exercise protocol consisted of 2 bouts of 3-h swimming with 45-min rest for each day, which effectively depleted glycogen in both red gastrocnemius (RG) and plantaris muscles. EX0 rats were sacrificed immediately after the last bout of exercise on second day. CON and EX16 rats were intubated with 1 g/kg glucose solution following exercise and recovery for 16 h before muscle tissue collection. Insulin (0.5 microU/kg) or saline was injected daily at the time when glucose was intubated. Insulin injection elevated muscle glycogen levels substantially in both muscles above saline-injected group at CON and EX16. With previous day insulin injection, EX0 preserved greater amount of postexercise glycogen above their saline-injected control. In the saline-injected rats, EX16 significantly increased GLUT4 protein level above CON, concurrent with muscle glycogen supercompensation. Insulin injection for EX16 rats significantly enhanced muscle glycogen level above their saline-injected control, but the increases in muscle GLUT4 protein and whole-body glucose tolerance were attenuated. In conclusion, the new finding of the study was that glycogen overload by postexercise insulin administration significantly abolished the exercise-induced increases in GLUT4 protein and glucose tolerance. PMID:16319996

  15. The Effect of Hemiscorpius lepturus (Scorpionida: Hemiscorpiidae Venom on Leukocytes and the Leukocyte Subgroups in Peripheral Blood of Rat

    Mehri Ghafourian


    Full Text Available Background: The aim of this study was to investigate the effect of Hemiscorpius lepturus venom on leukocytes and the leukocyte subgroups in peripheral blood of rat.Methods: In this experimental study, sixty N-Mari rats were divided into three groups of 20 rats. Then the rats in each group were divided into four subgroups based on the blood sampling time that was 2, 6, 24 and 48 hours after the venom injection, respectively. The control group did not receive anything, however, the first and the second ex­perimental groups received 0.1 and 0.01mg/kg of venom, subcutaneously. In accordance with a designated four sam­pling times, the blood sampling was carried out in three groups. After RBC lysis, the leukocytes and leukocyte sub­populations were determined and counted using appropriate hematological standard methods.Results: The leukocyte and the neutrophil count at two (P<0.05, six (P<0.01 and 24 (P<0.05 hours after the venom injection showed a significant decline compared with the control group, this decrease was significant at the dose of 0.1 mg/kg until 48 hours after the venom injection (P<0.05. The lymphocyte count showed a significant decline throughout the all hours of the experiment, compared with the control group (P<0.05.Conclusion: Leukocytes are probably affected by the cytotoxicity effect of the H. lepturus venom in a dose-dependent manner. This could be a wakeup call for the medical staff to perform quick and accurate treatment in the least time possible.

  16. Nomenclature for clusters of differentiation (CD) of antigens defined on human leukocyte populations*


    Evaluation of 139 monoclonal antibodies detecting human leukocyte differentiation antigens during the First International Workshop on Human Leucocyte Differentiation Antigens in 1982 permitted the designation of a nomenclature for the Clusters of Differentiation of antigens defined on human leukocyte populations.

  17. Indium-111 leukocyte accumulation in intramuscular injection sites

    We report four cases of indium-111 leukocyte concentration in previous intramuscular injection sites. Three patterns were observed: (1) small, discrete, and round; (2) linear; (3) irregular and large. The scintigraphic appearance did not necessarily correlate with the number of injections that the patient had received. (orig.)

  18. Improved survival of newborns receiving leukocyte transfusions for sepsis

    To determine the role of polymorphonuclear (PMN) leukocyte transfusions in neonates with sepsis, 23 consecutive newborns were prospectively randomly selected during an 18-month period in a treatment plan to receive polymorphonuclear leukocyte transfusions with supportive care or supportive care alone. Thirteen neonates received transfusions every 12 hours for a total of five transfusions. Each transfusion consisting of 15 mL/kg of polymorphonuclear leukocytes was subjected to 1,500 rads of radiation. The polymorphonuclear leukocytes were obtained by continuous-flow centrifugation leukapheresis and contained 0.5 to 1.0 X 10(9) granulocytes per 15 mL with less than 10% lymphocytes. Positive findings on blood cultures were obtained in 14/23 patients and seven were randomly selected for each treatment group. Absolute granulocyte counts were less than 1,500/microL in 13 patients but tibial bone marrow examinations revealed that the neutrophil supply pool was depleted in only three patients. The survival was significantly greater in the treatment group compared with the group that did not receive transfusions

  19. Uptake of radiolabeled leukocytes in prosthetic graft infection

    The utility of radionuclide labeled leukocytes in the demonstration of infection within vascular prostheses was examined. The infrarenal aorta was replaced with a 3 cm Dacron graft in 12 dogs. On the third postoperative day, six of the animals received an intravenous injection of 10(8) Staphylococcus aureus. Labeled leukocyte scans were performed at postoperative days one and three, and then weekly for 8 weeks with indium-111 and technetium-99 labeled autologous leukocytes. When scans showed focal uptake of isotope in the area of prosthetic material, the grafts were aseptically excised and cultured on mannitol-salt agar. Both control and infected animals had retroperitoneal isotope activity in the immediate postoperative period that disappeared by the end of the first week. By the eighth postoperative week, all of the animals that received the bacteremic challenge had both radionuclide concentration in the region of the vascular prosthesis and S. aureus cultured subsequently from the perigraft tissues. None of the control animals had either radionuclide or bacteriologic evidence of infection at the eighth postoperative week. The radiolabeled leukocyte scan is a highly sensitive and specific technique, clinically applicable for the diagnosis of vascular prosthetic infections

  20. Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome

    Jabbari Azad, Farahzad; Ardalan, Maryam; H.Rafati, Ali;


    Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl...

  1. Genetics Home Reference: leukocyte adhesion deficiency type 1

    ... M, Sperandio M. The molecular basis of leukocyte recruitment and its deficiencies. Mol Immunol. 2013 Aug;55( ... Reviewed : April 2014 Published : August 30, 2016 The resources on this site should not be used as a ... of Health & Human Services National Institutes of Health National Library of ...

  2. Scintigraphic differential diagnosis in painful hip endoprothesis with labelled leukocytes

    In patients with painful prosthetic joints of the hip scintigraphy with white blood cells is a useful method to differentiate between loosening and infection. Examinations of 34 patients after labelling of autologous leukocytes with 111In-oxinate or with 99mTc-DPO gave good results, involving decisive advantages (availability, acquisition time, costs) of 99mTc-DPO. (author)

  3. Production and characterization of monoclonal antibodies against mink leukocytes

    Chen, W.S.; Pedersen, Mikael; Gram-Nielsen, S.;


    Three monoclonal antibodies (mAbs) were generated against mink leukocytes. One antibody reacted with all T lymphocytes, one with all monocytes and one had platelet reactivity. Under reducing conditions, the T lymphocyte reactive antibody immunoprecipitated 18 kDa, 23 kDa, 25 kDa and 32-40 kDa pol...

  4. Compound 21 prevents endothelial inflammation and leukocyte adhesion in vitro and in vivo

    Sampson, Amanda K; Irvine, Jennifer C; Shihata, Waled A;


    BACKGROUND: The angiotensin AT2 (AT2R) is upregulated in disease states such as atherosclerosis; with blockade of the AT2R shown to exacerbate plaque formation. Direct stimulation of the AT2R has been shown to be anti-atherogenic but the mechanisms and pathways involved remain unknown. PURPOSE: T...... with C21 prevents TNFα-induced and HFD-induced vascular inflammation in vitro and in vivo. Our data provide strong evidence that the anti-atherosclerotic actions of C21 are due to AT2R-mediated vascular anti-inflammatory effects....... TNFα and IL-6 mRNA expression in M1 macrophages. The effects of C21 on TNFα-induced endothelial activation were abolished in the presence of the AT2R antagonist PD 123319 confirming the effects of C21 are AT2R-mediated. In addition, we observed high fat diet (HFD)-induced leukocyte adhesion and...

  5. File list: InP.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available InP.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 Input control Blood Polymorphonuclear... leukocytes ...

  6. File list: ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available ALL.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 ...

  7. File list: ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available ALL.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016679,SRX1016682,SRX1016681,SRX1016680 ...

  8. File list: NoD.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available NoD.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 No description Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 ...

  9. File list: InP.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available InP.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 Input control Blood Polymorphonuclear... leukocytes ...

  10. File list: NoD.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available NoD.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 No description Blood Polymorphonuclear... leukocytes SRX1016679,SRX1016682,SRX1016681,SRX1016680 ...

  11. File list: InP.Bld.05.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available InP.Bld.05.AllAg.Polymorphonuclear_leukocytes hg19 Input control Blood Polymorphonuclear... leukocytes ...

  12. File list: NoD.Bld.50.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available NoD.Bld.50.AllAg.Polymorphonuclear_leukocytes hg19 No description Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 ...

  13. File list: ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available ALL.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016681,SRX1016680 ...

  14. File list: InP.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available InP.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 Input control Blood Polymorphonuclear... leukocytes ...

  15. File list: NoD.Bld.10.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available NoD.Bld.10.AllAg.Polymorphonuclear_leukocytes hg19 No description Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016681,SRX1016680 ...

  16. File list: ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes [Chip-atlas[Archive

    Full Text Available ALL.Bld.20.AllAg.Polymorphonuclear_leukocytes hg19 All antigens Blood Polymorphonuclear... leukocytes SRX1016682,SRX1016679,SRX1016680,SRX1016681 ...

  17. Secretory leukocyte proteinase inhibitor is a major leukocyte elastase inhibitor in human neutrophils.

    Sallenave, J M; Si Tahar, M; Cox, G; Chignard, M; Gauldie, J


    Secretory leukocyte proteinase inhibitor (SLPI) is the main neutrophil elastase (HLE) inhibitor found in the upper airways during pulmonary inflammation. It has been shown to be synthesized and secreted in vitro by epithelial cells and has been localized in tracheal glands and bronchiolar epithelial cells by immunocytochemistry. In this study, using immunodetection and immunopurification techniques with specific anti-SLPI immunoglobulin G (IgG), we show that SLPI is present as a native 14-kDa molecule in neutrophil cytosol. In addition, we demonstrate that SLPI is the major inhibitor of HLE present in neutrophil cytosol because pre-incubation with specific anti-SLPI IgG was able to inhibit completely the anti-HLE activity of the cytosol. SLPI can be secreted (probably in an inactive form) by neutrophils and its secretion is enhanced when the cells are stimulated with phorbol myristate acetate (PMA). Elafin, an elastase-specific inhibitor, is also present in minute amounts in neutrophil cytosol and its secretion can be up-regulated. The presence of SLPI in the cytosol of neutrophils may serve as a protective screen against proteinases spilling from azurophilic granules. An alternative or supplementary role may be the maintenance of a differentiated phenotype. PMID:9201260

  18. Colchicine antimitosis abolishes resiliency of postnatally developing rats to chlordecone-amplified carbon tetrachloride hepatotoxicity and lethality.

    Dalu, A; Rao, P S; Mehendale, H M


    We have previously reported that rats are resilient to the hepatotoxic and lethal combination of chlordecone (CD) and carbon tetrachloride (CCl4) during early postnatal development. The overall findings pointed to stimulated cell division and tissue repair mechanisms as the underlying cause of resistance. The objective of the current study was to investigate if the antimitotic effect of colchicine (CLC) abolishes this resiliency to CD + CCl4 by inhibiting ongoing and stimulated cell division....

  19. A Paradoxical Effect of Presession Attention on Stereotypy: Antecedent Attention as an Establishing, Not an Abolishing, Operation

    Roantree, Christina F; Kennedy, Craig H


    Previous studies have shown that presession attention for problem behavior can serve as an abolishing operation when attention functions as a positive reinforcer. In the current study, we show that the stereotypy of a child with severe disabilities was undifferentiated during standard analogue functional analysis conditions. However, when noncontingent presession attention was provided, stereotypy occurred for social attention as a positive reinforcer, suggesting that the antecedent manipulat...

  20. Abolished thermal and mechanical antinociception but retained visceral chemical antinociception induced by butorphanol in μ-opioid receptor knockout mice

    Ide, Soichiro; Minami, Masabumi; Ishihara, Kumatoshi; Uhl, George R; Satoh, Masamichi; Sora, Ichiro; Ikeda, Kazutaka


    Butorphanol is hypothesized to induce analgesia via opioid pathways, although the precise mechanisms for its effects remain unknown. In this study, we investigated the role of the μ-opioid receptor (MOP) in thermal, mechanical, and visceral chemical antinociception induced by butorphanol using MOP knockout (KO) mice. Butorphanol-induced thermal antinociception, assessed by the hot-plate and tail-flick tests, was significantly reduced in heterozygous and abolished in homozygous MOP-KO mice com...

  1. Single-step transepithelial ASLA (SCHWIND with mitomycin-C for the correction of high myopia: long term follow-up

    Aslanides IM


    Full Text Available Ioannis M Aslanides, Panagiotis N Georgoudis, Vasilis D Selimis, Achyut N Mukherjee Emmetropia Mediterranean Eye Institute, Heraklion, Crete, Greece Purpose: We wanted to compare the outcomes of single-step modified transepithelial photorefractive keratectomy (tPRK termed a SCHWIND all surface laser ablation (ASLA versus conventional alcohol-assisted photorefractive keratectomy (PRK and laser-assisted in situ keratomileusis (LASIK for the correction of higher myopia of 6.00 diopters (D or more, in an area with high risk of haze due to high intensity of sunlight.Methods: We used a prospective interventional cohort with matched retrospective control groups. Patients with >6 D myopia and <3.5 D of astigmatism were included. All treatments were performed with the SCHWIND Amaris system using aspheric ablation profiles. Mitomycin C was used in all PRK and ASLA cases. Outcomes were postoperative refraction, visual acuity, stability, and complications. The follow-up period was up to 12 months.Results: In total, 101 eyes were included after exclusions. Mean preoperative spherical equivalent refraction was −7.9 D, −8.2 D, and −7.4 D in the ASLA (n=41, PRK (n=29, and LASIK (n=31 groups. Mean postoperative spherical equivalent at 12 months postoperatively was −0.1 (standard deviation [SD]: 0.34, −0.2 (SD: 0.59, and −0.08 (SD: 0.36 in the ASLA, PRK, and LASIK groups, with 91.4%, 85.7%, and 83.9% within 0.5 D of target, respectively. Refractive outcomes and regression at 12 months did not vary among groups (P>0.05. Mean logMAR (logarithm of the minimum angle of resolution uncorrected distance visual acuity at 12 months was 0.00 (SD: 0.05, 0.06 (SD: 0.1, and 0.05 (SD: 0.09 in the ASLA, PRK, and LASIK groups, with significantly better vision in the tPRK group versus LASIK (P=0.01 and PRK (P=0.01 groups.Conclusion: ASLA (SCHWIND tPRK with mitomycin C for high myopia demonstrates comparable refractive outcomes to LASIK and PRK, with relatively

  2. Combined bone scintigraphy and indium-111 leukocyte scans in neuropathic foot disease

    Schauwecker, D.S.; Park, H.M.; Burt, R.W.; Mock, B.H.; Wellman, H.N.


    It is difficult to diagnose osteomyelitis in the presence of neurotrophic osteoarthropathy. We performed combined (99mTc)MDP bone scans and indium-111 (111In) leukocyte studies on 35 patients who had radiographic evidence of neuropathic foot disease and clinically suspected osteomyelitis. The (111In)leukocyte study determined if there was an infection and the bone scan provided the anatomic landmarks so that the infection could be localized to the bone or the adjacent soft tissue. Seventeen patients had osteomyelitis and all showed increased (111In)leukocyte activity localized to the bone, giving a sensitivity of 100%. Among the 18 patients without osteomyelitis, eight had no accumulation of (111In)leukocytes, seven had the (111In)leukocyte activity correctly localized to the soft tissue, two had (111In)leukocyte activity mistakenly attributed to the bone, and one had (111In)leukocyte accumulation in a proven neuroma which was mistakenly attributed to bone. These three false-positive results for osteomyelitis reduced the specificity to 83%. Considering only the 27 patients with a positive (111In)leukocyte study, the combined bone scan and (111In)leukocyte study correctly localized the infection to the soft tissues or bone in 89%. Uninfected neurotrophic osteoarthropathy does not accumulate (111In)leukocytes. We found the combined bone scan and (111In) leukocyte study useful for the detection and localization of infection to soft tissue or bone in patients with neuropathic foot disease.

  3. Big insights from small volumes: deciphering complex leukocyte behaviors using microfluidics.

    Irimia, Daniel; Ellett, Felix


    Inflammation is an indispensable component of the immune response, and leukocytes provide the first line of defense against infection. Although the major stereotypic leukocyte behaviors in response to infection are well known, the complexities and idiosyncrasies of these phenotypes in conditions of disease are still emerging. Novel tools are indispensable for gaining insights into leukocyte behavior, and in the past decade, microfluidic technologies have emerged as an exciting development in the field. Microfluidic devices are readily customizable, provide tight control of experimental conditions, enable high precision of ex vivo measurements of individual as well as integrated leukocyte functions, and have facilitated the discovery of novel leukocyte phenotypes. Here, we review some of the most interesting insights resulting from the application of microfluidic approaches to the study of the inflammatory response. The aim is to encourage leukocyte biologists to integrate these new tools into increasingly more sophisticated experimental designs for probing complex leukocyte functions. PMID:27194799

  4. In-111-labeled leukocyte brain SPECT imaging in acute ischemic stroke in man

    Fujinuma, Kunihiko; Sakai, Fumihiko; Iizuka, Takahiro; Kitai, Norio [Kitasato Univ., Sagamihara, Kanagawa (Japan). School of Medicine


    This study was performed to investigate the role of leukocyte accumulation in human cerebral infarction and its association with neurological functional outcome. A total of 42 patients diagnosed as acute ischemic stroke (22 embolism, 17 thrombosis, 3 TIA) were examined. Leukocyte accumulation was studied using indium-111-labeled leukocyte brain SPECT. Volume of brain infarction was evaluated by CT and/or MRI. The data were compared with the cerebral blood flow (CBF) imaging. Immediately after CBF study by SPECT using either Tc-99m-HMPAO or Tc-99m-ECD, In-111-labeled autologous leukocytes were injected intravenously. Brain scan for leukocytes was performed after 48 hours. The European Stroke Scale was used for neurological assessment. Thirteen patients with cerebral embolism and three patients with cerebral thrombosis showed intensive accumulation of leukocytes in the region of low flow Leukocyte`s accumulation was not seen in patients with TIA. The accumulation of leukocytes was more noticeable in the central zone of the ischemia. Patients who showed negative leukocyte accumulation revealed clinically mild functional outcome and the size of infarction on CT and/or MRI was small. The regional accumulation of leukocytes was seen in all the patients with hemorrhagic infarction, but the degree of hemorrhage on CT did not have significant influence on the amount of leukocyte accumulation. Abnormal accumulation of leukocytes was associated with reduced CBF during the acute embolic stroke. The present clinical study revealed that leukocyte accumulation correlated with the poor neurological functional outcome in patients with acute embolic stroke. (K.H.)

  5. Effect of radiographic contrast agents on leukocyte metabolic response

    Barium, at clinical dilutions, causes a significant increase of baseline ''resting state'' phagocytic activity, which in turn leads to significant blunting of subsequent response to phagocytic challenge and adversely affects the response to all bacteria tested. There is no baseline activation of leukocytes by the water-soluble media, although there was some inhibition (rather than activation) of leukocyte metabolic activity. The effect of the water-soluble media in bacteria was more complex (although inhibition is minor compared to barium). Our data demonstrate that barium is a significant activator of phagocytic cells, which results in deactivation of phagocytic response when challenged; these data serve to explain the enhanced adverse effect of barium in cased of fecal peritonitis. (orig.)

  6. Diagnostic application of labelled leukocytes in gastroenterology and abdominal surgery

    A total of 18 patients suspected of inflammatory process or abcessus in the abdominal cavity have been studied by scintiscanning with autologous leukocytes labelled with 111In-oxine (10-12 MBq) or 99mTc-HMPAO (300 MBq). Evaluation of the process activity is done on the ground activity index adopted which is received after the computer processing of the results. Three levels of process activity are determined: 1) when the leukocyte accumulation (LA) corresponds to that in the bone marrow; 2) when the LA corresponds to that in the liver; 3) when the LA corresponds to that in the spleen. The recorded sensitivity, specificity and accuracy of the method amount to 87.5%, 100% and 92.9% respectively. The method allows localization of the inflammatory process and indicates the degree of affecting the intestines. 2 figs., 6 refs

  7. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency

    Qasim, Waseem; Cavazzana-Calvo, Marina; Davies, E Graham;


    of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International......, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early...... therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients....

  8. Derivation of Cinnamon Blocks Leukocyte Attachment by Interacting with Sialosides.

    Wei-Ling Lin

    Full Text Available Molecules derived from cinnamon have demonstrated diverse pharmacological activities against infectious pathogens, diabetes and inflammatory diseases. This study aims to evaluate the effect of the cinnamon-derived molecule IND02 on the adhesion of leukocytes to host cells. The anti-inflammatory ability of IND02, a pentameric procyanidin type A polyphenol polymer isolated from cinnamon alcohol extract, was examined. Pretreatment with IND02 significantly reduced the attachment of THP-1 cells or neutrophils to TNF-α-activated HUVECs or E-selectin/ICAM-1, respectively. IND02 also reduced the binding of E-, L- and P-selectins with sialosides. Furthermore, IND02 could agglutinate human red blood cells (RBC, and the agglutination could be disrupted by sialylated glycoprotein. Our findings demonstrate that IND02, a cinnamon-derived compound, can interact with sialosides and block the binding of selectins and leukocytes with sialic acids.

  9. The effect of probiotic Escherichia coli strain Nissle 1917 lipopolysaccharide on the 5-aminosalicylic acid transepithelial transport across Caco-2 cell monolayers.

    Stětinová, Věra; Smetanová, Libuše; Kholová, Dagmar; Květina, Jaroslav; Svoboda, Zbyněk; Zídek, Zdeněk; Tlaskalová-Hogenová, Helena


    The object of this study was to investigate the effect of probiotic Escherichia coli strain Nissle 1917 (EcN) (i) EcN lipopolysaccharide (EcN LPS) and (ii) bacteria-free supernatant of EcN suspension (EcN supernatant) on in vitro transepithelial transport of mesalazine (5-aminosalicylic acid, 5-ASA), the most commonly prescribed anti-inflammatory drug in inflammatory bowel disease (IBD). Effect of co-administered EcN LPS (100 µg/ml) or EcN supernatant (50 µg/ml) on the 5-ASA transport (300 µmol/l) was studied using the Caco-2 monolayer (a human colon carcinoma cell line) as a model of human intestinal absorption. Permeability characteristics for absorptive and secretory transport of parent drug and its intracellularly-formed metabolite were determined. The quantification of 5-ASA and its main metabolite N-acetyl-5-amino-salicylic acid (N-Ac-5-ASA) was performed by high performance liquid chromatography. Obtained results suggest that neither EcN LPS nor EcN supernatant had effect on the total 5-ASA transport (secretory flux greater than absorptive flux) and on the transport of intracellularly formed N-Ac-5-ASA (preferentially transported in the secretory direction). The percent cumulative transport of the total 5-ASA alone or in combination with EcN LPS or EcN supernatant did not exceed 1%. PMID:23846256

  10. Transepithelial permeability studies of flavan-3-ol-C-glucosides and procyanidin dimers and trimers across the Caco-2 cell monolayer.

    Hemmersbach, Sarah; Brauer, Susanne S; Hüwel, Sabine; Galla, Hans-Joachim; Humpf, Hans-Ulrich


    In this study the permeability of two flavanol-C-glucosides (FCglcs) and five dimeric and trimeric flavan-3-ols, namely, procyanidins (PCs), was investigated with the human colon carcinoma cell line (Caco-2) model. These compounds can be found especially in cocoa, and they are of great interest due to their assumed beneficial health effects. Transepithelial electrical resistance (TEER) and capacitance were measured online with a CellZscope device prior to and during the whole experiment to guarantee the maintenance of the barrier properties. The transport experiments with pure, single compounds (50-300 μM) from apical to basolateral side showed slight permeation of PCs A2, B2, and B5 and cinnamtannin B1 (CB1) as well as (-)-catechin-6-C-glucoside (C6Cglc) and (-)-catechin-8-C-glucoside (C8Cglc) of about 0.02-0.2% after 24 h. Transport of PC C1 could not be detected. Inhibition of P-glycoprotein (Pgp) increased the permeation of PC B2 and CB1 to the basolateral side, which indicates that Pgp counteracts the transport of these compounds. Metabolites (epicatechin, 3'- and 4'-O-epicatechin) in very small amounts were detectable only for PC B2. These are the first data concerning the permeability of flavan-3-ol-C-glucosides across the Caco-2 cell monolayer. PMID:23885956

  11. PECAM-1 is required for transendothelial migration of leukocytes


    Platelet/endothelial cell adhesion molecule 1 (PECAM-1; CD31) is crucial to the process of leukocyte transmigration through intercellular junctions of vascular endothelial cells. A monoclonal antibody to PECAM, or recombinant soluble PECAM, blocks transendothelial migration of monocytes by 70-90%. Pretreating either the monocytes or the endothelial junctions with antibody blocks transmigration. If the endothelium is first activated by cytokines, anti-PECAM antibody or soluble recombinant PECA...

  12. Derivation of Cinnamon Blocks Leukocyte Attachment by Interacting with Sialosides

    Wei-Ling Lin; Shih-Yun Guu; Chan-Chuan Tsai; Ekambaranellore Prakash; Mohan Viswaraman; Hsing-Bao Chen; Chuan-Fa Chang


    Molecules derived from cinnamon have demonstrated diverse pharmacological activities against infectious pathogens, diabetes and inflammatory diseases. This study aims to evaluate the effect of the cinnamon-derived molecule IND02 on the adhesion of leukocytes to host cells. The anti-inflammatory ability of IND02, a pentameric procyanidin type A polyphenol polymer isolated from cinnamon alcohol extract, was examined. Pretreatment with IND02 significantly reduced the attachment of THP-1 cells or...

  13. Binding of Pasteurella haemolytica leukotoxin to bovine leukocytes.

    Brown, J F; Leite, F; Czuprynski, C J


    Pasteurella haemolytica is the principal bacterial pathogen in the bovine respiratory disease complex. This organism produces an exotoxin (referred to as leukotoxin) during logarithmic-phase growth that is a potent leukocyte-modulating agent. At low concentrations, it activates neutrophils and mononuclear phagocytes to release inflammatory mediators, while at the same time making these cells destined to undergo apoptotic cell death. At higher concentrations, the toxin causes rapid swelling an...

  14. DNA damage in peripheral blood leukocytes in tobacco users

    Venkateswara Rao Guttikonda; Rekha Patil; G S Kumar


    Aim : To Quantify the DNA single-stranded breaks in the peripheral blood leukocytes (PBLs) of tobacco-habituated individuals with clinically normal mucosa and patients with oral carcinoma. Objectives: To evaluate DNA damage levels in PBLs of tobacco-habituated individuals with clinically normal mucosa and patients with oral carcinoma and compare with a control group of healthy volunteers. To evaluate the extent of DNA damage in PBLs using Single Cell Gel Electrophoresis (SCGE) in the above gr...

  15. Indium-111 leukocyte localization in infected prosthetic graft

    Infective endocarditis can be difficult to prove, even in the face of strong clinical suspicion. A case in which standard methods of diagnosis failed to demonstrate endocarditis in a patient with recurrent Staphylococcus aureus bacteremia and porcine aortic valve is reported. An In-111 labelled leukocyte SPECT study demonstrated uptake in the aortic root and leaflets, and autopsy demonstrated vegetations on the leaflets. In-111 may prove useful in demonstrating endocarditis in patients with prosthetic valve infection

  16. Quantitative and qualitative changes in leukocytes of psoriatic patients

    Background: Psoriasis is a disease concerned with inflammation and scaling of skin. In psoriasis, cells of the skin come on surface quickly before their complete maturation. In psoriatic patients, T-cells produce an abnormally large amount of toxic chemicals and cause inflammation. This study was undertaken to find out values of prognostic significance for worsening of the disease at early stage and to evaluate the changes (quantitative and qualitative) occurring in white blood cells of psoriatic patients. Methods: A total of 158 subjects, 79 psoriatic patients (44 males and 35 females) and same numbers of normal control volunteers were recruited. Total and Differential Leukocyte Counts (TLC and DLC) were determined. Morphological examination was also undertaken. All results of patients were compared with normal control volunteers. Results : In 47.7% male and 54.2% female patients TLC was higher than controls while variation in differential count was observed in 61.3% male and 62.8% female patients. Overall, neutrophils in 45% patients, basophils in 30.3%, eosinophils in 65.8%, and monocytes in 15% of patients were elevated. In 77.2% psoriatic patients, lymphocytes were decreased. In volunteers total and differential leukocyte counts were within normal range. Total leukocyte count in normal males was 5,136 +- 31, and in psoriatic male subjects it was 10,498 +- 43, and it was 5,023 +- 35 against 11,390 +- 31 in normal versus psoriatic females ( p<0.001). Conclusion: Total leukocyte count was elevated in psoriatics while on DLC neutrophils, eosinophils and neutrophils were significantly raised where as lymphocytes were significantly decreased in psoriatic patients. Morphological changes were also noted. (author)

  17. TGV-based flow estimation for 4D leukocyte transmigration

    Frerking, L.; M. Burger; Vestweber, D.; Brune, C.; Louis, Alfred K.; Arridge, Simon; Rundell, Bill


    The aim of this paper is to track transmigrating leukocytes via TGV flow estimation. Recent results have shown the advantages of the nonlinear and higher order terms of TGV regularizers, especially in static models for denoising and medical reconstruction. We present TGV-based models for flow estimation with the goal to get an exact recovery of simple intracellular and extracellular flows, as well as its implication on realistic tracking situations for transmigration through barriers. To stud...

  18. Maternal circulating leukocytes display early chemotactic responsiveness during late gestation

    Gomez-Lopez Nardhy


    Full Text Available Abstract Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD 17, 20 and 22 (term gestation. We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif ligand 2 (Ccl2 gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif ligand 1/CXCL1, and CXCL10 were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.

  19. Genetics of Leukocyte Telomere Length and its Role in Atherosclerosis

    Aviv, Abraham


    Humans display a large inter-individual variation in leukocyte telomere length (LTL), which is influenced by heredity, sex, race/ethnicity, paternal age at conception and environmental exposures. LTL dynamics (birth LTL and its age-dependent attrition thereafter) mirror telomere dynamics in hematopoietic stem cells (HSCs). LTL at birth is evidently a major determinant of LTL throughout the human lifespan, such that individuals endowed with short (or long) LTL at birth probably have short (or ...

  20. Dimensions of religious involvement and leukocyte telomere length.

    Hill, Terrence D; Ellison, Christopher G; Burdette, Amy M; Taylor, John; Friedman, Katherine L


    Although numerous studies suggest that religious involvement is associated with a wide range of favorable health outcomes, it is unclear whether this general pattern extends to cellular aging. In this paper, we tested whether leukocyte telomere length varies according to several dimensions of religious involvement. We used cross-sectional data from the Nashville Stress and Health Study (2011-2014), a large probability sample of 1252 black and white adults aged 22 to 69 living in Davidson County, TN, USA. Leukocyte telomere length was measured using the monochrome multiplex quantitative polymerase chain reaction method with albumin as the single-copy reference sequence. Dimensions of religious involvement included religiosity, religious support, and religious coping. Our multivariate analyses showed that religiosity (an index of religious attendance, prayer frequency, and religious identity) was positively associated with leukocyte telomere length, even with adjustments for religious support, religious coping, age, gender, race, education, employment status, income, financial strain, stressful life events, marital status, family support, friend support, depressive symptoms, smoking, heavy drinking, and allostatic load. Unlike religiosity, religious support and religious coping were unrelated to leukocyte telomere length across models. Depressive symptoms, smoking, heavy drinking, and allostatic load failed to explain any of the association between religiosity and telomere length. To our knowledge, this is the first population-based study to link religious involvement and cellular aging. Although our data suggest that adults who frequently attend religious services, pray with regularity, and consider themselves to be religious tend to exhibit longer telomeres than those who attend and pray less frequently and do not consider themselves to be religious, additional research is needed to establish the mechanisms underlying this association. PMID:27174242

  1. Drug addiction is associated with leukocyte telomere length

    Yang, Zhaoyang; Ye, Junyi; Li, Candong; Zhou, Daizhan; Shen, Qin; Wu, Ji; Cao, Lan; Wang, Ting; Cui, Daxiang; He, Shigang; Qi, Guoyang; He, Lin; Liu, Yun


    Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Telomere length is known to be associated with ageing and age-related diseases. To study the impairment of telomeres induced by drug abuse, we conducted an association study in the Chinese Han population. Multivariate linear regression analyses were performed to evaluate the correlation of leukocyte telomere length (LTL) with addiction control status adjusted for age and gender. The results s...

  2. Immunohistochemical Characterization of Leukocytic Subpopulations in Chronic Endometritis

    Ossama Tawfik; Susan Venuti; Sharla Brown; Julie Collins


    Objective: We analyzed the histologic and immunohistochemical changes in the endometrial leukocytic subpopulations to determine which of them are characteristic of chronic endometritis. Results: Endometrial biopsies from 25 cases of chronic endometritis and 35 controls were studied. Characteristic morphologic findings included the presence of a plasma cell infiltrate, and a prominent, albeit non-specific, lymphocytic infiltrate in all patients with endometritis. A neutrophilic infiltrate was ...

  3. Fecal leukocytes in children infected with diarrheagenic Escherichia coli.

    Mercado, Erik H; Ochoa, Theresa J; Ecker, Lucie; Cabello, Martin; Durand, David; Barletta, Francesca; Molina, Margarita; Gil, Ana I; Huicho, Luis; Lanata, Claudio F; Cleary, Thomas G


    The purpose of this study was to determine the presence and quantity of fecal leukocytes in children infected with diarrheagenic Escherichia coli and to compare these levels between diarrhea and control cases. We analyzed 1,474 stool samples from 935 diarrhea episodes and 539 from healthy controls of a cohort study of children younger than 2 years of age in Lima, Peru. Stools were analyzed for common enteric pathogens, and diarrheagenic E. coli isolates were studied by a multiplex real-time PCR. Stool smears were stained with methylene blue and read by a blinded observer to determine the number of polymorphonuclear leukocytes per high-power field (L/hpf). Fecal leukocytes at >10 L/hpf were present in 11.8% (110/935) of all diarrheal episodes versus 1.1% (6/539) in controls (P 10 L/hpf were present in 8.5% (18/212) of diarrhea versus 1.3% (2/157) of control samples (P 10 L/hpf) with an odds ratio (OR) of 4.1 (95% confidence interval [CI], 1.08 to 15.51; P < 0.05). Although diarrheagenic E. coli was isolated with similar frequencies in diarrhea and control samples, clearly it was associated with a more inflammatory response during symptomatic infection; however, in general, these pathogens elicited a mild inflammatory response. PMID:21325554

  4. Report: Nuclei segmentation of leukocytes in blood smear digital images.

    Abbas, Naveed; Mohamad, Dzulkifli; Abdullah, Abdul Hanan; Saba, Tanzila; Al-Rodhaan, Mznah; Al-Dhelaan, Abdullah


    The Leukocytes are differentiated from each other on the basis of their nuclei, demanded in many Medical studies, especially in all types of Leukemia by the Hematologists to note the disorder caused by specific type of Leukocyte. Leukemia is a life threatening disease. The work for diagnosing is manually carried out by the Hematologists involving much labor, time and human errors. The problems mentioned are easily addressed through computer vision techniques, but still accuracy and efficiency are demanded in terms of the basic and challenging step segmentation of Leukocyte's nuclei. The underlying study proposed better method in terms of accuracy and efficiency by designing a dynamic convolution filter for boosting low intensity values in the separated green channel of an RGB image and suppressing the high values in the same channel. The high values in the green channel become 255 (background) while the nuclei always have low values in the green channel and thus clearly appear as foreground. The proposed technique is tested on 365 images achieving an overall accuracy of 95.89%, while improving the efficiency by 10%. The proposed technique achieved its targets in a realistic way by improving the accuracy as well as the efficiency and both are highly required in the area. PMID:26408877

  5. Leukocyte adhesion defect type 1 presenting with recurrent pyoderma gangrenosum

    Neha Thakur


    Full Text Available Leukocyte adhesion deficiency 1 (LAD-1 is a rare autosomal recessive disorder of leukocyte function. LAD-1 affects about 1 per 10 million individuals and is characterized by recurrent bacterial and fungal infections and depressed inflammatory responses despite striking blood neutrophilia. Patients with the severe clinical form of LAD-1 express <0.3% of the normal amount of the β2 -integrin molecules, whereas patients with the moderate phenotype may express 2-7%. Skin infection may progress to large chronic ulcers with polymicrobial infection, including anaerobic organisms. The ulcers heal slowly, require months of antibiotic treatment, and often require plastic surgical grafting. The diagnosis of LAD-1 is established most readily by flow cytometric measurements of surface CD11b in stimulated and unstimulated neutrophils using monoclonal antibodies directed against CD11b. Pyoderma gangrenosum (PG is an uncommon condition characterized by recurrent sterile, inflammatory skin ulcers. Commonly, PG occurs in the context of inflammatory bowel disease or rheumatic, hematologic, or immunologic disorders. Here, we present a 5-year-old female with a long history of PG, which healed with atrophic scarring, who was ultimately diagnosed with leukocyte adhesion deficiency type 1 (LAD1. She had a good response to high-dose prednisone therapy (2 mg/kg and was discharged after 3 weeks of admission but only to be re-admitted 3 weeks later with severe pneumonia. During hospital stay, she developed pneumothorax and pneumomediastinum and later succumbed to her illness.

  6. Leukocyte recovery from umbilical cord blood by poligeline.

    Perutelli, P; Catellani, S


    Umbilical cord blood (UCB) collected at delivery is a source of transplantable stem/progenitor cells; it represents an alternative to bone marrow to restore hematopoiesis in patients affected by malignant and non-malignant disease. Therefore, large-scale UCB banks would be a natural complement to bone marrow donor registries. Storage of unmanipulated whole UCB units requires a great number of liquid nitrogen containers. Separation of leukocytes allows UCB storage in smaller space, thus lowering banking costs; unfortunately, UCB processing may cause significant losses of stem cells. We report about the use of poligeline to remove erythrocytes from UCB units. After erythrocyte sedimentation at 1xg (30' or 40') or 50xg, leukocyte-rich supernatant was collected and centrifuged to recover the leukocyte pool in view of stem cell transplantation. Erythrocyte depletion was always satisfactory, ranging from 82.6% to 88.9%, but 1xg sedimentation for 40' enabled us to achieve the best CD34+ cell recovery (mean value 80.5%). The proposed UCB-processing method allowed us to lower the final sample volume down to 1/10 of the initial one, in this way making UCB banking feasible. Erythrocyte depletion took place directly in the collection bag, thus reducing microbial contamination risk. PMID:10193639

  7. Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

    Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail:; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)


    Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

  8. Leukocyte Adhesion Deficiency: Report of Two Family Related Newborn Infants

    Zohreh Kavehmanesh


    Full Text Available "nLeukocyte adhesion deficiency type 1 (LAD 1 is an autosomal recessive hereditary disorder resulting from deficiency of CD18, characterized by recurrent bacterial infections. We report two consanguineous patients with Leukocyte adhesion deficiency type 1( LAD1. These two infant boy patients were referred to us, within a short period of time, with the complaints of recurrent infections at the age of 38 and 75 days -old, respectively. Parents of two patients were first cousins and their grandmothers also were first cousins. The history of delayed umbilical cord separation was shown in both patients. Patient 1 had history of omphalitis, conjunctivitis, skin lesion of groin area and abscess formation of vaccination site, and had infective wound of eye-lid at the last admission. Patient 2 had history of omphalitis and soft tissue infection of right wrist at the last admission. Laboratory findings showed marked leukocytosis and low CD18 levels (6.6% in Patient 1 and 2.4 % in Patient 2. In Patient 1 recurrent infections were treated with antibiotic regimens and received bone marrow transplantation but Patient 2 died because of septicemia, generalized edema, ascites and progression to acute renal failure at 4 months of age. Due to considerable rate of consanguineous marriages in parents of Leukocyte adhesion deficiency patients, sequence analysis especially for prenatal diagnosis in subsequent pregnancies and genetic counseling is recommended.

  9. Imaging leukocytes in vivo with third harmonic generation microscopy

    Tsai, Cheng-Kun; Chen, Chien-Kuo; Chen, Yu-Shing; Wu, Pei-Chun; Hsieh, Tsung-Yuan; Liu, Han-Wen; Yeh, Chiou-Yueh; Lin, Win-Li; Chia, Jean-San; Liu, Tzu-Ming


    Without a labeling, we demonstrated that lipid granules in leukocytes have distinctive third harmonic generation (THG) contrast. Excited by a 1230nm femtosecond laser, THG signals were generated at a significantly higher level in neutrophils than other mononuclear cells, whereas signals in agranular lymphocytes were one order smaller. These characteristic THG features can also be observed in vivo to trace the newly recruited leukocytes following lipopolysaccharide (LPS) challenge. Furthermore, using video-rate THG microscopy, we also captured images of blood cells in human capillaries. Quite different from red-blood-cells, every now and then, round and granule rich blood cells with strong THG contrast appeared in circulation. The corresponding volume densities in blood, evaluated from their frequencies of appearance and the velocity of circulation, fall within the physiological range of human white blood cell counts. These results suggested that labeling-free THG imaging may provide timely tracing of leukocyte movement and hematology inspection without disturbing the normal cellular or physiological status.

  10. Generation of reactive oxygen species by leukocytes of Prochilodus lineatus.

    de Faria, Marcos Tucunduva; Cury-Boaventura, Maria Fernanda; Lopes, Lucia Rossetti; da Silva, José Roberto Machado Cunha


    Prochilodus lineatus (curimbatá), from the Procholodontidae family, is a Brazilian freshwater fish, which is important commercially, nutritionally and ecologically. It is encountered in the Rio da Prata Bay in Southern South America. Studies on the immune system of this fish are scarce, but the physiological mechanisms of the species are analogous to those of other vertebrates. Thus, this work discusses the present study, which correlates P. lineatus leukocytes and the generation of reactive oxygen species after modulatory stimuli. Leukocytes were characterized by light and electron transmission microscopy and investigated by the generation of H2O2 and O2 (-), using phenol red, flow-cytometry and electron transmission histochemistry. The study determined that monocytes and neutrophils are the main cells responsible for generating O2 after stimulation with phorbol myristate acetate. Superoxide dismutase successfully inhibited the generation of reactive oxygen species in neutrophils and monocytes, but stimulated generation when in association with phorbol myristate acetate. Fish leukocyte samples from P. lineatus showed cross-reactivity with antibodies directed against human NADPH-oxidase antibody subunits (p47(phox) and p67(phox)). Thus, catalase enhanced the presence of p47(phox). Neutrophil mitochondria were shown to be generators of H2O2 (charged by cerium precipitate), being enlarged and changing their format. The present study contributes to a better understanding of the respiratory burst pathways in this species and suggests mitochondria as the organelle responsible for generation of reactive oxygen species. PMID:24068363

  11. Plasmodium vivax: paroxysm-associated lipids mediate leukocyte aggregation

    Mendis Kamini


    Full Text Available Abstract Background Paroxysms are recurrent febrile episodes, characteristic of Plasmodium vivax infections, which coincide with the rupture of schizont-infected erythrocytes in the patients' circulation. The present study describes the formation of prominent aggregates of leukocytes in vitro in the presence of parasite and host factors released during paroxysms. Methods Whole blood cells from uninfected malaria-naïve donors were incubated with plasma taken during a paroxysm or normal human plasma as a control and cell smears were observed under the microscope for the presence of leukocyte aggregates. Plasma factors involved in mediating the leukocyte aggregation were identified using immune depletion and reconstitution experiments. Furthermore, biochemical characterization was carried out to determine the chemical nature of the active moieties in plasma present during paroxysms. Results Leukocyte aggregates were seen exclusively when cells were incubated in plasma collected during a paroxysm. Immune depletion and reconstitution experiments revealed that the host cytokines TNF-alpha, GM-CSF, IL-6 and IL-10 and two lipid fractions of paroxysm plasma comprise the necessary and sufficient mediators of this phenomenon. The two lipid components of the paroxysm plasmas speculated to be of putative parasite origin, were a phospholipid-containing fraction and another containing cholesterol and triglycerides. The phospholipid fraction was dependent upon the presence of cytokines for its activity unlike the cholesterol/triglyceride-containing fraction which in the absence of added cytokines was much more active than the phospholipids fraction. The biological activity of the paroxysm plasmas from non-immune patients who presented with acute P. vivax infections was neutralized by immune sera raised against schizont extracts of either P. vivax or Plasmodium falciparum. However, immune sera against P. vivax were more effective than that against P. falciparum

  12. In-111-labeled leukocyte brain SPECT imaging in acute ischemic stroke in man

    This study was performed to investigate the role of leukocyte accumulation in human cerebral infarction and its association with neurological functional outcome. A total of 42 patients diagnosed as acute ischemic stroke (22 embolism, 17 thrombosis, 3 TIA) were examined. Leukocyte accumulation was studied using indium-111-labeled leukocyte brain SPECT. Volume of brain infarction was evaluated by CT and/or MRI. The data were compared with the cerebral blood flow (CBF) imaging. Immediately after CBF study by SPECT using either Tc-99m-HMPAO or Tc-99m-ECD, In-111-labeled autologous leukocytes were injected intravenously. Brain scan for leukocytes was performed after 48 hours. The European Stroke Scale was used for neurological assessment. Thirteen patients with cerebral embolism and three patients with cerebral thrombosis showed intensive accumulation of leukocytes in the region of low flow Leukocyte's accumulation was not seen in patients with TIA. The accumulation of leukocytes was more noticeable in the central zone of the ischemia. Patients who showed negative leukocyte accumulation revealed clinically mild functional outcome and the size of infarction on CT and/or MRI was small. The regional accumulation of leukocytes was seen in all the patients with hemorrhagic infarction, but the degree of hemorrhage on CT did not have significant influence on the amount of leukocyte accumulation. Abnormal accumulation of leukocytes was associated with reduced CBF during the acute embolic stroke. The present clinical study revealed that leukocyte accumulation correlated with the poor neurological functional outcome in patients with acute embolic stroke. (K.H.)

  13. Chronic Blockade of the Androgen Receptor Abolishes Age-Dependent Increases in Blood Pressure in Female Growth-Restricted Rats.

    Dasinger, John Henry; Intapad, Suttira; Rudsenske, Benjamin R; Davis, Gwendolyn K; Newsome, Ashley D; Alexander, Barbara T


    Intrauterine growth restriction induced via placental insufficiency programs a significant increase in blood pressure at 12 months of age in female growth-restricted rats that is associated with early cessation of estrous cyclicity, indicative of premature reproductive senescence. In addition, female growth-restricted rats at 12 months of age exhibit a significant increase in circulating testosterone with no change in circulating estradiol. Testosterone is positively associated with blood pressure after menopause in women. Thus, we tested the hypothesis that androgen receptor blockade would abolish the significant increase in blood pressure that develops with age in female growth-restricted rats. Mean arterial pressure was measured in animals pretreated with and without the androgen receptor antagonist, flutamide (8 mg/kg/day, SC for 2 weeks). Flutamide abolished the significant increase in blood pressure in growth-restricted rats relative to control at 12 months of age. To examine the mechanism(s) by which androgens contribute to increased blood pressure in growth-restricted rats, blood pressure was assessed in rats untreated or treated with enalapril (250 mg/L for 2 weeks). Enalapril eliminated the increase in blood pressure in growth-restricted relative to vehicle- and flutamide-treated controls. Furthermore, the increase in medullary angiotensin type 1 receptor mRNA expression was abolished in flutamide-treated growth-restricted relative to untreated counterparts and controls; cortical angiotensin-converting enzyme mRNA expression was reduced in flutamide-treated growth-restricted versus untreated counterparts. Thus, these data indicate that androgens, via activation of the renin-angiotensin system, are important mediators of increased blood pressure that develops by 12 months of age in female growth-restricted rats. PMID:27113045

  14. Altered Immunogenicity of Donor Lungs via Removal of Passenger Leukocytes Using Ex Vivo Lung Perfusion.

    Stone, J P; Critchley, W R; Major, T; Rajan, G; Risnes, I; Scott, H; Liao, Q; Wohlfart, B; Sjöberg, T; Yonan, N; Steen, S; Fildes, J E


    Passenger leukocyte transfer from the donor lung to the recipient is intrinsically involved in acute rejection. Direct presentation of alloantigen expressed on donor leukocytes is recognized by recipient T cells, promoting acute cellular rejection. We utilized ex vivo lung perfusion (EVLP) to study passenger leukocyte migration from donor lungs into the recipient and to evaluate the effects of donor leukocyte depletion prior to transplantation. For this purpose, female pigs received male left lungs either following 3 h of EVLP or retrieved using standard protocols. Recipients were monitored for 24 h and sequential samples were collected. EVLP-reduced donor leukocyte transfer into the recipient and migration to recipient lymph nodes was markedly reduced. Recipient T cell infiltration of the donor lung was significantly diminished via EVLP. Donor leukocyte removal during EVLP reduces direct allorecognition and T cell priming, diminishing recipient T cell infiltration, the hallmark of acute rejection. PMID:26366523

  15. The reducing agent dithiothreitol (DTT) does not abolish the inhibitory nicotinic response recorded from rat dorsolateral septal neurons

    Sorenson, E. M.; Gallagher, J. P.


    Previous intracellular recordings have demonstrated that dorsolateral septal nucleus (DLSN) neurons express a novel nicotinic receptor which produces a direct membrane hyperpolarization when activated by nicotinic agonists. Activation of the classical excitatory nicotinic receptors has been shown to require a disulfide bond involving the cysteines at positions 192 and 193 of the alpha subunits of the receptor. Reduction of this cystine bond with dithiothreitol (DTT) abolishes agonist activation of excitatory nicotinic receptors. We have now examined whether DTT treatment of the inhibitory nicotinic receptor on DLSN neurons also abolishes the inhibitory nicotinic response. We find that the inhibitory response persists after treatment of the neurons with 1 mM DTT, even if the reduction is followed by alkylation of the receptor with bromoacetylcholine to prevent possible reformation of disulfide bonds. This result suggests that the agonist binding site on the inhibitory nicotinic receptor does not require an intact disulfide bond, similar to the bond on the alpha subunit of the excitatory nicotinic receptor, for agonist activation of the receptor. Some of these results have been previously reported in abstract form.

  16. Arachidonic acid metabolism in polymorphonuclear leukocytes from patients with chronic granulomatous disease.

    Smith, D. M.; Walsh, C E; DeChatelet, L R; Waite, M.


    The effect of the calcium ionophore A23187 on the release and metabolism of [3H]arachidonic acid was examined in normal polymorphonuclear leukocytes and those obtained from patients with chronic granulomatous disease. The ionophore A23187 which stimulates oxidative metabolism in normal polymorphonuclear leukocytes was ineffective in increasing oxidative metabolism (chemiluminescence) in polymorphonuclear leukocytes from patients with chronic granulomatous disease. However, the ionophore A2318...

  17. Mechanisms of leukocyte transendothelial and interstitial migration during inflammation in vivo

    Khandoga, Alexander


    The emigration of leukocytes from the circulation is a critical step during immune surveillance and inflammatory reactions that is governed by a coordinated interplay involving a spectrum of adhesion and signal molecules. While a great deal has been learned about the early steps of leukocyte recruitment, i.e. rolling and adhesion, little is known about the subsequent steps, transendothelial and interstitial migration when leukocytes migrate across the endothelial layer lining the blood vessel...

  18. Inhibition of nitric oxide synthesis enhances leukocyte rolling and adhesion in human microvasculature

    Hossain Mokarram; Qadri Syed M; Liu Lixin


    Abstract Background Nitric oxide (NO) is a multifunctional signaling molecule that regulates important cellular events in inflammation including leukocyte recruitment. Previous studies have shown that pharmacological inhibition of NO synthesis induces leukocyte recruitment in various in vitro and animal models. However, it is not known whether NO modulation has similar effects on leukocyte-endothelial cell interactions within the human microvasculature. The present study explored the effect o...

  19. Production of fibrogenic cytokines by interleukin-2-treated peripheral blood leukocytes

    Kovacs, E J; Brock, B; Silber, I E;


    procollagen and fibronectin messenger RNAs was increased in human fibroblasts in response to leukocyte supernatants. Unstimulated leukocytes expressed minimal levels of transforming growth factor-beta or platelet-derived growth factor B chain messenger RNAs, but could be greatly enhanced by IL-2 treatment....... CONCLUSION: Mediators that induce connective tissue production are secreted by IL-2-treated peripheral blood leukocytes. These cytokines may be responsible, in part, for the stimulation of abdominal adhesions in patients receiving intraperitoneal immunotherapy....

  20. Comparing Electrolytes in Prestorage Leukocyte-Reduced Packed Cell versus Unfiltered Packed Cell

    Fallahi, L; Ghiliyan, R; Hashemi, A; A. Fatemi; M. Saeedi


    Background Blood transfusion is associated with side effects caused by residual leukocytes in blood and blood components. Using leukodepleted blood components can decrease some of these adverse effects. Among the various methods to remove leukocytes in blood components, prestorage leukoreduction has been most efficient, but the evidence of clinical side effects awaits further studies. We evaluated changes of electrolytes in prestorage leukocyte-reduced red blood cells. Materials and Methods I...

  1. Shorter telomere length in peripheral blood leukocytes is associated with childhood autism

    Li, Zongchang; Tang, Jinsong; LI Hong; Chen, Shan; He, Ying; Liao, Yanhui; Wei, Zhen; Wan, Guobin; XIANG, XI; Xia, Kun; Chen, Xiaogang


    Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Epidemiologic studies have shown that the abnormal telomere length in leukocytes is associated with some mental disorders and age-related diseases. However, the association between leukocyte telomere length and autism has not been investigated. Here we investigated the possible association between relative telomere length (RTL) in peripheral blood leukocytes and childhood autism by using an e...

  2. Constitutive and stimulus-induced phosphorylation of CD11/CD18 leukocyte adhesion molecules


    The leukocyte CD11/CD18 adhesion molecules (beta 2 integrins) are a family of three heterodimeric glycoproteins each with a distinct alpha subunit (CD11a, b, or c) and a common beta subunit (CD18). CD11/CD18 mediate crucial leukocyte adhesion functions such as chemotaxis, phagocytosis, adhesion to endothelium, aggregation, and cell-mediated cytotoxicity. The enhanced cell adhesion observed upon activation of leukocytes is associated with increased surface membrane expression of CD11/CD18, as ...

  3. The CpAL system regulates changes of the trans-epithelial resistance of human enterocytes during Clostridium perfringens type C infection.

    Nava, Porfirio; Vidal, Jorge E


    Clostridium perfringens type C strains produce severe disease in humans and animals including enterotoxaemia and hemorrhagic diarrhea. Type C disease is mediated by production of toxins that damage the site of infection inducing loss of bloody fluids. Production of type C toxins, such as CPA, PFO, and, CPB is regulated by the C. perfringens Agr-like (CpAL) quorum sensing (QS) system. The CpAL system is also required to recapitulate, in vivo, intestinal signs of C. perfringens type C-induced disease, including hemorrhagic diarrhea and accumulation of fluids. The intestinal epithelium forms a physical barrier, made up of a series of intercellular junctions including tight junctions (TJs), adherens junctions (AJs) and desmosomes (DMs). This selective barrier regulates important physiological processes, including paracellular movement of ions and solutes, which, if altered, results in loss of fluids into the intestinal lumen. In this work, the effects of C. perfringens infection on the barrier function of intestinal epithelial cells was evaluated by measuring trans-epithelial resistance (TEER). Our studies demonstrate that infection of human enterocytes with C. perfringens type C strain CN3685 induced a significant drop on TEER. Changes in TEER were mediated by the CpAL system as a CN3685ΔagrB mutant did not induce such a drop. Physical contact between bacteria and enterocytes produced more pronounced changes in TEER and this phenomenon appeared also to be mediated by the CpAL system. Finally, immunofluorescence studies demonstrate that C. perfringens type C infection redistribute TJs protein occludin, and Claudin-3, and DMs protein desmoglein-2, but did not affect the AJs protein E-cadherin. PMID:27063897

  4. Novel myopic refractive correction with transepithelial very high-fluence collagen cross-linking applied in a customized pattern: early clinical results of a feasibility study

    Kanellopoulos AJ


    Full Text Available Anastasios John Kanellopoulos Institute, Athens, Greece, and New York Medical School, New York, NY, USA Background: The purpose of this study is to report the safety and efficacy of a new application of collagen cross-linking using a novel device to achieve predictable refractive myopic changes in virgin corneas. Methods: Four cases were treated with a novel device employing very high-fluence collagen cross-linking applied in a myopic pattern. Prior to treatment, riboflavin solution was applied to the intact epithelium. The collagen cross-linking device was then engaged for a total of 12 J/cm2, to be applied transepithelially in a predetermined pattern. Cornea clarity, corneal keratometry, and corneal topography were evaluated by both Placido disc and Scheimpflug imaging, along with cornea anterior segment optical coherence tomography and endothelial cell counts. Results: An average of 2.3 diopters was achieved in the first week in all four cases treated with the very high-fluence myopic collagen cross-linking intervention. There was a slight regression to 1.44 diopters at 1 month, which remained stable at 6-month follow-up. The mean keratometry change was from 44.90 diopters to 43.46 diopters. There was no significant change in endothelial cell counts or corneal clarity. There was some mild change in epithelial thickness distribution, with the treated area showing a slight but homogeneous reduction in mean thickness from 52 µm to 44 µm. Conclusion: This report describes the novel application of very high-fluence collagen cross-linking with a predictable well defined myopic refractive (flattening corneal effect. This technique has the advantages of essentially no postoperative morbidity, immediate visual rehabilitation, and the potential for tapering until the desired result is achieved. Keywords: myopia, refractive correction, high-fluence collagen cross-linking, clinical results

  5. Hydrogen sulfide decreases β-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption.

    Agné, Alisa M; Baldin, Jan-Peter; Benjamin, Audra R; Orogo-Wenn, Maria C; Wichmann, Lukas; Olson, Kenneth R; Walters, Dafydd V; Althaus, Mike


    In pulmonary epithelia, β-adrenergic agonists regulate the membrane abundance of the epithelial sodium channel (ENaC) and, thereby, control the rate of transepithelial electrolyte absorption. This is a crucial regulatory mechanism for lung liquid clearance at birth and thereafter. This study investigated the influence of the gaseous signaling molecule hydrogen sulfide (H2S) on β-adrenergic agonist-regulated pulmonary sodium and liquid absorption. Application of the H2S-liberating molecule Na2S (50 μM) to the alveolar compartment of rat lungs in situ decreased baseline liquid absorption and abrogated the stimulation of liquid absorption by the β-adrenergic agonist terbutaline. There was no additional effect of Na2S over that of the ENaC inhibitor amiloride. In electrophysiological Ussing chamber experiments with native lung epithelia (Xenopus laevis), Na2S inhibited the stimulation of amiloride-sensitive current by terbutaline. β-adrenergic agonists generally increase ENaC abundance by cAMP formation and activation of PKA. Activation of this pathway by forskolin and 3-isobutyl-1-methylxanthine increased amiloride-sensitive currents in H441 pulmonary epithelial cells. This effect was inhibited by Na2S in a dose-dependent manner (5-50 μM). Na2S had no effect on cellular ATP concentration, cAMP formation, and activation of PKA. By contrast, Na2S prevented the cAMP-induced increase in ENaC activity in the apical membrane of H441 cells. H441 cells expressed the H2S-generating enzymes cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, and they produced H2S amounts within the employed concentration range. These data demonstrate that H2S prevents the stimulation of ENaC by cAMP/PKA and, thereby, inhibits the proabsorptive effect of β-adrenergic agonists on lung liquid clearance. PMID:25632025

  6. Imaging of leukocyte trafficking in Alzheimer’s disease

    Gabriela eConstantin


    Full Text Available Alzheimer’s disease (AD is the most common neurodegenerative disorder and is characterized by a progressive decline of cognitive functions. The neuropathological features of AD include amyloid beta (Aβ deposition, intracellular neurofibrillary tangles derived from the cytoskeletal hyperphosphorylated tau protein, amyloid angiopathy, the loss of synapses, and neuronal degeneration. In the last decade, inflammation has emerged as a key feature of AD, but most studies have focused on the role of microglia-driven neuroinflammation mechanisms. A dysfunctional blood–brain barrier (BBB has also been implicated in the pathogenesis of AD, and several studies have demonstrated that the vascular deposition of Aβ induces the expression of adhesion molecules and alters the expression of tight junction proteins, potentially facilitating the transmigration of circulating leukocytes. Two-photon laser scanning microscopy (TPLSM has become an indispensable tool to dissect the molecular mechanisms controlling leukocyte trafficking in the central nervous system (CNS. Recent TPLSM studies have shown that vascular deposition of Aβ in the CNS promotes intraluminal neutrophil adhesion and crawling on the brain endothelium, and also that neutrophils extravasate in the parenchyma preferentially in areas with Aβ deposits. These studies have also highlighted a role for LFA-1 integrin in neutrophil accumulation in the CNS of AD-like disease models, revealing that LFA-1 inhibition reduces the corresponding cognitive deficit and AD neuropathology. In this article, we consider how current imaging techniques can help to unravel new inflammation mechanisms in the pathogenesis of AD and identify novel therapeutic strategies to treat the disease by interfering with leukocyte trafficking mechanisms.

  7. Role of Gallium and labeled leukocyte scintigraphy in AIDS patient

    Because AIDS patients frequently present with minimal symptomatology, radionuclide imaging with its ability to survey the entire body, is especially valuable. Gallium-67 citrate, the most commonly performed radionuclide study for localizing infection in these patients, is most useful for detecting opportunistic infections, especially in the thorax. A negative gallium scan, particularly when the chest X-ray is unremarkable, rules strongly against pulmonary disease. A negative gallium scan in a patient with an abnormal chest X-ray and Kaposi's sarcoma, suggests that the patient's respiratory distress is related to the neoplasm. Diffuse pulmonary parenchymal uptake of gallium in the HIV (+) patient is most often associated with PCP. While there are other causes of diffuse pulmonary uptake, the more intense or heterogeneous the uptake, the more likely the patient is to have PCP. Focal pulmonary uptake is usually associated with bacterial pneumonia although PCP may occasionally present in this fashion. Lymph node uptake of gallium is usually associated with Mycob acterium avium complex, tuberculosis, or Iymphoma. When corresponding abnormalities are present on thallium scintigraphy lymphoma is likely. Gallium positive, thallium negative, studies suggest mycobacterial disease. Labeled leukocyte imaging is not useful for detecting opportunistic infections probably because of the inflammatory response incited by these organisms. Leukocyte imaging is, however, more sensitive for detecting bacterial pneumonia. In the abdomen, gallium imaging is most useful for identifying lymphadenopathy, while labeled leukocyte imaging is superior for detecting AlDS-associated colitides. In summary, radionuclide studies are valuable diagnostic modalities in AIDS. Their success can be maximized by tailoring the study to the individual's needs

  8. Kinetics of reversible-sequestration of leukocytes by the isolated perfused rat lung

    Goliaei, B.


    The kinetics and morphology of sequestration and margination of rat leukocytes were studied using an isolated perfused and ventilated rat lung preparation. Whole rat blood, bone marrow suspension, or leukocyte suspensions, were used to perfuse the isolated rat lung. The lung was also perfused with latex particle suspensions and the passage of particles through the lung capillaries was studied. When a leukocyte suspension was perfused through the lung in the single-pass mode, the rate of sequestration decreased as more cells were perfused. In contrast, latex particles of a size comparable to that of leukocytes were totally stopped by the lung. When the leukocyte suspension was recirculated through the lung, cells were rapidly removed from circulation until a steady state was reached, after which no net removal of cells by the lung occurred. These results indicate that leukocytes are reversibly sequestered from circulation. The sequestered cells marginated and attached to the luminal surface of the endothelium of post-capillary venules and veins. A mathematical model was developed based on the assumption that the attachment and detachment of leukocytes to blood vessel walls follows first-order kinetics. The model correctly predicts the following characteristics of the system: (a) the kinetics of the sequestration of leukocytes by the lung; (b) the existence of a steady state when a suspension of leukocytes is recirculated through the lung; and (c) the independence of the fraction of cells remaining in circulation from the starting concentration for all values of starting concentration. (ERB)

  9. Goat cathelicidin-2 is secreted by blood leukocytes regardless of lipopolysaccharide stimulation.

    Srisaikham, Supreena; Suksombat, Wisitiporn; Yoshimura, Yukinori; Isobe, Naoki


    It has been reported that goat cathelicidin-2, an antimicrobial peptide, localizes in leukocytes and is present in milk. Here, we examined whether cathelicidin-2 is secreted by leukocytes. Different concentrations (10(5) -10(8) cells/mL) of blood leukocytes were cultured for 0-48 h with or without lipopolysaccharide (LPS). After culture, the concentrations of cathelicidin-2 in the conditioned media were measured. Blood was collected from male goats 0-24 h after the intravenous injection of Escherichia coli O111:B4 LPS. The plasma cathelicidin-2 concentrations were determined and the blood leukocytes immunostained with anti-cathelicidin-2 antibody to calculate the proportion of cathelicidin-2-positive cells in the total leukocytes. When higher concentrations of leukocytes were cultured, the cathelicidin-2 concentrations in the media increased significantly, whereas the addition of LPS to the media caused no further increase. The plasma cathelicidin-2 concentrations did not increase with time after LPS infusion. The proportion of cathelicidin-2-positive cells in the total leukocytes was significantly reduced 1 h after LPS injection compared with that at 0 h, but increased again at 6 h and thereafter. These results suggest that cathlicidin-2 is secreted by leukocytes even without LPS stimulation, whereas LPS may be required for cathelicidin-2-containing leukocytes to be recruited from the blood to tissues showing inflammation. PMID:26212721

  10. Relationship etween Electroacupuncture and Spleen Function on Leukocyte

    孙平龙; 周玉宝; 毛慧娟; 吴会会; 卜凌林; 孙佳; 郭衡艳


    目的:观察电针治疗白细胞减少症的疗效、特点及其与脾脏超微结构改变的关系,探讨针灸调节白细胞的作用机制.方法:通过家兔静脉注射环磷酰胺复制白细胞减少症模型,采用电针治疗,分别每天于耳缘静脉采血进行外周血白细胞计数和分类,观察血象变化,并于处死前麻醉动物,开腹取脾组织电镜下观测脾血窦基膜小孔口径大小.结果:与模型对照组比较,电针治疗组动物外周血白细胞数量迅速上升,粒细胞发生核右移(P<0.01).电针治疗组脾血窦基膜小孔口径大于模型对照组(P<0.05).结论:电针可以使白细胞减少的机体白细胞数量迅速得到恢复,在治疗的早期主要与调节脾脏功能有关.%Objective: To explore the underlying mechanism by which acupuncture regulates the peripheral leukocyte count and observe the relationship between the effects of electroacupuncture (EA) and the spleen ultrastructure in leukopenia. Methods: Leukopenia models of rabbits were established by injecting cyclophosphamide (CY) into rabbits' ear vein,and then the rabbits were treated with acupuncture. The peripheral leukocyte count and classification were measured daily. At last, after the animals were anesthesized, the abdominal cavity was opened, and a piece of spleen tissue was cut. The diameter of splenic sinusoid basal lamina eyehole was measured under electric microscope. Results: The peripheral blood leukocyte count in the EA group increased significantly with shift to right of the granulocyte nuclei compared with model control group (P<0.01). Moreover, the calibers of splenic sinusoid basal lamina eyehole in the EA group were larger than those in the model control group (P<0.05). Conclusion: Acupuncture can enhance the peripheral leukocyte count by promoting spleen activity in the early phase of leukopenia.

  11. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca).

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra T; McBain, James; Dold, Christopher; Stott, Jeffrey L


    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify "insults" and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The immunologic


    Yabluchanskiy, A.


    Hemorrhagic stroke in response to intracerebral hemorrhage is considered an aseptic form of inflammation. With this in mind the dynamics of leukocytes changes in blood and in the hemorrhagic stroke zone as main factors of inflammation are examined. Sprague-Dawley rats (N = 24) underwent surgical procedures and were divided into two groups — control group and a hemorrhagic stroke group — an injection of 2 µL of sterile saline and 2 µL of 0,2U of Collagenase-IV (S) respectively. White blood cel...

  13. The tripeptide feG inhibits leukocyte adhesion

    Davison Joseph S; Christie Emily; Mathison Ronald D


    Abstract Background The tripeptide feG (D-Phe-D-Glu-Gly) is a potent anti-inflammatory peptide that reduces the severity of type I immediate hypersensitivity reactions, and inhibits neutrophil chemotaxis and adhesion to tissues. feG also reduces the expression of β1-integrin on circulating neutrophils, but the counter ligands involved in the anti-adhesive actions of the peptide are not known. In this study the effects of feG on the adhesion of rat peritoneal leukocytes and extravasated neutro...

  14. Longitudinal evaluation of leukocyte transcripts in killer whales (Orcinus Orca)

    Sitt, Tatjana; Bowen, Lizabeth; Lee, Chia-Shan; Blanchard, Myra; McBain, James; Dold, Christopher; Stott, Jeffrey L.


    Early identification of illness and/or presence of environmental and/or social stressors in free-ranging and domestic cetaceans is a priority for marine mammal health care professionals. Incorporation of leukocyte gene transcript analysis into the diagnostic tool kit has the potential to augment classical diagnostics based upon ease of sample storage and shipment, inducible nature and well-defined roles of transcription and associated downstream actions. Development of biomarkers that could serve to identify “insults” and potentially differentiate disease etiology would be of great diagnostic value. To this end, a modest number of peripheral blood leukocyte gene transcripts were selected for application to a domestic killer whale population with a focus on broad representation of inducible immunologically relevant genes. Normalized leukocyte transcript values, longitudinally acquired from 232 blood samples derived from 26 clinically healthy whales, were not visibly influenced temporally nor by sex or the specific Park in which they resided. Stability in leukocyte transcript number during periods of health enhances their potential use in diagnostics through identification of outliers. Transcript levels of two cytokine genes, IL-4 and IL-17, were highly variable within the group as compared to the other transcripts. IL-4 transcripts were typically absent. Analysis of transcript levels on the other genes of interest, on an individual animal basis, identified more outliers than were visible when analyzed in the context of the entire population. The majority of outliers (9 samples) were low, though elevated transcripts were identified for IL-17 from 2 animals and one each for Cox-2 and IL-10. The low number of outliers was not unexpected as sample selection was intentionally directed towards animals that were clinically healthy at the time of collection. Outliers may reflect animals experiencing subclinical disease that is transient and self-limiting. The

  15. The Many Faces of Human Leukocyte Antigen-G

    Dahl, Mette; Djurisic, Snezana; Hviid, Thomas Vauvert F


    Pregnancy is an immunological paradox, where fetal antigens encoded by polymorphic genes inherited from the father do not provoke a maternal immune response. The fetus is not rejected as it would be theorized according to principles of tissue transplantation. A major contribution to fetal tolerance...... is the human leukocyte antigen (HLA)-G, a nonclassical HLA protein displaying limited polymorphism, restricted tissue distribution, and a unique alternative splice pattern. HLA-G is primarily expressed in placenta and plays multifaceted roles during pregnancy, both as a soluble and a membrane...

  16. Production of antibodies which recognize opiate receptors on murine leukocytes

    Carr, D.J.J.; Bost, K.L.; Blalock, J.E.


    An antibody has been developed which recognizes opiate receptors on cells of the immune system. This antibody blocks specific binding of the radiolabeled opiate receptor ligand, /sup 3/H-dihydromorphine, to receptors on murine splenocytes. Additionally, the anti-receptor antibody competes with ..beta..-endorphin, meta-enkephalin, and naloxone for the same binding site on the leukocytes. Moreover, the anti-receptor antibody possesses agonist activity similar to ..beta..-endorphin in suppressing cAMP production by lymphocytes. These results suggest the development of an antibody which recognizes classical opiate receptors on cells of the immune system.

  17. Arginine does not exacerbate markers of inflammation in cocultures of human enterocytes and leukocytes

    Parlesak, Alexandr; Negrier, I.; Neveux, N.;


    Enteral arginine supplementation in the critically ill has become a matter of controversy. In this study, we investigated effects of the addition of 0.4 and 1.2 mmol/L arginine in a coculture model on markers of inflammation, enterocyte layer integrity, and amino acid transport. In this model, a...... transepithelial flux of 22 amino acids, their catabolism, and the integrity of the enterocyte layer assessed as permeability of fluorescein dextran (M(r) 4400). Bacterial stimulation of intestinal epithelial cells enhanced the basolateral concentration of nitric oxide and all cytokines measured. Supplementation...... the catabolism of serine, asparagine, and lysine, and reduced glutamine catabolism. Addition of arginine increased ornithine formation and moderately reduced transepithelial transport of methionine and other amino acids. Hence, arginine supplementation does not interfere with inflammation...

  18. Clinical application of Tc-99m HMPAO labeled leukocyte imaging in inflammatory disease

    A radionuclide imaging with Tc-99m HMPAO labeled leukocyte was performed in order to determine its clinical usefulness in inflammatory disease. The mixed leukocyte isolated from 40 ml of whole blood containing 5 ml of acid citrate dextrose A and 7 ml of 6% hydroxyethyl starch was incubated with 370 MBq (10 mCi) of Tc-99m HMPAO at 37degC for 30 minutes. Because the labeling efficiency of Tc-99m HMPAO labeled leukocyte was 60.2±6.3%, the procedure of washing Tc-99m leukocyte with 5 ml of physiological saline was necessary before intravenous injection, in order to remove the unlabeled Tc-99m HMPAO. The recoveries of Tc-99m leukocyte in the blood after intravenous injection were 41.1±6.7% at 5 minutes, 33.4±2.1% at 30 minutes, and 27.2±3.4% at 2 hours after injection. Moreover, the labeled leukocyte was not stained with trypan blue. Therefore, the biological activity of the Tc-99m leukocyte was maintained as that of In-111 oxine labeled leukocyte. In the 39 patients with clinical suspicion of inflammatory disease including 15 patients with acute and chronic infectious disease where both Tc-99m leukocyte and Ga-67 citrate imagings were performed, the sensitivity, specificity and accuracy for infectious disease were 47%, 100%, and 79% with Tc-99m leukocyte, and 67%, 79%, 74% with Ga-67 citrate. These results suggest that Tc-99m HMPAO labeled leukocyte imaging is promising for evaluating inflammatory disease because of much higher specificity, the ready availability of Tc-99m HMPAO, the good image quality, and the lower radiation dose to the patient. (author)

  19. Leukocyte Responsiveness to Exercise in Individuals Positive for Human Cytomegalovirus.

    Wilson, J N; Navalta, J W


    Human cytomegalovirus (HCMV) infects 50% of adults in the United States. HCMV can become a cause for concern in individuals who have a compromised immune system, which may occur after high-intensity exercise. The purpose of this preliminary study was to characterize the lymphocyte, monocyte, and neutrophil responses to exercise in HCMV+individuals. Participants were either positive (HCMV +) or negative (HCMV-) for HCMV. Participants visited the laboratory on 3 separate occasions: HCMV screening, 100% VO2max test, and 80% VO2max run. Mixed-model factorial ANOVA procedures with repeated measures on sampling condition were performed on absolute and relative circulating lymphocytes, monocytes, and neutrophils. Significant main effects for time for both absolute and relative values were seen for all leukocyte subsets regardless of virus status. Significant differences for absolute and relative values were seen between sampling conditions for all leukocyte subsets. We report for the first time that HCMV status does not affect circulating neutrophil responses to high-intensity exercise, though exercise-induced neutrocytosis is seen during the post-exercise and 60 min post-exercise sampling conditions, regardless of HCMV status. There is no HCMV effect on circulating monocyte responses to exercise, though exercise-induced monocytosis was seen during the post-exercise sampling condition regardless of HCMV status. PMID:26837931

  20. Peripheral blood and milk leukocytes subsets of lactating Sarda ewes

    Piero Bonelli


    Full Text Available Leukocytes subpopulations in blood and milk of lactating Sarda ewes were investigated. Animals characterized by a SSC level <500×103cells/mL and a negative bacteriological examination were sampled in early, mid and late lactation. Milk differential cell count evidenced that macrophage represented the main population (42.8%±3.5 followed by lymphocytes (40.2%±3.4 and neutrophils (8,6%±2.1. Flow cytometry analysis showed that lymphocytes subsets in milk were quite different from blood. High CD8+ and low CD4+ lymphocytes percentages determined a CD4/CD8 ratio inversion in milk compared to blood (0.3%±0.03 vs 1.8%±0.08. CD8+ decreased while, conversely, CD4+ increased in late lactation. γδ T cells were more represented in milk (12.6%±1.3 than in blood (6.8%±0.3 and their proportions appeared similar throughout lactation in both compartments. IL-2 receptor was mainly expressed in milk on T cytotoxic lymphocytes. Data obtained in uninfected mammary glands could allow an early discrimination between physiological and pathological changes occurring in ewe milk. Further phenotypical and functional studies on milk leukocytes subsets might help to understand defense mechanisms of the ovine mammary gland against IMI.

  1. Early and delayed indium 111 leukocyte imaging in Crohn's disease

    Twenty-seven patients with Crohn's disease were studied for the presence and location of activity by both early (4 h) and delayed (18-24 h) indium 111 leukocyte imaging. The results were compared with other parameters of disease activity including Crohn's disease activity index, barium studies, and endoscopy. There was a correlation between early images and Crohn's disease activity index (r = 0.78) and between delayed images and index (r = 0.82). Based upon the corresponding Crohn's disease activity index, the sensitivity of early and delayed imaging was 81.0% and 95.2%, respectively. Specificity of early and delayed imaging was 75.0% and 87.0%, respectively. Presence of activity on the early and delayed imaging agreed with activity on barium studies and colonoscopy in approximately 80% of cases. Correlation of location of disease by leukocyte imaging and x-ray was observed in 58.9% of early scans and 55.0% of delayed scans. Correlation of the location of disease by imaging and endoscopy was observed in 71.4% of early and 75.0% of delayed studies. Because of the possibility of occurrence of false-negative results in early images, delayed imaging should always be included in evaluation of disease activity in patients with Crohn's disease who are suspected of having mild activity. Delayed imaging is not required if the early imaging study clearly shows activity

  2. Spinal and locus coeruleus noradrenergic lesions abolish the analgesic effects of 5-methoxy-N,N-dimethyltryptamine.

    Danysz, W; Jonsson, G; Minor, B G; Post, C; Archer, T


    Two experiments were performed on Sprague-Dawley rats to study the effects of noradrenaline and 5-hydroxytryptamine depletion upon the antinociceptive effects of acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) administration. 6-Hydroxydopamine-induced lesions following microinjections to either the locus coeruleus or the spinal cord (lumbar) abolished completely 5-MeODMT-induced analgesia in the tail-flick, hot-plate, and shock titration tests whereas 5,7-dihydroxytryptamine-induced lesions of the nucleus raphe magnus and the lumbar spinal cord attenuated 5-MeODMT analgesia in the tail-flick and shock titration tests. Thus, the experiments serve to demonstrate an important interaction between descending noradrenergic and serotonergic pathways, possibly at a spinal locus. PMID:3015120

  3. Small RNA interference-mediated gene silencing of heparanase abolishes the invasion, metastasis and angiogenesis of gastric cancer cells

    Heparanase facilitates the invasion and metastasis of cancer cells, and is over-expressed in many kinds of malignancies. Our studies indicated that heparanase was frequently expressed in advanced gastric cancers. The aim of this study is to determine whether silencing of heparanase expression can abolish the malignant characteristics of gastric cancer cells. Three heparanase-specific small interfering RNA (siRNAs) were designed, synthesized, and transfected into cultured gastric cancer cell line SGC-7901. Heparanase expression was measured by RT-PCR, real-time quantitative PCR and Western blot. Cell proliferation was detected by MTT colorimetry and colony formation assay. The in vitro invasion and metastasis of cancer cells were measured by cell adhesion assay, scratch assay and matrigel invasion assay. The angiogenesis capabilities of cancer cells were measured by tube formation of endothelial cells. Transfection of siRNA against 1496-1514 bp of encoding regions resulted in reduced expression of heparanase, which started at 24 hrs and lasted for 120 hrs post-transfection. The siRNA-mediated silencing of heparanase suppressed the cellular proliferation of SGC-7901 cells. In addition, the in vitro invasion and metastasis of cancer cells were attenuated after knock-down of heparanase. Moreover, transfection of heparanase-specific siRNA attenuated the in vitro angiogenesis of cancer cells in a dose-dependent manner. These results demonstrated that gene silencing of heparanase can efficiently abolish the proliferation, invasion, metastasis and angiogenesis of human gastric cancer cells in vitro, suggesting that heparanase-specific siRNA is of potential values as a novel therapeutic agent for human gastric cancer

  4. The effect of high intensity interval exercise on postprandial triacylglycerol and leukocyte activation--monitored for 48 h post exercise.

    Brendan Morris Gabriel

    Full Text Available Postprandial phenomenon are thought to contribute to atherogenesis alongside activation of the immune system. A single bout of high intensity interval exercise attenuates postprandial triacylglycerol (TG, although the longevity and mechanisms underlying this observation are unknown. The aims of this study were to determine whether this attenuation in postprandial TG remained 2 days after high intensity interval exercise, to monitor markers of leukocyte activation and investigate the underlying mechanisms. Eight young men each completed two three day trials. On day 1: subjects rested (Control or performed 5 x 30 s maximal sprints (high intensity interval exercise. On day 2 and 3 subjects consumed high fat meals for breakfast and 3 h later for lunch. Blood samples were taken at various times and analysed for TG, glucose and TG-rich lipoprotein (TRL-bound LPL-dependent TRL-TG hydrolysis (LTTH. Flow cytometry was used to evaluate granulocyte, monocyte and lymphocyte CD11b and CD36 expression. On day 2 after high intensity interval exercise TG area under the curve was lower (P<0.05 (7.46 ± 1.53 mmol/l/7h compared to the control trial (9.47 ± 3 .04 mmol/l/7h with no differences during day 3 of the trial. LTTH activity was higher (P<0.05 after high intensity interval exercise, at 2 hours of day 2, compared to control. Granulocyte, monocyte and lymphocyte CD11b expression increased with time over day 2 and 3 of the study (P<0.0001. Lymphocyte and monocyte CD36 expression decreased with time over day 2 and 3 (P<0.05. There were no differences between trials in CD11b and CD36 expression on any leukocytes. A single session of high intensity interval exercise attenuated postprandial TG on day 2 of the study, with this effect abolished by day 3.The reduction in postprandial TG was associated with an increase in LTTH. High intensity interval exercise had no effect on postprandial responses of CD11b or CD36.

  5. Quantitation of acute experimental ocular inflammation with 111indium-leukocytes

    The cellular component of an acute ocular inflammation in rabbits was measured with autologous leukocytes exogenously labeled with 111Indium tropolonate. Inflammation was induced by intravitreal bacterial lipopolysaccharide (LPS). After 16 hr blood was removed, leukocytes separated, labeled with 111Indium tropolonate and reinjected. Three cell fractions were examined: a leukocyte rich fraction which had been prepared with Dextran; and polymorphonuclear and mononuclear leukocyte fractions which had been prepared using a discontinuous Percoll gradient. Two hours after labeled leukocytes were injected, measurements of 111Indium were made in blood, plasma, the whole eye and in ocular compartments. From these data the numbers of each leukocyte population present were estimated and compared directly to histopathologic changes. Both polymorphonuclear and mononuclear leukocytes entered ocular tissues during the 2 hr period beginning 20 hr after LPS injection. Altered ocular vascular permeability was successfully measured with 125Iodine-albumin in some of these same rabbits. Both the number and type of inflammatory cell entering ocular tissues during a set period of time of the inflammatory response could thus be measured. This technique provides an opportunity to define the relationship of leukocyte infiltration and altered ocular vascular permeability in ocular tissues during the inflammatory response


    The aims of the study were to develop a method for harvesting leukocytes from the mouse small intestinal lumen and to identify leukocytes which enter the intestinal lumen of mice infected with Giardia muris. Giardia-infected and uninfected BALB/c mice were anesthetized, and the s...

  7. Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560

    Paskauskas Saulius


    Full Text Available Abstract Background Nonsteroidal anti-inflammatory drugs (NSAID represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro. Results NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca2+]i. Conclusions NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.

  8. Vitamin C Prevents Cigarette Smoke-Induced Leukocyte Aggregation and Adhesion to Endothelium in vivo

    Lehr, Hans-Anton; Frei, Balz; Arfors, Karl-E.


    A common feature of cigarette-smoke (CS)-associated diseases such as atherosclerosis and pulmonary emphysema is the activation, aggregation, and adhesion of leukocytes to micro- and macrovascular endothelium. A previous study, using a skinfold chamber model for intravital fluorescence microscopy in awake hamsters, has shown that exposure of hamsters to the smoke generated by one research cigarette elicits the adhesion of fluorescently labeled leukocytes to the endothelium of arterioles and small venules. By the combined use of intravital microscopy and scanning electron microscopy, we now demonstrate in the same animal model that (i) CS-induced leukocyte adhesion is not confined to the microcirculation, but that leukocytes also adhere singly and in clusters to the aortic endothelium; (ii) CS induces the formation in the bloodstream of aggregates between leukocytes and platelets; and (iii) CS-induced leukocyte adhesion to micro- and macrovascular endothelium and leukocyte-platelet aggregate formation are almost entirely prevented by dietary or intravenous pretreatment with the water-soluble antioxidant vitamin C (venules, 21.4 ± 11.0 vs. 149.6 ± 38.7 leukocytes per mm^2, P dietary means or supplementation, suggesting that vitamin C effectively contributes to protection from CS-associated cardiovascular and pulmonary diseases in humans.

  9. Early effects of ganciclovir therapy on the quantity of cytomegalovirus DNA in leukocytes of immunocompromised patients.

    Boivin, G; Quirk, M R; Kringstad, B A; Germain, M.; Jordan, M C


    The cytomegalovirus (CMV) DNA load in leukocytes was measured in 26 immunocompromised patients with CMV disease before and after 10 days of intravenous ganciclovir therapy. Before therapy, the circulating DNA burden of bone marrow transplant recipients was significantly lower than that of other transplant or AIDS patients. Ganciclovir induction therapy significantly decreased the viral DNA load in the leukocyte populations of most patients.

  10. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge;


    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...