Generalized spheroidal wave equation and limiting cases

NASA Astrophysics Data System (ADS)

Figueiredo, B. D. Bonorino

2007-01-01

We find sets of solutions to the generalized spheroidal wave equation (GSWE) or, equivalently, to the confluent Heun equation. Each set is constituted by three solutions, one given by a series of ascending powers of the independent variable, and the others by series of regular and irregular confluent hypergeometric functions. For a fixed set, the solutions converge over different regions of the complex plane but present series coefficients proportional to each other. These solutions for the GSWE afford solutions to a double-confluent Heun equation by a taking-limit process due to Leaver. [E. W. Leaver, J. Math. Phys. 27, 1238 (1986)]. Another procedure, called Whittaker-Ince limit [B. D. Figueiredo, J. Math. Phys. 46, 113503 (2005)], provides solutions in series of powers and Bessel functions for two other equations with a different type of singularity at infinity. In addition, new solutions are obtained for the Whittaker-Hill and Mathieu equations [F. M. Arscott, Proc. R. Soc. Edinburg A67, 265 (1967)] by considering these as special cases of both the confluent and double-confluent Heun equations. In particular, we find that each of the Lindemann-Stieltjes solutions for the Mathieu equation [E. T. Whittaker and G. N. Watson, A Course of Modern Analysis, Cambridge University Press (1945)] is associated with two expansions in series of Bessel functions. We also discuss a set of solutions in series of hypergeometric and confluent hypergeometric functions for the GSWE and use their Leaver limits to obtain infinite-series solutions for the Schrödinger equation with an asymmetric double-Morse potential. Finally, the possibility of extending the solutions of the GSWE to the general Heun equation is briefly discussed.

Aggressive posterior retinopathy of prematurity in Asian Indian babies: spectrum of disease and outcome after laser treatment.

PubMed

Sanghi, Gaurav; Dogra, Mangat R; Das, Pranab; Vinekar, Anand; Gupta, Amod; Dutta, Saurabh

2009-10-01

To analyze the spectrum of aggressive posterior retinopathy of prematurity and outcome after laser treatment. This is a retrospective review of 81 eyes of 44 consecutive infants diagnosed to have aggressive posterior retinopathy of prematurity and treated between September 2005 and March 2007 from a large tertiary care center in North India. Qualitative variables were tested for statistical significance using the chi-square test and independent samples with the student's t-test. Mean birth weight and gestational age were 1,259.66 +/- 310.51 g (range, 660-2,000 g) and 29.75 +/- 2.35 weeks (range, 26-36 weeks), respectively. Twenty-one infants (47.72%) had a birth weight > 1,250 g. Thirty-three (40.74%) eyes had Zone 1, and 48 (59.26%) had posterior Zone 2 disease. All eyes underwent confluent laser photocoagulation at a mean postconceptional age of 34.58 +/- 2.19 weeks (range, 31-40.5 weeks). Mean follow-up was 12.8 months (range, 6-24 months). At the last follow-up visit, 55 (71.4%) of 77 eyes had a favorable outcome. Eighteen eyes (23.4%) had a localized (1-3 clock hours) partial peripheral tractional detachment (Stage 4a), which remained stable at last follow-up. Two eyes (2.6%) developed falciform fold involving the macular area, and 2 (2.6%) developed Stage 5 retinopathy of prematurity. Aggressive posterior retinopathy of prematurity is encountered not only in low birth weight infants, but also in heavier and more mature Asian Indian infants. Early, aggressive confluent laser photocoagulation is necessary to maximize outcomes in these eyes.

A Conditionally Integrable Bi-confluent Heun Potential Involving Inverse Square Root and Centrifugal Barrier Terms

NASA Astrophysics Data System (ADS)

Ishkhanyan, Tigran A.; Krainov, Vladimir P.; Ishkhanyan, Artur M.

2018-05-01

We present a conditionally integrable potential, belonging to the bi-confluent Heun class, for which the Schrödinger equation is solved in terms of the confluent hypergeometric functions. The potential involves an attractive inverse square root term x-1/2 with arbitrary strength and a repulsive centrifugal barrier core x-2 with the strength fixed to a constant. This is a potential well defined on the half-axis. Each of the fundamental solutions composing the general solution of the Schrödinger equation is written as an irreducible linear combination, with non-constant coefficients, of two confluent hypergeometric functions. We present the explicit solution in terms of the non-integer order Hermite functions of scaled and shifted argument and discuss the bound states supported by the potential. We derive the exact equation for the energy spectrum and approximate that by a highly accurate transcendental equation involving trigonometric functions. Finally, we construct an accurate approximation for the bound-state energy levels.

[Study on the term of eight confluent points].

PubMed

Zhao, Jing-Sheng

2012-08-01

In order to understand the connotation and the implication of the eight confluent points, relative modern and ancient literatures were studied systematically. It is discovered that the term of eight confluent points changed several times in its developing history. The term is called as Jiaojing Banue in the very beginning, and later Jingmai Jiaohui Baxue, Bamai Jiaohui Baxue, Ba fa Jiaohui Baxue, etc. Its short terms can be seen as Ba fa Jiaohui and Bafaxue. Other names even shorter can be Bahui, Ba fa and Baxue, etc. The above mentioned names are mixed during their application, and it is also once misunderstood as the concept of Bahuixue in Classic on Medical Problems. It is named as eight confluent points nowadays, and the extra meridians changed from the target meridians which are being intersected with into the major subject in the confluence. While the eight points changed from the main body of confluence into the object of intersection, which indicated that the concept has already changed.

Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jozan, S.; Faye, J.C.; Tournier, J.F.

1985-11-27

The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combinedmore » treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation.« less

Confluent/Humanistic/Affective Education: A Set of Bibliographies.

ERIC Educational Resources Information Center

Tolliver, J. Howard

Over 250 journal articles, ERIC documents, dissertations, and books dealing with confluent, humanistic, and affective education are listed in this annotated bibliography. Journal articles comprise those published since 1975. Other earlier works listed are considered of major importance in the field. The resources are listed under five categories:…

An experimental investigation of the flow physics of high-lift systems

NASA Technical Reports Server (NTRS)

Thomas, Flint O.; Nelson, R. C.

1995-01-01

This progress report, a series of viewgraphs, outlines experiments on the flow physics of confluent boundary layers for high lift systems. The design objective is to design high lift systems with improved C(sub Lmax) for landing approach and improved take-off L/D and simultaneously reduce acquisition and maintenance costs. In effect, achieve improved performance with simpler designs. The research objectives include: establish the role of confluent boundary layer flow physics in high-lift production; contrast confluent boundary layer structure for optimum and non-optimum C(sub L) cases; formation of a high quality, detailed archival data base for CFD/modeling; and examination of the role of relaminarization and streamline curvature.

Observations on the antibody-dependent cytotoxic cell by scanning electron microscopy.

PubMed Central

Inglis, J R; Penhale, W J; Farmer, A; Irvine, W J; Williams, A E

1975-01-01

The cytotoxic effect of human peripheral blood leucocytes on antibody-coated sheep erythrocyte monolayers has been investigated using scanning electron microscopy. Only a small proportion of leucocytes were found to adhere to the monolayers. A progressive destruction was observed beginning as small plaque-like areas of erythrocyte clearing which later became confluent. Three distinct cell types were found to be associated with the areas of lysis. No destruction was observed in control monolayers incubated for a similar period in the absence of either antibody of leucocytes. Surface changes in the erthrocytes adjacent to the leucocytes suggest that mechanical factors may be involved in erythrocyte lysis in this system. It is concluded that more than one leucocyte type may damage antibody-coated erythrocytes, possibly by a mechanism involving attachment to and mechanical disruption of the red cell membrane. Images FIG. 5 FIG. 2 FIG. 3 FIG. 1 FIG. 2 FIG. 4 PMID:1191386

Human Teaching and Human Learning in the Language Class: A Confluent Approach.

ERIC Educational Resources Information Center

Galyean, Beverly

Much attention has been given to the imbalance between thinking and feelings in the educative process. Human teaching calls for merging the cognitive and affective processes into one confluent learning experience. Language learning is viewed primarily as a means for affective reflective communication. Personal growth merges with language…

Static test-stand performance of the YF-102 turbofan engine with several exhaust configurations for the Quiet Short-Haul Research Aircraft (QSRA)

NASA Technical Reports Server (NTRS)

Mcardle, J. G.; Homyak, L.; Moore, A. S.

1979-01-01

The performance of a YF-102 turbofan engine was measured in an outdoor test stand with a bellmouth inlet and seven exhaust-system configurations. The configurations consisted of three separate-flow systems of various fan and core nozzle sizes and four confluent-flow systems of various nozzle sizes and shapes. A computer program provided good estimates of the engine performance and of thrust at maximum rating for each exhaust configuration. The internal performance of two different-shaped core nozzles for confluent-flow configurations was determined to be satisfactory. Pressure and temperature surveys were made with a traversing probe in the exhaust-nozzle flow for some confluent-flow configurations. The survey data at the mixing plane, plus the measured flow rates, were used to calculate the static-pressure variation along the exhaust nozzle length. The computed pressures compared well with experimental wall static-pressure data. External-flow surveys were made, for some confluent-flow configurations, with a large fixed rake at various locations in the exhaust plume.

Experimental study of the separating confluent boundary-layer. Volume 2: Experimental data

NASA Technical Reports Server (NTRS)

Braden, J. A.; Whipkey, R. R.; Jones, G. S.; Lilley, D. E.

1983-01-01

An experimental low speed study of the separating confluent boundary layer on a NASA GAW-1 high lift airfoil is described. The airfoil was tested in a variety of high lift configurations comprised of leading edge slat and trailing edge flap combinations. The primary test instrumentation was a two dimensional laser velocimeter (LV) system operating in a backscatter mode. Surface pressures and corresponding LV derived boundary layer profiles are given in terms of velocity components, turbulence intensities and Reynolds shear stresses as characterizing confluent boundary layer behavior up to and beyond stall. LV derived profiles and associated boundary layer parameters and those obtained from more conventional instrumentation such as pitot static transverse, Preston tube measurements and hot-wire surveys are compared.

Systems and methods to control multiple peripherals with a single-peripheral application code

DOEpatents

Ransom, Ray M.

2013-06-11

Methods and apparatus are provided for enhancing the BIOS of a hardware peripheral device to manage multiple peripheral devices simultaneously without modifying the application software of the peripheral device. The apparatus comprises a logic control unit and a memory in communication with the logic control unit. The memory is partitioned into a plurality of ranges, each range comprising one or more blocks of memory, one range being associated with each instance of the peripheral application and one range being reserved for storage of a data pointer related to each peripheral application of the plurality. The logic control unit is configured to operate multiple instances of the control application by duplicating one instance of the peripheral application for each peripheral device of the plurality and partitioning a memory device into partitions comprising one or more blocks of memory, one partition being associated with each instance of the peripheral application. The method then reserves a range of memory addresses for storage of a data pointer related to each peripheral device of the plurality, and initializes each of the plurality of peripheral devices.

Production of confluent hypergeometric beam by computer-generated hologram

NASA Astrophysics Data System (ADS)

Chen, Jiannong; Wang, Gang; Xu, Qinfeng

2011-02-01

Because of their spiral wave front, phase singularity, zero-intensity center and orbital angular momentum, dark hollow vortex beams have been found many applications in the field of atom optics such as atom cooling, atom transport and atom guiding. In this paper, a method for generating confluent hypergeometric beam by computer-generated hologram displayed on the spatial light modulator is presented. The hologram is formed by interference between a single ring Laguerre-Gaussian beam and a plane wave. The far-field Fraunhofer diffraction of this optical field transmitted from the hologram is the confluent hypergeometric beam. This beam is a circular symmetric beam which has a phase singularity, spiral wave front, zero-intensity center, and intrinsic orbital angular momentum. It is a new dark hollow vortex beam.

The generalized zero-mode supersymmetry scheme and the confluent algorithm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Contreras-Astorga, Alonso, E-mail: aloncont@iun.edu; Schulze-Halberg, Axel, E-mail: axgeschu@iun.edu; Department of Physics, Indiana University Northwest, 3400 Broadway, Gary IN 46408

We show the relationship between the mathematical framework used in recent papers by Rosu et al. (2014) [1–3] and the second-order confluent supersymmetric quantum mechanics. In addition, we point out several immediate generalizations of the approach taken in the latter references. Furthermore, it is shown how to apply the generalized scheme to the Dirac and to the Fokker–Planck equation.

Focal confluent fibrosis in cirrhotic liver: natural history studied with serial CT.

PubMed

Brancatelli, Giuseppe; Baron, Richard L; Federle, Michael P; Sparacia, Gianvincenzo; Pealer, Karen

2009-05-01

The objective of this study was to assess the long-term natural history of focal confluent fibrosis in cirrhotic liver with CT. Two radiologists retrospectively reviewed in consensus 118 liver CT examinations in 26 patients (19 men, seven women; age range, 32-68 years; mean age, 50 years) performed over approximately 6 years. Helical CT scans were obtained before and 30-35 and 65-70 seconds after injection of 125-150 mL of contrast medium at a rate of 4-5 mL/s. Proof of cirrhosis was based on liver transplantation (n = 6), biopsy (n = 9), or imaging findings (n = 11). The number, location, and attenuation of fibrotic lesions and presence of trapped vessels were evaluated. Variation of hepatic retraction associated with the development of focal confluent fibrosis lesions was assessed using the ellipsoid volume formula and an arbitrary retraction index. Each radiologist identified 41 focal confluent fibrosis lesions. All lesions were identified by both radiologists. Twelve patients (46%) had a single lesion, 13 (50%) had two lesions, and one (4%) had three lesions. Thirty-four (83%) of 41 lesions were located in segment IV, VII, or VIII. Thirty-two lesions (78%) were hypoattenuating on unenhanced images, 25 lesions (61%) were hypoattenuating on hepatic arterial phase images, and 20 lesions (49%) were isoattenuating on portal venous phase images. Seven lesions (17%) were or became hyperattenuating at follow-up on portal venous phase images. Trapped vessels were found in six lesions (15%). The retraction index showed a significant increase over time (r = 0.423, p < or = 0.0001). The degree of capsule retraction associated with focal confluent fibrosis evolves with time and relates to the natural evolution of cirrhosis.

Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

PubMed Central

Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

2011-01-01

BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

A novel method for measuring hydraulic conductivity at the human blood-nerve barrier in vitro.

PubMed

Helton, E Scott; Palladino, Steven; Ubogu, Eroboghene E

2017-01-01

Microvascular barrier permeability to water is an essential biophysical property required for the homeostatic maintenance of unique tissue microenvironments. This is of particular importance in peripheral nerves where strict control of ionic concentrations is needed for axonal signal transduction. Previous studies have associated inflammation, trauma, toxin exposure and metabolic disease with increases in water influx and hydrostatic pressure in peripheral nerves with resultant endoneurial edema that may impair axonal function. The regulation of water permeability across endoneurial microvessels that form the blood-nerve barrier (BNB) is poorly understood. Variations exist in apparatus and methods used to measure hydraulic conductivity. The objective of the study was to develop a simplified hydraulic conductivity system using commercially available components to evaluate the BNB. We determined the mean hydraulic conductivity of cultured confluent primary and immortalized human endoneurial endothelial cell layers as 2.00×10 -7 and 2.17×10 -7 cm/s/cm H₂O respectively, consistent with restrictive microvascular endothelial cells in vitro. We also determined the mean hydraulic conductivity of immortalized human brain microvascular endothelial cell layers, a commonly used blood-brain barrier (BBB) cell line, as 0.20×10 -7 cm/s/cm H₂O, implying a mean 10-fold higher resistance to transendothelial water flux in the brain compared to peripheral nerves. To our knowledge, this is the first reported measurement of human BNB and BBB hydraulic conductivities. This model represents an important tool to further characterize the human BNB and deduce the molecular determinants and signaling mechanisms responsible for BNB hydraulic conductivity in normal and disease states in vitro. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel mutations of the carbohydrate sulfotransferase-6 (CHST6) gene causing macular corneal dystrophy in India.

PubMed

Sultana, Afia; Sridhar, Mittanamalli S; Jagannathan, Aparna; Balasubramanian, Dorairajan; Kannabiran, Chitra; Klintworth, Gordon K

2003-12-22

Macular corneal dystrophy (MCD) is an autosomal recessive disorder characterized by progressive central haze, confluent punctate opacities and abnormal deposits in the cornea. It is caused by mutations in the carbohydrate sulfotransferase-6 (CHST6) gene, encoding corneal N-acetyl glucosamine-6-O-sulfotransferase (C-GlcNAc-6-ST). We screened the CHST6 gene for mutations in Indian families with MCD, in order to determine the range of pathogenic mutations. Genomic DNA was isolated from peripheral blood leukocytes of patients with MCD and normal controls. The coding regions of the CHST6 gene were amplified using three pairs of primers and amplified products were directly sequenced. We identified 22 (5 nonsense, 5 frameshift, 2 insertion, and 10 missense) mutations in 36 patients from 31 families with MCD, supporting the conclusion that loss of function of this gene is responsible for this corneal disease. Seventeen of these mutations are novel. These data highlight the allelic heterogeneity of macular corneal dystrophy in Indian patients.

Molecular markers of trichloroethylene-induced toxicity in human kidney cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lash, Lawrence H.; Putt, David A.; Hueni, Sarah E.

Difficulties in evaluation of trichloroethylene (TRI)-induced toxicity in humans and extrapolation of data from laboratory animals to humans are due to the existence of multiple target organs, multiple metabolic pathways, sex-, species-, and strain-dependent differences in both metabolism and susceptibility to toxicity, and the lack or minimal amount of human data for many target organs. The use of human tissue for mechanistic studies is thus distinctly advantageous. The kidneys are one target organ for TRI and metabolism by the glutathione (GSH) conjugation pathway is responsible for nephrotoxicity. The GSH conjugate is processed further to produce the cysteine conjugate, S-(1,2-dichlorovinyl)-L-cysteine (DCVC),more » which is the penultimate nephrotoxic species. Confluent, primary cultures of human proximal tubular (hPT) cells were used as the model system. Although cells in log-phase growth, which are undergoing more rapid DNA synthesis, would give lower LD{sub 50} values, confluent cells more closely mimic the in vivo proximal tubule. DCVC caused cellular necrosis only at relatively high doses (>100 {mu}M) and long incubation times (>24 h). In contrast, both apoptosis and enhanced cellular proliferation occurred at relatively low doses (10-100 {mu}M) and early incubation times (2-8 h). These responses were associated with prominent changes in expression of several proteins that regulate apoptosis (Bcl-2, Bax, Apaf-1, Caspase-9 cleavage, PARP cleavage) and cellular growth, differentiation and stress response (p53, Hsp27, NF-{kappa}B). Effects on p53 and Hsp27 implicate function of protein kinase C, the mitogen activated protein kinase pathway, and the cytoskeleton. The precise pattern of expression of these and other proteins can thus serve as molecular markers for TRI exposure and effect in human kidney.« less

An Experimental Investigation of the Confluent Boundary Layer on a High-Lift System

NASA Technical Reports Server (NTRS)

Thomas, F. O.; Nelson, R. C.

1997-01-01

This paper describes a fundamental experimental investigation of the confluent boundary layer generated by the interaction of a leading-edge slat wake with the boundary layer on the main element of a multi-element airfoil model. The slat and airfoil model geometry are both fully two-dimensional. The research reported in this paper is performed in an attempt to investigate the flow physics of confluent boundary layers and to build an archival data base on the interaction of the slat wake and the main element wall layer. In addition, an attempt is made to clearly identify the role that slat wake / airfoil boundary layer confluence has on lift production and how this occurs. Although complete LDV flow surveys were performed for a variety of slat gap and overhang settings, in this report the focus is on two cases representing both strong and weak wake boundary layer confluence.

The influence of tributary flow density differences on the hydrodynamic behavior of a confluent meander bend and implications for flow mixing

NASA Astrophysics Data System (ADS)

Herrero, Horacio S.; Díaz Lozada, José M.; García, Carlos M.; Szupiany, Ricardo N.; Best, Jim; Pagot, Mariana

2018-03-01

The goal of this study is to evaluate the influence of tributary flow density differences on hydrodynamics and mixing at a confluent meander bend. A detailed field characterization is performed using an Acoustic Doppler Current Profiler (ADCP) for quantification of the 3D flow field, flow discharge and bathymetry, as well as CTD measurements (conductivity, temperature, depth) to characterize the patterns of mixing. Satellite images of the confluence taken at complementary times to the field surveys were analyzed to evaluate the confluence hydrodynamics at different flow conditions. The results illustrate the differences in hydrodynamics and mixing length in relation to confluences with equal density tributaries. At low-density differences, and higher discharge ratio (Qr) between the two rivers, the flow is similar to equi-density confluent meander bends. In contrast, at high-density differences (low Qr), the tributary flow is confined to near the confluence but the density difference causes the flow to move across channel. In this case, the density difference causes the lateral spread of the tributary flow to be greater than at a greater Qr when the density difference is less. These results illustrate the potential importance of density differences between tributaries in determining the rate and spatial extent of mixing and sediment dispersal at confluent meander bends.

Histologic Evaluation of a Polylactic Acid Confluent Sheet in the Treatment of Osseous Defects,

DTIC Science & Technology

1992-01-01

Cobb, DDS, PhD * John C. Reed, DDS + Caesar E. Solano, DMD + W. Robert Hiatt, DDS + • Departments of Periodontics and Oral Biology, University of...may be employed as a matrix for osseous grafting, for the occlusion of large bony defects, for soft tissue contour defects, and also as a bone plating...trabecular bone. Further, the periosteum regenerated as a confluent layer of fibrous connective tissue covering the superior aspect of the implant material

Spatial Linear Instability of Confluent Wake/Boundary Layers

NASA Technical Reports Server (NTRS)

Liou, William W.; Liu, Feng-Jun; Rumsey, C. L. (Technical Monitor)

2001-01-01

The spatial linear instability of incompressible confluent wake/boundary layers is analyzed. The flow model adopted is a superposition of the Blasius boundary layer and a wake located above the boundary layer. The Orr-Sommerfeld equation is solved using a global numerical method for the resulting eigenvalue problem. The numerical procedure is validated by comparing the present solutions for the instability of the Blasius boundary layer and for the instability of a wake with published results. For the confluent wake/boundary layers, modes associated with the boundary layer and the wake, respectively, are identified. The boundary layer mode is found amplified as the wake approaches the wall. On the other hand, the modes associated with the wake, including a symmetric mode and an antisymmetric mode, are stabilized by the reduced distance between the wall and the wake. An unstable mode switching at low frequency is observed where the antisymmetric mode becomes more unstable than the symmetric mode when the wake velocity defect is high.

The Role of Gap Junction Communication and Oxidative Stress in the Propagation of Toxic Effects among High-Dose α-Particle-Irradiated Human Cells

PubMed Central

Autsavapromporn, Narongchai; de Toledo, Sonia M.; Little, John B.; Jay-Gerin, Jean-Paul; Harris, Andrew L.; Azzam, Edouard I.

2011-01-01

We investigated the roles of gap junction communication and oxidative stress in modulating potentially lethal damage repair in human fibroblast cultures exposed to doses of α particles or γ rays that targeted all cells in the cultures. As expected, α particles were more effective than γ rays at inducing cell killing; further, holding γ-irradiated cells in the confluent state for several hours after irradiation promoted increased survival and decreased chromosomal damage. However, maintaining α-particle-irradiated cells in the confluent state for various times prior to subculture resulted in increased rather than decreased lethality and was associated with persistent DNA damage and increased protein oxidation and lipid peroxidation. Inhibiting gap junction communication with 18-α-glycyrrhetinic acid or by knockdown of connexin43, a constitutive protein of junctional channels in these cells, protected against the toxic effects in α-particle-irradiated cell cultures during confluent holding. Upregulation of antioxidant defense by ectopic overexpression of glutathione peroxidase protected against cell killing by α particles when cells were analyzed shortly after exposure. However, it did not attenuate the decrease in survival during confluent holding. Together, these findings indicate that the damaging effect of α particles results in oxidative stress, and the toxic effects in the hours after irradiation are amplified by intercellular communication, but the communicated molecule(s) is unlikely to be a substrate of glutathione peroxidase. PMID:21388278

Neuropathology of leukoencephalopathy with brainstem and spinal cord involvement and high lactate caused by a homozygous mutation of DARS2.

PubMed

Yamashita, Sumimasa; Miyake, Noriko; Matsumoto, Naomichi; Osaka, Hitoshi; Iai, Mizue; Aida, Noriko; Tanaka, Yukichi

2013-04-01

We diagnosed three siblings from consanguineous east Asian parents with leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL) from characteristic MRI, MRS findings and a homozygous mutation in the DARS2 gene. The neurological symptoms of the three patients consisted of psychomotor developmental delay, cerebellar ataxia since infancy, spasticity in the initial phase and peripheral neuropathy in later stages. Their mental development was delayed, but did not deteriorate. MRI signal abnormalities included the same abnormalities reported previously but tended to be more extensive. Signal abnormalities in the cerebral and cerebellar white matter were homogeneous and confluent from early stages. In addition, other tract such as the central tegmental tract was involved. Furthermore, an atrophic change in the cerebral white matter was observed on follow-up in one case. Two of the patients were autopsied and neuropathological findings revealed characteristic vacuolar changes in the white matter of the cerebrum, cerebellum and the nerve tracts of the brain stem and spinal cord. The central myelin sheath showed intralamellar splitting by electron microscopy. These findings were consistent to a spongy degeneration in the diffuse white matter of the brain, or spongiform leukoencephalopathy. In addition, peripheral nerves showed both axonal degeneration and abnormal myelin structures. We discussed the relationship between deficits in mitochondrial aspartyl-tRNA synthetase activity and the neuropathology observed. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

[UV-irradiation-induced skin cancer as a new occupational disease].

PubMed

Diepgen, T L; Drexler, H; Elsner, P; Schmitt, J

2015-03-01

With the revision of the German Ordinance on Occupational Diseases, skin cancer due to UV irradiation was amended as a new occupational disease to the list of occupational diseases in Germany. The new occupational disease BK 5103 has the following wording: "Squamous cell carcinoma or multiple actinic keratosis of the skin caused by natural UV irradiation". Actinic keratoses are to be considered as multiple according to this new occupational diseases if they occur as single lesions of more than five annually, or are confluent in an area > 4 cm(2) (field cancerization). It is estimated that more than 2.5 million employees are exposed to natural UV irradiation due to their work (outdoor workers) in Germany and therefore have an increased risk of skin cancer. In this article the medical and technical prerequisites which have to be fulfilled for this new occupational disease in Germany are introduced.

Disseminate and recurrent infundibulo-folliculitis in an Indian patient: A case report with review of literature

PubMed Central

Nair, Sukumaran Pradeep; Gomathy, Mini; Kumar, Gopinathan Nanda

2017-01-01

A 17-year-old male patient presented with multiple discrete and confluent monomorphic skin-colored pinhead-sized follicular papules, with occasional pustules distributed on the neck, upper chest, upper posterior trunk, and proximal extremities of 4 months duration. The lesions were asymptomatic, and there was no prior history of topical application or history of atopic dermatitis. Routine investigations were normal. Histopathology of the papules showed a mononuclear infiltrate at the infundibulum of the hair follicle. We made a final diagnosis of disseminate and recurrent infundibulo-folliculitis. The patient was started on NB-UVB and topical tacrolimus. We are reporting an interesting case in an Indian patient. PMID:28217471

Electrostimulation of rat callus cells and human lymphocytes in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aro, H.; Eerola, E.; Aho, A.J.

1984-01-01

Asymmetrical pulsing low voltage current was supplied via electrodes to cultured rat fracture callus cells and human peripheral blood lymphocytes. The (/sup 3/H)thymidine incorporation of the callus cells and 5-(/sup 125/I)iodo-2'-deoxyuridine incorporation of the lymphocytes were determined. The growth pattern of callus cells (estimated by cellular density) did not respond to electrical stimulation. However, the uptake of (/sup 3/H)thymidine was increased at the early phase of cell proliferation and inhibited at later phases of proliferation. The (/sup 3/H)thymidine uptake of confluent callus cell cultures did not respond to electrical stimulation. Lymphocytes reacted in a similar way; stimulated cells took upmore » more DNA precursor than control cells at the early phase of stimulation. During cell division, induced by the mitogens phytohemagglutinin and Concanavalin-A, the uptake of DNA precursor by stimulated cells was constantly inhibited. The results suggest that electrical stimuli affect the uptake mechanisms of cell membranes. The duality of the effect seems to be dependent on the cell cycle.« less

Development of an Immunoassay for Rapid Detection of Ganglioside GM1 Mimicry in Campylobacter jejuni Strains

PubMed Central

Prendergast, Martina M.; Kosunen, Timo U.; Moran, Anthony P.

2001-01-01

Mimicry of peripheral nerve gangliosides by Campylobacter jejuni lipopolysaccharides (LPSs) has been proposed to induce cross-reacting antiganglioside antibodies in Guillain-Barré syndrome (GBS). Because current methods for LPS characterization are labor-intensive and inhibit the screening of large numbers of strains, a rapid GM1 epitope screening assay was developed. Biomass from two agar plates of confluent growth yielded sufficient LPS using a novel phenol-water and ether extraction procedure. Extracts of LPS were reacted with cholera toxin (GM1 ligand), peanut agglutinin (Galβ1→3GalNAc ligand), and anti-GM1 antibodies. After the assay was validated, 12 of 59 (20%) C. jejuni serostrains, including four serotypes that have not previously been associated with GBS, reacted with two or more anti-GM1 ganglioside reagents. Subsequently, LPS extracts from 5 of 7 (71%) C. jejuni isolates and 2 of 3 (67%) C. jejuni culture collection strains bore GM1 structures. Overall, the assay system was reliable, efficient, and reproducible and may be adapted for large-scale epidemiological studies. PMID:11283076

HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

PubMed

Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

2007-05-02

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

Cell culture density affects the stemness gene expression of adipose tissue-derived mesenchymal stem cells.

PubMed

Kim, Dae Seong; Lee, Myoung Woo; Lee, Tae-Hee; Sung, Ki Woong; Koo, Hong Hoe; Yoo, Keon Hee

2017-03-01

The results of clinical trials using mesenchymal stem cells (MSCs) are controversial due to the heterogeneity of human MSCs and differences in culture conditions. In this regard, it is important to identify gene expression patterns according to culture conditions, and to determine how the cells are expanded and when they should be clinically used. In the current study, stemness gene expression was investigated in adipose tissue-derived MSCs (AT-MSCs) harvested following culture at different densities. AT-MSCs were plated at a density of 200 or 5,000 cells/cm 2 . After 7 days of culture, stemness gene expression was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The proliferation rate of AT-MSCs harvested at a low density (~50% confluent) was higher than that of AT-MSCs harvested at a high density (~90% confluent). Although there were differences in the expression levels of stemness gene, such as octamer-binding transcription factor 4, nanog homeobox ( Nanog ), SRY-box 2, Kruppel like factor 4, v-myc avian myelocytomatosis viral oncogene homolog ( c-Myc ), and lin-28 homolog A, in the AT-MSCs obtained from different donors, RT-qPCR analysis demonstrated differential gene expression patterns according to the cell culture density. Expression levels of stemness genes, particularly Nanog and c-Myc , were upregulated in AT-MSCs harvested at a low density (~50% confluent) in comparison to AT-MSCs from the same donor harvested at a high density (~90% confluent). These results imply that culture conditions, such as the cell density at harvesting, modulate the stemness gene expression and proliferation of MSCs.

Non-invasive quality evaluation of confluent cells by image-based orientation heterogeneity analysis.

PubMed

Sasaki, Kei; Sasaki, Hiroto; Takahashi, Atsuki; Kang, Siu; Yuasa, Tetsuya; Kato, Ryuji

2016-02-01

In recent years, cell and tissue therapy in regenerative medicine have advanced rapidly towards commercialization. However, conventional invasive cell quality assessment is incompatible with direct evaluation of the cells produced for such therapies, especially in the case of regenerative medicine products. Our group has demonstrated the potential of quantitative assessment of cell quality, using information obtained from cell images, for non-invasive real-time evaluation of regenerative medicine products. However, image of cells in the confluent state are often difficult to evaluate, because accurate recognition of cells is technically difficult and the morphological features of confluent cells are non-characteristic. To overcome these challenges, we developed a new image-processing algorithm, heterogeneity of orientation (H-Orient) processing, to describe the heterogeneous density of cells in the confluent state. In this algorithm, we introduced a Hessian calculation that converts pixel intensity data to orientation data and a statistical profiling calculation that evaluates the heterogeneity of orientations within an image, generating novel parameters that yield a quantitative profile of an image. Using such parameters, we tested the algorithm's performance in discriminating different qualities of cellular images with three types of clinically important cell quality check (QC) models: remaining lifespan check (QC1), manipulation error check (QC2), and differentiation potential check (QC3). Our results show that our orientation analysis algorithm could predict with high accuracy the outcomes of all types of cellular quality checks (>84% average accuracy with cross-validation). Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Human brain microvascular endothelial cells resist elongation due to shear stress.

PubMed

Reinitz, Adam; DeStefano, Jackson; Ye, Mao; Wong, Andrew D; Searson, Peter C

2015-05-01

Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier. Copyright © 2015 Elsevier Inc. All rights reserved.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

Peripheral genetic structure of Helicoverpa zea indicates asymmetrical panmixia

USDA-ARS?s Scientific Manuscript database

Seasonal climatic shifts create peripheral habitats that alternate between habitable and uninhabitable for migratory species. Such dynamic peripheral habitats are potential sites where migratory species could evolve high genetic diversity resulting from convergence of immigrants from multiple region...

Type I collagen-induced YAP nuclear expression promotes primary cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L1 cells.

PubMed

Xu, Qian; Liu, Xiaoling; Liu, Weiwei; Hayashi, Toshihiko; Yamato, Masayuki; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2018-05-30

The extracellular matrix (ECM) is a major biomechanical environment for all cells in vivo, and tightly controls wound healing and cancer progression. Type I collagen (Col I) is the most abundant component in ECM and plays an essential role for cell motility control and migration beyond structural support. Our previous results showed that Col I increased the length of primary cilia and the expression of primary cilia-associated proteins in 3T3-L1 cells. The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes for the development and maintenance of tissue functions. In this study, we investigated the role of Hippo/YAP signaling in primary cilia growth of cells cultured on Col I-coated plate, as well as the potential link between primary cilia and migration. At 2-day post-confluence, YAP localization in the nucleus was dramatically increased when the cells were cultured on Col I-coated plate, accompanied by cilia growth. YAP inhibitor verteporfin repressed the growth of primary cilia as well as the expressions of ciliogenesis-associated proteins in confluent 3T3-L1 cells cultured on Col I-coated plate. Moreover, knockdown of either YAP or IFT88, one of the ciliogenesis-associated proteins, reversed the migration of confluent 3T3-L1 cells promoted by Col I-coating. In conclusion, activation of YAP pathway by Col I-coating of culture plate for confluent 3T3-L1 cells is positively associated with the primary cilia growth, which eventually results in promoted migration.

Exactly solvable Schrödinger equation with double-well potential for hydrogen bond

NASA Astrophysics Data System (ADS)

Sitnitsky, A. E.

2017-05-01

We construct a double-well potential for which the Schrödinger equation can be exactly solved via reducing to the confluent Heun's one. Thus the wave function is expressed via the confluent Heun's function. The latter is tabulated in Maple so that the obtained solution is easily treated. The potential is infinite at the boundaries of the final interval that makes it to be highly suitable for modeling hydrogen bonds (both ordinary and low-barrier ones). We exemplify theoretical results by detailed treating the hydrogen bond in KHCO3 and show their good agreement with literature experimental data.

Investigation of Bohr Hamiltonian in presence of Killingbeck potential using bi-confluent Heun functions

NASA Astrophysics Data System (ADS)

Sobhani, Hadi; Hassanabadi, Hassan; Chung, Won Sang

2018-05-01

In this study, Bohr Hamiltonian is studied for the triaxial and rotational cases. In both cases, Killingbeck potential is used as interaction. The wave function and energy of these cases are found using bi-confluent Heun functions. The results are examined by reproducing experimental data of some isotopes for each case. Energy levels of the isotopes are shown graphically as well as theoretical results for staggering in γ bands of the isotopes is discussed. In the next step, we argue about B (E 2) transition rates of the isotopes for each case. The results have a good agreement with experimental data.

Confluent Heun functions and the physics of black holes: Resonant frequencies, Hawking radiation and scattering of scalar waves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vieira, H.S., E-mail: horacio.santana.vieira@hotmail.com; Centro de Ciências, Tecnologia e Saúde, Universidade Estadual da Paraíba, CEP 58233-000, Araruna, PB; Bezerra, V.B., E-mail: valdir@fisica.ufpb.br

We apply the confluent Heun functions to study the resonant frequencies (quasispectrum), the Hawking radiation and the scattering process of scalar waves, in a class of spacetimes, namely, the ones generated by a Kerr–Newman–Kasuya spacetime (dyon black hole) and a Reissner–Nordström black hole surrounded by a magnetic field (Ernst spacetime). In both spacetimes, the solutions for the angular and radial parts of the corresponding Klein–Gordon equations are obtained exactly, for massive and massless fields, respectively. The special cases of Kerr and Schwarzschild black holes are analyzed and the solutions obtained, as well as in the case of a Schwarzschild blackmore » hole surrounded by a magnetic field. In all these special situations, the resonant frequencies, Hawking radiation and scattering are studied. - Highlights: • Charged massive scalar field in the dyon black hole and massless scalar field in the Ernst spacetime are analyzed. • The confluent Heun functions are applied to obtain the solution of the Klein–Gordon equation. • The resonant frequencies are obtained. • The Hawking radiation and the scattering process of scalar waves are examined.« less

Aggressive posterior retinopathy of prematurity in infants ≥ 1500 g birth weight.

PubMed

Sanghi, Gaurav; Dogra, Mangat R; Katoch, Deeksha; Gupta, Amod

2014-02-01

In this retrospective case series, we report the spectrum and outcomes of aggressive posterior retinopathy of prematurity (APROP) in infants ≥ 1500 g birth weight. Twenty-nine eyes of 15 infants are included. All infants were referred from level I or II nurseries, received supplemental unmonitored oxygen for prolonged duration (>1 week) and had multiple systemic co-morbidities. Of the 29 eyes, 10 (34.5%) had zone 1 and 19 (65.5%) had posterior zone 2 disease. Twenty-five (86.2%) eyes had flat neovascularization and 4 (13.8%) eyes had brush like proliferation. We noticed large vascular loops in 10 (34.5%) eyes. After confluent laser photocoagulation, 22 (75.9%) eyes had a favorable outcome. The study concludes that APROP in heavier (≥ 1500 g birth weight) premature infants occurs mostly in posterior zone 2 with flat neovascularization and atypical features like large vascular loops. Supplemental unmonitored oxygen for prolonged duration and multiple systemic co-morbidities could be a contributing factor.

Multiple mononeuropathy

MedlinePlus

Mononeuritis multiplex; Mononeuropathy multiplex; Multifocal neuropathy; Peripheral neuropathy - mononeuritis multiplex ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

CONTENT VALIDITY OF SYMPTOM-BASED MEASURES FOR DIABETIC, CHEMOTHERAPY, AND HIV PERIPHERAL NEUROPATHY

PubMed Central

GEWANDTER, JENNIFER S.; BURKE, LAURIE; CAVALETTI, GUIDO; DWORKIN, ROBERT H.; GIBBONS, CHRISTOPHER; GOVER, TONY D.; HERRMANN, DAVID N.; MCARTHUR, JUSTIN C.; MCDERMOTT, MICHAEL P.; RAPPAPORT, BOB A.; REEVE, BRYCE B.; RUSSELL, JAMES W.; SMITH, A. GORDON; SMITH, SHANNON M.; TURK, DENNIS C.; VINIK, AARON I.; FREEMAN, ROY

2017-01-01

Introduction No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. Methods This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Results Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Conclusions Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. PMID:27447116

Content validity of symptom-based measures for diabetic, chemotherapy, and HIV peripheral neuropathy.

PubMed

Gewandter, Jennifer S; Burke, Laurie; Cavaletti, Guido; Dworkin, Robert H; Gibbons, Christopher; Gover, Tony D; Herrmann, David N; Mcarthur, Justin C; McDermott, Michael P; Rappaport, Bob A; Reeve, Bryce B; Russell, James W; Smith, A Gordon; Smith, Shannon M; Turk, Dennis C; Vinik, Aaron I; Freeman, Roy

2017-03-01

No treatments for axonal peripheral neuropathy are approved by the United States Food and Drug Administration (FDA). Although patient- and clinician-reported outcomes are central to evaluating neuropathy symptoms, they can be difficult to assess accurately. The inability to identify efficacious treatments for peripheral neuropathies could be due to invalid or inadequate outcome measures. This systematic review examined the content validity of symptom-based measures of diabetic peripheral neuropathy, HIV neuropathy, and chemotherapy-induced peripheral neuropathy. Use of all FDA-recommended methods to establish content validity was only reported for 2 of 18 measures. Multiple sensory and motor symptoms were included in measures for all 3 conditions; these included numbness, tingling, pain, allodynia, difficulty walking, and cramping. Autonomic symptoms were less frequently included. Given significant overlap in symptoms between neuropathy etiologies, a measure with content validity for multiple neuropathies with supplemental disease-specific modules could be of great value in the development of disease-modifying treatments for peripheral neuropathies. Muscle Nerve 55: 366-372, 2017. © 2016 Wiley Periodicals, Inc.

[Axonopathy in the pathogenesis of multiple sclerosis, peripheral diffuse and local motor neuropathies and motor neuron disease].

PubMed

Merkulov, Iu A; Merkulova, D M; Iosifova, O A; Zavalishin, I A

2010-01-01

Two hundreds and seventy-six patients including 43 patients with multiple sclerosis, 24 - with acute inflammatory demyelinating polyneuropathy (AIDP), 144 - with chronic inflammatory demyelinating polyneuropathy (CIDP), 27 - with motor multifocal neuropathy (MMN), 38 - with lateral amyotrophic sclerosis (LAS) have been examined. Symptoms of axonal degeneration, manifested in denervation phenomena in both clinical and instrumental studies (electromyography, transcranial magnetic stimulation, MRT), were revealed in all groups of patients. The formation of excitation conduction blocks is an universal pathophysiological mechanism of the axonopathy development in AIDP, CIDP, MMN and LAS. Symptoms of axonopathy and peripheral demyelinization in patients with multiple sclerosis and LAS suggest the possibility of transformation of immunopathological process from the central nervous system to the peripheral one.

Managing hospitals in turbulent times: do organizational changes improve hospital survival?

PubMed Central

Lee, S Y; Alexander, J A

1999-01-01

OBJECTIVE: To examine (1) the degree to which organizational changes affected hospital survival; (2) whether core and peripheral organizational changes affected hospital survival differently; and (3) how simultaneous organizational changes affected hospital survival. DATA SOURCES: AHA Hospital Surveys, the Area Resource File, and the AHA Hospital Guides, Part B: Multihospital Systems. STUDY DESIGN: The study employed a longitudinal panel design. We followed changes in all community hospitals in the continental United States from 1981 through 1994. The dependent variable, hospital closure, was examined as a function of multiple changes in a hospital's core and peripheral structures as well as the hospital's organizational and environmental characteristics. Cox regression models were used to test the expectations that core changes increased closure risk while peripheral changes decreased such risk, and that simultaneous core and peripheral changes would lead to higher risk of closure. PRINCIPAL FINDINGS: Results indicated more peripheral than core changes in community hospitals. Overall, findings contradicted our expectations. Change in specialty, a core change, was beneficial for hospitals, because it reduced closure risk. The two most frequent peripheral changes, downsizing and leadership change, were positively associated with closure. Simultaneous organizational changes displayed a similar pattern: multiple core changes reduced closure risk, while multiple peripheral changes increased the risk. These patterns held regardless of the level of uncertainty in hospital environments. CONCLUSIONS: Organizational changes are not all beneficial for hospitals, suggesting that hospital leaders should be both cautious and selective in their efforts to turn their hospitals around. PMID:10536977

Severe brachial plexopathy after an ultrasound-guided single-injection nerve block for total shoulder arthroplasty in a patient with multiple sclerosis.

PubMed

Koff, Matthew D; Cohen, Jeffrey A; McIntyre, John J; Carr, Charles F; Sites, Brian D

2008-02-01

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.

Use of Orbital Conformer to Improve Speech in Patients with Confluent Maxillectomy and Orbital Defects

PubMed Central

Colebeck, Amanda C.; Kase, Michael T.; Nichols, Cindy B.; Golden, Marjorie; Huryn, Joseph M.

2016-01-01

The basic objective in prosthetic restoration of confluent maxillary and orbital defects is to achieve a comfortable, cosmetically acceptable prosthesis that restores speech, deglutition, and mastication. It is a challenging task complicated by the size and shape of the defects. The maxillary obturator prosthesis often satisfies the objective of adequate deglutition; however, orbital defects that are not obturated in the medial septal or posterior walls allow air to escape, negatively impacting phonation. This article describes a technique to achieve favorable prosthetic rehabilitation in a patient with a maxillectomy and ipsilateral orbital exenteration. The prosthetic components include maxillary obturator, orbital conformer, and orbital prosthesis connected using rigid magnetic attachments. PMID:25953143

Necrotizing retinitis of multifactorial etiology

PubMed Central

Pirvulescu, Ruxandra Angela; Popa, Cherecheanu Alina; Romanitan, Mihaela Oana; Obretin, Dana; Iancu, Raluca; Vasile, Danut

2017-01-01

Introduction. We present the case of a 73-year-old woman with osteoporosis, who presented to the emergency room with a sudden vision loss and ocular pain in the right eye, which appeared two days before. The patient mentioned loss of appetite, weight loss for three months and low fever for two weeks. Materials and methods. Among the ophthalmological findings, the most important were panuveitis, and large confluent necrotic areas in the peripheral retina. The patient was diagnosed with RE Panuveitis and acute necrotizing retinitis. Results. Blood exams showed leukocytosis and monocytosis, thrombocytosis and anemia. Further investigations showed high levels of Cytomegalovirus (CMV) anti IgG and Herpes Simplex (HS) type 1 virus anti IgM, urinary infection, and secondary hepatic cytolysis. The CT and MRI of the thorax and abdomen showed no sign of neoplastic disease, and no explanation for the CMV infection was found. The patient received general corticotherapy and antiviral therapy, and, after one month, RE BCVA was 20/ 30. Particularity of the case. Acute necrotizing retinitis in an old patient with CMV and HSV type 1, associated with secondary hepatic cytolysis, without any other immunosuppressive disease and very good outcome. PMID:29450371

How do generalized jamming transitions affect collective migration in confluent tissues?

NASA Astrophysics Data System (ADS)

Manning, M. Lisa

Recent experiments have demonstrated that tissues involved in embryonic development, lung function, wound healing, and cancer progression are close to fluid-to-solid, or ``jamming'' transitions. Theoretical models for confluent 2D tissues have also been shown to exhibit continuous rigidity transitions. However, in vivobiological systems can differ in significant ways from the simple 2D models. For example, many tissues are three-dimensional, mechanically heterogeneous, and/or composed of mechanosensitive cells interspersed with extracellular matrix. We have extended existing models for confluent tissues to capture these features, and we find interesting predictions for collective cell motion that are ultimately related to an underlying generalized jamming transition. For example, in 2D, we find that heterogeneous mixtures of cells spontaneously self-organize into rigid regions of stiffer cells interspersed with string-like groups of soft cells, reminiscent of cellular streaming seen in cancer. We also find that alignment interactions (of the sort often explored in self-propelled particle models) alter the transition and generate interesting flocked liquid and flocked solid collective migration patterns. Our model predicts that 3D tissues also exhibit a jamming transition governed by cell shape, as well as history-dependent aging, and we are currently exploring whether ECM-like interactions in 3D models might help explain compressional stiffening seen in experiments on human tissue.

Active unjamming of confluent cell layers

NASA Astrophysics Data System (ADS)

Marchetti, M. Cristina

Cell motion inside dense tissues governs many biological processes, including embryonic development and cancer metastasis, and recent experiments suggest that these tissues exhibit collective glassy behavior. Motivated by these observations, we have studied a model of dense tissues that combines self-propelled particle models and vertex models of confluent cell layers. In this model, referred to as self-propelled Voronoi (SPV), cells are described as polygons in a Voronoi tessellation with directed noisy cell motility and interactions governed by a shape energy that incorporates the effects of cell volume incompressibility, contractility and cell-cell adhesion. Using this model, we have demonstrated a new density-independent solid-liquid transition in confluent tissues controlled by cell motility and a cell-shape parameter measuring the interplay of cortical tension and cell-cell adhesion. An important insight of this work is that the rigidity and dynamics of cell layers depends sensitively on cell shape. We have also used the SPV model to test a new method developed by our group to determine cellular forces and tissue stresses from experimentally accessible cell shapes and traction forces, hence providing the spatio-temporal distribution of stresses in motile dense tissues. This work was done with Dapeng Bi, Lisa Manning and Xingbo Yang. MCM was supported by NSF-DMR-1305184 and by the Simons Foundation.

Presence of S100A8/Gr1-Positive Myeloid-Derived Suppressor Cells in Primary Tumors and Visceral Organs Invaded by Breast Carcinoma Cells.

PubMed

Tanriover, Gamze; Eyinc, Mehmet Berk; Aliyev, Elnur; Dilmac, Sayra; Erin, Nuray

2018-04-26

Increased S100A8/A9 expression in Gr1-positive cells has been shown in myeloid-derived suppressor cells and may play a role in the formation of a metastatic milieu. We aimed to determine S100A8/A9 expression alone and with coexpression of Gr1 (a myeloid marker) in primary tumor and visceral tissues invaded by metastatic breast carcinoma. Female BALB/c mice were injected with 4TLM, 4THM, and 67NR orthotopically. Confluent cells (75%-80%) were used. Primary tumor, lung, liver, and spleen tissue samples were removed 26 days after injection. Peripheral blood smears and metastasis assay were performed, as was immunohistochemistry and staining. S100A8/A9 immunoreactivity alone or coexpressed with Gr1 was found in primary tumors formed by 4TLM and 4THM cells, which was markedly higher than in primary tumors formed by nonmetastatic 67NR cells. Similarly, liver and lung tissues obtained from mice injected with 4TLM or 4THM cells were invaded by S100A8/A9-positive and Gr1-positive cells. Double-positive cells were markedly fewer in liver and lung tissues of animals injected with 67NR cells. S100A8/A9-positive cells were mostly localized in red pulp of spleens. We observed an increased number of neutrophils in the peripheral blood of mice injected with metastatic breast carcinoma cells. Tumor-derived factors may increase S100A8/A9-positive cells locally and systemically, and S100A8/A9-positive cells may provide an appropriate milieu for the formation of metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization and optimization of slanted well designs for microfluidic mixing under electroosmotic flow.

PubMed

Johnson, Timothy J; Locascio, Laurie E

2002-08-01

Recently, a series of slanted wells on the floor of a microfluidic channel were experimentally shown to successfully induce off-axis transport and mixing of two confluent streams when operating under electroosmotic (EO) flow. This paper will further explore, through numerical simulations, the parameters that affect off-axis transport under EO flow with an emphasis on optimizing the mixing rate of (a). two confluent streams in steady-state or (b). the transient scenario of two confluent plugs of material, which simulates mixing after an injection. For the steady-state scenario, the degree of mixing was determined to increase by changing any of the following parameters: (1). increasing the well depth, (2). decreasing the well angle relative to the axis of the channel, and (3). increasing the EO mobility of the well walls relative to the mobility of the main channel. Also, it will be shown that folding of the fluid can occur when the well angle is sufficiently reduced and/or when the EO mobility of the wells is increased relative to the channel. The optimum configuration for the transient problem of mixing two confluent plugs includes shallow wells to minimize the well residence time, and an increased EO mobility of the well walls relative to the main channel as well as small well angles to maximize off-axis transport. The final design reported here for the transient study reduces the standard deviation of the concentration across the channel by 72% while only increasing the axial dispersion of the injected plug by 8.6 % when compared to a plug injected into a channel with no wells present. These results indicate that a series of slanted wells on the wall of a microchannel provides a means for controlling and achieving a high degree of off-axis transport and mixing in a passive manner for micro total analysis system (microTAS) devices that are driven by electroosmosis.

Fitting the Elementary Rate Constants of the P-gp Transporter Network in the hMDR1-MDCK Confluent Cell Monolayer Using a Particle Swarm Algorithm

PubMed Central

Agnani, Deep; Acharya, Poulomi; Martinez, Esteban; Tran, Thuy Thanh; Abraham, Feby; Tobin, Frank; Ellens, Harma; Bentz, Joe

2011-01-01

P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the apical membrane. PMID:22028772

Safety and Efficacy of Pentostatin and Low Dose TBI With Allogenic Peripheral Blood Stem Cell Transplant

ClinicalTrials.gov

2018-01-22

Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Chronic Lymphocytic Leukemia; Myelodysplastic Syndromes; Multiple Myeloma; Non-Hodgkins Lymphoma; Hodgkins Disease; Peripheral T-cell Lymphoma

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

PubMed Central

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

SPECTRAL DOMAIN VERSUS SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE RETINAL CAPILLARY PLEXUSES IN SICKLE CELL MACULOPATHY.

PubMed

Jung, Jesse J; Chen, Michael H; Frambach, Caroline R; Rofagha, Soraya; Lee, Scott S

2018-01-01

To compare the spectral domain and swept source optical coherence tomography angiography findings in two cases of sickle cell maculopathy. A 53-year-old man and a 24-year-old man both with sickle cell disease (hemoglobin SS) presented with no visual complaints; Humphrey visual field testing demonstrated asymptomatic paracentral scotomas that extended nasally in the involved eyes. Clinical examination and multimodal imaging including spectral domain and swept source optical coherence tomography, and spectral domain optical coherence tomography angiography and swept source optical coherence tomography angiography (Carl Zeiss Meditec Inc, Dublin, CA) were performed. Fundus examination of both patients revealed subtle thinning of the macula. En-face swept source optical coherence tomography confirmed the extent of the thinning correlating with the functional paracentral scotomas on Humphrey visual field. Swept source optical coherence tomography B-scan revealed multiple confluent areas of inner nuclear thinning and significant temporal retinal atrophy. En-face 6 × 6-mm spectral domain optical coherence tomography angiography of the macula demonstrated greater loss of the deep capillary plexus compared with the superficial capillary plexus. Swept source optical coherence tomography angiography 12 × 12-mm imaging captured the same macular findings and loss of both plexuses temporally outside the macula. In these two cases of sickle cell maculopathy, deep capillary plexus ischemia is more extensive within the macula, whereas both the superficial capillary plexus and deep capillary plexus are involved outside the macula likely due to the greater oxygen demands and watershed nature of these areas. Swept source optical coherence tomography angiography clearly demonstrates the angiographic extent of the disease correlating with the Humphrey visual field scotomas and confluent areas of inner nuclear atrophy.

Which Measurement of Blood Pressure Is More Associated With Albuminuria in Patients With Type 2 Diabetes: Central Blood Pressure or Peripheral Blood Pressure?

PubMed

Kitagawa, Noriyuki; Okada, Hiroshi; Tanaka, Muhei; Hashimoto, Yoshitaka; Kimura, Toshihiro; Nakano, Koji; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto; Fukui, Michiaki

2016-08-01

The aim of this study was to investigate whether central systolic blood pressure (SBP) was associated with albuminuria, defined as urinary albumin excretion (UAE) ≥30 mg/g creatinine, and, if so, whether the relationship of central SBP with albuminuria was stronger than that of peripheral SBP in patients with type 2 diabetes. The authors performed a cross-sectional study in 294 outpatients with type 2 diabetes. The relationship between peripheral SBP or central SBP and UAE using regression analysis was evaluated, and the odds ratios of peripheral SBP or central SBP were calculated to identify albuminuria using logistic regression model. Moreover, the area under the receiver operating characteristic curve (AUC) of central SBP was compared with that of peripheral SBP to identify albuminuria. Multiple regression analysis demonstrated that peripheral SBP (β=0.255, P<.0001) or central SBP (r=0.227, P<.0001) was associated with UAE. Multiple logistic regression analysis demonstrated that peripheral SBP (odds ratio, 1.029; 95% confidence interval, 1.016-1.043) or central SBP (odds ratio, 1.022; 95% confidence interval, 1.011-1.034) was associated with an increased odds of albuminuria. In addition, AUC of peripheral SBP was significantly greater than that of central SBP to identify albuminuria (P=0.035). Peripheral SBP is superior to central SBP in identifying albuminuria, although both peripheral and central SBP are associated with UAE in patients with type 2 diabetes. © 2016 Wiley Periodicals, Inc.

Case report: MR imaging features of disseminated uterine leiomyosarcoma presenting after hysterectomy with morcellation.

PubMed

Ciszak, Tadi; Mittal, Pardeep K; Sullivan, Patrick; Cardona, Kenneth; Hanley, Krisztina Z; Khanna, Namita; Moreno, Courtney Coursey

2015-10-01

A 53-year-old woman underwent elective hysterectomy for symptomatic anemia secondary to abnormal uterine bleeding. She presented 15 months later with complaints of abdominal fullness. Abdominopelvic magnetic resonance imaging demonstrated multiple confluent enhancing solid masses centered in the pelvis and extending cranially to the level of the umbilicus. Additional separate nodules also were visible along the peritoneum. Biopsy demonstrated leiomyosarcoma. Additional clinical information was obtained, which revealed that the patient's prior hysterectomy was performed with morcellation. In November 2014, the United States Food and Drug Administration issued a warning discouraging the use of morcellation during hysterectomy and myomectomy because of the risk of seeding unsuspected malignancy. Radiologists should be aware of this potential complication of morcellation and its imaging appearance so that the correct diagnosis can be suggested in the imaging report.

[Autonomy in intensive care unit: let us start by caring ourselves].

PubMed

Vargas, Ambrosina Oliveira; Ramos, Flávia Regina Souza

2010-01-01

This study, a qualitative investigation anchored in Foucaltian analysis with approximations to post-structuralist theory, explores the question of autonomy as one of the tensions of nursing performance/knowledge which can be discursively articulated to bioethics and to techno biomedicine. From such perspective, from the multiples vies that may emerge to completing a critical reading of the analyzed texts (articles produced by nurses) and of the interviews with intensive care nurses, the theme of autonomy was analytically explored from the concept of self care, unfolding itself into categories which express privileging: morals as obedience to the Law; conduct and morals concerning technical knowledge; self-governing in its confront with technique. These are configured as ethical possibilities for the intensive care nurse/subject, not as sequential or competitive stages, but connected and confluent in the experience of the current historical period.

Gasoline sniffing multifocal neuropathy.

PubMed

Burns, T M; Shneker, B F; Juel, V C

2001-11-01

The polyneuropathy caused by chronic gasoline inhalation is reported to be a gradually progressive, symmetric, sensorimotor polyneuropathy. We report unleaded gasoline sniffing by a female 14 years of age that precipitated peripheral neuropathy. In contrast with the previously reported presentation of peripheral neuropathy in gasoline inhalation, our patient developed multiple mononeuropathies superimposed on a background of sensorimotor polyneuropathy. The patient illustrates that gasoline sniffing neuropathy may present with acute multiple mononeuropathies resembling mononeuritis multiplex, possibly related to increased peripheral nerve susceptibility to pressure in the setting of neurotoxic components of gasoline. The presence of tetraethyl lead, which is no longer present in modern gasoline mixtures, is apparently not a necessary factor in the development of gasoline sniffer's neuropathy.

Intercellular ice propagation: experimental evidence for ice growth through membrane pores.

PubMed Central

Acker, J P; Elliott, J A; McGann, L E

2001-01-01

Propagation of intracellular ice between cells significantly increases the prevalence of intracellular ice in confluent monolayers and tissues. It has been proposed that gap junctions facilitate ice propagation between cells. This study develops an equation for capillary freezing-point depression to determine the effect of temperature on the equilibrium radius of an ice crystal sufficiently small to grow through gap junctions. Convection cryomicroscopy and video image analysis were used to examine the incidence and pattern of intracellular ice formation (IIF) in the confluent monolayers of cell lines that do (MDCK) and do not (V-79W) form gap junctions. The effect of gap junctions on intracellular ice propagation was strongly temperature-dependent. For cells with gap junctions, IIF occurred in a directed wave-like pattern in 100% of the cells below -3 degrees C. At temperatures above -3 degrees C, there was a marked drop in the incidence of IIF, with isolated individual cells initially freezing randomly throughout the sample. This random pattern of IIF was also observed in the V-79W monolayers and in MDCK monolayers treated to prevent gap junction formation. The significant change in the low temperature behavior of confluent MDCK monolayers at -3 degrees C is likely the result of the inhibition of gap junction-facilitated ice propagation, and supports the theory that gap junctions facilitate ice nucleation between cells. PMID:11509353

The human insulin receptor mRNA contains a functional internal ribosome entry segment

PubMed Central

Spriggs, Keith A.; Cobbold, Laura C.; Ridley, Simon H.; Coldwell, Mark; Bottley, Andrew; Bushell, Martin; Willis, Anne E.; Siddle, Kenneth

2009-01-01

Regulation of mRNA translation is an important mechanism determining the level of expression of proteins in eukaryotic cells. Translation is most commonly initiated by cap-dependent scanning, but many eukaryotic mRNAs contain internal ribosome entry segments (IRESs), providing an alternative means of initiation capable of independent regulation. Here, we show by using dicistronic luciferase reporter vectors that the 5′-UTR of the mRNA encoding human insulin receptor (hIR) contains a functional IRES. RNAi-mediated knockdown showed that the protein PTB was required for maximum IRES activity. Electrophoretic mobility shift assays confirmed that PTB1, PTB2 and nPTB, but not unr or PTB4, bound to hIR mRNA, and deletion mapping implicated a CCU motif 448 nt upstream of the initiator AUG in PTB binding. The IR-IRES was functional in a number of cell lines, and most active in cells of neuronal origin, as assessed by luciferase reporter assays. The IRES was more active in confluent than sub-confluent cells, but activity did not change during differentiation of 3T3-L1 fibroblasts to adipocytes. IRES activity was stimulated by insulin in sub-confluent cells. The IRES may function to maintain expression of IR protein in tissues such as the brain where mRNA translation by cap-dependent scanning is less effective. PMID:19654240

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

Conduction block in the peripheral nervous system in experimental allergic encephalomyelitis

NASA Astrophysics Data System (ADS)

Pender, M. P.; Sears, T. A.

1982-04-01

Experimental allergic encephalomyelitis (EAE) has been widely studied as a model of multiple sclerosis, a central nervous system (CNS) disease of unknown aetiology. The clinical features of both EAE and multiple sclerosis provide the only guide to the progress and severity of these diseases, and are used to assess the response to treatment. In such comparisons the clinical features of EAE are assumed to be due to lesions in the CNS, but in this disease there is also histological evidence of damage to the peripheral nervous system1-8. However, the functional consequences of such peripheral lesions have been entirely ignored. To examine this we have studied nerve conduction in rabbits with EAE. We report here that most of the large diameter afferent fibres are blocked in the region of the dorsal root ganglion and at the dorsal root entry zone, thus accounting for the loss of tendon jerks and also, through the severe loss of proprioceptive information, the ataxia of these animals. We conclude that whenever clinical comparisons are made between EAE and multiple sclerosis, the pathophysiology associated with the histological damage of the peripheral nervous system must be taken into account.

Viscoelastic properties of normal and cancerous human breast cells are affected differently by contact to adjacent cells.

PubMed

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 stiffer and have lower fluidity than sparse normal cells, which appears to be governed by the formation of cell-cell contacts. Contrarily, confluent cancer cells do not stiffen and not have a decreased fluidity compared to sparse cancer cells and their viscoelastic properties are independent of cell-cell contact formation. While the observed behavior of normal cells appears to be crucial for providing the mechanical stability and therefore the integrity of the epithelial monolayer, the dysregulation of this behavior in cancer cells might be a central aspect of early stage cancer progression and metastasis in the epithelium. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effects of SOV-induced phosphatase inhibition and expression of protein tyrosine phosphatases in rat corneal endothelial cells.

PubMed

Chen, Wei-Li; Harris, Deshea L; Joyce, Nancy C

2005-11-01

Contact inhibition is an important mechanism for maintaining corneal endothelium in a non-replicative state. Protein tyrosine phosphatases (PTPs) play a role in regulating the integrity of cell-cell contacts, differentiation, and growth. In this study, we aimed to evaluate whether phosphatases are involved in the maintenance of contact-dependent inhibition of proliferation in corneal endothelial cells and to identify candidate PTPs that are expressed in these cells and might be involved in regulation of contact inhibition. Confluent cultures of rat corneal endothelial cells or endothelium in ex vivo corneas were treated with the general phosphatase inhibitor, sodium orthovanadate (SOV). Immunocytochemistry (ICC) evaluated the effect of SOV on cell-cell contacts by staining for ZO-1, and on cell cycle progression by staining for Ki67. Transverse sections of rat cornea and cultured rat corneal endothelial cells were used to test for expression of the candidate PTPs: PTP-mu, PTP-LAR, PTP1B, SHP-1, SHP-2, and PTEN using ICC and either Western blots or RT-PCR. ZO-1 staining demonstrated that SOV induced a time-dependent release of cell-cell contacts in confluent cultures of corneal endothelial cells and in the endothelium of ex vivo corneas. Staining for Ki67 indicated that SOV promoted limited cell cycle progression in the absence of serum. PTP-mu, PTP1B, SHP-1, SHP-2, and PTEN, but not PTP-LAR, were expressed in rat corneal endothelial cells in situ and in culture. The subcellular location of PTP-mu and PTP1B differed in subconfluent and confluent cells, while that of SHP-1, SHP-2, and PTEN was similar, regardless of confluent status. Western blots confirmed the expression of PTP1B, SHP-1, SHP-2, and PTEN. RT-PCR confirmed expression of PTP-mu mRNA. Phosphatases are involved in regulation of junctional integrity and of cell proliferation in corneal endothelial cells. PTP-mu, PTP1B, SHP-1, SHP-2, and PTEN are expressed in rat corneal endothelium and may be involved in regulation of contact inhibition in these normally non-proliferating cells.

Schwannomatosis Involving Peripheral Nerves: A Case Report

PubMed Central

Kim, Dong Hun; Park, Sung-Tae; Shin, Ji Hoon

2006-01-01

Schwannomatosis or neurilemmomatosis has been used to describe patients with multiple nonvestibular schwannomas with no other stigmata of neurofibromatosis type-2 (NF-2). In our case, schwannomatosis, multiple schwannomas were present in a 21-yr-old woman with no stigmata or family history of NF-1 or NF-2. She had no evidence of vestibular schwannoma or other intracranial tumors. Multiple peripheral tumors were found in the carotid space of the neck, and soft tissue of posterior shoulder, lower back, ankle and middle mediastinum. All of those tumors were completely limited to the right side of the body. All surgically removed tumor specimens in this patient proved to be schwannomas. PMID:17179704

Dependency of subcellular reactions during PDT on the metabolic state of cell cultures probed by different microscopic techniques

NASA Astrophysics Data System (ADS)

Rueck, Angelika C.; Schneckenburger, Herbert; Strauss, Wolfgang S. L.; Gschwend, Michael H.; Beck, Gerd C.; Kunzi-Rapp, Karin; Steiner, Rudolf W.

1994-02-01

Various microscopic techniques were used to study the dependency of photodynamically induced subcellular reactions on the metabolic state of cell cultures. TPPS4 and AlS2-3Pc were incubated in RR 1022 epithelial cells with varying cell density. To attain almost isolated cells (low cell density) or confluent growing cells (high cell density) 25 cells/mm2 or 500 cells/mm2 were seeded, respectively. Low cell density irradiation with blue light led to a change in the initial cytoplasmatic fluorescence pattern. For both sensitizers, TPPS4 as well as AlS2-3, a fluorescence relocalization and fluorescence intensity increase could be detected, moreover in the case of TPPS4 a fluorescence formation in the nucleus and nucleoli were detected. In contrast, for confluent growing cells no redistribution was observed.

Bilateral renal dysplasia, nephroblastomatosis, and bronchial stenosis. A new syndrome?

PubMed

Rodriguez, Maria Matilde; Correa-Medina, Mayrin; Whittington, Elizabeth E

2015-06-01

Bilateral nephroblastomatosis (NB) is an uncommon renal anomaly characterized by multiple confluent nephrogenic rests scattered through both kidneys, with only a limited number of cases reported in the medical literature. Some of these children may have associated either Perlman or Beckwith-Wiedemann syndrome and others do not demonstrate syndromic features. We report a full-term boy with anteverted nose, bilateral bronchial stenosis due to lack of cartilage, bilateral obstructive renal dysplasia and NB with glomeruloid features. The infant had visceromegaly, but neither gigantism nor hemihypertrophy. Immunohistochemistry for PAX2 (Paired box gene-2) and WT-1 (Wilms Tumor 1) were strongly positive in the areas of NB. GLEPP-1 (Glomerular Epithelial Protein) did not stain the areas of NB with a glomeruloid appearance, but was positive in the renal glomeruli as expected. We found neither associated bronchial stenosis nor the histology of NB resembling giant glomeruli in any of the reported cases of NB.

Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

PubMed

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

PubMed Central

Ayala-Caminero, Radamés; Pinzón-Herrera, Luis; Martinez, Carol A. Rivera; Almodovar, Jorge

2018-01-01

Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures. PMID:29515936

Just-in-time rescue plerixafor in combination with chemotherapy and granulocyte-colony stimulating factor for peripheral blood progenitor cell mobilization

PubMed Central

Smith, Veronica R.; Popat, Uday; Ciurea, Stefan; Nieto, Yago; Anderlini, Paolo; Rondon, Gabriela; Alousi, Amin; Qazilbash, Muzaffar; Kebriaei, Partow; Khouri, Issa; de Lima, Marcos; Champlin, Richard; Hosing, Chitra

2014-01-01

Plerixafor, a recently approved peripheral blood progenitor cell mobilizing agent, is often added to granulocyte-colony stimulating factor (G-CSF) to mobilize peripheral blood progenitor cells in patients with lymphoma or myeloma who cannot mobilize enough CD34+ cells with G-CSF alone to undergo autologous stem cell transplantation. However, data are lacking regarding the feasibility and efficacy of just-in-time plerixafor in combination with chemotherapy and G-CSF. We reviewed the peripheral blood stem cell collection data of 38 consecutive patients with lymphoma (Hodgkin’s and non-Hodgkin’s) and multiple myeloma who underwent chemomobilization and high-dose G-CSF and just-in-time plerixafor to evaluate the efficacy of this treatment combination. All patients with multiple myeloma and all but 1 patient with lymphoma collected the minimum required number of CD34+ cells to proceed with autologous stem cell transplantation (>2 × 106/kilogram of body weight). The median CD34+ cell dose collected in patients with non-Hodgkin lymphoma was 4.93 × 106/kilogram of body weight. The median CD34+ cell dose collected for patients with multiple myeloma was 8.81 × 106/kilogram of body weight. Plerixafor was well tolerated; no grade 2 or higher non- hematologic toxic effects were observed. PMID:23749720

Atomism, Pragmatism, Holism.

ERIC Educational Resources Information Center

Miller, John P.

1986-01-01

Examines three world views influencing curriculum development--atomism (underpinning competency-based education), pragmatism (promoting inquiry-based approaches), amd holism (associated with confluent or Waldorf education). Holism embodies the perennial philosophy and attempts to integrate cognitive, affective, and transpersonal dimensions,…

{sup 40}Ca+{sup 40}Ca reaction at {ital E}{sub lab}=35 MeV/nucleon: Filters and signatures to distinguish nearly central from peripheral collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pawl /owski, P.; Brzychczyk, J.; Benchekrovn, D.

1996-07-01

Multifragment emission of charged particles from the {sup 40}Ca + {sup 40}Ca reaction at 35 MeV/nucleon has been investigated. Multiplicity as well as event shape filters were used to distinguish nearly central from peripheral collisions. A correlation between higher multiplicities and random events from two reactions occurring in one beam burst is discussed. Signatures of different reaction scenarios are investigated using simulation techniques. {copyright} {ital 1996 The American Physical Society.}

In vitro effects of dental cements on hard and soft tissues associated with dental implants.

PubMed

Rodriguez, Lucas C; Saba, Juliana N; Chung, Kwok-Hung; Wadhwani, Chandur; Rodrigues, Danieli C

2017-07-01

Dental cements for cement-retained restorations are often chosen based on clinician preference for the product's material properties, mixing process, delivery mechanism, or viscosity. The composition of dental cement may play a significant role in the proliferation or inhibition of different bacterial strains associated with peri-implant disease, and the effect of dental cements on host cellular proliferation may provide further insight into appropriate cement material selection. The purpose of this in vitro study was to investigate the cellular host response of bone cells (osteoblasts) and soft tissue cells (gingival fibroblasts) to dental cements. Zinc oxide (eugenol and noneugenol), zinc phosphate, and acrylic resin cements were molded into pellets and directly applied to confluent preosteoblast (cell line MC3T3 E1) or gingival fibroblast cell cultures (cell line HGF) to determine cellular viability after exposure. Controls were defined as confluent cell cultures with no cement exposure. Direct contact cell culture testing was conducted following International Organization for Standardization 10993 methods, and all experiments were performed in triplicate. To compare either the MC3T3 E1 cell line, or the HGF cell line alone, a 1-way ANOVA test with multiple comparisons was used (α=.05). To compare the MC3T3 E1 cell line results and the HGF cell line results, a 2-way ANOVA test with multiple comparisons was used (α=.05). The results of this study illustrated that while both bone and soft tissue cell lines were vulnerable to the dental cement test materials, the soft tissue cell line (human gingival fibroblasts) was more susceptible to reduced cellular viability after exposure. The HGF cell line was much more sensitive to cement exposure. Here, the acrylic resin, zinc oxide (eugenol), and zinc phosphate cements significantly reduced cellular viability after exposure with respect to HGF cells only. Within the limitation of this in vitro cellular study, the results indicated that cell response to various implant cements varied significantly, with osteoblast proliferation much less affected than gingival fibroblast cells. Furthermore, the zinc oxide noneugenol dental cement appeared to affect the cell lines significantly less than the other test cements. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Place Names in Foreign Language Teaching

ERIC Educational Resources Information Center

Schmidt, Hugo

1978-01-01

Students find place names--and their origins--interesting. A number of German examples are given, ranging from the Familiar Koeln (Colonia) and Koblenz (Confluentes) to the less familiar Wien ( Celtic vindos, "white water") and Weimar (wihmari, sacred swamp). (WGA)

Smooth muscle architecture within cell-dense vascular tissues influences functional contractility.

PubMed

Win, Zaw; Vrla, Geoffrey D; Steucke, Kerianne E; Sevcik, Emily N; Hald, Eric S; Alford, Patrick W

2014-12-01

The role of vascular smooth muscle architecture in the function of healthy and dysfunctional vessels is poorly understood. We aimed at determining the relationship between vascular smooth muscle architecture and contractile output using engineered vascular tissues. We utilized microcontact printing and a microfluidic cell seeding technique to provide three different initial seeding conditions, with the aim of influencing the cellular architecture within the tissue. Cells seeded in each condition formed confluent and aligned tissues but within the tissues, the cellular architecture varied. Tissues with a more elongated cellular architecture had significantly elevated basal stress and produced more contractile stress in response to endothelin-1 stimulation. We also found a correlation between the contractile phenotype marker expression and the cellular architecture, contrary to our previous findings in non-confluent tissues. Taken with previous results, these data suggest that within cell-dense vascular tissues, smooth muscle contractility is strongly influenced by cell and tissue architectures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vieira, H.S., E-mail: horacio.santana.vieira@hotmail.com; Centro de Ciências, Tecnologia e Saúde, Universidade Estadual da Paraíba, CEP 58233-000, Araruna, PB; Bezerra, V.B., E-mail: valdir@fisica.ufpb.br

Charged massive scalar fields are considered in the gravitational and electromagnetic field produced by a dyonic black hole with a cosmic string along its axis of symmetry. Exact solutions of both angular and radial parts of the covariant Klein–Gordon equation in this background are obtained, and are given in terms of the confluent Heun functions. The role of the presence of the cosmic string in these solutions is showed up. From the radial solution, we obtain the exact wave solutions near the exterior horizon of the black hole, and discuss the Hawking radiation spectrum and the energy flux. -- Highlights:more » •A cosmic string is introduced along the axis of symmetry of the dyonic black hole. •The covariant Klein–Gordon equation for a charged massive scalar field in this background is analyzed. •Both angular and radial parts are transformed to a confluent Heun equation. •The resulting Hawking radiation spectrum and the energy flux are obtained.« less

'Presenting CXR phenotype of H1N1' flu compared with contemporaneous non-H1N1, community acquired pneumonia, during pandemic and post-pandemic outbreaks'.

PubMed

Minns, F C; Mhuineachain, A Ni; van Beek, E J R; Ritchie, G; Hill, A; Murchison, J T

2015-09-01

To review, phenotype and assess potential prognostic value of initial chest X-ray findings in patients with H1N1 influenza during seasonal outbreaks of 2009 and 2010, in comparison with non-H1N1, community acquired pneumonia (CAP). We retrospectively identified 72 patients admitted to hospital with pneumonia during the seasons of 2009 and 2010. H1N1 cases were confirmed by virology PCR. Presenting chest X-rays were jointly read by 2 radiologists, who were 'blinded' to further patient details and divided into 6 zones. Total number of opacified zones, the pattern and distribution of changes and length of hospital stay were recorded. Patients with H1N1 demonstrated more opacified zones (mean of 2.9 compared with 2.0; p=0.006), which were bilateral in two-thirds compared with a quarter of those with non-H1N1 CAP (p=0.001). H1N1 radiographs were more likely to be 'patchy' versus 'confluent' changes of non-H1N1 CAP (p=0.03) and more often demonstrated peripheral distribution (p=0.01). H1N1 patients tended to stay in hospital longer (not significant; p=0.08). A positive correlation existed between number of affected zones and length of inpatient stay, which was statistically significant for the cohorts combined (p=0.02). The findings were the same for the two evaluated seasons. H1N1 patients demonstrated more extensive disease, which was more likely bilateral, 'patchy', and peripheral in distribution. With increasing global cases of H1N1, knowledge of the typical findings of the H1N1 presenting chest X-ray may assist with early triage of patients, particularly where rapid viral testing is not available. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression.

PubMed

Lamour, Virginie; Detry, Cédric; Sanchez, Christelle; Henrotin, Yves; Castronovo, Vincent; Bellahcène, Akeila

2007-12-14

Bone sialoprotein (BSP) is a bone matrix glycoprotein whose expression coincides with terminal osteoblastic differentiation and the onset of mineralization. In this study we show that BSP expression is considerably increased in confluent Saos-2 human osteosarcoma cells and in differentiating normal human osteoblasts, concomitantly with the decrease of Runx2, a key transcription factor controlling bone formation. Therefore, we investigated the role of Runx2 in the regulation of BSP expression in Saos-2 cells. Using a mobility shift assay, we demonstrated that Runx2 binds to the BSP promoter only in preconfluent cells. Histone deacetylase 3 (HDAC3) has been recently shown to act as a Runx2 co-repressor. Chromatin immunoprecipitation assays demonstrated that both Runx2 and HDAC3 are detectable at the BSP promoter in preconfluent Saos-2 cells but not when they are confluent and overexpress BSP. Consistently, nuclear Runx2 protein level is down-regulated, whereas Saos-2 cells became increasingly confluent. Finally, the suppression of HDAC3, Runx2, or both by RNA interference induced the expression of BSP at both mRNA and protein levels in Saos-2 cells. Our data demonstrate that Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation. Both the nuclear disappearance of Runx2 and the non-recruitment of HDAC3 represent new means to relieve Runx2-mediated suppression of BSP expression, thus allowing the acquisition of a fully differentiated and mineralization-competent phenotype by osteoblast cells.

Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon.

PubMed

Tamraz, H; Raffoul, M; Kurban, M; Kibbi, A-G; Abbas, O

2013-01-01

Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

Thermal ablation of a confluent lesion in the porcine kidney with a clinically available MR-HIFU system

NASA Astrophysics Data System (ADS)

van Breugel, J. M. M.; de Greef, M.; Wijlemans, J. W.; Schubert, G.; van den Bosch, M. A. A. J.; Moonen, C. T. W.; Ries, M. G.

2017-07-01

The incidence of small renal masses (SRMs) sized  <4 cm has increased over the decades (as co-findings/or due to introduction of cross sectional imaging). Currently, partial nephrectomy (PN) or watchful waiting is advised in these patients. Ultimately, 80-90% of these SRMs require surgical treatment and PN is associated with a 15% complication rate. In this aging population, with possible comorbidities and poor health condition, both PN and watchful waiting are non-ideal treatment options. This resulted in an increased need for early, non-invasive treatment strategies such as MR-guided high intensity focused ultrasound (MR-HIFU). (i) To investigate the feasibility of creating a confluent lesion in the kidney using respiratory-gated MR-HIFU under clinical conditions in a pre-clinical study and (ii) to evaluate the reproducibility of the MR-HIFU ablation strategy. Healthy pigs (n  =  10) under general anesthesia were positioned on a clinical MR-HIFU system with integrated cooling. A honeycomb pattern of seven overlapping ablation cells (4  ×  4  ×  10 mm3, 450 W, <30 s) was ablated successively in the cortex of the porcine kidney. Both MR thermometry and acoustic energy delivery were respiratory gated using a pencil beam navigator on the contralateral kidney. The non-perfused volume (NPV) was visualized after the last sonication by contrast-enhanced (CE) T 1-weighted MR (T 1 w) imaging. Cell viability staining was performed to visualize the extent of necrosis. Results: a median NPV of 0.62 ml was observed on CE-T 1 w images (IQR 0.58-1.57 ml, range 0.33-2.75 ml). Cell viability staining showed a median damaged volume of 0.59 ml (IQR 0.24-1.35 ml, range 0-4.1 ml). Overlooking of the false rib, shivering of the pig, and too large depth combined with a large heat-sink effect resulted in insufficient heating in 4 cases. The NPV and necrosed volume were confluent in all cases in which an ablated volume could be observed. Our results demonstrated the feasibility of creating a confluent volume of ablated kidney cortical tissue in vivo with MR-HIFU on a clinically available system using respiratory gating and near-field cooling and showed its reproducibility.

Transient Gene and miRNA Expression Profile Changes of Confluent Human Fibroblast Cells in Space

NASA Technical Reports Server (NTRS)

Zhang, Ye; Lu, Tao; Wong, Michael; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Wang, Xiaoyu; Wu, Honglu

2015-01-01

Microgravity or an altered gravity environment from the static 1 gravitational constant has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of the cells. Whether non-dividing cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted on the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days for investigations of gene and miRNA (microRNA) expression profile changes in these cells. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly even though they were confluent, as measured by the expression of the protein Ki-67 positive cells, and the cells in space grew slightly faster. Gene and miRNA expression data indicated activation of NF(sub kappa)B (nuclear factor kappa-light-chain-enhancer of activated B cells) and other growth related pathways involving HGF and VEGF in the flown cells. On Day 14 when the cells were mostly non-dividing, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples in respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeleton changes by immunohistochemistry staining of the cells with antibodies for alpha-tubulin showed no difference between the flight and ground samples. Results of our study suggest that in true non-dividing human fibroblast cells, microgravity in space has little effect on the gene and miRNA expression. Gene and miRNA expression changes were observed in cells that were confluent, but still proliferating slowly. The faster growth in the flown cells was associated with the activation of NF(sub kappa)B pathways which triggers the expression of several growth factors and the suppression of the cell cycle checkpoint.

Field Investigation of Flow Structure and Channel Morphology at Confluent-Meander Bends

NASA Astrophysics Data System (ADS)

Riley, J. D.; Rhoads, B. L.

2007-12-01

The movement of water and sediment through drainage networks is inevitably influenced by the convergence of streams and rivers at channel confluences. These focal components of fluvial systems produce a complex hydrodynamic environment, where rapid changes in flow structure and sediment transport occur to accommodate the merging of separate channel flows. The inherent geometric and hydraulic change at confluences also initiates the development of distinct geomorphic features, reflected in the bedform and shape of the channel. An underlying assumption of previous experimental and theoretical models of confluence dynamics has been that converging streams have straight channels with angular configurations. This generalized conceptualization was necessary to establish confluence planform as symmetrical or asymmetrical and to describe subsequent flow structure and geomorphic features at confluences. However, natural channels, particularly those of meandering rivers, curve and bend. This property and observation of channel curvature at natural junctions have led to the hypothesis that natural stream and river confluences tend to occur on the concave outer bank of meander bends. The resulting confluence planform, referred to as a confluent-meander bend, was observed over a century ago but has received little scientific attention. This paper examines preliminary data on three-dimensional flow structure and channel morphology at two natural confluent-meander bends of varying size and with differing tributary entrance locations. The large river confluence of the Vermilion River and Wabash River in west central Indiana and the comparatively small junction of the Little Wabash River and Big Muddy Creek in southeastern Illinois are the location of study sites for field investigation. Measurements of time-averaged three-dimensional velocity components were obtained at these confluences with an acoustic Doppler current profiler for flow events with differing momentum ratios. Bed and channel morphology were also surveyed with a digital fathometer to document geomorphic change. Preliminary analysis of the velocity data reveals the presence of a well-defined shear layer between the converging flows and secondary circulation in the main channel. The tributary channel appears to oppose high velocity flow directed toward the outer bank by centrifugal acceleration through the meander bend of the main channel, thereby diminishing erosion along the cut bank and possibly stabilizing the meander bend channel. The flow structure and channel morphology of the study sites are compared to consider the effect of spatial scale and geometric characteristics on confluent-meander bend dynamics.

Just-in-time rescue plerixafor in combination with chemotherapy and granulocyte-colony stimulating factor for peripheral blood progenitor cell mobilization.

PubMed

Smith, Veronica R; Popat, Uday; Ciurea, Stefan; Nieto, Yago; Anderlini, Paolo; Rondon, Gabriela; Alousi, Amin; Qazilbash, Muzaffar; Kebriaei, Partow; Khouri, Issa; de Lima, Marcos; Champlin, Richard; Hosing, Chitra

2013-09-01

Plerixafor, a recently approved peripheral blood progenitor cell mobilizing agent, is often added to granulocyte-colony stimulating factor (G-CSF) to mobilize peripheral blood progenitor cells in patients with lymphoma or myeloma who cannot mobilize enough CD34+ cells with G-CSF alone to undergo autologous stem cell transplantation. However, data are lacking regarding the feasibility and efficacy of just-in-time plerixafor in combination with chemotherapy and G-CSF. We reviewed the peripheral blood stem cell collection data of 38 consecutive patients with lymphoma (Hodgkin's and non-Hodgkin's) and multiple myeloma who underwent chemomobilization and high-dose G-CSF and just-in-time plerixafor to evaluate the efficacy of this treatment combination. All patients with multiple myeloma and all but one patient with lymphoma collected the minimum required number of CD34+ cells to proceed with autologous stem cell transplantation (>2 × 10(6) /kg of body weight). The median CD34+ cell dose collected in patients with non-Hodgkin lymphoma was 4.93 × 10(6) /kg of body weight. The median CD34+ cell dose collected for patients with multiple myeloma was 8.81 × 10(6) /kg of body weight. Plerixafor was well tolerated; no grade 2 or higher non-hematologic toxic effects were observed. Copyright © 2013 Wiley Periodicals, Inc.

Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry

PubMed Central

Pessoa de Magalhães, Roberto J.; Vidriales, María-Belén; Paiva, Bruno; Fernandez-Gimenez, Carlos; García-Sanz, Ramón; Mateos, Maria-Victoria; Gutierrez, Norma C.; Lecrevisse, Quentin; Blanco, Juan F; Hernández, Jose; de las Heras, Natalia; Martinez-Lopez, Joaquin; Roig, Monica; Costa, Elaine Sobral; Ocio, Enrique M.; Perez-Andres, Martin; Maiolino, Angelo; Nucci, Marcio; De La Rubia, Javier; Lahuerta, Juan-Jose; San-Miguel, Jesús F.; Orfao, Alberto

2013-01-01

Multiple myeloma remains largely incurable. However, a few patients experience more than 10 years of relapse-free survival and can be considered as operationally cured. Interestingly, long-term disease control in multiple myeloma is not restricted to patients with a complete response, since some patients revert to having a profile of monoclonal gammopathy of undetermined significance. We compared the distribution of multiple compartments of lymphocytes and dendritic cells in the bone marrow and peripheral blood of multiple myeloma patients with long-term disease control (n=28), patients with newly diagnosed monoclonal gammopathy of undetermined significance (n=23), patients with symptomatic multiple myeloma (n=23), and age-matched healthy adults (n=10). Similarly to the patients with monoclonal gammopathy of undetermined significance and symptomatic multiple myeloma, patients with long-term disease control showed an expansion of cytotoxic CD8+ T cells and natural killer cells. However, the numbers of bone marrow T-regulatory cells were lower in patients with long-term disease control than in those with symptomatic multiple myeloma. It is noteworthy that B cells were depleted in patients with monoclonal gammopathy of undetermined significance and in those with symptomatic multiple myeloma, but recovered in both the bone marrow and peripheral blood of patients with long-term disease control, due to an increase in normal bone marrow B-cell precursors and plasma cells, as well as pre-germinal center peripheral blood B cells. The number of bone marrow dendritic cells and tissue macrophages differed significantly between patients with long-term disease control and those with symptomatic multiple myeloma, with a trend to cell count recovering in the former group of patients towards levels similar to those found in healthy adults. In summary, our results indicate that multiple myeloma patients with long-term disease control have a constellation of unique immune changes favoring both immune cytotoxicity and recovery of B-cell production and homing, suggesting improved immune surveillance. PMID:22773604

Immune Tolerance in Multiple Sclerosis

PubMed Central

Goverman, Joan M.

2011-01-01

Summary Multiple sclerosis is believed to be mediated by T cells specific for myelin antigens that circulate harmlessly in the periphery of healthy individuals until they are erroneously by an environmental stimulus. Upon activation, the T cells enter the central nervous system and orchestrate an immune response against myelin. To understand the initial steps in the pathogenesis of multiple sclerosis, it is important to identify the mechanisms that maintain T-cell tolerance to myelin antigens and to understand how some myelin-specific T cells escape tolerance and what conditions lead to their activation. Central tolerance strongly shapes the peripheral repertoire of myelin-specific T cells, as most myelin-specific T cells are eliminated by clonal deletion in the thymus. Self-reactive T cells that escape central tolerance are generally capable only of low-avidity interactions with antigen-presenting cells. Despite the low avidity of these interactions, peripheral tolerance mechanisms are required to prevent spontaneous autoimmunity. Multiple peripheral tolerance mechanisms for myelin-specific T cells have been indentified, the most important of which appears to be regulatory T cells. While most studies have focused on CD4+ myelin-specific T cells, interesting differences in tolerance mechanisms and the conditions that abrogate these mechanisms have recently been described for CD8+ myelin-specific T cells. PMID:21488900

Mobilization of Neural Precursors in the Circulating Blood of Patients with Multiple Sclerosis

DTIC Science & Technology

2013-09-01

Bongarzone ER. Expression of sonic hedgehog targeted genes in peripheral blood mononuclear cells of patients with multiple sclerosis. Society for...Print Program#/Poster#: 322.13 Presentation Title: Expression of sonic  hedgehog  targeted genes in peripheral blood mononuclear cells of patients with...analyses. Gene array hybridization showed up­ regulation of various components of the Sonic  hedgehog  (Shh) pathway including, Olig1 and Olig2. Taken

Pathophysiology of drug-induce peripheral neuropathy in patients with multiple myeloma.

PubMed

Luczkowska, K; Litwinska, Z; Paczkowska, E; Machalinski, B

2018-04-01

Multiple myeloma (MM) is a disease of unknown, complex etiology that affects primarily older adults. The course of the disease and the patients' survival time are very heterogeneous, but over the last decade, clear progress in the treatment of this incurable disease has been observed. Therapeutics that have proven to be highly effective include the immunomodulatory drug thalidomide and its newer analogs, lenalidomide and pomalidomide, as well as the proteasome inhibitors bortezomib and carfilzomib. However, the administration of some of the treatments, e.g., thalidomide or bortezomib, has also been associated with the occurrence of a serious and common adverse effect, drug-induced peripheral neuropathy. The mechanism of the development of the peripheral neuropathy is poorly understood. Nevertheless, one of its potential causes could be inadequate concentrations of crucial trophic factors, including neurotrophic and/or angiogenic factors, which are responsible for the proliferation, differentiation, survival and death of neuronal and nonneuronal cells.

Hyperpolarization of the plasma membrane potential provokes reorganization of the actin cytoskeleton and increases the stability of adherens junctions in bovine corneal endothelial cells in culture.

PubMed

Nin, Verónica; Hernández, Julio A; Chifflet, Silvia

2009-12-01

In previous works we showed that the depolarization of the plasma membrane potential (PMP) determines a reorganization of the cytoskeleton of diverse epithelia in culture, consisting mainly of a reallocation of peripheral actin toward the cell center, ultimately provoking intercellular disruption. In view of this evidence, we explored in this study the possible effects of membrane potential hyperpolarization on the cytoskeletal organization and adherens junction (AJ) morphology and the stability of confluent bovine corneal endothelial cells in culture. For this purpose, hyperpolarization was achieved by substitution of extracellular sodium by nondiffusible cations or via the incorporation of valinomycin to the control solution. Actin compactness at the cell periphery was assessed by quantitative analysis of fluorescence microscopy images. The stability of the AJ was challenged by calcium deprivation or temperature decrease. Our results showed that plasma membrane hyperpolarization provokes a compaction of AJ-associated actin filaments toward the plasma membrane and an increase in the stability of the AJs. We also observed that the hyperpolarizing procedures determined similar modifications in the actin cytoskeleton of endothelial cells in whole bovine corneas. Together with our previous work, the results of this study contribute to the idea that modifications in the PMP of nonexcitable cells participate in cellular adaptive responses involving reorganization of cytoskeletal components. (c) 2009 Wiley-Liss, Inc.

Peripheral Atherectomy: Applications and Techniques.

PubMed

Mittleider, Derek; Russell, Erich

2016-06-01

Peripheral atherectomy is a class of procedures that is rapidly increasing in volume. Multiple classes of devices exist, and newer variants are added to the market annually. The devices see wide application for de novo lesions, in-stent restenosis, and adjunctive therapy for drug-coated balloons. The body of evidence supporting atherectomy is less robust than for many other peripheral therapies. The frequency and severity of complications from atherectomy can be significant compared with angioplasty and stenting, and familiarity with preventative and bailout techniques is essential for the interventionalist. Copyright © 2016 Elsevier Inc. All rights reserved.

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

[Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies].

PubMed

Rafai, M A; Fadel, H; Boulaajaj, F Z; Gam, I; El Moutawakkil, B; Karkouri, M; Hakim, K; Slassi, I

2007-01-01

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.

SALT for Language Acquisition.

ERIC Educational Resources Information Center

Bancroft, W. Jane

1996-01-01

Discusses Schuster's Suggestive-Accelerative Learning Techniques (SALT) Method, which combines Lozanov's Suggestopedia with such American methods as Asher's Total Physical Response and Galyean's Confluent Education. The article argues that students trained with the SALT Method have higher achievement scores and better attitudes than others. (14…

[Innovating to support the development of outpatient surgery].

PubMed

Dubois, Ronan

Le Confluent private hospital in Nantes has opened a unit devoted to outpatient surgery. Its architecture, organisation, facilities and services have all been designed to treat patients in as short a timeframe as possible. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction.

PubMed

Arshad, Q; Roberts, R E; Ahmad, H; Lobo, R; Patel, M; Ham, T; Sharp, D J; Seemungal, B M

2017-04-01

We hypothesised that chronic vestibular symptoms (CVS) of imbalance and dizziness post-traumatic head injury (THI) may relate to: (i) the occurrence of multiple simultaneous vestibular diagnoses including both peripheral and central vestibular dysfunction in individual patients increasing the chance of missed diagnoses and suboptimal treatment; (ii) an impaired response to vestibular rehabilitation since the central mechanisms that mediate rehabilitation related brain plasticity may themselves be disrupted. We report the results of a retrospective analysis of both the comprehensive clinical and vestibular laboratory testing of 20 consecutive THI patients with prominent and persisting vestibular symptoms still present at least 6months post THI. Individual THI patients typically had multiple vestibular diagnoses and unique to this group of vestibular patients, often displayed both peripheral and central vestibular dysfunction. Despite expert neuro-otological management, at two years 20% of patients still had persisting vestibular symptoms. In summary, chronic vestibular dysfunction in THI could relate to: (i) the presence of multiple vestibular diagnoses, increasing the risk of 'missed' vestibular diagnoses leading to persisting symptoms; (ii) the impact of brain trauma which may impair brain plasticity mediated repair mechanisms. Apart from alerting physicians to the potential for multiple vestibular diagnoses in THI, future work to identify the specific deficits in brain function mediating poor recovery from post-THI vestibular dysfunction could provide the rationale for developing new therapy for head injury patients whose vestibular symptoms are resistant to treatment. Copyright © 2017. Published by Elsevier B.V.

Increased curvature of hollow fiber membranes could up-regulate differential functions of renal tubular cell layers.

PubMed

Shen, Chong; Meng, Qin; Zhang, Guoliang

2013-08-01

Tissue engineering devices as in vitro cell culture systems in scaffolds has encountered the bottleneck due to their much lower cell functions than real tissues/organs in vivo. Such situation has been improved in some extent by mimicking the cell microenvironments in vivo from either chemical or physical ways. However, microenvironmental curvature, commonly seen in real tissues/organs, has never been manipulated to regulate the cell performance in vitro. In this regard, this paper fabricated polysulfone membranes with or without polyethylene glycol modification to investigate the impact of curvature on two renal tubular cells. Regardless the varying membrane curvatures among hollow fiber membranes of different diameters and flat membrane of zero curvature, both renal cells could well attach at 4 h of seeding and form similar confluent layers at 6 days on each membrane. Nevertheless, the renal cells on hollow fibers, though showing confluent morphology as those on flat membranes, expressed higher renal functions and, moreover, the renal functions significantly increased with the membrane curvature among hollow fibers. Such upregulation on functions was unassociated with mass transport barrier of hollow fibers, because the cultures on lengthwise cut hollow fibers without mass transfer barrier showed same curvature effect on renal functions as whole hollow fibers. It could be proposed that the curvature of hollow fiber membrane approaching to the large curvature in kidney tubules increased the mechanical stress in the renal cells and thus might up-regulate the renal cell functions. In conclusion, the increase of substrate curvature could up-regulate the cell functions without altering the confluent cell morphology and this finding will facilitate the design of functional tissue engineering devices. Copyright © 2013 Wiley Periodicals, Inc.

Experiments on the flow field physics of confluent boundary layers for high-lift systems

NASA Technical Reports Server (NTRS)

Nelson, Robert C.; Thomas, F. O.; Chu, H. C.

1994-01-01

The use of sub-scale wind tunnel test data to predict the behavior of commercial transport high lift systems at in-flight Reynolds number is limited by the so-called 'inverse Reynolds number effect'. This involves an actual deterioration in the performance of a high lift device with increasing Reynolds number. A lack of understanding of the relevant flow field physics associated with numerous complicated viscous flow interactions that characterize flow over high-lift devices prohibits computational fluid dynamics from addressing Reynolds number effects. Clearly there is a need for research that has as its objective the clarification of the fundamental flow field physics associated with viscous effects in high lift systems. In this investigation, a detailed experimental investigation is being performed to study the interaction between the slat wake and the boundary layer on the primary airfoil which is known as a confluent boundary layer. This little-studied aspect of the multi-element airfoil problem deserves special attention due to its importance in the lift augmentation process. The goal of this research is is to provide an improved understanding of the flow physics associated with high lift generation. This process report will discuss the status of the research being conducted at the Hessert Center for Aerospace Research at the University of Notre Dame. The research is sponsored by NASA Ames Research Center under NASA grant NAG2-905. The report will include a discussion of the models that have been built or that are under construction, a description of the planned experiments, a description of a flow visualization apparatus that has been developed for generating colored smoke for confluent boundary layer studies and some preliminary measurements made using our new 3-component fiber optic LDV system.

IGF-I enhances cellular senescence via the reactive oxygen species-p53 pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Handayaningsih, Anastasia-Evi; Takahashi, Michiko; Fukuoka, Hidenori

2012-08-24

Highlights: Black-Right-Pointing-Pointer Cellular senescence plays an important role in tumorigenesis and aging process. Black-Right-Pointing-Pointer We demonstrated IGF-I enhanced cellular senescence in primary confluent cells. Black-Right-Pointing-Pointer IGF-I enhanced cellular senescence in the ROS and p53-dependent manner. Black-Right-Pointing-Pointer These results may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging. -- Abstract: Cellular senescence is characterized by growth arrest, enlarged and flattened cell morphology, the expression of senescence-associated {beta}-galactosidase (SA-{beta}-gal), and by activation of tumor suppressor networks. Insulin-like growth factor-I (IGF-I) plays a critical role in cellular growth, proliferation, tumorigenesis, and regulation of aging. In the presentmore » study, we show that IGF-I enhances cellular senescence in mouse, rat, and human primary cells in the confluent state. IGF-I induced expression of a DNA damage marker, {gamma}H2AX, the increased levels of p53 and p21 proteins, and activated SA-{beta}-gal. In the confluent state, an altered downstream signaling of IGF-I receptor was observed. Treatment with a reactive oxygen species (ROS) scavenger, N-acetylcystein (NAC) significantly suppressed induction of these markers, indicating that ROS are involved in the induction of cellular senescence by IGF-I. In p53-null mouse embryonic fibroblasts, the IGF-I-induced augmentation of SA-{beta}-gal and p21 was inhibited, demonstrating that p53 is required for cellular senescence induced by IGF-I. Thus, these data reveal a novel pathway whereby IGF-I enhances cellular senescence in the ROS and p53-dependent manner and may explain the underlying mechanisms of IGF-I involvement in tumorigenesis and in regulation of aging.« less

Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke

PubMed Central

Kilarski, Laura L.; Rutten-Jacobs, Loes C. A.; Bevan, Steve; Baker, Rob; Hassan, Ahamad; Hughes, Derralynn A.; Markus, Hugh S.

2015-01-01

Background and Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. Methods Caucasian patients with lacunar infarction, aged ≤70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI’s and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. Results Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade ≥2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. Conclusion CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected. PMID:26305465

The residual repair capacity of xeroderma pigmentosum complementation group C fibroblasts is highly specific for transcriptionally active DNA.

PubMed Central

Venema, J; van Hoffen, A; Natarajan, A T; van Zeeland, A A; Mullenders, L H

1990-01-01

We have measured removal of pyrimidine dimers in defined DNA sequences in confluent and actively growing normal human and xeroderma pigmentosum complementation group C (XP-C) fibroblasts exposed to 10 J/m2 UV-irradiation. In normal fibroblasts 45% and 90% of the dimers are removed from the transcriptionally active adenosine deaminase (ADA) gene within 4 and 24 hours after irradiation respectively. Equal repair efficiencies are found in fragments located entirely within the transcription unit or partly in the 3' flanking region of the ADA gene. The rate and extent of dimer removal from the dihydrofolate reductase (DHFR) gene is very similar to that of the ADA gene. Repair of the transcriptionally inactive 754 locus is less efficient: 18% and 52% of the dimers are removed within 4 and 24 hours respectively. In spite of the limited overall repair capacity, confluent XP-C fibroblasts efficiently remove dimers from the ADA and DHFR genes: about 90% and 50% within 24 hours respectively. The 3' end of the ADA gene is repaired as efficiently as in normal human fibroblasts, but less efficient repair occurs in DNA fragments located in the DHFR gene and at the 5' end of the ADA gene. Repair of the inactive 754 locus does not exceed the very slow rate of dimer removal from the genome overall. Confluent and actively growing XP-C cells show similar efficiencies of repair of the ADA, DHFR and 754 genes. Our findings suggest the existence of two independently operating pathways directed towards repair of pyrimidine dimers in either active or inactive chromatin. XP-C cells have lost the capacity to repair inactive chromatin, but are still able to repair active chromatin. Images PMID:2308842

The value of dual-source multidetector-row computed tomography in determining pulmonary blood supply in patients with pulmonary atresia with ventricular septal defect.

PubMed

Chaosuwannakit, N; Makarawate, P

2018-01-01

Primary evaluation of patients with pulmonary atresia with ventricular septal defect (PA-VSD) traditionally relies upon echocardiography and conventional cardiac angiography (CCA). Cardiac angiography is considered the gold standard for delineation of anatomy in children with PA-VSD. Data comparing CCA and dual-source multidetector-row computed tomography angiography (MDCT) in PA-VSD patients is limited. The objective of this study was to test the hypothesis that MDCT is equivalent to CCA for anatomic delineation in these patients. Twenty-eight patients with PA-VSD underwent CCA and MDCT in close proximity to each other without interval therapy. A retrospective review of these 28 patients was performed. All MDCT data of pulmonary artery morphology, major aortopulmonary collateral arteries (MAPCAs) and type of blood supply (dual vs. single supply) were evaluated by blinded experts and results were compared with CCA. Twenty-eight patients had adequate size right and left pulmonary arteries (21 confluent and 7 non-confluent). Seven patients had complete absence of native pulmonary artery and 3 patients had stenosis of distal branches of pulmonary arteries; all had MAPCAs from descending thoracic aorta and/or subclavian arteries. Sensitivity, specificity, positive and negative predictive value of MDCT for detecting confluent of pulmonary arteries, absence of native pulmonary artery and stenosis of pulmonary arteries were all 100%. Moreover, accuracy of detecting MAPCAs was excellent. These results suggest that MDCT and CCA are equivalent in their ability to delineate pulmonary artery anatomy and MAPCAs. Dual source MDCT provides high diagnostic accuracy in evaluation of pulmonary blood supply in patients with PA-VSD and allows precise characterisation of the condition of pulmonary arteries and MAPCAs which is of paramount importance in managing patients with PA-VSD. (Folia Morphol 2018; 77, 1: 116-122).

Properties of Dental Pulp-derived Mesenchymal Stem Cells and the Effects of Culture Conditions.

PubMed

Kawashima, Nobuyuki; Noda, Sonoko; Yamamoto, Mioko; Okiji, Takashi

2017-09-01

Dental pulp mesenchymal stem cells (DPMSCs) highly express mesenchymal stem cell markers and possess the potential to differentiate into neural cells, osteoblasts, adipocytes, and chondrocytes. Thus, DPMSCs are considered suitable for tissue regeneration. The colony isolation method has commonly been used to collect relatively large amounts of heterogeneous DPMSCs. Homogenous DPMSCs can be isolated by fluorescence-activated cell sorting using antibodies against mesenchymal stem cell markers, although this method yields a limited number of cells. Both quality and quantity of DPMSCs are critical to regenerative therapy, and cell culture methods need to be improved. We thus investigated the properties of DPMSCs cultured with different methods. DPMSCs in a three-dimensional spheroid culture system, which is similar to the hanging drop culture for differentiation of embryonic stem cells, showed upregulation of odonto-/osteoblastic markers and mineralized nodule formation. This suggests that this three-dimensional spheroid culturing system for DPMSCs may be suitable for inducing hard tissues. We further examined the effect of cell culture density on the properties of DPMSCs because the properties of stem cells can be altered depending on the cell density. DPMSCs cultured under the confluent cell density condition showed slight downregulation of some mesenchymal stem cell markers compared with those under the sparse condition. The ability of DPMSCs to differentiate into hard tissue-forming cells was found to be enhanced in the confluent condition, suggesting that the confluent culture condition may not be suitable for maintaining the stemness of DPMSCs. When DPMSCs are to be used for hard tissue regeneration, dense followed by sparse cell culture conditions may be a better alternative strategy. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Flow Structure and Channel Morphology at a Confluent-Meander Bend

NASA Astrophysics Data System (ADS)

Riley, J. D.; Rhoads, B. L.

2009-12-01

Flow structure and channel morphology in meander bends have been well documented. Channel curvature subjects flow through a bend to centrifugal acceleration, inducing a counterbalancing pressure-gradient force that initiates secondary circulation. Transverse variations in boundary shear stress and bedload transport parallel cross-stream movement of high velocity flow and determine spatial patterns of erosion along the outer bank and deposition along the inner bank. Laboratory experiments and numerical modeling of confluent-meander bends, a junction planform that develops when a tributary joins a meandering river along the outer bank of a bend, suggest that flow and channel morphology in such bends deviate from typical patterns. The purpose of this study is to examine three-dimensional (3-D) flow structure and channel morphology at a natural confluent-meander bend. Field data were collected in southeastern Illinois where Big Muddy Creek joins the Little Wabash River near a local maximum of curvature along an elongated meander loop. Measurements of 3-D velocity components were obtained with an acoustic Doppler current profiler (ADCP) for two flow events with differing momentum ratios. Channel bathymetry was also resolved from the four-beam depths of the ADCP. Analysis of velocity data reveals a distinct shear layer flanked by dual helical cells within the bend immediately downstream of the confluence. Flow from the tributary confines flow from the main channel along the inner part of the channel cross section, displacing the thalweg inward, limiting the downstream extent of the point bar, protecting the outer bank from erosion and enabling bar-building along this bank. Overall, this pattern of flow and channel morphology is quite different from typical patterns in meander bends, but is consistent with a conceptual model derived from laboratory experiments and numerical modeling.

Acute Toxicity Profile and Compliance to Accelerated Radiotherapy Plus Carbogen and Nicotinamide for Clinical Stage T2-4 Laryngeal Cancer: Results of a Phase III Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssens, Geert O., E-mail: g.janssens@rther.umcn.nl; Terhaard, Chris H.; Doornaert, Patricia A.

2012-02-01

Purpose: To report the acute toxicity profile and compliance from a randomized Phase III trial comparing accelerated radiotherapy (AR) with accelerated radiotherapy plus carbogen and nicotinamide (ARCON) in laryngeal cancer. Methods and Materials: From April 2001 to February 2008, 345 patients with cT2-4 squamous cell laryngeal cancer were randomized to AR (n = 174) and ARCON (n = 171). Acute toxicity was scored weekly until Week 8 and every 2-4 weeks thereafter. Compliance to carbogen and nicotinamide was reported. Results: Between both treatment arms (AR vs. ARCON) no statistically significant difference was observed for incidence of acute skin reactions (moistmore » desquamation: 56% vs. 58%, p = 0.80), acute mucosal reactions (confluent mucositis: 79% vs. 85%, p = 0.14), and symptoms related to acute mucositis (severe pain on swallowing: 53% vs. 58%, p = 0.37; nasogastric tube feeding: 28% vs. 28%, p = 0.98; narcotic medicines required: 58% vs. 58%, p = 0.97). There was a statistically significant difference in median duration of confluent mucositis in favor of AR (2.0 vs 3.0 weeks, p = 0.01). There was full compliance with carbogen breathing and nicotinamide in 86% and 80% of the patients, with discontinuation in 6% and 12%, respectively. Adjustment of antiemesis prophylaxis was needed in 42% of patients. Conclusion: With the exception of a slight increase in median duration of acute confluent mucositis, the present data reveal a similar acute toxicity profile between both regimens and a good compliance with ARCON for clinical stage T2-4 laryngeal cancers. Treatment outcome and late morbidity will determine the real therapeutic benefit.« less

Processing and Memory of Central versus Peripheral Information as a Function of Reading Goals: Evidence from Eye-Movements

ERIC Educational Resources Information Center

Yeari, Menahem; van den Broek, Paul; Oudega, Marja

2015-01-01

The present study examined the effect of reading goals on the processing and memory of central and peripheral textual information. Using eye-tracking methodology, we compared the effect of four common reading goals--entertainment, presentation, studying for a close-ended (multiple-choice) questions test, and studying for an open-ended questions…

Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

PubMed

Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

2011-06-01

Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

Comparative dermatology: elephantiasis nostra in verrucous form comparable to coral.

PubMed

Fernandes, Lana Bezerra; Fleury Junior, Luiz Fernando Fróes

2011-01-01

Study of a rare case of Elephantiasis Nostra in verrucous form on the dorsum of the foot of an 80 year-old male with a history of recurrent erysipelas infection. The vegetant, confluent lesions on the foot resemble Trumpet Coral (Caulastrea curvata).

From confluent human iPS cells to self-forming neural retina and retinal pigmented epithelium

PubMed Central

Reichman, Sacha; Terray, Angélique; Slembrouck, Amélie; Nanteau, Céline; Orieux, Gaël; Habeler, Walter; Nandrot, Emeline F.; Sahel, José-Alain; Monville, Christelle; Goureau, Olivier

2014-01-01

Progress in retinal-cell therapy derived from human pluripotent stem cells currently faces technical challenges that require the development of easy and standardized protocols. Here, we developed a simple retinal differentiation method, based on confluent human induced pluripotent stem cells (hiPSC), bypassing embryoid body formation and the use of exogenous molecules, coating, or Matrigel. In 2 wk, we generated both retinal pigmented epithelial cells and self-forming neural retina (NR)-like structures containing retinal progenitor cells (RPCs). We report sequential differentiation from RPCs to the seven neuroretinal cell types in maturated NR-like structures as floating cultures, thereby revealing the multipotency of RPCs generated from integration-free hiPSCs. Furthermore, Notch pathway inhibition boosted the generation of photoreceptor precursor cells, crucial in establishing cell therapy strategies. This innovative process proposed here provides a readily efficient and scalable approach to produce retinal cells for regenerative medicine and for drug-screening purposes, as well as an in vitro model of human retinal development and disease. PMID:24912154

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Sigler, Robert D.

1978-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of co-axially, confluent collimated light beams. A target cavity is defined by a pair of opposed inner ellipsoidal reflectors having respective first focal points within a target region and second focal points at a vertex opening in the opposing reflector. Outwardly of each inner reflector is the opposed combination of a spherical reflector, and an outer generally ellipsoidal reflector having an aberrated first focal point coincident with the focus of the opposing spherical reflector and a second focal point coincident with the second focal point of the opposing inner ellipsoidal reflector through a vertex opening in the spherical reflector. The confluent collimated beams are incident through vertex openings in the outer ellipsoidal reflectors onto respective opposing spherical reflectors. Each beam is reflected by the associated spherical reflector onto the opposing outer ellipsoidal reflector and focused thereby onto the opposing inner ellipsoidal reflector, and then onto the target region.

Flocking Transition in Confluent Tissues

NASA Astrophysics Data System (ADS)

Paoluzzi, Matteo; Giavazzi, Fabio; Macchi, Marta; Scita, Giorgio; Cerbino, Roberto; Manning, Lisa; Marchetti, Cristina

The emerging of collective migration in biological tissues plays a pivotal role in embryonic morphogenesis, wound healing and cancer invasion. While many aspects of single cell movements are well established, the mechanisms leading to coherent displacements of cohesive cell groups are still poorly understood. Some of us recently proposed a Self-Propelled Voronoi (SPV) model of dense tissues that combines self-propelled particle models and vertex models of confluent cell layers and exhibits a liquid-solid transition as a function of cell shape and cell motility. We now examine the role of cell polarization on collective cell dynamics by introducing an orientation mechanism that aligns cell polarization with local cell motility. The model predicts a density-independent flocking transition tuned by the strength of the aligning interaction, with both solid and liquid flocking states existing in different regions of parameter space. MP and MCM were supported by the Simons Foundation Targeted Grant in the Mathematical Modeling of Living Systems Number: 342354 and by the Syracuse Soft Matter Program.

Differential cellular responses by oncogenic levels of c-Myc expression in long-term confluent retinal pigment epithelial cells.

PubMed

Wang, Yiping; Cheng, Xiangdong; Samma, Muhammad Kaleem; Kung, Sam K P; Lee, Clement M; Chiu, Sung Kay

2018-06-01

c-Myc is a highly pleiotropic transcription factor known to control cell cycle progression, apoptosis, and cellular transformation. Normally, ectopic expression of c-Myc is associated with promoting cell proliferation or triggering cell death via activating p53. However, it is not clear how the levels of c-Myc lead to different cellular responses. Here, we generated a series of stable RPE cell clones expressing c-Myc at different levels, and found that consistent low level of c-Myc induced cellular senescence by activating AP4 in post-confluent RPE cells, while the cells underwent cell death at high level of c-Myc. In addition, high level of c-Myc could override the effect of AP4 on cellular senescence. Further knockdown of AP4 abrogated senescence-like phenotype in cells expressing low level of c-Myc, and accelerated cell death in cells with medium level of c-Myc, indicating that AP4 was required for cellular senescence induced by low level of c-Myc.

Impedance analysis of cultured cells: a mean-field electrical response model for electric cell-substrate impedance sensing technique.

PubMed

Urdapilleta, E; Bellotti, M; Bonetto, F J

2006-10-01

In this paper we present a model to describe the electrical properties of a confluent cell monolayer cultured on gold microelectrodes to be used with electric cell-substrate impedance sensing technique. This model was developed from microscopic considerations (distributed effects), and by assuming that the monolayer is an element with mean electrical characteristics (specific lumped parameters). No assumptions were made about cell morphology. The model has only three adjustable parameters. This model and other models currently used for data analysis are compared with data we obtained from electrical measurements of confluent monolayers of Madin-Darby Canine Kidney cells. One important parameter is the cell-substrate height and we found that estimates of this magnitude strongly differ depending on the model used for the analysis. We analyze the origin of the discrepancies, concluding that the estimates from the different models can be considered as limits for the true value of the cell-substrate height.

Derivatives of Horn hypergeometric functions with respect to their parameters

NASA Astrophysics Data System (ADS)

Ancarani, L. U.; Del Punta, J. A.; Gasaneo, G.

2017-07-01

The derivatives of eight Horn hypergeometric functions [four Appell F1, F2, F3, and F4, and four (degenerate) confluent Φ1, Φ2, Ψ1, and Ξ1] with respect to their parameters are studied. The first derivatives are expressed, systematically, as triple infinite summations or, alternatively, as single summations of two-variable Kampé de Fériet functions. Taking advantage of previously established expressions for the derivative of the confluent or Gaussian hypergeometric functions, the generalization to the nth derivative of Horn's functions with respect to their parameters is rather straightforward in most cases; the results are expressed in terms of n + 2 infinite summations. Following a similar procedure, mixed derivatives are also treated. An illustration of the usefulness of the derivatives of F1, with respect to the first and third parameters, is given with the study of autoionization of atoms occurring as part of a post-collisional process. Their evaluation setting the Coulomb charge to zero provides the coefficients of a Born-like expansion of the interaction.

The Importance of Rare Subtypes in Diagnosis and Treatment of Peripheral Neuropathy: A Review.

PubMed

Callaghan, Brian C; Price, Raymond S; Chen, Kevin S; Feldman, Eva L

2015-12-01

Peripheral neuropathy is a prevalent condition that usually warrants a thorough history and examination but has limited diagnostic evaluation. However, rare localizations of peripheral neuropathy often require more extensive diagnostic testing and different treatments. To describe rare localizations of peripheral neuropathy, including the appropriate diagnostic evaluation and available treatments. References were identified from PubMed searches conducted on May 29, 2015, with an emphasis on systematic reviews and randomized clinical trials. Articles were also identified through the use of the authors' own files. Search terms included common rare neuropathy localizations and their causes, as well as epidemiology, pathophysiology, diagnosis, and treatment. Diffuse, nonlength-dependent neuropathies, multiple mononeuropathies, polyradiculopathies, plexopathies, and radiculoplexus neuropathies are rare peripheral neuropathy localizations that often require extensive diagnostic testing. Atypical neuropathy features, such as acute/subacute onset, asymmetry, and/or motor predominant signs, are frequently present. The most common diffuse, nonlength-dependent neuropathies are Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and amyotrophic lateral sclerosis. Effective disease-modifying therapies exist for many diffuse, nonlength-dependent neuropathies including Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and some paraprotein-associated demyelinating neuropathies. Vasculitic neuropathy (multiple mononeuropathy) also has efficacious treatment options, but definitive evidence of a treatment effect for IgM anti-MAG neuropathy and diabetic amyotrophy (radiculoplexus neuropathy) is lacking. Recognition of rare localizations of peripheral neuropathy is essential given the implications for diagnostic testing and treatment. Electrodiagnostic studies are an important early step in the diagnostic evaluation and provide information on the localization and pathophysiology of nerve injury.

Cutaneous progressive angiomatosis on the muzzle of a dog, treated by laser photocoagulation therapy.

PubMed

Olivieri, Lara; Nardini, Giordano; Pengo, Graziano; Abramo, Francesca

2010-10-01

A 10-year old, female, cocker spaniel was presented with a bleeding lesion on the muzzle and nasal planum observed initially as a small raised nodule at 1 year of age. This became clinically more pronounced at 5 years of age, progressively enlarged thereafter and was diagnosed initially as a vascular tumour. On clinical examination, multiple confluent nodules of variable diameter (0.5-1.5 cm) deformed the outline of the nose. Histological examination revealed a progressive angiomatosis with multifocal infiltrative growth of increased dermal vascularization with different sized and type of anastomosing vessels lined by a monolayer of reactive endothelium, often arranged as papillary projections into the lumina. Partial nosectomy, the first therapeutic approach, was unsuccessful and the lesion relapsed within 6 months. However, subsequent laser photocoagulation therapy provided a good cosmetic outcome, no relapse 1 year later, and appeared to provide an effective alternative to ablation surgery. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

Necrotizing Fasciitis as a Complication of a Continuous Sciatic Nerve Catheter Using the Lateral Popliteal Approach.

PubMed

Dott, Daltry; Canlas, Christopher; Sobey, Christopher; Obremskey, William; Thomson, Andrew Brian

Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement.

Biology of Epstein-Barr virus during infectious mononucleosis.

PubMed

Sitki-Green, Diane L; Edwards, Rachel Hood; Covington, Mary M; Raab-Traub, Nancy

2004-02-01

Infectious mononucleosis is the clinical manifestation of primary infection with Epstein-Barr virus (EBV). We monitored primary infection during convalescence and during the establishment of persistent infection. The profiles of EBV strains in the oral cavity and in peripheral blood were determined by use of a heteroduplex tracking assay specific for the EBV gene encoding latent membrane protein 1. Multiple EBV strains were detected in most patients and persisted in and were possibly transmitted among 3 distinct compartments of infection, including the oral cavity, peripheral blood lymphocytes, and the cell-free fraction of the blood plasma. We also tracked transmission of multiple strains from an asymptomatic carrier to a patient diagnosed with primary EBV infection. These data reveal that primary EBV infection is complex, with transmission of multiple strains and clear differences in relative abundance of strains in distinct compartments.

A clinically feasible treatment protocol for magnetic resonance-guided high-intensity focused ultrasound ablation in the liver.

PubMed

Wijlemans, Joost W; de Greef, Martijn; Schubert, Gerald; Bartels, Lambertus W; Moonen, Chrit T W; van den Bosch, Maurice A A J; Ries, Mario

2015-01-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) allows for noninvasive thermal ablation under real-time temperature imaging guidance. The purpose of this study was to assess the feasibility and safety of MR-HIFU ablation of liver tissue in a clinically acceptable setting. The experimental protocol was designed with a clinical ablation procedure of a small malignant tumor in mind; the procedures were performed within a clinically feasible time frame and care was taken to avoid adverse events. The main outcome was the size and quality of the ablated liver tissue volume on imaging and histology. Secondary outcomes were safety and treatment time. Healthy pigs (n = 10) under general anesthesia were positioned on a clinical MR-HIFU system, which consisted of an HIFU tabletop with a skin cooling system integrated into a 1.5-T MR scanner. A liver tissue volume was ablated with multiple sonication cells (4 × 4 × 10 mm, 450 W). Both MR thermometry and sonication were respiratory-gated using a pencil beam navigator on the diaphragm. Contrast-enhanced T1-weighted (CE-T1w) imaging was performed for treatment evaluation. Targeted total treatment time was 3 hours. The abdominal wall, liver, and adjacent organs were inspected postmortem for thermal damage. Ablated tissue volumes were processed for cell viability staining. The ablated volumes were analyzed using MR imaging, MR thermometry, and cell viability histology. Eleven volume ablations were performed in 10 animals, resulting in a median nonperfused volume (NPV) on CE-T1w imaging of 1.6 mL (interquartile range [IQR], 0.8-2.3; range, 0.7-3.0). Cell viability histology showed a damaged volume of 1.5 mL (IQR, 1.1-1.8; range, 0.7-2.3). The NPV was confluent in 10 of the 11 cases. The ablated tissue volume on cell viability histology was confluent in all 9 available cases. In all cases, there was a good correspondence between the aspects of the NPV on CE-T1w and the ablated volume on cell viability histology. Two treatment-related adverse events occurred: 1 animal had a 7-mm skin burn and 1 animal showed evidence of thermal damage on the surface of the spleen. Median ablation time was 108 minutes (IQR, 101-120; range, 96-181 minutes) and median total treatment time was 180 minutes (IQR, 165-224; 130-250 minutes). Our results demonstrate the feasibility and safety of MR-HIFU ablation of liver tissue volumes. The imaging data and cell viability histology show, for the first time, that confluent ablation volumes can be achieved with motion-gated ablation and MR guidance. These results were obtained using a readily available MR-HIFU system with only minor modifications, within a clinically acceptable time frame, and with only minor adverse events. This shows that this technique is sufficiently reliable and safe to initiate a clinical trial.

MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH SUBRETINAL DEPOSITS.

PubMed

Gal-Or, Orly; Sorenson, John A; Gattoussi, Sarra; Dolz-Marco, Rosa; Freund, K Bailey

2017-06-13

To describe the multimodal imaging findings of transient subretinal deposits occurring in multiple evanescent white dot syndrome (MEWDS). The multimodal imaging characteristics of transient subretinal deposits occurring in MEWDS were investigated with ultra-widefield color and fundus autofluorescence, cross-sectional and en-face optical coherence tomography (OCT), en face OCT-angiography, and quantitative autofluorescence. A 28-year-old woman presented with photopsia and temporal visual field loss in her right eye. Her best-corrected visual acuity was 20/20 in her right eye and 20/25 in her left eye. Funduscopic examination showed characteristic peripapillary hyperautofluorescent white dots of MEWDS corresponding to ellipsoid zone disruption on OCT. These lesions became confluent throughout the posterior fundus over the next 4 weeks. As the patient's symptoms were resolving, a second type of transient hyperautofluorescent lesion was noted which corresponded to hyperreflective subretinal deposits on cross-sectional and en face structural OCT. These subretinal deposits were most evident at 10-week follow-up and had nearly resolved at 14-week follow-up. Quantitative autofluorescence showed that, unlike the acute MEWDS lesions, the hyperautoflurescence of the subretinal deposits persisted after photobleaching. At multiple time points over 14 weeks of follow-up, OCT angiography showed no evidence of retinal or choroidal flow abnormalities. Transient subretinal deposits may develop during MEWDS in areas of previous diffuse outer retinal disruption. As these deposits remain hyperautoflurescent on quantitative autofluorescence after photobleaching, they may represent accumulations of debris originating from damaged photoreceptor outer segments.

Compartmentalization and Transmission of Multiple Epstein-Barr Virus Strains in Asymptomatic Carriers

PubMed Central

Sitki-Green, Diane; Covington, Mary; Raab-Traub, Nancy

2003-01-01

Infection with the Epstein-Barr virus (EBV) is often subclinical in the presence of a healthy immune response; thus, asymptomatic infection is largely uncharacterized. This study analyzed the nature of EBV infection in 20 asymptomatic immunocompetent hosts over time through the identification of EBV strain variants in the peripheral blood and oral cavity. A heteroduplex tracking assay specific for the EBV gene LMP1 precisely identified the presence of multiple EBV strains in each subject. The strains present in the peripheral blood and oral cavity were often completely discordant, indicating the existence of distinct infections, and the strains present and their relative abundance changed considerably between time points. The possible transmission of strains between the oral cavity and peripheral blood compartments could be tracked within subjects, suggesting that reactivation in the oral cavity and subsequent reinfection of B lymphocytes that reenter the periphery contribute to the maintenance of persistence. In addition, distinct virus strains persisted in the oral cavity over many time points, suggesting an important role for epithelial cells in the maintenance of persistence. Asymptomatic individuals without tonsillar tissue, which is believed to be an important source of virus for the oral cavity, also exhibited multiple strains and a cyclic pattern of transmission between compartments. This study revealed that the majority of patients with infectious mononucleosis were infected with multiple strains of EBV that were also compartmentalized, suggesting that primary infection involves the transmission of multiple strains. Both the primary and carrier states of infection with EBV are more complex than previously thought. PMID:12525618

Compartmentalization and transmission of multiple epstein-barr virus strains in asymptomatic carriers.

PubMed

Sitki-Green, Diane; Covington, Mary; Raab-Traub, Nancy

2003-02-01

Infection with the Epstein-Barr virus (EBV) is often subclinical in the presence of a healthy immune response; thus, asymptomatic infection is largely uncharacterized. This study analyzed the nature of EBV infection in 20 asymptomatic immunocompetent hosts over time through the identification of EBV strain variants in the peripheral blood and oral cavity. A heteroduplex tracking assay specific for the EBV gene LMP1 precisely identified the presence of multiple EBV strains in each subject. The strains present in the peripheral blood and oral cavity were often completely discordant, indicating the existence of distinct infections, and the strains present and their relative abundance changed considerably between time points. The possible transmission of strains between the oral cavity and peripheral blood compartments could be tracked within subjects, suggesting that reactivation in the oral cavity and subsequent reinfection of B lymphocytes that reenter the periphery contribute to the maintenance of persistence. In addition, distinct virus strains persisted in the oral cavity over many time points, suggesting an important role for epithelial cells in the maintenance of persistence. Asymptomatic individuals without tonsillar tissue, which is believed to be an important source of virus for the oral cavity, also exhibited multiple strains and a cyclic pattern of transmission between compartments. This study revealed that the majority of patients with infectious mononucleosis were infected with multiple strains of EBV that were also compartmentalized, suggesting that primary infection involves the transmission of multiple strains. Both the primary and carrier states of infection with EBV are more complex than previously thought.

Completeness of the Coulomb Wave Functions in Quantum Mechanics

ERIC Educational Resources Information Center

Mukunda, N.

1978-01-01

Gives an explicit and elementary proof that the radial energy eigenfunctions for the hydrogen atom in quantum mechanics, bound and scattering states included, form a complete set. The proof uses some properties of the confluent hypergeometric functions and the Cauchy residue theorem from analytic function theory. (Author/GA)

Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

PubMed

Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

2014-01-01

Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

Novel technique for repair of severed peripheral nerves in rats using polyurea crosslinked silica aerogel scaffold.

PubMed

Sabri, Firouzeh; Gerth, David; Tamula, George-Rudolph M; Phung, Thien-Chuong N; Lynch, Kyle J; Boughter, John D

2014-10-01

To design, synthesize, and test in vivo an aerogel-based top-open peripheral nerve scaffold to simultaneously support and guide multiple completely severed peripheral nerves in a rat model. Also, to explore options for immobilizing severed nerves on the aerogel material without the use of sutures resulting in reduced surgical time. A novel material and approach was developed for the reattachment of severed peripheral nerves. Nerve confinement and alignment in this case relies on the surface properties of a lightweight, highly porous, polyurea crosslinked silica aerogel scaffold. The distal and proximal ends of completely transected nerve terminals were positioned inside prefabricated "top-open" corrugated channels that cradled approximately two thirds of the circumference of the nerve trunk and connectivity of the severed nerves was evaluated using sciatic function index (SFI) technique for five months post-surgery on 10 female Sprague-Dawley rats then compared with the gold standard for peripheral nerve repair. The interaction of nerves with the surface of the scaffold was investigated also. Multichannel aerogel-based nerve support scaffold showed similar SFI recovery trend as the case suture repair technique. Usage of an adhesion-promoting coating reduced the friction between the nerve and the scaffold leading to slippage and lack of attachment between nerve and surface. The aerogel scaffold used in this study did not collapse under pressure during the incubation period and allowed for a rapid and non-invasive peripheral nerve repair approach without the demands of microsurgery on both time and surgical expertise. This technique may allow for simultaneous repair and reconnection of multiple severed nerves particularly relevant to nerve branching sites.

Olivopontocerebellar atrophy

MedlinePlus

... degeneration; Multiple system atrophy cerebellar predominance; MSA-C Images Central nervous system and peripheral nervous system References Jankovic J, Lang AE. Diagnosis and assessment of Parkinson disease ...

Parallel, multi-stage processing of colors, faces and shapes in macaque inferior temporal cortex

PubMed Central

Lafer-Sousa, Rosa; Conway, Bevil R.

2014-01-01

Visual-object processing culminates in inferior temporal (IT) cortex. To assess the organization of IT, we measured fMRI responses in alert monkey to achromatic images (faces, fruit, bodies, places) and colored gratings. IT contained multiple color-biased regions, which were typically ventral to face patches and, remarkably, yoked to them, spaced regularly at four locations predicted by known anatomy. Color and face selectivity increased for more anterior regions, indicative of a broad hierarchical arrangement. Responses to non-face shapes were found across IT, but were stronger outside color-biased regions and face patches, consistent with multiple parallel streams. IT also contained multiple coarse eccentricity maps: face patches overlapped central representations; color-biased regions spanned mid-peripheral representations; and place-biased regions overlapped peripheral representations. These results suggest that IT comprises parallel, multi-stage processing networks subject to one organizing principle. PMID:24141314

[Multiple organ failure presumably due to alkylating agents used as preconditioning drugs for autologous peripheral blood stem cell transplantation in an acute promyelocytic leukemia].

PubMed

Ida, Tori; Hashimoto, Shigeo; Suzuki, Nobuaki; Ebe, Yusuke; Yano, Toshio; Sato, Naoko; Koike, Tadashi

2016-01-01

A 52-year-old male was diagnosed as having acute promyelocytic leukemia (APL) in 2006. He received induction chemotherapy including all-trans retinoic acid and initially achieved a complete remission (CR). After several courses of consolidation therapy combining anthracyclines and cytarabine, he maintained CR. In 2009, an APL relapse was diagnosed, and he was treated with arsenic trioxide. Since he achieved a second CR, he underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) with a conditioning regimen consisting of busulfan and melphalan. At four months after auto-PBSCT, he developed a pneumothorax and acute respiratory failure. He died despite intensive therapy. Autopsy findings included various atypical and apoptotic cells in his pulmonary tissue. These changes were confirmed in multiple organs throughout the body, suggesting them to be drug-induced. The findings in this case suggested multiple organ failure due to alkylating agents.

Radiculopathy in neuromyelitis optica. How does anti-AQP4 Ab involve PNS?

PubMed

Kim, Seungyeon; Park, Joonghyun; Kwon, Bum Sun; Park, Jin-Woo; Lee, Ho Jun; Choi, Jin-Ho; Nam, Kiyeun

2017-11-01

Until recently, the peripheral nervous system (PNS) had been known to be spared in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, some studies of late have reported PNS damage in demyelination diseases of the central nervous system (CNS) such as MS and NMOSD. Although multiple studies have reported characteristics reminiscent of peripheral neuropathy in MS, there have been limited reports in NMOSD. To investigate the incidence and pathology of peripheral neuropathy in NMOSD, we reviewed articles describing such cases including our own case. We performed a search of all clinical studies of peripheral neuropathy in NMOSD published up to December 17, 2016. We put no restrictions on language or year of publication in our search. The following keywords were searched: radiculopathy, peripheral nervous system diseases, neuromyelitis optica, neuromyelitis optica septrum disorder, aquaporin 4, electrodiagnosis, neural conduction and electromyography. We review ten cases (nine published reports and our own case study) of peripheral neuropathy in NMOSD. Each case could be confirmed as radiculopathy by electrodiagnostic (EDX) testing. Presently, there are two disparate viewpoints on peripheral neuropathy in NMOSD. In the first, aquaporin 4, which exists in the transitional zone of the CNS-PNS at the root level, may be the target of radiculitis in NMOSD. In the second, there may be some other unknown antibody to an axoglial antigen or something else that may play an active role in PNS damage. In our survey of ten case studies, the EDX results confirmed mixed axonal loss as well as demyelination type radiculopathy, which lends support to the first viewpoint. Pathophysiology of PNS damage in NMOSD might be due to radiculopathy. Although it seems to be rare, radiculopathy may actually be underestimated, and correspondingly underreported, due to its overlap with symptoms of myelitis. Therefore, further evaluation is needed to establish the incidence and pathophysiology of radiculopathy in NMOSD. Copyright © 2017 Elsevier B.V. All rights reserved.

High Levels of Peripheral Blood Circulating Plasma Cells as a Specific Risk Factor for Progression of Smoldering Multiple Myeloma

PubMed Central

Bianchi, Giada; Kyle, Robert A.; Larson, Dirk R.; Witzig, Thomas E.; Kumar, Shaji; Dispenzieri, Angela; Morice, William G.; Rajkumar, S. Vincent

2012-01-01

Smoldering multiple myeloma (SMM) carries a 50% risk of progression to multiple myeloma (MM) or related malignancy within the first 5 years following diagnosis. The goal of this study was to determine if high levels of circulating plasma cells (PCs) are predictive of SMM transformation within the first 2–3 years from diagnosis. Ninety-one patients diagnosed with SMM at Mayo Clinic from January 1994 through January 2007 who had testing for circulating PCs using an immunofluorescent assay and adequate follow up to ascertain disease progression, were studied. High level of circulating PCs was defined as absolute peripheral blood PCs >5000 ×106/L and/or > 5% cytoplasmic immunoglobulin (Ig) positive PCs per 100 peripheral blood mononuclear cells. Patients with high circulating PCs (14 of 91 patients, 15%) were significantly more likely to progress to active disease within 2 years compared with patients without high circulating PCs, 71% versus 25%, respectively, P=0.001. Corresponding rates for progression within 3 years were 86% versus 35%, respectively, P<0.001. Overall survival (OS) after both SMM diagnosis and MM diagnosis was also significantly different. High levels of circulating PCs identify SMM patients with an elevated risk of progression within the first 2 to 3 years following diagnosis. PMID:22902364

Molecular cloning of human T-cell lymphotrophic virus type I-like proviral genome from the peripheral lymphocyte DNA of a patient with chronic neurologic disorders.

PubMed Central

Reddy, E P; Mettus, R V; DeFreitas, E; Wroblewska, Z; Cisco, M; Koprowski, H

1988-01-01

Human T-cell lymphotropic virus type 1 (HTLV-I), the etiologic agent of human T-cell leukemia, has recently been shown to be associated with neurologic disorders such as tropical spastic paraparesis, HTLV-associated myelopathy, and possibly with multiple sclerosis. In this communication, we have examined one specific case of neurologic disorder that can be classified as multiple sclerosis or tropical spastic paraparesis. The patient suffering from chronic neurologic disorder was found to contain antibodies to HTLV-I envelope and gag proteins in his serum and cerebrospinal fluid. Lymphocytes from peripheral blood and cerebrospinal fluid of the patient were shown to express viral RNA sequences by in situ hybridization. Southern blot analysis of the patient lymphocyte DNA revealed the presence of HTLV-I-related sequences. Blot-hybridization analysis of the RNA from fresh peripheral lymphocytes stimulated with interleukin 2 revealed the presence of abundant amounts of genomic viral RNA with little or no subgenomic RNA. We have cloned the proviral genome from the DNA of the peripheral lymphocytes and determined its restriction map. This analysis shows that this proviral genome is very similar if not identical to that of the prototype HTLV-I genome. Images PMID:2897123

Role of Snf5 Mutations in Schwannomatosis Pain

DTIC Science & Technology

2016-10-01

National Multiple Sclerosis Society • Name: • Fatima Banine • Project Role: • Staff Scientist • Researcher Identifier (e.g. ORCID ID...and the subsequent data analysis and validation assays (e.g. qPCR) • Funding Support: • National Multiple Sclerosis Society • Name: • Scott...40,000 individuals worldwide. The disease is characterized by multiple peripheral nerve tumors, called schwannomas, and a predisposition to other

Confluent Language Approach Revisited: Towards Integrating Technology in Literacy Education.

ERIC Educational Resources Information Center

Suleiman, Mahmoud F.

Institutions of higher education have been on the forefront of technology integration. In particular, teacher education programs must respond to the training needs of prospective teachers who will in turn help young learners grow in the technologically advanced society. Several steps have been taken by universities and colleges to meet relevant…

Bridging the Gap: Technology and Veteran Academic Success

ERIC Educational Resources Information Center

Cass, David; Hammond, Shane

2015-01-01

This paper presents two unique yet confluent perspectives regarding the use of technology to support student veterans in college, and is meant to ignite discussion of the blending of high impact practices with technology to promote their academic success. The authors highlight the historical trends of student veterans in the academy and discuss…

Dietzia papillomatosis bacteremia.

PubMed

Rammer, Paul; Calum, Henrik; Moser, Claus; Björnsdóttir, Maria K; Smedegaard, Heidi; Høiby, Niels; Bjarnsholt, Thomas

2013-06-01

The clinical significance of Dietzia papillomatosis is for the moment limited to the rare skin disease confluent and reticulated papillomatosis. We present a case of infection with D. papillomatosis in a 2-year-old boy with known syringomyelia. The microbiological diagnosis was done using 16S rRNA gene sequencing. This is the first report of bacteremia with D. papillomatosis.

An Overview of Radical Education in Action

ERIC Educational Resources Information Center

Heron, John

2012-01-01

This article on peer learning was originally prepared for the Committee of the Institute for the Development of Human Potential (IDHP) in 1985. It outlines the history, structure and ideology of seventeen IDHP courses with their two primary dimensions--confluent and political. A holistic conceptual model is presented for each of these dimensions,…

Golovinomyces spadaceus causing powdery mildew on Coreopsis hybrid 'Full Moon' (Heliantheae, Asteraceae) in Washington State

USDA-ARS?s Scientific Manuscript database

Symptoms of powdery mildew were observed on a Coreopsis cultivar in the Horticulture and Landscape Architecture Garden on the Washington State University campus, Pullman, Whitman County, Washington. White to off-white sporulating mycelial areas were ~5mm in diam to confluent and confined to adaxial...

Senior Humanities: Interdisciplinary Education in English and Religion.

ERIC Educational Resources Information Center

Perry, Douglas Ross

An interdisciplinary approach to teaching English and religion can eliminate some of the educational problems posed by each subject. Part one of this thesis presents a philosophy of education which suggests that confluent and student-centered methods of teaching can best develop creativity and, thus, lead to greater humanization of students. Part…

Automatic Cell Segmentation in Fluorescence Images of Confluent Cell Monolayers Using Multi-object Geometric Deformable Model.

PubMed

Yang, Zhen; Bogovic, John A; Carass, Aaron; Ye, Mao; Searson, Peter C; Prince, Jerry L

2013-03-13

With the rapid development of microscopy for cell imaging, there is a strong and growing demand for image analysis software to quantitatively study cell morphology. Automatic cell segmentation is an important step in image analysis. Despite substantial progress, there is still a need to improve the accuracy, efficiency, and adaptability to different cell morphologies. In this paper, we propose a fully automatic method for segmenting cells in fluorescence images of confluent cell monolayers. This method addresses several challenges through a combination of ideas. 1) It realizes a fully automatic segmentation process by first detecting the cell nuclei as initial seeds and then using a multi-object geometric deformable model (MGDM) for final segmentation. 2) To deal with different defects in the fluorescence images, the cell junctions are enhanced by applying an order-statistic filter and principal curvature based image operator. 3) The final segmentation using MGDM promotes robust and accurate segmentation results, and guarantees no overlaps and gaps between neighboring cells. The automatic segmentation results are compared with manually delineated cells, and the average Dice coefficient over all distinguishable cells is 0.88.

Attributed relational graphs for cell nucleus segmentation in fluorescence microscopy images.

PubMed

Arslan, Salim; Ersahin, Tulin; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

2013-06-01

More rapid and accurate high-throughput screening in molecular cellular biology research has become possible with the development of automated microscopy imaging, for which cell nucleus segmentation commonly constitutes the core step. Although several promising methods exist for segmenting the nuclei of monolayer isolated and less-confluent cells, it still remains an open problem to segment the nuclei of more-confluent cells, which tend to grow in overlayers. To address this problem, we propose a new model-based nucleus segmentation algorithm. This algorithm models how a human locates a nucleus by identifying the nucleus boundaries and piecing them together. In this algorithm, we define four types of primitives to represent nucleus boundaries at different orientations and construct an attributed relational graph on the primitives to represent their spatial relations. Then, we reduce the nucleus identification problem to finding predefined structural patterns in the constructed graph and also use the primitives in region growing to delineate the nucleus borders. Working with fluorescence microscopy images, our experiments demonstrate that the proposed algorithm identifies nuclei better than previous nucleus segmentation algorithms.

Validation of the Zürich burn-biofilm model.

PubMed

Guggenheim, Merlin; Thurnheer, Thomas; Gmür, Rudolf; Giovanoli, Pietro; Guggenheim, Bernhard

2011-11-01

Despite advances in the use of topical and parenteral antimicrobial therapy and the practice of early tangential burn-wound excision, bacterial infection remains a major problem in the management of burn victims today. The purpose of this study was to design and evaluate a polyspecies biofilm model with bacteria known to cause severe infections in burn patients. The model is simple to prepare, maintain and analyse, and allows for short-term exposure to antimicrobials. Initial experiments showed that it was impossible to establish balanced polyspecies biofilms with an inoculum of Gram-positive and -negative bacteria. After 64.5 h of incubation, the Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) had suppressed the Gram-positives (Enterococcus faecalis, Staphylococcus aureus and Streptococcus intermedius). However, adding the Gram-negative bacteria after 41.5 h to an established biofilm of Gram-positives resulted in a balanced microbial consortium. After 64.5 h, all species were present in high numbers (10(7) to 10(8) colony forming units (CFU) per biofilm). Multiple repetitions showed high reproducibility of biofilm formation without significant differences between and within experiments. Combined fluorescence in situ hybridisation/confocal laser scanning microscopy (FISH/CLSM) analyses, for which biofilms had to be grown on a different non-flexible substrate (hydroxy apatite), revealed that, by 41.5 h, the biofilm consisted of an almost confluent layer of bacteria firmly adherent to the substratum. After 64.5 h (22 h after the addition of the Gram negatives), the biofilm consisted of a confluent mixture of single cells, an abundance of galaxies of bacteria with small lacunae and large amounts of extracellular matrix polysaccharides. The polyspecies biofilm model contains the most prevalent burn-associated Gram-positive and Gram-negative bacterial pathogens and mimics the Gram-negative shift observed in vivo. It shows excellent reproducibility. It should allow adaptation to the bacterial spectrum prevalent in different burn centres and lead to a much more reliable investigation of the efficiency of topical antimicrobial agents than models operating with planktonic bacteria. The experiments further open up the perspective to create an in vivo model using these biofilms as infectious agents. Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.

No-touch radiofrequency ablation using multiple electrodes: An in vivo comparison study of switching monopolar versus switching bipolar modes in porcine livers

PubMed Central

Chang, Won; Yoon, Jeong Hee; Lee, Dong Ho; Lee, Sang Min; Lee, Kyoung Bun; Kim, Bo Ram; Kim, Tae-Hyung; Lee, Seunghyun; Han, Joon Koo

2017-01-01

Objective To evaluate the in vivo technical feasibility, efficiency, and safety of switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation (RFA) as a no-touch ablation technique in the porcine liver. Materials and methods The animal care and use committee approved this animal study and 16 pigs were used in two independent experiments. In the first experiment, RFA was performed on 2-cm tumor mimickers in the liver using a no-touch technique in the SM mode (2 groups, SM1: 10 minutes, n = 10; SM2: 15 minutes, n = 10) and SB-mode (1 group, SB: 10 minutes, n = 10). The technical success with sufficient safety margins, creation of confluent necrosis, ablation size, and distance between the electrode and ablation zone margin (DEM), were compared between groups. In the second experiment, thermal injury to the adjacent anatomic organs was compared between SM-RFA (15 minutes, n = 13) and SB-RFA modes (10 minutes, n = 13). Results The rates of the technical success and the creation of confluent necrosis were higher in the SB group than in the SM1 groups (100% vs. 60% and 90% vs. 40%, both p < 0.05). The ablation volume in the SM2 group was significantly larger than that in the SB group (59.2±18.7 cm3 vs. 39.8±9.7 cm3, p < 0.05), and the DEM in the SM2 group was also larger than that in the SB group (1.39±0.21 cm vs. 1.07±0.10 cm, p < 0.05). In the second experiment, the incidence of thermal injury to the adjacent organs and tissues in the SB group (23.1%, 3/13) was significantly lower than that in the SM group (69.2%, 8/13) (p = 0.021). Conclusion SB-RFA was more advantageous for a no-touch technique for liver tumors, showing the potential of a better safety profile than SM-RFA. PMID:28445542

Restless legs syndrome

MedlinePlus

... often in people with: Chronic kidney disease Diabetes Iron, magnesium, or folic acid deficiency Parkinson disease Peripheral neuropathy Pregnancy Multiple sclerosis RLS may also occur in people who: Use ...

Comparative effectiveness and safety of thalidomide and lenalidomide in patients with multiple myeloma in the United States of America: A population-based cohort study.

PubMed

Luo, Jing; Gagne, Joshua J; Landon, Joan; Avorn, Jerry; Kesselheim, Aaron S

2017-01-01

The comparative effectiveness of thalidomide and lenalidomide in the treatment of multiple myeloma has not been established. We conducted an observational cohort study of multiple myeloma patients receiving either thalidomide or lenalidomide in routine care in the United States of America to assess their comparative survival and rates of peripheral neuropathy. Myeloma patients were identified and followed using administrative claims data from a large national health insurance provider (UnitedHealth). Patients were eligible if they initiated treatment with either lenalidomide or thalidomide between 2004 and 2013. Propensity score stratified Cox proportional hazards regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for death and new-onset peripheral neuropathy (defined by International Classification of Disease, Ninth Revision codes or a new prescription intended to treat neuropathic pain). Our cohort included 1264 myeloma patients who initiated either thalidomide or lenalidomide. Among 406 new users of thalidomide, 142 (35%) developed peripheral neuropathy during a mean 499 person-days of follow-up. Among 858 new users of lenalidomide, 244 (29%) developed neuropathy during 587 person-days. Compared with thalidomide initiators, lenalidomide initiators had a reduced risk of peripheral neuropathy (HR 0.71, 95% CI: 0.56-0.92). We found no difference in rates of death (HR 1.00, 95% CI: 0.71-1.41). Our results agree with the findings of recently published trials suggesting that thalidomide and lenalidomide are equivalent with respect to survival outcomes but different with respect to neurotoxicity in clinical practice settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detecting target changes in multiple object tracking with peripheral vision: More pronounced eccentricity effects for changes in form than in motion.

PubMed

Vater, Christian; Kredel, Ralf; Hossner, Ernst-Joachim

2017-05-01

In the current study, dual-task performance is examined with multiple-object tracking as a primary task and target-change detection as a secondary task. The to-be-detected target changes in conditions of either change type (form vs. motion; Experiment 1) or change salience (stop vs. slowdown; Experiment 2), with changes occurring at either near (5°-10°) or far (15°-20°) eccentricities (Experiments 1 and 2). The aim of the study was to test whether changes can be detected solely with peripheral vision. By controlling for saccades and computing gaze distances, we could show that participants used peripheral vision to monitor the targets and, additionally, to perceive changes at both near and far eccentricities. Noticeably, gaze behavior was not affected by the actual target change. Detection rates as well as response times generally varied as a function of change condition and eccentricity, with faster detections for motion changes and near changes. However, in contrast to the effects found for motion changes, sharp declines in detection rates and increased response times were observed for form changes as a function of the eccentricities. This result can be ascribed to properties of the visual system, namely to the limited spatial acuity in the periphery and the comparably receptive motion sensitivity of peripheral vision. These findings show that peripheral vision is functional for simultaneous target monitoring and target-change detection as saccadic information suppression can be avoided and covert attention can be optimally distributed to all targets. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pulmonary Abnormalities in Mice with Paracoccidioidomycosis: A Sequential Study Comparing High Resolution Computed Tomography and Pathologic Findings

PubMed Central

Hidalgo, José Miguel; de Oliveira Pascarelli, Bernardo Miguel; Patiño, Jairo Hernando; Lenzi, Henrique Leonel; Restrepo, Angela; Cano, Luz Elena

2010-01-01

Background Human paracoccidioidomycosis (PCM) is an endemic fungal disease of pulmonary origin. Follow-up of pulmonary lesions by image studies in an experimental model of PCM has not been previously attempted. This study focuses on defining patterns, topography and intensity of lung lesions in experimentally infected PCM mice by means of a comparative analysis between High Resolution Computed Tomography (HRCT) and histopathologic parameters. Methodology Male BALB/c mice were intranasally inoculated with 3×106 Paracoccidioides brasiliensis (Pb) conidia (n = 50) or PBS (n = 50). HRCT was done every four weeks to determine pulmonary lesions, quantify lung density, reconstruct and quantify lung air structure. Lungs were also analyzed by histopathology and histomorphometry. Results Three different patterns of lesions were evidenced by HRCT and histopathology, as follows: nodular-diffuse, confluent and pseudo-tumoral. The lesions were mainly located around the hilus and affected more frequently the left lung. At the 4th week post-challenge HRCT showed that 80% of the Pb-infected mice had peri-bronchial consolidations associated with a significant increase in upper lung density when compared with controls, (−263±25 vs. −422±10 HU, p<0.001). After the 8th and 12th weeks, consolidation had progressed involving also the middle regions. Histopathology revealed that consolidation as assessed by HRCT was equivalent histologically to a confluent granulomatous reaction, while nodules corresponded to individual compact granulomas. At the 16th week of infection, confluent granulomas formed pseudotumoral masses that obstructed large bronchi. Discrete focal fibrosis was visible gradually around granulomas, but this finding was only evident by histopathology. Conclusions/Significance This study demonstrated that conventional HRCT is a useful tool for evaluation and quantification of pulmonary damage occurring in experimental mouse PCM. The experimental design used decreases the need to sacrifice a large number of animals, and serves to monitor treatment efficacy by means of a more rational approach to the study of human lung disease. PMID:20614019

Glioma Invasiveness Responds Variably to Irradiation in a Co-Culture Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamura, Jean L.; Haas-Kogan, Daphne A.; Department of Neurological Surgery, University of California-San Francisco, San Francisco, CA

2007-11-01

Purpose: We developed a co-culture system to quantitate the growth and invasion of human malignant gliomas into a background of confluent normal human astrocytes, then used this assay to assess independently the effects of irradiating both cell types on glioma invasion. Methods and Materials: Enhanced green fluorescent protein (EGFP)-labeled immortalized human astrocytes, human malignant glioma cells, or transformed human astrocytes were focally plated onto a confluent layer of normal human astrocytes, and the invasiveness of EGFP-labeled cells was scored after 96 h. To address the consequences of irradiation on glioma invasion, the invasiveness of irradiated glioma cell lines and irradiatedmore » astrocytic backgrounds was assessed. Fluorescence-activated cell sorting was used to quantitate the total number of EGFP-labeled cells. Results: Growth in the co-culture assay consistently reflected transformation states of the plated cells. Immortalized, but untransformed human astrocytes failed even to establish growth on confluent normal human astrocytes. In contrast, all malignant human glioma cell lines and transformed human astrocytes demonstrated various degrees of infiltration into the astrocytic bed. Irradiation failed to alter the invasiveness of U87, A172, and U373. A 1-Gy dose slightly reduced the invasiveness of U251 MG by 75% (p < 0.05 by one-way analysis of variance and post hoc Neuman-Keuls), without reducing total cell numbers. Independently irradiating the human astrocytic bed did not alter the invasiveness of nonirradiated U251, whereas the matrix metalloproteinase (MMP) inhibitor GM6001 reduced U251 invasiveness in the co-culture assay. Conclusions: Growth in the co-culture assay reflects the transformation status and provides a useful in vitro model for assessing invasiveness. Human glioma invasiveness in the co-culture model responds variably to single low-dose fractions. MMP activity promotes invasiveness in the co-culture model. Reduced invasiveness in irradiated U251 appears to be mediated by MMP-independent mechanisms.« less

'Multi-associations': predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates.

PubMed

Pichler, Gerhard; Pocivalnik, Mirjam; Riedl, Regina; Pichler-Stachl, Elisabeth; Morris, Nicholas; Zotter, Heinz; Müller, Wilhelm; Urlesberger, Berndt

2011-08-01

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO(2)), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO(2)), oxygen consumption (VO(2)), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO(2)) were calculated. All demographic parameters except for Hbflow and DO(2) correlated with NIRS parameters. Heart rate correlated with TOI, SvO(2), VO(2) and VR. SaO(2) correlated with FOE/FTOE. MAP correlated with Hbflow, DO(2), VO(2) and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO(2). Hb-blood correlated with FOE and VR. pCO(2) levels correlated with TOI and SvO(2). The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data.

RESTOP: Retaining External Peripheral State in Intermittently-Powered Sensor Systems.

PubMed

Rodriguez Arreola, Alberto; Balsamo, Domenico; Merrett, Geoff V; Weddell, Alex S

2018-01-10

Energy harvesting sensor systems typically incorporate energy buffers (e.g., rechargeable batteries and supercapacitors) to accommodate fluctuations in supply. However, the presence of these elements limits the miniaturization of devices. In recent years, researchers have proposed a new paradigm, transient computing, where systems operate directly from the energy harvesting source and allow computation to span across power cycles, without adding energy buffers. Various transient computing approaches have addressed the challenge of power intermittency by retaining the processor's state using non-volatile memory. However, no generic approach has yet been proposed to retain the state of peripherals external to the processing element. This paper proposes RESTOP, flexible middleware which retains the state of multiple external peripherals that are connected to a computing element (i.e., a microcontroller) through protocols such as SPI or I 2 C. RESTOP acts as an interface between the main application and the peripheral, which keeps a record, at run-time, of the transmitted data in order to restore peripheral configuration after a power interruption. RESTOP is practically implemented and validated using three digitally interfaced peripherals, successfully restoring their configuration after power interruptions, imposing a maximum time overhead of 15% when configuring a peripheral. However, this represents an overhead of only 0.82% during complete execution of our typical sensing application, which is substantially lower than existing approaches.

Epithelioid Malignant Peripheral Nerve Sheath Tumor Arising in a Schwannoma, in a Patient with “Neuroblastoma-like” Schwannomatosis and a Novel Germline SMARCB1 mutation

PubMed Central

Carter, Jodi M.; O'Hara, Carolyn; Dundas, George; Gilchrist, Dawna; Collins, Mark S.; Eaton, Katherine; Judkins, Alexander R.; Biegel, Jaclyn A.; Folpe, Andrew L.

2011-01-01

Epithelioid malignant peripheral nerve sheath tumors arising in pre-existing schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but one of which showed “neuroblastoma-like” histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and three of her children, two of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain. PMID:22082606

Clinical and MRI characterization of MS patients with a pure and severe cognitive onset.

PubMed

Assouad, Rana; Louapre, Celine; Tourbah, Ayman; Papeix, Caroline; Galanaud, Damien; Lubetzki, Catherine; Stankoff, Bruno

2014-11-01

Cognitive and behavioural symptoms are common in multiple sclerosis (MS), but they are rarely the inaugural and predominant manifestation of the disease. Our objective is to characterize the clinical and radiological features of cognitive-multiple sclerosis (cog-MS), defined as MS subjects who entered into the disease with cognitive symptoms, which subsequently remain the predominant manifestation. We describe the disease course, and clinical and radiological features of 18 subjects with a cognitive form of MS. Memory loss and behavioural changes were the primary symptoms at disease onset. They remained prominent and led to severe cognitive impairment during disease course. The main associated manifestations were depression, pathological laughing and/or crying, urinary incontinence and gait disturbance suggestive of high-level gait disorder. Motor, sensory or cerebellar abnormalities were uncommon. During disease course, superimposed neurological relapses occurred in 61% of cases. Brain MRI revealed multiple periventricular lesions that were extensive and confluent in half of cases, and a severe atrophy measured as an increase in the third ventricular width compared to age-matched healthy controls. Gadolinium-enhancing lesions were common (72%). The mean diagnosis delay from disease onset was 2 years. A principal component analysis on the neuropsychological results revealed that verbal memory assessment is complementary to global cognitive functioning evaluation in these patients with severe cognitive deficit. Verbal memory deficit was associated with high EDSS. cog-MS patients might represent a challenging diagnosis, which needs to be individualized for an early management. Copyright © 2014 Elsevier B.V. All rights reserved.

Coronary artery aneurysm combined with other multiple aneurysms at multiple locations: A case report and systematic review.

PubMed

Jiang, Li-Cheng; Cao, Jia-Yu; Chen, Mao

2017-12-01

Coronary artery aneurysm (CAA) with concomitant aneurysms at multiple sites is quite unusual and rare. The characteristics and the etiology of this phenomenon are unknown. Herein, we present a case with right coronary aneurysm with concomitant abdominal aorta as well as right renal artery aneurysm. A systematic review of the literatures regarding CAA with other coexisting aneurysms at multiple locations was also conducted on Medline and Embase databases. A total of 76 patients (male gender: 58; age: 37.4 ± 26.5) including the present case were included in the final study. The most common etiology of CAA with multiple aneurysms was Kawasaki (43.3%) and atherosclerotic disease (16.4%). CAA was the most frequently found at the right coronary artery (62.7%), following, left anterior descending (51%), left main (43.1%), and left circumflex (35.3%). The most common concomitant aneurysms were abdominal aorta (52.6%) and iliac artery (50%). In addition, 60.5% of the patients had an involved bilateral peripheral artery. CAA with coexisting systemic aneurysms in multiple sites is quite rare. And it usually involves multiple aneurysms at the coronary and bilateral peripheral arteries simultaneously. Currently, there are no general consensus regarding the clinical characteristics, diagnostic method, and treatment of these cases. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Stackable Form-Factor Peripheral Component Interconnect Device and Assembly

NASA Technical Reports Server (NTRS)

Somervill, Kevin M. (Inventor); Ng, Tak-kwong (Inventor); Torres-Pomales, Wilfredo (Inventor); Malekpour, Mahyar R. (Inventor)

2013-01-01

A stackable form-factor Peripheral Component Interconnect (PCI) device can be configured as a host controller or a master/target for use on a PCI assembly. PCI device may comprise a multiple-input switch coupled to a PCI bus, a multiplexor coupled to the switch, and a reconfigurable device coupled to one of the switch and multiplexor. The PCI device is configured to support functionality from power-up, and either control function or add-in card function.

Quantitative analysis of peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography.

PubMed

Karampelas, Michael; Sim, Dawn A; Chu, Colin; Carreno, Ester; Keane, Pearse A; Zarranz-Ventura, Javier; Westcott, Mark; Lee, Richard W J; Pavesio, Carlos E

2015-06-01

To investigate the relationships between peripheral vasculitis, ischemia, and vascular leakage in uveitis using ultra-widefield fluorescein angiography (FA). Cross-sectional, consecutive case series. Consecutive ultra-widefield FA images were collected from 82 uveitis patients (82 eyes) in a single center. The extent of peripheral vasculitis, capillary nonperfusion, and vessel leakage were quantified. Parameters included: (1) foveal avascular zone area and macular leakage, (2) peripheral diffuse capillary leakage and ischemia, (3) peripheral vasculitis, and (4) leakage from neovascularization. Central macular thickness measurements were derived with optical coherence tomography. Main outcome measures were correlations between central and peripheral fluorangiographic changes as well as associations between visual function, ultra-widefield FA-derived metrics, and central macular thickness. Although central leakage was associated with peripheral leakage (r = 0.553, P = .001), there was no association between foveal avascular zone size and peripheral ischemia (r = 0.114, P = .324), regardless of the underlying uveitic diagnosis. Peripheral ischemia was, however, correlated to neovascularization-related leakage (r = 0.462, P = .001) and focal vasculitis (r = 0.441, P = .001). Stepwise multiple regression analysis revealed that a poor visual acuity was independently associated with foveal avascular zone size and central macular thickness (R(2)-adjusted = 0.45, P = .001). We present a large cohort of patients with uveitis imaged with ultra-widefield FA and further describe novel methods for quantification of peripheral vascular pathology, in an attempt to identify visually significant parameters. Although we observed that relationships exist between peripheral vessel leakage, vasculitis, and ischemia, it was only macular ischemia and increased macular thickness that were independently associated with a reduced visual acuity. Copyright © 2015 Elsevier Inc. All rights reserved.

Stimulated peripheral production of interferon-gamma is related to fatigue and depression in multiple sclerosis.

PubMed

Pokryszko-Dragan, A; Frydecka, I; Kosmaczewska, A; Ciszak, L; Bilińska, M; Gruszka, E; Podemski, R; Frydecka, D

2012-10-01

The aim of the study was to evaluate the stimulated production of interferon-gamma (IFNγ) by peripheral CD3+CD4+ T lymphocytes in patients with multiple sclerosis (MS) with regard to the degree of fatigue, and to investigate relationships between immunological parameters, level of depression and clinical variables. Forty MS patients (30 women, 10 men, aged 22-60 years): 20 fatigued and 20 non-fatigued were involved in the study. Fatigue was evaluated using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS), depression level - using Beck Depression Inventory (BDI). Production of IFNγ by stimulated peripheral blood CD3+CD4+ T lymphocytes, assessed using flow cytometry, was compared between MS patients with different levels of fatigue and controls. Correlations were searched out between immunological findings and BDI, age, duration and course of MS, relapse rate, disability (assessed in Expanded Disability Status Scale - EDSS) and its progression. Stimulated production of IFNγ by CD3+CD4+ T lymphocytes was higher in severely fatigued patients in comparison with non-fatigued ones and controls, tended to correlate with FSS and MFIS, and correlated with BDI. No relationships were found between immunological findings and disease-related variables. Stimulated production of IFNγ by peripheral CD3+CD4+ T lymphocytes is related to fatigue and depression in MS patients. Copyright © 2012 Elsevier B.V. All rights reserved.

A comparison of phase imaging and quantitative susceptibility mapping in the imaging of multiple sclerosis lesions at ultrahigh field.

PubMed

Cronin, Matthew John; Wharton, Samuel; Al-Radaideh, Ali; Constantinescu, Cris; Evangelou, Nikos; Bowtell, Richard; Gowland, Penny Anne

2016-06-01

The aim of this study was to compare the use of high-resolution phase and QSM images acquired at ultra-high field in the investigation of multiple sclerosis (MS) lesions with peripheral rings, and to discuss their usefulness for drawing inferences about underlying tissue composition. Thirty-nine Subjects were scanned at 7 T, using 3D T 2*-weighted and T 1-weighted sequences. Phase images were then unwrapped and filtered, and quantitative susceptibility maps were generated using a thresholded k-space division method. Lesions were compared visually and using a 1D profiling algorithm. Lesions displaying peripheral rings in the phase images were identified in 10 of the 39 subjects. Dipolar projections were apparent in the phase images outside of the extent of several of these lesions; however, QSM images showed peripheral rings without such projections. These projections appeared ring-like in a small number of phase images where no ring was observed in QSM. 1D profiles of six well-isolated example lesions showed that QSM contrast corresponds more closely to the magnitude images than phase contrast. Phase images contain dipolar projections, which confounds their use in the investigation of tissue composition in MS lesions. Quantitative susceptibility maps correct these projections, providing insight into the composition of MS lesions showing peripheral rings.

A novel NF1 mutation in a Chinese patient with giant café-au-lait macule in neurofibromatosis type 1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

PubMed

Tong, H-X; Li, M; Zhang, Y; Zhu, J; Lu, W-Q

2012-08-29

Neurofibromatosis type 1 (NF1; OMIM#162200) is a common neurocutaneous disorder that is characterized by multiple café-au-lait, skinfold freckling, Lisch nodules, and neurofibromas. Mutations in the NF1 gene, which encodes the neurofibromin protein, have been identified as the pathogenic gene of NF1. In this study, we present a clinical and molecular study of a Chinese patient with giant café-au-lait in NF1. The patient showed >6 café-au-lait spots on the body, axillary freckling, and multiple subcutaneous neurofibromas. He also had a malignant peripheral nerve sheath tumor and bone abnormalities. The germline mutational analysis of the NF1 gene revealed a novel missense mutation in exon 13. It is a novel heterozygous nucleotide G>A transition at position 2241 of the NF1 gene. We found no mutation in malignant peripheral nerve sheath tumor DNA from this patient. This expands the database for NF1 gene mutations in NF1. Its absence in the normal chromosomes suggests that it is responsible for the NF1 phenotype. To our knowledge, this is the first case of giant café-au-lait macule in NF1 associated with a malignant peripheral nerve sheath tumor and bone abnormality.

Improved Visual Cognition through Stroboscopic Training

PubMed Central

Appelbaum, L. Gregory; Schroeder, Julia E.; Cain, Matthew S.; Mitroff, Stephen R.

2011-01-01

Humans have a remarkable capacity to learn and adapt, but surprisingly little research has demonstrated generalized learning in which new skills and strategies can be used flexibly across a range of tasks and contexts. In the present work we examined whether generalized learning could result from visual–motor training under stroboscopic visual conditions. Individuals were assigned to either an experimental condition that trained with stroboscopic eyewear or to a control condition that underwent identical training with non-stroboscopic eyewear. The training consisted of multiple sessions of athletic activities during which participants performed simple drills such as throwing and catching. To determine if training led to generalized benefits, we used computerized measures to assess perceptual and cognitive abilities on a variety of tasks before and after training. Computer-based assessments included measures of visual sensitivity (central and peripheral motion coherence thresholds), transient spatial attention (a useful field of view – dual task paradigm), and sustained attention (multiple-object tracking). Results revealed that stroboscopic training led to significantly greater re-test improvement in central visual field motion sensitivity and transient attention abilities. No training benefits were observed for peripheral motion sensitivity or peripheral transient attention abilities, nor were benefits seen for sustained attention during multiple-object tracking. These findings suggest that stroboscopic training can effectively improve some, but not all aspects of visual perception and attention. PMID:22059078

Peripheral immunophenotype and viral promoter variants during the asymptomatic phase of feline immunodeficiency virus infection.

PubMed

Murphy, B; Hillman, C; McDonnel, S

2014-01-22

Feline immunodeficiency virus (FIV)-infected cats enter a clinically asymptomatic phase during chronic infection. Despite the lack of overt clinical disease, the asymptomatic phase is characterized by persistent immunologic impairment. In the peripheral blood obtained from cats experimentally infected with FIV-C for approximately 5 years, we identified a persistent inversion of the CD4/CD8 ratio. We cloned and sequenced the FIV-C long terminal repeat containing the viral promoter from cells infected with the inoculating virus and from in vivo-derived peripheral blood mononuclear cells and CD4 T cells isolated at multiple time points throughout the asymptomatic phase. Relative to the inoculating virus, viral sequences amplified from cells isolated from all of the infected animals demonstrated multiple single nucleotide mutations and a short deletion within the viral U3, R and U5 regions. A transcriptionally inactivating proviral mutation in the U3 promoter AP-1 site was identified at multiple time points from all of the infected animals but not within cell-associated viral RNA. In contrast, no mutations were identified within the sequence of the viral dUTPase gene amplified from PBMC isolated at approximately 5 years post-infection relative to the inoculating sequence. The possible implications of these mutations to viral pathogenesis are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells.

PubMed

Abdi, J; Garssen, J; Faber, J; Redegeld, F A

2014-12-01

The n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to enhance the effect of chemotherapeutic drugs in clinical studies in cancer patients and to induce apoptotic tumor cell death in vitro. Until now, EPA and DHA have never been investigated in multiple myeloma (MM). Human myeloma cells (L363, OPM-1, OPM-2 and U266) and normal peripheral blood mononuclear cells were exposed to EPA and DHA, and effects on mitochondrial function and apoptosis, caspase-3 activation, gene expression and drug toxicity were measured. Exposure to EPA and DHA induced apoptosis and increased sensitivity to bortezomib in MM cells. Importantly, they did not affect viability of normal human peripheral mononuclear cells. Messenger RNA expression arrays showed that EPA and DHA modulated genes involved in multiple signaling pathways including nuclear factor (NF) κB, Notch, Hedgehog, oxidative stress and Wnt. EPA and DHA inhibited NFκB activity and induced apoptosis through mitochondrial perturbation and caspase-3 activation. Our study suggests that EPA and DHA induce selective cytotoxic effects in MM and increase sensitivity to bortezomib and calls for further exploration into a potential application of these n-3 polyunsaturated fatty acids in the therapy of MM. Copyright © 2014 Elsevier Inc. All rights reserved.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-mediated deregulation of myeloid and sebaceous gland stem/progenitor cell homeostasis.

PubMed

Bock, Karl Walter

2017-06-01

Studies of TCDD toxicity stimulated identification of the responsible aryl hydrocarbon receptor (AHR), a multifunctional, ligand-activated transcription factor of the basic helix-loop-helix/Per-Arnt-Sim family. Accumulating evidence suggests a role of this receptor in homeostasis of stem/progenitor cells, in addition to its known role in xenobiotic metabolism. (1) Regulation of myelopoiesis is complex. As one example, AHR-mediated downregulation of human CD34+ progenitor differentiation to monocytes/macrophages is discussed. (2) Accumulation of TCDD in sebum leads to deregulation of sebocyte differentiation via Blimp1-mediated inhibition of c-Myc signaling and stimulation of Wnt-mediated proliferation of interfollicular epidermis. The resulting sebaceous gland atrophy and formation of dermal cysts may explain the pathogenesis of chloracne, the hallmark of TCDD toxicity. (3) TCDD treatment of confluent liver stem cell-like rat WB-F344 cells leads to release from cell-cell contact inhibition via AHR-mediated crosstalk with multiple signaling pathways. Further work is needed to delineate AHR function in crosstalk with other signaling pathways.

Multiple scale model for cell migration in monolayers: Elastic mismatch between cells enhances motility

NASA Astrophysics Data System (ADS)

Palmieri, Benoit; Bresler, Yony; Wirtz, Denis; Grant, Martin

2015-07-01

We propose a multiscale model for monolayer of motile cells that comprise normal and cancer cells. In the model, the two types of cells have identical properties except for their elasticity; cancer cells are softer and normal cells are stiffer. The goal is to isolate the role of elasticity mismatch on the migration potential of cancer cells in the absence of other contributions that are present in real cells. The methodology is based on a phase-field description where each cell is modeled as a highly-deformable self-propelled droplet. We simulated two types of nearly confluent monolayers. One contains a single cancer cell in a layer of normal cells and the other contains normal cells only. The simulation results demonstrate that elasticity mismatch alone is sufficient to increase the motility of the cancer cell significantly. Further, the trajectory of the cancer cell is decorated by several speed “bursts” where the cancer cell quickly relaxes from a largely deformed shape and consequently increases its translational motion. The increased motility and the amplitude and frequency of the bursts are in qualitative agreement with recent experiments.

Development of a Novel Synthetic Drug for Osteoporosis and Fracture Healing

DTIC Science & Technology

2014-09-01

jlg/ml of ascorbic acid (Wako Chemicals, Rich .. 󈧏ond, VA, USA) and 5 mi\\1. ~- glycerophosphate (Sigma) were added. The medium was changed every other...confluent, 50 lg/ml of ascorbic acid (Wako Chemicals, Richmond, VA, USA) and 5 mM b- glycerophosphate (Sigma) were added. The med- ium was changed every

Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy

PubMed Central

Douglas, Darlene S.; Popko, Brian

2009-01-01

Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics. PMID:18481175

Monoclonal Gammopathy Associated Peripheral Neuropathy: Diagnosis and Management

PubMed Central

Chaudhry, Hafsa M.; Mauermann, Michelle L.; Rajkumar, S. Vincent

2017-01-01

Monoclonal gammopathies consist of a spectrum of clonal plasma cell disorders that includes monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom Macroglobulinemia (WM). In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal gammopathy associated peripheral neuropathy. Monoclonal gammopathy of undetermined significance (MGUS) is relatively common in the general population, with a prevalence of 3–4% among those over the age of 50. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal gammopathy associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal gammopathy associated peripheral neuropathy and discuss available data and options for treatment. PMID:28473042

Motor-commands decoding using peripheral nerve signals: a review

NASA Astrophysics Data System (ADS)

Hong, Keum-Shik; Aziz, Nida; Ghafoor, Usman

2018-06-01

During the last few decades, substantial scientific and technological efforts have been focused on the development of neuroprostheses. The major emphasis has been on techniques for connecting the human nervous system with a robotic prosthesis via natural-feeling interfaces. The peripheral nerves provide access to highly processed and segregated neural command signals from the brain that can in principle be used to determine user intent and control muscles. If these signals could be used, they might allow near-natural and intuitive control of prosthetic limbs with multiple degrees of freedom. This review summarizes the history of neuroprosthetic interfaces and their ability to record from and stimulate peripheral nerves. We also discuss the types of interfaces available and their applications, the kinds of peripheral nerve signals that are used, and the algorithms used to decode them. Finally, we explore the prospects for future development in this area.

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

PubMed

Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

The Perception of Multiple Images

ERIC Educational Resources Information Center

Goldstein, E. Bruce

1975-01-01

A discussion of visual field, foveal and peripheral vision, eye fixations, recognition and recall of pictures, memory for meaning of pictures, and the relation between speed of presentation and memory. (Editor)

The Development of the CMS Zero Degree Calorimeters to Derive the Centrality of AA Collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wood, Jeffrey Scott

The centrality of РЬРЬ collisions is derived using correlations from the zero degree calorimeter (ZDC) signal and pixel multiplicity at the Compact Muon Solenoid (CMS) Experiment using data from the heavy ion run in 2010. The method to derive the centrality takes the two-dimensional correlation between the ZDC and pixels and linearizes it for sorting events. The initial method for deriving the centrality at CMS uses the energy deposit in the HF detector, and it is compared to the centrality derived Ьу the correlations in ZDC and pixel multiplicity. This comparison highlights the similarities between the results of both methodsmore » in central collisions, as expected, and deviations in the results in peripheral collisions. The ZDC signals in peripheral collisions are selected Ьу low pixel multiplicity to oЬtain а ZDC neutron spectrum, which is used to effectively gain match both sides of the ZDC« less

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dexterous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2017-10-01

potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm Subtask 3.1: Mapping of...neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion, extension, adduction...intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode array

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dexterous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2016-10-01

isolated action potentials or multi-action potential activity from residual peripheral nerve while patient intends movements of amputated hand/arm...Subtask 3.1: Mapping of neural activity (Months 4 – 36) • Patients will be asked to intend a number of individual finger and multiple finger flexion...during these intended movements. We will map the different intended movements onto the neural activity recorded on the electrodes of the micro-electrode

Pathogenesis of the limb manifestations and exercise limitations in peripheral artery disease.

PubMed

Hiatt, William R; Armstrong, Ehrin J; Larson, Christopher J; Brass, Eric P

2015-04-24

Patients with peripheral artery disease have a marked reduction in exercise performance and daily ambulatory activity irrespective of their limb symptoms of classic or atypical claudication. This review will evaluate the multiple pathophysiologic mechanisms underlying the exercise impairment in peripheral artery disease based on an evaluation of the current literature and research performed by the authors. Peripheral artery disease results in atherosclerotic obstructions in the major conduit arteries supplying the lower extremities. This arterial disease process impairs the supply of oxygen and metabolic substrates needed to match the metabolic demand generated by active skeletal muscle during walking exercise. However, the hemodynamic impairment associated with the occlusive disease process does not fully account for the reduced exercise impairment, indicating that additional pathophysiologic mechanisms contribute to the limb manifestations. These mechanisms include a cascade of pathophysiological responses during exercise-induced ischemia and reperfusion at rest that are associated with endothelial dysfunction, oxidant stress, inflammation, and muscle metabolic abnormalities that provide opportunities for targeted therapeutic interventions to address the complex pathophysiology of the exercise impairment in peripheral artery disease. © 2015 American Heart Association, Inc.

Donor Peripheral Stem Cell Transplant in Treating Patients With Advanced Hematologic Cancer or Other Disorders

ClinicalTrials.gov

2017-09-26

Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition

Multiple Lower Extremity Mononeuropathies by Segmental Schwannomatosis: A Case Report

PubMed Central

Kwon, Na Yeon; Oh, Hyun-Mi

2015-01-01

Schwannoma is an encapsulated nerve sheath tumor that is distinct from neurofibromatosis. It is defined as the occurrence of multiple schwannomas without any bilateral vestibular schwannomas. A 46-year-old man with multiple schwannomas involving peripheral nerves of the ipsilateral lower extremity presented with neurologic symptoms. Electrodiagnostic studies revealed multiple mononeuropathies involving the left sciatic, common peroneal, tibial, femoral and superior gluteal nerves. Histologic findings confirmed the diagnosis of schwannoma. We reported this rare case of segmental schwannomatosis that presented with neurologic symptoms including motor weakness, which was confirmed as multiple mononeuropathies by electrodiagnostic studies. PMID:26605183

Multiple Lower Extremity Mononeuropathies by Segmental Schwannomatosis: A Case Report.

PubMed

Kwon, Na Yeon; Oh, Hyun-Mi; Ko, Young Jin

2015-10-01

Schwannoma is an encapsulated nerve sheath tumor that is distinct from neurofibromatosis. It is defined as the occurrence of multiple schwannomas without any bilateral vestibular schwannomas. A 46-year-old man with multiple schwannomas involving peripheral nerves of the ipsilateral lower extremity presented with neurologic symptoms. Electrodiagnostic studies revealed multiple mononeuropathies involving the left sciatic, common peroneal, tibial, femoral and superior gluteal nerves. Histologic findings confirmed the diagnosis of schwannoma. We reported this rare case of segmental schwannomatosis that presented with neurologic symptoms including motor weakness, which was confirmed as multiple mononeuropathies by electrodiagnostic studies.

Efficacy of spinal cord stimulators in treating peripheral neuropathy: a case series.

PubMed

Abd-Elsayed, Alaa; Schiavoni, Nick; Sachdeva, Harsh

2016-02-01

Peripheral neuropathy is a common cause of pain, and it is increasing in prevalence. Peripheral neuropathic pain is very hard to treat and can be resistant to multiple pain management modalities. Our series aimed at testing the efficacy of spinal cord stimulators (SCSs) in treating resistant painful peripheral neuropathy. Case 1: A 79-year-old man presented to our clinic with long-standing history of painful peripheral diabetic neuropathy resistant to conservative management. After failure of all possible modalities, we offered the patient an SCS trial that was very successful, and we proceeded with the permanent implant that continued to help with his pain and allowed the patient to wean down his medications. Case 2: A 60-year-old man presented with chronic peripheral neuropathy secondary to HIV, patient failed all conservative and procedural management. Patient then had an SCS trial that relieved his pain significantly. Unfortunately, we did not proceed with the implant due to deterioration of the patient general health. Case 3: A 39-year-old woman presented with painful peripheral neuropathy secondary to chemotherapy for breast cancer. After failure of medication management and procedures, patient had a SCS trial that improved her pain and we then proceeded with performing the permanent implant that controlled her pain. We presented 3 cases with chronic painful peripheral neuropathy secondary to HIV, diabetes mellitus, and chemotherapy that was resistant to conservative pain management and procedures that was successfully treated with neurostimulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Cells, Biomarkers, and Posttraumatic Stress Disorder: Evidence for Peripheral Involvement in a Central Disease

DTIC Science & Technology

2012-01-01

including; Alzheimer’s disease (Mac- cioni et al. 2009), Parkinson’s disease (Hirsch and Hunot 2009), spinal cord injury (Chan 2008), multiple sclerosis ...states such as multiple sclerosis (Kraus et al. 2000), human immunodeficiency virus dementia (Fischer- Smith et al. 2001), and meningitis (Cauwels et al...Immunologic mechanisms of multiple sclerosis . Neuroi- maging Clin. N. Am. 18, 577–588. Gaylord K. M. (2006) The psychosocial effects of combat: the frequently

Bose-Einstein correlations in p p ,   p Pb , and PbPb collisions at s N N = 0.9 – 7 TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2018-06-14

Here, quantum-statistical (Bose-Einstein) two-particle correlations are measured in pp collisions at √s = 0.9, 2.76, and 7 TeV, as well as in pPb and peripheral PbPb collisions at nucleon-nucleon center-of-mass energies of 5.02 and 2.76 TeV, respectively, using the CMS detector at the Large Hadron Collider. Separate analyses are performed for same-sign unidentified charged particles as well as for same-sign pions and kaons identified via their energy loss in the silicon tracker. The characteristics of the one-, two-, and three-dimensional correlation functions are studied as functions of the pair average transverse momentum (k T) and the charged-particle multiplicity in themore » event. For all systems, the extracted correlation radii steadily increase with the event multiplicity, and decrease with increasing k T. The radii are in the range 1–5 fm, the largest values corresponding to very high multiplicity pPb interactions and to peripheral PbPb collisions with multiplicities similar to those seen in pPb data. It is also observed that the dependencies of the radii on multiplicity and k T largely factorize. At the same multiplicity, the radii are relatively independent of the colliding system and center-of-mass energy.« less

Bose-Einstein correlations in $$pp, p\\mathrm{Pb}$$, and PbPb collisions at $$\\sqrt{{s}_{NN}}=0.9-7$$ TeV

DOE PAGES

Sirunyan, Albert M; et al.

2018-06-15

Quantum-statistical (Bose-Einstein) two-particle correlations are measured in pp collisions at s=0.9, 2.76, and 7 TeV, as well as in pPb and peripheral PbPb collisions at nucleon-nucleon center-of-mass energies of 5.02 and 2.76 TeV, respectively, using the CMS detector at the Large Hadron Collider. Separate analyses are performed for same-sign unidentified charged particles as well as for same-sign pions and kaons identified via their energy loss in the silicon tracker. The characteristics of the one-, two-, and three-dimensional correlation functions are studied as functions of the pair average transverse momentum (kT) and the charged-particle multiplicity in the event. For all systems, the extractedmore » correlation radii steadily increase with the event multiplicity, and decrease with increasing kT. The radii are in the range 1–5 fm, the largest values corresponding to very high multiplicity pPb interactions and to peripheral PbPb collisions with multiplicities similar to those seen in pPb data. It is also observed that the dependencies of the radii on multiplicity and kT largely factorize. At the same multiplicity, the radii are relatively independent of the colliding system and center-of-mass energy.« less

Bose-Einstein correlations in $$pp, p\\mathrm{Pb}$$, and PbPb collisions at $$\\sqrt{{s}_{NN}}=0.9-7$$ TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, Albert M; et al.

Quantum-statistical (Bose-Einstein) two-particle correlations are measured in pp collisions at s=0.9, 2.76, and 7 TeV, as well as in pPb and peripheral PbPb collisions at nucleon-nucleon center-of-mass energies of 5.02 and 2.76 TeV, respectively, using the CMS detector at the Large Hadron Collider. Separate analyses are performed for same-sign unidentified charged particles as well as for same-sign pions and kaons identified via their energy loss in the silicon tracker. The characteristics of the one-, two-, and three-dimensional correlation functions are studied as functions of the pair average transverse momentum (kT) and the charged-particle multiplicity in the event. For all systems, the extractedmore » correlation radii steadily increase with the event multiplicity, and decrease with increasing kT. The radii are in the range 1–5 fm, the largest values corresponding to very high multiplicity pPb interactions and to peripheral PbPb collisions with multiplicities similar to those seen in pPb data. It is also observed that the dependencies of the radii on multiplicity and kT largely factorize. At the same multiplicity, the radii are relatively independent of the colliding system and center-of-mass energy.« less

Bose-Einstein correlations in p p ,   p Pb , and PbPb collisions at s N N = 0.9 – 7 TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

Here, quantum-statistical (Bose-Einstein) two-particle correlations are measured in pp collisions at √s = 0.9, 2.76, and 7 TeV, as well as in pPb and peripheral PbPb collisions at nucleon-nucleon center-of-mass energies of 5.02 and 2.76 TeV, respectively, using the CMS detector at the Large Hadron Collider. Separate analyses are performed for same-sign unidentified charged particles as well as for same-sign pions and kaons identified via their energy loss in the silicon tracker. The characteristics of the one-, two-, and three-dimensional correlation functions are studied as functions of the pair average transverse momentum (k T) and the charged-particle multiplicity in themore » event. For all systems, the extracted correlation radii steadily increase with the event multiplicity, and decrease with increasing k T. The radii are in the range 1–5 fm, the largest values corresponding to very high multiplicity pPb interactions and to peripheral PbPb collisions with multiplicities similar to those seen in pPb data. It is also observed that the dependencies of the radii on multiplicity and k T largely factorize. At the same multiplicity, the radii are relatively independent of the colliding system and center-of-mass energy.« less

RESTOP: Retaining External Peripheral State in Intermittently-Powered Sensor Systems

PubMed Central

Rodriguez Arreola, Alberto; Balsamo, Domenico

2018-01-01

Energy harvesting sensor systems typically incorporate energy buffers (e.g., rechargeable batteries and supercapacitors) to accommodate fluctuations in supply. However, the presence of these elements limits the miniaturization of devices. In recent years, researchers have proposed a new paradigm, transient computing, where systems operate directly from the energy harvesting source and allow computation to span across power cycles, without adding energy buffers. Various transient computing approaches have addressed the challenge of power intermittency by retaining the processor’s state using non-volatile memory. However, no generic approach has yet been proposed to retain the state of peripherals external to the processing element. This paper proposes RESTOP, flexible middleware which retains the state of multiple external peripherals that are connected to a computing element (i.e., a microcontroller) through protocols such as SPI or I2C. RESTOP acts as an interface between the main application and the peripheral, which keeps a record, at run-time, of the transmitted data in order to restore peripheral configuration after a power interruption. RESTOP is practically implemented and validated using three digitally interfaced peripherals, successfully restoring their configuration after power interruptions, imposing a maximum time overhead of 15% when configuring a peripheral. However, this represents an overhead of only 0.82% during complete execution of our typical sensing application, which is substantially lower than existing approaches. PMID:29320441

The Development, Implementation, and Evaluation of a Model for Teaching Composition Which Utilizes Gestalt Therapy Techniques.

ERIC Educational Resources Information Center

Tixier, Linda

As a solution to the problems presented by approaches to teaching English composition that are almost purely cognitive in nature, an experimental course was offered for freshmen at the Miami-Dade Community College. The course was designed to be holistic and confluent, synthesizing both the cognitive and affective domains by incorporating Gestalt…

Experiments with osteoblasts cultured under hypergravity conditions

NASA Technical Reports Server (NTRS)

Kacena, Melissa A.; Todd, Paul; Gerstenfeld, Louis C.; Landis, William J.

2004-01-01

To understand further the role of gravity in osteoblast attachment, osteoblasts were subjected to hypergravity conditions in vitro. Scanning electron microscopy of all confluent coverslips from FPA units show that the number of attached osteoblasts was similar among gravitational levels and growth durations (90 cells/microscopic field). Specifically, confluent 1.0 G control cultures contained an average of 91 +/- 8 cells/field, 3.3 G samples had 88 +/- 8 cells/field, and 4.0 G cultures averaged 90 +/- 7 cells/field. The sparsely plated cultures assessed by immunohistochemistry also had similar numbers of cells at each time point (l.0 G was similar to 3.3 and 4.0 G), but cell number changed from one time point to the next as those cells proliferated. Immunohistochemistry of centrifuged samples showed an increase in number (up to 160% increase) and thickness (up to 49% increase) of actin fibers, a decrease in intensity of fibronectin fluorescence (18-23% decrease) and an increase in number of vinculin bulbs (202-374% increase in number of vinculin bulbs/area). While hypergravity exposure did not alter the number of attached osteoblasts, it did result in altered actin, fibronectin, and vinculin elements, changing some aspects of osteoblast- substrate adhesion.

Detecting effects of low levels of cytochalasin B in 3T3 fibroblast cultures by analysis of electrical noise obtained from cellular micromotion

PubMed Central

Lovelady, Douglas C.; Friedman, Jennifer; Patel, Sonali; Rabson, David A.; Lo, Chun-Min

2009-01-01

We performed micromotion experiments using electric cell-substrate impedance sensing (ECIS) on a confluent layer of 3T3 fibroblasts exposed to different low levels of the toxin cytochalasin B. This toxin is know to affect actin polymerization and to disrupt cytoskeletal structure and function in cells, changing the morphology of confluent cell cultures and altering the nature of the cellular micromotion, which is measured by ECIS as changes in impedance. By looking at several measures to characterize the long- and short-term correlations in the noise of the impedance time series, we are able to detect the effects of the toxin at concentrations down to 1 μM; there are intriguing hints that the effects may be discernible at levels as low as 0.1 μM. These measures include the power spectrum, the Hurst and detrended-fluctuation-analysis exponents, and the first zero and first 1/e crossings of the autocorrelation function. While most published work with ECIS uses only average impedance values, we demonstrate that noise analysis provides a more sensitive probe. PMID:19026529

[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna].

PubMed

Ruckser, R; Kier, P; Sebesta, C; Kittl, E; Kurz, M; Selleny, S; Höniger, S; Scherz, M; Habertheuer, K H; Zelenka, P

1995-01-01

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

ClinicalTrials.gov

2017-10-23

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

A multiple camera tongue switch for a child with severe spastic quadriplegic cerebral palsy.

PubMed

Leung, Brian; Chau, Tom

2010-01-01

The present study proposed a video-based access technology that facilitated a non-contact tongue protrusion access modality for a 7-year-old boy with severe spastic quadriplegic cerebral palsy (GMFCS level 5). The proposed system featured a centre camera and two peripheral cameras to extend coverage of the frontal face view of this user for longer durations. The child participated in a descriptive case study. The participant underwent 3 months of tongue protrusion training while the multiple camera tongue switch prototype was being prepared. Later, the participant was brought back for five experiment sessions where he worked on a single-switch picture matching activity, using the multiple camera tongue switch prototype in a controlled environment. The multiple camera tongue switch achieved an average sensitivity of 82% and specificity of 80%. In three of the experiment sessions, the peripheral cameras were associated with most of the true positive switch activations. These activations would have been missed by a centre-camera-only setup. The study demonstrated proof-of-concept of a non-contact tongue access modality implemented by a video-based system involving three cameras and colour video processing.

Neutrophil to lymphocyte ratio as the main predictor of peripheral artery disease in regular hemodialysis patients

NASA Astrophysics Data System (ADS)

Siregar, R. H.; Muzasti, R. A.

2018-03-01

Cardiovascular disease is the most inducer of morbidity and mortality of chronic kidney disease (CKD) patients who have undergone dialysis. Today, neutrophil to lymphocyte ratio (NLR) is considered an indicator of the severity and extent of systemic inflammation and atherosclerosis in patients with renal and cardiovascular disorders. To examine the relationship between NLR with PAD in regular hemodialysis patients, a cross-sectional study, Ankle- Brachial Index (ABI) measurement and peripheral blood examination was on 72 regular hemodialysis patients ≥6 months. The ABI value ≤0.9 is considered PAD. NLR≥ 3.5 is considered abnormal based on some pre-existing research. Prevalence of PAD is 29.16%. Chi- square test showed significant correlation between NLR with PAD (p = 0.0001), multiplication of Calcium and Phosphorus (p = 0.0001), and type 2 Diabetes Mellitus (T2DM) (p = 0.039), multivariate analysis showed that NLR was an independent predictor for PAD in regular hemodialysis patients (RR = 2.271 p = 0.027). In conclusion, NLR, a new inflammatory marker of peripheral blood examination may serve as a marker of PAD in a regular hemodialysis patient, in addition to the multiplication of Calcium and Phosphorus as well as T2DM.

Pathophysiology of anorexia in the cancer cachexia syndrome

PubMed Central

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-01-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients. PMID:26675762

Alterations in bone marrow and blood mononuclear cell polyamine and methylglyoxal bis(guanylhydrazone) levels: phase I evaluation of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) treatment of human hematological malignancies.

PubMed

Maddox, A M; Freireich, E J; Keating, M J; Haddox, M K

1988-03-01

Nine patients with hematological malignancies were treated with difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The number of circulating blast cells decreased in all of the patients treated with DFMO and MGBG for longer than 1 wk. Morphological evidence of myeloid maturation was evident in four patients with leukemia and the circulating M Protein decreased in one patient with multiple myeloma. The polyamine content of the mononuclear cells in both the peripheral blood and bone marrow was transiently increased after the initial MGBG dose. During administration of DFMO decreases were achieved in the peripheral blood mononuclear cell putrescine levels in 7 patients, spermidine levels in 5 patients, and spermine levels in 4 patients. Alterations in bone marrow mononuclear cell polyamine levels were similar to those which occurred in the peripheral cells. An average of 9 days of DFMO treatment was required to lower mononuclear cell polyamine levels. Three of the 4 evaluable patients receiving multiple MGBG doses had an increased mononuclear cell content of MGBG after DFMO pretreatment. Enhancement of cellular MGBG levels was not directly correlated to the degree of cellular polyamine depletion.

Pathophysiology of anorexia in the cancer cachexia syndrome.

PubMed

Ezeoke, Chukwuemeka Charles; Morley, John E

2015-12-01

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2.

PubMed

Westhout, Franklin D; Mathews, Marlon; Paré, Laura S; Armstrong, William B; Tully, Patricia; Linskey, Mark E

2007-06-01

Schwannomatosis has become a newly recognized classification of neurofibromatosis. Although the genetic loci are on chromosome 22, it lacks the classic bilateral vestibular schwannomas as seen in NF-2. We present the surgical treatment of 4 patients with schwannomatosis, including a brother and sister. Case 1 presented with multiple progressively enlarging peripheral nerve sheath tumors. Case 4 presented with a trigeminal schwannoma and a vagal nerve schwannoma. Three of 4 patients had spinal intradural, extramedullary nerve sheath tumors. Surgery in all was multistaged and consisted of spinal laminectomies, site-specific explorations, and microsurgical tumor dissection and resection, with intraoperative neurophysiologic monitoring (including somatosensory-evoked and motor-evoked potentials, upper extremity electromyography and intraoperative nerve action potential monitoring, as appropriate). Intraoperatively the schwannomas had cystic and solid features and in all surgical cases the tumors arose from discrete fascicles of sensory nerve roots or sensory peripheral nerve branches. None of the patients experienced neurologic worsening as a result of their resections. Pathologic analysis of specimens from all cases demonstrated schwannoma. Not all patients with multiple schwannomas of cranial nerve, spinal nerve root, or peripheral nerve origin have NF-1 or NF-2. In schwannomatosis, these lesions are present in the absence of cutaneous stigmata, neurofibromas, vestibular schwannomas, or parenchymal brain tumors. Schwannomas in schwannomatosis can be large, cystic, and multiple. However, the predominant nerve involvement seems to be sensory and discrete fascicular in origin, facilitating microsurgical resection with minimal deficit.

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease

PubMed Central

Lee, Samuel M.; Chin, Lih-Shen; Li, Lian

2016-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy. PMID:26732592

Dysregulation of ErbB Receptor Trafficking and Signaling in Demyelinating Charcot-Marie-Tooth Disease.

PubMed

Lee, Samuel M; Chin, Lih-Shen; Li, Lian

2017-01-01

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy with the majority of cases involving demyelination of peripheral nerves. The pathogenic mechanisms of demyelinating CMT remain unclear, and no effective therapy currently exists for this disease. The discovery that mutations in different genes can cause a similar phenotype of demyelinating peripheral neuropathy raises the possibility that there may be convergent mechanisms leading to demyelinating CMT pathogenesis. Increasing evidence indicates that ErbB receptor-mediated signaling plays a major role in the control of Schwann cell-axon communication and myelination in the peripheral nervous system. Recent studies reveal that several demyelinating CMT-linked proteins are novel regulators of endocytic trafficking and/or phosphoinositide metabolism that may affect ErbB receptor signaling. Emerging data have begun to suggest that dysregulation of ErbB receptor trafficking and signaling in Schwann cells may represent a common pathogenic mechanism in multiple subtypes of demyelinating CMT. In this review, we focus on the roles of ErbB receptor trafficking and signaling in regulation of peripheral nerve myelination and discuss the emerging evidence supporting the potential involvement of altered ErbB receptor trafficking and signaling in demyelinating CMT pathogenesis and the possibility of modulating these trafficking and signaling processes for treating demyelinating peripheral neuropathy.

Meta-analysis of incidence and risk of peripheral neuropathy associated with intravenous bortezomib.

PubMed

Peng, Ling; Ye, Xianghua; Zhou, Yun; Zhang, Junyan; Zhao, Qiong

2015-09-01

Bortezomib is a proteasome inhibitor which has demonstrated activity against recurrent or newly diagnosed multiple myeloma (MM) and mantle cell lymphoma. Peripheral neuropathy has been described with this agent, although the overall incidence and relative risk remain unclear. We performed a meta-analysis to calculate the incidence of peripheral neuropathy associated with the use of intravenous bortezomib in MM and lymphoma and to compare the relative risk compared with placebo. We searched PubMed, Embase, Cochrane databases, and meeting proceedings from the American Society of Clinical Oncology (ASCO) for relevant clinical trials. Eligible studies included prospective phase 2 and 3 clinical trials with toxicity profile on peripheral neuropathy associated with intravenous bortezomib in patients with MM and lymphoma. Statistical analyses were done to calculate summary incidences, relative risks (RRs), and 95 % confidence intervals (CIs), employing fixed- or random-effects models depending on the heterogeneity of the included studies. Altogether, 34 clinical trials were selected for the meta-analysis, yielding a total of 6492 patients. The incidence of peripheral neuropathy (all grades) was 33.9 % (95 % CI, 29.9-38.5 %) and that of high-grade events was 8.1 % (95 % CI, 6.9-9.4 %). The relative risks of bortezomib-induced peripheral neuropathy compared to placebo were increased for all-grade (RR = 4.89; 95 % CI, 2.52-9.51) and high-grade (RR = 4.53; 95 % CI, 2.04-10.07) peripheral neuropathy (for randomized controlled trials only). Our analysis was also stratified by different underlying diseases, and patients with lymphoma had an increased incidence of all-grade peripheral neuropathy than those with MM when treated with intravenous bortezomib. Treatment with intravenous bortezomib is associated with an increased risk of developing peripheral neuropathy.

Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

ClinicalTrials.gov

2017-07-25

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

Pilot Study of Umbilical Cord Blood Transplantation in Adult Patient With Advanced Hematopoietic Malignancies

ClinicalTrials.gov

2013-08-13

Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Multiple Myeloma; Lymphoma, Large-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, T-Cell, Peripheral; T-NK Cell Lymphoma; Hodgkin Disease

Biological Therapy Following Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Cancer

ClinicalTrials.gov

2013-03-25

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Catastrophic secondary antiphospholipid syndrome with peripheral nervous system involvement: a case report.

PubMed

Erten, Nilgun; Saka, Bulent; Karan, M Akif; Parman, Yesim; Umman, Berrin; Tascioglu, Cemil

2004-04-01

A 34-year-old woman was admitted to our emergency room with a high fever, abdominal pain, dyspnea and confusion. High fever and abdominal pain had first occured after a cystocele operation 5 months earlier. Later, congestive heart failure with mural thrombus formation, peripheral polyneuropathy and ischemic cerebrovascular accident were identified in clinical follow-ups, and multiple arterial and venous thromboses were seen on cranial and abdominal magnetic resonance imaging angiography. The patient's symptoms improved with anticoagulant treatment. Antiphospholipid syndrome with elevated serum anticardiolipin IgG levels was diagnosed, and ischemic peripheral polyneuropathy with axonal degeneration was determined by sural nerve biopsy. In antiphospholipid syndrome, elevated anticardiolipin antibodies appear to be the most common acquired blood protein defect causing thrombosis. Disseminated vascular thrombosis in catastrophic antiphospholipid syndrome can result in multiorgan failure with increased morbidity and mortality. It rarely occurs secondary to various infections as in the case of our patient, who suffered postoperative intraabdominal infection. It is important to note that peripheral nervous system involvement is rare in antiphospholipid syndrome.

Prostate specific antigen and acinar density: a new dimension, the "Prostatocrit".

PubMed

Robinson, Simon; Laniado, Marc; Montgomery, Bruce

2017-01-01

Prostate-specific antigen densities have limited success in diagnosing prostate cancer. We emphasise the importance of the peripheral zone when considered with its cellular constituents, the "prostatocrit". Using zonal volumes and asymmetry of glandular acini, we generate a peripheral zone acinar volume and density. With the ratio to the whole gland, we can better predict high grade and all grade cancer. We can model the gland into its acinar and stromal elements. This new "prostatocrit" model could offer more accurate nomograms for biopsy. 674 patients underwent TRUS and biopsy. Whole gland and zonal volumes were recorded. We compared ratio and acinar volumes when added to a "clinic" model using traditional PSA density. Univariate logistic regression was used to find significant predictors for all and high grade cancer. Backwards multiple logistic regression was used to generate ROC curves comparing the new model to conventional density and PSA alone. Prediction of all grades of prostate cancer: significant variables revealed four significant "prostatocrit" parameters: log peripheral zone acinar density; peripheral zone acinar volume/whole gland acinar volume; peripheral zone acinar density/whole gland volume; peripheral zone acinar density. Acinar model (AUC 0.774), clinic model (AUC 0.745) (P=0.0105). Prediction of high grade prostate cancer: peripheral zone acinar density ("prostatocrit") was the only significant density predictor. Acinar model (AUC 0.811), clinic model (AUC 0.769) (P=0.0005). There is renewed use for ratio and "prostatocrit" density of the peripheral zone in predicting cancer. This outperforms all traditional density measurements. Copyright® by the International Brazilian Journal of Urology.

Rapid Link of Innate Immune Signal to Adaptive Immunity by Brain–Fat Axis

PubMed Central

Kim, Min Soo; Yan, Jingqi; Wu, Wenhe; Zhang, Guo; Zhang, Yalin; Cai, Dongsheng

2015-01-01

Innate immunity signals induced by pathogen/damage-associated molecular patterns are essential for adaptive immune responses, but it is unclear if the brain plays a role in this process. Here we show that while tumor necrosis factor (TNF) quickly increased in the brain of mice following bacterial infection, intra-brain TNF delivery mimicked bacterial infection to rapidly increase peripheral lymphocytes, especially in the spleen and fat. Multiple mouse models revealed that hypothalamic responses to TNF were accountable for this increase of peripheral lymphocytes in response to bacterial infection. Finally, hypothalamic induction of lipolysis was found to mediate the brain's action in promoting this increase in peripheral adaptive immune response. Thus, the brain-fat axis is important for rapidly linking innate immunity to adaptive immunity. PMID:25848866

The use of shock waves in peripheral nerve regeneration: new perspectives?

PubMed

Hausner, Thomas; Nógrádi, Antal

2013-01-01

Low-energy extracorporeal shock wave treatment (ESWT) is a relatively new therapeutic tool that is widely used for the treatment of epicondylitis and plantar fasciitis and to foster bone and wound healing. Shock waves, sonic pulses with high energy impact, are thought to induce biochemical changes within the targeted tissues through mechanotransduction. The biological effects of ESWT are manifested in improved vascularization, the local release of growth factors, and local anti-inflammatory effects, but the target cells too are influenced. ESWT appears to have differential effects on peripheral nerves and has been proved to promote axonal regeneration after axotomy. This review discusses the effects of ESWT on intact and injured peripheral nerves and suggests a multiple mechanism of action. © 2013 Elsevier Inc. All rights reserved.

Static and Dynamic Human Shape Modeling - A Review of the Literature and State of the Art

DTIC Science & Technology

2009-04-01

Figure 60. Confluent marker-based animation (Aguiar et al. 2006). Subsequent frames showing the female scan authentically performing a soccer kick ...Infoscitex Corp. 4027 Colonel Glenn Highway Suite 210 Dayton OH 45431-1672 Kathleen Robinette Biosciences and Protection Division Biomechanics ...Biosciences and Protection Division Biomechanics Branch Wright-Patterson AFB OH 45433 Approved for public release; distribution unlimited. NOTICE

Tay's syndrome: MRI.

PubMed

Porto, L; Weis, R; Schulz, C; Reichel, P; Lanfermann, H; Zanella, F E

2000-11-01

Tay's syndrome is a trichothiodystrophy associated with congenital ichthyosis. We report the findings on MRI and spectroscopy in a young girl with sparse, short, ruffled hair, dry skin and delayed milestones. T2-weighted images showed prominent diffuse confluent increase in signal symmetrically in all the supratentorial white matter. These findings are similar to those in a previously described case, and consistent with dysmyelination. Spectroscopy showed increased myoinositol and decreased choline.

Distinct pattern of lesion distribution in multiple sclerosis is associated with different circulating T-helper and helper-like innate lymphoid cell subsets.

PubMed

Gross, Catharina C; Schulte-Mecklenbeck, Andreas; Hanning, Uta; Posevitz-Fejfár, Anita; Korsukewitz, Catharina; Schwab, Nicholas; Meuth, Sven G; Wiendl, Heinz; Klotz, Luisa

2017-06-01

Distinct lesion topography in relapsing-remitting multiple sclerosis (RRMS) might be due to different antigen presentation and/or trafficking routes of immune cells into the central nervous system (CNS). To investigate whether distinct lesion patterns in multiple sclerosis (MS) might be associated with a predominance of distinct circulating T-helper cell subset as well as their innate counterparts. Flow cytometric analysis of lymphocytes derived from the peripheral blood of patients with exclusively cerebral (n = 20) or predominantly spinal (n = 12) disease manifestation. Patients with exclusively cerebral or preferential spinal lesion manifestation were associated with increased proportions of circulating granulocyte-macrophage colony-stimulating factor (GM-CSF) producing T H 1 cells or interleukin (IL)-17-producing T H 17 cells, respectively. In contrast, proportions of peripheral IL-17/IL-22-producing lymphoid tissue inducer (LTi), the innate counterpart of T H 17 cells, were enhanced in RRMS patients with exclusively cerebral lesion topography. Distinct T-helper and T-helper-like innate lymphoid cell (ILC) subsets are associated with different lesion topography in RRMS.

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

PubMed

Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

2011-09-01

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

Electrospun fibrinogen-PLA nanofibres for vascular tissue engineering.

PubMed

Gugutkov, D; Gustavsson, J; Cantini, M; Salmeron-Sánchez, M; Altankov, G

2017-10-01

Here we report on the development of a new type of hybrid fibrinogen-polylactic acid (FBG-PLA) nanofibres (NFs) with improved stiffness, combining the good mechanical properties of PLA with the excellent cell recognition properties of native FBG. We were particularly interested in the dorsal and ventral cell response to the nanofibres' organization (random or aligned), using human umbilical endothelial cells (HUVECs) as a model system. Upon ventral contact with random NFs, the cells developed a stellate-like morphology with multiple projections. The well-developed focal adhesion complexes suggested a successful cellular interaction. However, time-lapse analysis shows significantly lowered cell movements, resulting in the cells traversing a relatively short distance in multiple directions. Conversely, an elongated cell shape and significantly increased cell mobility were observed in aligned NFs. To follow the dorsal cell response, artificial wounds were created on confluent cell layers previously grown on glass slides and covered with either random or aligned NFs. Time-lapse analysis showed significantly faster wound coverage (within 12 h) of HUVECs on aligned samples vs. almost absent directional migration on random ones. However, nitric oxide (NO) release shows that endothelial cells possess lowered functionality on aligned NFs compared to random ones, where significantly higher NO production was found. Collectively, our studies show that randomly organized NFs could support the endothelization of implants while aligned NFs would rather direct cell locomotion for guided neovascularization. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Influence of neighboring adherent cells on laminar flow induced shear stress in vitro—A systematic study

PubMed Central

Djukelic, Mario; Westerhausen, Christoph

2017-01-01

Cells experience forces if subjected to laminar flow. These forces, mostly of shear force character, are strongly dependent not only on the applied flow field itself but also on hydrodynamic effects originating from neighboring cells. This particularly becomes important for the interpretation of data from in vitro experiments in flow chambers without confluent cell layers. By employing numerical Finite Element Method simulations of such assemblies of deformable objects under shear flow, we investigate the occurring stress within elastic adherent cells and the influence of neighboring cells on these quantities. For this, we simulate single and multiple adherent cells of different shapes fixed on a solid substrate under laminar flow parallel to the substrate for different velocities. We determine the local stress within the cells close to the cell-substrate-interface and the overall stress of the cells by surface integration over the cell surface. Comparing each measurand in the case of a multiple cell situation with the corresponding one of single cells under identical conditions, we introduce a dimensionless influence factor. The systematic variation of the distance and angle between cells, where the latter is with respect to the flow direction, flow velocity, Young's modulus, cell shape, and cell number, enables us to describe the actual influence on a cell. Overall, we here demonstrate that the cell density is a crucial parameter for all studies on flow induced experiments on adherent cells in vitro. PMID:28798851

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems.

PubMed

Harari, Colin M; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T; Lubner, Meghan G; Hinshaw, J Louis; Ziemlewicz, Timothy; Brace, Christopher L

2016-01-01

To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015.

3D tissue formation by stacking detachable cell sheets formed on nanofiber mesh.

PubMed

Kim, Min Sung; Lee, Byungjun; Kim, Hong Nam; Bang, Seokyoung; Yang, Hee Seok; Kang, Seong Min; Suh, Kahp-Yang; Park, Suk-Hee; Jeon, Noo Li

2017-03-23

We present a novel approach for assembling 3D tissue by layer-by-layer stacking of cell sheets formed on aligned nanofiber mesh. A rigid frame was used to repeatedly collect aligned electrospun PCL (polycaprolactone) nanofiber to form a mesh structure with average distance between fibers 6.4 µm. When human umbilical vein endothelial cells (HUVECs), human foreskin dermal fibroblasts, and skeletal muscle cells (C2C12) were cultured on the nanofiber mesh, they formed confluent monolayers and could be handled as continuous cell sheets with areas 3 × 3 cm 2 or larger. Thicker 3D tissues have been formed by stacking multiple cell sheets collected on frames that can be nested (i.e. Matryoshka dolls) without any special tools. When cultured on the nanofiber mesh, skeletal muscle, C2C12 cells oriented along the direction of the nanofibers and differentiated into uniaxially aligned multinucleated myotube. Myotube cell sheets were stacked (upto 3 layers) in alternating or aligned directions to form thicker tissue with ∼50 µm thickness. Sandwiching HUVEC cell sheets with two dermal fibroblast cell sheets resulted in vascularized 3D tissue. HUVECs formed extensive networks and expressed CD31, a marker of endothelial cells. Cell sheets formed on nanofiber mesh have a number of advantages, including manipulation and stacking of multiple cell sheets for constructing 3D tissue and may find applications in a variety of tissue engineering applications.

Perceptual training yields rapid improvements in visually impaired youth.

PubMed

Nyquist, Jeffrey B; Lappin, Joseph S; Zhang, Ruyuan; Tadin, Duje

2016-11-30

Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events.

Lymphocyte Infusion in Treating Patients With Relapsed Cancer After Bone Marrow or Peripheral Stem Cell Transplantation

ClinicalTrials.gov

2011-11-28

Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Kidney Cancer; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Neuroblastoma; Ovarian Cancer; Sarcoma; Testicular Germ Cell Tumor

Multiple cerebral and cerebellar infarcts as the first clinical manifestation in a patient with Churg-Strauss syndrome: case report and literature review.

PubMed

Cheng, Meng-Ju; Huang, Pai-Hao; Liao, Pin-Wen; Chen, Jen-Tse; Chiang, Tsuey-Ru

2012-12-01

Churg-Strauss syndrome (CSS) is a rare autoimmune disease with small-vessel vasculitis. Neurological manifestation of CSS is common. Central nervous system is less frequently involved than that of peripheral nervous system. We report a case of 60-year-old man who presented with acute onset of right hemiparesis and impaired cognition. The presence of hypereosinophilia, asthma, sinusitis and extravascular eosinophil accumulation led to the diagnosis of Churg-Strauss syndrome. Brain magnetic resonance imaging (MRI) revealed multiple infarcts in bilateral cerebral and cerebellar hemispheres. The neurophysiology study did not reveal peripheral neuropathy. The patient was effectively treated with methylprednisolone, cyclophosphamide and warfarin. Symptoms and signs of central nervous system can be the initial neurological manifestation of CSS patients. CSS should be considered while patients have stroke and hypereosinophilia. In our patient, there is a good response to timely steroid, immunosuppressant and anticoagulant therapies.

Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis.

PubMed

Donaldson, Laura; Rebello, Ryan; Rodriguez, Amadeo

2017-06-01

A 45-year-old man presented with a slowly progressive pupil-involving third nerve palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from the interpeduncular cistern through the cavernous sinus and into the left orbit where it branched into a superior and an inferior division, clearly outlining the anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged cranial nerves were noted. The differential diagnosis included chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of other muscle weakness and of sensory symptoms combined with normal peripheral nerve conduction studies effectively ruled out the hypertrophic polyneuropathies and pointed to a syndromic cause of multiple benign peripheral nerve sheath tumours (PNSTs). The authors are treating this case as presumed schwannomatosis, a syndrome similar to NF2 with much lower frequency of acoustic neuromas.

Massive Oculomotor Nerve Enlargement: A Case of Presumed Schwannomatosis

PubMed Central

Donaldson, Laura; Rebello, Ryan; Rodriguez, Amadeo

2017-01-01

ABSTRACT A 45-year-old man presented with a slowly progressive pupil-involving third nerve palsy. Magnetic resonance imaging (MRI) revealed a tubular lesion extending from the interpeduncular cistern through the cavernous sinus and into the left orbit where it branched into a superior and an inferior division, clearly outlining the anatomy of the third cranial nerve. Multiple other, less pronounced, enlarged cranial nerves were noted. The differential diagnosis included chronic inflammatory demyelinating polyneuropathy (CIDP), hereditary motor and sensory neuropathy (HMSN), neurofibromatosis (NF), and schwannomatosis. The absence of other muscle weakness and of sensory symptoms combined with normal peripheral nerve conduction studies effectively ruled out the hypertrophic polyneuropathies and pointed to a syndromic cause of multiple benign peripheral nerve sheath tumours (PNSTs). The authors are treating this case as presumed schwannomatosis, a syndrome similar to NF2 with much lower frequency of acoustic neuromas. PMID:28512503

Deficiencies of Circulating Mucosal-associated Invariant T Cells and Natural Killer T Cells in Patients with Multiple Trauma.

PubMed

Jo, Young Goun; Choi, Hyun Jung; Kim, Jung Chul; Cho, Young Nan; Kang, Jeong Hwa; Jin, Hye Mi; Kee, Seung Jung; Park, Yong Wook

2017-05-01

Mucosal-associated invariant T (MAIT) cells and natural killer T (NKT) cells are known to play important roles in autoimmunity, infectious diseases and cancers. However, little is known about the roles of these invariant T cells in multiple trauma. The purposes of this study were to examine MAIT and NKT cell levels in patients with multiple trauma and to investigate potential relationships between these cell levels and clinical parameters. The study cohort was composed of 14 patients with multiple trauma and 22 non-injured healthy controls (HCs). Circulating MAIT and NKT cell levels in the peripheral blood were measured by flow cytometry. The severity of injury was categorised according to the scoring systems, such as Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, and Injury Severity Score (ISS). Circulating MAIT and NKT cell numbers were significantly lower in multiple trauma patients than in HCs. Linear regression analysis showed that circulating MAIT cell numbers were significantly correlated with age, APACHE II, SAPS II, ISS category, hemoglobin, and platelet count. NKT cell numbers in the peripheral blood were found to be significantly correlated with APACHE II, SAPS II, and ISS category. This study shows numerical deficiencies of circulating MAIT cells and NKT cells in multiple trauma. In addition, these invariant T cell deficiencies were found to be associated with disease severity. These findings provide important information for predicting the prognosis of multiple trauma. © 2017 The Korean Academy of Medical Sciences.

Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves

PubMed Central

Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D.; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V.; Chavakis, Triantafyllos; Imhof, Beat A.; Feltri, M. Laura; Nourshargh, Sussan

2012-01-01

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.—Colom, B., Poitelon, Y., Huang, W., Woodfin, A., Averill, S., Del Carro, U., Zambroni, D., Brain, S. D., Perretti, M., Ahluwalia, A., Priestley, J. V., Chavakis, T., Imhof, B. A., Feltri, M. L., Nourshargh, S. Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves. PMID:22090315

Ultra-wide-field fundus autofluorescence in multiple evanescent white dot syndrome.

PubMed

Hashimoto, Hideaki; Kishi, Shoji

2015-04-01

To observe the progression of affected lesions using ultra-wide-field fundus autofluorescence (FAF) in multiple evanescent white dot syndrome. Retrospective, observational case series. setting: Institutional. 14 eyes of 13 patients (mean age, 35.8 years) with acute disease unilaterally. Patients underwent ultra-wide-field FAF, spectral-domain optical coherence tomography (SD OCT), multifocal electroretinography (mfERG), and Goldmann or automated perimetry; the best-corrected visual acuity (BCVA) and refractive error were measured. Ability of ultra-wide-field FAF to detect lesions with greater sensitivity compared with color fundus photography. Ultra-wide-field FAF imaging enabled improved visualization of the affected lesions and showed that the core lesion was in the posterior fundus involving the peripapillary retina and posterior pole and surrounded by hyper-autofluorescent spots outside the vascular arcade. The posterior lesions expanded rapidly and peripheral spots spread farther peripherally and reached a maximal extent during the acute stage. During follow-up, the peripheral hyper-autofluorescent spots resolved and then hyper-autofluorescence of the posterior fundus gradually faded. SD OCT showed diffuse disruption of the photoreceptor inner segment/outer segment junction (IS/OS) in the posterior fundus during the acute stage. The correlation between the IS/OS abnormality and hyper-autofluorescent areas was unclear. The disrupted IS/OS was restored with normalization of the FAF. Ultra-wide-field FAF showed that the lesions arise from the peripapillary retina and the posterior pole and spread peripherally in a centrifugal manner during the acute stage. The hyper-autofluorescent spots faded from the periphery in a centripetal manner. Copyright © 2015 Elsevier Inc. All rights reserved.

A Study of the Seastar Underwater Acoustic Local Area Network Concept

DTIC Science & Technology

2007-12-01

sense multiple access (CSMA) and multiple access with collision avoidance ( MACA ) are reviewed in [19, 22, 23, 34]. Peripheral nodes using ALOHA and...transmissions until the channel is clear. However, the long propagation time limits the effectiveness of CSMA for acoustic communications. MACA [22] uses... MACA protocol, if no ACK message is received after the transmission is completed, the full packet will be retransmitted until reception is

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

Impact of peripheral hearing loss on top-down auditory processing.

PubMed

Lesicko, Alexandria M H; Llano, Daniel A

2017-01-01

The auditory system consists of an intricate set of connections interposed between hierarchically arranged nuclei. The ascending pathways carrying sound information from the cochlea to the auditory cortex are, predictably, altered in instances of hearing loss resulting from blockage or damage to peripheral auditory structures. However, hearing loss-induced changes in descending connections that emanate from higher auditory centers and project back toward the periphery are still poorly understood. These pathways, which are the hypothesized substrate of high-level contextual and plasticity cues, are intimately linked to the ascending stream, and are thereby also likely to be influenced by auditory deprivation. In the current report, we review both the human and animal literature regarding changes in top-down modulation after peripheral hearing loss. Both aged humans and cochlear implant users are able to harness the power of top-down cues to disambiguate corrupted sounds and, in the case of aged listeners, may rely more heavily on these cues than non-aged listeners. The animal literature also reveals a plethora of structural and functional changes occurring in multiple descending projection systems after peripheral deafferentation. These data suggest that peripheral deafferentation induces a rebalancing of bottom-up and top-down controls, and that it will be necessary to understand the mechanisms underlying this rebalancing to develop better rehabilitation strategies for individuals with peripheral hearing loss. Copyright © 2016 Elsevier B.V. All rights reserved.

Peripheral neuropathy is a common manifestation of mitochondrial diseases: a single-centre experience.

PubMed

Luigetti, M; Sauchelli, D; Primiano, G; Cuccagna, C; Bernardo, D; Lo Monaco, M; Servidei, S

2016-06-01

Peripheral neuropathy in mitochondrial diseases (MDs) may vary from a subclinical finding in a multisystem syndrome to a severe, even isolated, manifestation in some patients. To investigate the involvement of the peripheral nervous system in MDs extensive electrophysiological studies were performed in 109 patients with morphological, biochemical and genetic diagnosis of MD [12 A3243G progressive external ophthalmoplegia (PEO)/mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), 16 myoclonic epilepsy with ragged-red fibres (MERRF), four mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), 67 PEO with single or multiple deletions of mitochondrial DNA, 10 others]. A neuropathy was found in 49 patients (45%). The incidence was very high in MNGIE (100%), MELAS (92%) and MERRF (69%), whilst 28% of PEO patients had evidence of peripheral involvement. The most frequent abnormality was a sensory axonal neuropathy found in 32/49 patients (65%). A sensory-motor axonal neuropathy was instead detected in 16% of the patients and sensory-motor axonal demyelinating neuropathy in 16%. Finally one Leigh patient had a motor axonal neuropathy. It is interesting to note that the great majority had preserved tendon reflexes and no sensory disturbances. In conclusion, peripheral involvement in MD is frequent even if often mild or asymptomatic. The correct identification and characterization of peripheral neuropathy through electrophysiological studies represents another tile in the challenge of MD diagnosis. © 2016 EAN.

Peripheral arterial stiffness is associated with higher baseline plasma uric acid: A prospective cohort study.

PubMed

Ding, Xiaohan; Ye, Ping; Wang, Xiaona; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

2017-03-01

This prospective cohort study aimed at identifying association between uric acid (UA) and peripheral arterial stiffness. A prospective cohort longitudinal study was performed according to an average of 4.8 years' follow-up. The demographic data, anthropometric parameters, peripheral arterial stiffness (carotid-radial pulse-wave velocity, cr-PWV) and biomarker variables including UA were examined at both baseline and follow-up. Pearson's correlations were used to identify the associations between UA and peripheral arterial stiffness. Further logistic regressions were employed to determine the associations between UA and arterial stiffness. At the end of follow-up, 1447 subjects were included in the analyses. At baseline, cr-PWV ( r  = 0.200, p  < 0.001) was closely associated with UA. Furthermore, the follow-up cr-PWV ( r  = 0.145, p  < 0.001) was also strongly correlated to baseline UA in Pearson's correlation analysis. Multiple regressions also indicated the association between follow-up cr-PWV ( β  = 0.493, p  = 0.013) and baseline UA level. Logistic regressions revealed that higher baseline UA level was an independent predictor of arterial stiffness severity assessed by cr-PWV at follow-up cross-section. Peripheral arterial stiffness is closely associated with higher baseline UA level. Furthermore, a higher baseline UA level is an independent risk factor and predictor for peripheral arterial stiffness.

A genetic variant of the anti-apoptotic protein Akt predicts natalizumab-induced lymphocytosis and post-natalizumab multiple sclerosis reactivation.

PubMed

Rossi, Silvia; Motta, Caterina; Studer, Valeria; Monteleone, Fabrizia; De Chiara, Valentina; Buttari, Fabio; Barbieri, Francesca; Bernardi, Giorgio; Battistini, Luca; Cutter, Gary; Stüve, Olaf; Salvetti, Marco; Centonze, Diego

2013-01-01

Multiple sclerosis (MS) patients discontinuing natalizumab treatment are at risk of disease reactivation. No clinical or surrogate parameters exist to identify patients at risk of post-natalizumab MS reactivation. To determine the role of natalizumab-induced lymphocytosis and of Akt polymorphisms in disease reactivation after natalizumab discontinuation. Peripheral leukocyte count and composition were monitored in 93 MS patients during natalizumab treatment, and in 56 of these subjects who discontinued the treatment. Genetic variants of the anti-apoptotic protein Akt were determined in all subjects because natalizumab modulates the apoptotic pathway and lymphocyte survival is regulated by the apoptotic cascade. Natalizumab-induced peripheral lymphocytosis protected from post-natalizumab MS reactivation. Subjects who relapsed or had magnetic resonance imaging (MRI) worsening after treatment cessation, in fact, had milder peripheral lymphocyte increases during the treatment, largely caused by less marked T cell increase. Furthermore, subjects carrying a variant of the gene coding for Akt associated with reduced anti-apoptotic efficiency (rs2498804T) had lower lymphocytosis and higher risk of disease reactivation. This study identified one functionally meaningful genetic variant within the Akt signaling pathway that is associated with both lymphocyte count and composition alterations during natalizumab treatment, and with the risk of disease reactivation after natalizumab discontinuation.

Schwann cell-specific JAM-C-deficient mice reveal novel expression and functions for JAM-C in peripheral nerves.

PubMed

Colom, Bartomeu; Poitelon, Yannick; Huang, Wenlong; Woodfin, Abigail; Averill, Sharon; Del Carro, Ubaldo; Zambroni, Desirée; Brain, Susan D; Perretti, Mauro; Ahluwalia, Amrita; Priestley, John V; Chavakis, Triantafyllos; Imhof, Beat A; Feltri, M Laura; Nourshargh, Sussan

2012-03-01

Junctional adhesion molecule-C (JAM-C) is an adhesion molecule expressed at junctions between adjacent endothelial and epithelial cells and implicated in multiple inflammatory and vascular responses. In addition, we recently reported on the expression of JAM-C in Schwann cells (SCs) and its importance for the integrity and function of peripheral nerves. To investigate the role of JAM-C in neuronal functions further, mice with a specific deletion of JAM-C in SCs (JAM-C SC KO) were generated. Compared to wild-type (WT) controls, JAM-C SC KO mice showed electrophysiological defects, muscular weakness, and hypersensitivity to mechanical stimuli. In addressing the underlying cause of these defects, nerves from JAM-C SC KO mice were found to have morphological defects in the paranodal region, exhibiting increased nodal length as compared to WTs. The study also reports on previously undetected expressions of JAM-C, namely on perineural cells, and in line with nociception defects of the JAM-C SC KO animals, on finely myelinated sensory nerve fibers. Collectively, the generation and characterization of JAM-C SC KO mice has provided unequivocal evidence for the involvement of SC JAM-C in the fine organization of peripheral nerves and in modulating multiple neuronal responses.

Real-time estimation of paracellular permeability of cerebral endothelial cells by capacitance sensor array

NASA Astrophysics Data System (ADS)

Hyun Jo, Dong; Lee, Rimi; Hyoung Kim, Jin; Oh Jun, Hyoung; Geol Lee, Tae; Hun Kim, Jeong

2015-06-01

Vascular integrity is important in maintaining homeostasis of brain microenvironments. In various brain diseases including Alzheimer’s disease, stroke, and multiple sclerosis, increased paracellular permeability due to breakdown of blood-brain barrier is linked with initiation and progression of pathological conditions. We developed a capacitance sensor array to monitor dielectric responses of cerebral endothelial cell monolayer, which could be utilized to evaluate the integrity of brain microvasculature. Our system measured real-time capacitance values which demonstrated frequency- and time-dependent variations. With the measurement of capacitance at the frequency of 100 Hz, we could differentiate the effects of vascular endothelial growth factor (VEGF), a representative permeability-inducing factor, on endothelial cells and quantitatively analyse the normalized values. Interestingly, we showed differential capacitance values according to the status of endothelial cell monolayer, confluent or sparse, evidencing that the integrity of monolayer was associated with capacitance values. Another notable feature was that we could evaluate the expression of molecules in samples in our system with the reference of real-time capacitance values. We suggest that this dielectric spectroscopy system could be successfully implanted as a novel in vitro assay in the investigation of the roles of paracellular permeability in various brain diseases.

Evidence from Human and Animal Studies: Pathological Roles of CD8+ T Cells in Autoimmune Peripheral Neuropathies

PubMed Central

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies. PMID:26528293

Evidence from Human and Animal Studies: Pathological Roles of CD8(+) T Cells in Autoimmune Peripheral Neuropathies.

PubMed

Yang, Mu; Peyret, Corentin; Shi, Xiang Qun; Siron, Nicolas; Jang, Jeong Ho; Wu, Sonia; Fournier, Sylvie; Zhang, Ji

2015-01-01

Autoimmune peripheral neuropathies such as Guillain-Barre Syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4(+) T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN). As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4(+) T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicates that CD8(+) T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8(+) T cells in autoimmune peripheral neuropathies. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice) in which the T cell co-stimulator molecule B7.2 (CD86) is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8(+) T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4(+) T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8(+) T cells in autoimmune peripheral neuropathies.

Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Calvo-Ortega, J.F., E-mail: jfcdrr@yahoo.es; Pozo, M.; Moragues, S.

To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom onmore » the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application ( (www.radiochromic.com)) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm{sup 2} region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed.« less

Les Industries de la langue: Au confluent de la linguistique et de l'informatique (The Language Utilities: At the Confluence of Linguistics and Computer Science).

ERIC Educational Resources Information Center

Bourret, Annie, Ed.; L'Homme, Marie-Claude, Ed.

A collection of essays addresses aspects of the "Language Utilities," the general term for the area of the conjunction of computer science and linguistics. The following are English translations of the titles of the articles in the collections: "Industrialization of the French Language and Its Maintenance as an Important Language of…

Actinic comedonal plaque.

PubMed

Eastern, J S; Martin, S

1980-12-01

Solitary plaques developed on the sun-exposed and damaged skin of five elderly, fair-skinned individuals. The lesions, erythematous to bluish confluent nodules and plaques with a cribriform appearance and comedone-like structures, presented a distinctive histologic picture of dilated, keratin-filled follicles within a matrix of amorphous, damaged collagen. We believe these cases demonstrate a distinct entity within the realm of actinic dermatoses, for which the name "actinic comedonal plaque" seems appropriate.

Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Igarashi, Kaori; Sakimoto, Ippei; Kataoka, Keiko

The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high-frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. The expression levels of genes associated with cell cycle progression and DNA replication were remarkably reduced in the IRSL ECs. Additionally, the in vitro invasion and migration activities of these cells through Matrigel were significantly suppressed. We also foundmore » that confluent ECs exhibited a high-frequency IRSL phenotype when they were replated immediately after irradiation, whereas incubation in plateau-phase conditions reduced the induction of this phenotype and enhanced colony formation. The kinetics of DNA double-strand break repair, which showed a faster time course in confluent ECs than in growing ECs, may contribute to the protective mechanism associated with the IRSL phenotype. These results imply that the IRSL phenotype may be important for determining the angiogenic activity of ECs following irradiation. The present study should contribute to the understanding of the effects of IR on tumor angiogenesis.« less

Cell-cell contact regulates gene expression in CDK4-transformed mouse podocytes.

PubMed

Sakairi, Toru; Abe, Yoshifusa; Jat, Parmijit S; Kopp, Jeffrey B

2010-10-01

We transformed mouse podocytes by ectopic expression of cyclin-dependent kinase 4 (CDK4). Compared with podocytes transformed with a thermo-sensitive SV40 large T antigen mutant tsA58U19 (tsT podocytes), podocytes transformed with CDK4 (CDK4 podocytes) exhibited significantly higher expression of nephrin mRNA. Synaptopodin mRNA expression was significantly lower in CDK4 podocytes and in tsT podocytes under growth-permissive conditions (33°C) compared with tsT podocytes under growth-restricted conditions (37°C), which suggests a role for cell cycle arrest in synaptopodin mRNA expression. Confluent CDK4 podocytes showed significantly higher mRNA expression levels for nephrin, synaptopodin, Wilms tumor 1, podocalyxin, and P-cadherin compared with subconfluent cultures. We carried out experiments to clarify roles of various factors in the confluent podocyte cultures; our findings indicate that cell-cell contact promotes expression of five podocyte marker genes studied, that cellular quiescence increases synaptopodin and podocalyxin mRNA expression, and that soluble factors play a role in nephrin mRNA expression. Our findings suggest that CDK4 podocytes are useful tools to study podocyte biology. Furthermore, the role of cell-cell contact in podocyte gene expression may have relevance for podocyte function in vivo.

The expression of native and cultured human retinal pigment epithelial cells grown in different culture conditions.

PubMed

Tian, J; Ishibashi, K; Honda, S; Boylan, S A; Hjelmeland, L M; Handa, J T

2005-11-01

To determine the transcriptional proximity of retinal pigment epithelium (RPE) cells grown under different culture conditions and native RPE. ARPE-19 cells were grown under five conditions in 10% CO(2): "subconfluent" in DMEM/F12+10% FBS, "confluent" in serum and serum withdrawn, and "differentiated" for 2.5 months in serum and serum withdrawn medium. Native RPE was laser microdissected. Total RNA was extracted, reverse transcribed, and radiolabelled probes were hybridised to an array containing 5,353 genes. Arrays were evaluated by hierarchical cluster analysis and significance analysis of microarrays. 78% of genes were expressed by native RPE while 45.3--47.7% were expressed by ARPE-19 cells, depending on culture condition. While the most abundant genes were expressed by native and cultured cells, significant differences in low abundance genes were seen. Hierarchical cluster analysis showed that confluent and differentiated, serum withdrawn cultures clustered closest to native RPE, and that serum segregated cultured cells from native RPE. The number of differentially expressed genes and their function, and profile of expressed and unexpressed genes, demonstrate differences between native and cultured cells. While ARPE-19 cells have significant value for studying RPE behaviour, investigators must be aware of how culture conditions can influence the mRNA phenotype of the cell.

Characteristic appearances of fundus autofluorescence in treatment-naive and active polypoidal choroidal vasculopathy: a retrospective study of 170 patients.

PubMed

Zhao, Xinyu; Xia, Song; Chen, Youxin

2018-06-01

To investigate the characteristic appearances of fundus autofluorescence (FAF) in patients with treatment-naive and active polypoidal choroidal vasculopathy (PCV). Cases with the diagnosis of treatment-naive and active PCV from November 2012 to May 2017 at Peking Union Medical College Hospital were retrospectively reviewed. All patients underwent comprehensive ophthalmologic examination. Autofluorescence (AF) findings were described at the retinal sites of the corresponding lesions identified and diagnosed using indocyanine green angiography and spectral-domain optical coherence tomography. One hundred seventy patients with 192 affected eyes were included. The logMAR BCVA of the patients were 0.53 ± 0.28. The six AF patterns of 243 polypoidal lesions were confluent hypo-AF with hyper-AF ring (49.8%), confluent hypo-AF (22.6%), hyper-AF with hypo-AF ring (3.7%), granular hypo-AF (7.0%), blocked hypo-AF due to hemorrhage (8.6%), and polyps without apparent AF changes (8.2%). For 146 branching vascular networks (BVNs), 97.3% were granular hypo-AF, and others were blocked hypo-AF due to hemorrhage. In eyes with treatment-naive and active PCV, the polypoidal lesions and BVNs induce characteristic FAF changes. FAF images provide reliable adjunct reference for the diagnosis of PCV.

Characteristics of a separating confluent boundary layer and the downstream wake

NASA Technical Reports Server (NTRS)

Adair, Desmond; Horne, W. Clifton

1987-01-01

Measurements of pressure and velocity characteristics are presented and analyzed for flow over and downstream of a NACA 4412 airfoil equipped with a NACA 4415 single-slotted flap at high angle of attack and close to maximum lift. The flow remained attached over the main element while a large region of recirculating flow occurred over the aft 61 percent of the flap. The airfoil configuration was tested at a Mach number of 0.09 and a chord Reynolds number of 1.8x10 to the 6th power in the NASA Ames Research Center 7- by 10-Foot Wind Tunnel. Measurement of mean and fluctuation velocities were obtained in regions of recirculation and high turbulence intensity using 3-D laser velocimetry. In regions where the flow had a preferred direction and relatively low turbulence intensity, hot-wire anemometry was used. Emphasis was placed on obtaining characteristics in the confluent boundary layer, the region of recirculating flow, and in the downstream wake. Surface pressure measurements were made on the main airfoil, flap, wind tunnel roof and floor. It is thought likely that because the model is large when compared to the wind tunnel cross section, the wind tunnel floor and ceiling interference should be taken into account when the flow field is calculated.

A simple in vitro model for investigating epithelial/mesenchymal interactions: keratinocyte inhibition of fibroblast proliferation and fibronectin synthesis.

PubMed

Harrison, Caroline A; Dalley, Andrew J; Mac Neil, Sheila

2005-01-01

Hypertrophic scarring and graft contracture are major causes of morbidity after burn injuries. It is well established that application of a split-thickness skin graft reduces scarring and contraction, and cultured epithelial autografts have a similar effect. To investigate the influence of keratinocytes on fibroblast proliferation and fibronectin synthesis, we used an in vitro separated co-culture model in which epithelial sheets were cultured above fibroblast monolayers without physical contact. We also investigated the response of fibroblasts to keratinocyte-conditioned medium (KCM) obtained from confluent and subconfluent keratinocyte monolayers. Both cultured epithelial sheets, composed of adherent fully confluent keratinocytes, and their conditioned medium, reduced fibroblast proliferation. However, KCM from subconfluent keratinocytes stimulated fibroblast proliferation at low concentrations while inhibiting it at higher concentrations, indicating that keratinocytes can produce both mitogenic and growth-inhibiting factors for fibroblasts. KCM, but not epithelial sheet co-culture, also inhibited fibroblast fibronectin synthesis. This indicates regulation of fibroblast phenotype by soluble factors released by the keratinocyte and also suggests that there is a dialogue between keratinocytes and fibroblasts with respect to fibronectin production. We conclude that this separated co-culture model is a simple way to study epithelial/mesenchymal communication particularly with respect to the role of the fibroblast in wound healing.

Adipose cell differentiation: evidence for a two-step process in the polyamine-dependent Ob1754 clonal line.

PubMed Central

Amri, E Z; Dani, C; Doglio, A; Etienne, J; Grimaldi, P; Ailhaud, G

1986-01-01

A subclone of preadipocyte Ob17 cells has been isolated (Ob1754 clonal line). Confluent Ob1754 cells treated with an inhibitor of spermidine and spermine synthesis, methylglyoxal bis(guanylhydrazone), were totally dependent upon putrescine addition for the expression of glycerol-3-phosphate dehydrogenase which behaved as a late marker of adipose conversion. Under these conditions, the early expression of lipoprotein lipase during growth arrest remained unchanged. Studies at the mRNA level showed that the expression of unidentified pOb24 and pGH3 mRNAs, which was parallel to that of lipoprotein lipase, is independent of polyamine addition whereas the late emergence of glycerol-3-phosphate dehydrogenase mRNA was putrescine-dependent and co-ordinated with the expression of pAL422 mRNA encoding for a myelin-P2 homologue [Bernlohr, Angus, Lane, Bolanowski & Kelly (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 5468-5472]. The appearance of lipoprotein lipase preceded DNA synthesis and post-confluent mitoses which were both putrescine-dependent and which took place before the appearance of glycerol-3-phosphate dehydrogenase. Thus the adipose conversion of Ob1754 cells involves the expression of at least two separate sets of markers which are differently regulated. Images Fig. 3. Fig. 6. PMID:3800927

Brain-derived neurotrophic factor levels under chronic natalizumab treatment in multiple sclerosis. A preliminary report.

PubMed

Văcăraş, Vitalie; Major, Zoltán Zsigmond; Buzoianu, Anca Dana

Our main purpose was to investigate if the chronic treatment with the disease-modifying drug natalizumab shows quantifiable effect on BDNF levels in multiple sclerosis patients. BDNF plasma concentration was evaluated using enzyme-linked immunosorbent assay in healthy individuals, not treated multiple sclerosis patients and patients treated with natalizumab. Multiple sclerosis patients have a significantly lower amount of peripheral BDNF than healthy individuals. Patients treated with natalizumab have significantly higher BDNF levels than not treated patients. Chronic natalizumab treatment is associated with significantly increased plasma BDNF concentration in multiple sclerosis. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Ultrasound assessment of peripheral nerve pathology in neurofibromatosis type 1 and 2.

PubMed

Winter, Natalie; Rattay, Tim W; Axer, Hubertus; Schäffer, Eva; Décard, Bernhard F; Gugel, Isabel; Schuhmann, Martin; Grimm, Alexander

2017-05-01

The neurofibromatoses (NF) type 1 and 2 are hereditary tumor predisposition syndromes caused by germline mutations in the NF1 and NF2 tumor suppressor genes. In NF1 and 2, peripheral nerve tumors occur regularly. For further characterizing nerve ultrasound was performed in patients with NF1 and 2. Patients with established diagnosis of NF1 (n=27) and NF2 (n=10) were included. Ultrasound of peripheral nerves and cervical roots was performed during routine follow-up visits. Healthy volunteers were studied for comparison. In patients with NF1, median cross-sectional area (CSA) of most nerves was significantly increased compared to controls and to NF2 due to generalized plexiform tumors, which arose out of multiple fascicles in 23 of 27 patients (85%). These were often accompanied by cutaneous or subcutaneous neurofibromas. In NF2, the overall aspect of peripheral nerves consisted of localized schwannomas (80%) and, apart from that, normal nerve segments. Nerve ultrasound is able to visualize different nerve pathologies in NF1 and NF2. It is a precise and inexpensive screening method for peripheral nerve manifestation in neurofibromatosis and should be considered as the first choice screening imaging modality for all peripheral nerves within reach of non-invasive ultrasound techniques. Ultrasound patterns of peripheral nerve pathologies are described for the first time in a large cohort of patients with NF1 and NF2. It is a suitable screening tool and enables targeted MRI analysis. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Schwannomatosis on a single foot: a case report.

PubMed

Min, Hak-Jin; Kim, Ki Chun; Jun, Sung Han; Lee, Young Gun

2015-06-01

Schwannomatosis has been recently recognized as the third major type of neurofibromatosis. It causes multiple schwannomas without the vestibular tumors that are diagnostic of neurofibromatosis type 2. Schwannoma is rarely found in the foot, and it is still rarer to find multiple schawannomas in a single peripheral nerve on the foot. In this article, we describe a case of schwannomatosis case on a single foot. Case report, Level IV. © 2014 The Author(s).

Simple Preoperative Ink Test as a Novel Adjunct to Intrastromal Keratopigmentation for Post-laser Peripheral Iridotomy Dysphotopsias.

PubMed

Ong Tone, Stephan; Li, Daniel Q; Ashkenazy, Zach; Borovik, Armand; Slomovic, Allan R; Rootman, David S; Chan, Clara C

2017-10-01

To describe a simple preoperative ink test as a novel adjunct to intrastromal keratopigmentation for post-laser peripheral iridotomy (LPI) dysphotopsias. A surgical marking pen is applied to the area over a peripheral iridotomy before intrastromal keratopigmentation. The patient can then assess whether there is any improvement in their symptoms of dysphotopsias. Manual intrastromal keratopigmentation can then be performed using a crescent blade into the clear cornea at 50% depth and tunneled centrally to create a pocket ensuring that the peripheral iridotomy is fully occluded. The crescent blade is coated with an alcohol-based commercially available black tattoo pigment, and the pocket is filled. We have used the preoperative ink marker test on 5 eyes in patients with post-LPI (4 temporal and 1 superior) dysphotopsias before performing intrastromal keratopigmentation, with good patient satisfaction. Patients report immediate symptomatic relief after the procedure. This ink marking technique can also be extended to help identify which iris defect is symptomatic in patients with multiple iris defects. The preoperative ink test before intrastromal keratopigmentation is a novel adjunct to the treatment of post-LPI dysphotopsias.

[Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

PubMed

Ogata, Katsuhisa

2016-03-01

Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.

Loss of Peripheral Sensory Function Explains Much of the Increase in Postural Sway in Healthy Older Adults

PubMed Central

Anson, Eric; Bigelow, Robin T.; Swenor, Bonnielin; Deshpande, Nandini; Studenski, Stephanie; Jeka, John J.; Agrawal, Yuri

2017-01-01

Postural sway increases with age and peripheral sensory disease. Whether, peripheral sensory function is related to postural sway independent of age in healthy adults is unclear. Here, we investigated the relationship between tests of visual function (VISFIELD), vestibular function (CANAL or OTOLITH), proprioceptive function (PROP), and age, with center of mass sway area (COM) measured with eyes open then closed on firm and then a foam surface. A cross-sectional sample of 366 community dwelling healthy adults from the Baltimore Longitudinal Study of Aging was tested. Multiple linear regressions examined the association between COM and VISFIELD, PROP, CANAL, and OTOLITH separately and in multi-sensory models controlling for age and gender. PROP dominated sensory prediction of sway across most balance conditions (β's = 0.09–0.19, p's < 0.001), except on foam eyes closed where CANAL function loss was the only significant sensory predictor of sway (β = 2.12, p < 0.016). Age was not a consistent predictor of sway. This suggests loss of peripheral sensory function explains much of the age-associated increase in sway. PMID:28676758

The role of the endocrine system in feeding-induced tissue-specific circadian entrainment.

PubMed

Sato, Miho; Murakami, Mariko; Node, Koichi; Matsumura, Ritsuko; Akashi, Makoto

2014-07-24

The circadian clock is entrained to environmental cycles by external cue-mediated phase adjustment. Although the light input pathway has been well defined, the mechanism of feeding-induced phase resetting remains unclear. The tissue-specific sensitivity of peripheral entrainment to feeding suggests the involvement of multiple pathways, including humoral and neuronal signals. Previous in vitro studies with cultured cells indicate that endocrine factors may function as entrainment cues for peripheral clocks. However, blood-borne factors that are well characterized in actual feeding-induced resetting have yet to be identified. Here, we report that insulin may be involved in feeding-induced tissue-type-dependent entrainment in vivo. In ex vivo culture experiments, insulin-induced phase shift in peripheral clocks was dependent on tissue type, which was consistent with tissue-specific insulin sensitivity, and peripheral entrainment in insulin-sensitive tissues involved PI3K- and MAPK-mediated signaling pathways. These results suggest that insulin may be an immediate early factor in feeding-mediated tissue-specific entrainment. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease

PubMed Central

Kash, John C.; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B.; Adams, Rick D.; Herbert, Andrew S.; James, Rebekah M.; Stonier, Spencer W.; Memoli, Matthew J.; Dye, John M.; Davey, Richard T.; Chertow, Daniel S.; Taubenberger, Jeffery K.

2017-01-01

The 2013–2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration–approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. PMID:28404864

Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

PubMed

Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

2018-01-11

Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

Central and Peripheral factors contributing to Obstructive Sleep Apneas

PubMed Central

Ramirez, Jan-Marino; Garcia, Alfredo J.; Anderson, Tatiana M.; Koschnitzky, Jenna E.; Peng, Ying-Jie; Kumar, Ganesh; Prabhakar, Nanduri

2013-01-01

Apnea, the cessation of breathing, is a common physiological and pathophysiological phenomenon with many basic scientific and clinical implications. Among the different forms of apnea, obstructive sleep apnea (OSA) is clinically the most prominent manifestation. OSA is characterized by repetitive airway occlusions that are typically associated with peripheral airway obstructions. However, it would be a gross oversimplification to conclude that OSA is caused by peripheral obstructions. OSA is the result of a dynamic interplay between chemo- and mechanosensory reflexes, neuromodulation, behavioral state and the differential activation of the central respiratory network and its motor outputs. This interplay has numerous neuronal and cardiovascular consequences that are initially adaptive but in the long-term become major contributors to the morbidity and mortality associated with OSA. However, not only OSA, but all forms of apnea have multiple, and partly overlapping mechanisms. In all cases the underlying mechanisms are neither “exclusively peripheral” nor “exclusively central” in origin. While the emphasis has long been on the role of peripheral reflex pathways in the case of OSA, and central mechanisms in the case of central apneas, we are learning that such a separation is inconsistent with the integration of these mechanisms in all cases of apneas. This review discusses the complex interplay of peripheral and central nervous components that characterizes the cessation of breathing. PMID:23770311

Perceptual training yields rapid improvements in visually impaired youth

PubMed Central

Nyquist, Jeffrey B.; Lappin, Joseph S.; Zhang, Ruyuan; Tadin, Duje

2016-01-01

Visual function demands coordinated responses to information over a wide field of view, involving both central and peripheral vision. Visually impaired individuals often seem to underutilize peripheral vision, even in absence of obvious peripheral deficits. Motivated by perceptual training studies with typically sighted adults, we examined the effectiveness of perceptual training in improving peripheral perception of visually impaired youth. Here, we evaluated the effectiveness of three training regimens: (1) an action video game, (2) a psychophysical task that combined attentional tracking with a spatially and temporally unpredictable motion discrimination task, and (3) a control video game. Training with both the action video game and modified attentional tracking yielded improvements in visual performance. Training effects were generally larger in the far periphery and appear to be stable 12 months after training. These results indicate that peripheral perception might be under-utilized by visually impaired youth and that this underutilization can be improved with only ~8 hours of perceptual training. Moreover, the similarity of improvements following attentional tracking and action video-game training suggest that well-documented effects of action video-game training might be due to the sustained deployment of attention to multiple dynamic targets while concurrently requiring rapid attending and perception of unpredictable events. PMID:27901026

“Can't Walk Nor Raise Arms to Head”

PubMed Central

Pendleton, Courtney; Dorsi, Michael J.; Belzberg, Allan J.; Cohen-Gadol, Aaron A.; Quiñones-Hinojosa, Alfredo

2015-01-01

Study Design This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. Objective To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. Summary of Background Data At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Methods Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Results Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. Conclusion While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century. PMID:21301395

"Can't walk nor raise arms to head": Harvey Cushing's surgical treatment of poliomyelitis.

PubMed

Pendleton, Courtney; Dorsi, Michael J; Belzberg, Allan J; Cohen-Gadol, Aaron A; Quiñones-Hinojosa, Alfredo

2012-02-15

This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century.

The BioStent: novel concept for a viable stent structure.

PubMed

Weinandy, Stefan; Rongen, Lisanne; Schreiber, Fabian; Cornelissen, Christian; Flanagan, Thomas Cormac; Mahnken, Andreas; Gries, Thomas; Schmitz-Rode, Thomas; Jockenhoevel, Stefan

2012-09-01

Percutaneous stenting of occluded peripheral vessels is a well-established technique in clinical practice. Unfortunately, the patency rates of small-caliber vessels after stenting remain unsatisfactory. The aim of the BioStent concept is to overcome in-stent restenosis by excluding the diseased vessel segment entirely from the blood stream, in addition to providing an intact endothelial cell layer. The concept combines the principles of vascular tissue engineering with a self-expanding stent: casting of the stent within a cellularized fibrin gel structure, followed by bioreactor conditioning, allows complete integration of the stent within engineered tissue. Small-caliber BioStents (Ø=6 mm; n=4) were produced by casting a nitinol stent within a thin fibrin/vascular smooth muscle cell (vSMC) mixture, followed by luminal endothelial cell seeding, and conditioning of the BioStent within a bioreactor system. The potential remodeling of the fibrin component into tissue was analyzed using routine histological methods. Scanning electron microscopy was used to assess the luminal endothelial cell coverage following the conditioning phase and crimping of the stent. The BioStent was shown to be noncytotoxic, with no significant effect on cell proliferation. Gross and microscopic analysis revealed complete integration of the nitinol component within a viable tissue structure. Hematoxylin and eosin staining revealed a homogenous distribution of vSMCs throughout the thickness of the BioStent, while a smooth, confluent luminal endothelial cell lining was evident and not significantly affected by the crimping/release process. The BioStent concept is a platform technology offering a novel opportunity to generate a viable, self-expanding stent structure with a functional endothelial cell lining. This platform technology can be transferred to different applications depending on the luminal cell lining required.

Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes ▿

PubMed Central

Snooks, Michelle J.; Bhat, Purnima; Mackenzie, Jason; Counihan, Natalie A.; Vaughan, Nicola; Anderson, David A.

2008-01-01

Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of HAV via the apical domain of polarized hepatocytes. We have developed a subclone of hepatocyte-derived HepG2 cells (clone N6) that maintains functional characteristics of polarized hepatocytes but displays morphology typical of columnar epithelial cells, rather than the complex morphology that is typical of hepatocytes. N6 cells form microcolonies of polarized cells when grown on glass and confluent monolayers of polarized cells on semipermeable membranes. When N6 microcolonies were exposed to HAV, infection was restricted to peripheral cells of polarized colonies, whereas all cells could be infected in colonies of nonpolarized HepG2 cells (clone C11) or following disruption of tight junctions in N6 colonies with EGTA. This suggests that viral entry occurs predominantly via the basolateral plasma membrane, consistent with uptake of virus from the bloodstream after enteric exposure, as expected. Viral export was also found to be markedly vectorial in N6 but not C11 cells. However, rather than being exported from the apical domain as expected, more than 95% of HAV was exported via the basolateral domain of N6 cells, suggesting that virus is first excreted from infected hepatocytes into the bloodstream rather than to the biliary tree. Enteric excretion of HAV may therefore rely on reuptake and transcytosis of progeny HAV across hepatocytes into the bile. These studies provide the first example of the interactions between viruses and polarized hepatocytes. PMID:18579610

Inequalities of extended beta and extended hypergeometric functions.

PubMed

Mondal, Saiful R

2017-01-01

We study the log-convexity of the extended beta functions. As a consequence, we establish Turán-type inequalities. The monotonicity, log-convexity, log-concavity of extended hypergeometric functions are deduced by using the inequalities on extended beta functions. The particular cases of those results also give the Turán-type inequalities for extended confluent and extended Gaussian hypergeometric functions. Some reverses of Turán-type inequalities are also derived.

[Petrous plasmacytoma revealed by a painful peripheral facial palsy].

PubMed

Lagarde, J; Cret, C; Karlin, L; Ameri, A

2011-01-01

The classical hypothesis of Bell's palsy, tempting in cases of peripheral facial palsy of rapid onset, must nevertheless be evoked with caution particularly if an intense pain is present, which should lead to search for a tumor of the skull base, especially the petrous bone. A 43-year-old man presented a peripheral facial palsy of rapidly progressive onset. A petrous bone tumor was diagnosed on the CT scan, which revealed an aspect of a glomic tumor or a metastatic lesion. The final histological diagnosis was plasmacytoma. This type of tumor has been rarely reported in this location. The radiological features are not specific at all, underlying the importance of searching for some associated signs such as a monoclonal protein and performing a histological examination when the firm diagnosis of a systemic disease like multiple myeloma has not been possible. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Systematically Ranking the Tightness of Membrane Association for Peripheral Membrane Proteins (PMPs)*

PubMed Central

Gao, Liyan; Ge, Haitao; Huang, Xiahe; Liu, Kehui; Zhang, Yuanya; Xu, Wu; Wang, Yingchun

2015-01-01

Large-scale quantitative evaluation of the tightness of membrane association for nontransmembrane proteins is important for identifying true peripheral membrane proteins with functional significance. Herein, we simultaneously ranked more than 1000 proteins of the photosynthetic model organism Synechocystis sp. PCC 6803 for their relative tightness of membrane association using a proteomic approach. Using multiple precisely ranked and experimentally verified peripheral subunits of photosynthetic protein complexes as the landmarks, we found that proteins involved in two-component signal transduction systems and transporters are overall tightly associated with the membranes, whereas the associations of ribosomal proteins are much weaker. Moreover, we found that hypothetical proteins containing the same domains generally have similar tightness. This work provided a global view of the structural organization of the membrane proteome with respect to divergent functions, and built the foundation for future investigation of the dynamic membrane proteome reorganization in response to different environmental or internal stimuli. PMID:25505158

Approach to Peripheral Neuropathy for the Primary Care Clinician.

PubMed

Doughty, Christopher T; Seyedsadjadi, Reza

2018-02-02

Peripheral neuropathy is commonly encountered in the primary care setting and is associated with significant morbidity, including neuropathic pain, falls, and disability. The clinical presentation of neuropathy is diverse, with possible symptoms including weakness, sensory abnormalities, and autonomic dysfunction. Accordingly, the primary care clinician must be comfortable using the neurologic examination-including the assessment of motor function, multiple sensory modalities, and deep tendon reflexes-to recognize and characterize neuropathy. Although the causes of peripheral neuropathy are numerous and diverse, careful review of the medical and family history coupled with limited, select laboratory testing can often efficiently lead to an etiologic diagnosis. This review offers an approach for evaluating suspected neuropathy in the primary care setting. It will describe the most common causes, suggest an evidence-based workup to aid in diagnosis, and highlight recent evidence that allows for selection of symptomatic treatment of patients with neuropathy. Copyright © 2018 Elsevier Inc. All rights reserved.

Registry Assessment of Peripheral Interventional Devices (RAPID)　- Registry Assessment of Peripheral Interventional Devices Core Data Elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L; Nc, Durham; Md, Silver Spring; Japan, Tokyo; Ny, New York; Ri, Providence; Vt, Burlington; Mass, Newton; Colo, Denver; Ariz, Tempe; Calif, Santa Clara; Minn, Minneapolis; Nh, Lebanon

2018-01-25

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible.Methods and Results:Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators.

Central and peripheral fat body mass have a protective effect on osteopenia or osteoporosis in adults and elderly?

PubMed

Freitas, P M S S; Garcia Rosa, M L; Gomes, A M; Wahrlich, V; Di Luca, D G; da Cruz Filho, R A; da Silva Correia, D M; Faria, C A; Yokoo, E M

2016-04-01

This cross-sectional study involves randomly selected men aged 50 to 99 years and postmenopausal women. Either central fat mass or peripheral fat mass were associated to osteoporosis or osteopenia independently from fat-free body mass and other confounding factors. Obesity and osteoporosis are public health problems that probably share common pathophysiological mechanisms. The question if body fat mass, central or peripheral, is protective or harmful for osteoporosis or osteopenia is not completely resolved. This study aims to investigate the association between osteoporosis or osteopenia, and fat body mass (central and peripheral) independently from fat-free body mass, in men aged 50 to 99 years old and postmenopausal women randomly selected in the community. This is a cross-sectional investigation with a random sample of registered population in Niterói Family Doctor Program (FDP), State of Rio de Janeiro, Brazil. Bone mineral density (BMD) and fat-free mass were assessed by dual X-ray absorptiometry (DXA). There was statistically significant bivariate association between bone loss with gender, age, skin color, alcohol consumption at risk dose, use of thiazide, fat-free body mass, and fat body mass (central and peripheral). In the multiple analysis of fat-free body mass, central and peripheral fat body mass showed an independent and protective effect on the presence of osteoporosis or osteopenia (p value <0.001). Since both obesity and osteoporosis are public health problems worldwide, strategies aimed at preventing both conditions should be encouraged during aging.

Persistence of Multiple Tumor-Specific T-Cell Clones Is Associated with Complete Tumor Regression in a Melanoma Patient Receiving Adoptive Cell Transfer Therapy

PubMed Central

Zhou, Juhua; Dudley, Mark E.; Rosenberg, Steven A.; Robbins, Paul F.

2007-01-01

Summary The authors recently reported that adoptive immunotherapy with autologous tumor-reactive tumor infiltrating lymphocytes (TILs) immediately following a conditioning nonmyeloablative chemotherapy regimen resulted in an enhanced clinical response rate in patients with metastatic melanoma. These observations led to the current studies, which are focused on a detailed analysis of the T-cell antigen reactivity as well as the in vivo persistence of T cells in melanoma patient 2098, who experienced a complete regression of all metastatic lesions in lungs and soft tissues following therapy. Screening of an autologous tumor cell cDNA library using transferred TILs resulted in the identification of novel mutated growth arrest-specific gene 7 (GAS7) and glyceral-dehyde-3-phosphate dehydrogenase (GAPDH) gene transcripts. Direct sequence analysis of the expressed T-cell receptor beta chain variable regions showed that the transferred TILs contained multiple T-cell clonotypes, at least six of which persisted in peripheral blood for a month or more following transfer. The persistent T cells recognized both the mutated GAS7 and GAPDH. These persistent tumor-reactive T-cell clones were detected in tumor cell samples obtained from the patient following adoptive cell transfer and appeared to be represented at higher levels in the tumor sample obtained 1 month following transfer than in the peripheral blood obtained at the same time. Overall, these results indicate that multiple tumor-reactive T cells can persist in the peripheral blood and at the tumor site for prolonged times following adoptive transfer and thus may be responsible for the complete tumor regression in this patient. PMID:15614045

Multiple binding sites involved in the effect of choline esters on decarbamoylation of monomethylcarbamoyl- or dimethylcarbamoly-acetylcholinesterase.

PubMed Central

Sok, D E; Kim, Y B; Choi, S J; Jung, C H; Cha, S H

1994-01-01

Multiple binding sites for inhibitory choline esters in spontaneous decarbamoylation of dimethylcarbamoyl-acetylcholinesterase (AChE) were suggested from a wide range of IC50 values, in contrast with a limited range of AC50 values (concentration giving 50% of maximal activation) at a peripheral activatory site. Association of choline esters containing a long acyl chain (C7-C12) with the hydrophobic zone in the active site could be deduced from a linear relationship between the size of the acyl group and the inhibitory potency in either spontaneous decarbamoylation or acetylthiocholine hydrolysis. Direct support for laurylcholine binding to the active site might come from the competitive inhibition (Ki 33 microM) of choline-catalysed decarbamoylation by laurylcholine. Moreover, its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE, where there is a greater steric hindrance at the active centre. In further support, the inhibition of pentanoylthiocholine-induced decarbamoylation by laurylcholine was suggested to be due to laurylcholine binding to a central site rather than a peripheral site, similar to the inhibition of spontaneous decarbamoylation by laurylcholine. Supportive data for acetylcholine binding to the active site are provided by the results that acetylcholine is a competitive inhibitor (Ki 7.6 mM) of choline-catalysed decarbamoylation, and its inhibitory action was greater for monomethylcarbamoyl-AChE than for dimethylcarbamoyl-AChE. Meanwhile, choline esters with an acyl group of an intermediate size (C4-C6), more subject to steric exclusion at the active centre, and less associable with the hydrophobic zone, appear to bind preferentially to a peripheral activity site. Thus the multiple effects of choline esters may be governed by hydrophobicity and/or a steric effect exerted by the acyl moiety at the binding sites. PMID:8053896

Effect of met-enkephalin on chromosomal aberrations in the lymphocytes of the peripheral blood of patients with multiple sclerosis.

PubMed

Rakanović-Todić, Maida; Burnazović-Ristić, Lejla; Ibrulj, Slavka; Mulbegović, Nedžad

2014-05-01

Endogenious opiod met-enkephalin throughout previous research manifested cytoprotective and anti-inflammatory effects. Previous research suggests that met-enkephalin has cytogenetic effects. Reducement in the frequency of structural chromosome aberrations as well as a suppressive effect on lymphocyte cell cycle is found. It also reduces apoptosis in the blood samples of the patients with immune-mediated diseases. Met-enkephalin exerts immunomodulatory properties and induces stabilization of the clinical condition in patients with multiple Sclerosis (MS). The goal of the present research was to evaluate met-enkephalin in vitro effects on the number and type of chromosome aberrations in the peripheral blood lymphocytes of patients with MS. Our research detected disappearance of ring chromosomes and chromosome fragmentations in the cultures of the peripheral blood lymphocytes treated with met-enkephalin (1.2 μg/mL). However, this research did not detect any significant effects of met-enkephalin on the reduction of structural chromosome aberrations and disappearance of dicentric chromosomes. Chromosomes with the greatest percent of inclusion in chromosome aberrations were noted as: chromosome 1, chromosome 2 and chromosome 9. Additionally, we confirmed chromosome 14 as the most frequently included in translocations. Furthermore, met-enkephalin effects on the increase of the numerical aberrations in both concentrations applied were detected. Those findings should be interpreted cautiously and more research in this field should be conducted.

Two-stage treatment protocol of keratocystic odontogenic tumour in young patients with Gorlin-Goltz syndrome: marsupialization and later enucleation with peripheral ostectomy. A 5-year-follow-up experience.

PubMed

Borgonovo, Andrea Enrico; Di Lascia, Stefano; Grossi, Giovanni; Maiorana, Carlo

2011-12-01

Keratocystic odontogenic tumour (KCOT) is a benign uni- or multicystic intraosseous odontogenic tumour with potential for local destruction and tendency for multiplicity, especially when associated with Gorlin-Goltz syndrome. We suggest a conservative surgical treatment based on marsupialization and later enucleation with peripheral ostectomy in order to preserve jaw's integrity in young patients. Three young patients affected of nevoid basal cell carcinoma syndrome (NBCCS or Gorlin-Goltz syndrome) presented large and multiple KCOTs, which have been treated following a two-stage surgical strategy. Initially marsupialization was performed and after a mean period of 10 months, contextually to evident reduction in radiological size image, enucleation with peripheral ostectomy was carried out. All the patients showed high collaboration in daily self-irrigation of the stomia with chlorhexidine 0.2% during the period of marsupialization. Definitive surgical intervention led to complete healing and no signs of recurrence have been observed during a 5-year-follow-up. The main advantage of this modality is the preservation of important anatomical structures involved in the lesion and jaw's continuity. Therefore in a selected group of cooperative patients, especially those affected of Gorlin-Goltz syndrome, the surgical protocol exposed allows for a less invasive approach with excellent results avoiding extensive disfiguring procedures. Copyright © 2011. Published by Elsevier Ireland Ltd.

Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling

PubMed Central

Kurian, S. M.; Williams, A. N.; Gelbart, T.; Campbell, D.; Mondala, T. S.; Head, S. R.; Horvath, S.; Gaber, L.; Thompson, R.; Whisenant, T.; Lin, W.; Langfelder, P.; Robison, E. H.; Schaffer, R. L.; Fisher, J. S.; Friedewald, J.; Flechner, S. M.; Chan, L. K.; Wiseman, A. C.; Shidban, H.; Mendez, R.; Heilman, R.; Abecassis, M. M.; Marsh, C. L.; Salomon, D. R.

2015-01-01

There are no minimally invasive diagnostic metrics for acute kidney transplant rejection (AR), especially in the setting of the common confounding diagnosis, acute dysfunction with no rejection (ADNR). Thus, though kidney transplant biopsies remain the gold standard, they are invasive, have substantial risks, sampling error issues and significant costs and are not suitable for serial monitoring. Global gene expression profiles of 148 peripheral blood samples from transplant patients with excellent function and normal histology (TX; n = 46), AR (n = 63) and ADNR (n = 39), from two independent cohorts were analyzed with DNA microarrays. We applied a new normalization tool, frozen robust multi-array analysis, particularly suitable for clinical diagnostics, multiple prediction tools to discover, refine and validate robust molecular classifiers and we tested a novel one-by-one analysis strategy to model the real clinical application of this test. Multiple three-way classifier tools identified 200 highest value probesets with sensitivity, specificity, positive predictive value, negative predictive value and area under the curve for the validation cohort ranging from 82% to 100%, 76% to 95%, 76% to 95%, 79% to 100%, 84% to 100% and 0.817 to 0.968, respectively. We conclude that peripheral blood gene expression profiling can be used as a minimally invasive tool to accurately reveal TX, AR and ADNR in the setting of acute kidney transplant dysfunction. PMID:24725967

Klotho gene expression decreases in peripheral blood mononuclear cells (PBMCs) of patients with relapsing-remitting multiple sclerosis.

PubMed

Karami, Masoumeh; Mehrabi, Farzad; Allameh, Abdolamir; Pahlevan Kakhki, Majid; Amiri, Mehdi; Emami Aleagha, Mohammad Sajad

2017-10-15

we recently showed that a hypothesized anti-aging and anti-inflammatory protein, namely Klotho, may contribute to the etiology and/or pathogenesis of multiple sclerosis (MS). In addition, Klotho function and its gene expression are dependent on inflammatory pathways. Accordingly, the aim of this study was to investigate the Klotho gene expression within peripheral blood mononuclear cells (PBMCs) of patients with MS. Altogether, 30 patients with relapsing-remitting MS (RRMS) along with 30 age and sex-matched healthy individuals were enrolled in this study. Blood samples were obtained from all participants and then PBMCs were isolated. The quantitative Real-Time PCR was carried out for Klotho mRNA derived from PBMCs. The results showed that klotho gene expression in the PBMCs of patients with RRMS is nearly 2.5-fold less than healthy individuals (P=0.0006). This is the first study demonstrating a possible role of Klotho in the PBMCs of MS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Multiple Local Repairs on Microstructure and Mechanical Properties of T24 Steel Welded Joint

NASA Astrophysics Data System (ADS)

Chaus, Alexander S.; Kuhajdová, Andrea; Marônek, Milan; Dománková, Mária

2018-05-01

The effect of multiple local repairs on the microstructure and mechanical properties of the T24 steel welded joints was studied. T24 steel tubes were butt-welded by the GTAW method. Peripheral welded joints were made in four locations of the tube. In order to simulate the repair procedure, the welds were cut off from the root and the first local repair was performed. Other two local repairs were carried out in the same way. After each local repair, the microstructure and mechanical properties of the joints were evaluated. The results of the mechanical tests demonstrate that only two local repairs can be performed on the T24 steel peripheral welded joint. After the third local repair, impact energy of the welded joint was lower than required value, which is attributed to the coarser martensite and the coarser carbide precipitates formed in the heat-affected zone, compared with the weld metal.

Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients.

PubMed

Harder, Anja; Wesemann, Martin; Hagel, Christian; Schittenhelm, Jens; Fischer, Susan; Tatagiba, Marcos; Nagel, Christoph; Jeibmann, Astrid; Bohring, Axel; Mautner, Victor-Felix; Paulus, Werner

2012-05-01

We analyzed the histologic features of peripheral nerve sheath tumors occurring in 14 patients with schwannomatosis. Among a total of 31 tumors, 19 tumors (61%) showed schwannoma-like nodules within a neurofibroma-like tumor, corresponding to hybrid neurofibroma/schwannoma. At least 1 hybrid tumor occurred in 10 of 14 (71%) schwannomatosis patients. We then retrieved cases of hybrid tumors without documented relation to schwannomatosis from our database and identified 41 tumors arising in 23 patients. More than half of these patients (14/23) were reported to suffer from multiple peripheral nerve sheath tumors, favoring a tumor syndrome. Indeed, analysis of clinical records revealed the diagnosis of neurofibromatosis type 2 (NF2) in 26% (6/23), neurofibromatosis type 1 (NF1) in 9% (2/23), definite schwannomatosis in 4% (1/23), and possible schwannomatosis in 13% (3/23) of patients with multiple nerve sheath tumors. Our findings suggest that hybrid neurofibroma/schwannoma represents a common tumor type in schwannomatosis and shows a striking association with neurofibromatoses.

Oscillator networks with tissue-specific circadian clocks in plants.

PubMed

Inoue, Keisuke; Araki, Takashi; Endo, Motomu

2017-09-08

Many organisms rely on circadian clocks to synchronize their biological processes with the 24-h rotation of the earth. In mammals, the circadian clock consists of a central clock in the suprachiasmatic nucleus and peripheral clocks in other tissues. The central clock is tightly coupled to synchronize rhythmicity and can organize peripheral clocks through neural and hormonal signals. In contrast to mammals, it has long been assumed that the circadian clocks in each plant cell is able to be entrained by external light, and they are only weakly coupled to each other. Recently, however, several reports have demonstrated that plants have unique oscillator networks with tissue-specific circadian clocks. Here, we introduce our current view regarding tissue-specific properties and oscillator networks of plant circadian clocks. Accumulating evidence suggests that plants have multiple oscillators, which show distinct properties and reside in different tissues. A direct tissue-isolation technique and micrografting have clearly demonstrated that plants have hierarchical oscillator networks consisting of multiple tissue-specific clocks. Copyright © 2017. Published by Elsevier Ltd.

Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

ClinicalTrials.gov

2017-04-14

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

[Esophageal pathology in patients with the AIDS virus. Etiology and diagnosis].

PubMed

Varsky, C G; Yahni, V D; Freire, M C; Patrizio, E; Balbo, V; Benetucci, J; Boffi, A; Mattoni, R A; Luis; Alicia, M

1991-01-01

From 180 patients infected with human immunodeficiency virus (HIV) and followed-up for one year, 17 cases (9.44%) were referred to detect oesophageal pathology. They were prospectively analyzed through fibroscopy, radiology, biopsies for histopathology, virology and mycology and brush cytology. Most frequent symptoms were dysphagia. Odynophagia and retrosternal pain, usually associated, and not providing an accurate diagnostic clue. The most common causes of symptoms were oesophageal candidiasis (47.70%), and herpetic ulcers (23.52%) caused by herpes simplex virus (HSV) type 2. Reflux pathology was also found (11.76%). Cytomegalovirus, other opportunistic infections and tumors were not detected. Seven (64%) of the eleven patients with oesophageal candidiasis also had oral involvement. Four (66%) of six oesophageal ulcers were herpetic; two of them (50%) showed oral ulcers too, and one (25%) had perioral herpetic blisters. Almost in every case endoscopic features allowed diagnosis. Endoscopy in candidiasis showed isolated or confluent white plaques of variable grade. Herpetic ulcers, alone or multiple, were deep with slightly elevated borders. Radiology yielded a poor diagnostic profit (50%), specially in case of multiple lesions. Cytology was highly specific and sensitive (both 90.9%) and suggested viral etiology in 100% of HSV patients. Histopathology was less sensitive than endoscopy and cytology (73% in candida and one HSV non-ulcer case). Both, cytology and histopathology showed koilocytosis in herpetic virus infected patients. The studies performed allowed to change the HIV disease stage in ten patients (62.5%) and to diagnose AIDS in seven (43.75%). In every case medical behavior was oriented or changed by these studies.

Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems

PubMed Central

Harari, Colin M.; Magagna, Michelle; Bedoya, Mariajose; Lee, Fred T.; Lubner, Meghan G.; Hinshaw, J. Louis; Ziemlewicz, Timothy

2016-01-01

Purpose To compare microwave ablation zones created by using sequential or simultaneous power delivery in ex vivo and in vivo liver tissue. Materials and Methods All procedures were approved by the institutional animal care and use committee. Microwave ablations were performed in both ex vivo and in vivo liver models with a 2.45-GHz system capable of powering up to three antennas simultaneously. Two- and three-antenna arrays were evaluated in each model. Sequential and simultaneous ablations were created by delivering power (50 W ex vivo, 65 W in vivo) for 5 minutes per antenna (10 and 15 minutes total ablation time for sequential ablations, 5 minutes for simultaneous ablations). Thirty-two ablations were performed in ex vivo bovine livers (eight per group) and 28 in the livers of eight swine in vivo (seven per group). Ablation zone size and circularity metrics were determined from ablations excised postmortem. Mixed effects modeling was used to evaluate the influence of power delivery, number of antennas, and tissue type. Results On average, ablations created by using the simultaneous power delivery technique were larger than those with the sequential technique (P < .05). Simultaneous ablations were also more circular than sequential ablations (P = .0001). Larger and more circular ablations were achieved with three antennas compared with two antennas (P < .05). Ablations were generally smaller in vivo compared with ex vivo. Conclusion The use of multiple antennas and simultaneous power delivery creates larger, more confluent ablations with greater temperatures than those created with sequential power delivery. © RSNA, 2015 PMID:26133361

The Escherichia coli Peripheral Inner Membrane Proteome*

PubMed Central

Papanastasiou, Malvina; Orfanoudaki, Georgia; Koukaki, Marina; Kountourakis, Nikos; Sardis, Marios Frantzeskos; Aivaliotis, Michalis; Karamanou, Spyridoula; Economou, Anastassios

2013-01-01

Biological membranes are essential for cell viability. Their functional characteristics strongly depend on their protein content, which consists of transmembrane (integral) and peripherally associated membrane proteins. Both integral and peripheral inner membrane proteins mediate a plethora of biological processes. Whereas transmembrane proteins have characteristic hydrophobic stretches and can be predicted using bioinformatics approaches, peripheral inner membrane proteins are hydrophilic, exist in equilibria with soluble pools, and carry no discernible membrane targeting signals. We experimentally determined the cytoplasmic peripheral inner membrane proteome of the model organism Escherichia coli using a multidisciplinary approach. Initially, we extensively re-annotated the theoretical proteome regarding subcellular localization using literature searches, manual curation, and multi-combinatorial bioinformatics searches of the available databases. Next we used sequential biochemical fractionations coupled to direct identification of individual proteins and protein complexes using high resolution mass spectrometry. We determined that the proposed cytoplasmic peripheral inner membrane proteome occupies a previously unsuspected ∼19% of the basic E. coli BL21(DE3) proteome, and the detected peripheral inner membrane proteome occupies ∼25% of the estimated expressed proteome of this cell grown in LB medium to mid-log phase. This value might increase when fleeting interactions, not studied here, are taken into account. Several proteins previously regarded as exclusively cytoplasmic bind membranes avidly. Many of these proteins are organized in functional or/and structural oligomeric complexes that bind to the membrane with multiple interactions. Identified proteins cover the full spectrum of biological activities, and more than half of them are essential. Our data suggest that the cytoplasmic proteome displays remarkably dynamic and extensive communication with biological membrane surfaces that we are only beginning to decipher. PMID:23230279

Analysis of mortality in a cohort of 650 cases of bacteremic osteoarticular infections.

PubMed

Gomez-Junyent, Joan; Murillo, Oscar; Grau, Imma; Benavent, Eva; Ribera, Alba; Cabo, Xavier; Tubau, Fe; Ariza, Javier; Pallares, Roman

2018-01-31

The mortality of patients with bacteremic osteoarticular infections (B-OAIs) is poorly understood. Whether certain types of OAIs carry higher mortality or interventions like surgical debridement can improve prognosis, are unclarified questions. Retrospective analysis of a prospective cohort of patients with B-OAIs treated at a teaching hospital in Barcelona (1985-2014), analyzing mortality (30-day case-fatality rate). B-OAIs were categorized as peripheral septic arthritis or other OAIs. Factors influencing mortality were analyzed using logistic regression models. The association of surgical debridement with mortality in patients with peripheral septic arthritis was evaluated with a multivariate logistic regression model and a propensity score matching analysis. Among 650 cases of B-OAIs, mortality was 12.2% (41.8% of deaths within 7 days). Compared with other B-OAI, cases of peripheral septic arthritis were associated with higher mortality (18.6% vs 8.3%, p < 0.001). In a multiple logistic regression model, peripheral septic arthritis was an independent predictor of mortality (adjusted odds ratio [OR] 2.12; 95% CI: 1.22-3.69; p = 0.008). Cases with peripheral septic arthritis managed with surgical debridement had lower mortality than those managed without surgery (14.7% vs 33.3%; p = 0.003). Surgical debridement was associated with reduced mortality after adjusting for covariates (adjusted OR 0.23; 95% CI: 0.09-0.57; p = 0.002) and in the propensity score matching analysis (OR 0.81; 95% CI: 0.68-0.96; p = 0.014). Among patients with B-OAIs, mortality was greater in those with peripheral septic arthritis. Surgical debridement was associated with decreased mortality in cases of peripheral septic arthritis. Copyright © 2018 Elsevier Inc. All rights reserved.

Reprogramming of blood cells into induced pluripotent stem cells as a new cell source for cartilage repair.

PubMed

Li, Yueying; Liu, Tie; Van Halm-Lutterodt, Nicholas; Chen, JiaYu; Su, Qingjun; Hai, Yong

2016-02-17

An attempt was made to reprogram peripheral blood cells into human induced pluripotent stem cell (hiPSCs) as a new cell source for cartilage repair. We generated chondrogenic lineage from human peripheral blood via hiPSCs using an integration-free method. Peripheral blood cells were either obtained from a human blood bank or freshly collected from volunteers. After transforming peripheral blood cells into iPSCs, the newly derived iPSCs were further characterized through karyotype analysis, pluripotency gene expression and cell differentiation ability. iPSCs were differentiated through multiple steps, including embryoid body formation, hiPSC-mesenchymal stem cell (MSC)-like cell expansion, and chondrogenic induction for 21 days. Chondrocyte phenotype was then assessed by morphological, histological and biochemical analysis, as well as the chondrogenic expression. hiPSCs derived from peripheral blood cells were successfully generated, and were characterized by fluorescent immunostaining of pluripotent markers and teratoma formation in vivo. Flow cytometric analysis showed that MSC markers CD73 and CD105 were present in monolayer cultured hiPSC-MSC-like cells. Both alcian blue and toluidine blue staining of hiPSC-MSC-chondrogenic pellets showed as positive. Immunohistochemistry of collagen II and X staining of the pellets were also positive. The sulfated glycosaminoglycan content was significantly increased, and the expression levels of the chondrogenic markers COL2, COL10, COL9 and AGGRECAN were significantly higher in chondrogenic pellets than in undifferentiated cells. These results indicated that peripheral blood cells could be a potential source for differentiation into chondrogenic lineage in vitro via generation of mesenchymal progenitor cells. This study supports the potential applications of utilizing peripheral blood cells in generating seed cells for cartilage regenerative medicine in a patient-specific and cost-effective approach.

Osteopontin (OPN) as a CSF and blood biomarker for multiple sclerosis: A systematic review and meta-analysis.

PubMed

Agah, Elmira; Zardoui, Arshia; Saghazadeh, Amene; Ahmadi, Mona; Tafakhori, Abbas; Rezaei, Nima

2018-01-01

Identifying a reliable biomarker may accelerate diagnosis of multiple sclerosis (MS) and lead to early management of the disease. Accumulating evidence suggest that cerebrospinal fluid (CSF) and peripheral blood concentration of osteopontin (OPN) may have diagnostic and prognostic value in MS. We conducted a systematic review and meta-analysis of studies that measured peripheral blood and CSF levels of OPN in MS patients and controls to evaluate the diagnostic potential of this biomarker better. We searched PubMed, Web of Science and Scopus databases to find articles that measured OPN concentration in peripheral blood and CSF samples from MS patients up to October 19, 2016. Q statistic tests and the I2 index were applied for heterogeneity assessment. If the I2 index was less than 40%, the fixed-effects model was used for meta-analysis. Random-effects meta-analysis was chosen if the I2 value was greater than 40%. After removal of duplicates, 918 articles were identified, and 27 of them fulfilled the inclusion criteria. We included 22 eligible studies in the final meta-analysis. MS patients, in general, had considerably higher levels of OPN in their CSF and blood when compared to all types of controls (p<0.05). When the comparisons were made between different subtypes of MS patients and controls, the results pointed to significantly higher levels of OPN in CSF of MS subgroups (p<0.05). All subtypes of MS patients, except CIS patients, had increased blood levels of OPN compared to controls (p<0.05). In the second set of meta-analyses, we compared the peripheral blood and CSF concentrations of OPN between MS patient subtypes. CIS patients had significantly lower levels of OPN both in their peripheral blood and CSF compared to patients with progressive subtypes of MS (p<0.05). CSF concentration of OPN was significantly higher among RRMS patients compared to the CIS patients and SPMS patients (P<0.05). Finally, patients with active MS had significantly higher OPN levels in their CSF compared to patients with stable disease (P = 0.007). The result of this study confirms that increased levels of OPN exist in CSF and peripheral blood of MS patients and strengthens the evidence regarding the clinical utility of OPN as a promising and validated biomarker for MS.

Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs).

PubMed

DeStefano, Jackson G; Xu, Zinnia S; Williams, Ashley J; Yimam, Nahom; Searson, Peter C

2017-08-04

The endothelial cells that form the lumen of capillaries and microvessels are an important component of the blood-brain barrier. Cell phenotype is regulated by transducing a range of biomechanical and biochemical signals in the local microenvironment. Here we report on the role of shear stress in modulating the morphology, motility, proliferation, apoptosis, and protein and gene expression, of confluent monolayers of human brain microvascular endothelial cells derived from induced pluripotent stem cells. To assess the response of derived human brain microvascular endothelial cells (dhBMECs) to shear stress, confluent monolayers were formed in a microfluidic device. Monolayers were subjected to a shear stress of 4 or 12 dyne cm -2 for 40 h. Static conditions were used as the control. Live cell imaging was used to assess cell morphology, cell speed, persistence, and the rates of proliferation and apoptosis as a function of time. In addition, immunofluorescence imaging and protein and gene expression analysis of key markers of the blood-brain barrier were performed. Human brain microvascular endothelial cells exhibit a unique phenotype in response to shear stress compared to static conditions: (1) they do not elongate and align, (2) the rates of proliferation and apoptosis decrease significantly, (3) the mean displacement of individual cells within the monolayer over time is significantly decreased, (4) there is no cytoskeletal reorganization or formation of stress fibers within the cell, and (5) there is no change in expression levels of key blood-brain barrier markers. The characteristic response of dhBMECs to shear stress is significantly different from human and animal-derived endothelial cells from other tissues, suggesting that this unique phenotype that may be important in maintenance of the blood-brain barrier. The implications of this work are that: (1) in confluent monolayers of dhBMECs, tight junctions are formed under static conditions, (2) the formation of tight junctions decreases cell motility and prevents any morphological transitions, (3) flow serves to increase the contact area between cells, resulting in very low cell displacement in the monolayer, (4) since tight junctions are already formed under static conditions, increasing the contact area between cells does not cause upregulation in protein and gene expression of BBB markers, and (5) the increase in contact area induced by flow makes barrier function more robust.

NaK-ATPase pump sites in cultured bovine corneal endothelium of varying cell density at confluence.

PubMed

Crawford, K M; Ernst, S A; Meyer, R F; MacCallum, D K

1995-06-01

The driving force for ion and water flow necessary for efficient deturgesence of the corneal stroma resides in the ouabain-sensitive sodium (Na) pump of corneal endothelial cells. Using a cell culture model of corneal endothelial cell hypertrophy, the authors examined the expression of Na pumps at the cell surface to see how this central element of the endothelial pump changed as corneal endothelial cell density decreased to a level associated with corneal decompensation in vivo. 3H-ouabain binding to NaK-ATPase at saturating conditions was used to quantitate the number of Na pump sites on cultured bovine corneal endothelial cells as the confluent density decreased from approximately 2750 cells/mm2 to approximately 275 cells/mm2. The mean number of Na pump sites per cell at confluence (1.92 +/- 0.07 x 10(6)) did not change as the cell density decreased 2.7-fold from 2763 cells/mm2 to 1000 cells/mm2. However, pump site expression doubled to approximately 4 x 10(6) sites/cell as the cell density decreased from 1000 cells/mm2 to 275 cells/mm2. Despite the incremental increase in Na pump site expression that occurred as the cells hypertrophied below a density of 1000/mm2 to achieve confluence, this increase was insufficient to prevent a decrease in Na pump site density of the intact monolayer, expressed as pump sites/mm2. The confluent cell density of cultured bovine corneal endothelial cells can be varied from that found in the normal native cornea to that associated with corneal decompensation. In confluent cultures with cell densities ranging from 2750 cells/mm2 to 1000 cells/mm2, the number of pump sites per cell remains relatively unchanged. Below cell densities of 1000 cells/mm2, the number of pump sites per cell progressively increases. The increased Na pump site abundance in markedly hypertrophied endothelial cells cannot adequately compensate for the progressive reduction in the number of transporting cells per unit area within the intact monolayer. Even when considered with the decrease in the size of the paracellular ion conductive pathway that is a consequence of progressive endothelial hypertrophy, the overall pumping capacity of the intact endothelial monolayer declines.

Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells.

PubMed

Singer, Bernhard B; Scheffrahn, Inka; Kammerer, Robert; Suttorp, Norbert; Ergun, Suleyman; Slevogt, Hortense

2010-01-18

CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation.

A theoretical framework for jamming in confluent biological tissues

NASA Astrophysics Data System (ADS)

Manning, M. Lisa

2015-03-01

For important biological functions such as wound healing, embryonic development, and cancer tumorogenesis, cells must initially rearrange and move over relatively large distances, like a liquid. Subsequently, these same tissues must undergo buckling and support shear stresses, like a solid. Our work suggests that biological tissues can accommodate these disparate requirements because the tissues are close to glass or jamming transition. While recent self propelled particle models generically predict a glass/jamming transition that is driven by packing density φ and happens at some critical φc less than unity, many biological tissues that are confluent with no gaps between cells appear to undergo a jamming transition at a constant density (φ = 1). I will discuss a new theoretical framework for predicting energy barriers and rates of cell migration in 2D tissue monolayers, and show that this model predicts a novel type of rigidity transition, which takes place at constant φ = 1 and depends only on single cell properties such as cell-cell adhesion, cortical tension and cell elasticity. This model additionally predicts that an experimentally observable parameter, the ratio between a cell's perimeter and the square root of its cross-sectional area, attains a specific, critical value at the jamming transition. We show that this prediction is precisely realized in primary epithelial cultures from human patients, with implications for asthma pathology.

Impact of jamming on collective cell migration

NASA Astrophysics Data System (ADS)

Nnetu, Kenechukwu David; Knorr, Melanie; Pawlizak, Steve; Fuhs, Thomas; Zink, Mareike; KäS, Josef A.

2012-02-01

Multi-cellular migration plays an important role in physiological processes such as embryogenesis, cancer metastasis and tissue repair. During migration, single cells undergo cycles of extension, adhesion and retraction resulting in morphological changes. In a confluent monolayer, there are inter-cellular interactions and crowding, however, the impact of these interactions on the dynamics and elasticity of the monolayer at the multi-cellular and single cell level is not well understood. Here we study the dynamics of a confluent epithelial monolayer by simultaneously measuring cell motion at the multi-cellular and single cell level for various cell densities and tensile elasticity. At the multi-cellular level, the system exhibited spatial kinetic transitions from isotropic to anisotropic migration on long times and the velocity of the monolayer decreased with increasing cell density. Moreover, the dynamics was spatially and temporally heterogeneous. Interestingly, the dynamics was also heterogeneous in wound-healing assays and the correlation length was fitted by compressed exponential. On the single cell scale, we observed transient caging effects with increasing cage rearrangement times as the system age due to an increase in density. Also, the density dependent elastic modulus of the monolayer scaled as a weak power law. Together, these findings suggest that caging effects at the single cell level initiates a slow and heterogeneous dynamics at the multi-cellular level which is similar to the glassy dynamics of deformable colloidal systems.

Acoustic and Laser Doppler Anemometer Results for Confluent, 22-Lobed, and Unique-Lobed Mixer Exhaust Systems for Subsonic Jet Noise Reduction

NASA Technical Reports Server (NTRS)

Salikuddin, M.; Martens, S.; Shin, H.; Majjigi, R. K.; Krejsa, Gene (Technical Monitor)

2002-01-01

The objective of this task was to develop a design methodology and noise reduction concepts for high bypass exhaust systems which could be applied to both existing production and new advanced engine designs. Special emphasis was given to engine cycles with bypass ratios in the range of 4:1 to 7:1, where jet mixing noise was a primary noise source at full power takeoff conditions. The goal of this effort was to develop the design methodology for mixed-flow exhaust systems and other novel noise reduction concepts that would yield 3 EPNdB noise reduction relative to 1992 baseline technology. Two multi-lobed mixers, a 22-lobed axisymmetric and a 21-lobed with a unique lobe, were designed. These mixers along with a confluent mixer were tested with several fan nozzles of different lengths with and without acoustic treatment in GEAE's Cell 41 under the current subtask (Subtask C). In addition to the acoustic and LDA tests for the model mixer exhaust systems, a semi-empirical noise prediction method for mixer exhaust system is developed. Effort was also made to implement flowfield data for noise prediction by utilizing MGB code. In general, this study established an aero and acoustic diagnostic database to calibrate and refine current aero and acoustic prediction tools.

White Matter Lesions: Prevalence and Clinical Phenotype in Asymptomatic Individuals Aged ≥50 Years.

PubMed

David, Jean-Philippe; Ferrat, Emilie; Parisot, Juliette; Naga, Henri; Lakroun, Samia; Menasria, Feriel; Saddedine, Sofiane; Natella, Pierre-André; Paillaud, Elena; Fromentin, Isabelle; Bastuji-Garin, Sylvie

2016-01-01

To assess the prevalence of early confluent/confluent white matter lesions (ec/cWMLs) in asymptomatic individuals aged ≥50 years and to identify associated clinical phenotypes. Cross-sectional analysis of 141 asymptomatic individuals aged ≥50 years assessed at an outpatient department in France. Brain magnetic resonance imaging was rated using the Fazekas scale. Age-adjusted odds ratios (ORs) and 95% confidence intervals were estimated using logistic models to investigate factors associated with ec/cWMLs; independent risk factors were identified by multivariate analysis. Median age was 63 years; 53.9% were women, 32.6% had hypertension, and 76.6% had ≥1 cardiovascular risk factors. The prevalence of ec/cWMLs was 26.2%. Apart from age, independent risk factors were family history of cardiovascular event (OR = 5.55; 1.13-27.32) and hypertension (2.47; 1.05-5.81). Patients with ec/cWMLs had lower cognitive dual-task walking speed (1.15; 0.98-1.40), MMSE (1.41; 1.06-1.89), and FAB scores (5.21; 1.49-19.84). The Scheltens score was independently associated with the WML severity score. ec/cWMLs are common in asymptomatic community-dwelling individuals aged ≥50 years. They are associated with cardiovascular risk factors, impairments in global and executive cognitive function, and Scheltens score elevation. © 2016 S. Karger AG, Basel.

Legionnaire's pneumonia: is there really an interstitial disease?

PubMed

Godet, C; Frat, J P; Le Moal, G; Roblot, F; Michalakis, G; Cabon, E; Tasu, J P

2007-01-01

Legionella pneumonia is usually classified as "atypical pneumonia", which suggests a predominance of interstitial patterns in chest X-rays. Based on a selection of recent clinical cases and a brief review of the literature, the aim of the study is to clarify, how far the actual radiological findings would be consistent with these expectations. A retrospective analysis of 18 epidemic personal cases and a review of the literature data were performed to describe the chest X-ray findings of Legionella pneumophila (LP) community acquired pneumonia. X-ray review was performed simultaneously and in consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). From our series, 17 patients had an abnormal chest X-ray on admission. Among these pathological X-ray cases, infiltrates were more often confluent (n=16), or patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates involving the lower lung fields. Bilateral distribution of abnormalities and pleural effusion were each observed in three cases. Radiological findings deteriorated between the second and seventh days following admission, particularly in the form of patchy infiltrates with pleural effusion. The review of the literature is consistent with these findings, by reporting prevalent confluent or patchy infiltrates. These findings are consistent with the physiopathological particularity of this affection and incite us to avoid the classification "atypical pneumonia" in radiologic terminology. This term is more appropriate for clinical and microbiological use.

PET/CT study performed after an oral administration of 18F-fluoride.

PubMed

Zacchi, Samara Riguete; Valadares, Agnes Araújo; Duarte, Paulo Schiavom; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto

2013-12-01

A 52-year-old woman with right breast cancer was referred for 18F-fluoride whole-body PET/CT for the assessment of bone metastases. The peripheral i.v. access was not obtained after multiple attempts. The radiopharmaceutical was administered by oral route.

Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice

USDA-ARS?s Scientific Manuscript database

Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprand...

The Prognostic Significance of Metastasis to Lymph Nodes in Aortopulmonary Zone (Stations 5 and 6) in Completely Resected Left Upper Lobe Tumors.

PubMed

Citak, Necati; Sayar, Adnan; Metin, Muzaffer; Büyükkale, Songül; Kök, Abdulaziz; Solak, Okan; Yurt, Sibel; Gürses, Atilla

2015-10-01

We investigated the prognostic effect of lymph nodes metastasis in aortopulmonary (AP) zone in resected non-small cell lung cancer of the left upper lobe (LUL). Between 1998 and 2010, 181 patients with LUL carcinoma underwent complete resection and were retrospectively analyzed. The patients were divided into four groups according to N status: N0 (n = 68, 37.6%), N1 (n = 64, 35.3%), N2(5,6+) (only metastasized to stations 5 and/or 6, n = 36, 19.9%), and N2(7+) (only metastasized to stations 7, n = 13, 7.2%). N1 were divided according to single and multiple (N1(single) n = 49, N1(multiple) n = 15) or peripheral and hilar (N1(peripheral) n = 39, N1(hilar) n = 25). Overall 5-year survival rate was 55.1%. Five-year survivals were 76.1% for N0, 54.3% for N1, and 20.7% for N2. N1(peripheral) had a better survival than N1(hilar) (60.3 vs. 29.4%, p = 0.09). Five-year survival of N1(single) was 60.1%, whereas it was 36.6% for N1(multiple) (p = 0.02). Five-year survival rate was 24.6% for N2(5,6+). Skip metastasis for lymph nodes in AP zone (n = 13) was a factor of better prognosis as compared to nonskip metastasis (n = 23) (29.9 vs. 19.2%). There was no statistically significant difference between the N2(5,6+) and N1(hilar) (p = 0.772), although N1(peripheral) had a significantly better survival than N2(5,6+) (p = 0.02). AP zone metastases alone had a significantly worse survival than N1(single) (p = 0.008), whereas there was no statistically significant difference between the N1(multiple) and N2(5,6+) (p = 0.248). N2(7+) was not expected to survive 3 years after operation. They had a significantly worse prognosis than N2(5,6+) (p = 0.02). LUL tumors with metastasis in the AP zone lymph nodes, especially skip metastasis, were associated with a more favorable prognosis than other mediastinal lymph nodes. However, the therapy of choice for lung cancer with N2(5,6+) has not been clarified yet. Georg Thieme Verlag KG Stuttgart · New York.

Nonlocal origin of response suppression from stimulation outside the classic receptive field in area 17 of the cat.

PubMed

Brown, H A; Allison, J D; Samonds, J M; Bonds, A B

2003-01-01

A stimulus located outside the classic receptive field (CRF) of a striate cortical neuron can markedly influence its behavior. To study this phenomenon, we recorded from two cortical sites, recorded and peripheral, with separate electrodes in cats anesthetized with Propofol and nitrous oxide. The receptive fields of each site were discrete (2-7.3 deg between centers). A control orientation tuning (OT) curve was measured for a single recorded cell with a drifting grating. The OT curve was then remeasured while stimulating simultaneously the cell's CRF as well as the peripheral site with a stimulus optimized for that location. For 22/60 cells, the peripheral stimulus suppressed the peak response and/or shifted the center of mass of the OT curve. For 19 of these 22 cells, we then reversibly blocked stimulus-driven activity at the peripheral site by iontophoretic application of GABA (0.5 M). For 6/19 cells, the response returned to control levels, implying that for these cells the inhibitory influence arose from the blocked site. The responses of nine cells remained reduced during inactivation of the peripheral site, suggesting that influence was generated outside the region of local block in area 17. This is consistent with earlier findings suggesting that modulatory influences can originate from higher cortical areas. Three cells had mixed results, suggesting multiple origins of influence. The response of each cell returned to suppressed levels after dissipation of the GABA and returned to baseline values when the peripheral stimulus was removed. These findings support a cortical model in which a cell's response is modulated by an inhibitory network originating from beyond the receptive field that supplants convergence of excitatory lateral geniculate neurons. The existence of cells that exhibit no change in peripherally inhibited responses during the GABA application suggests that peripheral influences may arise from outside area 17, presumably from other cortical areas (e.g. area 18).

Factors associated with developing a fear of falling in subjects with primary open-angle glaucoma.

PubMed

Adachi, Sayaka; Yuki, Kenya; Awano-Tanabe, Sachiko; Ono, Takeshi; Shiba, Daisuke; Murata, Hiroshi; Asaoka, Ryo; Tsubota, Kazuo

2018-02-13

To investigate the relationship between clinical risk factors, including visual field (VF) defects and visual acuity, and a fear of falling, among patients with primary open-angle glaucoma (POAG). All participants answered the following question at a baseline ophthalmic examination: Are you afraid of falling? The same question was then answered every 12 months for 3 years. A binocular integrated visual field was calculated by merging a patient's monocular Humphrey field analyzer VFs, using the 'best sensitivity' method. The means of total deviation values in the whole, superior peripheral, superior central, inferior central, and inferior peripheral VFs were calculated. The relationship between these mean VF measurements, and various clinical factors, against patients' baseline fear of falling and future fear of falling was analyzed using multiple logistic regression. Among 392 POAG subjects, 342 patients (87.2%) responded to the fear of falling question at least twice in the 3 years study period. The optimal regression model for patients' baseline fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. The optimal regression equation for future fear of falling included age, gender, mean of total deviation values in the inferior peripheral VF and number of previous falls. Defects in the inferior peripheral VF area are significantly related to the development of a fear of falling.

Longitudinal peripheral blood transcriptional analysis of a patient with severe Ebola virus disease.

PubMed

Kash, John C; Walters, Kathie-Anne; Kindrachuk, Jason; Baxter, David; Scherler, Kelsey; Janosko, Krisztina B; Adams, Rick D; Herbert, Andrew S; James, Rebekah M; Stonier, Spencer W; Memoli, Matthew J; Dye, John M; Davey, Richard T; Chertow, Daniel S; Taubenberger, Jeffery K

2017-04-12

The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance. Copyright © 2017, American Association for the Advancement of Science.

Photoperiodic responses of depression-like behavior, the brain serotonergic system, and peripheral metabolism in laboratory mice.

PubMed

Otsuka, Tsuyoshi; Kawai, Misato; Togo, Yuki; Goda, Ryosei; Kawase, Takahiro; Matsuo, Haruka; Iwamoto, Ayaka; Nagasawa, Mao; Furuse, Mitsuhiro; Yasuo, Shinobu

2014-02-01

Seasonal affective disorder (SAD) is characterized by depression during specific seasons, generally winter. The pathophysiological mechanisms underlying SAD remain elusive due to a limited number of animal models with high availability and validity. Here we show that laboratory C57BL/6J mice display photoperiodic changes in depression-like behavior and brain serotonin content. C57BL/6J mice maintained under short-day conditions, as compared to those under long-day conditions, demonstrated prolonged immobility times in the forced swimming test with lower brain levels of serotonin and its precursor l-tryptophan. Furthermore, photoperiod altered multiple parameters reflective of peripheral metabolism, including the ratio of plasma l-tryptophan to the sum of other large neutral amino acids that compete for transport across the blood-brain barrier, responses of circulating glucose and insulin to glucose load, sucrose intake under restricted feeding condition, and sensitivity of the brain serotonergic system to peripherally administered glucose. These data suggest that the mechanisms underlying SAD involve the brain-peripheral tissue network, and C57BL/6J mice can serve as a powerful tool for investigating the link between seasons and mood. Copyright © 2013 Elsevier Ltd. All rights reserved.

4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

PubMed Central

Boyer, Richard B.; Kelm, Nathaniel D.; Riley, D. Colton; Sexton, Kevin W.; Pollins, Alonda C.; Shack, R. Bruce; Dortch, Richard D.; Nanney, Lillian B.; Does, Mark D.; Thayer, Wesley P.

2015-01-01

Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries. PMID:26323827

Visualization of newt aragonitic otoconial matrices using transmission electron microscopy

NASA Technical Reports Server (NTRS)

Steyger, P. S.; Wiederhold, M. L.

1995-01-01

Otoconia are calcified protein matrices within the gravity-sensing organs of the vertebrate vestibular system. These protein matrices are thought to originate from the supporting or hair cells in the macula during development. Previous studies of mammalian calcitic, barrel-shaped otoconia revealed an organized protein matrix consisting of a thin peripheral layer, a well-defined organic core and a flocculent matrix inbetween. No studies have reported the microscopic organization of the aragonitic otoconial matrix, despite its protein characterization. Pote et al. (1993b) used densitometric methods and inferred that prismatic (aragonitic) otoconia have a peripheral protein distribution, compared to that described for the barrel-shaped, calcitic otoconia of birds, mammals, and the amphibian utricle. By using tannic acid as a negative stain, we observed three kinds of organic matrices in preparations of fixed, decalcified saccular otoconia from the adult newt: (1) fusiform shapes with a homogenous electron-dense matrix; (2) singular and multiple strands of matrix; and (3) more significantly, prismatic shapes outlined by a peripheral organic matrix. These prismatic shapes remain following removal of the gelatinous matrix, revealing an internal array of organic matter. We conclude that prismatic otoconia have a largely peripheral otoconial matrix, as inferred by densitometry.

Functional visual fields: relationship of visual field areas to self-reported function.

PubMed

Subhi, Hikmat; Latham, Keziah; Myint, Joy; Crossland, Michael D

2017-07-01

The aim of this study is to relate areas of the visual field to functional difficulties to inform the development of a binocular visual field assessment that can reflect the functional consequences of visual field loss. Fifty-two participants with peripheral visual field loss undertook binocular assessment of visual fields using the 30-2 and 60-4 SITA Fast programs on the Humphrey Field Analyser, and mean thresholds were derived. Binocular visual acuity, contrast sensitivity and near reading performance were also determined. Self-reported overall and mobility function were assessed using the Dutch ICF Activity Inventory. Greater visual field loss (0-60°) was associated with worse self-reported function both overall (R 2 = 0.50; p < 0.0001), and for mobility (R 2 = 0.64; p < 0.0001). Central (0-30°) and peripheral (30-60°) visual field areas were similarly related to mobility function (R 2 = 0.61, p < 0.0001 and R 2 = 0.63, p < 0.0001 respectively), although the peripheral (30-60°) visual field was the best predictor of mobility self-reported function in multiple regression analyses. Superior and inferior visual field areas related similarly to mobility function (R 2 = 0.56, p < 0.0001 and R 2 = 0.67, p < 0.0001 respectively). The inferior field was found to be the best predictor of mobility function in multiple regression analysis. Mean threshold of the binocular visual field to 60° eccentricity is a good predictor of self-reported function overall, and particularly of mobility function. Both the central (0-30°) and peripheral (30-60°) mean threshold are good predictors of self-reported function, but the peripheral (30-0°) field is a slightly better predictor of mobility function, and should not be ignored when considering functional consequences of field loss. The inferior visual field is a slightly stronger predictor of perceived overall and mobility function than the superior field. © 2017 The Authors Ophthalmic & Physiological Optics © 2017 The College of Optometrists.

Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions.

PubMed

Calvo-Ortega, J F; Pozo, M; Moragues, S; Casals, J

2017-01-01

To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom on the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application (www.radiochromic.com) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm 2 region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism.

PubMed

Rossmeisl, J H

2010-01-01

Hypothyroidism has been implicated in the development of multiple peripheral mono- and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. Eighteen purpose-bred, female dogs. Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic-tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic-tibial and ulnar F-wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (Por=.1) or sensory nerve conduction velocity (P>or=.24) or nerve roots (P>or=.16) throughout the study period, with values remaining within reference ranges in all dogs. Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.

Registry Assessment of Peripheral Interventional Devices (RAPID): Registry assessment of peripheral interventional devices core data elements.

PubMed

Jones, W Schuyler; Krucoff, Mitchell W; Morales, Pablo; Wilgus, Rebecca W; Heath, Anne H; Williams, Mary F; Tcheng, James E; Marinac-Dabic, J Danica; Malone, Misti L; Reed, Terrie L; Fukaya, Rie; Lookstein, Robert A; Handa, Nobuhiro; Aronow, Herbert D; Bertges, Daniel J; Jaff, Michael R; Tsai, Thomas T; Smale, Joshua A; Zaugg, Margo J; Thatcher, Robert J; Cronenwett, Jack L

2018-02-01

The current state of evaluating patients with peripheral artery disease and more specifically of evaluating medical devices used for peripheral vascular intervention (PVI) remains challenging because of the heterogeneity of the disease process, the multiple physician specialties that perform PVI, the multitude of devices available to treat peripheral artery disease, and the lack of consensus about the best treatment approaches. Because PVI core data elements are not standardized across clinical care, clinical trials, and registries, aggregation of data across different data sources and physician specialties is currently not feasible. Under the auspices of the U.S. Food and Drug Administration's Medical Device Epidemiology Network initiative-and its PASSION (Predictable and Sustainable Implementation of the National Registries) program, in conjunction with other efforts to align clinical data standards-the Registry Assessment of Peripheral Interventional Devices (RAPID) workgroup was convened. RAPID is a collaborative, multidisciplinary effort to develop a consensus lexicon and to promote interoperability across clinical care, clinical trials, and national and international registries of PVI. The current manuscript presents the initial work from RAPID to standardize clinical data elements and definitions, to establish a framework within electronic health records and health information technology procedural reporting systems, and to implement an informatics-based approach to promote the conduct of pragmatic clinical trials and registry efforts in PVI. Ultimately, we hope this work will facilitate and improve device evaluation and surveillance for patients, clinicians, health outcomes researchers, industry, policymakers, and regulators. Copyright © 2017 Society for Vascular Surgery. All rights reserved.

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

PubMed

Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

2015-11-15

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

A System for Controlled Presentation of the Arden Contrast Sensitivity Test.

DTIC Science & Technology

1985-12-01

and Woo,1978); I.?glaucoma (Atkin, et al,1979); amblyopia (Hess,1979); retinal degeneration (Woo and Long,1979); multiple sclerosis (Regan, et al...decrease, contrast sensitivity diminishes, and imaging L shifts to an area covering 12 -15 of the peripheral macula . The theoretical threshold grid

Extractive Regimes: Toward a Better Understanding of Indonesian Development

ERIC Educational Resources Information Center

Gellert, Paul K.

2010-01-01

This article proposes the concept of an extractive regime to understand Indonesia's developmental trajectory from 1966 to 1998. The concept contributes to world-systems, globalization, and commodity-based approaches to understanding peripheral development. An extractive regime is defined by its reliance on extraction of multiple natural resources…

INDUCTION, ACCUMULATION, AND PERSISTENCE OF SISTER CHROMATID EXCHANGES IN WOMEN WITH BREAST CANCER RECEIVING CYCLOPHOSPHAMIDE, ANDRIAMYCIN, AND 5-FLUOROACIL CHEMOTHERAPY

EPA Science Inventory

The induction, stimulation, and persistence of sister chromatid exchanges (SCE's) and high SCE frequency cells (HFC's) was measured in peripheral lymphocytes of women with breast cancer before chemotherapy and on multiple occasions during and after therapy. Chemotherapy consisted...

Accurate Region-of-Interest Recovery Improves the Measurement of the Cell Migration Rate in the In Vitro Wound Healing Assay.

PubMed

Bedoya, Cesar; Cardona, Andrés; Galeano, July; Cortés-Mancera, Fabián; Sandoz, Patrick; Zarzycki, Artur

2017-12-01

The wound healing assay is widely used for the quantitative analysis of highly regulated cellular events. In this essay, a wound is voluntarily produced on a confluent cell monolayer, and then the rate of wound reduction (WR) is characterized by processing images of the same regions of interest (ROIs) recorded at different time intervals. In this method, sharp-image ROI recovery is indispensable to compensate for displacements of the cell cultures due either to the exploration of multiple sites of the same culture or to transfers from the microscope stage to a cell incubator. ROI recovery is usually done manually and, despite a low-magnification microscope objective is generally used (10x), repositioning imperfections constitute a major source of errors detrimental to the WR measurement accuracy. We address this ROI recovery issue by using pseudoperiodic patterns fixed onto the cell culture dishes, allowing the easy localization of ROIs and the accurate quantification of positioning errors. The method is applied to a tumor-derived cell line, and the WR rates are measured by means of two different image processing software. Sharp ROI recovery based on the proposed method is found to improve significantly the accuracy of the WR measurement and the positioning under the microscope.

Altitude engine test of a turbofan exhaust gas mixer to conserve fuel

NASA Technical Reports Server (NTRS)

Cullom, R. R.; Johnsen, R. L.

1977-01-01

A comparison of the specific fuel consumption was made with and without an internal mixer installed in a low bypass ratio, confluent flow turbofan engine. Tests were conducted at several Mach numbers and altitudes for core to fan stream total temperature ratios of 2.0 and 2.5 and mixing lengths of L/D = 0.95 and 1.74. For these test conditions, the specific fuel consumption improvement varied from 2.5 to 4.0 percent.

Exact time-dependent solutions for a self-regulating gene.

PubMed

Ramos, A F; Innocentini, G C P; Hornos, J E M

2011-06-01

The exact time-dependent solution for the stochastic equations governing the behavior of a binary self-regulating gene is presented. Using the generating function technique to rephrase the master equations in terms of partial differential equations, we show that the model is totally integrable and the analytical solutions are the celebrated confluent Heun functions. Self-regulation plays a major role in the control of gene expression, and it is remarkable that such a microscopic model is completely integrable in terms of well-known complex functions.

Luigi Gatteschi's work on asymptotics of special functions and their zeros

NASA Astrophysics Data System (ADS)

Gautschi, Walter; Giordano, Carla

2008-12-01

A good portion of Gatteschi's research publications-about 65%-is devoted to asymptotics of special functions and their zeros. Most prominently among the special functions studied figure classical orthogonal polynomials, notably Jacobi polynomials and their special cases, Laguerre polynomials, and Hermite polynomials by implication. Other important classes of special functions dealt with are Bessel functions of the first and second kind, Airy functions, and confluent hypergeometric functions, both in Tricomi's and Whittaker's form. This work is reviewed here, and organized along methodological lines.

An Investigation Concerning the Potential for use of Polylactic/Polyglycolic Acid Confluent Sheets in the Treatment of Osseous Defects,

DTIC Science & Technology

1992-01-01

Periodontics and Oral Biology, University of Missouri-Kansas City, School of Dentistry, Kansas City, MO 64108. •* Departments of Hospital Dentistry and...as a matrix for osseous grafting, for the occlusion of large bony defects, for soft tissue contour defects, and also as a bone plating system. All of...Hunsck EE: Tissue reaction to biodegradable polylactide acid suture. Oral Surg, 31:134, 1971. 5. Kulkurni RK, Pani KC, Neuman C, et al.: Polylactic acid

A case of Diphyllobothrium nihonkaiense infection successfully treated by oral administration of Gastrografin.

PubMed

Yoshida, M; Hasegawa, H; Takaoka, H; Miyata, A

1999-08-01

A diphyllobothriid cestode infection found in a 54-year-old male residing in Oita, Japan, was successfully treated by oral administration of Gastrografin in combination with a intramuscular injection of Vagostigmin. The strobila expelled was 6.14 m long with a scolex, and morphologically identical with Diphyllobothrium nihonkaiense except unusual ovaries of which posterior horns were confluent in each proglottid. This is the first case of treatment of cestode infection by oral administration of Gastrografin.

Survival Signaling in Prostate Cancer: Role of Androgen Receptor and Integrins in Regulating Survival

DTIC Science & Technology

2010-01-01

basal cells with the monoamine oxidase A inhibitor clorgyline, 1,25-dihydroxyvitamin D3, all-trans retinoic acid and TGF-1 induced AR expression and...41, 85-97. Zhao, H., Nolley, R., Chen, Z., Reese, S. W. and Peehl, D. M. (2008). Inhibition of monoamine oxidase A promotes secretory differentiation...Confluent primary human prostate epithelial cell cultures were treated with KGF and androgen (DHT). After two weeks, a suprabasal cell layer formed in

Analyses of the peripheral immunome following multiple administrations of avelumab, a human IgG1 anti-PD-L1 monoclonal antibody.

PubMed

Donahue, Renee N; Lepone, Lauren M; Grenga, Italia; Jochems, Caroline; Fantini, Massimo; Madan, Ravi A; Heery, Christopher R; Gulley, James L; Schlom, Jeffrey

2017-01-01

Multiple anti-PD-L1/PD-1 checkpoint monoclonal antibodies (MAb) have shown clear evidence of clinical benefit. All except one have been designed or engineered to omit the possibility to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) as a second potential mode of anti-tumor activity; the reason for this is the concern of lysis of PD-L1 positive immune cells. Avelumab is a fully human IgG1 MAb which has been shown in prior in vitro studies to mediate ADCC versus a range of human tumor cells, and clinical studies have demonstrated anti-tumor activity versus a range of human cancers. This study was designed to investigate the effect on immune cell subsets in the peripheral blood of cancer patients prior to and following multiple administrations of avelumab. One hundred twenty-three distinct immune cell subsets in the peripheral blood of cancer patients ( n  = 28) in a phase I trial were analyzed by flow cytometry prior to and following one, three, and nine cycles of avelumab. Changes in soluble (s) CD27 and sCD40L in plasma were also evaluated. In vitro studies were also performed to determine if avelumab would mediate ADCC of PBMC. No statistically significant changes in any of the 123 immune cell subsets analyzed were observed at any dose level, or number of doses, of avelumab. Increases in the ratio of sCD27:sCD40L were observed, suggesting potential immune activation. Controlled in vitro studies also showed lysis of tumor cells by avelumab versus no lysis of PBMC from five donors. These studies demonstrate the lack of any significant effect on multiple immune cell subsets, even those expressing PD-L1, following multiple cycles of avelumab. These results complement prior studies showing anti-tumor effects of avelumab and comparable levels of adverse events with avelumab versus other anti-PD-1/PD-L1 MAbs. These studies provide the rationale to further exploit the potential ADCC mechanism of action of avelumab as well as other human IgG1 checkpoint inhibitors. ClinicalTrials.gov identifier: NCT01772004 (first received: 1/14/13; start date: January 2013) and NCT00001846 (first received date: 11/3/99; start date: August 1999).

Coronary and peripheral stenting in aorto-ostial protruding stents: The balloon assisted access to protruding stent technique.

PubMed

Helmy, Tarek A; Sanchez, Carlos E; Bailey, Steven R

2016-03-01

Treatment of aorto-ostial in-stent restenosis lesions represents a challenge for interventional cardiologists. Excessive protrusion of the stent into the aorta may lead to multiple technical problems, such as difficult catheter reengagement of the vessel ostium or inability to re-wire through the stent lumen in repeat interventions. We describe a balloon assisted access to protruding stent technique in cases where conventional coaxial engagement of an aorto-ostial protruding stent with the guide catheter or passage of the guide wire through the true lumen is not feasible. This technique is applicable both in coronary and peripheral arteries. © 2015 Wiley Periodicals, Inc.

Exercise considerations in coronary artery disease, peripheral vascular disease, and diabetes mellitus.

PubMed

Armen, Joseph; Smith, Bryan W

2003-01-01

Physical inactivity is a risk factor for cardiovascular disease. Regular aerobic and resistance training increases exercise capacity and plays a role both in the primary and secondary prevention of cardiovascular disease. Patients with coronary artery disease, peripheral vascular disease, or diabetes mellitus must be considered individually when prescribing exercise because their clinical status can vary greatly. In addition, a majority of these patients have multiple comorbid disorders such as renal, neurologic, and retinal disease that may affect their ability to exercise safely. Therefore, a preparticipation medical evaluation is required. An exercise prescription should be tailored to each person's unique set of circumstances and reflect an effort to maximize the anticipated benefits while minimizing the risks.

Therapeutic activities of intravenous immunoglobulins in multiple sclerosis involve modulation of chemokine expression.

PubMed

Pigard, Nadine; Elovaara, Irina; Kuusisto, Hanna; Paalavuo, Raija; Dastidar, Prasun; Zimmermann, Klaus; Schwarz, Hans-Peter; Reipert, Birgit

2009-04-30

The objective of this study was to identify genes that are differentially expressed in peripheral T cells of patients with MS exacerbation receiving treatment with IVIG. Using microarray analysis, we identified 360 genes that were at least two-fold up- or down-regulated. The expression of four representative genes (PTGER4, CXCL5, IL11 and CASP2) was confirmed by quantitative PCR. Four of the differentially expressed genes encode chemokines (CXCL3, CXCL5, CCL13 and XCL2) that are involved in directing leukocyte migration. We suggest that the modulation of chemokine expression in peripheral T cells contributes to the beneficial activity of IVIG in patients with MS exacerbation.

Multiple Biomarker Panels for Early Detection of Breast Cancer in Peripheral Blood

PubMed Central

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers. PMID:24371830

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease.

PubMed

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S; Johnson, Kipp W; Ze, Yi; Tomlinson, Max S; Readhead, Ben; Dudley, Joel T; Kullo, Iftikhar J

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

PubMed

Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

A Network-Biology Informed Computational Drug Repositioning Strategy to Target Disease Risk Trajectories and Comorbidities of Peripheral Artery Disease

PubMed Central

Shameer, Khader; Dow, Garrett; Glicksberg, Benjamin S.; Johnson, Kipp W.; Ze, Yi; Tomlinson, Max S.; Readhead, Ben; Dudley, Joel T.; Kullo, Iftikhar J.

2018-01-01

Currently, drug discovery approaches focus on the design of therapies that alleviate an index symptom by reengineering the underlying biological mechanism in agonistic or antagonistic fashion. For example, medicines are routinely developed to target an essential gene that drives the disease mechanism. Therapeutic overloading where patients get multiple medications to reduce the primary and secondary side effect burden is standard practice. This single-symptom based approach may not be scalable, as we understand that diseases are more connected than random and molecular interactions drive disease comorbidities. In this work, we present a proof-of-concept drug discovery strategy by combining network biology, disease comorbidity estimates, and computational drug repositioning, by targeting the risk factors and comorbidities of peripheral artery disease, a vascular disease associated with high morbidity and mortality. Individualized risk estimation and recommending disease sequelae based therapies may help to lower the mortality and morbidity of peripheral artery disease. PMID:29888052

Surgical resection of peripheral odontogenic fibromas in African pygmy hedgehog (Atelerix albiventris): a case study.

PubMed

Wozniak-Biel, Anna; Janeczek, Maciej; Janus, Izabela; Nowak, Marcin

2015-07-04

Neoplastic lesions of the mammary gland, lymph nodes, or oral cavity in African pygmy hedgehogs (Atelerix albiventris) are common in captive animals. Chemotherapy and radiotherapy protocols have not yet been established for the African pygmy hedgehog. Thus, surgical resection is the current treatment of choice in this species. A 5-year-old male African pygmy hedgehog showed multiple erythematous, round small tumors located in the oral cavity, on both sides of maxilla. The treatment of choice was surgical resection of tumors using a surgical knife under general anesthesia. Excised neoplastic lesions were diagnosed as peripheral odontogenic fibroma by histopathology. Six months after surgery relapse of tumors in the oral cavity was not observed. The treatment adopted in this case report is safe for the patient and provides the best solution for mild proliferative lesions of the oral cavity. To our knowledge this is the first report of surgical resection of oral tumors (peripheral odontogenic fibroma) in the African pygmy hedgehog.

Multiple biomarker panels for early detection of breast cancer in peripheral blood.

PubMed

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

Safety and Efficacy of Pralatrexate in the Management of Relapsed or Refractory Peripheral T-cell Lymphoma

PubMed Central

Rodd, Annabelle L.; Ververis, Katherine; Karagiannis, Tom C.

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This antimetabolite was designed to have a higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS). RFC is the principal transporter for cell entrance of folates and antifolates. Once inside the cell, pralatrexate is efficiently polyglutamated by FPGS. Pralatrexate has demonstrated varying degrees of efficacy in peripheral T-cell lymphoma, with response rates differing between the multiple subtypes of the disease. While phase III studies are still to be completed, early clinical trials indicate that pralatrexate is promising new therapeutic for PTCL. PMID:23032692

Safety and efficacy of pralatrexate in the management of relapsed or refractory peripheral T-cell lymphoma.

PubMed

Rodd, Annabelle L; Ververis, Katherine; Karagiannis, Tom C

2012-01-01

Peripheral T-cell lymphoma (PTCL) represents a relatively rare group of heterogeneous non-Hodgkin lymphomas, with generally poor prognosis. Historically, there has been a lack of consensus regarding appropriate therapeutic measures for the disease, with conventional frontline chemotherapies being utilized in most cases. Following promising results obtained in 2009, the methotrexate analogue, pralatrexate, became the first drug to gain US FDA approval for the treatment of refractory PTCL. This antimetabolite was designed to have a higher affinity for reduced folate carrier (RFC) and folylpolyglutamate synthetase (FPGS). RFC is the principal transporter for cell entrance of folates and antifolates. Once inside the cell, pralatrexate is efficiently polyglutamated by FPGS. Pralatrexate has demonstrated varying degrees of efficacy in peripheral T-cell lymphoma, with response rates differing between the multiple subtypes of the disease. While phase III studies are still to be completed, early clinical trials indicate that pralatrexate is promising new therapeutic for PTCL.

Raman spectroscopy coupled with advanced statistics for differentiating menstrual and peripheral blood.

PubMed

Sikirzhytskaya, Aliaksandra; Sikirzhytski, Vitali; Lednev, Igor K

2014-01-01

Body fluids are a common and important type of forensic evidence. In particular, the identification of menstrual blood stains is often a key step during the investigation of rape cases. Here, we report on the application of near-infrared Raman microspectroscopy for differentiating menstrual blood from peripheral blood. We observed that the menstrual and peripheral blood samples have similar but distinct Raman spectra. Advanced statistical analysis of the multiple Raman spectra that were automatically (Raman mapping) acquired from the 40 dried blood stains (20 donors for each group) allowed us to build classification model with maximum (100%) sensitivity and specificity. We also demonstrated that despite certain common constituents, menstrual blood can be readily distinguished from vaginal fluid. All of the classification models were verified using cross-validation methods. The proposed method overcomes the problems associated with currently used biochemical methods, which are destructive, time consuming and expensive. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fibered fluorescence microscopy (FFM) of intra epidermal nerve fibers--translational marker for peripheral neuropathies in preclinical research: processing and analysis of the data

NASA Astrophysics Data System (ADS)

Cornelissen, Frans; De Backer, Steve; Lemeire, Jan; Torfs, Berf; Nuydens, Rony; Meert, Theo; Schelkens, Peter; Scheunders, Paul

2008-08-01

Peripheral neuropathy can be caused by diabetes or AIDS or be a side-effect of chemotherapy. Fibered Fluorescence Microscopy (FFM) is a recently developed imaging modality using a fiber optic probe connected to a laser scanning unit. It allows for in-vivo scanning of small animal subjects by moving the probe along the tissue surface. In preclinical research, FFM enables non-invasive, longitudinal in vivo assessment of intra epidermal nerve fibre density in various models for peripheral neuropathies. By moving the probe, FFM allows visualization of larger surfaces, since, during the movement, images are continuously captured, allowing to acquire an area larger then the field of view of the probe. For analysis purposes, we need to obtain a single static image from the multiple overlapping frames. We introduce a mosaicing procedure for this kind of video sequence. Construction of mosaic images with sub-pixel alignment is indispensable and must be integrated into a global consistent image aligning. An additional motivation for the mosaicing is the use of overlapping redundant information to improve the signal to noise ratio of the acquisition, because the individual frames tend to have both high noise levels and intensity inhomogeneities. For longitudinal analysis, mosaics captured at different times must be aligned as well. For alignment, global correlation-based matching is compared with interest point matching. Use of algorithms working on multiple CPU's (parallel processor/cluster/grid) is imperative for use in a screening model.

Bladder sensory physiology: neuroactive compounds and receptors, sensory transducers, and target-derived growth factors as targets to improve function

PubMed Central

Gonzalez, Eric J.; Merrill, Liana

2014-01-01

Urinary bladder dysfunction presents a major problem in the clinical management of patients suffering from pathological conditions and neurological injuries or disorders. Currently, the etiology underlying altered visceral sensations from the urinary bladder that accompany the chronic pain syndrome, bladder pain syndrome (BPS)/interstitial cystitis (IC), is not known. Bladder irritation and inflammation are histopathological features that may underlie BPS/IC that can change the properties of lower urinary tract sensory pathways (e.g., peripheral and central sensitization, neurochemical plasticity) and contribute to exaggerated responses of peripheral bladder sensory pathways. Among the potential mediators of peripheral nociceptor sensitization and urinary bladder dysfunction are neuroactive compounds (e.g., purinergic and neuropeptide and receptor pathways), sensory transducers (e.g., transient receptor potential channels) and target-derived growth factors (e.g., nerve growth factor). We review studies related to the organization of the afferent limb of the micturition reflex and discuss neuroplasticity in an animal model of urinary bladder inflammation to increase the understanding of functional bladder disorders and to identify potential novel targets for development of therapeutic interventions. Given the heterogeneity of BPS/IC and the lack of consistent treatment benefits, it is unlikely that a single treatment directed at a single target in micturition reflex pathways will have a mass benefit. Thus, the identification of multiple targets is a prudent approach, and use of cocktail treatments directed at multiple targets should be considered. PMID:24760999

Abnormal center-periphery gradient in spatial attention in simultanagnosia.

PubMed

Balslev, Daniela; Odoj, Bartholomaeus; Rennig, Johannes; Karnath, Hans-Otto

2014-12-01

Patients suffering from simultanagnosia cannot perceive more than one object at a time. The underlying mechanism is incompletely understood. One hypothesis is that simultanagnosia reflects "tunnel vision," a constricted attention window around gaze, which precludes the grouping of individual objects. Although this idea has a long history in neuropsychology, the question whether the patients indeed have an abnormal attention gradient around the gaze has so far not been addressed. Here we tested this hypothesis in two simultanagnosia patients with bilateral parieto-occipital lesions and two control groups, with and without brain damage. We assessed the participants' ability to discriminate letters presented briefly at fixation with and without a peripheral distractor or in the visual periphery, with or without a foveal distractor. A constricted span of attention around gaze would predict an increased susceptibility to foveated versus peripheral distractors. Contrary to this prediction and unlike both control groups, the patients' ability to discriminate the target decreased more in the presence of peripheral compared with foveated distractors. Thus, the attentional spotlight in simultanagnosia does not fall on foveated objects as previously assumed, but rather abnormally highlights the periphery. Furthermore, we found the same center-periphery gradient in the patients' ability to recognize multiple objects. They detected multiple, but not single objects more accurately in the periphery than at fixation. These results suggest that an abnormal allocation of attention around the gaze can disrupt the grouping of individual objects into an integrated visual scene.

Characterization of γδ regulatory T cells from peripheral blood in patients with multiple myeloma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Yongyong; Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000; Lei, Huyi

γδ regulatory T cells are able to inhibit the activation and function of T cells involved in antigen-specific immune responses. This study aimed to investigate the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in patients diagnosed as multiple myeloma (MM). We measured the levels of γδ T cells, the distribution and clonally amplified TCR Vγ and VδT cells in peripheral blood of healthy donors, patients recently diagnosed with MM, and MM patients in remission cohorts. In addition, we evaluated the ability of γδ regulatory T cells to inhibit the proliferation of CD4+CD25- T cells andmore » detected the expression of immunoregulatory-associated molecules. We found that the levels of γδ regulatory T cells from the peripheral blood in patients of MM were significantly higher than those in healthy donors. Comparison of γδT regulatory cells function in MM and healthy donors showed similarly inhibitory effects on the proliferation of T cells. Additionally, TLR8 expression level increased significantly in MM patients compared to healthy donors, while the expression levels of Foxp3, CD25, CTLA4, GITR, GATA3 and Tbet in MM patients and healthy donors showed no significant difference. Taken together, our study reveals the potential role of γδ regulatory T cells in inhibiting anti-tumor immune responses in MM patients.« less

High Altitude Cerebral Edema

DTIC Science & Technology

1986-03-01

described neuropathological findings of cerebral edema and wi4espread petechial hemorrhages in two HAPE fatalities and later reported (52...lethargy, thirst, indigestion, hysterical outburst o: other behavior disturbances, decreased concentration, fever , couhh and peripheral edema (52...autopsy results from the two fatalities in their series. In both cases multiple, widespread petechial hemorrhages were noted throughout the brain. One

A Genome-wide Trans-ethnic Interaction Study Links the PIGR-FCAMR Locus to Coronary Atherosclerosis Via Interactions Between Genetic Variants and Residential Exposure to Traffic

EPA Science Inventory

Air pollution is a worldwide contributor to cardiovascular disease mortality and morbidity. Traffic air pollution is a ubiquitous source of air pollution in developed nations, and is associated with multiple cardiovascular outcomes such as: coronary atherosclerosis, peripheral ar...

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

Central hemodynamics and arterial stiffness in idiopathic and multiple system atrophy.

PubMed

Franzen, Klaas; Fliegen, Sabine; Koester, Jelena; Martin, Rafael Campos; Deuschl, Günther; Reppel, Michael; Mortensen, Kai; Schneider, Susanne A

2017-02-01

Blood pressure is commonly abnormal in parkinsonian disorders, but central hemodynamics and arterial stiffness, well-established predictors of total cardiovascular risk, have rarely been studied in these disorders. 32 patients [27 with idiopathic Parkinson's disease (iPD); 5 with multiple system atrophy (MSA)] and 15 controls matched for cardiac risk factors underwent 24 h-ambulatory blood pressure recordings using an I.E.M. device (Mobil-O-Graph™), measuring peripheral pressure and calculating central pressures and arterial stiffness. Mean augmentation indices corrected for heart rate (AIx@75) were significantly lower and pulse wave velocities were significantly elevated in patients compared to controls. Central systolic blood pressure, cardiac output and daytime total vascular resistance were significantly elevated in patients. Mean nocturnal systolic peripheral blood pressure and nocturnal heart rates were also significantly higher; 56.3% of patients had nocturnal hypertension (80% of the MSA group); 85.2% showed non-dipping. This supports previous findings of reduced vulnerability to systemic atherosclerosis and end-organ damage in treated PD. Yet, hemodynamic abnormalities were common and often remained asymptomatic.

Broadening the spectrum of SMARCB1-associated malignant tumors: a case of uterine leiomyosarcoma in a patient with schwannomatosis.

PubMed

Paganini, Irene; Sestini, Roberta; Cacciatore, Matilde; Capone, Gabriele L; Candita, Luisa; Paolello, Concetta; Sbaraglia, Marta; Dei Tos, Angelo P; Rossi, Sabrina; Papi, Laura

2015-08-01

Schwannomatosis is a tumor predisposition syndrome characterized by development of multiple intracranial, spinal, and peripheral schwannomas. Constitutional alterations in either SMARCB1 or LZTR1 on 22q are responsible of the phenotype. We describe a 34-year-old woman who developed multiple benign peripheral sheath tumors and a uterine leiomyosarcoma. The patient carried a de novo constitutional alteration in exon 8 of SMARCB1, c.1118G > A, which destroyed the splice donor site of intron 8. Two schwannomas and the leiomyosarcoma of the patient retained the SMARCB1 mutation; in addition, the tumors showed loss of the normal chromosome 22. In conclusion, our findings enlarged the spectrum of SMARCB1-predisposing tumors and demonstrated, for the first time, the association of a malignant smooth muscle tumor to schwannomatosis. Therefore, clinicians should definitely be aware that a constitutional SMARCB1 mutation, which mainly predisposes to benign nerve sheath tumors, may also predispose to aggressive neoplasms throughout life, within an unexpected spectrum. Copyright © 2015 Elsevier Inc. All rights reserved.

Phenytoin: neuroprotection or neurotoxicity?

PubMed

Keppel Hesselink, Jan M; Kopsky, David J

2017-06-01

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin. We have reviewed the literature and concluded there is some supportive evidence for a reversible polyneuropathy after the oral use of phenytoin, though with no evidence for clear neurotoxicity on the level of peripheral nerves. This is probably due to the fact that the pharmacological effects of phenytoin, based on the stabilizing effect of the voltage-gated sodium channels, make impairment of nerve conduction in asymptomatic and symptomatic reversible polyneuropathies plausible. Clear toxically-induced phenytoin-related polyneuropathies, however, are extremely rare and are always related to high dose or high plasma levels of phenytoin, mostly developing during many years of therapy. We could only find one case of a probable reversible chronic phenytoin intoxication resulting in a biopsy proven axonal atrophy with secondary demyelination and signs of remyelination. All case series and case reports published are insufficient in detail to prove a clear causal relation between phenytoin intake and the induction of a peripheral polyneuropathy. Phenytoin does not lead to irreversible toxicity of the peripheral nerves and might, on the other hand, have neuroprotective properties.

Sleep-Disordered Breathing in Acute Ischemic Stroke: A Mechanistic Link to Peripheral Endothelial Dysfunction.

PubMed

Scherbakov, Nadja; Sandek, Anja; Ebner, Nicole; Valentova, Miroslava; Nave, Alexander Heinrich; Jankowska, Ewa A; Schefold, Jörg C; von Haehling, Stephan; Anker, Stefan D; Fietze, Ingo; Fiebach, Jochen B; Haeusler, Karl Georg; Doehner, Wolfram

2017-09-11

Sleep-disordered breathing (SDB) after acute ischemic stroke is frequent and may be linked to stroke-induced autonomic imbalance. In the present study, the interaction between SDB and peripheral endothelial dysfunction (ED) was investigated in patients with acute ischemic stroke and at 1-year follow-up. SDB was assessed by transthoracic impedance records in 101 patients with acute ischemic stroke (mean age, 69 years; 61% men; median National Institutes of Health Stroke Scale, 4) while being on the stroke unit. SDB was defined by apnea-hypopnea index ≥5 episodes per hour. Peripheral endothelial function was assessed using peripheral arterial tonometry (EndoPAT-2000). ED was defined by reactive hyperemia index ≤1.8. Forty-one stroke patients underwent 1-year follow-up (390±24 days) after stroke. SDB was observed in 57% patients with acute ischemic stroke. Compared with patients without SDB, ED was more prevalent in patients with SDB (32% versus 64%; P <0.01). After adjustment for multiple confounders, presence of SDB remained independently associated with ED (odds ratio, 3.1; [95% confidence interval, 1.2-7.9]; P <0.05). After 1 year, the prevalence of SDB decreased from 59% to 15% ( P <0.001). Interestingly, peripheral endothelial function improved in stroke patients with normalized SDB, compared with patients with persisting SDB ( P <0.05). SDB was present in more than half of all patients with acute ischemic stroke and was independently associated with peripheral ED. Normalized ED in patients with normalized breathing pattern 1 year after stroke suggests a mechanistic link between SDB and ED. URL: https://drks-neu.uniklinik-freiburg.de. Unique identifier: DRKS00000514. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke.

PubMed

Hung, Ching-Hsia; Chang, Nen-Chung; Cheng, Bor-Chih; Lin, Mao-Tsun

2005-05-01

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.

Osteosclerotic myeloma with polyneuropathy and hypocalcemia.

PubMed

Ludescher, C; Grünewald, K; Fend, F; Dietze, O; Thaler, J; Schmid, K W

1989-04-01

A case is presented of a 46-year-old man with multifocal osteosclerotic bone lesions, peripheral polyneuropathy and hypocalcemia. Histologic examination of a bone marrow biopsy disclosed a multiple myeloma. Immunoelectrophoresis revealed a small M-component identified as IgG-lambda. Osteosclerotic myeloma lacking any osteolytic lesions seems to be very rare and shows several different features as compared with classical myeloma. A review of the current literature suggests that multiple myeloma is not a uniform disease but rather a group of clinical syndromes characterized by the special properties of their proliferating plasma cell clones.

Central neurotoxicity of immunomodulatory drugs in multiple myeloma.

PubMed

Patel, Urmeel H; Mir, Muhammad A; Sivik, Jeffrey K; Raheja, Divisha; Pandey, Manoj K; Talamo, Giampaolo

2015-02-24

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy.

Central Neurotoxicity of Immunomodulatory Drugs in Multiple Myeloma

PubMed Central

Patel, Urmeel H.; Mir, Muhammad A.; Sivik, Jeffrey K.; Raheja, Divisha; Pandey, Manoj K.; Talamo, Giampaolo

2015-01-01

Immunomodulatory drugs (IMiDs) currently used in the treatment of multiple myeloma, are thalidomide, lenalidomide and pomalidomide. One of the most common side effects of thalidomide is neurotoxicity, predominantly in the form of peripheral neuropathy. We report 6 cases of significant central neurotoxicity associated with IMiD therapy. Treatment with thalidomide (1 patient), lenalidomide (4 patients), and pomalidomide (1 patient) was associated with various clinical manifestations of central neurotoxicity, including reversible coma, amnesia, expressive aphasia, and dysarthria. Central neurotoxicity should be recognized as an important side effect of IMiD therapy. PMID:25852850

High frequency of telomeric association in a family with multiple congenital neoplasia.

PubMed

Dhaliwal, M K; Satya-Prakash, K L; Davis, P C; Pathak, S

1994-01-01

Chromosomal analysis of the peripheral blood cultures of a married couple whose second pregnancy gave birth to twin daughters with multiple congenital malignancies revealed normal karyotypes of 46,XX and 46,XY, respectively. However, in the father's blood, 23.3% of metaphases showed telomere-telomere associations involving single-single and double-double chromatids. Such associations were not observed in the metaphases of the mother. We speculate from these observations that the father's genotype may somehow be responsible for the congenital malignancies in their twin daughters.

Peripheral corneal infiltrates associated with contact lens wear.

PubMed Central

Donshik, P C; Suchecki, J K; Ehlers, W H

1995-01-01

PURPOSE: A retrospective study was performed to review the clinical characteristics of peripheral corneal infiltrates in contact lens wearers. METHODS: The charts of all contact lens patients with peripheral corneal infiltrates 1.5 mm or less in size who presented to the office from 1987 to 1994 were reviewed. RESULTS: The epidemiological and clinical characteristics of peripheral corneal infiltrates associated with contact lens wear were reviewed in 52 patients (64 infiltrates). Forty-four patients presented with a single infiltrate, while the remaining 8 patients had multiple infiltrates. While there was no predilection for a specific quadrant of the cornea, when a subgroup of patients who wore extended wear lenses was analyzed, 19 of the 40 infiltrates were located in the superior quadrant. Forty percent of the patients were wearing disposable extended wear contact lenses, 21% were wearing conventional extended wear lenses, 33% were wearing conventional or frequent replacement/disposable daily wear contact lenses and 6% were wearing rigid gas permeable lenses. The majority of patients had minimal conjunctival inflammation, an anterior stromal cellular reaction and minimal anterior chamber activity. A subgroup of 16 patients had corneal cultures of their infiltrates. In this group, 8 of the 16 had positive cultures. All patients had a resolution of the infiltrates without complications and the majority were refitted to daily wear soft or rigid contact lenses. CONCLUSION: Peripheral corneal infiltrates in contact lens wearers appears to be more common in patients wearing extended wear soft contact lenses. While often considered "sterile" in the literature, a significant number have been shown to be culture-positive. The organisms that have been associated with peripheral infiltrates appear to be less "pathogenic" than those that have been reported to be associated with central corneal ulcer. However, it is probably advisable that patients with peripheral corneal ulcers secondary to contact lens wear should be initially treated with topical antibiotics. PMID:8719670

SU-F-T-372: Surface and Peripheral Dose in Compensator-Based FFF Beam IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, D; Feygelman, V; Moros, E

2016-06-15

Purpose: Flattening filter free (FFF) beams produce higher dose rates. Combined with compensator IMRT techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or compensator-based IMRT. This ‘snap shot’ IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, surface doses in FFF beam treatment are usually higher than those from flattened beams. Because of less scattering due to no flattening filter, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introducemore » beam hardening effects and scattering such that the surface dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? Methods: This study applied Monte Carlo techniques to investigate the surface and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides various thicknesses of copper slabs to simulate various thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC defined FFF and flattened beams with various openings. After normalized to Dmax, the surface and peripheral dose was compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. Results: The surface dose at the central 0.5mm depth was close between the compensator and 6FFF MLC dose distributions, and about 8% (of Dmax) higher than the flattened 6MV MLC dose. At 8cm off axis at dmax, the peripheral dose between the 6FFF and flattened 6MV MLC demonstrated similar doses, while the compensator dose was about 1% higher. Conclusion: Compensator does not reduce the surface doses but slightly increases the peripheral doses due to scatter inside compensator.« less

The growth and differentiation of transitional epithelium in vitro.

PubMed

Chlapowski, F J; Haynes, L

1979-12-01

The development of rat transitional epithelial cells grown on conventional non-permeable surfaces was compared with development on permeable collagen supports. On glass or plastic surfaces, cells grew as expanding nomolayer sheets. Once confluent, growth continued with a bilayer being formed in most areas and apical cells being continuously sloughed off. Although most cells were interconnected by desmosomes, and junctional complexes were formed, no other indications of differentiation were observed. After 2-3 wk of growth, division stopped and cel death ensued. In contrast, single-cell suspensions plated on collagen-coated nylon disks reassociated into multicellular islands and commenced growth. Mitoses were confined to the basal cells in contact with the permeable substrate. The islands developed into epithelial trilayers, tapering to monolayers along spreading edges. Once the islands were confluent, stratification was completed and appeared similar to that observed in vivo. Germinal cells formed a basal lamina, and the upper layer was composed of large, flattened cells with an unusually thick asymmetrical plasma membrane on the apical surface. Electron microscopic and radioactive tracers demonstrated "leaky" zonulae occludentes with a restricted permeability to small molecules. The movement of urea was retarded in comparison to water. Unlike the slow turnover of adult epithelium in vivo, maturation and sloughing of apical cells were measurable. Transfer of cells could be effected and growth maintained for up to 4 mo. These results may indicate the necessity of a nutrient-permeable growth surface for the polarized differentiation of adult transitional epithelium.

The growth and differentiation of transitional epithelium in vitro

PubMed Central

1979-01-01

The development of rat transitional epithelial cells grown on conventional non-permeable surfaces was compared with development on permeable collagen supports. On glass or plastic surfaces, cells grew as expanding nomolayer sheets. Once confluent, growth continued with a bilayer being formed in most areas and apical cells being continuously sloughed off. Although most cells were interconnected by desmosomes, and junctional complexes were formed, no other indications of differentiation were observed. After 2-3 wk of growth, division stopped and cel death ensued. In contrast, single-cell suspensions plated on collagen-coated nylon disks reassociated into multicellular islands and commenced growth. Mitoses were confined to the basal cells in contact with the permeable substrate. The islands developed into epithelial trilayers, tapering to monolayers along spreading edges. Once the islands were confluent, stratification was completed and appeared similar to that observed in vivo. Germinal cells formed a basal lamina, and the upper layer was composed of large, flattened cells with an unusually thick asymmetrical plasma membrane on the apical surface. Electron microscopic and radioactive tracers demonstrated "leaky" zonulae occludentes with a restricted permeability to small molecules. The movement of urea was retarded in comparison to water. Unlike the slow turnover of adult epithelium in vivo, maturation and sloughing of apical cells were measurable. Transfer of cells could be effected and growth maintained for up to 4 mo. These results may indicate the necessity of a nutrient-permeable growth surface for the polarized differentiation of adult transitional epithelium. PMID:574872

Collective and single cell behavior in epithelial contact inhibition.

PubMed

Puliafito, Alberto; Hufnagel, Lars; Neveu, Pierre; Streichan, Sebastian; Sigal, Alex; Fygenson, D Kuchnir; Shraiman, Boris I

2012-01-17

Control of cell proliferation is a fundamental aspect of tissue physiology central to morphogenesis, wound healing, and cancer. Although many of the molecular genetic factors are now known, the system level regulation of growth is still poorly understood. A simple form of inhibition of cell proliferation is encountered in vitro in normally differentiating epithelial cell cultures and is known as "contact inhibition." The study presented here provides a quantitative characterization of contact inhibition dynamics on tissue-wide and single cell levels. Using long-term tracking of cultured Madin-Darby canine kidney cells we demonstrate that inhibition of cell division in a confluent monolayer follows inhibition of cell motility and sets in when mechanical constraint on local expansion causes divisions to reduce cell area. We quantify cell motility and cell cycle statistics in the low density confluent regime and their change across the transition to epithelial morphology which occurs with increasing cell density. We then study the dynamics of cell area distribution arising through reductive division, determine the average mitotic rate as a function of cell size, and demonstrate that complete arrest of mitosis occurs when cell area falls below a critical value. We also present a simple computational model of growth mechanics which captures all aspects of the observed behavior. Our measurements and analysis show that contact inhibition is a consequence of mechanical interaction and constraint rather than interfacial contact alone, and define quantitative phenotypes that can guide future studies of molecular mechanisms underlying contact inhibition.

Mapping the Dynamics of Shear Stress—Induced Structural Changes in Endothelial Cells

PubMed Central

Mott, Rosalind E.; Helmke, Brian P.

2009-01-01

Hemodynamic shear stress regulates endothelial cell biochemical processes that govern cytoskeletal contractility, focal adhesion dynamics, and extracellular matrix assembly. Since shear stress causes rapid strain focusing at discrete locations in the cytoskeleton, we hypothesized that shear stress coordinately alters structural dynamics in the cytoskeleton, focal adhesion sites, and extracellular matrix on a time scale of minutes. Using multi-wavelength 4-D fluorescence microscopy, we measured the displacement of rhodamine-fibronectin and of GFP-labeled actin, vimentin, paxillin, and/or vinculin in aortic endothelial cells before and after onset of steady unidirectional shear stress. In the cytoskeleton, the onset of shear stress increased actin polymerization into lamellipodia, altered the angle of lateral displacement of actin stress fibers and vimentin filaments, and decreased centripetal remodeling of actin stress fibers in both subconfluent and confluent cell layers. Shear stress induced the formation of new focal complexes and reduced the centripetal remodeling of focal adhesions in regions of new actin polymerization. The structural dynamics of focal adhesions and the fibronectin matrix varied with cell density. In subconfluent cell layers, shear stress onset decreased the displacement of focal adhesions and fibronectin fibrils. In confluent monolayers, the direction of fibronectin and focal adhesion displacement shifted significantly towards the downstream direction within one minute after onset of shear stress. These spatially coordinated rapid changes in the structural dynamics of cytoskeleton, focal adhesions, and extracellular matrix are consistent with focusing of mechanical stress and/or strain near major sites of shear stress-mediated mechanotransduction. PMID:17855768

White-nose syndrome pathology grading in Nearctic and Palearctic bats

PubMed Central

Pikula, Jiri; Amelon, Sybill K.; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G.; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity. PMID:28767673

An Automated Statistical Technique for Counting Distinct Multiple Sclerosis Lesions.

PubMed

Dworkin, J D; Linn, K A; Oguz, I; Fleishman, G M; Bakshi, R; Nair, G; Calabresi, P A; Henry, R G; Oh, J; Papinutto, N; Pelletier, D; Rooney, W; Stern, W; Sicotte, N L; Reich, D S; Shinohara, R T

2018-04-01

Lesion load is a common biomarker in multiple sclerosis, yet it has historically shown modest association with clinical outcome. Lesion count, which encapsulates the natural history of lesion formation and is thought to provide complementary information, is difficult to assess in patients with confluent (ie, spatially overlapping) lesions. We introduce a statistical technique for cross-sectionally counting pathologically distinct lesions. MR imaging was used to assess the probability of a lesion at each location. The texture of this map was quantified using a novel technique, and clusters resembling the center of a lesion were counted. Validity compared with a criterion standard count was demonstrated in 60 subjects observed longitudinally, and reliability was determined using 14 scans of a clinically stable subject acquired at 7 sites. The proposed count and the criterion standard count were highly correlated ( r = 0.97, P < .001) and not significantly different (t 59 = -.83, P = .41), and the variability of the proposed count across repeat scans was equivalent to that of lesion load. After accounting for lesion load and age, lesion count was negatively associated ( t 58 = -2.73, P < .01) with the Expanded Disability Status Scale. Average lesion size had a higher association with the Expanded Disability Status Scale ( r = 0.35, P < .01) than lesion load ( r = 0.10, P = .44) or lesion count ( r = -.12, P = .36) alone. This study introduces a novel technique for counting pathologically distinct lesions using cross-sectional data and demonstrates its ability to recover obscured longitudinal information. The proposed count allows more accurate estimation of lesion size, which correlated more closely with disability scores than either lesion load or lesion count alone. © 2018 by American Journal of Neuroradiology.

White-nose syndrome pathology grading in Nearctic and Palearctic bats.

PubMed

Pikula, Jiri; Amelon, Sybill K; Bandouchova, Hana; Bartonička, Tomáš; Berkova, Hana; Brichta, Jiri; Hooper, Sarah; Kokurewicz, Tomasz; Kolarik, Miroslav; Köllner, Bernd; Kovacova, Veronika; Linhart, Petr; Piacek, Vladimir; Turner, Gregory G; Zukal, Jan; Martínková, Natália

2017-01-01

While white-nose syndrome (WNS) has decimated hibernating bat populations in the Nearctic, species from the Palearctic appear to cope better with the fungal skin infection causing WNS. This has encouraged multiple hypotheses on the mechanisms leading to differential survival of species exposed to the same pathogen. To facilitate intercontinental comparisons, we proposed a novel pathogenesis-based grading scheme consistent with WNS diagnosis histopathology criteria. UV light-guided collection was used to obtain single biopsies from Nearctic and Palearctic bat wing membranes non-lethally. The proposed scheme scores eleven grades associated with WNS on histopathology. Given weights reflective of grade severity, the sum of findings from an individual results in weighted cumulative WNS pathology score. The probability of finding fungal skin colonisation and single, multiple or confluent cupping erosions increased with increase in Pseudogymnoascus destructans load. Increasing fungal load mimicked progression of skin infection from epidermal surface colonisation to deep dermal invasion. Similarly, the number of UV-fluorescent lesions increased with increasing weighted cumulative WNS pathology score, demonstrating congruence between WNS-associated tissue damage and extent of UV fluorescence. In a case report, we demonstrated that UV-fluorescence disappears within two weeks of euthermy. Change in fluorescence was coupled with a reduction in weighted cumulative WNS pathology score, whereby both methods lost diagnostic utility. While weighted cumulative WNS pathology scores were greater in the Nearctic than Palearctic, values for Nearctic bats were within the range of those for Palearctic species. Accumulation of wing damage probably influences mortality in affected bats, as demonstrated by a fatal case of Myotis daubentonii with natural WNS infection and healing in Myotis myotis. The proposed semi-quantitative pathology score provided good agreement between experienced raters, showing it to be a powerful and widely applicable tool for defining WNS severity.

Computerized tomographic findings of hepatic fascioliasis compared with melioidosis-caused liver abscesses.

PubMed

Chamadol, Nittaya; Laopaiboon, Vallop; Techasatian, Pennapa; Sukeepaisanjaroen, Wattana; Sripanuskul, Anan

2010-07-01

To compare the computerized tomographic (CT) findings of hepatic fascioliasis (HF) vs. melioidosis-caused liver (ML) abscesses. CT images of 15 patients with hepatic fascioliasis (HF) and 16 patients with melioidosis-caused liver (ML) abscesses were retrospectively reviewed. The authors evaluated and compared HF and ML abscesses (by chi2 and Fisher exact tests) vis-a-vis their location of liver involvement, size, shape, number margins, enhancement patterns, subcapsular lesions, internal architecture, dilatation of intrahepatic bile duct and combination with splenic abscesses. Fourteen HF patients had only liver abscesses and 1 had combined liver and splenic abscesses. Four ML patients had liver abscesses alone while 12 had combined liver and splenic abscesses (p = 0.000). Eight of the 15 HF (53.3%) and 2 of the 16 ML (12.5%) patients had subcapsular lesions (p = 0.019). The liver abscesses were round or oval with linear tracts in 8 of the 15 HF (53.3%) and none of the ML patients (p = 0.001). Between the respective HF and ML patients, there was a significant difference in those with round shaped in ML (p = 0.008), multiple and conglomerately distributed in HF (p = 0.050), multiple and discretely distributed in ML (p = 0.001) no (or minimal) peripheral contrast enhancement in HF (p = 0.011) and moderate or mark peripheral enhancement in ML (p = 0.011). The CT findings of liver abscesses that helped to differentiate hepatic fascioliasis from melioidosis liver abscesses were: their number shape, enhancement pattern, presence of subcapsular lesion (s) and co-occurrence with splenic abscesses. The diagnosis of hepatic fascioliasis by CT is suggested when the following characteristics were seen: (1) multiple, small round or oval (with linear tracts) conglomerates presenting as hypodense lesions; (2) no (or minimal) peripheral contrast enhancement; (3) subcapsular lesions; or (4) less frequent co-occurrence with splenic abscesses.

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface.

PubMed

Langhals, Nicholas B; Woo, Shoshana L; Moon, Jana D; Larson, John V; Leach, Michelle K; Cederna, Paul S; Urbanchek, Melanie G

2014-01-01

Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.

Kimura's Disease without Peripheral Eosinophilia: An Unusual and Challenging Case Simulating Venous Malformation on Imaging Studies-Case Report and Review of literature.

PubMed

Dokania, Vivek; Patil, Digvijay; Agarwal, Ketan; Thakur, Prajakta; Prajapati, Piyush

2017-06-01

Kimura's Disease (KD) is a rare chronic inflammatory disorder presenting as multiple painless solitary subcutaneous nodules, predominantly in the head and neck region and frequently associated with regional lymphadenopathy and/or salivary gland involvement. Because of painless nature and indolent course, there is usually a delay in the patient's presentation. KD may radiologically mimic other chronic inflammatory conditions like tuberculosis, vascular malformations and neoplasms. Clinical correlation and histological evaluation along with elevated peripheral eosinophil and serum IgE level are considered important for confirmatory diagnosis. We report a case of painless swelling over right submandibular region extending to the right superficial parotid. The haematological reports were within normal limits. Ultrasound (USG), Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiogram (MRA) favoured a diagnosis of venous malformation. However, histopathological examination of excised lesion confirmed a diagnosis of KD. This case proves the possibility of the KD even in the absence of peripheral eosinophilia and/ or elevated serum IgE level, and may mimic venous malformation on imaging studies. Therefore, KD must find a place in the differentials of solitary painless neck swelling even in the absence of peripheral eosinophilia and/or elevated IgE level.

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4+ T Cells following Simian Immunodeficiency Virus Infection.

PubMed

Rahmberg, Andrew R; Rajakumar, Premeela A; Billingsley, James M; Johnson, R Paul

2017-04-01

Although multiple restriction factors have been shown to inhibit HIV/SIV replication, little is known about their expression in vivo Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4 + T cells from peripheral blood and the jejunum in rhesus macaques, revealing distinct expression patterns in naive and memory subsets. In both peripheral blood and the jejunum, memory CD4 + T cells expressed higher levels of multiple restriction factors compared to naive cells. However, relative to their expression in peripheral blood CD4 + T cells, jejunal CCR5 + CD4 + T cells exhibited significantly lower expression of multiple restriction factors, including APOBEC3G , MX2 , and TRIM25 , which may contribute to the exquisite susceptibility of these cells to SIV infection. In vitro stimulation with anti-CD3/CD28 antibodies or type I interferon resulted in upregulation of distinct subsets of multiple restriction factors. After infection of rhesus macaques with SIVmac239, the expression of most confirmed and putative restriction factors substantially increased in all CD4 + T cell memory subsets at the peak of acute infection. Jejunal CCR5 + CD4 + T cells exhibited the highest levels of SIV RNA, corresponding to the lower restriction factor expression in this subset relative to peripheral blood prior to infection. These results illustrate the dynamic modulation of confirmed and putative restriction factor expression by memory differentiation, stimulation, tissue microenvironment and SIV infection and suggest that differential expression of restriction factors may play a key role in modulating the susceptibility of different populations of CD4 + T cells to lentiviral infection. IMPORTANCE Restriction factors are genes that have evolved to provide intrinsic defense against viruses. HIV and simian immunodeficiency virus (SIV) target CD4 + T cells. The baseline level of expression in vivo and degree to which expression of restriction factors is modulated by conditions such as CD4 + T cell differentiation, stimulation, tissue location, or SIV infection are currently poorly understood. We measured the expression of 45 confirmed and putative restriction factors in primary CD4 + T cells from rhesus macaques under various conditions, finding dynamic changes in each state. Most dramatically, in acute SIV infection, the expression of almost all target genes analyzed increased. These are the first measurements of many of these confirmed and putative restriction factors in primary cells or during the early events after SIV infection and suggest that the level of expression of restriction factors may contribute to the differential susceptibility of CD4 + T cells to SIV infection. Copyright © 2017 American Society for Microbiology.

Intravascular lymphoma involving the central and peripheral nervous systems in a dog.

PubMed

Bush, William W; Throop, Juliene L; McManus, Patricia M; Kapatkin, Amy S; Vite, Charles H; Van Winkle, Tom J

2003-01-01

A 5-year-old, castrated male mixed-breed dog was presented for paraparesis, ataxia, hyperesthesia, and thrombocytopenia of 5 months' duration and recurrent seizures during the preceding 2 weeks. Multifocal neurological, ophthalmological, pulmonary, and cardiac diseases were identified. Magnetic resonance imaging and cerebrospinal fluid analysis supported a tentative diagnosis of neoplastic or inflammatory disease. A computed tomography-guided biopsy provided both cytopathological and histopathological evidence of intravascular lymphoma. The disease progressed despite chemotherapy with prednisone, L-asparginase, and vincristine. Postmortem histopathological examinations suggested intravascular lymphoma in the central and peripheral nervous systems as well as in multiple other organ systems. This is the first description of an antemortem diagnosis and treatment of intravascular lymphoma involving the central nervous system of a dog.

Plasma cell leukemia: update on biology and therapy.

PubMed

Mina, Roberto; D'Agostino, Mattia; Cerrato, Chiara; Gay, Francesca; Palumbo, Antonio

2017-07-01

Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10 9 /l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM. Novel agents have revolutionized the outcomes of MM patients and have been introduced also for the treatment of PCL. Here, we provide an update on biology and treatment options for PCL.

Two Discrete RuCp* (Cp*=Pentamethylcyclopentadienyl) Binding Modes of N-Confused Porphyrins: Peripheral π Complex and Sitting Atop Ruthenocenophane Complex by Skeletal Transformation.

PubMed

Yamamoto, Takaaki; Mitsuno, Koki; Mori, Shigeki; Itoyama, Shuhei; Shiota, Yoshihito; Yoshizawa, Kazunari; Ishida, Masatoshi; Furuta, Hiroyuki

2018-05-07

Complexation of a RuCp* cation with N-confused tetraarylporphyrins (NCPs) forms directly bound ruthenium(II) pentamethylcyclopentadienyl (Cp*) π-complex on a specific meso-aryl group (e.g., phenyl) neighboring peripheral imino nitrogen of NCPs in high yields. In contrast, in the case of NCPs bearing bulky meso-substituents (e.g., 3,5-di-tert-butylphenyl), new ruthenocenophane-like complex embedded on an N-confused calix[4]phyrin was formed through multiple C-H bond activation of methyl groups of Cp* ligand. The mechanistic insight into the formation of the ruthenocenophane was derived from DFT calculations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rho0 production and possible modification in Au+Au and p+p collisions at square root [sNN] = 200 GeV.

PubMed

Adams, J; Adler, C; Aggarwal, M M; Ahammed, Z; Amonett, J; Anderson, B D; Arkhipkin, D; Averichev, G S; Badyal, S K; Balewski, J; Barannikova, O; Barnby, L S; Baudot, J; Bekele, S; Belaga, V V; Bellwied, R; Berger, J; Bezverkhny, B I; Bhardwaj, S; Bhati, A K; Bichsel, H; Billmeier, A; Bland, L C; Blyth, C O; Bonner, B E; Botje, M; Boucham, A; Brandin, A; Bravar, A; Cadman, R V; Cai, X Z; Caines, H; Calderón de la Barca Sánchez, M; Carroll, J; Castillo, J; Cebra, D; Chaloupka, P; Chattopadhyay, S; Chen, H F; Chen, Y; Chernenko, S P; Cherney, M; Chikanian, A; Christie, W; Coffin, J P; Cormier, T M; Cramer, J G; Crawford, H J; Das, D; Das, S; Derevschikov, A A; Didenko, L; Dietel, T; Dong, W J; Dong, X; Draper, J E; Du, F; Dubey, A K; Dunin, V B; Dunlop, J C; Dutta Majumdar, M R; Eckardt, V; Efimov, L G; Emelianov, V; Engelage, J; Eppley, G; Erazmus, B; Estienne, M; Fachini, P; Faine, V; Faivre, J; Fatemi, R; Filimonov, K; Filip, P; Finch, E; Fisyak, Y; Flierl, D; Foley, K J; Fu, J; Gagliardi, C A; Gagunashvili, N; Gans, J; Ganti, M S; Gaudichet, L; Geurts, F; Ghazikhanian, V; Ghosh, P; Gonzalez, J E; Grachov, O; Grebenyuk, O; Gronstal, S; Grosnick, D; Guertin, S M; Gupta, A; Gutierrez, T D; Hallman, T J; Hamed, A; Hardtke, D; Harris, J W; Heinz, M; Henry, T W; Heppelmann, S; Hippolyte, B; Hirsch, A; Hjort, E; Hoffmann, G W; Horsley, M; Huang, H Z; Huang, S L; Hughes, E; Humanic, T J; Igo, G; Ishihara, A; Jacobs, P; Jacobs, W W; Janik, M; Jiang, H; Johnson, I; Jones, P G; Judd, E G; Kabana, S; Kaplan, M; Keane, D; Khodyrev, V Yu; Kiryluk, J; Kisiel, A; Klay, J; Klein, S R; Klyachko, A; Koetke, D D; Kollegger, T; Kopytine, M; Kotchenda, L; Kovalenko, A D; Kramer, M; Kravtsov, P; Kravtsov, V I; Krueger, K; Kuhn, C; Kulikov, A I; Kumar, A; Kunde, G J; Kunz, C L; Kutuev, R Kh; Kuznetsov, A A; Lamont, M A C; Landgraf, J M; Lange, S; Lasiuk, B; Laue, F; Lauret, J; Lebedev, A; Lednický, R; LeVine, M J; Li, C; Li, Q; Lindenbaum, S J; Lisa, M A; Liu, F; Liu, L; Liu, Z; Liu, Q J; Ljubicic, T; Llope, W J; Long, H; Longacre, R S; Lopez-Noriega, M; Love, W A; Ludlam, T; Lynn, D; Ma, J; Ma, Y G; Magestro, D; Mahajan, S; Mangotra, L K; Mahapatra, D P; Majka, R; Manweiler, R; Margetis, S; Markert, C; Martin, L; Marx, J; Matis, H S; Matulenko, Yu A; McClain, C J; McShane, T S; Meissner, F; Melnick, Yu; Meschanin, A; Miller, M L; Milosevich, Z; Minaev, N G; Mironov, C; Mischke, A; Mishra, D; Mitchell, J; Mohanty, B; Molnar, L; Moore, C F; Mora-Corral, M J; Morozov, D A; Morozov, V; De Moura, M M; Munhoz, M G; Nandi, B K; Nayak, S K; Nayak, T K; Nelson, J M; Netrakanti, P K; Nikitin, V A; Nogach, L V; Norman, B; Nurushev, S B; Odyniec, G; Ogawa, A; Okorokov, V; Oldenburg, M; Olson, D; Paic, G; Pal, S K; Panebratsev, Y; Panitkin, S Y; Pavlinov, A I; Pawlak, T; Peitzmann, T; Perevoztchikov, V; Perkins, C; Peryt, W; Petrov, V A; Phatak, S C; Picha, R; Planinic, M; Pluta, J; Porile, N; Porter, J; Poskanzer, A M; Potekhin, M; Potrebenikova, E; Potukuchi, B V K S; Prindle, D; Pruneau, C; Putschke, J; Rai, G; Rakness, G; Raniwala, R; Raniwala, S; Ravel, O; Ray, R L; Razin, S V; Reichhold, D; Reid, J G; Renault, G; Retiere, F; Ridiger, A; Ritter, H G; Roberts, J B; Rogachevski, O V; Romero, J L; Rose, A; Roy, C; Ruan, L J; Sahoo, R; Sakrejda, I; Salur, S; Sandweiss, J; Savin, I; Schambach, J; Scharenberg, R P; Schmitz, N; Schroeder, L S; Schweda, K; Seger, J; Seyboth, P; Shahaliev, E; Shao, M; Shao, W; Sharma, M; Shestermanov, K E; Shimanskii, S S; Singaraju, R N; Simon, F; Skoro, G; Smirnov, N; Snellings, R; Sood, G; Sorensen, P; Sowinski, J; Speltz, J; Spinka, H M; Srivastava, B; Stanislaus, T D S; Stock, R; Stolpovsky, A; Strikhanov, M; Stringfellow, B; Struck, C; Suaide, A A P; Sugarbaker, E; Suire, C; Sumbera, M; Surrow, B; Symons, T J M; Szanto de Toledo, A; Szarwas, P; Tai, A; Takahashi, J; Tang, A H; Thein, D; Thomas, J H; Timoshenko, S; Tokarev, M; Tonjes, M B; Trainor, T A; Trentalange, S; Tribble, R E; Tsai, O; Ullrich, T; Underwood, D G; Van Buren, G; VanderMolen, A M; Varma, R; Vasilevski, I; Vasiliev, A N; Vernet, R; Vigdor, S E; Viyogi, Y P; Voloshin, S A; Vznuzdaev, M; Waggoner, W; Wang, F; Wang, G; Wang, G; Wang, X L; Wang, Y; Wang, Z M; Ward, H; Watson, J W; Webb, J C; Wells, R; Westfall, G D; Whitten, C; Wieman, H; Willson, R; Wissink, S W; Witt, R; Wood, J; Wu, J; Xu, N; Xu, Z; Xu, Z Z; Yamamoto, E; Yepes, P; Yurevich, V I; Yuting, B; Zanevski, Y V; Zhang, H; Zhang, W M; Zhang, Z P; Zhaomin, Z P; Zizong, Z P; Zołnierczuk, P A; Zoulkarneev, R; Zoulkarneeva, J; Zubarev, A N

2004-03-05

We report results on rho(770)(0)-->pi(+)pi(-) production at midrapidity in p+p and peripheral Au+Au collisions at sqrt[s(NN)]=200 GeV. This is the first direct measurement of rho(770)(0)-->pi(+)pi(-) in heavy-ion collisions. The measured rho(0) peak in the invariant mass distribution is shifted by approximately 40 MeV/c(2) in minimum bias p+p interactions and approximately 70 MeV/c(2) in peripheral Au+Au collisions. The rho(0) mass shift is dependent on transverse momentum and multiplicity. The modification of the rho(0) meson mass, width, and shape due to phase space and dynamical effects are discussed.

Herbal Remedies: A Boon for Diabetic Neuropathy.

PubMed

Tiwari, Reshu; Siddiqui, Mohd Haris; Mahmood, Tarique; Bagga, Paramdeep; Ahsan, Farogh; Shamim, Arshiya

2018-03-26

Diabetic neuropathy is a chronic complication of diabetes mellitus affecting about 50% of patients. Its symptoms include decreased motility and severe pain in peripheral parts. The pathogenesis involved is an abnormality in blood vessels that supply the peripheral nerves, metabolic disorders such as myo-inositol depletion, and increased nonenzymatic glycation. Moreover, oxidative stress in neurons results in activation of multiple biochemical pathways, which results in the generation of free radicals. Apart from available marketed formulations, extensive research is being carried out on herbal-based natural products to control hyperglycemia and its associated complications. This review is focused to provide a summary on diabetic neuropathy covering its etiology, types, and existing work on herbal-based therapies, which include pure compounds isolated from plant materials, plant extracts, and Ayurvedic preparations.

An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation.

PubMed

Toms, Jamie; Harrison, Jason; Richard, Hope; Childers, Adrienne; Reiter, Evan R; Graham, Robert S

2016-01-01

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.

Prediction of peripheral neuropathy in multiple myeloma patients receiving bortezomib and thalidomide: a genetic study based on a single nucleotide polymorphism array.

PubMed

García-Sanz, Ramón; Corchete, Luis Antonio; Alcoceba, Miguel; Chillon, María Carmen; Jiménez, Cristina; Prieto, Isabel; García-Álvarez, María; Puig, Noemi; Rapado, Immaculada; Barrio, Santiago; Oriol, Albert; Blanchard, María Jesús; de la Rubia, Javier; Martínez, Rafael; Lahuerta, Juan José; González Díaz, Marcos; Mateos, María Victoria; San Miguel, Jesús Fernando; Martínez-López, Joaquín; Sarasquete, María Eugenia

2017-12-01

Bortezomib- and thalidomide-based therapies have significantly contributed to improved survival of multiple myeloma (MM) patients. However, treatment-induced peripheral neuropathy (TiPN) is a common adverse event associated with them. Risk factors for TiPN in MM patients include advanced age, prior neuropathy, and other drugs, but there are conflicting results about the role of genetics in predicting the risk of TiPN. Thus, we carried out a genome-wide association study based on more than 300 000 exome single nucleotide polymorphisms in 172 MM patients receiving therapy involving bortezomib and thalidomide. We compared patients developing and not developing TiPN under similar treatment conditions (GEM05MAS65, NCT00443235). The highest-ranking single nucleotide polymorphism was rs45443101, located in the PLCG2 gene, but no significant differences were found after multiple comparison correction (adjusted P = .1708). Prediction analyses, cytoband enrichment, and pathway analyses were also performed, but none yielded any significant findings. A copy number approach was also explored, but this gave no significant results either. In summary, our study did not find a consistent genetic component associated with TiPN under bortezomib and thalidomide therapies that could be used for prediction, which makes clinical judgment essential in the practical management of MM treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Learning of goal-relevant and -irrelevant complex visual sequences in human V1.

PubMed

Rosenthal, Clive R; Mallik, Indira; Caballero-Gaudes, Cesar; Sereno, Martin I; Soto, David

2018-06-12

Learning and memory are supported by a network involving the medial temporal lobe and linked neocortical regions. Emerging evidence indicates that primary visual cortex (i.e., V1) may contribute to recognition memory, but this has been tested only with a single visuospatial sequence as the target memorandum. The present study used functional magnetic resonance imaging to investigate whether human V1 can support the learning of multiple, concurrent complex visual sequences involving discontinous (second-order) associations. Two peripheral, goal-irrelevant but structured sequences of orientated gratings appeared simultaneously in fixed locations of the right and left visual fields alongside a central, goal-relevant sequence that was in the focus of spatial attention. Pseudorandom sequences were introduced at multiple intervals during the presentation of the three structured visual sequences to provide an online measure of sequence-specific knowledge at each retinotopic location. We found that a network involving the precuneus and V1 was involved in learning the structured sequence presented at central fixation, whereas right V1 was modulated by repeated exposure to the concurrent structured sequence presented in the left visual field. The same result was not found in left V1. These results indicate for the first time that human V1 can support the learning of multiple concurrent sequences involving complex discontinuous inter-item associations, even peripheral sequences that are goal-irrelevant. Copyright © 2018. Published by Elsevier Inc.

Nonoperative Management of Extravasation Injuries Associated With Neonatal Parenteral Nutrition Using Multiple Punctures and a Hydrocolloid Dressing.

PubMed

Sung, Kun-Yong; Lee, Sang-Yeul

2016-05-01

Neonatal extravasation injuries are often associated with peripheral parenteral nutrition. Several treatment modalities have been developed and used for managing these injuries with variable results. However, there is a lack of consensus regarding the management of neonatal extravasation injuries. The aim of this paper is to introduce a new nonoperative method for the treatment of neonatal extravasation injuries associated with parenteral nutrition. The authors made multiple punctures on the extravasated wound using a No. 11 scalpel blade tip and applying a DuoDERM Extra Thin (ConvaTec Inc, Princeton, NJ) dressing, a hydrocolloid dressing. The dressing was changed every 6 hours on the first day, and dressing changes were continued with decreasing frequency according to the amount of exudate until the wound healed. After the devitalized tissue began to demarcate and autolyse, surgical debridement was gradually performed. Twelve neonatal extravasation injuries, which occurred between November 2010 and June 2014, were evaluated. The mean follow-up duration was 10 months. The average duration of treatment for wound healing was 25 days. All wounds healed without func- tional deficits and conspicuous scars. The authors suggest their new method of using multiple punctures and a hydrocolloid dressing is an easy, effective, and minimally invasive treatment for neonatal extravasation injuries associated with peripheral parenteral nutrition, and it can be used as an alternative treatment option.

Dynamics of photogenerated carriers near magnetic field driven quantum phase transition in aperiodic multiple quantum wells

NASA Astrophysics Data System (ADS)

Tito, M. A.; Pusep, Yu A.

2018-01-01

Time-resolved magneto-photoluminescence was employed to study the magnetic field induced quantum phase transition separating two phases with different distributions of electrons over quantum wells in an aperiodic multiple quantum well, embedded in a wide AlGaAs parabolic quantum well. Intensities, broadenings and recombination times attributed to the photoluminescence lines emitted from individual quantum wells of the multiple quantum well structure were measured as a function of the magnetic field near the transition. The presented data manifest themselves to the magnetic field driven migration of the free electrons between the quantum wells of the studied multiple quantum well structure. The observed charge transfer was found to influence the screening of the multiple quantum well and disorder potentials. Evidence of the localization of the electrons in the peripheral quantum wells in strong magnetic field is presented.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

has also been shown to produce human-beta-3-defensin. These antimicrobial peptides are implicated in the resistance of epithelial surfaces to...gonadotrophin receptors that regulate prostaglandin production and activity. Epithelial cells manufacture multiple vasoactive peptides , growth factors...200734 P-RCT (n Z 102) PT burns Processed Amnion vs topical antimicrobials . Significantly less dressing changes with amnion. Time to healing, length

Screening the ToxCast Phase 1, 2, and e1k Chemical Libraries for Inhibition of Deiodinase Type 1, 2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by converting the pro-hormone thyroxine (T4) to...

GW-1000. GW Pharmaceuticals.

PubMed

Smith, Paul F

2004-07-01

GW Pharmaceuticals is developing GW-1000 (Sativex), a narrow ratio delta9-tetrahydrocannabinol:cannabidiol product for the potential treatment of multiple sclerosis, spinal cord injury, neurogenic pain and peripheral neuropathy. In March 2003, the company filed for approval for the treatment of MS with the UK Medicines Control Agency, and in May 2004, filed for new drug submission with Health Canada.

Screening the ToxCast Phase 1, 2, and e1k chemical libraries for inhibition of Deiodinase Types 1, 2 and 3 enzyme activity

EPA Science Inventory

Thyroid hormone (TH) homeostasis is dependent on multiple proteins for TH synthesis, transport, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting THs between active and inactive forms by deiodinating the pro-hormone thyroxine (T4) ...

Your Divided Attention, Please! The Maintenance of Multiple Attentional Control Sets over Distinct Regions in Space

ERIC Educational Resources Information Center

Adamo, Maha; Pun, Carson; Pratt, Jay; Ferber, Susanne

2008-01-01

When non-informative peripheral cues precede a target defined by a specific feature, cues that share the critical feature will capture attention while cues that do not will be effectively ignored. We tested whether different attentional control sets can be simultaneously maintained over distinct regions of space. Participants were instructed to…

Radiation-related lymphopenia is associated with spleen irradiation dose during radiotherapy in patients with hepatocellular carcinoma.

PubMed

Liu, Jing; Zhao, Qianqian; Deng, Weiye; Lu, Jie; Xu, Xiaoqing; Wang, Renben; Li, Xia; Yue, Jinbo

2017-05-30

The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC). The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT. Spleen dose-volume variables, including the percentage of the organ volume receiving ≥ n Gy (V n ) and the mean spleen dose (MSD), were calculated using Eclipse treatment planning. Potential associations between dosimetric variables and the Min ALC were assessed by multiple linear regression analysis. Peripheral lymphocytes decreased during RT (P < 0.001). The Min ALC correlated with the MSD (P = 0.005), spleen V 5 (P = 0.001), spleen V 25 (P = 0.026) and spleen V 30 (P = 0.018). Controlling for the Karnofsky performance status (KPS), sex, age, Child-Pugh grade, total dose and tumour stage, a multiple linear regression model with bootstrap analysis of 1000 replicates showed that only the spleen V 5 was correlated with the decrease in the Min ALC (P < 0.05). According to the receiver-operating characteristic (ROC) curve analysis, the predictive cutoff values of the MSD, V 5 , V 25 and V 30 of the spleen for the Min ALC were 227.72 cGy, 17.84, 0.98 and 0.42%, respectively (P = 0.002, P = 0.004, P = 0.007 and P = 0.002, respectively). Furthermore, an MSD ≥ 227.72 cGy (OR = 14.39; 95% CI, 12.18 to 16.60) and V 5 (OR = 7.99; 95% CI, 6.91 to 9.07) of the spleen significantly predicted the Min ALC. Higher spleen irradiation doses were significantly correlated with lower Min ALC during RT for HCC. V 5 should be limited in clinical practice. Maximum sparing for spleen irradiation during RT is recommended to preserve peripheral blood lymphocytes, which may decrease immunosuppression.

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

PubMed

Gallo, O; Sardi, I; Pepe, G; Franchi, A; Attanasio, M; Giusti, B; Bocciolini, C; Abbate, R

1999-07-19

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Effects of peripheral cooling on intention tremor in multiple sclerosis

PubMed Central

Feys, P; Helsen, W; Liu, X; Mooren, D; Albrecht, H; Nuttin, B; Ketelaer, P

2005-01-01

Objective: To investigate the effect of peripheral sustained cooling on intention tremor in patients with multiple sclerosis (MS). MS induced upper limb intention tremor affects many functional activities and is extremely difficult to treat. Materials/Methods: Deep (18°C) and moderate (25°C) cooling interventions were applied for 15 minutes to 23 and 11 tremor arms of patients with MS, respectively. Deep and moderate cooling reduced skin temperature at the elbow by 13.5°C and 7°C, respectively. Evaluations of physiological variables, the finger tapping test, and a wrist step tracking task were performed before and up to 30 minutes after cooling. Results: The heart rate and the central body temperature remained unchanged throughout. Both cooling interventions reduced overall tremor amplitude and frequency proportional to cooling intensity. Tremor reduction persisted during the 30 minute post cooling evaluation period. Nerve conduction velocity was decreased after deep cooling, but this does not fully explain the reduction in tremor amplitude or the effects of moderate cooling. Cooling did not substantially hamper voluntary movement control required for accurate performance of the step tracking task. However, changes in the mechanical properties of muscles may have contributed to the tremor amplitude reduction. Conclusions: Cooling induced tremor reduction is probably caused by a combination of decreased nerve conduction velocity, changed muscle properties, and reduced muscle spindle activity. Tremor reduction is thought to relate to decreased long loop stretch reflexes, because muscle spindle discharge is temperature dependent. These findings are clinically important because applying peripheral cooling might enable patients to perform functional activities more efficiently. PMID:15716530

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings.

PubMed

Zhang, C; Chen, X-H; Zhang, X; Gao, L; Gao, L; Kong, P-Y; Peng, X-G; Sun, A-H; Gong, Y; Zeng, D-F; Wang, Q-Y

2010-06-01

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34(+) cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of >or=6 x10(6) kg(-1) recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34(+) cell yield, BM was an alternative source.

Ulcerative colitis masked by giant urticaria.

PubMed

Caroselli, C; Plocco, M; Pratticò, F; Bruno, C; Antonaglia, C; Rota, F; Curreli, I; Caroselli, A; Bruno, G

2007-01-01

The occurrence of giant urticaria and ulcerative colitis is very infrequent. A 23 year-old female reported the initial eruption of short-lived cutaneous itchy weals on her arms. Then lesions ran together and became confluent, extending to her legs, followed by undefined abdominal pain and a slight increase of body temperature. Exams showed hystologically confirmed ulcerative colitis, with perinuclear anti-neutrophil cytoplasmic antibody positivity. Ulcerative colitis therapy led not only to the remission of the colitic symptoms, but also to the prompt recovery of skin manifestations. Urticaria was the epiphenomenon of ulcerative colitis.

Extension of Nikiforov-Uvarov method for the solution of Heun equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karayer, H., E-mail: hale.karayer@gmail.com; Demirhan, D.; Büyükkılıç, F.

2015-06-15

We report an alternative method to solve second order differential equations which have at most four singular points. This method is developed by changing the degrees of the polynomials in the basic equation of Nikiforov-Uvarov (NU) method. This is called extended NU method for this paper. The eigenvalue solutions of Heun equation and confluent Heun equation are obtained via extended NU method. Some quantum mechanical problems such as Coulomb problem on a 3-sphere, two Coulombically repelling electrons on a sphere, and hyperbolic double-well potential are investigated by this method.

Root and Root Canal Morphology of Human Third Molar Teeth.

PubMed

Mohammadi, Zahed; Jafarzadeh, Hamid; Shalavi, Sousan; Bandi, Shilpa; Patil, Shankargouda

2015-04-01

Successful root canal treatment depends on having comprehensive information regarding the root(s)/canal(s) anatomy. Dentists may have some complication in treatment of third molars because the difficulty in their access, their aberrant occlusal anatomy and different patterns of eruption. The aim of this review was to review and address the number of roots and root canals in third molars, prevalence of confluent canals in third molars, C-shaped canals, dilaceration and fusion in third molars, autotransplantation of third molars and endodontic treatment strategies for third molars.

Opacités nodulaires diffuses et calcifiées

PubMed Central

Jabri, Hasna; Bopaka, Régis Gothard; Lakhdar, Nawal; Moubachir, Houda; Khattabi, Wiam El; Afif, Hicham

2016-01-01

L’adénocarcinome pulmonaire est difficile à évoquer d’emblée devant les données anamnestiques et même radiologiques. Nous rapportons une observation d’une femme présentant une dyspnée avec la radiographie une opacité micronodulaire disséminée, confluente dans les deux champs pulmonaires avec des calcifications par endroit. L’histologie à travers les biopsies transbronchiques a permis de poser le diagnostic. Le pronostic était sombre par le décès de la patiente. PMID:27795800

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia.

PubMed

Horga, Alejandro; Pitceathly, Robert D S; Blake, Julian C; Woodward, Catherine E; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E; Plant, Gordon T; Houlden, Henry; Sweeney, Mary G; Hanna, Michael G; Reilly, Mary M

2014-12-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P<0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P=0.002; odds ratio 8.43, 95% confidence interval 2.24-31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Peripheral neuropathy predicts nuclear gene defect in patients with mitochondrial ophthalmoplegia

PubMed Central

Pitceathly, Robert D. S.; Blake, Julian C.; Woodward, Catherine E.; Zapater, Pedro; Fratter, Carl; Mudanohwo, Ese E.; Plant, Gordon T.; Houlden, Henry; Sweeney, Mary G.; Hanna, Michael G.; Reilly, Mary M.

2014-01-01

Progressive external ophthalmoplegia is a common clinical feature in mitochondrial disease caused by nuclear DNA defects and single, large-scale mitochondrial DNA deletions and is less frequently associated with point mutations of mitochondrial DNA. Peripheral neuropathy is also a frequent manifestation of mitochondrial disease, although its prevalence and characteristics varies considerably among the different syndromes and genetic aetiologies. Based on clinical observations, we systematically investigated whether the presence of peripheral neuropathy could predict the underlying genetic defect in patients with progressive external ophthalmoplegia. We analysed detailed demographic, clinical and neurophysiological data from 116 patients with genetically-defined mitochondrial disease and progressive external ophthalmoplegia. Seventy-eight patients (67%) had a single mitochondrial DNA deletion, 12 (10%) had a point mutation of mitochondrial DNA and 26 (22%) had mutations in either POLG, C10orf2 or RRM2B, or had multiple mitochondrial DNA deletions in muscle without an identified nuclear gene defect. Seventy-seven patients had neurophysiological studies; of these, 16 patients (21%) had a large-fibre peripheral neuropathy. The prevalence of peripheral neuropathy was significantly lower in patients with a single mitochondrial DNA deletion (2%) as compared to those with a point mutation of mitochondrial DNA or with a nuclear DNA defect (44% and 52%, respectively; P < 0.001). Univariate analyses revealed significant differences in the distribution of other clinical features between genotypes, including age at disease onset, gender, family history, progressive external ophthalmoplegia at clinical presentation, hearing loss, pigmentary retinopathy and extrapyramidal features. However, binomial logistic regression analysis identified peripheral neuropathy as the only independent predictor associated with a nuclear DNA defect (P = 0.002; odds ratio 8.43, 95% confidence interval 2.24–31.76). Multinomial logistic regression analysis identified peripheral neuropathy, family history and hearing loss as significant predictors of the genotype, and the same three variables showed the highest performance in genotype classification in a decision tree analysis. Of these variables, peripheral neuropathy had the highest specificity (91%), negative predictive value (83%) and positive likelihood ratio (5.87) for the diagnosis of a nuclear DNA defect. These results indicate that peripheral neuropathy is a rare finding in patients with single mitochondrial DNA deletions but that it is highly predictive of an underlying nuclear DNA defect. This observation may facilitate the development of diagnostic algorithms. We suggest that nuclear gene testing may enable a more rapid diagnosis and avoid muscle biopsy in patients with progressive external ophthalmoplegia and peripheral neuropathy. PMID:25281868

The pattern of peripheral nerve injuries among Pakistani soldiers in the war against terror.

PubMed

Razaq, Sarah; Yasmeen, Rehana; Butt, Aamir Waheed; Akhtar, Noreen; Mansoor, Sahibzada Nasir

2015-05-01

To determine the pattern of peripheral nerve injuries in Pakistani soldiers in the War against terror. Case series. Department of Electrodiagnosis at Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi, Pakistan, from June 2008 to June 2011. All new cases of war wounded soldiers with peripheral nerve injuries were consecutively enrolled. Physical examination and electrodiagnostic study was carried out by experienced physiatrists. Data was entered in pretested especially designed questionnaire which was analysed using SPSS version 17.0. Seddon's classification system was used to assess the severity of injury. There were 418 cases of peripheral nerve injuries with 504 different nerve segments. Mean age was 29.41 ±8 years. Blast was the main cause of nerve injury in 244 (48.5%) cases followed by gunshot in 215 (42.7%) and 45 (8.9%) cases had nerve injuries secondary to fall, burial under debris and motor vehicle accidents. Eighty six (17%) cases had multiple nerve injuries. Most commonly injured nerve was ulnar (20.6%) followed by sciatic (16.7%), median (16.5%), radial (16.3%), peroneal (8.7%), brachial plexus (8.5%), axillary (4.8%), tibial (2%), femoral (1.8%), long thoracic (0.4%) and others (3.8%). Axonotmesis was seen in 459 (91.1%) cases, 44 (8.7%) cases revealed neurotmesis and 1 (0.2%) case had neuropraxia. Peripheral nerve injuries are a major component of war related injuries mainly involving the upper limbs. Electrodiagnostic studies help in assessing severity and determining prognosis. Precise documentation of severity of nerve injuries is important to estimate the burden on our resources and to extend rehabilitation services.

Development of regenerative peripheral nerve interfaces for motor control of neuroprosthetic devices

NASA Astrophysics Data System (ADS)

Kemp, Stephen W. P.; Urbanchek, Melanie G.; Irwin, Zachary T.; Chestek, Cynthia A.; Cederna, Paul S.

2017-05-01

Traumatic peripheral nerve injuries suffered during amputation commonly results in debilitating neuropathic pain in the affected limb. Modern prosthetic technologies allow for intuitive, simultaneous control of multiple degrees of freedom. However, these state-of-the-art devices require separate, independent control signals for each degree of freedom, which is currently not possible. As a result, amputees reject up to 75% of myoelectric devices preferring instead to use body-powered artificial limbs which offer subtle sensory feedback. Without meaningful and intuitive sensory feedback, even the most advanced myoelectric prostheses remain insensate, burdensome, and are associated with enormous cognitive demand and mental fatigue. The ideal prosthetic device is one which is capable of providing intuitive somatosensory feedback essential for interaction with the environment. Critical to the design of such a bioprosthetic device is the development of a reliable biologic interface between human and machine. This ideal patient-prosthetic interface allows for transmission of both afferent somatosensory information and efferent motor signals for a closed-loop feedback system of neural control. Our lab has developed the Regenerative Peripheral Nerve Interface (RPNI) as a biologic nerve interface designed for stable integration of a prosthetic device with transected peripheral nerves in a residual limb. The RPNI is constructed by surgically implanting the distal end of a transected peripheral nerve into an autogenous muscle graft. Animal experiments in our lab have shown recording of motor signals from RPNI's implanted into both rodents and monkeys. Here, we achieve high amplitude EMG signals with a high signal to noise (SNR) ratio.

Using transcriptional profiling to develop a diagnostic test of operational tolerance in liver transplant recipients.

PubMed

Martínez-Llordella, Marc; Lozano, Juan José; Puig-Pey, Isabel; Orlando, Giuseppe; Tisone, Giuseppe; Lerut, Jan; Benítez, Carlos; Pons, Jose Antonio; Parrilla, Pascual; Ramírez, Pablo; Bruguera, Miquel; Rimola, Antoni; Sánchez-Fueyo, Alberto

2008-08-01

A fraction of liver transplant recipients are able to discontinue all immunosuppressive therapies without rejecting their grafts and are said to be operationally tolerant to the transplant. However, accurate identification of these recipients remains a challenge. To design a clinically applicable molecular test of operational tolerance in liver transplantation, we studied transcriptional patterns in the peripheral blood of 80 liver transplant recipients and 16 nontransplanted healthy individuals by employing oligonucleotide microarrays and quantitative real-time PCR. This resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and nontolerant recipients with high accuracy. Multiple peripheral blood lymphocyte subsets contributed to the tolerance-associated transcriptional patterns, although NK and gammadeltaTCR+ T cells exerted the predominant influence. These data suggest that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.

Impaired humoral immunity and tolerance in K14-VEGFR-3-Ig mice that lack dermal lymphatic drainage

PubMed Central

Thomas, Susan N.; Rutkowski, Joseph M.; Pasquier, Miriella; Kuan, Emma L.; Alitalo, Kari; Randolph, Gwendalyn J.; Swartz, Melody A.

2012-01-01

Lymphatic vessels transport interstitial fluid, soluble antigen, and immune cells from peripheral tissues to lymph nodes (LNs), yet the contribution of peripheral lymphatic drainage to adaptive immunity remains poorly understood. We examined immune responses to dermal vaccination and contact hypersensitivity (CHS) challenge in K14-VEGFR-3-Ig mice, which lack dermal lymphatic capillaries and experience markedly depressed transport of solutes and dendritic cells from the skin to draining LNs. In response to dermal immunization, K14-VEGFR-3-Ig mice produced lower antibody titers. In contrast, although delayed, T cell responses were robust after 21 days, including high levels of antigen-specific CD8+ T cells and production of IFN-γ, IL-4 and IL-10 upon restimulation. T cell-mediated CHS responses were strong in K14-VEGFR-3-Ig mice, but importantly, their ability to induce CHS tolerance in the skin was impaired. Additionally, one-year-old mice displayed multiple signs of autoimmunity. These data suggest that lymphatic drainage plays more important roles in regulating humoral immunity and peripheral tolerance than in effector T cell immunity. PMID:22844119

CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

PubMed

Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

2009-12-01

While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

Sch proteins are localized on endoplasmic reticulum membranes and are redistributed after tyrosine kinase receptor activation.

PubMed Central

Lotti, L V; Lanfrancone, L; Migliaccio, E; Zompetta, C; Pelicci, G; Salcini, A E; Falini, B; Pelicci, P G; Torrisi, M R

1996-01-01

The intracellular localization of Shc proteins was analyzed by immunofluorescence and immunoelectron microscopy in normal cells and cells expressing the epidermal growth factor receptor or the EGFR/erbB2 chimera. In unstimulated cells, the immunolabeling was localized in the central perinuclear area of the cell and mostly associated with the cytosolic side of rough endoplasmic reticulum membranes. Upon epidermal growth factor treatment and receptor tyrosine kinase activation, the immunolabeling became peripheral and was found to be associated with the cytosolic surface of the plasma membrane and endocytic structures, such as coated pits and endosomes, and with the peripheral cytosol. Receptor activation in cells expressing phosphorylation-defective mutants of Shc and erbB-2 kinase showed that receptor autophosphorylation, but not Shc phosphorylation, is required for redistribution of Shc proteins. The rough endoplasmic reticulum localization of Shc proteins in unstimulated cells and their massive recruitment to the plasma membrane, endocytic structures, and peripheral cytosol following receptor tyrosine kinase activation could account for multiple putative functions of the adaptor protein. PMID:8628261

Microsurgery for lymphedema: clinical research and long-term results.

PubMed

Campisi, Corradino; Bellini, Carlo; Campisi, Corrado; Accogli, Susanna; Bonioli, Eugenio; Boccardo, Francesco

2010-05-01

To report the wide clinical experience and the research studies in the microsurgical treatment of peripheral lymphedema. More than 1800 patients with peripheral lymphedema have been treated with microsurgical techniques. Derivative lymphatic microvascular procedures recognize today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). In case of associated venous disease reconstructive lymphatic microsurgery techniques have been developed. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume. Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 10 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. Microsurgical LVA have a place in the treatment of peripheral lymphedema, and should be the therapy of choice in patients who are not sufficiently responsive to nonsurgical treatment. 2010 Wiley-Liss, Inc. Microsurgery, 2010.

A model for diagnosing and explaining multiple disorders.

PubMed

Jamieson, P W

1991-08-01

The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.

An automated live imaging platform for studying merozoite egress-invasion in malaria cultures.

PubMed

Crick, Alex J; Tiffert, Teresa; Shah, Sheel M; Kotar, Jurij; Lew, Virgilio L; Cicuta, Pietro

2013-03-05

Most cases of severe and fatal malaria are caused by the intraerythrocytic asexual reproduction cycle of Plasmodium falciparum. One of the most intriguing and least understood stages in this cycle is the brief preinvasion period during which dynamic merozoite-red-cell interactions align the merozoite apex in preparation for penetration. Studies of the molecular mechanisms involved in this process face formidable technical challenges, requiring multiple observations of merozoite egress-invasion sequences in live cultures under controlled experimental conditions, using high-resolution microscopy and a variety of fluorescent imaging tools. Here we describe a first successful step in the development of a fully automated, robotic imaging platform to enable such studies. Schizont-enriched live cultures of P. falciparum were set up on an inverted stage microscope with software-controlled motorized functions. By applying a variety of imaging filters and selection criteria, we identified infected red cells that were likely to rupture imminently, and recorded their coordinates. We developed a video-image analysis to detect and automatically record merozoite egress events in 100% of the 40 egress-invasion sequences recorded in this study. We observed a substantial polymorphism of the dynamic condition of pre-egress infected cells, probably reflecting asynchronies in the diversity of confluent processes leading to merozoite release. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Electromagnetic Navigation Bronchoscopy-directed Pleural Tattoo to Aid Surgical Resection of Peripheral Pulmonary Lesions.

PubMed

Tay, Jun H; Wallbridge, Peter D; Larobina, Marco; Russell, Prudence A; Irving, Louis B; Steinfort, Daniel P

2016-07-01

Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically with conversion to open thoracotomy or incomplete resection being potential limitations to this approach. Multiple methods have been described to aid video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules, including hookwire localization, percutaneous tattoo, or intraoperative ultrasound. We report on our experience using electromagnetic navigation bronchoscopic dye marking of small subpleural lesions to aid VATS wedge resection. A retrospective cohort study of consecutive patients undergoing VATS wedge resection of peripheral lesions. Preoperative bronchoscopy with electromagnetic navigation was utilized to guide a 25 G needle to within/adjacent to the target lesion with injection of 1 mL of methylene blue or indigo carmine under fluoroscopic vision. Six patients underwent bronchoscopic marking of peripheral pulmonary lesions, navigation deemed successful in all patients, with no procedural complications. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all 6 lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining. Electromagnetic navigation bronchoscopic dye marking of peripheral lesions is feasible, without complications commonly associated with percutaneous marking procedures. Further experience is required but early findings suggest that this method may have utility in aiding minimally invasive resection of small subpleural lesions.

Peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations.

PubMed

van Sloten, Thomas T; Savelberg, Hans H C M; Duimel-Peeters, Inge G P; Meijer, Kenneth; Henry, Ronald M A; Stehouwer, Coen D A; Schaper, Nicolaas C

2011-01-01

We evaluated the associations of diabetic complications and underlying pathology with daily walking activity in type 2 diabetic patients without manifest mobility limitations. 100 persons with type 2 diabetes (mean age 64.5 ± 9.4 years) were studied. Persons with manifest mobility limitations were excluded. Possible determinants measured: peripheral neuropathy, neuropathic pain, peripheral arterial disease, cardiovascular disease, decreased muscle strength (handgrip strength), BMI, depression, falls and fear of falling. Walking activity was measured during one week with a pedometer. Functional capacity was measured with the 6 min walk test, the timed "up and go" test and a stair climbing test. prevalence of neuropathy (40%) and obesity (53%) was high. Persons took a median of 6429 steps/day. In multivariate regression analysis, adjusted for age and sex, neuropathy was associated with a reduction of 1967 steps/day, decreased muscle strength with 1782 steps/day, and an increase in BMI of 1 kg/m(2) with a decrease of 210 steps/day (all p<0.05). Decreased muscle strength and BMI, but not neuropathy, were associated with outcome of functional capacity tests in multiple regression analysis. peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations. 2010 Elsevier Ireland Ltd. All rights reserved.

Evaluation of radiation necrosis and malignant glioma in rat models using diffusion tensor MR imaging

PubMed Central

Wang, Silun; Chen, Yifei; Lal, Bachchu; Ford, Eric; Tryggestad, Erik; Armour, Michael; Yan, Kun; Laterra, John; Zhou, Jinyuan

2011-01-01

Standard MRI cannot distinguish between radiation necrosis and tumor progression; however, this distinction is critical in the assessment of tumor response to therapy. In this study, one delayed radiation necrosis model (dose, 40 Gy; radiation field, 10 × 10 mm2; n = 13) and two orthotopic glioma models in rats (9L gliosarcoma, n = 8; human glioma xenografts, n = 5) were compared using multiple DTI indices. A visible isotropic apparent diffusion coefficient (ADC) pattern was observed in the lesion due to radiation necrosis, which consisted of a hypointense central zone and a hyperintense peripheral zone. There were significantly lower ADC, parallel diffusivity, and perpendicular diffusivity in the necrotic central zone than in the peripheral zone (all p < 0.001). When radiation-induced necrosis was compared with viable tumor, radiation necrosis had significantly lower ADC than 9L gliosarcoma and human glioma xenografts (both p < 0.01) in the central zone, and significantly lower FA than 9L gliosarcoma (p = 0.005) and human glioma xenografts (p = 0.012) in the peripheral zone. Histological analysis revealed parenchymal coagulative necrosis in the central zone, and damaged vessels and reactive astrogliosis in the peripheral zone. These data suggest that qualitative and quantitative analysis of the DTI maps can provide useful information by which to distinguish between radiation necrosis and viable glioma. PMID:21948114

Reversible metronidazole-induced cerebellar toxicity in a multiple transplant recipient.

PubMed

Graves, Tracey D; Condon, Marie; Loucaidou, Marina; Perry, Richard J

2009-10-15

Metronidazole-induced central nervous system (CNS) toxicity causes a spectrum of neurological symptoms including ataxia, encephalopathy and peripheral neuropathy. It is associated with characteristic MRI changes of high signal intensity in the dentate nuclei. Given the increasing use of metronidazole, it is import to recognise this drug as a cause of ataxia, as it is entirely reversible on drug withdrawal.

Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients.

PubMed

Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D'Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria

2016-11-30

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis.

Dysregulated Homeostasis of Acetylcholine Levels in Immune Cells of RR-Multiple Sclerosis Patients

PubMed Central

Di Bari, Maria; Reale, Marcella; Di Nicola, Marta; Orlando, Viviana; Galizia, Sabrina; Porfilio, Italo; Costantini, Erica; D’Angelo, Chiara; Ruggieri, Serena; Biagioni, Stefano; Gasperini, Claudio; Tata, Ada Maria

2016-01-01

Multiple sclerosis (MS) is characterized by pro-inflammatory cytokine production. Acetylcholine (ACh) contributes to the modulation of central and peripheral inflammation. We studied the homeostasis of the cholinergic system in relation to cytokine levels in immune cells and sera of relapsing remitting-MS (RR-MS) patients. We demonstrated that lower ACh levels in serum of RR-MS patients were inversely correlated with the increased activity of the hydrolyzing enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, the expression of the ACh biosynthetic enzyme and the protein carriers involved in non-vesicular ACh release were found overexpressed in peripheral blood mononuclear cells of MS patients. The inflammatory state of the MS patients was confirmed by increased levels of TNFα, IL-12/IL-23p40, IL-18. The lower circulating ACh levels in sera of MS patients are dependent on the higher activity of cholinergic hydrolyzing enzymes. The smaller ratio of ACh to TNFα, IL-12/IL-23p40 and IL-18 in MS patients, with respect to healthy donors (HD), is indicative of an inflammatory environment probably related to the alteration of cholinergic system homeostasis. PMID:27916909

Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.

PubMed

Karim, Hawra; Kim, Sung Hoon; Lapato, Andrew S; Yasui, Norio; Katzenellenbogen, John A; Tiwari-Woodruff, Seema K

2018-06-12

Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis. Copyright © 2018 the Author(s). Published by PNAS.

Cellular and molecular basis of wound healing in diabetes

PubMed Central

Brem, Harold; Tomic-Canic, Marjana

2007-01-01

Diabetic foot ulcers (DFUs), a leading cause of amputations, affect 15% of people with diabetes. A series of multiple mechanisms, including decreased cell and growth factor response, lead to diminished peripheral blood flow and decreased local angiogenesis, all of which can contribute to lack of healing in persons with DFUs. In this issue of the JCI, Gallagher and colleagues demonstrate that in diabetic mice, hyperoxia enhances the mobilization of circulating endothelial progenitor cells (EPCs) from the bone marrow to the peripheral circulation (see the related article beginning on page 1249). Local injection of the chemokine stromal cell–derived factor–1α then recruits these EPCs to the cutaneous wound site, resulting in accelerated wound healing. Thus, Gallagher et al. have identified novel potential targets for therapeutic intervention in diabetic wound healing. PMID:17476353

The synergy of the refugee crisis and the financial crisis in Greece: Impact on mental health.

PubMed

Anagnostopoulos, Dimitris C; Giannakopoulos, George; Christodoulou, Nikos G

2017-06-01

The current global financial crisis that started in 2008 resulted in a significant decline in global trade, slowing/reversing economic growth worldwide, and a dramatic increase in public sector debt. At the same time, the global migrant/refugee crisis has reached extreme rates, with millions of people being forced to abandon their homes and communities because of war, political violence or related threats. There is a broad consensus about the deleterious consequences of these crises on psychological well-being, depression, anxiety disorders, insomnia, alcohol abuse and suicidal behavior. Although the separate consequences of economic recession and immigration are extensively discussed in previous research, we know very little about the processes through which the intersection of economic crisis and migrant crisis contributes to the vulnerabilities of natives and migrants during these crises. Of particular concern is the status of children, adolescents and their families, who constitute one of the most vulnerable groups in society. To discuss the contexts that economic and migrant crises shape and suggest possible effects of this intersection on mental health risks, especially among children, adolescents and their families, through reflecting on the recent experience in Greece. Review of the literature and critical analysis of the effects of the confluent crises. The interactive effects of these two crises need further exploration. Novel and diverse models of psychological understanding need to be developed in order to manage the effects of the confluent crises. The role of mental health professionals is crucial in this respect, offering culturally flexible, accommodating and empathetic approaches, allowing healing and acceptance in the face of adversity.

CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of L-Arg via a NO-independent mechanism.

PubMed

Guo, Lu; Tian, Shuang; Chen, Yuguo; Mao, Yun; Cui, Sumei; Hu, Aihua; Zhang, Jianliang; Xia, Shen-Ling; Su, Yunchao; Du, Jie; Block, Edward R; Wang, Xing Li; Cui, Zhaoqiang

2015-10-01

Interendothelial junctions play an important role in the maintenance of endothelial integrity and the regulation of vascular functions. We report here that cationic amino acid transporter-1 (CAT-1) is a novel interendothelial cell adhesion molecule (CAM). We identified that CAT-1 protein localized at cell-cell adhesive junctions, similar to the classic CAM of VE-cadherin, and knockdown of CAT-1 with siRNA led to an increase in endothelial permeability. In addition, CAT-1 formed a cis-homo-dimer and showed Ca(2+)-dependent trans-homo-interaction to cause homophilic cell-cell adhesion. Co-immunoprecipitation assays showed that CAT-1 can associate with β-catenin. Furthermore, we found that the sub-cellular localization and function of CAT-1 are associated with cell confluency, in sub-confluent ECs CAT-1 proteins distribute on the entire surface and function as L-Arg transporters, but most of the CAT-1 in the confluent ECs are localized at interendothelial junctions and serve as CAMs. Further functional characterization has disclosed that extracellular L-Arg exposure stabilizes endothelial integrity via abating the cell junction disassembly of CAT-1 and blocking the cellular membrane CAT-1 internalization, which provides the new mechanisms for L-Arg paradox and trans-stimulation of cationic amino acid transport system (CAAT). These results suggest that CAT-1 is a novel CAM that directly regulates endothelial integrity and mediates the protective actions of L-Arg to endothelium via a NO-independent mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cell Adhesion on Surface-Functionalized Magnesium.

PubMed

Wagener, Victoria; Schilling, Achim; Mainka, Astrid; Hennig, Diana; Gerum, Richard; Kelch, Marie-Luise; Keim, Simon; Fabry, Ben; Virtanen, Sannakaisa

2016-05-18

The biocompatibility of commercially pure magnesium-based (cp Mg) biodegradable implants is compromised of strong hydrogen evolution and surface alkalization due to high initial corrosion rates of cp Mg in the physiological environment. To mitigate this problem, the addition of corrosion-retarding alloying elements or coating of implant surfaces has been suggested. In the following work, we explored the effect of organic coatings on long-term cell growth. cp Mg was coated with aminopropyltriehtoxysilane + vitamin C (AV), carbonyldiimidazole (CDI), or stearic acid (SA). All three coatings have been previously suggested to reduce initial corrosion and to enhance protein adsorption and hence cell adhesion on magnesium surfaces. Endothelial cells (DH1+/+) and osteosarcoma cells (MG63) were cultured on coated samples for up to 20 days. To quantify Mg corrosion, electrochemical impedance spectroscopy (EIS) was measured after 1, 3, and 5 days of cell culture. We also investigated the speed of initial cell spreading after seeding using fluorescently labeled fibroblasts (NIH/3T3). Hydrogen evolution after contact with cell culture medium was markedly decreased on AV- and SA-coated Mg compared to uncoated Mg. These coatings also showed improved cell adhesion and spreading after 24 h of culture comparable to tissue-treated plastic surfaces. On AV-coated cp Mg, a confluent layer of endothelial cells formed after 5 days and remained intact for up to 20 days. Together, these data demonstrate that surface coating with AV is a viable strategy for improving long-term biocompatibility of cp Mg-based implants. EIS measurements confirmed that the presence of a confluent cell layer increased the corrosion resistance.

Polyamine-dependent migration of retinal pigment epithelial cells.

PubMed

Johnson, Dianna A; Fields, Carolyn; Fallon, Amy; Fitzgerald, Malinda E C; Viar, Mary Jane; Johnson, Leonard R

2002-04-01

Migration of retinal pigment epithelial (RPE) cells can be triggered by disruption of the RPE monolayer or injury to the neural retina. Migrating cells may re-establish a confluent monolayer, or they may invade the neural retina and disrupt visual function. The purpose of this study was to examine the role of endogenous polyamines in mechanisms of RPE migration. Endogenous polyamine levels were determined in an immortalized RPE cell line, D407, using HPLC. Activities of the two rate-limiting enzymes for polyamine synthesis, ornithine decarboxylase (ODC), and S-adenosylmethionine decarboxylase (SAMdc), were measured by liberation of ((14)CO(2))(.) Migration was assessed in confluent cultures by determining the number of cells migrating into a mechanically denuded area. All measurements were obtained both in control cultures and in cultures treated with synthesis inhibitors that deplete endogenous polyamines. Subcellular localization of endogenous polyamines was determined using a polyamine antibody. The polyamines, spermidine and spermine, as well as their precursor, putrescine, were normal constituents of RPE cells. The two rate-limiting synthetic enzymes were also present, and their activities were stimulated dramatically by addition of serum to the culture medium. Cell migration was similarly stimulated by serum exposure. When endogenous polyamines were depleted, migration was blocked. When polyamines were replenished through uptake, migration was restored. Polyamine immunoreactivity was limited to membrane patches in quiescent cells. In actively migrating and dividing cells, immunoreactivity was enhanced throughout the cytoplasm. Polyamines are essential for RPE migration. Pharmacologic manipulation of the polyamine pathway could provide a therapeutic strategy for regulating anomalous migration.

Hydrophilic bile acids protect human blood-brain barrier endothelial cells from disruption by unconjugated bilirubin: an in vitro study

PubMed Central

Palmela, Inês; Correia, Leonor; Silva, Rui F. M.; Sasaki, Hiroyuki; Kim, Kwang S.; Brites, Dora; Brito, Maria A.

2015-01-01

Ursodeoxycholic acid and its main conjugate glycoursodeoxycholic acid are bile acids with neuroprotective properties. Our previous studies demonstrated their anti-apoptotic, anti-inflammatory, and antioxidant properties in neural cells exposed to elevated levels of unconjugated bilirubin (UCB) as in severe jaundice. In a simplified model of the blood-brain barrier, formed by confluent monolayers of a cell line of human brain microvascular endothelial cells, UCB has shown to induce caspase-3 activation and cell death, as well as interleukin-6 release and a loss of blood-brain barrier integrity. Here, we tested the preventive and restorative effects of these bile acids regarding the disruption of blood-brain barrier properties by UCB in in vitro conditions mimicking severe neonatal hyperbilirubinemia and using the same experimental blood-brain barrier model. Both bile acids reduced the apoptotic cell death induced by UCB, but only glycoursodeoxycholic acid significantly counteracted caspase-3 activation. Bile acids also prevented the upregulation of interleukin-6 mRNA, whereas only ursodeoxycholic acid abrogated cytokine release. Regarding barrier integrity, only ursodeoxycholic acid abrogated UCB-induced barrier permeability. Better protective effects were obtained by bile acid pre-treatment, but a strong efficacy was still observed by their addition after UCB treatment. Finally, both bile acids showed ability to cross confluent monolayers of human brain microvascular endothelial cells in a time-dependent manner. Collectively, data disclose a therapeutic time-window for preventive and restorative effects of ursodeoxycholic acid and glycoursodeoxycholic acid against UCB-induced blood-brain barrier disruption and damage to human brain microvascular endothelial cells. PMID:25821432

Glucose starvation impairs DNA repair in tumour cells selectively by blocking histone acetylation.

PubMed

Ampferl, Rena; Rodemann, Hans Peter; Mayer, Claus; Höfling, Tobias Tim Alexander; Dittmann, Klaus

2018-03-01

Tumour cells are characterized by aerobic glycolysis and thus have high glucose consumption. Because repairing radiation-induced DNA damage is an energy-demanding process, we hypothesized that glucose starvation combined with radiotherapy could be an effective strategy to selectively target tumour cells. We glucose-starved tumour cells (A549, FaDu) in vitro and analysed their radiation-induced cell responses compared to normal fibroblasts (HSF7). Irradiation depleted intracellular ATP levels preferentially in cancer cells. Consequently, glucose starvation impaired DNA double-strand break (DSB) repair and radiosensitized confluent tumour cells but not normal fibroblasts. In proliferating tumour cells glucose starvation resulted in a reduction of proliferation, but failed to radiosensitize cells. Glucose supply was indispensable during the late DSB repair in confluent tumour cells starting approximately 13 h after irradiation, and glucose starvation inhibited radiation-induced histone acetylation, which is essential for chromatin relaxation. Sirtinol - an inhibitor of histone deacetylases - reverted the effects of glucose depletion on histone acetylation and DNA DSB repair in tumour cells. Furthermore, a glucose concentration of 2.8 mmol/L was sufficient to impair DSB repair in tumour cells and reduced their clonogenic survival under a fractionated irradiation regimen. In resting tumour cells, glucose starvation combined with irradiation resulted in the impairment of late DSB repair and the reduction of clonogenic survival, which was associated with disrupted radiation-induced histone acetylation. However, in normal cells, DNA repair and radiosensitivity were not affected by glucose depletion. Copyright © 2017 Elsevier B.V. All rights reserved.

Adaptation of vestibular signals for self-motion perception

PubMed Central

St George, Rebecca J; Day, Brian L; Fitzpatrick, Richard C

2011-01-01

A fundamental concern of the brain is to establish the spatial relationship between self and the world to allow purposeful action. Response adaptation to unvarying sensory stimuli is a common feature of neural processing, both peripherally and centrally. For the semicircular canals, peripheral adaptation of the canal-cupula system to constant angular-velocity stimuli dominates the picture and masks central adaptation. Here we ask whether galvanic vestibular stimulation circumvents peripheral adaptation and, if so, does it reveal central adaptive processes. Transmastoidal bipolar galvanic stimulation and platform rotation (20 deg s−1) were applied separately and held constant for 2 min while perceived rotation was measured by verbal report. During real rotation, the perception of turn decayed from the onset of constant velocity with a mean time constant of 15.8 s. During galvanic-evoked virtual rotation, the perception of rotation initially rose but then declined towards zero over a period of ∼100 s. For both stimuli, oppositely directed perceptions of similar amplitude were reported when stimulation ceased indicating signal adaptation at some level. From these data the time constants of three independent processes were estimated: (i) the peripheral canal-cupula adaptation with time constant 7.3 s, (ii) the central ‘velocity-storage’ process that extends the afferent signal with time constant 7.7 s, and (iii) a long-term adaptation with time constant 75.9 s. The first two agree with previous data based on constant-velocity stimuli. The third component decayed with the profile of a real constant angular acceleration stimulus, showing that the galvanic stimulus signal bypasses the peripheral transformation so that the brainstem sees the galvanic signal as angular acceleration. An adaptive process involving both peripheral and central processes is indicated. Signals evoked by most natural movements will decay peripherally before adaptation can exert an appreciable effect, making a specific vestibular behavioural role unlikely. This adaptation appears to be a general property of the internal coding of self-motion that receives information from multiple sensory sources and filters out the unvarying components regardless of their origin. In this instance of a pure vestibular sensation, it defines the afferent signal that represents the stationary or zero-rotation state. PMID:20937715

Dynamics of prolonged salt movement in the Glückstadt Graben (NW Germany) driven by tectonic and sedimentary processes

NASA Astrophysics Data System (ADS)

Warsitzka, Michael; Kley, Jonas; Jähne-Klingberg, Fabian; Kukowski, Nina

2017-01-01

The formation of salt structures exerted a major influence on the evolution of subsidence and sedimentation patterns in the Glückstadt Graben, which is part of the Central European Basin System and comprises a post-Permian sediment thickness of up to 11 km. Driven by regional tectonics and differential loading, large salt diapirs, salt walls and salt pillows developed. The resulting salt flow significantly influenced sediment distribution in the peripheral sinks adjacent to the salt structures and overprinted the regional subsidence patterns. In this study, we investigate the geometric and temporal evolution of salt structures and subsidence patterns in the central Glückstadt Graben. Along a key geological cross section, the post-Permian strata were sequentially decompacted and restored in order to reconstruct the subsidence history of minibasins between the salt structures. The structural restoration reveals that subsidence of peripheral sinks and salt structure growth were initiated in Early to Middle Triassic time. From the Late Triassic to the Middle Jurassic, salt movement and salt structure growth never ceased, but were faster during periods of crustal extension. Following a phase from Late Jurassic to the end of the early Late Cretaceous, in which minor salt flow occurred, salt movement was renewed, particularly in the marginal parts of the Glückstadt Graben. Subsidence rates and tectonic subsidence derived from backstripping of 1D profiles reveal that especially the Early Triassic and Middle Keuper times were periods of regional extension. Three specific types of salt structures and adjacent peripheral sinks could be identified: (1) Graben centre salt walls possessing deep secondary peripheral sinks on the sides facing away from the basin centre, (2) platform salt walls, whose main peripheral sinks switched multiple times from one side of the salt wall to the other, and (3) Graben edge pillows, which show only one peripheral sink facing the basin centre.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

PubMed

Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy

PubMed Central

KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem

2016-01-01

Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type. PMID:28360761

Comparison of the effects of three oral bisphosphonate therapies on the peripheral skeleton in postmenopausal osteoporosis: the TRIO study.

PubMed

Paggiosi, M A; Peel, N; McCloskey, E; Walsh, J S; Eastell, R

2014-12-01

We compared the effects of oral alendronate, ibandronate and risedronate on the central and peripheral skeleton over 2 years. We report differences in effect on the central skeleton but not on the peripheral skeleton. Greater effects were observed for ibandronate (and alendronate) than risedronate at the spine but not the hip. Generally, comparative clinical trials of bisphosphonates have examined changes in bone within central skeletal regions. We have examined the effects of bisphosphonate treatment on the peripheral skeleton. We conducted a 2-year, open-label, parallel randomised control trial of three orally administered bisphosphonates, at their licensed dose, to examine and compare their effects on the peripheral skeleton using multiple modes of measurement. We studied 172 postmenopausal women (53-84 years) who had either a bone mineral density (BMD) T-score of  ≤ -2.5 at the spine and/or total hip or  < -1.0 at either site plus a previous low trauma fracture. Participants were randomised to receive either (i) ibandronate 150 mg/month, (ii) alendronate 70 mg/week or (iii) risedronate 35 mg/week, plus calcium (1,200 mg/day) and vitamin D (800 IU/day), for 2 years. Premenopausal women (33-40 years, n = 226) were studied to monitor device stability. We measured central BMD of the lumbar spine, total hip, total body and forearm using dual-energy X-ray absorptiometry. We measured calcaneus BMD (using dual-energy X-ray absorptiometry plus laser), radius and tibia BMD (using peripheral quantitative computed tomography), finger BMD (using radiographic absorptiometry), and phalangeal and calcaneal ultrasound variables (using quantitative ultrasound). Mixed effects regression models were used to evaluate effects of time and treatment allocation on BMD change. By 2 years, there were significant increases (p < 0.05) in central BMD sites (lumbar spine, total hip). In the peripheral skeleton, only significant changes in calcaneus BMD, 33 % total radius BMD and quantitative ultrasound (QUS)-2 broadband ultrasound attenuation (BUA) were evident for women receiving oral bisphosphonates. The increases in lumbar spine and total body BMD were greater with ibandronate and alendronate than with risedronate. Treatment effects on peripheral measurements did not differ between the three bisphosphonates.

Agent Orange exposure and prevalence of self-reported diseases in Korean Vietnam veterans.

PubMed

Yi, Sang-Wook; Ohrr, Heechoul; Hong, Jae-Seok; Yi, Jee-Jeon

2013-09-01

The aim of this study was to evaluate the association between Agent Orange exposure and self-reported diseases in Korean Vietnam veterans. A postal survey of 114 562 Vietnam veterans was conducted. The perceived exposure to Agent Orange was assessed by a 6-item questionnaire. Two proximity-based Agent Orange exposure indices were constructed using division/brigade-level and battalion/company-level unit information. Adjusted odds ratios (ORs) for age and other confounders were calculated using a logistic regression model. The prevalence of all self-reported diseases showed monotonically increasing trends as the levels of perceived self-reported exposure increased. The ORs for colon cancer (OR, 1.13), leukemia (OR, 1.56), hypertension (OR, 1.03), peripheral vasculopathy (OR, 1.07), enterocolitis (OR, 1.07), peripheral neuropathy (OR, 1.07), multiple nerve palsy (OR, 1.14), multiple sclerosis (OR, 1.24), skin diseases (OR, 1.05), psychotic diseases (OR, 1.07) and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the division/brigade-level proximity-based exposure analysis, compared to the low exposure group. The ORs for cerebral infarction (OR, 1.08), chronic bronchitis (OR, 1.05), multiple nerve palsy (OR, 1.07), multiple sclerosis (OR, 1.16), skin diseases (OR, 1.05), and lipidemia (OR, 1.05) were significantly elevated for the high exposure group in the battalion/company-level analysis. Korean Vietnam veterans with high exposure to Agent Orange experienced a higher prevalence of several self-reported chronic diseases compared to those with low exposure by proximity-based exposure assessment. The strong positive associations between perceived self-reported exposure and all self-reported diseases should be evaluated with discretion because the likelihood of reporting diseases was directly related to the perceived intensity of Agent Orange exposure.

NLR-Dependent Regulation of Inflammation in Multiple Sclerosis

PubMed Central

Gharagozloo, Marjan; Gris, Katsiaryna V.; Mahvelati, Tara; Amrani, Abdelaziz; Lukens, John R.; Gris, Denis

2018-01-01

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) associated with inappropriate activation of lymphocytes, hyperinflammatory responses, demyelination, and neuronal damage. In the past decade, a number of biological immunomodulators have been developed that suppress the peripheral immune responses and slow down the progression of the disease. However, once the inflammation of the CNS has commenced, it can cause serious permanent neuronal damage. Therefore, there is a need for developing novel therapeutic approaches that control and regulate inflammatory responses within the CNS. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are intracellular regulators of inflammation expressed by many cell types within the CNS. They redirect multiple signaling pathways initiated by pathogens and molecules released by injured tissues. NLR family members include positive regulators of inflammation, such as NLRP3 and NLRC4 and anti-inflammatory NLRs, such as NLRX1 and NLRP12. They exert immunomodulatory effect at the level of peripheral immune responses, including antigen recognition and lymphocyte activation and differentiation. Also, NLRs regulate tissue inflammatory responses. Understanding the molecular mechanisms that are placed at the crossroad of innate and adaptive immune responses, such as NLR-dependent pathways, could lead to the discovery of new therapeutic targets. In this review, we provide a summary of the role of NLRs in the pathogenesis of MS. We also summarize how anti-inflammatory NLRs regulate the immune response within the CNS. Finally, we speculate the therapeutic potential of targeting NLRs in MS. PMID:29403486

Allelic imbalance of multiple sclerosis susceptibility genes IKZF3 and IQGAP1 in human peripheral blood.

PubMed

Keshari, Pankaj K; Harbo, Hanne F; Myhr, Kjell-Morten; Aarseth, Jan H; Bos, Steffan D; Berge, Tone

2016-04-14

Multiple sclerosis is a chronic inflammatory, demyelinating disease of the central nervous system. Recent genome-wide studies have revealed more than 110 single nucleotide polymorphisms as associated with susceptibility to multiple sclerosis, but their functional contribution to disease development is mostly unknown. Consistent allelic imbalance was observed for rs907091 in IKZF3 and rs11609 in IQGAP1, which are in strong linkage disequilibrium with the multiple sclerosis associated single nucleotide polymorphisms rs12946510 and rs8042861, respectively. Using multiple sclerosis patients and healthy controls heterozygous for rs907091 and rs11609, we showed that the multiple sclerosis risk alleles at IKZF3 and IQGAP1 are expressed at higher levels as compared to the protective allele. Furthermore, individuals homozygous for the multiple sclerosis risk allele at IQGAP1 had a significantly higher total expression of IQGAP1 compared to individuals homozygous for the protective allele. Our data indicate a possible regulatory role for the multiple sclerosis-associated IKZF3 and IQGAP1 variants. We suggest that such cis-acting mechanisms may contribute to the multiple sclerosis association of single nucleotide polymorphisms at IKZF3 and IQGAP1.

The Neuropathology of Obesity: Insights from Human Disease

PubMed Central

Lee, Edward B.; Mattson, Mark P.

2013-01-01

Obesity, a pathologic state defined by excess adipose tissue, is a significant public health problem as it affects a large proportion of individuals and is linked with increased risk for numerous chronic diseases. Obesity is the result of fundamental changes associated with modern society including overnutrition and sedentary lifestyles. Proper energy homeostasis is dependent on normal brain function as the master metabolic regulator which integrates peripheral signals, modulates autonomic outflow and controls feeding behavior. Therefore, many human brain diseases are associated with obesity. This review explores the neuropathology of obesity by examining brain diseases which either cause or are influenced by obesity. First, several genetic and acquired brain diseases are discussed as a means to understand the central regulation of peripheral metabolism. These diseases range from monogenetic causes of obesity (leptin deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and neurodegenerative conditions (frontotemporal dementia and Gourmand’s syndrome) and serve to highlight the central regulatory mechanisms which have evolved to maintain energy homeostasis. Next, to examine the effect of obesity on the brain, chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer’s disease) are discussed as examples of obesity leading to maladaptive processes which exacerbate chronic disease. Thus obesity is associated with multiple pathways including abnormal metabolism, altered hormonal signaling and increased inflammation which act in concert to promote downstream neuropathology. Finally, the effect of anti-obesity interventions is discussed in terms of brain structure and function. Together, understanding human diseases and anti-obesity interventions leads to insights into the bidirectional interaction between peripheral metabolism and central brain function, highlighting the need for continued clinicopathologic and mechanistic studies of the neuropathology of obesity. PMID:24096619

Graded hypoxia acts through a network of distributed peripheral oxygen chemoreceptors to produce changes in respiratory behaviour and plasticity.

PubMed

Janes, Tara A; Xu, Fenglian; Syed, Naweed I

2015-07-01

Respiratory behaviour relies critically upon sensory feedback from peripheral oxygen chemoreceptors. During environmental or systemic hypoxia, chemoreceptor input modulates respiratory central pattern generator activity to produce reflex-based increases in respiration and also shapes respiratory plasticity over longer timescales. The best-studied oxygen chemoreceptors are undoubtedly the mammalian carotid bodies; however, questions remain regarding this complex organ's role in shaping respiration in response to varying oxygen levels. Furthermore, many taxa possess distinct oxygen chemoreceptors located within the lungs, airways and cardiovasculature, but the functional advantage of multiple chemoreceptor sites is unclear. In this study, it is demonstrated that a distributed network of peripheral oxygen chemoreceptors exists in Lymnaea stagnalis and significantly modulates aerial respiration. Specifically, Lymnaea breath frequency and duration represent parameters that are shaped by interactions between hypoxic severity and its time-course. Using a combination of behaviour and electrophysiology approaches, the chemosensory pathways underlying hypoxia-induced changes in breath frequency/duration were explored. The current findings demonstrate that breath frequency is uniquely modulated by the known osphradial ganglion oxygen chemoreceptors during moderate hypoxia, while a newly discovered area of pneumostome oxygen chemoreception serves a similar function specifically during more severe hypoxia. Together, these findings suggest that multiple oxygen chemosensory sites, each with their own sensory and modulatory properties, act synergistically to form a functionally distributed network that dynamically shapes respiration in response to changing systemic or environmental oxygen levels. These distributed networks may represent an evolutionarily conserved strategy vis-à-vis respiratory adaptability and have significant implications for the understanding of fundamental respiratory control systems. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis.

PubMed

Mostafa, Aliehossadat; Jalilvand, Somayeh; Shoja, Zabihollah; Nejati, Ahmad; Shahmahmoodi, Shohreh; Sahraian, Mohammad Ali; Marashi, Sayed Mahdi

2017-07-01

The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration. MSRV DNA copy number were significantly higher in RRMS patients than healthy controls (P < 0.0001). Interestingly, an inverse correlation was found between MSRV DNA copy number and serum vitamin D concentration (P < 0.01), but not for EBV load or anti-EBNA-1 IgG antibody. © 2017 Wiley Periodicals, Inc.

Relationship between sensorimotor peripheral nerve function and indicators of cardiovascular autonomic function in older adults from the Health, Aging and Body Composition Study.

PubMed

Lange-Maia, Brittney S; Newman, Anne B; Jakicic, John M; Cauley, Jane A; Boudreau, Robert M; Schwartz, Ann V; Simonsick, Eleanor M; Satterfield, Suzanne; Vinik, Aaron I; Zivkovic, Sasa; Harris, Tamara B; Strotmeyer, Elsa S

2017-10-01

Age-related peripheral nervous system (PNS) impairments are highly prevalent in older adults. Although sensorimotor and cardiovascular autonomic function have been shown to be related in persons with diabetes, the nature of the relationship in general community-dwelling older adult populations is unknown. Health, Aging and Body Composition participants (n=2399, age=76.5±2.9years, 52% women, 38% black) underwent peripheral nerve testing at the 2000/01 clinic visit. Nerve conduction amplitude and velocity were measured at the peroneal motor nerve. Sensory nerve function was assessed with vibration detection threshold and monofilament (1.4-g/10-g) testing at the big toe. Symptoms of lower-extremity peripheral neuropathy were collected by self-report. Cardiovascular autonomic function indicators included postural hypotension, resting heart rate (HR), as well as HR response to and recovery from submaximal exercise testing (400m walk). Multivariable modeling adjusted for demographic/lifestyle factors, medication use and comorbid conditions. In fully adjusted models, poor motor nerve conduction velocity (<40m/s) was associated with greater odds of postural hypotension, (OR=1.6, 95% CI: 1.0-2.5), while poor motor amplitude (<1mV) was associated with 2.3beats/min (p=0.003) higher resting HR. No associations were observed between sensory nerve function or symptoms of peripheral neuropathy and indicators of cardiovascular autonomic function. Motor nerve function and indicators of cardiovascular autonomic function remained significantly related even after considering many potentially shared risk factors. Future studies should investigate common underlying processes for developing multiple PNS impairments in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

PubMed Central

Ghafoor, Usman; Kim, Sohee; Hong, Keum-Shik

2017-01-01

For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive), direct-to-peripheral-nerve (invasive), and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques. PMID:29163122

Fate of combat nerve injury.

PubMed

Beltran, Michael J; Burns, Travis C; Eckel, Tobin T; Potter, Benjamin K; Wenke, Joseph C; Hsu, Joseph R

2012-11-01

Assess a cohort of combat-related type III open tibia fractures with peripheral nerve injury to determine the injury mechanism and likelihood for recovery or improvement in nerve function. Retrospective study. Three military medical centers. Out of a study cohort of 213 type III open tibia fractures, 32 fractures (in 32 patients) with a total of 43 peripheral nerve injuries (peroneal or tibial) distal to the popliteal fossa met inclusion criteria and were available for follow-up at an average of 20 months (range, 2-48 months). Clinical assessment of motor and sensory nerve improvement. There was a 22% incidence of peripheral nerve injury in the study cohort. At an average follow-up of 20 months (range, 2-48 months), 89% of injured motor nerves were functional, whereas the injured sensory nerves had function in 93%. Fifty percent and 27% of motor and sensory injuries demonstrated improvement, respectively (P = 0.043). With the numbers available, there was no difference in motor or sensory improvement based on mechanism of injury, fracture severity or location, soft tissue injury, or specific nerve injured. In the subset of patients with an initially impaired sensory examination, full improvement was related to fracture location (P = 0.0164). Type III open tibia fractures sustained in combat are associated with a 22% incidence of peripheral nerve injury, and the majority are due to multiple projectile penetrating injury. Despite the severe nature of these injuries, the vast majority of patients had a functional nerve status by an average of 2-year follow-up. Based on these findings, discussions regarding limb salvage and amputation should not be overly influenced by the patient's peripheral nerve status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

Six cases of sporadic schwannomatosis: Topographic distribution and outcomes of peripheral nerve tumors.

PubMed

Chick, G; Victor, J; Hollevoet, N

2017-10-01

The diagnosis of schwannomatosis is often overestimated and is based on the existence of multiple peripheral nerve tumors composed exclusively of schwannomas, in the absence of clinical signs of neurofibromatosis type 2 (NF2). Sporadic forms are much more frequent than familial forms. The objective of this study was to describe the distribution of peripheral nerve tumors and investigate the outcomes of schwannomas in the context of sporadic schwannomatosis. We conducted a retrospective study of patients who fulfilled clinical diagnostic criteria for sporadic schwannomatosis. Six patients were reviewed with a mean follow-up of 38.5months (27-60months). Patients' demographic, clinical, radiographic, and pathologic data were extracted. All patients underwent slit-lamp examination, enhanced brain magnetic resonance imaging (MRI) and a spinal MRI. Enucleation that preserved nerve continuity was performed in symptomatic patients. On average, patients were 36years of age at the time of diagnosis with no sex predominance. The topographic distribution of the peripheral nerve tumors was always unilateral and most frequently targeted the upper limb. In four cases, the tumors involved the same peripheral nerve exclusively. The average number of nerve tumors observed per patient was 4.7 (2-8). The outcome after enucleation was marked by the systematic appearance of new tumors. After enucleation, no recurrence or malignant transformation was observed at the final follow-up. There was no transition to a NF2 configuration. The absence of neurofibroma and NF2 criteria makes schwannomatosis a diagnosis of exclusion. While a good prognosis can be expected following enucleation, two risks related to neurofibromatosis type 3 (NF3) are worth monitoring: the transition to NF2, particularly in young patients, and the appearance of new tumors. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Doody, Catherine M

2017-02-01

Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted. © 2016 World Institute of Pain.

Temperature Regulation of Shigella Virulence: Identification of Temperature-Regulated Shigella Invasion Genes by the Isolation of inv::lacZ Operon Fusions and the Characterization of the Virulence Gene Regulator virR

DTIC Science & Technology

1991-04-10

Partial nucleotide sequence of viri? clone pAEH122 102 14. Effects of VirR’ activity on Ipa expression 106 15. Sequencing strategy for the 2.3 kb EcoRl...Confluent monolayers of mammalian cells are challenged with virulent organisms and invasion and intercellular spread result in a cytopathic effect ...destruction of the mucosal surface and an inflammatory response ensues which mimics the effects of invasion and intercellular spread in the mucosa of the

All-reflective optical target illumination system with high numerical aperture

DOEpatents

Thomas, Carlton E.; Sigler, Robert D.; Hoeger, John G.

1979-01-01

An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of confluent collimated light beams. The collimated beams are each incident upon an associated concave eccentric pupil paraboloidal reflective surface, and thereby each focused through an opening in an associated outer ellipsoidal reflective surface onto a plane reflector. Each beam is reflected by its associated plane reflector onto the opposing concave surface of the outer ellipsoids to be focused through an opening in the plane surface onto an opposing inner concave ellipsoidal reflective surface, and thence onto the target region.

Exact solutions and phenomenological constraints from massive scalars in a gravity's rainbow spacetime

NASA Astrophysics Data System (ADS)

Bezerra, V. B.; Christiansen, H. R.; Cunha, M. S.; Muniz, C. R.

2017-07-01

We obtain the exact (confluent Heun) solutions to the massive scalar field in a gravity's rainbow Schwarzschild metric. With these solutions at hand, we study the Hawking radiation resulting from the tunneling rate through the event horizon. We show that the emission spectrum obeys nonextensive statistics and is halted when a certain mass remnant is reached. Next, we infer constraints on the rainbow parameters from recent LHC particle physics experiments and Hubble STIS astrophysics measurements. Finally, we study the low frequency limit in order to find the modified energy spectrum around the source.

Elementary functions in thermodynamic Bethe ansatz

NASA Astrophysics Data System (ADS)

Suzuki, J.

2015-05-01

Some years ago, Fendley found an explicit solution to the thermodynamic Bethe ansatz (TBA) equation for an N=2 supersymmetric theory in 2D with a specific F-term. Motivated by this, we seek explicit solutions for other super-potential cases utilizing the idea from the ODE/IM correspondence. We find that the TBA equations, corresponding to a wider class of super-potentials, admit solutions in terms of elementary functions such as modified Bessel functions and confluent hyper-geometric series. Based on talks given at ‘Infinite Analysis 2014’ (Tokyo, 2014) and at ‘Integrable lattice models and quantum field theories’ (Bad Honnef, 2014).

Fractional dynamics using an ensemble of classical trajectories

NASA Astrophysics Data System (ADS)

Sun, Zhaopeng; Dong, Hao; Zheng, Yujun

2018-01-01

A trajectory-based formulation for fractional dynamics is presented and the trajectories are generated deterministically. In this theoretical framework, we derive a new class of estimators in terms of confluent hypergeometric function (F11) to represent the Riesz fractional derivative. Using this method, the simulation of free and confined Lévy flight are in excellent agreement with the exact numerical and analytical results. In addition, the barrier crossing in a bistable potential driven by Lévy noise of index α is investigated. In phase space, the behavior of trajectories reveal the feature of Lévy flight in a better perspective.

Microviscoelasticity of the apical cell surface of human umbilical vein endothelial cells (HUVEC) within confluent monolayers.

PubMed

Feneberg, Wolfgang; Aepfelbacher, Martin; Sackmann, Erich

2004-08-01

We studied the local viscoelasticity of the apical membrane of human umbilical vein endothelial cells within confluent layers by magnetic tweezers microrheometry. Magnetic beads are coupled to various integrins by coating with fibronectin or invasin. By analyzing the deflection of beads evoked by various force scenarios we demonstrate that the cell envelope behaves as a linear viscoelastic body if forces up to 2 nN are applied for short times (<20 s) but can respond in an adaptive way if stress pulses are applied longer (>30 s). The time-dependent shear relaxation modulus G(t) exhibits three time regimes: a fast response (t < 0.05 s) where the relaxation modulus G(t) obeys a power law G(t) approximately t(-0.82+/-0.02); a plateau-like behavior (at 0.05 s < t < 0.15 s); and a slow flow-like response which is, however, partially reversible. Strain field mapping experiments with colloidal probes show that local forces induce a strain field exhibiting a range of zeta = 10 +/- 1 microm, but which could only be observed if nonmagnetic beads were coupled to the cell surface by invasin. By application of the theory of elasticity of planar bodies we estimated a surface shear modulus of 2.5 x10(-4) N/m. By assuming a thickness of the actin cortex of approximately 0.5 microm we estimate a Young modulus micro approximately 400 Pa for the apical membrane. The value agrees with a plateau modulus of an entangled or weakly cross-linked actin network of an actin concentration of 100 microM (mesh size 0.2 microm). This result together with our observation of a strong reduction of the shear modulus by the actin destabilizing agent latrunculin A suggests that the shear modulus measured by our technique is determined by the actin cortex. The effect of two ligands inducing actin stress fiber formation and centripetal contraction of cells (associated with the formation of gaps in the confluent cell monolayer) on the viscoelastic responses were studied: histamine and lysophosphatidic acid (LPA). Histamine evoked a dramatic increase of the cell stiffness by >1 order of magnitude within <30 s, which is attributed to a transient rise of the intracellular Ca(2+) level, since DMSO exerted a similar effect. The stiffening is accompanied by a concomitant rounding of the cells as observed by microinterferometry and relaxes partially in the timescale of 5 min, whereas gaps between cells close after approximately 30 min. LPA did not exert a remarkable and reproducible effect other than an occasional very weak transient increase of the shear stiffness, which shows that the gap formation activated by LPA is mediated by a different mechanism than that induced by histamine.

Gulf War Illness Inflammation Reduction Trial

DTIC Science & Technology

2015-10-01

study comparing blood samples from Gulf War veterans with and without multiple symptoms of pain, fatigue, and cognitive dysfunction. The goal of the...pilot study was to identify a potential therapeutic target for the treatment of GWI. Examination to the peripheral blood revealed the biomarker...understood. Therefore, we performed a pilot study comparing blood samples from Gulf War veterans who very GWI- with blood 6 from veterans who were

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 2, February/March 1998

DTIC Science & Technology

1998-03-01

comment: Leprosy is a chronic disease, caused by Mycobacterium leprae , that affects the skin and peripheral nerves of human hosts. Individuals with...untreated infections shed M. leprae in high concentrations in their nasal secretions; however, transmission from infected to uninfected persons generally...Individuals infected with M. leprae quickly become noninfectious after initiating multiple drug therapy (MDT). Thus, aggressive case finding linked to MDT

The NUP98 Gene as a Potential Modifier of NF2 Associated Tumors

DTIC Science & Technology

2017-06-01

limited to observation, surgical removal, and stereotactic radiation [ 1 ]. However, surgery may not be possible if the tumor is inaccessible or when...there are too many tumors. Radiation treatment may cause malignant transformation and/or growth acceleration of benign tumor cells. In addition...genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas

The Role of Protein Radicals in Chronic Neuroimmune Dysfunction and Neuropathology in Response to a Multiple-Hit Model of Gulf War Exposure

DTIC Science & Technology

2014-10-01

potential neurotoxicants and triggers of inflammation, such as persistent peripheral inflammation and the organophosphate pesticide chlorpyrifos (CPF...War Illness Mouse Model, Chlorpyrifos , LPS, NF-KB p50, microglia, chronic neuroinflammation, serum markers, neuropathology 16. SECURITY...neurotoxicants and triggers of inflammation, such as persistent infections, and the organophosphate pesticide chlorpyrifos (CPF) may interact to

Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-26

B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

Polyradiculopathies from schwannomatosis.

PubMed

Jia, Yuxia; Kraus, James A; Reddy, Hasini; Groff, Michael; Wong, Eric T

2011-01-01

We describe a case of schwannomatosis presenting as radicular pain and numbness in multiple radicular nerve distributions. There were multiple peripheral nerve tumors detected by magnetic resonance imaging (MRI) at the left vestibular nerve, cauda equina, right radial nerve, thoracic paraspinal nerve, and brachial plexi. Several resected tumors have features of schwannomas, including hypercellular Antoni A areas, hypocellular Antoni B areas, Verocay bodies, and hyalinized blood vessels. The specimens are also positive for immunohistochemical staining for INI1 with diffuse nuclear staining. The findings are consistent with sporadic form of schwannomatosis. This case highlights the importance of using MRI and INI1 immunohistochemistry to differentiate familial schwannomatosis, neurofibromatosis 2 (NF2)-associated schwannomatosis, and sporadic schwannomatosis.

Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data.

PubMed

Matsushita, Kunihiro; Ballew, Shoshana H; Coresh, Josef; Arima, Hisatomi; Ärnlöv, Johan; Cirillo, Massimo; Ebert, Natalie; Hiramoto, Jade S; Kimm, Heejin; Shlipak, Michael G; Visseren, Frank L J; Gansevoort, Ron T; Kovesdy, Csaba P; Shalev, Varda; Woodward, Mark; Kronenberg, Florian

2017-09-01

Some evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease. In this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics. We analysed 817 084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18 261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m 2 , adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m 2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m 2 . Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m 2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m 2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups. Even mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease. American Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biophysics of α-Synuclein Membrane Interactions

PubMed Central

Pfefferkorn, Candace M.; Jiang, Zhiping; Lee, Jennifer C.

2011-01-01

Membrane proteins participate in nearly all cellular processes; however, because of experimental limitations, their characterization lags far behind that of soluble proteins. Peripheral membrane proteins are particularly challenging to study because of their inherent propensity to adopt multiple and/or transient conformations in solution and upon membrane association. In this review, we summarize useful biophysical techniques for the study of peripheral membrane proteins and their application in the characterization of the membrane interactions of the natively unfolded and Parkinson’s disease (PD) related protein, α-synuclein (α-syn). We give particular focus to studies that have led to the current understanding of membrane-bound α-syn structure and the elucidation of specific membrane properties that affect α-syn-membrane binding. Finally, we discuss biophysical evidence supporting a key role for membranes and α-syn in PD pathogenesis. PMID:21819966

Two stage gear tooth dynamics program

NASA Technical Reports Server (NTRS)

Boyd, Linda S.

1989-01-01

The epicyclic gear dynamics program was expanded to add the option of evaluating the tooth pair dynamics for two epicyclic gear stages with peripheral components. This was a practical extension to the program as multiple gear stages are often used for speed reduction, space, weight, and/or auxiliary units. The option was developed for either stage to be a basic planetary, star, single external-external mesh, or single external-internal mesh. The two stage system allows for modeling of the peripherals with an input mass and shaft, an output mass and shaft, and a connecting shaft. Execution of the initial test case indicated an instability in the solution with the tooth paid loads growing to excessive magnitudes. A procedure to trace the instability is recommended as well as a method of reducing the program's computation time by reducing the number of boundary condition iterations.

Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury*

PubMed Central

van Niekerk, Erna A.; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

2016-01-01

Following axotomy, a complex temporal and spatial coordination of molecular events enables regeneration of the peripheral nerve. In contrast, multiple intrinsic and extrinsic factors contribute to the general failure of axonal regeneration in the central nervous system. In this review, we examine the current understanding of differences in protein expression and post-translational modifications, activation of signaling networks, and environmental cues that may underlie the divergent regenerative capacity of central and peripheral axons. We also highlight key experimental strategies to enhance axonal regeneration via modulation of intraneuronal signaling networks and the extracellular milieu. Finally, we explore potential applications of proteomics to fill gaps in the current understanding of molecular mechanisms underlying regeneration, and to provide insight into the development of more effective approaches to promote axonal regeneration following injury to the nervous system. PMID:26695766

Formation of various types of nanostructures on germanium surface by nanosecond laser pulses

NASA Astrophysics Data System (ADS)

Mikolutskiy, S. I.; Khasaya, R. R.; Khomich, Yu V.; Yamshchikov, V. A.

2018-03-01

The paper describes the formation of micro- and nanostructures in different parts of irradiation zone on germanium surface by multiple action of nanosecond pulses of ArF-laser. It proposes a simple method using only one laser beam without any optional devices and masks for surface treatment. Hexa- and pentagonal cells with submicron dimensions along the surface were observed in peripheral zone of irradiation spot by atomic-force microscopy. Nanostructures in the form of bulbs with rounded peaks with lateral sizes of 40-120 nm were obtained in peripheral low-intensity region of the laser spot. Considering experimental data on material processing by nanosecond laser pulses, a classification of five main types of surface reliefs formed by nanosecond laser pulses with energy density near or slightly above ablation threshold was proposed.

Patients' health beliefs and coping prior to autologous peripheral stem cell transplantation.

PubMed

Frick, E; Fegg, M J; Tyroller, M; Fischer, N; Bumeder, I

2007-03-01

The aim of this study was to determine the associations between health locus of control (LoC), causal attributions and coping in tumour patients prior to autologous peripheral blood stem cell transplantation. Patients completed the Questionnaire of Health Related Control Expectancies, the Questionnaire of Personal Illness Causes (QPIC), and the Freiburg Questionnaire of Coping with Illness. A total of 126 patients (45% women; 54% suffering from a multiple myeloma, 29% from non-Hodgkin lymphomas, and 17% from other malignancies) participated in the study. Cluster analysis yielded four LoC clusters: 'fatalistic external', 'powerful others', 'yeah-sayer' and 'double external'. Self-blaming QPIC items were positively correlated with depressive coping, and 'fate or destiny' attributions with religious coping (P<0.001). The highest scores were found for 'active coping' in the LoC clusters 'powerful others' and 'yeah-sayer'. External LoC and an active coping style prevail before undergoing autologous peripheral blood stem cell transplantation, whereas the depressive coping is less frequent, associated with self-blaming causal attributions. Health beliefs include causal and control attributions, which can improve or impair the patient's adjustment. A mixture between internal and external attributions seems to be most adaptive.

Chromosome instability on children with asthma.

PubMed

Lialiaris, Theodore; Polyzou, Aggeliki; Mpountoukas, Panagiotis; Tsiggene, Anthi; Kouskoukis, Alexandros; Pouliliou, Stamatia; Paraskakis, Emmanouil; Tentes, Ioannis; Trypsianis, Grigorios; Chatzimichail, Athanasios

2009-10-01

Asthma is a complex disease with multiple interactions between genetic and environmental factors. The aim of our study was to investigate the possible genetic instability in asthmatic patients (AP) with asthma in human cultured peripheral blood lymphocytes. Furthermore, the presence of either cytostaticity or cytotoxicity was demonstrated. Human peripheral blood lymphocytes were cultured from 18 admitted children to the Pediatric Clinic of the University Hospital of Alexandroupolis (average age 7.2 years), and 9 healthy blood donors were used as control subjects (average age 6.5 years), none of whom was receiving drugs for medical or other reasons. A significant (p < 0.05) increase in spontaneous sister chromatid exchanges (SCEs) frequency in asthmatic patients compared with control subjects was observed. No statistically significant modification in the spontaneous proliferation rate index (PRI) in AP compared with the controls was demonstrated. Finally, MMC induced a statistically significant increase in SCEs frequency both to controls and to AP, with the MMC-induced SCEs rates in AP being statistically (p < 0.01) higher compared to the MMC-induced SCEs in controls. We try to improve a new diagnostic process of possible genetic instability by a combination of genotoxic, cytostatic and cytotoxic effects of asthma on human peripheral lymphocytes.

Unusual Voltage-Gated Sodium Currents as Targets for Pain.

PubMed

Barbosa, C; Cummins, T R

2016-01-01

Pain is a serious health problem that impacts the lives of many individuals. Hyperexcitability of peripheral sensory neurons contributes to both acute and chronic pain syndromes. Because voltage-gated sodium currents are crucial to the transmission of electrical signals in peripheral sensory neurons, the channels that underlie these currents are attractive targets for pain therapeutics. Sodium currents and channels in peripheral sensory neurons are complex. Multiple-channel isoforms contribute to the macroscopic currents in nociceptive sensory neurons. These different isoforms exhibit substantial variations in their kinetics and pharmacology. Furthermore, sodium current complexity is enhanced by an array of interacting proteins that can substantially modify the properties of voltage-gated sodium channels. Resurgent sodium currents, atypical currents that can enhance recovery from inactivation and neuronal firing, are increasingly being recognized as playing potentially important roles in sensory neuron hyperexcitability and pain sensations. Here we discuss unusual sodium channels and currents that have been identified in nociceptive sensory neurons, describe what is known about the molecular determinants of the complex sodium currents in these neurons. Finally, we provide an overview of therapeutic strategies to target voltage-gated sodium currents in nociceptive neurons. Copyright © 2016 Elsevier Inc. All rights reserved.

A Pilot Study to Examine Maturation of Body Temperature Control in Preterm Infants

PubMed Central

Knobel, Robin B.; Levy, Janet; Katz, Laurence; Guenther, Bob; Holditch-Davis, Diane

2013-01-01

Objective To test instrumentation and develop analytic models to use in a larger study to examine developmental trajectories of body temperature and peripheral perfusion from birth in extremely low birth weight (EBLW) infants. Design A case study design. Setting The study took place in a level four neonatal intensive care unit (NICU) in North Carolina. Participants Four ELBW infants, less than 29 weeks gestational age at birth. Methods Physiologic data were measured every minute for the first 5 days of life: peripheral perfusion using perfusion index by Masimo and body temperature using thermistors. Body temperature was also measured using infrared thermal imaging. Stimulation and care events were recorded over the first 5 days using video which was coded with Noldus Observer software. Novel analytical models using the state space approach to time series analysis were developed to explore maturation of neural control over central and peripheral body temperature. Results/Conclusion Results from this pilot study confirmed the feasibility of using multiple instruments to measure temperature and perfusion in ELBW infants. This approach added rich data to our case study design and set a clinical context with which to interpret longitudinal physiological data. PMID:24004312

Exercise Prevents Mental Illness

NASA Astrophysics Data System (ADS)

Purnomo, K. I.; Doewes, M.; Giri, M. K. W.; Setiawan, K. H.; Wibowo, I. P. A.

2017-03-01

Multiple current studies show that neuroinflammation may contribute to mental illness such as depression, anxiety, and mood disorder. Chronic inflammation in peripheral tissues is indicated by the increase of inflammatory marker like cytokine IL-6, TNF-α, and IL-1β. Pro-inflammatory cytokine in peripheral tissues can reach brain tissues and activate microglia and it causes neuroinflammation. Psychological stress may led peripheral and central inflammation. Activated microglia will produce pro-inflammatory cytokine, ROS, RNS, and tryptophan catabolizes. This neuroinflammation can promote metabolism changes of any neurotransmitter, such as serotonin, dopamine, and glutamate that will influence neurocircuit in the brain including basal ganglia and anterior cingulated cortex. It leads to mental illness. Exercise give contribution to reduce tissue inflammation. When muscle is contracting in an exercise, muscle will produce the secretion of cytokine like IL-6, IL-1ra, and IL-10. It will react as anti-inflammation and influence macrophage, T cell, monosit, protein Toll-Like Receptor (TLR), and then reduce neuroinflammation, characterised by the decrease of pro-inflammatory cytokine and prevent the activation of microglia in the brain. The objective of the present study is to review scientific articles in the literature related to the contribution of exercise to prevent and ease mental illness.

Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster.

PubMed

Landgren, Ola; Zeig-Owens, Rachel; Giricz, Orsolya; Goldfarb, David; Murata, Kaznouri; Thoren, Katie; Ramanathan, Lakshmi; Hultcrantz, Malin; Dogan, Ahmet; Nwankwo, George; Steidl, Ulrich; Pradhan, Kith; Hall, Charles B; Cohen, Hillel W; Jaber, Nadia; Schwartz, Theresa; Crowley, Laura; Crane, Michael; Irby, Shani; Webber, Mayris P; Verma, Amit; Prezant, David J

2018-06-01

The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS. Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781). WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002. Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS. Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93). Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Surgical Decompression of Painful Diabetic Peripheral Neuropathy: The Role of Pain Distribution

PubMed Central

Liao, Chenlong; Zhang, Wenchuan; Yang, Min; Ma, Qiufeng; Li, Guowei; Zhong, Wenxiang

2014-01-01

Objective To investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved. Methods A total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography (cross-sectional area, CSA) were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups (focal and diffuse pain) according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery. Results The levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05). Conclusions Efficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group. PMID:25290338

Biomarkers of Plasmodium falciparum Infection during Pregnancy in Women Living in Northeastern Tanzania

PubMed Central

Boström, Stéphanie; Ibitokou, Samad; Oesterholt, Mayke; Schmiegelow, Christentze; Persson, Jan-Olov; Minja, Daniel; Lusingu, John; Lemnge, Martha; Fievet, Nadine; Deloron, Philippe; Luty, Adrian J. F.; Troye-Blomberg, Marita

2012-01-01

In pregnant women, Plasmodium falciparum infections are an important cause of maternal morbidity as well as fetal and neonatal mortality. Erythrocytes infected by these malaria-causing parasites accumulate through adhesive interactions in placental intervillous spaces, thus evading detection in peripheral blood smears. Sequestered infected erythrocytes induce inflammation, offering the possibility of detecting inflammatory mediators in peripheral blood that could act as biomarkers of placental infection. In a longitudinal, prospective study in Tanzania, we quantified a range of different cytokines, chemokines and angiogenic factors in peripheral plasma samples, taken on multiple sequential occasions during pregnancy up to and including delivery, from P. falciparum-infected women and matched uninfected controls. The results show that during healthy, uninfected pregnancies the levels of most of the panel of molecules we measured were largely unchanged except at delivery. In women with P. falciparum, however, both comparative and longitudinal assessments consistently showed that the levels of IL-10 and IP-10 increased significantly whilst that of RANTES decreased significantly, regardless of gestational age at the time the infection was detected. ROC curve analysis indicated that a combination of increased IL-10 and IP-10 levels and decreased RANTES levels might be predictive of P. falciparum infections. In conclusion, our data suggest that host biomarkers in peripheral blood may represent useful diagnostic markers of P. falciparum infection during pregnancy, but placental histology results would need to be included to verify these findings. PMID:23155405

Embolization of peripheral high-flow arteriovenous malformations with Onyx.

PubMed

Saeed Kilani, M; Lepennec, V; Petit, P; Magalon, G; Casanova, D; Bartoli, J-M; Vidal, V

2017-03-01

The aim of this study was to report our experience in embolization of high flow peripheral arteriovenous malformations (AVMs) with Onyx. Nineteen patients (10 men, 9 women) with peripheral high-flow AVMs who were treated with arteruial embolization using Onyx were retrospectively included. AVMs were located in the head and neck (6), extremities (5), chest (2), kidney (2), uterus (2), pelvis (1) and parietal (1). In 13 patients, embolization was done using Onyx only. One patient underwent embolization by direct puncture, the others by transarterial approach. Embolization was performed in one or multiple sessions (up to 5). A total of 28 sessions were performed. Follow-up was performed with a delay between 10 and 34 months. Technical success was achieved in all patients. Complete devascularization was obtained in 12 patients. Surgical excision was performed in 9 patients. Non-target Onyx embolization was not observed. One patient developed stroke. In 1 patient microcatheter fracture occured. One patient presented severe pain and bradycardia during the procedure that disappeared shortly after. One patient had persistent but less frequent epistaxis after embolization. Another patient had persistent pain without improvement. One patient was lost to follow-up. Other patients were free of symptoms on follow-up. Embolization with Onyx ® is an interesting option for management of peripheral high-flow AVMs either preoperatively or as a single treatment. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Homeostatic 'bystander' proliferation of human peripheral blood B cells in response to polyclonal T-cell stimulation in vitro.

PubMed

Jasiulewicz, Aleksandra; Lisowska, Katarzyna A; Pietruczuk, Krzysztof; Frąckowiak, Joanna; Fulop, Tamas; Witkowski, Jacek M

2015-11-01

The mechanisms of maintenance of adequate numbers of B lymphocytes and of protective levels of immunoglobulins in the absence of antigenic (re)stimulation remain not fully understood. Meanwhile, our results presented here show that both peripheral blood naive and memory B cells can be activated strongly and non-specifically (in a mitogen-like fashion) in 5-day in vitro cultures of anti-CD3- or concanavalin A (Con A)-stimulated peripheral blood mononuclear cells of healthy people. This polyclonal, bystander activation of the B cells includes multiple divisions of most of them (assessed here by the flow cytometric technique of dividing cell tracking) and significant antibody [immunoglobulin M (IgM) and IgG] secretion. Observed proliferation of the CD19(+) B cells depends on contact with stimulated T helper (Th) cells (via CD40-CD40L interaction) and on the response of B cells to secreted interleukins IL-5, IL-10 and IL-4, and is correlated with the levels of these Th-derived molecules, while it does not involve the ligation of the BCR/CD19 complex. We suggest that the effect might reflect the situation occurring in vivo as the homeostatic proliferation of otherwise non-stimulated, peripheral B lymphocytes, providing an always ready pool for efficient antibody production to any new (or cognate) antigen challenge. © The Japanese Society for Immunology. 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Whole gene expression profile in blood reveals multiple pathways deregulation in R6/2 mouse model

PubMed Central

2013-01-01

Background Huntington Disease (HD) is a progressive neurological disorder, with pathological manifestations in brain areas and in periphery caused by the ubiquitous expression of mutant Huntingtin protein. Transcriptional dysregulation is considered a key molecular mechanism responsible of HD pathogenesis but, although numerous studies investigated mRNA alterations in HD, so far none evaluated a whole gene expression profile in blood of R6/2 mouse model. Findings To discover novel pathogenic mechanisms and potential peripheral biomarkers useful to monitor disease progression or drug efficacy, a microarray study was performed in blood of R6/2 at manifest stage and wild type littermate mice. This approach allowed to propose new peripheral molecular processes involved in HD and to suggest different panels of candidate biomarkers. Among the discovered deregulated processes, we focused on specific ones: complement and coagulation cascades, PPAR signaling, cardiac muscle contraction, and dilated cardiomyopathy pathways. Selected genes derived from these pathways were additionally investigated in other accessible tissues to validate these matrices as source of biomarkers, and in brain, to link central and peripheral disease manifestations. Conclusions Our findings validated the skeletal muscle as suitable source to investigate peripheral transcriptional alterations in HD and supported the hypothesis that immunological alteration may contribute to neurological degeneration. Moreover, the identification of altered signaling in mouse blood enforce R6/2 transgenic mouse as a powerful HD model while suggesting novel disease biomarkers for pre-clinical investigation. PMID:24252798

Lipopolysaccharide effects on the proliferation of NRK52E cells via alternations in gap-junction function.

PubMed

Hei, Ziqing; Zhang, Ailan; Wei, Jing; Gan, Xiaoliang; Wang, Yanling; Luo, Gangjian; Li, Xiaoyun

2012-07-01

Gap junctions regulate proper kidney function by facilitating intercellular communication, vascular conduction, and tubular purinergic signaling. However, no clear relationship has been described between gap-junction function and acute kidney injury induced by the endotoxin lipopolysaccharide (LPS). Normal rat kidney epithelial cells (NRK52E cells) were seeded at high and low densities to promote or impede gap-junction formation, respectively, and establish distinctive levels of intercellular communication in culture. Cells were then challenged with LPS at various concentrations (10-1,000 ng/mL). LPS-induced formation and function of gap junctions were assessed by measuring changes in cell proliferation and colony-forming rates, fluorescent dye transmission to adjacent cells, expression levels of connexin43, and repositioning of confluent cells in response to the gap junction inhibitor oleamide or agonist retinoic acid. The cell proliferation rate and colony-forming rate of high- and low-density NRK52E cells were decreased upon LPS challenge, in a dose-dependent manner. The colony-forming rate of confluent high-density cells was significantly lower than that of low-density cells. Oleamide treatment raised the LPS-induced colony-forming rate of high-density cells, whereas retinoic acid decreased the rate. Neither oleamide nor retinoic acid significantly affected the LPS-induced colony-forming rate of low-density cells. Fluorescence transmission of high-density cells was reduced by LPS challenge, in a dose-dependent manner, but inclusion of retinoic acid increased the LPS-induced transmission of fluorescence. LPS challenge of either high- or low-density NRK52E cells resulted in down-regulated connexin43 expression. Gap-junction function plays an important role in concentration-dependent cytotoxic effect of LPS on normal rat kidney cells in vitro.

Toll-like receptor 2-mediated peptidoglycan uptake by immature intestinal epithelial cells from apical side and exosome-associated transcellular transcytosis

PubMed Central

Bu, Heng-Fu; Wang, Xiao; Tang, Yi; Koti, Viola; Tan, Xiao-Di

2015-01-01

Peptidoglycan is a potent immune adjuvant derived from bacterial cell walls. Previous investigations suggest that intestinal epithelium may absorb peptidoglycan from the lumen. Nonetheless, how peptidoglycan is taken up and crosses intestinal epithelium remains largely unclear. Here, we first characterized peptidoglycan transport in vitro using IEC-18 and HT29-CL19A cells, which represent less mature epithelial cells in intestinal crypts. With fluorescent microscopy, we visualized internalization of dual-labeled peptidoglycan by enterocytes. Engulfed peptidoglycan was found to form a complex with peptidoglycan recognition protein-3, which may facilitate delivering peptidoglycan in vivo. Utilizing electronic microscopy, we revealed that uptake of apical peptidoglycan across intestinal epithelial monolayers was involved in phagocytosis, multivesicular body formation, and exosome secretion. We also studied transport of peptidoglycan using the transwell system. Our data indicated that apically loaded peptidoglycan was exocytosed to the basolateral compartment with exosomes by HT29-CL19A cells. The peptidoglycan-contained basolateral exosome extracts induced macrophage activation. Through gavaging mice with labeled peptidoglycan, we found that luminal peptidoglycan was taken up by columnar epithelial cells in crypts of the small intestine. Furthermore, we showed that pre-confluent immature but not post-confluent mature C2BBe1 cells engulfed peptidoglycan via a toll-like receptor 2-dependent manner. Together, our findings suggest that (1) crypt-based immature intestinal epithelial cells play an important role in transport of luminal peptidoglycan over the intestinal epithelium; and (2) luminal peptidoglycan is transcytosed across intestinal epithelia via a toll-like receptor 2-meciated phagocytosis-multivesicular body-exosome pathway. The absorbed peptidoglycan and its derivatives may facilitate maintenance of intestinal immune homeostasis. PMID:20020500

Assessment of Lung Ultrasound B-Lines in Dogs with Different Stages of Chronic Valvular Heart Disease.

PubMed

Vezzosi, T; Mannucci, T; Pistoresi, A; Toma, F; Tognetti, R; Zini, E; Domenech, O; Auriemma, E; Citi, S

2017-05-01

In dogs with chronic valvular heart disease (CVHD), early recognition of pulmonary edema (PE) is of paramount importance. Recent studies in dogs showed that lung ultrasound examination (LUS) is a useful technique to diagnose cardiogenic PE. To describe LUS features in dogs with different stages of CVHD, and to determine its diagnostic accuracy in detecting PE using thoracic radiography as the reference standard. Sixty-three dogs with CVHD. Prospective, multicenter, cross-sectional study. Each dog underwent physical examination, echocardiography, thoracic radiography, and LUS. The LUS findings were classified as absent, rare, numerous, or confluent B-lines. Sensitivity, specificity, and positive and negative predictive values of LUS B-lines to identify PE were calculated using thoracic radiography as the reference standard. Dogs in stage B1 had absent or rare B-lines in 14 of 15 cases (93.3%). Dogs in stage B2 had absent or rare B-lines in 16 of 18 cases (88.9%). All dogs in stage C, without radiographic signs of PE, had absent or rare B-lines. Dogs in stage C, with radiographic signs of PE, had numerous or confluent B-lines in 18 of 20 cases (90%). Lung ultrasound examination detected PE with a sensitivity of 90%, specificity of 93%, and with positive and negative predictive values of 85.7 and 95.2%, respectively. Lung ultrasound examination showed good diagnostic accuracy to identify cardiogenic PE and might be helpful in staging dogs with CVHD. Lung ultrasound examination should be considered as a new, noninvasive diagnostic tool for clinicians managing CVHD in dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Characterization of cell cultures derived from Lutzomyia spinicrassa (Diptera: Psychodidae) and their susceptibility to infection with Leishmania (Viannia) braziliensis.

PubMed

Zapata Lesmes, Angela Cristina; Cárdenas Castro, Estrella; Bello, Felio

2005-12-01

The sand fly Lutzomyia spinicrassa (Morales, Osorno-Mesa, Osorno & de Hoyos, 1969) is a vector of Leishmania (Viannia) braziliensis, an etiological agent of cutaneous leishmaniasis in Colombia. The present article describes, for the first time, the morphological, karyotypical, and isozymatic characteristics of cell cultures derived from L. Spinicrassa embryonic tissues as well as the interaction of L. Braziliensis with these cell cultures. L. Spinicrassa embryonated eggs and neonate larvae were taken for tissue explants. These were seeded in Grace, L-15, Grace/L-15, MM/VP12, and MK/VP12 culture media. The pH range in these media was 6.7 to 6.9 and the cultures were incubated at 28 degrees C. The MHOM/CO/86/CL250 strain of L. Braziliensis was used for experimental infection of cell cultures of L. Spinicrassa. Cell growth was achieved in L-15 medium and a confluent monolayer was obtained 180 days after the embryonated eggs were explanted. The cell morphology of the primary cell cultures was initially heterogeneous, but in the confluent monolayer of these cell cultures and in the subcultures the predominant cell types were later fibroblast-like and epithelial-like. Cultured cells were predominantly diploid (2n=8); however, significant percentages of aneuploids were also recorded. The cell culture isozyme patterns of L. Spinicrassa coincided with pupae samples from the same species. Promastigote forms of L. Braziliensis could invade cells and transform into amastigote-like forms inside them. The characteristics of cell cultures derived from L. Spinicrassa embryonic tissues were determined. These cultures emerge as a new model to study the life-cycle of L. Braziliensis.

Occurrence of Escherichia coli O157, O111 and O26 in raw ewe's milk and performance of two enrichment broths and two plating media used for its assessment.

PubMed

Caro, Irma; Mateo, Javier; Rúa, Javier; Del Rosario García-Armesto, María

2011-03-15

The occurrence of Escherichia coli O157, O111 and O26 in 159 raw ewe's milk samples was examined. Sample-aliquots were incubated simultaneously in TSB added with yeast extract (YETSB) and mTSB with novobiocin (N-mTSB). Serogroup-specific immunomagnetic separation (IMS) was then used and IMS beads were plated in a cefixime tellurite (CT)-containing media (CT-SMAC, CT-SBMAC and CT-RMAC for E. coli O157, O111 and O26, respectively) and E. coli O157:H7 chromogenic ID agar. A sweep of confluent growth from each medium was examined for the presence of E. coli O157 and O111 using PCR, and for E. coli O26 using a latex agglutination test. Enumeration of E. coli O157 and O111 was performed in the samples tested positive for the correspondent serogroup using the most probable number (MPN) method combined with PCR. Percentage occurrences of E. coli O157, O111 and O26 were 18.2, 8.2 and 5.7, respectively. Mean E. coli O157 and O111 levels were 0.22 and <0.04 MPN/mL, respectively. Enrichment in YETSB resulted in higher detection rates of E. coli O157 and O26 than in N-mTSB. When YETSB was used as enrichment broth and for these last two serogroups, the analysis of the confluent growth from the CT-media gave more positive results than that from E. coli O157:H7-ID medium. Copyright © 2010 Elsevier B.V. All rights reserved.

Maximising the use of freshly isolated human hepatocytes.

PubMed

Evans, Peter J

2016-01-01

Freshly isolated human hepatocytes are the best model for predicting adverse drug reactions. However, their preparation and use present the investigator with many variables that are beyond their control. These include operation continuity and timing, size and number of cut surfaces on liver tissue and the prior history of the patient. To exploit the potential of freshly isolated human hepatocytes a method is required to preserve the cells in their initial in vivo like state. This experimental pausing allows experiments to be prioritised at convenient times of the day. A novel approach for selecting viable human hepatocytes by functional attachment to a gelatin gel is described rather than relying on their physical characteristics. The cells are preserved as a monolayer on the semi-solid support at 10°C as single spherical entities. The hepatocytes can be released into suspension, when required, by a temperature transition to 37°C for 20min. The cells can be used in suspension or as a monolayer. The length of preservation depends upon the source tissue. Hepatocytes from normal liver can be maintained for at least 4days and demonstrated to have the same level of CYP3A4 and the enzymes involved in glucuronidation and sulphation as freshly isolated cells. Cells from fatty liver, attached to gelatin, vary in their preservation time but it is at least 24h and so confluent monolayers, that survive at 37°C can be generated the following day. The technique enables freshly isolated human hepatocytes to be used more effectively. They can be preserved in times of plenty so more experimentation is possible. Alternatively, with poorer fatty cells the initial attachment on gelatin enables confluent monolayers of lipid rich cells to be studied. Copyright © 2015 Elsevier Inc. All rights reserved.

Epidermal regulation of dermal fibroblast activity.

PubMed

Garner, W L

1998-07-01

Although the association between delayed burn wound healing and subsequent hypertrophic scar formation is well-established, the mechanism for this relationship is unknown. Unhealed burn wounds lack an epidermis, suggesting a possible regulatory role for the epidermis in controlling dermal fibroblast matrix synthesis. Therefore, we examined the effect of epidermal cells and media conditioned by epidermal cells on fibroblast collagen synthesis and replication. Purified fibroblast and keratinocyte cell strains were developed from discarded normal adult human skin. Conditioned media were created by incubation of cytokine-free and serum-free medium with either confluent fibroblast or keratinocyte cultures for 18 hours (n = 3). Nearly confluent fibroblast cultures were exposed for 48 hours to graded concentrations of either unconditioned medium (control), conditioned medium, or varying numbers of keratinocytes. Replication was quantified by the incorporation of 3H-thymidine. Collagen synthesis was measured by the incorporation of 3H-proline into collagenase-sensitive protein. Data were compared using analysis of variance (ANOVA) and linear regression. Keratinocyte conditioned medium induced a significant increase in replication (n = 3) (p = 0.004) and a decrease in collagen synthesis (n = 6) (p < 0.001). In contrast, neither fibroblast conditioned medium nor control medium had an effect on fibroblast replication or collagen synthesis. Co-culture of fibroblast with a graded number of keratinocytes similarly decreased collagen synthesis (n = 6) (p < 0.001). Dermal fibroblast collagen synthesis appears to be regulated by a soluble keratinocyte product. This result suggests a mechanism for the clinical observation that unhealed burn wounds, which lack the epidermis, demonstrate excess collagen production and scar. Clinical strategies to decrease hypertrophic scar should include an attempt at early wound closure with skin grafting or the application of cultured epithelial autografts.

Modulation of epidermal growth factor effects on epithelial ion transport by intestinal trefoil factor.

PubMed Central

Chinery, R.; Cox, H. M.

1995-01-01

1. The direct epithelial effects of epidermal growth factor (EGF) and its modulation by intestinal trefoil factor (ITF) have been studied in a human colonic adenocarcinoma cell line called Colony-29 (Col-29). 2. When grown in culture as confluent monolayers and voltage-clamped in Ussing chambers, these epithelia responded with an increase in short circuit current (SCC) to basolateral as well as to apically applied EGF although the latter responses (at 10 nM) were only 25% of those observed following basolateral peptide. 3. Recombinant rat ITF (added to the basolateral surface) did not alter basal SCC levels, but it did enhance the electrogenic effects of basolateral EGF. The EC50 values for EGF-induced ion transport were 0.25 nM in control, and 0.26 nM in ITF pretreated Col-29 epithelia. A significant increase in the size of EGF responses (0.1 nM-10 nM) was observed in the presence of 10 nM ITF and the half-maximal concentration for this modulatory effect of ITF was 7.6 nM. 4. The EGF-induced increases in SCC were partially inhibited (50%) by piretanide pretreatment, indicating that Cl- secretion is involved. EGF responses either in the presence or absence of ITF were also significantly reduced (84% and 66% respectively) by the cyclo-oxygenase inhibitor, piroxicam, therefore implicating prostaglandins as mediators of EGF-stimulated anion secretion. 5. We conclude that in confluent Col-29 epithelia, basolateral EGF stimulates a predominantly prostaglandin-dependent increase in Cl- secretion that is enhanced by basolateral ITF, and that these two peptides may interact in normal and damaged mucosa to alter the local apical solute and fluid environment. PMID:7647987

Modification of a sonographic enthesitis score to differentiate between psoriatic arthritis and young healthy volunteers.

PubMed

Wervers, K; Vis, M; Rasappu, N; van der Ven, M; Tchetverikov, I; Kok, M R; Gerards, A H; Hazes, Jmw; Luime, J J

2018-01-02

We aimed to describe sonographic structural and inflammatory changes in entheses of patients with recently diagnosed psoriatic arthritis (PsA), patients with established PsA, and young healthy volunteers, and to investigate whether the MAdrid Sonographic Enthesitis Index (MASEI) enables us to distinguish these groups in an extreme comparison. New and established PsA patients and healthy volunteers (aged 20-30 years) were recruited. The triceps, quadriceps, patellar, Achilles and elbow extensor tendon insertion, and plantar fascia entheses were investigated sonographically for structural changes, erosions, calcifications, increased thickness, bursitis, and power Doppler (PD) signal according to the MASEI. The study included 25 new and 25 established PsA patients, and 25 healthy volunteers. Increased thickness and PD signal in knee entheses were common for patients and healthy volunteers, while changes at other locations predominantly occurred in patients only. PD was recoded (1, one spot; 1.5, two or three spots; 2, confluent signal; 3, severe confluent signal) and thickness of knee entheses excluded. This resulted in different modified MASEI scores between PsA patients and young healthy controls: median (interquartile range) modified MASEI of 13 (10-22.5) in new PsA, 13.5 (9.5-18) in established PsA, and 3 (1-8.5) in healthy volunteers (p = 0.002). Structural ultrasound changes and PD in entheses are common in both new and established PsA and healthy controls. MASEI score did not differentiate PsA patients from young healthy volunteers. After recoding of PD severity and excluding thickness of knee entheses, marked differences between PsA patients and healthy controls were observed.

No-Touch Radiofrequency Ablation: A Comparison of Switching Bipolar and Switching Monopolar Ablation in Ex Vivo Bovine Liver

PubMed Central

Chang, Won; Lee, Sang Min; Han, Joon Koo

2017-01-01

Objective To evaluate the feasibility, efficiency, and safety of no-touch switching bipolar (SB) and switching monopolar (SM) radiofrequency ablation (RFA) using ex vivo bovine livers. Materials and Methods A pork loin cube was inserted as a tumor mimicker in the bovine liver block; RFA was performed using the no-touch technique in the SM (group A1; 10 minutes, n = 10, group A2; 15 minutes, n = 10) and SB (group B; 10 minutes, n = 10) modes. The groups were compared based on the creation of confluent necrosis with sufficient safety margins, the dimensions, and distance between the electrode and ablation zone margin (DEM). To evaluate safety, small bowel loops were placed above the liver surface and 30 additional ablations were performed in the same groups. Results Confluent necroses with sufficient safety margins were created in all specimens. SM RFA created significantly larger volumes of ablation compared to SB RFA (all p < 0.001). The DEM of group B was significantly lower than those of groups A1 and A2 (all p < 0.001). Although thermal injury to the small bowel was noted in 90%, 100%, and 30% of the cases in groups A1, A2, and B, respectively, full depth injury was noted only in 60% of group A2 cases. Conclusion The no-touch RFA technique is feasible in both the SB and SM modes; however, SB RFA appears to be more advantageous compared to SM RFA in the creation of an ablation zone while avoiding the unnecessary creation of an adjacent parenchymal ablation zone or adjacent small bowel injuries. PMID:28246508

'Leukodystrophy-like' phenotype in children with myelin oligodendrocyte glycoprotein antibody-associated disease.

PubMed

Hacohen, Yael; Rossor, Thomas; Mankad, Kshitij; Chong, Wk 'Kling'; Lux, Andrew; Wassmer, Evangeline; Lim, Ming; Barkhof, Frederik; Ciccarelli, Olga; Hemingway, Cheryl

2018-04-01

To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Of the 31 children studied, 14 presented with acute disseminated encephalomyelitis (ADEM); they were younger (mean 4.1y) than the remainder (mean 8.5y) who presented with optic neuritis and/or transverse myelitis (p<0.001). Similarly, children who had an abnormal brain magnetic resonance imaging (MRI) at onset (n=20) were younger than patients with normal MRI at onset (p=0.001) or at follow-up (p<0.001). 'Leukodystrophy-like' MRI patterns of confluent largely symmetrical lesions was seen during the course of the disease in 7 out of 14 children with a diagnosis of ADEM, and was only seen in children younger than 7 years of age. Their disability after a 3-year follow-up was mild to moderate, and most patients continued to relapse, despite disease-modifying treatments. MOG antibody should be tested in children presenting with relapsing neurological disorders associated with confluent, bilateral white matter changes, and distinct enhancement pattern. Children with MOG antibody-associated disease present with age-related differences in phenotypes, with a severe leukoencephalopathy phenotype in the very young and normal intracranial MRI in the older children. This finding suggests a susceptibility of the very young and myelinating brain to MOG antibody-mediated mechanisms of damage. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination manifest with an age-related phenotype. Children with MOG antibody and 'leukodystrophy-like' imaging patterns tend to have poor response to second-line immunotherapy. © 2017 Mac Keith Press.

Silibinin negatively contributes to primary cilia length via autophagy regulated by histone deacetylase 6 in confluent mouse embryo fibroblast 3T3-L1 cells.

PubMed

Xu, Qian; Liu, Wei; Liu, Xiaoling; Liu, Weiwei; Wang, Hongju; Yao, Guodong; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2016-09-01

Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that silibinin, a natural flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells. This study was designed to investigate the significance of silibinin-induced autophagy in primary ciliary structure in confluent mouse embryo fibroblast 3T3-L1 cells. Either blocking the autophagic flux with pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), or transfection of siRNA targeting LC3 inhibited the reduction of cilia length caused by silibinin exposure. Autophagy induced by silibinin decreased expressions of the cilia-associated proteins, such as IFT88, KIF3a and Ac-tubulin, while 3-MA restored it, indicating that autophagy induced by silibinin led to a reduction of primary cilia length. Histone deacetylase 6 (HDAC6), which was suggested as a mediator of autophagy, was up-regulated by silibinin in a time-dependent manner. In addition, 3T3-L1 cells treated with siRNA against HDAC6 had a reduced autophagic level and were protected from silibinin-induced cilia shortening. Taken together, we conclude that the HDAC6-mediated autophagy negatively regulates primary cilia length during silibinin treatment and has the potential to serve as a therapeutic target for primary cilia-associated ciliopathies. These findings thus provide new information about the potential link between autophagy and primary cilia.

Cellular responses and gene expression profile changes due to bleomycin-induced DNA damage in human fibroblasts in space

PubMed Central

Kidane, Yared; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Ramesh, Govindarajan; Rohde, Larry; Wu, Honglu

2017-01-01

Living organisms in space are constantly exposed to radiation, toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage is essential for assessing the radiation risk for astronauts and the mutation rate in microorganisms. In a study conducted on the International Space Station, confluent human fibroblasts in culture were treated with bleomycin for three hours in the true microgravity environment. The degree of DNA damage was quantified by immunofluorescence staining for γ-H2AX, which is manifested in three types of staining patterns. Although similar percentages of these types of patterns were found between flight and ground cells, there was a slight shift in the distribution of foci counts in the flown cells with countable numbers of γ-H2AX foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. We also performed a microarray analysis of gene expressions in response to bleomycin treatment. A qualitative comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. The microarray data was confirmed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly upregulated in both flight and ground cells after bleomycin treatment. Our results suggest that whether microgravity affects DNA damage response in space can be dependent on the cell type and cell growth condition. PMID:28248986

Transient gene and microRNA expression profile changes of confluent human fibroblast cells in space

NASA Astrophysics Data System (ADS)

Wu, Honglu; Story, Michael; Karouia, Fathi; Stodieck, Louis; Zhang, Ye; Lu, Tao

2016-07-01

Microgravity, or an altered gravity environment from the Earth1g, has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of these cells. Whether non-proliferating cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted onboard the International Space Station (ISS), confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days, respectively, for investigations of gene and miRNA expression profile changes in these cells. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly, as measured by the percentage of Ki-67 positive cells. Gene and miRNA expression data indicated activation of NFkB and other growth related pathways involving HGF and Vegf along with down regulation of the Let-7 miRNA family. On Day 14 when the cells were mostly non-proliferating, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples with respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeletal changes via immunohistochemistry staining of the cells with antibodies for αa-tubulin and fibronectin showed no difference between flown and ground samples. Taken together, our study suggests that in true non-dividing human fibroblast cells in culture, microgravity experienced in space has little effect on the gene and miRNA expression profiles.

Characterization of release of basic fibroblast growth factor from bovine retinal endothelial cells in monolayer cultures.

PubMed Central

Brooks, R A; Burrin, J M; Kohner, E M

1991-01-01

Release of basic fibroblast growth factor (bFGF) was investigated in bovine retinal endothelial cells (BREC) maintained in monolayer culture. Confluent cells released bFGF into serum-free culture medium or medium containing 5% serum at rates of up to 105.2 and 61.3 pM/day respectively. bFGF release coincided with a decrease in monolayer cell number and increases in lactate dehydrogenase (LDH) concentration and cells and cell-debris particles in the medium, which suggested that cell damage and lysis were responsible for growth-factor release. Maximum bFGF release at 24 h (230 +/- 10 pM) occurred when the cells were treated with lipopolysaccharide (10 micrograms/ml), which also produced the greatest changes in parameters of cell damage. Sub-confluent cells showed little overt damage at 24 h, but released bFGF (78 +/- 20 pM) along with LDH, indicating that some cell lysis had occurred. Insulin-like growth factor 1 (IGF-1) was also released into serum-free culture medium at a rate of 0.34 nM/day, but not into medium containing serum or when the cells were treated with lipopolysaccharide. This implies that the mechanism of IGF-1 release is different from that of bFGF and is not related to cell damage. Culture medium conditioned by BREC stimulated the proliferation of these cells, as measured by an increase in their incorporation of [methyl-3H]thymidine from 7550 +/- 479 to 10467 +/- 924 d.p.m. These results demonstrate that bFGF is released from damaged BREC and that medium conditioned by these cells can stimulate retinal-endothelial-cell proliferation. This strengthens the case for an involvement of this growth factor in retinal neovascularization. Images Fig. 1. PMID:2039465

Notch Signaling Modulates MUC16 Biosynthesis in an In Vitro Model of Human Corneal and Conjunctival Epithelial Cell Differentiation

PubMed Central

Xiong, Linjie; Woodward, Ashley M.

2011-01-01

Purpose. Notch proteins are a family of transmembrane receptors that coordinate binary cell fate decisions and differentiation in wet-surfaced epithelia. We sought to determine whether Notch signaling contributes to maintaining mucosal homeostasis by modulating the biosynthesis of cell surface-associated mucins in an in vitro model of human corneal (HCLE) and conjunctival (HCjE) epithelial cell differentiation. Methods. HCLE and HCjE cells were grown at different stages of differentiation, representing nondifferentiated (preconfluent and confluent) and differentiated (stratified) epithelial cultures. Notch signaling was blocked with the γ-secretase inhibitor dibenzazepine (DBZ). The presence of Notch intracellular domains (Notch1 to Notch3) and mucin protein (MUC1, -4, -16) was evaluated by electrophoresis and Western blot analysis. Mucin gene expression was determined by TaqMan real-time polymerase chain reaction. Results. Here we demonstrate that Notch3 is highly expressed in undifferentiated and differentiated HCLE and HCjE cells, and that Notch1 and Notch2 biosynthesis is enhanced by induction of differentiation with serum-containing media. Inhibition of Notch signaling with DBZ impaired MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells at both preconfluent and confluent stages, but not in postmitotic stratified cells. In contrast to protein levels, the amount of MUC16 transcripts were not significantly reduced after DBZ treatment, suggesting that Notch regulates MUC16 posttranscriptionally. Immunoblots of DBZ-treated epithelial cells grown at different stages of differentiation revealed no differences in the levels of MUC1 and MUC4. Conclusions. These results indicate that MUC16 biosynthesis is posttranscriptionally regulated by Notch signaling at early stages of epithelial cell differentiation, and suggest that Notch activation contributes to maintaining a mucosal phenotype at the ocular surface. PMID:21508102

Establishment and Characterization of an Embryonic Cell Line from Sarconesiopsis magellanica

PubMed Central

Cruz, Mónica; Bello, Felio J.

2013-01-01

Sarconesiopsis magellanica (Le Guillou) (Diptera: Calliphoridae) is a necrophagous fly that is important in both human and veterinary medicines. This insect has been registered in Colombia as a biological indicator in estimating post-mortem interval. Insect cell cultures are an important biotechnological tool for basic and applied studies, and cell cultures derived from S. magellanica embryonic tissues are described in this study. S. magellanica embryonated eggs were taken for tissue explants. These were seeded in L-15, Grace/L-15, Eagle MEM, MM, VP12, MM/VP12, and Schneider culture media. The morphological, cytogenetic, biochemical, and molecular characteristics of the cell cultures were examined. Cell growth was achieved in the L15, Grace/L15, and Schneider culture media, and the confluent monolayers were obtained 8, 10, and 19 days after the embryonated eggs were explanted. However, the Schneider medium was the most efficient to develop the subcultures, and 21 passages have been maintained. The cell morphology of the primary cell cultures was initially heterogeneous, but in the confluent monolayer and in the subcultures there was greater cell morphology uniformity, fibroblastoid types being predominant. Cultured cells had a chromosomal number of 12, and the karyotypic complement consisted of five pairs of somatic chromosomes and one sexual pair. The cell culture isozyme patterns of S. magellanica coincided with adult samples from the same species. The molecular analysis, using RAPD-PCR, demonstrated the authentication of the cell cultures of this fly and their differentiation from other cultures derived from two sand flies species. This cell line is a new in vitro model that will be used in biomedical and biotechnological studies. PMID:24766352

Clinicopathological and diagnostic characterization of confluent and reticulate papillomatosis of Gougerot and Carteaud: a retrospective study in a South-East Asian population.

PubMed

Huang, Wenhui; Ong, Gavin; Chong, Wei-Sheng

2015-04-01

Confluent and reticulate papillomatosis of Gougerot and Carteaud (CRP) is a rare dermatological condition, which has not been reported widely in Asian populations. To characterize the clinicopathological and diagnostic features of CRP in a South-East Asian population. The medical records of 29 patients accorded the diagnosis of CRP at the National Skin Centre, Singapore, from 1990 to 2011, were analyzed. The male to female ratio was 2.6:1. Eight patients were Indians. The mean age at the onset of skin eruptions was 29.1 years (range 16-55 years), while the mean duration was 19.9 months (range 0.5-120 months). CRP itself was the most common preliminary diagnosis. Fungal smears were negative in all 22 instances. All 29 patients had received a trial of antifungal therapy before being seen at our center. Antifungal therapy was repeated in three subjects, and the response was uniformly poor. Conversely, the treatment response with tetracyclines was excellent, yielding more than a 50% response in all 14 patients. Four patients suffered recurrence of CRP. According to the diagnostic criteria set forth by Davis et al., 25/29 patients (86.2%) and 19/29 patients (65.6%) fulfilled at least three and four criteria, respectively. A predilection for male gender and Indian ethnicity were noted in our study. The diagnosis of CRP was often made clinically, and investigations were mainly ancillary. The treatment response was poor with antifungal agents but excellent with tetracyclines. The diagnostic criteria proposed by Davis et al. were found to be useful in our cohort of patients.

Axonal flip-flops and oscillators.

PubMed

Baker, M D

2000-11-01

The strange and unpleasant sensations (paraesthesiae) or asynchronous motor-unit activation (fasciculation) that result from a period of limb ischaemia are examples of ectopic discharge in peripheral nerves. Ectopic activity also results from demyelination and is associated with serious neurological conditions, such as multiple sclerosis. A build-up of extracellular K(+) in the internode and persistent Na(+) currents are now implicated in generating the different forms of activity arising in normal and demyelinated axons.

The Role of Protein Radicals in Chronic Neuroimmune Dysfunction and Neuropathology in Response to a Multiple-Hit Model of Gulf War Exposures

DTIC Science & Technology

2015-10-01

neurotoxicants and triggers of inflammation, such as persistent peripheral inflammation and the organophosphate pesticide chlorpyrifos (CPF) may interact to...Model, Chlorpyrifos , LPS, NF-KB p50, microglia, chronic neuroinflammation, serum markers, neuropathology 16. SECURITY CLASSIFICATION OF: 17...potential neurotoxicants and triggers of inflammation, such as persistent infections, and the organophosphate pesticide chlorpyrifos (CPF) may

Refractory Pain Management in Amyloid-Associated Peripheral Neuropathy.

PubMed

Warner, Nafisseh S; Watson, James C; Bendel, Markus A; Moeschler, Susan M

2018-05-01

Systemic amyloidosis is a disease that often involves multiple organ systems, including the peripheral nervous system. Patients may present with severe, refractory neuropathic pain; however, the optimal treatment approach for pain for these patients remains unclear. A man with severe, refractory neuropathic pain in his bilateral upper and lower extremities and the trunk secondary to amyloid neuropathy is presented. Multiple medication trials, including neuropathic and opioid agents, produced considerable adverse effects and minimal relief. Scrambler therapy, a novel electrical stimulation modality, was used and was associated with substantial short-term but nonsustained benefit. Spinal cord stimulation was considered, but given his diffuse symptoms, it was deemed a less-than-optimal approach. Ultimately, an intrathecal drug delivery system was placed with infusion of hydromorphone, resulting in substantial pain reduction in all involved areas and with an improved adverse effect profile. This intervention resulted in immense improvement in the patient's quality of life, despite progression of his systemic amyloidosis. Severe pain in the setting of amyloid neuropathy is often difficult to treat. To our knowledge, this represents the first report of Scrambler therapy or an implanted intrathecal drug delivery system used for a patient with refractory amyloidosis-related neuropathic pain, resulting in substantial analgesic benefit and improved quality of life.

The Comparison between Circadian Oscillators in Mouse Liver and Pituitary Gland Reveals Different Integration of Feeding and Light Schedules

PubMed Central

Bur, Isabelle M.; Zouaoui, Sonia; Fontanaud, Pierre; Coutry, Nathalie; Molino, François; Martin, Agnès O.; Mollard, Patrice; Bonnefont, Xavier

2010-01-01

The mammalian circadian system is composed of multiple peripheral clocks that are synchronized by a central pacemaker in the suprachiasmatic nuclei of the hypothalamus. This system keeps track of the external world rhythms through entrainment by various time cues, such as the light-dark cycle and the feeding schedule. Alterations of photoperiod and meal time modulate the phase coupling between central and peripheral oscillators. In this study, we used real-time quantitative PCR to assess circadian clock gene expression in the liver and pituitary gland from mice raised under various photoperiods, or under a temporal restricted feeding protocol. Our results revealed unexpected differences between both organs. Whereas the liver oscillator always tracked meal time, the pituitary circadian clockwork showed an intermediate response, in between entrainment by the light regimen and the feeding-fasting rhythm. The same composite response was also observed in the pituitary gland from adrenalectomized mice under daytime restricted feeding, suggesting that circulating glucocorticoids do not inhibit full entrainment of the pituitary clockwork by meal time. Altogether our results reveal further aspects in the complexity of phase entrainment in the circadian system, and suggest that the pituitary may host oscillators able to integrate multiple time cues. PMID:21179516

Combined central and peripheral stimulation to facilitate motor recovery after stroke: the effect of number of sessions on outcome.

PubMed

Lindenberg, Robert; Zhu, Lin L; Schlaug, Gottfried

2012-06-01

Proof-of-principle studies have demonstrated transient beneficial effects of transcranial direct current stimulation (tDCS) on motor function in stroke patients, mostly after single treatment sessions. To assess the efficacy of multiple treatment sessions on motor outcome. The authors examined the effects of two 5-day intervention periods of bihemispheric tDCS and simultaneous occupational/physical therapy on motor function in a group of 10 chronic stroke patients. The first 5-day period yielded an increase in Upper-Extremity Fugl-Meyer (UE-FM) scores by 5.9 ± 2.4 points (16.6% ± 10.6%). The second 5-day period resulted in further meaningful, although significantly lower, gains with an additional improvement of 2.3 ± 1.4 points in UE-FM compared with the end of the first 5-day period (5.5% ± 4.2%). The overall mean change after the 2 periods was 8.2 ± 2.2 points (22.9% ± 11.4%). The results confirm the efficacy of bihemispheric tDCS in combination with peripheral sensorimotor stimulation. Furthermore, they demonstrate that the effects of multiple treatment sessions in chronic stroke patients may not necessarily lead to a linear response function, which is of relevance for the design of experimental neurorehabilitation trials.

Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population

PubMed Central

Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei

2016-01-01

The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (AAA) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 AAA patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and AAA but no significant association between MTHFR C677T polymorphism and AAA. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and AAA, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and AAA. In conclusion, HHcy is an independent risk factor of AAA in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327

Analysis of factors predicting speed of hematologic recovery after transplantation with 4-hydroperoxycyclophosphamide-purged autologous bone marrow grafts.

PubMed

Rowley, S D; Piantadosi, S; Marcellus, D C; Jones, R J; Davidson, N E; Davis, J M; Kennedy, J; Wiley, J M; Wingard, J R; Yeager, A M

1991-03-01

We previously described the predictive value of graft colony-forming units granulocyte macrophage (CFU-GM) content after 4-hydroperoxycyclophosphamide (4-HC) purging for the duration of aplasia after autologous bone marrow transplantation. Despite the uniform 4-HC concentration, we observed heterogeneity in CFU-GM survival and the kinetics of engraftment. We have now analysed patient and graft characteristics for 154 patients undergoing autologous transplantation with 4-HC purged grafts to further define this heterogeneity. Patients transplanted for the treatment of malignant lymphoma reached a peripheral blood granulocyte count of greater than 0.5 x 10(9)/l (median, 20 versus 40 days; p less than 0.001) and platelet transfusion independence (median, 30 versus 70 days; p less than 0.001) significantly faster than patients transplanted for acute non-lymphoblastic leukemia. Other diagnostic groups were intermediate. These differences were independent of graft CFU-GM content. Multiple other patient and graft factors including patient age, peripheral blood counts on day of harvest, and amounts of other hematopoietic progenitors also predicted the kinetics of engraftment in univariate and multivariate analysis. Cytomegalovirus infection during the aplastic period predicted a delay in granulocyte (p = 0.024) but not platelet recovery (p = 0.174). This analysis demonstrates that multiple patient, graft, and post-transplant factors predict the engraftment capacity of autografts, and the kinetics of engraftment with 4-HC purged grafts. The multiple predictive factors explain a significant portion of the variability in engraftment kinetics observed after transplantation with 4-HC purged autografts.

Efficacy of peripheral lidocaine application (neural therapy) in the treatment of neurogenic detrusor overactivity in multiple sclerosis patients.

PubMed

Tamam, Yusuf; Özdemir, Hasan Hüseyin; Gedik, Abdullah; Tamam, Cüneyt; Nazlıkul, Hüseyin

2017-09-01

Many agents and treatments are used in the treatment of neurogenic detrusor overactivity (NDO) in MS patients, but no study has been conducted on the use of peripheric lidocaine (neural therapy-NT) on MS patients. We evaluated the effects of local administration of lidocaine on NDO in Multiple Sclerosis (MS) patients. For each patient local anesthetic lidocaine was injected at each session. Sessions were held once a week for 5 weeks. At each session, Th 10-L1, urogenital segment intradermal injections, Frankenhauser, and sacral epidural injections were given. The patients had clinical and urodynamic assessment 1 month before and 3, 9, and 12 months after NT. In addition, multiple sclerosis quality of life inventory (MSQL-54) and bladder control scale (BLCS) was performed for patients. Twenty-eight patients were included in the study (8 males, 20 females). The patients' average age was 31.7 ± 8.1 years. The injection therapy significantly improved volume at first involuntary bladder contraction (FCV), maximal detrusor pression during filling (P det. max.), maximal cystometric bladder capacity (MCC) after 3 months. Also, the MSQL-54 and BLCS scores were improved with treatment. However, these improvements reached a maximum 3 months after treatment, but from the 9 month a regression was seen in the parameters, and after 12 months the findings were seen to be slightly above their basal levels. These results suggest that NDO treatment in MS patients could be an effective treatment which is easy and has very few side effects, and is cost effective. © 2017 Wiley Periodicals, Inc.

Correlation analyses revealed global microRNA-mRNA expression associations in human peripheral blood mononuclear cells.

PubMed

Wang, Lan; Zhu, Jiang; Deng, Fei-Yan; Wu, Long-Fei; Mo, Xing-Bo; Zhu, Xiao-Wei; Xia, Wei; Xie, Fang-Fei; He, Pei; Bing, Peng-Fei; Qiu, Ying-Hua; Lin, Xiang; Lu, Xin; Zhang, Lei; Yi, Neng-Jun; Zhang, Yong-Hong; Lei, Shu-Feng

2018-02-01

MicroRNAs (miRNAs) can regulate gene expression through binding to complementary sites in the 3'-untranslated regions of target mRNAs, which will lead to existence of correlation in expression between miRNA and mRNA. However, the miRNA-mRNA correlation patterns are complex and remain largely unclear yet. To establish the global correlation patterns in human peripheral blood mononuclear cells (PBMCs), multiple miRNA-mRNA correlation analyses and expression quantitative trait locus (eQTL) analysis were conducted in this study. We predicted and achieved 861 miRNA-mRNA pairs (65 miRNAs, 412 mRNAs) using multiple bioinformatics programs, and found global negative miRNA-mRNA correlations in PBMC from all 46 study subjects. Among the 861 pairs of correlations, 19.5% were significant (P < 0.05) and ~70% were negative. The correlation network was complex and highlighted key miRNAs/genes in PBMC. Some miRNAs, such as hsa-miR-29a, hsa-miR-148a, regulate a cluster of target genes. Some genes, e.g., TNRC6A, are regulated by multiple miRNAs. The identified genes tend to be enriched in molecular functions of DNA and RNA binding, and biological processes such as protein transport, regulation of translation and chromatin modification. The results provided a global view of the miRNA-mRNA expression correlation profile in human PBMCs, which would facilitate in-depth investigation of biological functions of key miRNAs/mRNAs and better understanding of the pathogenesis underlying PBMC-related diseases.

Maternal Blood Pressure During Pregnancy and Early Childhood Blood Pressures in the Offspring

PubMed Central

Lim, Wai-Yee; Lee, Yung-Seng; Yap, Fabian Kok-Peng; Aris, Izzudin Mohd; Ngee, Lek; Meaney, Michael; Gluckman, Peter D.; Godfrey, Keith M.; Kwek, Kenneth; Chong, Yap-Seng; Saw, Seang-Mei; Pan, An

2015-01-01

Abstract Although epidemiological studies suggest that offspring of women with preeclampsia are at increased risk to higher blood pressures and cardiovascular disease, little is known about the nature of blood pressures between the mother and her offspring. As blood pressures comprise of both pulsatile (systolic blood pressure [SBP] and pulse pressure [PP]) and stable (diastolic blood pressure [DBP]) components, and they differ between central and peripheral sites, we sought to examine maternal peripheral and central blood pressure components in relation to offspring early childhood blood pressures. A prospective birth cohort of 567 Chinese, Malay, and Indian mother–offspring with complete blood pressure information were studied. Maternal brachial artery SBP, DBP, and PP were measured at 26 to 28 weeks gestation; and central SBP and PP were estimated from radial artery waveforms. Offspring brachial artery SBP, DBP, and PP were measured at 3 years of age. Associations between continuous variables of maternal blood pressures (peripheral SBP, DBP, PP, central SBP, and PP) and offspring blood pressures (peripheral SBP, DBP, and PP) were examined using multiple linear regression with adjustment for maternal characteristics (age, education level, parity, smoking status, alcohol consumption and physical activity during pregnancy, and pre-pregnancy BMI) and offspring characteristics (sex, ethnicity, BMI, and height at 3 years of age). In the multivariate models, offspring peripheral SBP increased by 0.08 (95% confidence interval 0.00–0.17, P = 0.06) mmHg with every 1-mmHg increase in maternal central SBP, and offspring peripheral PP increased by 0.10 (0.01–0.18, P = 0.03) mmHg for every 1-mmHg increase in maternal central PP. The relations of maternal-offspring peripheral blood pressures (SBP, DBP, and PP) were positive but not statistically significant, and the corresponding values were 0.05 (−0.03 to 0.13; P = 0.21), 0.03 (−0.04 to 0.10; P = 0.35), and 0.05 (−0.02 to 0.13; P = 0.14), respectively. Maternal central pulsatile blood pressure components (SBP and PP) during pregnancy are associated with higher blood pressures in the offspring. This positive correlation is already evident at 3-years old. Studies are needed to further evaluate the effects of maternal central pulsatile blood pressure components during pregnancy and long-term cardiovascular health in the offspring. PMID:26559279

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia.

PubMed

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J; Robinson, Benjamin M; Ruffle, Abigail; Hahn, Britta; Gold, James M; Luck, Steven J

2017-04-05

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. Copyright © 2017 the authors 0270-6474/17/373813-11$15.00/0.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia

PubMed Central

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J.; Robinson, Benjamin M.; Ruffle, Abigail; Hahn, Britta; Gold, James M.

2017-01-01

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. PMID:28283557

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy.

PubMed

Ahmed, Marwan A; Muntingh, George; Rheeder, Paul

2016-10-07

The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053). Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.

A case of refractory polyarteritis nodosa successfully treated with rituximab.

PubMed

Seri, Yu; Shoda, Hirofumi; Hanata, Norio; Nagafuchi, Yasuo; Sumitomo, Shuji; Fujio, Keishi; Yamamoto, Kazuhiko

2017-07-01

A 59-year-old man who presented with continuous fever, livedo reticularis, and left leg ischemia with multiple tibial artery stenosis and renal artery aneurysm, as demonstrated by arteriography, was diagnosed with polyarteritis nodosa (PAN) 6 years ago. Although he frequently relapsed in spite of intensive immunosuppressive therapies, the disease activity of PAN was controlled with repeated rituximab (RTX) therapies and steroid doses were tapered safely. Peripheral CD19 + B-cells disappeared soon after the 1st administration of RTX. Although CD19 + B-cells remained absent, 3.1% of CD3 + CD20 + T-cells were observed in the peripheral blood prior to the 2nd administration of RTX. Recent studies have suggested the pathogenic role of CD3 + CD20 + T-cells in autoimmune diseases in the context of RTX therapy; therefore, their roles in the pathogenesis of PAN also need to be considered.

Biophysics of α-synuclein membrane interactions.

PubMed

Pfefferkorn, Candace M; Jiang, Zhiping; Lee, Jennifer C

2012-02-01

Membrane proteins participate in nearly all cellular processes; however, because of experimental limitations, their characterization lags far behind that of soluble proteins. Peripheral membrane proteins are particularly challenging to study because of their inherent propensity to adopt multiple and/or transient conformations in solution and upon membrane association. In this review, we summarize useful biophysical techniques for the study of peripheral membrane proteins and their application in the characterization of the membrane interactions of the natively unfolded and Parkinson's disease (PD) related protein, α-synuclein (α-syn). We give particular focus to studies that have led to the current understanding of membrane-bound α-syn structure and the elucidation of specific membrane properties that affect α-syn-membrane binding. Finally, we discuss biophysical evidence supporting a key role for membranes and α-syn in PD pathogenesis. This article is part of a Special Issue entitled: Membrane protein structure and function. Copyright © 2011. Published by Elsevier B.V.

Manifestations of fulminant CD8 T-cell post-transplant lymphoproliferative disorder following the administration of rituximab for lymphadenopathy with a high level of Epstein-Barr Virus (EBV) replication after allogeneic hematopoietic stem cell transplantation.

PubMed

Tanaka, Tomoyuki; Takizawa, Jun; Miyakoshi, Shukuko; Kozakai, Takashi; Fuse, Kyoko; Shibasaki, Yasuhiko; Moriyama, Masato; Ohshima, Koichi; Toba, Ken; Furukawa, Tatsuo; Sone, Hirohito; Masuko, Masayoshi

2014-01-01

We herein report the case of a 22-year-old woman with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation (HSCT). After HSCT, the Epstein-Barr virus (EBV)-DNA load in the peripheral blood gradually increased, and the patient presented with a fever and lymphadenopathy on day 56 post-HSCT. Although we administered rituximab, her clinical condition worsened. After rituximab treatment, CD8 T-cells emerged and became dominant in the peripheral blood, some of which were positive on an EBV-specific tetramer analysis. However, an open biopsy of the lymphadenopathy lesions revealed the CD8 T-cells to be infected with EBV, exhibiting proliferation with oligoclonality. The patient ultimately died of multiple organ failure on day 99 post-HSCT.

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

PubMed

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.