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Sample records for normal human myocardium

  1. Fatty acid uptake in normal human myocardium

    International Nuclear Information System (INIS)

    Vyska, K.; Meyer, W.; Stremmel, W.; Notohamiprodjo, G.; Minami, K.; Machulla, H.J.; Gleichmann, U.; Meyer, H.; Koerfer, R.

    1991-01-01

    Fatty acid binding protein has been found in rat aortic endothelial cell membrane. It has been identified to be a 40-kDa protein that corresponds to a 40-kDa fatty acid binding protein with high affinity for a variety of long chain fatty acids isolated from rat heart myocytes. It is proposed that this endothelial membrane fatty acid binding protein might mediate the myocardial uptake of fatty acids. For evaluation of this hypothesis in vivo, influx kinetics of tracer-labeled fatty acids was examined in 15 normal subjects by scintigraphic techniques. Variation of the plasma fatty acid concentration and plasma perfusion rate has been achieved by modulation of nutrition state and exercise conditions. The clinical results suggest that the myocardial fatty acid influx rate is saturable by increasing fatty acid plasma concentration as well as by increasing plasma flow. For analysis of these data, functional relations describing fatty acid transport from plasma into myocardial tissue in the presence and absence of an unstirred layer were developed. The fitting of these relations to experimental data indicate that the free fatty acid influx into myocardial tissue reveals the criteria of a reaction on a capillary surface in the vicinity of flowing plasma but not of a reaction in extravascular space or in an unstirred layer and that the fatty acid influx into normal myocardium is a saturable process that is characterized by the quantity corresponding to the Michaelis-Menten constant, Km, and the maximal velocity, Vmax, 0.24 ± 0.024 mumol/g and 0.37 ± 0.013 mumol/g(g.min), respectively. These data are compatible with a nondiffusional uptake process mediated by the initial interaction of fatty acids with the 40-kDa membrane fatty acid binding protein of cardiac endothelial cells

  2. Interaction between Hsp60 and Bax in normal human myocardium and in myocardium affected by dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Tykhonkova I. O.

    2009-04-01

    Full Text Available The main functional compartments of molecular chaperone Hsp60 are mitochondria and cytoplasm. Up to 30 % of Hsp60 are located in cytoplasm of cardiomyocytes. The interaction between molecular chaperone Hsp60 and proapoptotic Bax protein in the cytoplasmic fraction from normal human heart tissue has been revealed by co-immunoprecipitation in contrast to myocardium affected by dilated cardiomyopathy, where this interaction has not been observed

  3. Bioengineering Human Myocardium on Native Extracellular Matrix

    Science.gov (United States)

    Guyette, Jacques P.; Charest, Jonathan M; Mills, Robert W; Jank, Bernhard J.; Moser, Philipp T.; Gilpin, Sarah E.; Gershlak, Joshua R.; Okamoto, Tatsuya; Gonzalez, Gabriel; Milan, David J.; Gaudette, Glenn R.; Ott, Harald C.

    2015-01-01

    Rationale More than 25 million individuals suffer from heart failure worldwide, with nearly 4,000 patients currently awaiting heart transplantation in the United States. Donor organ shortage and allograft rejection remain major limitations with only about 2,500 hearts transplanted each year. As a theoretical alternative to allotransplantation, patient-derived bioartificial myocardium could provide functional support and ultimately impact the treatment of heart failure. Objective The objective of this study is to translate previous work to human scale and clinically relevant cells, for the bioengineering of functional myocardial tissue based on the combination of human cardiac matrix and human iPS-derived cardiac myocytes. Methods and Results To provide a clinically relevant tissue scaffold, we translated perfusion-decellularization to human scale and obtained biocompatible human acellular cardiac scaffolds with preserved extracellular matrix composition, architecture, and perfusable coronary vasculature. We then repopulated this native human cardiac matrix with cardiac myocytes derived from non-transgenic human induced pluripotent stem cells (iPSCs) and generated tissues of increasing three-dimensional complexity. We maintained such cardiac tissue constructs in culture for 120 days to demonstrate definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction. To show that functional myocardial tissue of human scale can be built on this platform, we then partially recellularized human whole heart scaffolds with human iPSC-derived cardiac myocytes. Under biomimetic culture, the seeded constructs developed force-generating human myocardial tissue, showed electrical conductivity, left ventricular pressure development, and metabolic function. Conclusions Native cardiac extracellular matrix scaffolds maintain matrix components and structure to support the seeding and engraftment of human iPS-derived cardiac myocytes, and enable

  4. Myocardial thallium-201 kinetics in normal and ischemic myocardium

    International Nuclear Information System (INIS)

    Grunwald, A.M.; Watson, D.D.; Holzgrefe, H.H. Jr.; Irving, J.F.; Beller, G.A.

    1981-01-01

    The net myocardial accumulation of thallium-201 after injection depends upon the net balance between continuing myocardial extraction from low levels of recirculating thallium in the blood compartment and the net rate of efflux of thallium from the myocardium into the extracardiac blood pool. These experiments were designed to measure separately the myocardial extraction and intrinsic myocardial efflux of thallium-201 at normal and at reduced rates of myocardial blood flow. The average myocardial extraction fraction at normal blood flow in 10 anesthetized dogs was 82 +/- 6% (+/- SD) at normal coronary arterial perfusion pressures and increased insignificantly, to 85 +/- 7%, at coronary perfusion pressures of 10--35 mm Hg. At normal coronary arterial perfusion pressures in 12 additional dogs, the intrinsic thallium washout in the absence of systemic recirculation had a half-time (T 1/2) of 54 +/- 7 minutes. The intrinsic cellular washout rate began to increase as distal perfusion pressures fell below 60 mm Hg and increased markedly to a T 1/2 of 300 minutes at perfusion pressures of 25--30 mm Hg. A second, more rapid component of intrinsic thallium washout (T 1/2 2.5 minutes) representing approximately 7% of the total initially extracted myocardial thallium was observed. The faster washout component is presumed to be due to washout of interstitial thallium unextracted by myocardial cells, whereas the slower component is presumed due to intracellular washout. The net clearance time of thallium measured after i.v. injection is much longer than the intrinsic myocardial cellular washout rate because of continuous replacement of myocardial thallium from systemic recirculation. Myocardial redistribution of thallium-201 in states of chronically reduced perfusion cannot be the result of increased myocardial extraction efficiency, but rather, is the result of the slower intrinsic cellular washout rate at reduced perfusion levels

  5. Wave propagation simulation in normal and infarcted myocardium: computational and modelling issues

    NARCIS (Netherlands)

    Maglaveras, N.; van Capelle, F. J.; de Bakker, J. M.

    1998-01-01

    Simulation of propagating action potentials (PAP) in normal and abnormal myocardium is used for the understanding of mechanisms responsible for eliciting dangerous arrhythmias. One- and two-dimensional models dealing with PAP properties are reviewed in this paper viewed both from the computational

  6. Metabolic reserve in normal myocardium assessed by positron emission tomography with C-11 palmitate

    International Nuclear Information System (INIS)

    Tamaki, Nagara; Kawamoto, Masahide; Takahashi, Norio; Yonekura, Yoshiharu; Magata, Yasuhiro; Nohara, Ryuji; Kambara, Hirofumi; Kawai, Chuichi; Konishi, Junji

    1991-01-01

    Positron emission tomography (PET) with C-11 palmitate has been used in estimating the myocardial utilization of free fatty acid. To assess the metabolic reserve in normal subjects, a PET study was performed at control and during dobutamine infusion at 2 hour intervals in 5 normal subjects. Following monoexponential curve fitting of the time activity curve of the myocardium, the clearance half time (min) and residual fraction (%) were calculated as indices of β-oxydation of free fatty acid. A significant increase in the heart rate and systolic blood pressure were observed during dobutamine infusion (65±5 vs 100±29 bpm, p<0.05 and 119±12 vs 144±16 mmHg, p<0.01, respectively). The clearance half-time and the residual fraction were significantly decreased (23.4±2.6 vs 15.8±2.3 min and 67.0±2.5 vs 58.6±4.0%, p<0.05, each). When the left ventricular myocardium was divided into 4 segments, these indices were similar at control and uniformly decreased without regional differences during dobutamine infusion. These data suggest that β-oxydation of free fatty acid may be uniformly increased in the left ventricular myocardium in relation to the increase in cardiac work in normal subjects. PET with C-11 palmitate at control and during dobutamine infusion is considered to be promising in assessing metabolic reserve in the myocardium. (author)

  7. Wave propagation simulation in normal and infarcted myocardium: computational and modelling issues.

    Science.gov (United States)

    Maglaveras, N; Van Capelle, F J; De Bakker, J M

    1998-01-01

    Simulation of propagating action potentials (PAP) in normal and abnormal myocardium is used for the understanding of mechanisms responsible for eliciting dangerous arrhythmias. One- and two-dimensional models dealing with PAP properties are reviewed in this paper viewed both from the computational and mathematical aspects. These models are used for linking theoretical and experimental results. The discontinuous nature of the PAP is demonstrated through the combination of experimental and theoretically derived results. In particular it can be shown that for increased intracellular coupling resistance the PAP upstroke phase properties (Vmax, dV/dtmax and tau foot) change considerably, and in some cases non-monotonically with increased coupling resistance. It is shown that tau foot) is a parameter that is very sensitive to the cell's distance to the stimulus site, the stimulus strength and the coupling resistance. In particular it can be shown that in a one-dimensional structure the tau foot value can increase dramatically for lower coupling resistance values near the stimulus site and subsequently can be reduced as we move to distances larger than five resting length constants from the stimulus site. The tau foot variability is reduced with increased coupling resistance, rendering the lower coupling resistance structures, under abnormal excitation sequences, more vulnerable to conduction block and arrhythmias. Using the theory of discontinuous propagation of the PAP in the myocardium it is demonstrated that for specific abnormal situations in the myocardium, such as infarcted tissue, one- and two-dimensional models can reliably simulate propagation characteristics and explain complex phenomena such as propagation at bifurcation sites and mechanisms of block and re-entry. In conclusion it is shown that applied mathematics and informatics can help in elucidating electrophysiologically complex mechanisms such as arrhythmias and conduction disturbances in the myocardium.

  8. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    Energy Technology Data Exchange (ETDEWEB)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Mongillo, Marco; Khan, Muhammad T. [Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); Depre, Christophe [University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, New Jersey, NJ (United States); University of Medicine and Dentistry New Jersey, Cardiovascular Research Institute, Department of Medicine, New Jersey, NJ (United States); Rimoldi, Ornella E. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom); New York Medical College, Cardiovascular Research Institute, Department of Medicine, Valhalla, NY (United States); Camici, Paolo G. [Imperial College, Hammersmith Hospital, National Heart and Lung Institute, London (United Kingdom); Imperial College, Hammersmith Hospital, Medical Research Council Clinical Sciences Centre, London (United Kingdom)

    2007-12-15

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([{sup 11}C]meta-hydroxy-ephedrine; HED) and {beta}-adrenoceptor ({beta}-AR) density ([{sup 11}C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V{sub d}) of HED in HM (47.95{+-}28.05 ml/g) and infarcted myocardium (42.69{+-}25.76 ml/g) was significantly reduced compared with controls (66.09{+-}14.48 ml/g). The V{sub d} of HED in normal myocardium (49.93{+-}20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial {beta}-AR density was significantly lower in HM (5.49{+-}2.35 pmol/g), infarcted (4.82{+-}2.61 pmol/g) and normal (5.86{+-}1.81 pmol/g) segments of patients compared with healthy controls (8.61{+-}1.32 pmol/g). Noradrenaline uptake-1 mechanism and {beta}-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  9. Apolipoprotein H, a new mediator in the inflammatory changes ensuring in jeopardised human myocardium

    NARCIS (Netherlands)

    Niessen, H. W.; Lagrand, W. K.; Rensink, H. J.; Meijer, C. J.; Aarden, L.; Hack, C. E.; Visser, C.

    2000-01-01

    AIM: To investigate the presence of membrane "flip flop" in ischaemic human myocardium, we assessed depositions of apolipoprotein H (apoH; beta 2-glycoprotein 1) in ischaemic myocardium. Serum protein apoH can bind to negatively charged phospholipids and can also inhibit blood coagulation in vitro.

  10. Dynamic changes in cardiac fatty acid metabolism in the stunned human myocardium

    International Nuclear Information System (INIS)

    Ito, Kazuki; Kawasaki, Tatsuya; Katoh, Shuji

    2001-01-01

    The chronological changes or mechanisms in cardiac fatty acid metabolism under clinical conditions of hypoxia and ischemia have not been fully elucidated. 123 I-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) can be used with single photon emission computed tomography (SPECT) to evaluate myocardial fatty acid metabolism. We investigated chronological changes in energy metabolism in the stunned human myocardium by means of 123 I-BMIPP myocardial SPECT. We conducted 123 I-BMIPP myocardial SPECT in 10 patients with stunned myocardium during the acute, subacute and chronic phases after onset. The left ventricle was divided into 9 regions on SPECT, and the degree of abnormalities in each region was scored in four grades from normal (0) to defect (4). We also examined wash-out rates on BMIPP images. The scores on early BMIPP images in the acute, subacute and chronic phases were 5.6±1.8, 13.4±3.5 and 2.5±1.1, respectively, and the score was highest in the subacute phase (p<0.001). Similarly, scores on the late images were 2.3±1.7, 18.3±4.5 and 4.7±2.6, respectively, and highest in the subacute phase (p<0.001). The wash-out rates (normal: 18.2±2.1%) in the acute, subacute and chronic phases were 12.1±4.8%, 44.9±10.0% and 23.1±4.6%, respectively, with the value being lowest during the acute phase (p<0.05), and highest during the subacute phase (p<0.001). There results suggested that fatty acid metabolism in the stunned human myocardium changes dynamically over time. (author)

  11. RNA extraction from healthy and failing human myocardium: a comparative evaluation.

    Science.gov (United States)

    Hong, Yaejee H; Martin, Lisa A; Mulvaney, Jason M; Burhans, Michael S; Blaxall, Burns C; Hinton, Robert B

    2015-04-01

    Isolation of high-quality RNA from tissue is mandatory for producing reliable data for downstream applications. In heart tissue, the relative strengths and weaknesses of different approaches to isolate total RNA are unknown. The objective of this study was to compare different RNA isolation methods in healthy and diseased human myocardium. Frozen left ventricular myocardium was obtained from individuals with heart failure and individuals who died from non-cardiac causes with normal heart function (control). Three extraction methods, including guanidine isothiocyanate (TRIzol), silica-gel column (RNeasy), and the combination method (TRIzol/RNeasy), were assessed for their effect on the yield, integrity, and gene expression levels of RNA using quantitative real-time PCR. In the control group (n=5), the highest RNA yield per tissue mass was obtained with TRIzol, and a significantly higher RNA integrity was obtained from the RNeasy method. The quantification cycle (Cq) values for both the reference gene GAPDH and two target genes were lower with TRIzol. Normalization by GAPDH showed the highest gene expression levels with RNeasy. Similar patterns were observed in the heart failure group (n=5), suggesting assays were not negatively impacted by myocardial disease processes. In both healthy and diseased heart tissue, the TRIzol method provides the highest RNA yield, while the RNeasy method shows superior RNA integrity, demonstrating comparable RNA quality in studies examining myocardial disease. A balanced approach to RNA quality is necessary for the successful downstream applications of RNA.

  12. Pre- and post-synaptic sympathetic function in human hibernating myocardium

    International Nuclear Information System (INIS)

    John, Anna S.; Pepper, John R.; Dreyfus, Gilles D.; Pennell, Dudley J.; Mongillo, Marco; Khan, Muhammad T.; Depre, Christophe; Rimoldi, Ornella E.; Camici, Paolo G.

    2007-01-01

    Impaired pre-synaptic noradrenaline uptake-1 mechanism has been reported in a swine model of hibernating myocardium (HM). To ascertain whether adrenergic neuroeffector abnormalities are present in human HM, we combined functional measurements in vivo using cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) to assess pre- and post-synaptic sympathetic function. Twelve patients with coronary artery disease and chronic left ventricular (LV) dysfunction underwent CMR at baseline and 6 months after bypass for assessment of regional and global LV function and identification of segments with reversible dysfunction. Before surgery, myocardial noradrenaline uptake-1 ([ 11 C]meta-hydroxy-ephedrine; HED) and β-adrenoceptor (β-AR) density ([ 11 C]CGP-12177) were measured with PET. Patient PET data were compared with those in 18 healthy controls. The volume of distribution (V d ) of HED in HM (47.95±28.05 ml/g) and infarcted myocardium (42.69±25.76 ml/g) was significantly reduced compared with controls (66.09±14.48 ml/g). The V d of HED in normal myocardium (49.93±20.48 ml/g) of patients was also lower than that in controls and the difference was close to statistical significance (p=0.06). Myocardial β-AR density was significantly lower in HM (5.49±2.35 pmol/g), infarcted (4.82±2.61 pmol/g) and normal (5.86±1.81 pmol/g) segments of patients compared with healthy controls (8.61±1.32 pmol/g). Noradrenaline uptake-1 mechanism and β-AR density are reduced in the myocardium of patients with chronic LV dysfunction and evidence of HM. The increased sympathetic activity to the heart in these patients is a generalised rather than regional phenomenon which is likely to contribute to the remodelling process of the whole LV rather than playing a causative role in HM. (orig.)

  13. Myocardial kinetics of thallium-201 after stress in normal and perfusion-reduced canine myocardium

    International Nuclear Information System (INIS)

    Okada, R.D.

    1985-01-01

    Despite the emerging use of quantitative computer programs for assessing myocardial thallium uptake and clearance after exercise, little is known about the kinetics of thallium after exercise stress. Accordingly, 11 mongrel dogs with experimental left anterior descending coronary stenoses were given thallium during norepinephrine infusion to simulate exercise. The infusion was discontinued and thallium activity was monitored regionally using miniature radiation detectors for 3 hours. Heart rate, arterial pressure and double product all increased significantly during norepinephrine infusion. The mean fractional myocardial thallium clearance was lower (0.47 +/- 0.03 [+/- standard error of the mean]) for the stenosis zone than for the no-stenosis zone (0.57 +/- 0.03) (p less than 0.0001). The stress blood flow ratio (stenosis/no-stenosis zone = 0.27 +/- 0.06) was significantly lower than the final thallium activity ratio (0.68 +/- 0.07) (p less than 0.001), consistent with thallium redistribution occurring over the 3-hour period. Myocardial thallium activity in the stenosis zone peaked in a mean of 2.2 minutes, then washed out biexponentially with a final decay constant of 0.0035 +/- 0.0005 min-1. Myocardial thallium activity in the no-stenosis zone peaked within 1 minute in all dogs, then washed out biexponentially, with a final decay constant of 0.0043 +/- 0.0003 (p less than 0.001 compared with stenosis zone). In conclusion, fractional clearance of thallium can differentiate myocardium distal to a coronary artery stenosis from that supplied by a normal coronary vessel

  14. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    NARCIS (Netherlands)

    X.Y. Du (Xiaoyi); R.G. Schoemaker (Regien); E. Bos (Egbert); P.R. Saxena (Pramod Ranjan)

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised

  15. Distribution and function of sodium channel subtypes in human atrial myocardium

    NARCIS (Netherlands)

    Kaufmann, Susann G.; Westenbroek, Ruth E.; Maass, Alexander H.; Lange, Volkmar; Renner, Andre; Wischmeyer, Erhard; Bonz, Andreas; Muck, Jenny; Ertl, Georg; Catterall, William A.; Scheuer, Todd; Maier, Sebastian K. G.

    Voltage-gated sodium channels composed of a pore-forming alpha subunit and auxiliary beta subunits are responsible for the upstroke of the action potential in cardiac muscle. However, their localization and expression patterns in human myocardium have not yet been clearly defined. We used

  16. The Frank-Starling mechanism involves deceleration of cross-bridge kinetics and is preserved in failing human right ventricular myocardium.

    Science.gov (United States)

    Milani-Nejad, Nima; Canan, Benjamin D; Elnakish, Mohammad T; Davis, Jonathan P; Chung, Jae-Hoon; Fedorov, Vadim V; Binkley, Philip F; Higgins, Robert S D; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2015-12-15

    Cross-bridge cycling rate is an important determinant of cardiac output, and its alteration can potentially contribute to reduced output in heart failure patients. Additionally, animal studies suggest that this rate can be regulated by muscle length. The purpose of this study was to investigate cross-bridge cycling rate and its regulation by muscle length under near-physiological conditions in intact right ventricular muscles of nonfailing and failing human hearts. We acquired freshly explanted nonfailing (n = 9) and failing (n = 10) human hearts. All experiments were performed on intact right ventricular cardiac trabeculae (n = 40) at physiological temperature and near the normal heart rate range. The failing myocardium showed the typical heart failure phenotype: a negative force-frequency relationship and β-adrenergic desensitization (P kinetics in human myocardium. Decreasing muscle length accelerated the rate of cross-bridge reattachment (ktr) in both nonfailing and failing myocardium (P 0.05), indicating that this regulatory mechanism is preserved in heart failure. Length-dependent assessment of twitch kinetics mirrored these findings; normalized dF/dt slowed down with increasing length of the muscle and was virtually identical in diseased tissue. This study shows for the first time that muscle length regulates cross-bridge kinetics in human myocardium under near-physiological conditions and that those kinetics are preserved in the right ventricular tissues of heart failure patients. Copyright © 2015 the American Physiological Society.

  17. Kinetics of adenylate metabolism in human and rat myocardium

    NARCIS (Netherlands)

    M. Tavenier (M.); A.C. Skladanowski (A.); R.A. de Abreu (Ronney); J.W. de Jong (Jan Willem)

    1995-01-01

    textabstractPathways producing and converting adenosine have hardly been investigated in human heart, contrasting work in other species. We compared the kinetics of enzymes associated with purine degradation and salvage in human and rat heart cytoplasm assaying for adenosine deaminase, nucleoside

  18. Characterization of the positive and negative inotropic effects of acetylcholine in the human myocardium

    OpenAIRE

    Du, Xiaoyi; Schoemaker, Regien; Bos, Egbert; Saxena, Pramod Ranjan

    1995-01-01

    textabstractIn the human isolated myocardium, acetylcholine (10−9 to 10−3 M) elicited a biphasic inotropic effect (a decrease in the lower and an increase in the higher concentration range) in atrial and a positive inotropic effect in ventricular trabeculae. However, under conditions of raised contractility achieved by exposure to noradrenaline (10−5 M), only negative inotropic effects were observed in both atria and ventricles. Atropine (10−6 M), but not propranolol (10−6 M), antagonized bot...

  19. Anisotropy of the Elastic Properties of Normal and Pathological Myocardium: Angular Dependence of Ultrasonic Backscatter, Attenuation, and Velocity.

    Science.gov (United States)

    Verdonk, Edward Dennis

    The focus of this thesis is the measurement of anisotropies in the ultrasonic parameters of soft tissues. The goal is to contribute to a better understanding of the physics which underlies the interaction of ultrasonic waves with inhomogeneous and anisotropic media. Broadband measurements using a piezoelectric transducer are reported for investigations of excised specimens of human and canine myocardial tissue. Emphasis is placed on identifying the effect that the muscle fiber orientation, relative to the direction of insonification, has on the propagation and scattering properties of ultrasonic waves. Results of the anisotropy of backscatter, the anisotropy of attenuation, and the anisotropy of quasilongitudinal velocity are presented for data obtained in 2^ circ increments through the full 360 ^circ relative to the myofibers. Measured velocities are used in conjunction with measured specimen densities to determine the elastic stiffness constants c_{11} and c_ {33} and to estimate specific mechanical moduli for thin layers of myocardium.

  20. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents.

    Science.gov (United States)

    Liu, Alexander; Wijesurendra, Rohan S; Francis, Jane M; Robson, Matthew D; Neubauer, Stefan; Piechnik, Stefan K; Ferreira, Vanessa M

    2016-01-01

    The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p stress can differentiate between normal, infarcted, ischemic, and remote myocardium with distinctive T1 profiles. Stress/rest T1 mapping holds promise for ischemia detection without the need for gadolinium contrast. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Enhanced Electrical Integration of Engineered Human Myocardium via Intramyocardial versus Epicardial Delivery in Infarcted Rat Hearts.

    Directory of Open Access Journals (Sweden)

    Kaytlyn A Gerbin

    Full Text Available Cardiac tissue engineering is a promising approach to provide large-scale tissues for transplantation to regenerate the heart after ischemic injury, however, integration with the host myocardium will be required to achieve electromechanical benefits. To test the ability of engineered heart tissues to electrically integrate with the host, 10 million human embryonic stem cell (hESC-derived cardiomyocytes were used to form either scaffold-free tissue patches implanted on the epicardium or micro-tissue particles (~1000 cells/particle delivered by intramyocardial injection into the left ventricular wall of the ischemia/reperfusion injured athymic rat heart. Results were compared to intramyocardial injection of 10 million dispersed hESC-cardiomyocytes. Graft size was not significantly different between treatment groups and correlated inversely with infarct size. After implantation on the epicardial surface, hESC-cardiac tissue patches were electromechanically active, but they beat slowly and were not electrically coupled to the host at 4 weeks based on ex vivo fluorescent imaging of their graft-autonomous GCaMP3 calcium reporter. Histologically, scar tissue physically separated the patch graft and host myocardium. In contrast, following intramyocardial injection of micro-tissue particles and suspended cardiomyocytes, 100% of the grafts detected by fluorescent GCaMP3 imaging were electrically coupled to the host heart at spontaneous rate and could follow host pacing up to a maximum of 300-390 beats per minute (5-6.5 Hz. Gap junctions between intramyocardial graft and host tissue were identified histologically. The extensive coupling and rapid response rate of the human myocardial grafts after intramyocardial delivery suggest electrophysiological adaptation of hESC-derived cardiomyocytes to the rat heart's pacemaking activity. These data support the use of the rat model for studying electromechanical integration of human cardiomyocytes, and they

  2. Myocardial perfusion of infarcted and normal myocardium in propofol-anesthetized minipigs using 82Rubidium PET

    DEFF Research Database (Denmark)

    Rasmussen, Thomas; Larsen, Bjarke Follin; Kastrup, Jens

    2016-01-01

    propofol, used for anesthesia, can influence myocardial perfusion and coronary flow reserve due to its vasorelaxant effect, and interactions might exist between propofol and used stress agents, potentially affecting the result of the examination. We present cardiac 82Rb-PET studies performed in propofol......Cardiac Rubidium-82 (82Rb) positron-emission-tomography (PET) is a good method for quantification of myocardial blood flow in man. Quantification of myocardial blood flow in animals to evaluate new treatment strategies or to understand underlying disease is also of great interest but raises some...... challenges. Animals, which have been anesthetized during PET acquisition, might react differently to used stress medications, and therefore difficulties might exist while evaluating the resulting PET images using standard software packages from commercial vendors optimized for human hearts. Furthermore...

  3. Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

    Directory of Open Access Journals (Sweden)

    Lucio Barile

    2012-01-01

    Full Text Available The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34+ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an “off-the-shelf” product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  4. Synchronous In Situ ATPase Activity, Mechanics, and Ca2+ Sensitivity of Human and Porcine Myocardium

    Czech Academy of Sciences Publication Activity Database

    Griffiths, P. J.; Isackson, H.; Pelc, Radek; Redwood, C.S.; Funari, S.S.; Watkins, H.; Ashley, C. C.

    2009-01-01

    Roč. 97, č. 9 (2009), s. 2503-2512 ISSN 0006-3495 R&D Projects: GA MŠk(CZ) LC06063 Grant - others:EC(XE) RII3-CT-2004-506008 Institutional research plan: CEZ:AV0Z50110509 Keywords : myocardium * actomyosin- ATPase * synchrotron-radiation Subject RIV: ED - Physiology Impact factor: 4.390, year: 2009

  5. Regional heterogeneity of myocardial perfusion in healthy human myocardium: assessment with magnetic resonance perfusion imaging.

    Science.gov (United States)

    Muehling, Olaf M; Jerosch-Herold, Michael; Panse, Prasad; Zenovich, Andrey; Wilson, Betsy V; Wilson, Robert F; Wilke, Norbert

    2004-01-01

    The knowledge of myocardial perfusion in healthy volunteers is fundamental for evaluation of patients with ischemic heart disease. The study was conducted to determine range, regional variability, and transmural gradient of myocardial perfusion in normal volunteers with Magnetic Resonance Perfusion Imaging (MRPI). Perfusion was assessed in 17 healthy volunteers (age: 20-47 yr, 11 males) at rest and adenosine-induced hyperemia using a 1.5 T MR scanner. Perfusion was quantified (mL/g/min) for the transmural myocardium and separately for the endo- and epimyocardium in the anterior, lateral, posterior, and septal left ventricular wall using the Fermi model for constrained deconvolution. Regional variabilities for resting, hyperemic perfusion, and perfusion reserve were 22 +/- 8%, 21 +/- 10%, and 35 +/- 18%. Mean resting, hyperemic perfusion, and perfusion reserve were 1.1 +/- 0.4 mL/g/min, 4.2 +/- 1.1 mL/g/min, and 4.1 +/- 1.4. Perfusion in the septum was higher at rest (1.3 +/- 0.3 mL/g/min vs. 1.0 +/- 0.3 mL/g/min, p < 0.05) and lower during hyperemia (3.6 +/- 0.8 mL/g/min vs. 4.5 +/- 1.1 mL/g/min, p < 0.03), resulting in a reduced perfusion reserve (PR) (3.2 +/- 0.9 vs. 4.5 +/- 1.4, p < 0.01) in the septum vs. the combined anterior, lateral, and posterior segments. Resting (0.9 +/- 0.3 mL/g/min vs. 1.4 +/- 0.5 mL/g/min, p < 0.01), but not hyperemic perfusion, was lower in the epi- vs. endomyocardium, resulting in a higher epimyocardial PR (4.8 +/- 1.8 vs. 3.5 +/- 1.4, p < 0.01) in all regions but the septum, where endo- and epimyocardial perfusion and perfusion reserve were not different. A considerable regional variability of myocardial perfusion was confirmed with MRPI. The exceptional anatomical position of the septum is reflected by the lack of a perfusion gradient, which was demonstrated in all other regions but the septum.

  6. Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial.

    Science.gov (United States)

    Deja, Marek A; Wiaderkiewicz, Ryszard; Czekaj, Piotr; Czech, Ewa; Malinowski, Marcin; Machej, Leszek; Węglarzy, Andrzej; Kowalówka, Adam; Piekarska, Magda; Szurlej, Bartosz; Latusek, Tomasz

    2018-01-01

    Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical

  7. Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium

    DEFF Research Database (Denmark)

    Urbonavicius, Sigitas; Wiggers, Henrik; Bøtker, Hans Erik

    2009-01-01

    Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM)....

  8. Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

    Science.gov (United States)

    Garg, Pankaj; Broadbent, David A; Swoboda, Peter P; Foley, James R J; Fent, Graham J; Musa, Tarique A; Ripley, David P; Erhayiem, Bara; Dobson, Laura E; McDiarmid, Adam K; Haaf, Philip; Kidambi, Ananth; Crandon, Saul; Chew, Pei G; van der Geest, R J; Greenwood, John P; Plein, Sven

    2017-09-25

    Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

  9. Increased cross-bridge recruitment contributes to transient increase in force generation beyond maximal capacity in human myocardium.

    Science.gov (United States)

    Milani-Nejad, Nima; Chung, Jae-Hoon; Canan, Benjamin D; Fedorov, Vadim V; Whitson, Bryan A; Kilic, Ahmet; Mohler, Peter J; Janssen, Paul M L

    2018-01-01

    Cross-bridge attachment allows force generation to occur, and rate of tension redevelopment (k tr ) is a commonly used index of cross-bridge cycling rate. Tension overshoots have been observed briefly after a slack-restretch k tr maneuver in various species of animal models and humans. In this study, we set out to determine the properties of these overshoots and their possible underlying mechanism. Utilizing human cardiac trabeculae, we have found that tension overshoots are temperature-dependent and that they do not occur at resting states. In addition, we have found that myosin cross-bridge cycle is vital to these overshoots as inhibition of the cycle results in the blunting of the overshoots and the magnitude of the overshoots are dependent on the level of myofilament activation. Lastly, we show that the number of cross-bridges transiently increase during tension overshoots. These findings lead us to conclude that tension overshoots are likely due to a transient enhancement of the recruitment of myosin heads into the cross-bridge cycling, regulated by the myocardium, and with potential physiological significance in determining cardiac output. We show that isolated human myocardium is capable of transiently increasing its maximal force generation capability by increasing cross-bridge recruitment following slack-restretch maneuver. This process can potentially have important implications and significance in cardiac contraction in vivo. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Phosphorus JCoupling Constants of ATP in Human Myocardium and Calf Muscle

    Science.gov (United States)

    Jung, Wulf-Ingo; Widmaier, Stefan; Seeger, Uwe; Bunse, Michael; Staubert, Andreas; Sieverding, Ludger; Straubinger, Klaus; van Erckelens, Franz; Schick, Fritz; Dietze, Günther; Lutz, Otto

    1996-01-01

    Proton-decoupled31P NMR spectroscopy of the heart and calf muscle of healthy volunteers was performed with a 1.5 T whole-body imager. By use of two-dimensional chemical-shift imaging in combination with slice-selective excitation, well-resolved localized spectra (elements of 38 ml) were obtained within 20 to 35 min from which the homonuclear J coupling constants of ATP could be determined. In myocardium,Jγβ= 16.03 ± 0.17 Hz andJαβ= 15.82 ± 0.23 Hz were obtained, while the values in calf muscle wereJγβ= 17.16 ± 0.12 Hz andJαβ= 16.04 ± 0.09 Hz. The difference inJγβwas significant. According to the literature, a possible reason for greater ATP J coupling constants is a smaller fraction of ATP complexed to magnesium. However, the chemical-shift difference between α- and β-ATP, which is also a measure for the fraction of ATP complexed to magnesium, showed only a small difference in ATP complexation: 88% in myocardium and 90% in calf muscle. This small difference cannot account for the observed difference in Jγβ.

  11. Normalization in human somatosensory cortex.

    Science.gov (United States)

    Brouwer, Gijs Joost; Arnedo, Vanessa; Offen, Shani; Heeger, David J; Grant, Arthur C

    2015-11-01

    Functional magnetic resonance imaging (fMRI) was used to measure activity in human somatosensory cortex and to test for cross-digit suppression. Subjects received stimulation (vibration of varying amplitudes) to the right thumb (target) with or without concurrent stimulation of the right middle finger (mask). Subjects were less sensitive to target stimulation (psychophysical detection thresholds were higher) when target and mask digits were stimulated concurrently compared with when the target was stimulated in isolation. fMRI voxels in a region of the left postcentral gyrus each responded when either digit was stimulated. A regression model (called a forward model) was used to separate the fMRI measurements from these voxels into two hypothetical channels, each of which responded selectively to only one of the two digits. For the channel tuned to the target digit, responses in the left postcentral gyrus increased with target stimulus amplitude but were suppressed by concurrent stimulation to the mask digit, evident as a shift in the gain of the response functions. For the channel tuned to the mask digit, a constant baseline response was evoked for all target amplitudes when the mask was absent and responses decreased with increasing target amplitude when the mask was concurrently presented. A computational model based on divisive normalization provided a good fit to the measurements for both mask-absent and target + mask stimulation. We conclude that the normalization model can explain cross-digit suppression in human somatosensory cortex, supporting the hypothesis that normalization is a canonical neural computation. Copyright © 2015 the American Physiological Society.

  12. Activation of prosurvival signaling pathways during the memory phase of volatile anesthetic preconditioning in human myocardium: a pilot study.

    Science.gov (United States)

    Mellidis, Kyriakos; Ordodi, Valentin; Galatou, Eleftheria; Săndesc, Dorel; Bubenek, Serban; Duicu, Oana; Muntean, Danina; Lazou, Antigone

    2014-03-01

    According to a compelling body of evidence anesthetic preconditioning (APC) attenuates the deleterious consequences of ischemia-reperfusion and protects the heart through a mechanism similar to ischemic preconditioning. The present study was purported to investigate the intracellular signaling pathways activated in human myocardium in response to a preconditioning protocol with two different volatile anesthetics, namely isoflurane and sevoflurane. To this aim, phosphorylation of PKCα and -δ, ERK1/2, Akt, and GSK3β was determined at the end of the APC protocol, in human atrial samples harvested from patients undergoing open-heart surgery. The results demonstrate that preconditioning with volatile anesthetics triggers the activation of PKCδ and -α isoforms and of prosurvival kinases, ERK1/2, and Akt, while inhibiting their downstream target GSK3β during the memory phase.

  13. Kinetics of different 123-I and 14-C fatty acids in normal and diabetic rat myocardium in vivo

    International Nuclear Information System (INIS)

    Beckurts, T.E.; Shreeve, W.W.; Machulla, H.-J.; Feinendegen, L.E.

    1984-01-01

    For measuring myocardial metabolism by single photon scintigraphy various iodinated substrate analogues have been proposed. The present study compares in normal and diabetic rats the metabolic pathways of 14-C-palmitic acid (PA), 123-I-para-phenylpentadecanoic acid (I-pPPDA), 123-I-ortho-phenylpentadecanoic acid (I-oPPDA), 14-C-stearic acid (SA) and 123-I-w-heptadecanoic acid (I-ωHDA). In normal and diabetic rats free fatty acids showed a rapid tracer accumulation and an initial rapid, then a slow rate component of release. PA and I-pPPDA were preferentially esterified into triglycerides, whereas SA and I-ωHDA equally distributed between triglycerides and phospholipids. I-oPPDA nearly exclusively labelled the free fatty acid pool. - Turnover of SA and I-ωHDA was similar in triglycerides and phospholipids; yet PA and I-pPPDA continued to increase in triglycerides for 3-5 minutes after injection but decreased in phospholipids. - Following induction of diabetes by Streptocotocin, the primary effect was an inhibition of incorporation of all substrates tested into triglycerides and phospholipids with an initial rapid turnover in the total lipid fraction. - Of the total myocardial activities a considerable fraction was water soluble and another bound to solid tissue residue, with an early maximum and subsequent decline; the values for 14-C-labelled substrates remained below those of radioiodine. Thus different labelled fatty acids behave metabolically differently and promise to be useful for differentiating various intracellular metabolic pathways. External analysis of myocardial fatty acids metabolism requires correction for labelled catabolites. (Author)

  14. [Effect of compound danshen dripping pill combined with intravenous transplantation of human umbilical cord blood mononuclear cells on local inflammatory response in the myocardium of rabbits with acute myocardial infarction].

    Science.gov (United States)

    Deng, Liu-xia; Yu, Guo-long; Al, Qi; Yuan, Chun-ju

    2013-11-01

    To investigate effect of Compound Danshen Dripping Pill (CDDP) on the inflammatory response of the myocardium of acute myocardial infarction (AMI) rabbits, to observe the therapeutic effect of CDDP combined intravenous transplantation of human umbilical cord blood mononuclear cells (HUCBMCs) on inflammatory response, pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) , and heart function in the myocardium of AMI rabbits, and to explore the possible protective mechanisms of the combined therapy. The AMI model was successfully established by ligation of the left anterior coronary artery (LAD) in 40 healthy rabbits.Then they were randomly divided into four groups, i.e., the control group, the CDDP group, the transplantation group, and the combined group, 10 in each group. Rabbits in the control group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the CDDP group received intravenous injection of 0.5 mL normal saline via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. Rabbits in the transplantation group received intravenous injection of 0.5 mL normal saline labeled with green fluorescent protein (GFP) containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of normal saline at 5 mL per day. Rabbits in the combined group received intravenous injection of 0.5 mL normal saline labeled with GFP containing 3 x 10(7) of HUCBMCs via ear vein within 24 h after AMI and then intragastric infusion of solution obtained by solving 270 mg CDDP in 5 mL normal saline per day. At week 1 and 4 after treatment, cardiac function indices such as left ventricular fractional shorting (LVFS) and left ventricular ejection fraction (LVEF) were performed by echocardiography; the number of transplanted cells in the myocardium was found

  15. Interstitial collagen is increased in the non-infarcted human myocardium after myocardial infarction

    NARCIS (Netherlands)

    Volders, P. G.; Willems, I. E.; Cleutjens, J. P.; Arends, J. W.; Havenith, M. G.; Daemen, M. J.

    1993-01-01

    In this study we report the changes of interstitial collagen in the human non-infarcted interventricular septum after a myocardial infarction as well as in hypertrophic human hearts with or without hypertension. The collagen amount was determined with the Sirius Red morphometry technique, which

  16. Backscatter and attenuation characterization of ventricular myocardium

    Science.gov (United States)

    Gibson, Allyson Ann

    2009-12-01

    This Dissertation presents quantitative ultrasonic measurements of the myocardium in fetal hearts and adult human hearts with the goal of studying the physics of sound waves incident upon anisotropic and inhomogeneous materials. Ultrasound has been used as a clinical tool to assess heart structure and function for several decades. The clinical usefulness of this noninvasive approach has grown with our understanding of the physical mechanisms underlying the interaction of ultrasonic waves with the myocardium. In this Dissertation, integrated backscatter and attenuation analyses were performed on midgestational fetal hearts to assess potential differences in the left and right ventricular myocardium. The hearts were interrogated using a 50 MHz transducer that enabled finer spatial resolution than could be achieved at more typical clinical frequencies. Ultrasonic data analyses demonstrated different patterns and relative levels of backscatter and attenuation from the myocardium of the left ventricle and the right ventricle. Ultrasonic data of adult human hearts were acquired with a clinical imaging system and quantified by their magnitude and time delay of cyclic variation of myocardial backscatter. The results were analyzing using Bayes Classification and ROC analysis to quantify potential advantages of using a combination of two features of cyclic variation of myocardial backscatter over using only one or the other feature to distinguish between groups of subjects. When the subjects were classified based on hemoglobin A1c, the homeostasis model assessment of insulin resistance, and the ratio of triglyceride to high-density lipoprotein-cholesterol, differences in the magnitude and normalized time delay of cyclic variation of myocardial backscatter were observed. The cyclic variation results also suggested a trend toward a larger area under the ROC curve when information from magnitude and time delay of cyclic variation is combined using Bayes classification than when

  17. Collateral blood supply to the myocardium at risk in human myocardial infarction: a quantitative postmortem assessment

    NARCIS (Netherlands)

    Piek, J. J.; Becker, A. E.

    1988-01-01

    The relation between the type and size of myocardial infarcts and collateral development was studied in postmortem human hearts with a new approach that allows quantification of vascular beds. The coronary arteries were perfused with radioactive microspheres and were visualized by injecting a

  18. Tracking chromatid segregation to identify human cardiac stem cells that regenerate extensively the infarcted myocardium.

    Science.gov (United States)

    Kajstura, Jan; Bai, Yingnan; Cappetta, Donato; Kim, Junghyun; Arranto, Christian; Sanada, Fumihiro; D'Amario, Domenico; Matsuda, Alex; Bardelli, Silvana; Ferreira-Martins, João; Hosoda, Toru; Leri, Annarosa; Rota, Marcello; Loscalzo, Joseph; Anversa, Piero

    2012-09-14

    According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening. Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration. Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs. Additionally, their growth properties were determined by a series of in vitro and in vivo studies. We report that a small class of hCSCs retain during replication the mother DNA and generate 2 daughter cells, which carry the old and new DNA, respectively. hCSCs with immortal DNA form a pool of nonsenescent cells with longer telomeres and higher proliferative capacity. The self-renewal and long-term repopulating ability of these cells was shown in serial-transplantation assays in the infarcted heart; these cells created a chimeric organ, composed of spared rat and regenerated human cardiomyocytes and coronary vessels, leading to a remarkable restoration of cardiac structure and function. The documentation that hCSCs divide by asymmetrical and symmetrical chromatid segregation supports the view that the human heart is a self-renewing organ regulated by a compartment of resident hCSCs. The impressive recovery in ventricular hemodynamics and anatomy mediated by clonal hCSCs carrying the "mother" DNA underscores the clinical relevance of this stem cell class for the management of heart failure in humans.

  19. Beta(2) adrenergic receptors mediate important electrophysiological effects in human ventricular myocardium.

    Science.gov (United States)

    Lowe, M D; Rowland, E; Brown, M J; Grace, A A

    2001-07-01

    To define the effects of beta(2) adrenergic receptor stimulation on ventricular repolarisation in vivo. Prospective study. Tertiary referral centre. 85 patients with coronary artery disease and 22 normal controls. Intravenous and intracoronary salbutamol (a beta(2) adrenergic receptor selective agonist; 10-30 microg/min and 1-10 microg/min), and intravenous isoprenaline (a mixed beta(1)/beta(2) adrenergic receptor agonist; 1-5 microg/min), infused during fixed atrial pacing. QT intervals, QT dispersion, monophasic action potential duration. In patients with coronary artery disease, salbutamol decreased QT(onset) and QT(peak) but increased QT(end) duration; QT(onset)-QT(peak) and QT(peak)-QT(end) intervals increased, resulting in T wave prolongation (mean (SEM): 201 (2) ms to 233 (2) ms; p salbutamol (controls), and 70 (1) ms baseline v 108 (3) ms salbutamol (coronary artery disease); p action potential duration at 90% repolarisation shortened during intracoronary infusion of salbutamol, from 278 (4.1) ms to 257 (3.8) ms (p mechanism whereby catecholamines acting through this receptor subtype may trigger ventricular arrhythmias.

  20. Morfometria do miocárdio humano em indivíduos senis Morphometry of human myocardium in senile individuals

    Directory of Open Access Journals (Sweden)

    José Antonio Cardoso

    2006-05-01

    Full Text Available OBJETIVO: Realizar uma avaliação quantitativa nas células do miocárdio humano de indivíduos senis, nas regiões ventriculares direita, esquerda e septal. MÉTODOS: Foram utilizados cinco corações de cadáveres de indivíduos sem enfermidades cardíacas, de ambos os sexos, com idade entre 67 e 87 anos. Foram avaliados os seguintes parâmetros: área da secção transversa unitária do miócito (a o mioc; comprimento do perímetro unitário do miócito (l o mioc; volume unitário do miócito (v o mioc; densidade volumétrica dos miócitos (Vv mioc; número de miócitos por unidade de volume (Nmm ^³mio. Na análise estatística utilizou-se o teste "t" de Student. RESULTADOS: A análise das diferenças (pOBJECTIVE: To carry out a quantitative assessment in human myocardium cells of senile individuals, in right, left and septal ventricular regions. METHODS: Five hearts from corpses of individuals without heart diseases, of both sexes, with age between 67 and 87 years old were used. The following parameters were assessed: myocyte unit cross section area (myoc. a o; myocyte unit perimeter length (myoc. l o; myocyte unit volume (myoc. v o; myocyte volumetric density (myoc. Vv; number of myocytes per volume unit (Nmm ^³myoc.. The t-test of Student was used in statistic analysis. RESULTS: The analysis of differences (p < 0.05 among right (RV, left (LV and septal (S ventricular regions of human heart showed that myoc. a o values were lower in RV (1.51 ± 0.10 µm² and in S (1.55 ± 0.07 µm² in relation to LV (1.84 ± 0.24 µm². Values of myoc. l o were also shown lower in S (5.11 ± 0.46 µm comparing to LV (6.2 ± 0.97 µm. Likewise, myoc. v o and myoc. Vv showed lower values in RV (88.75 ± 25.37 µm ³; 0.39 ± 0.03% in relation to LV (122.41 ± 16.31 µm ³; 0.41 ± 0.01%. CONCLUSION: Results obtained show that there may be changes in dimensions of left ventricular wall myocyte cell during senescent stage. However, those differences are

  1. {sup 31}P magnetic resonance spectroscopy to measure in vivo cardiac energetics in normal myocardium and hypertrophic cardiomyopathy: Experiences at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Shivu, Ganesh Nallur [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom)], E-mail: drgani23@gmail.com; Abozguia, Khalid; Phan, Thanh Trung; Ahmed, Ibrar [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom); Henning, Anke [Institute for Biomedical Engineering, University and ETH Zurich, Gloriastrasse 35, CH-8092, Zurich CH ETZ F97 (Switzerland); Frenneaux, Michael [Department of Cardiovascular Medicine, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2010-02-15

    Background: {sup 31}P magnetic resonance spectroscopy (MRS) allows measurement of in vivo high-energy phosphate kinetics in the myocardium. While traditionally {sup 31}P cardiac spectroscopy is performed at 1.5 T, cardiac MRS at higher field strength can theoretically increase signal to noise ratio (SNR) and spectral resolution therefore improving sensitivity and specificity of the cardiac spectra. The reproducibility and feasibility of performing cardiac spectroscopy at 3 T is presented here in this study in healthy volunteers and patients with hypertrophic cardiomyopathy. Methods: Cardiac spectroscopy was performed using a Phillips 3T Achieva scanner in 37 healthy volunteers and 26 patients with hypertrophic cardiomyopathy (HCM) to test the feasibility of the protocol. To test the reproducibility a single volunteer was scanned eight times on separate occasions. A single voxel {sup 31}P MRS was performed using Image Selected In vivo Spectroscopy (ISIS) volume localization. Results: The mean phosphocreatine/adenosine triphosphate (PCr/ATP) ratio of the eight measurements performed on one individual was 2.11 {+-} 0.25. Bland Altman plots showed a variance of 12% in the measurement of PCr/ATP ratios. The PCr/ATP ratio was significantly reduced in HCM patients compared to controls, 1.42 {+-} 0.51 and 2.11 {+-} 0.57, respectively, P < 0.0001. (All results are expressed as mean {+-} standard deviation). Conclusions: Here we demonstrate that cardiac {sup 31}P MRS at 3 T is a reliable method of measuring in vivo high-energy phosphate kinetics in the myocardium for clinical studies and diagnostics. Based on our data an impairment of cardiac energetic state in patients with hypertrophic cardiomyopathy is indisputable.

  2. Research on Normal Human Plantar Pressure Test

    Directory of Open Access Journals (Sweden)

    Liu Xi Yang

    2016-01-01

    Full Text Available FSR400 pressure sensor, nRF905 wireless transceiver and MSP40 SCM are used to design the insole pressure collection system, LabVIEW is used to make HMI of data acquisition, collecting a certain amount of normal human foot pressure data, statistical analysis of pressure distribution relations about five stages of swing phase during walking, using the grid closeness degree to identify plantar pressure distribution pattern recognition, and the algorithm simulation, experimental results demonstrated this method feasible.

  3. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium.

    Science.gov (United States)

    Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel

    2014-03-28

    Myocardial infarction (MI) is associated with depressed cardiac contractile function and progression to heart failure. Cardiac myosin-binding protein C, a cardiac-specific myofilament protein, is proteolyzed post-MI in humans, which results in an N-terminal fragment, C0-C1f. The presence of C0-C1f in cultured cardiomyocytes results in decreased Ca(2+) transients and cell shortening, abnormalities sufficient for the induction of heart failure in a mouse model. However, the underlying mechanisms remain unclear. Here, we investigate the association between C0-C1f and altered contractility in human cardiac myofilaments in vitro. To accomplish this, we generated recombinant human C0-C1f (hC0C1f) and incorporated it into permeabilized human left ventricular myocardium. Mechanical properties were studied at short (2 μm) and long (2.3 μm) sarcomere length (SL). Our data demonstrate that the presence of hC0C1f in the sarcomere had the greatest effect at short, but not long, SL, decreasing maximal force and myofilament Ca(2+) sensitivity. Moreover, hC0C1f led to increased cooperative activation, cross-bridge cycling kinetics, and tension cost, with greater effects at short SL. We further established that the effects of hC0C1f occur through direct interaction with actin and α-tropomyosin. Our data demonstrate that the presence of hC0C1f in the sarcomere is sufficient to induce depressed myofilament function and Ca(2+) sensitivity in otherwise healthy human donor myocardium. Decreased cardiac function post-MI may result, in part, from the ability of hC0C1f to bind actin and α-tropomyosin, suggesting that cleaved C0-C1f could act as a poison polypeptide and disrupt the interaction of native cardiac myosin-binding protein C with the thin filament.

  4. Parietal podocytes in normal human glomeruli.

    Science.gov (United States)

    Bariety, Jean; Mandet, Chantal; Hill, Gary S; Bruneval, Patrick

    2006-10-01

    Although parietal podocytes along the Bowman's capsule have been described by electron microscopy in the normal human kidney, their molecular composition remains unknown. Ten human normal kidneys that were removed for cancer were assessed for the presence and the extent of parietal podocytes along the Bowman's capsule. The expression of podocyte-specific proteins (podocalyxin, glomerular epithelial protein-1, podocin, nephrin, synaptopodin, and alpha-actinin-4), podocyte synthesized proteins (vascular endothelial growth factor and novH), transcription factors (WT1 and PAX2), cyclin-dependent kinase inhibitor p57, and intermediate filaments (cytokeratins and vimentin) was tested. In addition, six normal fetal kidneys were studied to track the ontogeny of parietal podocytes. The podocyte protein labeling detected parietal podocytes in all of the kidneys, was found in 76.6% on average of Bowman's capsule sections, and was prominent at the vascular pole. WT1 and p57 were expressed in some parietal cells, whereas PAX2 was present in all or most of them, so some parietal cells coexpressed WT1 and PAX2. Furthermore, parietal podocytes coexpressed WT1 and podocyte proteins. Cytokeratin-positive cells covered a variable part of the capsule and did not express podocyte proteins. Tuft-capsular podocyte bridges were present in 15.5 +/- 3.7% of the glomerular sections. Parietal podocytes often covered the juxtaglomerular arterioles and were present within the extraglomerular mesangium. Parietal podocytes were present in fetal kidneys. Parietal podocytes that express the same epitopes as visceral podocytes do exist along Bowman's capsule in the normal adult kidney. They are a constitutive cell type of the Bowman's capsule. Therefore, their role in physiology and pathology should be investigated.

  5. Glycoprotein biosynthesis by human normal platelets

    International Nuclear Information System (INIS)

    Rodriguez, P.; Bello, O.; Apitz-Castro, R.

    1987-01-01

    Incorporation of radioactive Man, Gal, Fuc, Glc-N, and NANA into washed human normal platelets and endogenous glycoproteins has been found. Both parameters were time dependent. Analysis of hydrolyzed labeled glycoproteins by paper chromatography revealed that the radioactive monosaccharide incubated with the platelets had not been converted into other sugars. Acid hydrolysis demonstrates the presence of a glycosidic linkage. All the effort directed to the demonstration of the existence of a lipid-sugar intermediate in intact human platelets yielded negative results for Man and Glc-N used as precursors. The incorporation of these sugars into glycoproteins is insensitive to bacitracin, suggesting no involvement of lipid-linked saccharides in the synthesis of glycoproteins in human blood platelets. The absence of inhibition of the glycosylation process in the presence of cycloheximide suggests that the sugars are added to proteins present in the intact platelets. These results support the contention that glycoprotein biosynthesis in human blood platelets observed under our experimental conditions is effected through direct sugar nucleotide glycosylation

  6. Ocular torsional movements in normal humans.

    Science.gov (United States)

    Kushner, B J; Kraft, S

    1983-06-01

    We conducted three studies of compensatory ocular torsional movements in normal human subjects, using changes in the axis of astigmatism, afterimages, and direct observation with cinematography. Measurements of changes in the axis of astigmatism and the subjects' subjective perception of afterimages with a superimposed Maddox rod showed a partial compensatory intorsion on head tilt to the ipsilateral side and extorsion on head tilt to the contralateral side. Cinematography demonstrated that the eye lags behind the head in a slow rolling movement as the head is tilted. Periodic rotary movements in the direction of the head tilt partially correct the lag and result in a partial compensatory torsion. A fourth experiment excluded false torsion as an artifact in these studies.

  7. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  8. Plasma Amino Acid Abnormalities in Chronic Heart Failure. Mechanisms, Potential Risks and Targets in Human Myocardium Metabolism

    Directory of Open Access Journals (Sweden)

    Roberto Aquilani

    2017-11-01

    Full Text Available The goal of this study was to measure arterial amino acid levels in patients with chronic heart failure (CHF, and relate them to left ventricular function and disease severity. Amino acids (AAs play a crucial role for heart protein-energy metabolism. In heart failure, arterial AAs, which are the major determinant of AA uptake by the myocardium, are rarely measured. Forty-one subjects with clinically stable CHF (New York Heart Association (NYHA class II to IV were analyzed. After overnight fasting, blood samples from the radial artery were taken to measure AA concentrations. Calorie (KcalI, protein-, fat-, carbohydrate-intake, resting energy expenditure (REE, total daily energy expenditure (REE × 1.3, and cardiac right catheterization variables were all measured. Eight matched controls were compared for all measurements, with the exception of cardiac catheterization. Compared with controls, CHF patients had reduced arterial AA levels, of which both their number and reduced rates are related to Heart Failure (HF severity. Arterial aspartic acid correlated with stroke volume index (r = 0.6263; p < 0.0001 and cardiac index (r = 0.4243; p = 0.0028. The value of arterial aspartic acid (µmol/L multiplied by the cardiac index was associated with left ventricular ejection fraction (r = 0.3765; p = 0.0076. All NYHA groups had adequate protein intake (≥1.1 g/kg/day and inadequate calorie intake (KcalI < REE × 1.3 was found only in class IV patients. This study showed that CHF patients had reduced arterial AA levels directly related to clinical disease severity and left ventricular dysfunction.

  9. Consideration of Normal Variation of Perfusion Measurements in the Quantitative Analysis of Myocardial Perfusion SPECT: Usefulness in Assessment of Viable Myocardium

    International Nuclear Information System (INIS)

    Paeng, Jin Chul; Lim, Il Han; Kim, Ki Bong; Lee, Dong Soo

    2008-01-01

    Although automatic quantification software of myocardial perfusion SPECT provides highly objective and reproducible quantitative measurements, there is still some limitation in the direct use of quantitative measurements. In this study we derived parameters using normal variation of perfusion measurements, and tried to test the usefulness of these parameters. In order to calculate normal variation of perfusion measurements on myocardial perfusion SPECT, 55 patients (M:F=28:27) of low-likelihood for coronary artery disease were enrolled and 201 Tl rest / 99m Tc-MIBI stress SPECT studies were performed. Using 20-segment model, mean (m) and standard deviation (SD) of perfusion were calculated in each segment. As a myocardial viability assessment group, another 48 patients with known coronary artery disease, who underwent coronary artery bypass graft surgery (CABG) were enrolled. 201 Tl rest / 99m Tc-MIBI stress / 201 Tl 24-hr delayed SPECT was performed before CABG and SPECT was followed up 3 months after CABG. From the preoperative 24-hr delayed SPECT, Q delay (perfusion measurement), Δ delay (Q delay .m) and Z delay ((Q delay .m)/SD) were defined and diagnostic performances of them for myocardial viability were evaluated using area under curve (AUC) on receiver operating characteristic (ROC) curve analysis. Segmental perfusion measurements showed considerable normal variations among segments. In men, the lowest segmental perfusion measurement was 51.8±6.5 and the highest segmental perfusion was 87.0±5.9, and they are 58.7±8.1 and 87.3±6.0, respectively in women. In the viability assessment, Q delay showed AUC of 0.633, while those for Δ delay and Z delay were 0.735 and 0.716, respectively. The AUCs of Δ delay and Z delay were significantly higher than that of Q delay (p=0.001 and 0.018, respectively). The diagnostic performance of Δ delay , which showed highest AUC, was 85% of sensitivity and 53% of specificity at the optimal cutoff of -24.7. On automatic

  10. Capillary permeability of 99mTc-DTPA and blood flow rate in the human myocardium determined by intracoronary bolus injection and residue detection

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Efsen, F; Haunsø, S

    1992-01-01

    .7 ml.(100 g.min)-1 (SD 13.0). Similar values of blood flow rate, capillary extraction fraction and the PS product were determined in 6 patients with localized coronary atheroma without hemodynamically significant coronary artery stenosis (25-50% luminal narrowing). The values for the regional......The aims of the present study were to quantitate blood flow rate and capillary permeability of 99mTc-DTPA in the human myocardium and to assess whether capillary permeability is influenced by the presence of small degree atherosclerotic lesions. Myocardial blood flow rate and capillary permeability......, a mean value of the capillary permeability-surface area (PS) product of 54.0 ml.(100 g.min)-1 (SD 13.0) was determined from a capillary extraction of 55.0% (SD 9.4%) and a regional myocardial plasma flow rate of 74.6 ml.(100 g.min)-1 (SD 6.3) equivalent with a regional myocardial blood flow rate of 121...

  11. Imaging hypoxic myocardium

    International Nuclear Information System (INIS)

    Bae, Sang Kyun

    2005-01-01

    Hypoxia (decreased tissue oxygen tension) is a component of many diseases such as tumors, cerebrovascular diseases and ischemic heart diseases. Although hypoxia can be secondary to a low inspired pO 2 or a variety of lung disorders, the most common cause is ischemia due to an oxygen demand greater than the local oxygen supply. In the heart tissue, hypoxia is often observed in persistent low-flow states, such as hibernating myocardium. Direct 'hot spot' imaging of myocardial tissue hypoxia is potentially of great clinical importance because it may provide a means of identifying dysfunctional chronically ischemic but viable hibernating myocardium. A series of radiopharmaceuticals that incorporate nitroimidazole moieties have been synthesized to detect decreased local tissue pO 2 . In contrast to agents that localize in proportion to perfusion, these agents concentrate in hypoxic tissue. However, the ideal agents are not developed yet and the progress is very slow. Furthermore, the research focus is on tumor hypoxia nowadays. This review introduces the myocardial hypoxia imaging with summarizing the development of radiopharmaceuticals

  12. Experimental study of 99Tcm-HL91 in rat models with ischemic myocardium

    International Nuclear Information System (INIS)

    Liu Gang; Wu Hua

    2004-01-01

    Objective: To investigate the representation of 99 Tc m -HL91 in the ischemic myocardium, evaluate the diagnosis value of 99 Tc m -HL91 on hypoxic but viable myocardium. Methods: 18 rats were randomly divided into two groups of 99 Tc m -MIBI and 99 Tc m -HL91, established model of urgent ischemic myocardium, ischemic/viable regions were defined as Even' s blue and 2, 3, 5 triphenyl tetrazolium chloride (TTC), macroscopic autoradiography of heart short axis and electro- microscope were done, ischemic myocardium and normal myocardium of two groups were weighted, the radioactivity(id/g) were measured. got their uptake by counting the radioactivity ratios of ischemic myocardium to normal myocardium(T/NT). Results: In models of 99 Tc m -HL91, the normal myocardium was stained blue by Even's blue, but the ischemic myocardium and infarcted myocardium was negative. The ischemic and normal regions were stained brick red by TTC, the pathologic injury degree in ischemic regions were more severe than in normal region. One rat was dead in operation, two rats of autoradiography didn't obviously get tracer higher in the ischemic regions, six rats all visible were clearly, their density on ischemic regions were contrasted the higher contrast ratio against the normal myocardium organizations. the specific radioactivity ratio of ischemic regions to normal regions was l.634±0.354. Conclusion: 99 Tc m -HL91 can be selectively uptaken by ischemic and hypoxic but viable myocardium. Thus significant information may be obtained for in clinical diagnosis and treatment. (authors)

  13. Morphological evaluation of normal human corneal epithelium.

    DEFF Research Database (Denmark)

    Ehlers, Niels; Heegaard, Steffen; Hjortdal, Jesper Østergaard

    2010-01-01

    of corneas from 100 consecutively selected paraffin-embedded eyes were stained with hematoxylin-eosin and Periodic Acid-Schiff (PAS). All specimens were evaluated by light microscopy. The eyes were enucleated from patients with choroidal melanoma. Corneas were considered to be normal. RESULTS: Ninety of 100...... eyes were evaluated. The central epithelial, stromal and total corneal thickness was measured as 36.0 µm, 618 µm and 651µm, respectively, with a variation coefficient from 0.21 to 0.22. Pathological appearances were found in 27% of corneas, including thickened basement membrane and alterations....... The high number of pathological observations suggests that 'normal' eyes harbour and potentially accumulate considerable pathology....

  14. The variability problem of normal human walking

    DEFF Research Database (Denmark)

    Simonsen, Erik B; Alkjær, Tine

    2012-01-01

    a group of normal subjects and to test whether or not the expected differences would prove to be statistically significant. Fifteen healthy male subjects were recorded on video while they walked across two force platforms. Ten kinematic and kinetic parameters were selected and input to a statistical...... cluster analysis to determine whether or not the 15 subjects could be divided into different 'families' (clusters) of walking strategy. The net joint moments showed a variability corroborating earlier reports. The cluster analysis showed that the 15 subjects could be grouped into two clusters of 5 and 10...

  15. Glucose metabolism in ischemic myocardium

    International Nuclear Information System (INIS)

    Takahashi, Akira; Ono, Yukihiko; Sudo, Makiko; Araki, Kazuhiro; Shishido, Fumio; Uemura, Kazuo; Kadowaki, Ken; Kumagai, Tadayuki.

    1986-01-01

    We determined the myocardial metabolic rate for glucose (MMRGlc) in the ischemic or infarcted myocardium using 18-F-fluorodeoxyglucose (18-FDG) with positron emission tomography (PET), and studied energy metabolism in the ischemic myocardium. In some cases, we compared glucose metabolism images by 18-FDG with myocardial blood flow images using 15-oxygen water. Two normal subjects, seven patients with myocardial infarction and four patients with angina pectoris were studied. Coronary angiography was performed within two weeks before or after the PET study to detect ischemic areas. PET studies were performed for patients who did not eat for 5 to 6 hours after breakfast. Cannulation was performed in the pedal artery to measure free fatty acid, blood sugar, and insulin. After recording the transmission scan for subsequent correction of photon attenuation, blood pool images were recorded for two min. after the inhalation of carbon monoxide (oxygen-15) which labeled the red blood cells in vivo. After 20 min., oxygen-15 water (15 to 20 mCi) was injected for dynamic scans, and flow images were obtained. Thirty min. after this procedure, 18-FDG (5 to 6 mCi) was injected, and 60 min later, a static scan was performed and glucose metabolism images were obtained. Arterial blood sampling for the time activity curve of the tracer was performed at the same time. According to the method of Phelps et al, MMRGlc was calculated in each of the region of interest (ROI) which was located in the left ventricular wall. MMRGlc obtained from each ROI was 0 to 17 mg/100 ml/min. In normal subjects MMRGlc was 0.4 to 7.3 mg/100 ml/min. In patients with myocardial infarction, it ranged from 3 to 5 mg/100 ml/min in the infarcted lesion. In patients with angina pectoris and subendocardial infarction, MMRGlc was 7 to 17 mg/100 ml/min in the ischemic lesion. In this lesion, myocardial blood flow was relatively low by oxygen-15 imagings (so-called mismatch). (J.P.N.)

  16. Faecal Endotoxin in Human Volunteers: Normal Values

    OpenAIRE

    Van Saene, J. J. M.; Stoutenbeek, C. P.; Van Saene, H. K. F.

    2011-01-01

    This paper presents a study measuring endotoxin levels in faeces of healthy adults using the Limulus amoebocyte lysate (LAL) microassay. Data showed mean faecal endotoxin levels of 1 mg (range 0.01-100 mg) per gram of faeces. No correlation was found with the concentration of Enterobacteriaceae in faeces and free Faecal endotoxin levels.Keywords: Endotoxin; LAL micro-assay; LPS; Faeccs; Human volunteers: Enterobacteriaceae.

  17. Normal human bone marrow and its variations in MRI

    International Nuclear Information System (INIS)

    Vahlensieck, M.; Schmidt, H.M.

    2000-01-01

    Physiology and age dependant changes of human bone marrow are described. The resulting normal distribution patterns of active and inactive bone marrow including the various contrasts on different MR-sequences are discussed. (orig.) [de

  18. SIRT1 Promotes Differentiation of Normal Human Keratinocytes

    OpenAIRE

    Blander, Gil; Bhimavarapu, Anupama; Mammone, Thomas; Maes, Daniel; Elliston, Keith; Reich, Christian; Matsui, Mary Steidl; Guarente, Leonard; Loureiro, Joseph Jorge

    2008-01-01

    Sir2 regulates lifespan in model organisms, which has stimulated interest in understanding human Sir2 homolog functions. The human Sir2 gene family comprises seven members (SIRT1–SIRT7). SIRT1, the human ortholog of the yeast Sir2 by closest sequence similarity, is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase with enzymatic properties indistinguishable from the yeast enzyme. We studied the involvement of SIRT1 in normal human keratinocyte physiology by a transcriptional mi...

  19. Establishing the proteome of normal human cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Steven E Schutzer

    2010-06-01

    Full Text Available Knowledge of the entire protein content, the proteome, of normal human cerebrospinal fluid (CSF would enable insights into neurologic and psychiatric disorders. Until now technologic hurdles and access to true normal samples hindered attaining this goal.We applied immunoaffinity separation and high sensitivity and resolution liquid chromatography-mass spectrometry to examine CSF from healthy normal individuals. 2630 proteins in CSF from normal subjects were identified, of which 56% were CSF-specific, not found in the much larger set of 3654 proteins we have identified in plasma. We also examined CSF from groups of subjects previously examined by others as surrogates for normals where neurologic symptoms warranted a lumbar puncture but where clinical laboratory were reported as normal. We found statistically significant differences between their CSF proteins and our non-neurological normals. We also examined CSF from 10 volunteer subjects who had lumbar punctures at least 4 weeks apart and found that there was little variability in CSF proteins in an individual as compared to subject to subject.Our results represent the most comprehensive characterization of true normal CSF to date. This normal CSF proteome establishes a comparative standard and basis for investigations into a variety of diseases with neurological and psychiatric features.

  20. Absorption of orally administered 65Zn by normal human subjects

    International Nuclear Information System (INIS)

    Aamodt, R.L.; Rumble, W.F.; Johnston, G.S.; Markley, E.J.; Henkin, R.I.

    1981-01-01

    Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption

  1. Bacteriostatic enterochelin-specific immunoglobulin from normal human serum

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.G.; Yancey, R.J.; Lankford, C.E.; Earhart, C.F.

    1980-02-01

    Heat-inactivated normal human serum produces iron-reversible bacteriostasis of a number of microorganisms. This inhibitory effect was abolished by adsorption of serum with ultraviolet-killed cells of species that produce the siderophore enterochelin. Bacteriostasis also was alleviated by asorption of serum with 2,3-dihydroxy-N-benzoyl-L-serine, a degradation product of enterochelin, bound to the insoluble matrix AH-Sepharose 4B. Our results indicate that enterochelin-specific immunoglobulins exist in normal human serum. These immunoglobulins may act synergistically with transferrin to effect bacteriostasis of enterochelin-producing pathogens.

  2. [Effects of intravenous transplantation of human umbilical cord blood mononuclear cells combined compound Danshen dripping pills on the microenvironment and apoptosis in the myocardium of the rabbits with acute myocardial infarction].

    Science.gov (United States)

    Yuan, Chunjun; Ai, Qi; Deng, Liuxia; Yu, Guolong

    2013-08-01

    To explore the effects of compound Danshen dripping pills (CDDP) and CDDP combined with transplantation of human umbilical cord blood cells (HUMNCs) on the inflammatory response, oxidative stress, myocardial cell apoptosis and cardiac function, and also to investigate the possible mechanisms of the combined therapy in the acute myocardial infarction (AMI). Rabbit model of AMI successfully established by ligation of the left anterior coronary artery (LAD). Forty rabbits were randomly divided into 4 groups (n=10 per group): a control group, injected with 0.5 mL of saline in 24 h after AMI and then gavaged with 5 mL of saline daily; a CDDP group, injected with saline 0.5 mL after AMI and then gavaged with CDDP (270 mg/d) daily; a transplantation group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs [labeled with green fluorescent protein (GFP)] and then gavaged with 5 mL of saline daily; a combined group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs (labeled with GFP) and then gavaged with CDDP (270 mg/d) daily. Cardiac function index such as left ventricular fractional shorting (LVFS) and ejection fraction(LVEF) were measured by echocardiography; the pathological changes were observed by HE staining and the white blood cells in the myocardium were determined by light microscopy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected by nitrotetrazolium blue chloride (NBT) and thiobarbituric acid colorimetric measurement respectively. The number of transplanted cells in the myocardium was examined by GFP positive cells counted with fluorescence microscopy. 1) Compared with the control group (at 1 or 4 week), LVEF and LVFS were significant improved in the CDDP group, the transplantation group and the combined groups (all Pmyocardial cell apoptosis ratio were decreased significantly in the CDDP group, the transplantation group and the combined groups (all Pmyocardial infarction area in the

  3. Pyrophosphate scan of the temporarily ischemized dog myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F.; Novak, J.; Vizda, J.; Kubicek, J.; Kafka, P.; Veverkova, O.

    1981-12-01

    In 9 dogs a transient myocardial ischemia was provoked using complete occlusion of the ramus interventricularis anterior of the left coronary artery. The occlusion was removed after 5, 10 or 15 min. Four hrs after removal of the occlusion a scan of the myocardium was carried out using sup(99m)Tc-labelled pyrophosphate. In 7 out of 9 dogs under study the scan was markedly positive, in 2 dogs negative. ECG demonstrated ischemic changes practically in all dogs; the changes became normal after removal of the occlusion, namely in 5 to 35 min. The histological examination of the tissue demonstrated in all 9 dogs only a slight impairment of the myocardium.

  4. Noncompaction myocardium in association with type Ib glycogen storage disease.

    Science.gov (United States)

    Goeppert, Benjamin; Lindner, Martin; Vogel, Monika Nadja; Warth, Arne; Stenzinger, Albrecht; Renner, Marcus; Schnabel, Philipp; Schirmacher, Peter; Autschbach, Frank; Weichert, Wilko

    2012-10-15

    Noncompaction myocardium is a rare disorder assumed to occur as an arrest of the compaction process during the normal development of the heart. Left ventricular noncompaction has been reported to be associated with a variety of cardiac and extracardiac, especially neuromuscular abnormalities. Moreover, it has been suggested that metabolic alterations could be responsible for the noncompaction. However, no association of noncompaction myocardium with type Ib glycogen storage disease (GSD) has been reported so far. Type Ib GSD is due to a defect of a transmembrane protein which results, similar to type Ia GSD, in hypoglycemia, a markedly enlarged liver and, additionally, in neutropenia, recurrent infections, and inflammatory bowel disease. Until now, no muscular or cardiac involvement has been described in type Ib GSD patients. The present case represents the first report of a noncompaction myocardium in a child with type Ib GSD who died of sudden clinical deterioration at the age of four. Copyright © 2012 Elsevier GmbH. All rights reserved.

  5. Loss of Brain Aerobic Glycolysis in Normal Human Aging.

    Science.gov (United States)

    Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

    2017-08-01

    The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...... localized adjacent to the nucleus, usually on the luminal aspect, corresponding to the localization of the Golgi complex. The latter staining pattern was seen predominantly in secretory epithelial cells. The present study thus confirms previous studies and elaborates new localizations of TGF-alpha in normal...

  7. From hundreds to thousands: Widening the normal human Urinome

    Directory of Open Access Journals (Sweden)

    Laura Santucci

    2014-12-01

    The data are related to Santucci et al. (in press [1] and available both here and at ChorusProject.org under project name “From hundreds to thousands: widening the normal human Urinome”. The material supplied to Chorus Progect.org includes technical MS spectra data only.

  8. Normalization.

    Science.gov (United States)

    Cuevas, Eduardo J.

    1997-01-01

    Discusses cornerstone of Montessori theory, normalization, which asserts that if a child is placed in an optimum prepared environment where inner impulses match external opportunities, the undeviated self emerges, a being totally in harmony with its surroundings. Makes distinctions regarding normalization, normalized, and normality, indicating how…

  9. Dynamic MRI of ferumoxide-labeled bone mesenchmal stem cells after transplantation in infarcted myocardium

    International Nuclear Information System (INIS)

    Liu Qiong; Zhao Shihua; Lu Minjie; Jiang Shiliang; Yan Chaowu; Zhang Yan; Meng Liang; Tang Yue; Meng Xianmin; Wei Yingjie; Wang Qingzhi

    2009-01-01

    Objective: To investigate the ability of magnetic resonance imaging (MRI) in tracking magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Methods: Adult Chinese mini-pigs (n=6) were subjected to open-chest experimental MI operation. Their autogeneic bone marrow-derived mesenchymal stem cells (MSCs) was cultured and doubly labeled with ferumoxides and DAPI. On the 14 th day after MSCs transplantation, the size and location of the myocardial infarction were assessed by using delayed-enhancement MRI (DE-MRI). Then the labeled MSCs were injected intramyocardially into peri-infarct zone and normal myocardium. At 24 hrs and 3 weeks after injection, the contrast and the volume of the MR-MSCs hypointense lesion from the MR images were acquired, and the contrast was determined using the difference in signal intensity between the hypointense and normal myocardium divided by signal intensity of the normal region. After humane euthanasia, the heart was excised and histology corresponding to MRI slices that demonstrated MR-MSCs lesions was performed. Repeated-measures ANOVA and a paired t test were used for comparison of the contrast and the volume of the MR-MSCs hypointense lesion at different time points. Comparisons between independent groups were performed with the standard Student t test. Results: The labeling efficiency of ferumoxides and DAPI was 100%. On the 14 th day after the MI operation, the average percentage of infracted myocardial area was (33.6±8.9)%. Twenty- four hours after MSCs transplantation, MSCs injection sites appeared as ovoid hypointensive lesions with sharp border on T 2 * images. At 24 h after injection, the signal contrast [(67.00±5.48)% vs (61.92±7.76)%,t=1.65, P=0.1158] and the size [(0.56±0.24) cm 2 vs (0.52±0.25) cm 2 , t=0.39, P=0.7044] of the lesions showed no statistical difference between the peri-infarct zone and the normal myocardium. At 3 weeks after injection, the signal contrast

  10. Radiosensitivity of normal human epidermal cells in culture

    International Nuclear Information System (INIS)

    Dover, R.; Potten, C.S.

    1983-01-01

    Using an in vitro culture system the authors have derived #betta#-radiation survival curves over a dose range 0-8 Gy for the clonogenic cells of normal human epidermis. The culture system used allows the epidermal cells to stratify and form a multi-layered sheet of keratinizing cells. The cultures appear to be a very good model for epidermis in vivo. The survival curves show a population which is apparently more sensitive than murine epidermis in vivo. It remains unclear whether this is an intrinsic difference between the species or is a consequence of the in vitro cultivation of the human cells. (author)

  11. The comparison of nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201Tl re-injection imaging to detect viable myocardium

    International Nuclear Information System (INIS)

    Gao Zhou; Shi yu; Chen Hongyan; Jia Shaowei

    2002-01-01

    Objective: Employing the differences in physical properties of 99m Tc-MIBI and 201 Tl, the authors discuss the contrast result of nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging to detect viable myocardium so that authors can enhance the image quality and shorten the examination time. Method: 34 OMI patients took the 99m Tc-MIBI and 201 Tl dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging respectively in two weeks. During the peak of normal dipyridamole stress i.v. 201 Tl 100 MBq was given and myocardium imaging was taken 15 min later. The dual-isotope group was given nitroglycerin 1mg under the tongue. Five min later, i.v. 99m Tc-MIBI 1110 mBq was given. In 201 Tl re-injection group i.v. 201 Tl 40 MBq was given 4 hour later and were imaged. Among the 34 OMI patients, 19 patients undertook another 99m Tc-MIBI static imaging. Results: There are no obvious differences between nitroglycerin interventional dual-isotope myocardium perfusion imaging and 201 Tl re-injection imaging in detection rate of viable myocardium, χ 2 =0.823, p>0.25. But they have great difference in perfusion changed sectional myocardium absorb rate, t=2.73, p 2 =27.867, p 201 Tl re-injection imaging

  12. Tropical diseases of the myocardium: a review

    Directory of Open Access Journals (Sweden)

    Groom ZC

    2017-04-01

    Full Text Available Zoe C Groom,1 Aristotle D Protopapas,2 Vasileios Zochios3,4 1Costello Medical Consulting Limited, Cambridge, 2Department of Surgery, Division of Surgery and Cancer, Imperial College London, London, 3Department of Intensive Care Medicine, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, 4College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK Abstract: Cardiovascular diseases are widely distributed throughout the world. Human parasitic infections are ubiquitous. Tropical parasites are increasingly recognized as causes of cardiovascular diseases. In this review, we address the most frequently reported parasites that directly infect the myocardium, including Trypanosoma cruzi, the protozoal causative agent of American trypanosomiasis (Chagas disease, and Taenia solium, the cestode causative agent of taeniasis and cysticercosis. We also discuss tropical endomyocardial fibrosis, trichinellosis and schistosomiasis. Health systems, attitudes, the perceptions of both patients and physicians as well as socioeconomic factors should all be explored and recognized as crucial factors for improving the control of cardiovascular diseases in the tropics. Clinicians throughout the world must remain aware of imported parasites as potential causes of cardiac diseases. Keywords: cardiomyopathy, Chagas disease, myocardium, parasitic infection, tropical infections

  13. INTESTINAL VIROME AND NORMAL MICROFLORA OF HUMAN: FEATURES OF INTERACTION

    Directory of Open Access Journals (Sweden)

    Bobyr V.V.

    2015-05-01

    Full Text Available Summary: Intestinal bacteria defend the host organism and narrow pathogenic bacterial colonization. However, the microbiome effect to enteric viruses is unexplored largely as well as role of microbiota in the pathogenesis of viral infections in general. This review focuses on precisely these issues. Keywords: microbiome, virome, normal microflora, enteric viruses, contagiousness. In this review article, facts about viral persistence in the human gut are summarized. It is described the role of viral populations during health and diseases. After analyzing of the literary facts it was concluded that the gastrointestinal tract is an environment for one from the most complex microbial ecosystems, which requires of more deeper study of its composition, role in physiological processes, as well as the dynamics of changes under influence of the environment. Normal microflora performs a different important functions providing the physiological homeostasis of the human body, including, in particular, an important role in the human metabolic processes, supporting of homeostasis, limiting of colonization by infectious bacteria. The multifactorial significance of the normal gastrointestinal microflora can be divided into immunological, structural and metabolic functions. At the same time, interaction between intestinal microflora and enteric viruses has not been studied largely. In recent years, much attention is paid to study of viruses-bacteria associations, and it is possible, obtained results should change our understanding of microbiota role in the systematic pathogenesis of the diseases with viral etiology. In contrast to the well-known benefits of normal microflora to the host, the viruses can use intestinal microflora as a trigger for replication at the optimal region. Recent studies give a reason for assumption that depletion of normal microflora with antibiotics can determining the antiviral effect. Thus, the role of commensal bacteria in viral

  14. General anesthesia suppresses normal heart rate variability in humans

    Science.gov (United States)

    Matchett, Gerald; Wood, Philip

    2014-06-01

    The human heart normally exhibits robust beat-to-beat heart rate variability (HRV). The loss of this variability is associated with pathology, including disease states such as congestive heart failure (CHF). The effect of general anesthesia on intrinsic HRV is unknown. In this prospective, observational study we enrolled 100 human subjects having elective major surgical procedures under general anesthesia. We recorded continuous heart rate data via continuous electrocardiogram before, during, and after anesthesia, and we assessed HRV of the R-R intervals. We assessed HRV using several common metrics including Detrended Fluctuation Analysis (DFA), Multifractal Analysis, and Multiscale Entropy Analysis. Each of these analyses was done in each of the four clinical phases for each study subject over the course of 24 h: Before anesthesia, during anesthesia, early recovery, and late recovery. On average, we observed a loss of variability on the aforementioned metrics that appeared to correspond to the state of general anesthesia. Following the conclusion of anesthesia, most study subjects appeared to regain their normal HRV, although this did not occur immediately. The resumption of normal HRV was especially delayed on DFA. Qualitatively, the reduction in HRV under anesthesia appears similar to the reduction in HRV observed in CHF. These observations will need to be validated in future studies, and the broader clinical implications of these observations, if any, are unknown.

  15. Distribution of Dendritic Cells in Normal Human Salivary Glands

    International Nuclear Information System (INIS)

    Le, An; Saverin, Michele; Hand, Arthur R.

    2011-01-01

    Dendritic cells (DC) are believed to contribute to development of autoimmune sialadenitis, but little is known about their distribution in normal salivary glands. In this study, DC were identified and their distribution was determined in normal human parotid and submandibular glands. For light microscopy, salivary gland sections were stained with H&E or immunocytochemically using antibodies to DC markers. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of DC. In H&E sections, elongated, irregularly shaped nuclei were occasionally seen in the striated and excretory duct epithelium. Immunolabeling with anti-HLA-DR, anti-CD11c and anti-S100 revealed DC with numerous processes extending between ductal epithelial cells, often close to the lumen. Morphometric analyses indicated that HLA-DR-positive DC occupied approximately 4–11% of the duct wall volume. Similar reactive cells were present in acini, intercalated ducts and interstitial tissues. TEM observations revealed cells with indented nuclei containing dense chromatin, pale cytoplasm with few organelles, and lacking junctional attachments to adjacent cells. These results indicate that DC are abundant constituents of normal human salivary glands. Their location within ductal and acinar epithelium suggests a role in responding to foreign antigens and/or maintaining immunological tolerance to salivary proteins

  16. Super Normal Vector for Human Activity Recognition with Depth Cameras.

    Science.gov (United States)

    Yang, Xiaodong; Tian, YingLi

    2017-05-01

    The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

  17. Human papillomavirus infection in Brazilian women with normal cervical cytology.

    Science.gov (United States)

    Miranda, P M; Pitol, B C V; Moran, M S; Silva, N N T; Felix, P M; Lima-Filho, J L; Carneiro, C M; Silva, I D C G; Carvalho, R F; Lima, A A; Beçak, W; Stocco, R C

    2012-06-29

    We examined the prevalence of human papillomavirus (HPV) infection in a sample of Brazilian women presenting normal cervical cytology. Possible interactions between patient characteristics and HPV infection were analyzed in order to provide background data to improve cervical cancer screening and prophylaxis. Cervical samples of 399 women, received for routine evaluation in the Health Department of Ouro Preto, MG, Brazil, were subjected to HPV-DNA testing by PCR with MY09/11 primers. HPV-positive specimens were typed by RFLP. A structured epidemiological questionnaire was administered to each woman. HPV prevalence among these cytologically normal women was 11%. Twelve viral types were detected, the most common being HPV-16, -6, -61, -83, and -66. HPV was more prevalent in younger women; high-risk viral types were detected in 61% of the infected women and 27% of the infected women had multiple HPV infections. Significant associations of HPV infection were found with age, literacy, residence, marital status, lifetime number of sexual partners, and parity. We detected a great diversity of HPV types in women with normal cytology. This kind of information about local populations is useful for HPV prevention and vaccination strategies.

  18. Terahertz spectroscopic investigation of human gastric normal and tumor tissues.

    Science.gov (United States)

    Hou, Dibo; Li, Xian; Cai, Jinhui; Ma, Yehao; Kang, Xusheng; Huang, Pingjie; Zhang, Guangxin

    2014-09-21

    Human dehydrated normal and cancerous gastric tissues were measured using transmission time-domain terahertz spectroscopy. Based on the obtained terahertz absorption spectra, the contrasts between the two kinds of tissue were investigated and techniques for automatic identification of cancerous tissue were studied. Distinctive differences were demonstrated in both the shape and amplitude of the absorption spectra between normal and tumor tissue. Additionally, some spectral features in the range of 0.2~0.5 THz and 1~1.5 THz were revealed for all cancerous gastric tissues. To systematically achieve the identification of gastric cancer, principal component analysis combined with t-test was used to extract valuable information indicating the best distinction between the two types. Two clustering approaches, K-means and support vector machine (SVM), were then performed to classify the processed terahertz data into normal and cancerous groups. SVM presented a satisfactory result with less false classification cases. The results of this study implicate the potential of the terahertz technique to detect gastric cancer. The applied data analysis methodology provides a suggestion for automatic discrimination of terahertz spectra in other applications.

  19. Effects of isoproterenol on myocardium

    International Nuclear Information System (INIS)

    Barker, M.E.; Lieber, J.G.; Budinger, T.F.

    1982-01-01

    In the course of autoradiographic studies designed to localize 14 C-taurine within the cells of the rat myocardium, severe tissue damage was noted after stimulation by very low levels of isoproterenol. This β-adrenergic agonist had previously been shown by others to modulate taurine uptake by what appeared to be a very specific mechanism, but our studies have led to a different mechanism. Within four hours after injection of isoproterenol at all concentrations used, pronounced edema of myocytes in the subendocardium was noted; this was followed by an inflammatory reation and degeneration of mitochondria and myofilaments

  20. Normalization of Deviation: Quotation Error in Human Factors.

    Science.gov (United States)

    Lock, Jordan; Bearman, Chris

    2018-05-01

    Objective The objective of this paper is to examine quotation error in human factors. Background Science progresses through building on the work of previous research. This requires accurate quotation. Quotation error has a number of adverse consequences: loss of credibility, loss of confidence in the journal, and a flawed basis for academic debate and scientific progress. Quotation error has been observed in a number of domains, including marine biology and medicine, but there has been little or no previous study of this form of error in human factors, a domain that specializes in the causes and management of error. Methods A study was conducted examining quotation accuracy of 187 extracts from 118 published articles that cited a control article (Vaughan's 1996 book: The Challenger Launch Decision: Risky Technology, Culture, and Deviance at NASA). Results Of extracts studied, 12.8% ( n = 24) were classed as inaccurate, with 87.2% ( n = 163) being classed as accurate. A second dimension of agreement was examined with 96.3% ( n = 180) agreeing with the control article and only 3.7% ( n = 7) disagreeing. The categories of accuracy and agreement form a two by two matrix. Conclusion Rather than simply blaming individuals for quotation error, systemic factors should also be considered. Vaughan's theory, normalization of deviance, is one systemic theory that can account for quotation error. Application Quotation error is occurring in human factors and should receive more attention. According to Vaughan's theory, the normal everyday systems that promote scholarship may also allow mistakes, mishaps, and quotation error to occur.

  1. Inhibition of normal human lung fibroblast growth by beryllium.

    Science.gov (United States)

    Lehnert, N M; Gary, R K; Marrone, B L; Lehnert, B E

    2001-03-07

    Inhalation of particulate beryllium (Be) and its compounds causes chronic Be disease (CBD) in a relatively small subset ( approximately 1-6%) of exposed individuals. Hallmarks of this pulmonary disease include increases in several cell types, including lung fibroblasts, that contribute to the fibrotic component of the disorder. In this regard, enhancements in cell proliferation appear to play a fundamental role in CBD development and progression. Paradoxically, however, some existing evidence suggests that Be actually has antiproliferative effects. In order to gain further information about the effects of Be on cell growth, we: (1) assessed cell proliferation and cell cycle effects of low concentrations of Be in normal human diploid fibroblasts, and (2) investigated the molecular pathway(s) by which the cell cycle disturbing effects of Be may be mediated. Treatment of human lung and skin fibroblasts with Be added in the soluble form of BeSO(4) (0.1-100 microM) caused inhibitions of their growth in culture in a concentration-dependent manner. Such growth inhibition was found to persist, even after cells were further cultured in Be(2+)-free medium. Flow cytometric analyses of cellular DNA labeled with the DNA-binding fluorochrome DAPI revealed that Be causes a G(0)-G(1)/pre-S phase arrest. Western blot analyses indicated that the Be-induced G(0)-G(1)/pre-S phase arrest involves elevations in TP53 (p53) and the cyclin-dependent kinase inhibitor CDKN1A (p21(Waf-1,Cip1)). That Be at low concentrations inhibits the growth of normal human fibroblasts suggests the possibility of the existence of abnormal cell cycle inhibitory responses to Be in individuals who are sensitive to the metal and ultimately develop CBD.

  2. Quantification of resting myocardial blood flow velocity in normal humans using real-time contrast echocardiography. A feasibility study

    Science.gov (United States)

    Malm, Siri; Frigstad, Sigmund; Helland, Frode; Oye, Kjetil; Slordahl, Stig; Skjarpe, Terje

    2005-01-01

    Background Real-time myocardial contrast echocardiography (MCE) is a novel method for assessing myocardial perfusion. The aim of this study was to evaluate the feasibility of a very low-power real-time MCE for quantification of regional resting myocardial blood flow (MBF) velocity in normal human myocardium. Methods Twenty study subjects with normal left ventricular (LV) wall motion and normal coronary arteries, underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during constant IV. infusion of SonoVue®. Following transient microbubble destruction, the contrast replenishment rate (β), reflecting MBF velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function; y (t) =A (1-e-β(t-t0)) + C. Results Quantification was feasible in 82%, 49% and 63% of four-chamber, two-chamber and apical long-axis view segments, respectively. The LAD (left anterior descending artery) and RCA (right coronary artery) territories could potentially be evaluated in most, but contrast detection in the LCx (left circumflex artery) bed was poor. Depending on localisation and which frames to be analysed, mean values of were 0.21–0.69 s-1, with higher values in medial than lateral, and in basal compared to apical regions of scan plane (p = 0.03 and p < 0.01). Higher β-values were obtained from end-diastole than end-systole (p < 0.001), values from all-frames analysis lying between. Conclusion Low-power real-time MCE did have the potential to give contrast enhancement for quantification of resting regional MBF velocity. However, the technique is difficult and subjected to several limitations. Significant variability in β suggests that this parameter is best suited for with-in patient changes, comparing values of stress studies to baseline. PMID:15958173

  3. Quantification of resting myocardial blood flow velocity in normal humans using real-time contrast echocardiography. A feasibility study

    Directory of Open Access Journals (Sweden)

    Slordahl Stig

    2005-06-01

    Full Text Available Abstract Background Real-time myocardial contrast echocardiography (MCE is a novel method for assessing myocardial perfusion. The aim of this study was to evaluate the feasibility of a very low-power real-time MCE for quantification of regional resting myocardial blood flow (MBF velocity in normal human myocardium. Methods Twenty study subjects with normal left ventricular (LV wall motion and normal coronary arteries, underwent low-power real-time MCE based on color-coded pulse inversion Doppler. Standard apical LV views were acquired during constant IV. infusion of SonoVue®. Following transient microbubble destruction, the contrast replenishment rate (β, reflecting MBF velocity, was derived by plotting signal intensity vs. time and fitting data to the exponential function; y (t =A (1-e-β(t-t0 + C. Results Quantification was feasible in 82%, 49% and 63% of four-chamber, two-chamber and apical long-axis view segments, respectively. The LAD (left anterior descending artery and RCA (right coronary artery territories could potentially be evaluated in most, but contrast detection in the LCx (left circumflex artery bed was poor. Depending on localisation and which frames to be analysed, mean values of were 0.21–0.69 s-1, with higher values in medial than lateral, and in basal compared to apical regions of scan plane (p = 0.03 and p Conclusion Low-power real-time MCE did have the potential to give contrast enhancement for quantification of resting regional MBF velocity. However, the technique is difficult and subjected to several limitations. Significant variability in β suggests that this parameter is best suited for with-in patient changes, comparing values of stress studies to baseline.

  4. Reproducible pattern of microRNA in normal human skin

    DEFF Research Database (Denmark)

    Holst, Line; Kaczkowski, Bogumil; Gniadecki, Robert

    2010-01-01

    MicroRNAs (miRNAs) regulate cell growth, differentiation and apoptosis via specific targeting of messenger RNA (mRNA). Aberrant mRNA expression contributes to pathological processes such as carcinogenesis. To take advantage of miRNA profiling in skin disease it is essential to investigate mi......RNA expression pattern in normal human skin. Here we investigated miRNA expression profiles from skin biopsies of 8 healthy volunteers taken from sun protected and mildly photo damaged skin using the modified protocol for miRNA extraction. We were able to show a constant pattern of miRNA expression between...... different individuals. We did not find any significant differences in miRNA expression between sun protected and mildly photodamaged skin. These results may be valuable for future design of studies on miRNA expression in skin disease....

  5. Incidence of stunned, hibernating and scarred myocardium in ischaemic cardiomyopathy

    International Nuclear Information System (INIS)

    Hernandez-Pampaloni, Miguel; Morita, Koichi; Dutka, David P.; Camici, Paolo G.; Bax, Jeroen J.

    2005-01-01

    Different criteria to identify residual viability in chronically dysfunctioning myocardium in patients with coronary artery disease (CAD) can be derived by the combined assessment of myocardial blood flow (MBF) and glucose utilisation (MRG) using positron emission tomography (PET). The aim of this study was to evaluate, in a large number of patients, the prevalence of these different patterns by purely quantitative means. One hundred and sixteen consecutive patients with ischaemic cardiomyopathy (LVEF ≤40%) underwent resting 2D echocardiography to assess regional contractile function (16-segment model). PET with 15 O-labelled water (H 2 15 O) and 18 F-fluorodeoxyglucose (FDG) was used to quantify MBF and MRG during hyperinsulinaemic euglycaemic clamp. Dysfunctional segments with normal MBF (≥0.6 ml min -1 g -1 ) were classified as stunned, and segments with reduced MBF ( -1 g -1 ) as hibernating if MRG was ≥0.25 μmol min -1 g -1 . Segments with reduced MBF and MRG -1 g -1 were classified as transmural scars and segments with reduced MBF and MRG between 0.20 and 0.25 μmol min -1 g -1 as non-transmural scars. Eight hundred and thirty-four (46%) segments were dysfunctional. Of these, 601 (72%) were chronically stunned, with 368 (61%) having normal MRG (0.47±0.20 μmol min -1 g -1 ) and 233 (39%) reduced MRG (0.16±0.05 μmol min -1 g -1 ). Seventy-four (9%) segments with reduced MBF had preserved MRG (0.40±0.18 μmol min -1 g -1 ) and were classified as hibernating myocardium. In addition, 15% of segments were classified as transmural and 4% as non-transmural scar. The mean MBF was highest in stunned myocardium (0.95±0.32 ml min -1 g -1 ), intermediate in hibernating myocardium and non-transmural scars (0.47±0.09 ml min -1 g -1 and 0.48±0.08 ml min -1 g -1 , respectively), and lowest in transmural scars (0.40±0.14 ml min -1 g -1 , P -1 g -1 vs 0.46±0.20 μmol min -1 g -1 , NS), and lowest in stunned myocardium with reduced MRG and transmural scars

  6. Effect of dioxin on normal and leukemic human hematopoietic cells

    Energy Technology Data Exchange (ETDEWEB)

    Lambertenghi-Deliliers, G.; Soligo, D. [Univ. degli Studi, Milan (Italy). Dipt. die Ematologia, Ospedale Maggiore Policlinico IRCCS; Fracchiolla, N.S. [Ospedale Maggiore Policlinico IRCCS, Milan (Italy). Dipt. di Ematologia; Servida, F. [Fondazione Matarelli, Milan (Italy); Bertazzi, P.A. [Istituti Clinici di Perfezionamento, Milan (Italy). Dipt. di Medicina del Lavoro

    2004-09-15

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) arises from chlorination of phenolic substrates or from partial combustion of organic materials in the presence of chlorine sources. TCDD has a large number of biological effects such as long-lasting skin disease, cardiovascular disease, diabete and cancer. TCDD is the prototypical agonist of the aryl hydrocarbon receptor (AhR), a member of the erb-A family that also includes the receptors for steroids, thyroid hormones, peroxisome proliferators and retinoids. When bound to dioxin, the AhR can bind to DNA and alter the expression of some genes including cytokines and growth factors. In this study, we analyzed the effect of escalating doses of TCDD on human CD34{sup +} progenitor cells from the leukapheresis of normal donors stimulated with G-CSF as well as the human myeloid leukemic cell lines HL60 (promyelocytic leukemia) and K562 (chronic myelogenous leukemia). The possible specific modulation of gene expression induced by the TCDD exposure was then tested by means of microarray analyses.

  7. Differentiation of necrotic from hibernating and stunned myocardium

    International Nuclear Information System (INIS)

    Parodi, O.; Sambuceti, G.; Marcassa, C.; Neglia, D.

    1990-01-01

    The physiological significance of a coronary stenosis can be assessed by positron-emitting flow tracers which, quantifying regional myocardial blood flow, can measure the extent of hyperfusion. The metabolic consequences of flow reduction can be evaluated by positron emitting metabolic tracers, providing a tool to identify viable, hibernating myocardium. Prolonged ischemia can result in metabolic alterations (increase in FDG uptake) which can normalize slowly after reperfusion; the metabolic follow-up of recovered oxidative pathway can be achieved noninvasively by 11 C-Acetate and PET. Finally, after thrombolysis, a mismatch between flow and FDG uptake is an indicator of viable (stunned) Myocardium, indicating successful myocardial salvage after reperfusion and the need for a complete restoration of flow. (author). 13 refs.; 2 figs.; 1 tab

  8. The alteration of interelemental ratios in myocardium under the congenital heart disease (SRXRF)

    International Nuclear Information System (INIS)

    Trunova, V.A.; Zvereva, V.V.; Okuneva, G.N.; Levicheva, E.N.

    2007-01-01

    It is the myocardium that bears the basic functional loading during heart working, including muscle contractility and enzyme activity. The elemental concentrations in myocardium tissue of heart were determined by SRXRF technique. Our investigation is systematical: the elemental content in each compartment (left and right ventricles, left and right auricles) of hearts of healthy and diseased children (congenital heart diseases, transposition of main vessels (TMV)) was analyzed. The elemental distribution in myocardium of four heart chambers of human fetuses was also analyzed. Following elements were determined: S, Cl, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb, Sr. It was revealed that the elemental concentrations in myocardium of both ventricles are almost constant in heart of fetuses and healthy children. The transition from pre-natal study (fetus) to post-natal study is accompanied by the redistribution of chemical elements in myocardium. The higher concentrations of S, Fe, Ca, Sr and Cu in myocardium of children are observed, the content of K, Br, Rb and especially Se is lower than in heart of fetuses. The elemental distribution in myocardium of children TMV is considerably different in comparison with the healthy children: the higher levels of Cu are observed. The content of Se is lower

  9. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models.

    Directory of Open Access Journals (Sweden)

    Fang Peng

    Full Text Available BACKGROUND: Hypoxic tumor cells can reduce the efficacy of radiation. Antiangiogenic therapy may transiently "normalize" the tumor vasculature to make it more efficient for oxygen delivery. The aim of this study is to investigate whether the recombinant human endostatin (endostar can create a "vascular normalization window" to alleviate hypoxia and enhance the inhibitory effects of radiation therapy in human nasopharyngeal carcinoma (NPC in mice. METHODOLOGY/PRINCIPAL FINDINGS: Transient changes in morphology of tumor vasculature and hypoxic tumor cell fraction in response to endostar were detected in mice bearing CNE-2 and 5-8F human NPC xenografts. Various treatment schedules were tested to assess the influence of endostar on the effect of radiation therapy. Several important factors relevant to the angiogenesis were identified through immunohistochemical staining. During endostar treatment, tumor vascularity decreased, while the basement membrane and pericyte coverage associated with endothelial cells increased, which supported the idea of vessel normalization. Hypoxic tumor cell fraction also decreased after the treatment. The transient modulation of tumor physiology caused by endostar improved the effect of radiation treatment compared with other treatment schedules. The expressions of vascular endothelial growth factor (VEGF, matrix metalloproteinase-2 (MMP-2, MMP-9, and MMP-14 decreased, while the level of pigment epithelium-derived factor (PEDF increased. CONCLUSIONS: Endostar normalized tumor vasculature, which alleviated hypoxia and significantly sensitized the function of radiation in anti-tumor in human NPC. The results provide an important experimental basis for combining endostar with radiation therapy in human NPC.

  10. Reference man models based on normal data from human populations

    International Nuclear Information System (INIS)

    Tanaka, Gi-ichiro; Kawamura, Hisao

    2000-01-01

    Quantitative description of the physical, and metabolic parameters of the human body is the very basic for internal dosimetry. Compilation of anatomical and other types of data Asian populations for internal (and external) dosimetry is of grate significance because of the potential spread of nuclear energy use in the Asian region and the major contribution of the region to the world population (about 58%). It has been observed that some differences exist for habitat, race, body sizes and pattern of food consumption. In the early stage of revision of ICRP Reference man by the Task Group, Characteristics of the human body of non-European populations received considerable attention as well as those of the European populations of different sexes and ages. In this context, an IAEA-RCA Co-ordinated Research Program on Compilation of Anatomical, Physiological and Metabolic Characteristics for a Reference Asian Man endorsed. In later stages of reference Man revision, anatomical data for Asians was discusses together with those of European populations, presumably due to ICRP's decision of unanimous use of the Reference Man for radiation protection. Reference man models for adults and 15, 10, 5, 1, 0 year-old males and females of Asian populations were developed for use in internal and external dosimetry. Based on the concept of ICRP Reference Man (Publication 23), the reference values were derived from the normal organ mass data for Japanese and statistical data on the physique and nutrition of Japanese and Chinese. Also incorporated were variations in physical measurements, as observed in the above mentioned IAEA-RCA Co-ordinated Research Program. The work was partly carried out within the activities of the ICRP Task Group on Reference Man. The weight of the skeleton was adjusted following the revised values in Publication 70. This paper will report basic shared and non-shared characteristics of Reference Man' for Asians and ICRP Reference Man. (author)

  11. Mechanical compression attenuates normal human bronchial epithelial wound healing

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    Malavia Nikita

    2009-02-01

    Full Text Available Abstract Background Airway narrowing associated with chronic asthma results in the transmission of injurious compressive forces to the bronchial epithelium and promotes the release of pro-inflammatory mediators and the denudation of the bronchial epithelium. While the individual effects of compression or denudation are well characterized, there is no data to elucidate how these cells respond to the application of mechanical compression in the presence of a compromised epithelial layer. Methods Accordingly, differentiated normal human bronchial epithelial cells were exposed to one of four conditions: 1 unperturbed control cells, 2 single scrape wound only, 3 static compression (6 hours of 30 cmH2O, and 4 6 hours of static compression after a scrape wound. Following treatment, wound closure rate was recorded, media was assayed for mediator content and the cytoskeletal network was fluorescently labeled. Results We found that mechanical compression and scrape injury increase TGF-β2 and endothelin-1 secretion, while EGF content in the media is attenuated with both injury modes. The application of compression after a pre-existing scrape wound augmented these observations, and also decreased PGE2 media content. Compression stimulated depolymerization of the actin cytoskeleton and significantly attenuated wound healing. Closure rate was partially restored with the addition of exogenous PGE2, but not EGF. Conclusion Our results suggest that mechanical compression reduces the capacity of the bronchial epithelium to close wounds, and is, in part, mediated by PGE2 and a compromised cytoskeleton.

  12. Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

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    Ana Paula Santin Bertoni

    2015-01-01

    Full Text Available Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P<0.0001; 2.39 times, P=0.01; 1.58 times, P=0.0003; and 1.87 times, P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P<0.0001; 1.75 times, P=0.037; and 1.95 times, P<0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P=0.069. These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

  13. Expression of interleukin-17RC protein in normal human tissues

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    Ge Dongxia

    2008-10-01

    Full Text Available Abstract Background Interleukin-17 (IL-17 cytokines and receptors play an important role in many autoimmune and inflammatory diseases. IL-17 receptors IL-17RA and IL-17RC have been found to form a heterodimer for mediating the signals of IL-17A and IL-17F cytokines. While the function and signaling pathway of IL-17RA has been revealed, IL-17RC has not been well characterized. The function and signaling pathway of IL-17RC remain largely unknown. The purpose of the present study was to systematically examine IL-17RC protein expression in 53 human tissues. Results IL-17RC expression in 51 normal human tissues and two benign tumors (i.e., lymphangioma and parathyroid adenoma on the tissue microarrays was determined by immunohistochemical staining, using two polyclonal antibodies against IL-17RC. IL-17RC protein was expressed in many cell types including the myocardial cells, vascular and lymphatic endothelial cells, glandular cells (of the adrenal, parathyroid, pituitary, thyroid, pancreas, parotid salivary, and subepidermal glands, epithelial cells (of the esophagus, stomach, intestine, anus, renal tubule, breast, cervix, Fallopian tube, epididymis, seminal vesicle, prostate, gallbladder, bronchus, lung, and skin, oocytes in the ovary, Sertoli cells in the testis, motor neurons in the spinal cord, autonomic ganglia and nerves in the intestine, skeletal muscle cells, adipocytes, articular chondrocytes, and synovial cells. High levels of IL-17RC protein expression were observed in most vascular and lymphatic endothelium and squamous epithelium. The epithelium of the breast, cervix, Fallopian tube, kidney, bladder and bronchus also expressed high levels of IL-17RC, so did the glandular cells in the adrenal cortex, parotid salivary and subepidermal glands. In contrast, IL-17RC protein was not detectable in the smooth muscle cells, fibroblasts, antral mucosa of the stomach, mucosa of the colon, endometrium of the uterus, neurons of the brain

  14. High spatial resolution and temporally resolved T2* mapping of normal human myocardium at 7.0 Tesla: an ultrahigh field magnetic resonance feasibility study.

    Directory of Open Access Journals (Sweden)

    Fabian Hezel

    Full Text Available Myocardial tissue characterization using T(2(* relaxation mapping techniques is an emerging application of (preclinical cardiovascular magnetic resonance imaging. The increase in microscopic susceptibility at higher magnetic field strengths renders myocardial T(2(* mapping at ultrahigh magnetic fields conceptually appealing. This work demonstrates the feasibility of myocardial T(2(* imaging at 7.0 T and examines the applicability of temporally-resolved and high spatial resolution myocardial T(2(* mapping. In phantom experiments single cardiac phase and dynamic (CINE gradient echo imaging techniques provided similar T(2(* maps. In vivo studies showed that the peak-to-peak B(0 difference following volume selective shimming was reduced to approximately 80 Hz for the four chamber view and mid-ventricular short axis view of the heart and to 65 Hz for the left ventricle. No severe susceptibility artifacts were detected in the septum and in the lateral wall for T(2(* weighting ranging from TE = 2.04 ms to TE = 10.2 ms. For TE >7 ms, a susceptibility weighting induced signal void was observed within the anterior and inferior myocardial segments. The longest T(2(* values were found for anterior (T(2(* = 14.0 ms, anteroseptal (T(2(* = 17.2 ms and inferoseptal (T(2(* = 16.5 ms myocardial segments. Shorter T(2(* values were observed for inferior (T(2(* = 10.6 ms and inferolateral (T(2(* = 11.4 ms segments. A significant difference (p = 0.002 in T(2(* values was observed between end-diastole and end-systole with T(2(* changes of up to approximately 27% over the cardiac cycle which were pronounced in the septum. To conclude, these results underscore the challenges of myocardial T(2(* mapping at 7.0 T but demonstrate that these issues can be offset by using tailored shimming techniques and dedicated acquisition schemes.

  15. A human morphologically normal spermatozoon may have noncondensed chromatin.

    Science.gov (United States)

    Boitrelle, F; Pagnier, M; Athiel, Y; Swierkowski-Blanchard, N; Torre, A; Alter, L; Muratorio, C; Vialard, F; Albert, M; Selva, J

    2015-10-01

    According to numerous assisted reproductive medicine practitioners, semen with normal characteristics might not require further investigation. However, on the scale of the individual spermatozoon, it is well known that normal morphology does not guarantee optimal nuclear quality. Here, for 20 patients with normal sperm characteristics and a high proportion of spermatozoa with noncondensed chromatin, we subsequently assessed chromatin condensation status (aniline blue staining) and morphology (Papanicolaou staining) of the same 3749 spermatozoa. Although the overall proportion of morphologically normal spermatozoa was not correlated with the overall proportion of spermatozoa with noncondensed chromatin, an individual spermatozoon's morphology appeared to be closely related to its chromatin condensation status. Morphologically normal spermatozoa with noncondensed chromatin were seen in all patients; the proportion averaged 23.3% [min 10.9%-max 44.4%]. Morphologically abnormal spermatozoa were more likely to have noncondensed chromatin than morphologically normal ones (P 80% for each type), and more than half the vacuolated spermatozoa also presented noncondensed chromatin. However, a morphologically normal spermatozoon may also have a noncondensed chromatin. © 2014 Blackwell Verlag GmbH.

  16. Quantitative proteome profiling of normal human circulating microparticles

    DEFF Research Database (Denmark)

    Østergaard, Ole; Nielsen, Christoffer T; Iversen, Line V

    2012-01-01

    Circulating microparticles (MPs) are produced as part of normal physiology. Their numbers, origin, and composition change in pathology. Despite this, the normal MP proteome has not yet been characterized with standardized high-resolution methods. We here quantitatively profile the normal MP...... proteome using nano-LC-MS/MS on an LTQ-Orbitrap with optimized sample collection, preparation, and analysis of 12 different normal samples. Analytical and procedural variation were estimated in triply processed samples analyzed in triplicate from two different donors. Label-free quantitation was validated...... by the correlation of cytoskeletal protein intensities with MP numbers obtained by flow cytometry. Finally, the validity of using pooled samples was evaluated using overlap protein identification numbers and multivariate data analysis. Using conservative parameters, 536 different unique proteins were quantitated...

  17. Survival of human osteosarcoma cells and normal human fibroblasts following alpha particle irradiation

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.

    1981-01-01

    Cell survival of human osteosarcoma cells in culture following alpha particle irradiation is reported here for the first time. The osteosarcoma cell line (TE-85) is found to be less sensitive to inactivation by 5.6 MeV alpha particles (LET 86 keV/μm) than normal diploid human fibroblasts (NFS). Values for the mean lethal doses were estimated to be 103 rads for the TE-85 cells compared with 68 rads for the NFS cultures irradiated under identical conditions. It is postulated that the aneuploidy of the tumor cells with increased DNA chromosomal material may confer a selective advantage for the survival of tumor cells relative to normal cells with diploid chromosomes

  18. Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension.

    Science.gov (United States)

    Badr Eslam, Roza; Croce, Kevin; Mangione, Fernanda Marinho; Musmann, Robert; Leopold, Jane A; Mitchell, Richard N; Waxman, Aaron B

    2017-06-01

    In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH). Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12 ± 2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging. hMSCs were injected in the marginal branch of the right coronary artery. Tissues were harvested 6, 9 or 24 days after infusion. After 12 ± 2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6 ± 3.6 versus 30.8 ± 4.5 mm Hg, P cells in the right ventricle (RV) that were Ki67 + . This was confirmed by fluorescence in situ hybridization. CD45 + porcine inflammatory cells were identified, commonly seen adjacent to areas of healing microscopic infarction that likely dated to the time of the original hMSC injection. Anti-CD31 staining produced strong signals in areas of injected hMSCs. Immunohistochemistry staining for vascular cell adhesion molecule-1 showed upregulation in the clusters, where mononuclear cells were located. hMSCs injected via intracoronary infusion survived up to 24 days and demonstrated proliferative capacity. hMSCs can persist long term in the RV and are potential cell source for tissue repair in RV dysfunction. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  19. Gene expression signatures affected by ethanol and/or nicotine in normal human normal oral keratinocytes (NHOKs

    Directory of Open Access Journals (Sweden)

    Jeffrey J. Kim

    2014-12-01

    Full Text Available It has been reported that nicotine/alcohol alters epigenetic control and leads to abrogated DNA methylation and histone modifications, which could subsequently perturb transcriptional regulation critically important in cellular transformation. The aim of this study is to determine the molecular mechanisms of nicotine/alcohol-induced epigenetic alterations and their mechanistic roles in transcriptional regulation in human adult stem cells. We hypothesized that nicotine/alcohol induces deregulation of epigenetic machinery and leads to epigenetic alterations, which subsequently affect transcriptional regulation in oral epithelial stem cells. As an initiating step we have profiled transcriptomic alterations induced by the combinatory administration of EtOH and nicotine in primary normal human oral keratinocytes. Here we provide detailed experimental methods, analysis and information associated with our data deposited into Gene Expression Omnibus (GEO under GSE57634. Our data provide comprehensive transcriptomic map describing molecular changes induced by EtOH and nicotine on normal human oral keratinocytes.

  20. Human papillomavirus in normal cervical smears from Cape Town ...

    African Journals Online (AJOL)

    The types of HPV found in normal cervical tissue from Cape Town did not differ significantly from those found elsewhere in the world. Nine per cent (17/192) were positive for 'high-risk' HPV types which are associated with premalignant and malignant cervical lesions. In the age group 20 - 39 years, 15 of 92 (16%) were ...

  1. Cardiovascular, endocrine, and renal effects of urodilatin in normal humans

    DEFF Research Database (Denmark)

    Bestle, M H; Olsen, Niels Vidiendal; Christensen, P

    1999-01-01

    Effects of urodilatin (5, 10, 20, and 40 ng. kg-1. min-1) infused over 2 h on separate study days were studied in eight normal subjects with use of a randomized, double-blind protocol. All doses decreased renal plasma flow (hippurate clearance, 13-37%) and increased fractional Li+ clearance (7-22...

  2. Normal RNAi response in human fragile x fibroblasts

    DEFF Research Database (Denmark)

    Madsen, Charlotte; Grønskov, Karen; Brøndum-Nielsen, Karen

    2009-01-01

    BACKGROUND: Fragile x syndrome is caused by loss of expression of the FMRP protein involved in the control of a large number of mRNA targets. The Drosophila ortholog dFXR interacts with a protein complex that includes Argonaute2, an essential component of the RNA-induced silencing complex (RISC......). Furthermore dFXR associates with Dicer, another essential processing enzyme of the RNAi pathway. Both microRNA and microRNA precursors can co-immunoprecipitate with dFXR. Consequently it has been suggested that the Fragile x syndrome may be due to a defect in an RNAi-related apparatus. FINDINGS: We have...... investigated the RNAi response in Fragile x patient cells lacking FMRP compared with normal controls. RNAi responses were successfully detected, but no statistically significant difference between the response in normal cells compared to patients cells was found - neither one nor two days after transfection...

  3. Gene expression of 17beta-estradiol-metabolizing isozymes: comparison of normal human mammary gland to normal human liver and to cultured human breast adenocarcinoma cells.

    Science.gov (United States)

    Lehmann, Leane; Wagner, Jörg

    2008-01-01

    Metabolic activation of 17beta-estradiol (E2) to catechols and quinones together with lack of deactivation constitute risk factors in human breast carcinogenesis. E2-catchols are generated by cytochrome P450-dependent monooxygenases (CYPs). Deactivation of E2, E2-catechols, and E2-quinones is mediated by UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), catechol-O-methyltransferase (COMT), glutathione-S-transferase (GST), and NADPH-quinone-oxidoreductase (QR) isozymes, respectively. The aim of the present study was to quantify mRNA levels of E2-metabolizing isozymes expressed in MCF-7 cells cultured in the presence/absence of steroids by reverse transcription/competitive PCR in relation to the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase and compare them with expression levels in normal human mammary gland (MG) and liver tissue. CYP1A1, 1B1, SULT1A1, 1A2, membrane-bound and soluble COMT, GSTT1, QR1, and UGT2B7 were detected in both tissues and MCF-7 cells; however, most enzymes were expressed at least tenfold higher in liver. Yet, CYP1B1 was expressed as high in breast as in liver and UGTs were not detected in MCF-7 cells cultured with steroids. MCF-7 cells cultured steroid-free additionally expressed CYP1A2 as well as UGT1A4, 1A8, and 1A9. Normal human liver but not MG expressed CYP1A2, 3A4, UGT1A1, 1A3, 1A4, 1A9, and SULT2A1. UGT1A8 was only detected in MCF7 cells but was not found in human liver. Thus, our study provides a comprehensive overview of expression levels of E2-metabolizing enzymes in a popular in vitro model and in human tissues, which will contribute to the interpretation of in vitro studies concerning the activation/deactivation of E2.

  4. Effects of organophosphorus flame retardant TDCPP on normal human corneal epithelial cells: Implications for human health.

    Science.gov (United States)

    Xiang, Ping; Liu, Rong-Yan; Li, Chao; Gao, Peng; Cui, Xin-Yi; Ma, Lena Q

    2017-11-01

    Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is one of the most detected organophosphorus flame retardants (OPFRs) in the environment, especially in indoor dust. Continuous daily exposure to TDCPP-containing dust may adversely impact human cornea. However, its detrimental effects on human corneal epithelium are largely unknown. In this study, we investigated the cell apoptosis in normal human corneal epithelial cells (HCECs) after TDCPP exposure and elucidated the underlying molecular mechanisms. Our data indicated a dose-dependent decrease of cell viability after TDCPP exposure with LC 50 at 202 μg/mL. A concentration-dependent apoptotic sign was observed in HCECs after exposing to ≥2 μg/mL TDCPP. Endoplasmic reticulum stress induction was evidenced by up-regulation of its biomarker genes (ATF-4, CHOP, BiP, and XBP1). Furthermore, alternation of Bcl-2/Bax expression, mitochondrial membrane potential loss, cellular ATP content decrease, and caspase-3 and -9 activity increase were observed after exposing to 2 or 20 μg/mL TDCPP. Taken together, the data implicated the involvement of endoplasmic reticulum stress in TDCPP-induced HCEC apoptosis, probably mediated by mitochondrial apoptotic pathway. Our findings showed TDCPP exposure induced toxicity to human cornea. Due to TDCPP's presence at high levels in indoor dust, further study is warranted to evaluate its health risk on human corneas. Published by Elsevier Ltd.

  5. Radioimmunoassay for human parathyroid hormone for differentiation between patients with hypoparathyroidism, hyperparathyroidism and normals

    International Nuclear Information System (INIS)

    Streibl, W.; Minne, H.; Raue, F.; Ziegler, R.

    1979-01-01

    A RIA system for human PTH is presented using a goat antibody (Code name 017-spring-78) against C-terminal hPTH fragments, as well as a human PTH standard from hemodiafiltration of a hyperparathyroid patient. It proved to be useful for the differentiation not only between hyperparathyroid patients and normals, but even within the normal range, and hypoparathyroid states. (orig.) [de

  6. Integrin expression on normal and neoplastic human breast epithelium.

    Science.gov (United States)

    Damjanovich, L; Fülöp, B; Adány, R; Nemes, Z

    1997-01-01

    Integrin adhesion receptor expression of different benign and malignant breast tumours was examined by means of immunohistochemical techniques. A panel of seven different anti-alpha and two different anti-beta subunit antibodies was used. Normal breast epithelium displayed a well characterized and constant pattern of integrin expression consisting of strong alpha 1,2,3,6 and alpha v, and a relatively weaker beta 1 and beta 3 staining. No staining for alpha 4 or alpha 5 could be detected on the epithelial cells. Benign fibroadenomas did not show changes in their receptor expression compared to normal tissues. In the cases of different types of breast cancer, there was a significant downregulation of all subunits. The staining pattern was distinct if there could a basement membrane like structure be detected around the invading tumour nodules. When laminin and collagen type IV surrounded the tumour cells, those cells in contact with the extracellular matrix components still displayed strong positivity for the integrin subunits. Other cells inside the tumour cell nests or not surrounded by basement membrane did not express integrins. The positively staining cells might be more differentiated owing to the effect the basement membrane. Myoepithelial labeling of the integrin expressing cells gave negative results. The observed integrin expression heterogeneity renders the histologic picture difficult to interpret with regard to clinical behavior of the tumour.

  7. Vulnerability of Normal Human Mammary Epithelial Cells to Oncogenic Transformation

    Science.gov (United States)

    2012-04-01

    cells. Proc Nat Acad Sci USA 108:3264-69. 2011 Chin, K, Ortiz de Solorzano , C, Knowles, D, Jones, A, Chou, W, Rodriguez, E, Kuo, W-L, Ljung, B-M...Transformation of human mammary epithelial cells by oncogenic retro- viruses. Cancer Res 1988;48:4689–94. 13. Chin K, de Solorzano CO, Knowles D, et al

  8. Object Detection and Tracking-Based Camera Calibration for Normalized Human Height Estimation

    Directory of Open Access Journals (Sweden)

    Jaehoon Jung

    2016-01-01

    Full Text Available This paper presents a normalized human height estimation algorithm using an uncalibrated camera. To estimate the normalized human height, the proposed algorithm detects a moving object and performs tracking-based automatic camera calibration. The proposed method consists of three steps: (i moving human detection and tracking, (ii automatic camera calibration, and (iii human height estimation and error correction. The proposed method automatically calibrates camera by detecting moving humans and estimates the human height using error correction. The proposed method can be applied to object-based video surveillance systems and digital forensic.

  9. Bioprinting 3D microfibrous scaffolds for engineering endothelialized myocardium and heart-on-a-chip.

    Science.gov (United States)

    Zhang, Yu Shrike; Arneri, Andrea; Bersini, Simone; Shin, Su-Ryon; Zhu, Kai; Goli-Malekabadi, Zahra; Aleman, Julio; Colosi, Cristina; Busignani, Fabio; Dell'Erba, Valeria; Bishop, Colin; Shupe, Thomas; Demarchi, Danilo; Moretti, Matteo; Rasponi, Marco; Dokmeci, Mehmet Remzi; Atala, Anthony; Khademhosseini, Ali

    2016-12-01

    Engineering cardiac tissues and organ models remains a great challenge due to the hierarchical structure of the native myocardium. The need of integrating blood vessels brings additional complexity, limiting the available approaches that are suitable to produce integrated cardiovascular organoids. In this work we propose a novel hybrid strategy based on 3D bioprinting, to fabricate endothelialized myocardium. Enabled by the use of our composite bioink, endothelial cells directly bioprinted within microfibrous hydrogel scaffolds gradually migrated towards the peripheries of the microfibers to form a layer of confluent endothelium. Together with controlled anisotropy, this 3D endothelial bed was then seeded with cardiomyocytes to generate aligned myocardium capable of spontaneous and synchronous contraction. We further embedded the organoids into a specially designed microfluidic perfusion bioreactor to complete the endothelialized-myocardium-on-a-chip platform for cardiovascular toxicity evaluation. Finally, we demonstrated that such a technique could be translated to human cardiomyocytes derived from induced pluripotent stem cells to construct endothelialized human myocardium. We believe that our method for generation of endothelialized organoids fabricated through an innovative 3D bioprinting technology may find widespread applications in regenerative medicine, drug screening, and potentially disease modeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Neurophysiological model of the normal and abnormal human pupil

    Science.gov (United States)

    Krenz, W.; Robin, M.; Barez, S.; Stark, L.

    1985-01-01

    Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

  11. Plasma catecholamine responses to physiologic stimuli in normal human pregnancy.

    Science.gov (United States)

    Barron, W M; Mujais, S K; Zinaman, M; Bravo, E L; Lindheimer, M D

    1986-01-01

    The dynamic response of the sympathoadrenal system was evaluated during and after pregnancy in 13 healthy women with a protocol that compared cardiovascular parameters and plasma catecholamine levels during the basal state, after postural maneuvers, and following isometric exercise. Plasma epinephrine and norepinephrine levels were similar during and after gestation when the women rested on their sides, but heart rate was greater in pregnancy. Ten minutes of supine recumbency produced minimal changes, but attenuation of the anticipated increases in heart rate and plasma norepinephrine levels during standing and isometric exercise were observed during pregnancy. In contrast, alterations in plasma epinephrine appeared unaffected by gestation. Plasma renin activity and aldosterone levels were, as expected, greater during pregnancy; however, increments in response to upright posture were similar in pregnant and postpartum women. To the extent that circulating catecholamines may be considered indices of sympathoadrenal function, these data suggest that normal pregnancy alters cardiovascular and sympathetic nervous system responses to physiologic stimuli.

  12. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  13. Specific binding of beta-endorphin to normal human erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chenet, B.; Hollis, V. Jr.; Kang, Y.; Simpkins, C.

    1986-03-05

    Beta-endorphin (BE) exhibits peripheral functions which may not be mediated by interactions with receptors in the brain. Recent studies have demonstrated binding of BE to both opioid and non-opioid receptors on lymphocytes and monocytes. Abood has reported specific binding of /sup 3/H-dihydromorphine in erythrocytes. Using 5 x 10/sup -11/M /sup 125/I-beta-endorphin and 10/sup -5/M unlabeled BE, they have detected 50% specific binding to human erythrocytes. This finding is supported by results from immunoelectron microscopy using rabbit anti-BE antibody and biotinylated secondary antibody with avidin-biotin complexes horseradish peroxidase. Binding is clearly observed and is confined to only one side of the cells. Conclusions: (1) BE binding to human erythrocytes was demonstrated by radioreceptor assay and immunoelectron microscopy, and (2) BE binding sites exist on only one side of the cells.

  14. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  15. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  16. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    Energy Technology Data Exchange (ETDEWEB)

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. (Dana-Farber Cancer Institute, Boston, MA (USA))

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  17. Accelerated aging syndromes, are they relevant to normal human aging?

    OpenAIRE

    Dreesen, Oliver; Stewart, Colin L.

    2011-01-01

    Hutchinson-Gilford Progeria (HGPS) and Werner syndromes are diseases that clinically resemble some aspects of accelerated aging. HGPS is caused by mutations in theLMNA gene resulting in post-translational processing defects that trigger Progeria in children. Werner syndrome, arising from mutations in the WRN helicase gene, causes premature aging in young adults. What are the molecular mechanism(s) underlying these disorders and what aspects of the diseases resemble physiological human aging? ...

  18. Quantitation of small intestinal permeability during normal human drug absorption

    OpenAIRE

    Levitt, David G

    2013-01-01

    Background Understanding the quantitative relationship between a drug?s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorpti...

  19. Quantitation of small intestinal permeability during normal human drug absorption

    Science.gov (United States)

    2013-01-01

    Background Understanding the quantitative relationship between a drug’s physical chemical properties and its rate of intestinal absorption (QSAR) is critical for selecting candidate drugs. Because of limited experimental human small intestinal permeability data, approximate surrogates such as the fraction absorbed or Caco-2 permeability are used, both of which have limitations. Methods Given the blood concentration following an oral and intravenous dose, the time course of intestinal absorption in humans was determined by deconvolution and related to the intestinal permeability by the use of a new 3 parameter model function (“Averaged Model” (AM)). The theoretical validity of this AM model was evaluated by comparing it to the standard diffusion-convection model (DC). This analysis was applied to 90 drugs using previously published data. Only drugs that were administered in oral solution form to fasting subjects were considered so that the rate of gastric emptying was approximately known. All the calculations are carried out using the freely available routine PKQuest Java (http://www.pkquest.com) which has an easy to use, simple interface. Results Theoretically, the AM permeability provides an accurate estimate of the intestinal DC permeability for solutes whose absorption ranges from 1% to 99%. The experimental human AM permeabilities determined by deconvolution are similar to those determined by direct human jejunal perfusion. The small intestinal pH varies with position and the results are interpreted in terms of the pH dependent octanol partition. The permeability versus partition relations are presented separately for the uncharged, basic, acidic and charged solutes. The small uncharged solutes caffeine, acetaminophen and antipyrine have very high permeabilities (about 20 x 10-4 cm/sec) corresponding to an unstirred layer of only 45 μm. The weak acid aspirin also has a large AM permeability despite its low octanol partition at pH 7.4, suggesting

  20. HISTOLOGICAL AND HISTOCHEMICAL CHARACTERISTICS OF RAT MYOCARDIUM IN CADMIUM TOXICOSIS

    Directory of Open Access Journals (Sweden)

    Novica Bojanić

    2013-01-01

    Full Text Available Carcinogenic effects of cadmium on lungs, testicles and prostate are well known, so as cumulative and toxic effects on kidney, liver and bones; however, there have not been many published articles about the effects of cadmium on myocardium. The aim of this study was to estimate the morphological changes in rat myocardium chronically treated by cadmium. The study was carried out on male albino Wistar rats (n=30, age=35-37 days, body mass 120g +/- 10g. The animals were raised in controlled laboratory conditions and provided with standard laboratory rat food and tap water ad libitum. The rats were divided into two groups: ten animals composed the control group and did not undergo any treatment. The 20 experimental rats were exposed to 10mg of CdCl2 /L drinking water for 90 days. After 90 days, all animals were victimized and after the macroscopic inspection of the heart, myocardial tissue was routinely processed and embedded in paraffin. Sections 5 micrometers thick were stained by HE method and histochemical PAS-AB (pH 2, 5, Masson trichrome method for demonstrating collagen fibers and Toluidine blue for mast cells identification. Cross-striated banding pattern of cardiac cells was ruined. Noticeable atrophy and hydropic degeneration of subendocardial localized cardiac cells were found, with the focal presence of myocytolysis. Endothelial cell hyperplasia and edema of the intima were present on arteriolar type blood vessels causing the focal subocclusion. Fibrocytes, histiocytes and mast cells were numerous, perivascularly localized. Mast cells were polymorphic, larger than normal, oval and mostly degranulated. Instead of scanty endomysium, there is a noticeable interstitial fibrillar fibrosis with few fields of collagen in all myocardium layers between cardiac cells, which is particularly prominent around the larger blood vessels. Cadmium has pronounced vasculotropic properties causing morphological changes of cardiomyocytes, myocardial

  1. Ionizing radiation response of primary normal human lens epithelial cells.

    Directory of Open Access Journals (Sweden)

    Nobuyuki Hamada

    Full Text Available Whilst the cataractogenic potential of ionizing radiation has been known for over the past 120 years, little is known about radiation responses of lens cells. Our previous work was the first to evaluate the radiosensitivity of lens cells with the clonogenic assay, documenting that the survival of HLEC1 human lens epithelial cells is comparable to that of WI-38 human lung fibroblasts. Moreover, HLEC1 cells were found to contain subsets where irradiation stimulates proliferation or facilitates formation of abortive colonies with fewer cells than human fibroblasts. This study aims to gain insights into these mechanisms. Irradiation of HLEC1 cells with 10% survival dose caused a growth delay but did not reduce viability. HLEC1 cells at high cumulative population doubling level were more susceptible to radiogenic premature senescence than WI-38 cells. Concerning p53 binding protein 1 (53BP1 foci, HLEC1 cells harbored less spontaneous foci but more radiogenic foci than in WI-38 cells, and the focus number returned to spontaneous levels within 48 h postirradiation both in HLEC1 and WI-38. The chemical inhibition of DNA repair kinases ataxia telangiectasia mutated, DNA-dependent protein kinase or both delayed and attenuated the appearance and disappearance of radiogenic 53BP1 foci, increased radiogenic premature senescence and enhanced clonogenic inactivation. The DNA microarray analysis suggested both radiogenic stimulation and inhibition of cell proliferation. Treatment with conditioned medium from irradiated cells did not change growth and the plating efficiency of nonirradiated cells. These results partially explain mechanisms of our previous observations, such that unrepaired or incompletely repaired DNA damage causes a growth delay in a subset of HLEC1 cells without changing viability through induction of premature senescence, thereby leading to clonogenic inactivation, but that growth is stimulated in another subset via as yet unidentified

  2. Different methods of measuring ADC values in normal human brain

    International Nuclear Information System (INIS)

    Wei Youping; Sheng Junkang; Zhang Caiyuan

    2009-01-01

    Objective: To investigate better method of measuring ADC values of normal brain, and provide reference for further research. Methods: Twenty healthy people's MR imaging were reviewed. All of them underwent routine MRI scans and echo-planar diffusion-weighted imaging (DWI), and ADC maps were reconstructed on work station. Six regions of interest (ROI) were selected for each object, the mean ADC values were obtained for each position on DWI and ADC maps respectively. Results: On the anisotropic DWI map calculated in the hypothalamus, ADC M , ADC P , ADC S values were no significant difference (P>0.05), in the frontal white matter and internal capsule hindlimb, there was a significant difference (P ave value exist significant difference to direct measurement on the anisotropic (isotropic) ADC map (P<0.001). Conclusion: Diffusion of water in the frontal white matter and internal capsule are anisotropic, but it is isotropic in the hypothalamus; different quantitative methods of diffusion measurement of 4ADC values have significant difference, but ADC values calculated through the DWI map is more accurate, quantitative diffusion study of brain tissue should also consider the diffusion measurement method. (authors)

  3. Control engineering and electromyographic kinesiology analyses of normal human gait.

    Science.gov (United States)

    Hashimoto, F; Ogawa, R; Kameyama, O

    2000-01-01

    In this study, we analyzed the electrical activity patterns of the antagonistic bi-articular and mono-articular muscles of both legs during normal gait cycles, in terms of electromyographic (EMG) kinesiology and control engineering. For control engineering analyses, we utilized a mechanical two-joint link model equipped with antagonistic pairs of bi-articular and mono-articular muscles. It was confirmed that the coordinated activity pattern, in which the bi-articular muscles of the rectus femoris (Rf) and the medial hamstrings (Mh) showed criss-cross EMG patterns, and the mono-articular muscles of the gluteus maximus and the vastus medialis showed sustained activities during the early stance phase in the gait cycle, contributed to the output force control and the output force direction control. Reversal of Rf and Mh activities was responsible for changes in the output force direction during the heel contact period. The results obtained here strongly highlight the importance of and necessity for control engineering evaluation of coordinated muscle activities of bi-articular and mono-articular antagonistic muscles for analyses not only of gait but also of sports injuries.

  4. Regulation of normal human polyrnorphonuclear leucocytes by carnitine

    Directory of Open Access Journals (Sweden)

    Andrea Fattorossi

    1993-01-01

    Full Text Available The effect of carnitine, a drug that plays an essential role in mitochondria metabolism, on some of the most important human polymorphonuclear leucocytes (PMN activation steps including modulation of adhesion molecule density, reactive oxygen species production, and tumour necrosis factor-α (TNFα production was investigated. The capability of carnitine in protecting PMN from deter ioration on storage was also studied. Data shows that carnitine exerts considerable effects on all PMN functions investigated. Although the ultimate effect was often donor dependent, TNFα production was exceptional in that carnitine was able to consistently reduce TNFα production in Staphylococcus aureus stimulated PMN in a clear dose-dependent fashion. It is concluded that carnitine may represent a useful active agent in situations characterized by PMN mobilization/activation.

  5. Nonlinear time series analysis of normal and pathological human walking

    Science.gov (United States)

    Dingwell, Jonathan B.; Cusumano, Joseph P.

    2000-12-01

    Characterizing locomotor dynamics is essential for understanding the neuromuscular control of locomotion. In particular, quantifying dynamic stability during walking is important for assessing people who have a greater risk of falling. However, traditional biomechanical methods of defining stability have not quantified the resistance of the neuromuscular system to perturbations, suggesting that more precise definitions are required. For the present study, average maximum finite-time Lyapunov exponents were estimated to quantify the local dynamic stability of human walking kinematics. Local scaling exponents, defined as the local slopes of the correlation sum curves, were also calculated to quantify the local scaling structure of each embedded time series. Comparisons were made between overground and motorized treadmill walking in young healthy subjects and between diabetic neuropathic (NP) patients and healthy controls (CO) during overground walking. A modification of the method of surrogate data was developed to examine the stochastic nature of the fluctuations overlying the nominally periodic patterns in these data sets. Results demonstrated that having subjects walk on a motorized treadmill artificially stabilized their natural locomotor kinematics by small but statistically significant amounts. Furthermore, a paradox previously present in the biomechanical literature that resulted from mistakenly equating variability with dynamic stability was resolved. By slowing their self-selected walking speeds, NP patients adopted more locally stable gait patterns, even though they simultaneously exhibited greater kinematic variability than CO subjects. Additionally, the loss of peripheral sensation in NP patients was associated with statistically significant differences in the local scaling structure of their walking kinematics at those length scales where it was anticipated that sensory feedback would play the greatest role. Lastly, stride-to-stride fluctuations in the

  6. The Impact of Energy Substrates, Hormone Level and Subject-Related Factors on Physiologic Myocardial {sup 18}F-FDG Uptake in Normal Humans

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Juhye; Kong, Eunjung; Chun, Kyungah; Cho, Ihnho [Yeung-Nam Univ. Hoepital, Daegu (Korea, Republic of)

    2013-12-15

    In a whole-body {sup 18}F-FDG PET/CT, non-specific {sup 18}F-FDG uptake of the myocardium is a common finding and can be very variable, ranging from background activity to intense accumulation and inhomogeneity. We investigated the effect of energy substrates and plasma/serum hormones that may have an influence on myocardial {sup 18}F-FDG uptake. F-FDG PET/CT was performed on 100 normal volunteers from November 2007 to August 2008. Blood samples were taken just before {sup 18}F-FDG injection from all subjects. Myocardial {sup 18}F-FDG uptake was measured as the mean (SUVmean) and maximal (SUV{sub max}) standardized uptake value. The myocardium was delineated on the PET/CT image by a manual volume of interest (VOI).We analyzed the influence of age, sex, presence of diabetes, fasting duration, insulin, glucagon, fasting glucose, lactate, free fatty acid (FFA), epinephrine (EPi), norepinephrine (NEp), free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH) and body mass index (BMI). Overall, 92 subjects (mean age 50.28±8.30, male 57) were enrolled. The average of myocardial SUVmean was 2.08 and of myocardial SUV{sub max} was 4.57, respectively and there was a strong linear correlation between SUVmean and SUV{sub max} (r =0.98). FFA and fasting duration showed significant negative correlation with myocardial {sup 18}F-FDG uptake, respectively (r =-0.40 in FFA; r =-0.41 in fasting duration). No significant relationships were observed between myocardial uptake and age, sex, presence of diabetics, insulin, glucagon, fasting glucose, lactate, EPi, NEp, free T3, free T4, TSH and BMI. Myocardial {sup 18}F-FDG uptake decreases with longer fasting duration and higher FFA level in normal humans. Modulating myocardial uptake could improve {sup 18}F-FDG PET/CT imaging for specific oncologic and cardiovascular indications.

  7. The physiology of the normal human breast: an exploratory study.

    Science.gov (United States)

    Mills, Dixie; Gordon, Eva J; Casano, Ashley; Lahti, Sarah Michelle; Nguyen, Tinh; Preston, Alex; Tondre, Julie; Wu, Kuan; Yanase, Tiffany; Chan, Henry; Chia, David; Esfandiari, Mahtash; Himmel, Tiffany; Love, Susan M

    2011-12-01

    The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

  8. Histochemical and radioautographic studies of normal human fetal colon

    International Nuclear Information System (INIS)

    Lev, R.; Orlic, D.; New York Medical Coll., N.Y.

    1974-01-01

    Twenty fetal and infant colons ranging from 10 weeks in utero to 20 months postpartum, and 12 adult human colons were examined using histochemical techniques in conjunction with in vitro radioautography using Na 2 35 SO 4 as a sulfomucin precursor. Only the sulfated components of mucus in fetal goblet cells was found to differ significantly from adult colonic mucins. In the fetus sulfomucin staining was much weaker than in the adult, and was more intense in the left colon which is the reverse of the adult pattern. Sulfomucin was concentrated in the crypts throughout the fetal colon whereas in the adult right colon it predominated in the surface cells. As in the adult, saponification liberated carboxyl groups, possibly belonging to sialic acid, and vicinal hydroxyl groups from fetal mucins suggesting that this procedure hydrolyses an ester linkage between these 2 reactive groups. During the middle trimester of fetal life the colon possesses villi whose constituent cells display alkaline phosphatase in their surface coat. These and other morphological and histochemical similarities to fetal small intestine suggest that the fetal colon may have a limited capacity to absorb materials contained within swallowed amniotic fluid during this period. (orig.) [de

  9. Magnetic resonance elastography in normal human brain: preliminary study

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2007-01-01

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  10. The sinusoidal lining cells in "normal" human liver. A scanning electron microscopic investigation

    DEFF Research Database (Denmark)

    Horn, T; Henriksen, Jens Henrik Sahl; Christoffersen, P

    1986-01-01

    The scanning electron microscopic was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3...

  11. From The Cover: Reconstruction of functionally normal and malignant human breast tissues in mice

    Science.gov (United States)

    Kuperwasser, Charlotte; Chavarria, Tony; Wu, Min; Magrane, Greg; Gray, Joe W.; Carey, Loucinda; Richardson, Andrea; Weinberg, Robert A.

    2004-04-01

    The study of normal breast epithelial morphogenesis and carcinogenesis in vivo has largely used rodent models. Efforts at studying mammary morphogenesis and cancer with xenotransplanted human epithelial cells have failed to recapitulate the full extent of development seen in the human breast. We have developed an orthotopic xenograft model in which both the stromal and epithelial components of the reconstructed mammary gland are of human origin. Genetic modification of human stromal cells before the implantation of ostensibly normal human mammary epithelial cells resulted in the outgrowth of benign and malignant lesions. This experimental model allows for studies of human epithelial morphogenesis and differentiation in vivo and underscores the critical role of heterotypic interactions in human breast development and carcinogenesis.

  12. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably...... to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers...

  13. Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

    1980-07-01

    High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

  14. A Novel Generalized Normal Distribution for Human Longevity and other Negatively Skewed Data

    Science.gov (United States)

    Robertson, Henry T.; Allison, David B.

    2012-01-01

    Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution. PMID:22623974

  15. A novel generalized normal distribution for human longevity and other negatively skewed data.

    Science.gov (United States)

    Robertson, Henry T; Allison, David B

    2012-01-01

    Negatively skewed data arise occasionally in statistical practice; perhaps the most familiar example is the distribution of human longevity. Although other generalizations of the normal distribution exist, we demonstrate a new alternative that apparently fits human longevity data better. We propose an alternative approach of a normal distribution whose scale parameter is conditioned on attained age. This approach is consistent with previous findings that longevity conditioned on survival to the modal age behaves like a normal distribution. We derive such a distribution and demonstrate its accuracy in modeling human longevity data from life tables. The new distribution is characterized by 1. An intuitively straightforward genesis; 2. Closed forms for the pdf, cdf, mode, quantile, and hazard functions; and 3. Accessibility to non-statisticians, based on its close relationship to the normal distribution.

  16. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells.......Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...

  17. Identification of markers for quiescent pancreatic stellate cells in the normal human pancreas

    DEFF Research Database (Denmark)

    Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Detlefsen, Sönke

    2017-01-01

    microarray consisting of cores with normal human pancreatic tissue. Cores with normal human liver served as control. Antibodies directed against adipophilin, α-SMA, CD146, CRBP-1, cytoglobin, desmin, GFAP, nestin, S100A4 and vinculin were examined, with special emphasis on their expression in periacinar...... of histochemical stains for the identification of human qPSCs was examined, and their ultrastructure was revisited by electron microscopy. Adipophilin, CRBP-1, cytoglobin and vinculin were expressed in qHSCs in the liver, whereas cytoglobin and adipophilin were expressed in qPSCs in the pancreas. Adipophilin...

  18. The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

    DEFF Research Database (Denmark)

    Volck, B; Ostergaard, K; Johansen, J S

    1999-01-01

    YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL......-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found...... staining for YKL-40 was in general low in normal cartilage. The present findings, together with previous observations, suggests that YKL-40 may be of importance in cartilage remodelling/degradation of osteoarthritic joints....

  19. Enhanced reactivation of ultraviolet-irradiated human cytomegalovirus in normal host cells

    International Nuclear Information System (INIS)

    Dion, M.; Hamelin, C.

    1987-01-01

    Enhanced survival of UV-irradiated human cytomegalovirus (HCMV) is demonstrated in normal human cells exposed to UV light prior to infection. The UV fluence that gave rise to maximum UV reactivation falls in the range of 15 J/m 2 . A large number of temperature-sensitive HCMV mutants were found under the peak of reactivation. These results confirm the existence of inducible SOS functions in human cells. 18 refs.; 2 figs.; 1 table

  20. Subacute ghrelin administration inhibits apoptosis and improves ultrastructural abnormalities in remote myocardium post-myocardial infarction.

    Science.gov (United States)

    Eid, Refaat A; Zaki, Mohamed Samir Ahmed; Al-Shraim, Mubarak; Eleawa, Samy M; El-Kott, Attalla Farag; Al-Hashem, Fahaid H; Eldeen, Muhammad Alaa; Ibrahim, Hoja; Aldera, Hussain; Alkhateeb, Mahmoud A

    2018-05-01

    This study investigated the effect of ghrelin on cardiomyocytes function, apoptosis and ultra-structural alterations of remote myocardium of the left ventricle (LV) of rats, 21 days post myocardial infarction (MI). Rats were divided into 4 groups as a control, a sham-operated rats, a sham-operated+ghrelin, an MI + vehicle and an MI + ghrelin-treated rats. MI was induced by LAD ligation and then rats were recievd a concomitant doe of either normal saline as a vehicle or treated with ghrelin (100 μg/kg S.C., 2x/day) for 21 consecutive days. Ghrelin enhanced myocardial contractility in control rats and reversed the decreases in myocardial contractility and the increases in the serum levels of CK-MB and LDH in MI-induced rats. Additionally, it inhibited the increases in levels of Bax and cleaved caspase 3 and increased those for Bcl-2 in the remote myocardium of rat's LV, post-MI. At ultra-structural level, while ghrelin has no adverse effects on LV myocardium obtained from control or sham-treated rats, ghrelin post-administration to MI-induced rats reduced vascular formation, restored normal microfilaments appearance and organization, preserved mitochondria structure, and prevented mitochondrial swelling, collagen deposition and number of ghost bodies in the remote areas of their LV. Concomitantly, in remote myocardium of MI-induced rats, ghrelin enhanced endoplasmic reticulum intracellular organelles count, decreased number of atrophied nuclei and phagocytes, diminished the irregularity in the nuclear membranes and inhibited chromatin condensation. In conclusion, in addition to the physiological, biochemical and molecular evidence provided, this is the first study that confirms the anti-apoptotic effect of ghrelin in the remote myocardium of the LV during late MI at the level of ultra-structural changes. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  2. Relationship between enhanced reactivation and mutagenesis of u.v.-irradiated human cytomegalovirus in normal human cells

    International Nuclear Information System (INIS)

    Dion, Michel; Hamelin, Claude

    1987-01-01

    The survival of u.v.-irradiated human cytomegalovirus (HCMV) on u.v.-irradiated human IAFP-1 cells was increased over that on unirradiated cells. Irradiated virus had a higher forward mutation frequency towards temperature sensitivity in irradiated than in unirradiated cells. Enhanced reactivation of u.v.-irradiated HCMV is thus mutagenic in normal human cells. This observation supports the possible induction of an error-prone mode of DNA repair in u.v.-irradiated mammalian cells. (author)

  3. Effects of adrenergic drugs on aqueous humour dynamics in the normal human eye. I. Salbutamol.

    Science.gov (United States)

    Coakes, R L; Siah, P B

    1984-06-01

    The immediate effects of topical salbutamol, a beta 2 adrenergic agonist, on the aqueous humour dynamics of 22 normal subjects was studied by fluorophotometry and tonography. Significant lowering of intraocular pressure was accompanied by a significant increase in both aqueous flow rate and tonographic facility of outflow. Uveoscleral outflow was calculated and found to be significantly increased by salbutamol. This appeared to be the predominant acute pressure lowering effect of beta receptor stimulation in the normal human eye.

  4. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

    Science.gov (United States)

    Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

    2014-08-01

    The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

    Science.gov (United States)

    Sakhnini, Lama

    2003-05-01

    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  6. Metastatic Midgut Carcinoid in the Myocardium.

    Science.gov (United States)

    Bukowczan, Jakub; Lois, Konstantinos B; Skinner, Jane; Petrides, George; James, Robert Andrew; Perros, Petros

    2015-09-01

    Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

  7. Deep sequencing as a probe of normal stem cell fate and preneoplasia in human epidermis.

    Science.gov (United States)

    Simons, Benjamin D

    2016-01-05

    Using deep sequencing technology, methods based on the sporadic acquisition of somatic DNA mutations in human tissues have been used to trace the clonal evolution of progenitor cells in diseased states. However, the potential of these approaches to explore cell fate behavior of normal tissues and the initiation of preneoplasia remain underexploited. Focusing on the results of a recent deep sequencing study of eyelid epidermis, we show that the quantitative analysis of mutant clone size provides a general method to resolve the pattern of normal stem cell fate and to detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia.

  8. Distinct p53 genomic binding patterns in normal and cancer-derived human cells

    Energy Technology Data Exchange (ETDEWEB)

    Botcheva K.; McCorkle S. R.; McCombie W. R.; Dunn J. J.; Anderson C. W.

    2011-12-15

    We report here genome-wide analysis of the tumor suppressor p53 binding sites in normal human cells. 743 high-confidence ChIP-seq peaks representing putative genomic binding sites were identified in normal IMR90 fibroblasts using a reference chromatin sample. More than 40% were located within 2 kb of a transcription start site (TSS), a distribution similar to that documented for individually studied, functional p53 binding sites and, to date, not observed by previous p53 genome-wide studies. Nearly half of the high-confidence binding sites in the IMR90 cells reside in CpG islands, in marked contrast to sites reported in cancer-derived cells. The distinct genomic features of the IMR90 binding sites do not reflect a distinct preference for specific sequences, since the de novo developed p53 motif based on our study is similar to those reported by genome-wide studies of cancer cells. More likely, the different chromatin landscape in normal, compared with cancer-derived cells, influences p53 binding via modulating availability of the sites. We compared the IMR90 ChIPseq peaks to the recently published IMR90 methylome1 and demonstrated that they are enriched at hypomethylated DNA. Our study represents the first genome-wide, de novo mapping of p53 binding sites in normal human cells and reveals that p53 binding sites reside in distinct genomic landscapes in normal and cancer-derived human cells.

  9. Cdx2 modulates proliferation in normal human intestinal epithelial crypt cells

    International Nuclear Information System (INIS)

    Escaffit, Fabrice; Pare, Frederic; Gauthier, Remy; Rivard, Nathalie; Boudreau, Francois; Beaulieu, Jean-Francois

    2006-01-01

    The homeobox gene Cdx2 is involved in the regulation of the expression of intestine specific markers such as sucrase-isomaltase and lactase-phlorizin hydrolase. Previous studies performed with immortalized or transformed intestinal cell lines have provided evidence that Cdx2 can promote morphological and functional differentiation in these experimental models. However, no data exist concerning the implication of this factor in normal human intestinal cell physiology. In the present work, we have investigated the role of Cdx2 in normal human intestinal epithelial crypt (HIEC) cells that lack this transcription factor. The establishment of HIEC cells expressing Cdx2 in an inducible manner shows that forced expression of Cdx2 significantly alters the proliferation of intestinal crypt cells and stimulates dipeptidylpeptidase IV expression but is not sufficient to trigger intestinal terminal differentiation. These observations suggest that Cdx2 requires additional factors to activate the enterocyte differentiation program in normal undifferentiated cells

  10. Identification of normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections

    Science.gov (United States)

    Zhou, Yi; Chen, Zhifen; Kang, Deyong; li, Lianhuang; Zhuo, Shuangmu; Zhu, Xiaoqin; Guan, Guoxian; Chen, Jianxin

    2016-01-01

    Multiphoton microscopy (MPM) based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) as a potential diagnostic tool is attractive. MPM can effectively provide information about morphological and biochemical changes in biological tissues at the molecular level. In this paper, we attempt to identify normal and cancerous human colorectal muscularis propria by multiphoton microscopy in different sections (both in transverse and longitudinal sections). The results show that MPM can display different microstructure changes in the transverse and longitudinal sections of colorectal muscularis propria. MPM also can quantitatively describe the alteration of collagen content between normal and cancerous muscle layers. These are important pathological findings that MPM images can bring more detailed complementary information about tissue architecture and cell morphology through observing the transverse and longitudinal sections of colorectal muscularis propria. This work demonstrates that MPM can be better for identifying the microstructural characteristics of normal and cancerous human colorectal muscularis propria in different sections.

  11. Natural Antibodies in Normal Human Serum Inhibit Staphylococcus aureus Capsular Polysaccharide Vaccine Efficacy

    OpenAIRE

    Skurnik, David; Kropec, Andrea; Roux, Damien; Theilacker, Christian; Huebner, Johannes; Pier, Gerald B.

    2012-01-01

    Antibodies to Staphylococcus aureus capsular polysaccharides (CP) and poly-N-acetyl glucosamine (PNAG) antigens interfere in protection. Active immunization of mice failed to overcome interference. Natural nonprotective antibodies to PNAG in normal human serum may prevent effective vaccination against S. aureus CP antigens.

  12. Assessing the Toxicities of Regulated and Unregulated Disinfection By-products in Normal Human Colon Cells.

    Science.gov (United States)

    The presence of over six hundred disinfection by-products (DBPs) and less than half of the total organic halides present in finished water has created a need for short-term in vitro assays to address toxicities that might be associated with human exposure. . We are using a normal...

  13. Imaging of matrix-disorder in normal and pathological human dermis using nonlinear optical microscopy

    Science.gov (United States)

    Zhuo, Shuangmu; Chen, Jianxin; Xie, Shusen; Zheng, Liqin; Jiang, Xingshan

    2009-11-01

    In dermis, collagen and elastin are important structural proteins of extracellular maxtrix. The matrix-disorder is associated with various physiologic processes, such as localized scleroderma, anetoderma, photoaging. In this work, we demonstrate the capability of nonlinear optical microscopy in imaging structural proteins in normal and pathological human dermis.

  14. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  15. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

    Science.gov (United States)

    Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

    2015-11-01

    To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CI<0.01%-0.7%) after a partial hydatidiform mole, and in 0/13 patients (0%; 95% CI 0%-27%) after a twin molar pregnancy. The median time to GTN diagnosis after hCG normalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CI<0.01%-0.5%; p=0.008). All patients presented with symptoms at the time of GTN diagnosis. GTN after spontaneous hCG normalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Cell survival of human tumor cells compared with normal fibroblasts following 60Co gamma irradiation

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Henning, C.B.; Reynolds, S.D.; Holmblad, G.L.; Trier, J.E.

    1982-01-01

    Three tumor cell lines, two of which were shown to be HeLa cells, were irradiated with 60 Co gamma irradiation, together with two cell cultures of normal human diploid fibroblasts. Cell survival was studied in three different experiments over a dose range of 2 to 14 gray. All the tumor cell lines showed a very wide shoulder in the dose response curves in contrast to the extremely narrow shoulder of the normal fibroblasts. In addition, the D/sub o/ values for the tumor cell lines were somewhat greater. These two characteristics of the dose response curves resulted in up to 2 orders of magnitude less sensitivity for cell inactivation of HeLa cells when compared with normal cells at high doses (10 gray). Because of these large differences, the extrapolation of results from the irradiation of HeLa cells concerning the mechanisms of normal cell killing should be interpreted with great caution

  17. Nuclear techniques in detection of dysfunctional but viable myocardium

    International Nuclear Information System (INIS)

    Jarski, P.

    1996-01-01

    The paper presents an assessment of dysfunctional but viable myocardium, which is caused by 'stunned' and 'hibernating' myocardium. 'Stunned' myocardium refers to prolonged but reversible postischemic left ventricular dysfunction after a period of acute ischemia and coronary reperfusion. The regional dysfunction associated with 'stunning' represents the combinated effects of ischemic injury and reperfusion injury. 'Hibernating' myocardium refers to chronic left ventricular regional dysfunction arising from prolonged myocardium hypoperfusion in which myocytes remain viable but contraction is chronically depressed. This may be a protective response of the myocytes to reduce oxygen demand in the setting of reduced oxygen availability. Such nuclear imaging techniques as: thallium-201 myocardial scintigraphy, sestamibi myocardial scintigraphy and positron emission tomography are employed for evaluation dysfunctional but viable myocardium. For detection of 'stunned' myocardium all of this techniques are equal but sestamibi myocardial scintigraphy is more costless. For detection 'hibernating' myocardium the best sensitivity and specificity show positron emission tomography and thallium-201 reinjection imaging but sestamibi myocardial scintigraphy is also useful for this reason. (author)

  18. Detection of genomic instability in normal human bronchial epithelial cells exposed to 238Pu

    International Nuclear Information System (INIS)

    Kennedy, C.H.; Fukushima, N.H.; Neft, R.E.; Lechner, J.F.

    1994-01-01

    Alpha particle-emitting radon daughters constitute a risk for development of lung cancer in humans. The development of this disease involves multiple genetic alterations. These changes and the time course they follow are not yet defined despite numerous in vitro endeavors to transform human lung cells with various physical or chemical agents. However, genomic instability, characterized both by structural and numerical chromosomal aberrations and by elevated rates of point mutations, is a common feature of tumor cells. Further, both types of genomic instability have been reported in the noncancerous progeny of normal murine hemopoietic cells exposed in vitro to α-particles. The purpose of this investigation was to determine if genomic instability is also a prominent feature of normal human bronchial epithelial cells exposed to α-particle irradiation from the decay of inhaled radon daughters

  19. A Comparative Pathophysiological Study of Normal and Growth Retarded Human Placental Tissue

    Directory of Open Access Journals (Sweden)

    Adam Moyosore Afodun

    2014-01-01

    Full Text Available This study compares the pathophysiology of normal and growth retarded human placental tissues. Female patients were recruited from the Antenatal Clinic of Dolu Specialist Hospital, Mafoluku, Oshodi, Lagos, between 2008 and 2012. A total of 48 normal term placentas and 15 placentas of known IUGR cases were used for this study. IUGR cases were confirmed on the basis of ultrasound follow-up and diagnosis. Normal term placentas were collected at the point of delivery by a consultant gynaecologist, the cords were clamped, and membranes were then carefully trimmed after which each placenta was weighed. About 1 cm thickness of both normal and growth retarded placenta tissues was cut, processed for hematoxylin and eosin stain, while tissues for enzyme (ALP assay were homogenized in cold 0.5 M sucrose solution. Comparative analysis of the data was done using ANOVA; P<0.05 was taken as significant. The photomicrographs were observed/studied under light microscope, using the X150 and X600 magnifications. It was revealed therein that placental tissues are homogenous (regionally, compromised of maternal spiral arterioles and deregulated villous vasculogenesis, and that there is a significant difference in the level of alkaline phosphatase enzyme. We therefore concluded that there is a distinct difference between the normal and growth retarded human placenta tissue.

  20. Human secretory phospholipase A(2), group IB in normal eyes and in eye diseases

    DEFF Research Database (Denmark)

    Kolko, Miriam; Prause, Jan U; Bazan, Nicolas G

    2007-01-01

    study was to identify human GIB (hGIB) in the normal human eye and investigate the pattern of expression in patients with eye diseases involving hGIB-rich cells. METHODS: Human GIB mRNA was identified in the human retina by means of in situ hybridization and polymerase chain reaction. Antibodies against...... hGIB-rich cells and found downregulation of hGIB in proliferating RPE cells as well as in diseased corneal endothelial cells. CONCLUSIONS: Human GIB is highly expressed in cells with neurodermal origin. The pattern of expression of hGIB in diseases involving hGIB-rich cells demonstrated......PURPOSE: Secretory phospholipases A(2) (sPLA(2)) are enzymes involved in lipid turnover. We recently identified sPLA(2) group IB (GIB) in the rat retina as well as in cerebral neurons and found upregulation to occur in response to light damage and seizures, respectively. The purpose of the present...

  1. Extension of the Lifespan of Cultured Normal Human Diploid Cells by Vitamin E

    Science.gov (United States)

    Packer, Lester; Smith, James R.

    1974-01-01

    Inclusion of vitamin E (DL-α-tocopherol) in the culture medium for human diploid cells greatly prolongs their in vitro lifespan. The addition of 100 μg of DL-α-tocopherol per ml of medium has allowed us to culture WI-38 cells for more than 100 population doublings to date. (These cells normally have an in vitro lifespan of 50 ± 10 population doublings.) Cells at the 100th population doubling have a normal diploid karyotype, appear to behave in all other respects like young WI-38 cells, and are still actively dividing. We interpret this result as support for the free radical theory of aging. Images PMID:4531015

  2. The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts

    OpenAIRE

    Chotikasemsri, Pongsathorn; Tangtrakulwanich, Boonsin; Sangkhathat, Surasak

    2017-01-01

    The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm2 each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activ...

  3. [Morphology of the soft palate in normal humans with digital cephalometry].

    Science.gov (United States)

    Niu, Yu-Ming; Wang, Hu; Zheng, Qian; He, Xing; Zhang, Jing; Li, Xiao-Min; Lu, Yong

    2006-08-01

    To study the morphology of the soft palate in normal humans with digital radiography and to provide the references for therapy of the cleft. 106 normal people were involved. The morphology of the soft palate was observed with digital cephalometry. All static images of soft palate could be divided into six types: Shuttle-shaped, crescent-shaped, strip-shaped, S-shaped, hamulus-shaped and anomalous shaped. The dynamic image was knee-shaped. The morphology of the soft palate is varied.

  4. Fetal myocardium in the kidney capsule: an in vivo model of repopulation of myocytes by bone marrow cells.

    Directory of Open Access Journals (Sweden)

    Eric Y Zhang

    Full Text Available Debate surrounds the question of whether the heart is a post-mitotic organ in part due to the lack of an in vivo model in which myocytes are able to actively regenerate. The current study describes the first such mouse model--a fetal myocardial environment grafted into the adult kidney capsule. Here it is used to test whether cells descended from bone marrow can regenerate cardiac myocytes. One week after receiving the fetal heart grafts, recipients were lethally irradiated and transplanted with marrow from green fluorescent protein (GFP-expressing C57Bl/6J (B6 donors using normal B6 recipients and fetal donors. Levels of myocyte regeneration from GFP marrow within both fetal myocardium and adult hearts of recipients were evaluated histologically. Fetal myocardium transplants had rich neovascularization and beat regularly after 2 weeks, continuing at checkpoints of 1, 2, 4, 6, 8 and12 months after transplantation. At each time point, GFP-expressing rod-shaped myocytes were found in the fetal myocardium, but only a few were found in the adult hearts. The average count of repopulated myocardium with green rod-shaped myocytes was 996.8 cells per gram of fetal myocardial tissue, and 28.7 cells per adult heart tissue, representing a thirty-five fold increase in fetal myocardium compared to the adult heart at 12 months (when numbers of green rod-shaped myocytes were normalized to per gram of myocardial tissue. Thus, bone marrow cells can differentiate to myocytes in the fetal myocardial environment. The novel in vivo model of fetal myocardium in the kidney capsule appears to be valuable for testing repopulating abilities of potential cardiac progenitors.

  5. Prostate stem cell antigen is expressed in normal and malignant human brain tissues.

    Science.gov (United States)

    Ono, Hiroe; Sakamoto, Hiromi; Yoshida, Teruhiko; Saeki, Norihisa

    2018-03-01

    Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein and exhibits an organ-dependent expression pattern in cancer. PSCA is upregulated in prostate cancer and downregulated in gastric cancer. PSCA is expressed in a variety of human organs. Although certain studies previously demonstrated its expression in the mammalian and avian brain, its expression in the human brain has not been thoroughly elucidated. Additionally, it was previously reported that PSCA is weakly expressed in the astrocytes of the normal human brain but aberrantly expressed in glioma, suggesting that PSCA is a promising target of glioma therapy and prostate cancer therapy. The current study identified PSCA expression in the neural and choroid plexus cells of the normal human brain by immunohistochemistry. In brain tumors, PSCA was expressed in medulloblastoma and glioma, and its expression was also observed in papilloma and papillary carcinoma of the choroid plexus, ependymoma and meningioma. The results suggest that PSCA may have a tumor-promoting function in brain tumors and is a potential target for their therapy. However, its expression in normal neuronal and choroid plexus cells implies that a PSCA-targeted therapy may lead to certain adverse phenomena.

  6. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    International Nuclear Information System (INIS)

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-01-01

    Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  7. Human-Machine interface for off normal and emergency situations in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Kee Choon [Korea Atomic Energy Research Institute, Taejeon (Korea)

    2000-01-01

    Many nuclear power plants (NPPs) have reported that a high percentage of all major failures in the plants are caused by human errors. Therefore, there has been much focus on elimination of human errors, enhancement of human performance, and general improvement of human machine interface (HMI). Both the utility management and the regulators are demanding improvement in this area. The International Atomic Energy Agency (IAEA) Specialists' Meeting on 'Human-Machine Interface for Off Normal and Emergency Situations in Nuclear Power Plants' was co-organized by the Korea Atomic Energy Research Institute (KAERI) and the Korea Power Engineering Company, INC (KOPEC), and took place in Taejeon, Republic of Korea, 1999 October 26-28. Fifty eight participants, representing nine member countries reviewed recent developments and discussed directions for future efforts in the Human-Machine Interface for Off Normal and Emergency Situations in NPPs. Twenty papers were presented, covering a wide spectrum of technical and scientific subjects including recent experience and benefits from Operational Experience with HMI, Development of HMI System, Licensing Issues for HMI and Future Development and Trends. (Author)

  8. The effect of percutaneous transmyocardial laser revascularization on left ventricular function in a porcine model of hibernating myocardium

    International Nuclear Information System (INIS)

    Almeda, Francis Q.; Glock, Dana; Sandelski, Joanne; Ibrahim, Osama; Macioch, James E.; Allen, Trisha; Dainauskas, John R.; Parrillo, Joseph E.; Snell, R. Jeffrey; Schaer, Gary L.

    2004-01-01

    Background: Hibernating myocardium is defined as a state of persistently impaired myocardial function at rest due to reduced coronary blood flow that can partially or completely be restored to normal if the myocardial oxygen supply/demand relationship is favorably altered. Percutaneous laser revascularization (PMR) is an emerging catheter-based technique that involves creating channels in the myocardium, directly through a percutaneous approach with a laser delivery system, and has been shown to reduce symptoms in patients with severe refractory angina; however, its effect on improving regional wall motion abnormalities in hibernating myocardium has not been clearly established. We sought to determine the effect of PMR using the Eclipse System (Cardiogenesis) on left ventricular function in a porcine model of hibernating myocardium. Methods: A model of hibernating myocardium was created by placement of an ameroid constrictor in the proximal left anterior descending artery of a 35 kg male Yorkshire pig. The presence of hibernating myocardium was confirmed with dobutamine stress echocardiography (DSE) and defined as severe hypocontractility at rest, with an improvement in systolic wall thickening with low-dose dobutamine in myocardial regions with a subsequent deterioration in function at peak stress (biphasic response). After the demonstration of hibernating myocardium, PMR was performed in the area of hypocontractile function, and the serial echocardiography was performed. The echocardiograms were reviewed by an experienced echocardiologist blinded to the results, and regional wall motion was assessed using the American Society of Echocardiography Wall Motion Score. Six weeks after PMR, the animal was sacrificed and the heart sent for histopathologic studies. Results: A comparison of the regional wall motion function of the area distal to the ameroid constrictor and in the contralateral wall at baseline, post-ameroid placement, and post-PMR was performed

  9. Kinetics of thallium-201 in reperfused canine myocardium after coronary artery occlusion

    International Nuclear Information System (INIS)

    Okada, R.D.

    1984-01-01

    To study the kinetics of thallium-201 in nonsalvaged acutely infarcted myocardium and salvaged myocardium, the tracer was administered after experimental left anterior descending coronary artery reperfusion 2 hours after occlusion. In 19 dogs, thallium activity was then monitored for 4 hours in the reperfused anterior wall and normal posterior wall using miniature cadmium telluride radiation detectors. After sacrifice, 13 of the dogs were found to have an infarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean (+/- standard deviation) fractional 4 hour thallium clearance was 0.33 +/- 0.08 for the infarct zone and 0.15 +/- 0.06 for the normal control zone (p less than 0.001). When computer-modeled, the clearance curve from the infarct zone was biexponential. The second exponential clearance curve from the infarct zone began 19.1 +/- 3.2 minutes after tracer administration, and was indistinguishable from the monoexponential clearance curve from the normal control zone. Thallium clearance from the blood pool was triexponential, the final exponential clearance curve being indistinguishable from the normal control zone clearance curve. Six dogs were found to have a salvaged noninfarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean fractional 4 hour thallium clearance was 0.20 +/- 0.07 for the reperfused zone, and 0.19 +/- 0.08 for the normal control zone (p . NS). When computer-modeled, clearance curves for the reperfused and control zones were monoexponential. The monoexponential clearance curve for the salvaged reperfused zone was indistinguishable from the monoexponential clearance curve for normal myocardium

  10. Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

    Science.gov (United States)

    2011-01-01

    Background We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model. Methods Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h. Results In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05). Conclusion MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model. PMID:21244680

  11. Enhanced normal short-term human myelopoiesis in mice engineered to express human-specific myeloid growth factors.

    Science.gov (United States)

    Miller, Paul H; Cheung, Alice M S; Beer, Philip A; Knapp, David J H F; Dhillon, Kiran; Rabu, Gabrielle; Rostamirad, Shabnam; Humphries, R Keith; Eaves, Connie J

    2013-01-31

    Better methods to characterize normal human hematopoietic cells with short-term repopulating activity cells (STRCs) are needed to facilitate improving recovery rates in transplanted patients.We now show that 5-fold more human myeloid cells are produced in sublethally irradiated NOD/SCID-IL-2Receptor-γchain-null (NSG) mice engineered to constitutively produce human interleukin-3, granulocyte-macrophage colony-stimulating factor and Steel factor (NSG-3GS mice) than in regular NSG mice 3 weeks after an intravenous injection of CD34 human cord blood cells. Importantly, the NSG-3GS mice also show a concomitant and matched increase in circulating mature human neutrophils. Imaging NSG-3GS recipients of lenti-luciferase-transduced cells showed that human cells being produced 3 weeks posttransplant were heterogeneously distributed, validating the blood as a more representative measure of transplanted STRC activity. Limiting dilution transplants further demonstrated that the early increase in human granulopoiesis in NSG-3GS mice reflects an expanded output of differentiated cells per STRC rather than an increase in STRC detection. NSG-3GS mice support enhanced clonal outputs from human short-term repopulating cells (STRCs) without affecting their engrafting efficiency. Increased human STRC clone sizes enable their more precise and efficient measurement by peripheral blood monitoring.

  12. Contribution to the study of thallium 201 myocardium scintigraphy

    International Nuclear Information System (INIS)

    Annweiler, Marc.

    1976-01-01

    In this work a new isotope was tested in the field of myocardium scintigraphy: thallium 201. The different radioisotopes used so far in myocardium scintigraphy are reviewed to begin with. The main biological and physical characteristics of thallium and the scintillation camera used for this work are described next. In our opinion thallium 201 owing to its biological behavior similar to that of potassium and to its physical characteristics, appears as one of the better -if not the best- known tracer suitable for use in myocardium scintigraphy. Its properties are suited to the use of a scintillation camera, which considerably shortens the examination time and thus allows an isotopic exploration of the myocardium from several incidences. The only disadvantage of this cyclotron-produced isotope seems to be its high price which will probably limit its use on a large scale. Fifty thallium 201 myocardium scintigraphs were practised on forty-eight coronary thrombosis patients. From this was established a precise topographic correlation between the electrocardiographic diagnosis and the scintigraph. The two corresponded in 47 cases out of 50. The few disagreements between ECG and scintigraphic results seem to be due either to poor-quality images or to an overall myocardium hypofixation connected with a very extensive necrosis. This means that thallium 201 myocardium scintigraphy is a reliable method of examination in the great majority of cases, giving a direct picture of the heart muscle and its necrotic lesions [fr

  13. Transient metabolic changes observed with proton MR spectroscopy in normal human brain after radiation therapy

    International Nuclear Information System (INIS)

    Esteve, Francois; Rubin, Christophe; Grand, Sylvie; Kolodie, Helene; Le Bas, Jean-Francois

    1998-01-01

    Purpose: To observe the time course of the proton magnetic resonance spectroscopy ( 1 H-MRS) variations due to radiation therapy on normal human brain. Methods and Materials: We followed 11 patients receiving an exclusive external radiation therapy for brain tumor for 8 months. They underwent proton MRS scans before any radiation exposure and 1, 4, and 8 months after they began the radiation therapy. The patients received 60 Gy in tumoral area fractionated over 6 weeks. The contralateral normal brain hemisphere received a radiation dose from 20 to 50 Gy. The main metabolite concentrations (N-acetylaspartate (NAA), choline compounds (Cho), creatine (Cr), and lactate (Lac) were evaluated by the areas of the peaks after peak fitting. Normalized values (NV) were obtained by processing the ratio of the peak area of a given metabolite to the sum of all the spectrum peak areas; ratios (NAA/Cho, NAA/Cr, and Cho/Cr) were processed. One patient, who received panencephalic radiotherapy (30 Gy) after metastasectomy from a primary kidney adenocarcinoma, has been monitored with 1 H-MRS eight times for 6 months to observe the onset of the metabolic changes. Results: Changes were observed in irradiated normal brain tissue 4 months after radiation therapy began: the NAA/Cho and NAA/Cr ratios and the NAA (NV) decreased while the Choline (NV) increased. Four months later, normal values were recovered. Conclusion: 1 H-MRS has the potentiality to detect and to evaluate in vivo early adverse metabolic effects of radiation therapy in the normal human brain. These changes are significant 4 months after the radiation therapy began and appear to resolve over time

  14. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    Science.gov (United States)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  15. Distortion-Product Otoacoustic Emission Measured Below 300 Hz in Normal-Hearing Human Subjects

    DEFF Research Database (Denmark)

    Christensen, Anders Tornvig; Ordoñez Pizarro, Rodrigo Eduardo; Hammershøi, Dorte

    2017-01-01

    , a custom-built low-frequency acoustic probe was put to use in 21 normal-hearing human subjects (of 34 recruited). Distortion-product otoacoustic emission (DPOAE) was measured in the enclosed ear canal volume as the response to two simultaneously presented tones with frequencies f1 and f2. The stimulus......Physiological noise levels in the human ear canal often exceed naturally low levels of otoacoustic emissions (OAEs) near the threshold of hearing. Low-frequency noise, and electronic filtering to cope with it, has effectively limited the study of OAE to frequencies above about 500 Hz. Presently...

  16. Simple mucin-type carbohydrates in normal and malignant human endometrium

    DEFF Research Database (Denmark)

    Ravn, V; Mandel, U; Svenstrup, B

    1995-01-01

    The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human...... and malignant endometrium, and the expression of s-T antigen was positively correlated with E2 levels in serum. Our findings suggest a hormonal influence on expression of simple mucin-type carbohydrates in human endometrium. However, the accumulation of Tn and s-Tn antigens in malignant endometrial cells seem...

  17. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  18. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

  19. Normalizing and scaling of data to derive human response corridors from impact tests.

    Science.gov (United States)

    Yoganandan, Narayan; Arun, Mike W J; Pintar, Frank A

    2014-06-03

    It is well known that variability is inherent in any biological experiment. Human cadavers (Post-Mortem Human Subjects, PMHS) are routinely used to determine responses to impact loading for crashworthiness applications including civilian (motor vehicle) and military environments. It is important to transform measured variables from PMHS tests (accelerations, forces and deflections) to a standard or reference population, termed normalization. The transformation process should account for inter-specimen variations with some underlying assumptions used during normalization. Scaling is a process by which normalized responses are converted from one standard to another (example, mid-size adult male to large-male and small-size female adults, and to pediatric populations). These responses are used to derive corridors to assess the biofidelity of anthropomorphic test devices (crash dummies) used to predict injury in impact environments and design injury mitigating devices. This survey examines the pros and cons of different approaches for obtaining normalized and scaled responses and corridors used in biomechanical studies for over four decades. Specifically, the equal-stress equal-velocity and impulse-momentum methods along with their variations are discussed in this review. Methods ranging from subjective to quasi-static loading to different approaches are discussed for deriving temporal mean and plus minus one standard deviation human corridors of time-varying fundamental responses and cross variables (e.g., force-deflection). The survey offers some insights into the potential efficacy of these approaches with examples from recent impact tests and concludes with recommendations for future studies. The importance of considering various parameters during the experimental design of human impact tests is stressed. Published by Elsevier Ltd.

  20. Topographical Distribution of Arsenic, Manganese, and Selenium in the Normal Human Brain

    DEFF Research Database (Denmark)

    Larsen, Niels Agersnap; Pakkenberg, H.; Damsgaard, Else

    1979-01-01

    The concentrations of arsenic, manganese and selenium per gram wet tissue weight were determined in samples from 24 areas of normal human brains from 5 persons with ages ranging from 15 to 81 years of age. The concentrations of the 3 elements were determined for each sample by means of neutron......% for selenium. The results seem to indicate that arsenic is associated with the lipid phase, manganese with the dry matter and selenium with the aqueous phase of brain tissue....

  1. Identification of an Antigen from Normal Human Tissue That Crossreacts with the Carcinoembryonic Antigen

    Science.gov (United States)

    Kleist, S. Von; Chavanel, G.; Burtin, P.

    1972-01-01

    A glycoprotein present in normal human tissue is characterized that is neither organ- nor tumor-specific (nonspecific crossreacting antigen) and that crossreacts (by the Ouchterlony double-diffusion technique) with the carcinoembryonic antigen. This immunological relationship indicates common determinants on the molecules of both antigens. We demonstrate that the nonspecific crossreacting antigen is not a fragment of the carcinoembryonic antigen molecule. Images PMID:4115954

  2. Incorporation of 14C-linoleic acid in lipids of normal and psoriatic human skin

    International Nuclear Information System (INIS)

    Ruestow, B.; Metz, D.; Kunze, D.; Meffert, H.

    1980-01-01

    The 14 C-linoleic acid incorporation in lipids of surviving epidermis and corium of normal and psoriatic human skin was investigated. Changes of lipid metabolism were found in both epidermis and corium. Particularly the turnover of phospholipids was increased in the uninvolved psoriatic epidermis in relation to the involved psoriatic epidermis or to healthy controls. Possible reasons of these phenomena and the significance of structural lipids in psoriasis are discussed. (author)

  3. Spontaneous regression of anterior mediastinal seminoma with normalization of ?-human chorionic gonadotropin levels

    OpenAIRE

    Yu, Zaiqiang; Kimura, Daisuke; Tsushima, Takao; Fukuda, Ikuo

    2017-01-01

    Introduction: Although spontaneous regression (SR) of anterior mediastinal seminoma is very rare with normalization of β-human chorionic gonadotropin (β-hCG) level, video-assisted thoracic surgery (VATS) is the most effective solution for definite diagnosis of indeterminate anterior mediastinal masses. Diagnosis, therapeutic interventions, and outcomes: A rare case of an asymptomatic 37-year-old man with an anterior mediastinal mass that was detected on a routine chest X-ray is presented. ...

  4. Proton MR spectroscopic features of the human liver: in-vivo application to the normal condition

    International Nuclear Information System (INIS)

    Cho, Soon Gu; Kim, Mi Young; Kim, Young Soo; Choi, Won; Shin, Seok Hwan; Ok, Chul Soo; Suh, Chang Hae

    1999-01-01

    To determine the feasibility of MR spectroscopy in the living human liver, and to evaluate the corresponding proton MR spectroscopic features. In fifteen normal volunteers with neither previous nor present liver disease, the proton MR spectroscopic findings were reviewed. Twelve subjects were male and three were female ; they were aged between 28 and 32 (mean, 30) years. MR spectroscopy involved the use of a 1.5T GE Signa Horizon system with body coil(GE Medical System, Milwaukee, U.S.A). We used STEAM (Stimulated Echo-Acquisition Mode) with 3000/30 msec of TR/TE for signal acquisition, and the prone position without respiratory interruption. Mean and standard deviation of the ratios of glutamate+glutamine/lipids, phosphomonoesters/lipids, and glycogen+glucose/lipids were calculated from the area of their peaks. The proton MR spectroscopic findings of normal human livers showed four distinctive peaks, i.e. lipids, glutamate and glutamine complex, phosphomonoesters, and glycogen and glucose complex. The mean and standard deviation of the ratios of glutamate+glutamine/lipids, phosphomonoesters/lipids, and glycogen+glucose/lipids were 0.02±0.01, 0.01±0.01, and 0.04±0.03, respectively. In living normal human livers, MR spectroscopy can be successfully applied. When applied to a liver whose condition is pathologic, the findings can be used as a standard

  5. An integrated proteomic and peptidomic assessment of the normal human urinome.

    Science.gov (United States)

    Di Meo, Ashley; Batruch, Ihor; Yousef, Arsani G; Pasic, Maria D; Diamandis, Eleftherios P; Yousef, George M

    2017-02-01

    Urine represents an ideal source of clinically relevant biomarkers as it contains a large number of proteins and low molecular weight peptides. The comprehensive characterization of the normal urinary proteome and peptidome can serve as a reference for future biomarker discovery. Proteomic and peptidomic analysis of urine can also provide insight into normal physiology and disease pathology, especially for urogenital diseases. We developed an integrated proteomic and peptidomic analytical protocol in normal urine. We employed ultrafiltration to separate protein and peptide fractions, which were analyzed separately using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) on the Q-Exactive mass spectrometer. By analyzing six urines from healthy individuals with advanced age, we identified 1754 proteins by proteomic analysis and 4543 endogenous peptides, arising from 566 proteins by peptidomic analysis. Overall, we identified 2091 non-redundant proteins by this integrated approach. In silico protease activity analysis indicated that metalloproteases are predominantly involved in the generation of the endogenous peptide signature. In addition, a number of proteins that were detected in normal urine have previously been implicated in various urological malignancies, including bladder cancer and renal cell carcinoma (RCC). We utilized a highly sensitive proteomics approach that enabled us to identify one of the largest sets of protein identifications documented in normal human urine. The raw proteomics and peptidomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD003595.

  6. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    Science.gov (United States)

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-09-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-soluble fraction in the 100-300-kD range. Plasma proteins with anti-H2O2 properties were in insufficient concentrations to provide the antioxidant protection observed. However, catalase, a normal intracellular antioxidant, was present in sufficient concentration to account for most of the observed anti-H2O2 properties of ELF. Depletion of ELF with an anticatalase antibody abolished the anti-H2O2 macromolecular defenses of ELF. Since catalase is not normally released by cells, a likely explanation for its presence in high concentrations in normal ELF is that it is released by lung inflammatory and parenchymal cells onto the epithelial surface of the lower respiratory tract during their normal turnover and collects there due to the slow turnover of ELF. It is likely that catalase in the ELF of normal individuals plays a role in protecting lung parenchymal cells against oxidants present in the extracellular milieu.

  7. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

    Directory of Open Access Journals (Sweden)

    Ann-Marie Baker

    2014-08-01

    Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

  8. PARP Inhibitors in Clinical Use Induce Genomic Instability in Normal Human Cells.

    Directory of Open Access Journals (Sweden)

    Shuhei Ito

    Full Text Available Poly(ADP-ribose polymerases (PARPs are the first proteins involved in cellular DNA repair pathways to be targeted by specific inhibitors for clinical benefit. Tumors harboring genetic defects in homologous recombination (HR, a DNA double-strand break (DSB repair pathway, are hypersensitive to PARP inhibitors (PARPi. Early phase clinical trials with PARPi have been promising in patients with advanced BRCA1 or BRCA2-associated breast, ovary and prostate cancer and have led to limited approval for treatment of BRCA-deficient ovary cancer. Unlike HR-defective cells, HR-proficient cells manifest very low cytotoxicity when exposed to PARPi, although they mount a DNA damage response. However, the genotoxic effects on normal human cells when agents including PARPi disturb proficient cellular repair processes have not been substantially investigated. We quantified cytogenetic alterations of human cells, including primary lymphoid cells and non-tumorigenic and tumorigenic epithelial cell lines, exposed to PARPi at clinically relevant doses by both sister chromatid exchange (SCE assays and chromosome spreading. As expected, both olaparib and veliparib effectively inhibited poly-ADP-ribosylation (PAR, and caused marked hypersensitivity in HR-deficient cells. Significant dose-dependent increases in SCEs were observed in normal and non-tumorigenic cells with minimal residual PAR activity. Clinically relevant doses of the FDA-approved olaparib led to a marked increase of SCEs (5-10-fold and chromatid aberrations (2-6-fold. Furthermore, olaparib potentiated SCE induction by cisplatin in normal human cells. Our data have important implications for therapies with regard to sustained genotoxicity to normal cells. Genomic instability arising from PARPi warrants consideration, especially if these agents will be used in people with early stage cancers, in prevention strategies or for non-oncologic indications.

  9. Focalized contractile impairment at hypertrophied myocardium proven in consideration of wall stress in patients with hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Yamazaki, Tadashi; Suzuki, Jun-ichi; Shimamoto, Ryoichi; Tsuji, Taeko; Ohmoto, Yuki; Toyo-oka, Teruhiko; Omata, Masao; Ohtomo, Kuni; Nagai, Ryozo

    2006-01-01

    In hypertrophic cardiomyopathy (HCM) a hyperkinetic state is sometimes observed in spite of impaired systolic function in the hypertrophied myocardium. The aim of the present study was to determine the mechanism of this paradox. Seventeen patients with HCM and 10 normal subjects underwent cine magnetic resonance (MR) imaging to measure percent systolic wall thickening and percent fractional shortening. The ratio of systolic radial wall stress of the LV at the hypertrophied myocardium over that at the nonhypertrophied myocardium was evaluated to describe the focal advantageous condition for wall thickening. The ratio was 0.66±0.36 at the start of contraction and 0.78±0.31 at early-systole, indicating consistently smaller radial wall stress at the hypertrophied myocardium. Although the condition for contraction was favorable (a ratio less than 1.00), percent systolic wall thickening at the hypertrophied myocardium (23.0±11.8%) was smaller than that at the nonhypertrophied myocardium (70.5±32.3%). Smaller end-diastolic dimension (HCM group; 45.2±4.2 mm, reference group; 48.9±4.1 mm, P=0.04) with a statistically identical value of systolic decrease in intraventricular dimension (HCM group; 19.7±3.9 mm, reference group; 18.9±3.2 mm, P=0.60) yielded high percent fractional shortening in patients with HCM (43.5±7.6%). Although contractile impairment was proven at the hypertrophied region with low radial wall stress in the HCM group, the smaller end-diastolic dimension in this group resulted in high percent fractional shortening. (author)

  10. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  11. Collagen content and distribution in the normal and transplanted human heart: A postmortem quantitative light microscopic analysis

    NARCIS (Netherlands)

    R-J. van Suylen (Robert-Jan); E. van Bekkum; H. Boersma (Eric); L.B. de Kok (L.); A.H.M.M. Balk (Aggie); E. Bos (Egbert); F.T.B. Bosman (Fré)

    1996-01-01

    textabstractEndomyocardial biopsies in heart transplant patients offer the opportunity to study the myocardial interstitium in the context of myocardial function. For that purpose endomyocardial biopsies should reliably reflect the composition of the entire myocardium. We determined whether the

  12. [Effect of Qishen Yiqi droplet on adenylate contents in myocardium of cor pulmonale rats].

    Science.gov (United States)

    Geng, Shi-Han; Shan, Qiu-Yue; Xu, Meng-Xi; Zhang, Yi-Dan; Song, Li-Li; Hou, Ning; Zhang, Wen; Zhang, Mi-Xia; Zhuang, Peng-Wei; Zhang, Yan-Jun

    2017-01-01

    Cor pulmonale rat models were induced by a single intraperitoneal injection of monocrotaline(MCT), and the sham group received a single intraperitioneal injection of normal saline. After the model rats received intragastric administration of Qishen Yiqi droplet(QS) for 6 weeks, the contents of adenylate(ATP, ADP and AMP) in right myocardial tissues were measured by HPLC, and then the metabolism changes in myocardium of cor pulmonale rats with QS were investigated. The results showed that ATP, ADP, and AMP were well separated, with a good linearity within a certain range of concentration; and the recovery rates were within the range of 90%-108%. As compared with model group, the level of ATP was significantly elevated in high-dose treatment group; ADP contents showed an increasing trend and AMP contents showed a decreasing trend, indicating that QS could significantly improve energy metabolism system in myocardium. By using the HPLC, a qualitative and quantitative analysis method was given for the determination of ATP, ADP and AMP contents in myocardium, providing a method for energy metabolism measurement in biological samples. Copyright© by the Chinese Pharmaceutical Association.

  13. Evaluation of MCF10A as a Reliable Model for Normal Human Mammary Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Ying Qu

    Full Text Available Breast cancer is the most common cancer in women and a leading cause of cancer-related deaths for women worldwide. Various cell models have been developed to study breast cancer tumorigenesis, metastasis, and drug sensitivity. The MCF10A human mammary epithelial cell line is a widely used in vitro model for studying normal breast cell function and transformation. However, there is limited knowledge about whether MCF10A cells reliably represent normal human mammary cells. MCF10A cells were grown in monolayer, suspension (mammosphere culture, three-dimensional (3D "on-top" Matrigel, 3D "cell-embedded" Matrigel, or mixed Matrigel/collagen I gel. Suspension culture was performed with the MammoCult medium and low-attachment culture plates. Cells grown in 3D culture were fixed and subjected to either immunofluorescence staining or embedding and sectioning followed by immunohistochemistry and immunofluorescence staining. Cells or slides were stained for protein markers commonly used to identify mammary progenitor and epithelial cells. MCF10A cells expressed markers representing luminal, basal, and progenitor phenotypes in two-dimensional (2D culture. When grown in suspension culture, MCF10A cells showed low mammosphere-forming ability. Cells in mammospheres and 3D culture expressed both luminal and basal markers. Surprisingly, the acinar structure formed by MCF10A cells in 3D culture was positive for both basal markers and the milk proteins β-casein and α-lactalbumin. MCF10A cells exhibit a unique differentiated phenotype in 3D culture which may not exist or be rare in normal human breast tissue. Our results raise a question as to whether the commonly used MCF10A cell line is a suitable model for human mammary cell studies.

  14. Evaluation of MCF10A as a Reliable Model for Normal Human Mammary Epithelial Cells.

    Science.gov (United States)

    Qu, Ying; Han, Bingchen; Yu, Yi; Yao, Weiwu; Bose, Shikha; Karlan, Beth Y; Giuliano, Armando E; Cui, Xiaojiang

    2015-01-01

    Breast cancer is the most common cancer in women and a leading cause of cancer-related deaths for women worldwide. Various cell models have been developed to study breast cancer tumorigenesis, metastasis, and drug sensitivity. The MCF10A human mammary epithelial cell line is a widely used in vitro model for studying normal breast cell function and transformation. However, there is limited knowledge about whether MCF10A cells reliably represent normal human mammary cells. MCF10A cells were grown in monolayer, suspension (mammosphere culture), three-dimensional (3D) "on-top" Matrigel, 3D "cell-embedded" Matrigel, or mixed Matrigel/collagen I gel. Suspension culture was performed with the MammoCult medium and low-attachment culture plates. Cells grown in 3D culture were fixed and subjected to either immunofluorescence staining or embedding and sectioning followed by immunohistochemistry and immunofluorescence staining. Cells or slides were stained for protein markers commonly used to identify mammary progenitor and epithelial cells. MCF10A cells expressed markers representing luminal, basal, and progenitor phenotypes in two-dimensional (2D) culture. When grown in suspension culture, MCF10A cells showed low mammosphere-forming ability. Cells in mammospheres and 3D culture expressed both luminal and basal markers. Surprisingly, the acinar structure formed by MCF10A cells in 3D culture was positive for both basal markers and the milk proteins β-casein and α-lactalbumin. MCF10A cells exhibit a unique differentiated phenotype in 3D culture which may not exist or be rare in normal human breast tissue. Our results raise a question as to whether the commonly used MCF10A cell line is a suitable model for human mammary cell studies.

  15. Differential Effects of Tea Extracts on Growth and Cytokine Production by Normal and Leukemic Human Leukocytes

    Directory of Open Access Journals (Sweden)

    Diana Bayer

    2012-04-01

    Full Text Available Background: Tea is one of the world’s most highly consumed beverages, second only to water. It is affordable and abundant and thus has great potential for improving health of those in both developed and developing areas. Green, oolong, and black teas differ in the extent of fermentation and types of bioactive polyphenols produced. Green tea and its major polyphenol decrease growth of some cancer cells and effect production of immune system cytokines. This study compares the effects of different types of tea extracts on viability and cytokine production by normal and leukemic human T lymphocytes. Generation of the toxic reactive oxygen species H2O2 by extracts was also examined.Methods: The Jurkat T lymphoblastic leukemia cells and mitogen-stimulated normal human peripheral blood mononuclear cells were used in this study. Cell viability was determined by (3-4,5-dimethylthiamizol-2-yl-diphenyltetrazolium bromide assay and production of interleukin-2 by Enzyme-Linked ImmunoSorbent Assay. Levels of H2O2 generated by tea extracts were determined using the xylenol-orange method.Results: We found that green, oolong, and black tea extracts differentially effect the growth and viability of T lymphoblastic leukemia cells and normal peripheral blood mononuclear cells, substantially decreasing both growth and viability of leukemic T lymphocytes and having much lesser effects on their normal counterparts. Tea extracts also had differential effects on the production of the T lymphocyte growth factor interleukin-2, significantly decreasing production by leukemic cells while having only minor effects on normal cells. All three extracts induced H2O2 generation, with green and oolong tea extracts having the greatest effect. Leukemic cells were much more susceptible to growth inhibition and killing by H2O2 than normal lymphocytes.Functional Foods in Health and Disease 2012, 2(4:72-85 Conclusions: The three tea extracts studied altered leukemic T lymphocyte

  16. Human respiratory syncytial virus load normalized by cell quantification as predictor of acute respiratory tract infection.

    Science.gov (United States)

    Gómez-Novo, Miriam; Boga, José A; Álvarez-Argüelles, Marta E; Rojo-Alba, Susana; Fernández, Ana; Menéndez, María J; de Oña, María; Melón, Santiago

    2018-01-05

    Human respiratory syncytial virus (HRSV) is a common cause of respiratory infections. The main objective is to analyze the prediction ability of viral load of HRSV normalized by cell number in respiratory symptoms. A prospective, descriptive, and analytical study was performed. From 7307 respiratory samples processed between December 2014 to April 2016, 1019 HRSV-positive samples, were included in this study. Low respiratory tract infection was present in 729 patients (71.54%). Normalized HRSV load was calculated by quantification of HRSV genome and human β-globin gene and expressed as log10 copies/1000 cells. HRSV mean loads were 4.09 ± 2.08 and 4.82 ± 2.09 log10 copies/1000 cells in the 549 pharyngeal and 470 nasopharyngeal samples, respectively (P respiratory tract infection and 4.22 ± 2.28 log10 copies/1000 cells with upper respiratory tract infection or febrile syndrome (P < 0.05). A possible cut off value to predict LRTI evolution was tentatively established. Normalization of viral load by cell number in the samples is essential to ensure an optimal virological molecular diagnosis avoiding that the quality of samples affects the results. A high viral load can be a useful marker to predict disease progression. © 2018 Wiley Periodicals, Inc.

  17. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    DEFF Research Database (Denmark)

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

    2010-01-01

    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo......BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response...... to chemotherapy. Pulmonary lobectomy was performed, and hCG rapidly declined. During further chemotherapy, liver metastasis was detected by positron emission tomography. Right hepatectomy was performed, and hCG declined for 28 days, but increased again despite chemotherapy. This patient died from hepatic failure...... 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2...

  18. Analysis of differential protein expression in normal and neoplastic human breast epithelial cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Williams, K.; Chubb, C.; Huberman, E.; Giometti, C.S.

    1997-07-01

    High resolution two dimensional get electrophoresis (2DE) and database analysis was used to establish protein expression patterns for cultured normal human mammary epithelial cells and thirteen breast cancer cell lines. The Human Breast Epithelial Cell database contains the 2DE protein patterns, including relative protein abundances, for each cell line, plus a composite pattern that contains all the common and specifically expressed proteins from all the cell lines. Significant differences in protein expression, both qualitative and quantitative, were observed not only between normal cells and tumor cells, but also among the tumor cell lines. Eight percent of the consistently detected proteins were found in significantly (P < 0.001) variable levels among the cell lines. Using a combination of immunostaining, comigration with purified protein, subcellular fractionation, and amino-terminal protein sequencing, we identified a subset of the differentially expressed proteins. These identified proteins include the cytoskeletal proteins actin, tubulin, vimentin, and cytokeratins. The cell lines can be classified into four distinct groups based on their intermediate filament protein profile. We also identified heat shock proteins; hsp27, hsp60, and hsp70 varied in abundance and in some cases in the relative phosphorylation levels among the cell lines. Finally, we identified IMP dehydrogenase in each of the cell lines, and found the levels of this enzyme in the tumor cell lines elevated 2- to 20-fold relative to the levels in normal cells.

  19. Preferential orientation of biological apatite in normal and osteoporotic human vertebral trabeculae

    Science.gov (United States)

    Miyabe, S.; Ishimoto, T.; Nakano, T.

    2009-05-01

    The preferential orientation of biological apatite (BAp) is a possible bone quality parameter for the comparison of the bone mechanical property. The preferential BAp orientation undergoes sensitive changes according to the change in the in vivo stress distribution, bone turnover rate etc., resulting in a variation of bone function. Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone microstructure. The effect of osteoporosis on the preferential BAp orientation is however unknown. In this study, a microbeam-X-ray diffraction (μXRD) study was carried out on a trabecula extracted from osteoporotic and normal human vertebral bones and the degree of orientation for the BAp c-axis along its craniocaudal axis was analysed based on our previous report. A micro-computed tomography (μCT) measurement was also performed to analyze trabecular density and structure. In osteoporotic human vertebra, the trabecular number is markedly lower than that in normal vertebra. To sustain increased stress because of bone loss, the primary trabeculae, which are aligned parallel to the craniocaudal axis, tend to selectively remain while the secondary trabeculae, which are perpendicular to the craniocaudal axis, mostly disappear. Moreover, the primary trabecula from osteoporotic vertebra showed a significantly higher degree of BAp preferential orientation than the normal bone. This suggests that the remaining primary trabecula in osteoporotic vertebra is further reinforced by an increase in applied stress in vivo by enhancing the preferred BAp c-axis orientation along the trabecular direction.

  20. Preferential orientation of biological apatite in normal and osteoporotic human vertebral trabeculae

    Energy Technology Data Exchange (ETDEWEB)

    Miyabe, S; Ishimoto, T; Nakano, T [Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: nakano@mat.eng.osaka-u.ac.jp

    2009-05-01

    The preferential orientation of biological apatite (BAp) is a possible bone quality parameter for the comparison of the bone mechanical property. The preferential BAp orientation undergoes sensitive changes according to the change in the in vivo stress distribution, bone turnover rate etc., resulting in a variation of bone function. Osteoporosis is a metabolic bone disease characterized by reduced bone mass and deterioration of bone microstructure. The effect of osteoporosis on the preferential BAp orientation is however unknown. In this study, a microbeam-X-ray diffraction ({mu}XRD) study was carried out on a trabecula extracted from osteoporotic and normal human vertebral bones and the degree of orientation for the BAp c-axis along its craniocaudal axis was analysed based on our previous report. A micro-computed tomography ({mu}CT) measurement was also performed to analyze trabecular density and structure. In osteoporotic human vertebra, the trabecular number is markedly lower than that in normal vertebra. To sustain increased stress because of bone loss, the primary trabeculae, which are aligned parallel to the craniocaudal axis, tend to selectively remain while the secondary trabeculae, which are perpendicular to the craniocaudal axis, mostly disappear. Moreover, the primary trabecula from osteoporotic vertebra showed a significantly higher degree of BAp preferential orientation than the normal bone. This suggests that the remaining primary trabecula in osteoporotic vertebra is further reinforced by an increase in applied stress in vivo by enhancing the preferred BAp c-axis orientation along the trabecular direction.

  1. Effects of myocardial infarction on the distribution and transport of nutrients and oxygen in porcine myocardium.

    Science.gov (United States)

    Davis, Bryce H; Morimoto, Yoshihisa; Sample, Chris; Olbrich, Kevin; Leddy, Holly A; Guilak, Farshid; Taylor, Doris A

    2012-10-01

    One of the primary limitations of cell therapy for myocardial infarction is the low survival of transplanted cells, with a loss of up to 80% of cells within 3 days of delivery. The aims of this study were to investigate the distribution of nutrients and oxygen in infarcted myocardium and to quantify how macromolecular transport properties might affect cell survival. Transmural myocardial infarction was created by controlled cryoablation in pigs. At 30 days post-infarction, oxygen and metabolite levels were measured in the peripheral skeletal muscle, normal myocardium, the infarct border zone, and the infarct interior. The diffusion coefficients of fluorescein or FITC-labeled dextran (0.3-70 kD) were measured in these tissues using fluorescence recovery after photobleaching. The vascular density was measured via endogenous alkaline phosphatase staining. To examine the influence of these infarct conditions on cells therapeutically used in vivo, skeletal myoblast survival and differentiation were studied in vitro under the oxygen and glucose concentrations measured in the infarct tissue. Glucose and oxygen concentrations, along with vascular density were significantly reduced in infarct when compared to the uninjured myocardium and infarct border zone, although the degree of decrease differed. The diffusivity of molecules smaller than 40 kD was significantly higher in infarct center and border zone as compared to uninjured heart. Skeletal myoblast differentiation and survival were decreased stepwise from control to hypoxia, starvation, and ischemia conditions. Although oxygen, glucose, and vascular density were significantly reduced in infarcted myocardium, the rate of macromolecular diffusion was significantly increased, suggesting that diffusive transport may not be inhibited in infarct tissue, and thus the supply of nutrients to transplanted cells may be possible. in vitro studies mimicking infarct conditions suggest that increasing nutrients available to

  2. Effects of hyperthermia and ionizing radiation in normal and ataxia telangiectasia human fibroblast lines

    International Nuclear Information System (INIS)

    Mitchel, R.E.J.; Chan, A.; Smith, B.P.; Child, S.D.; Paterson, M.C.

    1984-01-01

    The effects of 45 0 C hyperthermia and γ radiation have been studied in three normal human fibroblast lines (GM38, GM730, WI38) and compared to the effects in two lines derived from patients with the hereditary disease ataxia telangiectasia (AR3BI, AT5BI). All lines, both normal and γ-sensitive AT, showed a similar resistance to killing by heat alone, suggesting that the defect responsible for the increased radiation sensitivity in AT lines does not confer increased heat sensitivity. Shouldered survival curves were obtained in each case indicating the ability to accumulate sublethal heat damage. All normal and AT cell lines exhibited increased resistance to the lethal effects of heat in response to a thermal stress, indicating that the defect that causes radiosensitivity in AT cell lines does not prevent the induction of thermotolerance. It was hypothesized that in normal cells, this heat treatment inactivates the process which is already defective in AT lines, and that this process may be required for the proper rejoining of double-strand breaks produced during the repair of other radiation-induced lesions

  3. Dynamic knee alignment and collateral knee laxity and its variations in normal humans

    Directory of Open Access Journals (Sweden)

    Kamal eDeep

    2015-11-01

    Full Text Available Alignment of normal, arthritic and replaced human knees is a much debated subject as is the collateral ligamentous laxity. Traditional quantitative values have been challenged. Methods used to measure these are also not without flaws. Authors review the recent literature and a novel method of measurement of these values has been included. This method includes use of computer navigation technique in clinic setting for assessment of the normal or affected knee before the surgery. Computer navigation has been known for achievement of alignment accuracy during knee surgery. Now its use in clinic setting has added to the inventory of measurement methods. Authors dispel the common myth of straight mechanical axis in normal knees and also look at quantification of amount of collateral knee laxity. Based on the scientific studies it has been shown that the mean alignment is in varus in normal knees. It changes from lying non weight bearing position to standing weight bearing position in both coronal and the sagittal planes. It also varies with gender and race. The collateral laxity is also different for males and females. Further studies are needed to define the ideal alignment and collateral laxity which the surgeon should aim for individual knees.

  4. Genetic determination of human facial morphology: links between cleft-lips and normal variation.

    Science.gov (United States)

    Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred

    2011-11-01

    Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

  5. Cardiac Telocytes in Regeneration of Myocardium After Myocardial Infarction.

    Science.gov (United States)

    Zhaofu, Liao; Dongqing, Cai

    2016-01-01

    Recent research progress has revealed that a novel type of interstitial cells termed cardiac telocytes (CTs) is found in the interstitium of the heart. We demonstrated that CTs are distributed both longitudinally and within the cross network in the myocardium and that the density of CTs in the atrium-atria and base of the myocardium is higher than that in the middle of the myocardium, while the density of CTs in the epicardium is higher than that in the endocardium. In addition, we documented, for the first time, that the network of CTs in the infarct zone of the myocardium is destroyed during myocardial infarction (MI). This fact shows that, in addition to the death of cardiac myocytes, the previously unrecognized death of CTs is an important mechanism that contributes to the structural damage and poor healing and regeneration observed in the infarcted myocardium. Furthermore, we demonstrated, for the first time, that transplantation of CTs in cases of MI decreases the infarct size and improves myocardial function. The mechanisms behind the beneficial effects of CT transplantation are increased angiogenesis at the infarct site and the border zone, decreased fibrosis in the infarct and non-infarct zones, improved pathological reconstruction of the left ventricle, and increased regeneration of CTs in the infarct zone. Our findings reveal that CTs can be specifically identified by the following characteristics: very small cell bodies, extreme prolongation with some dilation, predisposition to cell death under ischemia, and expression of molecular markers such as c-Kit, CD34, vimentin, and PDGFR-β. CTs act as a structural and functional niche microenvironment in the myocardium and play an essential role in maintaining the integrity of the myocardium and in the regeneration of damaged myocardium.

  6. Chronic microelectrode investigations of normal human brain physiology using a hybrid depth electrode.

    Science.gov (United States)

    Howard, M A; Volkov, I O; Noh, M D; Granner, M A; Mirsky, R; Garell, P C

    1997-01-01

    Neurosurgeons have unique access to in vivo human brain tissue, and in the course of clinical treatment important scientific advances have been made that further our understanding of normal brain physiology. In the modern era, microelectrode recordings have been used to systematically investigate the cellular properties of lateral temporal cerebral cortex. The current report describes a hybrid depth electrode (HDE) recording technique that was developed to enable neurosurgeons to simultaneously investigate normal cellular physiology during chronic intracranial EEG recordings. The HDE combines microelectrode and EEG recordings sites on a single shaft. Multiple microelectrode recordings are obtained from MRI defined brain sites and single-unit activity is discriminated from these data. To date, over 60 HDEs have been placed in 20 epilepsy surgery patients. Unique physiologic data have been gathered from neurons in numerous brain regions, including amygdala, hippocampus, frontal lobe, insula and Heschl's gyrus. Functional activation studies were carried out without risking patient safety or comfort.

  7. Effects of sterilizing radiation dose on the amino acid composition of normal human Ig(G)

    International Nuclear Information System (INIS)

    Kaupert, N.L.; Mariano, E.E.

    1981-01-01

    In order to verify gamma radiation effect of 60 Co, samples of Normal human Ig(G) in a) pH 7 solutions with different concentrations, and b) in liophilized state, were irradiated. In both, the quali and quantitative amino acid compositions have been studied. No changes in amino acid composition were observed, for doses up to 10 Mrad delivered to the liophilized samples. Nevertheless, when 5 mg/ml and 10 mg/ml solutions of Ig(G) were irradiated with a 2 Mrad gamma dose, both were affected. The damage appeared in greater proportion in the samples with lower concentration. Cistine was the amino acid most damaged and the loss of methionine, proline histidine, arginine, tirosine and phenilalanine, decreased in this order. The analysis of the experimental data shows that liophilized human Ig(G) can be treated with doses higher than those required to achieve sterilization, without modifying its immunologic and primary proteic structure properties. Therefore, gamma sterilization feasibility has been proved for normal human Ig(G) only in the liophilized state. (author) [es

  8. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    Science.gov (United States)

    Ryan, James; Curran, Catherine E.; Hennessy, Emer; Newell, John; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M.

    2011-01-01

    Introduction The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Methods Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. Results The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log10 Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log10RQ, pbreast tissue (1.18(0.07) Log10RQ, pbreast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones. PMID:21283523

  9. Pulse wave imaging in normal, hypertensive and aneurysmal human aortas in vivo: a feasibility study

    Science.gov (United States)

    Li, Ronny X.; Luo, Jianwen; Balaram, Sandhya K.; Chaudhry, Farooq A.; Shahmirzadi, Danial; Konofagou, Elisa E.

    2013-07-01

    Arterial stiffness is a well-established biomarker for cardiovascular risk, especially in the case of hypertension. The progressive stages of an abdominal aortic aneurysm (AAA) have also been associated with varying arterial stiffness. Pulse wave imaging (PWI) is a noninvasive, ultrasound imaging-based technique that uses the pulse wave-induced arterial wall motion to map the propagation of the pulse wave and measure the regional pulse wave velocity (PWV) as an index of arterial stiffness. In this study, the clinical feasibility of PWI was evaluated in normal, hypertensive, and aneurysmal human aortas. Radiofrequency-based speckle tracking was used to estimate the pulse wave-induced displacements in the abdominal aortic walls of normal (N = 15, mean age 32.5 ± 10.2 years), hypertensive (N = 13, mean age 60.8 ± 15.8 years), and aneurysmal (N = 5, mean age 71.6 ± 11.8 years) human subjects. Linear regression of the spatio-temporal variation of the displacement waveform in the anterior aortic wall over a single cardiac cycle yielded the slope as the PWV and the coefficient of determination r2 as an approximate measure of the pulse wave propagation uniformity. The aortic PWV measurements in all normal, hypertensive, and AAA subjects were 6.03 ± 1.68, 6.69 ± 2.80, and 10.54 ± 6.52 m s-1, respectively. There was no significant difference (p = 0.15) between the PWVs of the normal and hypertensive subjects while the PWVs of the AAA subjects were significantly higher (p pathologies that regionally alter the arterial wall mechanics.

  10. Change in C3G protein expression in the peri-infarct myocardium and its significance in rats

    Directory of Open Access Journals (Sweden)

    Li-ping WANG

    2012-08-01

    Full Text Available Objective To investigate the change in expression of C3G protein, a Crk SH3 domain-binding guanine nucleotide-releasing factor, in the peri-infarct myocardium in rats. Methods Male SD rats were randomly divided into experimental myocardial infarction (MI group and sham-operated (SO group using Litwin method. The rats in the MI and SO groups were sacrificed at 24 hours and 12 weeks after the operation, and the myocardium was harvested from the cardiac apex in the SO group and the infarct area in the MI group for determination of types Ⅰand Ⅲcollagen and C3G protein expression with picric acid-sirius red staining and immunohistochemistry. Non-infarcted myocardium in the MI group and the normal myocardium in the SO group were havrested for measuring the relative expression level of C3G protein by Western blotting. Results The picric acid-sirius red staining showed that typesⅠand Ⅲcollagen volume was respectively 14.01±2.73 and 4.80±0.64 12 weeks after MI, 3.15±0.70 and 1.42±0.48 24 hours after SO, 3.68±0.95 and 1.53±0.61 24 hours after MI, and 3.27±0.65 and 1.47±0.52 (P 0.05. Western blotting revealed that the C3G protein expression 12 weeks after MI was significantly increased compared with that in the other three groups (P 0.05. C3G protein expression in the non-infarct myocardium at 12-week post MI (0.56±0.06, n=8 was significantly higher as compared with that in the cardiac apex 12 weeks (0.22±0.04, n=8, 24 hours (0.22±0.04, n=8 after SO and in the non-infarct myocardium 24 hours after MI (0.29±0.02, n=8 respectively (All P < 0.05. Conclusions C3G protein exists in the myocardium in rats. C3G protein expression could significantly increase in the peri-infarct myocardium. The increased C3G protein expression could be involved in post-infarction cardiac remodeling.

  11. Transcription factors GATA-4 and GATA-6 in normal and neoplastic human gastrointestinal mucosa

    Directory of Open Access Journals (Sweden)

    Mäki Markku

    2008-04-01

    Full Text Available Abstract Background Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastrointestinal mucosa, but their role in human gastrointestinal tract remains unexplored. We studied in detail the expression patterns of these two GATA factors and a GATA-6 down-stream target, Indian hedgehog (Ihh, in normal human gastrointestinal mucosa. Since these factors are considered important for proliferation and differentiation, we also explored the possible alterations in their expression in gastrointestinal neoplasias. The expression of the carcinogenesis-related protein Indian hedgehog was also investigated in comparison to GATA factors. Methods Samples of normal and neoplastic gastrointestinal tract from children and adults were subjected to RNA in situ hybridization with 33P labelled probes and immunohistochemistry, using an avidin-biotin immunoperoxidase system. The pathological tissues examined included samples of chronic and atrophic gastritis as well as adenomas and adenocarcinomas of the colon and rectum. Results GATA-4 was abundant in the differentiated epithelial cells of the proximal parts of the gastrointestinal tract but was absent from the distal parts. In contrast, GATA-6 was expressed throughout the gastrointestinal epithelium, and in the distal gut its expression was most intense at the bottom of the crypts, i.e. cells with proliferative capacity. Both factors were also present in Barrett's esophagus and metaplasia of the stomach. GATA-6 expression was reduced in colon carcinoma. Ihh expression overlapped with that of GATA-6 especially in benign gastrointestinal neoplasias. Conclusion The results suggest differential but overlapping functions for GATA-4 and

  12. Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

    Directory of Open Access Journals (Sweden)

    Norwood Thomas H

    2006-07-01

    Full Text Available Abstract Background X chromosome inactivation (XCI is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi in normal female cells, leaving them with a single active X (Xa as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1 that normal development requires a ratio of one Xa per diploid autosomal set, and 2 that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default. Results Triploids provide a test of these ideas because the ratio of one Xa per diploid autosomal set cannot be achieved, yet this abnormal ratio should not necessarily affect the one-Xa choice mechanism for XCI. Previous studies of XCI patterns in murine triploids support the single-Xa model, but human triploids mostly have two-Xa cells, whether they are XXX or XXY. The XCI patterns we observe in fibroblast cultures from different XXX human triploids suggest that the two-Xa pattern of XCI is selected for, and may have resulted from rare segregation errors or Xi reactivation. Conclusion The initial X inactivation pattern in human triploids, therefore, is likely to resemble the pattern that predominates in murine triploids, i.e., a single Xa, with the remaining X's inactive. Furthermore, our studies of XIST RNA accumulation and promoter methylation suggest that the basic features of XCI are normal in triploids despite the abnormal X:autosome ratio.

  13. Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota.

    Science.gov (United States)

    Rashid, Mamun-Ur; Rosenborg, Staffan; Panagiotidis, Georgios; Söderberg-Löfdal, Karin; Weintraub, Andrej; Nord, Carl Erik

    2015-08-01

    Ceftaroline-avibactam is a new combination of the antibiotic ceftaroline with a novel non-β-lactam β-lactamase inhibitor, avibactam. The purpose of the present study was to investigate the effect of ceftaroline-avibactam on the human intestinal microbiota. Fourteen healthy volunteers received ceftaroline-avibactam (600 mg ceftaroline fosamil and 600 mg avibactam) intravenously over 2 h every 8 h on days 1 to 6 and as a single dose on day 7. Fecal samples were collected on day -1 (within 24 h of the first infusion on day 1) and on days 2, 5, 7, 9, 14, and 21. Escherichia coli numbers decreased during the study and normalized on day 21. An increased number of Klebsiella bacteria appeared on day 14 and normalized on day 21. The number of other enterobacteria decreased during the study, and the number of enterococci decreased from days 2 to 7 and normalized on day 9. Candida numbers increased from days 5 to 9 and normalized after day 14. The number of lactobacilli decreased during the study and recovered on day 14. The number of bifidobacteria decreased on day 2 and normalized on day 21. The number of Bacteroides bacteria was unchanged. Clostridium difficile numbers decreased on days 7 and 9 and increased on days 14 and 21. A toxigenic C. difficile strain was detected in one volunteer on day 21 with no reported adverse events. Plasma samples were collected on days -1, 2, 5, and 7. Ceftaroline and avibactam concentrations were 0 to 34.5 mg/liter and 0 to 61.6 mg/liter, respectively, in plasma and 0 to 35.4 mg/kg and 0 to 98.5 mg/kg, respectively, in feces. (This study is registered in the European Clinical Trials Database [https://eudract.ema.europa.eu/] under number EudraCT 2012 004921-25.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Nystagmus responses in a group of normal humans during earth-horizontal axis rotation

    Science.gov (United States)

    Wall, Conrad, III; Furman, Joseph M. R.

    1989-01-01

    Horizontal eye movement responses to earth-horizontal yaw axis rotation were evaluated in 50 normal human subjects who were uniformly distributed in age (20-69 years) and each age group was then divided by gender. Subjects were rotated with eyes open in the dark, using clockwise and counter-clockwise 60 deg velocity trapezoids. The nystagmus slow component velocity is analyzed. It is shown that, despite large intersubject variability, parameters which describe earth-horizontal yaw axis responses are loosely interrelated, and some of them vary significantly with gender and age.

  15. Reconstruction and Visualization of Fiber and Laminar Structure inthe Normal Human Heart from Ex Vivo DTMRI Data

    Energy Technology Data Exchange (ETDEWEB)

    Rohmer, Damien; Sitek, Arkadiusz; Gullberg, Grant T.

    2006-12-18

    Background - The human heart is composed of a helicalnetwork of muscle fibers. These fibers are organized to form sheets thatare separated by cleavage surfaces. This complex structure of fibers andsheets is responsible for the orthotropic mechanical properties ofcardiac muscle. The understanding of the configuration of the 3D fiberand sheet structure is important for modeling the mechanical andelectrical properties of the heart and changes in this configuration maybe of significant importance to understand the remodeling aftermyocardial infarction.Methods - Anisotropic least square filteringfollowed by fiber and sheet tracking techniques were applied to DiffusionTensor Magnetic Resonance Imaging (DTMRI) data of the excised humanheart. The fiber configuration was visualized by using thin tubes toincrease 3-dimensional visual perception of the complex structure. Thesheet structures were reconstructed from the DTMRI data, obtainingsurfaces that span the wall from the endo- to the epicardium. Allvisualizations were performed using the high-quality ray-tracing softwarePOV-Ray. Results - The fibers are shown to lie in sheets that haveconcave or convex transmural structure which correspond to histologicalstudies published in the literature. The fiber angles varied depending onthe position between the epi- and endocardium. The sheets had a complexstructure that depended on the location within the myocardium. In theapex region the sheets had more curvature. Conclusions - A high-qualityvisualization algorithm applied to demonstrated high quality DTMRI datais able to elicit the comprehension of the complex 3 dimensionalstructure of the fibers and sheets in the heart.

  16. Differential gene expression induced by high LET charged particles in normal human fibroblasts

    International Nuclear Information System (INIS)

    Shingyoji, Masato; Ding, Liang-Hao; Chen, D.J.; Eguchi-Kasai, Kiyomi

    2004-01-01

    We investigated differential gene expression of normal human skin HSF42 fibroblasts induced by heavy ions using cDNA microarray technology. Irradiation with 3 types of heavy ions was performed at Heavy Ion Medical Accelerator in Chiba (HIMAC) facility. Out of 7458 genes, we found 61 significant genes (40 up-regulated and 21 down-regulated) that distinguished between human skin fibroblast HSF42 cells non-irradiated and irradiated with 1 Gy of neon particles and 62 significant genes (48 up-regulated and 14 down-regulated) that distinguished between HSF42 cells non-irradiated and irradiated with 1 Gy of silicon particles. Furthermore, we are going to analyze profiles of HSF42 cells exposed to carbon particles and compare those profiles between different types of beams. (author)

  17. Visual Acuity of Simulated Thalamic Visual Prostheses in Normally Sighted Humans

    Science.gov (United States)

    Jeffries, Ailsa; Pezaris, John S.

    2013-01-01

    Simulation in normally sighted individuals is a crucial tool to evaluate the performance of potential visual prosthesis designs prior to human implantation of a device. Here, we investigated the effects of electrode count on visual acuity, learning rate and response time in 16 normally sighted subjects using a simulated thalamic visual prosthesis, providing the first performance reports for thalamic designs. A new letter recognition paradigm using a multiple-optotype two-alternative forced choice task was adapted from the Snellen eye chart, and specifically devised to be readily communicated to both human and non-human primate subjects. Validation of the method against a standard Snellen acuity test in 21 human subjects showed no significant differences between the two tests. The novel task was then used to address three questions about simulations of the center-weighted phosphene patterns typical of thalamic designs: What are the expected Snellen acuities for devices with varying numbers of contacts, do subjects display rapid adaptation to the new visual modality, and can response time in the task provide clues to the mechanisms of perception in low-resolution artificial vision? Population performance (hit rate) was significantly above chance when viewing Snellen 20/200 optotypes (Log MAR 1.0) with 370 phosphenes in the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6) with 25 central phosphenes. Furthermore, subjects demonstrated learning within the 1–2 hours of task experience indicating the potential for an effective rehabilitation and possibly better visual performance after a longer period of training. Response time differences suggest that direct letter perception occurred when hit rate was above 75%, whereas a slower strategy like feature-based pattern matching was used in conditions of lower relative resolution. As pattern matching can substantially boost effective acuity, these results suggest post-implant therapy should specifically

  18. Visual acuity of simulated thalamic visual prostheses in normally sighted humans.

    Directory of Open Access Journals (Sweden)

    Béchir Bourkiza

    Full Text Available Simulation in normally sighted individuals is a crucial tool to evaluate the performance of potential visual prosthesis designs prior to human implantation of a device. Here, we investigated the effects of electrode count on visual acuity, learning rate and response time in 16 normally sighted subjects using a simulated thalamic visual prosthesis, providing the first performance reports for thalamic designs. A new letter recognition paradigm using a multiple-optotype two-alternative forced choice task was adapted from the Snellen eye chart, and specifically devised to be readily communicated to both human and non-human primate subjects. Validation of the method against a standard Snellen acuity test in 21 human subjects showed no significant differences between the two tests. The novel task was then used to address three questions about simulations of the center-weighted phosphene patterns typical of thalamic designs: What are the expected Snellen acuities for devices with varying numbers of contacts, do subjects display rapid adaptation to the new visual modality, and can response time in the task provide clues to the mechanisms of perception in low-resolution artificial vision? Population performance (hit rate was significantly above chance when viewing Snellen 20/200 optotypes (Log MAR 1.0 with 370 phosphenes in the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6 with 25 central phosphenes. Furthermore, subjects demonstrated learning within the 1-2 hours of task experience indicating the potential for an effective rehabilitation and possibly better visual performance after a longer period of training. Response time differences suggest that direct letter perception occurred when hit rate was above 75%, whereas a slower strategy like feature-based pattern matching was used in conditions of lower relative resolution. As pattern matching can substantially boost effective acuity, these results suggest post-implant therapy

  19. The effects of pravastatin on the normal human placenta: Lessons from ex-vivo models.

    Directory of Open Access Journals (Sweden)

    Adelina Balan

    Full Text Available Research in animal models and preliminary clinical studies in humans support the use of pravastatin for the prevention of preeclampsia. However, its use during pregnancy is still controversial due to limited data about its effect on the human placenta and fetus.In the present study, human placental cotyledons were perfused in the absence or presence of pravastatin in the maternal reservoir (PraM. In addition, placental explants were treated with pravastatin for 5, 24 and 72 h under normoxia and hypoxia. We monitored the secretion of placental growth factor (PlGF, soluble fms-like tyrosine kinase-1 (sFlt-1, soluble endoglin (sEng, endothelial nitric oxide synthase (eNOS expression and activation and the fetal vasoconstriction response to angiotensin-II.The concentrations of PlGF, sFlt-1 and sEng were not significantly altered by pravastatin in PraM cotyledons and in placental explants compared to control. Under hypoxic conditions, pravastatin decreased sFlt-1 concentrations. eNOS expression was significantly increased in PraM cotyledons but not in pravastatin-treated placental explants cultured under normoxia or hypoxia. eNOS phosphorylation was not significantly affected by pravastatin. The feto-placental vascular tone and the fetal vasoconstriction response to angiotensin-II, did not change following exposure of the maternal circulation to pravastatin.We found that pravastatin does not alter the essential physiological functions of the placenta investigated in the study. The relevance of the study lays in the fact that it expands the current knowledge obtained thus far regarding the effect of the drug on the normal human placenta. This data is reassuring and important for clinicians that consider the treatment of high-risk patients with pravastatin, a treatment that exposes some normal pregnancies to the drug.

  20. Normal and stenotic human aortic valve opening: in vitro assessment of orifice area changes with flow.

    Science.gov (United States)

    Montarello, J K; Perakis, A C; Rosenthal, E; Boyd, E G; Yates, A K; Deverall, P B; Sowton, E; Curry, P V

    1990-06-01

    The ability to measure aortic valve area clinically has emphasized the need to understand the changes in aortic valve orifice area during flow. To compare the performance of normal and stenotic human aortic valves we used a pulsatile flow model that simulated in vivo flow conditions. Five normal autopsy specimens and 15 stenotic valves removed at operation were mounted into the model. Valve function was assessed by analysis of video recordings of valve leaflet motion during flow. Over the flow rates tested normal valves demonstrated a linear increase in orifice area. There was no resistance to leaflet opening and valve closure was rapid. The majority of stenotic valves demonstrated an increase in orifice area at low flow rates. No valve showed any increase in maximal area beyond flow rates of 3 l min-1. Increased leaflet resistance of these abnormal valves resulted in notably slower opening and closing rates. In patients with a high cardiac output and severe stenosis, overestimation of the anatomic orifice area derived by the Gorlin equation can result. This is not related to variability in maximal orifice area.

  1. The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts

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    Pongsathorn Chotikasemsri

    2017-01-01

    Full Text Available The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm, green (520 nm, and blue (465 nm LED light for 10 minutes at 0.67 J/cm2 each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET. Therefore, genetic screening before phototherapy treatment may be required.

  2. The Effect of Phototherapy on Cancer Predisposition Genes of Diabetic and Normal Human Skin Fibroblasts.

    Science.gov (United States)

    Chotikasemsri, Pongsathorn; Tangtrakulwanich, Boonsin; Sangkhathat, Surasak

    2017-01-01

    The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm 2 each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET. Therefore, genetic screening before phototherapy treatment may be required.

  3. Three-dimensional counting of morphologically normal human red blood cells via digital holographic microscopy

    Science.gov (United States)

    Yi, Faliu; Moon, Inkyu; Lee, Yeon H.

    2015-01-01

    Counting morphologically normal cells in human red blood cells (RBCs) is extremely beneficial in the health care field. We propose a three-dimensional (3-D) classification method of automatically determining the morphologically normal RBCs in the phase image of multiple human RBCs that are obtained by off-axis digital holographic microscopy (DHM). The RBC holograms are first recorded by DHM, and then the phase images of multiple RBCs are reconstructed by a computational numerical algorithm. To design the classifier, the three typical RBC shapes, which are stomatocyte, discocyte, and echinocyte, are used for training and testing. Nonmain or abnormal RBC shapes different from the three normal shapes are defined as the fourth category. Ten features, including projected surface area, average phase value, mean corpuscular hemoglobin, perimeter, mean corpuscular hemoglobin surface density, circularity, mean phase of center part, sphericity coefficient, elongation, and pallor, are extracted from each RBC after segmenting the reconstructed phase images by using a watershed transform algorithm. Moreover, four additional properties, such as projected surface area, perimeter, average phase value, and elongation, are measured from the inner part of each cell, which can give significant information beyond the previous 10 features for the separation of the RBC groups; these are verified in the experiment by the statistical method of Hotelling's T-square test. We also apply the principal component analysis algorithm to reduce the dimension number of variables and establish the Gaussian mixture densities using the projected data with the first eight principal components. Consequently, the Gaussian mixtures are used to design the discriminant functions based on Bayesian decision theory. To improve the performance of the Bayes classifier and the accuracy of estimation of its error rate, the leaving-one-out technique is applied. Experimental results show that the proposed method can

  4. Analysis of normal human retinal vascular network architecture using multifractal geometry

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    Ştefan Ţălu

    2017-03-01

    Full Text Available AIM: To apply the multifractal analysis method as a quantitative approach to a comprehensive description of the microvascular network architecture of the normal human retina. METHODS: Fifty volunteers were enrolled in this study in the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and January 2014. A set of 100 segmented and skeletonised human retinal images, corresponding to normal states of the retina were studied. An automatic unsupervised method for retinal vessel segmentation was applied before multifractal analysis. The multifractal analysis of digital retinal images was made with computer algorithms, applying the standard box-counting method. Statistical analyses were performed using the GraphPad InStat software. RESULTS: The architecture of normal human retinal microvascular network was able to be described using the multifractal geometry. The average of generalized dimensions (Dq for q=0, 1, 2, the width of the multifractal spectrum (Δα=αmax - αmin and the spectrum arms’ heights difference (│Δf│ of the normal images were expressed as mean±standard deviation (SD: for segmented versions, D0=1.7014±0.0057; D1=1.6507±0.0058; D2=1.5772±0.0059; Δα=0.92441±0.0085; │Δf│= 0.1453±0.0051; for skeletonised versions, D0=1.6303±0.0051; D1=1.6012±0.0059; D2=1.5531±0.0058; Δα=0.65032±0.0162; │Δf│= 0.0238±0.0161. The average of generalized dimensions (Dq for q=0, 1, 2, the width of the multifractal spectrum (Δα and the spectrum arms’ heights difference (│Δf│ of the segmented versions was slightly greater than the skeletonised versions. CONCLUSION: The multifractal analysis of fundus photographs may be used as a quantitative parameter for the evaluation of the complex three-dimensional structure of the retinal microvasculature as a potential marker for early detection of topological changes associated with retinal diseases.

  5. The Fate of a Normal Human Cell Traversed by a Single Charged Particle

    Science.gov (United States)

    Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

    2012-01-01

    The long-term “fate” of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability. PMID:22966418

  6. Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models.

    Science.gov (United States)

    Wetmore, Cynthia

    2003-02-01

    Cancer arises when a cell accumulates multiple genetic changes that allow it to elude the highly regulated balance between proliferation and apoptosis that an organism employs to suppress inappropriate growth. It has become evident that malignant transformation of a cell or group of cells often involves pathways that are active during normal development but are inappropriately regulated in neoplastic proliferation. Signaling via the Sonic hedgehog pathway is critical to vertebrate development and also appears to play an integral role in the initiation and propagation of some tumors of the muscle, skin and nervous system. Analyses of human tumors have revealed mutations in various components of the Sonic hedgehog signaling pathway that appear to result in the activation of this pathway, as inferred by the increased expression of the transcription factor, Gli1. Interestingly, a proportion of the human tumors and most of those arising in mouse models continue to express the normal Patched allele, suggesting the involvement of additional molecular events in the transformation of the haploinsufficient cells.

  7. Raman Spectroscopy of DNA Packaging in Individual Human Sperm Cells distinguishes Normal from Abnormal Cells

    Energy Technology Data Exchange (ETDEWEB)

    Huser, T; Orme, C; Hollars, C; Corzett, M; Balhorn, R

    2009-03-09

    Healthy human males produce sperm cells of which about 25-40% have abnormal head shapes. Increases in the percentage of sperm exhibiting aberrant sperm head morphologies have been correlated with male infertility, and biochemical studies of pooled sperm have suggested that sperm with abnormal shape may contain DNA that has not been properly repackaged by protamine during spermatid development. We have used micro-Raman spectroscopy to obtain Raman spectra from individual human sperm cells and examined how differences in the Raman spectra of sperm chromatin correlate with cell shape. We show that Raman spectra of individual sperm cells contain vibrational marker modes that can be used to assess the efficiency of DNA-packaging for each cell. Raman spectra obtained from sperm cells with normal shape provide evidence that DNA in these sperm is very efficiently packaged. We find, however, that the relative protein content per cell and DNA packaging efficiencies are distributed over a relatively wide range for sperm cells with both normal and abnormal shape. These findings indicate that single cell Raman spectroscopy should be a valuable tool in assessing the quality of sperm cells for in-vitro fertilization.

  8. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Sivapragasam Gothai

    2016-03-01

    Full Text Available Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for treatment of cuts, wounds and burns. Moringa oleifera is an herb used as traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of M. oleifera leaves extract are completely unknown. Methods: In the current study, ethyl acetate fraction of Moringa oleifera leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml of ethyl acetate fraction of M. oleifera leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: The present study suggested that ethyl acetate fraction of M. oleifera leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. [J Complement Med Res 2016; 5(1.000: 1-6

  9. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts.

    Science.gov (United States)

    Gothai, Sivapragasam; Arulselvan, Palanisamy; Tan, Woan Sean; Fakurazi, Sharida

    2016-01-01

    Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for the treatment of cuts, wounds and burns. Moringa oleifera (MO) is an herb used as a traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of MO leaves extract are completely unknown. In the current study, ethyl acetate fraction of MO leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate) in human normal dermal fibroblast cells. Results revealed that lower concentration (12.5 µg/ml, 25 µg/ml, and 50 µg/ml) of ethyl acetate fraction of MO leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. This study suggested that ethyl acetate fraction of MO leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use.

  10. HSP10 selective preference for myeloid and megakaryocytic precursors in normal human bone marrow

    Directory of Open Access Journals (Sweden)

    F Cappello

    2009-06-01

    Full Text Available Heat shock proteins (HSPs constitute a heterogeneous family of proteins involved in cell homeostasis. During cell life they are involved in harmful insults, as well as in immune and inflammatory reactions. It is known that they regulate gene expression, and cell proliferation, differentiation and death. HSP60 is a mitochondrial chaperonin, highly preserved during evolution, responsible of protein folding. Its function is strictly dependent on HSP10 in both prokaryotic and eukaryotic elements. We investigated the presence and the expression of HSP60 and HSP10 in a series of 20 normal human bone marrow specimens (NHBM by the means of immunohistochemistry. NHBM showed no expression of HSP60, probably due to its being below the detectable threshold, as already demonstrated in other normal human tissues. By contrast, HSP10 showed a selective positivity for myeloid and megakaryocytic lineages. The positivity was restricted to precursor cells, while mature elements were constantly negative.We postulate that HSP10 plays a role in bone marrow cell differentiation other than being a mitochondrial co-chaperonin. The present data emphasize the role of HSP10 during cellular homeostasis and encourage further investigations in this field.

  11. The Fate of a Normal Human Cell Traversed by a Single Charged Particle

    Science.gov (United States)

    Fournier, C.; Zahnreich, S.; Kraft, D.; Friedrich, T.; Voss, K.-O.; Durante, M.; Ritter, S.

    2012-09-01

    The long-term ``fate'' of normal human cells after single hits of charged particles is one of the oldest unsolved issues in radiation protection and cellular radiobiology. Using a high-precision heavy-ion microbeam we could target normal human fibroblasts with exactly one or five carbon ions and measured the early cytogenetic damage and the late behaviour using single-cell cloning. Around 70% of the first cycle cells presented visible aberrations in mFISH after a single ion traversal, and about 5% of the cells were still able to form colonies. In one third of selected high-proliferative colonies we observed clonal (radiation-induced) aberrations. Terminal differentiation and markers of senescence (PCNA, p16) in the descendants of cells traversed by one carbon ion occurred earlier than in controls, but no evidence of radiation-induced chromosomal instability was found. We conclude that cells surviving single-ion traversal, often carrying clonal chromosome aberrations, undergo accelerated senescence but maintain chromosomal stability.

  12. Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart.

    Science.gov (United States)

    Caracausi, Maria; Piovesan, Allison; Vitale, Lorenza; Pelleri, Maria Chiara

    2017-04-01

    A systematic meta-analysis of the available gene expression profiling datasets for the whole normal human heart generated a quantitative transcriptome reference map of this organ. Transcriptome Mapper (TRAM) software integrated 32 gene expression profile datasets from different sources returning a reference value of expression for each of the 43,360 known, mapped transcripts assayed by any of the experimental platforms used in this regard. Main findings include the visualization at the gene and chromosomal levels of the classical description of the basic histology and physiology of the heart, the identification of suitable housekeeping reference genes, the analysis of stoichiometry of gene products, and the focusing on chromosome 21 genes, which are present in one excess copy in Down syndrome subjects, presenting cardiovascular defects in 30-40% of cases. Independent in vitro validation showed an excellent correlation coefficient (r = 0.98) with the in silico data. Remarkably, heart/non-cardiac tissue expression ratio may also be used to anticipate that effects of mutations will most probably affect or not the heart. The quantitative reference global portrait of gene expression in the whole normal human heart illustrates the structural and functional aspects of the whole organ and is a general model to understand the mechanisms underlying heart pathophysiology. J. Cell. Physiol. 232: 759-770, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Wound healing properties of ethyl acetate fraction of Moringa oleifera in normal human dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Sivapragasam Gothai

    2016-03-01

    Full Text Available Background/Aim: Wounds are the outcome of injuries to the skin that interrupt the soft tissue. Healing of a wound is a complex and long-drawn-out process of tissue repair and remodeling in response to injury. A large number of plants are used by folklore traditions for treatment of cuts, wounds and burns. Moringa oleifera is an herb used as traditional folk medicine for the treatment of various skin wounds and associated diseases. The underlying mechanisms of wound healing activity of ethyl acetate fraction of M. oleifera leaves extract are completely unknown. Methods: In the current study, ethyl acetate fraction of Moringa oleifera leaves was investigated for its efficacy on cell viability, proliferation and migration (wound closure rate in human normal dermal fibroblast cells. Results: Results revealed that lower concentration (12.5 and micro;g/ml, 25 and micro;g/ml, and 50 and micro;g/ml of ethyl acetate fraction of M. oleifera leaves showed remarkable proliferative and migratory effect on normal human dermal fibroblasts. Conclusion: The present study suggested that ethyl acetate fraction of M. oleifera leaves might be a potential therapeutic agent for skin wound healing by promoting fibroblast proliferation and migration through increasing the wound closure rate corroborating its traditional use. [J Intercult Ethnopharmacol 2016; 5(1.000: 1-6

  14. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    Science.gov (United States)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  15. Vesicular Stomatitis Virus Variants Selectively Infect and Kill Human Melanomas but Not Normal Melanocytes

    Science.gov (United States)

    Wollmann, Guido; Davis, John N.; Bosenberg, Marcus W.

    2013-01-01

    Metastatic malignant melanoma remains one of the most therapeutically challenging forms of cancer. Here we test replication-competent vesicular stomatitis viruses (VSV) on 19 primary human melanoma samples and compare these infections with those of normal human melanocyte control cells. Even at a low viral concentration, we found a strong susceptibility to viral oncolysis in over 70% of melanomas. In contrast, melanocytes displayed strong resistance to virus infection and showed complete protection by interferon. Several recombinant VSVs were compared, and all infected and killed most melanomas with differences in the time course with increasing rates of melanoma infection, as follows: VSV-CT9-M51 melanoma xenografts in SCID mice after tail vein virus application. Sequence analysis of mutations in the melanomas used revealed that BRAF but not NRAS gene mutation status was predictive for enhanced susceptibility to infection. In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation. Similar to human melanocytes, mouse melanocytes resisted VSV-rp30 infection. This study confirms the general susceptibility of the majority of human melanoma types for VSV-mediated oncolysis. PMID:23552414

  16. Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

    Science.gov (United States)

    Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

    2017-03-01

    - Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

  17. Comparison of cerebral metabolism of glucose in normal human and cancer patients

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: Objective: To determine whether the cerebral metabolism in various regions of the normal human brain differs from those of cancer patients in aging by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples so called 'normal group' (ranging 21 to 88; mean age+/-SD: 50+/-14) and 290 cancer patients called 'cancer group' (ranging 21 to 85; mean age+/-SD: 54+/-14) who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They were selected with: (i) absence of clear focal brain lesions (epilepsy, cerebrovascular diseases etc.); (ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes; (iii) absence of psychiatric disorders and abuse of drugs and alcohol;( iiii) cancer patients were diagnosed definitely of variable cancers except brain cancer or brain metastasis. Both groups were sub grouped into six with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose are matched. All 12 subgroups were compared to the subgroup of normal 31-40 years old called 'control subgroup' (84 samples; mean age+/-SD: 37.15+/- 2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later; their brains were scanned for 10 minutes. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2). The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three dimensional localized by MNI Space utility (MSU) software. Results:1.With increasing of age interval, similar hypometabolic brain areas are detected in both 'normal group' and 'cancer group', they are mainly in the cortical structures such as bilateral prefrontal cortex (BA9), superior temporal gyrus (BA22), parietal cortex (inferior parietal lobule and precuneus(BA40), insula (BA13

  18. Myocardial sympathetic innervation, function, and oxidative metabolism in non-infarcted myocardium in patients with prior myocardial infarction.

    Science.gov (United States)

    Aoki, Hirofumi; Matsunari, Ichiro; Nomura, Yusuke; Fujita, Wataru; Komatsu, Ryoko; Miyazaki, Yoshiharu; Nekolla, Stephan G; Kajinami, Kouji

    2013-07-01

    The purpose of this study was to investigate the relationship between sympathetic innervation, contractile function, and the oxidative metabolism of the non-infarcted myocardium in patients with prior myocardial infarction. In 19 patients (14 men, 5 women, 65 ± 9 years) after prior myocardial infarction, sympathetic innervation was assessed by (11)C-hydroxyephedrine (HED) positron emission tomography (PET). Oxidative metabolism was quantified using (11)C-acetate PET. Left ventricular systolic function was measured by echocardiography with speckle tracking technique. The (11)C-HED retention was positively correlated with left ventricular ejection fraction (LVEF) (r = 0.566, P infarcted myocardium (r = -0.561, P infarcted myocardium. When the patients were divided into two groups based on the median value of left ventricular end-systolic volume index (LVESVI) (41 mL), there were no significant differences in age, sex, and rate pressure product between the groups. However, the large LVESVI group (>41 mL) was associated with reduced (11)C-HED retention and peak longitudinal strain in systole, whereas Kmono was similar between the groups. This study indicates that remodeled LV after myocardial infarction is associated with impaired sympathetic innervation and function even in the non-infarcted myocardial tissue. Furthermore, oxidative metabolism in the non-infarcted myocardium seems to be operated by normal regulatory mechanisms rather than pre-synaptic sympathetic neuronal function.

  19. Volume of myocardium perfused by coronary artery branches as estimated from 3D micro-CT images of rat hearts

    Science.gov (United States)

    Lund, Patricia E.; Naessens, Lauren C.; Seaman, Catherine A.; Reyes, Denise A.; Ritman, Erik L.

    2000-04-01

    Average myocardial perfusion is remarkably consistent throughout the heart wall under resting conditions and the velocity of blood flow is fairly reproducible from artery to artery. Based on these observations, and the fact that flow through an artery is the product of arterial cross-sectional area and blood flow velocity, we would expect the volume of myocardium perfused to be proportional to the cross-sectional area of the coronary artery perfusing that volume of myocardium. This relationship has been confirmed by others in pigs, dogs and humans. To test the body size-dependence of this relationship we used the hearts from rats, 3 through 25 weeks of age. The coronary arteries were infused with radiopaque microfil polymer and the hearts scanned in a micro- CT scanner. Using these 3D images we measured the volume of myocardium and the arterial cross-sectional area of the artery that perfused that volume of myocardium. The average constant of proportionality was found to be 0.15 +/- 0.08 cm3/mm2. Our data showed no statistically different estimates of the constant of proportionality in the rat hearts of different ages nor between the left and right coronary arteries. This constant is smaller than that observed in large animals and humans, but this difference is consistent with the body mass-dependence on metabolic rate.

  20. Diagnosis of the human fetal age based on the development of the normal kidney

    Directory of Open Access Journals (Sweden)

    Lizardo-Daudt Helena Maria

    2002-01-01

    Full Text Available Background and aims: The diagnosis of human fetal age is usually estimated based on the measurement of crown-rump length or crown-heel length and the weight of the fetus. However, this estimate is not totally accurate and sometimes is necessary to combine other data to determine the fetal age. An analysis of the normal embryological development of the kidney may assist in this determination. The histology of this process, although well described, lacks photographic documentation. We intend to fill this gap by providing histologists and pathologists, especially inexperienced ones, with information about the staging of the renal development through microphotography. The objective of the present study was to achieve greater accuracy for the diagnosis of human fetal age through the proposed classification and the photographic documentation presented. Material and methods: Normal embryological development of the human kidney was studied by light microscopy. The fetal period from 6 to 40 weeks of gestation was observed according the stage of maturity of glomeruli and tubules; localization of glomeruli, occurrence of nephrogenic tissue and cortico-medullary differentiation. At least 5 different exams were observed from each week of development. Two hundred four exams were analyzed in the whole study. The histological characteristics were quantified and the process was documented by microphotography. Results and final considerations: The fetal development of the kidney was divided into 8 stages, which was documented through microphotography. Nephron structural formation occurred until the 34th week of prenatal development. From the 35th week on, tubules and glomeruli continued to mature without the formation of new nephrons. The proposed classification intends to improve the accuracy of the fetal age diagnosis.

  1. Antibacterial potential and genetic profile of Enterococcus faecium strains isolated from human normal flora.

    Science.gov (United States)

    Karimaei, Samira; Sadeghi, Javad; Asadian, Mahla; Esghaei, Maryam; Pourshafie, Mohammad Reza; Talebi, Malihe

    2016-07-01

    Enterococci have a widespread attendance in the circumference and belongs to the enteric commensal microbiota. Most of them produce the antimicrobial compounds and have an inhibition effect on pathogenic microorganisms. The objective of this study was to characterize the enterococcal strains isolated from human normal flora and assess their antibacterial activity. Enterococcal isolates were obtained from the feces of eighteen healthy humans. All enterococcal species were identified by biochemical and species-specific polymerase chain reaction (PCR). These isolates were investigated further to examine their ability to inhibit growth of Salmonella typhi, Shigella flexneri and Escherichia coli by well diffusion assay. Furthermore, antibiotic susceptibility test was performed and genetic relatedness of all isolates was evaluated by Pulse Field Gel Electrophoresis (PFGE). In all, 432 isolates were obtained from fecal samples. All of the isolates identified as Enterococcus faecium by biochemical and molecular (PCR) methods. Using repetitive element palindromic (REP)-PCR method 54 patterns have been obtained and were selected for further evaluation. The results indicated that 66%, 38% and 24% of our isolates had antimicrobial effect against S. typhi, S flexneri and enteroaggregative Escherichia coli (EAEC), respectively. On the other hand, there was no significant inhibition effect against enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli (ETEC). All isolates were sensitive to vancomycin, teicoplanin, linezolid, ampicillin, chloramphenicol and gentamicin. On the other hand, the resistance rates for erythromycin, tetracycline and ciprofloxacin were 20%, 22%, and 1.8% respectively. In addition, the analysis of PFGE showed forty patterns with eight (40.7%) common types (CT) and thirty two (59.2%) single types (ST). Among eight common types, only one common type (CT5) had similar antimicrobial effect. These results suggested that enterococcal isolates obtained from

  2. Angiogenesis with intramyocardial administration of basic fibroblast growth factor in canine ischemic myocardium

    International Nuclear Information System (INIS)

    Sun Lijun; Liu Ying; Zhao Haitao; Huan Yi; Ge Yali; Gao Fabao

    2004-01-01

    Objective: To evaluate the effect of intramyocardial administration of basic fibroblast growth factor on angiogenesis of infarcted myocardium in dogs. Methods: Twenty-four mongrel dogs were randomized into control group and therapeutic group. Acute myocardial infarction was made by ligation of the left anterior descending coronary artery distal to its first diagonal branch. As soon as coronary artery was occluded, 50 mg of basic fibroblast growth factor in 15 ml of saline was injected into the infarcted and border zone in therapeutic group, whereas 15 ml saline alone was used in the same way in control dogs. Every 3 dogs in each group was studied on the 1 st day, the 3 rd day, the 10 th day, and the 17 th day, respectively. Electron microscope was used to observe the growth of capillaries. Angiogenesis was evaluated by immunohistochemical studies with VIII factor. With sensitivity encoded technique, cine MR and MR perfusion imaging were performed on each dog within 3 hours after surgery and before euthanasia to evaluate cardiac function and the characteristics of myocardial perfusion. Results: In therapeutic group, LVEF improved markedly since the 10 th day (on the 10 th day: control group 24.09 ± 3.32, therapeutic group 45.71 ± 6.27; on the 17 th day: control group 31.46 ± 4.60, therapeutic group 53.46 ± 5.24). Hypoenhancement on first pass and hyperenhancement on delayed phase appeared in infarcted myocardium. There were significant differences for the time of upslope, peak time of signal intensity, upslope curves ratio, and contrast enhancement ratio between infarcted and normal myocardium. The size of infarcted myocardium was markedly decreased on the 17 th day [control group (9.04 ± 1.59)%, therapeutic group (4.07 ± 1.20)%]. The capillaries grew actively in therapeutic group and microvessel density was higher in therapeutic group than in control group except the first day (control group and therapeutic group respectively on the 3 rd day: 92.3 ± 11

  3. Study of cerebral metabolism of glucose in normal human brain correlated with age

    International Nuclear Information System (INIS)

    Si, M.

    2007-01-01

    Full text: The objective was to determine whether cerebral metabolism in various regions of the brain differs with advancing age by using 18F-FDG PET instrument and SPM software. Materials and Methods We reviewed clinical information of 295 healthy normal samples who were examined by a whole body GE Discovery LS PET-CT instrument in our center from Aug. 2004 to Dec. 2005.They (with the age ranging from 21 to 88; mean age+/-SD: 49.77+/-13.51) were selected with: (i)absence of clear focal brain lesions (epilepsy.cerebrovascular diseases etc);(ii) absence of metabolic diseases, such as hyperthyroidism, hypothyroidism and diabetes;(iii) absence of psychiatric disorders and abuse of drugs and alcohol. They were sub grouped into six groups with the interval of 10 years old starting from 21, and the gender, educational background and serum glucose were matched. All subgroups were compared to the control group of 31-40 years old (84 samples; mean age+/-SD: 37.15+/-2.63). All samples were injected with 18F-FDG (5.55MBq/kg), 45-60 minutes later, their brains were scanned for 10min. Pixel-by-pixel t-statistic analysis was applied to all brain images using the Statistical parametric mapping (SPM2) .The hypometabolic areas (p < 0. 01 or p<0.001, uncorrected) were identified in the Stereotaxic coordinate human brain atlas and three-dimensional localized by MNI Space utility (MSU) software. Results:Relative hypometabolic brain areas detected are mainly in the cortical structures such as bilateral prefrontal cortex, superior temporal gyrus(BA22), parietal cortex (inferior parietal lobule and precuneus(BA40, insula(BA13)), parahippocampal gyrus and amygdala (p<0.01).It is especially apparent in the prefrontal cortex (BA9)and sensory-motor cortex(BA5, 7) (p<0.001), while basal ganglia and cerebellum remained metabolically unchanged with advancing age. Conclusions Regional cerebral metabolism of glucose shows a descent tendency with aging, especially in the prefrontal cortex (BA9)and

  4. Transfection of normal human bronchial epithelial cells with the bcl-2 oncogene

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, C.H.; Kenyon, K.D.; Tesfaigzi, J. [and others

    1995-12-01

    In vitro, studies examining the transformation of virus-immortalized human bronchial epithelial (HBE) cells after exposure to chemical and physical carcinogens have contributed to our understanding of the mechanisms that underlie the development of lung cancer. Virus-immortalized HBE cells have been used because of both the limited life span of normal human bronchial epithelial (NHBE) cells in culture (approximately 30-35 population doublins) and their resistance to in vitro malignant transformation. For example, human papillomavirus (HPV)-immortalized HBE cells have been used to study the genetic changes that occur after exposure to {alpha}-particles in vitro. Although this model may prove to be useful for studying the 18% or less of bronchogenic carcinomas found to contain HPV sequences, it is not an appropriate model for studying the majority of lung epithelial malignancies in which HPV DNA is not detected. This view is supported by the fact that HPV-immortalized cell lines commonly exhibit aneuploidy. This results of this study suggest that: (1) NHBE cells can be transiently transfected with the pCMV{Beta} vector; and (2) the antibiotic hygromycin-resistant transfected cells.

  5. Ecological Effect of Solithromycin on Normal Human Oropharyngeal and Intestinal Microbiota.

    Science.gov (United States)

    Rashid, Mamun-Ur; Rosenborg, Staffan; Panagiotidis, Georgios; Holm, Johan; Söderberg Löfdal, Karin; Weintraub, Andrej; Nord, Carl Erik

    2016-07-01

    Solithromycin is a new fluoroketolide. The purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. Thirteen healthy volunteers (median age, 27.3 years) received oral solithromycin at 800 mg on day 1 followed by 400 mg daily on days 2 to 7. Fecal and saliva samples were collected at baseline and on days 2, 5, 7, 9, 14, and 21 for pharmacokinetic and microbiological analyses. Plasma samples were collected predose on days 2, 5, and 7 as proof of exposure, and solithromycin concentration ranges were 21.9 to 258 ng/ml, 18.0 to 386 ng/ml, and 16.9 to 417 ng/ml, respectively. The solithromycin concentrations in feces were 15.8 to 65.4 mg/kg, 24.5 to 82.7 mg/kg, 21.4 to 82.7 mg/kg, 12.1 to 72.4 mg/kg, 0.2 to 25.6 mg/kg, and 0 to 0.5 mg/kg on days 2, 5, 7, 9, 14, and 21, respectively. The numbers of enterobacteria and enterococci decreased and were normalized on day 14. The numbers of lactobacilli and bifidobacteria decreased from day 2 to day 14 and were normalized on day 21. The clostridia decreased on days 2, 7, and 14 and were normalized on day 21. No Clostridium difficile strains or toxins were detected during the study period. The number of Bacteroides strains was not significantly changed. The solithromycin concentrations in saliva were 0 to 1.2 mg/liter, 0 to 0.5 mg/liter, 0 to 0.5 mg/liter, and 0 to 0.1 mg/liter on days 2, 5, 7, and 9, respectively. The numbers of streptococci decreased on day 2 and were normalized on day 5. The numbers of lactobacilli, prevotellae, fusobacteria, and leptotrichiae decreased from day 2 and were normalized on day 21. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2010-01-01

    The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size.......The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size....

  7. Conjugation of gold nanoparticles and recombinant human endostatin modulates vascular normalization via interruption of anterior gradient 2-mediated angiogenesis.

    Science.gov (United States)

    Pan, Fan; Yang, Wende; Li, Wei; Yang, Xiao-Yan; Liu, Shuhao; Li, Xin; Zhao, Xiaoxu; Ding, Hui; Qin, Li; Pan, Yunlong

    2017-07-01

    Several studies have revealed the potential of normalizing tumor vessels in anti-angiogenic treatment. Recombinant human endostatin is an anti-angiogenic agent which has been applied in clinical tumor treatment. Our previous research indicated that gold nanoparticles could be a nanoparticle carrier for recombinant human endostatin delivery. The recombinant human endostatin-gold nanoparticle conjugates normalized vessels, which improved chemotherapy. However, the mechanism of recombinant human endostatin-gold nanoparticle-induced vascular normalization has not been explored. Anterior gradient 2 has been reported to be over-expressed in many malignant tumors and involved in tumor angiogenesis. To date, the precise efficacy of recombinant human endostatin-gold nanoparticles on anterior gradient 2-mediated angiogenesis or anterior gradient 2-related signaling cohort remained unknown. In this study, we aimed to explore whether recombinant human endostatin-gold nanoparticles could normalize vessels in metastatic colorectal cancer xenografts, and we further elucidated whether recombinant human endostatin-gold nanoparticles could interrupt anterior gradient 2-induced angiogenesis. In vivo, it was indicated that recombinant human endostatin-gold nanoparticles increased pericyte expression while inhibit vascular endothelial growth factor receptor 2 and anterior gradient 2 expression in metastatic colorectal cancer xenografts. In vitro, we uncovered that recombinant human endostatin-gold nanoparticles reduced cell migration and tube formation induced by anterior gradient 2 in human umbilical vein endothelial cells. Treatment with recombinant human endostatin-gold nanoparticles attenuated anterior gradient 2-mediated activation of MMP2, cMyc, VE-cadherin, phosphorylation of p38, and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human umbilical vein endothelial cells. Our findings demonstrated recombinant human endostatin-gold nanoparticles might normalize

  8. Human Papillomavirus in Oral Leukoplakia, Verrucous Carcinoma, Squamous Cell Carcinoma, and Normal Mucous Membrane

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2015-11-01

    Full Text Available Objectives: Squamous cell carcinoma (SCC is the most common oral malignancy, and verrucous carcinoma (VC is a less invasive type of SCC. Leukoplakia (LP is the most frequent premalignant lesion in the oral cavity. The human papillomavirus (HPV has been recognized as one of the etiologic factors of these conditions. The association of anogenital and cervical cancers with HPV particularly its high-risk subtypes (HPV HR has been demonstrated. The purpose of our study was to investigate the hypothetical association between HPV and the mentioned oral cavity lesions.  Methods: One hundred and seventy-three samples (114 SCCs, 21 VCs, 20 LPs and 18 normal mucosa samples (as a control group were retrieved from the Department of Oral and Maxillofacial Pathology of Mashhad Dental School, Iran. The association of HPV genotypes in LP, VC, and SCC was compared to normal oral mucosa using the polymerase chain reaction.  Results: The results showed the absence of HPV in normal mucosa and LP lesions. In three samples of VC (14.3%, we observed the presence of HPV HR (types 16 and 18. All VCs were present in the mandibular ridge of females aged over 65 years old. No statistically significant correlation between HPV and VC was observed (p=0.230. Additionally, 15 (13.1% SCCs showed HPV positivity, but this was not significant (p=0.830. The prevalence of SCC was higher on the tongue with the dominant presence of less carcinogenic species of HPV (types 6 and 11. A statistically significant association was not observed between HPV and SCC or VC in the oral cavity.  Conclusions: More studies are necessary to better understand the relationship between HPV and malignant/premalignant oral cavity lesions.

  9. Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary

    DEFF Research Database (Denmark)

    Fenger, M; Johnsen, A H

    1988-01-01

    Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well...... as their glycine-extended precursors, were characterized by sequence-specific radioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of the POMC-derived products [calculated as the sum of adrenocorticotropic hormone...... (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders...

  10. Nocturnal variations in subcutaneous blood flow rate in lower leg of normal human subjects

    DEFF Research Database (Denmark)

    Sindrup, J H; Kastrup, J; Jørgensen, B

    1991-01-01

    in central and local postural sympathetic vasoconstrictor activity. During sleep, characteristic variations in subcutaneous blood flow were disclosed. The 133Xe washout curve could be divided into three segments with significantly different slopes. Approximately 90 min after the subject went to sleep......Subcutaneous adipose tissue blood flow rate was measured in the lower leg of 22 normal human subjects over 12- to 20-h ambulatory conditions. The 133Xe washout technique, portable CdTe(Cl) detectors, and a portable data storage unit were used. The tracer depot was applied on the medial aspect...... of the right lower leg 10 cm proximal to the malleolar level by means of the epicutaneous, atraumatic labeling technique. The change from upright to supine position from day 1 in the beginning of the night period elicited an instantaneous blood flow rate increment of 30-40% in accordance with a decrease...

  11. Positron emission tomography studies in the normal and abnormal ageing of human brain

    International Nuclear Information System (INIS)

    Comar, D.; Baron, J.C.

    1987-01-01

    Until recently, the investigation of the neurophysiological correlates of normal and abnormal ageing of the human brain was limited by methodological constraints, as the technics available provided only a few parameters (e.g. electroencephalograms, cerebral blood flow) monitored in superficial brain structures in a grossly regional and poorly quantitative way. Lately several non invasive techniques have been developed which allow to investigate in vivo both quantitatively and on local basis a number of previously inaccessible important aspects of brain function. Among these techniques, such as single photon emission tomography imaging of computerized electric events, nuclear magnetic resonance, positron emission tomography stands out as the most powerful and promising method since it allows the in vivo measurement of biochemical and pharmacological parameters

  12. BIOCOMPATIBILITY OF IN HOUSE β-TRICALCIUM PHOSPHATE CERAMICS WITH NORMAL HUMAN OSTEOBLAST CELL

    Directory of Open Access Journals (Sweden)

    NURSHUHADA MOHD NAZIR

    2012-04-01

    Full Text Available β-Tricalcium Phosphate (β–TCP have been widely used as an implant materials. It has been successfully produced locally using two different method which is hydrothermal and precipitation. The aim of the study was to determine the biocompatibility of β-TCP prepared by hydrothermal and precipitation method with normal human osteoblast (NHOst cells. For this purpose cytotoxicity of the material was assessed using an Alamar Blue method to determine the viability of NHOst cells grown with extracts of β-TCP in various concentrations. In addition NHOst grown on β-TCP ceramics were examined under an inverted microscope after 4, 24, 48 and 72 hours to verify cell attachment. Staining was done using Calcein AM and Ethidium homodimers to assess viability using a Confocal Laser Scanning Microscope (CLSM. The results showed that neither hydrothermal β-TCP nor precipitation β-TCP were cytotoxic with either of the method applied.

  13. Alpha subunit and human chorionic gonadotropin in normal pregnancy and gestational trophoblastic disease.

    Science.gov (United States)

    Elegbe, R A; Pattillo, R A; Hussa, R O; Hoffmann, R G; Damole, I O; Finlayson, W E

    1984-03-01

    The reported incidence of gestational trophoblastic disease is an order of magnitude higher in Nigeria than in the United States. Sera from a total of 283 pregnant black patients, 138 United States and 148 Nigerian pregnant patients, were analyzed for their serum levels of alpha subunit and human chorionic gonadotropin (hCG). The patterns of hCG secretion were similar in the two populations during normal pregnancy. However, the level of alpha subunit was persistently higher in Nigerian women than in comparable pregnant United States patients. A statistically significantly higher alpha subunit level in the Nigerian patients was found only in the ten- to 13-week gestational period (P less than .005). The higher level of alpha subunit in pregnancy in Nigerian women may signal a population of trophoblastic cells which may be at higher risk for malignancy development in the Nigerian woman.

  14. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells

    DEFF Research Database (Denmark)

    Jørgensen, N; Rajpert-De Meyts, E; Graem, N

    1995-01-01

    study. EXPERIMENTAL DESIGN: Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental......-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. RESULTS: The vast majority of the germ cells (75-100%) in the first......-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out of the ten first-trimester gonads. The relative number of germ cells positive for all the markers studied declined rapidly during the first part of the second trimester...

  15. Effects of vasopressin administration on diuresis of water immersion in normal humans

    Science.gov (United States)

    Epstein, M.; Denunzio, A. G.; Loutzenhiser, R. D.

    1981-01-01

    The influence of vasopressin suppression on the diuresis encountered during water immersion is investigated in studies on normal humans immersed to the neck. Six hydrated male subjects were studied on two occasions while undergoing 6 h of immersion without or during the administration of aqueous vasopressin for the initial 4 h. Neck immersion is found to result in a significant increase in urinary flow rate beginning in the first hour and persisting throughout the immersion. The administration of vasopressin markedly attenuated the diuretic response throughout the period of infusion, while cessation of vasopressin administration during the final 2 h of immersion resulted in a marked offset of the antidiuresis. Results thus support the view that the suppression of antidiuretic hormone contributes to the immersion diuresis of hydrated subjects.

  16. Glucagon Receptor Blockade With a Human Antibody Normalizes Blood Glucose in Diabetic Mice and Monkeys.

    Science.gov (United States)

    Okamoto, Haruka; Kim, Jinrang; Aglione, JohnPaul; Lee, Joseph; Cavino, Katie; Na, Erqian; Rafique, Ashique; Kim, Jee Hae; Harp, Joyce; Valenzuela, David M; Yancopoulos, George D; Murphy, Andrew J; Gromada, Jesper

    2015-08-01

    Antagonizing glucagon action represents an attractive therapeutic option for reducing hepatic glucose production in settings of hyperglycemia where glucagon excess plays a key pathophysiological role. We therefore generated REGN1193, a fully human monoclonal antibody that binds and inhibits glucagon receptor (GCGR) signaling in vitro. REGN1193 administration to diabetic ob/ob and diet-induced obese mice lowered blood glucose to levels observed in GCGR-deficient mice. In diet-induced obese mice, REGN1193 reduced food intake, adipose tissue mass, and body weight. REGN1193 increased circulating levels of glucagon and glucagon-like peptide 1 and was associated with reversible expansion of pancreatic α-cell area. Hyperglucagonemia and α-cell hyperplasia was observed in fibroblast growth factor 21-deficient mice treated with REGN1193. Single administration of REGN1193 to diabetic cynomolgus monkeys normalized fasting blood glucose and glucose tolerance and increased circulating levels of glucagon and amino acids. Finally, administration of REGN1193 for 8 weeks to normoglycemic cynomolgus monkeys did not cause hypoglycemia or increase pancreatic α-cell area. In summary, the GCGR-blocking antibody REGN1193 normalizes blood glucose in diabetic mice and monkeys but does not produce hypoglycemia in normoglycemic monkeys. Thus, REGN1193 provides a potential therapeutic modality for diabetes mellitus and acute hyperglycemic conditions.

  17. Comparative Proteomic Profile of the Human Placenta in Normal and Fetal Growth Restriction Subjects

    Directory of Open Access Journals (Sweden)

    Zhijing Miao

    2014-11-01

    Full Text Available Background: Fetal growth restriction (FGR is the main cause of intrauterine fetal death and the second leading cause of death in the neonatal period. A large body of evidence suggests that FGR may be associated with the placenta, although its etiology and pathogenesis remain to be fully elucidated. Methods and Results: To better understand the molecular mechanisms underlying the pathological development of the placenta in FGR, we used tandem mass tags (TMTs to construct a large-scale comparative proteomic profile of human placentas from normal and FGR pregnancies. A total of 1,198 kinds of proteins were identified in the control and FGR placentas, of which 95 were differentially expressed between two groups. Ingenuity Pathway Analysis (IPA was used to organize these differentially expressed proteins into networks of interacting proteins and to identify the modules of functionally related proteins. Western blotting was used to verify the expression patterns of several randomly selected proteins. Conclusion: The placentas of women with FGR displayed significant proteome differences compared with normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of FGR. Further studies and validations are required to elucidate the exact roles of these proteins in FGR pathogenesis.

  18. Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus.

    Science.gov (United States)

    Hunt, Nicholas J; Rodriguez, Michael L; Waters, Karen A; Machaalani, Rita

    2015-01-01

    Animal studies have shown that decreased orexin expression changes sleep regulation with normal aging. This study examined orexin A and B expression in the tuberal hypothalamus in infants (0-1 year; n = 8), children (4-10 years; n = 7), young adults (22-32 years; n = 4), and older (48-60 years; n = 7) adults. Neuronal expression was defined by the percentage positive orexin immunoreactive (Ox-ir) neurons in the whole tuberal hypothalamus, and in the dorsal medial (DMH), perifornical, and lateral hypothalamus. In addition, the number of Ox-ir neurons/mm(2), regional distribution, and co-localization were examined. Within the whole tuberal hypothalamic section, there was a 23% decrease in the percentage of Ox-ir neurons between infants and older adults (p changes were confined to the DMH and/or perifornical hypothalamus. There was a 9%-24% decrease in Ox neurons/mm(2) in adults compared with infants and/or children (p ≤ 0.001). These results demonstrate a decrease in Ox expression with normal human maturation and aging. This may contribute to changes in sleep regulation during development and with aging. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Digital music exposure reliably induces temporary threshold shift in normal-hearing human subjects.

    Science.gov (United States)

    Le Prell, Colleen G; Dell, Shawna; Hensley, Brittany; Hall, James W; Campbell, Kathleen C M; Antonelli, Patrick J; Green, Glenn E; Miller, James M; Guire, Kenneth

    2012-01-01

    One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is the availability of an established clinical paradigm with real-world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal-hearing human subjects. Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93 to 95 (n = 10), 98 to 100 (n = 11), or 100 to 102 (n = 12) dBA in-ear exposure level for a period of 4 hr. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured before and after music exposure. Postmusic tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and 1 week later. Changes in thresholds after the lowest-level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a "notch" configuration, with the largest changes observed at 4 kHz (mean = 6.3 ± 3.9 dB; range = 0-14 dB). Recovery was largely complete within the first 4 hr postexposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1 week postexposure. These data provide insight into the variability of TTS induced by music-player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function after digital music-player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be taken to fully inform potential subjects in

  20. Digital music exposure reliably induces temporary threshold shift (TTS) in normal hearing human subjects

    Science.gov (United States)

    Le Prell, C. G.; Dell, S.; Hensley, B.; Hall, J. W.; Campbell, K. C. M.; Antonelli, P. J.; Green, G. E.; Miller, J. M.; Guire, K.

    2012-01-01

    Objectives One of the challenges for evaluating new otoprotective agents for potential benefit in human populations is availability of an established clinical paradigm with real world relevance. These studies were explicitly designed to develop a real-world digital music exposure that reliably induces temporary threshold shift (TTS) in normal hearing human subjects. Design Thirty-three subjects participated in studies that measured effects of digital music player use on hearing. Subjects selected either rock or pop music, which was then presented at 93–95 (n=10), 98–100 (n=11), or 100–102 (n=12) dBA in-ear exposure level for a period of four hours. Audiograms and distortion product otoacoustic emissions (DPOAEs) were measured prior to and after music exposure. Post-music tests were initiated 15 min, 1 hr 15 min, 2 hr 15 min, and 3 hr 15 min after the exposure ended. Additional tests were conducted the following day and one week later. Results Changes in thresholds after the lowest level exposure were difficult to distinguish from test-retest variability; however, TTS was reliably detected after higher levels of sound exposure. Changes in audiometric thresholds had a “notch” configuration, with the largest changes observed at 4 kHz (mean=6.3±3.9dB; range=0–13 dB). Recovery was largely complete within the first 4 hours post-exposure, and all subjects showed complete recovery of both thresholds and DPOAE measures when tested 1-week post-exposure. Conclusions These data provide insight into the variability of TTS induced by music player use in a healthy, normal-hearing, young adult population, with music playlist, level, and duration carefully controlled. These data confirm the likelihood of temporary changes in auditory function following digital music player use. Such data are essential for the development of a human clinical trial protocol that provides a highly powered design for evaluating novel therapeutics in human clinical trials. Care must be

  1. Normality and naturalness: a comparison of the meanings of concepts used within veterinary medicine and human medicine.

    Science.gov (United States)

    Lerner, Henrik; Hofmann, Bjørn

    2011-12-01

    This article analyses the different connotations of "normality" and "being natural," bringing together the theoretical discussion from both human medicine and veterinary medicine. We show how the interpretations of the concepts in the different areas could be mutually fruitful. It appears that the conceptions of "natural" are more elaborate in veterinary medicine, and can be of value to human medicine. In particular they can nuance and correct conceptions of nature in human medicine that may be too idealistic. Correspondingly, the wide ranging conceptions of "normal" in human medicine may enrich conceptions in veterinary medicine, where the discussions seem to be sparse. We do not argue that conceptions from veterinary medicine should be used in human medicine and vice versa, but only that it could be done and that it may well be fruitful. Moreover, there are overlaps between some notions of normal and natural, and further conceptual analysis on this overlap is needed.

  2. Fluctuations in C-reactive protein concentration and neutrophil activation during normal human pregnancy.

    Science.gov (United States)

    Belo, Luís; Santos-Silva, Alice; Rocha, Susana; Caslake, Muriel; Cooney, Josephine; Pereira-Leite, Luís; Quintanilha, Alexandre; Rebelo, Irene

    2005-11-01

    To clarify the changes in serum C-reactive protein (CRP) levels and in the neutrophil activation state during normal human pregnancy. A longitudinal study (n=23) was performed during the three trimesters of pregnancy; a group of non-pregnant women (n=24) was used as control. Total and differential leukocyte count, serum concentration of CRP and plasma levels of granulocyte-macrophage colony stimulating factor (GM-CSF) and of lactoferrin and elastase (two indirect markers of neutrophil activation) were measured. Pregnancy imposed an inflammatory response in the mother, observed by the significant increment in total white blood cell (WBC) and neutrophil counts and in the circulating levels of CRP, GM-CSF and lactoferrin, in all trimesters of gestation compared with non-pregnant controls. Plasma elastase concentration was also significantly higher in pregnant women, but only in the first trimester of gestation. Regarding the ratios of lactoferrin and elastase per neutrophil, they were significantly lower in pregnant women (all trimesters). During gestation, WBC and neutrophil count increased significantly from the first to the second trimester and remained high in the third period. In contrast, the ratios of lactoferrin and elastase per neutrophil decreased significantly from the first to the second trimester, remaining low in the last trimester. Concerning CRP levels, no consistent changes were observed throughout gestation; 12 cases (52.2%) presented fluctuations, whereas 7 (30.4%) showed progressive reductions and 4 (17.4%) progressive increments throughout pregnancy. Changes in CRP levels vary in a wide manner between subjects along pregnancy, even though median values are consistently elevated throughout pregnancy. Moreover, circulating levels of neutrophil-activation products are higher in normal human gestation.

  3. Genome-Wide Association Study Reveals Multiple Loci Influencing Normal Human Facial Morphology.

    Directory of Open Access Journals (Sweden)

    John R Shaffer

    2016-08-01

    Full Text Available Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array imputed to the 1000 Genomes reference panel (Phase 3. We observed genome-wide significant associations (p < 5 x 10-8 for cranial base width at 14q21.1 and 20q12, intercanthal width at 1p13.3 and Xq13.2, nasal width at 20p11.22, nasal ala length at 14q11.2, and upper facial depth at 11q22.1. Several genes in the associated regions are known to play roles in craniofacial development or in syndromes affecting the face: MAFB, PAX9, MIPOL1, ALX3, HDAC8, and PAX1. We also tested genotype-phenotype associations reported in two previous genome-wide studies and found evidence of replication for nasal ala length and SNPs in CACNA2D3 and PRDM16. These results provide further evidence that common variants in regions harboring genes of known craniofacial function contribute to normal variation in human facial features. Improved understanding of the genes associated with facial morphology in healthy individuals can provide insights into the pathways and mechanisms controlling normal and abnormal facial morphogenesis.

  4. Noncanonical microRNAs and endogenous siRNAs in normal and psoriatic human skin.

    Science.gov (United States)

    Xia, Jing; Joyce, Cailin E; Bowcock, Anne M; Zhang, Weixiong

    2013-02-15

    Noncanonical microRNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs) are key gene regulators in eukaryotes. Noncanonical miRNAs, which bypass part of the canonical miRNA biogenesis pathway, can originate from a variety of genomic loci, which include small nucleolar RNAs (snoRNAs), transfer RNAs (tRNAs) and introns, whereas endo-siRNAs can arise from repetitive elements, some of which are transposable. The roles of noncanonical miRNAs and endo-siRNAs in complex diseases have yet to be characterized. To investigate their potential expression and function in psoriasis, we carried out a comprehensive, genome-wide search for noncanonical miRNAs and endo-siRNAs in small RNA deep-sequencing data sets from normal and psoriatic human skin. By analyzing more than 670 million qualified reads from 67 small RNA libraries, we identified 21 novel, noncanonical miRNAs (3 snoRNA-derived and 2 tRNA-derived miRNAs and 16 miRtrons) and 39 novel endo-siRNAs that were expressed in skin. The expression of four novel small RNAs was validated by qRT-PCR in human skin, and their Argonaute association was confirmed by co-immunoprecipitation of ectopic small RNAs in HEK293 cells. Fifteen noncanonical miRNAs or endo-siRNAs were significantly differentially expressed in psoriatic-involved versus normal skin, including an Alu-short interspersed element-derived siRNA which was 17-fold up-regulated in psoriatic-involved skin. These and other differentially expressed small noncoding RNAs may function as regulators of gene expression in skin and potentially play a role in psoriasis pathogenesis.

  5. Low Density Lipoprotein and Non-Newtonian Oscillating Flow Biomechanical Parameters for Normal Human Aorta.

    Science.gov (United States)

    Soulis, Johannes V; Fytanidis, Dimitrios K; Lampri, Olga P; Giannoglou, George D

    2016-04-01

    The temporal variation of the hemodynamic mechanical parameters during cardiac pulse wave is considered as an important atherogenic factor. Applying non-Newtonian blood molecular viscosity simulation is crucial for hemodynamic analysis. Understanding low density lipoprotein (LDL) distribution in relation to flow parameters will possibly spot the prone to atherosclerosis aorta regions. The biomechanical parameters tested were averaged wall shear stress (AWSS), oscillatory shear index (OSI) and relative residence time (RRT) in relation to the LDL concentration. Four non-Newtonian molecular viscosity models and the Newtonian one were tested for the normal human aorta under oscillating flow. The analysis was performed via computational fluid dynamic. Tested viscosity blood flow models for the biomechanical parameters yield a consistent aorta pattern. High OSI and low AWSS develop at the concave aorta regions. This is most noticeable in downstream flow region of the left subclavian artery and at concave ascending aorta. Concave aorta regions exhibit high RRT and elevated LDL. For the concave aorta site, the peak LDL value is 35.0% higher than its entrance value. For the convex site, it is 18.0%. High LDL endothelium regions located at the aorta concave site are well predicted with high RRT. We are in favor of using the non-Newtonian power law model for analysis. It satisfactorily approximates the molecular viscosity, WSS, OSI, RRT and LDL distribution. Concave regions are mostly prone to atherosclerosis. The flow biomechanical factor RRT is a relatively useful tool for identifying the localization of the atheromatic plaques of the normal human aorta.

  6. The effects of apoptosis vulnerability markers on the myocardium in depression after myocardial infarction.

    Science.gov (United States)

    Wang, Yiming; Liu, Xingde; Zhang, Dongfeng; Chen, Jianhui; Liu, Shuzheng; Berk, Michael

    2013-02-08

    There is an increased incidence of major depressive disorder (MDD) in individuals after myocardial infarction (MI), but the pathophysiological processes mediating this association are unclear. Our previous study demonstrated an increase in pro-apoptotic pathways in the myocardium and hippocampus in MDD, which was reversed by venlafaxine. This study aimed to attempt to confirm the effects of apoptosis vulnerability markers on the myocardium in a model of depression after myocardial infarction. Rats were divided into four groups: sham (N = 8), depression (N = 8, chronic mild unpredictable stress and separation were used in the depression group), MI (N = 13) and post-MI depression (N = 7). The rats in all four groups underwent the same open field and sucrose preference behavioral tests. Evan Blue staining was used to determine the area at risk of myocardial infarction in the left ventricle, and 2,3,5-triphenyl tetrazolium chloride (1.5% TTC) dye was used to detect the size of the myocardial infarction. The expression of bax and bcl-2 protein in the myocardium was investigated by immunohistochemistry, and the mRNA expression of bax, bcl-2 and caspase-3 in the myocardium was investigated by real time RT-PCR. Apoptosis was estimated in the myocardium by measuring the Bax:Bcl-2 ratio. In the depression and post-MI depression rats, there were significantly decreased movements and total sucrose consumption, modeling behavioral deficits and an anhedonic-like state. In terms of myocardial infarction size, no difference was seen between the MI and post-MI depression groups. There was an up-regulated Bax:Bcl-2 ratio in the depression, MI and post-MI depression groups. Furthermore, in the latter group, there was a greater up-regulated Bax:Bcl-2 ratio. However, caspase-3 did not differ among the four groups. These results of this animal model suggest that active pro-apoptotic pathways may be involved in the nexus between myocardial infarction and depression. This mechanism may be

  7. Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction.

    Science.gov (United States)

    Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven; Motiwala, Shweta R; Addae, Gifty; Manning, Warren J; Nezafat, Reza

    2017-10-01

    To compare remote myocardium native T 1 in patients with chronic myocardial infarction (MI) and controls without MI and to elucidate the relationship of infarct size and native T 1 in the remote myocardium for the prediction of left ventricular (LV) systolic dysfunction after MI. A total of 41 chronic MI (18 anterior MI) patients and 15 age-matched volunteers with normal LV systolic function and no history of MI underwent cardiac magnetic resonance imaging (MRI) at 1.5T. Native T 1 map was performed using a slice interleaved T 1 mapping and late gadolinium enhancement (LGE) imaging. Cine MR was acquired to assess LV function and mass. The remote myocardium native T 1 time was significantly elevated in patients with prior MI, compared to controls, for both anterior MI and nonanterior MI (anterior MI: 1099 ± 30, nonanterior MI: 1097 ± 39, controls: 1068 ± 25 msec, P Remote myocardium native T 1 moderately correlated with LV volume, mass index, and ejection fraction (r = 0.38, 0.50, -0.49, respectively, all P remote myocardium was independently associated with reduced LV ejection fraction, after adjusting for age, gender, infarct size, and comorbidity (β = -0.34, P = 0.03). In chronic MI, the severity of LV systolic dysfunction after MI is independently associated with native T 1 in the remote myocardium. Diffuse myocardial fibrosis in the remote myocardium may play an important pathophysiological role of post-MI LV dysfunction. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1073-1081. © 2017 International Society for Magnetic Resonance in Medicine.

  8. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

    Science.gov (United States)

    Braff, D L; Geyer, M A; Swerdlow, N R

    2001-07-01

    Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome

  9. The development of hepatic stellate cells in normal and abnormal human fetuses – an immunohistochemical study

    Science.gov (United States)

    Loo, Christine K C; Pereira, Tamara N; Pozniak, Katarzyna N; Ramsing, Mette; Vogel, Ida; Ramm, Grant A

    2015-01-01

    The precise embryological origin and development of hepatic stellate cells is not established. Animal studies and observations on human fetuses suggest that they derive from posterior mesodermal cells that migrate via the septum transversum and developing diaphragm to form submesothelial cells beneath the liver capsule, which give rise to mesenchymal cells including hepatic stellate cells. However, it is unclear if these are similar to hepatic stellate cells in adults or if this is the only source of stellate cells. We have studied hepatic stellate cells by immunohistochemistry, in developing human liver from autopsies of fetuses with and without malformations and growth restriction, using cellular Retinol Binding Protein-1 (cRBP-1), Glial Fibrillary Acidic Protein (GFAP), and α-Smooth Muscle Actin (αSMA) antibodies, to identify factors that influence their development. We found that hepatic stellate cells expressing cRBP-1 are present from the end of the first trimester of gestation and reduce in density throughout gestation. They appear abnormally formed and variably reduced in number in fetuses with abnormal mesothelial Wilms Tumor 1 (WT1) function, diaphragmatic hernia and in ectopic liver nodules without mesothelium. Stellate cells showed similarities to intravascular cells and their presence in a fetus with diaphragm agenesis suggests they may be derived from circulating stem cells. Our observations suggest circulating stem cells as well as mesothelium can give rise to hepatic stellate cells, and that they require normal mesothelial function for their development. PMID:26265759

  10. Human BLCAP transcript: new editing events in normal and cancerous tissues.

    Science.gov (United States)

    Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

    2010-07-01

    Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

  11. Q-switched ruby laser irradiation of normal human skin. Histologic and ultrastructural findings.

    Science.gov (United States)

    Hruza, G J; Dover, J S; Flotte, T J; Goetschkes, M; Watanabe, S; Anderson, R R

    1991-12-01

    The Q-switched ruby laser is used for treatment of tatoos. The effects of Q-switched ruby laser pulses on sun-exposed and sun-protected human skin, as well as senile lentigines, were investigated with clinical observation, light microscopy, and transmission electron microscopy. A pinpricklike sensation occurred at radiant exposures as low as 0.2 J/cm2. Immediate erythema, delayed edema, and immediate whitening occurred with increasing radiant exposure. The threshold for immediate whitening varied inversely with skin pigmentation, ranging from a mean of 1.4 J/cm2 in lentigines to 3.1 J/cm2 in sun-protected skin. Transmission electron microscopy showed immediate alteration of mature melanosomes and nuclei within keratinocytes and melanocytes, but stage I and II melanosomes were unaffected. Histologically, immediate injury was confined to the epidermis. There was minimal inflammatory response 1 day after exposure. After 1 week, subthreshold exposures induced hyperpigmentation, with epidermal hyperplasia and increased melanin staining noted histologically. At higher radiant exposures, hypopigmentation occurred with desquamation of a pigmented scale/crust. All sites returned to normal skin color and texture without scarring within 3 to 6 months. These observations suggest that the human skin response to selective photothermolysis of pigmented cells is similar to that reported in animal models, including low radiant exposure stimulation of melanogenesis and high radiant exposure lethal injury to pigmented epidermal cells.

  12. Modulation of Melanogenesis by Heme Oxygenase-1 via p53 in Normal Human Melanocytes.

    Science.gov (United States)

    Lim, Hee-Sun; Jin, Suna; Yun, Sook Jung

    2016-01-01

    As a key regulator of melanogenesis, p53 controls microphthalmia-associated transcription factor (MITF) and tyrosinase expression. The anti-oxidant enzyme heme oxygenase-1 (HO-1) is induced by various forms of cellular stress and diverse oxidative stimuli. However, few studies have examined the role of HO-1 in melanogenesis. Therefore, the aim of this study was to determine the role of HO-1 in melanogenesis and the mechanism underlying this relationship. Cultures of normal human melanocytes were treated with the HO-1 inducer cobalt protoporphyrin (CoPP) or the HO-1 inhibitor zinc protoporphyrin (ZnPP). We then measured the melanin content of the cells. Additional analyses consisted of Western blotting and RT-PCR. The results showed that the cellular melanin content was increased by CoPP and decreased by ZnPP. The Western blot and RT-PCR analyses showed that CoPP increased p53, MITF and tyrosinase levels, and ZnPP reduced all of them. The knockdown of p53 by siRNA transfection was followed by large decreases in the expression levels of p53, MITF and tyrosinase at 3 h of transfection. The presence of CoPP or ZnPP had no significant increased or decreased effects on MITF and tyrosinase levels from 15 h in the siRNA transfectants. Our results suggest that HO-1 modulates melanogenesis in human melanocytes via a p53-dependent pathway.

  13. Selection of Candidate Housekeeping Genes for Normalization in Human Postmortem Brain Samples

    Directory of Open Access Journals (Sweden)

    Aldo Pagano

    2011-08-01

    Full Text Available The most frequently used technique to study the expression profile of genes involved in common neurological disorders is quantitative real-time RT-PCR, which allows the indirect detection of very low amounts of selected mRNAs in tissue samples. Expression analysis by RT-qPCR requires an appropriate normalization to the expression level of genes characterized by a stable, constitutive transcription. However, the identification of a gene transcribed at a very stable level is difficult if not impossible, since significant fluctuations of the level of mRNA synthesis often accompanies changes of cell behavior. The aim of this study is to identify the most stable genes in postmortem human brain samples of patients affected by Alzheimer’s disease (AD suitable as reference genes. The experiments analyzed 12 commonly used reference genes in brain samples from eight individuals with AD and seven controls. After a careful analysis of the results calculated by geNorm and NormFinder algorithms, we found that CYC1 and EIF4A2 are the best reference genes. We remark on the importance of the determination of the best reference genes for each sample to be analyzed and suggest a practical combination of reference genes to be used in the analysis of human postmortem samples.

  14. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    Science.gov (United States)

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  15. In vitro assessment of antiproliferative action selectivity of dietary isothiocyanates for tumor versus normal human cells

    Directory of Open Access Journals (Sweden)

    Konić-Ristić Aleksandra

    2016-01-01

    Full Text Available Background/Aim. Numerous epidemiological studies have shown beneficial effects of cruciferous vegetables consumption in cancer chemoprevention. Biologically active compounds of different Brassicaceae species with antitumor potential are isothiocyanates, present in the form of their precursors - glucosinolates. The aim of this study was to determine the selectivity of antiproliferative action of dietary isothiocyanates for malignant versus normal cells. Methods. Antiproliferative activity of three isothiocyanates abundant in human diet: sulforaphane, benzyl isothiocyanate (BITC and phenylethyl isothiocyanate, on human cervix carcinoma cell line - HeLa, melanoma cell line - Fem-x, and colon cancer cell line - LS 174, and on peripheral blood mononuclear cells (PBMC, with or without mitogen, were determined by MTT colorimetric assay 72 h after their continuous action. Results. All investigated isothiocyanates inhibited the proliferation of HeLa, Fem-x and LS 174 cells. On all cell lines treated, BITC was the most potent inhibitor of cell proliferation with half-maximum inhibitory concentration (IC50 values of 5.04 mmoL m-3 on HeLa cells, 2.76 mmol m-3 on Fem-x, and 14.30 mmol m-3 on LS 174 cells. Antiproliferative effects on human PBMC were with higher IC50 than on malignant cells. Indexes of selectivity, calculated as a ratio between IC50 values obtained on PBMC and malignant cells, were between 1.12 and 16.57, with the highest values obtained for the action of BITC on melanoma Fem-x cells. Conclusion. Based on its antiproliferative effects on malignant cells, as well as the selectivity of the action to malignant vs normal cells, benzyl isothiocyanate can be considered as a promising candidate in cancer chemoprevention. In general, the safety of investigated compounds, in addition to their antitumor potential, should be considered as an important criterion in cancer chemoprevention. Screening of selectivity is a plausible approach to the evaluation

  16. METHODS USED FOR THE VIRTUAL HUMAN BONES AND JOINTS RECONSTRUCTION. NORMAL AND PATHOLOGICAL HUMAN JOINTS VIRTUAL SIMULATIONS

    Directory of Open Access Journals (Sweden)

    POPA Laurentiu Dragos

    2015-06-01

    Full Text Available To understand the problems, which appear in every human joint, it is very important to know the anatomy and morphology of the human bones and the way in which the components are working together to realize a normal functionality. For this purpose was used a CAD parametric software which permits to define models with a high degree of difficulty. First, it was used a CT or MRI device to obtain the parallel sections to study each component of the bone. A 3D scanner can be used only for the outer geometry. In the second step the images were transferred to a 2D CAD software, like AutoCAD, where the outer and inner contours of the bone were approximate to polygonal lines composed by many segments. After this, the contours were transferred to a 3D CAD software, like SolidWorks, where, step by step, and section by section, was defined the virtual bone component. Additionally to the main shape can be attached other Loft, Round or Dome shapes. For some components, as vertebrae, mandible or skull bones, can be used a preliminary model obtained by parallel sections. Starting from this, the model can be defined using the main 3D curves and we can get the final virtual solid model. In some simulations, the soft components, as muscles or ligaments, were included in simulations using non-linear virtual springs. Also, sometimes were used implants or prosthetic elements. In the final of the paper, were extracted important conclusions.

  17. VALUE OF STRESS ECHOCARDIOGRAPHY IN DIAGNOSIS OF VIABLE MYOCARDIUM IN PATIENTS WITH ISCHEMIC HEART DISEASE

    OpenAIRE

    D. N. Perutskiy; T. I. Makeeva; S. L. Konstantinov

    2011-01-01

    The main methods of viable myocardium diagnosis in patients with ischemic heart disease are discussed. Сurrent opportunities of stress echocardiography and tissue Doppler echocardiography in viable myocardium detection are presented.

  18. Identification of a single chromosome in the normal human genome essential for suppression of hamster cell transformation.

    OpenAIRE

    Stoler, A; Bouck, N

    1985-01-01

    Normal human fibroblasts were fused to carcinogen-transformed baby hamster kidney (BHK) cells and found to be able to suppress the anchorage-independent transformed phenotype of the hamster cells. This suppression was not due to interspecies incompatibility, for transformation could be effectively expressed in hybrids if either the human or the BHK parent had initially been transformed by a dominantly acting viral genome. Upon growth of suppressed hybrids, loss of human chromosomes was accomp...

  19. Scalable production in human cells and biochemical characterization of full-length normal and mutant huntingtin.

    Directory of Open Access Journals (Sweden)

    Bin Huang

    Full Text Available Huntingtin (Htt is a 350 kD intracellular protein, ubiquitously expressed and mainly localized in the cytoplasm. Huntington's disease (HD is caused by a CAG triplet amplification in exon 1 of the corresponding gene resulting in a polyglutamine (polyQ expansion at the N-terminus of Htt. Production of full-length Htt has been difficult in the past and so far a scalable system or process has not been established for recombinant production of Htt in human cells. The ability to produce Htt in milligram quantities would be a prerequisite for many biochemical and biophysical studies aiming in a better understanding of Htt function under physiological conditions and in case of mutation and disease. For scalable production of full-length normal (17Q and mutant (46Q and 128Q Htt we have established two different systems, the first based on doxycycline-inducible Htt expression in stable cell lines, the second on "gutless" adenovirus mediated gene transfer. Purified material has then been used for biochemical characterization of full-length Htt. Posttranslational modifications (PTMs were determined and several new phosphorylation sites were identified. Nearly all PTMs in full-length Htt localized to areas outside of predicted alpha-solenoid protein regions. In all detected N-terminal peptides methionine as the first amino acid was missing and the second, alanine, was found to be acetylated. Differences in secondary structure between normal and mutant Htt, a helix-rich protein, were not observed in our study. Purified Htt tends to form dimers and higher order oligomers, thus resembling the situation observed with N-terminal fragments, although the mechanism of oligomer formation may be different.

  20. Bioinformatic screening of human ESTs for differentially expressed genes in normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Mouchiroud Dominique

    2006-04-01

    Full Text Available Abstract Background Owing to the explosion of information generated by human genomics, analysis of publicly available databases can help identify potential candidate genes relevant to the cancerous phenotype. The aim of this study was to scan for such genes by whole-genome in silico subtraction using Expressed Sequence Tag (EST data. Methods Genes differentially expressed in normal versus tumor tissues were identified using a computer-based differential display strategy. Bcl-xL, an anti-apoptotic member of the Bcl-2 family, was selected for confirmation by western blot analysis. Results Our genome-wide expression analysis identified a set of genes whose differential expression may be attributed to the genetic alterations associated with tumor formation and malignant growth. We propose complete lists of genes that may serve as targets for projects seeking novel candidates for cancer diagnosis and therapy. Our validation result showed increased protein levels of Bcl-xL in two different liver cancer specimens compared to normal liver. Notably, our EST-based data mining procedure indicated that most of the changes in gene expression observed in cancer cells corresponded to gene inactivation patterns. Chromosomes and chromosomal regions most frequently associated with aberrant expression changes in cancer libraries were also determined. Conclusion Through the description of several candidates (including genes encoding extracellular matrix and ribosomal components, cytoskeletal proteins, apoptotic regulators, and novel tissue-specific biomarkers, our study illustrates the utility of in silico transcriptomics to identify tumor cell signatures, tumor-related genes and chromosomal regions frequently associated with aberrant expression in cancer.

  1. Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

    Science.gov (United States)

    Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

    2014-01-01

    Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

  2. Age-dependent changes in contractile function and passive elastic properties of myocardium from mice lacking muscle LIM protein (MLP).

    Science.gov (United States)

    Unsöld, Bernhard; Schotola, Hanna; Jacobshagen, Claudius; Seidler, Tim; Sossalla, Samuel; Emons, Julius; Klede, Stefanie; Knöll, Ralph; Guan, Kaomei; El-Armouche, Ali; Linke, Wolfgang A; Kögler, Harald; Hasenfuss, Gerd

    2012-04-01

    Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy. So far, little is known about the time course and pathomechanisms leading to the development of the adult phenotype. We systematically analysed the contractile phenotype, myofilament calcium (Ca(2)(+)) responsiveness, passive myocardial mechanics, histology, and mRNA expression in mice aged 4 and 12 weeks. In 4-week-old animals, there was no significant difference in the force-frequency relationship (FFR) and catecholamine response of intact isolated papillary muscles between wild-type (WT) and MLP null myocardium. In 12-week-old animals, WT myocardium exhibited a significantly positive FFR, while that of MLP null mice was significantly negative, and the inotropic response to catecholamines was significantly reduced in MLP null mice. This time course of decline in contractile function was confirmed in vivo by echocardiography. Whereas at 4 weeks of age MLP null mice and WT littermates showed similar levels of SERCA2a (sarcoplasmic reticulum Ca(2+) ATPase) expression, the expression was significantly lower in 12-week-old MLP null mice compared with littermate controls. Myofilament Ca(2)(+) responsiveness was not affected by the lack of MLP, irrespective of age. Whereas in 4-week-old animals MLP null myocardium showed a trend to an increased compliance compared with the WT, myocardium of 12-week-old MLP null mice was significantly less compliant than WT myocardium. Parallel to the decrease in compliance there was an increase in fibrosis in the MLP null animals. Our data suggest that MLP deficiency does not primarily influence myocardial contractility. A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis.

  3. Transforming Education for a Transition into Human-centered Economy and Post-normal Times

    Directory of Open Access Journals (Sweden)

    Elif Çepni

    2017-10-01

    Full Text Available Solutions to the major problems of our time require a radical shift in our perceptions, thinking and values. Post-normal times (characterized by complexity, chaos and contradictions, post-normal science (characterized by uncertainties, systems view of thinking, alternative perspectives, unknown unknowns, values and human-centered economy are conceptions that we need to take into consideration to define a new role for science. Managing the transition from the knowledge economy (mainly dominated by the use of analytical skills to human-centered economy (mainly dominated by the use of creativity, character, passion requires visionary leadership and a wide range of partnerships, and developing new and more comprehensive, flexible, innovative models of learning. Education today should prepare current generations for the continuously changing world of the future. The critique on modern education ranges across the political spectrum (from ‘the Right’ to ‘the Left’; across countries (both ‘western’ and ‘non-western’; across genders (within men’s, queer and feminist movements; and across worldviews (e.g. post-modernism, critical theory, neo-Marxism, critical traditionalism. These critiques all imply that ‘modern’ education has now become ‘outdated’ (Milojevic, 2005. Technology and globalization are significantly transforming work. However, education and training systems, having remained mostly static and under-invested in for decades, are largely inadequate to meet the needs of the new labour markets. How the disconnect between education systems and labour markets can be eliminated is a much disputed topic and it may require a paradigm shift in current thinking. Citizens and consumers today are experiencing a growing sense of alienation, loss of values and flexibility (Zajda, 2009. There is no form of education which would meet different needs worldwide. Education is a basic human right and it cannot be purely demand

  4. Multimodality imaging demonstrates trafficking of liposomes preferentially to ischemic myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Lipinski, Michael J., E-mail: mjlipinski12@gmail.com [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Albelda, M. Teresa [GIBI2" 3" 0, Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia (Spain); Frias, Juan C. [Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia (Spain); Anderson, Stasia A. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Luger, Dror; Westman, Peter C.; Escarcega, Ricardo O.; Hellinga, David G.; Waksman, Ron [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States); Arai, Andrew E. [Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Epstein, Stephen E. [MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC (United States)

    2016-03-15

    Introduction: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia–reperfusion murine myocardial infarction model. Methods: Mice underwent ischemia–reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24 h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. Results: The mean size of the liposomes was 100 nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163 ± 31% vs. 13 ± 14%, p = 0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. Conclusions: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.

  5. Natural antibodies in normal human serum inhibit Staphylococcus aureus capsular polysaccharide vaccine efficacy.

    Science.gov (United States)

    Skurnik, David; Kropec, Andrea; Roux, Damien; Theilacker, Christian; Huebner, Johannes; Pier, Gerald B

    2012-11-01

    Vaccines against Streptococcus pneumoniae, Neisseria meningitidis, and Hemophilus influenzae type b induce functional opsonic or bactericidal antibodies to surface capsular polysaccharides (CP). Targeting the comparable Staphylococcus aureus CP seems logical, but to date such efforts have failed in human trials. Studies using immunization-induced animal antibodies have documented interference in opsonic and protective activities of antibodies to CP by antibodies to another S. aureus cell surface polysaccharide, poly-N-acetyl glucosamine (PNAG). Here we evaluated whether natural antibody to PNAG in normal human serum (NHS) had a similar deleterious effect. Functional and/or protective activities of antibody to S. aureus CP and PNAG antigens in patients with bacteremia, in mice immunized with combinations of CP and PNAG conjugate vaccines, and in serum samples of healthy subjects with natural antibody to PNAG, to which immunization-induced animal antibodies to CP antigens were added, were evaluated. Antibodies to PNAG and CP that mutually interfered with opsonic killing of S. aureus were detected in 9 of 15 bacteremic patients. Active immunization of mice with combinations of PNAG and CP conjugate antigens always induced antibodies that interfered with each other's functional activity. Non-opsonic natural antibodies to PNAG found in NHS interfered with the functional and protective activities of immunization-induced antibody to CP antigens during experimental infection with S. aureus. Both immunization-induced animal antibodies and natural antibodies to PNAG in NHS interfere with the protective activities of immunization-induced antibody to S. aureus CP5 and CP8 antigens, representing potential barriers to successful use of CP-specific vaccines.

  6. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  7. Relationship between eye dominance and pattern electroretinograms in normal human subjects.

    Science.gov (United States)

    Kamis, Umit; Gunduz, Kemal; Okudan, Nilsel; Gokbel, Hakki; Bodur, Sait; Tan, Uner

    2005-02-01

    The authors conducted a study in 100 non-smoker healthy normal human subjects to find a relationship between eye dominance and macular function as tested by using transient stimulus and electroretinography. Eye preference procedure was carried out using two reference points and pattern electroretinograms (PERGs) were recorded using black and white checks, each check subtending 23'. Trace averager was retriggered every 300 milliseconds (ms) with data collection time of 150 ms. The difference in PERG P50 amplitudes between right and left eyes was analyzed using Student's t test. There was no significant difference in PERG P50 amplitudes between the right and left eye dominant subjects as well as no significant differences between the right and left eyes in right eye dominants and left eye dominants, but in the left-eye dominant group the left eye PERG P50 amplitudes were significantly higher in females than males. Although pattern-reversal visual evoked potentials of healthy subjects provide electrophysiological evidence of lateralization in the nervous system, sensory eye dominance seems to have no correlation with macular function.

  8. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    Energy Technology Data Exchange (ETDEWEB)

    Czapla-Masztafiak, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland); Lis, G.J.; Gajda, M.; Jasek, E. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków (Poland); Czubek, U. [Department of Coronary Disease, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Kraków (Poland); Bolechała, F. [Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków (Poland); Borca, C. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Kwiatek, W.M. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland)

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe{sup 3+} is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe{sup 3+} form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  9. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  10. BIOACTIVATION, PROTEIN HAPTENATION, AND TOXICITY OF SULFAMETHOXAZOLE AND DAPSONE IN NORMAL HUMAN DERMAL FIBROBLASTS1

    Science.gov (United States)

    Bhaiya, Payal; Roychowdhury, Sanjoy; Vyas, Piyush M.; Doll, Mark A.; Hein, David W.; Svensson, Craig K.

    2006-01-01

    Cutaneous drug reactions (CDRs) associated with sulfonamides are believed to be mediated through the formation of reactive metabolites that result in cellular toxicity and protein haptenation. We evaluated the bioactivation and toxicity of sulfamethoxazole (SMX) and dapsone (DDS) in normal human dermal fibroblasts (NHDF). Incubation of cells with DDS or its metabolite (D-NOH) resulted in protein haptenation readily detected by confocal microscopy and ELISA. While the metabolite of SMX (S-NOH) haptenated intracellular proteins, adducts were not evident in incubations with SMX. Cells expressed abundant N-acetyltransferase-1 (NAT1) mRNA and activity, but little NAT2 mRNA or activity. Neither NAT1 nor NAT2 protein were detectable. Incubation of NHDF with S-NOH or D-NOH increased reactive oxygen species formation and reduced glutathione content. NHDF were less susceptible to the cytotoxic effect of S-NOH and D-NOH than are keratinocytes. Our studies provide the novel observation that NHDF are able to acetylate both arylamine compounds and bioactivate the sulfone, DDS, giving rise to haptenated proteins. The reactive metabolites of SMX and DDS also provoke oxidative stress in these cells in a time- and concentration-dependent fashion. Further work is needed to determine the role of the observed toxicity in mediating CDRs observed with these agents. PMID:16603214

  11. Genomic instability induced by 60Co γ ray radiation in normal human liver cells

    International Nuclear Information System (INIS)

    Gen Xiaohua; Guo Xianhua; Zuo Yahui; Wang Xiaoli; Wang Zhongwen

    2007-01-01

    Objective: To explore the genomic instability induced by 60 Co γ rays. Methods: The cloning efficiency and micronucleus efficiency of normal human liver cell irradiated by 60 Co γ rays were detected, and the method of single cell gel electrophoresis (SCGE) was carried out to measure DNA chains damage. The fast-growing cells were divided into different dose-groups and then irradiated by 60 Co γ rays. After 40 populations doubling, the progenies were secondly irradiated with 2 Gy 60 Co γ rays. Results: The cloning efficiency decreased with the increase of doses after the initial irradiation. After the survival cells were given second irradiation, both results of SCGE and micronucleus frequency showed that the second damage was correlated with the original irradiation doses. Conclusions: 60 Co γ rays can not only induce the immediate biological effects in liver cells, but also lead to the genomic instability in the descendants that leads to an enhanced frequency of genetic changes occurring among the progeny of the original irradiated cell. The expanding effect of second event helps to study the genomic instability. (authors)

  12. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions

    International Nuclear Information System (INIS)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-01-01

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/μm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to 137 Cs γ-rays. The mutation frequency increased up to 105 keV/μm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/μm showed all or partial deletions of exons, while among γ-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not

  13. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    Directory of Open Access Journals (Sweden)

    Raghu Dhanapal

    2015-01-01

    Full Text Available Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC, epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  14. Normal level of sepsis-associated phenylcarboxylic acids in human serum.

    Science.gov (United States)

    Beloborodova, N V; Moroz, V V; Osipov, A A; Bedova, A Yu; Olenin, A Yu; Getsina, M L; Karpova, O V; Olenina, E G

    2015-03-01

    Previous studies showed that large amounts of phenylcarboxylic acids (PhCAs) are accumulated in a septic patient's blood due to increased endogenous and microbial phenylalanine and tyrosine biotransformation. Frequently, biochemical aromatic amino acid transformation into PhCAs is considered functionally insignificant for people without monogenetic hereditary diseases. The blood of healthy people contains the same PhCAs that are typical for septic patients as shown in this paper. The overall serum PhCAs level was 6 µM on average as measured by gas chromatography with flame ionization detection. This level is a stable biochemical parameter indicating the normal metabolism of aromatic amino acids. The concentrations of PhCAs in the metabolic profile of healthy people are distributed as follows: phenylacetic ≈ p-hydroxyphenyllactic > p-hydroxyphenylacetic > phenyllactic ≈ phenylpropionic > benzoic. We conclude that maintaining of stable PhCAs level in the serum is provided as the result of integration of human endogenous metabolic pathways and microbiota.

  15. Profile of Human TERT and P73 in Oral Squamous Cell Carcinoma Cell Lines Compared to Normal Human Oral Mucosa: a Preliminary Study

    Directory of Open Access Journals (Sweden)

    Ambar Kusuma Astuti

    2013-05-01

    Full Text Available Genetic alteration on p53 allows cellular immortalization and predisposes cells to neoplastic transformation. This immortalization is related to telomere length maintenance by telomerase. Human TERT is a key compo-nent of telomerase, which activity is suppressed by p53. The p73, the homolog of p53, has a similar ability in tumor suppression. The P73 is expressed at a different level in various cancer cells and normal tissues. Profile of human TERT and P73 in mutant p53 OSCC cell line and normal human oral mucosa have not been known. Objective: To observe human TERT and P73 profile in mutant p53 OSCC cell lines and normal human oral mucosa. Methods: The extracted protein of HSC-3 and HSC-4 cell lines and normal mucosal tissues were ana-lyzed with SDS PAGE to detect human TERT and p73 expression based on the molecular weight. Results: The HSC-3 cell line showed thicker band density of P73 compared to its density of HSC-4. Only 50% of normal oral mucosa tissue showed thick P73 band density. The human TERT band was clearly shown in HSC-3 and HSC-4 cell lines but not in normal oral mucosa. Conclusion: Different profile of human TERT and P73 in OSCC cell lines and normal oral mucosa might be cell-type specific and influenced by the status of p53. Analy-sis of the role of p73 in these cancers might need further research to determine possible p73 substitution for p53 function.DOI: 10.14693/jdi.v18i1.55

  16. A study of chromium in human cataractous lenses and whole blood of diabetics, senile, and normal population.

    Science.gov (United States)

    Pineau, A; Guillard, O; Risse, J F

    1992-01-01

    Chromium (Cr) is of known biological importance, necessary for the maintenance of normal glucose metabolism. There is a lower level of blood Cr concentrations in cases of diabetes. Diabetes carries a risk of cataract development, so the potential effects of Cr on the eye may need to be studied in more depth. The presence of this trace element in both normal and cataractous human lenses has to our knowledge not been investigated so far. The concentration of total Cr in 61 human lenses and 38 blood samples was determined by electrothermal atomic absorption spectrometry with Zeeman effect (EAASZ). Analysis of the levels of Cr in human lenses shows a significant difference between normal and diabetic populations, and an absence of difference between senile and diabetic populations.

  17. Production of glycosylated physiologically normal human α1-antitrypsin by mouse fibroblasts modified by insertion of a human α1-antitrypsin cDNA using a retroviral vector

    International Nuclear Information System (INIS)

    Garver, R.I. Jr.; Chytil, A.; Karlsson, S.

    1987-01-01

    α 2 -Antitrypsin (α 1 AT) deficiency is a hereditary disorder characterized by reduced serum levels of α 1 AT, resulting in destruction of the lower respiratory tract by neutrophil elastase. As an approach to augment α 1 AT levels in this disorder with physiologically normal human α 1 AT, the authors have integrated a full-length normal human α 1 AT cDNA into the genome of mouse fibroblasts. To accomplish this, the retroviral vector N2 was modified by inserting the simian virus 40 early promoter followed by the α 1 AT cDNA. Southern analysis demonstrated that the intact cDNA was present in the genome of selected clones of the transfected murine fibroblasts psi2 and infected NIH 3T3. The clones produced three mRNA transcripts containing human α 1 AT sequences, secreted an α 1 AT molecule recognized by an anti-human α 1 AT antibody, with the same molecular mass as normal human α 1 AT and that complexed with and inhibited human neutrophil elastase. The psi2 produced α 1 AT was glycosylated, and when infused intravenously into mice, it had a serum half-life similar to normal α 1 AT purified from human plasma and markedly longer than that of nonglycosylated human α 1 AT cDNA-directed yeast-produced α 1 AT. These studies demonstrate the feasibility of using a retroviral vector to insert the normal human α 1 AT cDNA into non-α 1 AT-producing cells, resulting in the synthesis and secretion of physiologically normal α 1 AT

  18. Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-05-01

    Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

  19. AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

    International Nuclear Information System (INIS)

    Fuhrmann, A; Staunton, J R; Banyai, N; Davies, P C W; Ros, R; Nandakumar, V

    2011-01-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial–mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force–indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their

  20. AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

    Science.gov (United States)

    Fuhrmann, A; Staunton, J R; Nandakumar, V; Banyai, N; Davies, P C W; Ros, R

    2011-01-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division, and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett’s Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope (FLIM) to study the mechanical properties of single adherent cells. 64 force indentation curves were taken over the nucleus of each cell in an 8×8 grid pattern. Analyzing the force indentation curves, indentation depth dependent Young’s moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young’s moduli were calculated to 4.7 kPa for EPC2 (n=18 cells), 3.1 kPa for CP-A (n=10), and 2.6 kPa for CP-D (n=19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n=5), significant stiffening was found (9.9 kPa), while CP-A cells (n=5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n=16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these ‘breakthrough events’ to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells, and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to ‘crumble and yield’ rather than their ability to ‘bend and flex’. PMID

  1. AFM stiffness nanotomography of normal, metaplastic and dysplastic human esophageal cells

    Science.gov (United States)

    Fuhrmann, A.; Staunton, J. R.; Nandakumar, V.; Banyai, N.; Davies, P. C. W.; Ros, R.

    2011-02-01

    The mechanical stiffness of individual cells is important in tissue homeostasis, cell growth, division and motility, and the epithelial-mesenchymal transition in the initiation of cancer. In this work, a normal squamous cell line (EPC2) and metaplastic (CP-A) as well as dysplastic (CP-D) Barrett's Esophagus columnar cell lines are studied as a model of pre-neoplastic progression in the human esophagus. We used the combination of an atomic force microscope (AFM) with a scanning confocal fluorescence lifetime imaging microscope to study the mechanical properties of single adherent cells. Sixty four force indentation curves were taken over the nucleus of each cell in an 8 × 8 grid pattern. Analyzing the force indentation curves, indentation depth-dependent Young's moduli were found for all cell lines. Stiffness tomograms demonstrate distinct differences between the mechanical properties of the studied cell lines. Comparing the stiffness for indentation forces of 1 nN, most probable Young's moduli were calculated to 4.7 kPa for EPC2 (n = 18 cells), 3.1 kPa for CP-A (n = 10) and 2.6 kPa for CP-D (n = 19). We also tested the influence of nuclei and nucleoli staining organic dyes on the mechanical properties of the cells. For stained EPC2 cells (n = 5), significant stiffening was found (9.9 kPa), while CP-A cells (n = 5) showed no clear trend (2.9 kPa) and a slight softening was observed (2.1 kPa) in the case of CP-D cells (n = 16). Some force-indentation curves show non-monotonic discontinuities with segments of negative slope, resembling a sawtooth pattern. We found the incidence of these 'breakthrough events' to be highest in the dysplastic CP-D cells, intermediate in the metaplastic CP-A cells and lowest in the normal EPC2 cells. This observation suggests that the microscopic explanation for the increased compliance of cancerous and pre-cancerous cells may lie in their susceptibility to 'crumble and yield' rather than their ability to 'bend and flex'.

  2. Effects of acute and chronic uremia on active cation transport in rat myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Druml, W.; Kelly, R.A.; England, B.K.; O' Hara, D.S.; Mitch, W.E. (Brigham and Women' s Hospital, Boston, MA (USA))

    1990-12-01

    As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously. Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, (3H)ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity (3H)ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.

  3. Body mass index and myocardium at risk in patients with acute coronary syndrome.

    Science.gov (United States)

    Arrebola-Moreno, A L; Marfil-Alvarez, R; Catena, A; García-Retamero, R; Arrebola, J P; Melgares-Moreno, R; Ramirez-Hernández, J A; Kaski, J C

    2014-04-01

    Whilst traditional studies have shown that obese individuals are at a higher risk of cardiovascular events compared to lean subjects, recent studies in patients with acute myocardial infarction (AMI) have suggested that obesity may exert protective effects (the "obesity paradox"). We sought to assess the relationship between body mass index (BMI) and the BARI score (BARIsc), a validated tool used to assess myocardium at risk, in patients with acute coronary syndrome. Participants were 116 consecutive patients (mean age, 60.6 years; 97 men) with AMI (68 ST elevated myocardial infarction, STEMI; 48 non-ST elevated myocardial infarction, NSTEMI). Demographics, BMI, risk factors, biochemistry data, left ventricular function, angiographic data and the BARIsc were assessed in every patient. Multiple linear regression analyses showed that BMI significantly correlated with BARIsc; β=.23, p<0.02. This was found only in the overweight/obese patients, β=.27, p<0.01, but not in patients with normal BMIs, β=0.08, p=0.71. An increased body weight is associated with an increased area of myocardium at risk in patients with ACS. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  4. Revisiting vocal perception in non-human animals: a review of vowel discrimination, speaker voice recognition, and speaker normalization.

    Science.gov (United States)

    Kriengwatana, Buddhamas; Escudero, Paola; Ten Cate, Carel

    2014-01-01

    The extent to which human speech perception evolved by taking advantage of predispositions and pre-existing features of vertebrate auditory and cognitive systems remains a central question in the evolution of speech. This paper reviews asymmetries in vowel perception, speaker voice recognition, and speaker normalization in non-human animals - topics that have not been thoroughly discussed in relation to the abilities of non-human animals, but are nonetheless important aspects of vocal perception. Throughout this paper we demonstrate that addressing these issues in non-human animals is relevant and worthwhile because many non-human animals must deal with similar issues in their natural environment. That is, they must also discriminate between similar-sounding vocalizations, determine signaler identity from vocalizations, and resolve signaler-dependent variation in vocalizations from conspecifics. Overall, we find that, although plausible, the current evidence is insufficiently strong to conclude that directional asymmetries in vowel perception are specific to humans, or that non-human animals can use voice characteristics to recognize human individuals. However, we do find some indication that non-human animals can normalize speaker differences. Accordingly, we identify avenues for future research that would greatly improve and advance our understanding of these topics.

  5. Revisiting vocal perception in non-human animals: a review of vowel discrimination, speaker voice recognition, and speaker normalization

    Directory of Open Access Journals (Sweden)

    Buddhamas eKriengwatana

    2015-01-01

    Full Text Available The extent to which human speech perception evolved by taking advantage of predispositions and pre-existing features of vertebrate auditory and cognitive systems remains a central question in the evolution of speech. This paper reviews asymmetries in vowel perception, speaker voice recognition, and speaker normalization in non-human animals – topics that have not been thoroughly discussed in relation to the abilities of non-human animals, but are nonetheless important aspects of vocal perception. Throughout this paper we demonstrate that addressing these issues in non-human animals is relevant and worthwhile because many non-human animals must deal with similar issues in their natural environment. That is, they must also discriminate between similar-sounding vocalizations, determine signaler identity from vocalizations, and resolve signaler-dependent variation in vocalizations from conspecifics. Overall, we find that, although plausible, the current evidence is insufficiently strong to conclude that directional asymmetries in vowel perception are specific to humans, or that non-human animals can use voice characteristics to recognize human individuals. However, we do find some indication that non-human animals can normalize speaker differences. Accordingly, we identify avenues for future research that would greatly improve and advance our understanding of these topics.

  6. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Argo Aug

    Full Text Available E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1 to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1's maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes.

  7. Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts.

    Science.gov (United States)

    Kitamura, Hodaka; Ozono, Eiko; Iwanaga, Ritsuko; Bradford, Andrew P; Okuno, Junko; Shimizu, Emi; Kurayoshi, Kenta; Kugawa, Kazuyuki; Toh, Hiroyuki; Ohtani, Kiyoshi

    2015-09-01

    The transcription factor E2F is the principal target of the tumor suppressor pRB. E2F plays crucial roles not only in cell proliferation by activating growth-related genes but also in tumor suppression by activating pro-apoptotic and growth-suppressive genes. We previously reported that, in human normal fibroblasts, the tumor suppressor genes ARF, p27(Kip1) and TAp73 are activated by deregulated E2F activity induced by forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. In contrast, growth-related E2F targets are activated by both E2F activities, underscoring the roles of deregulated E2F in tumor suppression in the context of dysfunctional pRB. In this study, to further understand the roles of deregulated E2F, we explored new targets that are specifically activated by deregulated E2F using DNA microarray. The analysis identified nine novel targets (BIM, RASSF1, PPP1R13B, JMY, MOAP1, RBM38, ABTB1, RBBP4 and RBBP7), many of which are involved in the p53 and RB tumor suppressor pathways. Among these genes, the BIM gene was shown to be activated via atypical E2F-responsive promoter elements and to contribute to E2F1-mediated apoptosis. Our results underscore crucial roles of deregulated E2F in growth suppression to counteract loss of pRB function. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

  8. Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation.

    Science.gov (United States)

    Mastrofrancesco, Arianna; Ottaviani, Monica; Aspite, Nicaela; Cardinali, Giorgia; Izzo, Enzo; Graupe, Klaus; Zouboulis, Christos C; Camera, Emanuela; Picardo, Mauro

    2010-09-01

    Azelaic acid (AzA), a nine-carbon dicarboxylic acid, is an agent for the topical treatment of acne. It has also been shown to be effective in rosacea; however, the mechanism of action has not been clarified. Because inflammation is a common feature of both conditions, we investigated the effects of azelaic acid on the inflammatory response of normal human keratinocytes to ultraviolet B light, which is a photosensitizer agent in rosacea. AzA, at 20 mM, a concentration achievable following topical application of a 15% gel, suppresses ultraviolet B light-induced interleukins-1beta, -6 and tumor necrosis factor-alpha mRNA expression and protein secretion. Mechanistically, azelaic acid significantly reduced the ultraviolet B light-induced nuclear translocation of nuclear factor kB p65 subunit and the phosphorylation of the p38 mitogen and stress-activated protein kinase. Moreover, as peroxisome proliferators-activated receptor gamma, (PPARgamma) which has a crucial role in the control of inflammation, is activated by fatty acids and products of lipid peroxidation, we further investigated the effect of azelaic acid on the expression of this nuclear receptor. AzA induced peroxisome proliferators-activated receptor-gamma mRNA and its transcriptional activity. The PPARgamma antagonist GW9662 abrogated the inhibitory effects of AzA on the UVB-induced pro-inflammatory cytokines release and on the cell proliferation. Our study provides new insights into the molecular mechanisms of the activity of azelaic acid and lands additional evidences for its therapeutic effects on inflammatory skin diseases, such as rosacea.

  9. The pharmacokinetics, safety and endocrine effects of authentic biosynthetic human growth hormone in normal subjects.

    Science.gov (United States)

    Ho, K Y; Weissberger, A J; Stuart, M C; Day, R O; Lazarus, L

    1989-04-01

    The pharmacokinetics, safety and endocrine effects of an authentic human growth hormone (bio-hGH), produced by the expression of genomic hGH in a mammalian cell line, were studied in six healthy young men who were administered 0.2 U/kg/day subcutaneously for five consecutive days. Changes in sodium balance and in thyroid function were studied during the week of bio-hGH administration and safety parameters were monitored over a 3-week period. Growth hormone levels reached a mean (+/- SD) peak of 106 +/- 10 mIU/l at 3.3 +/- 0.5 h following the first dose and resulted in a significant rise of somatomedin C. free fatty acids, fasting blood glucose and insulin concentrations. Bio-hGH administration resulted in a significant increase in body weight (80.0 +/- 4.5 to 81.1 +/- 4.3 kg; P less than 0.01) which was associated with a marked reduction in urinary sodium excretion (196 +/- 38 to 45 +/- 20 mmol/day; P less than 0.025). Serum T3 increased during bio-hGH administration and was associated with reciprocal changes in free thyroxine and TSH concentrations. Cardiac, hepatic, renal, biochemical, haematological, endocrinological and immunological functions remained normal throughout the study. No antibodies to hGH or to host cell protein developed during the study. The results show that bio-hGH is safe in the short term, well tolerated, possesses pharmacokinetic and biological properties similar to pituitary hGH, and has distinct effects on sodium balance and on thyroid function. This study stresses the need to monitor patients for effects on sodium retention, carbohydrate metabolism and thyroid function when using hGH doses of 1.0 U/kg/week (40 U/m2/week) or more in patients with GH responsive short stature.

  10. Chamber-dependent expression of brain natriuretic peptide and its mRNA in normal and diabetic pig heart

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Goetze, Jens P; Bartels, Emil D

    2002-01-01

    BNP mRNA transcript and a mature BNP mRNA transcript in normal porcine hearts. In normal pigs, the amount of precursor BNP mRNA was similar in atrial and ventricular myocardium, whereas the mature BNP transcript was 10- to 50-fold more abundant in atrial than in ventricular myocardium. Quantitation...... of proBNP in normal porcine hearts by radioimmunoassay disclosed abundant proBNP in the atria, whereas proBNP was undetectable in the ventricles. Laser confocal microscopy revealed proBNP in secretory granules of atrial but not in the ventricular myocardium of normal pigs. Mild streptozotocin...

  11. In vivo modelling of normal and pathological human T-cell development

    NARCIS (Netherlands)

    Wiekmeijer, A.S.

    2016-01-01

    This thesis describes novel insights in human T-cell development by transplanting human HSPCs in severe immunodeficient NSG mice. First, an in vivo model was optimized to allow engraftment of hematopoietic stem cells derived from human bone marrow. This model was used to study aberrant human T-cell

  12. Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells

    NARCIS (Netherlands)

    Cereser, B. (Biancastella); M. Jansen (Marnix); Austin, E. (Emily); Elia, G. (George); Mcfarlane, T. (Taneisha); C.H.M. van Deurzen (Carolien); A.M. Sieuwerts (Anieta); M.G. Daidone (Maria Grazia); Tadrous, P.J. (Paul J); Wright, N.A. (Nicholas A); L. Jones (Louise); Mcdonald, S.A. (Stuart Ac)

    2017-01-01

    textabstractIt is widely accepted that the cell of origin of breast cancer is the adult mammary epithelial stem cell; however, demonstrating the presence and location of tissue stem cells in the human breast has proved difficult. Furthermore, we do not know the clonal architecture of the normal and

  13. Normal development of the pulmonary veins in human embryos and formulation of a morphogenetic concept for sinus venosus defects

    NARCIS (Netherlands)

    Blom, N. A.; Gittenberger-de Groot, A. C.; Jongeneel, T. H.; DeRuiter, M. C.; Poelmann, R. E.; Ottenkamp, J.

    2001-01-01

    A sinus venosus defect is a form of interatrial communication associated with abnormal drainage of the right pulmonary veins. Its morphogenesis still remains unclear. We therefore studied the normal development of pulmonary veins in human embryos in relation to the sinus venosus and the dorsal

  14. First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

    NARCIS (Netherlands)

    Pratt, JJ; de Wolf, BTHM; Mantingh, A

    Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down

  15. A comparison of the predicted and observed low energy radiation from the thorax of a normal human male

    International Nuclear Information System (INIS)

    Speight, R.G.

    1967-07-01

    The normal human male emits a continuum of low energy photons (< 100 KeV) whose magnitude depends on the body content of potassium-40 and caesium-137 and the physical parameters of the body. An experiment is described from which it has been possible to devise a method of forecasting the level of this continuum with an accuracy of ± 6%. (author)

  16. Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Lang-Jensen, T; Hansen, J M

    1994-01-01

    The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two...

  17. Troponin I phosphorylation in human myocardium in health and disease

    NARCIS (Netherlands)

    Wijnker, P.J.M.; Murphy, A.M.; Stienen, G.J.M.; van der Velden, J.

    2014-01-01

    Cardiac troponin I (cTnI) is well known as a biomarker for the diagnosis of myocardial damage. However, because of its central role in the regulation of contraction and relaxation in heart muscle, cTnI may also be a potential target for the treatment of heart failure. Studies in rodent models of

  18. [Neurogenic stunned myocardium in Pediatrics. A case report].

    Science.gov (United States)

    Alados Arboledas, F J; Millán-Miralles, L; Millán-Bueno, M P; Expósito-Montes, J F; Santiago-Gutierrez, C; Martínez Padilla, M C

    2015-10-01

    Neurogenic stunned myocardium is an unusual clinical entity. It mimics an acute coronary syndrome with electrocardiographic abnormalities, cardiac dysfunction and elevated cardiac enzymes with absence of obstructive coronary disease. It may occur after a neurosurgical procedure. A case is presented of neurogenic stunned myocardium occurring in a child after removal of a posterior fossa medulloblastoma. The patient developed nodal tachycardia with hemodynamic impairment. The clinical course was satisfactory due to antiarrhythmic therapy, with biochemical, echocardiographic, and clinical improvement within a week. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

    OpenAIRE

    Wu, C-H; Chen, Y-F; Wang, J-Y; Hsieh, M-C; Yeh, C-S; Lian, S-T; Shin, S-J; Lin, S-R

    2002-01-01

    The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adre...

  20. Lethality and the depression on DNA synthesis in UV-irradiated normal human and xeroderma pigmentosum cells

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, K. (Kobe Univ. (Japan). School of Medicine)

    1983-12-01

    Ultraviolet radiation suppresses the semiconservative DNA replication in mammalian cells. The rate of DNA synthesis is initially depressed and later recovers after low doses of UV radiation in human cells. Such a response is more sensitive to UV radiation in cells derived from patients with xeroderma pigmentosum (XP) than that in normal human cells. The relative rate of DNA synthesis is not always correlated with cell survival because, unlike cell survival, the dose-response curve of the relative rate of DNA synthesis shows the biphasic nature of the sensitivity. In the experiments reported herein, the total amount (not the rate) of DNA synthesized during a long interval of incubation which covers the period of inhibition and recovery (but not longer than one generation time) after irradiation with various doses of UV radiation was examined in normal human and XP cells, and was found to be well correlated with cell survival in all the cells tested.

  1. 99m Technetium pyrophosphate myocardium scintigraphy. First results

    International Nuclear Information System (INIS)

    Toussaint, Paul.

    1976-01-01

    99m technetium pyrophosphate myocardium scintigraphy is a very recent examination technique. This work gives the results obtained on 61 patients. As a vector of the isotope, pyrophosphate has the advantage over polyphosphate of a fast bone uptake there it should be stressed that a 90 minute pause is necessary between the intraveinous injection of the isotope and the photographic recording so that the reading is not troubled by the labelled intracardiac blood pool image, an image quality criterion being the estimation of a good costal fixation which in fact appears sooner or later according to the subject. The role of pyrophosphate, chelator of calcium in fixation of the isotope on the myocardium, could be explained by the fast appearance of 'dense bodies', made up of calcium hydroxyapathice crystals, in the mitochondria of myocardium cells having undergone an irreversible necrotic process. The choice of 99 m technetium is based on its ease of use: 6 hour half-life, high-energy pure gamma emission at 140 keV. The fixed image studied under two incidences, front and left anterior oblique, is obtained from mobile images given by the scintillation camera used in connection with a data processing system. Several facts are underlined, explaining the disadvantages, advantages and indications of the method [fr

  2. Evaluation of hibernating myocardium with exercise thallium-201 myocardial SPECT

    International Nuclear Information System (INIS)

    Hashimoto, Yasunori; Yamabe, Hiroshi; Yasaka, Yoshinori; Namura, Hiroyuki; Maeda, Kazumi; Yokoyama, Mitsuhiro

    1991-01-01

    Seven patients with left ventricular wall motion abnormality underwent exercise thallium-201 myocardial SPECT before and after percutaneous transluminal coronary angioplasty (PTCA) for the infarct-related artery. Both redistribution (Rd) images and %Tl uptake were examined to evaluate the capability of SPECT to diagnose pre-PTCA hibernation of the myocardium. Of 7 patients (18 segments), 5 (13 segments) were found to have an improvement of wall motion abnormality on left ventricular cineangiogram, leading to a diagnosis of hibernating myocardium. For all of the 5 patients, delayed SPECT images showed complete Rd in one patient (2 segments) and incomplete Rd in 4 patients (11 segments). In addition, %Tl uptake on early images was 54.3±19.4% before PTCA and 78.8±19.2% after PTCA. These results indicated that exercise thallium-201 myocardial SPECT may be useful for diagnosis of hibernating myocardium. It should, however, be noted that of 13 segments diagnosed with hibernation, 6 had Rd on post-PTCA SPECT in spite of the absence of restenosis. (N.K.)

  3. Study of shape memory alloy fibers for the development of artificial myocardium.

    Science.gov (United States)

    Hassoulas, Ioannis A; Ladopoulos, Vlassios S; Kalogerakos, Paris-Dimitrios K

    2010-01-01

    Circulatory support devices are employed to treat heart failure. Such a device could be made from shape memory alloy (SMA) fibers. These Ni-Ti fibers contract when electric current flows through them, thus resembling artificial muscles. An artificial myocardium device made from SMA fibers can directly compress the epicardial surface of a failing heart, thus contributing to the pumping action. Unlike modern mechanical circulatory support devices, there is no blood-contacting surface to provoke thromboembolism, hemorrhage, inflammatory response or hemolysis. The experimental setup permitted a detailed study of a sample SMA fiber with great accuracy while the ambient temperature was controlled to resemble that of the human body. The current profile through the fiber was controlled (current shaping, CS) by a microcontroller and a portable computer. Parameters such as strain, contraction and relaxation velocities and the effect of ambient temperature were measured. The contraction and relaxation velocities were measured after applying various effective currents. It was found that the contraction velocity could be manipulated to reach that of the healthy myocardium through CS. On the other hand, the relaxation velocity was independent of the contraction velocity. A cardiac assist device can be made from SMA fibers. More studies need to be conducted in this direction.

  4. Time-dose response of human tumors and normal tissues during and after fractionated radiation treatment

    International Nuclear Information System (INIS)

    Van de Geijn, J.

    1988-01-01

    The background and some results of initial applications of a new model of time-dose response of tumors as well as fast-renewing normal tissues to fractionated radiation therapy are presented. Both the linear-quadratic and the single-hit/single-target, single-hit/multi-target model may be used for the single-dose survival of both the viable stem cells and the clonogenic tumor cells. Normal tissue tolerance is expressed as a minimum acceptable level of normal tissue functionality, due to insufficient production of replacement cells, which in turn is caused by radiation-induced depletion of the viable stem cell population. A logistic function describes the homeostatically controlled inter-fraction and post-treatment normal tissue stem cell repopulation. The onset of stem cell repopulation may be delayed, and the doubling rate of clonogenic tumor cells may increase, upon the onset of treatment. Criteria for the selection of acceptable parameter values for normal tissue as well as tumors are described. An interactive Fortran77 program has been developed to assist in the search for acceptable parameter values, the simulation of the time-dose response of normal tissues and tumors to conventional clinical fractionation schemes and the exploration of alternative schedules, including hyperfractionation. Some provisional results are presented. 29 refs.; 11 figs.; 2 tabs

  5. Microstructure, length, and connection of limbic tracts in normal human brain development

    Directory of Open Access Journals (Sweden)

    Qiaowen eYu

    2014-08-01

    Full Text Available The cingulum and fornix play an important role in memory, attention, spatial orientation and feeling functions. Both microstructure and length of these limbic tracts can be affected by mental disorders such as Alzheimer’s disease, depression, autism, anxiety, and schizophrenia. To date, there has been little systematic characterization of their microstructure, length and functional connectivity in normally developing brains. In this study, diffusion tensor imaging (DTI and resting state functional MRI (rs-fMRI data from 65 normally developing right-handed subjects from birth to young adulthood was acquired. After cingulate gyrus part of the cingulum (cgc, hippocampal part of the cingulum (cgh and fornix (fx were traced with DTI tractography, absolute and normalized tract lengths and DTI-derived metrics including fractional anisotropy, mean, axial and radial diffusivity were measured for traced limbic tracts. Free water elimination (FWE algorithm was adopted to improve accuracy of the measurements of DTI-derived metrics. The role of these limbic tracts in the functional network at birth and adulthood was explored. We found a logarithmic age-dependent trajectory for FWE-corrected DTI metric changes with fast increase of microstructural integrity from birth to 2-year-old followed by a slow increase to 25-year-old. Normalized tract length of cgc increases with age, while no significant relationship with age was found for normalized tract lengths of cgh and fx. Stronger microstructural integrity on the left side compared to that of right side was found. With integrated DTI and rs-fMRI, the key connectional role of cgc and cgh in the default mode network (DMN was confirmed as early as birth. Systematic characterization of length and DTI metrics after FWE correction of limbic tracts offers insight into their morphological and microstructural developmental trajectories. These trajectories may serve as a normal reference for pediatric patients with

  6. Human paraoxonase and HDL-cholesterol in pakistan patients with acute myocardial infarction and normal healthy adults

    International Nuclear Information System (INIS)

    Iqbal, I.P.; Khan, A.H.; Mehboobali, N.

    2007-01-01

    Human serum paraoxonase is a high density lipoprotein (HDL)-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction (AMI) compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol (serum levels < 40mg/dl) compared to the value in those with normal levels of HDL-cholesterol (P=0.04). In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol (Pearson's r= 0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls). Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population. (author)

  7. MicroRNA miR-1 is up-regulated in remote myocardium in patients with myocardial infarction.

    Science.gov (United States)

    Bostjancic, E; Zidar, N; Stajner, D; Glavac, D

    2010-01-01

    MicroRNAs are small regulatory RNA molecules that mediate regulation of gene expression, thus affecting a variety of physiological, developmental and pathological conditions. They are believed to be new promising therapeutic targets. In recent studies two muscle-specific microRNAs were discovered to contribute to heart diseases and development: miR-1 and miR-133, but there is little data on their expression patterns in human myocardial infarction. We performed simultaneous expression analysis of miR-1, miR-133a, miR-133b in samples of infarcted tissue and remote myocardium from twenty- four patients with acute myocardial infarction. MicroRNA expression was analysed using quantitative real-time PCR and compared to the expression patterns in myocardium of eight healthy adults who died in accidents. We found ~3.8-fold miR-1 up-regulation in remote myocardium when compared to infarcted tissue or healthy adult hearts. As miR-1 has been shown in animal models and clinical studies to contribute to arrhythmogenesis by regulating pacemaker channel genes, our finding of miR-1 up-regulation in patients with myocardial infarction indicates that it might be responsible for the higher risk for arrhythmias in these patients. In addition, miR-133a/b down-regulation in infarcted tissue and remote myocardium was observed, indicating miR-133a/b involvement in the heart response to myocardial infarction. We conclude that miR-1 and miR-133 seem to be important regulators of heart adaptation after ischaemic stress.

  8. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    Science.gov (United States)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  9. Histological versus stereological methods applied at spermatogonia during normal human development

    DEFF Research Database (Denmark)

    Cortes, Dina

    1990-01-01

    The number of spermatogonia per tubular transverse section (S/T), and the percentage of seminiferous tubulus containing spermatogonia (the fertility index (FI] were measured in 40 pairs of normal autopsy testes aged 28 weeks of gestation-40 years. S/T and FI showed similar changes during the whol...

  10. NIH Human Microbiome Project defines normal bacterial makeup of the body

    Science.gov (United States)

    Microbes inhabit just about every part of the human body, living on the skin, in the gut, and up the nose. Sometimes they cause sickness, but most of the time, microorganisms live in harmony with their human hosts, providing vital functions essential for

  11. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  12. Differential production of proteolytic enzymes by normal human fibroblasts and their counterparts transformed by treatment with 60Co gamma rays

    International Nuclear Information System (INIS)

    Nishitani, Koji; Namba, Masayoshi; Ohkubo, Shigeki; Kimoto, Tetsuo

    1985-01-01

    Production of proteolytic enzymes by human fibroblasts in the process of transformation was investigated. The cells used were normal human fibroblasts (KSM-6) and their in vitro counterparts transformed by treatment with 60 Co gamma rays (KMST-6). Cells seeded by treatment with EDTA were cultured in a serum free medium. Proteolytic enzymes in the culture medium of cells were assayed using a synthetic substrate, N-α-(p-tosyl)-L-arginine ( 3 H) methyl ester hydrochloride. The transformed cells (KMST-6) produced a larger amount of enzymes than normal cells (KMS-6). The enzyme production in both cell lines was high in the exponential growth stage and then decreased as the cells reached confluency. The proteolytic enzymes produced by these cells were trypsin- and thrombin-like enzymes. Cell growth of KMST-6 or KMS-6 was not inhibited by the addition of protease inhibitors to the culture medium. (author)

  13. Cloning and characterization of the complementary DNA for the B chain of normal human serum C1q.

    Science.gov (United States)

    Reid, K B; Bentley, D R; Wood, K J

    1984-09-06

    Normal human C1q is a serum glycoprotein of 460 kDa containing 18 polypeptide chains (6A, 6B, 6C) each 226 amino acids long and each containing an N-terminal collagen-like domain and a C-terminal globular domain. Two unusual forms of C1q have been described: a genetically defective form, which has a molecular mass of approximately 160 kDa and is found in the sera of homozygotes for the defect who show a marked susceptibility to immune complex related disease; a fibroblast form, shown to be synthesized and secreted, in vitro, with a molecular mass of about 800 kDa and with chains approximately 16 kDa greater than those of normal C1q. A higher than normal molecular mass form of C1q has also been described in human colostrum and a form of C1q has been claimed to represent one of the types of Fc receptor on guinea-pig macrophages. To initiate studies, at the genomic level, on these various forms of C1q, and to investigate the possible relation between the C1q genes and the procollagen genes, the complementary DNA corresponding to the B chain of normal C1q has been cloned and characterized.

  14. Neutrophil attractant protein-1-immunoglobulin G immune complexes and free anti-NAP-1 antibody in normal human serum.

    OpenAIRE

    Sylvester, I; Yoshimura, T; Sticherling, M; Schröder, J M; Ceska, M; Peichl, P; Leonard, E J

    1992-01-01

    After obtaining data indicating the presence of a neutrophil attractant protein-1 (NAP-1)-IgG complex in normal human serum, we developed sandwich ELISAs that could quantify NAP-1 and NAP-1-IgG in mixtures of the two moieties. The ELISA for free NAP-1 used a monoclonal capture antibody that did not bind NAP-1-IgG. The ELISA for NAP-1-IgG was based on omission of the anti-NAP-1 detection antibody (required for the free NAP-1 ELISA) and on interaction of phosphatase-conjugated anti-human IgG wi...

  15. A rapid and simple procedure for the establishment of human normal and cancer renal primary cell cultures from surgical specimens.

    Directory of Open Access Journals (Sweden)

    Maria João Valente

    Full Text Available The kidney is a target organ for the toxicity of several xenobiotics and is also highly susceptible to the development of malignant tumors. In both cases, in vitro studies provide insight to cellular damage, and represent adequate models to study either the mechanisms underlying the toxic effects of several nephrotoxicants or therapeutic approaches in renal cancer. The development of efficient methods for the establishment of human normal and tumor renal cell models is hence crucial. In this study, a technically simple and rapid protocol for the isolation and culture of human proximal tubular epithelial cells and human renal tumor cells from surgical specimens is presented. Tumor and normal tissues were processed by using the same methodology, based on mechanical disaggregation of tissue followed by enzymatic digestion and cell purification by sequential sieving. The overall procedure takes roughly one hour. The resulting cell preparations have excellent viabilities and yield. Establishment of primary cultures from all specimens was achieved successfully. The origin of primary cultured cells was established through morphological evaluation. Normal cells purity was confirmed by immunofluorescent staining and reverse transcription-polymerase chain reaction analysis for expression of specific markers.

  16. The metabolism of 14C-labelled α-methyldopa in normal and hypertensive human subjects

    Science.gov (United States)

    Au, W. Y. W.; Dring, L. G.; Grahame-Smith, D. G.; Isaac, P.; Williams, R. T.

    1972-01-01

    1. The fate of orally administered 14C-labelled l-α-methyldopa has been examined in three normal men and in eight hypertensive patients who responded to the drug and three who did not. 2. The output of 14C in the urine in 2 days and in the faeces in 4 days was not very different in any of the subjects. The normals excreted about 40% of the dose in the urine and 60% in the faeces, the responders 52% (range 35–60%) and 45% and the non-responders 42% and 41%. Most of the urinary 14C radioactivity was eliminated in 24h after dosing. 3. The main metabolite in the urine was free and conjugated α-methyldopa (normal men, 23%; responders, 37%; non-responders, 25% of the dose). Free and conjugated 3-O-methyl-α-methyldopa was about 4% in all subjects, total amines (α-methyldopamine and 3-O-methyl-α-methyldopamine) about 6% and ketones (mainly 3,4-dihydroxyphenylacetone) about 3%. 4. The output of α-methyldopamine (2–4% of dose), 3-O-methyl-α-methyldopamine (0.3%) and 3,4-dihydroxyphenylacetone (3–5%) was similar in the one normal and two responders examined. 5. The faecal 14C in all subjects was unchanged l-α-methyldopa. 6. In general, the amounts of the metabolites in the urine in normal men and in responding and non-responding patients were quantitatively similar, except in one non-responding patient who converted nearly two-thirds of the absorbed drug into amines and ketones. There appeared to be no correlation between metabolites in the urine and response or lack of response to the drug. 7. In two normal subjects 70–80% of d-α-methyldopa was excreted unchanged in the faeces. Of the absorbed compound most (9–14% of the dose) was excreted as the free and conjugated drug together with a small amount (1–2%) of 3-O-methyl-α-methyldopa. No amines and only traces of ketone were excreted. PMID:4646774

  17. Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT Retinal Changes in Normal Human Retina.

    Science.gov (United States)

    Kogachi, Kaitlin; Wolfe, Jeremy D; Kashani, Amir H

    2017-10-01

    Induction of focal retinal detachment (RD) for subretinal delivery of stem cells and gene therapy is increasingly common. In order to determine if this procedure has an adverse impact on the retina, we use spectral-domain optical coherence tomography (SD-OCT) to evaluate the pre- and postoperative retinal anatomy of the incidentally detached normal retina surrounding large submacular hemorrhages (SMH) during surgical displacement procedures. Retrospective, observational study of human subjects with monocular SMH evaluated before and after surgical displacement using clinical exam, fundus photography, and SD-OCT. Manual measurements of the inner retinal thickness (IRT), outer retinal thickness (ORT), and full retinal thickness (FRT) were made in regions involving the SMH and surrounding normal retina. Comparison of retinal thickness measurements was made using the Wilcoxon signed-rank test. Seven eyes were included in this study. All eyes successfully underwent surgical displacement of SMH. Visual acuity improved in 6/7 subjects and was unchanged in the remaining subject. Incidental RD of the normal retinal regions surrounding the SMH did not cause any significant change in IRT, ORT, or FRT that was detectable by SD-OCT. In contrast, mean FRT overlying regions with SMH was significantly greater before surgery compared to after displacement of SMH or normal adjacent retina. Surgically induced focal RD does not cause detectable retinal changes in the incidentally detached normal retina surrounding large SMH. Therefore, surgical induction of focal RD should not be considered to have the same adverse impact on the retina as pathologic RD.

  18. Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

    International Nuclear Information System (INIS)

    Vafai, A.; Wellish, M.; Devlin, M.; Gilden, D.H.; Murray, R.S.

    1988-01-01

    Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteins in human sensory ganglia

  19. Nitroglycerin provocation in normal subjects is not a useful human migraine model?

    DEFF Research Database (Denmark)

    Tvedskov, J F; Iversen, Helle Klingenberg; Olesen, J

    2010-01-01

    Provoking delayed migraine with nitroglycerin in migraine sufferers is a cumbersome model. Patients are difficult to recruit, migraine comes on late and variably and only 50-80% of patients develop an attack. A model using normal volunteers would be much more useful, but it should be validated...... aspirin 1000 mg, zolmitriptan 5 mg or placebo to normal healthy volunteers. The design was double-blind, placebo-controlled three-way crossover. Our hypothesis was that these drugs would be effective in the treatment of the mild constant headache induced by long-lasting GTN infusion. The headaches did...... experiment suggests that headache caused by direct nitric oxide (NO) action in the continued presence of NO is very resistance to analgesics and to specific acute migraine treatments. This suggests that NO works very deep in the cascade of events associated with vascular headache, whereas tested drugs work...

  20. Ecto- and cytosolic 5'-nucleotidases in normal and AMP deaminase-deficient human skeletal muscle

    DEFF Research Database (Denmark)

    Hanisch, Frank; Hellsten, Ylva; Zierz, Stephan

    2006-01-01

    In skeletal muscle, adenosine monophosphate (AMP) is mainly deaminated by AMP deaminase. However, the C34T mutation in the AMPD1 gene severely reduces AMP deaminase activity. Alternatively, intracellular AMP is dephosphorylated to adenosine via cytosolic AMP 5'-nucleotidase (cN-I). In individuals...... with a homozygous C34T mutation, cN-I might be a more important pathway for AMP removal. We determined activities of AMP deaminase, cN-I, total cytosolic 5'-nucleotidase (total cN), ecto-5'-nucleotidase (ectoN) and whole homogenate 5'-nucleotidase activity in skeletal muscle biopsies from patients with different...... AMPD1 genotypes [homozygotes for C34T mutation (TT); heterozygotes for C34T mutation (CT); and homozygotes for wild type (CC): diseased controls CC; and normal controls CC]. AMP deaminase activity showed genotype-dependent differences. Total cN activity in normal controls accounted for 57...

  1. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  2. A Computational Study of the Respiratory Airflow Characteristics in Normal and Obstructed Human Airways

    Science.gov (United States)

    2014-01-01

    Boucher, Normal and cystic fibrosis airway surface liquid homeostasis. The effects of phasic shear stress and viral infections, J. Biol. Chem. 280 (2005...Thus, early detection and correct diagnosis are critical. However, some airway conditions remain hard to diagnose, especially those pertaining to the...dyspnea, one quarter (25 patients) had no specific diagnosis even after a comprehensive standard evalua- tion [7]. Understanding the airflow

  3. Kinetics of the human thyroid trap: experience in normal subjects and in thyroid disease

    International Nuclear Information System (INIS)

    Hays, M.T.

    1979-01-01

    Kinetics of the thyroid pertechnetate trap were assessed in 39 normal subjects, five untreated patients with Graves' disease (two before and after treatment), two hypothyroid patients, and in one patient each with Hashimoto's thyroiditis of recent onset, subacute thyroiditis, and massive anaplastic carcinoma. In normal subjects, the effects of sex, time of day, and order of experimental sessions were studied. A three-compartment model was assumed for all studies. Data on thyroidal and neck-background pertechnetate were collected with a multicrystal camera during 40 min after iv injection. The two thyroidal compartments in the model - the follicular cell, v 2 , and the colloidal plasma-equivalent space, V 3 - is a multi-exponential function of plasma radioactivity, V 1 . None of the model parameters was systematically affected by sex and order of session did not consistently alter any parameter, except for V 3 , which was greater in session 2 than in session 1. That increase was not consistent and is believed to be spurious. Time of day affected only the exit rate constant from the colloid Λ 23 , which was increased later in the day (P 2 is increased (P 3 and in Λ 21 (the clearance into the thyroid from serum) are more dramatic (P -8 ). After treatment, V 3 and Λ 21 fell toward normal. The hypothyroid patients showed no trap activity, and the trap was normal in the patient with early Hashimoto's thyroiditis. The patients with subacute thyroiditis and anaplastic carcinoma had increases in V 2 , V 3 , and Λ 21 , but the pattern differed from that of Graves' disease

  4. Effects of adrenergic drugs on aqueous humour dynamics in the normal human eye. I. Salbutamol.

    OpenAIRE

    Coakes, R. L.; Siah, P. B.

    1984-01-01

    The immediate effects of topical salbutamol, a beta 2 adrenergic agonist, on the aqueous humour dynamics of 22 normal subjects was studied by fluorophotometry and tonography. Significant lowering of intraocular pressure was accompanied by a significant increase in both aqueous flow rate and tonographic facility of outflow. Uveoscleral outflow was calculated and found to be significantly increased by salbutamol. This appeared to be the predominant acute pressure lowering effect of beta recepto...

  5. Sensitivity to radiation of human normal, hyperthyroid, and neoplastic thyroid epithelial cells in primary culture

    International Nuclear Information System (INIS)

    Miller, R.C.; Hiraoka, Toshio; Kopecky, K.J.; Nakamura, Nori; Jones, M.P.; Ito, Toshio; Clifton, K.H.

    1986-09-01

    Samples of thyroid tissue removed surgically from 63 patients were cultured in vitro and X-irradiated to investigate the radiosensitivities of various types of thyroid epithelial cells. A total of 76 samples were obtained, including neoplastic cells from patients with papillary carcinoma (PC) or follicular adenoma (FA), cells from hyperthyroidism (HY) patients, and normal cells from the surgical margins of PC and FA patients. Culturing of the cells was performed in a manner which has been shown to yield a predominance of epithelial cells. Results of colony formation assays indicated that cells from HY and FA patients were the least radiosensitive: when adjusted to the overall geometric mean plating efficiency of 5.5 %, the average mean lethal dose D 0 was 97.6 cGy for HY cells, and 96.7 cGy and 94.3 cGy, respectively, for neoplastic and normal cells from FA patients. Cells from PC patients were more radiosensitive, normal cells having an adjusted average D 0 of 85.0 cGy and PC cells a significantly (p = .001) lower average D 0 of 74.4 cGy. After allowing for this variation by cell type, in vitro radiosensitivity was not significantly related to age at surgery (p = .82) or sex (p = .10). These results suggest that malignant thyroid cells may be especially radiosensitive. (author)

  6. Maximal thickness of the normal human pericardium assessed by electron-beam computed tomography

    International Nuclear Information System (INIS)

    Delille, J.P.; Hernigou, A.; Sene, V.; Chatellier, G.; Boudeville, J.C.; Challande, P.; Plainfosse, M.C.

    1999-01-01

    The purpose of this study was to determine the maximal value of normal pericardial thickness with an electron-beam computed tomography unit allowing fast scan times of 100 ms to reduce cardiac motion artifacts. Electron-beam computed tomography was performed in 260 patients with hypercholesterolemia and/or hypertension, as these pathologies have no effect on pericardial thickness. The pixel size was 0.5 mm. Measurements could be performed in front of the right ventricle, the right atrioventricular groove, the right atrium, the left ventricle, and the interventricular groove. Maximal thickness of normal pericardium was defined at the 95th percentile. Inter-observer and intra-observer reproducibility studies were assessed from additional CT scans by the Bland and Altman method [24]. The maximal thickness of the normal pericardium was 2 mm for 95 % of cases. For the reproducibility studies, there was no significant relationship between the inter-observer and intra-observer measurements, but all pericardial thickness measurements were ≤ 1.6 mm. Using electron-beam computed tomography, which assists in decreasing substantially cardiac motion artifacts, the threshold of detection of thickened pericardium is statistically established as being 2 mm for 95 % of the patients with hypercholesterolemia and/or hypertension. However, the spatial resolution available prevents a reproducible measure of the real thickness of thin pericardium. (orig.)

  7. Maximal thickness of the normal human pericardium assessed by electron-beam computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Delille, J.P.; Hernigou, A.; Sene, V.; Chatellier, G.; Boudeville, J.C.; Challande, P.; Plainfosse, M.C. [Service de Radiologie Centrale, Hopital Broussais, Paris (France)

    1999-08-01

    The purpose of this study was to determine the maximal value of normal pericardial thickness with an electron-beam computed tomography unit allowing fast scan times of 100 ms to reduce cardiac motion artifacts. Electron-beam computed tomography was performed in 260 patients with hypercholesterolemia and/or hypertension, as these pathologies have no effect on pericardial thickness. The pixel size was 0.5 mm. Measurements could be performed in front of the right ventricle, the right atrioventricular groove, the right atrium, the left ventricle, and the interventricular groove. Maximal thickness of normal pericardium was defined at the 95th percentile. Inter-observer and intra-observer reproducibility studies were assessed from additional CT scans by the Bland and Altman method [24]. The maximal thickness of the normal pericardium was 2 mm for 95 % of cases. For the reproducibility studies, there was no significant relationship between the inter-observer and intra-observer measurements, but all pericardial thickness measurements were {<=} 1.6 mm. Using electron-beam computed tomography, which assists in decreasing substantially cardiac motion artifacts, the threshold of detection of thickened pericardium is statistically established as being 2 mm for 95 % of the patients with hypercholesterolemia and/or hypertension. However, the spatial resolution available prevents a reproducible measure of the real thickness of thin pericardium. (orig.) With 6 figs., 1 tab., 31 refs.

  8. Cell-Type-Specific Gene Programs of the Normal Human Nephron Define Kidney Cancer Subtypes.

    Science.gov (United States)

    Lindgren, David; Eriksson, Pontus; Krawczyk, Krzysztof; Nilsson, Helén; Hansson, Jennifer; Veerla, Srinivas; Sjölund, Jonas; Höglund, Mattias; Johansson, Martin E; Axelson, Håkan

    2017-08-08

    Comprehensive transcriptome studies of cancers often rely on corresponding normal tissue samples to serve as a transcriptional reference. In this study, we performed in-depth analyses of normal kidney tissue transcriptomes from the TCGA and demonstrate that the histological variability in cellularity, inherent in the kidney architecture, lead to considerable transcriptional differences between samples. This should be considered when comparing expression profiles of normal and cancerous kidney tissues. We exploited these differences to define renal-cell-specific gene signatures and used these as a framework to analyze renal cell carcinoma (RCC) ontogeny. Chromophobe RCCs express FOXI1-driven genes that define collecting duct intercalated cells, whereas HNF-regulated genes, specific for proximal tubule cells, are an integral part of clear cell and papillary RCC transcriptomes. These networks may be used as a framework for understanding the interplay between genomic changes in RCC subtypes and the lineage-defining regulatory machinery of their non-neoplastic counterparts. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Viscoelastic properties of normal and cancerous human breast cells are affected differently by contact to adjacent cells.

    Science.gov (United States)

    Schierbaum, Nicolas; Rheinlaender, Johannes; Schäffer, Tilman E

    2017-06-01

    Malignant transformation drastically alters the mechanical properties of the cell and its response to the surrounding cellular environment. We studied the influence of the physical contact between adjacent cells in an epithelial monolayer on the viscoelastic behavior of normal MCF10A, non-invasive cancerous MCF7, and invasive cancerous MDA-MB-231 human breast cells. Using an atomic force microscopy (AFM) imaging technique termed force clamp force mapping (FCFM) to record images of the viscoelastic material properties, we found that normal MCF10A cells are stiffer and have a lower fluidity at confluent than at sparse density. Contrarily, cancerous MCF7 and MDA-MB-231 cells do not stiffen and do not decrease their fluidity when progressing from sparse to confluent density. The behavior of normal MCF10A cells appears to be governed by the formation of stable cell-cell contacts, because their disruption with a calcium-chelator (EGTA) causes the stiffness and fluidity values to return to those at sparse density. In contrast, EGTA-treatment of MCF7 and MDA-MB-231 cells does not change their viscoelastic properties. Confocal fluorescence microscopy showed that the change of the viscoelastic behavior in MCF10A cells when going from sparse to confluent density is accompanied by a remodeling of the actin cytoskeleton into thick stress fiber bundles, while in MCF7 and MDA-MB-231 cells the actin cytoskeleton is only composed of thin and short fibers, regardless of cell density. While the observed behavior of normal MCF10A cells might be crucial for providing mechanical stability and thus in turn integrity of the epithelial monolayer, the dysregulation of this behavior in cancerous MCF7 and MDA-MB-231 cells is possibly a central aspect of cancer progression in the epithelium. We measured the viscoelastic properties of normal and cancerous human breast epithelial cells in different states of confluency using atomic force microscopy. We found that confluent normal cells are

  10. Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?

    International Nuclear Information System (INIS)

    Teramoto, Daisuke; Ushioda, Yuichi; Sasaki, Ayaka; Sakurai Yuki; Nagahama, Hiroshi; Nakamura, Manami; Sugimori, Hiroyuki; Sakata, Motomichi

    2013-01-01

    Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in Japanese Society of Radiological Technology (JSRT). However, custom-made phantoms that correctly match the T 1 -value and T 2 -values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T 1 - and T 2 -weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T 1 and T 2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI. (author)

  11. Myocardium scintigraphy and coronaries scanner: results and respective contribution of these two examinations; Scintigraphie myocardique et scanner coronaire: resultats et apport respectif des deux examens

    Energy Technology Data Exchange (ETDEWEB)

    Songy, B.; Balestrini, V.; Sablayrolles, J.L.; Vigoni, F.; Lussato, D. [Centre cardiologique du Nord (CCN), Saint-Denis, (France); Faccio, F. [fondation San Geronimo, Santa Fe, (Argentina)

    2009-05-15

    The objective were to evaluate the results and the respective contribution of the myocardium scintigraphy and the coro-scanner. It exists an excellent correlation between a normal scanner and a normal scintigraphy (97%). 30% of patients having non tight stenosis at scanner and 60% of these ones having tight stenosis have a scintigraphy ischemia; An abnormal scanner, whatever be the the degree of stenosis must be completed by a test of myocardium ischemia. The actual limitations of the coro-scanner (64 gills) are in relation with its spatial resolution (quantification) and temporal resolution (right coronary). The choice of the diagnosis examination to realize in first intention must depend on the age and prevalence of the coronary disease. (N.C.)

  12. [The protective action of nimodipine on the ischemic myocardium].

    Science.gov (United States)

    Tsorin, I B; Kazanova, G V; Kirsanova, G Iu; Chirkova, E Iu; Chichkanov, G G

    1992-01-01

    The experiments with unconscious cats and dogs have demonstrated that the calcium antagonist nimodipine has a profound anti-ischemic property. The drug reduces the average value of ST-segment elevation in multiple epicardial ECG leads, during acute myocardial ischemia. Nimodipine maintains cardiac pump and contractile functions, elevates ATP levels in the arbitrarily intact and ischemic myocardium of the left ventricle during 40-min occlusion and 60-min reperfusion of the coronary artery. The protective action of the drug is unassociated with enhanced collateral coronary circulation.

  13. Characterization of ultraviolet light-induced diphtheria toxin-resistant mutations in normal and Xeroderma pigmentosum human fibroblasts

    International Nuclear Information System (INIS)

    Glover, T.W.

    1979-01-01

    Quantitative mutagenesis studies in human cells have been severely limited by the lack of reliable genetic markers. Experiments were therefore performed to develop and characterize a better quantitative mutation assay for human cells. The uv-induction of diphtheria toxin resistant (DT/sup r/) mutations in normal and excision repair defective xeroderma pigmentosum (XP) fibroblasts has been quantitatively characterized. A concentration of diphtheria toxin to use in the selection of resistant mutants was determined whereby DT/sup r/ cells are cross-resistant to Pseudomonas aeurginosa exotoxin A, indicating mutants have altered elongation factor-2 (EF-2) which is not susceptible to ADP-ribosylation by either toxin. Results of this study indicate that XP fibroblasts have higher uv-induced mutation frequencies per unit uv-dose but similar frequencies per unit survival compared to normal cells as measured using a new genetic marker for quantitative mutagenesis. Furthermore, these results support a prediction of the mutation theory of cancer, namely, that cells from individuals with certain human syndromes that predispose the individual to cancer will have higher induced mutation frequencies than cells from non-susceptible individuals. This newly characterized genetic marker should be useful in quantitative mutagenesis studies in human cells

  14. New perspectives in the treatment of damaged myocardium using autologous skeletal myoblasts

    International Nuclear Information System (INIS)

    Rigatelli, Gianluca; Rossini, Katia; Vindigni, Vincenzo; Mazzoleni, Francesco; Rigatelli, Giorgio; Carraro, Ugo

    2004-01-01

    Autologous skeletal myoblast transplantation may be used to ameliorate the healing process following myocardium infarct and, hopefully, cardiomyopathies. Despite successful animal experimentation, several issues need to be addressed in clinical settings, i.e., the impact of the delivery route, the extent of short- and long-term survival, and differentiation of the injected skeletal myoblasts. The authors offer some new hypotheses resulting from basic research, i.e., where and when to inject the myogenic cells, whatever their source, how to decrease new myofiber atrophy and improve their regeneration. Although these new hypotheses still need to be tested in humans, they may be decisive for future experimental studies and will lead to making endovascular cell implantation a more effective way to treat ischemic heart disease and failure

  15. Quantitative assessment of lactate and progerin production in normal human cutaneous cells during normal ageing: effect of an Alaria esculenta extract.

    Science.gov (United States)

    Verdy, C; Branka, J-E; Mekideche, N

    2011-10-01

    Anti-ageing products are of a great importance in cosmetic fields. However, even if numerous strategies have been proposed to fight against skin ageing or to minimize its aesthetic impact since the beginning of the 'scientific cosmetology' era, the products basing their efficacy on the observation of pathological situations are rare. The most obvious pathology linked to the ageing of skin (notably) consists in the Hutchinson-Gilford Progeria Syndrome (HGPS), a rare disorder characterized by accelerated ageing and early death. In this disease the lamin A, a protein participating (with others lamins) in the formation of the nuclear lamina and implicated in nuclear stability, chromatin structure and gene expression, is present in a truncated version called progerin. In this study, we have examined the lactate and the progerin production of human normal cutaneous cells issued from subjects of different ages. Using a sensitive and specific progerin ELISA assay developed in house, we so provide the first quantitative demonstration of an increased progerin expression and lactate production in skin during ageing. Moreover, we have also demonstrated that in the selected experimental conditions, it was possible to down-regulate the progerin production of aged cells by using an algae extract. As this extract, an Alaria esculenta extract, could be used in cosmetic formulations, we suggest that a better understanding of the skin pathologies could be a useful tool in developing efficient active compounds, attractive for but not limited to cosmetic purposes. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  16. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging

    International Nuclear Information System (INIS)

    Dilsizian, V.; Rocco, T.P.; Freedman, N.M.; Leon, M.B.; Bonow, R.O.

    1990-01-01

    The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not fill in on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium. We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed. Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty

  17. Reduced microvascular density in non-ischemic myocardium of patients with recent non-ST-segment-elevation myocardial infarction.

    Science.gov (United States)

    Campbell, Duncan J; Somaratne, Jithendra B; Jenkins, Alicia J; Prior, David L; Yii, Michael; Kenny, James F; Newcomb, Andrew E; Kelly, Darren J; Black, Mary Jane

    2013-08-10

    Myocardial microvascular dysfunction has been implicated in the pathogenesis of myocardial infarction (MI). We tested the hypothesis that patients with MI have lower microvasculature density in myocardium remote from the site of infarction than patients with similar extent of coronary artery disease (CAD) without MI and examined the relationship between myocardial capillary length density and plasma levels of angiogenesis-related biomarkers. We analyzed biopsies from non-ischemic left ventricular (LV) myocardium and measured plasma levels of angiogenesis-related biomarkers in patients undergoing coronary artery bypass graft surgery, 57 without previous MI (no-MI) and 27 with recent non-ST-segment-elevation MI (NSTEMI). Comparison was made with biopsies from 31 aortic stenosis (AS) patients and 6 patients with "normal" LV without CAD. Myocardial microvascular density of NSTEMI patients was approximately half the density of no-MI patients, and similar to AS patients. Whereas the reduced microvascular density of AS patients was accounted for by their cardiomyocyte hypertrophy, this was not the case for NSTEMI patients, who had higher diffusion radius/cardiomyocyte width ratio than no-MI, "normal" LV, and AS patients. NSTEMI patients had lower plasma levels of carboxymethyl lysine and low molecular weight fluorophores, higher vascular endothelial growth factor (VEGF) receptor-1/VEGF-A ratio, and higher endostatin and hepatocyte growth factor levels than no-MI patients. Recent MI was associated with reduced microvasculature density in myocardium remote from the site of infarction and alteration in plasma levels of angiogenesis-related biomarkers. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  18. Comparison of global gene expression profiles of microdissected human foetal Leydig cells with their normal and hyperplastic adult equivalents

    DEFF Research Database (Denmark)

    Lottrup, Grete; Belling, Kirstine González-Izarzugaza; Leffers, Henrik

    2017-01-01

    was performed on Agilent whole human genome microarray 4 x 44 K chips. Microarray data pre-processing and statistical analysis were performed using the limma R/Bioconductor package in the R software, and differentially expressed genes were further analysed for gene set enrichment using the DAVID Bioinformatics......-section).STUDY DESIGN, SIZE, DURATION: A genome-wide microarray study of LCs microdissected from human foetal and adult tissue samples (n = 12). Additional tissue specimens (n = 15) were used for validation of the mRNA expression data at the protein level.PARTICIPANTS/MATERIALS, SETTING, METHODS: Frozen human tissue...... software. Selected genes were studied at the protein level by immunohistochemistry.MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptomes of FLCs and ALCs differed significantly from each other, whereas the profiles of the normally clustered and hyperplastic ALCs were similar despite morphological...

  19. Histological versus stereological methods applied at spermatogonia during normal human development

    DEFF Research Database (Denmark)

    Cortes, Dina

    1990-01-01

    The number of spermatogonia per tubular transverse section (S/T), and the percentage of seminiferous tubulus containing spermatogonia (the fertility index (FI] were measured in 40 pairs of normal autopsy testes aged 28 weeks of gestation-40 years. S/T and FI showed similar changes during the whole...... period, and were minimal between 1 and 4 years. The number of spermatogonia per testis (S/testis) and the number of spermatogonia per cm3 testis tissue (S/cm3) were estimated by stereological methods in the same testes. S/T and FI respectively were significantly correlated both to S/testis and S/cm3. So...

  20. Non-postural serial changes in renal function during the third trimester of normal human pregnancy.

    Science.gov (United States)

    Ezimokhai, M; Davison, J M; Philips, P R; Dunlop, W

    1981-05-01

    Seventeen healthy women were investigated near the beginning and again near the end of the third trimester of their normal pregnancies. Infusion studies were performed in the left lateral position. There was a highly significant decrease in effective renal plasma flow but not in glomerular filtration rate, measured as inulin clearance. Plasma creatinine concentration increased significantly, but the renal handling of creatinine was unchanged; simultaneous 24-hour creatinine clearance showed a tendency to decrease. Serum urate concentration also increased significantly, apparently due to an increase in net tubular reabsorption of urate.

  1. Miocárdio hibernante: uma realidade clínica Hibernant myocardium: a clinical reality

    Directory of Open Access Journals (Sweden)

    J.A. Marin-Neto

    1997-12-01

    Full Text Available O conceito da hibernação miocárdica implica a ocorrência de disfunção ventricular crônica, potencialmente reversível, causada por dissinergia regional, dependente de isquemia prolongada. Não tem fisiopatologia elucidada, em parte porque não existem modelos experimentais satisfatórios para seu estudo. Diversos métodos são capazes de demonstrar viabilidade miocárdica nas regiões que não exibem capacidade contrátil basal. O desmascaramento da hibernação nesses territórios pode ser feito mediante demonstração de reserva contrátil, de funcionamento normal da membrana celular, ou de metabolismo preservado. A correta identificação de miocárdio hibernante reveste-se de especial significado clínico, por suas implicações prognósticas quanto a intervenções de revascularização miocárdica, destinadas a reabilitar a função ventricular em muitos pacientes coronariopatas crônicos.Myocardial hibernation is believed to occur in ventricular dyssynergic regions chronically deprived of coronary flow enough to warrant the preservation of contractile function. Pathophysiology of this condition remains largely unclear, mainly because good experimental models for its study are still lacking. Various methods can be clinically employed to detect hibernation in patients with chronic ventricular dysfunction. These methods use the principle of unmasking contractile reserve, or are based on the demonstration of preserved membrane function or myocardium metabolism in the dyssynergic regions. The correct identification of viable hibernating myocardium is crucial in the process of deciding which coronary disease patients would potentially benefit from revascularization procedures.

  2. Increased Hemodynamic Load in Early Embryonic Stages Alters Myofibril and Mitochondrial Organization in the Myocardium

    Directory of Open Access Journals (Sweden)

    Madeline Midgett

    2017-08-01

    Full Text Available Normal blood flow is essential for proper heart formation during embryonic development, as abnormal hemodynamic load (blood pressure and shear stress results in cardiac defects seen in congenital heart disease (CHD. However, the detrimental remodeling processes that relate altered blood flow to cardiac malformation and defects remain unclear. Heart development is a finely orchestrated process with rapid transformations that occur at the tissue, cell, and subcellular levels. Myocardial cells play an essential role in cardiac tissue maturation by aligning in the direction of stretch and increasing the number of contractile units as hemodynamic load increases throughout development. This study elucidates the early effects of altered blood flow on myofibril and mitochondrial configuration in the outflow tract myocardium in vivo. Outflow tract banding was used to increase hemodynamic load in the chicken embryo heart between Hamburger and Hamilton stages 18 and 24 (~24 h during tubular heart stages. 3D focused ion beam scanning electron microscopy analysis determined that increased hemodynamic load induced changes in the developing myocardium, characterized by thicker myofibril bundles that were more disbursed in circumferential orientation, and mitochondria that organized in large clusters around the nucleus. Proteomic mass-spectrometry analysis quantified altered protein composition after banding that is consistent with altered myofibril thin filament assembly and function, and mitochondrial maintenance and organization. Additionally, pathway analysis of the proteomics data identified possible activation of signaling pathways in response to banding, including the renin-angiotensin system (RAS. Imaging and proteomic data combined indicate that myofibril and mitochondrial arrangement in early embryonic stages is a critical developmental process that when disturbed by altered blood flow may contribute to cardiac malformation and defects.

  3. Normal human gait patterns in Peruvian individuals: an exploratory assessment using VICON motion capture system

    Science.gov (United States)

    Dongo, R.; Moscoso, M.; Callupe, R.; Pajaya, J.; Elías, D.

    2017-11-01

    Gait analysis is of clinical relevance for clinicians. However, normal gait patterns used in foreign literature could be different from local individuals. The aim of this study was to determine the normal gait patterns and parameters of Peruvian individuals in order to have a local referent for clinical assessments and making diagnosis and treatment Peruvian people with lower motor neuron injuries. A descriptive study with 34 subjects was conducted to assess their gait cycle. VICON® cameras were used to capture body movements. For the analyses, we calculated spatiotemporal gait parameters and average angles of displacement of the hip, knee, and ankle joints with their respective 95% confidence intervals. The results showed gait speed was 0.58m/s, cadence was 102.1steps/min, and the angular displacement of the hip, knee and ankle joints were all lower than those described in the literature. In the graphs, gait cycles were close to those reported in previous studies, but the parameters of speed, cadence and angles of displacements are lower than the ones shown in the literature. These results could be used as a better reference pattern in the clinical setting.

  4. Modelling whole blood oxygen equilibrium: comparison of nine different models fitted to normal human data.

    Science.gov (United States)

    O'Riordan, J F; Goldstick, T K; Vida, L N; Honig, G R; Ernest, J T

    1985-01-01

    The ability of nine different models, prominent in the literature, to meaningfully characterize the oxygen-hemoglobin equilibrium curve (OHEC) of normal individuals was examined. Previously reported data (N = 33), obtained using the DCA-1 (Radiometer, Copenhagen), and new data (N = 8), obtained using the Hemox-Analyzer (TCS, Southampton, PA), from blood samples of normal, non-smoking volunteers were used and these devices were found to give statistically similar results. The OHECs were digitized and fitted to the models using least-squares techniques developed in this laboratory. The "goodness-of-fit" was determined by the root-mean-squared (RMS) error, the number of parameters, and the parameter redundancy, i.e., correlation between the parameters. The best RMS error did not necessarily indicate the best model. Most literature models consist of ratios of similar-order polynomials. These showed considerable parameter redundancy which made the curve fitting difficult. The best fits gave RMS errors as low as 0.2% saturation. The Hill model gave a good characterization over the saturation range 20%-98% with RMS errors of about 0.6% saturation. On the other hand, good characterizations over the entire range were given by several other models. The relative advantages and disadvantages of each model have been compared as well as the difficulties in fitting several of the models. No single model is best under all circumstances. The best model depends upon the particular circumstances for which it is to be utilized.

  5. Stereological Analysis of Human Placenta in Cases of Placenta Previa in Comparison with Normally Implanted Controls

    Science.gov (United States)

    Heidari, Zahra; Sakhavar, Nahid; Mahmoudzadeh-Sagheb, Hamidreza; Ezazi-Bojnourdi, Tahmine

    2015-01-01

    Background Placenta previa (PP) is an obstetric complication that can affect maternal and fetal morbidity and mortality. Its prevalence is rising due to cesarean sections. There is no quantitative data of placenta in PP. In this study, quantitative parameters of placenta in cases with PP in comparison with normally implanted controls were investigated. Methods In this quasi experimental study, placentas from pregnancies with PP and normally implanted controls (n = 10) were obtained from women who underwent cesarean section. Three full-thickness columns of each placenta were sampled using systematic uniform random sampling (SURS). Columns were cut into slices and slices were sectioned with 4 µm thickness. SURS selected sections were stained by Masson's trichrome. Stereological analysis was done on 8-10 SURS microscopic fields of each section. Absolute volume and volume density of chorionic villi, intervillous space, syncytiotrophoblast, fibrin and blood vessels in chorionic villi were estimated in both groups. Statistical analysis was done using Mann Whitney-U test and significant level was set at p placenta. These changes probably can be influential on the evolution and survival of fetus. PMID:25927025

  6. Kinetic analysis of zinc metabolism and its regulation in normal humans

    International Nuclear Information System (INIS)

    Wastney, M.E.; Aamodt, R.L.; Rumble, W.F.; Henkin, R.I.

    1986-01-01

    Zinc metabolism was studied in 32 normal volunteers after oral or intravenous administration of 65 Zn. Data were collected from the blood, urine, feces, whole body, and over the liver and thigh regions for 9 mo while the subjects consumed their regular diets (containing 10 mg Zn ion/day) and for an additional 9 mo while the subjects received an exogenous oral supplement of 100 mg Zn ion/day. Data from each subject were fitted by a compartmental model for zinc metabolism that was developed previously for patients with taste and smell dysfunction. These data from normal subjects were used to determine the absorption, distribution, and excretion of zinc and the mass of zinc in erythrocytes, liver, thigh, and whole body. By use of additional data obtained from the present study, the model was refined further such that a large compartment, which was previously determined to contain 90% of the body zinc, was subdivided into two compartments to represent zinc in muscle and bone. When oral zinc intake was increased 11-fold three new sites of regulation of zinc metabolism were identified in addition to the two sites previously defined in patients with taste and smell dysfunction (absorption of zinc from gut and excretion of zinc in urine). The three new sites are exchange of zinc with erythrocytes, release of zinc by muscle, and secretion of zinc into gut. Regulation at these five sites appears to maintain some tissue concentrations of zinc when dietary zinc increases

  7. Inflammatory Cytokine Tumor Necrosis Factor α Confers Precancerous Phenotype in an Organoid Model of Normal Human Ovarian Surface Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Joseph Kwong

    2009-06-01

    Full Text Available In this study, we established an in vitro organoid model of normal human ovarian surface epithelial (HOSE cells. The spheroids of these normal HOSE cells resembled epithelial inclusion cysts in human ovarian cortex, which are the cells of origin of ovarian epithelial tumor. Because there are strong correlations between chronic inflammation and the incidence of ovarian cancer, we used the organoid model to test whether protumor inflammatory cytokine tumor necrosis factor α would induce malignant phenotype in normal HOSE cells. Prolonged treatment of tumor necrosis factor α induced phenotypic changes of the HOSE spheroids, which exhibited the characteristics of precancerous lesions of ovarian epithelial tumors, including reinitiation of cell proliferation, structural disorganization, epithelial stratification, loss of epithelial polarity, degradation of basement membrane, cell invasion, and overexpression of ovarian cancer markers. The result of this study provides not only an evidence supporting the link between chronic inflammation and ovarian cancer formation but also a relevant and novel in vitro model for studying of early events of ovarian cancer.

  8. Gonadotropin-releasing hormone radioimmunoassay and its measurement in normal human plasma, secondary amenorrhea, and postmenopausal syndrome

    International Nuclear Information System (INIS)

    Rosenblum, N.G.; Schlaff, S.

    1976-01-01

    A sensitive and specific double antibody radioimmunoassay for gonadotropin-releasing hormone (GnRH) has been developed for measurement in ethanol extracts of human plasma. Iodinated hormone was prepared with the use of the chloramine-T method, and antibodies were developed in rabbits over a six-month period with a GnRH synthetic copolymer immunogen. A Scatchard plot revealed at least three species of antibody. The assay can measure conservatively at the 5 pg. per milliliter level and shows no cross-reactivity with other available hypothalamic and pituitary hormones. The releasing hormone was quantitatively recovered from human plasma with immunologic identity to native hormone. Unextracted plasma could not be used because of nonspecific displacement. The measurement of GnRH in individuals receiving 100 μg of intravenous bolus infusions of the synthetic decapeptide show extremely elevated values with two half-lives: one of two to four minutes and another of 35 to 40 minutes. In our experiments, we have found measurable GnRH in patients with secondary amenorrhea and at the midcycle in normal women. In the normal cycling woman during the follicular and luteal phases, GnRH was undetectable. In postmenopausal women with extreme hypoestrogenism and markedly elevated luteinizing hormone values, GnRH was also undetectable. No bursts of GnRH could be detected in normal men when sampled every ten minutes over a two-hour period and every two hours throughout the day

  9. Cytidine triphosphate synthase activity and mRNA expression in normal human blood cells

    NARCIS (Netherlands)

    Verschuur, A. C.; van Gennip, A. H.; Muller, E. J.; Voûte, P. A.; Vreken, P.; van Kuilenburg, A. B.

    1999-01-01

    Cytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine nucleotide anabolic pathways. The activity of this enzyme is elevated in various malignancies including acute lymphocytic leukemia (ALL). In this study we investigated the activity of CTP synthase in various human blood

  10. Dose-dependent micronuclei formation in normal human fibroblasts exposed to proton radiation

    Czech Academy of Sciences Publication Activity Database

    Litvinchuk, Alexandra; Vachelová, Jana; Michaelidesová, Anna; Wagner, Richard; Davídková, Marie

    2015-01-01

    Roč. 54, č. 3 (2015), s. 327-334 ISSN 0301-634X R&D Projects: GA ČR(CZ) GBP108/12/G108; GA MŠk LM2011019 Institutional support: RVO:61389005 Keywords : human fibroblasts * proton radiation * micronuclei assay * biodosimetry Subject RIV: BO - Biophysics Impact factor: 1.923, year: 2015

  11. Vasopressin (VP) and neuropeptide FF (NPFF) systems in the normal and hypertensive human brainstem

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; Buijs, Ruud M.; Jhamandas, Jack H.; Swaab, Dick F.

    2011-01-01

    Vasopressin (VP)-, neuropeptide FF (NPFF)-, and tyrosine hydroxylase (TH)-expressing neurons were studied by means of single and double immunocytochemistry in the human brainstem of controls who died suddenly due to trauma and of patients who suffered from essential hypertension and died due to

  12. Extracting morphologies from third harmonic generation images of structurally normal human brain tissue

    NARCIS (Netherlands)

    Zhang, Zhiqing; Kuzmin, Nikolay V.; Groot, Marie Louise; de Munck, Jan C.

    2017-01-01

    Motivation: The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering,

  13. Constitutive expression of inducible nitric oxide synthase in the normal human colonic epithelium

    DEFF Research Database (Denmark)

    Perner, A; Andresen, Lars; Normark, M

    2002-01-01

    Inducible nitric oxide synthase (iNOS) in the human colon is considered expressed only in inflammatory states such as ulcerative or collagenous colitis. As subtle iNOS labelling was previously observed in some colonic mucosal biopsies from a heterogeneous group of controls with non-inflamed bowel...

  14. Lack of expression of preproorexin and orexin receptors genes in human normal and prostate cancer cell lines.

    Science.gov (United States)

    Szyszka, Marta; Paschke, Lukasz; Tyczewska, Marianna; Rucinski, Marcin; Grabowska, Paulina; Malendowicz, Ludwik K

    2015-01-01

    Studies on expression of orexins (OXs) and their receptors in human prostate gland and human prostatic cell lines are scanty and their results contradictory. Regarding this, we carefully reinvestigated this problem on human prostatic cell lines. Expression of preproorexin (ppOX) (6 primer pairs), and orexin receptors 1 and 2 (OXR1, OXR2) (4 and 2 primer pairs, respectively) was assessed by conventional PCR and QPCR in human normal (PrEC, PrSc, PrSmC) and prostate carcinoma (Du145, LNCaP, and PC3) cell lines. We designed intron spanning primers and also we applied primers from earlier publications and commercially available ones. With the designed primer pairs, in all studied cell lines we failed to demonstrate expression of ppOX, OXR1 and OXR2 genes at the mRNA level, while reaction products were observed in control tissues (human placenta and adrenals). Primers applied in earlier studies did not form amplification products specific for preproorexin or orexin 1 receptor. Some commercially available primers for orexin receptor 1 produced false positive results. We found no evidence for the presence of preproorexin-orexin receptors system genes' mRNAs in human prostate cell lines. The reported premises for these genes’ expression in prostate and prostatic cell lines may have arisen either from the presence of non-prostate cells included in the samples or from faulty PCR settings.

  15. Estimating the concentration of urea and creatinine in the human serum of normal and dialysis patients through Raman spectroscopy.

    Science.gov (United States)

    de Almeida, Maurício Liberal; Saatkamp, Cassiano Junior; Fernandes, Adriana Barrinha; Pinheiro, Antonio Luiz Barbosa; Silveira, Landulfo

    2016-09-01

    Urea and creatinine are commonly used as biomarkers of renal function. Abnormal concentrations of these biomarkers are indicative of pathological processes such as renal failure. This study aimed to develop a model based on Raman spectroscopy to estimate the concentration values of urea and creatinine in human serum. Blood sera from 55 clinically normal subjects and 47 patients with chronic kidney disease undergoing dialysis were collected, and concentrations of urea and creatinine were determined by spectrophotometric methods. A Raman spectrum was obtained with a high-resolution dispersive Raman spectrometer (830 nm). A spectral model was developed based on partial least squares (PLS), where the concentrations of urea and creatinine were correlated with the Raman features. Principal components analysis (PCA) was used to discriminate dialysis patients from normal subjects. The PLS model showed r = 0.97 and r = 0.93 for urea and creatinine, respectively. The root mean square errors of cross-validation (RMSECV) for the model were 17.6 and 1.94 mg/dL, respectively. PCA showed high discrimination between dialysis and normality (95 % accuracy). The Raman technique was able to determine the concentrations with low error and to discriminate dialysis from normal subjects, consistent with a rapid and low-cost test.

  16. An investigation of UV-induced chromosome changes in relation to lethality in normal and UV-sensitive human cells

    International Nuclear Information System (INIS)

    Scott, D.; Mashall, R.R.

    1978-01-01

    Cultured fibroblasts of excision-repair xeroderma pigmentosum (XP) cells sustain more conventional chromosome structural aberrations than normal human fibroblasts when exposed to UV. By measuring cell cycle times after UV-irradiation it is found that whereas in normal cells such aberrations are primarily confined to cells at their first post-irradiation mitosis, XP cells aberrations occur mainly in later cell cycles. The frequency of cells with chromosomal aberrations is totally inadequate to explain the degree of cell killing. Neither can an explanation be offered for the mechanism of cell killing in terms of abnormal segregation of chromosomes at mitosis (multipolarity) or failure to undergo first post-irradiation mitosis (interphase death), the frequency of the latter being small compared with the proportion of cells that die. Chromosomally normal cells pass through several cell cycles before dying. UV-sensitive cells from an individual (designated 11961), who is not an XP and has no detectable DNA repair defects, exhibit no chromosome aberrations or multipolar mitoses above control values even after UV doses that kill over 90% of cells. A small increase in sister chromatid exchange (SCE) frequencies is observed after these UV doses and the spontaneous frequency of SCEs in 11961 cells is a little higher than in normal cells studies in parallel. Cell death cannot be attributed to visible UV-induced chromosome changes. (author)

  17. Detection of viable myocardium in canine model with myocardial ischemia and ischemia-reperfusion by 125I-BMIPP: relation to regional blood flow

    International Nuclear Information System (INIS)

    Huang Gang; Zhao Huiyang; Shen Xuedong; Li Qing; Yuan Jimin; Zhu Cuiying

    1999-01-01

    Objective: The effects of BMIPP (β-methyl-iodophenyl pentadecanoic acid) on detecting viable myocardium and the relation between regional blood flow and the uptake of BMIPP were evaluated in canine model of myocardial ischemia and ischemia-reperfusion. Methods: 12 open-chest dogs under anesthesia were divided into two groups. Group I (ischemia group) had left circumflex coronary arterial occlusion for 2 h and group II (ischemia-reperfusion group) was occluded for 1 h and followed by 2 h reperfusion. Myocardial blood flow was measured with 99 Tc m -microspheres. 30 min after intravenous injection of 125 I-BMIPP and 99 Tc m -microspheres, the heart was excised rapidly and stained with Evans blue and NBT. Tissue samples (divided into approximately 1 g) of left ventricle were obtained, weighed and counted for 125 I and 99 Tc m . Regional blood flow and the uptake of BMIPP were expressed as percentages of average values in non-ischemic myocardium (two to three tissue samples) from the normal myocardium. Results: In ischemic myocardium (NBT positive samples), the uptake of BMIPP was relatively higher compared with regional blood flow [(67 +- 23)% vs (42 +- 19)%, P 0.05]. In ischemia-reperfusion group, regional blood flow was increased in ischemic and necrotic tissues, but the uptake of BMIPP was not enhanced with the increasing blood flow. Conclusions: BMIPP uptake seems to provide metabolic information independent of regional blood flow. The mismatching between regional blood flow and BMIPP uptake may indicate myocardial viability in the regions of hypoperfusion and the uptake of BMIPP in ischemic myocardium was related to existence of cellular metabolism

  18. Evaluation of noncoronary sources of left ventricular perfusion to intercoronary collateral-dependent myocardium due to chronic major vessel occlusion: absent contribution of luminal and extracardiac channels

    International Nuclear Information System (INIS)

    Crystal, G.J.; Downey, H.F.; Bashour, F.A.

    1981-01-01

    Liminal contribution to perfusion of collateral-dependent left ventricular (LV) myocardium was evaluated in six dogs. A portion of LV free wall was rendered collateral-dependent by gradual occlusion of left circumflex artery with Ameroid constrictor. Eight to 10 weeks after implantation of constrictor, measurements of LV myocardial flow were made by left atrial injections of 9-10 micro radioactive microspheres. To measure total collateral flow, microspheres were injected under control conditions, and to measure luminal contribution to collateral flow, microspheres were injected after ligation of right coronary artery during extracorporeal perfusion of left common coronary artery (LCCA) with microsphere-free arterial blood, and during stoppage of flow through LCCA. Under control conditions, myocardial blood flow in collateral-dependent region, 1.01 +/- 0.31 ml/min/gm, was not significantly different from that in normal region, 1.06 +/- 0.32 ml/min/gm. Flow from luminal collateral vessels was negligible (less than 0.005 ml/min/gm) in both collateral-dependent and normal myocardium, and was not affected by stoppage of flow through LCCA. These results indicate that luminal collateral vessels, as well as collateral vessels originating from other noncoronary sources, do not contribute significantly to perfusion of normal or collateral-dependent LV myocardium

  19. Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue

    NARCIS (Netherlands)

    Parmentier, H. K.; van Wichen, D. F.; Meyling, F. H.; Goudsmit, J.; Schuurman, H. J.

    1992-01-01

    The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to

  20. Anatomy of the pig heart: comparisons with normal human cardiac structure.

    Science.gov (United States)

    Crick, S J; Sheppard, M N; Ho, S Y; Gebstein, L; Anderson, R H

    1998-07-01

    Transgenic technology has potentially solved many of the immunological difficulties of using pig organs to support life in the human recipient. Nevertheless, other problems still remain. Knowledge of cardiac anatomy of the pig (Sus scrofa) is limited despite the general acceptance in the literature that it is similar to that of man. A qualitative analysis of porcine and human cardiac anatomy was achieved by gross examination and dissection of hearts with macrophotography. The porcine organ had a classic 'Valentine heart' shape, reflecting its location within the thorax and to the orientation of the pig's body (unguligrade stance). The human heart, in contrast, was trapezoidal in silhouette, reflecting man's orthograde posture. The morphologically right atrium of the pig was characterised by the tubular shape of its appendage (a feature observed on the left in the human heart). The porcine superior and inferior caval veins opened into the atrium at right angles to one another, whereas in man the orifices were directly in line. A prominent left azygous vein (comparable to the much reduced left superior caval or oblique vein in man) entered on the left side of the pig heart and drained via the coronary sinus. The porcine left atrium received only 2 pulmonary veins, whereas 4 orifices were generally observed in man. The sweep between the inlet and outlet components of the porcine right ventricle was less marked than in man, and a prominent muscular moderator band was situated in a much higher position within the porcine right ventricle compared with that of man. The apical components of both porcine ventricles possessed very coarse trabeculations, much broader than those observed in the human ventricles. In general, aortic-mitral fibrous continuity was reduced in the outlet component of the porcine left ventricle, with approximately two-thirds of the aortic valve being supported by left ventricular musculature. Several potentially significant differences exist between

  1. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  2. Ginsenoside Rg3 induces DNA damage in human osteosarcoma cells and reduces MNNG-induced DNA damage and apoptosis in normal human cells.

    Science.gov (United States)

    Zhang, Yue-Hui; Li, Hai-Dong; Li, Bo; Jiang, Sheng-Dan; Jiang, Lei-Sheng

    2014-02-01

    Panax ginseng is a Chinese medicinal herb. Ginsenosides are the main bioactive components of P. ginseng, and ginsenoside Rg3 is the primary ginsenoside. Ginsenosides can potently kill various types of cancer cells. The present study was designed to evaluate the potential genotoxicity of ginsenoside Rg3 in human osteosarcoma cells and the protective effect of ginsenoside Rg3 with respect to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced DNA damage and apoptosis in a normal human cell line (human fibroblasts). Four human osteosarcoma cell lines (MG-63, OS732, U-2OS and HOS cells) and a normal human cell line (human fibroblasts) were employed to investigate the cytotoxicity of ginsenosides Rg3 by MTT assay. Alkaline comet assay and γH2AX focus staining were used to detect the DNA damage in MG-63 and U-2OS cells. The extent of cell apoptosis was determined by flow cytometry and a DNA ladder assay. Our results demonstrated that the cytotoxicity of ginsenoside Rg3 was dose-dependent in the human osteosarcoma cell lines, and MG-63 and U-2OS cells were the most sensitive to ginsenoside Rg3. As expected, compared to the negative control, ginsenoside Rg3 significantly increased DNA damage in a concentration-dependent manner. In agreement with the comet assay data, the percentage of γH2AX-positive MG-63 and U-2OS cells indicated that ginsenoside Rg3 induced DNA double-strand breaks in a concentration-dependent manner. The results also suggest that ginsenoside Rg3 reduces the extent of MNNG-induced DNA damage and apoptosis in human fibroblasts.

  3. A neocentromere on human chromosome 3 without detectable alpha-satellite DNA forms morphologically normal kinetochores

    DEFF Research Database (Denmark)

    Wandall, A; Tranebjaerg, L; Tommerup, Niels

    1998-01-01

    A neocentromere at 3q26 was observed in a father and his daughter on a chromosome 3 with deleted centromeric region. No alpha-satellite DNA was detectable at the 3q26 neocentromere, but it was weakly positive with anticentromere (CREST) antibodies. Electron microscopy showed that the neocentromere...... formed microtubule-associated kinetochores with normal morphology and of the same size as the kinetochores of other large chromosomes. The deleted centromere formed a small linear marker chromosome that reacted strongly with anticentromere antibodies, but showed reduced kinetochore size. The 3q26...... neokinetochore was stable under adverse growth conditions, which often caused kinetochore loss in the original 3-centromere on the small marker....

  4. Distinguishing human normal or cancerous esophagus tissue ex vivo using multiphoton microscopy

    Science.gov (United States)

    Liu, N. R.; Chen, G. N.; Wu, S. S.; Chen, R.

    2014-02-01

    Application of multiphoton microscopy (MPM) to clinical cancer research has greatly developed over the last few years. In this paper, we mainly focus on two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) for investigating esophageal cancer. We chiefly discuss the SHG/TPEF image and spectral characteristics of normal and cancerous esophagus submucosa with the combined multi-channel imaging mode and Lambda mode of a multiphoton microscope (LSM 510 META). Great differences can be detected, such as collagen content and morphology, glandular-shaped cancer cells, TPEF/SHG intensity ratio, and so on, which demonstrate that the multiphoton imaging technique has the potential ability for minimally-invasive early cancer diagnosis.

  5. High Efficiency of Human Normal Immunoglobulin for Intravenous Administration in a Patient with Kawasaki Syndrome Diagnosed in the Later Stages

    Directory of Open Access Journals (Sweden)

    Tatyana V. Sleptsova

    2016-01-01

    Full Text Available The article describes a case of late diagnosis of mucocutaneous lymphonodular syndrome (Kawasaki syndrome. At the beginning of the therapy, the child had fever, conjunctivitis, stomatitis, rash, solid swelling of hands and feet, and coronaritis with the development of aneurysms. The article describes the successful use of normal human immunoglobulin for intravenous administration at a dose of 2 g/kg body weight per course in combination with acetylsalicylic acid at the dose of 80 mg/kg per day. After 3 days of treatment, the rash disappeared; limb swelling and symptoms of conjunctivitis significantly reduced; and laboratory parameters of disease activity became normal (erythrocyte sedimentation rate, C-reactive protein concentration. After 3 months, inflammation in the coronary arteries was stopped. After 6 months, a regression of coronary artery aneurysms was recorded. No adverse effects during the immunoglobulin therapy were observed.

  6. Artichoke compound cynarin differentially affects the survival, growth and stress response of normal, immortalized and cancerous human cells

    DEFF Research Database (Denmark)

    Gezer, Ceren; Yücecan, Sevinç; Rattan, Suresh Inder Singh

    2015-01-01

    of CYN on the proliferative potential, survival, morphology, and stress response (SR) markers haemoxygenase-1 (HO-1) and heat shock protein-70 (HSP70) in normal human skin fibroblasts (FSF-1), telomerase-immortalized mesenchymal stem cells (hTERT-MSC) and cervical cancer cells, HeLa. Effects of CYN....... Furthermore, CYN induced oxidative SR marker HO-1 in both fibroblasts and stem cells in a biphasic manner, but a slight induction of HSP70 was observed only in the stem cells. Thus, CYN may be useful as a protection against the growth and survival of potentially cancerous cells and may promote longevity...... of normal cells by induction of SR proteins. Further advanced researches related with CYN and artichoke are recommended....

  7. Quantitative analysis of nucleoli and nucleolar organizer regions in cultured primary human normal, reactive and malignant mesothelial cells.

    Science.gov (United States)

    Ribotta, M; Donna, A; Betta, P G; Libener, R; Bellingeri, D; Robutti, F

    1992-06-01

    The number and the size of silver-stained intranuclear granules, which correspond to the nucleolus and nucleolar organizer regions, have been determined by means of quantitative methods in cultured primary human mesothelial cells obtained from normal, reactive and malignant mesothelium. The mean values per nucleus of the number, the total area, the average area, and the relative area of the silver-stained granules and the mean nuclear area were determined for each of the three conditions. Normal, reactive and malignant mesothelial cells differed significantly in all the features. These findings at the optical level reflect the differing rate of the nucleolar biosynthetic activity related to the different biological properties of the three cell types, and the features can be useful morphometric descriptors in the diagnostic pathology of the mesothelium.

  8. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    International Nuclear Information System (INIS)

    Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

    2012-01-01

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

  9. Blood pressure and heart rate variability analysis of orthostatic challenge in normal human pregnancies.

    Science.gov (United States)

    Heiskanen, Nonna; Saarelainen, Heli; Valtonen, Pirjo; Lyyra-Laitinen, Tiina; Laitinen, Tomi; Vanninen, Esko; Heinonen, Seppo

    2008-11-01

    The aim of the present study was to evaluate pregnancy-related changes in autonomic regulatory functions in healthy subjects. We studied cardiovascular autonomic responses to head-up tilt (HUT) in 28 pregnant women during the third trimester of pregnancy and 3 months after parturition. The maternal ECG and non-invasive beat-to-beat blood pressure were recorded in the horizontal position (left-lateral position) and during HUT in the upright position. Stroke volume was assessed from blood pressure signal by using the arterial pulse contour method. Heart rate variability (HRV) was analysed in frequency domain, and baroreflex sensitivity by the cross-spectral and the sequence methods. In the horizontal position, all frequency components of HRV were lower during pregnancy than 3 months after parturition (P pregnancy had no influence on normalized low frequency and high frequency powers. During pregnancy haemodynamics was well balanced with only minor changes in response to postural change while haemodynamic responses to HUT were more remarkable after parturition. In pregnant women HRV and especially its very low frequency component increased in response to HUT, whereas at 3 months after parturition the direction of these changes was opposite. Parasympathetic deactivation towards term is likely to contribute to increased heart rate and cardiac output at rest, whereas restored sympathetic modulation with modest responses may contribute stable peripheral resistance and sufficient placental blood supply under stimulated conditions. It is important to understand cardiovascular autonomic nervous system and haemodynamic control in normal pregnancy before being able to judge whether they are dysregulated in complicated pregnancies.

  10. Fidelity of DNA Replication in Normal and Malignant Human Breast Cells.

    Science.gov (United States)

    1997-08-01

    polymerase. Biochemical and Biophysical Research Communications 21:6, 1965. 3.Farber, E. and Rubin, H. Cellular adaptation in the origin and development of...for DNA polymerase ca and in vitro SV40 DNA Cell culture. Suspension cultures of MDA MB-468 replication activities. human breast cells were adapted ...A vatit"Y Of DNA synthesis and the typt of DNA replica~tion Products " celular prca including DNA rsplicatlon. DNA repsair. R~NA formed in experiments

  11. The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc

    International Nuclear Information System (INIS)

    Nikolova, Ekaterina; Mitev, Vanio; Zhelev, Nikolai; Deroanne, Christophe F.; Poumay, Yves

    2007-01-01

    Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity

  12. The pharmacokinetics, distribution and degradation of human recombinant interleukin 1 beta in normal rats

    DEFF Research Database (Denmark)

    Reimers, J; Wogensen, L D; Welinder, B

    1991-01-01

    Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half-lives of distribut......Based upon in vivo rat experiments it was recently suggested that interleukin 1 in the circulation may be implicated in the initial events of beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) in humans. The aim of the present study was to estimate half......-lives of distribution (T1/2 alpha) and elimination phases (T1/2 beta) of human recombinant interleukin 1 beta (rIL-1 beta), and its tissue distribution and cellular localization by means of mono-labelled, biologically active 125I-rIL-1 beta. After intravenous (i.v.) injection, 125I-rIL-1 beta was eliminated from...... of administration was of importance for the biological effects of rIL-1 beta, as demonstrated by a reduced food intake, increased rectal temperature and blood glucose after s.c. injection of rIL-1 beta compared with i.p. The present demonstration of intact rIL-1 beta in the circulation and the islets of Langerhans...

  13. Factors modifying 3-aminobenzamide cytotoxicity in normal and repair-deficient human fibroblasts

    International Nuclear Information System (INIS)

    Boorstein, R.J.; Pardee, A.B.

    1984-01-01

    3-Aminobenzamide (3-AB), an inhibitor of poly(ADP-ribosylation), is lethal to human fibroblasts with damaged DNA. Its cytotoxicity was determined relative to a number of factors including the types of lesions, the kinetics of repair, and the availability of alternative repair systems. A variety of alkylating agent, UV or gamma irradiation, or antimetabolites were used to create DNA lesions. 3-AB enhanced lethality with monofunctional alkylating agents only. Within this class of compounds, methylmethanesulfonate (MMS) treatments made cells more sensitive to 3-AB than did treatment with methylnitrosourea (MNU) or methylnitronitrosoguanidine (MNNG). 3-AB interfered with a dynamic repair process lasting several days, since human fibroblasts remained sensitive to 3-AB for 36-48 hours following MMS treatment. During this same interval 3-AB caused these cells to arrest in G 2 phase. Alkaline elution analysis also revealed that this slow repair was delayed further by 3-AB. Human mutant cell defective in DNA repair differed in their responses to 3-AB. Greater lethality with 3-AB could be dependent on inability of the mutant cells to repair damage by other processes

  14. Role of C-type natriuretic peptide in the function of normal human sperm.

    Science.gov (United States)

    Xia, Hui; Chen, Yao; Wu, Ke-Jia; Zhao, Hu; Xiong, Cheng-Liang; Huang, Dong-Hui

    2016-01-01

    C-type natriuretic peptide (CNP) is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B). Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot), and then to evaluate the influence of CNP on sperm function i n vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

  15. Role of C-type natriuretic peptide in the function of normal human sperm

    Directory of Open Access Journals (Sweden)

    Hui Xia

    2016-01-01

    Full Text Available C-type natriuretic peptide (CNP is a newly discovered type of local regulatory factor that mediates its biological effects through the specific, membrane-bound natriuretic peptide receptor-B (NPR-B. Recent studies have established that CNP is closely related to male reproductive function. The aims of this study were to determine the distribution of CNP/NPR-B in human ejaculated spermatozoa through different methods (such as immunolocalization, real time polymerase chain reaction and Western Blot, and then to evaluate the influence of CNP on sperm function i n vitro, such as motility and acrosome reaction. Human semen samples were collected from consenting donors who met the criteria of the World Health Organization for normozoospermia. Our results show that the specific receptor NPR-B of CNP is localized in the acrosomal region of the head and the membrane of the front-end tail of the sperm, and there is no signal of CNP in human sperm. Compared with the control, CNP can induce a significant dose-dependent increase in spermatozoa motility and acrosome reaction. In summary, CNP/NPR-B can affect sperm motility and acrosome reaction, thus regulating the reproductive function of males. CNP may be a new key factor in regulating sperm function.

  16. Shape-dependent regulation of proliferation in normal and malignant human cells and its alteration by interferon

    International Nuclear Information System (INIS)

    Kulesh, D.A.; Greene, J.J.

    1986-01-01

    The relationship between cell morphology, proliferation, and contact inhibition was studied in normal and malignant human cells which varied in their sensitivity to contact inhibition. Their ability to proliferate was examined under conditions where the cells were constrained into different shapes by plating onto plastic surfaces coated with poly(2-hydroxyethyl methacrylate). Poly(2-hydroxyethyl methacrylate) can precisely vary the shape of cells without toxicity. Cell proliferation was quantitated by cell counts and labeling indices were determined by autoradiography. The normal JHU-1 foreskin fibroblasts and IMR-90 lung fibroblasts exhibited contact-inhibited growth with a saturation density of 2.9 X 10(5) and 2.0 X 10(5) cells/cm2, respectively. These cells also exhibited stringent dependency on cell shape with a mitotic index of less than 3% at poly(2-hydroxyethyl methacrylate) concentrations at which the cells were rounded versus a labeling index of 75-90% when the cells were flat. The malignant bladder carcinoma line RT-4 exhibited partial contact-inhibited growth. Its dependency on cell shape was less stringent than that of normal cells with a mitotic index of 37-40% when rounded and 79% when flat. The malignant fibrosarcoma line, HT1080, was not contact inhibited and was entirely shape independent with a mitotic index of 70-90% regardless of cell shape. Treatment of HT1080 cells with low concentration of human fibroblast interferon (less than 40 units/ml) restored shape-dependent proliferation while having little effect on normal cells. Subantiproliferative doses of interferon were also shown to restore contact-inhibited proliferation control to malignant cells previously lacking it

  17. Effect of capping agents on the cytotoxicity of silver nanoparticles in human normal and cancer skin cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Netchareonsirisuk, Ponsawan [Chulalongkorn University, Program in Biotechnology, Faculty of Science (Thailand); Puthong, Songchan [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand); Dubas, Stephan [Chulalongkorn University, Petroleum and Petrochemical College (Thailand); Palaga, Tanapat [Chulalongkorn University, Department of Microbiology, Faculty of Science (Thailand); Komolpis, Kittinan, E-mail: kittinan.k@chula.ac.th [Chulalongkorn University, Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering (Thailand)

    2016-11-15

    Silver nanoparticles (AgNPs) are among the most widely used nanomaterials in medical and consumer products. However, safety in the uses of AgNPs is still controversial. The toxicity of AgNPs toward various cell types has been reported to depend on the surface properties of the nanoparticles. In this study, the effect of AgNPs with the average size of 5–15 nm on the viability of the CCD-986SK human normal skin fibroblast cell line and A375 human malignant melanoma cell line was evaluated. Comparative toxicity studies, based on MTT assay, were performed by using either sodium alginate or poly (4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA) as capping agent in the nanoparticle preparation. The cytotoxicity tests revealed that AgNO{sub 3} alone was highly toxic to both cell types while both alginate and PSSMA alone were not toxic. AgNPs capped with alginate were selectively toxic to the cancer cell line but not to the normal cell line while AgNPs capped with PSSMA were toxic to both cancer and normal cell lines. Judging from the 50 % inhibition concentration (IC{sub 50}), it was found that the cancer cell line was more sensitive to AgNPs than the normal cell line. Study on the mode of cell death by annexin V and propidium iodide staining revealed that AgNPs induced more apoptotic cell death (84–90 %) than necrosis (8–12 %) in the skin cancer cell line. These results suggest that the toxicity of AgNPs depended on the type of capping agent and the type of cell line.

  18. Correlation Between Placental Matrix Metalloproteinase 9 and Tumor Necrosis Factor-α Protein Expression Throughout Gestation in Normal Human Pregnancy.

    Science.gov (United States)

    Basu, Jayasri; Agamasu, Enyonam; Bendek, Bolek; Salafia, Carolyn M; Mishra, Aruna; Lopez, Julia Vasquez; Kroes, Jessica; Dragich, Sharon Claire; Thakur, Ashley; Mikhail, Magdy

    2018-04-01

    Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-α (TNF-α) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-α expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (7 0/7 -13 0/7 , 13 1/7 -23 6/7 , and 37 0/7 -42 4/7 weeks, respectively). Chorionic villous TNF-α and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-α protein expressions among the trimester groups ( P = .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-α peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester ( r = 0.364, P = .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-α and MMP-9 only in the second trimester ( r = 0.300, P = .018). We hypothesize that the TNF-α peak and the positive correlation between TNF-α and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

  19. Attenuation of radiation-induced DNA damage due to paracrine interactions between normal human epithelial and stromal cells

    International Nuclear Information System (INIS)

    Saenko, V.A.; Nakazawa, Yu.; Rogounovitch, T.I.; Suzuki, K.; Mitsutake, N.; Matsuse, M.; Yamashita, S.

    2007-01-01

    Complete text of publication follows. Objective: Developmentally, every tissue accommodates different types of cells, such as epitheliocytes and stromal cells in parenchymal organs. To better understand the complexity of radiation response, it is necessary to evaluate possible cross-talk between different tissue components. This work was set out to investigate reciprocal influence of normal human epithelial cells and fibroblasts on the extent of radiation-induced DNA damage. Methods: Model cultures of primary human thyrocytes (PT), normal diploid fibroblasts (BJ), PT/BJ cell co-culture and conditioned medium transfer were used to examine DNA damage in terms of γ-H2AX foci number per cell or by Comet assay after exposure to different doses of γ-rays. Results: In co-cultures, the kinetics of γ-H2AX foci number change was dose-dependent and similar to that in individual PT and BJ cultures. The number of γ-H2AX foci in co-cultures was significantly lower (∼25%) in both types of cells comparing to individual cultures. Reciprocal conditioned medium transfer to individual counterpart cells prior to irradiation resulted in approximately 35% reduction in the number γ-H2AX foci at 1 Gy and lower doses in both PT and BJ demonstrating the role of paracrine soluble factors. Comet assay corroborated the results of γ-H2AX foci counting in conditioned medium transfer experiments. In contrast to medium conditioned on PT cells, conditioned medium collected from several human thyroid cancer cell lines failed to establish DNA-protected state in BJ fibroblasts. In its turn, medium conditioned on BJ cells did not change the extent of radiation-induced DNA damage in cancer cell lines tested. Conclusion: The results imply the existence of a network of soluble factor-mediated paracrine interactions between normal epithelial and stromal cells that could be a part of natural mechanism by which cells protect DNA from genotoxic stress.

  20. A study on the kinetics of high-energy phosphates in myocardium by phosphorous nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Kusuoka, Hideo; Tsuneoka, Yutaka; Inoue, Michitoshi; Abe, Hiroshi; Watari, Hiroshi.

    1982-01-01

    Effect of artificial blood, FC 43 (Perfluorochemicals) on the kinetics of high-energy phosphate in the myocardium was evaluated by 31 P-NMR which permits a continuous and non-invasive assessment of in vivo phosphorus compounds. Cardiac perfusion was carried out on a excised rat heart with a Krebs-Henseleit modified solution and FC 43 alternately. Under the normal condition, ischemic condition, and at second perfusion amounts of intramyocardial creatine phosphoric acid, ATP, and inorganic phosphorus were determined by 31 P-NMR. Coronary flow was simultaneously estimated. The ischemic state due to interruption of perfusion resulted in a decrease in creatine phosphoric acid, which was associated with an increase in inorganic phosphorus and intracellular acidosis. No change of ATP amount was observed under ischemic state. With resumption of perfusion, the levels of creatine phosphoric acid and inorganic phosphorus rapidly returned to the normal. In the group of FC 43, coronary flow was 2.68 ml/min/g of the heart weight, about 1/2 of that of the Krebs-Henseleit group (5.68 ml/min/g of the heart weight). In controls, there was no difference between the two groups concerning creatine phosphoric acid level and recovery of creatine phospohric acid level after ischemia. These results showed that FC 43 supplies sufficient oxygen, and has no effect on the kinetics of energy in the myocardium. (Ueda, J.)

  1. Dynamic visual acuity during transient and sinusoidal yaw rotation in normal and unilaterally vestibulopathic humans.

    Science.gov (United States)

    Tian, J R; Shubayev, I; Demer, J L

    2001-03-01

    The vestibulo-ocular reflex (VOR) stabilizes gaze to permit clear vision during head movements. It has been supposed that VOR function might be inferred from dynamic visual acuity (DVA), the acuity during imposed head motion. We sought to determine effectiveness of DVA for detection and lateralization of unilateral vestibulopathy, using rigorous psychophysical methods. Seventeen normal and 11 unilaterally vestibulopathic subjects underwent measurement of optically best corrected DVA during head motion. A variable size letter "E" 6 m distant was displayed in oblique random orientations to determine binocular DVA by a computer controlled, forced choice method. Three types of whole-body yaw rotation were delivered by a servo-controlled chair synchronized with optotype presentation. Two types of motion were predictable: (1) steady-state 2.0-Hz rotation at 10-130 degrees/s peak velocity with repetitive optotype presentation only during head velocity exceeding 80% of peak; and (2) directionally predictable transients at peak accelerations of 1000, 1600 and 2800 degrees/s2 with optotype presentation for 300 ms. For neither of these predictable motions did DVA in vestibulopathic subjects significantly differ from normal, with suggestions from search coil recordings that this was due to predictive slow and saccadic eye movements. Unilaterally vestibulopathic subjects experienced a significant decrease in DVA from the static condition during ipsilesional rotation for all three peak head accelerations. Only during directionally unpredictable transients with 75 ms or 300 ms optotype presentation was the sensitivity of DVA in unilaterally vestibulopathic subjects significantly abnormal during ipsilesional rotation. The ipsilesional decrease in DVA with head motion was greater for 75 ms than 300 ms optotype presentation. Search coil recordings confirmed hypometric compensatory eye movements during DVA testing with unpredictable, ipsilesional rotation. Receiver

  2. Extension of the lifespan of cultured normal human diploid cells by vitamin E: a reevaluation

    Energy Technology Data Exchange (ETDEWEB)

    Packer, L. (Univ. of California, Berkeley); Smith, J.R.

    1977-04-01

    Previously we reported that the lifespan of WI-38 human diploid fibroblasts in vitro was significantly increased by continuously growing the cell cultures in the presence of vitamin E (dl-..cap alpha..-tocopherol), but in 19 subsequent subcultivation series we were unable to reproduce these findings. While vitamin E is incorporated into the cells and is able to act effectively as an antioxidant, apparently its intracellular antioxidant properties alone do not routinely result in an increase of cell lifespan. A synergism between vitamin E and some component(s) in the first of two lots of serum used in the original experiments seems the most likely explanation for our earlier findings.

  3. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract.

    OpenAIRE

    Cantin, A M; Fells, G A; Hubbard, R C; Crystal, R G

    1990-01-01

    We hypothesized that the alveolar structures may contain extracellular macromolecules with antioxidant properties to defend against oxidants. To evaluate this 51Cr-labeled human lung fibroblasts (HFL-1) and cat lung epithelial cells (AKD) were exposed to a H2O2-generating system and alveolar epithelial lining fluid (ELF) from healthy nonsmokers was tested for its ability to protect the lung cells from H2O2-mediated injury. The ELF provided marked antioxidant protection, with most from a H2O-s...

  4. OCT angiography by absolute intensity difference applied to normal and diseased human retinas

    Science.gov (United States)

    Ruminski, Daniel; Sikorski, Bartosz L.; Bukowska, Danuta; Szkulmowski, Maciej; Krawiec, Krzysztof; Malukiewicz, Grazyna; Bieganowski, Lech; Wojtkowski, Maciej

    2015-01-01

    We compare four optical coherence tomography techniques for noninvasive visualization of microcapillary network in the human retina and murine cortex. We perform phantom studies to investigate contrast-to-noise ratio for angiographic images obtained with each of the algorithm. We show that the computationally simplest absolute intensity difference angiographic OCT algorithm that bases only on two cross-sectional intensity images may be successfully used in clinical study of healthy eyes and eyes with diabetic maculopathy and branch retinal vein occlusion. PMID:26309740

  5. Normal Collagen and Bone Production by Gene-targeted Human Osteogenesis Imperfecta iPSCs

    Science.gov (United States)

    Deyle, David R; Khan, Iram F; Ren, Gaoying; Wang, Pei-Rong; Kho, Jordan; Schwarze, Ulrike; Russell, David W

    2012-01-01

    Osteogenesis imperfecta (OI) is caused by dominant mutations in the type I collagen genes. In principle, the skeletal abnormalities of OI could be treated by transplantation of patient-specific, bone-forming cells that no longer express the mutant gene. Here, we develop this approach by isolating mesenchymal cells from OI patients, inactivating their mutant collagen genes by adeno-associated virus (AAV)-mediated gene targeting, and deriving induced pluripotent stem cells (iPSCs) that were expanded and differentiated into mesenchymal stem cells (iMSCs). Gene-targeted iMSCs produced normal collagen and formed bone in vivo, but were less senescent and proliferated more than bone-derived MSCs. To generate iPSCs that would be more appropriate for clinical use, the reprogramming and selectable marker transgenes were removed by Cre recombinase. These results demonstrate that the combination of gene targeting and iPSC derivation can be used to produce potentially therapeutic cells from patients with genetic disease. PMID:22031238

  6. Ability of the normal human small intestine to absorb fructose: evaluation by breath testing.

    Science.gov (United States)

    Rao, Satish S C; Attaluri, Ashok; Anderson, Leslie; Stumbo, Phyllis

    2007-08-01

    Fructose consumption is increasing, and its malabsorption causes common gastrointestinal symptoms. Because its absorption capacity is poorly understood, there is no standard method of assessing fructose absorption. We performed a dose-response study of fructose absorption in healthy subjects to develop a breath test to distinguish normal from abnormal fructose absorption capacity. In a double-blind study, 20 healthy subjects received 10% solutions of 15, 25, and 50 g of fructose and 33% solution of 50-g fructose on 4 separate days at weekly intervals. Breath samples were assessed for hydrogen (H2) and methane (CH4) during a period of 5 hours, and symptoms were recorded. No subject tested positive with 15 g. Two (10%) tested positive with 25 g fructose but were asymptomatic. Sixteen (80%) tested positive with 50 g (10% solution), and 11 (55%) had symptoms. Breath H2 was elevated in 13 (65%), CH4 in 1 (5%), and both in 2 (10%). Twelve (60%) tested positive with 50 g (33% solution), and 9 (45%) experienced symptoms. The area under the curve for H2 and CH4 was higher (P fructose, whereas many exhibit malabsorption and intolerance with 50 g fructose. Hence, we recommend 25 g as the dose for testing subjects with suspected fructose malabsorption. Breath samples measured for H2 and CH4 concentration at 30-minute intervals and for 3 hours will detect most subjects with fructose malabsorption.

  7. The Ability of the Normal Human Small Intestine to Absorb Fructose: Evaluation by Breath Testing

    Science.gov (United States)

    Rao, Satish S.C; Attaluri, Ashok; Anderson, Leslie; Stumbo, Phyllis

    2007-01-01

    Background Fructose consumption is rising and its malabsorption causes common gastrointestinal symptoms. Because its absorption capacity is poorly understood, there is no standard method of assessing fructose absorption. We performed a dose response study of fructose absorption in healthy subjects in order to develop a breath test to distinguish normal from abnormal fructose absorption capacity. Methods In a double-blind study, 20 healthy subjects received 10% solutions of 15g, 25g and 50g of fructose and 33 % solution of 50g fructose on 4 separate days, at weekly intervals. Breath samples were assessed for hydrogen and methane over five hours, and symptoms were recorded. Results No subject tested positive with 15g. Two (10%) tested positive with 25g fructose but were asymptomatic. Sixteen (80 %) tested positive with 50g (10% solution) and 11 (55%) had symptoms. Breath H2 was elevated in 13 (65%), CH4 in 1 (5%) and both in 2 (10%). Twelve (60%) tested positive with 50g (33% solution) and 9 (45%) experienced symptoms. The area under the curve for H2 and CH4 was higher (pfructose whereas many exhibit malabsorption and intolerance with 50g fructose. Hence, we recommend 25g as the dose for testing subjects with suspected fructose malabsorption. Breath samples measured for H2 and CH4 concentration at 30 minute intervals and for 3 hours will detect most subjects with fructose malabsorption. PMID:17625977

  8. Mathematical representation of the normal proximal human femur: application in planning of cam hip surgery.

    Science.gov (United States)

    Masjedi, Milad; Harris, Simon J; Davda, Kinner; Cobb, Justin P

    2013-04-01

    Precise modelling of the proximal femur can be used for detecting and planning corrective surgery for subjects with deformed femurs using robotic technology or navigation systems. In this study, the proximal femoral geometry has been modelled mathematically. It is hypothesised that it is possible to fit a quadratic surface or combinations of them onto different bone surfaces with a relatively good fit. Forty-six computed tomography datasets of normal proximal femora were segmented. A least-squares fitting algorithm was used to fit a quadratic surface on the femoral head and neck such that the sum of distances between a set of points on the femoral neck and the quadratic surface was minimised. Furthermore, the position of the head-neck articular margin was also measured. The femoral neck was found to be represented as a good fit to a hyperboloid with an average root mean-squared error of 1.0 ± 0.13 mm while the shape of the femoral articular margin was a reproducible sinusoidal wave form with two peaks. The mathematical description in this study can be used for planning corrective surgery for subjects with cam-type femoroacetabular impingement.

  9. Normal variations in the isotopic composition of metabolically relevant transition metals in human blood

    Science.gov (United States)

    Van Heghe, L.; Cloquet, C.; Vanhaecke, F.

    2012-04-01

    Cu, Fe and Zn are transition metals with great catalytic, structural and regulating importance in the human body. Hence, an aberrant metabolism of these elements can have serious implications on the health of a person. It is assumed that, due to differences in isotope fractionation, the isotopic composition of these elements in whole blood of patients can be different from that in blood of healthy subjects. Therefore, isotopic analysis of the element affected by the disease can be a promising approach for early diagnosis. A method for isotopic analysis of Cu, Fe and Zn in human whole blood was developed. The simultaneous chromatographic isolation of these elements and the conditions for isotope ratio measurement via multi-collector ICP - mass spectrometry (MC-ICP-MS) were optimized. So far, only whole blood of supposedly healthy volunteers (reference population) was analyzed. Results for Fe confirmed the known differences in isotopic composition between male and female blood. It is also shown that other parameters can have influence as well, e.g., the isotopic composition of Zn seems to be governed by the diet.

  10. Identification of androgen receptors in normal human osteoblast-like cells

    International Nuclear Information System (INIS)

    Colvard, D.S.; Eriksen, E.F.; Keeting, P.E.; Riggs, B.L.; Spelsberg, T.C.; Wilson, E.M.; Lubahn, D.B.; French, F.S.

    1989-01-01

    The sex steroids, androgens and estrogens, are major regulators of bone metabolism. However, whether these hormones act on bone cells through direct or indirect mechanisms has remained unclear. A nuclear binding assay recently used to demonstrate estrogen receptors in bone was used to identify specific nuclear binding of a tritiated synthetic androgen, [ 3 H]R1881 (methyltrienolone), in 21 of 25 (84%) human osteoblast-like cell strains and a concentration of bound steroid receptors of 821 ± 140 molecules per cell nucleus. Binding was saturable and steroid-specific. Androgen receptor gene expression in osteoblasts was confirmed by RNA blot analysis. Relative concentrations of androgen and estrogen receptors were compared by measuring specific nuclear estrogen binding. Nuclear binding of [ 3 H]estradiol was observed in 27 of 30 (90%) cell strains; the concentration of bound estradiol receptor was 1537 ± 221 molecules per cell nucleus. The concentrations of nuclear binding sites were similar in males and females for both [ 3 H]R1881 and [ 3 H]estradiol. The authors conclude that both androgens and estrogens act directly on human bone cells through their respective receptor-mediated mechanisms

  11. Interleukin-17A induces bicarbonate secretion in normal human bronchial epithelial cells

    Science.gov (United States)

    Kreindler, James L.; Bertrand, Carol A.; Lee, Robert J.; Karasic, Thomas; Aujla, Shean; Pilewski, Joseph M.; Frizzell, Raymond A.; Kolls, Jay K.

    2009-01-01

    The innate immune functions of human airways include mucociliary clearance and antimicrobial peptide activity. Both functions may be affected by changes in epithelial ion transport. Interleukin-17A (IL-17A), which has a receptor at the basolateral membrane of airway epithelia, is a T cell cytokine that has been shown to increase mucus secretion and antimicrobial peptide production by human bronchial epithelial (HBE) cells. Furthermore, IL-17A levels are increased in sputum from patients during pulmonary exacerbations of cystic fibrosis. Therefore, we investigated the effects of IL-17A on basal, amiloride-sensitive, and forskolin-stimulated ion transport in mature, well-differentiated HBE cells. Exposure of HBE monolayers to IL-17A for 48 h induced a novel forskolin-stimulated bicarbonate secretion in addition to forskolin-stimulated chloride secretion and resulted in alkalinization of liquid on the mucosal surface of polarized cells. IL-17A-induced bicarbonate secretion was cystic fibrosis transmembrane conductance regulator (CFTR)-dependent, mucosal chloride-dependent, partially Na+-dependent, and sensitive to serosal, but not mucosal, stilbene inhibition. These data suggest that IL-17A modulates epithelial bicarbonate secretion and implicate a mechanism by which airway surface liquid pH changes may be abnormal in cystic fibrosis. PMID:19074559

  12. Using the Optical Fractionator to Estimate Total Cell Numbers in the Normal and Abnormal Developing Human Forebrain

    DEFF Research Database (Denmark)

    Larsen, Karen B

    2017-01-01

    Human fetal brain development is a complex process which is vulnerable to disruption at many stages. Although histogenesis is well-documented, only a few studies have quantified cell numbers across normal human fetal brain growth. Due to the present lack of normative data it is difficult to gauge...... abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples...... are unreliable due to unpredictable shrinking artifacts, and the fragility of the fetal brain requires particular care in handling and processing. The optical fractionator design offers a direct and robust estimate of total cell numbers in the fetal brain with a minimum of handling of the tissue. Bearing...

  13. Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype

    DEFF Research Database (Denmark)

    Hopkinson, Branden Michael; Klitgaard, Marie Christine; Petersen, Ole William

    2017-01-01

    Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor......-positive (ERpos) MCF7 cell line. However, luminal specific comparisons have suffered from the lack of a relevant non-malignant counterpart. Our previous work has shown that transforming growth factor-β receptor (TGFβR) inhibition suffices to propagate prospectively isolated ERpos human breast luminal cells from...... reduction mammoplasties (HBEC). Here we demonstrate that transduction of these cells with hTERT/shp16 renders them immortal while remaining true to the luminal lineage including expression of functional ER (iHBECERpos). Under identical culture conditions a major difference between MCF7 and normal...

  14. Production of a Marfan cellular phenotype by expressing a mutant human fibrillin allele on a normal human or murine genetic background

    Energy Technology Data Exchange (ETDEWEB)

    Eldadah, Z.A.; Dietz, H.C. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Brenn, T. [Stanford Univ. Medical Center, CA (United States)] [and others

    1994-09-01

    The Marfan Syndrome (MFS) is a heritable disorder of connective tissue caused by defects in fibrillin (FBN1), a 350 kD glycoprotein and principal component of the extracellular microfibril. Previous correlations of mutant transcript level and disease severity suggested a dominant negative model of MFS pathogenesis. To address this hypothesis we assembled an expression construct containing the mutant allele from a patient with severe MFS. This mutation causes skipping of FBN1 exon 2 and a frame shift, leading to a premature termination codon in exon 4. The predicted peptide would thus consist of 55 wild type and 45 missense amino acids. The construct was stably transfected into cultured human and mouse fibroblasts, and several clonal cell populations were established. Human and mouse cells expressing the truncated peptide exhibited markedly diminished fibrillin deposition and disorganized microfibrillar architecture by immunofluorescence. Pulse-chase analysis of these cells demonstrated normal levels of fibrillin synthesis but substantially decreased fibrillin deposition into the extracellular matrix. These data illustrate that expression of a mutant FBN1 allele, on a background of two normal alleles, is sufficient to disrupt normal fibrillin aggregation and reproduce the MFS cellular phenotype. This provides confirmation of a dominant negative model of MFS pathogenesis and may offer mutant allele knockout as a strategy for gene therapy. In addition, these data underscore the importance of the FBN1 amino-terminus in normal multimer formation and suggest that expression of the human extreme 5{prime} FBN1 coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Indeed, transgenic mice harboring this mutant allele have been produced, and phenotype analysis is currently in progress.

  15. Surface and protein analyses of normal human cell attachment on PIII-modified chitosan membranes

    Energy Technology Data Exchange (ETDEWEB)

    Saranwong, N. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Inthanon, K. [Human and Animal Cell Technology Research Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Wongkham, W., E-mail: weerah@chiangmai.ac.th [Human and Animal Cell Technology Research Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Wanichapichart, P. [Nanotechnology Center of Excellence and Membrane Science and Technology Research Center, Department of Physics, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla 90110 (Thailand); Suwannakachorn, D. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Yu, L.D., E-mail: yuld@fnrf.science.cmu.ac.th [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand)

    2012-02-01

    Surface of chitosan membrane was modified with argon (Ar) and nitrogen (N) plasma immersion ion implantation (PIII) for human skin fibroblasts F1544 cell attachment. The modified surfaces were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Cell attachment patterns were evaluated by scanning electron microscopy (SEM). The enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of focal adhesion kinase (FAK). The results showed that Ar PIII had an enhancement effect on the cell attachment while N-PIII had an inhibition effect. Filopodial analysis revealed more microfilament cytoplasmic spreading on the edge of cells attached on the Ar-treated membranes than N-treated membranes. Higher level FAK was found in Ar-treated membranes than that in N-treated membranes.

  16. Development of a radioreceptor assay for human chorion gonadotropin: Application in normal and pathological pregnancies

    International Nuclear Information System (INIS)

    Koch, R.

    1978-01-01

    Rats testes were homogenised, and the binding capacity of several dilutions of these were tested with iodine 125 -labelled human choriongonadotropin. Investigations about binding over a period of 36 hrs. with 3 different temperatures, inhibition tests and cross reaction analyses for determining the specificity were carried out. 2 assay systems could be developed. The highly sensitive assay was applied at early pregnancy, at suspected disturbed or ectopic gravidity and allowed to measure the hCG-serum concentration above the physiological basal secretion of hLH. The less sensitive assay was used for measuring hCG in later stages of pregnancy, chorionepitheliomas and other hCG producing tumours. With the highly sensitive and specific assay, hCG was determinable 8 to 10 days post conceptionem. (orig.) [de

  17. Aspirin effects on lymphocyte cyclic AMP levels in normal human subjects.

    Science.gov (United States)

    Snider, D E; Parker, C W

    1976-01-01

    In purified lymphocytes from the peripheral blood of healthy human subjects who had ingested therapeutic doses of aspirin, there was a significant decrease in resting cyclic AMP levels as well as a partial inhibition of the rise in cyclic AMP with isoproterenol or prostaglandin E1. These changes were seen as early as 30 min after aspirin ingestion and did not appear to result from aspirin effects on lymphocyte recovery, purity, viability, or relative number of thymus- or bone marrow-derived lymphocytes. In contrast, the direct addition of aspirin to suspensions of purified peripheral lymphocytes did not significantly alter their cyclic AMP levels. However, an effect of aspirin could be obtained in vitro if aspirin was added to unprocessed whole blood during the dextran sedimentation phase of the cell purification. Thus the effect of aspirin on lymphocyte cyclic AMP metabolism, may be indirect, through other cells present in the peripheral blood. PMID:182720

  18. Neural coding and perception of pitch in the normal and impaired human auditory system

    DEFF Research Database (Denmark)

    Santurette, Sébastien

    2011-01-01

    investigated using psychophysical methods. First, hearing loss was found to affect the perception of binaural pitch, a pitch sensation created by the binaural interaction of noise stimuli. Specifically, listeners without binaural pitch sensation showed signs of retrocochlear disorders. Despite adverse effects......Pitch is an important attribute of hearing that allows us to perceive the musical quality of sounds. Besides music perception, pitch contributes to speech communication, auditory grouping, and perceptual segregation of sound sources. In this work, several aspects of pitch perception in humans were...... of reduced frequency selectivity on binaural pitch perception, the ability to accurately process the temporal fine structure (TFS) of sounds at the output of the cochlear filters was found to be essential for perceiving binaural pitch. Monaural TFS processing also played a major and independent role...

  19. Iso-effect tables for tolerance of irradiated normal human tissues

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on a radiation injury to human tissues (lung, brain, kidney and intestine) was surveyed. A parameter search program (RAD3) was used to derive best-fitting cell kinetic parameters, on the assumption that radiation injury arises from depletion of parenchymal cells in the irradiated organs. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals, for each tissue. The tables provide a set of limiting doses, above which the risk of radiation injury becomes substantial. Tolerance limits and dose-time-factors were substantially different in the four tissues. It is concluded that computed iso-effect tables provide a more reliable guide to treatment than conventional time-dose equations

  20. Sildenafil Effect on Nitric Oxide Secretion by Normal Human Endometrial Epithelial Cells Cultured In vitro

    Directory of Open Access Journals (Sweden)

    Farzaneh Chobsaz

    2011-01-01

    Full Text Available Background: Sildenafil is a selective inhibitor of cyclic-guanosine monphosphat-specificphosphodiesterase type 5. It increases intracellular nitric oxide (NO production in some cells.There are reports on its positive effect on uterine circulation, endometrial thickness, and infertilityimprovement. Endometrial epithelial cells (EEC play an important role in embryo attachment andimplantation. The present work investigates the effect of sildenafil on human EEC and their NOsecretion in vitro.Materials and Methods: In this experimental in vitro study, endometrial biopsies (n=10 werewashed in a phosphate buffered solution (PBS and digested with collagenase I (2 mg/ml in DMEM/F12 medium at 37°C for 90 minutes. Epithelial glands were collected by sequential filtrationthrough nylon meshes (70 and 40 μm pores, respectively. Epithelial glands were then treated withtrypsin to obtain individual cells. The cells were counted and divided into four groups: control and1, 10, and 20 μM sildenafil concentrations. Cells were cultured for 15 days at 37ºC and 5% CO2; themedia were changed every 3 days, and their supernatants were collected for the NO assay. NO wasmeasured by standard Greiss methods. Data were analyzed by one way ANOVA.Results: There was no significant difference between groups in cell count and NO secretion, but thelevel of NO increased slightly in the experimental groups. The 10 μM dose showed the highest cellcount. EEC morphology changed into long spindle cells in the case groups.Conclusion: Sildenafil (1, 10, and 20 μM showed a mild proliferative effect on human EECnumbers, but no significant change was seen in NO production.

  1. Vasopressin (VP) and neuropeptide FF (NPFF) systems in the normal and hypertensive human brainstem.

    Science.gov (United States)

    Goncharuk, Valeri D; Buijs, Ruud M; Jhamandas, Jack H; Swaab, Dick F

    2011-01-01

    Vasopressin (VP)-, neuropeptide FF (NPFF)-, and tyrosine hydroxylase (TH)-expressing neurons were studied by means of single and double immunocytochemistry in the human brainstem of controls who died suddenly due to trauma and of patients who suffered from essential hypertension and died due to acute myocardial infarction, while in one case there was brain hemorrhage. In the control and hypertensive groups VP fibers and NPFF neurons and fibers were the most abundantly present in the dorsal vagal complex, especially in the dorsal motor nucleus of the vagus. Numerous VP and NPFF fibers formed synaptic-like contacts with neuronal profiles in the dorsointermediate, centrointermediate, ventrointermediate, caudointermediate, and caudal parts of the dorsal motor nucleus of vagus as well as adjacent medial and intermediate subnuclei of the solitary nucleus. VP, but not NPFF, positive fibers were found to vastly contact TH-positive neuronal profiles in A2/C2, A2, and ambiguus nucleus (Amb). The density of VP fibers in the dorsal motor nucleus of the vagus and Amb did not differ between hypertensive patients and controls, whereas the density of NPFF fibers in hypertensives was 3.19 times lower in the dorsal motor nucleus of vagus and markedly decreased in the Amb. In both groups, VP and NPFF were scarcely present in the pain pathways, suggesting that these peptides are not crucially involved in nociceptive control in human. The reduction of NPFF release within the dorsal motor nucleus and Amb could serve as a possible cause of the impairment of cardiac vagal control in hypertensive patients.

  2. Cancerous and normal human tissues investigated by near-infrared time-resolved and spectroscopic imaging techniques

    Science.gov (United States)

    Alrubaiee, Mohammad; Gayen, Swapan K.; Koutcher, Jason A.; Alfano, Robert R.

    2003-07-01

    Spectroscopic and time-sliced two-dimensional (2-D) transillumination imaging methods were used to investigate ex vivo tumor and normal tissues of human breast and parotid gland. The experimental arrangement for time-sliced optical imaging uses 120-fs, 1 kHz repetition-rate, 800-nm light pulses from a Ti:sapphire laser system for sample illumination and a charge coupled device (CCD) camera coupled to a gated image intensifier for recording 2-D images. The spectroscopic imaging arrangement uses 1210-1325 nm tunable output of a Cr: forsterite laser for sample illumination, a Fourier space gate to discriminate against multiple-scattered light, and a near-infrared (NIR) area camera to record 2-D images. Images recorded with earlier temporal slices of transmitted light highlighted tumors, while those recorded with later slices accentuated normal tissues. When light was tuned closer to the 1203 nm absorption resonance of adipose tissues, a marked enhancement in contrast between the images of adipose and fibrous tissues was observed. A similar wavelength-dependent difference between normal and cancerous tissues was observed. These results correlate well with pathology and nuclear magnetic resonance based analyses of the samples. This work demonstrates the advantages of time-resolved spectroscopic approach for imaging tumors in body organs.

  3. Prevalence of human papillomavirus, Chlamydia trachomatis, and Trichomonas vaginalis infections in Amazonian women with normal and abnormal cytology.

    Science.gov (United States)

    Costa-Lira, E; Jacinto, A H V L; Silva, L M; Napoleão, P F R; Barbosa-Filho, R A A; Cruz, G J S; Astolfi-Filho, S; Borborema-Santos, C M

    2017-04-28

    Sexually transmitted infections are an important cause of morbidity among sexually active women worldwide, and have been implicated as cofactors in the pathogenesis of cervical cancer. We investigated the prevalence of human papillomavirus (HPV), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV), and accessed the diversity of HPV in women with normal and abnormal cytology in Manaus, Brazil. We used polymerase chain reaction and HPV genotyping by direct sequencing. The chi-square test was used to calculate the absolute and relative frequencies of the categorical variables, and Fisher's test was used when P TV and CT DNA were 18.04 and 9.02% in the normal group, respectively. The percentages of HPV/TV and HPV/CT coinfection were 12.5% each in women with normal cytology. These findings improve our understanding of HPV, CT, and TV, and the distribution of HPV types, which may be relevant to vaccination strategies for protecting women from the north of Brazil from cervical cancers and precancerous lesions.

  4. Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

    International Nuclear Information System (INIS)

    Rude, J.M.; Friedberg, E.C.

    1977-01-01

    Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to UV radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a UV fluence of 5 J/m 2 . At this same UV fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the UV fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in UV-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semiconservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity

  5. Pst I restriction fragment length polymorphism of the human placental alkaline phosphatase gene in normal placentae and tumors

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Kam, W.; Sussman, H.H.

    1987-01-01

    The structure of the human placental alkaline phosphatase gene from normal term placentae was studied by restriction enzyme digestion and Southern blot analysis using a cDNA probe to the gene for the placental enzyme. The DNA digests fall into three distinct patterns based on the presence and intensity of an extra 1.1-kilobase Pst I Band. The extra 1.1-kilobase band is present in 9 of 27 placenta samples, and in 1 of these samples the extra band is present at double intensity. No polymorphism was revealed by digestion with restriction enzymes EcoRI, Sma I, BamHI, or Sac I. The extra Pst I-digestion site may lie in a noncoding region of the gene because no correlation was observed between the restriction fragment length polymorphism and the common placental alkaline phosphatase alleles identified by starch gel electrophoresis. In addition, because placental alkaline phosphatase is frequently re-expressed in neoplasms, the authors examined tissue from ovarian, testicular, and endometrial tumors and from BeWo choriocarcinoma cells in culture. The Pst I-DNA digestion patterns from these cells and tissues were identical to those seen in the normal ovary and term placentae. The consistent reproducible digestion patterns seen in DNA from normal and tumor tissue indicate that a major gene rearrangement is not the basis for the ectopic expression of placental alkaline phosphatase in neoplasia

  6. Semi-conservative deoxyribonucleic acid synthesis in unirradiated and ultraviolet-irradiated xeroderma pigmentosum and normal human skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Rude' e, J.M.; Friedberg, E.C.

    1977-03-01

    Rates of semiconservative DNA synthesis have been investigated in asynchronous xeroderma pigmentosum (XP), XP variant, and normal human skin fibroblasts using the technique of cellular autoradiography. In unirradiated cells, no differences in DNA synthesis rates were detected among the three cell strains. Exposure to uv radiation caused the rate of DNA synthesis to decrease for at least three hours in all three cell strains. In the normal cell strain, recovery of the DNA synthetic rate occurred at later times following a uv fluence of 5 J/m2. At this same uv fluence, recovery was absent in classical XP cells during a 24 h post-irradiation period while it was slower than normal in XP variant cells. When the uv fluence to classical XP and XP variant cells was reduced so that survival in all three cell strains was approximately the same (25%), recovery of the DNA synthetic rate was similar in all three cell strains. These results are discussed in terms of current models of DNA replication in uv-irradiated cells and indicate: (1) that pyrimidine dimers are very effective blocks to DNA synthesis and (2) that there is no inherent defect in semi-conservative DNA synthesis in either classical XP or XP variant cells which is independent of a defect in DNA repair capacity.

  7. Blood flow, flow reserve, and glucose utilization in viable and nonviable myocardium in patients with ischemic cardiomyopathy.

    Science.gov (United States)

    Zhang, Xiaoli; Schindler, Thomas H; Prior, John O; Sayre, James; Dahlbom, Magnus; Huang, Sung-Cheng; Schelbert, Heinrich R

    2013-04-01

    The aim of the study was to determine whether glucose uptake in viable myocardium of ischemic cardiomyopathy patients depends on rest myocardial blood flow (MBF) and the residual myocardial flow reserve (MFR). Thirty-six patients with ischemic cardiomyopathy (left ventricular ejection fraction 25 ± 10 %) were studied with (13)N-ammonia and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Twenty age-matched normals served as controls. Regional MBF was determined at rest and during dipyridamole hyperemia and regional FDG extraction was estimated from regional FDG to (13)N-ammonia activity ratios. Rest MBF was reduced in viable (0.42 ± 0.18 ml/min per g) and nonviable regions (0.32 ± 0.09 ml/min per g) relative to remote regions (0.68 ± 0.23 ml/min per g, p MFRs did not differ significantly (p > 0.05). Compared to MFR in remote myocardium, MFRs in viable regions were similar (1.39 ± 0.56 vs 1.70 ± 0.45, p > 0.05) but were significantly lower in nonviable regions (1.23 ± 0.43, p MFRs (r =-0.424, p MFRs in viable myocardium are associated with increasing glucose extraction that likely reflects a metabolic adaptation of remodeling hibernating myocytes.

  8. Serum from calorie-restricted animals delays senescence and extends the lifespan of normal human fibroblasts in vitro.

    Science.gov (United States)

    de Cabo, Rafael; Liu, Lijuan; Ali, Ahmed; Price, Nathan; Zhang, Jing; Wang, Mingyi; Lakatta, Edward; Irusta, Pablo M

    2015-03-01

    The cumulative effects of cellular senescence and cell loss over time in various tissues and organs are considered major contributing factors to the ageing process. In various organisms, caloric restriction (CR) slows ageing and increases lifespan, at least in part, by activating nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylases of the sirtuin family. Here, we use an in vitro model of CR to study the effects of this dietary regime on replicative senescence, cellular lifespan and modulation of the SIRT1 signaling pathway in normal human diploid fibroblasts. We found that serum from calorie-restricted animals was able to delay senescence and significantly increase replicative lifespan in these cells, when compared to serum from ad libitum fed animals. These effects correlated with CR-mediated increases in SIRT1 and decreases in p53 expression levels. In addition, we show that manipulation of SIRT1 levels by either over-expression or siRNA-mediated knockdown resulted in delayed and accelerated cellular senescence, respectively. Our results demonstrate that CR can delay senescence and increase replicative lifespan of normal human diploid fibroblasts in vitro and suggest that SIRT1 plays an important role in these processes.

  9. Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles.

    Science.gov (United States)

    Andersen, Claus Yding; Schmidt, Kirsten Tryde; Kristensen, Stine Gry; Rosendahl, Mikkel; Byskov, Anne Grete; Ernst, Erik

    2010-05-01

    The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size. A group of 103 women having one ovary removed for fertility preservation by cryopreservation prior to gonadotoxic treatment served as a source of a total of 272 human small antral follicles. Prior to cryopreservation of the ovarian cortex, fluid from small antral follicles were collected. On the basis of the follicular volume, the diameter was calculated and follicles with diameters from 3 to 12 mm were included. Concentrations of AMH decreased significantly (P younger than 10 years showed the same range of AMH concentrations as those from older girls or women. The intrafollicular concentrations of AMH become progressively lower with increasing follicle diameters. In contrast, concentrations of inhibin-B increased with increasing follicle diameter with peak values at around 9 mm in diameter. This suggests that AMH and inhibin-B undertake important intrafollicular functions around the time of normal follicular selection in the mid-follicular phase of the menstrual cycle.

  10. Procalcitonin NH2-terminal cleavage peptide has no mitogenic effect on normal human osteoblast-like cells

    International Nuclear Information System (INIS)

    Hassager, C.; Bonde, S.K.; Anderson, M.A.; Rink, H.; Spelsberg, T.C.; Riggs, B.L.

    1991-01-01

    The NH2-terminal cleavage peptide of procalcitonin (N-proCT) recently was reported to be a bone cell mitogen. The authors have investigated the effect of N-proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N-proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 microM did not significantly increase [3H]thymidine uptake (means ranged from -19% to 38% of control, no significant differences) in hOB cells (6-10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor β (3 ng/ml), bovine insulin (300 micrograms/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus they data do not support the hypothesis that N-proCT is a potent mitogen for normal human osteoblasts

  11. Cytotoxic effect of wine polyphenolic extracts and resveratrol against human carcinoma cells and normal peripheral blood mononuclear cells.

    Science.gov (United States)

    Matić, Ivana; Zizak, Zeljko; Simonović, Mladen; Simonović, Branislav; Godevac, Dejan; Savikin, Katarina; Juranić, Zorica

    2010-08-01

    Red and white wine polyphenols have been reported to provide substantial health benefits. In this study, the cytotoxic activity of red and white wine polyphenolic extracts and of resveratrol was evaluated against different cancer cell lines--human cervix adenocarcinoma HeLa, human breast adenocarcinoma MDA-MB-361, and human breast carcinoma MDA-MB-453--and normal human peripheral blood mononuclear cells (PBMCs). Qualitative and quantitative compositions of wine polyphenolic extracts obtained by fractional vacuum distillation of corresponding wines were determined using spectrophotometric methods and high-performance liquid chromatography with diode array detection and liquid chromatography with electrospray ionization-time of flight mass spectrometry analysis. It was demonstrated that wine polyphenolic extracts and resveratrol exerted higher cytotoxic activity against HeLa and MDA-MB-453 cells in comparison to MDA-MB-361 cells and unstimulated and stimulated PBMCs. Furthermore, white wine polyphenolic extract exhibited a significantly higher antiproliferative action on cancer cell lines than red wine extract. The presence of condensed or fragmented nuclei in HeLa cells, pretreated with extract of white wine and stained with a mixture of acridine orange and ethidium bromide, pointed to the morphological signs of apoptosis. In addition, HeLa cells in late stages of apoptosis or secondary necrosis were also observed. Results from our study suggest that polyphenolic extracts from red and white wine may have anticarcinogenic potential.

  12. Experience with Subgam, a Subcutaneously Administered Human Normal Immunoglobulin (ClinicalTrials.gov--NCT02247141.

    Directory of Open Access Journals (Sweden)

    Clive Dash

    Full Text Available A multi-centre, non-comparative study examining the efficacy and safety of Subgam, a normal immunoglobulin (IgG given weekly as a rapid subcutaneous infusion to patients with primary immune deficiency (PID, is reported. Also included is a summary of adverse drug reactions associated with the use of marketed Subgam in the UK.50 patients with stable PID on IgG therapy were enrolled: Stage 1 included three infusions with prior IgG product followed by 6 months with Subgam, Stage 2 involved long-term Subgam therapy up to 4 years.Stage 1, 85% of the subjects aged >12 years and 93% of the subjects aged <12 years achieved IgG levels ≥6 and ≥4 g/L, respectively at all observations. There were 3.62 infections/patient/year during Subgam treatment. The most common product-related events were infusion site reactions (50% of patients. Recent post-hoc pharmacokinetics analysis of the post-infusion serum total IgG concentration indicated that the mean dose-normalised incremental IgG AUCτ following intravenous dosing (120.5 g.day/L was 1.64-fold that of the dose-normalised mean incremental IgG AUCτ following subcutaneous dosing (73.6 g.day/L, corresponding to an estimated IgG bioavailability for subcutaneous dosing of 61%. Only 34 post-licensing adverse reactions have been received in 30 patients over a period of 10 years; fourteen were classed as serious as defined by the ICH guidelines on good clinical practice. The most common post-licensing adverse reaction was infusion site reaction (7 reports. There were 7 reports of flu-like symptoms (pyrexia/shivering/rigors/feeling hot or cold, 2 other reports of combined flu-like symptoms and infusion site reactions, 5 reports of generalised skin reactions, and 3 reports of combined infusion site and skin reactions. There were also reports of anaphylaxis (2 reports and 8 other adverse events (including headache. In conclusion, Subgam is effective and well tolerated in the treatment of PID.ClinicalTrials.gov NCT

  13. Dynamic CT perfusion imaging of the myocardium: a technical note on improvement of image quality.

    Directory of Open Access Journals (Sweden)

    Daniela Muenzel

    Full Text Available OBJECTIVE: To improve image and diagnostic quality in dynamic CT myocardial perfusion imaging (MPI by using motion compensation and a spatio-temporal filter. METHODS: Dynamic CT MPI was performed using a 256-slice multidetector computed tomography scanner (MDCT. Data from two different patients-with and without myocardial perfusion defects-were evaluated to illustrate potential improvements for MPI (institutional review board approved. Three datasets for each patient were generated: (i original data (ii motion compensated data and (iii motion compensated data with spatio-temporal filtering performed. In addition to the visual assessment of the tomographic slices, noise and contrast-to-noise-ratio (CNR were measured for all data. Perfusion analysis was performed using time-density curves with regions-of-interest (ROI placed in normal and hypoperfused myocardium. Precision in definition of normal and hypoperfused areas was determined in corresponding coloured perfusion maps. RESULTS: The use of motion compensation followed by spatio-temporal filtering resulted in better alignment of the cardiac volumes over time leading to a more consistent perfusion quantification and improved detection of the extend of perfusion defects. Additionally image noise was reduced by 78.5%, with CNR improvements by a factor of 4.7. The average effective radiation dose estimate was 7.1±1.1 mSv. CONCLUSION: The use of motion compensation and spatio-temporal smoothing will result in improved quantification of dynamic CT MPI using a latest generation CT scanner.

  14. Dynamic CT Perfusion Imaging of the Myocardium: A Technical Note on Improvement of Image Quality

    Science.gov (United States)

    Gramer, Bettina; Leber, Vivian; Vembar, Mani; Schmitt, Holger; Wildgruber, Moritz; Fingerle, Alexander A.; Rummeny, Ernst J.; Huber, Armin; Noël, Peter B.

    2013-01-01

    Objective To improve image and diagnostic quality in dynamic CT myocardial perfusion imaging (MPI) by using motion compensation and a spatio-temporal filter. Methods Dynamic CT MPI was performed using a 256-slice multidetector computed tomography scanner (MDCT). Data from two different patients–with and without myocardial perfusion defects–were evaluated to illustrate potential improvements for MPI (institutional review board approved). Three datasets for each patient were generated: (i) original data (ii) motion compensated data and (iii) motion compensated data with spatio-temporal filtering performed. In addition to the visual assessment of the tomographic slices, noise and contrast-to-noise-ratio (CNR) were measured for all data. Perfusion analysis was performed using time-density curves with regions-of-interest (ROI) placed in normal and hypoperfused myocardium. Precision in definition of normal and hypoperfused areas was determined in corresponding coloured perfusion maps. Results The use of motion compensation followed by spatio-temporal filtering resulted in better alignment of the cardiac volumes over time leading to a more consistent perfusion quantification and improved detection of the extend of perfusion defects. Additionally image noise was reduced by 78.5%, with CNR improvements by a factor of 4.7. The average effective radiation dose estimate was 7.1±1.1 mSv. Conclusion The use of motion compensation and spatio-temporal smoothing will result in improved quantification of dynamic CT MPI using a latest generation CT scanner. PMID:24130697

  15. Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test.

    Science.gov (United States)

    Keller, Marla J; Burk, Robert D; Massad, L Stewart; Eltoum, Isam-Eldin; Hessol, Nancy A; Castle, Philip E; Anastos, Kathryn; Xie, Xianhong; Minkoff, Howard; Xue, Xiaonan; D'Souza, Gypsyamber; Flowers, Lisa; Levine, Alexandra M; Colie, Christine; Rahangdale, Lisa; Fischl, Margaret A; Palefsky, Joel M; Strickler, Howard D

    2015-11-15

    Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Biphasic and region-specific MAO-B response to aging in normal human brain.

    Science.gov (United States)

    Saura, J; Andrés, N; Andrade, C; Ojuel, J; Eriksson, K; Mahy, N

    1997-01-01

    Variations of monoamine oxidases (MAO) A and B were studied during aging in 27 human subjects (age range 17-93 years) in 18 brain structures of temporal cortex, frontal gyrus, hippocampal formation, striatum, cerebellum, and brainstem. [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. Postmortem delay or time of tissue storage did not affect MAO-A or MAO-B levels. There was, moreover, no evidence of sexual dimorphism. A marked age-related increase in MAO-B was observed in most structures. This increase started at the age of 50-60 years. Before this age, MAO-B levels were constant in all structures studied. MAO-B-rich senile plaques were observed in some cortical areas but they did not significantly influence the age-related MAO-B increase. Surprisingly, no age-related MAO-B changes were observed in the substantia nigra. In contrast to MAO-B, no clear age-related changes in MAO-A were observed, indicating an independent regulation of the two isoenzymes, also suggested by the cross-correlation analysis of these data.

  17. Birth weight correlates with size but not shape of the normal human placenta.

    Science.gov (United States)

    Haeussner, E; Schmitz, C; von Koch, F; Frank, H-G

    2013-07-01

    Studies on developmental programming rely on various measures of size and form of the human placenta. Size and form are not independent of each other and covariation patterns were not determined systematically. Twenty-two morphologic parameters were determined on 418 placentas from uncomplicated singleton pregnancies. We determined (i) placenta weight and birth weight, (ii) form parameters such as diameters, thickness, roundness, and eccentricity of cord insertion, and (iii) shape variability by geometric morphometry. Geometric morphometry analyzes shape variability independent of size. We define the technical terms form and shape according to the language of geometric morphometry. Placenta weight correlated with birth weight. The form parameters correlated variably with placenta weight and shape. Shape variability did not correlate with birth weight and placenta weight. The correlation of placenta weight with birth weight stays a cornerstone of prenatal programming. Shape analysis shows that form parameters are hybrids of size and shape. Shape variability can be interpreted as an outcome of adaptation of a placenta to maternal factors and the associated uterine habitat. Correlation analysis of the whole data array provides a rigorous statistical frame to interpret published data and plan new studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Early kinetics of thyroid trap in normal human patients and in thyroid diseases

    International Nuclear Information System (INIS)

    Bazin, J.P.; Fragu, P.; Paola, R. di; Paola, M. di; Tubiana, M.

    1981-01-01

    A six-compartment model is proposed for the study of early iodine kinetics in the human thyroid gland including three compartments for extrathyroidal spaces. The results were compared with those obtained with an open two-compartment thyroidal model. In six euthyroid subjects the values of the unidirectional thyroid clearance and of the irreversible clearance were consistent with those generally accepted. With TSH stimulation a clear increase in the thyroidal pump effectiveness was found without an increase in the irreversible clearance. In four untreated thyrotoxic patients a tenfold increase in the unidirectional thyroid clearance was found. The unidirectional clearance remained elevated in seven patients after Carbimazole treatment and the binding rates were reduced. The six-compartment model demonstrated a rapid exit from the bound iodine compartment. In three of four goitrous patients studied, the thyroid unidirectional clearance was significantly increased. The volumes of the iodide compartments were much higher than those observed in the other groups. The method was applied to analyse the kinetics of different parts of the thyroid. (orig./MG)

  19. Secondhand smoke inhibits both Cl- and K+ conductances in normal human bronchial epithelial cells

    Directory of Open Access Journals (Sweden)

    Cohen Noam A

    2009-11-01

    Full Text Available Abstract Secondhand smoke (SHS exposure is an independent risk factor for asthma, rhinosinusitis, and more severe respiratory tract infections in children and adults. Impaired mucociliary clearance with subsequent mucus retention contributes to the pathophysiology of each of these diseases, suggesting that altered epithelial salt and water transport may play an etiological role. To test the hypothesis that SHS would alter epithelial ion transport, we designed a system for in vitro exposure of mature, well-differentiated human bronchial epithelial cells to SHS. We show that SHS exposure inhibits cAMP-stimulated, bumetanide-sensitive anion secretion by 25 to 40% in a time-dependent fashion in these cells. Increasing the amount of carbon monoxide to 100 ppm from 5 ppm did not increase the amount of inhibition, and filtering SHS reduced inhibition significantly. It was determined that SHS inhibited cAMP-dependent apical membrane chloride conductance by 25% and Ba2+-sensitive basolateral membrane potassium conductance by 50%. These data confirm previous findings that cigarette smoke inhibits chloride secretion in a novel model of smoke exposure designed to mimic SHS exposure. They also extend previous findings to demonstrate an effect on basolateral K+ conductance. Therefore, pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance might be of therapeutic benefit in patients with diseases related to SHS exposure.

  20. Secondhand smoke inhibits both Cl- and K+ conductances in normal human bronchial epithelial cells.

    Science.gov (United States)

    Savitski, Amy N; Mesaros, Clementina; Blair, Ian A; Cohen, Noam A; Kreindler, James L

    2009-11-27

    Secondhand smoke (SHS) exposure is an independent risk factor for asthma, rhinosinusitis, and more severe respiratory tract infections in children and adults. Impaired mucociliary clearance with subsequent mucus retention contributes to the pathophysiology of each of these diseases, suggesting that altered epithelial salt and water transport may play an etiological role. To test the hypothesis that SHS would alter epithelial ion transport, we designed a system for in vitro exposure of mature, well-differentiated human bronchial epithelial cells to SHS. We show that SHS exposure inhibits cAMP-stimulated, bumetanide-sensitive anion secretion by 25 to 40% in a time-dependent fashion in these cells. Increasing the amount of carbon monoxide to 100 ppm from 5 ppm did not increase the amount of inhibition, and filtering SHS reduced inhibition significantly. It was determined that SHS inhibited cAMP-dependent apical membrane chloride conductance by 25% and Ba2+-sensitive basolateral membrane potassium conductance by 50%. These data confirm previous findings that cigarette smoke inhibits chloride secretion in a novel model of smoke exposure designed to mimic SHS exposure. They also extend previous findings to demonstrate an effect on basolateral K+ conductance. Therefore, pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance might be of therapeutic benefit in patients with diseases related to SHS exposure.

  1. Morphological aspects of myocardium energy deficiency at the chronic hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    M. V. Danylishyna

    2012-08-01

    Full Text Available Experimental chronic hypercholesterolemia manifests itself by morphological heterogeneity of cardiomyocytes which is caused by parallel proceeding of alteration and adaptation processes in cells. These processes arise against the background of gradually increasing energy deficiency that is testified by changes of activity of oxidation-reduction enzymes. Morphologically these changes show rearrangement and disorder of glycocalix and receptor apparatus of cardiomyocytes, modification of cytomembranes with the change of activity of associated enzymes, dislipoproteinemia and oxidative stress; electrolyte homeostasis disturbance; dysfunction and discoordination of intracellular depot Са2+; adaptive hypertrophy, atrophy and small-focal alteration of some cells. These morphological changes lead to myocardial deficiency and can be accompanied by manifestation of the electric instability of myocardium.

  2. Pathomorphological Changes of the Myocardium in Canine Dilated Cardiomyopathy (DCM

    Directory of Open Access Journals (Sweden)

    Janus Izabela

    2015-04-01

    Full Text Available The study was conducted on ventricular and atrial wall preparations from 11 dogs with clinically diagnosed dilated cardiomyopathy. After fixation, the specimens were stained with haematoxylin and eosin and Masson-Goldner trichrome technique. Parenchymal changes (fibrosis and fatty infiltration, vascular changes (congestion and coronary vessel wall hypertrophy, degenerative changes (loss of striation, changes in cardiomycyte and nuclei structure, and presence of inflammatory infiltrates (mononuclear and polynuclear were estimated. Complex histological changes in both ventricular and atrial muscles were shown. It was not determined whether the processes occurring in the myocardium have a primary character, or are a consequence of developing heart failure. Such issues will be put under further and more detailed examination.

  3. Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage.

    Science.gov (United States)

    Manicourt, D H; Druetz-Van Egeren, A; Haazen, L; Nagant de Deuxchaisnes, C

    1994-01-01

    1. As nonsteroidal anti-inflammatory drugs may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan (PG) and hyaluronan (HA) molecules produced by tenoxicam and aspirin in human normal cartilage explants and in osteoarthritic (OA) cartilage from age-matched donors. 2. Explants were sampled from the medial femoral condyle and were classified by use of Mankin's histological-histochemical grading system. Cartilage specimens were normal in 10 subjects, exhibited moderate OA (MOA) in 10 and had severe OA (SOA) in 10. 3. Cartilage explants were pulsed with [3H]-glucosamine and chased in the absence and in the presence of either aspirin (190 micrograms ml-1) or tenoxicam (4-16 micrograms ml-1). After papain digestion, the labelled chondroitin sulphate ([3H]-PGs) and HA([3H]-HA) molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In normal cartilage as well as in explants with MOA and SOA aspirin reduced more strongly PG and HA synthesis than the loss of [3H]-HA and [3H]-PGs. 5. In normal cartilage, tenoxicam did not affect PG metabolism whereas it reduced HA synthesis in a dose-dependent manner and did not change or even increased the net loss of [3H]-HA. In contrast, in OA cartilage, tenoxicam produced a stronger reduction in the loss of [3H]-PGs than in PG synthesis and this decrease occurred at lower concentrations in cartilage with SOA (4-8 micrograms ml-1) than in cartilage with MOA (8-16 micrograms ml-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889262

  4. Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin

    Energy Technology Data Exchange (ETDEWEB)

    Yamakoshi, Takako [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Makino, Teruhiko, E-mail: tmakino@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Ur Rehman, Mati; Yoshihisa, Yoko [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Sugimori, Michiya [Department of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Shimizu, Tadamichi, E-mail: shimizut@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan)

    2013-03-01

    Highlights: ► Trichohyalin-like 1 protein is a member of the fused-type S100 protein gene family. ► Specific antibodies against the C-terminus of the TCHHL1 protein were generated. ► TCHHL1 proteins were expressed in the basal layer of the normal epidermis. ► TCHHL1 proteins were strongly expressed in tumor nests of BCC and SCC. ► The expression of TCHHL1 proteins increased in epidermis of psoriasis vulgaris. - Abstract: Trichohyalin-like 1 (TCHHL1) protein is a novel member of the fused-type S100 protein gene family. The deduced amino acid sequence of TCHHL1 contains an EF-hand domain in the N-terminus, one trans-membrane domain and a nuclear localization signal. We generated specific antibodies against the C-terminus of the TCHHL1 protein and examined the expression of TCHHL1 proteins in normal and pathological human skin. An immunohistochemical study showed that TCHHL1 proteins were expressed in the basal layer of the normal epidermis. In addition, signals of TCHHL1 proteins were observed around the nuclei of cultured growing keratinocytes. Accordingly, TCHHL1 mRNA has been detected in normal skin and cultured growing keratinocytes. Furthermore, TCHHL1 proteins were strongly expressed in the peripheral areas of tumor nests in basal cell carcinomas and squamous cell carcinomas. A dramatic increase in the number of Ki67 positive cells was observed in TCHHL1-expressing areas. The expression of TCHHL1 proteins also increased in non-cancerous hyperproliferative epidermal tissues such as those of psoriasis vulgaris and lichen planus. These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes.

  5. Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin

    International Nuclear Information System (INIS)

    Yamakoshi, Takako; Makino, Teruhiko; Ur Rehman, Mati; Yoshihisa, Yoko; Sugimori, Michiya; Shimizu, Tadamichi

    2013-01-01

    Highlights: ► Trichohyalin-like 1 protein is a member of the fused-type S100 protein gene family. ► Specific antibodies against the C-terminus of the TCHHL1 protein were generated. ► TCHHL1 proteins were expressed in the basal layer of the normal epidermis. ► TCHHL1 proteins were strongly expressed in tumor nests of BCC and SCC. ► The expression of TCHHL1 proteins increased in epidermis of psoriasis vulgaris. - Abstract: Trichohyalin-like 1 (TCHHL1) protein is a novel member of the fused-type S100 protein gene family. The deduced amino acid sequence of TCHHL1 contains an EF-hand domain in the N-terminus, one trans-membrane domain and a nuclear localization signal. We generated specific antibodies against the C-terminus of the TCHHL1 protein and examined the expression of TCHHL1 proteins in normal and pathological human skin. An immunohistochemical study showed that TCHHL1 proteins were expressed in the basal layer of the normal epidermis. In addition, signals of TCHHL1 proteins were observed around the nuclei of cultured growing keratinocytes. Accordingly, TCHHL1 mRNA has been detected in normal skin and cultured growing keratinocytes. Furthermore, TCHHL1 proteins were strongly expressed in the peripheral areas of tumor nests in basal cell carcinomas and squamous cell carcinomas. A dramatic increase in the number of Ki67 positive cells was observed in TCHHL1-expressing areas. The expression of TCHHL1 proteins also increased in non-cancerous hyperproliferative epidermal tissues such as those of psoriasis vulgaris and lichen planus. These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes

  6. Sesame oil enhances endogenous antioxidants in ischemic myocardium of rat

    Directory of Open Access Journals (Sweden)

    T. S. Mohamed Saleem

    2012-06-01

    Full Text Available The present study was designed to evaluate the potency of antioxidant activity of sesame oil in-vitro model of myocardial ischemic reperfusion injury of rat. Sesame oil was administered orally to Wistar albino rats (180-200 g in two different doses (n=6, by gastric gavage at a dose of 5 mL/kg b.w. (S1 and 10 mL/kg b.w (S2 daily for thirty days. Control and sesame oil treated rat hearts were subjected to invitro global ischemic reperfusion injury (5 min perfusion, 9 min noflow and 12 min reperfusion. A significant rise in TBARS and decrease of GSH, catalase, LDH, CK and AST occurred in the hearts subjected to in-vitro myocardial ischemic reperfusion injury indicate the myocardial damage through oxidative stress. In sesame oil treated rats there was a significant decrease in TBARS and significant increase in endogenous antioxidants and myocardial marker enzymes in all the groups. In 10 mL/kg treatment group, a significant rise in the levels of GSH, SOD and catalase were observed with marker enzymes, and it shows better recovery profile than the other groups subjected to in-vitro ischemic reperfusion injury. In histological studies, control rats which subjected to IR injury show extensive myocardial damage and all the treatment groups, shows preserved myocardium. The effect of sesame oil was compared with reference compound captopril. The present study demonstrates that the sesame oil treated by the dose 10 mL/kg augments endogenous antioxidant compounds of the rat heart and also prevents the myocardium from in-vitro model of myocardial ischemic reperfusion injury

  7. Charged-particle mutagenesis II. Mutagenic effects of high energy charged particles in normal human fibroblasts

    Science.gov (United States)

    Chen, D. J.; Tsuboi, K.; Nguyen, T.; Yang, T. C.

    1994-10-01

    The biological effects of high LET charged particles are a subject of great concern with regard to the prediction of radiation risk in space. In this report, mutagenic effects of high LET charged particles are quantitatively measured using primary cultures of human skin fibroblasts, and the spectrum of induced mutations are analyzed. The LET of the charged particles ranged from 25 KeV/μm to 975 KeV/gmm with particle energy (on the cells) between 94 - 603 MeV/u. The X-chromosome linked hypoxanthine guanine phosphoribosyl transferase (hprt) locus was used as the target gene. Exposure to these high LET charged particles resulted in exponential survival curves; whereas, mutation induction was fitted by a linear model. The Relative Biological Effect (RBE) for cell-killing ranged from 3.73 to 1.25, while that for mutant induction ranged from 5.74 to 0.48. Maximum RBE values were obtained at the LET of 150 keV/μm. The inactivation cross-section (αi) and the action-section for mutant induction (αm) ranged from 2.2 to 92.0 μm2 and 0.09 to 5.56 × 10-3 μm2, respectively. The maximum values were obtained by 56Fe with an LET of 200 keV/μm. The mutagenicity (αm/αi) ranged from 2.05 to 7.99 × 10-5 with the maximum value at 150 keV/μm. Furthermore, molecular analysis of mutants induced by charged particles indicates that higher LET beams are more likely to cause larger deletions in the hprt locus.

  8. Conantokin probes of NMDA receptors in normal and Alzheimer disease human cerebral cortex

    International Nuclear Information System (INIS)

    Ragnarsson, L.; Dodd, P.R.; Lewis, R.J.

    2002-01-01

    Full text: The pharmacology of the N-methyl-D-aspartate (NMDA) receptor site was examined in pathologically affected and relatively spared regions of cerebral cortex tissue obtained at autopsy from Alzheimer disease cases and matched controls. The affinity and density of the [ 3 H]MK-801 binding site were delineated along with the enhancement of [ 3 H]MK-801 binding by glutamate and spermine. Sites with distinct pharmacologies were distributed regionally through the cortex. The differences could not be explained by variations in the parameters of [ 3 H]MK-801 binding; rather, the data suggest that the subunit composition of NMDA receptors may be locally variable. Selective differences were also found between controls and Alzheimer disease cases in certain brain regions. The interactions of human NMDA sites with the Ala(7) and Lys(7) derivatives of conantokin-G (Con-G) were also characterized. Ala(7)-con-G showed the higher affinity of the two peptides, and also defined two distinct binding sites in controls. In distinction to the Ala(7) peptide, Lys(7)- con-G showed preferential binding to receptor sites in Alzheimer disease cf. control brain. Modified conantokins are useful for identifying differences in subunit composition of the NMDA receptors between brain areas. They may also have potential as protective agents against over-excitation mediated by specific NMDA receptors, which might contribute to localized brain damage in Alzheimer disease. For further characterization of the pharmacology of different NMDA receptor subunits, a mammalian expression system has been developed for the analysis of their responses to selected ligands, including conantokins. Copyright (2002) Australian Neuroscience Society

  9. [The influence of two-month treatment with bromocryptine on activity of the adenylyl cyclase signaling system in the myocardium and testes of rats with type 2 diabetes mellitus].

    Science.gov (United States)

    Derkach, K V; Bondareva, V M; Moyseyuk, I V; Shpakov, A O

    2014-01-01

    One of the common complications of type 2 diabetes mellitus (DM2) are cardiovascular diseases and dysfunctions of the reproductive system, indicating the urgency of developing new approaches to their correction. Last years for the treatment of DM2 began to use bromocryptine (BC), the agonist of type 2 dopamine receptors, which not only restores the energy metabolism, but also prevents the development of cardiovascular diseases. However, the mechanisms and targets of BC action are poorly understood. The purpose of this study was to investigate the effect of BC treatment on functional activity of adenylyl cyclase signaling system (ACSS) in the myocardium and testes of male rats with DM2, which is caused by high-fat diet and treatment with streptozotocin (25 mg/kg). The treatment with BC (60 days, orally at a dose of 0.6 mg/kg once every two days) was started 90 days after the beginning of high-fat diet. Diabetic rats had an increased body weight, elevated triglycerides level, impaired glucose tolerance, and insulin resistance. The treatment with BC resulted in the restoration of glycometabolic indicators and in the improvement of insulin sensitivity. Adenylyl cyclase (AC) stimulating effects of guanylylimidodiphosphate (GppNHp), relaxin, and agonists of β-adrenergic receptors (β3-AR)--isoproterenol and norepinephrine were decreased in the miocardium of the diabetic rats. The corresponding effects of the β-agonists BRL-37344 and CL-316243 was preserved. The inhibitory effect of somatostatin on forskolin-stimulated AC activity was attenuated, while the inhibitory effect of noradrenaline mediated through α2-AR increased. The treatment with BC resulted in the normalization of the adrenergic signaling in the myocardium and partially restoration of AC effects of relaxin and somatostatin. In the testes of diabetic rats, the basal and stimulated by GppNHp, forskolin, human chorionic gonadotropin and pituitary AC-activating polypeptide AC activity were decreased, and the

  10. Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation

    Directory of Open Access Journals (Sweden)

    Sung Yoon Catherine Kang

    2015-12-01

    Full Text Available Human palatine tonsils are oropharyngeal lymphoid tissues containing multiple invaginations (crypts in which the continuity of the outer surface epithelium is disrupted and the isolated epithelial cells intermingle with other cell types. We now show that primitive epithelial cells detectable in vitro in 2D colony assays and in a 3D culture system are CD44+NGFR+ and present in both surface and crypt regions. Transcriptome analysis indicated a high similarity between CD44+NGFR+ cells in both regions, although those isolated from the crypt contained a higher proportion of the most primitive (holoclonogenic cells. Lentiviral transduction of CD44+NGFR+ cells from both regions with human papillomavirus 16-encoded E6/E7 prolonged their growth in 2D cultures and caused aberrant differentiation in 3D cultures. Our findings therefore reveal a shared, site-independent, hierarchical organization, differentiation potential, and transcriptional profile of normal human tonsillar epithelial progenitor cells. They also introduce a new model for investigating the mechanisms of their transformation.

  11. Pitx2 confers left morphological, molecular, and functional identity to the sinus venosus myocardium.

    Science.gov (United States)

    Ammirabile, Grazia; Tessari, Alessandra; Pignataro, Viviana; Szumska, Dorota; Sutera Sardo, Fabio; Benes, Jiri; Balistreri, Mariangela; Bhattacharya, Shoumo; Sedmera, David; Campione, Marina

    2012-02-01

    The sinus venous myocardium, comprising the sinoatrial node (SAN) and sinus horns (SH), is a region subject to congenital malformations and cardiac arrhythmias. It differentiates from symmetric bilateral mesenchymal precursors, but morphological, molecular, and functional left/right differences are progressively established through development. The role of the laterality gene Pitx2 in this process is unknown. We aimed to elucidate the molecular events driving left/right patterning in the sinus venosus (SV) myocardium by using a myocardial Pitx2 knockout mouse. We generated a myocardial specific Pitx2 knockout model (cTP mice). cTP embryos present several features of Pitx2 null, including right atrial isomerism with bilateral SANs and symmetric atrial entrance of the systemic veins. By in situ hybridization and optical mapping analysis, we compared throughout development the molecular and functional properties of the SV myocardium in wt and mutant embryos. We observed that Pitx2 prevents the expansion of the left-SAN primordium at the onset of its differentiation into myocardium; Pitx2 promotes expansion of the left SH through development; Pitx2 dose-dependently represses the autorhythmic properties of the left SV myocardium at mid-gestation (E14.5); Pitx2 modulates late foetal gene expression at the left SH-derived superior caval vein. Pitx2 drives left/right patterning of the SV myocardium through multiple developmental steps. Overall, Pitx2 plays a crucial functional role by negatively modulating a nodal-type programme in the left SV myocardium.

  12. Analysis of activin/TGFB-signaling modulators within the normal and dysfunctional adult human testis reveals evidence of altered signaling capacity in a subset of seminomas

    DEFF Research Database (Denmark)

    Dias, Vinali L; Rajpert-De Meyts, Ewa; McLachlan, Robert

    2009-01-01

    cancer patients and from normal men subjected to gonadotropin suppression with androgen-based contraceptives. Our findings identify distinct differences between normal and gonadotropin-deprived human testis in the expression and cellular localization of activin/TGFB-signaling modulators. The presence...

  13. Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

    Science.gov (United States)

    Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small

  14. Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Lang-Jensen, T; Hansen, J M

    1994-01-01

    The present study investigated the contribution of adrenergic beta 1-receptor stimulation to the cardiovascular and renal effects of low-dose dopamine in eight normal, water-loaded humans. Metoprolol (100 mg) or placebo was administered orally at 08.00 h in a randomized, double-blind fashion on two...... outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi...... and sodium clearance (CLNa) by 19% (P Metoprolol blunted the dopamine-induced increases in heart rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P metoprolol, P

  15. The distribution of trace elements in normal human liver determined by semi-automated radiochemical neutron activation analysis

    International Nuclear Information System (INIS)

    Lievens, P.; Cornelis, R.; Hoste, J.; Versieck, J.

    1977-01-01

    The eight segments of five normal human livers are analysed for 25 trace elements by radiochemical NAA. This consists of an automated wet destruction of the samples and two distillations, followed by ion exchange procedures. Ru is used as triplecomparator for the standardization. Short-lived and matrixisotopes are standardized by the Bowen's kale powder. The results reveal that the coefficient of variation within the liver is smaller than 10% for the elements Cd, Cl, Cs, Cu, Fe, K, Mg, Mn, Rb, Se and Zn. The highest range observed for the elements As, Br, Co, Cr, Hg, La, Mo, Na and Sb within a liver is smaller than the range observed between the five livers. (T.G.)

  16. Anatomy and metabolism of the normal human brain studied by magnetic resonance at 1.5 Tesla

    International Nuclear Information System (INIS)

    Bottomley, P.A.; Hart, H.R. Jr.; Edelstein, W.A.; Schenck, J.F.; Smith, L.S.; Leue, W.M.; Mueller, O.M.; Redington, R.W.

    1984-01-01

    Proton magnetic resonance (MR) images were obtained of the human head in magnetic fields as high as 1.5 Tesla (T) using slotted resonator high radio-frequency (RF) detection coils. The images showed no RF field penetration problems and exhibited an 11 (+/-1)-fold improvement in signal-to-noise ratio over a .12-T imaging system. The first localized phosphorus 31, carbon 13, and proton MR chemical shift spectra recorded with surface coils from the head and body in the same instrument showed relative concentrations of phosphorus metabolites, triglycerides, and, when correlated with proton images, negligible lipid (-CH 2 -) signal from brain tissue on the time scale of the imaging experiment. Sugar phosphate and phosphodiester concentrations were significantly elevated in the head compared with muscle. This method should allow the combined assessment of anatomy, metabolism, and biochemistry in both the normal and diseased brain

  17. Short communication: Effects of Lactobacillus helveticus-fermented milk on the differentiation of cultured normal human epidermal keratinocytes.

    Science.gov (United States)

    Baba, H; Masuyama, A; Takano, T

    2006-06-01

    Effects of Lactobacillus helveticus-fermented milk whey on the differentiation of normal human epidermal keratinocytes were studied. Analysis using real-time reverse transcription-polymerase chain reaction revealed that addition of Lactobacillus helveticus-fermented milk whey to the culture medium enhanced mRNA expression of keratin 10, an early differentiation marker, as well as involucrin, a late differentiation marker. Whey of artificially acidified milk, prepared by the addition of dl-lactic acid to milk instead of fermentation, also promoted expression of both markers, but Lactobacillus helveticus-fermented milk whey was more effective in increasing expression of those markers. These results indicate that milk whey has the potential to induce multiple stages of keratinocyte differentiation and that fermentation with Lactobacillus helveticus increases that activity. Furthermore, we examined the expression of profilaggrin, which increases with epidermal terminal differentiation, and found that Lactobacillus helveticus-fermented milk whey enhanced expression of profilaggrin mRNA in a dose-dependent manner. Expression also occurred to a greater extent than with artificially acidified milk whey or other whey samples prepared with several lactic acid bacterial species. Because the proteolytically processed form of profilaggrin, filaggrin, is very important for normal epidermal hydration and flexibility, our results indicate that Lactobacillus helveticus-fermented milk whey has the potential to enhance the production of filaggrin-related natural moisturizing factor, because of its effect on the induction of epidermal differentiation, and is expected to be a useful skin moisturizing agent.

  18. Regulation of tight junctions by sex hormones in normal human endometrial epithelial cells and uterus cancer cell line Sawano.

    Science.gov (United States)

    Someya, Masayuki; Kojima, Takashi; Ogawa, Marie; Ninomiya, Takafumi; Nomura, Kazuaki; Takasawa, Akira; Murata, Masaki; Tanaka, Satoshi; Saito, Tsuyoshi; Sawada, Norimasa

    2013-11-01

    The number of patients with uterine endometrial carcinoma, the cause of which involves sex hormones, has recently been growing rapidly because of increases in life expectancy and obesity. Tight junction proteins claudin-3 and -4 are receptors of Clostridium perfringens enterotoxin (CPE) and increase during endometrial carcinogenesis. In the present study of normal human endometrial epithelial (HEE) cells and the uterus cancer cell line Sawano, we investigate changes in the expression of tight junction proteins including claudin-3 and -4, the fence and barrier functions of the tight junction and the cytotoxic effects of CPE by sex hormones. In primary cultured HEE cells, treatment with progesterone (P4) but not estradiol (E2), induced claudin-1, -3, -4 and -7 and occludin, together with the downregulation of the barrier function but not the fence function. In Sawano cells, claudin-3 and -4 were upregulated by E2 but not by P4, together with a disruption of both the barrier and fence function. In primary cultured HEE cells, claudin-3 and -4 were localized at the apicalmost regions (tight junction areas) and no cytotoxicity of CPE was observed. In Sawano cells, claudin-3 and -4 were found not only in the apicalmost regions but also at the basolateral membrane and the cytotoxicity of CPE was enhanced by E2. Thus, tight junctions are physiological regulated by sex hormones in normal HEE cells during the menstrual cycle suggesting that safer and more effective therapeutic methods targeting claudins in uterine cancer can be developed.

  19. Accumulation of abasic sites induces genomic instability in normal human gastric epithelial cells during Helicobacter pylori infection.

    Science.gov (United States)

    Kidane, D; Murphy, D L; Sweasy, J B

    2014-11-24

    Helicobacter pylori infection of the human stomach is associated with inflammation that leads to the release of reactive oxygen and nitrogen species (RONs), eliciting DNA damage in host cells. Unrepaired DNA damage leads to genomic instability that is associated with cancer. Base excision repair (BER) is critical to maintain genomic stability during RONs-induced DNA damage, but little is known about its role in processing DNA damage associated with H. pylori infection of normal gastric epithelial cells. Here, we show that upon H. pylori infection, abasic (AP) sites accumulate and lead to increased levels of double-stranded DNA breaks (DSBs). In contrast, downregulation of the OGG1 DNA glycosylase decreases the levels of both AP sites and DSBs during H. pylori infection. Processing of AP sites during different phases of the cell cycle leads to an elevation in the levels of DSBs. Therefore, the induction of oxidative DNA damage by H. pylori and subsequent processing by BER in normal gastric epithelial cells has the potential to lead to genomic instability that may have a role in the development of gastric cancer. Our results are consistent with the interpretation that precise coordination of BER processing of DNA damage is critical for the maintenance of genomic stability.

  20. Screening between normal and cancer human thyroid cells through comparative adhesion studies using the Quartz Crystal Microbalance

    Directory of Open Access Journals (Sweden)

    Dimitra Chronaki

    2016-12-01

    Full Text Available In this work, the Quartz Crystal Microbalance with Dissipation monitoring (QCM-D was used to distinguish the dynamic cell adhesion behavior of human normal (Nthy thyroid epithelial cells from poorly differentiated anaplastic carcinoma cells (ARO. The surfaces used to facilitate cell adhesion were bare titanium (Ti, gold (Au and fibrinogen-coated gold (Fg-Au. The pattern of cell adhesion for both cell lines was that the largest acoustic signals were observed on Ti, followed by Au and last by Fg-Au; in addition, ARO cells always produced smaller acoustic signals than Nthy cells on the same surface and for the same number of cells in suspension. Moreover, the calculated acoustic ratio of energy dissipation over frequency change suggests a higher ability of Nthy cells to spread and potentially form more attachment points on the surface than the ARO cells, something observed in SEM images. Finally, we demonstrated that the application of two surfaces for cell adhesion experiments, one of which is Au and the other either Ti or Fg-Au, can discriminate with accuracy between the two particular cell types and potentially form a platform for differentiation between normal and cancer thyroid cell types.

  1. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  2. A branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts.

    Science.gov (United States)

    Sakashita, Tetsuya; Hamada, Nobuyuki; Kawaguchi, Isao; Hara, Takamitsu; Kobayashi, Yasuhiko; Saito, Kimiaki

    2014-05-01

    A single cell can form a colony, and ionizing irradiation has long been known to reduce such a cellular clonogenic potential. Analysis of abortive colonies unable to continue to grow should provide important information on the reproductive cell death (RCD) following irradiation. Our previous analysis with a branching process model showed that the RCD in normal human fibroblasts can persist over 16 generations following irradiation with low linear energy transfer (LET) γ-rays. Here we further set out to evaluate the RCD persistency in abortive colonies arising from normal human fibroblasts exposed to high-LET carbon ions (18.3 MeV/u, 108 keV/µm). We found that the abortive colony size distribution determined by biological experiments follows a linear relationship on the log-log plot, and that the Monte Carlo simulation using the RCD probability estimated from such a linear relationship well simulates the experimentally determined surviving fraction and the relative biological effectiveness (RBE). We identified the short-term phase and long-term phase for the persistent RCD following carbon-ion irradiation, which were similar to those previously identified following γ-irradiation. Taken together, our results suggest that subsequent secondary or tertiary colony formation would be invaluable for understanding the long-lasting RCD. All together, our framework for analysis with a branching process model and a colony formation assay is applicable to determination of cellular responses to low- and high-LET radiation, and suggests that the long-lasting RCD is a pivotal determinant of the surviving fraction and the RBE.

  3. A branching process model for the analysis of abortive colony size distributions in carbon ion-irradiated normal human fibroblasts

    International Nuclear Information System (INIS)

    Sakashita, Tetsuya; Kobayashi, Yasuhiko; Hamada, Nobuyuki; Kawaguchi, Isao; Hara, Takamitsu; Saito, Kimiaki

    2014-01-01

    A single cell can form a colony, and ionizing irradiation has long been known to reduce such a cellular clonogenic potential. Analysis of abortive colonies unable to continue to grow should provide important information on the reproductive cell death (RCD) following irradiation. Our previous analysis with a branching process model showed that the RCD in normal human fibroblasts can persist over 16 generations following irradiation with low linear energy transfer (LET) γ-rays. Here we further set out to evaluate the RCD persistency in abortive colonies arising from normal human fibroblasts exposed to high-LET carbon ions (18.3 MeV/u, 108 keV/μm). We found that the abortive colony size distribution determined by biological experiments follows a linear relationship on the log–log plot, and that the Monte Carlo simulation using the RCD probability estimated from such a linear relationship well simulates the experimentally determined surviving fraction and the relative biological effectiveness (RBE). We identified the short-term phase and long-term phase for the persistent RCD following carbon-ion irradiation, which were similar to those previously identified following γ-irradiation. Taken together, our results suggest that subsequent secondary or tertiary colony formation would be invaluable for understanding the long-lasting RCD. All together, our framework for analysis with a branching process model and a colony formation assay is applicable to determination of cellular responses to low- and high-LET radiation, and suggests that the long-lasting RCD is a pivotal determinant of the surviving fraction and the RBE. (author)

  4. Responses of human normal osteoblast cells and osteoblast-like cell line, MG-63 cells, to pulse electromagnetic field (PEMF

    Directory of Open Access Journals (Sweden)

    Suttatip Kamolmatyakul

    2008-01-01

    Full Text Available The objective of this in vitro study is to investigate the effect of pulsed electromagnetic field (PEMF on cellular proliferation and osteocalcin production of osteoblast-like cell line, MG-63 cells, and human normal osteoblast cells (NHOC obtained from surgical bone specimens. The cells were placed in 24-well culture plates in the amount of 3x104 cell/wells with 2 ml αMEM media supplemented with 10% FBS. The experimental plates were placed between a pair of Helmoltz coils powered by a pulse generator (PEMF, 50 Hz, 1.5 mV/cm in the upper compartment of a dual incubator (Forma. The control plates were placed in the lower compartment of the incubator without Helmotz coils. After three days, the cell proliferation was measured by the method modified from Mossman (J. Immunol Methods 1983; 65: 55-63. Other sets of plates were used for osteocalcin production assessment. Media from these sets were collected after 6 days and assessed for osteocalcin production using ELISA kits. The data were analyzed using a one-way analysis of variance (ANOVA. The results showed that MG-63 cells from the experimental group proliferated significantly more than those from the control group (20% increase, p<0.05. No significant difference in osteocalcin production was detected between the two groups. On the other hand, NHOC from the experimental group produced larger amount of osteocalcin (25% increase, p<0.05 and proliferated significantly more than those from the control group (100% increase, p<0.05. In conclusion, PEMF effect on osteoblasts might depend on their cell type of origin. For osteoblast-like cell line, MG-63 cells, PEMF increased proliferation rate but not osteocalcin production of the cells. However, PEMF stimulation effect on human normal osteoblast cells was most likely associated with enhancement of both osteocalcin production and cell proliferation.

  5. Does interstitial adenosine mediate acute hibernation of guinea pig myocardium?

    Science.gov (United States)

    Gao, Z P; Downey, H F; Fan, W L; Mallet, R T

    1995-06-01

    The aim was to test the role of interstitial adenosine in protective downregulation of myocardial energy demand during myocardial hibernation. Isolated working guinea pig hearts, perfused with glucose fortified Krebs-Henseleit, were subjected to 60 min global low flow ischaemia followed by 30 min reperfusion. Left ventricular performance was assessed from heart rate-developed pressure product and pressure-volume work. Cytosolic energy level was indexed by creatine phosphate and ATP phosphorylation potentials measured in snap frozen myocardium. Lactate and purine nucleosides (adenosine, inosine) were measured in venous effluent. When coronary flow was lowered by 80% for 60 min, heart rate-pressure product and pressure-volume work fell 87% and 75%, respectively, and stabilised at these low levels, but fully recovered when flow was restored. Myocardial ATP phosphorylation potential fell by 67% during the first 10 min of ischaemia, but subsequently recovered to preischaemic levels despite continuing ischaemia, indicating down-regulation of myocardial energy demand. Lactate release increased about 10-fold during ischaemia and remained increased until reperfusion. Purine nucleoside release varied reciprocally with phosphorylation potential, peaking at 10 min of ischaemia, then gradually returning to the preischaemic level during the subsequent 50 min of ischaemia. The ecto 5'-nucleotidase inhibitor alpha,beta-methylene adenosine 5'-diphosphonate (50 microM) decreased ischaemic purine nucleoside release by 41%, but did not attenuate postischaemic contractile recovery. The unspecific adenosine receptor antagonist 8-p-sulphophenyl theophylline (8-SPT, 20 microM) doubled ischaemic lactate release and lowered coronary venous purine nucleoside release by 21%. 8-SPT increased phosphorylation potential at 10 min ischaemia relative to untreated hearts, but blunted the subsequent rebound of phosphorylation potential. 8-SPT treatment during ischaemia resulted in a significantly

  6. Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.

    Directory of Open Access Journals (Sweden)

    Didik Priyandoko

    Full Text Available The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera leaf extract on methoxyacetic acid (MAA induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.

  7. The antiproliferative effect of beta-carotene requires p21waf1/cip1 in normal human fibroblasts.

    Science.gov (United States)

    Stivala, L A; Savio, M; Quarta, S; Scotti, C; Cazzalini, O; Rossi, L; Scovassi, I A; Pizzala, R; Melli, R; Bianchi, L; Vannini, V; Prosperi, E

    2000-04-01

    In normal human fibroblasts, beta-carotene induces a cell-cycle delay in the G1 phase independent of its provitamin A activity via a mechanism not yet elucidated. In this study we provide biochemical evidence showing that delayed progression through the G1 phase occurs concomitantly with: an increase in both nuclear-bound and total p21waf1/cip1 protein levels; an increase in the amount of p21waf1/cip1 associated with cdk4; the inhibition of cyclin D1-associated cdk4 kinase activity; and a reduction in the levels of hyperphosphorylated forms of retinoblastoma protein, and particularly, in phosphorylated Ser780. The role of p21waf1/cip1 in the antiproliferative effect of the carotenoid was further supported by genetic evidence that neither changes in cell-cycle progression nor in the phosphorylation status of retinoblastoma protein were observed in p21waf1/cip1-deficient human fibroblasts treated with beta-carotene. These results clearly demonstrate that p21waf1/cip1 is involved directly in the molecular pathway by which beta-carotene inhibits cell-cycle progression.

  8. Low doses of nanodiamonds and silica nanoparticles have beneficial hormetic effects in normal human skin fibroblasts in culture.

    Science.gov (United States)

    Mytych, Jennifer; Wnuk, Maciej; Rattan, Suresh I S

    2016-04-01

    Nanodiamonds (ND) and silica nanoparticles (SiO2-NP) have been much investigated for their toxicity at high doses, little is known about their biological activity at low concentrations. Here we report the biphasic dose response of ND and SiO2-NP in modulating normal human facial skin fibroblasts (FSF1) in culture. ND and SiO2-NP at low concentration (up to 0.5 μg/ml) had beneficial effects on FSF1 in terms of increasing their proliferation and metabolic activity. Exposure of FSF1 cells to low levels of NP enhanced their wound healing ability in vitro and slowed down aging during serial passaging as measured by maintenance of youthful morphology, reduction in the rate of loss of telomeres, and the over all proliferative characteristics. Furthermore, NP treatment induced the activation of Nrf2- and FOXO3A-mediated cellular stress responses, including an increased expression of heme oxygenease (HO-1), sirtuin (SIRT1), and DNA methyltransferase II (DNMT2). These results imply that ND and SiO2-NP at low doses are potential hormetins, which exert mild stress-induced beneficial hormetic effects through improved survival, longevity, maintenance, repair and function of human cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Acrolein-exposed normal human lung fibroblasts in vitro: cellular senescence, enhanced telomere erosion, and degradation of Werner's syndrome protein.

    Science.gov (United States)

    Jang, Jun-Ho; Bruse, Shannon; Huneidi, Salam; Schrader, Ronald M; Monick, Martha M; Lin, Yong; Carter, A Brent; Klingelhutz, Aloysius J; Nyunoya, Toru

    2014-09-01

    Acrolein is a ubiquitous environmental hazard to human health. Acrolein has been reported to activate the DNA damage response and induce apoptosis. However, little is known about the effects of acrolein on cellular senescence. We examined whether acrolein induces cellular senescence in cultured normal human lung fibroblasts (NHLF). We cultured NHLF in the presence or absence of acrolein and determined the effects of acrolein on cell proliferative capacity, senescence-associated β-galactosidase activity, the known senescence-inducing pathways (e.g., p53, p21), and telomere length. We found that acrolein induced cellular senescence by increasing both p53 and p21. The knockdown of p53 mediated by small interfering RNA (siRNA) attenuated acrolein-induced cellular senescence. Acrolein decreased Werner's syndrome protein (WRN), a member of the RecQ helicase family involved in DNA repair and telomere maintenance. Acrolein-induced down-regulation of WRN protein was rescued by p53 knockdown or proteasome inhibition. Finally, we found that acrolein accelerated p53-mediated telomere shortening. These results suggest that acrolein induces p53-mediated cellular senescence accompanied by enhanced telomere attrition and WRN protein down-regulation.

  10. Axial compressive strength of human vertebrae trabecular bones classified as normal, osteopenic and osteoporotic by quantitative ultrasonometry of calcaneus

    Directory of Open Access Journals (Sweden)

    Reinaldo Cesar

    2017-06-01

    Full Text Available Abstract Introduction Biomechanical assessment of trabecular bone microarchitecture contributes to the evaluation of fractures risk associated with osteoporosis and plays a crucial role in planning preventive strategies. One of the most widely clinical technics used for osteoporosis diagnosis by health professionals is bone dual-energy X-ray absorptiometry (DEXA. However, doubts about its accuracy motivate the introduction of congruent technical analysis such as calcaneal ultrasonometry (Quantitative Ultrasonometry - QUS. Methods Correlations between Bone Quality Index (BQI, determined by calcaneal ultrasonometry of thirty (30 individuals classified as normal, osteopenic and osteoporotic, and elastic modulus (E and ultimate compressive strength (UCS from axial compression tests of ninety (90 proof bodies from human vertebrae trabecular bone, which were extracted from cadavers in the twelfth thoracic region (T12, first and fourth lumbar (L1 and L4. Results Analysis of variance (ANOVA showed significant differences for E (p = 0.001, for UCS (p = 0.0001 and BQI. Spearman’s rank correlation coefficient (rho between BQI and E (r = 0.499 and BQI and UCS (r = 0.508 were moderate. Discussion Calcaneal ultrasonometry technique allowed a moderate estimate of bone mechanical strength and fracture risk associated with osteoporosis in human vertebrae.

  11. Analysis of the expression of SDF-1 splicing variants in human colorectal cancer and normal mucosa tissues.

    Science.gov (United States)

    Allami, Risala Hussain; Graf, Claudine; Martchenko, Ksenia; Voss, Beatrice; Becker, Marc; Berger, Martin R; Galle, Peter R; Theobald, Matthias; Wehler, Thomas C; Schimanski, Carl C

    2016-03-01

    C-X-C motif chemokine ligand 12 (CXCL12), also termed stromal cell-derived factor-1 (SDF-1) is a small protein 8-14 kDa in length that is expressed as six isoforms, consisting of SDF-1α, SDF-1β, SDF-1γ, SDF-1δ, SDF-1ε and SDF-1θ. All six isoforms are encoded by the single CXCL12 gene on chromosome 10. This gene regulates leukocyte trafficking and is variably expressed in a number of normal and cancer tissues. The potential role of the novel CXCL12 splice variants as components of the CXCR4 axis in cancer development is not fully understood. The present study aimed to analyze the expression profile of the various SDF-1 isoforms and SDF-1 polymorphisms, and the association with the clinicopathological features and overall survival of patients with colorectal cancer (CRC). SDF-1 polymorphism analysis was performed using restriction fragment length polymorphism (RFLP) analysis in 73 histologically confirmed human CRC tissue samples at various stages of disease. The expression pattern of the SDF-1 isoforms was analyzed by reverse transcription-polymerase chain reaction in 40 histologically confirmed human CRC tissue samples obtained at various stages of disease, as well as in matched adjacent normal mucosa samples. The presence of the CXCL12 gene polymorphism rs1801157 demonstrated an association with local progression of the primary tumor, as indicated by the T stage. The frequency of the GG genotype was slightly increased in patients with stage 3 and 4 tumors (78.0%) compared with the incidence of the GA/AA genotype (69.5%; P=0.067). The expression of SDF-1β was associated with the presence of metastases (P=0.0656) and the expression of SDF-1γ was significantly associated with tumor size (P=0.0423). The present study is the first to analyze the association between the expression profile of the chemokine CXCL12 splice variants in human CRC tissues and their clinical relevance. The present results reveal that the CXCL12 G801A polymorphism is a low

  12. Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Rabya Saraf

    Full Text Available Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome.Yorkshire swine (n = 8 per group were fed a normal diet (ND or a high-cholesterol (HCD for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD.There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002 and Bcl-xL (p = 0.05 and p = 0.01 in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01, pSmad1/5 (p = 0.03 and MMP-9 (p = 0.005 were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively. Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and-dp/dt (p = 0.05 and p = 0.007 respectively in the HCD group.Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

  13. What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

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    Lorena Ruiz

    2017-06-01

    Full Text Available Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα, acquired immunity factors (IL2, IL4, IL10, IL13, IL17, chemokines (IL8, Groα, MCP1, MIP1β, growth factors [IL5, IL7, epidermal growth factor (EGF, granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM, in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02670278.

  14. Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

    Science.gov (United States)

    Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

    2016-10-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PA