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Sample records for single neuron hodgkin

  1. Computation in a single neuron: Hodgkin and Huxley revisited

    OpenAIRE

    Arcas, Blaise Aguera y; Fairhall, Adrienne L.; Bialek, William

    2002-01-01

    A spiking neuron ``computes'' by transforming a complex dynamical input into a train of action potentials, or spikes. The computation performed by the neuron can be formulated as dimensional reduction, or feature detection, followed by a nonlinear decision function over the low dimensional space. Generalizations of the reverse correlation technique with white noise input provide a numerical strategy for extracting the relevant low dimensional features from experimental data, and information t...

  2. Unidirectional synchronization of Hodgkin-Huxley neurons

    International Nuclear Information System (INIS)

    Cornejo-Perez, Octavio; Femat, Ricardo

    2005-01-01

    Synchronization dynamics of two noiseless Hodgkin-Huxley (HH) neurons under the action of feedback control is studied. The spiking patterns of the action potentials evoked by periodic external modulations attain synchronization states under the feedback action. Numerical simulations for the synchronization dynamics of regular-irregular desynchronized spiking sequences are displayed. The results are discussed in context of generalized synchronization. It is also shown that the HH neurons can be synchronized in face of unmeasured states

  3. Unidirectional synchronization of Hodgkin-Huxley neurons

    Energy Technology Data Exchange (ETDEWEB)

    Cornejo-Perez, Octavio [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: octavio@ipicyt.edu.mx; Femat, Ricardo [Division de Matematicas Aplicadas y Sistemas, Computacionales, IPICYT, Apdo. Postal 3-74 Tangamanga, 78231 San Luis Potosi (Mexico)]. E-mail: rfemat@ipicyt.edu.mx

    2005-07-01

    Synchronization dynamics of two noiseless Hodgkin-Huxley (HH) neurons under the action of feedback control is studied. The spiking patterns of the action potentials evoked by periodic external modulations attain synchronization states under the feedback action. Numerical simulations for the synchronization dynamics of regular-irregular desynchronized spiking sequences are displayed. The results are discussed in context of generalized synchronization. It is also shown that the HH neurons can be synchronized in face of unmeasured states.

  4. A self-organizing state-space-model approach for parameter estimation in hodgkin-huxley-type models of single neurons.

    Directory of Open Access Journals (Sweden)

    Dimitrios V Vavoulis

    Full Text Available Traditional approaches to the problem of parameter estimation in biophysical models of neurons and neural networks usually adopt a global search algorithm (for example, an evolutionary algorithm, often in combination with a local search method (such as gradient descent in order to minimize the value of a cost function, which measures the discrepancy between various features of the available experimental data and model output. In this study, we approach the problem of parameter estimation in conductance-based models of single neurons from a different perspective. By adopting a hidden-dynamical-systems formalism, we expressed parameter estimation as an inference problem in these systems, which can then be tackled using a range of well-established statistical inference methods. The particular method we used was Kitagawa's self-organizing state-space model, which was applied on a number of Hodgkin-Huxley-type models using simulated or actual electrophysiological data. We showed that the algorithm can be used to estimate a large number of parameters, including maximal conductances, reversal potentials, kinetics of ionic currents, measurement and intrinsic noise, based on low-dimensional experimental data and sufficiently informative priors in the form of pre-defined constraints imposed on model parameters. The algorithm remained operational even when very noisy experimental data were used. Importantly, by combining the self-organizing state-space model with an adaptive sampling algorithm akin to the Covariance Matrix Adaptation Evolution Strategy, we achieved a significant reduction in the variance of parameter estimates. The algorithm did not require the explicit formulation of a cost function and it was straightforward to apply on compartmental models and multiple data sets. Overall, the proposed methodology is particularly suitable for resolving high-dimensional inference problems based on noisy electrophysiological data and, therefore, a

  5. Thermal impact on spiking properties in Hodgkin-Huxley neuron ...

    Indian Academy of Sciences (India)

    Thermal impact on spiking properties in Hodgkin-Huxley neuron with synaptic stimulus. Shenbing ... Department of Physical Science and Technology, Wuhan University of Technology, Wuhan, 430070, China; State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan, 430070, China ...

  6. Single neuron computation

    CERN Document Server

    McKenna, Thomas M; Zornetzer, Steven F

    1992-01-01

    This book contains twenty-two original contributions that provide a comprehensive overview of computational approaches to understanding a single neuron structure. The focus on cellular-level processes is twofold. From a computational neuroscience perspective, a thorough understanding of the information processing performed by single neurons leads to an understanding of circuit- and systems-level activity. From the standpoint of artificial neural networks (ANNs), a single real neuron is as complex an operational unit as an entire ANN, and formalizing the complex computations performed by real n

  7. Neuronal Synchronization of Electrical Activity, Using the Hodgkin-Huxley Model and RCLSJ Circuit

    OpenAIRE

    Diaz M, Jose A; Téquita, Oscar; Naranjo, Fernando

    2016-01-01

    We simulated the neuronal electrical activity using the Hodgkin-Huxley model (HH) and a superconductor circuit, containing Josephson junctions. These HH model make possible simulate the main neuronal dynamics characteristics such as action potentials, firing threshold and refractory period. The purpose of the manuscript is show a method to syncronize a RCLshunted Josephson junction to a neuronal dynamics represented by the HH model. Thus the RCLSJ circuit is able to mimics the behavior of the...

  8. Synchronization of two Hodgkin-Huxley neurons due to internal noise

    International Nuclear Information System (INIS)

    Casado, Jose Manuel

    2003-01-01

    It is well known that a strong coupling can synchronize a population of nonlinear oscillators. This fact has deep implications for the current understanding of information processing by the brain. The focus of this Letter is on the role of conductance noise on a system of two coupled Hodgkin-Huxley neurons in the so-called excitable region, where both neurons are at rest in the absence of noise. It is shown that, in this region, conductance noise allows the neurons to achieve both frequency and phase synchronization. This suggests that internal noise could play a role in the emergence of synchronous neural activity in populations of weakly coupled neurons

  9. Channel noise effects on first spike latency of a stochastic Hodgkin-Huxley neuron

    Science.gov (United States)

    Maisel, Brenton; Lindenberg, Katja

    2017-02-01

    While it is widely accepted that information is encoded in neurons via action potentials or spikes, it is far less understood what specific features of spiking contain encoded information. Experimental evidence has suggested that the timing of the first spike may be an energy-efficient coding mechanism that contains more neural information than subsequent spikes. Therefore, the biophysical features of neurons that underlie response latency are of considerable interest. Here we examine the effects of channel noise on the first spike latency of a Hodgkin-Huxley neuron receiving random input from many other neurons. Because the principal feature of a Hodgkin-Huxley neuron is the stochastic opening and closing of channels, the fluctuations in the number of open channels lead to fluctuations in the membrane voltage and modify the timing of the first spike. Our results show that when a neuron has a larger number of channels, (i) the occurrence of the first spike is delayed and (ii) the variation in the first spike timing is greater. We also show that the mean, median, and interquartile range of first spike latency can be accurately predicted from a simple linear regression by knowing only the number of channels in the neuron and the rate at which presynaptic neurons fire, but the standard deviation (i.e., neuronal jitter) cannot be predicted using only this information. We then compare our results to another commonly used stochastic Hodgkin-Huxley model and show that the more commonly used model overstates the first spike latency but can predict the standard deviation of first spike latencies accurately. We end by suggesting a more suitable definition for the neuronal jitter based upon our simulations and comparison of the two models.

  10. Biomechanics of single cortical neurons.

    Science.gov (United States)

    Bernick, Kristin B; Prevost, Thibault P; Suresh, Subra; Socrate, Simona

    2011-03-01

    This study presents experimental results and computational analysis of the large strain dynamic behavior of single neurons in vitro with the objective of formulating a novel quantitative framework for the biomechanics of cortical neurons. Relying on the atomic force microscopy (AFM) technique, novel testing protocols are developed to enable the characterization of neural soma deformability over a range of indentation rates spanning three orders of magnitude, 10, 1, and 0.1 μm s(-1). Modified spherical AFM probes were utilized to compress the cell bodies of neonatal rat cortical neurons in load, unload, reload and relaxation conditions. The cell response showed marked hysteretic features, strong non-linearities, and substantial time/rate dependencies. The rheological data were complemented with geometrical measurements of cell body morphology, i.e. cross-diameter and height estimates. A constitutive model, validated by the present experiments, is proposed to quantify the mechanical behavior of cortical neurons. The model aimed to correlate empirical findings with measurable degrees of (hyper)elastic resilience and viscosity at the cell level. The proposed formulation, predicated upon previous constitutive model developments undertaken at the cortical tissue level, was implemented in a three-dimensional finite element framework. The simulated cell response was calibrated to the experimental measurements under the selected test conditions, providing a novel single cell model that could form the basis for further refinements. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  11. Synchronization control of Hodgkin-Huxley neurons exposed to ELF electric field

    International Nuclear Information System (INIS)

    Che Yanqiu; Wang Jiang; Zhou Sisi; Deng Bin

    2009-01-01

    This paper presents an adaptive neural network H ∞ control for unidirectional synchronization of modified Hodgkin-Huxley (HH) neurons exposed to extremely low frequency (ELF) electric field. The proposed modified HH neurons exhibit periodic and chaotic dynamics in response to sinusoidal electric field stimulation. Based on the Lyapunov stability theory, we derive the updated laws of neural network for approximating the nonlinear uncertain functions of the error dynamical system. The H ∞ design technique makes the controller robust to unmodeled dynamics, disturbances and approximate errors. The proposed controller not only ensures closed-loop stability, but also guarantees an H ∞ performance for the synchronization error system. The states of the controlled slave system exponentially synchronize with that of the master one after control. The simulation results demonstrate the validity of the proposed method.

  12. Homoclinic bifurcation in a Hodgkin-Huxley model of thermally sensitive neurons

    International Nuclear Information System (INIS)

    Feudel, Ulrike; Neiman, Alexander; Pei, Xing; Wojtenek, Winfried; Braun, Hans; Huber, Martin; Moss, Frank

    2000-01-01

    We study global bifurcations of the chaotic attractor in a modified Hodgkin-Huxley model of thermally sensitive neurons. The control parameter for this model is the temperature. The chaotic behavior is realized over a wide range of temperatures and is visualized using interspike intervals. We observe an abrupt increase of the interspike intervals in a certain temperature region. We identify this as a homoclinic bifurcation of a saddle-focus fixed point which is embedded in the chaotic attractors. The transition is accompanied by intermittency, which obeys a universal scaling law for the average length of trajectory segments exhibiting only short interspike intervals with the distance from the onset of intermittency. We also present experimental results of interspike interval measurements taken from the crayfish caudal photoreceptor, which qualitatively demonstrate the same bifurcation structure. (c) 2000 American Institute of Physics

  13. Homoclinic bifurcation in a Hodgkin-Huxley model of thermally sensitive neurons

    Energy Technology Data Exchange (ETDEWEB)

    Feudel, Ulrike [Department of Physics, University of Potsdam, Potsdam 14415, (Germany); Neiman, Alexander [Center for Neurodynamics, University of Missouri at St. Louis, St. Louis, Missouri 63121 (United States); Pei, Xing [Center for Neurodynamics, University of Missouri at St. Louis, St. Louis, Missouri 63121 (United States); Wojtenek, Winfried [Center for Neurodynamics, University of Missouri at St. Louis, St. Louis, Missouri 63121 (United States); Braun, Hans [Institute of Physiology, University of Marburg, Marburg 35037, (Germany); Huber, Martin [Institute of Physiology, University of Marburg, Marburg 35037, (Germany); Moss, Frank [Center for Neurodynamics, University of Missouri at St. Louis, St. Louis, Missouri 63121 (United States)

    2000-03-01

    We study global bifurcations of the chaotic attractor in a modified Hodgkin-Huxley model of thermally sensitive neurons. The control parameter for this model is the temperature. The chaotic behavior is realized over a wide range of temperatures and is visualized using interspike intervals. We observe an abrupt increase of the interspike intervals in a certain temperature region. We identify this as a homoclinic bifurcation of a saddle-focus fixed point which is embedded in the chaotic attractors. The transition is accompanied by intermittency, which obeys a universal scaling law for the average length of trajectory segments exhibiting only short interspike intervals with the distance from the onset of intermittency. We also present experimental results of interspike interval measurements taken from the crayfish caudal photoreceptor, which qualitatively demonstrate the same bifurcation structure. (c) 2000 American Institute of Physics.

  14. Stochastic differential equation models for ion channel noise in Hodgkin-Huxley neurons

    Science.gov (United States)

    Goldwyn, Joshua H.; Imennov, Nikita S.; Famulare, Michael; Shea-Brown, Eric

    2011-04-01

    The random transitions of ion channels between conducting and nonconducting states generate a source of internal fluctuations in a neuron, known as channel noise. The standard method for modeling the states of ion channels nonlinearly couples continuous-time Markov chains to a differential equation for voltage. Beginning with the work of R. F. Fox and Y.-N. Lu [Phys. Rev. EMTHDE91539-375510.1103/PhysRevE.49.3421 49, 3421 (1994)], there have been attempts to generate simpler models that use stochastic differential equation (SDEs) to approximate the stochastic spiking activity produced by Markov chain models. Recent numerical investigations, however, have raised doubts that SDE models can capture the stochastic dynamics of Markov chain models.We analyze three SDE models that have been proposed as approximations to the Markov chain model: one that describes the states of the ion channels and two that describe the states of the ion channel subunits. We show that the former channel-based approach can capture the distribution of channel noise and its effects on spiking in a Hodgkin-Huxley neuron model to a degree not previously demonstrated, but the latter two subunit-based approaches cannot. Our analysis provides intuitive and mathematical explanations for why this is the case. The temporal correlation in the channel noise is determined by the combinatorics of bundling subunits into channels, but the subunit-based approaches do not correctly account for this structure. Our study confirms and elucidates the findings of previous numerical investigations of subunit-based SDE models. Moreover, it presents evidence that Markov chain models of the nonlinear, stochastic dynamics of neural membranes can be accurately approximated by SDEs. This finding opens a door to future modeling work using SDE techniques to further illuminate the effects of ion channel fluctuations on electrically active cells.

  15. Hodgkin's Lymphoma

    Science.gov (United States)

    Hodgkin's lymphoma (Hodgkin's disease) Overview Hodgkin's lymphoma — formerly known as Hodgkin's disease — is a cancer of the lymphatic system, which ... prognosis continues to improve for people with Hodgkin's lymphoma. Hodgkin's lymphoma care at Mayo Clinic Symptoms Signs and ...

  16. Optimal size of stochastic Hodgkin-Huxley neuronal systems for maximal energy efficiency in coding pulse signals.

    Science.gov (United States)

    Yu, Lianchun; Liu, Liwei

    2014-03-01

    The generation and conduction of action potentials (APs) represents a fundamental means of communication in the nervous system and is a metabolically expensive process. In this paper, we investigate the energy efficiency of neural systems in transferring pulse signals with APs. By analytically solving a bistable neuron model that mimics the AP generation with a particle crossing the barrier of a double well, we find the optimal number of ion channels that maximizes the energy efficiency of a neuron. We also investigate the energy efficiency of a neuron population in which the input pulse signals are represented with synchronized spikes and read out with a downstream coincidence detector neuron. We find an optimal number of neurons in neuron population, as well as the number of ion channels in each neuron that maximizes the energy efficiency. The energy efficiency also depends on the characters of the input signals, e.g., the pulse strength and the interpulse intervals. These results are confirmed by computer simulation of the stochastic Hodgkin-Huxley model with a detailed description of the ion channel random gating. We argue that the tradeoff between signal transmission reliability and energy cost may influence the size of the neural systems when energy use is constrained.

  17. Current Source Density Estimation for Single Neurons

    Directory of Open Access Journals (Sweden)

    Dorottya Cserpán

    2014-03-01

    Full Text Available Recent developments of multielectrode technology made it possible to measure the extracellular potential generated in the neural tissue with spatial precision on the order of tens of micrometers and on submillisecond time scale. Combining such measurements with imaging of single neurons within the studied tissue opens up new experimental possibilities for estimating distribution of current sources along a dendritic tree. In this work we show that if we are able to relate part of the recording of extracellular potential to a specific cell of known morphology we can estimate the spatiotemporal distribution of transmembrane currents along it. We present here an extension of the kernel CSD method (Potworowski et al., 2012 applicable in such case. We test it on several model neurons of progressively complicated morphologies from ball-and-stick to realistic, up to analysis of simulated neuron activity embedded in a substantial working network (Traub et al, 2005. We discuss the caveats and possibilities of this new approach.

  18. Non-Hodgkin's lymphoma presenting as a single liver mass; Linfoma nao-Hodgkin apresentando-se como massa hepatica unica

    Energy Technology Data Exchange (ETDEWEB)

    Peixoto, Mila Correia Gois; Peixoto Filho, Anibal Araujo Alves; D' Ippolito, Giuseppe [Hospital Sao Luiz, Sao Paulo, SP (Brazil). Setor de US/TC/RM]. E-mail: scoposl@uol.com.br; Ribeiro, Alessandra Caivano Rodrigues [Hospital Sao Luiz, Sao Paulo, SP (Brazil). Setor de Diagnostico por Imagem

    2009-01-15

    Objective: to describe the main imaging findings of non-Hodgkin's lymphoma presenting as a single liver mass. Materials and methods: a retrospective study was developed with analysis of cases where a single liver mass was observed at ultrasonography, computed tomography and magnetic resonance imaging, and histologically diagnosed as non-Hodgkin's lymphoma. The studies were reviewed by two observers in consensus. Results: three male patients in the fifth decade of life, with non-specific clinical manifestations and single liver mass diagnosed as non-Hodgkin's lymphoma were identified. A hepatic lesion with target sign was observed at ultrasonography in all of the cases. At computed tomography, all the patients presented a heterogeneous, hypodense mass with a ring enhancement. At magnetic resonance imaging, the lesions were heterogeneous and hypointense on T1-weighted and hyperintense on T2-weighted images. Additionally, a ring enhancement was observed in all of the cases after contrast injection. At the moment of the diagnosis, none of the patients presented lymphadenomegaly or involvement of other solid viscera. Conclusion: the diagnosis of hepatic lymphoma should be considered in the presence of a ring-enhanced single liver mass. (author)

  19. Membrane capacitive memory alters spiking in neurons described by the fractional-order Hodgkin-Huxley model.

    Directory of Open Access Journals (Sweden)

    Seth H Weinberg

    Full Text Available Excitable cells and cell membranes are often modeled by the simple yet elegant parallel resistor-capacitor circuit. However, studies have shown that the passive properties of membranes may be more appropriately modeled with a non-ideal capacitor, in which the current-voltage relationship is given by a fractional-order derivative. Fractional-order membrane potential dynamics introduce capacitive memory effects, i.e., dynamics are influenced by a weighted sum of the membrane potential prior history. However, it is not clear to what extent fractional-order dynamics may alter the properties of active excitable cells. In this study, we investigate the spiking properties of the neuronal membrane patch, nerve axon, and neural networks described by the fractional-order Hodgkin-Huxley neuron model. We find that in the membrane patch model, as fractional-order decreases, i.e., a greater influence of membrane potential memory, peak sodium and potassium currents are altered, and spike frequency and amplitude are generally reduced. In the nerve axon, the velocity of spike propagation increases as fractional-order decreases, while in a neural network, electrical activity is more likely to cease for smaller fractional-order. Importantly, we demonstrate that the modulation of the peak ionic currents that occurs for reduced fractional-order alone fails to reproduce many of the key alterations in spiking properties, suggesting that membrane capacitive memory and fractional-order membrane potential dynamics are important and necessary to reproduce neuronal electrical activity.

  20. Membrane capacitive memory alters spiking in neurons described by the fractional-order Hodgkin-Huxley model.

    Science.gov (United States)

    Weinberg, Seth H

    2015-01-01

    Excitable cells and cell membranes are often modeled by the simple yet elegant parallel resistor-capacitor circuit. However, studies have shown that the passive properties of membranes may be more appropriately modeled with a non-ideal capacitor, in which the current-voltage relationship is given by a fractional-order derivative. Fractional-order membrane potential dynamics introduce capacitive memory effects, i.e., dynamics are influenced by a weighted sum of the membrane potential prior history. However, it is not clear to what extent fractional-order dynamics may alter the properties of active excitable cells. In this study, we investigate the spiking properties of the neuronal membrane patch, nerve axon, and neural networks described by the fractional-order Hodgkin-Huxley neuron model. We find that in the membrane patch model, as fractional-order decreases, i.e., a greater influence of membrane potential memory, peak sodium and potassium currents are altered, and spike frequency and amplitude are generally reduced. In the nerve axon, the velocity of spike propagation increases as fractional-order decreases, while in a neural network, electrical activity is more likely to cease for smaller fractional-order. Importantly, we demonstrate that the modulation of the peak ionic currents that occurs for reduced fractional-order alone fails to reproduce many of the key alterations in spiking properties, suggesting that membrane capacitive memory and fractional-order membrane potential dynamics are important and necessary to reproduce neuronal electrical activity.

  1. Sincronización de la actividad eléctrica neuronal, utilizando el modelo de Hodgkin-Huxley y el circuito RCLSJ

    OpenAIRE

    Diaz M, Jose A; Téquita, Oscar; Naranjo, Fernando

    2016-01-01

    Simulamos la actividad eléctrica neuronal mediante el modelo de Hodgkin-Huxley (HH) y un circuito superconductor, que contiene uniones Josephson. El modelo HH simulan las características principales de la dinámica neuronal tales como potenciales de acción, umbrales de disparo y el períodos refractarios. El propósito del manuscrito es mostrar un método para sincronizar un circuito con union Josephson RCLSJ a una dinámica neuronal representado por el modelo HH. Así, el circuito RCLSJ es capaz d...

  2. Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy

    DEFF Research Database (Denmark)

    Specht, L; Nordentoft, A M; Cold, Søren

    1987-01-01

    One hundred and forty-two patients with Hodgkin's disease PS I or II were treated with total or subtotal nodal irradiation as part of a prospective randomized trial in the Danish National Hodgkin Study during the period 1971-83. They were followed till death or--at the time of this analysis......--from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival...

  3. Linfoma não-Hodgkin apresentando-se como massa hepática única Non-Hodgkin's lymphoma presenting as a single liver mass

    Directory of Open Access Journals (Sweden)

    Mila Correia Góis Peixoto

    2009-02-01

    Full Text Available OBJETIVO: Descrever as principais características de imagem do linfoma não-Hodgkin apresentando-se como massa hepática única. MATERIAIS E MÉTODOS: Realizamos estudo retrospectivo mediante análise de casos de pacientes com massa hepática única aos exames de ultrassonografia, tomografia computadorizada e ressonância magnética, com diagnóstico histológico de linfoma não-Hodgkin. Esses exames foram analisados por dois examinadores em consenso. RESULTADOS: Identificamos três pacientes, todos do sexo masculino, na quinta década de vida, com quadro clínico inespecífico e que apresentavam massa hepática única e com diagnóstico de linfoma não-Hodgkin. Na ultrassonografia a lesão hepática apresentava-se como massa com aspecto "em alvo" nos três casos estudados. Na tomografia computadorizada observou-se massa hipodensa e heterogênea, com realce anelar em todos os casos. Na ressonância magnética as lesões apresentavam-se heterogêneas, hipointensas em T1 e hiperintensas em T2, e também com realce anelar após a injeção do contraste. Nenhum paciente apresentava linfonodomegalia ou comprometimento de outras vísceras sólidas no momento do diagnóstico. CONCLUSÃO: Na presença de massa hepática solitária e com aspecto "em alvo" deve-se considerar, entre as hipóteses, o diagnóstico de linfoma.OBJECTIVE: To describe the main imaging findings of non-Hodgkin's lymphoma presenting as a single liver mass. MATERIALS AND METHODS: A retrospective study was developed with analysis of cases where a single liver mass was observed at ultrasonography, computed tomography and magnetic resonance imaging, and histologically diagnosed as non-Hodgkin's lymphoma. The studies were reviewed by two observers in consensus. RESULTS: Three male patients in the fifth decade of life, with non-specific clinical manifestations and single liver mass diagnosed as non-Hodgkin's lymphoma were identified. A hepatic lesion with target sign was observed at

  4. Teaching and learning the Hodgkin-Huxley model based on software developed in NEURON's programming language hoc.

    Science.gov (United States)

    Hernández, Oscar E; Zurek, Eduardo E

    2013-05-15

    We present a software tool called SENB, which allows the geometric and biophysical neuronal properties in a simple computational model of a Hodgkin-Huxley (HH) axon to be changed. The aim of this work is to develop a didactic and easy-to-use computational tool in the NEURON simulation environment, which allows graphical visualization of both the passive and active conduction parameters and the geometric characteristics of a cylindrical axon with HH properties. The SENB software offers several advantages for teaching and learning electrophysiology. First, SENB offers ease and flexibility in determining the number of stimuli. Second, SENB allows immediate and simultaneous visualization, in the same window and time frame, of the evolution of the electrophysiological variables. Third, SENB calculates parameters such as time and space constants, stimuli frequency, cellular area and volume, sodium and potassium equilibrium potentials, and propagation velocity of the action potentials. Furthermore, it allows the user to see all this information immediately in the main window. Finally, with just one click SENB can save an image of the main window as evidence. The SENB software is didactic and versatile, and can be used to improve and facilitate the teaching and learning of the underlying mechanisms in the electrical activity of an axon using the biophysical properties of the squid giant axon.

  5. Discrimination of communication vocalizations by single neurons and groups of neurons in the auditory midbrain.

    Science.gov (United States)

    Schneider, David M; Woolley, Sarah M N

    2010-06-01

    Many social animals including songbirds use communication vocalizations for individual recognition. The perception of vocalizations depends on the encoding of complex sounds by neurons in the ascending auditory system, each of which is tuned to a particular subset of acoustic features. Here, we examined how well the responses of single auditory neurons could be used to discriminate among bird songs and we compared discriminability to spectrotemporal tuning. We then used biologically realistic models of pooled neural responses to test whether the responses of groups of neurons discriminated among songs better than the responses of single neurons and whether discrimination by groups of neurons was related to spectrotemporal tuning and trial-to-trial response variability. The responses of single auditory midbrain neurons could be used to discriminate among vocalizations with a wide range of abilities, ranging from chance to 100%. The ability to discriminate among songs using single neuron responses was not correlated with spectrotemporal tuning. Pooling the responses of pairs of neurons generally led to better discrimination than the average of the two inputs and the most discriminating input. Pooling the responses of three to five single neurons continued to improve neural discrimination. The increase in discriminability was largest for groups of neurons with similar spectrotemporal tuning. Further, we found that groups of neurons with correlated spike trains achieved the largest gains in discriminability. We simulated neurons with varying levels of temporal precision and measured the discriminability of responses from single simulated neurons and groups of simulated neurons. Simulated neurons with biologically observed levels of temporal precision benefited more from pooling correlated inputs than did neurons with highly precise or imprecise spike trains. These findings suggest that pooling correlated neural responses with the levels of precision observed in the

  6. Effects of dynamic synapses on noise-delayed response latency of a single neuron

    Science.gov (United States)

    Uzuntarla, M.; Ozer, M.; Ileri, U.; Calim, A.; Torres, J. J.

    2015-12-01

    The noise-delayed decay (NDD) phenomenon emerges when the first-spike latency of a periodically forced stochastic neuron exhibits a maximum for a particular range of noise intensity. Here, we investigate the latency response dynamics of a single Hodgkin-Huxley neuron that is subject to both a suprathreshold periodic stimulus and a background activity arriving through dynamic synapses. We study the first-spike latency response as a function of the presynaptic firing rate f . This constitutes a more realistic scenario than previous works, since f provides a suitable biophysically realistic parameter to control the level of activity in actual neural systems. We first report on the emergence of classical NDD behavior as a function of f for the limit of static synapses. Second, we show that when short-term depression and facilitation mechanisms are included at the synapses, different NDD features can be found due to their modulatory effect on synaptic current fluctuations. For example, an intriguing double NDD (DNDD) behavior occurs for different sets of relevant synaptic parameters. Moreover, depending on the balance between synaptic depression and synaptic facilitation, single NDD or DNDD can prevail, in such a way that synaptic facilitation favors the emergence of DNDD whereas synaptic depression favors the existence of single NDD. Here we report the existence of the DNDD effect in the response latency dynamics of a neuron.

  7. Stochastic differential equation models for ion channel noise in Hodgkin-Huxley neurons

    OpenAIRE

    Goldwyn, Joshua H.; Imennov, Nikita S.; Famulare, Michael; Shea-Brown, Eric

    2011-01-01

    The random transitions of ion channels between conducting and nonconducting states generate a source of internal fluctuations in a neuron, known as channel noise. The standard method for modeling the states of ion channels nonlinearly couples continuous-time Markov chains to a differential equation for voltage. Beginning with the work of R. F. Fox and Y.-N. Lu [Phys. Rev. E 49, 3421 (1994)], there have been attempts to generate simpler models that use stochastic differential equation (SDEs) t...

  8. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  9. Single neuron dynamics during experimentally induced anoxic depolarization

    NARCIS (Netherlands)

    Zandt, B.; Stigen, Tyler; ten Haken, Bernard; Netoff, Theoden; van Putten, Michel Johannes Antonius Maria

    2013-01-01

    We studied single neuron dynamics during anoxic depolarizations, which are often observed in cases of neuronal energy depletion. Anoxic and similar depolarizations play an important role in several pathologies, notably stroke, migraine, and epilepsy. One of the effects of energy depletion was

  10. Training a Single Sigmoidal Neuron is Hard

    Czech Academy of Sciences Publication Activity Database

    Šíma, Jiří

    2002-01-01

    Roč. 14, č. 11 (2002), s. 2709-2729 ISSN 0899-7667 R&D Projects: GA MŠk LN00A056 Keywords : sigmoidal neuron * loading problem * NP-hardness Subject RIV: BA - General Mathematics Impact factor: 2.313, year: 2002

  11. Neural Plasticity: Single Neuron Models for Discrimination and Generalization and an Experimental Ensemble Approach.

    Science.gov (United States)

    1983-06-01

    in pamp/cm has been computed by Agin (1964) from the equations of Hodgkin and Huxley (1952) to give the response frequency (pulses/sec) of an axon...J.- Y . (1981) lumunocytochem- ical localization of glutamic acid decarboxylase in monkey striate cortex. Nature2i2.: 605-607. Hodgkin . A. L. and...used to express the output y of a neuron to its inputs zi (1). The coefficients ei i_____i___i __ i_______’____’_____,________’__’___"___i 10 are the

  12. Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    Science.gov (United States)

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-07-01

    The purpose of this study was to demonstrate how single cell quantitative and subcellular metallomics inform us about both the spatial distribution and cellular mechanisms of metal buffering and homeostasis in primary cultured neurons from embryonic rat brain, which are often used as models of human disease involving metal dyshomeostasis. The present studies utilized synchrotron radiation X-ray fluorescence (SRXRF) and focused primarily on zinc and iron, two abundant metals in neurons that have been implicated in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Total single cell contents for calcium, iron, zinc, copper, manganese, and nickel were determined. Resting steady state zinc showed a diffuse distribution in both soma and processes, best defined by the mass profile of the neuron with an enrichment in the nucleus compared with the cytoplasm. Zinc buffering and homeostasis was studied using two modes of cellular zinc loading - transporter and ionophore (pyrithione) mediated. Single neuron zinc contents were shown to statistically significantly increase by either loading method - ionophore: 160 million to 7 billion; transporter 160 million to 280 million atoms per neuronal soma. The newly acquired and buffered zinc still showed a diffuse distribution. Soma and processes have about equal abilities to take up zinc via transporter mediated pathways. Copper levels are distributed diffusely as well, but are relatively higher in the processes relative to zinc levels. Prior studies have observed iron puncta in certain cell types, but others have not. In the present study, iron puncta were characterized in several primary neuronal types. The results show that iron puncta could be found in all neuronal types studied and can account for up to 50% of the total steady state content of iron in neuronal soma. Although other metals can be present in iron puncta, they are predominantly iron containing and do not appear to be

  13. Stochastic models for spike trains of single neurons

    CERN Document Server

    Sampath, G

    1977-01-01

    1 Some basic neurophysiology 4 The neuron 1. 1 4 1. 1. 1 The axon 7 1. 1. 2 The synapse 9 12 1. 1. 3 The soma 1. 1. 4 The dendrites 13 13 1. 2 Types of neurons 2 Signals in the nervous system 14 2. 1 Action potentials as point events - point processes in the nervous system 15 18 2. 2 Spontaneous activi~ in neurons 3 Stochastic modelling of single neuron spike trains 19 3. 1 Characteristics of a neuron spike train 19 3. 2 The mathematical neuron 23 4 Superposition models 26 4. 1 superposition of renewal processes 26 4. 2 Superposition of stationary point processe- limiting behaviour 34 4. 2. 1 Palm functions 35 4. 2. 2 Asymptotic behaviour of n stationary point processes superposed 36 4. 3 Superposition models of neuron spike trains 37 4. 3. 1 Model 4. 1 39 4. 3. 2 Model 4. 2 - A superposition model with 40 two input channels 40 4. 3. 3 Model 4. 3 4. 4 Discussion 41 43 5 Deletion models 5. 1 Deletion models with 1nd~endent interaction of excitatory and inhibitory sequences 44 VI 5. 1. 1 Model 5. 1 The basic de...

  14. Parameter estimation in neuronal stochastic differential equation models from intracellular recordings of membrane potentials in single neurons

    DEFF Research Database (Denmark)

    Ditlevsen, Susanne; Samson, Adeline

    2016-01-01

    Dynamics of the membrane potential in a single neuron can be studied by estimating biophysical parameters from intracellular recordings. Diffusion processes, given as continuous solutions to stochastic differential equations, are widely applied as models for the neuronal membrane potential evolut...

  15. Responses of single neurons and neuronal ensembles in frog first- and second-order olfactory neurons

    Czech Academy of Sciences Publication Activity Database

    Rospars, J. P.; Šanda, Pavel; Lánský, Petr; Duchamp-Viret, P.

    2013-01-01

    Roč. 1536, NOV 6 (2013), s. 144-158 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GBP304/12/G069; GA ČR(CZ) GAP103/11/0282 Institutional support: RVO:67985823 Keywords : olfaction * spiking activity * neuronal model Subject RIV: JD - Computer Applications, Robotics Impact factor: 2.828, year: 2013

  16. Stimulus-response functions of single avian olfactory bulb neurones.

    Science.gov (United States)

    McKeegan, Dorothy E F; Demmers, Theodorus G M; Wathes, Christopher M; Jones, R Bryan; Gentle, Michael J

    2002-10-25

    This study investigated olfactory processing in a functional context by examining the responses of single avian olfactory bulb neurones to two biologically important gases over relevant concentration ranges. Recordings of extracellular spike activity were made from 80 single units in the left olfactory bulb of 11 anaesthetised, freely breathing adult hens (Gallus domesticus). The units were spontaneously active, exhibiting widely variable firing rates (0.07-47.28 spikes/s) and variable temporal firing patterns. Single units were tested for their response to an ascending concentration series of either ammonia (2.5-100 ppm) or hydrogen sulphide (1-50 ppm), delivered directly to the olfactory epithelium. Stimulation with a calibrated gas delivery system resulted in modification of spontaneous activity causing either inhibition (47% of units) or excitation (53%) of firing. For ammonia, 20 of the 35 units tested exhibited a response, while for hydrogen sulphide, 25 of the 45 units tested were responsive. Approximate response thresholds for ammonia (median threshold 3.75 ppm (range 2.5-60 ppm, n=20)) and hydrogen sulphide (median threshold 1 ppm (range 1-10 ppm, n=25)) were determined with most units exhibiting thresholds near the lower end of these ranges. Stimulus response curves were constructed for 23 units; 16 (the most complete) were subjected to a linear regression analysis to determine whether they were best fitted by a linear, log or power function. No single function provided the best fit for all the curves (seven were linear, eight were log, one was power). These findings show that avian units respond to changes in stimulus concentration in a manner generally consistent with reported responses in mammalian olfactory bulb neurones. However, this study illustrates a level of fine-tuning to small step changes in concentration (<5 ppm) not previously demonstrated in vertebrate single olfactory bulb neurones.

  17. Comparison of current-driven and conductance-driven neocortical model neurons with Hodgkin-Huxley voltage-gated channels.

    Science.gov (United States)

    Tiesinga, P H; José, J V; Sejnowski, T J

    2000-12-01

    Intrinsic noise and random synaptic inputs generate a fluctuating current across neuron membranes. We determine the statistics of the output spike train of a biophysical model neuron as a function of the mean and variance of the fluctuating current, when the current is white noise, or when it derives from Poisson trains of excitatory and inhibitory postsynaptic conductances. In the first case, the firing rate increases with increasing variance of the current, whereas in the latter case it decreases. In contrast, the firing rate is independent of variance (for constant mean) in the commonly used random walk, and perfect integrate-and-fire models for spike generation. The model neuron can be in the current-dominated state, representative of neurons in the in vitro slice preparation, or in the fluctuation-dominated state, representative of in vivo neurons. We discuss the functional relevance of these states to cortical information processing.

  18. Non-Hodgkin's Lymphoma

    Science.gov (United States)

    ... more common than the other general type of lymphoma — Hodgkin lymphoma. Many different subtypes of non-Hodgkin's lymphoma ... helps to determine your treatment options. Where non-Hodgkin's lymphoma occurs Non-Hodgkin's lymphoma generally involves the presence ...

  19. Hodgkin Lymphoma (For Teens)

    Science.gov (United States)

    ... check for disease, including lymphoma. What Is Hodgkin Lymphoma? Hodgkin lymphoma is a type of cancer called a ... they are divided into two broad categories: Hodgkin lymphoma and non-Hodgkin lymphoma. Lymphomas that involve a particular type of ...

  20. Single-Incision Pediatric Endosurgery (SIPES oophoropexy in an adolescent with Hodgkin lymphoma prior to pelvic irradiation

    Directory of Open Access Journals (Sweden)

    Aaron D. Seims

    2015-07-01

    Full Text Available Oophoropexy for fertility preservation during pelvic irradiation dates back to the mid-1960s. For Hodgkin lymphoma (HL, this was performed during a staging laparotomy. Laparoscopic ovarian fixation has supplanted open pexy with advancements in technology and abandonment of staging laparotomies. Single-Incision Pediatric Endosurgery (SIPES is applicable to numerous multi-port operations. Use of this technique for oophoropexy prior to pelvic irradiation, however, has not been reported. A 19 year-old with stage IVb HL involving the left iliac node basin was to receive radiotherapy and was evaluated for bilateral oophoropexy. An Olympus TriPort™ was introduced at the umbilicus, through which a 5 mm zero-degree laparoscope and a needle driver were introduced. Transabdominal passage of a ski needle through a 2 mm nick in the skin of the anterolateral wall allowed for right sided fixation of the ovaries. Operative recovery was uncomplicated, and post-operative imaging demonstrated satisfactory positioning of the gonads outside the planned radiation field. In conclusion, SIPES oophoropexy is a technically simple method for fertility preservation that offers improved cosmesis.

  1. Spiking irregularity and frequency modulate the behavioral report of single-neuron stimulation.

    Science.gov (United States)

    Doron, Guy; von Heimendahl, Moritz; Schlattmann, Peter; Houweling, Arthur R; Brecht, Michael

    2014-02-05

    The action potential activity of single cortical neurons can evoke measurable sensory effects, but it is not known how spiking parameters and neuronal subtypes affect the evoked sensations. Here, we examined the effects of spike train irregularity, spike frequency, and spike number on the detectability of single-neuron stimulation in rat somatosensory cortex. For regular-spiking, putative excitatory neurons, detectability increased with spike train irregularity and decreasing spike frequencies but was not affected by spike number. Stimulation of single, fast-spiking, putative inhibitory neurons led to a larger sensory effect compared to regular-spiking neurons, and the effect size depended only on spike irregularity. An ideal-observer analysis suggests that, under our experimental conditions, rats were using integration windows of a few hundred milliseconds or more. Our data imply that the behaving animal is sensitive to single neurons' spikes and even to their temporal patterning. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Clinical manifestations of autoimmune disease-related non-Hodgkin lymphoma: a Korean single-center, retrospective clinical study.

    Science.gov (United States)

    Jeon, Young-Woo; Yoon, Jae-Ho; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Kim, Hee-Je; Lee, Seok; Min, Chang-Ki; Lee, Jong Wook; Min, Woo-Sung; Cho, Seok-Goo

    2016-09-01

    Recently, large cohort studies regarding associations between autoimmune disease and lymphomas have been reported in a few Western countries. However, Asian data concerning autoimmune-related lymphomas are limited. Therefore, we evaluated the clinical characteristics and prognostic factors of patients with autoimmune disease-related non-Hodgkin lymphoma (NHL) in a single center in Korea. We analyzed the data from 11 patients with autoimmune-related NHL. Patients were categorized into two groups, those with rheumatoid arthritis (RA) and those with non-RA-related NHL. Then patients were re-categorized into a group with methotrexate (MTX) usage and a MTX non-usage group. Histological subtype, MTX duration, autoimmune disease duration, treatment modalities, and other data were collected and analyzed. Our study revealed that older RA patients have a greater likelihood of occurrence of NHL (p = 0.042). We confirmed that MTX duration and cumulative dose of MTX have no significant correlation with autoimmune disease and NHL (p = 0.073). In the management of autoimmune disease-related NHL, all patients were directly treated with systemic chemotherapy instead of employing a wait and watch approach. Overall survival (OS) and progression-free survival (PFS) in all autoimmune disease-related NHL were 100% and 87.5%, with no treatment-related mortality during the 2-year follow-up period of our study. Our study suggests that patients with RA-NHL are characterized by older age at onset compared to those with non-RA-NHL. Also considering of OS and PFS, intensive treatment strategy instead of delayed watchful managements may be required for autoimmune disease-related NHL including of old age group.

  3. Rituximab for the first-line maintenance treatment of follicular non-Hodgkin's lymphoma : a NICE single technology appraisal.

    Science.gov (United States)

    Greenhalgh, Janette; Bagust, Adrian; Boland, Angela; Blundell, Michaela; Oyee, James; Beale, Sophie; Dundar, Yenal; Hockenhull, Juliet; Proudlove, Chris; Chu, Patrick

    2013-05-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.

  4. Deep learning and shapes similarity for joint segmentation and tracing single neurons in SEM images

    Science.gov (United States)

    Rao, Qiang; Xiao, Chi; Han, Hua; Chen, Xi; Shen, Lijun; Xie, Qiwei

    2017-02-01

    Extracting the structure of single neurons is critical for understanding how they function within the neural circuits. Recent developments in microscopy techniques, and the widely recognized need for openness and standardization provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. In order to look into the fine structure of neurons, we use the Automated Tape-collecting Ultra Microtome Scanning Electron Microscopy (ATUM-SEM) to get images sequence of serial sections of animal brain tissue that densely packed with neurons. Different from other neuron reconstruction method, we propose a method that enhances the SEM images by detecting the neuronal membranes with deep convolutional neural network (DCNN) and segments single neurons by active contour with group shape similarity. We joint the segmentation and tracing together and they interact with each other by alternate iteration that tracing aids the selection of candidate region patch for active contour segmentation while the segmentation provides the neuron geometrical features which improve the robustness of tracing. The tracing model mainly relies on the neuron geometrical features and is updated after neuron being segmented on the every next section. Our method enables the reconstruction of neurons of the drosophila mushroom body which is cut to serial sections and imaged under SEM. Our method provides an elementary step for the whole reconstruction of neuronal networks.

  5. Reward-timing-dependent bidirectional modulation of cortical microcircuits during optical single-neuron operant conditioning.

    Science.gov (United States)

    Hira, Riichiro; Ohkubo, Fuki; Masamizu, Yoshito; Ohkura, Masamichi; Nakai, Junichi; Okada, Takashi; Matsuzaki, Masanori

    2014-11-24

    Animals rapidly adapt to environmental change. To reveal how cortical microcircuits are rapidly reorganized when an animal recognizes novel reward contingency, we conduct two-photon calcium imaging of layer 2/3 motor cortex neurons in mice and simultaneously reinforce the activity of a single cortical neuron with water delivery. Here we show that when the target neuron is not relevant to a pre-trained forelimb movement, the mouse increases the target neuron activity and the number of rewards delivered during 15-min operant conditioning without changing forelimb movement behaviour. The reinforcement bidirectionally modulates the activity of subsets of non-target neurons, independent of distance from the target neuron. The bidirectional modulation depends on the relative timing between the reward delivery and the neuronal activity, and is recreated by pairing reward delivery and photoactivation of a subset of neurons. Reward-timing-dependent bidirectional modulation may be one of the fundamental processes in microcircuit reorganization for rapid adaptation.

  6. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    Science.gov (United States)

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  7. Zooming Out of Single Neurons Reveals Structure in Mnemonic Representations.

    Science.gov (United States)

    Jazayeri, Mehrdad

    2017-12-20

    In this issue of Neuron, Rossi-Pool et al. (2017) show that the complex and heterogeneous response profiles of individual neurons in the dorsal premotor cortex during comparison of tactile temporal patterns can be understood in terms of two robust activity patterns that emerge across the population. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Hodgkin lymphoma - children

    Science.gov (United States)

    ... children; Hodgkin disease - children; Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... of cancer is unknown. But, certain factors may play a role in ... Common early childhood infections also may increase the risk.

  9. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    Full Text Available The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC, plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat.

  10. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

    Directory of Open Access Journals (Sweden)

    Julia P Brandt

    Full Text Available Many animals possess neurons specialized for the detection of carbon dioxide (CO(2, which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2. The ETS-5 transcription factor is necessary for the specification of CO(2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2-detection and transforms neurons into CO(2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2-sensing neurons in other phyla.

  11. Binaural response characteristics of single neurons in the medial superior olivary nucleus of the albino rat.

    Science.gov (United States)

    Inbody, S B; Feng, A S

    1981-04-06

    Binaural response properties of single neurons in the medial superior olivary nucleus (MSO) were investigated in the anesthetized rat. Stimulus parameters studied included interaural time difference and interaural intensity difference. In the present study, of the two cell types observed in the rat MSO nucleus, EE and EI, variations in the binaural response properties of the MSO neurons permitted further subclassifications, which may be related to the dendritic dominance of the MSO neurons.

  12. Laser capture microdissection of enriched populations of neurons or single neurons for gene expression analysis after traumatic brain injury.

    Science.gov (United States)

    Boone, Deborah R; Sell, Stacy L; Hellmich, Helen Lee

    2013-04-10

    Long-term cognitive disability after TBI is associated with injury-induced neurodegeneration in the hippocampus-a region in the medial temporal lobe that is critical for learning, memory and executive function. Hence our studies focus on gene expression analysis of specific neuronal populations in distinct subregions of the hippocampus. The technique of laser capture microdissection (LCM), introduced in 1996 by Emmert-Buck, et al., has allowed for significant advances in gene expression analysis of single cells and enriched populations of cells from heterogeneous tissues such as the mammalian brain that contains thousands of functional cell types. We use LCM and a well established rat model of traumatic brain injury (TBI) to investigate the molecular mechanisms that underlie the pathogenesis of TBI. Following fluid-percussion TBI, brains are removed at pre-determined times post-injury, immediately frozen on dry ice, and prepared for sectioning in a cryostat. The rat brains can be embedded in OCT and sectioned immediately, or stored several months at -80 °C before sectioning for laser capture microdissection. Additionally, we use LCM to study the effects of TBI on circadian rhythms. For this, we capture neurons from the suprachiasmatic nuclei that contain the master clock of the mammalian brain. Here, we demonstrate the use of LCM to obtain single identified neurons (injured and degenerating, Fluoro-Jade-positive, or uninjured, Fluoro-Jade-negative) and enriched populations of hippocampal neurons for subsequent gene expression analysis by real time PCR and/or whole-genome microarrays. These LCM-enabled studies have revealed that the selective vulnerability of anatomically distinct regions of the rat hippocampus are reflected in the different gene expression profiles of different populations of neurons obtained by LCM from these distinct regions. The results from our single-cell studies, where we compare the transcriptional profiles of dying and adjacent surviving

  13. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity

    DEFF Research Database (Denmark)

    Brandt, Julia P; Aziz-Zaman, Sonya; Juozaityte, Vaida

    2012-01-01

    . We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient...

  14. Single photon emission computed tomography in motor neuron disease with dementia.

    Science.gov (United States)

    Sawada, H; Udaka, F; Kishi, Y; Seriu, N; Mezaki, T; Kameyama, M; Honda, M; Tomonobu, M

    1988-01-01

    Single photon emission computed tomography with [123 I] isopropylamphetamine was carried out on a patient with motor neuron disease with dementia. [123 I] uptake was decreased in the frontal lobes. This would reflect the histopathological findings such as neuronal loss and gliosis in the frontal lobes.

  15. Stochastic optimal control of single neuron spike trains

    DEFF Research Database (Denmark)

    Iolov, Alexandre; Ditlevsen, Susanne; Longtin, Andrë

    2014-01-01

    stimulation of a neuron to achieve a target spike train under the physiological constraint to not damage tissue. Approach. We pose a stochastic optimal control problem to precisely specify the spike times in a leaky integrate-and-fire (LIF) model of a neuron with noise assumed to be of intrinsic or synaptic...... to the spike times (open-loop control). Main results. We have developed a stochastic optimal control algorithm to obtain precise spike times. It is applicable in both the supra-threshold and sub-threshold regimes, under open-loop and closed-loop conditions and with an arbitrary noise intensity; the accuracy...... into account physiological constraints on the control. A precise and robust targeting of neural activity based on stochastic optimal control has great potential for regulating neural activity in e.g. prosthetic applications and to improve our understanding of the basic mechanisms by which neuronal firing...

  16. Carbon nanotubes: artificial nanomaterials to engineer single neurons and neuronal networks.

    Science.gov (United States)

    Fabbro, Alessandra; Bosi, Susanna; Ballerini, Laura; Prato, Maurizio

    2012-08-15

    In the past decade, nanotechnology applications to the nervous system have often involved the study and the use of novel nanomaterials to improve the diagnosis and therapy of neurological diseases. In the field of nanomedicine, carbon nanotubes are evaluated as promising materials for diverse therapeutic and diagnostic applications. Besides, carbon nanotubes are increasingly employed in basic neuroscience approaches, and they have been used in the design of neuronal interfaces or in that of scaffolds promoting neuronal growth in vitro. Ultimately, carbon nanotubes are thought to hold the potential for the development of innovative neurological implants. In this framework, it is particularly relevant to document the impact of interfacing such materials with nerve cells. Carbon nanotubes were shown, when modified with biologically active compounds or functionalized in order to alter their charge, to affect neurite outgrowth and branching. Notably, purified carbon nanotubes used as scaffolds can promote the formation of nanotube-neuron hybrid networks, able per se to affect neuron integrative abilities, network connectivity, and synaptic plasticity. We focus this review on our work over several years directed to investigate the ability of carbon nanotube platforms in providing a new tool for nongenetic manipulations of neuronal performance and network signaling.

  17. High-Throughput Mapping of Single-Neuron Projections by Sequencing of Barcoded RNA.

    Science.gov (United States)

    Kebschull, Justus M; Garcia da Silva, Pedro; Reid, Ashlan P; Peikon, Ian D; Albeanu, Dinu F; Zador, Anthony M

    2016-09-07

    Neurons transmit information to distant brain regions via long-range axonal projections. In the mouse, area-to-area connections have only been systematically mapped using bulk labeling techniques, which obscure the diverse projections of intermingled single neurons. Here we describe MAPseq (Multiplexed Analysis of Projections by Sequencing), a technique that can map the projections of thousands or even millions of single neurons by labeling large sets of neurons with random RNA sequences ("barcodes"). Axons are filled with barcode mRNA, each putative projection area is dissected, and the barcode mRNA is extracted and sequenced. Applying MAPseq to the locus coeruleus (LC), we find that individual LC neurons have preferred cortical targets. By recasting neuroanatomy, which is traditionally viewed as a problem of microscopy, as a problem of sequencing, MAPseq harnesses advances in sequencing technology to permit high-throughput interrogation of brain circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Stable long-term chronic brain mapping at the single-neuron level.

    Science.gov (United States)

    Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

    2016-10-01

    Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

  19. Specific expression of channelrhodopsin-2 in single neurons of Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Cornelia Schmitt

    Full Text Available Optogenetic approaches using light-activated proteins like Channelrhodopsin-2 (ChR2 enable investigating the function of populations of neurons in live Caenorhabditis elegans (and other animals, as ChR2 expression can be targeted to these cells using specific promoters. Sub-populations of these neurons, or even single cells, can be further addressed by restricting the illumination to the cell of interest. However, this is technically demanding, particularly in free moving animals. Thus, it would be helpful if expression of ChR2 could be restricted to single neurons or neuron pairs, as even wide-field illumination would photostimulate only this particular cell. To this end we adopted the use of Cre or FLP recombinases and conditional ChR2 expression at the intersection of two promoter expression domains, i.e. in the cell of interest only. Success of this method depends on precise knowledge of the individual promoters' expression patterns and on relative expression levels of recombinase and ChR2. A bicistronic expression cassette with GFP helps to identify the correct expression pattern. Here we show specific expression in the AVA reverse command neurons and the aversive polymodal sensory ASH neurons. This approach shall enable to generate strains for optogenetic manipulation of each of the 302 C. elegans neurons. This may eventually allow to model the C. elegans nervous system in its entirety, based on functional data for each neuron.

  20. Kaleido: Visualizing Big Brain Data with Automatic Color Assignment for Single-Neuron Images.

    Science.gov (United States)

    Wang, Ting-Yuan; Chen, Nan-Yow; He, Guan-Wei; Wang, Guo-Tzau; Shih, Chi-Tin; Chiang, Ann-Shyn

    2018-03-03

    Effective 3D visualization is essential for connectomics analysis, where the number of neural images easily reaches over tens of thousands. A formidable challenge is to simultaneously visualize a large number of distinguishable single-neuron images, with reasonable processing time and memory for file management and 3D rendering. In the present study, we proposed an algorithm named "Kaleido" that can visualize up to at least ten thousand single neurons from the Drosophila brain using only a fraction of the memory traditionally required, without increasing computing time. Adding more brain neurons increases memory only nominally. Importantly, Kaleido maximizes color contrast between neighboring neurons so that individual neurons can be easily distinguished. Colors can also be assigned to neurons based on biological relevance, such as gene expression, neurotransmitters, and/or development history. For cross-lab examination, the identity of every neuron is retrievable from the displayed image. To demonstrate the effectiveness and tractability of the method, we applied Kaleido to visualize the 10,000 Drosophila brain neurons obtained from the FlyCircuit database ( http://www.flycircuit.tw/modules.php?name=kaleido ). Thus, Kaleido visualization requires only sensible computer memory for manual examination of big connectomics data.

  1. Crypt neurons express a single V1R-related ora gene.

    Science.gov (United States)

    Oka, Yuichiro; Saraiva, Luis R; Korsching, Sigrun I

    2012-03-01

    Both ciliated and microvillous olfactory sensory neuron populations express large families of olfactory receptor genes. However, individual neurons generally express only a single receptor gene according to the "one neuron-one receptor" rule. We report here that crypt neurons, the third type of olfactory neurons in fish species, use an even more restricted mode of expression. We recently identified a novel olfactory receptor family of 6 highly conserved G protein-coupled receptors, the v1r-like ora genes. We show now that a single member of this family, ora4 is expressed in nearly all crypt neurons, whereas the other 5 ora genes are not found in this cell type. Consistent with these findings, ora4 is never coexpressed with any of the remaining 5 ora genes. Furthermore, several lines of evidence indicate the absence of any other olfactory receptor families in crypt neurons. These results suggest that the vast majority of the crypt neuron population may select one and the same olfactory receptor gene, a "one cell type-one receptor" mode of expression. Such an expression pattern is familiar in the visual system, with rhodopsin as the sole light receptor of rod photoreceptor cells, but unexpected in the sense of smell.

  2. Stages of Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  3. Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.

    Science.gov (United States)

    Alam, Gelareh; Edler, Melissa; Burchfield, Shelbie; Richardson, Jason R

    2017-05-01

    Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH + ), and total neuron number (Nissl + ) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH + and Nissl + ) only in the group treated with 20mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2mg/kg) only showed significant loss of TH + neurons rather than TH + and Nissl + neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH + cells in determining dopamine neuron loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Racing to learn: statistical inference and learning in a single spiking neuron with adaptive kernels.

    Science.gov (United States)

    Afshar, Saeed; George, Libin; Tapson, Jonathan; van Schaik, André; Hamilton, Tara J

    2014-01-01

    This paper describes the Synapto-dendritic Kernel Adapting Neuron (SKAN), a simple spiking neuron model that performs statistical inference and unsupervised learning of spatiotemporal spike patterns. SKAN is the first proposed neuron model to investigate the effects of dynamic synapto-dendritic kernels and demonstrate their computational power even at the single neuron scale. The rule-set defining the neuron is simple: there are no complex mathematical operations such as normalization, exponentiation or even multiplication. The functionalities of SKAN emerge from the real-time interaction of simple additive and binary processes. Like a biological neuron, SKAN is robust to signal and parameter noise, and can utilize both in its operations. At the network scale neurons are locked in a race with each other with the fastest neuron to spike effectively "hiding" its learnt pattern from its neighbors. The robustness to noise, high speed, and simple building blocks not only make SKAN an interesting neuron model in computational neuroscience, but also make it ideal for implementation in digital and analog neuromorphic systems which is demonstrated through an implementation in a Field Programmable Gate Array (FPGA). Matlab, Python, and Verilog implementations of SKAN are available at: http://www.uws.edu.au/bioelectronics_neuroscience/bens/reproducible_research.

  5. A chimeric path to neuronal synchronization

    Energy Technology Data Exchange (ETDEWEB)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L. [School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287-9709 (United States)

    2015-01-15

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  6. A chimeric path to neuronal synchronization

    International Nuclear Information System (INIS)

    Essaki Arumugam, Easwara Moorthy; Spano, Mark L.

    2015-01-01

    Synchronization of neuronal activity is associated with neurological disorders such as epilepsy. This process of neuronal synchronization is not fully understood. To further our understanding, we have experimentally studied the progression of this synchronization from normal neuronal firing to full synchronization. We implemented nine FitzHugh-Nagumo neurons (a simplified Hodgkin-Huxley model) via discrete electronics. For different coupling parameters (synaptic strengths), the neurons in the ring were either unsynchronized or completely synchronized when locally coupled in a ring. When a single long-range connection (nonlocal coupling) was introduced, an intermediate state known as a chimera appeared. The results indicate that (1) epilepsy is likely not only a dynamical disease but also a topological disease, strongly tied to the connectivity of the underlying network of neurons, and (2) the synchronization process in epilepsy may not be an “all or none” phenomenon, but can pass through an intermediate stage (chimera)

  7. Reconstruction of neuronal input through modeling single-neuron dynamics and computations

    International Nuclear Information System (INIS)

    Qin, Qing; Wang, Jiang; Yu, Haitao; Deng, Bin; Chan, Wai-lok

    2016-01-01

    Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is.

  8. Reconstruction of neuronal input through modeling single-neuron dynamics and computations

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Qing; Wang, Jiang; Yu, Haitao; Deng, Bin, E-mail: dengbin@tju.edu.cn; Chan, Wai-lok [School of Electrical Engineering and Automation, Tianjin University, Tianjin 300072 (China)

    2016-06-15

    Mathematical models provide a mathematical description of neuron activity, which can better understand and quantify neural computations and corresponding biophysical mechanisms evoked by stimulus. In this paper, based on the output spike train evoked by the acupuncture mechanical stimulus, we present two different levels of models to describe the input-output system to achieve the reconstruction of neuronal input. The reconstruction process is divided into two steps: First, considering the neuronal spiking event as a Gamma stochastic process. The scale parameter and the shape parameter of Gamma process are, respectively, defined as two spiking characteristics, which are estimated by a state-space method. Then, leaky integrate-and-fire (LIF) model is used to mimic the response system and the estimated spiking characteristics are transformed into two temporal input parameters of LIF model, through two conversion formulas. We test this reconstruction method by three different groups of simulation data. All three groups of estimates reconstruct input parameters with fairly high accuracy. We then use this reconstruction method to estimate the non-measurable acupuncture input parameters. Results show that under three different frequencies of acupuncture stimulus conditions, estimated input parameters have an obvious difference. The higher the frequency of the acupuncture stimulus is, the higher the accuracy of reconstruction is.

  9. On the Non-Learnability of a Single Spiking Neuron

    Czech Academy of Sciences Publication Activity Database

    Šíma, Jiří; Sgall, Jiří

    2005-01-01

    Roč. 17, č. 12 (2005), s. 2635-2647 ISSN 0899-7667 R&D Projects: GA ČR GA201/02/1456; GA AV ČR 1ET100300517; GA MŠk LN00A056; GA MŠk(CZ) 1M0545 Institutional research plan: CEZ:AV0Z10300504; CEZ:AV0Z10190503 Keywords : spiking neuron * consistency problem * NP-completness * PAC model * robust learning * representation problem Subject RIV: BA - General Mathematics Impact factor: 2.591, year: 2005

  10. Induction of associative olfactory memory by targeted activation of single olfactory neurons in Drosophila larvae.

    Science.gov (United States)

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-04-25

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by ChR2-mediated optical activation of a specific class of olfactory neurons. We show that targeted activation of the olfactory receptor and the octopaminergic neurons is indeed sufficient for the formation of associative olfactory memory in the larval brain. We also show that targeted stimulation of only a single type of olfactory receptor neurons is sufficient to induce olfactory memory that is indistinguishable from natural memory induced by the activation of multiple olfactory receptor neurons.

  11. Single Ih channels in pyramidal neuron dendrites: properties, distribution, and impact on action potential output

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Hallermann, Stefan; Stuart, Greg J.

    2006-01-01

    The hyperpolarization-activated cation current (Ih) plays an important role in regulating neuronal excitability, yet its native single-channel properties in the brain are essentially unknown. Here we use variance-mean analysis to study the properties of single Ih channels in the apical dendrites of

  12. Noisy Neurons

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 20; Issue 1. Noisy Neurons: Hodgkin-Huxley Model and Stochastic Variants. Shurti Paranjape. General Article Volume 20 Issue 1 January 2015 pp 34-43. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Creation of defined single cell resolution neuronal circuits on microelectrode arrays

    Science.gov (United States)

    Pirlo, Russell Kirk

    2009-12-01

    The way cell-cell organization of neuronal networks influences activity and facilitates function is not well understood. Microelectrode arrays (MEAs) and advancing cell patterning technologies have enabled access to and control of in vitro neuronal networks spawning much new research in neuroscience and neuroengineering. We propose that small, simple networks of neurons with defined circuitry may serve as valuable research models where every connection can be analyzed, controlled and manipulated. Towards the goal of creating such neuronal networks we have applied microfabricated elastomeric membranes, surface modification and our unique laser cell patterning system to create defined neuronal circuits with single-cell precision on MEAs. Definition of synaptic connectivity was imposed by the 3D physical constraints of polydimethylsiloxane elastomeric membranes. The membranes had 20mum clear-through holes and 2-3mum deep channels which when applied to the surface of the MEA formed microwells to confine neurons to electrodes connected via shallow tunnels to direct neurite outgrowth. Tapering and turning of channels was used to influence neurite polarity. Biocompatibility of the membranes was increased by vacuum baking, oligomer extraction, and autoclaving. Membranes were bound to the MEA by oxygen plasma treatment and heated pressure. The MEA/membrane surface was treated with oxygen plasma, poly-D-lysine and laminin to improve neuron attachment, survival and neurite outgrowth. Prior to cell patterning the outer edge of culture area was seeded with 5x10 5 cells per cm and incubated for 2 days. Single embryonic day 7 chick forebrain neurons were then patterned into the microwells and onto the electrodes using our laser cell patterning system. Patterned neurons successfully attached to and were confined to the electrodes. Neurites extended through the interconnecting channels and connected with adjacent neurons. These results demonstrate that neuronal circuits can be

  14. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    OpenAIRE

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally per...

  15. Functional adaptation to loading of a single bone is neuronally regulated and involves multiple bones.

    Science.gov (United States)

    Sample, Susannah J; Behan, Mary; Smith, Lesley; Oldenhoff, William E; Markel, Mark D; Kalscheur, Vicki L; Hao, Zhengling; Miletic, Vjekoslav; Muir, Peter

    2008-09-01

    Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 +/- 16 days of age). After a single period of loading at -760-, -2000-, or -3750-microepsilon initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.

  16. Neurons the decision makers, Part I: The firing function of a single neuron.

    Science.gov (United States)

    Saaty, Thomas

    2017-02-01

    This paper is concerned with understanding synthesis of electric signals in the neural system based on making pairwise comparisons. Fundamentally, every person and every animal are born with the talent to compare stimuli from things that share properties in space or over time. Comparisons always need experience to distinguish among things. Pairwise comparisons are numerically reciprocal. If a value is assigned to the larger of two elements that have a given property when compared with the smaller one, then the smaller has the reciprocal of that value when compared with the larger. Because making comparisons requires the reciprocal property, we need mathematics that can cope with division. There are four division algebras that would allow us to use our reciprocals arising from comparisons: The real numbers, the complex numbers, the non-commutative quaternions and the non-associative octonions. Rather than inferring function as from electric flow in a network, in this paper we infer the flow from function. Neurons fire in response to stimuli and their firings vary relative to the intensities of the stimuli. We believe neurons use some kind of pairwise comparison mechanism to determine when to fire based on the stimuli they receive. The ideas we develop here about flows are used to deduce how a system based on this kind of firing determination works and can be described. Furthermore the firing of neurons requires continuous comparisons. To develop a formula describing the output of these pairwise comparisons requires solving Fredholm's equation of the second kind which is satisfied if and only if a simple functional equation has solutions. The Fourier transform of the real solution of this equation leads to inverse square laws like those that are common in physics. The Fourier transform applied to a complex valued solution leads to Dirac type of firings. Such firings are dense in the very general fields of functions known as Sobolev spaces and thus can be used to

  17. Hodgkin Lymphoma (For Kids)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this ... of the cool things he's missed. What Is Hodgkin Lymphoma? Lymphoma (say: lim-FOH-mah) is cancer of ...

  18. Integrative Single-Cell Transcriptomics Reveals Molecular Networks Defining Neuronal Maturation During Postnatal Neurogenesis.

    Science.gov (United States)

    Gao, Yu; Wang, Feifei; Eisinger, Brian E; Kelnhofer, Laurel E; Jobe, Emily M; Zhao, Xinyu

    2017-03-01

    In mammalian hippocampus, new neurons are continuously produced from neural stem cells throughout life. This postnatal neurogenesis may contribute to information processing critical for cognition, adaptation, learning, and memory, and is implicated in numerous neurological disorders. During neurogenesis, the immature neuron stage defined by doublecortin (DCX) expression is the most sensitive to regulation by extrinsic factors. However, little is known about the dynamic biology within this critical interval that drives maturation and confers susceptibility to regulatory signals. This study aims to test the hypothesis that DCX-expressing immature neurons progress through developmental stages via activity of specific transcriptional networks. Using single-cell RNA-seq combined with a novel integrative bioinformatics approach, we discovered that individual immature neurons can be classified into distinct developmental subgroups based on characteristic gene expression profiles and subgroup-specific markers. Comparisons between immature and more mature subgroups revealed novel pathways involved in neuronal maturation. Genes enriched in less mature cells shared significant overlap with genes implicated in neurodegenerative diseases, while genes positively associated with neuronal maturation were enriched for autism-related gene sets. Our study thus discovers molecular signatures of individual immature neurons and unveils potential novel targets for therapeutic approaches to treat neurodevelopmental and neurological diseases. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    Science.gov (United States)

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  20. The role of dendritic non-linearities in single neuron computation

    Directory of Open Access Journals (Sweden)

    Boris Gutkin

    2014-05-01

    Full Text Available Experiment has demonstrated that summation of excitatory post-synaptic protientials (EPSPs in dendrites is non-linear. The sum of multiple EPSPs can be larger than their arithmetic sum, a superlinear summation due to the opening of voltage-gated channels and similar to somatic spiking. The so-called dendritic spike. The sum of multiple of EPSPs can also be smaller than their arithmetic sum, because the synaptic current necessarily saturates at some point. While these observations are well-explained by biophysical models the impact of dendritic spikes on computation remains a matter of debate. One reason is that dendritic spikes may fail to make the neuron spike; similarly, dendritic saturations are sometime presented as a glitch which should be corrected by dendritic spikes. We will provide solid arguments against this claim and show that dendritic saturations as well as dendritic spikes enhance single neuron computation, even when they cannot directly make the neuron fire. To explore the computational impact of dendritic spikes and saturations, we are using a binary neuron model in conjunction with Boolean algebra. We demonstrate using these tools that a single dendritic non-linearity, either spiking or saturating, combined with somatic non-linearity, enables a neuron to compute linearly non-separable Boolean functions (lnBfs. These functions are impossible to compute when summation is linear and the exclusive OR is a famous example of lnBfs. Importantly, the implementation of these functions does not require the dendritic non-linearity to make the neuron spike. Next, We show that reduced and realistic biophysical models of the neuron are capable of computing lnBfs. Within these models and contrary to the binary model, the dendritic and somatic non-linearity are tightly coupled. Yet we show that these neuron models are capable of linearly non-separable computations.

  1. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior

    Directory of Open Access Journals (Sweden)

    Anupama Sathyamurthy

    2018-02-01

    Full Text Available To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease.

  2. Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity during Behavior.

    Science.gov (United States)

    Sathyamurthy, Anupama; Johnson, Kory R; Matson, Kaya J E; Dobrott, Courtney I; Li, Li; Ryba, Anna R; Bergman, Tzipporah B; Kelly, Michael C; Kelley, Matthew W; Levine, Ariel J

    2018-02-20

    To understand the cellular basis of behavior, it is necessary to know the cell types that exist in the nervous system and their contributions to function. Spinal networks are essential for sensory processing and motor behavior and provide a powerful system for identifying the cellular correlates of behavior. Here, we used massively parallel single nucleus RNA sequencing (snRNA-seq) to create an atlas of the adult mouse lumbar spinal cord. We identified and molecularly characterized 43 neuronal populations. Next, we leveraged the snRNA-seq approach to provide unbiased identification of neuronal populations that were active following a sensory and a motor behavior, using a transcriptional signature of neuronal activity. This approach can be used in the future to link single nucleus gene expression data with dynamic biological responses to behavior, injury, and disease. Published by Elsevier Inc.

  3. Single photon emission computed tomography in motor neuron disease with dementia

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, H.; Udaka, F.; Kishi, Y.; Seriu, N.; Ohtani, S.; Abe, K.; Mezaki, T.; Kameyama, M.; Honda, M.; Tomonobu, M.

    1988-12-01

    Single photon emission computed tomography with (123 I) isopropylamphetamine was carried out on a patient with motor neutron disease with dementia. (123 I) uptake was decreased in the frontal lobes. This would reflect the histopathological findings such as neuronal loss and gliosis in the frontal lobes.

  4. Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1

    Directory of Open Access Journals (Sweden)

    Soham Chanda

    2014-08-01

    Full Text Available Direct conversion of nonneural cells to functional neurons holds great promise for neurological disease modeling and regenerative medicine. We previously reported rapid reprogramming of mouse embryonic fibroblasts (MEFs into mature induced neuronal (iN cells by forced expression of three transcription factors: ASCL1, MYT1L, and BRN2. Here, we show that ASCL1 alone is sufficient to generate functional iN cells from mouse and human fibroblasts and embryonic stem cells, indicating that ASCL1 is the key driver of iN cell reprogramming in different cell contexts and that the role of MYT1L and BRN2 is primarily to enhance the neuronal maturation process. ASCL1-induced single-factor neurons (1F-iN expressed mature neuronal markers, exhibited typical passive and active intrinsic membrane properties, and formed functional pre- and postsynaptic structures. Surprisingly, ASCL1-induced iN cells were predominantly excitatory, demonstrating that ASCL1 is permissive but alone not deterministic for the inhibitory neuronal lineage.

  5. Demographics and outcome in paediatric non-hodgkin lymphoma: single centre experience at the children hospital, lahore, pakistan

    International Nuclear Information System (INIS)

    Faizan, M.; Khan, S.

    2018-01-01

    To describe the patient demographics and outcome analysis in paediatric non-Hodgkin lymphoma (NHL) patients. Study Design:An observational study. Place and Duration of Study:The Hematology/Oncology Unit of The Children's Hospital and Institute of Child Health, Lahore, from January 2012 till December 2014. Methodology:Demographics including age, gender, histopathology, stage and outcome data, in biopsy proven NHL patients were analyzed. Burkitts/B Cell and Diffuse Large B Cell lymphoma patients were treated with MCP 842 Protocol while T/B-cell lymphoblastic lymphoma (LL) patients were treated with EURO-LB 02 protocol. Results:Ninety-one patients were treated during the study period at CHL. Data was insufficient in 18 patients, so they were excluded from the study. Patients included were 73. Males were 53 (72.6%). Thirty-seven (50.7%) were 5-10 years of age, and 22 (30.1%) 10-16 years old. Abdominal mass was the commonest presentation seen in 32 (43.8%), lymphadenopathy in 27 (37%), intussusception in 5 (6.8%), while intestinal obstruction, obstructive uropathy, nasopharyngeal mass, gastric mass, primary bone lymphoma, pericardial effusion, jaw swelling, cheek swelling and paraspinal mass present in one (1%) each. Histopathological subtypes consist of Burkitt's lymphoma (BL) in 32 (43.8%), B cell NHL in 10 (13.7%), lymphoblastic lymphoma (LL) in 26 (35.6%), diffuse large B cell lymphoma (DLBCL) in 2 (2.8%), and anaplastic large cell lymphoma (ALCL) in 1 (1.4%). Sixty-seven (91%) presented in stage III, and six (8.4%) in stage IV. Forty-eight (65.8%) patients had completed treatment and are well to date, 16 (21.9%) died, 5 (6.8%) left against medical advice (LAMA), and 4 (5.5%) patients relapsed. Conclusion:Burkitt's lymphoma was the commonest type of NHL seen in this cohort that predominantly presented with an abdominal mass. Children usually presented in advanced stage with delayed diagnosis. Better supportive care can improve the prognosis

  6. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography.

    Science.gov (United States)

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K(+)-probe thallium (Tl(+)) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl(+) after crossing the blood-brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl(+) uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl(+) uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl(+) uptake. At 24 hours, the areas of reduced Tl(+)uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of (201)TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K(+) metabolism and prediction of tissue viability in cerebral ischemia.

  7. Single-cell resolution mapping of neuronal damage in acute focal cerebral ischemia using thallium autometallography

    Science.gov (United States)

    Stöber, Franziska; Baldauf, Kathrin; Ziabreva, Iryna; Harhausen, Denise; Zille, Marietta; Neubert, Jenni; Reymann, Klaus G; Scheich, Henning; Dirnagl, Ulrich; Schröder, Ulrich H; Wunder, Andreas; Goldschmidt, Jürgen

    2014-01-01

    Neuronal damage shortly after onset or after brief episodes of cerebral ischemia has remained difficult to assess with clinical and preclinical imaging techniques as well as with microscopical methods. We here show, in rodent models of middle cerebral artery occlusion (MCAO), that neuronal damage in acute focal cerebral ischemia can be mapped with single-cell resolution using thallium autometallography (TlAMG), a histochemical technique for the detection of the K+-probe thallium (Tl+) in the brain. We intravenously injected rats and mice with thallium diethyldithiocarbamate (TlDDC), a lipophilic chelate complex that releases Tl+ after crossing the blood–brain barrier. We found, within the territories of the affected arteries, areas of markedly reduced neuronal Tl+ uptake in all animals at all time points studied ranging from 15 minutes to 24 hours after MCAO. In large lesions at early time points, areas with neuronal and astrocytic Tl+ uptake below thresholds of detection were surrounded by putative penumbral zones with preserved but diminished Tl+ uptake. At 24 hours, the areas of reduced Tl+uptake matched with areas delineated by established markers of neuronal damage. The results suggest the use of 201TlDDC for preclinical and clinical single-photon emission computed tomography (SPECT) imaging of hyperacute alterations in brain K+ metabolism and prediction of tissue viability in cerebral ischemia. PMID:24129748

  8. Neural Plasticity: Single Neuron Models for Discrimination and Generalization and AN Experimental Ensemble Approach.

    Science.gov (United States)

    Munro, Paul Wesley

    A special form for modification of neuronal response properties is described in which the change in the synaptic state vector is parallel to the vector of afferent activity. This process is termed "parallel modification" and its theoretical and experimental implications are examined. A theoretical framework has been devised to describe the complementary functions of generalization and discrimination by single neurons. This constitutes a basis for three models each describing processes for the development of maximum selectivity (discrimination) and minimum selectivity (generalization) by neurons. Strengthening and weakening of synapses is expressed as a product of the presynaptic activity and a nonlinear modulatory function of two postsynaptic variables--namely a measure of the spatially integrated activity of the cell and a temporal integration (time-average) of that activity. Some theorems are given for low-dimensional systems and computer simulation results from more complex systems are discussed. Model neurons that achieve high selectivity mimic the development of cat visual cortex neurons in a wide variety of rearing conditions. A role for low-selectivity neurons is proposed in which they provide inhibitory input to neurons of the opposite type, thereby suppressing the common component of a pattern class and enhancing their selective properties. Such contrast-enhancing circuits are analyzed and supported by computer simulation. To enable maximum selectivity, the net inhibition to a cell must become strong enough to offset whatever excitation is produced by the non-preferred patterns. Ramifications of parallel models for certain experimental paradigms are analyzed. A methodology is outlined for testing synaptic modification hypotheses in the laboratory. A plastic projection from one neuronal population to another will attain stable equilibrium under periodic electrical stimulation of constant intensity. The perturbative effect of shifting this intensity level

  9. Single bumps in a 2-population homogenized neuronal network model

    Science.gov (United States)

    Kolodina, Karina; Oleynik, Anna; Wyller, John

    2018-05-01

    We investigate existence and stability of single bumps in a homogenized 2-population neural field model, when the firing rate functions are given by the Heaviside function. The model is derived by means of the two-scale convergence technique of Nguetseng in the case of periodic microvariation in the connectivity functions. The connectivity functions are periodically modulated in both the synaptic footprint and in the spatial scale. The bump solutions are constructed by using a pinning function technique for the case where the solutions are independent of the local variable. In the weakly modulated case the generic picture consists of two bumps (one narrow and one broad bump) for each admissible set of threshold values for firing. In addition, a new threshold value regime for existence of bumps is detected. Beyond the weakly modulated regime the number of bumps depends sensitively on the degree of heterogeneity. For the latter case we present a configuration consisting of three coexisting bumps. The linear stability of the bumps is studied by means of the spectral properties of a Fredholm integral operator, block diagonalization of this operator and the Fourier decomposition method. In the weakly modulated regime, one of the bumps is unstable for all relative inhibition times, while the other one is stable for small and moderate values of this parameter. The latter bump becomes unstable as the relative inhibition time exceeds a certain threshold. In the case of the three coexisting bumps detected in the regime of finite degree of heterogeneity, we have at least one stable bump (and maximum two stable bumps) for small and moderate values of the relative inhibition time.

  10. Single-molecule folding mechanism of an EF-hand neuronal calcium sensor

    DEFF Research Database (Denmark)

    Heiðarsson, Pétur Orri; Otazo, Mariela R.; Bellucci, Luca

    2013-01-01

    EF-hand calcium sensors respond structurally to changes in intracellular Ca2+ concentration, triggering diverse cellular responses and resulting in broad interactomes. Despite impressive advances in decoding their structure-function relationships, the folding mechanism of neuronal calcium sensors...... is still elusive. We used single-molecule optical tweezers to study the folding mechanism of the human neuronal calcium sensor 1 (NCS1). Two intermediate structures induced by Ca2+ binding to the EF-hands were observed during refolding. The complete folding of the C domain is obligatory for the folding...

  11. A Route to Chaotic Behavior of Single Neuron Exposed to External Electromagnetic Radiation.

    Science.gov (United States)

    Feng, Peihua; Wu, Ying; Zhang, Jiazhong

    2017-01-01

    Non-linear behaviors of a single neuron described by Fitzhugh-Nagumo (FHN) neuron model, with external electromagnetic radiation considered, is investigated. It is discovered that with external electromagnetic radiation in form of a cosine function, the mode selection of membrane potential occurs among periodic, quasi-periodic, and chaotic motions as increasing the frequency of external transmembrane current, which is selected as a sinusoidal function. When the frequency is small or large enough, periodic, and quasi-periodic motions are captured alternatively. Otherwise, when frequency is in interval 0.778 electromagnetic radiation. The frequency apparently plays a more important role in determining the system behavior.

  12. Synergistic combinations of five single drugs from Centella asiatica for neuronal differentiation.

    Science.gov (United States)

    Lin, Jinjin; Jiang, Hui; Ding, Xianting

    2017-01-01

    To identify alternatives of nerve growth factor, which could promote NF68 protein expression and contribute toward neuronal differentiation, five compounds namely: asiatic acid, madecassic, madecassoside, quercetin, and isoquercetin, obtained from Centella asiatica, were examined for their neuronal differentiation effects on PC12 cells. C. asiatica has been applied as an effective herbal medicine for the treatment of various diseases, including depression. According to a statistical design of experiments, both single compound and compound combinations were evaluated. A further statistical analysis indicated quantitative interactions between these five single compounds and led to the identification of the optimal drug combinations. Asiatic acid and madecassic appeared to show profound synergistic effects on neurofilaments expression in vitro. The optimized drug combinations were significantly more potent than single drugs and further investigation suggested that the optimal drug combination could be an analogue of nerve growth factor and could represent a potential treatment for neurodegenerative diseases.

  13. Development of Hodgkin's disease in a patient with leprosy.

    Science.gov (United States)

    Weshler, Z; Leviatan, A; Gordon, R; Kopolovic, J

    1978-01-01

    We present a patient with leprosy who developed Hodgkin's disease of the nodular sclerosing type. There are two previous reports describing the combination of leprosy and Hodgkin's disease in a single patient [3, 9]. Hodgkin's disease was diagnosed 14 months after the complete disappearance of mycobacterium leprae from the skin lesions, under treatment with DDS (diamino-diphenyl-sulfone). Hodgkin's disease was treated by irradiation and chemotherapy. Obstructive jaundice developed which resolved under treatment by irradiation of the hilar area of the liver, chemotherapy and hormones. During two years of immuno-suppressive therapy, without DDS, no exacerbation of the leprosy occurred.

  14. G gene-deficient single-round rabies viruses for neuronal circuit analysis.

    Science.gov (United States)

    Ghanem, Alexander; Conzelmann, Karl-Klaus

    2016-05-02

    Rhabdoviruses like the neurotropic rabies virus are fully amenable to pseudotyping with homologous and heterologous membrane proteins, which is being harnessed for the study of viral envelope proteins, viral retargeting, or immunization purposes. Particularly, pseudotyped delta G rabies viruses are emerging as safe and superb tools for mapping direct synaptic connections and analyzing neuronal circuits in the central and peripheral nervous system, which is a fundamental pillar of modern neuroscience. Such retrograde rabies mono-transsynaptic tracers in combination with optogenetics and modern in vivo imaging methods are opening entirely new avenues of investigation in neuroscience and help in answering major outstanding questions of connectivity and function of the nervous system. Here, we provide a brief overview on the biology and life cycle of rabies virus with emphasis on neuronal infection via axon ends, transport, and transsynaptic transmission of the virus. Pseudotyping of single-round, G-deleted virus with foreign glycoproteins allows to determine tropism and entry route, resulting in either retro- or anterograde labeling of neurons. Pseudotyping in vitro also allows specific targeting of cells that serve as starter cells for transsynaptic tracing, and pseudotyping in situ for a single (mono-transsynaptic) step of transmission to presynaptic neurons. We describe principle and experimental variations for defining "starter" cells for mono-transsynaptic tracing with ΔG rabies virus and outline open questions and limitations of the approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Audio-vocal interaction in single neurons of the monkey ventrolateral prefrontal cortex.

    Science.gov (United States)

    Hage, Steffen R; Nieder, Andreas

    2015-05-06

    Complex audio-vocal integration systems depend on a strong interconnection between the auditory and the vocal motor system. To gain cognitive control over audio-vocal interaction during vocal motor control, the PFC needs to be involved. Neurons in the ventrolateral PFC (VLPFC) have been shown to separately encode the sensory perceptions and motor production of vocalizations. It is unknown, however, whether single neurons in the PFC reflect audio-vocal interactions. We therefore recorded single-unit activity in the VLPFC of rhesus monkeys (Macaca mulatta) while they produced vocalizations on command or passively listened to monkey calls. We found that 12% of randomly selected neurons in VLPFC modulated their discharge rate in response to acoustic stimulation with species-specific calls. Almost three-fourths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of vocalization. Based on these audio-vocal interactions, the VLPFC might be well positioned to combine higher order auditory processing with cognitive control of the vocal motor output. Such audio-vocal integration processes in the VLPFC might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2015 the authors 0270-6474/15/357030-11$15.00/0.

  16. Synaptic and intrinsic homeostasis cooperate to optimize single neuron response properties and tune integrator circuits

    Science.gov (United States)

    2016-01-01

    Homeostatic processes that provide negative feedback to regulate neuronal firing rate are essential for normal brain function, and observations suggest that multiple such processes may operate simultaneously in the same network. We pose two questions: why might a diversity of homeostatic pathways be necessary, and how can they operate in concert without opposing and undermining each other? To address these questions, we perform a computational and analytical study of cell-intrinsic homeostasis and synaptic homeostasis in single-neuron and recurrent circuit models. We demonstrate analytically and in simulation that when two such mechanisms are controlled on a long time scale by firing rate via simple and general feedback rules, they can robustly operate in tandem to tune the mean and variance of single neuron's firing rate to desired goals. This property allows the system to recover desired behavior after chronic changes in input statistics. We illustrate the power of this homeostatic tuning scheme by using it to regain high mutual information between neuronal input and output after major changes in input statistics. We then show that such dual homeostasis can be applied to tune the behavior of a neural integrator, a system that is notoriously sensitive to variation in parameters. These results are robust to variation in goals and model parameters. We argue that a set of homeostatic processes that appear to redundantly regulate mean firing rate may work together to control firing rate mean and variance and thus maintain performance in a parameter-sensitive task such as integration. PMID:27306675

  17. Variations in interpulse interval of double action potentials during propagation in single neurons.

    Science.gov (United States)

    Villagran-Vargas, Edgar; Rodríguez-Sosa, Leonardo; Hustert, Reinhold; Blicher, Andreas; Laub, Katrine; Heimburg, Thomas

    2013-02-01

    In this work, we analyzed the interpulse interval (IPI) of doublets and triplets in single neurons of three biological models. Pulse trains with two or three spikes originate from the process of sensory mechanotransduction in neurons of the locust femoral nerve, as well as through spontaneous activity both in the abdominal motor neurons and the caudal photoreceptor of the crayfish. We show that the IPI for successive low-frequency single action potentials, as recorded with two electrodes at two different points along a nerve axon, remains constant. On the other hand, IPI in doublets either remains constant, increases or decreases by up to about 3 ms as the pair propagates. When IPI increases, the succeeding pulse travels at a slower speed than the preceding one. When IPI is reduced, the succeeding pulse travels faster than the preceding one and may exceed the normal value for the specific neuron. In both cases, IPI increase and reduction, the speed of the preceding pulse differs slightly from the normal value, therefore the two pulses travel at different speeds in the same nerve axon. On the basis of our results, we may state that the effect of attraction or repulsion in doublets suggests a tendency of the spikes to reach a stable configuration. We strongly suggest that the change in IPI during spike propagation of doublets opens up a whole new realm of possibilities for neural coding and may have major implications for understanding information processing in nervous systems. Copyright © 2012 Wiley Periodicals, Inc.

  18. Somatosensory neuron types identified by high-coverage single-cell RNA-sequencing and functional heterogeneity

    Science.gov (United States)

    Li, Chang-Lin; Li, Kai-Cheng; Wu, Dan; Chen, Yan; Luo, Hao; Zhao, Jing-Rong; Wang, Sa-Shuang; Sun, Ming-Ming; Lu, Ying-Jin; Zhong, Yan-Qing; Hu, Xu-Ye; Hou, Rui; Zhou, Bei-Bei; Bao, Lan; Xiao, Hua-Sheng; Zhang, Xu

    2016-01-01

    Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases. PMID:26691752

  19. Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron-tracing study using virus vectors.

    Science.gov (United States)

    Kuramoto, Eriko; Pan, Shixiu; Furuta, Takahiro; Tanaka, Yasuhiro R; Iwai, Haruki; Yamanaka, Atsushi; Ohno, Sachi; Kaneko, Takeshi; Goto, Tetsuya; Hioki, Hiroyuki

    2017-01-01

    The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple-area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166-185, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. A path integral approach to the Hodgkin-Huxley model

    Science.gov (United States)

    Baravalle, Roman; Rosso, Osvaldo A.; Montani, Fernando

    2017-11-01

    To understand how single neurons process sensory information, it is necessary to develop suitable stochastic models to describe the response variability of the recorded spike trains. Spikes in a given neuron are produced by the synergistic action of sodium and potassium of the voltage-dependent channels that open or close the gates. Hodgkin and Huxley (HH) equations describe the ionic mechanisms underlying the initiation and propagation of action potentials, through a set of nonlinear ordinary differential equations that approximate the electrical characteristics of the excitable cell. Path integral provides an adequate approach to compute quantities such as transition probabilities, and any stochastic system can be expressed in terms of this methodology. We use the technique of path integrals to determine the analytical solution driven by a non-Gaussian colored noise when considering the HH equations as a stochastic system. The different neuronal dynamics are investigated by estimating the path integral solutions driven by a non-Gaussian colored noise q. More specifically we take into account the correlational structures of the complex neuronal signals not just by estimating the transition probability associated to the Gaussian approach of the stochastic HH equations, but instead considering much more subtle processes accounting for the non-Gaussian noise that could be induced by the surrounding neural network and by feedforward correlations. This allows us to investigate the underlying dynamics of the neural system when different scenarios of noise correlations are considered.

  1. Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy

    DEFF Research Database (Denmark)

    Specht, L; Nordentoft, A M; Cold, Søren

    1987-01-01

    --from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival....... Other known prognostic factors such as number of involved regions, mediastinal size, pathological stage, systemic symptoms, and ESR were related to tumour burden and lost their prognostic significance in a multivariate analysis. The only other factors of independent significance were histologic subtype...

  2. Comprehensive Identification and Spatial Mapping of Habenular Neuronal Types Using Single-Cell RNA-Seq.

    Science.gov (United States)

    Pandey, Shristi; Shekhar, Karthik; Regev, Aviv; Schier, Alexander F

    2018-04-02

    The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq (scRNA-seq) with anatomical brain registration to create a comprehensive map of the zebrafish habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ∼13,000 habenular cells with 4× cellular coverage identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a reference atlas created a resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult habenula. This study provides a gene expression atlas to dissect habenular development and function and offers a general framework for the comprehensive characterization of other brain regions. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Simultaneous transcranial magnetic stimulation and single-neuron recording in alert non-human primates.

    Science.gov (United States)

    Mueller, Jerel K; Grigsby, Erinn M; Prevosto, Vincent; Petraglia, Frank W; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V; Sommer, Marc A; Egner, Tobias; Platt, Michael L; Grill, Warren M

    2014-08-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report new methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in awake monkeys (Macaca mulatta). We recorded action potentials within ∼1 ms after 0.4-ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared with sham stimulation. This methodology is compatible with standard equipment in primate laboratories, allowing easy implementation. Application of these tools will facilitate the refinement of next generation TMS devices, experiments and treatment protocols.

  4. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    Science.gov (United States)

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally perturbed by stimulation artifact in intact, awake monkeys (Macaca mulatta). We recorded action potentials within ~1 ms after 0.4 ms TMS pulses and observed changes in activity that differed significantly for active stimulation as compared to sham stimulation. The methodology is compatible with standard equipment in primate laboratories, allowing for easy implementation. Application of these new tools will facilitate the refinement of next generation TMS devices, experiments, and treatment protocols. PMID:24974797

  5. A Route to Chaotic Behavior of Single Neuron Exposed to External Electromagnetic Radiation

    Directory of Open Access Journals (Sweden)

    Peihua Feng

    2017-10-01

    Full Text Available Non-linear behaviors of a single neuron described by Fitzhugh-Nagumo (FHN neuron model, with external electromagnetic radiation considered, is investigated. It is discovered that with external electromagnetic radiation in form of a cosine function, the mode selection of membrane potential occurs among periodic, quasi-periodic, and chaotic motions as increasing the frequency of external transmembrane current, which is selected as a sinusoidal function. When the frequency is small or large enough, periodic, and quasi-periodic motions are captured alternatively. Otherwise, when frequency is in interval 0.778 < ω < 2.208, chaotic motion characterizes the main behavior type. The mechanism of mode transition from quasi-periodic to chaotic motion is also observed when varying the amplitude of external electromagnetic radiation. The frequency apparently plays a more important role in determining the system behavior.

  6. Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks Involved in the Central Circadian Clock.

    Science.gov (United States)

    Park, James; Zhu, Haisun; O'Sullivan, Sean; Ogunnaike, Babatunde A; Weaver, David R; Schwaber, James S; Vadigepalli, Rajanikanth

    2016-01-01

    Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies toward understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  7. Single-cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes and Interaction Networks involved In the Central Circadian Clock

    Directory of Open Access Journals (Sweden)

    James Park

    2016-10-01

    Full Text Available Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN. Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular phenotypes, we characterized the transcriptional, spatial, and functional organization of 352 SCN neurons from mice experiencing phase-shifts in their circadian cycle. Using the community structure detection method and multivariate analytical techniques, we identified previously undescribed neuronal phenotypes that are likely to participate in regulatory networks with known SCN cell types. Based on the newly discovered neuronal phenotypes, we developed a data-driven neuronal network structure in which multiple cell types interact through known synaptic and paracrine signaling mechanisms. These results provide a basis from which to interpret the functional variability of SCN neurons and describe methodologies towards understanding how a population of heterogeneous single cells organizes into cellular networks that underlie tissue-level function.

  8. Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor.

    Science.gov (United States)

    Fink, Ann E; Bender, Kevin J; Trussell, Laurence O; Otis, Thomas S; DiGregorio, David A

    2012-01-01

    Minimally invasive measurements of neuronal activity are essential for understanding how signal processing is performed by neuronal networks. While optical strategies for making such measurements hold great promise, optical sensors generally lack the speed and sensitivity necessary to record neuronal activity on a single-trial, single-neuron basis. Here we present additional biophysical characterization and practical improvements of a two-component optical voltage sensor (2cVoS), comprised of the neuronal tracer dye, DiO, and dipicrylamine (DiO/DPA). Using laser spot illumination we demonstrate that membrane potential-dependent fluorescence changes can be obtained in a wide variety of cell types within brain slices. We show a correlation between membrane labeling and the sensitivity of the magnitude of fluorescence signal, such that neurons with the brightest membrane labeling yield the largest ΔF/F values per action potential (AP; ∼40%). By substituting a blue-shifted donor for DiO we confirm that DiO/DPA works, at least in part, via a Förster resonance energy transfer (FRET) mechanism. We also describe a straightforward iontophoretic method for labeling multiple neurons with DiO and show that DiO/DPA is compatible with two-photon (2P) imaging. Finally, exploiting the high sensitivity of DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs) recorded from single spines of hippocampal pyramidal neurons and single-trial measurements of subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage fluctuations with very high spatial and temporal resolution, properties well suited for monitoring electrical signals from multiple neurons within intact neuronal networks.

  9. Two-photon compatibility and single-voxel, single-trial detection of subthreshold neuronal activity by a two-component optical voltage sensor.

    Directory of Open Access Journals (Sweden)

    Ann E Fink

    Full Text Available Minimally invasive measurements of neuronal activity are essential for understanding how signal processing is performed by neuronal networks. While optical strategies for making such measurements hold great promise, optical sensors generally lack the speed and sensitivity necessary to record neuronal activity on a single-trial, single-neuron basis. Here we present additional biophysical characterization and practical improvements of a two-component optical voltage sensor (2cVoS, comprised of the neuronal tracer dye, DiO, and dipicrylamine (DiO/DPA. Using laser spot illumination we demonstrate that membrane potential-dependent fluorescence changes can be obtained in a wide variety of cell types within brain slices. We show a correlation between membrane labeling and the sensitivity of the magnitude of fluorescence signal, such that neurons with the brightest membrane labeling yield the largest ΔF/F values per action potential (AP; ∼40%. By substituting a blue-shifted donor for DiO we confirm that DiO/DPA works, at least in part, via a Förster resonance energy transfer (FRET mechanism. We also describe a straightforward iontophoretic method for labeling multiple neurons with DiO and show that DiO/DPA is compatible with two-photon (2P imaging. Finally, exploiting the high sensitivity of DiO/DPA, we demonstrate AP-induced fluorescence transients (fAPs recorded from single spines of hippocampal pyramidal neurons and single-trial measurements of subthreshold synaptic inputs to granule cell dendrites. Our findings suggest that the 2cVoS, DiO/DPA, enables optical measurements of trial-to-trial voltage fluctuations with very high spatial and temporal resolution, properties well suited for monitoring electrical signals from multiple neurons within intact neuronal networks.

  10. Retrograde labeling of single neurons in conjunction with MALDI high-energy collision-induced dissociation MS/MS analysis for peptide profiling and structural characterization

    NARCIS (Netherlands)

    El Filali, Z.; Hornshaw, M.; Smit, A.B.; Li, K.W.

    2003-01-01

    To reveal the peptide contents of the visually nonidentifiable neurons from a neuronal circuit of interest, we combined retrograde labeling of neurons with mass spectrometric single cell analysis. We used the neuronal circuit involved in the copulation behavior of a freshwater snail, Lymnaea

  11. Radiotherapy for Hodgkin lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Specht, Lena [Rigshospitalet Copenhagen Univ. (Denmark). Depts. of Oncology and Haematology; Yahalom, Joachim (eds.) [Memorial Sloan-Kettering Cancer, New York, NY (United States). Dept. of Radiation Oncology

    2011-07-01

    This book deals in detail with all aspects of the best practice in modern radiotherapy for Hodgkin lymphoma. It provides the background and rationale for the inclusion of radiotherapy in today's combined-modality approach, including special clinical situations such as Hodgkin lymphoma in children, in the pregnant patient, and in the elderly. Radiotherapy planning using state-of-the-art imaging, target definition, planning software, and treatment equipment is expounded in detail. Acute and long-term side effects of radiotherapy are analyzed, and the implications for modern radiotherapy approaches in Hodgkin lymphomas are explained. (orig.)

  12. Radiotherapy for Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Specht, Lena; Yahalom, Joachim

    2011-01-01

    This book deals in detail with all aspects of the best practice in modern radiotherapy for Hodgkin lymphoma. It provides the background and rationale for the inclusion of radiotherapy in today's combined-modality approach, including special clinical situations such as Hodgkin lymphoma in children, in the pregnant patient, and in the elderly. Radiotherapy planning using state-of-the-art imaging, target definition, planning software, and treatment equipment is expounded in detail. Acute and long-term side effects of radiotherapy are analyzed, and the implications for modern radiotherapy approaches in Hodgkin lymphomas are explained. (orig.)

  13. NONLINEAR SYSTEM MODELING USING SINGLE NEURON CASCADED NEURAL NETWORK FOR REAL-TIME APPLICATIONS

    Directory of Open Access Journals (Sweden)

    S. Himavathi

    2012-04-01

    Full Text Available Neural Networks (NN have proved its efficacy for nonlinear system modeling. NN based controllers and estimators for nonlinear systems provide promising alternatives to the conventional counterpart. However, NN models have to meet the stringent requirements on execution time for its effective use in real time applications. This requires the NN model to be structurally compact and computationally less complex. In this paper a parametric method of analysis is adopted to determine the compact and faster NN model among various neural network architectures. This work proves through analysis and examples that the Single Neuron Cascaded (SNC architecture is distinct in providing compact and simpler models requiring lower execution time. The unique structural growth of SNC architecture enables automation in design. The SNC Network is shown to combine the advantages of both single and multilayer neural network architectures. Extensive analysis on selected architectures and their models for four benchmark nonlinear theoretical plants and a practical application are tested. A performance comparison of the NN models is presented to demonstrate the superiority of the single neuron cascaded architecture for online real time applications.

  14. General Information about Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  15. Treatment Option Overview (Childhood Hodgkin Lymphoma)

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  16. Treatment Options for Childhood Hodgkin Lymphoma

    Science.gov (United States)

    ... and skin. There are two general types of lymphoma : Hodgkin lymphoma and non-Hodgkin lymphoma . (See the PDQ ... more information.) There are two types of childhood Hodgkin lymphoma. The two types of childhood Hodgkin lymphoma are: ...

  17. Single-photon emission computed tomographic findings and motor neuron signs in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Terao, Shin-ichi; Sobue, Gen; Higashi, Naoki; Takahashi, Masahiko; Suga, Hidemichi; Mitsuma, Terunori

    1995-01-01

    123 I-amphetamine-single photon emission computed tomography (SPECT) was performed on 16 patients with amyotrophic lateral sclerosis (ALS) to investigate the correlation between regional cerebral blood flow (rCBF) and upper motor neuron signs. Significant decreased blood flow less than 2 SDs below the mean of controls was observed in the frontal lobe in 4 patients (25%) and in the frontoparietal lobe including the cortical motor area in 4 patients, respectively. The severity of extermity muscular weakness was significantly correlate with decrease in blood flow through the frontal lobe (p<0.05) and through the frontoparietal lobe (p<0.001). A significant correlation was also noted to exist between the severity of bulbar paralysis and decrease in blood flow through the frontoparietal lobe. No correlation, however, was observed between rCBF and severity of spasticity, presence or absence of Babinski's sign and the duration of illness. Although muscular weakness in the limbs and bulbar paralysis are not pure upper motor neuron signs, the observed reduction in blood flow through the frontal or frontoparietal lobes appears to reflect extensive progression of functional or organic lesions of cortical neurons including the motor area. (author)

  18. Diversity of bilateral synaptic assemblies for binaural computation in midbrain single neurons.

    Science.gov (United States)

    He, Na; Kong, Lingzhi; Lin, Tao; Wang, Shaohui; Liu, Xiuping; Qi, Jiyao; Yan, Jun

    2017-11-01

    Binaural hearing confers many beneficial functions but our understanding of its underlying neural substrates is limited. This study examines the bilateral synaptic assemblies and binaural computation (or integration) in the central nucleus of the inferior colliculus (ICc) of the auditory midbrain, a key convergent center. Using in-vivo whole-cell patch-clamp, the excitatory and inhibitory postsynaptic potentials (EPSPs/IPSPs) of single ICc neurons to contralateral, ipsilateral and bilateral stimulation were recorded. According to the contralateral and ipsilateral EPSP/IPSP, 7 types of bilateral synaptic assemblies were identified. These include EPSP-EPSP (EE), E-IPSP (EI), E-no response (EO), II, IE, IO and complex-mode (CM) neurons. The CM neurons showed frequency- and/or amplitude-dependent EPSPs/IPSPs to contralateral or ipsilateral stimulation. Bilateral stimulation induced EPSPs/IPSPs that could be larger than (facilitation), similar to (ineffectiveness) or smaller than (suppression) those induced by contralateral stimulation. Our findings have allowed our group to characterize novel neural circuitry for binaural computation in the midbrain. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Overexpression of cypin alters dendrite morphology, single neuron activity, and network properties via distinct mechanisms

    Science.gov (United States)

    Rodríguez, Ana R.; O'Neill, Kate M.; Swiatkowski, Przemyslaw; Patel, Mihir V.; Firestein, Bonnie L.

    2018-02-01

    Objective. This study investigates the effect that overexpression of cytosolic PSD-95 interactor (cypin), a regulator of synaptic PSD-95 protein localization and a core regulator of dendrite branching, exerts on the electrical activity of rat hippocampal neurons and networks. Approach. We cultured rat hippocampal neurons and used lipid-mediated transfection and lentiviral gene transfer to achieve high levels of cypin or cypin mutant (cypinΔPDZ PSD-95 non-binding) expression cellularly and network-wide, respectively. Main results. Our analysis revealed that although overexpression of cypin and cypinΔPDZ increase dendrite numbers and decrease spine density, cypin and cypinΔPDZ distinctly regulate neuronal activity. At the single cell level, cypin promotes decreases in bursting activity while cypinΔPDZ reduces sEPSC frequency and further decreases bursting compared to cypin. At the network level, by using the Fano factor as a measure of spike count variability, cypin overexpression results in an increase in variability of spike count, and this effect is abolished when cypin cannot bind PSD-95. This variability is also dependent on baseline activity levels and on mean spike rate over time. Finally, our spike sorting data show that overexpression of cypin results in a more complex distribution of spike waveforms and that binding to PSD-95 is essential for this complexity. Significance. Our data suggest that dendrite morphology does not play a major role in cypin action on electrical activity.

  20. STDP allows close-to-optimal spatiotemporal spike pattern detection by single coincidence detector neurons.

    Science.gov (United States)

    Masquelier, Timothée

    2017-06-29

    Repeating spatiotemporal spike patterns exist and carry information. How this information is extracted by downstream neurons is unclear. Here we theoretically investigate to what extent a single cell could detect a given spike pattern and what the optimal parameters to do so are, in particular the membrane time constant τ. Using a leaky integrate-and-fire (LIF) neuron with homogeneous Poisson input, we computed this optimum analytically. We found that a relatively small τ (at most a few tens of ms) is usually optimal, even when the pattern is much longer. This is somewhat counter-intuitive as the resulting detector ignores most of the pattern, due to its fast memory decay. Next, we wondered if spike-timing-dependent plasticity (STDP) could enable a neuron to reach the theoretical optimum. We simulated a LIF equipped with additive STDP, and repeatedly exposed it to a given input spike pattern. As in previous studies, the LIF progressively became selective to the repeating pattern with no supervision, even when the pattern was embedded in Poisson activity. Here we show that, using certain STDP parameters, the resulting pattern detector is optimal. These mechanisms may explain how humans learn repeating sensory sequences. Long sequences could be recognized thanks to coincidence detectors working at a much shorter timescale. This is consistent with the fact that recognition is still possible if a sound sequence is compressed, played backward, or scrambled using 10-ms bins. Coincidence detection is a simple yet powerful mechanism, which could be the main function of neurons in the brain. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Glatstein, E.; Wasserman, T.H.

    1987-01-01

    Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

  2. Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Teens For Kids For Parents MORE ON THIS TOPIC Dealing With Cancer Cancer Center Cancer: Readjusting to Home and School Blood Transfusions Stem Cell Transplants Hodgkin Lymphoma Types of Cancer ...

  3. A single GABAergic neuron mediates feedback of odor-evoked signals in the mushroom body of larval Drosophila

    Directory of Open Access Journals (Sweden)

    Liria Monica Masuda-Nakagawa

    2014-04-01

    Full Text Available Inhibition has a central role in defining the selectivity of the responses of higher order neurons to sensory stimuli. However, the circuit mechanisms of regulation of these responses by inhibitory neurons are still unclear. In Drosophila, the mushroom bodies (MBs are necessary for olfactory memory, and by implication for the selectivity of learned responses to specific odors. To understand the circuitry of inhibition in the calyx (the input dendritic region of the MBs, and its relationship with MB excitatory activity, we used the simple anatomy of the Drosophila larval olfactory system to identify any inhibitory inputs that could contribute to the selectivity of MB odor responses. We found that a single neuron accounts for all detectable GABA innervation in the calyx of the MBs, and that this neuron has presynaptic terminals in the calyx and postsynaptic branches in the MB lobes (output axonal area. We call this neuron the larval anterior paired lateral (APL neuron, because of its similarity to the previously described adult APL neuron. Reconstitution of GFP partners (GRASP suggests that the larval APL makes extensive contacts with the MB intrinsic neurons, Kenyon Cells (KCs, but few contacts with incoming projection neurons. Using calcium imaging of neuronal activity in live larvae, we show that the larval APL responds to odors, in a mannner that requires output from KCs. Our data suggest that the larval APL is the sole GABAergic neuron that innervates the MB input region and carries inhibitory feedback from the MB output region, consistent with a role in modulating the olfactory selectivity of MB neurons.

  4. Dorothy Crowfoot Hodgkin

    Science.gov (United States)

    Montalvo, Jessica

    2009-10-01

    Born in 1910 in Cairo, Egypt, Dorothy Crowfoot Hodgkin would later be known as the third woman in history to win the Nobel Prize in Chemistry for her research on the structure of vitamin B-12. Her X-ray crystallography work also included discovering the molecular structure of penicillin and insulin. Dr. Hodgkin's work has aided in determining the structures of molecules for others to expand the technology necessary for today's medicine.

  5. Primary gastric Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Koak Yashwant

    2007-10-01

    Full Text Available Abstract Background Primary Hodgkin's disease of the stomach is an extremely rare entity. Nearly all cases of primary gastric lymphoma are of the non-Hodgkin's variety. Diagnoses in such cases are difficult due to considerable histological similarities between the 2 disease entities. Case presentation We report the case of a 77 year old lady with a 1 year history of weight loss and poor appetite. Physical examination was unremarkable. Subsequent multiple upper GI endoscopies revealed a large malignant looking ulcer which was deemed to be histologically benign. Following CT imaging the patient underwent a radical gastrectomy. Postoperatively histology and immunohistochemistry failed to confirm a diagnosis. As such a second opinion was sought. Employing an extended array of immunohistological staining a diagnosis of 'Classical Hodgkin's' disease of the stomach was achieved. Conclusion Our case illustrates the significant difficulties in achieving a rare diagnosis of primary Hodgkin's lymphoma of the stomach. The non-specific nature of symptoms and a lack of histological features make a preoperative diagnosis extremely difficult. While immunohistochemistry is widely employed in aiding the evaluation of such cases, one should be wary of the considerable overlap in differentiating between Hodgkin's and non-Hodgkin's disease entities using this technique.

  6. Orientation selectivity in inhibition-dominated networks of spiking neurons: effect of single neuron properties and network dynamics.

    Science.gov (United States)

    Sadeh, Sadra; Rotter, Stefan

    2015-01-01

    The neuronal mechanisms underlying the emergence of orientation selectivity in the primary visual cortex of mammals are still elusive. In rodents, visual neurons show highly selective responses to oriented stimuli, but neighboring neurons do not necessarily have similar preferences. Instead of a smooth map, one observes a salt-and-pepper organization of orientation selectivity. Modeling studies have recently confirmed that balanced random networks are indeed capable of amplifying weakly tuned inputs and generating highly selective output responses, even in absence of feature-selective recurrent connectivity. Here we seek to elucidate the neuronal mechanisms underlying this phenomenon by resorting to networks of integrate-and-fire neurons, which are amenable to analytic treatment. Specifically, in networks of perfect integrate-and-fire neurons, we observe that highly selective and contrast invariant output responses emerge, very similar to networks of leaky integrate-and-fire neurons. We then demonstrate that a theory based on mean firing rates and the detailed network topology predicts the output responses, and explains the mechanisms underlying the suppression of the common-mode, amplification of modulation, and contrast invariance. Increasing inhibition dominance in our networks makes the rectifying nonlinearity more prominent, which in turn adds some distortions to the otherwise essentially linear prediction. An extension of the linear theory can account for all the distortions, enabling us to compute the exact shape of every individual tuning curve in our networks. We show that this simple form of nonlinearity adds two important properties to orientation selectivity in the network, namely sharpening of tuning curves and extra suppression of the modulation. The theory can be further extended to account for the nonlinearity of the leaky model by replacing the rectifier by the appropriate smooth input-output transfer function. These results are robust and do not

  7. Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis

    Science.gov (United States)

    Sikora, Grzegorz; Wyłomańska, Agnieszka; Gajda, Janusz; Solé, Laura; Akin, Elizabeth J.; Tamkun, Michael M.; Krapf, Diego

    2017-12-01

    Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K+ channel Kv1.4 and the Na+ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.

  8. Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector.

    Science.gov (United States)

    Koshimizu, Yoshinori; Fujiyama, Fumino; Nakamura, Kouichi C; Furuta, Takahiro; Kaneko, Takeshi

    2013-06-15

    The subthalamic nucleus (STN) of the basal ganglia plays a key role in motor control, and STN efferents are known to mainly target the external segment of the globus pallidus (GPe), entopeduncular nucleus (Ep), and substantia nigra (SN) with some axon collaterals to the other regions. However, it remains to be clarified how each STN neuron projects axon fibers and collaterals to those target nuclei of the STN. Here we visualized the whole axonal arborization of single STN neurons in the rat brain by using a viral vector expressing membrane-targeted green fluorescent protein, and examined the distribution of axon boutons in those target nuclei. The vast majority (8-9) of 10 reconstructed STN neurons projected to the GPe, SN, caudate-putamen (CPu), and Ep, which received, on average ± SD, 457 ± 425, 400 ± 347, 126 ± 143, and 106 ± 100 axon boutons per STN neuron, respectively. Furthermore, the density of axon boutons in the GPe was highest among these nuclei. Although these target nuclei were divided into calbindin-rich and -poor portions, STN projection showed no exclusive preference for those portions. Since STN neurons mainly projected not only to the GPe, SN, and Ep but also to the CPu, the subthalamostriatal projection might serve as a positive feedback path for the striato-GPe-subthalamic disinhibitory pathway, or work as another route of cortical inputs to the striatum through the corticosubthalamostriatal disynaptic excitatory pathway. Copyright © 2012 Wiley Periodicals, Inc.

  9. A single hidden layer feedforward network with only one neuron in the hidden layer can approximate any univariate function

    OpenAIRE

    Guliyev, Namig; Ismailov, Vugar

    2016-01-01

    The possibility of approximating a continuous function on a compact subset of the real line by a feedforward single hidden layer neural network with a sigmoidal activation function has been studied in many papers. Such networks can approximate an arbitrary continuous function provided that an unlimited number of neurons in a hidden layer is permitted. In this paper, we consider constructive approximation on any finite interval of $\\mathbb{R}$ by neural networks with only one neuron in the hid...

  10. Plasticity of marrow mesenchymal stem cells from human first-trimester fetus: from single-cell clone to neuronal differentiation.

    Science.gov (United States)

    Zhang, Yihua; Shen, Wenzheng; Sun, Bingjie; Lv, Changrong; Dou, Zhongying

    2011-02-01

    Recent results have shown that bone marrow mesenchymal stem cells (BMSCs) from human first-trimester abortus (hfBMSCs) are closer to embryonic stem cells and perform greater telomerase activity and faster propagation than mid- and late-prophase fetal and adult BMSCs. However, no research has been done on the plasticity of hfBMSCs into neuronal cells using single-cell cloned strains without cell contamination. In this study, we isolated five single cells from hfBMSCs and obtained five single-cell cloned strains, and investigated their biological property and neuronal differentiation potential. We found that four of the five strains showed similar expression profile of surface antigen markers to hfBMSCs, and most of them differentiated into neuron-like cells expressing Nestin, Pax6, Sox1, β-III Tubulin, NF-L, and NSE under induction. One strain showed different expression profile of surface antigen markers from the four strains and hfBMSCs, and did not differentiate toward neuronal cells. We demonstrated for the first time that some of single-cell cloned strains from hfBMSCs can differentiate into nerve tissue-like cell clusters under induction in vitro, and that the plasticity of each single-cell cloned strain into neuronal cells is different.

  11. Auditory and audio-vocal responses of single neurons in the monkey ventral premotor cortex.

    Science.gov (United States)

    Hage, Steffen R

    2018-03-20

    Monkey vocalization is a complex behavioral pattern, which is flexibly used in audio-vocal communication. A recently proposed dual neural network model suggests that cognitive control might be involved in this behavior, originating from a frontal cortical network in the prefrontal cortex and mediated via projections from the rostral portion of the ventral premotor cortex (PMvr) and motor cortex to the primary vocal motor network in the brainstem. For the rapid adjustment of vocal output to external acoustic events, strong interconnections between vocal motor and auditory sites are needed, which are present at cortical and subcortical levels. However, the role of the PMvr in audio-vocal integration processes remains unclear. In the present study, single neurons in the PMvr were recorded in rhesus monkeys (Macaca mulatta) while volitionally producing vocalizations in a visual detection task or passively listening to monkey vocalizations. Ten percent of randomly selected neurons in the PMvr modulated their discharge rate in response to acoustic stimulation with species-specific calls. More than four-fifths of these auditory neurons showed an additional modulation of their discharge rates either before and/or during the monkeys' motor production of the vocalization. Based on these audio-vocal interactions, the PMvr might be well positioned to mediate higher order auditory processing with cognitive control of the vocal motor output to the primary vocal motor network. Such audio-vocal integration processes in the premotor cortex might constitute a precursor for the evolution of complex learned audio-vocal integration systems, ultimately giving rise to human speech. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Deriving Behaviour of Hodgkin Huxley model with fever dynamics: A computational study

    Directory of Open Access Journals (Sweden)

    Hasan ESKALEN

    2017-10-01

    Full Text Available A single neuron can be modeled by the set of differential equations. Hodgkin-Huxley (HH model, the one of the most famous neuron model, can be considered as a dynamical system with four independent variables. Here we studied to reduce the number of differential equation required for conductance based HH model under strong inhibitory noise. Exponential Integrate and Fire (EIF model, one independent variable, is used as a reduced model of HH model by using current-voltage (I-V curve of the original model. The required reduction parameters are determined from this curve. The behaviour of HH model and its reduced EIF (rEIF model are in good agreement in sub-threshold level. Above-threshold behaviour of reduced EIF model and original model compared in terms of threshold voltage under strong inhibitory noise. Our numerical simulations clearly show that sub-threshold behaviour of HH model perfectly reduced to rEIF model.

  13. Divisive normalization and neuronal oscillations in a single hierarchical framework of selective visual attention

    Directory of Open Access Journals (Sweden)

    Jorrit Steven Montijn

    2012-05-01

    Full Text Available In divisive normalization models of covert attention, spike rate modulations are commonly used as indicators of the effect of top-down attention. In addition, an increasing number of studies have shown that top-down attention increases the synchronization of neuronal oscillations as well, particularly those in gamma-band frequencies (25 to 100 Hz. Although modulations of spike rate and synchronous oscillations are not mutually exclusive as mechanisms of attention, there has thus far been little effort to integrate these concepts into a single framework of attention. Here, we aim to provide such a unified framework by expanding the normalization model of attention with a time dimension; allowing the simulation of a recently reported backward progression of attentional effects along the visual cortical hierarchy. A simple hierarchical cascade of normalization models simulating different cortical areas however leads to signal degradation and a loss of discriminability over time. To negate this degradation and ensure stable neuronal stimulus representations, we incorporate oscillatory phase entrainment into our model, a mechanism previously proposed as the communication-through-coherence (CTC hypothesis. Our analysis shows that divisive normalization and oscillation models can complement each other in a unified account of the neural mechanisms of selective visual attention. The resulting hierarchical normalization and oscillation (HNO model reproduces several additional spatial and temporal aspects of attentional modulation.

  14. Hodgkin Lymphoma Mimicking Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Aneela Majeed

    2017-06-01

    Full Text Available Hodgkin lymphoma with symptomatic osseous involvement can have a similar presentation to osteomyelitis. Common findings in symptoms, laboratory workup, and imaging can make it very difficult to distinguish between the two diseases. Excisional biopsy should be pursued if fine-needle biopsy is equivocal and suspicion of lymphoma is high. We report a case of a 40-year-old man who presented with a history of marine animal sting on his neck and later developed erythema in the area, chest pain, constitutional symptoms, adenopathy, and imaging classic for sternal osteomyelitis. Fortunately, initial biopsy prompted the possibility of lymphoma, and further workup was initiated, which confirmed Hodgkin lymphoma. This case is a good reminder that malignancies and infections can share many common features, and keeping a broad differential diagnosis can be lifesaving. Proper staging and risk stratification of Hodgkin lymphoma help determine the optimal treatment.

  15. Predicting the functional states of human iPSC-derived neurons with single-cell RNA-seq and electrophysiology.

    Science.gov (United States)

    Bardy, C; van den Hurk, M; Kakaradov, B; Erwin, J A; Jaeger, B N; Hernandez, R V; Eames, T; Paucar, A A; Gorris, M; Marchand, C; Jappelli, R; Barron, J; Bryant, A K; Kellogg, M; Lasken, R S; Rutten, B P F; Steinbusch, H W M; Yeo, G W; Gage, F H

    2016-11-01

    Human neural progenitors derived from pluripotent stem cells develop into electrophysiologically active neurons at heterogeneous rates, which can confound disease-relevant discoveries in neurology and psychiatry. By combining patch clamping, morphological and transcriptome analysis on single-human neurons in vitro, we defined a continuum of poor to highly functional electrophysiological states of differentiated neurons. The strong correlations between action potentials, synaptic activity, dendritic complexity and gene expression highlight the importance of methods for isolating functionally comparable neurons for in vitro investigations of brain disorders. Although whole-cell electrophysiology is the gold standard for functional evaluation, it often lacks the scalability required for disease modeling studies. Here, we demonstrate a multimodal machine-learning strategy to identify new molecular features that predict the physiological states of single neurons, independently of the time spent in vitro. As further proof of concept, we selected one of the potential neurophysiological biomarkers identified in this study-GDAP1L1-to isolate highly functional live human neurons in vitro.

  16. What's the Difference between Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma?

    Science.gov (United States)

    ... What's the difference? What's the difference between Hodgkin's lymphoma and non-Hodgkin's lymphoma? Answers from Rajiv K. Pruthi, M.B.B.S. Both Hodgkin's lymphoma and non-Hodgkin's lymphoma are lymphomas — a type of cancer that ...

  17. Hodgkin's disease and age

    DEFF Research Database (Denmark)

    Specht, L; Nissen, N I

    1989-01-01

    506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

  18. Single-neuron diversity generated by Protocadherin-β cluster in mouse central and peripheral nervous systems

    Directory of Open Access Journals (Sweden)

    Keizo eHirano

    2012-08-01

    Full Text Available The generation of complex neural circuits depends on the correct wiring of neurons with diverse individual characteristics. To understand the complexity of the nervous system, the molecular mechanisms for specifying the identity and diversity of individual neurons must be elucidated. The clustered protocadherins (Pcdh in mammals consist of approximately 50 Pcdh genes (Pcdh-α, Pcdh-β, and Pcdh-γ that encode cadherin-family cell surface adhesion proteins. Individual neurons express a random combination of Pcdh-α and Pcdh-γ, whereas the expression patterns for the Pcdh-β genes, 22 one-exon genes in mouse, are not fully understood. Here we show that the Pcdh-β genes are expressed in a 3’-polyadenylated form in mouse brain. In situ hybridization using a pan-Pcdh-β probe against a conserved Pcdh-β sequence showed widespread labeling in the brain, with prominent signals in the olfactory bulb, hippocampus, and cerebellum. In situ hybridization with specific probes for individual Pcdh-β genes showed their expression to be scattered in Purkinje cells from P10 to P150. The scattered expression patterns were confirmed by performing a newly developed single-cell 3’-RACE analysis of Purkinje cells, which clearly demonstrated that the Pcdh-β genes are expressed monoallelically and combinatorially in individual Purkinje cells. Scattered expression patterns of individual Pcdh-β genes were also observed in pyramidal neurons in the hippocampus and cerebral cortex, neurons in the trigeminal and dorsal root ganglion, GABAergic interneurons, and cholinergic neurons. Our results extend previous observations of diversity at the single-neuron level generated by Pcdh expression and suggest that the Pcdh-β cluster genes contribute to specifying the identity and diversity of individual neurons.

  19. Hodgkin, Prof. Dorothy Crowfoot

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1972 Honorary. Hodgkin, Prof. Dorothy Crowfoot Nobel Laureate (Chemistry) - 1964. Date of birth: 12 May 1910. Date of death: 29 July 1994. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the ...

  20. Hodgkin, Prof. Alan Lloyd

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1975 Honorary. Hodgkin, Prof. Alan Lloyd Nobel Laureate (Medicine) - 1963. Date of birth: 5 February 1914. Date of death: 20 December 1998. YouTube; Twitter; Facebook; Blog. Academy News. IAS Logo. Theory Of Evolution. Posted on 23 January 2018. Joint Statement by the ...

  1. Task-dependent changes in cross-level coupling between single neurons and oscillatory activity in multiscale networks.

    Directory of Open Access Journals (Sweden)

    Ryan T Canolty

    Full Text Available Understanding the principles governing the dynamic coordination of functional brain networks remains an important unmet goal within neuroscience. How do distributed ensembles of neurons transiently coordinate their activity across a variety of spatial and temporal scales? While a complete mechanistic account of this process remains elusive, evidence suggests that neuronal oscillations may play a key role in this process, with different rhythms influencing both local computation and long-range communication. To investigate this question, we recorded multiple single unit and local field potential (LFP activity from microelectrode arrays implanted bilaterally in macaque motor areas. Monkeys performed a delayed center-out reach task either manually using their natural arm (Manual Control, MC or under direct neural control through a brain-machine interface (Brain Control, BC. In accord with prior work, we found that the spiking activity of individual neurons is coupled to multiple aspects of the ongoing motor beta rhythm (10-45 Hz during both MC and BC, with neurons exhibiting a diversity of coupling preferences. However, here we show that for identified single neurons, this beta-to-rate mapping can change in a reversible and task-dependent way. For example, as beta power increases, a given neuron may increase spiking during MC but decrease spiking during BC, or exhibit a reversible shift in the preferred phase of firing. The within-task stability of coupling, combined with the reversible cross-task changes in coupling, suggest that task-dependent changes in the beta-to-rate mapping play a role in the transient functional reorganization of neural ensembles. We characterize the range of task-dependent changes in the mapping from beta amplitude, phase, and inter-hemispheric phase differences to the spike rates of an ensemble of simultaneously-recorded neurons, and discuss the potential implications that dynamic remapping from oscillatory activity to

  2. What You Need to Know about Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... Reports What You Need To Know About™ Non-Hodgkin Lymphoma This booklet is about non-Hodgkin lymphoma, a ... doctor visit. This booklet is not about Hodgkin lymphoma (also called Hodgkin disease). Hodgkin lymphoma is a different type of ...

  3. Optimal stimulus shapes for neuronal excitation.

    Directory of Open Access Journals (Sweden)

    Daniel B Forger

    2011-07-01

    Full Text Available An important problem in neuronal computation is to discern how features of stimuli control the timing of action potentials. One aspect of this problem is to determine how an action potential, or spike, can be elicited with the least energy cost, e.g., a minimal amount of applied current. Here we show in the Hodgkin & Huxley model of the action potential and in experiments on squid giant axons that: 1 spike generation in a neuron can be highly discriminatory for stimulus shape and 2 the optimal stimulus shape is dependent upon inputs to the neuron. We show how polarity and time course of post-synaptic currents determine which of these optimal stimulus shapes best excites the neuron. These results are obtained mathematically using the calculus of variations and experimentally using a stochastic search methodology. Our findings reveal a surprising complexity of computation at the single cell level that may be relevant for understanding optimization of signaling in neurons and neuronal networks.

  4. Coordinate control of integral reactor based on single neuron PID controller

    International Nuclear Information System (INIS)

    Liu Yan; Xia Hong

    2014-01-01

    As one of the main type of reactors in the future, the development of the integral reactor has attracted worldwide attention. On the basis of understanding the background of the integral reactor, the author will be familiar with and master the power control of reactor and the feedwater flow control of steam generator, and the speed control of turbine (turbine speed control is associated with the turbine load control). According to the expectative program 'reactor power following turbine load' of the reactor, it will make coordinate control of the three and come to a overall control scheme. The author will use the supervisory learning algorithm of Hebb for single neuron PID controller with self-adaptation to study the coordinate control of integral reactor. Compared with conventional PI or PID controller, to a certain extent, it solves the problems that traditional PID controller is not easy to tune real-time parameters and lack of effective control for a number of complex processes and slow-varying parameter systems. It improves the security, reliability, stability and flexibility of control process and achieves effective control of the system. (authors)

  5. Spike Train SIMilarity Space (SSIMS): a frame-work for single neuron and ensemble data analysis

    Science.gov (United States)

    Vargas-Irwin, Carlos E.; Brandman, David M.; Zimmermann, Jonas B.; Donoghue, John P.; Black, Michael J.

    2014-01-01

    Increased emphasis on circuit level activity in the brain makes it necessary to have methods to visualize and evaluate large scale ensemble activity, beyond that revealed by raster-histograms or pairwise correlations. We present a method to evaluate the relative similarity of neural spiking patterns by combining spike train distance metrics with dimensionality reduction. Spike train distance metrics provide an estimate of similarity between activity patterns at multiple temporal resolutions. Vectors of pair-wise distances are used to represent the intrinsic relationships between multiple activity patterns at the level of single units or neuronal ensembles. Dimensionality reduction is then used to project the data into concise representations suitable for clustering analysis as well as exploratory visualization. Algorithm performance and robustness are evaluated using multielectrode ensemble activity data recorded in behaving primates. We demonstrate how Spike train SIMilarity Space (SSIMS) analysis captures the relationship between goal directions for an 8-directional reaching task and successfully segregates grasp types in a 3D grasping task in the absence of kinematic information. The algorithm enables exploration of virtually any type of neural spiking (time series) data, providing similarity-based clustering of neural activity states with minimal assumptions about potential information encoding models. PMID:25380335

  6. Single neuron recordings of bilinguals performing in a continuous recognition memory task.

    Directory of Open Access Journals (Sweden)

    Erika K Hussey

    Full Text Available We report the results of a bilingual continuous recognition memory task during which single- and multi-neuron activity was recorded in human subjects with intracranial microwire implants. Subjects (n = 5 were right-handed Spanish-English bilinguals who were undergoing evaluation prior to surgery for severe epilepsy. Subjects were presented with Spanish and English words and the task was to determine whether any given word had been seen earlier in the testing session, irrespective of the language in which it had appeared. Recordings in the left and right hippocampus revealed notable laterality, whereby both Spanish and English items that had been seen previously in the other language (switch trials triggered increased neural firing in the left hippocampus. Items that had been seen previously in the same language (repeat trials triggered increased neural firings in the right hippocampus. These results are consistent with theories that propose roles of both the left- and right-hemisphere in real-time linguistic processing. Importantly, this experiment presents the first instance of intracranial recordings in bilinguals performing a task with switching demands.

  7. Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis.

    Science.gov (United States)

    Aransay, Ana; Rodríguez-López, Claudia; García-Amado, María; Clascá, Francisco; Prensa, Lucía

    2015-01-01

    Pathways arising from the ventral tegmental area (VTA) release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VTA projections is well-known, the actual axonal wiring of individual VTA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VTA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VTA cells with iontophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VTA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells), and neurons with multibranched axons targeting both the forebrain and the brainstem (F + BSPN cells). Dopaminergic phenotype was observed in FPN cells. Moreover, four "subtypes" could be distinguished among the FPN cells based on their projection targets: (1) "Mesocorticolimbic" FPN projecting to both neocortex and basal forebrain; (2) "Mesocortical" FPN innervating the neocortex almost exclusively; (3) "Mesolimbic" FPN projecting to the basal forebrain, accumbens and caudateputamen; and (4) "Mesostriatal" FPN targeting only the caudateputamen. While the F + BSPN cells were scattered within VTA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VTA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.

  8. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

    Science.gov (United States)

    Luhmann, Heiko J; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits.

  9. Not a single but multiple populations of GABAergic neurons control sleep.

    Science.gov (United States)

    Luppi, Pierre-Hervé; Peyron, Christelle; Fort, Patrice

    2017-04-01

    The role of gamma-amino butyric acid (GABA) in sleep induction and maintenance is well accepted since most insomnia treatments target GABAa receptors. However, the population(s) of GABAergic neurons involved in the beneficial effect of GABA on sleep remains to be identified. This is not an easy task since GABAergic neurons are widely distributed in all brain structures. A recently growing number of populations of GABAergic neurons have been involved in sleep control. We first review here possible candidates for inducing non-rapid eye movement (NREM) sleep including the GABAergic neurons of the ventrolateral preoptic area, the parafacial zone in the brainstem, the nucleus accumbens and the cortex. We also discuss the role of several populations of GABAergic neurons in rapid eye movement (REM) sleep control. Indeed, it is well accepted that muscle atonia occurring during REM sleep is due to a GABA/glycinergic hyperpolarization of motoneurons. Recent evidence strongly suggests that these neurons are located in the ventral medullary reticular formation. It has also recently been shown that neurons containing the neuropeptide melanin concentrating hormone and GABA located in the lateral hypothalamic area control REM sleep expression. Finally, a population of REM-off GABAergic neurons located in the ventrolateral periaqueductal gray has been shown to gate REM sleep by inhibiting glutamatergic neurons located in the sublaterodorsal tegmental nucleus. In summary, recent data clearly indicate that multiple populations of GABAergic neurons located throughout the brain from the cortex to the medulla oblongata control NREM and REM sleep. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Hodgkin's disease and age

    DEFF Research Database (Denmark)

    Specht, L.; Nissen, N.I.

    1989-01-01

    506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... nodal tumour burden, intraabdominal nodal tumour burden, and number of involved extranodal sites), pretreatment ESR, lymphocytopenia, and treatment modality were examined in multivariate analyses. The only factors of independent prognostic significance for disease-free survival proved to be treatment...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

  11. Hodgkin's disease in childhood

    International Nuclear Information System (INIS)

    Misol Perez, A.; Dabezies Antia, A.

    1994-01-01

    Actually, the majority of the children that suffer from Hodgkin illness can have long period of survive. The cures are related with the continuous achievements in biology molecular; techniques of different state, radiotherapy, chemotherapy, imagenology, proceedings and to the multidisciplinary handling. This article summarizes those aspects related with the illness and its treatment, taking in count the biggest impact of the secondary effects on children and adolescents that are in growth and active development. (Au) [es

  12. Different cortical projections from three subdivisions of the rat lateral posterior thalamic nucleus: a single-neuron tracing study with viral vectors.

    Science.gov (United States)

    Nakamura, Hisashi; Hioki, Hiroyuki; Furuta, Takahiro; Kaneko, Takeshi

    2015-05-01

    The lateral posterior thalamic nucleus (LP) is one of the components of the extrageniculate pathway in the rat visual system, and is cytoarchitecturally divided into three subdivisions--lateral (LPl), rostromedial (LPrm), and caudomedial (LPcm) portions. To clarify the differences in the dendritic fields and axonal arborisations among the three subdivisions, we applied a single-neuron labeling technique with viral vectors to LP neurons. The proximal dendrites of LPl neurons were more numerous than those of LPrm and LPcm neurons, and LPrm neurons tended to have wider dendritic fields than LPl neurons. We then analysed the axonal arborisations of LP neurons by reconstructing the axon fibers in the cortex. The LPl, LPrm and LPcm were different from one another in terms of the projection targets--the main target cortical regions of LPl and LPrm neurons were the secondary and primary visual areas, whereas those of LPcm neurons were the postrhinal and temporal association areas. Furthermore, the principal target cortical layers of LPl neurons in the visual areas were middle layers, but that of LPrm neurons was layer 1. This indicates that LPl and LPrm neurons can be categorised into the core and matrix types of thalamic neurons, respectively, in the visual areas. In addition, LPl neurons formed multiple axonal clusters within the visual areas, whereas the fibers of LPrm neurons were widely and diffusely distributed. It is therefore presumed that these two types of neurons play different roles in visual information processing by dual thalamocortical innervation of the visual areas. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  13. Non-Hodgkin Lymphoma (For Parents)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Non-Hodgkin Lymphoma KidsHealth / For Parents / Non-Hodgkin Lymphoma What's in ... harmful things out of the body. About Non-Hodgkin Lymphoma No n-Hodgkin lymphoma is a disease in ...

  14. μ-Opioid receptor activation and noradrenaline transport inhibition by tapentadol in rat single locus coeruleus neurons.

    Science.gov (United States)

    Sadeghi, Mahsa; Tzschentke, Thomas M; Christie, MacDonald J

    2015-01-01

    Tapentadol is a novel analgesic that combines moderate μ-opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule. Both mechanisms of action are involved in producing analgesia; however, the potency and efficacy of tapentadol in individual neurons has not been characterized. Whole-cell patch-clamp recordings of G-protein-coupled inwardly rectifying K(+) (KIR 3.x) currents were made from rat locus coeruleus neurons in brain slices to investigate the potency and relative efficacy of tapentadol and compare its intrinsic activity with other clinically used opioids. Tapentadol showed agonist activity at μ receptors and was approximately six times less potent than morphine with respect to KIR 3.x current modulation. The intrinsic activity of tapentadol was lower than [Met]enkephalin, morphine and oxycodone, but higher than buprenorphine and pentazocine. Tapentadol inhibited the noradrenaline transporter (NAT) with potency similar to that at μ receptors. The interaction between these two mechanisms of action was additive in individual LC neurons. Tapentadol displays similar potency for both µ receptor activation and NAT inhibition in functioning neurons. The intrinsic activity of tapentadol at the μ receptor lies between that of buprenorphine and oxycodone, potentially explaining the favourable profile of side effects, related to μ receptors. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2013 The British Pharmacological Society.

  15. Treatment of Hodgkin`s disease; Tratamento da doenca de Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Silva, E.M. [Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti, Rio de Janeiro, RJ (Brazil). Servico de Hematologia Clinica

    1993-12-31

    This study consists of a revision of the treatment and prognosis of Hodgkin`s disease, comparing the chemotherapeutic and radiotherapeutic therapy and the complications both as a direct result of the disease and a result of the treatment. (author). 34 refs, 1 tab.

  16. Single Neurons in the Avian Auditory Cortex Encode Individual Identity and Propagation Distance in Naturally Degraded Communication Calls.

    Science.gov (United States)

    Mouterde, Solveig C; Elie, Julie E; Mathevon, Nicolas; Theunissen, Frédéric E

    2017-03-29

    One of the most complex tasks performed by sensory systems is "scene analysis": the interpretation of complex signals as behaviorally relevant objects. The study of this problem, universal to species and sensory modalities, is particularly challenging in audition, where sounds from various sources and localizations, degraded by propagation through the environment, sum to form a single acoustical signal. Here we investigated in a songbird model, the zebra finch, the neural substrate for ranging and identifying a single source. We relied on ecologically and behaviorally relevant stimuli, contact calls, to investigate the neural discrimination of individual vocal signature as well as sound source distance when calls have been degraded through propagation in a natural environment. Performing electrophysiological recordings in anesthetized birds, we found neurons in the auditory forebrain that discriminate individual vocal signatures despite long-range degradation, as well as neurons discriminating propagation distance, with varying degrees of multiplexing between both information types. Moreover, the neural discrimination performance of individual identity was not affected by propagation-induced degradation beyond what was induced by the decreased intensity. For the first time, neurons with distance-invariant identity discrimination properties as well as distance-discriminant neurons are revealed in the avian auditory cortex. Because these neurons were recorded in animals that had prior experience neither with the vocalizers of the stimuli nor with long-range propagation of calls, we suggest that this neural population is part of a general-purpose system for vocalizer discrimination and ranging. SIGNIFICANCE STATEMENT Understanding how the brain makes sense of the multitude of stimuli that it continually receives in natural conditions is a challenge for scientists. Here we provide a new understanding of how the auditory system extracts behaviorally relevant information

  17. Induction of specific neuron types by overexpression of single transcription factors.

    Science.gov (United States)

    Teratani-Ota, Yusuke; Yamamizu, Kohei; Piao, Yulan; Sharova, Lioudmila; Amano, Misa; Yu, Hong; Schlessinger, David; Ko, Minoru S H; Sharov, Alexei A

    2016-10-01

    Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types.

  18. Energetics based spike generation of a single neuron: simulation results and analysis

    Directory of Open Access Journals (Sweden)

    Nagarajan eVenkateswaran

    2012-02-01

    Full Text Available Existing current based models that capture spike activity, though useful in studying information processing capabilities of neurons, fail to throw light on their internal functioning. It is imperative to develop a model that captures the spike train of a neuron as a function of its intra cellular parameters for non-invasive diagnosis of diseased neurons. This is the first ever article to present such an integrated model that quantifies the inter-dependency between spike activity and intra cellular energetics. The generated spike trains from our integrated model will throw greater light on the intra-cellular energetics than existing current models. Now, an abnormality in the spike of a diseased neuron can be linked and hence effectively analyzed at the energetics level. The spectral analysis of the generated spike trains in a time-frequency domain will help identify abnormalities in the internals of a neuron. As a case study, the parameters of our model are tuned for Alzheimer disease and its resultant spike trains are studied and presented.

  19. A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster.

    Science.gov (United States)

    Haynes, Paula R; Christmann, Bethany L; Griffith, Leslie C

    2015-01-07

    Sleep promotes memory consolidation in humans and many other species, but the physiological and anatomical relationships between sleep and memory remain unclear. Here, we show the dorsal paired medial (DPM) neurons, which are required for memory consolidation in Drosophila, are sleep-promoting inhibitory neurons. DPMs increase sleep via release of GABA onto wake-promoting mushroom body (MB) α'/β' neurons. Functional imaging demonstrates that DPM activation evokes robust increases in chloride in MB neurons, but is unable to cause detectable increases in calcium or cAMP. Downregulation of α'/β' GABAA and GABABR3 receptors results in sleep loss, suggesting these receptors are the sleep-relevant targets of DPM-mediated inhibition. Regulation of sleep by neurons necessary for consolidation suggests that these brain processes may be functionally interrelated via their shared anatomy. These findings have important implications for the mechanistic relationship between sleep and memory consolidation, arguing for a significant role of inhibitory neurotransmission in regulating these processes.

  20. Treatment of Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Petrov, M.

    1986-01-01

    The data pertinent to 101 patients with Hodgkin's disease who had been subjected to splenectomy and combined radiation therapy and chemotherapy are analyzed. The efficacy of the treatment was relatively dependent on the initial localization and the degree of the generalization and appresiveness of the disease. Acceleration of the disease gene realization stemmed from totally deranged antitumor immunity. The modern therapeutic remedies have reached the peak of their potentialities. This prompt the necessity of the search for new, still unknown biological methods, permitting the attainment of a more complete demalignancy

  1. Positron emission tomography with 2-[18F]-Fluoro-2-Deoxy-D-Glucose for initial staging of hodgkin lymphoma: a single center experience in Brazil

    Directory of Open Access Journals (Sweden)

    Juliano Julio Cerci

    2009-06-01

    Full Text Available BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS methods, including computed tomography (CT and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively. FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively. FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82 of the patients and downstaged 11% (9/82 of the patients. As a result of these changes in staging, 15% (13/82 of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients brought about by the addition of PET to the staging algorithm

  2. Operant conditioning of synaptic and spiking activity patterns in single hippocampal neurons.

    Science.gov (United States)

    Ishikawa, Daisuke; Matsumoto, Nobuyoshi; Sakaguchi, Tetsuya; Matsuki, Norio; Ikegaya, Yuji

    2014-04-02

    Learning is a process of plastic adaptation through which a neural circuit generates a more preferable outcome; however, at a microscopic level, little is known about how synaptic activity is patterned into a desired configuration. Here, we report that animals can generate a specific form of synaptic activity in a given neuron in the hippocampus. In awake, head-restricted mice, we applied electrical stimulation to the lateral hypothalamus, a reward-associated brain region, when whole-cell patch-clamped CA1 neurons exhibited spontaneous synaptic activity that met preset criteria. Within 15 min, the mice learned to generate frequently the excitatory synaptic input pattern that satisfied the criteria. This reinforcement learning of synaptic activity was not observed for inhibitory input patterns. When a burst unit activity pattern was conditioned in paired and nonpaired paradigms, the frequency of burst-spiking events increased and decreased, respectively. The burst reinforcement occurred in the conditioned neuron but not in other adjacent neurons; however, ripple field oscillations were concomitantly reinforced. Neural conditioning depended on activation of NMDA receptors and dopamine D1 receptors. Acutely stressed mice and depression model mice that were subjected to forced swimming failed to exhibit the neural conditioning. This learning deficit was rescued by repetitive treatment with fluoxetine, an antidepressant. Therefore, internally motivated animals are capable of routing an ongoing action potential series into a specific neural pathway of the hippocampal network.

  3. What You Need to Know about Hodgkin Lymphoma

    Science.gov (United States)

    ... Publications Reports What You Need To Know About™ Hodgkin Lymphoma This booklet is about Hodgkin lymphoma. This type ... visit. This booklet is not about non-Hodgkin lymphoma. Non-Hodgkin lymphoma is a different disease with different treatments ...

  4. Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma.

    Science.gov (United States)

    Shahid, Ruqaiya; Gulzar, Rubina; Avesi, Lubna; Hassan, Saba; Danish, Farheen; Mirza, Talat

    2016-02-01

    To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Cross-sectional analytical study. Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Out of the 318 cases, 79 (25%) were Hodgkin Lymphomas (HL) and 239 (75%) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95%) were B cell lymphomas and 24 (10.05%) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95% of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HLwas significantly higher in the younger age group and that of NHLwas higher in the older age group (p Hodgkin lymphoma comprises 25% and non-Hodgkin lymphoma comprises 75% of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHLis three times more common than T-cell lymphoma. DLBCLis the most frequent lymphoma. ALCLis the most common T-cell, and mixed cellularity is the most common Hodgkin lymphoma.

  5. Stability and Hopf Bifurcation of Fractional-Order Complex-Valued Single Neuron Model with Time Delay

    Science.gov (United States)

    Wang, Zhen; Wang, Xiaohong; Li, Yuxia; Huang, Xia

    2017-12-01

    In this paper, the problems of stability and Hopf bifurcation in a class of fractional-order complex-valued single neuron model with time delay are addressed. With the help of the stability theory of fractional-order differential equations and Laplace transforms, several new sufficient conditions, which ensure the stability of the system are derived. Taking the time delay as the bifurcation parameter, Hopf bifurcation is investigated and the critical value of the time delay for the occurrence of Hopf bifurcation is determined. Finally, two representative numerical examples are given to show the effectiveness of the theoretical results.

  6. Bayesian nonparametric modeling for comparison of single-neuron firing intensities.

    Science.gov (United States)

    Kottas, Athanasios; Behseta, Sam

    2010-03-01

    We propose a fully inferential model-based approach to the problem of comparing the firing patterns of a neuron recorded under two distinct experimental conditions. The methodology is based on nonhomogeneous Poisson process models for the firing times of each condition with flexible nonparametric mixture prior models for the corresponding intensity functions. We demonstrate posterior inferences from a global analysis, which may be used to compare the two conditions over the entire experimental time window, as well as from a pointwise analysis at selected time points to detect local deviations of firing patterns from one condition to another. We apply our method on two neurons recorded from the primary motor cortex area of a monkey's brain while performing a sequence of reaching tasks.

  7. Wireless Sensor Network Congestion Control Based on Standard Particle Swarm Optimization and Single Neuron PID.

    Science.gov (United States)

    Yang, Xiaoping; Chen, Xueying; Xia, Riting; Qian, Zhihong

    2018-04-19

    Aiming at the problem of network congestion caused by the large number of data transmissions in wireless routing nodes of wireless sensor network (WSN), this paper puts forward an algorithm based on standard particle swarm⁻neural PID congestion control (PNPID). Firstly, PID control theory was applied to the queue management of wireless sensor nodes. Then, the self-learning and self-organizing ability of neurons was used to achieve online adjustment of weights to adjust the proportion, integral and differential parameters of the PID controller. Finally, the standard particle swarm optimization to neural PID (NPID) algorithm of initial values of proportion, integral and differential parameters and neuron learning rates were used for online optimization. This paper describes experiments and simulations which show that the PNPID algorithm effectively stabilized queue length near the expected value. At the same time, network performance, such as throughput and packet loss rate, was greatly improved, which alleviated network congestion and improved network QoS.

  8. [Pulmonary alterations in Hodgkin lymphoma].

    Science.gov (United States)

    Jóna, Ádám; Illés, Árpád; Szemes, Katalin; Miltényi, Zsófia

    2016-01-31

    Most of Hodgkin lymphoma patients survive due to combined chemo/radiotherapy. Improved survival brings long-term side effects to the front, which may determine the patients' subsequent quality of life and expected lifetime. This manuscript aims to analyze lung manifestations of Hodgkin lymphoma and treatment related pulmonary complications, demonstrated with own cases. The lung involvement in Hodgkin lymphoma is often secondary, and primary pulmonary involvement is very rare. The authors found 8-12% of lung involvement among their patients. Side effects of treatment consist of pulmonary infections in conjuction with immunosuppression, while on the other hand bleomycin and chest irradiation as part of current standard of care induced pneumonitis and fibrosis are reported. The pulmonary involvement in Hodgkin lymphoma may cause differential diagnostic difficulty. Lung involvement could modify stage and consequently treatment, and the development of side effects might determine later quality of life and expected lifetime. Therefore, identification of lung involvement is crucial.

  9. Radiotherapy in the Hodgkin's disease

    International Nuclear Information System (INIS)

    Pinto, A.C.L.C.; Moura, J.E.F.M. de; Leite, M.T.T.; Santa Casa de Misericordia de Belo Horizonte

    1983-01-01

    An up-to-date summary of Hodgkin's disease is presented taking into account its natural history, dissemination patterns, history, staging and therapeutic sugestions, with special regard to radiotherapy. (Author) [pt

  10. Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2018-04-02

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  11. A Phase II Trial of Panobinostat and Lenalidomide in Patients With Relapsed or Refractory Hodgkin's Lymphoma

    Science.gov (United States)

    2017-11-09

    Adult Lymphocyte Depletion Hodgkin Lymphoma; Adult Lymphocyte Predominant Hodgkin Lymphoma; Adult Mixed Cellularity Hodgkin Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Adult Nodular Sclerosis Hodgkin Lymphoma; Recurrent Adult Hodgkin Lymphoma

  12. Hodgkin Lymphoma: Diagnosis and Treatment.

    Science.gov (United States)

    Ansell, Stephen M

    2015-11-01

    Hodgkin lymphoma is a rare B-cell malignant neoplasm affecting approximately 9000 new patients annually. This disease represents approximately 11% of all lymphomas seen in the United States and comprises 2 discrete disease entities--classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Within the subcategorization of classical Hodgkin lymphoma are defined subgroups: nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich Hodgkin lymphoma. Staging of this disease is essential for the choice of optimal therapy. Prognostic models to identify patients at high or low risk for recurrence have been developed, and these models, along with positron emission tomography, are used to provide optimal therapy. The initial treatment for patients with Hodgkin lymphoma is based on the histologic characteristics of the disease, the stage at presentation, and the presence or absence of prognostic factors associated with poor outcome. Patients with early-stage Hodgkin lymphoma commonly receive combined-modality therapies that include abbreviated courses of chemotherapy followed by involved-field radiation treatment. In contrast, patients with advanced-stage Hodgkin lymphoma commonly receive a more prolonged course of combination chemotherapy, with radiation therapy used only in selected cases. For patients with relapse or refractory disease, salvage chemotherapy followed by high-dose treatment and an autologous stem cell transplant is the standard of care. For patients who are ineligible for this therapy or those in whom high-dose therapy and autologous stem cell transplant have failed, treatment with brentuximab vedotin is a standard approach. Additional options include palliative chemotherapy, immune checkpoint inhibitors, nonmyeloablative allogeneic stem cell transplant, or participation in a clinical trial testing novel agents. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All

  13. Targeted immunotherapy in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin

    2015-01-01

    In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13.......In this issue of Blood, Rothe et al introduce a new principle of targeted Hodgkin lymphoma (HL) immunotherapy in their report from a phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13....

  14. PET-Directed Therapy With Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Classical Hodgkin Lymphoma

    Science.gov (United States)

    2017-10-18

    Classical Hodgkin Lymphoma; Lymphocyte-Depleted Classical Hodgkin Lymphoma; Lymphocyte-Rich Classical Hodgkin Lymphoma; Mixed Cellularity Classical Hodgkin Lymphoma; Nodular Sclerosis Classical Hodgkin Lymphoma

  15. Hodgkin Lymphomas epidemiology

    International Nuclear Information System (INIS)

    Diaz, Carlos; Barroso, Maria; Alvarez, Julio; Sarmiento, Sofia; Diaz, Jose

    2003-01-01

    The interest of this study has been to learn the bio demographic characteristics of the Hodgkin lymphoma in our surrounding in accord with different clinical statistics that are considered of interest taken as references the results obtained in each on them. The clinical histories of the patients were evaluated retrospectively with diagnosis of Hodgkin, and registered in the national Institute of Oncology in Havana during the years 1980-1985 (group1) and the 1990-1995 (group 2). The sample was constituted by 242 patients (156 group 1, 86 group 2). The disease was slightly more frequent in males (1.3:1) in both groups. The biggest incidence fell upon the patients under 30 year of age with 74 (31%) in the group 1, and 41 (17%) group 2; followed by the group of patients between 30 and 49 years old with 24% in group 1 and 12 in group 2. The histological subtype most frequently found was the mixed cellularity 55% of the patients followed by nodular sclerosis in 32% clinical stage III was the most frequent with 138 patients (55%) the cervical adenopathy was the most consulted symptom referred by 199 (82%) of the patients. The ionizing radiation as only treatment were used in 115 patients (48%) while 80 (33%) were treated in conjunction with polychemotherapy, and in 40 (17%) polychemotherapy was used alone. A total of 204 (84%) patients showed complete remission when ended the initial treatment while 96 (40.9%) showed a relapse and 55 (62%) of them obtained a second CR. Until the last news, there are 196 (81%) alive patients and 43 (18%) dead. (The author)

  16. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  17. Integration of Plasticity Mechanisms within a Single Sensory Neuron of C. elegans Actuates a Memory.

    Science.gov (United States)

    Hawk, Josh D; Calvo, Ana C; Liu, Ping; Almoril-Porras, Agustin; Aljobeh, Ahmad; Torruella-Suárez, María Luisa; Ren, Ivy; Cook, Nathan; Greenwood, Joel; Luo, Linjiao; Wang, Zhao-Wen; Samuel, Aravinthan D T; Colón-Ramos, Daniel A

    2018-01-17

    Neural plasticity, the ability of neurons to change their properties in response to experiences, underpins the nervous system's capacity to form memories and actuate behaviors. How different plasticity mechanisms act together in vivo and at a cellular level to transform sensory information into behavior is not well understood. We show that in Caenorhabditis elegans two plasticity mechanisms-sensory adaptation and presynaptic plasticity-act within a single cell to encode thermosensory information and actuate a temperature preference memory. Sensory adaptation adjusts the temperature range of the sensory neuron (called AFD) to optimize detection of temperature fluctuations associated with migration. Presynaptic plasticity in AFD is regulated by the conserved kinase nPKCε and transforms thermosensory information into a behavioral preference. Bypassing AFD presynaptic plasticity predictably changes learned behavioral preferences without affecting sensory responses. Our findings indicate that two distinct neuroplasticity mechanisms function together through a single-cell logic system to enact thermotactic behavior. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Induction of Associative Olfactory Memory by Targeted Activation of Single Olfactory Neurons in Drosophila Larvae

    OpenAIRE

    Honda, Takato; Lee, Chi-Yu; Yoshida-Kasikawa, Maki; Honjo, Ken; Furukubo-Tokunaga, Katsuo

    2014-01-01

    It has been postulated that associative memory is formed by at least two sets of external stimuli, CS and US, that are transmitted to the memory centers by distinctive conversing pathways. However, whether associative memory can be induced by the activation of only the olfactory CS and a biogenic amine-mediated US pathways remains to be elucidated. In this study, we substituted the reward signals with dTrpA1-mediated thermogenetic activation of octopaminergic neurons and the odor signals by C...

  19. Non-Hodgkin lymphoma after radio- and chemotherapy for Hodgkin's disease

    International Nuclear Information System (INIS)

    Fedder, G.; Somers, R.

    1982-01-01

    A description is presented of a patient in remission of Hodgkin's disease after radio- and chemotherapy. Thirteen years after the diagnosis had been made, a non-Hodgkin lymphoma of the intestine developed. The possible relationship between the occurrence of the non-Hodgkin lymphoma and the treatment for Hodgkin's disease is discussed. (Auth.)

  20. The finding of a non-Hodgkin's lymphoma after treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Yang Hongying; Gu Dazhong; Liu Fusheng; Ying Jianming; Zheng Shan; Sun Yuntian

    2002-01-01

    Objective: To investigate the pathological type, biological behavior and clinical-pathological relationship of a non-Hodgkin's lymphoma occurring after treatment of Hodgkin's disease. Methods: Four cases of non-Hodgkin's lymphoma occurring after treatment of Hodgkin's disease collected from 1983 to 1992 were reviewed. Results: All cases complete with clinical data and two cases with autopsy data, had been diagnosed as Hodgkin's disease before treatment. During or after treatment, non-Hodgkin's lymphoma was found. Their clinical characteristics were in accordance with the pathological findings. Conclusions: Non-Hodgkin's lymphoma may occur after a successful radiotherapy or chemotherapy for Hodgkin's disease. Also non-Hodgkin's lymphoma and Hodgkin's disease may occur simultaneously

  1. Drugs Approved for Non-Hodgkin Lymphoma

    Science.gov (United States)

    ... about Your Treatment Research Drugs Approved for Non-Hodgkin Lymphoma This page lists cancer drugs approved by the ... are not listed here. Drugs Approved for Non-Hodgkin Lymphoma Abitrexate (Methotrexate) Acalabrutinib Adcetris (Brentuximab Vedotin) Aliqopa (Copanlisib ...

  2. [Effects of blokade of the dopaminergic D1/D2 receptors on the single and network neuronal activity in the frontal and visual cortices and behavior of cats].

    Science.gov (United States)

    Kuleshova, E P; Zaleshin, A V; Sidorina, V V; Merzhanova, G Kh

    2010-01-01

    The results obtained at the levels of single and network neuronal activity in the frontal and visual cortices of cats with different types of behavior revealed features of activity of these structures in normal conditions and after local introductions of antagonists of DI/D2 receptors (SCH23390 and raclopride) into the n. accumbens and frontal cortex. Under the influence of the antagonists, long-latency reactions were characterized by a significant increase in the average frequency of neuronal activity in the frontal cortex, whereas in the visual cortex the average frequency decreased as compared to norm. At the same time, the network activity of the same neurons in the frontal cortex did not change but weakened in the visual cortex, which was expressed in a reduction of the number of neuronal interactions within the visual cortex and between the neurons of the frontal and visual cortices. Normally, during the long-latency conditioned reactions, the average frequency of single neuronal activity and the rate of neuronal interactions in the structures under study were significantly higher as compared to the loss of conditioned reactions. Administration of the dopamine antagonists did not change these features. The results suggest different dopamine modulations of the network activity of the cortical zones under study during the conditioned performance, which is expressed in responsiveness of the cortical projection of a trigger signal (the visual cortex) and visual-frontal networks generated in the course of training.

  3. Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Shahid, R.; Gulzar, R.; Avesi, L.; Hassan, S.; Danish, F.; Mirza, T.

    2016-01-01

    Objective: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Methodology: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Results: Out of the 318 cases, 79 (25 percentage) were Hodgkin Lymphomas (HL) and 239 (75 percentage) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95 percentage) were B cell lymphomas and 24 (10.05percentage) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95 percentage of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HL was significantly higher in the younger age group and that of NHL was higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55 percentage) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29 percentage) of all cases and was reported in 87 (36.4 percentage) of NHL and 6 (7.5 percentage) of HL. The most common extra nodal site was the gastrointestinal tract. Conclusion: Hodgkin lymphoma comprises 25 percentage and non-Hodgkin lymphoma comprises 75 percentage of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHL is three times more common than T-cell lymphoma. DLBCL is the most frequent lymphoma. ALCL is the most common T-cell, and mixed

  4. Prevalence of Common Non-Hodgkin Lymphomas and Subtypes of Hodgkin Lymphoma by Nodal Site of Involvement

    Science.gov (United States)

    Laurent, Camille; Do, Catherine; Gourraud, Pierre-Antoine; de Paiva, Geisilene Russano; Valmary, Séverine; Brousset, Pierre

    2015-01-01

    Abstract Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) represent a heterogeneous group of malignant lymphoid tumors, which have distinct histological and/or biological characteristics with preferential nodal involvement. However, none of the previous studies have assessed the prevalence of common NHL and HL subtypes at each nodal site of involvement. The aim of our study was to determine the prevalence of HL and NHL subtypes depending on their nodal sites of involvement. We conducted a single-center retrospective study of 938 lymphoma cases diagnosed in the Pathology Department of Toulouse Purpan Hospital in France between 2001 and 2008, taking into account the site that corresponded to the diagnostic biopsy. The most frequent sites were cervical lymph nodes (36.8% of all cases), inguinal lymph nodes (16.4%), axillary lymph nodes (11.9%), and supraclavicular lymph nodes (11%). We found an unexpected association between intraparotid nodes and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and between inguinal nodes and follicular lymphoma. The risk of having classical Hodgkin lymphoma (CHL) was 15 times greater in patients with mediastinal lymphoma compared to those with other sites of involvement. Regarding HL, nodal and extranodal mediastinal sites and supraclavicular nodes were more likely to be involved by nodular sclerosis Hodgkin lymphoma (NSCHL). In addition, intra-abdominal lymph nodes were more frequently involved by lymphocyte depleted Hodgkin lymphoma compared to inguinal nodes where NLPHL predominated. Our study shows that some lymph node sites have a disproportionate prevalence of specific subtypes of lymphoma. Identifying these sites may aid to diagnose and better elucidate the pathogenesis of these tumors. PMID:26107683

  5. Enhanced Peptide Detection Toward Single-Neuron Proteomics by Reversed-Phase Fractionation Capillary Electrophoresis Mass Spectrometry

    Science.gov (United States)

    Choi, Sam B.; Lombard-Banek, Camille; Muñoz-LLancao, Pablo; Manzini, M. Chiara; Nemes, Peter

    2017-11-01

    The ability to detect peptides and proteins in single cells is vital for understanding cell heterogeneity in the nervous system. Capillary electrophoresis (CE) nanoelectrospray ionization (nanoESI) provides high-resolution mass spectrometry (HRMS) with trace-level sensitivity, but compressed separation during CE challenges protein identification by tandem HRMS with limited MS/MS duty cycle. Here, we supplemented ultrasensitive CE-nanoESI-HRMS with reversed-phase (RP) fractionation to enhance identifications from protein digest amounts that approximate to a few mammalian neurons. An 1 to 20 μg neuronal protein digest was fractionated on a RP column (ZipTip), and 1 ng to 500 pg of peptides were analyzed by a custom-built CE-HRMS system. Compared with the control (no fractionation), RP fractionation improved CE separation (theoretical plates 274,000 versus 412,000 maximum, resp.), which enhanced detection sensitivity (2.5-fold higher signal-to-noise ratio), minimized co-isolation spectral interferences during MS/MS, and increased the temporal rate of peptide identification by up to 57%. From 1 ng of protein digest (development of the brain, including those involved in synaptic transmission and plasticity and cytoskeletal organization. [Figure not available: see fulltext.

  6. Study of GABAergic extra-synaptic tonic inhibition in single neurons and neural populations by traversing neural scales: application to propofol-induced anaesthesia.

    Science.gov (United States)

    Hutt, Axel; Buhry, Laure

    2014-12-01

    Anaesthetic agents are known to affect extra-synaptic GABAergic receptors, which induce tonic inhibitory currents. Since these receptors are very sensitive to small concentrations of agents, they are supposed to play an important role in the underlying neural mechanism of general anaesthesia. Moreover anaesthetic agents modulate the encephalographic activity (EEG) of subjects and hence show an effect on neural populations. To understand better the tonic inhibition effect in single neurons on neural populations and hence how it affects the EEG, the work considers single neurons and neural populations in a steady-state and studies numerically and analytically the modulation of their firing rate and nonlinear gain with respect to different levels of tonic inhibition. We consider populations of both type-I (Leaky Integrate-and-Fire model) and type-II (Morris-Lecar model) neurons. To bridge the single neuron description to the population description analytically, a recently proposed statistical approach is employed which allows to derive new analytical expressions for the population firing rate for type-I neurons. In addition, the work shows the derivation of a novel transfer function for type-I neurons as considered in neural mass models and studies briefly the interaction of synaptic and extra-synaptic inhibition. We reveal a strong subtractive and divisive effect of tonic inhibition in type-I neurons, i.e. a shift of the firing rate to higher excitation levels accompanied by a change of the nonlinear gain. Tonic inhibition shortens the excitation window of type-II neurons and their populations while maintaining the nonlinear gain. The gained results are interpreted in the context of recent experimental findings under propofol-induced anaesthesia.

  7. Gastrointestinal non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Makepeace, A.R.; Fermont, D.C.; Bennett, M.H.

    1987-01-01

    Seventy-two patients with gastrointestinal non-Hodgkin's lymphoma treated between 1952 and 1980 are reviewed. The small intestine was involved in 49% of cases and the stomach in 29%. Surgical resection of the tumour was performed whenever feasible. Radiotherapy was used either adjuvantly or for incompletely excised tumours and chemotherapy was more often reserved for advanced, unresected disease. The overall 5 year survival was 36% and the 5 year relapse free survival was 22%. Forty-one (57%) patients relapsed of whom 33 (80%) subsequently died of non-Hodgkin's lymphoma. The histology in each case was reviewed using the British National Lymphoma Investigation criteria and 94% of cases were reclassified as Grade 2 non-Hodgkin's lymphoma. (author)

  8. Nodular lymphocyte predominant Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Siddiqui, Neelam; Al-Diab, Abdulrahman I.

    2005-01-01

    To describe the clinicopathological features, treatment, treatment outcome and sequelae of patients with nodular lymphocyte, predominant Hodgkin's lymphoma (NLPHL) in Saudi population. This is a retrospective review of 29 patients with lymphocyte predominant Hodgkin's lymphoma treated at two major hospitals (King Khalid University Hospital and Security Forces Hospital) in Riyadh, Kingdom of Saudi Arabia from 1985 to 2000. Histological subtypes were confirmed by review of hematoxylin and eosin paraffin sections and immunochemistry. Details of clinical presentation, stage, treatment and results of treatment were analyzed. On pathological reappraisal of the 29 cases, 3 patients had nodular sclerosis Hodgkin's lymphoma and 4 patients were reclassified as lymphocyte rich classical Hodgkin's lymphoma. Twenty-two patients were identified to have nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). These patients comprised of 18 mails and 4 female patients with a median age at presentation of 25 years. Nineteen (86%) patients had an early stage (Ann Arbor stage I and II) disease, 2 had stage III and one patient had stage IV. The majority of patients presented with peripheral lymphadenopathy and long duration of symptoms. For 16 patients, details of treatment and follow-up were available. All of these achieved a complete response to initial treatment. Four patients relapsed following the primary therapy. Our results are consistent with the previous series reported from Western countries and confirmed that the patients with NLPHL have characteristic clinical and pathological profile that distinguish it from other types of Hodgkin's lymphoma. The disease tends to run an unusual course and although most patients achieve an excellent response to therapy there is a tendency to replace. treatment remains controversial; however, recent understanding of the molecular pathogenesis of NLPHL could lead to modification of current therapeutic approach to this disease. (author)

  9. Real-time subpixel-accuracy tracking of single mitochondria in neurons reveals heterogeneous mitochondrial motion.

    Science.gov (United States)

    Alsina, Adolfo; Lai, Wu Ming; Wong, Wai Kin; Qin, Xianan; Zhang, Min; Park, Hyokeun

    2017-11-04

    Mitochondria are essential for cellular survival and function. In neurons, mitochondria are transported to various subcellular regions as needed. Thus, defects in the axonal transport of mitochondria are related to the pathogenesis of neurodegenerative diseases, and the movement of mitochondria has been the subject of intense research. However, the inability to accurately track mitochondria with subpixel accuracy has hindered this research. Here, we report an automated method for tracking mitochondria based on the center of fluorescence. This tracking method, which is accurate to approximately one-tenth of a pixel, uses the centroid of an individual mitochondrion and provides information regarding the distance traveled between consecutive imaging frames, instantaneous speed, net distance traveled, and average speed. Importantly, this new tracking method enables researchers to observe both directed motion and undirected movement (i.e., in which the mitochondrion moves randomly within a small region, following a sub-diffusive motion). This method significantly improves our ability to analyze the movement of mitochondria and sheds light on the dynamic features of mitochondrial movement. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Proteomic signatures and aberrations of mouse embryonic stem cells containing a single human chromosome 21 in neuronal differentiation: an in vitro model of Down syndrome.

    Science.gov (United States)

    Kadota, M; Nishigaki, R; Wang, C C; Toda, T; Shirayoshi, Y; Inoue, T; Gojobori, T; Ikeo, K; Rogers, M S; Oshimura, M

    2004-01-01

    Neurodegeneration in fetal development of Down syndrome (DS) patients is proposed to result in apparent neuropathological abnormalities and to contribute to the phenotypic characteristics of mental retardation and premature development of Alzheimer disease. In order to identify the aberrant and specific genes involved in the early differentiation of DS neurons, we have utilized an in vitro neuronal differentiation system of mouse ES cells containing a single human chromosome 21 (TT2F/hChr21) with TT2F parental ES cells as a control. The paired protein extracts from TT2F and TT2F/hChr21 cells at several stages of neuronal differentiation were subjected to two-dimensional polyacrylamide gel electrophoresis protein separation followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry to identify the proteins differentially expressed between TT2F and TT2F/hChr21 cells. We provide here a novel set of specific gene products altered in early differentiating DS neuronal cells, which differs from that identified in adult or fetal brain with DS. The aberrant protein expression in early differentiating neurons, due to the hChr21 gene dosage effects or chromosomal imbalance, may affect neuronal outgrowth, proliferation and differentiation, producing developmental abnormalities in neural patterning, which eventually leads to formation of a suboptimal functioning neuronal network in DS.

  11. Single Cell Electroporation Method for Mammalian CNS Neurons in Organotypic Slice Cultures

    Science.gov (United States)

    Uesaka, Naofumi; Hayano, Yasufumi; Yamada, Akito; Yamamoto, Nobuhiko

    Axon tracing is an essential technique to study the projection pattern of neurons in the CNS. Horse radish peroxidase and lectins have contributed to revealing many neural connection patterns in the CNS (Itaya and van Hoesen, 1982; Fabian and Coulter, 1985; Yoshihara, 2002). Moreover, a tracing method with fluorescent dye has enabled the observation of growing axons in living conditions, and demon strated a lot of developmental aspects in axon growth and guidance (Harris et al., 1987; O'Rourke and Fraser, 1990; Kaethner and Stuermer, 1992; Halloran and Kalil, 1994; Yamamoto et al., 1997). More recently, genetically encoded fluores cent proteins can be used as a powerful tool to observe various biological events. Several gene transfer techniques such as microinjection, biolistic gene gun, viral infection, lipofection and transgenic technology have been developed (Feng et al., 2000; Ehrengruber et al., 2001; O'Brien et al., 2001; Ma et al., 2002; Sahly et al., 2003). In particular, the electroporation technique was proved as a valuable tool, since it can be applied to a wide range of tissues and cell types with little toxicity and can be performed with relative technical easiness. Most methods, including a stand ard electroporation technique, are suitable for gene transfer to a large number of cells. However, this is not ideal for axonal tracing, because observation of individ ual axons is occasionally required. To overcome this problem, we have developed an electroporation method using glass micropipettes containing plasmid solutions and small current injection. Here we introduce the method in detail and exemplified results with some example applications and discuss its usefulness.

  12. INTRAOCULAR NON-HODGKINS-LYMPHOMA

    NARCIS (Netherlands)

    HOOYMANS, JMM; TIMMERMAN, Z

    1990-01-01

    Usually eye symptoms precede the infiltration of non-Hodgkin's lymphoma in the central nervous system or in other organs. Early treatment of the tumor by irradiation, to which it is highly sensitive, can preserve the vision and prolong the life of the patient. Such therapy however is often delayed

  13. Drugs Approved for Hodgkin Lymphoma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for Hodgkin lymphoma. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  14. Action potential initiation in the hodgkin-huxley model.

    Directory of Open Access Journals (Sweden)

    Lucy J Colwell

    2009-01-01

    Full Text Available A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span and the rapidity of action potential initiation (the onset rapidity. This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in vitro. Here we apply a method from theoretical physics to derive an analytical characterization of this problem. We analytically compute the probability distribution of onset potentials and analytically derive the inverse relationship between onset span and onset rapidity. We find that the relationship between onset span and onset rapidity depends on the level of synaptic background activity. Hence we are able to elucidate the regions of parameter space for which the Hodgkin-Huxley model is able to accurately describe the behavior of this system.

  15. Hodgkin`s disease: internal mammary lymph nodes relapse diagnosed by Gallium-67 scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Ruiz Hernandez, G.; Ampudia, J.; Castillo, F.J.; Romero, C. [Hospital Clinico Univ., Valencia (Spain). Servicio de Medicina Nuclear; Pallardo, Y. [Hospital Clinico Univ., Valencia (Spain). Servicio de Radiologia; Garcia Conde, J. [Hospital Clinico Univ., Valencia (Spain). Servicio de Hematologia y Oncologia Medica; Ramos, D. [Hospital Clinico Univ., Valencia (Spain). Servicio de Anatomia Patologica

    1999-04-01

    This article presents the case of a 62-year-old man with treated Hodgkin`s disease who had internal mammary lymph nodes relapse after a complete initial response. These masses were gallium avid. These findings were explained by histologically documented Hodgkin`s relapse, the first such case reported in that localization without chest wall involvement. The literature on mediastinal Hodgkin`s disease and diagnostic procedures are reviewed. (orig.) [Deutsch] Beschrieben wird der Fall eines 62jaehrigen Mannes, der nach initial erfolgreicher Therapie eines Morbus Hodgkin ein Lymphknotenrezidiv im Bereich der Brust aufweist. Die Lymphknoten reicherten Gallium an. Histologisch wurde das Hodgkinrezidiv gesichert. Es handelt sich um den ersten in diesem Bereich beschriebenen Fall ohne Infiltration der Brustwand. Die Literatur ueber mediastinalen Morbus Hodgkin und diagnostisches Vorgehen wurde ueberprueft. (orig.)

  16. Prefrontal Single-Neuron Responses after Changes in Task Contingencies during Trace Eyeblink Conditioning in Rabbits.

    Science.gov (United States)

    Siegel, Jennifer J

    2016-01-01

    A number of studies indicate that the medial prefrontal cortex (mPFC) plays a role in mediating the expression of behavioral responses during tasks that require flexible changes in behavior. During trace eyeblink conditioning, evidence suggests that the mPFC provides the cerebellum with a persistent input to bridge the temporal gap between conditioned and unconditioned stimuli. Therefore, the mPFC is in a position to directly mediate the expression of trace conditioned responses. However, it is unknown whether persistent neural responses are associated with the flexible expression of behavior when task contingencies are changed during trace eyeblink conditioning. To investigate this, single-unit activity was recorded in the mPFC of rabbits during extinction and reacquisition of trace eyeblink conditioning, and during training to a different conditional stimulus. Persistent responses remained unchanged after full extinction, and also did not change during reacquisition training. During training to a different tone, however, the generalization of persistent responses to the new stimulus was associated with an animal's performance-when persistent responses generalized to the new tone, performance was high (>50% response rate). When persistent responses decreased to baseline rates, performance was poor (<50% response rate). The data suggest that persistent mPFC responses do not appear to mediate flexible changes in the expression of the original learning, but do appear to play a role in the generalization of that learning when the task is modified.

  17. Radiological diagnosis of thoracic Hodgkin- and Non-Hodgkin lymphomas

    International Nuclear Information System (INIS)

    Uffmann, M.; Schaefer-Prokop, C.

    2004-01-01

    Malignant lymphomas belong to the most important malignant diseases in western countries with an increasing incidence of Non-Hodgkin lymphoma. The thorax is the location of primary manifestation especially in patients with Hodgkin's disease. Progression of disease and therapy associated complications are frequently located in the chest. Based on morphological imaging criteria the two types of lymphoma cannot be differentiated, helpful for differentiation is, however, the way of disease spread. Primary and secondary thoracic lymphoma represent a diagnostic challenge in radiology: the patterns are variable in radiography as well as in computed tomography and alter under therapy. Radiological studies, especially CT, are an integral part of the staging process. MRI is considered advantageous for chest wall disease. PET as functional imaging technique has its proven role for staging of high grade lymphomas, the combination of functional and morphological information provided by PET-CT will become the first diagnostic standard in the future. (orig.) [de

  18. Four Lymphomas in 1 Patient: A Unique Case of Triple Composite Non-Hodgkin Lymphoma Followed by Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Tennese, Alysa; Skrabek, Pamela J; Nasr, Michel R; Sekiguchi, Debora R; Morales, Carmen; Brown, Theresa C; Weisenburger, Dennis D; Perry, Anamarija M

    2017-05-01

    Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

  19. Morphine dependence in single enteric neurons from the mouse colon requires deletion of β‐arrestin2

    OpenAIRE

    Smith, Tricia H.; Ngwainmbi, Joy; Hashimoto, Atsushi; Dewey, William L.; Akbarali, Hamid I.

    2014-01-01

    Abstract Chronic administration of morphine results in the development of tolerance to the analgesic effects and to inhibition of upper gastrointestinal motility but not to colonic motility, resulting in persistent constipation. In this study we examined the effect of chronic morphine in myenteric neurons from the adult mouse colon. Similar to the ileum, distinct neuronal populations exhibiting afterhyperpolarization (AHP)‐positive and AHP‐negative neurons were identified in the colon. Acute ...

  20. A single cDNA encodes two isoforms of stathmin, a developmentally regulated neuron-enriched phosphoprotein.

    Science.gov (United States)

    Doye, V; Soubrier, F; Bauw, G; Boutterin, M C; Beretta, L; Koppel, J; Vandekerckhove, J; Sobel, A

    1989-07-25

    Stathmin, a 19-kDa neuron-enriched soluble phosphoprotein, has been recently proposed as an ubiquitous intracellular relay for the diverse extracellular signals regulating cell proliferation, differentiation, and functions through various second messenger pathways (Sobel, A., Boutterin, M.C., Beretta, L., Chneiweiss, H., Doye, V., and peyro-Saint-Paul, H. (1989) J. Biol. Chem. 264, 3765-3772). Internal sequences of the protein from rat brain were determined after purification by two-dimensional polyacrylamide gel electrophoresis, electrotransfer onto Immobilon, and in situ proteolysis. Oligonucleotide mixtures based on these sequences were used to clone a cDNA for stathmin from a rat PC12 cell lambda gt 10 library. The deduced amino acid sequence reveals partial homologies with the coiled coil structural regions of several intracellular matrix phosphoproteins. Using this cDNA as a probe, we show that the expression of stathmin mRNA parallels that of the protein during brain ontogenesis, reaching a maximum at the neonatal stage. In vitro translation of the derived cRNA yielded all the known molecular forms of stathmin, namely its alpha and beta isoforms in their unphosphorylated and phosphorylated states. Thus, a single cDNA codes for both biologically relevant isoforms of the protein, indicating that they differ by co- or post-translational modifications.

  1. Attending to and remembering tactile stimuli: a review of brain imaging data and single-neuron responses.

    Science.gov (United States)

    Burton, H; Sinclair, R J

    2000-11-01

    Clinical and neuroimaging observations of the cortical network implicated in tactile attention have identified foci in parietal somatosensory, posterior parietal, and superior frontal locations. Tasks involving intentional hand-arm movements activate similar or nearby parietal and frontal foci. Visual spatial attention tasks and deliberate visuomotor behavior also activate overlapping posterior parietal and frontal foci. Studies in the visual and somatosensory systems thus support a proposal that attention to the spatial location of an object engages cortical regions responsible for the same coordinate referents used for guiding purposeful motor behavior. Tactile attention also biases processing in the somatosensory cortex through amplification of responses to relevant features of selected stimuli. Psychophysical studies demonstrate retention gradients for tactile stimuli like those reported for visual and auditory stimuli, and suggest analogous neural mechanisms for working memory across modalities. Neuroimaging studies in humans using memory tasks, and anatomic studies in monkeys support the idea that tactile information relayed from the somatosensory cortex is directed ventrally through the insula to the frontal cortex for short-term retention and to structures of the medial temporal lobe for long-term encoding. At the level of single neurons, tactile (such as visual and auditory) short-term memory appears as a persistent response during delay intervals between sampled stimuli.

  2. [Hodgkin's disease and glomerulonefritis (author's transl)].

    Science.gov (United States)

    Gómez, S; Valbuena, C; Peral, J I

    1977-12-01

    A case of infradiaphragmatic Hodgkin's disease (mixed pattern) associated with glomerulonephritis in the childhood is reported. The pathogenic relationship between Hodking's disease and the renal lesion is discussed.

  3. Primary multifocal osseous Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Kohler Janice

    2008-03-01

    Full Text Available Abstract Background Hodgkin's disease (HD most commonly presents with progressive painless enlargement of peripheral lymph nodes, especially around the cervical region. A few children have systemic symptoms and weight loss. At the time of diagnosis, osseous involvement is uncommon Case presentation A case is described of Primary Multifocal Osseous Hodgkin's Lymphoma in a seven-year-old boy. He presented with a painful swelling in the sternum, and further investigations revealed deposits in his L1 vertebra, the left sacro-iliac joint and the right acetabulum. Conclusion The clinical, radiological and histological features of this disease can mimic other medical conditions, including Tuberculosis, making the diagnosis difficult and often leading to delays in treatment. This is a very rare condition and we believe this to be the youngest reported case in the literature.

  4. Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Ballova, V.

    2008-01-01

    The treatment of Hodgkin's lymphoma has changed considerably in the last decades. This entity is now one of the most curable human malignancies. With improved survival and extended follow-up, relevance of treatment induced late effects became more evident. Therefore modern therapeutic strategies must maximize chance of cure and minimize the risk of therapy associated toxicity. Here we review the pathology of Hodgkin’s lymphoma, clinical presentation, risk stratification, current treatment approaches and toxicity of the treatment. (author)

  5. Characteristics of Hodgkin's lymphoma after infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, Henrik; Askling, Johan; Rostgaard, Klaus

    2003-01-01

    BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population-bas...

  6. Postradiation sarcoma of bone in Hodgkin disease

    International Nuclear Information System (INIS)

    Smith, J.

    1987-01-01

    We report 16 cases seen in the Memorial Sloan-Kettering Cancer Center (MSKCC) during the past 50 years. These patients had been treated with external radiation for Hodgkin disease and had developed sarcomas in the field 4-31 years after the diagnosis of Hodgkin disease. Most of the tumors (12 of 16) occurred in the chest wall. There were three tumors of the pelvis and an unusual osteosarcoma of the femur following treatment for a primary Hodgkin disease of the femur. The tumors were predominantly osteosarcomas. In addition, there were five malignant fibrous histiocytomas, one fibrosarcoma, and one chondrosarcoma. Prognosis was poor; the mean survival was 12 months. Survival of patients with other primary cancers who developed radiation sarcomas was not significantly different from that of patients with Hodgkin disease. Hodgkin disease is now the most common tumor among radiation-induced sarcomas in previously normal bone and has surpassed breast cancer, which was previously the most common original tumor. (orig.)

  7. The nigrostriatal pathway in the rat: A single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments.

    Science.gov (United States)

    Prensa, L; Parent, A

    2001-09-15

    Axons from dorsal/ventral tiers of substantia nigra pars compacta (SNc), ventral tegmental area (VTA), and retrorubral field (RRF) were traced after injecting their cell body with biotinylated dextran amine. Fifty-three single axons were reconstructed from serial sagittal sections with a camera lucida, and mu-opiate receptor immunostaining served to differentiate the striosome/matrix striatal compartments. Most dorsal tier SNc axons terminate within the matrix of the dorsal striatum, but their patterns of arborization vary markedly; some axons innervate one specific matriceal area, whereas others arborize in multiple discontinuous loci. Some dorsal tier SNc axons also project to both striosomes and matrix. Other dorsal tier SNc axons, as well as VTA axons, innervate the ventral striatum and send collaterals to striosomes lying ventrally in the dorsal striatum or to the ventral sector of the subcallosal streak (SS). Ventral tier SNc axons arborize principally in striosomes, but some ramify in both compartments or in striosomes and the SS. Ventral tier neurons that form deep clusters in substantia nigra pars reticulata innervate principally the matrix and the SS. The amygdala and ventral pallidum receive secondary collaterals from striatal axons of dorsal/ventral tier neurons or RRF neurons. The subthalamic nucleus receives collaterals from striatal axons of SNc clustered neurons, whereas the globus pallidus gets collaterals from striatal axons of dorsal/ventral tier SNc neurons. These findings reveal that the nigrostriatal pathway is composed of several neuronal subsystems, each endowed with a widely distributed axonal arborization that allows them to exert a multifaceted influence on striatal and/or extrastriatal structures.

  8. Avascular osteonecrosis in patients treated for Hodgkin`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Enrici, R.M.; Donato, V.; Santoro, M. [La Sapienza Univ. of Rome, Inst. of Radiology, Chair of Radiation Oncology, Rome (Italy); Tombolini, V. [Univ of L`Aquila, Hospital S. Maria di Collemaggio, Dept. of Radiation Oncology, L`Aquila (Italy); Anselmo, A.P. [La Sapienza Univ. of Rome, Dept. of Human Biopathology, Haematology Section, Rome (Italy)

    1998-09-01

    The aim of this study is to assess the risk of avascular osteonecrosis (AVN) of the femoral head in patients treated for Hodgkin`s disease (HD), in relation to the type of treatment they have received. For this purpose, a cohort of 1391 patients treated for HD at University of Rome between 1972 and 1996 was divided into 2 groups according to their initial treatment. The first group contained 784 patients treated, at the onset of HD, either with chemotherapy (CT) containing steroids, combined in some cases with subdiaphragmatic radiotherapy (RT), or with subdiaphragmatic RT combined with CT without steroids. The second group was made up of 607 patients who had received, initially, supradiaphragmatic RT alone or supradiaphragmatic RT combined with CT without steroids. For the purpose of this study, only the 784 patients belonging to the first group were observed for the appearance of AVN, which occurred in 9 cases. The period of time which elapsed between the end of treatment and the radiological evidence of AVN ranged from 23 to 97 months, with an average of 35 months. Because the number of cases of AVN was so small, the pathogenesis of this complication could not be identified. (au) 55 refs.

  9. Prognostic Factors in Hodgkin's Disease

    DEFF Research Database (Denmark)

    Specht

    1996-01-01

    Prognostic factors in Hodgkin's disease (HD) are reviewed. The Ann Arbor staging classification remains the basis for evaluation of patients with HD. However, subgroups of patients with differing prognoses exist within the individual stages. In pathological stages I and II, the number of involved...... of extent of disease such as erythrocyte sedimentation rate, anemia, and serum albumin. In advanced disease the number of involved nodal and extranodal regions, the total tumor burden, B symptoms, age, gender, histology, and a number of hematologic and biochemical indicators are significant. Research...

  10. A single exposure to alcohol during brain development induces microencephaly and neuronal losses in genetically susceptible mice, but not in wild type mice.

    Science.gov (United States)

    de Licona, Hannah Klein; Karacay, Bahri; Mahoney, Jo; McDonald, Elizabeth; Luang, Thirath; Bonthius, Daniel J

    2009-05-01

    Maternal alcohol abuse during pregnancy can damage the fetal brain and lead to fetal alcohol syndrome (FAS). Despite public warnings discouraging alcohol use during pregnancy, many pregnant women continue to drink intermittently because they do not believe that occasional exposures to alcohol can be harmful to a fetus. However, because of genetic differences, some fetuses are much more susceptible than others to alcohol-induced brain injury. Thus, a relatively low quantity of alcohol that may be innocuous to most fetuses could damage a genetically susceptible fetus. Neuronal nitric oxide synthase (nNOS) can protect developing mouse neurons against alcohol toxicity by synthesizing neuroprotective nitric oxide. This study examined whether a single exposure to alcohol, which causes no evident injury in wild type mice, can damage the brains of mice genetically deficient for nNOS (nNOS-/- mice). Wild type and nNOS-/- mice received intraperitoneal injections of alcohol (0.0, 2.2, or 4.4mg/g body weight) either as a single dose on postnatal day (PD) 4 or as repeated daily doses over PD4-9. Brain volumes and neuronal numbers within the hippocampus and cerebral cortex were determined on PD10. Alcohol exposure on PD4-9 restricted brain growth and caused neuronal death in both strains of mice, but the severity of microencephaly and neuronal loss were more severe in the nNOS-/- mice than in wild type. The 4.4 mg/g alcohol dose administered on PD4 alone caused significant neuronal loss and microencephaly in the nNOS-/- mice, while this same dose caused no evident injury in the wild type mice. Thus, during development, a single exposure to alcohol can injure a genetically vulnerable brain, while it leaves a wild type brain unaffected. Since the genes that confer alcohol resistance and vulnerability in developing humans are unknown, any particular human fetus is potentially vulnerable. Thus, women should be counseled to consume no alcohol during pregnancy.

  11. Curcumin protects dopaminergic neurons against inflammation-mediated damage and improves motor dysfunction induced by single intranigral lipopolysaccharide injection.

    Science.gov (United States)

    Sharma, Neha; Sharma, Sheetal; Nehru, Bimla

    2017-06-01

    Various studies have indicated a lower incidence and prevalence of neurological conditions in people consuming curcumin. The ability of curcumin to target multiple cascades, simultaneously, could be held responsible for its neuroprotective effects. The present study was designed to investigate the potential of curcumin in minimizing microglia-mediated damage in lipopolysaccharide (LPS) induced model of PD. Altered microglial functions and increased inflammatory profile of the CNS have severe behavioral consequences. In the current investigation, a single injection of LPS (5 ug/5 µl PBS) was injected into the substantia nigra (SN) of rats, and curcumin [40 mg/kg b.wt (i.p.)] was administered daily for a period of 21 days. LPS triggered an inflammatory response characterized by glial activation [Iba-1 and glial fibrillary acidic protein (GFAP)] and pro-inflammatory cytokine production (TNF-α and IL-1β) leading to extensive dopaminergic loss and behavioral abnormality in rats. The behavioral observations, biochemical markers, quantification of dopamine and its metabolites (DOPAC and HVA) using HPLC followed by IHC of tyrosine hydroxylase (TH) were evaluated after 21 days of LPS injection. Curcumin supplementation prevented dopaminergic degeneration in LPS-treated animals by normalizing the altered levels of biomarkers. Also, a significant improvement in TH levels as well as behavioral parameters (actophotometer, rotarod, beam walking and grid walking tests) were seen in LPS injected rats. Curcumin shielded the dopaminergic neurons against LPS-induced inflammatory response, which was associated with suppression of glial activation (microglia and astrocytes) and transcription factor NF-κB as depicted from RT-PCR and EMSA assay. Curcumin also suppressed microglial NADPH oxidase activation as observed from NADPH oxidase activity. The results suggested that one of the important mechanisms by which curcumin mediates its protective effects in the LPS-induced PD

  12. Non-Hodgkin's lymphomas following radiation therapy alone for Hodgkin's disease

    International Nuclear Information System (INIS)

    Trenkner, D.A.; Wasserman, T.H.; Brownell, M.

    1986-01-01

    The authors have recently treated three patients who developed a non-Hodgkin's lymphoma after therapy with radiation alone for Hodgkin's disease. The secondary non-Hodgkin's lymphomas occurred 4 years and 11.5 years after receiving irradiation. Thirteen additional cases have been reported and are reviewed with attention to the subsequent histology and response to treatment of these secondary non-Hodgkin's lymphomas. The pathogenesis is unknown, but, may be therapy-related or part of the natural history of the lymphocyte predominance subtype of Hodgkin's disease. Possible mechanisms will be discussed. A subset of the patients with secondary lymphomas following radiation therapy alone are curable with chemotherapy. New sites of disease after apparent control of Hodgkin's disease require pathology for confirmation of the disease process and appropriate therapy. (Auth.)

  13. Occurrence of non-Hodgkin's lymphoma after therapy for Hodgkin's disease

    International Nuclear Information System (INIS)

    Krikorian, J.G.; Burke, J.S.; Rosenberg, S.A.; Kaplan, H.S.

    1979-01-01

    We studied the clinical and pathological features of six cases of non-Hodgkin's lymphoma occuring in patients treated for Hodgkin's disease. All six patients had received both radiation therapy and chemotherapy. Abdominal or gastrointestinal involvement was present in five of the six cases. None of the patients had evidence of Hodgkin's disease when the diagnosis of non-Hodgkin's lymphoma was made. Five of the six patients were among a study group of 579 patients with Hodgkin's disease, prospectively followed since diagnosis. At 10 years the actuarial risk of development of non-Hodgkin's lymphoma in this study group is 4.4 per cent and is similar to that of developing acute leukemia: 2.0 per cent. Non-Hodgkin's lymphoma is a second tumor that may occur late in the course of patients treated for Hodgkin's disease, particularly in patients who have received both radiation therapy and chemotherapy. Like acute leukemia, non-Hodgkin's lymphoma may be another cancer that represents a substantial late risk of combined-modality therapy

  14. Memristor, Hodgkin-Huxley, and edge of chaos.

    Science.gov (United States)

    Chua, Leon

    2013-09-27

    From a pedagogical point of view, the memristor is defined in this tutorial as any 2-terminal device obeying a state-dependent Ohm's law. This tutorial also shows that from an experimental point of view, the memristor can be defined as any 2-terminal device that exhibits the fingerprints of 'pinched' hysteresis loops in the v-i plane. It also shows that memristors endowed with a continuum of equilibrium states can be used as non-volatile analog memories. This tutorial shows that memristors span a much broader vista of complex phenomena and potential applications in many fields, including neurobiology. In particular, this tutorial presents toy memristors that can mimic the classic habituation and LTP learning phenomena. It also shows that sodium and potassium ion-channel memristors are the key to generating the action potential in the Hodgkin-Huxley equations, and that they are the key to resolving several unresolved anomalies associated with the Hodgkin-Huxley equations. This tutorial ends with an amazing new result derived from the new principle of local activity, which uncovers a minuscule life-enabling 'Goldilocks zone', dubbed the edge of chaos, where complex phenomena, including creativity and intelligence, may emerge. From an information processing perspective, this tutorial shows that synapses are locally-passive memristors, and that neurons are made of locally-active memristors.

  15. Patterns of spontaneous activity in single rat olfactory receptor neurons are different in normally breathing and tracheotomized animals

    Czech Academy of Sciences Publication Activity Database

    Duchamp-Viret, P.; Košťál, Lubomír; Chaput, M.; Lánský, Petr; Rospars, J. P.

    2005-01-01

    Roč. 65, č. 2 (2005), s. 97-114 ISSN 0022-3034 R&D Projects: GA AV ČR(CZ) 1ET400110401 Grant - others:Barrande(FR) 9146 QL Institutional research plan: CEZ:AV0Z50110509 Keywords : olfactory neurons * unit activity * receptors Subject RIV: ED - Physiology Impact factor: 4.170, year: 2005

  16. Targeting CD30 Using Brentuximab Vedotin in the Treatment of Hodgkin Lymphoma

    Science.gov (United States)

    Alperovich, Anna; Younes, Anas

    2016-01-01

    The expression of CD30 receptors is one of the defining characteristics of the malignant Reed-Sternberg cells of Hodgkin lymphoma. CD30 is rarely expressed by normal cells, and is rapidly internalized, making it an ideal therapeutic target for monoclonal antibodies and for antibody-drug conjugates (ADCs). Brentuximab vedotin is the first ADC to be approved by regulatory agencies for the treatment of patients with relapsed HL, with a single agent response rate of 75%. In this review article we will discuss the current and ongoing development of brentuximab vedotin in patients with relapsed and newly diagnosed Hodgkin lymphoma. PMID:26841013

  17. Acute dysautonomia associated with Hodgkin's disease

    NARCIS (Netherlands)

    van Lieshout, J. J.; Wieling, W.; van Montfrans, G. A.; Settels, J. J.; Speelman, J. D.; Endert, E.; Karemaker, J. M.

    1986-01-01

    A patient is described with acute dysautonomia associated with Hodgkin's disease. Testing of cardiovascular reflex control showed that this patient had a rare manifestation of autonomic cardiovascular neuropathy, namely intact parasympathetic heart rate control in combination with a sympathetic

  18. Prognostic factors in Hodgkin's disease stage III with special reference to tumour burden

    DEFF Research Database (Denmark)

    Specht, L.; Nissen, N.I.

    1988-01-01

    of lymphographically involved regions), histologic subtype, B-symptoms, number of involved regions, mediastinal involvement, pretreatment ESR, sex, age, laparotomy, and substage were examined in multivariate analysis. With regard to disease-free survival, total tumour burden (intraabdominal and peripheral...... regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease....

  19. Challenging the neuronal MIBG uptake by pharmacological intervention: effect of a single dose of oral amitriptyline on regional cardiac MIBG uptake

    Energy Technology Data Exchange (ETDEWEB)

    Estorch, Montserrat; Carrio, Ignasi; Mena, Esther; Flotats, Albert; Camacho, Valle; Fuertes, Jordi [Autonomous University of Barcelona, Department of Nuclear Medicine, Hospital Sant Pau, Barcelona (Spain); Kulisewsky, Jaume [Autonomous University of Barcelona, Department of Neurology, Hospital Sant Pau, Barcelona (Spain); Narula, Jagat [Irvine College of Medicine, Division of Cardiology, University of California, Irvine, CA (United States)

    2004-12-01

    Imaging with metaiodobenzylguanidine (MIBG) is used for the assessment of neuronal dysfunction in various cardiovascular disorders. Although valuable information is obtained by resting MIBG imaging, it is conceivable that competitive interference with the re-uptake mechanism would exaggerate MIBG defects and might unmask subclinical neuronal dysfunction. Tricyclic antidepressants, such as amitriptyline, have been reported to significantly increase cardiac MIBG washout and inhibit uptake into presynaptic neurons. This study was undertaken to assess whether a single oral dose of amitriptyline could influence cardiac MIBG distribution. Six patients (aged 62-81 years; four males, two females) who had demonstrated a normal cardiac MIBG scan during work-up for movement disorders were studied. The patients underwent a second {sup 123}I-MIBG study after oral administration of 25 mg amitriptyline within 1 week. Single-photon emission computed tomography images were acquired at 4 h to assess the regional distribution of MIBG, after generation of polar maps and employing a 20-segment model. Mean percentage of peak activity was calculated for each segment at rest and after amitriptyline administration. After amitriptyline administration, there was a decrease in regional MIBG uptake in 10{+-}4 segments per patient [62/120 segments (52%): 37 segments with a 5-10% decrease, 25 segments with a >10% decrease]. This change was statistically significant in lateral (P=0.003), apical (P<0.0001) and inferior (P=0.03) regions. A single oral dose of amitriptyline can induce changes in the uptake and retention of cardiac MIBG, indicating the feasibility of use of pharmacological intervention in cardiac neurotransmission imaging. (orig.)

  20. Pediatric Hodgkin's disease - up, up, and beyond

    International Nuclear Information System (INIS)

    Donaldson, Sarah S.

    2002-01-01

    Juan A. del Regato, 1909-1999, was a superb clinician-educator who recognized the radiocurability of Hodgkin's disease but questioned treatment without late effects, particularly in children. The remarkable progress in pediatric Hodgkin's disease today is a tribute to this influential pioneer, who served as a role model to many. Combined modality therapy using low-dose, involved-field radiation and multiagent chemotherapy today results in a 5-year relative survival rate of 94% among American children with Hodgkin's disease. However, several areas hold promise for future advances, including a new pathology classification and biology studies that distinguish classic Hodgkin's disease from other lymphomas; new noninvasive staging techniques, including 18F-fluorodeoxyglucose-positron emission tomography; the definition of risk groups to segregate low-, intermediate-, and high-risk groups on the basis of a prognostic index, facilitating risk-adapted therapy; and myeloablative therapy followed by hematopoietic stem cell transplantation. Currently used for children with relapse, it is associated with a 5-year survival of 65% and should be considered as the initial therapy for high-risk groups. Idiopathic diffuse pulmonary toxicity after autologous transplantation is high among children with an atopic history; thus, atopy should be considered when selecting children appropriate for transplantation. Finally, novel therapies, such as the anti-CD20 antibody, rituximab, may be useful for children with CD20+, lymphocyte-predominant Hodgkin's disease. The universal goal of cure without late effects is realistic for almost all children with Hodgkin's disease today

  1. Primary Mediastinal Classical Hodgkin Lymphoma.

    Science.gov (United States)

    Piña-Oviedo, Sergio; Moran, Cesar A

    2016-09-01

    Primary mediastinal Classical Hodgkin lymphoma (CHL) is rare. Nodular sclerosis CHL (NS-CHL) is the most common subtype involving the anterior mediastinum and/or mediastinal lymph nodes. Primary thymic CHL is exceedingly rare. The disease typically affects young women and is asymptomatic in 30% to 50% of patients. Common symptoms include fatigue, chest pain, dyspnea and cough, but vary depending on the location and size of the tumor. B-symptoms develop in 30% of cases. By imaging, primary mediastinal CHL presents as mediastinal widening/mediastinal mass that does not invade adjacent organs but may compress vital structures as bulky disease. Histopathology is the gold standard for diagnosis. Primary mediastinal NS-CHL consists of nodules of polymorphous inflammatory cells surrounded by broad fibrous bands extending from a thickened lymph node capsule. The cellular nodules contain variable numbers of large Hodgkin/Reed-Sternberg cells, required for diagnosis. Primary thymic CHL may exhibit prominent cystic changes. The histopathologic recognition of NS-CHL can be challenging in cases with prominent fibrosis, scant cellularity, artifactual cell distortion, or an exuberant granulomatous reaction. The differential diagnosis includes primary mediastinal non-HLs, mediastinal germ cell tumors, thymoma, and metastatic carcinoma or melanoma to the mediastinum. Distinction from primary mediastinal non-HLs is crucial for adequate therapeutic decisions. Approximately 95% of patients with primary mediastinal CHL will be alive and free of disease at 10 years after treatment with short courses of combined chemoradiotherapy. In this review, we discuss the history, classification, epidemiology, clinicoradiologic features, histopathology, immunohistochemistry, differential diagnosis, and treatment of primary mediastinal CHL.

  2. Single-molecule folding mechanisms of the apo- and Mg2+-bound states of human neuronal calcium sensor-1

    DEFF Research Database (Denmark)

    Naqvi, Mohsin M; Heiðarsson, Pétur Orri; Otazo, Mariela R

    2015-01-01

    Neuronal calcium sensor-1 (NCS-1) is the primordial member of a family of proteins responsible primarily for sensing changes in neuronal Ca(2+) concentration. NCS-1 is a multispecific protein interacting with a number of binding partners in both calcium-dependent and independent manners, and acting...... in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca(2+)-activated state of NCS proteins, little is known about the conformational dynamics of the Mg(2+)-bound and apo states, both of which are populated...... by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions...

  3. Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Shepherd, Leah; Ryom, Lene; Law, Matthew

    2018-01-01

    Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data fro...

  4. Radiation-induced splenic atrophy in patients with Hodgkin's disease and non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Dailey, M.O.; Coleman, C.N.; Kaplan, H.S.

    1980-01-01

    Effective treatment of Hodgkin's disease requires the determination of the extent of the disease. This usually involves staging laparotomy, which includes splenectomy and biopsies of the para-aortic lymph nodes, liver, and bone marrow. Absence of the spleen predisposes a person to fulminant septicemia from encapsulated bacteria, a risk even greater in patients undergoing treatment for Hodgkin's disease. For this reason, some investigators have suggested that spleens not be removed for diagnosis but, rather, that they be included within the fields of radiation, which would preserve normal splenic function. We present a case of fatal spontaneous pneumococcal sepsis in a patient with splenic atrophy; the sepsis occurred 12 years after successful treatment of Hodgkin's disease by total nodal and splenic irradiation. A retrospective study of patients treated for Hodgkin's and non-Hodgkin's lymphomas indicated that atrophy and functional asplenia may be an important sequela of splenic irradiation

  5. Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning

    Directory of Open Access Journals (Sweden)

    Osacka J.

    2017-04-01

    Full Text Available Objective. Fos protein expression in catecholamine-synthesizing neurons of the substantia nigra (SN pars compacta (SNC, A8, pars reticulata (SNR, A9, and pars lateralis (SNL, the ventral tegmental area (VTA, A10, the locus coeruleus (LC, A6 and subcoeruleus (sLC, the ventrolateral pons (PON-A5, the nucleus of the solitary tract (NTS-A2, the area postrema (AP, and the ventrolateral medulla (VLM-A1 was quantitatively evaluated aft er a single administration of asenapine (ASE (designated for schizophrenia treatment in male Wistar rats preconditioned with a chronic unpredictable variable mild stress (CMS for 21 days. Th e aim of the present study was to reveal whether a single ASE treatment may 1 activate Fos expression in the brain areas selected; 2 activate tyrosine hydroxylase (TH-synthesizing cells displaying Fos presence; and 3 be modulated by CMS preconditioning.

  6. p53 gene analysis in childhood B non - Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Claudete Esteves Nogueira Pinto Klumb

    Full Text Available CONTEXT: Mutations or deletions in the tumor-suppressor gene p53 are among the commonest genetic changes found in human neoplasms including breast, lung and bowel cancers. In hematological malignancies, p53 is most often mutated in Burkitt's lymphoma, with p53 mutations present in 30 to 40% of tumor samples and in 70% of cell lines. OBJECTIVE: To analyze the p53 gene alterations in child patients with B non-Hodgkin's lymphoma. DESIGN: Descriptive study. SETTING: Tertiary oncology care center. PARTICIPANTS: The study investigated 12 patients with childhood B non-Hodgkin's lymphoma (Burkitt's lymphoma. Screening for p53 mutations was done by polymerase chain reaction - single strand conformational polymorphism (PCR-SSCP analysis of exon 5 to 8/9 of the gene. RESULTS: Abnormal polymerase chain reaction - single strand conformational polymorphism migration pattern was observed in 4 patients (33.3%, one on exon 6 and three on exon 7. Positive cases included 2 patients who died from disease. CONCLUSION: These preliminary results suggest that p53 mutations are quite frequent in children with Burkitt's lymphoma and may play a role in lymphoma genesis or disease progression.

  7. Non –Hodgkin lymphoma in Sudanese Children | Osman | Sudan ...

    African Journals Online (AJOL)

    Background: Non-Hodgkin Lymphoma is a very heterogeneous lymphoproliferative disease with clinical and histological pattern different from children to adults. Objective: To characterize the clinical and pathological pattern of Non -Hodgkin`s lymphoma among Sudanese children. Materials and Methods: This study was ...

  8. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta

    2010-07-01

    Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  9. Comparison of Langevin and Markov channel noise models for neuronal signal generation.

    Science.gov (United States)

    Sengupta, B; Laughlin, S B; Niven, J E

    2010-01-01

    The stochastic opening and closing of voltage-gated ion channels produce noise in neurons. The effect of this noise on the neuronal performance has been modeled using either an approximate or Langevin model based on stochastic differential equations or an exact model based on a Markov process model of channel gating. Yet whether the Langevin model accurately reproduces the channel noise produced by the Markov model remains unclear. Here we present a comparison between Langevin and Markov models of channel noise in neurons using single compartment Hodgkin-Huxley models containing either Na+ and K+, or only K+ voltage-gated ion channels. The performance of the Langevin and Markov models was quantified over a range of stimulus statistics, membrane areas, and channel numbers. We find that in comparison to the Markov model, the Langevin model underestimates the noise contributed by voltage-gated ion channels, overestimating information rates for both spiking and nonspiking membranes. Even with increasing numbers of channels, the difference between the two models persists. This suggests that the Langevin model may not be suitable for accurately simulating channel noise in neurons, even in simulations with large numbers of ion channels.

  10. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Science.gov (United States)

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B; Niven, Jeremy E

    2010-07-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+) and K(+) currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+) and K(+) channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  11. PET imaging in pediatric Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Hudson, M.M.; Krasin, M.J.; Kaste, S.C.

    2004-01-01

    Advances in diagnostic imaging technology, especially functional imaging modalities like positron emission tomography (PET), have significantly influenced the staging and treatment approaches used for pediatric Hodgkin's lymphoma. Today, the majority of children and adolescents diagnosed with Hodgkin's lymphoma will be cured following treatment with noncross-resistant combination chemotherapy alone or in combination with low-dose, involved-field radiation. This success produced a greater appreciation of long-term complications related to radiation, chemotherapy, and surgical staging that prompted significant changes in staging and treatment protocols for children and adolescents with Hodgkin's lymphoma. Contemporary treatment for pediatric Hodgkin's lymphoma uses a risk-adapted approach that reduces the number of combination chemotherapy cycles and radiation treatment fields and doses for patients with localized favorable disease presentation. Advances in diagnostic imaging technology have played a critical role in the development of these risk-adapted treatment regimens. The introduction of computed tomography (CT) provided an accurate and non-invasive modality to define nodal involvement below the diaphragm that motivated the change from surgical to clinical staging. The introduction of functional imaging modalities, like positron emission tomography (PET) scanning, provided the means to correlate tumor activity with anatomic features generated by CT and modify treatment based on tumor response. For centers with access to this modality, PET imaging plays an important role in staging, evaluating tumor response, planning radiation treatment fields, and monitoring after completion of therapy for pediatric Hodgkin's lymphoma. (orig.)

  12. Hodgkin's Lymphoma; Lymphome de Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Drouet, F.; Mahe, M.A. [Service de radiotherapie du Centre Rene-Gauducheau, CRLCC Nantes-Atlantiques, 44 - Saint-Herblain (France); Cahu, X. [Service d' hematologie clinique CHU de Rennes, hopital Pontchaillou, 35 - Rennes (France); Pointreau, Y. [Service de radiotherapie, centre regional universitaire de cancerologie Henry-S.-Kaplan CHU de Tours, Hpital Bretonneau, 37 - Tours (France); Denis, F. [Centre Jean-Bernard, Service de radiotherapie 72 - Le Mans (France)

    2010-07-01

    With approximately 1500 cases per year in France, Hodgkin's lymphoma (HL) represents only 10 to 15 % of new cases of lymphomas, and 0.5 to 1 % of new cases of cancers. The management of this lympho-proliferative disease has undergone profound conceptual changes over time, allowing at present to obtain a cure rate of 75 to 80 % of all confused stage, and up to 90 % in case of early stage HL. If initial treatment consisted in an exclusive extensive (total or sub-total lymphoid) irradiation whatever the stage may be, the place of radiotherapy in the management of HL has evolved over time but remains today one of the cornerstones of the treatment. It becomes integrated within the framework of combined modality therapies associating chemotherapy then irradiation for the early stage HL, and stays a therapeutic alternative in all situations (in advanced stage and/or recurrent disease) which raises the issue of increasing the locoregional tumor control. Despite the undeniable contribution of radiotherapy in controlling the disease, delayed side effects of treatments are not negligible. So the long-term monitoring of treated patients is essential, mainly because of an increased risk of morbi-mortality due to cardiovascular events and/or secondary cancers. It is important to remember that even today the 'Involved Field' irradiation type remains the gold standard, even if we witness at present the emergence of new types of irradiation, which aim to reduce the amount of irradiated tissues to try to limit the risks of delayed radio-induced complications. The purpose of this article is to clarify the specific aspects (epidemiological, radio-anatomical and prognostic characteristics) of HL, as well as the practical modalities of the irradiation (illustrated by a clinical case record) when an indication of radiotherapy is placed for its treatment. (authors)

  13. Bilateral breast cancer after cured Hodgkin's disease

    International Nuclear Information System (INIS)

    Anderson, N.; Lokich, J.

    1990-01-01

    Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions

  14. Hodgkin Lymphoma, Version 2.2015

    Science.gov (United States)

    Hoppe, Richard T.; Advani, Ranjana H.; Ai, Weiyun Z.; Ambinder, Richard F.; Aoun, Patricia; Bello, Celeste M.; Benitez, Cecil M.; Bierman, Philip J.; Blum, Kristie A.; Chen, Robert; Dabaja, Bouthaina; Forero, Andres; Gordon, Leo I.; Hernandez-Ilizaliturri, Francisco J.; Hochberg, Ephraim P.; Huang, Jiayi; Johnston, Patrick B.; Khan, Nadia; Maloney, David G.; Mauch, Peter M.; Metzger, Monika; Moore, Joseph O.; Morgan, David; Moskowitz, Craig H.; Mulroney, Carolyn; Poppe, Matthew; Rabinovitch, Rachel; Seropian, Stuart; Tsien, Christina; Winter, Jane N.; Yahalom, Joachim; Burns, Jennifer L.; Sundar, Hema

    2016-01-01

    Hodgkin lymphoma (HL) is an uncommon malignancy involving lymph nodes and the lymphatic system. Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma are the 2 main types of HL. CHL accounts for most HL diagnosed in the Western countries. Chemotherapy or combined modality therapy, followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale), is the standard initial treatment for patients with newly diagnosed CHL. Brentuximab vedotin, a CD30-directed antibody-drug conjugate, has produced encouraging results in the treatment of relapsed or refractory disease. The potential long-term effects of treatment remain an important consideration, and long-term follow-up is essential after completion of treatment. PMID:25964641

  15. Hodgkin's Lymphomas: A Tumor Recognized by Its Microenvironment

    Directory of Open Access Journals (Sweden)

    S. Montes-Moreno

    2011-01-01

    Full Text Available Thomas Hodgkin's and Samuel Wilks first recognized Hodgkin disease in the first half of the 19th century. Initially described as lymphogranulomatosis, it was later recognized to be a lymphoid neoplasm derived from B cells and was classified on the basis of its histopathological features. Hodgkin lymphomas are now regarded as encompassing two clearly defined entities according to the WHO classification: nodular lymphocyte-predominant Hodgkin Lymphoma (NLPHL and classical Hodgkin Lymphoma (CHL. This paper focuses on the current knowledge about the biological features that characterize both NLPHL and CHL, highlighting those relevant to correct pathological diagnosis and those that might be associated with patient outcome.

  16. FDG-PET in Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Kobe, C.; Dietlein, M.; Schicha, H.; Sabri, O.; Kluge, R.; Schober, O.

    2008-01-01

    The high negative predictive value of FDG-PET in therapy control of Hodgkin lymphoma is proven by the data acquired up to now. Thus, the analysis of the HD15 trial has shown that consolidation radiotherapy might be omitted in PET negative patients after effective chemotherapy. Further response adapted therapy guided by PET seems to be a promising approach in reducing the toxicity for patients undergoing chemotherapy. The criteria used for the PET interpretation have been standardized by the German study groups for Hodgkin lymphoma patients and will be reevaluated in the current studies. (orig.)

  17. CT assessment of splenic involvement by Hodgkin's disease and Non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Neumann, C.H.; Castellino, R.A.

    1984-01-01

    The experience at Stanford University Medical Center (SUMC) with computerized tomography (CT) for determination of splenic involvement by Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) between 1978 and 1982 is presented. Ninety-eight patients had CT during their staging work-up prior to laparotomy and splenectomy. Based on the presence of detectable parenchymal defects before and after intravenous water soluble contrast media, CT sensitivity, specificity and accuracy was 2%, 98% and 54%, with little difference between Hodgkin's disease and non-Hodgkin's lymphoma. Based on weight criterion, the comparable accuracy data was 56%, 72% and 64%. We conclude that CT scanning with and without water soluble contrast media is of no value in detecting splenic involvement by lymphomas, and should not be relied upon when exact knowledge about presence of disease in this organ is needed for further treatment decisions. (orig.) [de

  18. Profiling neuronal ion channelopathies with non-invasive brain imaging and dynamic causal models: Case studies of single gene mutations.

    Science.gov (United States)

    Gilbert, Jessica R; Symmonds, Mkael; Hanna, Michael G; Dolan, Raymond J; Friston, Karl J; Moran, Rosalyn J

    2016-01-01

    Clinical assessments of brain function rely upon visual inspection of electroencephalographic waveform abnormalities in tandem with functional magnetic resonance imaging. However, no current technology proffers in vivo assessments of activity at synapses, receptors and ion-channels, the basis of neuronal communication. Using dynamic causal modeling we compared electrophysiological responses from two patients with distinct monogenic ion channelopathies and a large cohort of healthy controls to demonstrate the feasibility of assaying synaptic-level channel communication non-invasively. Synaptic channel abnormality was identified in both patients (100% sensitivity) with assay specificity above 89%, furnishing estimates of neurotransmitter and voltage-gated ion throughput of sodium, calcium, chloride and potassium. This performance indicates a potential novel application as an adjunct for clinical assessments in neurological and psychiatric settings. More broadly, these findings indicate that biophysical models of synaptic channels can be estimated non-invasively, having important implications for advancing human neuroimaging to the level of non-invasive ion channel assays. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future.

    Science.gov (United States)

    Richardson, S E; McNamara, C

    2011-01-01

    The management of classical Hodgkin's lymphoma (CHL) is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT) demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP) and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT). Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

  20. The Management of Classical Hodgkin's Lymphoma: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    S. E. Richardson

    2011-01-01

    Full Text Available The management of classical Hodgkin's lymphoma (CHL is a success story of modern multi-agent haemato-oncology. Prior to the middle of the twentieth century CHL was fatal in the majority of cases. Introduction of single agent radiotherapy (RT demonstrated for the first time that these patients could be cured. Developments in chemotherapy including the mechlorethamine, vincristine, procarbazine and prednisolone (MOPP and Adriamycin, bleomycin, vinblastine and dacarbazine (ABVD regimens have resulted in cure rates of over 80%. Even in relapse, CHL patients can be salvaged with high dose chemotherapy and autologous haematopoietic stem cell transplantation (ASCT. Challenges remain, however, in finding new strategies to manage the small number of patients who continue to relapse or progress. In addition, the young age of many Hodgkin's patients forces difficult decisions in balancing the benefit of early disease control against the survival disadvantage of late toxicity. In this article we aim to summarise past trials, define the current standard of care and appraise future developments in the management of CHL.

  1. Multiple primary cancer risk after therapy for Hodgkins's disease

    International Nuclear Information System (INIS)

    Brody, R.S.; Schottenfeld, D.; Reid, A.

    1977-01-01

    Forty-four antecedent, synchronous, and metachronous multiple primary cancers were identified among 41 patients who constituted 4.0% of 1028 patients initially treated for Hodgkin's disease during the years 1950--1954, 1960--1964, and 1968--1972. At 5 years post-therapy the cumulative probabilities of developing a multiple primary cancer for patients treated in 1950--1954, 1960--1964, and 1968--1972, were 1.14%, 1.48%, and 4.43%, respectively. At 10 years the cumulative probability of a multiple primary cancer was 2.54% for the 1950--1954 treatment group and 6.52% for the 1960--1964 treatment group. Among those patients 16-39 years of age, initially treated during the period 1960--1964, who had survived 6-10 years after receiving radiation plus single agent chemotherapy, we observed a significant 18-fold increase in the number of multiple primary cancers. A significant occurrence of two multiple primary cancers in a relatively small group of patients treated with chemotherapy only during the period 1968--1972 was also noted. Continued surveillance of patients extensively treated with combination chemotherapy and radiotherapy will enable assessment of the oncogenic potential of these modern therapeutic approaches to the management of Hodgkin's disease

  2. Single neurons with both form/color differential responses and saccade-related responses in the nonretinotopic pulvinar of the behaving macaque monkey.

    Science.gov (United States)

    Benevento, L A; Port, J D

    1995-01-01

    The nonretinotopic portion of the macaque pulvinar complex is interconnected with the occipitoparietal and occipitotemporal transcortical visual systems where information about the location and motion of a visual object or its form and color are modulated by eye movements and attention. We recorded from single cells in and about the border of the dorsal portion of the lateral pulvinar and the adjacent medial pulvinar of awake behaving Macaca mulatta in order to determine how the properties of these two functionally dichotomous cortical systems were represented. We found a class of pulvinar neurons that responded differentially to ten different patterns or broadband wavelengths (colors). Thirty-four percent of cells tested responded to the presentation of at least one of the pattern or color stimuli. These cells often discharged to several of the patterns or colors, but responded best to only one or two of them, and 86% were found to have statistically significant pattern and/or color preferences. Pattern/color preferential cells had an average latency of 79.1 +/- 46.0 ms (range 31-186 ms), responding well before most inferotemporal cortical cell responses. Visually guided and memory-guided saccade tasks showed that 58% of pattern/color preferential cells also had saccade-related properties, e.g. directional presaccadic and postsaccadic discharges, and inhibition of activity during the saccade. In the pulvinar, the mean presacadic response latency was earlier, and the mean postsaccadic response latency was later, than those reported for parietal cortex. We also discovered that the strength of response to patterns or colors changed depending upon the behavioral setting. In comparison to trials in which the monkey fixated dead ahead during passive presentations of pattern and color stimuli, 92% of the cells showed attenuated responses to the same passive presentation of patterns and colors during fixation when these trials were interleaved with trials which also

  3. Potential benefits of therapeutic splenectomy for patients with Hodgkin's disease and non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Schreiber, D.P.; Jacobs, C.; Rosenberg, S.A.; Cox, R.S.; Hoppe, R.T.

    1985-01-01

    Thirty-four patients with Hodgkin's disease and non-Hodgkin's lymphoma underwent therapeutic splenectomies to improve hematologic tolerance for chemotherapy. The mean age was 40 years; there were 16 males and 18 females. Fourteen had Hodgkin's disease, 19 had non-Hodgkin's lymphoma, and 1 had malignant histocytosis. Nineteen had palpable splenomegaly, 19 had marrow involvement and 20 had splenic involvement by lymphoma. The following data were analyzed before and after splenectomy: mean white blood cell count (WBC) and platelet count on planned first day of cycle, delay ratio of chemotherapy delivery and percent maximal dose rate. Thirteen patients had non-Hodgkin's lymphoma, splenomegaly and positive bone marrow and showed significant benefit in all of the aforementioned parameters. Of the patients with prior irradiation, only those who completed their radiation greater than six months prior to splenectomy showed benefit. Ten patients had Hodgkin's disease, negative bone marrow and no splenomegaly. This group showed significant improvement in mean platelet count but more limited benefit in delay ratio and percent maximal dose rate. Thus, selected patients with lymphoma who are experiencing delays in chemotherapy because of poor count tolerance may benefit from splenectomy

  4. Clinical significance of the serum IL-2R level and Ga-67 scan findings in making a differential diagnosis between sarcoidosis and non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Kita, Tamotsu; Watanabe, Sadahiro; Yano, Fuzuki; Hayashi, Katsumi; Yamamoto, Masayoshi; Iwasaki, Yoshie; Kosuda, Shigeru

    2007-01-01

    The objective of this study was to compare the serum-soluble interleukin-2 receptor (sIL-2R) levels of non-Hodgkin's lymphoma patients and active sarcoidosis patients in relation to the 67 Ga scan findings. A total of 29 adenopathy patients suspected of having non-Hodgkin's lymphoma or sarcoidosis were enrolled in the study. All patients underwent a whole-body 67 Ga scan and single-photon emission computed tomography studies 48 h after intravenous injection of 67 Ga citrate. The sIL-2R levels were compared between the sarcoidosis patients and non-Hodgkin's lymphoma patients, the patients with and without the panda and/or lambda sign, the lymphoma patients with stage I/II disease and with stage III/IV disease, and the sarcoidosis patients and non-Hodgkin's lymphoma patients with stage III/IV disease. The range of the sIL-2R levels was 195-3750 U/ml in sarcoidosis and 240-62300 U/ml in non-Hodgkin's lymphoma. The sIL-2R levels of the six non-Hodgkin's lymphoma patients with stage III/IV disease were significantly higher than those of the 15 sarcoidosis patients (P<0.001). The sIL-2R levels of the sarcoidosis patients with the panda and/or lambda sign were significantly higher than those with neither sign (P<0.005). The sIL-2R levels of the non-Hodgkin's lymphoma patients with stage III/IV disease were significantly higher than those of the patients with stage I/II disease (P<0.005). Measurement of sIL-2R levels was sometimes useful in differentiating between sarcoidosis and stage III/IV non-Hodgkin's lymphoma, staging non-Hodgkin's lymphoma, and predicting the presence of the panda and/or lambda sign in sarcoidosis patients. (author)

  5. Novel treatment concepts in Hodgkin lymphoma

    NARCIS (Netherlands)

    Glimelius, I.; Diepstra, A.

    Treatment of classical Hodgkin's lymphoma (HL) has been a success story, with cure of localized disease with radiotherapy in the 1930s, cure of advanced stages with combination chemotherapy with/without radiotherapy in the mid-1960s and continuous improvements since then. Nonetheless, at present

  6. Late cardiotoxicity after treatment for Hodgkin lymphoma

    NARCIS (Netherlands)

    B.M.P. Aleman (Berthe); A.W. van den Belt-Dusebout (Alexandra); M.L. de Bruin (Marie); M.B. van 't Veer (Mars); M. Baaijens (Margreet); J.P. De Boer (Jan Paul); A.A.M. Hart (Augustinus); W.J. Klokman (Willem); M.A. Kuenen (Marianne); G.M. Ouwens (Gabey); H. Bartelink (Harry); F.E. van Leeuwen (Flora)

    2007-01-01

    textabstractWe assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7

  7. Late effects after treatment for Hodgkin lymphoma

    NARCIS (Netherlands)

    Daniëls, Laurien Aletta

    2014-01-01

    Although modern treatment strategies have made Hodgkin Lymphoma (HL) a highly curable disease, there is a life-long increased risk of morbidity and mortality due to treatment. Over time it has become increasingly evident that the historically used extensive treatment fields can potentially lead to

  8. Immune reactions in classical Hodgkin's lymphoma

    NARCIS (Netherlands)

    Poppema, S; Potters, M; Emmens, R; Visser, L; van den Berg, A.

    The immune reaction in classical Hodgkin's lymphoma (HL) can be separated into an inflammatory response in the involved tissues and a generalized immune response in the patient. The local immune reaction in HL is by far the most prominent among all tumors, with the exception of so called T-cell-rich

  9. Immunohistochemical analysis of hodgkin's disease in Kampala ...

    African Journals Online (AJOL)

    Background: Histopathological examination remains crucial for diagnosis and classification of Hodgkin's disease (HD) but poses problems when characteristic features of HD are not present and hence the value of immunohistochemistry. Experience with immunohistochemistry in developing countries is limited due to cost.

  10. Doença de Hodgkin

    Directory of Open Access Journals (Sweden)

    Marina Pereira

    1999-05-01

    Full Text Available RESUMO: Os autores descrevem um caso de doença de Hodgkin, do subtipo esclerose nodular, numa mulher de 24 anos de idade. A forma de apresentação clínica, pouco habitual, é constituída por uma massa na regão esternal e parede anterior do hemitórax esquerdo, a qual adquire grande volume ao fim de 2 anos e meio de evolução natural da doença. Esta é tratada com quimioterapia (MOPP e radioterapia adjuvante, sofrendo uma reeressão total das suas manifestações clínicas.REV PORT PNEUMOL 1999; V (3: 349-355 ABSTRACT: A case of a 24 years old woman with Hodgkin’s disease, nodular sclerosis subtype, is reported. The disease present with an anterior chest wall mass, an unusual clinical presentation form. The patient receive MOPP chemotherapy and adjuvant radio-therapy with complete resolution of her clinical manifestations.REV PORT PNEUMOL 1999; V (3: 349-355 Palavras-chave: Doença de Hodgkin, Massa da parede torácica anterior, Forma de apresentação clinica, Key-words: Hodgkin’s disease, Anterior chest wall mass, Clinical presentation form

  11. High resolution imaging of calcium dynamics in single spines of CA1 pyramidal neurons in the hippocampus

    Science.gov (United States)

    Conti, Rossella

    2001-08-01

    Whole-cell recordings and confocal fluorescence imaging were used to investigate the properties of intracellular Ca2+ dynamics in CA1 hippocampal pyramidal cells in acute slices. We first measured the properties of Ca2+ entry during AP firing of a cell and synaptic stimulation. The back-propagation of a single AP into the dendrites caused [Ca2+]; to rise in dendrites and spines simultaneously and it invaded the whole dendritic tree. The measured synaptically evoked Ca2+ signals in individual spines were different depending on the intracellular solution. In K +-based solution, synaptic stimulation evoked a Ca2+ signal that was restricted to single spines (dendritic spread 4 microns). This suggests an important role for K+ channels in regulating dendritic Ca2+ signals. I also describe a result which gave us the first view of synaptic function at a single connection. In one experiment the recorded electrical responses was demonstrated to arise from a single optically identified synapse. The surprisingly high coefficient of variation of the recorded signals suggests that either vesicles have different neurotransmitter concentration or the synapse generates responses to multiple released vesicles. We then investigated the role of Ca2+ entry during the pairing protocol for UP induction. We found that the post-synaptic depolarization required for LTP induction leads to a large maintained elevation of [Ca 2+]; in all spines due to VDCC activation; the [Ca2+]; elevation was greatly reduced by intracellular application of D890, a VDCC blocker. D890 almost completely blocked LTP, suggesting that Ca2+ entry through VDCC could be essential for LTP induction. The effect of D890 is not due to L-type Ca2+ channels, since a specific blocker of these channels did not affect LTP. When tested by Tom Soderling, high concentrations of D890 (IC-50 = 1mM) inhibited CaMKII, an enzyme whose activity is required for LTP induction. These results leave the role of VDCC in LTP induction

  12. Frequency of epstein-barr virus in classical hodgkin Lymphoma.

    Science.gov (United States)

    Azhar, Muhammad; Din, Hafeez Ud; Muhammad, Iqbal; Hashmi, Shoaib Naiyar; Akhtar, Farhan

    2016-01-01

    Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.

  13. Radiotherapy Does Not Influence the Severe Pulmonary Toxicity Observed With the Administration of Gemcitabine and Bleomycin in Patients With Advanced-Stage Hodgkin's Lymphoma Treated With the BAGCOPP Regimen: A Report by the German Hodgkin's Lymphoma Study Group

    International Nuclear Information System (INIS)

    Macann, Andrew; Bredenfeld, Henning; Mueller, Rolf-Peter; Diehl, Volker; Engert, Andreas; Eich, Hans Theodor

    2008-01-01

    Purpose: To evaluate the effect of radiotherapy on the severe pulmonary toxicity observed in the pilot study of BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine) for advanced-stage Hodgkin's lymphoma. Methods and Materials: Patients with Stage III or IV Hodgkin's lymphoma or Stage IIB with risk factors participated in this single-arm, multicenter pilot study. Results: Twenty-seven patients were enrolled on the study before its premature closure as a result of the development of serious pulmonary toxicity in 8 patients. The pulmonary toxicity occurred either during or immediately after the BAGCOPP chemotherapy course. Pulmonary toxicity contributed to one early fatality but resolved in the other 7 patients after cessation of gemcitabine and bleomycin, allowing continuation of therapy. Fifteen patients received consolidative radiotherapy, including 4 who previously had pulmonary toxicity. There were no reported cases of radiation pneumonitis and no exacerbation of pulmonary symptoms in the 4 patients who had had previous pulmonary toxicity. Conclusions: The severe pulmonary toxicity observed in this study has been attributed to an interaction between gemcitabine and bleomycin. Gemcitabine (when administered without bleomycin) remains of interest in Hodgkin's lymphoma and is being incorporated into a new German Hodgkin's Lymphoma Study Group protocol that also includes consolidative radiotherapy. This study supports the concept of the integration of radiotherapy in gemcitabine-containing regimens in Hodgkin's lymphoma if there is an interval of at least 4 weeks between the two modalities and with a schedule whereby radiotherapy follows the chemotherapy

  14. The evaluation of CT scan in renal involvement of children with non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Li Yuhua; Shen Jie; Zhu Ming; Tang Jingyan; Xue Huiliang

    2001-01-01

    Objective: To understand the incidence of renal involvement of children with non-Hodgkin's lymphoma and to recognize its different CT findings. Methods: The thoracic and abdominal plain and contrast enhanced CT of 30 cases of NHL in children were reviewed and all cases were confirmed by pathology. The changes in both pre- and post chemotherapy were analysed in the 10 selected cases with renal involvement. Results: CT demonstrated 6 cases of multiple masses and 1 case of multiple patchy lesions in bilateral kidneys. Two cases of single mass and 1 case of multiple masses were detected in single kidney. Conclusion: The incidence of renal involvement of children with non-Hodgkin's lymphoma is relatively high. CT can clearly demonstrate the renal involvement of NHL, which is helpful for clinical stage, especially in the evaluation of the therapeutic effects. Hence, abdominal plain and contrast-enhanced CT scan should be done in children with NHL

  15. Kappe neurons, a novel population of olfactory sensory neurons.

    Science.gov (United States)

    Ahuja, Gaurav; Bozorg Nia, Shahrzad; Zapilko, Veronika; Shiriagin, Vladimir; Kowatschew, Daniel; Oka, Yuichiro; Korsching, Sigrun I

    2014-02-10

    Perception of olfactory stimuli is mediated by distinct populations of olfactory sensory neurons, each with a characteristic set of morphological as well as functional parameters. Beyond two large populations of ciliated and microvillous neurons, a third population, crypt neurons, has been identified in teleost and cartilaginous fishes. We report here a novel, fourth olfactory sensory neuron population in zebrafish, which we named kappe neurons for their characteristic shape. Kappe neurons are identified by their Go-like immunoreactivity, and show a distinct spatial distribution within the olfactory epithelium, similar to, but significantly different from that of crypt neurons. Furthermore, kappe neurons project to a single identified target glomerulus within the olfactory bulb, mdg5 of the mediodorsal cluster, whereas crypt neurons are known to project exclusively to the mdg2 glomerulus. Kappe neurons are negative for established markers of ciliated, microvillous and crypt neurons, but appear to have microvilli. Kappe neurons constitute the fourth type of olfactory sensory neurons reported in teleost fishes and their existence suggests that encoding of olfactory stimuli may require a higher complexity than hitherto assumed already in the peripheral olfactory system.

  16. Robust Master-Slave Synchronization of Neuronal Systems

    Directory of Open Access Journals (Sweden)

    Hector Puebla

    2017-01-01

    Full Text Available The desire to understand physiological mechanisms of neuronal systems has led to the introduction of engineering concepts to explain how the brain works. The synchronization of neurons is a central topic in understanding the behavior of living organisms in neurosciences and has been addressed using concepts from control engineering. We introduce a simple and reliable robust synchronization approach for neuronal systems. The proposed synchronization method is based on a master-slave configuration in conjunction with a coupling input enhanced with compensation of model uncertainties. Our approach has two nice features for the synchronization of neuronal systems: (i a simple structure that uses the minimum information and (ii good robustness properties against model uncertainties and noise. Two benchmark neuronal systems, Hodgkin-Huxley and Hindmarsh-Rose neurons, are used to illustrate our findings. The proposed synchronization approach is aimed at gaining insight into the effect of external electrical stimulation of nerve cells.

  17. Stochastic resonance of ensemble neurons for transient spike trains: Wavelet analysis

    International Nuclear Information System (INIS)

    Hasegawa, Hideo

    2002-01-01

    By using the wavelet transformation (WT), I have analyzed the response of an ensemble of N (=1, 10, 100, and 500) Hodgkin-Huxley neurons to transient M-pulse spike trains (M=1 to 3) with independent Gaussian noises. The cross correlation between the input and output signals is expressed in terms of the WT expansion coefficients. The signal-to-noise ratio (SNR) is evaluated by using the denoising method within the WT, by which the noise contribution is extracted from the output signals. Although the response of a single (N=1) neuron to subthreshold transient signals with noises is quite unreliable, the transmission fidelity assessed by the cross correlation and SNR is shown to be much improved by increasing the value of N: a population of neurons plays an indispensable role in the stochastic resonance (SR) for transient spike inputs. It is also shown that in a large-scale ensemble, the transmission fidelity for suprathreshold transient spikes is not significantly degraded by a weak noise which is responsible to SR for subthreshold inputs

  18. Linear stability analysis of retrieval state in associative memory neural networks of spiking neurons

    Science.gov (United States)

    Yoshioka, Masahiko

    2002-12-01

    We study associative memory neural networks of the Hodgkin-Huxley type of spiking neurons in which multiple periodic spatiotemporal patterns of spike timing are memorized as limit-cycle-type attractors. In encoding the spatiotemporal patterns, we assume the spike-timing-dependent synaptic plasticity with the asymmetric time window. Analysis for periodic solution of retrieval state reveals that if the area of the negative part of the time window is equivalent to the positive part, then crosstalk among encoded patterns vanishes. Phase transition due to the loss of the stability of periodic solution is observed when we assume fast α function for direct interaction among neurons. In order to evaluate the critical point of this phase transition, we employ Floquet theory in which the stability problem of the infinite number of spiking neurons interacting with α function is reduced to the eigenvalue problem with the finite size of matrix. Numerical integration of the single-body dynamics yields the explicit value of the matrix, which enables us to determine the critical point of the phase transition with a high degree of precision.

  19. Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Alison Maggioncalda

    2011-01-01

    Full Text Available Epidemiological studies suggest unique occurrence patterns of Hodgkin lymphoma (HL worldwide. In most Western countries there is a clear bimodal age distribution with an early peak in young adults followed by a second peak in older adults, particularly among males. In the Middle East and Asia, HL is more common in early childhood. There also are marked racial differences in the presentations of HL and HL subtypes, and particular single nucleotide polymorphisms (SNPs have been identified as etiological factors suggesting that gene-gene and gene-environment interactions are involved. Personal health choices such as exercise and smoking may modify an individual's chances of developing HL. Numerous studies highlight the impact that exposure to Epstein-Barr virus and other environmental factors have on HL risk. Understanding the relative importance of each of these findings and their links to HL development and survival will help clinical researchers expand curative therapies and create preventative strategies for HL.

  20. A rare transition of non-Hodgkin lymphoma into classical Hodgkin disease

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2016-10-01

    Full Text Available An uncommon case of blood cancer non-Hodg- kin lymphoma developing into classical  Hodgkin lymphoma was recently described by researchers from the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida in a case report published in this issue of AMOR.“Through a series of biopsies, we report a unique case of diffuse large B-cell lymphoma (DLBCL with stepwise development of classical Hodgkin lymphoma (cHL,” said pathologists Dr. Haipeng Shao and Pardis Vafaii from the Department of Hematopathology and Laboratory Medicine. “To the best of our knowledge, this is the first report of an intermediate stage of transformation from DLBCL into cHL,” they added.Lymphoma, or cancer in the infection-fighting lymphatic part of a human’s immune system, is categorized into two types: Hodgkin lymphoma and non-Hodgkin lymphoma – both with distinct behaviors and different treatment requirements. Classical Hodgkin lymphoma – named after the 19th century British physician Thomas Hodgkin who first described the abnormalities in lymphatic system – is a less frequently diagnosed lymphoma subtype with tell-tale signs of abnormal lymphoid cells called ‘Reed­Sternberg cells’ which are observed as giant purple nucleoli when examined under light microscopy.However, 90% of lymphomas are of the non-Hodgkin lymphoma variety and do not exhibit the Reed­Sternberg cells. Of all the non-Hodgkin lymphomas, DLBCL is the most common type, which develops when white blood cells called lymphocytes (specifically the B-cell lymphocytes start dividing uncontrollably. The distinction between DLBCL and cHL is clinically important as both respond differently to chemotherapeutic regimens, according to Shao and Vafaii. Moreover, “classical Hodgkin lymphoma and non-Hodgkin lymphoma rarely develop in the same patient,” they explained.In their published case report, however, DLBCL and cHL was found to develop on the same anatomic sites, particularly on the

  1. Discrete peritoneal and pericardial implants of non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Eckel, C.G.; Davis, M.; Mettler, F.A. Jr.; Rosenberg, R.

    1987-01-01

    Peritoneal spread of non-Hodgkin lymphoma is rare: fewer than three percent of persons afflicted with this disease develop peritoneal spread. Pericardial involvement by non-Hodgkin lymphoma is equally rare. We report an instance of peritoneal and pericardial spread in a patient with non-Hodgkin lymphoma that was detected only by CT scan. The peritoneal lesions were not visible by ultrasound examination. A pertinent review of the literature is presented. (author)

  2. Non-Hodgkin lymphoma of oral cavity; a case report

    Directory of Open Access Journals (Sweden)

    Z. Tohidast Ekrad

    1994-07-01

    Full Text Available Malignant lymphoma is the neoplastic transformation of Cells, mostly originating from lymphoid tissues. Malignant lymphoma has two major subtypes: Hodgkin and non-Hodgkin lymphoma. Malignant lymphoma is the most common neoplasm in 3rd and 4th decades of life and more than two third of affected patients presented painless peripheral lymphadenopathy. Involvement of waldeyer’s ring, epitrochlear and mesenteric lymph nodes is more likely in non-Hodgkin lymphoma. Approximately 20% of patients with non-Hodgkin lymphoma have mediastinal adenopathy. Most often, these patients may suffer from persistent cough, chest discomfort or maybe referred without any complaint and just with an abnormal chest radiograph.

  3. Correlating Anatomy and Function with Gene Expression in Individual Neurons by Combining in Vivo Labeling, Patch Clamp, and Single Cell RNA-seq

    Directory of Open Access Journals (Sweden)

    Carsten K. Pfeffer

    2017-11-01

    Full Text Available The classification of neurons into distinct types is an ongoing effort aimed at revealing and understanding the diversity of the components of the nervous system. Recently available methods allow us to determine the gene expression pattern of individual neurons in the mammalian cerebral cortex to generate powerful categorization schemes. For a thorough understanding of neuronal diversity such genetic categorization schemes need to be combined with traditional classification parameters like position, axonal projection or response properties to sensory stimulation. Here we describe a method to link the gene expression of individual neurons with their position, axonal projection, or sensory response properties. Neurons are labeled in vivo based on their anatomical or functional properties and, using patch clamp pipettes, their RNA individually harvested in vitro for RNAseq. We validate the methodology using multiple established molecularly and anatomically distinct cell populations and explore molecular differences between uncharacterized neurons in mouse visual cortex. Gene expression patterns between L5 neurons projecting to frontal or contralateral cortex are distinct while L2 neurons differing in position, projection, or function are molecularly similar. With this method we can determine the genetic expression pattern of functionally and anatomically identified individual neurons.

  4. The Energy Coding of a Structural Neural Network Based on the Hodgkin-Huxley Model.

    Science.gov (United States)

    Zhu, Zhenyu; Wang, Rubin; Zhu, Fengyun

    2018-01-01

    Based on the Hodgkin-Huxley model, the present study established a fully connected structural neural network to simulate the neural activity and energy consumption of the network by neural energy coding theory. The numerical simulation result showed that the periodicity of the network energy distribution was positively correlated to the number of neurons and coupling strength, but negatively correlated to signal transmitting delay. Moreover, a relationship was established between the energy distribution feature and the synchronous oscillation of the neural network, which showed that when the proportion of negative energy in power consumption curve was high, the synchronous oscillation of the neural network was apparent. In addition, comparison with the simulation result of structural neural network based on the Wang-Zhang biophysical model of neurons showed that both models were essentially consistent.

  5. Optimizing therapy in advanced stage Hodgkin Lymphoma

    OpenAIRE

    Lim, Sean; Johnson, Peter

    2018-01-01

    The treatment of Hodgkin Lymphoma has evolved continuously since the introduction of extended-field radiotherapy in the 1960s to involved-field then involved-node radiotherapy, multi-agent chemotherapy, combined chemo-radiotherapy, risk-adapted and response-adapted modulation, and most recently, introduction of antibody-drug conjugates and immune checkpoint-blocking antibodies. These changes have translated into progressively increasing cure rates, so that 10-year survival figures now exceed ...

  6. Thyrotoxic thyroiditis after radiotherapy for Hodgkin's disease

    International Nuclear Information System (INIS)

    Blitzer, J.B.; Paolozzi, F.P.; Gottlieb, A.J.; Zamkoff, K.W.; Chung, C.T.

    1985-01-01

    Exposure of the thyroid gland to ionizing radiation has been associated with a variety of abnormalities. Among these are tardive hypothyroidism and an increased risk of developing thyroid nodules and cancer. Although acute thyroiditis has been known to complicate radioactive iodine 131 therapy, it has rarely been associated with external beam irradiation. Thyrotoxic painless thyroiditis developed in two patients after mantle-field irradiation for Hodgkin's disease

  7. Recurrence of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Watanabe, Toshikazu; Kiyono, Kunihiro; Niibe, Hideo; Horiuchi, Junichi; Kaneta, Koichi; Morita, Kozo; Masaki, Norie; Hayabuchi, Naofumi.

    1988-01-01

    563 patients with Stage I and II non-Hodgkin's lymphoma were treated by radiotherapy. 34 recurrences that occured after 3 years from initial treatment were seen in those patients. 15 (44 %) of 34 recurrences occured after 5 years. 20 patients (59 %) had remission by re-treatment, and 13 (38 %) survived more than 2 years. 20 (59 %) of recurrences were seen on head and neck lesions and superficial lymph nodes. (author)

  8. Recurrence of non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Watanabe, Toshikazu; Oguchi, Masahiko; Niibe, Hideo; Horiuchi, Junichi; Kaneta, Koichi; Morita, Kozo; Masaki, Norie; Hayabuchi, Naofumi.

    1988-01-01

    From 1972 to 1982, 563 patients with Stage I and II non-Hodgkin's lymphoma received radiation therapy in the department of radiology which belongs to the JLRTS group. Local control failures were seen in only 5 cases (0.9 %). The regional recurrences were found in 30 cases (5 %). 17 of recurrences occured during the first 5 years. 17 cases had remissions again, and 5 cases had 5 year survivals. (author)

  9. Lung cancer following therapy for Hodgkin's disease

    OpenAIRE

    Oliphant, Lawrie; McFadden, Robin G.

    1985-01-01

    We describe a patient in whom lung cancer developed several years after he had received combined-modality therapy for Hodgkin's disease. The literature concerning second malignant diseases, particularly thoracic tumours, that occur following combined-modality therapy for cancer is reviewed. It is important to recognize these entities, because chest symptoms or findings on x-ray films may be misinterpreted as representing late recrudescence of the first neo-plastic disease.

  10. Interleukin-12 in Treating Patients With Previously Treated Non-Hodgkin's Lymphoma or Hodgkin's Disease

    Science.gov (United States)

    2015-04-14

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell 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; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  11. Autonomic dysfunction in Hodgkin and non-Hodgkin lymphoma. A paraneoplastic syndrome?

    Directory of Open Access Journals (Sweden)

    Franca Bilora

    2010-11-01

    Full Text Available We wanted to determine whether autonomic dysfunction in patients with lymphoma is related to chemotherapy or represent a paraneoplastic syndrome. 40 patients with current or cured Hodgkin or non-Hodgkin lymphoma and 40 healthy controls, matched for age, gender, hypertension and diabetes mellitus underwent autonomic evaluation (Deep Breath, Valsalva Maneuver, Hand Grip, Lying to Standing, Tilt Test. Current patients also suffering from diabetes or hypertension, or still on chemotherapy revealed autonomic changes, while cured or healthy subjects did not. Autonomic dysfunction in lymphoma is a transient manifestation of a paraneoplastic syndrome.

  12. The management of patients with limited-stage classical Hodgkin lymphoma.

    Science.gov (United States)

    Gospodarowicz, Mary K; Meyer, Ralph M

    2006-01-01

    The term limited-stage Hodgkin lymphoma refers to those patients with stage I-II disease and an absence of bulky disease. Among those patients with classical Hodgkin lymphoma, approximately one-third of patients will fall into this category. As long-term disease control can now be anticipated in more than 90% of these patients, management strategies must increasingly address the need to reduce the long-term treatment-related risks. Current treatment options include use of combined modality therapy that includes an abbreviated course of chemotherapy and involved-field radiation or treatment with chemotherapy, currently consisting of ABVD, as a single modality. The choice of treatment between these two options involves specific trade-offs that must balance issues of disease control against long-term risk of late effects.

  13. Primary cerebellar lymphoma with Hodgkin lymphoma-like morphology in a cat.

    Science.gov (United States)

    Yoshino, Yuka; Chambers, James K; Nakamori, Taichi; Goto-Koshino, Yuko; Nishigaki, Kazuo; Tsujimoto, Hajime; Matsuki, Naoaki; Nakayama, Hiroyuki; Uchida, Kazuyuki

    2017-09-01

    A 4-y-old cat exhibited neurologic signs such as wobbling, right head tilt, and intention tremor, and MRI revealed a mass in the cerebellum. The cat died 5 mo after initial presentation, and no neoplastic lesions, other than the cerebellar mass, were observed at autopsy. Histologically, large atypical cells resembling Hodgkin cells, with single large inclusion-like nucleoli, and those resembling Reed-Sternberg cells, with symmetrically arranged nuclei, had infiltrated the left side of the cerebellum and were admixed with small lymphocytes. These atypical cells were positive for feline leukemia virus (FeLV), CD20, BLA36, vimentin, p16, p53, and Pax5, and negative for CD3, CD79a, and Iba1 by immunohistochemistry. Multiplex PCR for immunoglobulin heavy-chain gene rearrangement revealed monoclonal proliferation of B-lymphocytes. We describe this feline primary cerebellar B-cell lymphoma that displayed Hodgkin lymphoma-like tumor cells with FeLV protein expression.

  14. The influence of single neuron dynamics and network topology on time delay-induced multiple synchronous behaviors in inhibitory coupled network

    International Nuclear Information System (INIS)

    Zhao, Zhiguo; Gu, Huaguang

    2015-01-01

    Highlights: • Time delay-induced multiple synchronous behaviors was simulated in neuronal networks. • Multiple behaviors appear at time delays shorter than a bursting period of neurons. • The more spikes per burst of bursting, the more synchronous regions of time delay. • From regular to random via small-world networks, synchronous degree becomes weak. • An interpretation of the multiple behaviors and the influence of network are provided. - Abstract: Time delay induced-multiple synchronous behaviors are simulated in neuronal network composed of many inhibitory neurons and appear at different time delays shorter than a period of endogenous bursting of individual neurons. It is different from previous investigations wherein only one of multiple synchronous behaviors appears at time delay shorter than a period of endogenous firing and others appear at time delay longer than the period duration. The bursting patterns of the synchronous behaviors are identified based on the dynamics of an individual neuron stimulated by a signal similar to the inhibitory coupling current, which is applied at the decaying branch of a spike and suitable phase within the quiescent state of the endogenous bursting. If a burst of endogenous bursting contains more spikes, the synchronous behaviors appear at more regions of time delay. As the coupling strength increases, the multiple synchronous behaviors appear in a sequence because the different threshold of coupling current or strength is needed to achieve synchronous behaviors. From regular, to small-world, and to random networks, synchronous degree of the multiple synchronous behaviors becomes weak, and synchronous bursting patterns with lower spikes per burst disappear, which is properly interpreted by the difference of coupling current between neurons induced by different degree and the high threshold of coupling current to achieve synchronization for the absent synchronous bursting patterns. The results of the influence of

  15. Chylothorax in non-Hodgkin's lymphoma managed by mediastinal radiotherapy

    International Nuclear Information System (INIS)

    Daley, M.M.; Kunkler, I.H.

    1995-01-01

    Chylothorax is a rare complication of both Hodgkin's and non-Hodgkin's lymphoma (NHL). We describe a patient with a diagnosis of low grade NHL who had a persistent chylothorax unresponsive to chemotherapy, who had been diagnosed with low grade NHL. The condition rapidly resolved following mediastinal radiotherapy and did not recur despite the subsequent relapse of the NHL. (Author)

  16. Cigarette smoking and risk of Hodgkin lymphoma and its subtypes

    DEFF Research Database (Denmark)

    Kamper-Jørgensen, Mads; Rostgaard, K; Glaser, S L

    2013-01-01

    The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes.......The etiology of Hodgkin lymphoma (HL) remains incompletely characterized. Studies of the association between smoking and HL have yielded ambiguous results, possibly due to differences between HL subtypes....

  17. Stomach cancer risk after treatment for hodgkin lymphoma

    DEFF Research Database (Denmark)

    Morton, Lindsay M; Dores, Graça M; Curtis, Rochelle E

    2013-01-01

    Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear.......Treatment-related stomach cancer is an important cause of morbidity and mortality among the growing number of Hodgkin lymphoma (HL) survivors, but risks associated with specific HL treatments are unclear....

  18. Metallothionein as a useful marker in Hodgkin lymphoma subclassification

    DEFF Research Database (Denmark)

    Penkowa, Milena; Sørensen, Brit Ladegaard; Nielsen, Signe Lidou

    2009-01-01

    Metallothionein (MT) expression is considered to be a prognostic factor that promotes tumor resistance to apoptosis. In non-Hodgkin lymphomas, MT is differentially expressed and constitutes a risk factor. We have characterised MT in lymph nodes of Hodgkin lymphoma (HL) [patients with nodular...

  19. Linfoma no-Hodgkin del sistema nervioso central

    OpenAIRE

    Iglesias Rozas, José Rafael, 1942-

    2000-01-01

    Diecisiete imágenes de un linfoma no-Hodgkin del sistema nervioso central en una paciente de 66 años. Seventeen pictures of a non-Hodgkin lymphoma of the central nervous system in a 66-year-old female patient.

  20. Non-hodgkin's lymphomas at Kenyatta the National Hospital Nairobi ...

    African Journals Online (AJOL)

    Design: Retrospective study of patients with non-Hodgkin's Iymphoma. Setting: Kenyatta National Hospital, Nairobi, Kenya, between January 1990 and January 2000 inclusive. Subjects: Patients aged 13 years and above, with non-Hodgkin's Iymphomas. Results: Case records were available for 207 patients, 146 males and ...

  1. A Neuron-Based Model of Sleep-Wake Cycles

    Science.gov (United States)

    Postnova, Svetlana; Peters, Achim; Braun, Hans

    2008-03-01

    In recent years it was discovered that a neuropeptide orexin/hypocretin plays a main role in sleep processes. This peptide is produced by the neurons in the lateral hypothalamus, which project to almost all brain areas. We present a computational model of sleep-wake cycles, which is based on the Hodgkin-Huxley type neurons and considers reciprocal glutaminergic projections between the lateral hypothalamus and the prefrontal cortex. Orexin is released as a neuromodulator and is required to keep the neurons firing, which corresponds to the wake state. When orexin is depleted the neurons are getting silent as observed in the sleep state. They can be reactivated by the circadian signal from the suprachiasmatic nucleus and/or external stimuli (alarm clock). Orexin projections to the thalamocortical neurons also can account for their transition from tonic firing activity during wakefulness to synchronized burst discharges during sleep.

  2. Predictors of Radiation Pneumonitis in Patients Receiving Intensity-Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

    Science.gov (United States)

    Pinnix, Chelsea C.; Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F.; Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, Alma; Ahmed, Sairah; Nieto, Yago; Dabaja, Bouthaina

    2015-01-01

    Purpose Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP per the Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ2 test and logistic multivariate regression. Results Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grade 1–3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation (10%, P=0.019). Several dosimetric parameters predicted RP, including mean lung dose (MLD) >13.5 Gy, V20 >30%, V15 >35%, V10 >40% and V5>55%. The likelihood ratio (LR) χ2 value was highest for V5mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation were at higher risk for symptomatic RP

  3. Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Pinnix, Chelsea C.; Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F.; Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, M. Alma

    2015-01-01

    Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ 2 test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V 20 of >30%, V 15 of >35%, V 10 of >40%, and V 5 of >55%. The likelihood ratio χ 2 value was highest for V 5 >55% (χ 2  = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received

  4. Predictors of radiation pneumonitis in patients receiving intensity modulated radiation therapy for Hodgkin and non-Hodgkin lymphoma.

    Science.gov (United States)

    Pinnix, Chelsea C; Smith, Grace L; Milgrom, Sarah; Osborne, Eleanor M; Reddy, Jay P; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K; Wogan, Christine F; Fanale, Michele A; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B; Rodriguez, M Alma; Ahmed, Sairah; Nieto, Yago; Dabaja, Bouthaina

    2015-05-01

    Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ(2) test and logistic multivariate regression. Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V20 of >30%, V15 of >35%, V10 of >40%, and V5 of >55%. The likelihood ratio χ(2) value was highest for V5 >55% (χ(2) = 19.37). In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed or refractory lymphoma who received salvage chemotherapy and hematopoietic stem cell transplantation

  5. Hodgkin lymphoma in children and adolescents-optimization of treatment

    International Nuclear Information System (INIS)

    Hraskova, A.; Kolenova, A.

    2016-01-01

    Hodgkin lymphoma in children and adolescents is thanks to modern treatment highly curable systemic malignant disease. Elaboration of „standard treatment recommendations“ is hampered by efforts to reduce acute and late toxicity reduction after chemo- and radiotherapy without decreasing overall survival. Such attitude has contributed to treatment strategies often different from those used in adults. Demands for more appropriate stratification for Hodgkin lymphoma patients, chemo sensitivity evaluation by imaging methods and bio markers identification has risen. Better understanding of Hodgkin lymphoma biology has led to targeted therapy identification mostly in recurrent/refractory Hodgkin lymphoma, but many questions still remain regarding its usage and efficacy. International cooperation among Hodgkin lymphoma working groups for children, adolescents and adults should be beneficial in solving these issues. (author)

  6. Long-term neuronal damage and recovery after a single dose of MDMA: expression and distribution of serotonin transporter in the rat brain.

    Science.gov (United States)

    Kirilly, Eszter

    2010-09-01

    "Ecstasy", 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analogue is one of the most widely used recreational drugs. In spite of the fact that neurotoxic effects of MDMA has been found in several species from rodents to non-human primates, and results increasingly point to damage also in human MDMA users, data about the sensitivity of different brain areas and the recovery after neuronal damage are scarce. Serotonin transporter (5-HTT) mRNA in the raphe nuclei also has not been examined. Humans with genetic predisposition for the slow metabolism of MDMA, the so-called "poor metabolizers" of debrisoquin are at higher risk. Five- 9% of the Caucasian population is considered to carry this phenotype. These studies were carried out in Dark Agouti rats, a special strain that show decreased microsomal CYP2D1 isoenzyme activity, and thus may serve as a model of vulnerable human users. These works were designed to characterize MDMA-induced damage and recovery of the serotonergic system including sleep and morphological changes within 180 days. In our experiments we investigated the 5-HTT mRNA expression in the brainstem and medullary raphe nuclei, 5-HTT immunoreactive (IR) fibre densities in several brain areas, and 16 functional measures of sleep in response to a single dose of +/- MDMA (15mg\\kg). Furthermore, behavioural experiments were performed 21 days after MDMA treatment. We found similar changes in 5-HTT mRNA expression in the examined raphe nuclei, namely transient increases 7 days after MDMA treatment followed by transient decreases at 21 days. Significant (20-40%), widespread reductions in 5-HTT-IR fibre density were detected in most brain areas at 7 and 21 days after MDMA administration. All cortical, but only some brainstem areas were damaged. Parallel to the neuronal damage we observed significant reductions in rapid eye movement (REM) sleep latency, increased fragmentation of sleep and increases in delta power spectra in non-REM sleep. At 180 days

  7. Dendritic Cell Therapy, Cryosurgery, and Pembrolizumab in Treating Patients With Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Aggressive Non-Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Small Lymphocytic Lymphoma

  8. Mucormicosis yeyunal en paciente con linfoma de Hodgkin Jejunal mucormycosis in a patient with Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    B. Madrigal

    2008-08-01

    Full Text Available Comunicamos un caso de mucormicosis intestinal en un hombre de 46 años de edad, diagnosticado de enfermedad de Hodgkin clásica, estadio IV-B. Durante la primera fase de la quimioterapia, sufrió una hemorragia digestiva masiva secundaria a una úlcera yeyunal por zigomicosis tipo mucor, diagnosticada por biopsia endoscópica. El paciente fue tratado con antifúngicos y resección quirúrgica del intestino afectado. En la cirugía, se apreció una doble perforación yeyunal cubierta. El estudio anatomopatológico de la pieza confirmó el diagnóstico previo. Tras un año de seguimiento, el paciente está recuperado y su linfoma de Hodgkin en remisión completa. Tras una extensa revisión de la literatura, según nuestro conocimiento, este es el segundo caso publicado en la literatura de mucormicosis intestinal en un paciente con linfoma de Hodgkin.We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.

  9. Anti-electromagnetic interference analysis of equivalent circuit of ion channel based on the Hodgkin-Huxley model

    International Nuclear Information System (INIS)

    Chu, J; Chang, X L; Zhao, M; Man, M H; Wei, M; Yuan, L

    2013-01-01

    With the continuous improvement of circuit integration and working clock frequency in the electronic system, it is increasingly easy for the system to be affected by electromagnetic waves, and electromagnetic susceptibility and vulnerability become more severe. However, living beings in nature have shown extraordinary compatibility, immunity and adaptability to the electromagnetism at the same time. In addition, the ion channel on the neuron cytomembrane is a typical representation of b ioelectrical immunity . So the Hodgkin-Huxley circuit model with one capacitor in parallel with some power supplies and resistors was adopted to simulate the ion channel on the neuron cytomembrane. Through analysis, the circuit model can be used to simulate some electrical characteristics of biological neuron cells, and then acquire a certain level of anti-electromagnetic interference ability. This method will be useful for improving the reliability, compatibility and anti-interference capability of the electronic system in the complicated electromagnetic environment.

  10. Prognostic factors in non-Hodgkin lymphomas

    Directory of Open Access Journals (Sweden)

    Karin Zattar Cecyn

    2000-01-01

    Full Text Available CONTEXT: In Hodgkin's disease, each clinical or pathologic stage can be related to the extent of the area involved and predicts the next anatomical region at risk for tumor dissemination. OBJECTIVE: To determine the best prognostic factors that could predict survival in non-Hodgkin lymphoma cases. DESIGN: A retrospective study. LOCATION: Department of Hematology and Transfusion Medicine, Universidade Federal de São Paulo - Escola Paulista de Medicina. PARTICIPANTS: 142 patients with non-Hodgkin lymphoma diagnosed between February 1988 and March 1993. MAIN MEASUREMENTS: Histological subset, Sex, Age, Race, B symptoms, Performance status, Stage, Extranodal disease, Bulk disease, Mediastinal disease, CNS involvement, BM infiltration, Level of DHL, Immunophenotype. RESULTS: In the first study (113 patients, the following variables had a worse influence on survival: yellow race (P<0.1; ECOG II, III e IV (P<0.1 and extranodal disease (P<0.1 for high grade lymphomas; constitutional symptoms (P<0.1, ECOG II, III e IV (P<0.1 and involvement of CNS (P<0.1 for intermediate grade and the subtype lymphoplasmocytoid (P=0.0186 for low grade lymphomas. In the second survey (93 patients, when treatment was included, the variables related to NHL survival were: CNS involvement (P<0.1 for high grade lymphomas, constitutional symptoms (P<0.1, ECOG II, III, IV (P=0.0185 and also CNS involvement (P<0.1 for the intermediate group. There were no variables related to the survival for low-grade lymphomas. CONCLUSIONS: The intermediate grade lymphomas were more compatible with data found in the literature, probably because of the larger number of patients. In this specific case, the treatment did not have an influence on the survival.

  11. Altered neuronal activity patterns in the visual cortex of the adult rat after partial optic nerve crush--a single-cell resolution metabolic mapping study.

    Science.gov (United States)

    Macharadze, Tamar; Pielot, Rainer; Wanger, Tim; Scheich, Henning; Gundelfinger, Eckart D; Budinger, Eike; Goldschmidt, Jürgen; Kreutz, Michael R

    2012-08-01

    Thallium autometallography (TIAMG) is a novel method for high-resolution mapping of neuronal activity. With this method, we found that a general depression of neuronal activity occurs in response to optic nerve crush (ONC) within the first 2 weeks postinjury in the contralateral dorsal lateral geniculate nucleus (dLGN) as well as in the contralateral primary visual cortex (V1). Interestingly, the neuronal activity recovered thereafter in both brain regions and reached a plateau in the tenth week postinjury in layers IV and V of V1, monocular area (V1m). Several clusters of highly active neurons in V1m were found 6 weeks after ONC in layers IV and V on the side contralateral to the lesion. We reasoned that these clusters appeared due to a reorganization of the corticocolliucular projections. Employing a combination of biotinylated dextran amine retrograde tract tracing from the superior colliculus (SC) with TIAMG in the same animal, we indeed found that the clusters of neurons with high Tl(+) uptake in V1m are spatially in register with those neuronal subpopulations that project to the SC. These data suggest that extensive reorganization plasticity exists in the adult rat visual cortex following ONC.

  12. Clinical presentation and staging of Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Gallamini, Andrea; Hutchings, Martin; Ramadan, Safaa

    2016-01-01

    In the present chapter the authors present a brief overview of the diagnostic methods proposed over time for Hodgkin lymphoma (HL) spread detection, moving from surgical procedures, through standard radiological and functional imaging techniques to the present state of the art for HL staging....... The main body of the review will be dedicated to the recently published guidelines for lymphoma staging (including HL) agreed by the experts during the 12th International Congress for Malignant Lymphoma in Lugano. The recommendations of the panel on how to integrate flurodeoxyglucose positron emission...

  13. Management of Hodgkins Lymphoma: ICMR Consensus Document.

    Science.gov (United States)

    Radhakrishnan, Venkatraman; Kapoor, Gauri; Arora, Brijesh; Bansal, Deepak; Vora, Tushar; Prasad, Maya; Chinnaswamy, Girish; Laskar, Siddharth; Agarwala, Sandeep; Kaur, Tanvir; Rath, G K; Bakhshi, Sameer

    2017-05-01

    Pediatric Hodgkins lymphoma is a highly curable disease even in the developing world. Current treatment paradigms follow a risk and response based approach. The goal is to minimise treatment related short and long-term toxicity while maintaining excellent survival. A confirmed histopathological diagnosis and full staging work-up are essential prior to embarking on treatment and guidelines for these are provided in the text. All patients require combination chemotherapy while radiotherapy is usually reserved for a select subgroup depending on the protocol used. It is important to follow these patients for relapse in the first five years and life-long for late effects as most of them will be cured.

  14. Management of breast cancer following Hodgkin's disease

    International Nuclear Information System (INIS)

    Wolden, Suzanne L.; Carlson, Robert W.; Jeffrey, Stefanie S.; Hancock, Steven L.

    1997-01-01

    Purpose: To evaluate the incidence, histology, risk factors, treatment, and prognosis of breast cancer occurring after Hodgkin's disease. Materials and Methods: Sixty-five cases of breast cancer in 61 survivors of Hodgkin's lymphoma were analyzed. The median age at treatment for Hodgkin's disease was 24.1 [range (R): 13.3 - 71.8] years. Fifty-one percent had received radiotherapy alone, 47% radiation and chemotherapy, and 2% chemotherapy only. Relative and absolute risks were calculated based on 47 invasive breast cancers in 1049 women treated for Hodgkin's disease at Stanford. Results: The median age at diagnosis of breast cancer was 41.9 (R: 23.0 - 79.1) years; 76% of women were premenopausal. The median interval between Hodgkin's disease and breast cancer was 17.6 (R: 1.5 - 32.7) years with an increasing incidence beginning eight years after radiotherapy. The current relative risk of invasive breast cancer following Hodgkin's disease is 4.7 [95% confidence interval (CI): 3.4 - 6.1] with an absolute risk of 29.5 (CI: 18.8 - 40.2) excess cases per 10,000 person-years. Eighty-seven percent of breast cancers occurred in or at the margin of a prior radiotherapy field where a mean dose of 43.5 (R: 24.0 - 51.0) Gy was delivered. There was a family history of breast cancer in 31% of women. Cancers were detected by self examination (66%), screening mammography (27%), and physician examination (7%). Many tumors (60%) were located in the upper outer quadrants, corresponding to the axillary portion of a mantle field. There were seven cases of carcinoma in situ: six DCIS and one LCIS. The histologic distribution of invasive tumors paralleled that reported in the general population: 4% pure lobular, 35% high grade ductal, 45% intermediate grade ductal, 7% low-grade ductal, 4% tubular, 2% medullary, and 2% mucinous. Estrogen receptors were positive in 59% of evaluable cases. While 90% of invasive tumors were smaller than four centimeters, 96% were managed with mastectomy

  15. AIDS-related non-Hodgkin-lymphoma

    International Nuclear Information System (INIS)

    Deweese, T.L.; Hazuka, M.B.; Hommel, D.J.; Kinzie, J.J.; Daniel, W.E.

    1989-01-01

    Patients with acquired immunodeficiency syndrome (AIDS) have shown an increased propensity for developing non-Hodgkins lymphoma (NHL). In order to assess the response to and overall treatment benefit of radiation therapy in AIDS-related lymphoma, the authors have reviewed the records of 15 patients with AIDS and NHL treated with radiation therapy. Of those patients with central nervous system (CNS) involvement, 54% showed disease progression or no improvement during treatment. Conversely, AIDS patients with lymphoma outside the CNS were more likely to respond to radiation therapy and have longer survival. The authors conclude that the efficacy of radiation therapy in AIDS patients with lymphoma might depend on CNS involvement

  16. Immunological Deregulation in Classic Hodgkin Lymphoma

    Science.gov (United States)

    Romano, Alessandra; Vetro, Calogero; Caocci, Giovanni; Greco, Marianna; Parrinello, Nunziatina Laura; Di Raimondo, Francesco; La Nasa, Giorgio

    2014-01-01

    Classic Hodgkin Lymphoma (cHL) has a unique histology since only a few neoplastic cells are surrounded by inflammatory accessory cells that in the last years have emerged as crucial players in sustaining the course of disease. In addition, recent studies suggest that the abnormal activity of these inflammatory cells (such as deregulation in regulatory T cells signaling, expansion of myeloid derived suppressor cells, HLA-G signaling and natural killer cells dysfunction) may have prognostic significance. This review is focused on summarizing recent advanced in immunological defects in cHL with translational implications. PMID:24959336

  17. [Treatment of early stage Hodgkin disease

    DEFF Research Database (Denmark)

    Specht, Lena; Carde, P.; Mauch, P.

    1993-01-01

    In early stage Hodgkin's disease the optimal choice of treatment is still an unresolved issue. Twenty-two randomized trials of radiotherapy alone versus radiotherapy plus combination chemotherapy have been carried out world-wide. The preliminary results of a global meta-analysis of these trials...... a relapse is avoided in many patients. The major argument against early chemotherapy is: that by careful staging and selection of patients and by careful radiotherapy techniques the number of patients exposed to potentially toxic chemotherapy may be kept at a minimum. Recently, trials have been carried out...

  18. Curcuma Contra Cancer? Curcumin and Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Stefanie Kewitz

    2013-01-01

    Full Text Available Curcumin, a phytochemical isolated from curcuma plants which are used as coloring ingredient for the preparation of curry powder, has several activities which suggest that it might be an interesting drug for the treatment or prevention of cancer. Curcumin targets different pathways which are involved in the malignant phenotype of tumor cells, including the nuclear factor kappa B (NFKB pathway. This pathway is deregulated in multiple tumor entities, including Hodgkin's lymphoma (HL. Indeed, curcumin can inhibit growth of HL cell lines and increases the sensitivity of these cells for cisplatin. In this review we summarize curcumin activities with special focus on possible activities against HL cells.

  19. Central nervous system complications in non-Hodgkin-lymphomas and radiotherapy

    International Nuclear Information System (INIS)

    Liffers, R.

    1981-01-01

    261 case historys of malignant non-Hodgkin-lymphomas were analysed in the years from 1969 until 1978 in the 'Radiologische Universitaetsklinik Kiel'/West-Germany. 18 Patients got a central nervous complication of Non Hodgkin-Lymphoma earlier or later, a percentage of about 7. There were 7 cases of lymphoblastic lymphoma (LB), a percentage of 10 for this entity. In the group of immunoblastic lymphoma (IB) 6 cases of central nervous infiltration were detected, that is a ratio of 7.7 percent. 4 case histories M. Brill-Symmers (CC/CB) were complicated by central nervous dissemination, a percentage of 5.3. Patients with lymphoblastic lymphoma have the highest risk of central nervous complication. The beginning of central nervous dissemination in the single case histories is very different between the histological groups. Patients with lymphoblastic lymphoma suffered from central nervous complication in an early phase of history, in cases of M. Brill-Symmers central nervous infiltration can occur also in a late phase. The results may determine the discussion about stratifying of radiotherapy. Early radiotherapy including central nervous system may be discussed and investigated in special histological entities of malignant non-Hodgkin-lymphoma. (orig.) [de

  20. Epstein-Barr Virus in Classical Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Azhar, M.; Din, H. U.; Muhammad, I.; Hashmi, S. N.; Akhtar, F.

    2016-01-01

    Background: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. Method: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Results: Out of 55 patients, 38 (69 percent) were male and 17 (31 percent) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80 percent) were positive for latent membrane protein-1. Among positive cases 32 (72.72 percent) were male and 12 (27.28 percent) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3 percent as well as among both genders. Out of total 55 cases, 79.16 percent (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33 percent (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100 percent (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80 percent of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16 percent cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100 percent of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. Conclusion: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma

  1. Noisy Neurons

    Indian Academy of Sciences (India)

    IAS Admin

    Nerves are fibres that conduct electrical signals and hence pass on information from and to the brain. Nerves are made of nerve cells called neurons (Figure 1). Instructions in our body are sent via electrical signals that present themselves as variations in the potential across neuronal membranes. These potential differences ...

  2. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus.

    Science.gov (United States)

    Kay, A R; Wong, R K

    1987-11-01

    1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.

  3. [Brentuximab vedotin treatment in patients with relapsed or refractory Hodgkin lymphoma. A Hungarian retrospective study].

    Science.gov (United States)

    Molnár, Zsuzsa; Pinczés, László Imre; Piukovics, Klára; Istenes, Ildikó; Wolf, Krisztina; Csukly, Zoltán; Szomor, Árpád; Illés, Árpád; Miltényi, Zsófia

    2017-10-01

    The treatment of relapsed or refractory Hodgkin lymphoma is still a major therapeutic challenge. The use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, represents a promising approach for these patients, however clinical outcomes have not yet been evaluated in Hungary. Our aim was to assess the efficacy, safety and outcome of brentuximab vedotin treatment in Hungarian Hodgkin lymphoma patients. In this retrospective case note review we enrolled patients at 6 clinical sites countrywide who were diagnosed with Hodgkin lymphoma and received brentuximab vedotin between 1 January 2013 and 31 December 2016. A total of 86 patients were treated with brentuximab vedotin during the examined period. Before therapy initiation 66% of our patients had advanced-stage disease. Overall response rate to brentuximab vedotin, administered before autologous hematopoietic stem cell transplantation (n = 54) was 66.6%, complete remission rate was 42.6%. Thirty patients received brentuximab vedotin after AHSCT, 46.67% responded to treatment, 30% achieved complete remission. Thirty-six patients received the drug as a single-agent therapy, 50 patients were given brentuximab vedotin in combination, 39 of them with bendamustin. Toxicity was observed only in 13.95% of our patients, most common symptom was skin rash. Based on our analysis the estimated 5-year overall survival rate was 78.7%, the estimated progression free survival rate was 23.59 months (95% CI: 19.50-27.68). Brentuximab vedotin carries a substantial improvement in the treatment of relapsed or refractory Hodgkin lymphoma. Our results underline prior observations published in the literature. The use of brentuximab vedotin in combination can be beneficial, however further investigation is needed on the subject. Orv Hetil. 2017; 158(41): 1630-1634.

  4. β-Arrestin-2 knockout prevents development of cellular μ-opioid receptor tolerance but does not affect opioid-withdrawal-related adaptations in single PAG neurons.

    Science.gov (United States)

    Connor, M; Bagley, E E; Chieng, B C; Christie, M J

    2015-01-01

    Tolerance to the behavioural effects of morphine is blunted in β-arrestin-2 knockout mice, but opioid withdrawal is largely unaffected. The cellular mechanisms of tolerance have been studied in some neurons from β-arrestin-2 knockouts, but tolerance and withdrawal mechanisms have not been examined at the cellular level in periaqueductal grey (PAG) neurons, which are crucial for central tolerance and withdrawal phenomena. μ-Opioid receptor (MOPr) inhibition of voltage-gated calcium channel currents (ICa ) was examined by patch-clamp recordings from acutely dissociated PAG neurons from wild-type and β-arrestin-2 knockout mice treated chronically with morphine (CMT) or vehicle. Opioid withdrawal-induced activation of GABA transporter type 1 (GAT-1) currents was determined using perforated patch recordings from PAG neurons in brain slices. MOPr inhibition of ICa in PAG neurons was unaffected by β-arrestin-2 deletion. CMT impaired coupling of MOPrs to ICa in PAG neurons from wild-type mice, but this cellular tolerance was not observed in neurons from CMT β-arrestin-2 knockouts. However, β-arrestin-2 knockouts displayed similar opioid-withdrawal-induced activation of GAT-1 currents as wild-type PAG neurons. In β-arrestin-2 knockout mice, the central neurons involved in the anti-nociceptive actions of opioids also fail to develop cellular tolerance to opioids following chronic morphine. The results also provide the first cellular physiological evidence that opioid withdrawal is not disrupted by β-arrestin-2 deletion. However, the unaffected basal sensitivity to opioids in PAG neurons provides further evidence that changes in basal MOPr sensitivity cannot account for the enhanced acute nociceptive response to morphine reported in β-arrestin-2 knockouts. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British

  5. Classical Hodgkin's lymphoma: the Lymphoma Study Association guidelines for relapsed and refractory adult patients eligible for transplant.

    Science.gov (United States)

    Van Den Neste, Eric; Casasnovas, Olivier; André, Marc; Touati, Mohamed; Senecal, Delphine; Edeline, Véronique; Stamatoullas, Aspasia; Fornecker, Luc; Deau, Bénédicte; Gastinne, Thomas; Reman, Oumédaly; Gaillard, Isabelle; Borel, Cécile; Brice, Pauline; Fermé, Christophe

    2013-08-01

    The Hodgkin's Lymphoma Committee of the Lymphoma Study Association (LYSA) gathered in 2012 to prepare guidelines on the management of transplant-eligible patients with relapsing or refractory Hodgkin's lymphoma. The working group is made up of a multidisciplinary panel of experts with a significant background in Hodgkin's lymphoma. Each member of the panel of experts provided an interpretation of the evidence and a systematic approach to obtain consensus was used. Grades of recommendation were not required since levels of evidence are mainly based on phase II trials or standard practice. Data arising from randomized trials are emphasized. The final version was endorsed by the scientific council of the LYSA. The expert panel recommends a risk-adapted strategy (conventional treatment, or single/double transplantation and/or radiotherapy) based on three risk factors at progression (primary refractory disease, remission duration < 1 year, stage III/IV), and an early evaluation of salvage chemosensitivity, including (18)fluorodeoxy glucose-positron emission tomography interpreted according to the Deauville scoring system. Most relapsed or refractory Hodgkin's lymphoma patients chemosensitive to salvage should receive high-dose therapy and autologous stem-cell transplantation as standard. Efforts should be made to increase the proportion of chemosensitive patients by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

  6. Hodgkin's disease: Analysis of 75 patients

    International Nuclear Information System (INIS)

    Akram, M.; Cheema, M. H.; Sana, S.; Aziz, Z.

    2001-01-01

    Objective: To evaluate patients suffering from Hodgkin's disease to identify its epidemiological characteristics, modalities of treatment and features of survival. Place and Duration of Study: The study was conducted between July 1997 to June 1999 at the Oncology Department of Jinnah Hospital, Lahore. Subjects and Methods: A total 75 patient with Hodgkin's disease underwent Cotswold staging classification, complete hematological, renal and hepatic profile, LDH and uric acid. Chest radiograph abdominal and pelvic ultrasonography and CT scan/MRI bone marrow biopsies. All the patients received combination chemotherapy. Patients with bulky disease received field radiation. Results: Median age was eight ( 18 years). Male to female ratio was 3.5:1, advanced disease accounted for 68%, mixed cellularity was documented in 61% of patients. Eighty-two percent of patients belonged to lower socioeconomic strata. Forty-six patients (65.4%) achieved complete remission (CR) Major toxicities were hematological with febrile neutropenia in 14.6% patients. OS of patients achieving CR with good socioeconomic status was superior compared to patients with lower socioeconomic status (p<0.02). Treatment delays were due to economic constraints, illiteracy, malnutrition and co-morbid conditions. Conclusion: Advanced disease, mixed cellularity and male predominance was common. Socioeconomic status had a significant impact on the presentation of the disease. Poor tolerance to chemotherapy and enhanced toxicities are especially seen in the low socioeconomic group. (author)

  7. Second cancers following non-Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Travis, L.B.; Curtis, R.E.; Boice, J.D. Jr.; Hankey, B.F.; Fraumeni, J.F. Jr.

    1991-01-01

    The risk of second malignancies following non-Hodgkin's lymphoma (NHL) was estimated in 29,153 patients diagnosed with NHL between 1973 and 1987 in one of nine areas participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Compared with the general population, NHL patients were at a significantly increased risk of developing second cancers (observed/expected [O/E] = 1.18; O = 1231). The O/E ratio increased significantly with time to reach 1.77 in 10-year survivors. Significant excesses were noted for acute nonlymphocytic leukemia (O/E = 2.88), cancers of the bladder (O/E = 1.30), kidney (O/E = 1.47), and lung (O/E = 1.57), malignant melanoma (O/E = 2.44), and Hodgkin's disease (O/E = 4.16). Chemotherapy appeared related to subsequent acute nonlymphocytic leukemia (ANLL) and bladder cancer. Radiation therapy was associated with ANLL and possibly cancers of the lung, bladder, and bone. Malignant melanoma was not clearly related to initial NHL treatment

  8. Non-Hodgkin's lymphomas: clinical governance issues.

    Science.gov (United States)

    Fields, P A; Goldstone, A H

    2002-09-01

    Every patient in every part of the world has the right to expect the best possible quality of care from health care providers. Non-Hodgkin's lymphomas (NHL) are an extremely heterogeneous group of conditions which require important decisions to be taken at many points along the treatment pathway. To get this right every time requires that high-quality standards are instituted and adhered to, so that the best possible outcome is achieved. In the past this has not always been the case because of the failure of clinicians sometimes to adhere to an optimal management plan. In 1995, the UK government commissioned an inquiry into the running of cancer services in the United Kingdom, which culminated in a series of recommendations to improve them. Subsequently, these recommendations were implemented as objectives of the NHS Cancer Plan which is the framework by which the UK government wishes to improve cancer services. Concurrently another general concept has emerged which is designed to ensure that the highest quality standards may be achieved for all patients across the whole National Health Service (NHS). This concept, termed 'clinical governance', brings together a corporate responsibility of all health care workers to deliver high quality standards, in the hope that this will translate into better long-term survival of patients with malignant disease. This chapter focuses on the issues surrounding clinical governance and how the principles of this concept relate to non-Hodgkin's lymphomas.

  9. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  10. Indikationer for radioimmunterapi til patienter med non-Hodgkins lymfom

    DEFF Research Database (Denmark)

    Frølund, Ulf Christian; Hansen, Per Boye

    2011-01-01

    Radioimmunotherapy is a well-known treatment for non-Hodgkin's lymphoma. (90)yttrium (Y)-ibritumomab-tiuxetan consists of a radioisotope conjugated to a monoclonal anti-cluster of differentiation 20 antibody, which is targeted against B-lymphocytes. Initially the treatment indication was relapse...... of low-grade non-Hodgkin's lymphoma. However, (90)Y-ibritumomab-tiuxetan has later been used in clinical trials in the treatment of other types of non-Hodgkin's lymphoma and prior to stem cell transplantation. Based on the literature this systematic review aims to throw light on the future possibilities...

  11. Quadratic sinusoidal analysis of voltage clamped neurons.

    Science.gov (United States)

    Magnani, Christophe; Moore, Lee E

    2011-11-01

    Nonlinear biophysical properties of individual neurons are known to play a major role in the nervous system, especially those active at subthreshold membrane potentials that integrate synaptic inputs during action potential initiation. Previous electrophysiological studies have made use of a piecewise linear characterization of voltage clamped neurons, which consists of a sequence of linear admittances computed at different voltage levels. In this paper, a fundamentally new theory is developed in two stages. First, analytical equations are derived for a multi-sinusoidal voltage clamp of a Hodgkin-Huxley type model to reveal the quadratic response at the ionic channel level. Second, the resulting behavior is generalized to a novel Hermitian neural operator, which uses an algebraic formulation capturing the entire quadratic behavior of a voltage clamped neuron. In addition, this operator can also be used for a nonlinear identification analysis directly applicable to experimental measurements. In this case, a Hermitian matrix of interactions is built with paired frequency probing measurements performed at specific harmonic and interactive output frequencies. More importantly, eigenanalysis of the neural operator provides a concise signature of the voltage dependent conductances determined by their particular distribution on the dendritic and somatic membrane regions of neurons. Finally, the theory is concretely illustrated by an analysis of an experimentally measured vestibular neuron, providing a remarkably compact description of the quadratic responses involved in the nonlinear processing underlying the control of eye position during head rotation, namely the neural integrator.

  12. Use of Computed Tomography Angiography in Hodgkin Lymphoma Survivors

    Directory of Open Access Journals (Sweden)

    Serhan Kupeli

    2013-08-01

    Full Text Available In the treatment of Hodgkin lymphoma, anthracyclines known to be cardiotoxic and radiotherapy to the involved lymphatic areas are frequently used. In literature deaths from myocardial infarction at young ages after Hodgkin lymphoma have been reported. The real incidence of cardiovascular diseases in patients treated for Hodgkin lymphoma is not known. There is a significant correlation between mediastinal radiotherapy and development of a coronary artery abnormality. Coronary computed tomography angiography is an useful and noninvasive tool for early diagnosis of coronary artery disease in patients who were treated with mediastinal radiotherapy and/or cardiotoxic chemotherapy like most of the cases with Hodgkin lymphoma. [Archives Medical Review Journal 2013; 22(4.000: 543-564

  13. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...... in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed...... by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, PHodgkin lymphoma patients (n=176), levels were correlated...

  14. Risk of Hodgkin's disease and other cancers after infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, H; Askling, J; Sørensen, P

    2000-01-01

    BACKGROUND: Infectious mononucleosis, which is caused by the Epstein-Barr virus, has been associated with an increased risk for Hodgkin's disease. Little is known, however, about how infectious mononucleosis affects long-term risk of Hodgkin's disease, how this risk varies with age at infectious...... mononucleosis diagnosis, or how the risk for Hodgkin's disease varies in different age groups. In addition, the general cancer profile among patients who have had infectious mononucleosis has been sparsely studied. METHODS: Population-based cohorts of infectious mononucleosis patients in Denmark and Sweden were...... statistical tests including the trend tests were two-sided. RESULTS: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1...

  15. Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20(+) Indolent B-Cell Non-Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Sehn, L. H.; Goy, A.; Offner, F. C.

    2015-01-01

    Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with r...

  16. Neuronal avalanches and learning

    Energy Technology Data Exchange (ETDEWEB)

    Arcangelis, Lucilla de, E-mail: dearcangelis@na.infn.it [Department of Information Engineering and CNISM, Second University of Naples, 81031 Aversa (Italy)

    2011-05-01

    Networks of living neurons represent one of the most fascinating systems of biology. If the physical and chemical mechanisms at the basis of the functioning of a single neuron are quite well understood, the collective behaviour of a system of many neurons is an extremely intriguing subject. Crucial ingredient of this complex behaviour is the plasticity property of the network, namely the capacity to adapt and evolve depending on the level of activity. This plastic ability is believed, nowadays, to be at the basis of learning and memory in real brains. Spontaneous neuronal activity has recently shown features in common to other complex systems. Experimental data have, in fact, shown that electrical information propagates in a cortex slice via an avalanche mode. These avalanches are characterized by a power law distribution for the size and duration, features found in other problems in the context of the physics of complex systems and successful models have been developed to describe their behaviour. In this contribution we discuss a statistical mechanical model for the complex activity in a neuronal network. The model implements the main physiological properties of living neurons and is able to reproduce recent experimental results. Then, we discuss the learning abilities of this neuronal network. Learning occurs via plastic adaptation of synaptic strengths by a non-uniform negative feedback mechanism. The system is able to learn all the tested rules, in particular the exclusive OR (XOR) and a random rule with three inputs. The learning dynamics exhibits universal features as function of the strength of plastic adaptation. Any rule could be learned provided that the plastic adaptation is sufficiently slow.

  17. Hodgkin lymphoma: Evolution and dilemma in radiation treatments

    International Nuclear Information System (INIS)

    Girinsky, T.; Ghalibafian, M.; Paumier, A.; Ghalibafian, M.

    2009-01-01

    Multiple new developments in the treatments of patients with Hodgkin lymphoma have occurred in the last 10 years. Radiation treatments have become extremely precise in localized Hodgkin lymphomas, on the other hand, they have almost completely disappeared in advanced stages. For patients with refractory or recurrent disease, it is strongly advocated, whenever feasible, to deliver a mantle field radiation treatment after an autologous stem cell transplant to avoid any further recurrence of the disease. (authors)

  18. Clinical aspects and therapy of non-Hodgkin lymphomas

    International Nuclear Information System (INIS)

    Meissner, K.; Jaenner, M.

    1981-01-01

    Definition, incidence and distribution of age and sex of cutaneous non-Hodgkin lymphomas are presented. Clinical appearance of cutaneous non-Hodgkin lymphomas may exhibit specific and unspecific cutaneous lesions. Histological examination is of greatest importance for subsequent diagnostic and therapeutic procedures. Topical treatment, X-ray- or photochemotherapy are performed in the early stages, in case of therapeutic resistance and in advanced disease systemical chemotherapy is indicated. (orig.) [de

  19. Two stable steady states in the Hodgkin-Huxley axons

    OpenAIRE

    Aihara, K.; Matsumoto, G.

    1983-01-01

    Two stable steady states were found in the numerical solution of the Hodgkin-Huxley equations for the intact squid axon bathed in potassium-rich sea water with an externally applied inward current. Under the conditions the two stable steady-states exist, the Hodgkin-Huxley equations have a complex bifurcation structure including, in addition to the two stable steady-states, a stable limit cycle, two unstable equilibrium points, and one asymptotically stable equilibrium point. It was also conc...

  20. Hodgkin's lymphoma with exuberant granulomatous reaction

    International Nuclear Information System (INIS)

    Al-Maghrabi, Jaudah A.; Kanaan, Hassan D.; Sawan, Ali S.

    2006-01-01

    We report a 36-year-old woman, presented with cervical lymphadenopathy and low-grade fever. Two fine needle aspiration cytology and one excisional biopsy were performed in the referral hospital, all showed granulomatous lesions without necrosis. A tentative diagnosis of tuberculosis was made, and she started on antituberculous treatment. However, there was no clinical improvement. She presented to our institution one year after the initial diagnosis, and a new biopsy from the cervical lymph node revealed effacement of the whole node by marked non-necrotizing granulomatous reaction. However, there were scattered large cells with few classic Reed-Sternberg cells between the granulomas. Immunohistochemistry reveals strong reaction of CD15 and CD30, and negative staining for CD45RB, CD45RO, and CD20. These findings confirmed the diagnosis of Hodgkin's lymphoma with remarkable granulomatous reaction that almost masked the malignant component. She was treated with chemotherapy, and she showed an excellent response. (author)

  1. Modern Radiation Therapy for Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Specht, Lena; Yahalom, Joachim; Illidge, Tim

    2014-01-01

    on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy...... optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than...... (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG...

  2. Late cardiotoxicity after treatment for Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Aleman, Berthe M P; van den Belt-Dusebout, Alexandra W; De Bruin, Marie L

    2007-01-01

    We assessed cardiovascular disease (CVD) incidence in 1474 survivors of Hodgkin lymphoma (HL) younger than 41 years at treatment (1965-1995). Multivariable Cox regression and competing risk analyses were used to quantify treatment effects on CVD risk. After a median follow-up of 18.7 years, risks...... remained increased for at least 25 years and were more strongly elevated in younger patients. Mediastinal radiotherapy significantly increased the risks of MI, angina pectoris, CHF, and valvular disorders (2- to 7-fold). Anthracyclines significantly added to the elevated risks of CHF and valvular disorders...... from mediastinal RT (hazard ratios [HRs] were 2.81 and 2.10, respectively). The 25-year cumulative incidence of CHF after mediastinal radiotherapy and anthracyclines in competing risk analyses was 7.9%. In conclusion, risks of several CVDs are 3- to 5-fold increased in survivors of HL compared...

  3. Imaging of non-hodgkin lymphomas

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Hutchings, Martin

    2015-01-01

    interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance......Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods...... for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since...

  4. Management and controversies of classical Hodgkin lymphoma in pregnancy.

    Science.gov (United States)

    Eyre, Toby A; Lau, I-Jun; Mackillop, Lucy; Collins, Graham P

    2015-06-01

    The goal of managing classical Hodgkin lymphoma (cHL) in pregnancy is to obtain good long-term outcomes for both the mother and fetus. Given the excellent outcomes outside of pregnancy, the goal of treatment should remain curative. There remains a tension and debate regarding the timing of chemotherapy, the curative nature of such treatment and the timing of delivery. Moreover, the aim during pregnancy should be to minimize fetal toxicity and optimize perinatal outcomes. The management of cHL within pregnancy was covered within the excellent recent British Committee for Standards in Haematology guidelines, but with necessary brevity. By reviewing the literature over the last 30 years, herein we discuss the options for management during each trimester. Critical organogenesis occurs between 2 and 8 weeks post-conception; during which time the immature fetus is vulnerable to cytotoxic exposure. We discuss the evidence for using ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and single agent vinblastine in the first trimester. cHL presenting in pregnancy raises complex and difficult ethical dilemmas that can cause anxiety for patients, families and physicians. Decision-making must be multi-disciplinary and holistic, taking into account the patient's wishes, psycho-social and religious beliefs and personal circumstances. Clear communication between the haemato-oncologist, medical obstetrician, nurse specialists, midwives and neonatologists is paramount to a successful outcome. © 2015 John Wiley & Sons Ltd.

  5. Outcome of Very Late Relapse in Patients with Hodgkin's Lymphomas

    Directory of Open Access Journals (Sweden)

    Francesco Gaudio

    2011-01-01

    Full Text Available Recurrences of Hodgkin's Lymphoma (HL 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85% achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8% within 5 years and 16 over 5 years (3.5%, very late relapses. Very late relapses occurred after a median disease-free interval of 7 years (range: 5–18. Salvage treatment induced complete remission in 14 pts (87.5%. At a median of 4 years after therapy for very late relapse, 10 pts (63% are still alive and free of disease and 6 (37% died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection. The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications.

  6. Gastrointestinal cancer after treatment of Hodgkin's disease

    International Nuclear Information System (INIS)

    Birdwell, Sandra H.; Hancock, Steven L.; Varghese, Anna K.; Cox, Richard S.; Hoppe, Richard T.

    1995-01-01

    Purpose/Objective: To quantify the risk of gastrointestinal cancer (GI) following Hodgkin's disease treatment according to type of therapy, age at treatment, latency interval, attained age, and specific GI cancer sites. Materials and Methods: Cases were identified from the records of 2441 patients treated for Hodgkin's disease between 1961 and 1994. The mean follow-up was 10.9 years, representing 26,590 person-years of observation. Relative risks (RR) for GI cancer incidence and mortality were computed by comparison with expected annualized rates for the general U.S. population from SEER data matched for age, sex, and race. Results: Twenty-five patients have developed invasive GI cancer, yielding a RR of 2.5 [95% confidence interval (CI)=1.5-3.5] and an absolute risk of 5.6 excess cases/10,000 person-years. The sites included: esophagus-1, stomach-8, small intestine-2, pancreas-4, colon-7, and rectum-3. There were 23 cases of adenocarcinoma, one SCCA, and one leiomyosarcoma. Second cancer risks were significantly increased for cancer of the stomach, RR 7.26 (CI=3.4-13.8), small intestine, RR 11.58 (CI=1.9-38.3), and pancreas, RR 3.5 (CI=1.1-8.5). Risk was not elevated for cancers of the esophagus, RR 1.69 (CI=0.0-8.3) or colorectum, RR 1.67 (CI=0.8-3.0). Combined modality therapy (CMT) for Hodgkin's disease was associated with significantly increased risk: RR 3.56 (CI=2.2-5.6). However, risk with radiotherapy alone was not significantly elevated: RR 1.97 (C.I.=1.0-3.4). There were no events in 86 patients treated with chemotherapy alone. This increased risk with CMT held consistent for gastric and colorectal cancer: In gastric cancer, RR with radiotherapy alone was 4.84 (CI=1.2-13.2), whereas for CMT it was 12.48 (CI=4.6-27.7); in colorectal cancer, RR with radiotherapy alone was 1.18 (CI=0.4-2.9), whereas for CMT it was 2.82 (CI=1.1-5.9). Age at time of Hodgkin's disease treatment influenced risk: patients treated before 25 years of age demonstrated a RR of 7

  7. Hodgkin lymphoma: Evolution and dilemma in radiation treatments; Evolution et dilemmes dans les traitements du lymphome de Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Girinsky, T.; Ghalibafian, M.; Paumier, A. [Institut Gustave-Roussy, Dept. des Radiations, 94 - Villejuif (France); Ghalibafian, M. [Hopital Marak, Dept. des radiations, Teheran (Iran, Islamic Republic of)

    2009-10-15

    Multiple new developments in the treatments of patients with Hodgkin lymphoma have occurred in the last 10 years. Radiation treatments have become extremely precise in localized Hodgkin lymphomas, on the other hand, they have almost completely disappeared in advanced stages. For patients with refractory or recurrent disease, it is strongly advocated, whenever feasible, to deliver a mantle field radiation treatment after an autologous stem cell transplant to avoid any further recurrence of the disease. (authors)

  8. BlastNeuron for Automated Comparison, Retrieval and Clustering of 3D Neuron Morphologies.

    Science.gov (United States)

    Wan, Yinan; Long, Fuhui; Qu, Lei; Xiao, Hang; Hawrylycz, Michael; Myers, Eugene W; Peng, Hanchuan

    2015-10-01

    Characterizing the identity and types of neurons in the brain, as well as their associated function, requires a means of quantifying and comparing 3D neuron morphology. Presently, neuron comparison methods are based on statistics from neuronal morphology such as size and number of branches, which are not fully suitable for detecting local similarities and differences in the detailed structure. We developed BlastNeuron to compare neurons in terms of their global appearance, detailed arborization patterns, and topological similarity. BlastNeuron first compares and clusters 3D neuron reconstructions based on global morphology features and moment invariants, independent of their orientations, sizes, level of reconstruction and other variations. Subsequently, BlastNeuron performs local alignment between any pair of retrieved neurons via a tree-topology driven dynamic programming method. A 3D correspondence map can thus be generated at the resolution of single reconstruction nodes. We applied BlastNeuron to three datasets: (1) 10,000+ neuron reconstructions from a public morphology database, (2) 681 newly and manually reconstructed neurons, and (3) neurons reconstructions produced using several independent reconstruction methods. Our approach was able to accurately and efficiently retrieve morphologically and functionally similar neuron structures from large morphology database, identify the local common structures, and find clusters of neurons that share similarities in both morphology and molecular profiles.

  9. Predictors of Radiation Pneumonitis in Patients Receiving Intensity Modulated Radiation Therapy for Hodgkin and Non-Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Pinnix, Chelsea C., E-mail: ccpinnix@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Smith, Grace L.; Milgrom, Sarah; Osborne, Eleanor M.; Reddy, Jay P.; Akhtari, Mani; Reed, Valerie; Arzu, Isidora; Allen, Pamela K.; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fanale, Michele A.; Oki, Yasuhiro; Turturro, Francesco; Romaguera, Jorge; Fayad, Luis; Fowler, Nathan; Westin, Jason; Nastoupil, Loretta; Hagemeister, Fredrick B.; Rodriguez, M. Alma [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); and others

    2015-05-01

    Purpose: Few studies to date have evaluated factors associated with the development of radiation pneumonitis (RP) in patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), especially in patients treated with contemporary radiation techniques. These patients represent a unique group owing to the often large radiation target volumes within the mediastinum and to the potential to receive several lines of chemotherapy that add to pulmonary toxicity for relapsed or refractory disease. Our objective was to determine the incidence and clinical and dosimetric risk factors associated with RP in lymphoma patients treated with intensity modulated radiation therapy (IMRT) at a single institution. Methods and Materials: We retrospectively reviewed clinical charts and radiation records of 150 consecutive patients who received mediastinal IMRT for HL and NHL from 2009 through 2013. Clinical and dosimetric predictors associated with RP according to Radiation Therapy Oncology Group (RTOG) acute toxicity criteria were identified in univariate analysis using the Pearson χ{sup 2} test and logistic multivariate regression. Results: Mediastinal radiation was administered as consolidation therapy in 110 patients with newly diagnosed HL or NHL and in 40 patients with relapsed or refractory disease. The overall incidence of RP (RTOG grades 1-3) was 14% in the entire cohort. Risk of RP was increased for patients who received radiation for relapsed or refractory disease (25%) versus those who received consolidation therapy (10%, P=.019). Several dosimetric parameters predicted RP, including mean lung dose of >13.5 Gy, V{sub 20} of >30%, V{sub 15} of >35%, V{sub 10} of >40%, and V{sub 5} of >55%. The likelihood ratio χ{sup 2} value was highest for V{sub 5} >55% (χ{sup 2} = 19.37). Conclusions: In using IMRT to treat mediastinal lymphoma, all dosimetric parameters predicted RP, although small doses to large volumes of lung had the greatest influence. Patients with relapsed

  10. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy

    DEFF Research Database (Denmark)

    Wiberg, Sebastian; Hassager, Christian; Stammet, Pascal

    2017-01-01

    of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition......, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population. METHODS: This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients...

  11. Non-linear leak currents affect mammalian neuron physiology

    Directory of Open Access Journals (Sweden)

    Shiwei eHuang

    2015-11-01

    Full Text Available In their seminal works on squid giant axons, Hodgkin and Huxley approximated the membrane leak current as Ohmic, i.e. linear, since in their preparation, sub-threshold current rectification due to the influence of ionic concentration is negligible. Most studies on mammalian neurons have made the same, largely untested, assumption. Here we show that the membrane time constant and input resistance of mammalian neurons (when other major voltage-sensitive and ligand-gated ionic currents are discounted varies non-linearly with membrane voltage, following the prediction of a Goldman-Hodgkin-Katz-based passive membrane model. The model predicts that under such conditions, the time constant/input resistance-voltage relationship will linearize if the concentration differences across the cell membrane are reduced. These properties were observed in patch-clamp recordings of cerebellar Purkinje neurons (in the presence of pharmacological blockers of other background ionic currents and were more prominent in the sub-threshold region of the membrane potential. Model simulations showed that the non-linear leak affects voltage-clamp recordings and reduces temporal summation of excitatory synaptic input. Together, our results demonstrate the importance of trans-membrane ionic concentration in defining the functional properties of the passive membrane in mammalian neurons as well as other excitable cells.

  12. Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

    Directory of Open Access Journals (Sweden)

    Ji Yeon Jang

    Full Text Available We identified a novel neuroprotective compound, 1-methoxyoctadecan-1-ol, from Uncaria sinensis (Oliv. Havil and investigated its effects and mechanisms in primary cortical neurons and in a photothrombotic ischemic model. In primary rat cortical neurons against glutamate-induced neurotoxicity, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced neuronal death in a dose-dependent manner. In addition, treatment with 1-methoxyoctadecan-1-ol resulted in decreased neuronal apoptotic death, as assessed by nuclear morphological approaches. To clarify the neuroprotective mechanism of 1-methoxyoctadecan-1-ol, we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR with calpain activation. Treatment with glutamate leads to early activation of NMDAR, which in turn leads to calpain-mediated cleavage of striatal-enriched protein tyrosine phosphatase (STEP and subsequent activation of p38 mitogen activated protein kinase (MAPK. However, pretreatment with 1-methoxyoctadecan-1-ol resulted in significantly attenuated activation of GluN2B-NMDAR and a decrease in calpain-mediated STEP cleavage, leading to subsequent attenuation of p38 MAPK activation. We confirmed the critical role of p38 MAPK in neuroprotective effects of 1-methoxyoctadecan-1-ol using specific inhibitor SB203580. In the photothrombotic ischemic injury in mice, treatment with 1-methoxyoctadecan-1-ol resulted in significantly reduced infarct volume, edema size, and improved neurological function. 1-methoxyoctadecan-1-ol effectively prevents cerebral ischemic damage through down-regulation of calpain-mediated STEP cleavage and activation of p38 MAPK. These results suggest that 1-methoxyoctadecan-1-ol showed neuroprotective effects through down-regulation of calpain-mediated STEP cleavage with activation of GluN2B-NMDAR, and subsequent alleviation of p38 MAPK activation. In addition, 1-methoxyoctadecan-1-ol might be a useful therapeutic agent for

  13. [Mirror neurons].

    Science.gov (United States)

    Rubia Vila, Francisco José

    2011-01-01

    Mirror neurons were recently discovered in frontal brain areas of the monkey. They are activated when the animal makes a specific movement, but also when the animal observes the same movement in another animal. Some of them also respond to the emotional expression of other animals of the same species. These mirror neurons have also been found in humans. They respond to or "reflect" actions of other individuals in the brain and are thought to represent the basis for imitation and empathy and hence the neurobiological substrate for "theory of mind", the potential origin of language and the so-called moral instinct.

  14. Treatment Options for Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents

    Science.gov (United States)

    ... Primary Refractory/Recurrent Hodgkin Lymphoma in Children and Adolescents Primary refractory Hodgkin lymphoma is lymphoma that continues ... treated with an adult treatment regimen . Children and adolescents may have treatment-related side effects that appear ...

  15. History of radiotherapy of Hodgkin's disease (Now Hodgkin´s lymphoma)

    DEFF Research Database (Denmark)

    Specht, Lena; Rosenberg, Saul

    2011-01-01

    Hodgkin lymphoma (HL) is seen in patients over the age of 60 in 20–40% of cases. Prognosis is poorer, largely due to suboptimal staging and treatment in some patients due to concurrent disease. If possible, older patients should be treated along the same principles as younger patients. HL in the ...... involvement is relatively rare in HL, although it may be found more frequently with modern imaging techniques. Treatment is as for nodal disease, and prognosis is in general not influenced by extranodal involvement when other factors are taken into account....

  16. Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-07

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

  17. The genetics of Hodgkin lymphoma: an overview and clinical implications.

    Science.gov (United States)

    Borchmann, Sven; Engert, Andreas

    2017-09-01

    The goal of this review is to give an overview of the genetics of classical Hodgkin lymphoma. Copy number changes, somatic mutations, genome-wide association studies, changes in gene expression, familial classical Hodgkin lymphoma and epigenetic changes will be reviewed. In doing so, special focus is placed on the way recent discoveries have influenced clinical research, diagnostics, treatment and remission monitoring. Furthermore, emphasis is put on how these advances can help to advance the treatment of elderly patients who have a markedly worse prognosis than younger patients. Frequent amplifications of the 9p24.1 locus in classical Hodgkin lymphoma could be the basis for the success of immune checkpoint inhibitors targeting PD-1 or PD-L1 in this disease. The same amplification also affects the JAK/STAT pathway, which has also been targeted in recent clinical trials. Hodgkin lymphoma-specific copy number alterations and mutations have recently been found to be detectable in cell-free DNA. This could provide the basis for advances in the detection of residual disease during treatment and while monitoring patients in remission. The advent of new technologies such as massive parallel sequencing has improved our understanding of the genetics of classical Hodgkin lymphoma. Some of these discoveries are now being translated into clinical research in the form of new diagnostics and treatments.

  18. Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles

    Directory of Open Access Journals (Sweden)

    Chaitanya Medini

    2012-01-01

    Full Text Available The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.

  19. Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

    Science.gov (United States)

    Eichenauer, Dennis A; Engert, Andreas

    2017-12-08

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease. © 2016 by The American Society of Hematology. All rights reserved.

  20. Mediastinal Choriocarcinoma Masquerading as Relapsed Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Selay Lam

    2011-10-01

    Full Text Available Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL. A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone alternating with ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine. He achieved a complete remission after 6 cycles. Ten years after treatment, the patient presented with a persistent cough, haemoptysis, right supraclavicular lymphadenopathy, and weight loss. His chest X-ray showed opacification of the lower right hemithorax with a widened mediastinum. Given unresponsiveness to several antibiotics and lack of evidence for lung volume loss, there were concerns over lung infiltration with relapsed lymphoma. Transbronchial fine needle aspiration biopsy suggested recurrence of his HL. MOPP alternating with ABVD was again given. Due to disease progression, brachytherapy as well as a cocktail of dexamethasone, cytarabine, and cisplatin were also tried. However, on a subsequent excisional lymph node biopsy, it turned out that the tumour was in fact choriocarcinoma and not relapsed HL. Unfortunately, despite aggressive therapy, the patient’s disease rapidly progressed, and he died within 2 weeks.

  1. Hodgkin's disease: thyroid dysfunction following external irradiation

    International Nuclear Information System (INIS)

    Tamura, K.; Shimaoka, K.

    1981-01-01

    The thyroid gland is commonly included in the field of radiation therapy for patients with malignant lymphoma and with head and neck tumors. The radiation dose for malignant diseases varies considerably depending on the purpose of treatment and the institutional policies. A substantial number of these patients are developing subclinical and clinical hypothyroidism. The risk of developing hypothyroidism after a moderate radiation dose of 2000 to 4500 rads has been reported to be 10 to 20 percent. In addition, subclinical hypothyroidism is induced further in one third of the patients. There are also suggestions that external irradiation of the thyroid gland in patients with malignant lymphomas, as well as internal irradiation with radioiodine of the normal and hyperthyroid human thyroid glands, would induce elevations of serum antithyroid autoantibody titers. However, only a few cases of Graves disease following irradiation to the thyroid gland have been reported. We encountered a young woman who received radiation therapy to the mantle field for her Hodgkin's disease and developed hypothyroxinemia without overt signs and symptoms of hypothyroidism, followed by appearance of nodular goiter and then full-blown Graves disease

  2. [Hodgkin lymphoma: Current and future therapeutic strategies].

    Science.gov (United States)

    Turpin, Anthony; Michot, Jean-Marie; Kempf, Emmanuelle; Mazeron, Renaud; Dartigues, Peggy; Terroir, Marie; Boros, Angela; Bonnetier, Serge; Castilla-Llorente, Cristina; Coman, Tereza; Danu, Alina; Ghez, David; Pilorge, Sylvain; Arfi-Rouche, Julia; Dercle, Laurent; Soria, Jean-Charles; Carde, Patrice; Ribrag, Vincent; Fermé, Christophe; Lazarovici, Julien

    2018-01-01

    Hodgkin lymphoma (HL) is a cancer that mostly affects young people, in which modern therapeutic strategies using chemotherapy and radiotherapy result in a cure rate exceeding 80%. Survivors are exposed to long-term consequences of treatments, such as secondary malignancies and cardiovascular diseases, whose mortality exceeds the one of the disease itself, with long-term follow-up. The current therapeutic strategy in HL, based on the assessment of initial risk factors, is the result of large clinical trials led by the main international cooperating groups. More recently, several groups have tried to develop treatment strategies adapted to the response to chemotherapy, evaluated by interim PET/CT scan. However to date, the combined treatment with chemotherapy followed by radiation therapy remains a standard in most of the above-diaphragmatic localized forms. Immune checkpoint inhibitors, and especially anti-PD1 antibodies, have shown dramatic results in some serious forms of relapsed or refractory HL, with limited toxicity, and may contribute in the future to reduce the toxicities of treatments. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  3. Radiotherapy of adult nodal non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Gamen, G.; Thirion, P.

    1999-01-01

    The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

  4. Pesticides and non-Hodgkin's lymphoma.

    Science.gov (United States)

    Zahm, S H; Blair, A

    1992-10-01

    The incidence of non-Hodgkin's lymphoma (NHL) has increased over 50% in the last 15 years. This paper reviews the possible role of pesticides in this increase. While small increases in risk of NHL among farmers have been observed in general occupational surveys, recent studies focusing on specific pesticides have observed much larger risks. Frequent use of phenoxyacetic acid herbicides, in particular, 2,4-dichlorophenoxyacetic acid, has been associated with 2- to 8-fold increases of NHL in studies conducted in Sweden, Kansas, Nebraska, Canada, and elsewhere. Canine malignant lymphoma has also been associated with dog owner use of 2,4-dichlorophenoxyacetic acid and commercial lawn pesticide treatments. There are much fewer data linking NHL to other types of pesticides, but triazine herbicides, organophosphate insecticides, fungicides, and fumigants have also been associated with increased risk of NHL. Pesticide exposures are not limited to agricultural populations but are widespread in the general population through use on lawns, golf courses, rights-of-way, and elsewhere. Since the use of pesticides, particularly phenoxy herbicides, has increased dramatically preceding and during the time period in which the incidence of NHL has increased, they could have contributed to the rising incidence of NHL.

  5. Motor Neurons

    DEFF Research Database (Denmark)

    Hounsgaard, Jorn

    2017-01-01

    Motor neurons translate synaptic input from widely distributed premotor networks into patterns of action potentials that orchestrate motor unit force and motor behavior. Intercalated between the CNS and muscles, motor neurons add to and adjust the final motor command. The identity and functional...... properties of this facility in the path from synaptic sites to the motor axon is reviewed with emphasis on voltage sensitive ion channels and regulatory metabotropic transmitter pathways. The catalog of the intrinsic response properties, their underlying mechanisms, and regulation obtained from motoneurons...... in in vitro preparations is far from complete. Nevertheless, a foundation has been provided for pursuing functional significance of intrinsic response properties in motoneurons in vivo during motor behavior at levels from molecules to systems....

  6. Bilateral breast cancer after cured Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, N.; Lokich, J. (New England Baptist Hospital, Boston, MA (USA))

    1990-01-15

    Three patients developed bilateral breast cancer at 10 to 24 years after mantle irradiation for locally or systemically advanced Hodgkin's disease (HD). Four of the six cancers in the three patients were detected only by mammography. Pathologically, five of the cancers were intraductal carcinomas (four with an invasive component) with one being a lobular carcinoma. Five of the six lesions were Stage I pathologically without evidence of axillary nodal involvement. It is recommended that female patients with Hodgkin's disease who have received mantle irradiation as part of the therapy for their Hodgkin's disease and who are observed for 10 or more years after completion of mantle irradiation be considered at risk for the development of breast cancer. Such patients should be monitored appropriately by routine bilateral mammograms to increase the early detection of early stage lesions.

  7. Breast Cancer After Treatment of Hodgkin's Lymphoma: General Review

    International Nuclear Information System (INIS)

    Alm El-Din, Mohamed A.; El-Badawy, Samy A.; Taghian, Alphonse G.

    2008-01-01

    The improved survival rates among patients with Hodgkin's lymphoma over the past few decades have come with increased incidence of second malignancies. One of the major concerns among female survivors is the significantly elevated risk of breast cancer that appears with extended follow-up. In this review, we include the published literature regarding the risk of breast cancer after irradiation for Hodgkin's lymphoma. We also present the possible long-term surveillance strategies and the optimal time to start screening these women. This could potentially help in early detection of secondary breast cancers and consequently improve outcomes. Furthermore, because of prior radiotherapy, the management of the breast cancer among this unique population has been controversial. We discuss the characteristics of breast cancer that occurs after Hodgkin's lymphoma and also treatment options that could be implemented

  8. Hodgkin's Lymphoma in Crohn's Disease Treated with Infliximab

    Directory of Open Access Journals (Sweden)

    Diana Carvalho

    2017-09-01

    Full Text Available Introduction: Lymphoproliferative disorders, particularly non-Hodgkin's and Hodgkin's lymphomas, are rare in patients with inflammatory bowel diseases. The use of thiopurines and infection by Epstein-Barr virus are well-known cofactors that can raise its prevalence. Other risk factors such as disease activity and biological treatment are the subject of discussion, without enough data in the literature to confirm a potential association. Methods: We report a case of Hodgkin's lymphoma in a patient who had been treated with azathioprine and was on long-term monotherapy with infliximab. Conclusions: We stress the importance of recognizing the possible occurrence of a lymphoproliferative disorder in association with anti-tumor necrosis factor-α therapy

  9. Female reproductive potential after treatment for Hodgkin's disease

    International Nuclear Information System (INIS)

    Horning, S.J.; Hoppe, R.T.; Kaplan, H.S.; Rosenberg, S.A.

    1981-01-01

    The probability of maintaining ovarian function, becoming pregnant, and delivering a normal child is important to young women anticipating successful therapy for Hodgkin's disease. In this study, reproductive function was retrospectively examined in 103 women 40 years old or younger who had undergone treatment for Hodgkin's disease with total-lymphoid irradiation (TLI) alone, combination chemotherapy, or combined TLI and chemotherapy. Infertility was directly related to gonadal exposure to therapy and to age at treatment. Twenty women became pregnant after receiving total-nodal irradiation or combination chemotherapy or both. No fetal wastage occurred, and no birth defects were seen in the 24 infants born to these women. Even after intensive treatment programs, women successfully treated for Hodgkin's disease have become pregnant and delivered phenotypically normal children

  10. Neurons other than motor neurons in motor neuron disease.

    Science.gov (United States)

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  11. Orbital involvement by non-Hodgkin lymphoma NK T cells.

    Science.gov (United States)

    Hervás-Ontiveros, A; España-Gregori, E; Hernández-Martínez, P; Vera-Sempere, F J; Díaz-Llopis, M

    2014-11-01

    The case is presented of 37 year-old male with a history of nasal obstruction with right rhinorrhea, headache, hearing loss and right exophthalmos of 4 months progression. The MRI revealed that the ethmoidal and maxillary sinuses contained inflammatory tissue extending into the orbital region. The biopsy confirmed a non-Hodgkin lymphoma of natural killer (NK) T cells. Non-Hodgkin's T NK lymphoma is a rare tumor in the orbital area that requires an early detection and multi-disciplinary care to ensure appropriate monitoring and treatment. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  12. Paediatric non-Hodgkin lymphoma - perspectives in translational biology

    Science.gov (United States)

    Shiramizu, Bruce; Mussolin, Lara; Woessmann, Wilhelm; Klapper, Wolfram

    2016-01-01

    Summary Exciting advances have been achieved for infants, children and adolescents diagnosed with, and treated for, non-Hodgkin lymphoma (NHL). In spite of these successes, new frontiers are being paved to improve the prognosis for those who relapse or have resistant disease. This review summarizes some of the novel approaches and ideas in NHL monitoring, diagnosis and treatment as discussed at the 5th International Symposium on Childhood, Adolescent and Young Adult Non-Hodgkin Lymphoma on October 22nd to 24th 2015 in Varese, Italy. PMID:27009921

  13. Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

    Science.gov (United States)

    Bose, Sumit; Ganesan, Chitra; Pant, Manish; Lai, Catherine; Tabbara, Imad A

    2013-02-01

    Lymphocyte-predominant Hodgkin disease is a rare form of Hodgkin lymphoma that is recognized as a separate histopathological entity. This disease tends to have multiple relapses, but has an overall good prognosis. Owing to its rarity, and the prolonged time period between recurrence and transformation events, there is no consensus regarding optimal management. However, the National Comprehensive Cancer Network guidelines indicate that for early stages, appropriate treatment is radiotherapy. Several management options have been reported including observation, radiation, chemotherapy, combined chemoradiotherapy, and anti-CD20 antibody therapy. Salvage therapy remains effective in inducing prolonged remission in patients with relapsed/refractory disease.

  14. Hydrocele following treatment for Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Duffey, P.; Campbell, E.W.; Wiernik, P.H.

    1982-07-15

    Thirteen Hodgkin's disease patients developed hydrocele after treatment with radiotherapy (12 patients) or chemotherapy (one patient). An additional patient developed testicular swelling following radiotherapy and chemotherapy. Eleven of 13 patients were staged with laparotomy (nine initially, two at restaging) which included pelvic and aortic node biopsies prior to development of hydrocele. Five of the patients developed radiation-related pericarditis. These data suggest that staging and treatment of Hodgkin's disease may disrupt pelvic lymphatic flow and lead to hydrocele formation. The high incidence of treatment-related pericarditis may suggest unusual sensitivity to radiation in this group of patients.

  15. Thyroid Malignancies in Survivors of Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Michaelson, Evan M.; Chen, Yu-Hui; Silver, Barbara; Tishler, Roy B.; Marcus, Karen J.; Stevenson, Mary Ann; Ng, Andrea K.

    2014-01-01

    Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes. Methods and Materials: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model. Results: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, ≥10 years, ≥15 years, and ≥20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively. Conclusions: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and ≥10 years from HL treatment owing to their higher risk, which increases over time

  16. Thyroid Malignancies in Survivors of Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Michaelson, Evan M. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute, and the Children' s Hospital, Boston, Massachusetts (United States); Chen, Yu-Hui [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Silver, Barbara; Tishler, Roy B.; Marcus, Karen J. [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute, and the Children' s Hospital, Boston, Massachusetts (United States); Stevenson, Mary Ann [Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Brigham and Women' s Hospital, Dana-Farber Cancer Institute, and the Children' s Hospital, Boston, Massachusetts (United States)

    2014-03-01

    Purpose: To quantify the incidence of thyroid cancer after Hodgkin lymphoma (HL) and determine disease characteristics, risk factors, and treatment outcomes. Methods and Materials: Thyroid cancer cases were retrospectively identified from a multi-institutional database of 1981 HL patients treated between 1969 and 2008. Thyroid cancer risk factors were evaluated by a Poisson regression model. Results: With a median follow-up duration of 14.3 years (range, 0-41.2 years), 28 patients (1.4%) developed a thyroid malignancy. The overall incidence rate (expressed as the number of cases per 10,000 person-years) and 10-year cumulative incidence of thyroid cancer were 9.6 and 0.26%, respectively. There were no observed cases of thyroid malignancy in patients who received neck irradiation for HL after age 35 years. Age <20 years at HL diagnosis and female sex were significantly associated with thyroid cancer. The incidence rates of females aged <20 at HL diagnosis in the first 10 years, ≥10 years, ≥15 years, and ≥20 years after treatment were 5, 31, 61, and 75 cases per 10,000 person-years of follow-up, respectively. At a median follow-up of 3.5 years after the thyroid cancer diagnosis, 26 patients (93%) were alive without disease, 1 (4%) was alive with metastatic disease, and 1 (4%) died of metastatic disease, at 6 and 3.6 years after the thyroid cancer diagnosis, respectively. Conclusions: Although HL survivors have an increased risk for thyroid cancer, the overall incidence is low. Routine thyroid cancer screening may benefit females treated at a young age and ≥10 years from HL treatment owing to their higher risk, which increases over time.

  17. Yttrium Y 90 Basiliximab and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With Mature T-cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-10

    Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma

  18. Hepatitis C: crioglobulinemia y linfoma no-Hodgkin Hepatitis C: cryoglobulinemia and non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    M. Romero-Gómez

    2008-03-01

    Full Text Available La infección por el virus de la hepatitis C juega un papel principal en la patogénesis de la crioglobulinemia mixta, promoviendo la activación y expansión de las células B. Estos reajustes moleculares inducen la síntesis de crioglobulinas y la aparición de la vasculitis crioglobulinémica. El aclaramiento del virus provoca la resolución de las manifestaciones clínicas y de las alteraciones inmunológicas observados en la crioglobulinemia mixta en un alto porcentaje de los pacientes, pero no en todos. En algunos casos, la crioglobulinemia puede aparecer tras la respuesta virológica sostenida. Muchos mecanismos de la patogénesis de la crioglobulinemia mixta están fuertemente relacionados con la infección por VHC y, cuando el virus es eliminado, hay una mejoría en el curso de la enfermedad. Aun así, los pasos independientes relacionados con otros factores no mejoran tras la erradicación del virus. En algunos tipos de linfomas no-Hodgkin de bajo grado (linfoma linfoplasmocítico y linfoma de la zona marginal la respuesta sostenida tras el aclaramiento viral induce una remisión de la neoplasia. El VHC tiene un papel secundario en los linfomas agresivos y el aclaramiento del virus puede no inducir la remisión, pero puede disminuir la hepatotoxicidad asociada a la quimioterapia. Por tanto, en la hepatitis C crónica, la combinación de interferón pegilado y ribavirina es altamente recomendable en el tratamiento de la crioglobulinemia mixta sintomática y los linfomas no-Hodgkin asociados al VHC.Hepatitis C virus infection plays a major role in the pathogenesis of mixed cryoglobulinemia, promoting activation and expansion of B cells. These molecular rearrangements induce synthesis of cryoglobulins and the appearance of cryoglobulinemic vasculitis. Clearance of the virus promotes resolution of the clinical manifestations and immunological disorders seen in mixed cryoglobulinemia in a large percentage of patients, but not in all. In

  19. History of radiotherapy of Hodgkin's disease (Now Hodgkin´s lymphoma)

    DEFF Research Database (Denmark)

    Specht, Lena; Rosenberg, Saul

    2011-01-01

    This chapter outlines the increasingly important role of advanced imaging methods in the radiotherapy for Hodgkin lymphoma (HL). CT has become the cornerstone in modern conformal lymphoma radiotherapy. The use of PET/CT before, during and after chemotherapy has an important impact on the selection...... of early- and advanced-stage patients who receive radiotherapy. PET/CT is more sensitive for HL staging than CT alone, and the method results in upstaging of a significant proportion of patients. Some studies suggest that this may also result in larger radiotherapy volumes. On the other hand, the more...... precise determination of disease extent can also be used to allow more patient-tailored and less-toxic radiotherapy to the patients....

  20. Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

    Science.gov (United States)

    Specht, Lena

    2016-01-01

    Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

  1. Ctip2-, Satb2-, Prox1-, and GAD65-Expressing Neurons in Rat Cultures: Preponderance of Single- and Double-Positive Cells, and Cell Type-Specific Expression of Neuron-Specific Gene Family Members, Nsg-1 (NEEP21) and Nsg-2 (P19).

    Science.gov (United States)

    Digilio, Laura; Yap, Chan Choo; Winckler, Bettina

    2015-01-01

    The brain consists of many distinct neuronal cell types, but which cell types are present in widely used primary cultures of embryonic rodent brain is often not known. We characterized how abundantly four cell type markers (Ctip2, Satb2, Prox1, GAD65) were represented in cultured rat neurons, how easily neurons expressing different markers can be transfected with commonly used plasmids, and whether neuronal-enriched endosomal proteins Nsg-1 (NEEP21) and Nsg-2 (P19) are ubiquitously expressed in all types of cultured neurons. We found that cultured neurons stably maintain cell type identities that are reflective of cell types in vivo. This includes neurons maintaining simultaneous expression of two transcription factors, such as Ctip2+/Satb2+ or Prox1+/Ctip2+ double-positive cells, which have also been described in vivo. Secondly, we established the superior efficiency of CAG promoters for both Lipofectamine-mediated transfection as well as for electroporation. Thirdly, we discovered that Nsg-1 and Nsg-2 were not expressed equally in all neurons: whereas high levels of both Nsg-1 and Nsg-2 were found in Satb2-, Ctip2-, and GAD65-positive neurons, Prox1-positive neurons in hippocampal cultures expressed low levels of both. Our findings thus highlight the importance of identifying neuronal cell types for doing cell biology in cultured neurons: Keeping track of neuronal cell type might uncover effects in assays that might otherwise be masked by the mixture of responsive and non-responsive neurons in the dish.

  2. Traveling-wave solutions of a modified Hodgkin-Huxley type neural model via Novel analytical results for nonlinear transmission lines with arbitrary I(V) characteristics

    OpenAIRE

    Valentino Anthony Simpao

    2000-01-01

    Herein an enhanced Hodgkin-Huxley (H-H) type model of neuron dynamics is solved analytically via formal methods. Our model is a variant of an earlier one by M.A. Mahrous and H.Y. Alkahby [1]. Their modified model is realized by a hyperbolic quasi-linear diffusion operator with time-delay parameters; this compared to the original H-H model with standard parabolic quasi-linear diffusion operator and no time-delay parameters. Besides these features, the present model also incorporates terms desc...

  3. Diet and non-Hodgkin's lymphoma risk | Mozaheb | Pan African ...

    African Journals Online (AJOL)

    Background: The role of dietary factors in the epidemiology of Non-Hodgkin's lymphoma (NHL) remains largely undefined. Dietary habits may play a role in the etiology of NHL by influencing the immune system. Methods: Dietary patterns and the risk of NHL were analyzed in a case control study; including 170 NHL cases ...

  4. Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Biggar, R.J.; Johansen, J.S.; Smedby, K.E.

    2008-01-01

    PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially...

  5. UK Government: New postgraduate scheme - Dorothy Hodgkin awards

    CERN Multimedia

    2003-01-01

    The UK Prime Minister today announced a new GBP10m initiative, the Dorothy Hodgkin Postgraduate Awards, which will allow over 100 PhD students from India, China, Hong Kong, Russia and the developing world to study in top UK universities (1 page).

  6. Cardiovascular disease after hodgkin lymphoma treatment: 40-year disease risk

    NARCIS (Netherlands)

    van Nimwegen, Frederika A.; Schaapveld, Michael; Janus, Cécile P. M.; Krol, Augustinus D. G.; Petersen, Eefke J.; Raemaekers, John M. M.; Kok, Wouter E. M.; Aleman, Berthe M. P.; van Leeuwen, Flora E.

    2015-01-01

    Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases. To examine relative and absolute excess risk up to 40 years since HL treatment compared

  7. Cardiovascular disease after Hodgkin lymphoma treatment: 40-year disease risk

    NARCIS (Netherlands)

    Nimwegen, F.A. van; Schaapveld, M.; Janus, C.P.; Krol, A.D.; Petersen, E.J.; Raemaekers, J.M.M.; Kok, W.E.; Aleman, B.M.; Leeuwen, F.E. van

    2015-01-01

    IMPORTANCE: Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases. OBJECTIVES: To examine relative and absolute excess risk up to 40 years since

  8. Autoimmune and Atopic Disorders and Risk of Classical Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Hollander, Peter; Rostgaard, Klaus; Smedby, Karin E

    2015-01-01

    Results from previous investigations have shown associations between the risk of Hodgkin lymphoma (HL) and a history of autoimmune and atopic diseases, but it remains unknown whether these associations apply to all types of HL or only to specific subtypes. We investigated immune diseases...

  9. FDA Expands Approval of Brentuximab for Hodgkin Lymphoma

    Science.gov (United States)

    The FDA has expanded the approved uses of brentuximab (Adcetris) in people with Hodgkin lymphoma. As this Cancer Currents post explains, it can now be used in combination with three chemotherapy drugs as an initial treatment in patients with advanced disease.

  10. Recurrent chylothorax in a patient with non-hodgkins lymphoma ...

    African Journals Online (AJOL)

    Spontaneous chylothorax could arise as a complication of Iymphoma. There are no reports on the frequency of it's occurrence. It is associated with a high mortality rate. This is mainly due to severe nutritional deficiencies and wasting. This case describes a patient with non-hodgkins Iymphoma who developed recurrent ...

  11. An unusual hotspot in a young woman with Hodgkin's lymphoma

    NARCIS (Netherlands)

    ten Hove, C. H.; Zijlstra-Baalbergen, J. M.; Comans, E. F. I.; van Elburg, R. M.

    2008-01-01

    A young woman has started cancer treatment because of a Hodgkin's lymphoma. After four months of chemotherapy, a PET scan showed an unexplained hotspot in the right lower abdomen. This was later explained by an unsuspected pregnancy. Our case emphasizes the importance of a pregnancy test in all

  12. Persisting fatigue in Hodgkin lymphoma survivors : A systematic review

    NARCIS (Netherlands)

    Daniëls, L.A.; Oerlemans, S.; Krol, A.D.; van de Poll-Franse, L.V.; Creutzberg, C.L.

    2013-01-01

    Hodgkin Lymphoma (HL) survivors are at risk for adverse psychosocial events as a result from cancer diagnosis and treatment. Fatigue is one of the most frequently reported long-term symptoms and is often reported to interfere with daily life. We conducted a systematic review to determine prevalence,

  13. The histologic pattern of non-Hodgkin's lymphomas in Ethiopians ...

    African Journals Online (AJOL)

    Non-Hodgkin's lymphomas (NHLs) are among the malignancies that can arise in advanced stages of infection in patients with human immunodefiency virus (HIV). However, the pattern of this malignancy has not been reported in Ethiopia. A sixteen year retrospective review has been carried out to determine the trend, age, ...

  14. The therapeutic use of rituximab in non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Marcus, Robert; Hagenbeek, Anton

    2007-01-01

    The non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of lymphoproliferative malignancies, which are most common in people aged over 55 years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL, accounting for approximately 30% of all new patients. Follicular

  15. Multifocal nodular episcleritis and scleritis with undiagnosed Hodgkin's lymphoma.

    Science.gov (United States)

    Thakker, Manoj M; Perez, Victor L; Moulin, Alexandre; Cremers, Sandra L; Foster, C Stephen

    2003-05-01

    To report the case of a patient with undiagnosed Hodgkin's lymphoma who presented with coexistent unilateral nodular episcleritis and scleritis. Interventional case report and literature review Review of clinical history, laboratory findings, histology of episcleral and cervical lymph node biopsies, and follow-up. A 20-year-old female presented with a 5-month history of redness and pain in her left eye, with associated symptoms of dyspnea, malaise, and fever. The patient was found to have multifocal nodular episcleritis and scleritis that was not responsive to topical steroids or systemic nonsteroidal anti-inflammatory treatment. Laboratory tests subsequently revealed evidence of systemic inflammation, and radiologic studies showed extensive mediastinal and cervical adenopathy. A cervical lymph node biopsy showed Reed-Sternberg cells and a chronic lymphocytic infiltrate consistent with nodular sclerosing Hodgkin's lymphoma. Histopathologic analysis of an episcleral nodule revealed a necrotizing granuloma with vasculitis. Systemic chemotherapy was instituted for the Hodgkin's disease; this therapy abolished the nodular scleritis. This case raises the possibility of concurrent undiagnosed systemic vasculitis with only an ocular manifestation with Hodgkin's lymphoma, either as a coincidence or as a paraneoplastic syndrome. Moreover, it emphasizes the important role of tissue biopsy in establishing diagnosis and directing treatment. Copyright 2003 by the American Academy of Ophthalmology.

  16. Dorothy Crowfoot Hodgkin – A Tribute The word 'scientist' evokes ...

    Indian Academy of Sciences (India)

    milind1

    Then there is a current image of a scientist-manager raising large funds, filing patents, hopping from meeting to meeting, leading large teams and producing results of great import to science as well as industry. These or other images do not fit Dorothy Crowfoot Hodgkin. Undoubtedly, she was an outstanding scientist with.

  17. Anatomical site predilections of non-Hodgkin's lymphoma in Human ...

    African Journals Online (AJOL)

    Anatomical site predilections of non-Hodgkin's lymphoma in Human Immunodeficiency Virus infection: A report on 54 cases. OW Mwanda, C Whalen, CR Scot, M Lederman, J Orem, C Banura. Abstract. No Abstract Available East African Medical Journal August (Supplement) 2004: S90-S96.

  18. Treatment of Hodgkin lymphoma: the past, present, and future

    DEFF Research Database (Denmark)

    Evens, A.M.; Hutchings, M.; Diehl, V.

    2008-01-01

    Significant advances in the biology and treatment of Hodgkin lymphoma (HL) have been accomplished over the past decades. In a landmark study, DeVita and colleagues showed that half of patients with advanced-stage HL experienced long-term disease-free survival following treatment with a four-drug ...

  19. Amyloidosis in Hodgkin's Disease | Falkson | South African Medical ...

    African Journals Online (AJOL)

    A patient with a 13-year history of Hodgkin's disease, who developed the terminal complication of amyloidosis manifesting in a nephrotic syndrome resulting in death, is reported. The incidence of this rare complication is reviewed from reports in the literature; to date only 53 unequivocal cases of amyloidosis, in association ...

  20. Economic evaluations in aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    M. van Agthoven (Michel)

    2004-01-01

    textabstractNon-Hodgkin's lymphoma (NHL) has the highest incidence rate of all haematological malignancies in the Western world 1 • In the USA, the number of deaths attributable to NHL currently ranks in the top five of cancer related deaths2 In the Netherlands, haematological malignancies rank 8 in

  1. Recurrent chylothorax in a patient with non-hodgkins lymphoma ...

    African Journals Online (AJOL)

    This is mainly due to severe nutritional deficiencies and wasting. This case describes a patient with non-hodgkins Iymphoma who developed recurrent bilateral chylothorax requiring repeated pleural aspirations and eventually talc pleurodesis which failed. East African Medical Journal Vol. 81 No. 4 April 2004: 215-217 ...

  2. Therapy for stage I aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke

    2002-01-01

    Although radiotherapy was considered sufficient for stage I and limited stage II aggressive non-Hodgkin's lymphoma in the past, new data from randomized studies have shown that intensified chemotherapy or combined modality therapy (multiagent chemotherapy followed by involved field radiotherapy) can

  3. Monoamine oxidase A is highly expressed in classical Hodgkin lymphoma.

    Science.gov (United States)

    Li, Pei Chuan; Siddiqi, Imran N; Mottok, Anja; Loo, Eric Y; Wu, Chieh Hsi; Cozen, Wendy; Steidl, Christian; Shih, Jean Chen

    2017-10-01

    Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes oxidative deamination of neurotransmitters and dietary amines and produces H 2 O 2 . It facilitates the progression of gliomas and prostate cancer, but its expression and functional relevance have not been studied in lymphoma. Here, we evaluated MAOA in 427 cases of Hodgkin and non-Hodgkin lymphoma and in a spectrum of reactive lymphoid tissues by immunohistochemistry on formalin-fixed, paraffin-embedded specimens. MAOA was expressed by Hodgkin Reed-Sternberg (HRS) cells in the majority of classical Hodgkin lymphomas (cHLs) (181/241; 75%), with 34.8% showing strong expression. Weak MAOA was also noted in a minority of primary mediastinal large B-cell lymphomas (8/47; 17%) and in a mediastinal gray-zone lymphoma. In contrast, no MAOA was found in non-neoplastic lymphoid tissues, nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL; 0/8) or any other non-Hodgkin lymphomas studied (0/123). MAOA was more common in Epstein-Barr virus (EBV)-negative compared to EBV-positive cHL (p lymphoma specimens, most cHL-derived cell lines displayed MAOA activity, whereas non-Hodgkin-lymphoma-derived cell lines did not. The MAOA inhibitor clorgyline reduced the growth of L1236 cells and U-HO1 cells, and shRNA knockdown of MAOA reduced the growth of L1236 cells. Conversely, ectopic overexpression of MAOA increased the growth of MAOA-negative HDLM2 cells. Combined treatment with clorgyline and ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) was more effective in reducing cell growth than either regimen alone. In summary, MAOA is highly expressed in cHL and may reflect the distinct biology of this lymphoma. Further studies on the potential utility of MAOA as a diagnostic marker and therapeutic target are warranted. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John

  4. Inventing atomic resolution scanning dielectric microscopy to see a single protein complex operation live at resonance in a neuron without touching or adulterating the cell.

    Science.gov (United States)

    Agrawal, Lokesh; Sahu, Satyajit; Ghosh, Subrata; Shiga, Takashi; Fujita, Daisuke; Bandyopadhyay, Anirban

    2016-12-01

    A substantial ion flow in a normally wet protein masks any other forms of signal transmission. We use hysteresis and linear conduction (both are artifacts) as a marker to precisely wet a protein, which restricts the ionic conduction (hysteresis disappears), and at the same time, it is not denatured (quantized conductance and Raman spectra are intact). Pure electric visualization of proteins at work by eliminating the screening of ions, electrons, would change the way we study biology. Here we discuss the technical challenges resolved for imaging a protein or live cell using nonlinear dielectric response (spatial distribution of conductance, capacitance and phase, GCP trio). We electromagnetically triggered electrical, mechanical, thermal and ionic resonant vibrations in a protein. During resonant oscillations, we imaged the protein using resonant scanning tunneling microscopy of biomaterials (Brestum) and during ionic firing we imaged live what happens inside an axon core of a neuron by using our atomic scale scanning dielectric microscopy (Asadim). Both Asadim and Brestum are housed in a homebuilt scanning tunneling microscope (bio-STM) and a special micro-grid developed by us (patent JP-5187804) for fractal supercomputing. We found the trick to turn a membrane transparent and see inside without making any physical contact. We image live that a protein molecule adopts a unique configuration for each resonance frequency, - thus far unknown to biology. "Membrane alone fires" is found to be wrong after a century, micro-neuro-filaments communicate prior to firing to decide its necessity and then regulate it suitably. We introduce a series of technologies e.g., fractal grid, point contact, micro THz antenna, to discover that from atomic structure to a living cell, the biomaterials vibrate collectively.

  5. Dorothy Reed and Hodgkin's disease: a reflection after a century

    International Nuclear Information System (INIS)

    Zwitter, Matjaz; Cohen, Joel R.; Barrett, Ann; Robinton, Elizabeth D.

    2002-01-01

    It has now been 100 years since Dorothy Reed, at the age of 28, wrote her paper on Hodgkin's disease. Her biography reveals the difficult lives of women entering the hitherto male-dominated field of medicine, let alone medical research. Her historic paper on Hodgkin's disease is remarkable for its brilliant observations and concise scientific reasoning. Nevertheless, she was told that as a woman she could not hope for a career as an academic pathologist. After marriage to Charles Elwood Mendenhall, Professor of Physics at the University of Wisconsin and after giving birth to four children, the second part of her career began. Motivated by the loss of her firstborn, she began a study of infant mortality, an interest that lasted throughout her career. In 1926, Mendenhall undertook a survey comparing infant and maternal mortality rates in Denmark and the United States. This influential study concluded that American mortality rates were higher because of unnecessary interference in the natural process of childbirth and recommended the education of midwives follow the Danish model. In 1937, her efforts were rewarded when Madison, WI received recognition for having the lowest infant mortality of any city in the United States. Reading Reed's paper on Hodgkin's disease, we see that her observations go far beyond a description of a specific cell. Her presentation of macroscopic and microscopic features is remarkable for the distinction between 'young' and 'old' growths: Reed saw Hodgkin's disease as a process, rather than the spreading of a cancer. She was the first to note that those most commonly affected are boys or young adults, especially those whose general health before the disease had been excellent. She was also the first to note anergy to tuberculin. Dorothy Reed defined Hodgkin's disease in relation to tuberculosis, described its pathologic features, and offered comments on its pathogenesis, epidemiology, and immunology that still deserve to be discussed

  6. What do mirror neurons mirror?

    NARCIS (Netherlands)

    Uithol, S.; Rooij, I.J.E.I. van; Bekkering, H.; Haselager, W.F.G.

    2011-01-01

    Single cell recordings in monkeys provide strong evidence for an important role of the motor system in action understanding. This evidence is backed up by data from studies of the (human) mirror neuron system using neuroimaging or TMS techniques, and behavioral experiments. Although the data

  7. Computed tomography of the liver in newly diagnosed Hodgkin disease and non-Hodgkin lymphoma: Staging implications

    International Nuclear Information System (INIS)

    Neumann, C.H.; Hussain, S.; Seltzer, S.E.; Chiles, C.; Castellino, R.A.; Brigham and Women's Hospital, Boston, MA; Stanford Univ., CA

    1986-01-01

    In newly diagnosed patients with Hodgkin disease and non-Hodgkin lymphoma, the value of computed tomography (CT) of the liver was assessed as regards impact on the staging process. 201 patients at two medical centers had pretreatment abdominal CT within two weeks of liver biopsy. CT sensitivity, specificity and accuracy in both groups were determined and sensitivity in both groups was very low (8%). If liver biopsy results had been omitted, reliance on CT and other clinical staging procedures alone would have led to important staging errors in 18 of these 201 patients (9%) - overstaging would have occurred twice and understaging 16 times. In 7 additional patients, the lack of demonstration by CT of documented liver disease was without clinical consequence because disseminated extranodal lymphoma was visible at other sites or at extrahepatic regions of the same CT scan. In patients with newly diagnosed Hodgkin disease and non-Hodgkin lymphoma, CT is an unreliable indicator of liver status and cannot replace liver biopsy in supplying the data required for optimal management. (orig.) [de

  8. Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

    Science.gov (United States)

    2015-05-06

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved 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; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal 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 Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  9. Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Hertel, Christina B; Zhou, Xiao-ge; Hamilton-Dutoit, Stephen J

    2002-01-01

    In classical Hodgkin lymphoma the malignant Hodgkin/Reed-Sternberg (HRS) cells characteristically constitute only a small minority of the tumour load. Their origin has been debated for decades, but on the basis of rearrangement and somatic hypermutations of their immunoglubulin (Ig) genes, HRS...

  10. Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-02-05

    Aggressive Non-Hodgkin Lymphoma; CD20 Positive; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  11. SU-F-R-14: PET Based Radiomics to Predict Outcomes in Patients with Hodgkin Lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, J; Aristophanous, M; Akhtari, M; Milgrom, S; Bouthaina, D; Pinnix, C; Narang, S; Rao, A; Court, L; Smith, G [The University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To identify PET-based radiomics features associated with high refractory/relapsed disease risk for Hodgkin lymphoma patients. Methods: A total of 251 Hodgkin lymphoma patients including 19 primary refractory and 9 relapsed patients were investigated. All patients underwent an initial pre-treatment diagnostic FDG PET/CT scan. All cancerous lymph node regions (ROIs) were delineated by an experienced physician based on thresholding each volume of disease in the anatomical regions to SUV>2.5. We extracted 122 image features and evaluated the effect of ROI selection (the largest ROI, the ROI with highest mean SUV, merged ROI, and a single anatomic region [e.g. mediastinum]) on classification accuracy. Random forest was used as a classifier and ROC analysis was used to assess the relationship between selected features and patient’s outcome status. Results: Each patient had between 1 and 9 separate ROIs, with much intra-patient variability in PET features. The best model, which used features from a single anatomic region (the mediastinal ROI, only volumes>5cc: 169 patients with 12 primary refractory) had a classification accuracy of 80.5% for primary refractory disease. The top five features, based on Gini index, consist of shape features (max 3D-diameter and volume) and texture features (correlation and information measure of correlation1&2). In the ROC analysis, sensitivity and specificity of the best model were 0.92 and 0.80, respectively. The area under the ROC (AUC) and the accuracy were 0.86 and 0.86, respectively. The classification accuracy was less than 60% for other ROI models or when ROIs less than 5cc were included. Conclusion: This study showed that PET-based radiomics features from the mediastinal lymph region are associated with primary refractory disease and therefore may play an important role in predicting outcomes in Hodgkin lymphoma patients. These features could be additive beyond baseline tumor and clinical characteristics, and may warrant

  12. SU-F-R-14: PET Based Radiomics to Predict Outcomes in Patients with Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Lee, J; Aristophanous, M; Akhtari, M; Milgrom, S; Bouthaina, D; Pinnix, C; Narang, S; Rao, A; Court, L; Smith, G

    2016-01-01

    Purpose: To identify PET-based radiomics features associated with high refractory/relapsed disease risk for Hodgkin lymphoma patients. Methods: A total of 251 Hodgkin lymphoma patients including 19 primary refractory and 9 relapsed patients were investigated. All patients underwent an initial pre-treatment diagnostic FDG PET/CT scan. All cancerous lymph node regions (ROIs) were delineated by an experienced physician based on thresholding each volume of disease in the anatomical regions to SUV>2.5. We extracted 122 image features and evaluated the effect of ROI selection (the largest ROI, the ROI with highest mean SUV, merged ROI, and a single anatomic region [e.g. mediastinum]) on classification accuracy. Random forest was used as a classifier and ROC analysis was used to assess the relationship between selected features and patient’s outcome status. Results: Each patient had between 1 and 9 separate ROIs, with much intra-patient variability in PET features. The best model, which used features from a single anatomic region (the mediastinal ROI, only volumes>5cc: 169 patients with 12 primary refractory) had a classification accuracy of 80.5% for primary refractory disease. The top five features, based on Gini index, consist of shape features (max 3D-diameter and volume) and texture features (correlation and information measure of correlation1&2). In the ROC analysis, sensitivity and specificity of the best model were 0.92 and 0.80, respectively. The area under the ROC (AUC) and the accuracy were 0.86 and 0.86, respectively. The classification accuracy was less than 60% for other ROI models or when ROIs less than 5cc were included. Conclusion: This study showed that PET-based radiomics features from the mediastinal lymph region are associated with primary refractory disease and therefore may play an important role in predicting outcomes in Hodgkin lymphoma patients. These features could be additive beyond baseline tumor and clinical characteristics, and may warrant

  13. Power laws from linear neuronal cable theory

    DEFF Research Database (Denmark)

    Pettersen, Klas H; Lindén, Henrik Anders; Tetzlaff, Tom

    2014-01-01

    suggested to be at the root of this phenomenon, we here demonstrate a possible origin of such power laws in the biophysical properties of single neurons described by the standard cable equation. Taking advantage of the analytical tractability of the so called ball and stick neuron model, we derive general...... expressions for the PSD transfer functions for a set of measures of neuronal activity: the soma membrane current, the current-dipole moment (corresponding to the single-neuron EEG contribution), and the soma membrane potential. These PSD transfer functions relate the PSDs of the respective measurements...... to the PSDs of the noisy input currents. With homogeneously distributed input currents across the neuronal membrane we find that all PSD transfer functions express asymptotic high-frequency [Formula: see text] power laws with power-law exponents analytically identified as [Formula: see text] for the soma...

  14. Early therapy monitoring with FDG-PET in aggressive non-Hodgkin's lymphoma and Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Torizuka, Tatsuo; Nakamura, Fumitoshi; Kanno, Toshihiko; Ouchi, Yasuomi; Futatsubashi, Masami; Yoshikawa, Etsuji; Okada, Hiroyuki; Kobayashi, Masahide

    2004-01-01

    This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkin's lymphoma and three patients with Hodgkin's lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1-2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1-2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24-34 months) while the other six have relapsed (PFS 8-16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1-2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1-2 cycles of therapy as compared with the non-responders (81.2%±9.5% vs 35.0%±20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma. (orig.)

  15. Linfoma não Hodgkin gástrico Gastric non-Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Renata O. Costa

    2010-02-01

    Full Text Available Os linfomas extralinfonodais representam aproximadamente 1/3 de todos os linfomas não Hodgkin (LNH e, embora possam ter início em qualquer tecido, mais frequentemente acometem o trato gastrointestinal, sendo o estômago o órgão responsável pela grande maioria dos casos. Os linfomas primários gástricos são comumente LNH, sendo representados em mais de 95% dos casos pelo linfoma difuso de grandes células B e pelo linfoma MALT (mucosa associated lymphoid tissue. De evolução indolente, o linfoma MALT destaca-se por ser um modelo de câncer secundário à estimulação antigênica crônica exercida por uma bactéria denominada Helicobacter pylori (HP. No outro polo, situa-se o linfoma difuso de células B (LDGCB, que, de patogênese duvidosa, pode tratar-se de uma transformação de LNH MALT ou ainda se caracterizar por um linfoma "de novo". Neste estudo, revisamos a literatura, enfatizando aspectos importantes à prática clínica destes linfomas.Extranodal lymphomas account for about 30% of all non-Hodgkin lymphomas (NHL, and although they can originate in any tissue, the gastrointestinal tract is the most commonly affected structure with the stomach being the most common subtype. Diffuse Large B cell lymphoma (DLBCL and MALT (mucosa associated lymphoid tissue lymphoma account for more than 95% of the cases of gastric lymphoma. The indolent development of MALT lymphoma stands out as it is a type of cancer subject to chronic antigen stimulation by the Helicobacter pylori bacteria. Conversely, diffuse large B cell lymphomas, whose pathogenesis is uncertain, can be a transformation from MALT NHL or perhaps a new type of lymphoma. In this study we carried out a review of the literature, stressing the key aspects of these lymphomas in the clinical practice.

  16. Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

    Science.gov (United States)

    Tyran, Marguerite; Gonzague, Laurence; Bouabdallah, Reda; Resbeut, Michel

    2014-01-01

    Localized Nodular Lymphocyte Predominant Hodgkin Lymphoma is a rare disease with an overall good prognosis but frequent late relapses. Due to it's rarity there is no standard therapeutic approach and pathological diagnosis may be hard. In this paper we discuss the technical aspects of the radiation therapy and histological issues. The new fields reductions proposed for classical Hodgkin lymphoma cannot be applied to early stages Nodular Lymphocyte Predominant Hodgkin lymphomas which are usually treated with radiation therapy without systemic chemotherapy.

  17. Hodgkin's disease: internal mammary lymph nodes relapse diagnosed by Gallium-67 scintigraphy

    International Nuclear Information System (INIS)

    Ruiz Hernandez, G.; Ampudia, J.; Castillo, F.J.; Romero, C.; Pallardo, Y.; Garcia Conde, J.; Ramos, D.

    1999-01-01

    This article presents the case of a 62-year-old man with treated Hodgkin's disease who had internal mammary lymph nodes relapse after a complete initial response. These masses were gallium avid. These findings were explained by histologically documented Hodgkin's relapse, the first such case reported in that localization without chest wall involvement. The literature on mediastinal Hodgkin's disease and diagnostic procedures are reviewed. (orig.) [de

  18. Recent Advances in the Pathobiology of Hodgkin's Lymphoma: Potential Impact on Diagnostic, Predictive, and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Diponkar Banerjee

    2011-01-01

    Full Text Available From its first description by Thomas Hodgkin in 1832, Hodgkin's disease, now called Hodgkin's lymphoma, has continued to be a fascinating neoplasm even to this day. In this review, historical aspects, epidemiology, diagnosis, tumor biology, new observations related to host-microenvironment interactions, gene copy number variation, and gene expression profiling in this complex neoplasm are described, with an exploration of chemoresistance mechanisms and potential novel therapies for refractory disease.

  19. APPLICATION OF UKRAINIAN GRID INFRASTRUCTURE FOR INVESTIGATION OF NONLINEAR DYNAMICS IN LARGE NEURONAL NETWORKS

    Directory of Open Access Journals (Sweden)

    O. О. Sudakov

    2015-12-01

    Full Text Available In present work the Ukrainian National Grid (UNG infrastructure was applied for investigation of synchronization in large networks of interacting neurons. This application is important for solving of modern neuroscience problems related to mechanisms of nervous system activities (memory, cognition etc. and nervous pathologies (epilepsy, Parkinsonism, etc.. Modern non-linear dynamics theories and applications provides powerful basis for computer simulations of biological neuronal networks and investigation of phenomena which mechanisms hardly could be clarified by other approaches. Cubic millimeter of brain tissue contains about 105 neurons, so realistic (Hodgkin-Huxley model and phenomenological (Kuramoto-Sakaguchi, FitzHugh-Nagumo, etc. models simulations require consideration of large neurons numbers.

  20. A new model of artificial neuron: cyberneuron and its use

    OpenAIRE

    Polikarpov, S. V.; Dergachev, V. S.; Rumyantsev, K. E.; Golubchikov, D. M.

    2009-01-01

    This article describes a new type of artificial neuron, called the authors "cyberneuron". Unlike classical models of artificial neurons, this type of neuron used table substitution instead of the operation of multiplication of input values for the weights. This allowed to significantly increase the information capacity of a single neuron, but also greatly simplify the process of learning. Considered an example of the use of "cyberneuron" with the task of detecting computer viruses.

  1. Synaptic Plasticity and Spike Synchronisation in Neuronal Networks

    Science.gov (United States)

    Borges, Rafael R.; Borges, Fernando S.; Lameu, Ewandson L.; Protachevicz, Paulo R.; Iarosz, Kelly C.; Caldas, Iberê L.; Viana, Ricardo L.; Macau, Elbert E. N.; Baptista, Murilo S.; Grebogi, Celso; Batista, Antonio M.

    2017-12-01

    Brain plasticity, also known as neuroplasticity, is a fundamental mechanism of neuronal adaptation in response to changes in the environment or due to brain injury. In this review, we show our results about the effects of synaptic plasticity on neuronal networks composed by Hodgkin-Huxley neurons. We show that the final topology of the evolved network depends crucially on the ratio between the strengths of the inhibitory and excitatory synapses. Excitation of the same order of inhibition revels an evolved network that presents the rich-club phenomenon, well known to exist in the brain. For initial networks with considerably larger inhibitory strengths, we observe the emergence of a complex evolved topology, where neurons sparsely connected to other neurons, also a typical topology of the brain. The presence of noise enhances the strength of both types of synapses, but if the initial network has synapses of both natures with similar strengths. Finally, we show how the synchronous behaviour of the evolved network will reflect its evolved topology.

  2. Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma. New study concepts of the German Hodgkin Study Group

    Energy Technology Data Exchange (ETDEWEB)

    Baues, C.; Semrau, R.; Marnitz, S. [University of Cologne, Medical Faculty, Department of Radiooncology, Cologne (Germany); University of Cologne, German Hodgkin Study Group (GHSG), Cologne (Germany); Gaipl, U.S. [University Hospital Erlangen, Department of Radiooncology, Erlangen (Germany); Broeckelmann, P.J.; Engert, A. [University of Cologne, German Hodgkin Study Group (GHSG), Cologne (Germany); University of Cologne, Medical Faculty, Department of Internal Medicine I, Cologne (Germany); Rosenbrock, J. [University of Cologne, Medical Faculty, Department of Radiooncology, Cologne (Germany)

    2017-02-15

    Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL. (orig.) [German] Patienten mit einem klassischen Hodgkin-Lymphom (cHL) haben ueber alle Stadien hinweg eine gute Prognose. Allerdings treten unter der kombinierten Therapie mit Chemotherapie und Bestrahlung therapieabhaengige Toxizitaeten wie z. B. Organschaeden, Sekundaertumoren, Fatigue oder Langzeit-Fatigue auf. Viele Patienten leiden trotz einer Heilung an diesen Symptomen. Daher bietet die nachgewiesene Wirksamkeit der Anti-PD1/PD-L1-Antikoerper bei soliden Tumoren, aber auch beim HL neue Behandlungsoptionen. Bei intensiv vorbehandelten Patienten mit rezidiviertem cHL wurde bei guter Vertraeglichkeit eine hohe Ansprechrate mit z. T. langanhaltenden Remissionen beobachtet. Im Rahmen der Planung prospektiver randomisierter Studien im

  3. [Limphomatous meningitis as recurrence site in Hodgkin's disease].

    Science.gov (United States)

    Greco, Martín; Valsecchi, Matías; Niccodemi, Cecilia; Presas, José; Corrado, Claudia; Winkel, Martín

    2006-01-01

    Intracraneal manifestations of Hodgkin's Disease (HD) are extremely rare, with an estimated incidence rate of approximately 0.5%. They can be classified as: 1) treatment-related leucoencephalopathy, 2) central nervous system infections, 3) paraneoplasic syndromes and 4) intracraneal lymphomas, which could be sub-classified into intraparenchymal or intradural masses. We describe a case of a 40 year-old male with mixed cellularity type HD who developed neurological manifestations as relapsed disease. Magnetic resonance imaging suggested leptomeningeal metastases and atypical cells were found in cerebrospinal fluid. The patient died from progressive disease refractory to third line chemotherapy. There are less than 50 similar cases reported in the literature. We review the clinical features and differential diagnosis of leptomeningeal metastases in Hodgkin's disease.

  4. Clinico-pathologic correlation in non-Hodgkins's lymphoma. IV

    International Nuclear Information System (INIS)

    Lenner, P.; Lundgren, E.; Damber, L.

    1981-01-01

    A retrospective analysis of 140 patients with non-Hodgkin's lymphoma in clinical stage I or II classified according to a modified Lukes and Collins scheme was performed. Three major groups were found according to cell type, with different clinical features: (1) Small cell lymphomas with a relatively favourable survival in spite of high relapse rates. (2) Large cell lymphomas with lower relapse rates, but short time between relapse and death, and unfavourable survival. (3) Mixed small/large cleaved follicular centre cell lymphoma which was most favourable with respect to relapse and survival. Nodular lymphoma had the same overall relapse rate as diffuse lymphoma, but had a significantly longer survival. Tumours stage I were associated with significantly longer relapse-free survival and survival than stage II. The importance of separating the majority of non-Hodgkin's lymphomas into three main groups according to cell type is emphasized. These major groups require clinical approaches in terms of staging and treatment. (Auth.)

  5. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    Science.gov (United States)

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  6. Concurrent Presentation of Hodgkin Lymphoma and Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Rekha Chandran

    2013-01-01

    Full Text Available The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72-year-old patient who initially presented with generalized pruritis. Workup led to a diagnosis of multiple myeloma which progressed and required treatment. As part of his pretreatment workup, an MRI was performed to evaluate skeletal lesions. This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy of an axillary node was consistent with the nodular sclerosing type Hodgkin lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD chemotherapy × 6 resulting in complete resolution of his adenopathy and pruritis as well as improvement in his myeloma.

  7. Gallium scan in recurrent Hodgkin's disease in children

    International Nuclear Information System (INIS)

    Yeh, S.D.; Benua, R.S.; Tan, C.T.

    1979-01-01

    In 18 of 88 children with biopsy proven and previously untreated Hodgkin's disease, recurrence developed during a period from four to 53 months after therapy (median period, 22 months). In 16 patients in whom gallium scans were performed, 21 positive gallium scans were obtained during 26 episodes of recurrence. Abnormalities were noted in half of them during a period from one to 10 months prior to physical, laboratory, radiographic or histologic confirmation of recurrence (median period about 5 months). We have concluded that the gallium scan is very useful in initial workup and is sensitive in detecting early recurrence in children with Hodgkin's disease. Such scans are indicated when there is clinical suspicion of recurrence, when other modalities are unavailable or when the results of other studies are equivocal

  8. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-01-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently

  9. Graves disease with ophthalmopathy following radiotherapy for Hodgkin's disease

    International Nuclear Information System (INIS)

    Jacobson, D.R.; Fleming, B.J.

    1984-01-01

    The number of patients achieving long-term survival following neck irradiation for Hodgkin's disease and other malignancies is increasing. Paralleling this increase in survivors is the development of late complications of the therapy itself. Eleven patients have previously been reported who developed Graves ophthalmopathy 18 months to seven years after receiving neck radiotherapy for nonthyroidal malignancies. The seven patients who had HLA typing were all HLA-B8 negative, despite the reported association of the HLA-B8 antigen with Graves disease. A patient who is HLA-B8 positive who developed Graves ophthalmopathy and hyperthyroidism nine years after receiving mantle radiotherapy for Hodgkin's disease is reported. It is recommended that Graves disease be included among the thyroid diseases that receive consideration during follow-up of patients who have received mantle radiotherapy

  10. Stomach Cancer Following Hodgkin Lymphoma, Testicular Cancer and Cervical Cancer

    DEFF Research Database (Denmark)

    Gilbert, Ethel S; Curtis, Rochelle E; Hauptmann, Michael

    2017-01-01

    To further understand the risk of stomach cancer after fractionated high-dose radiotherapy, we pooled individual-level data from three recent stomach cancer case-control studies. These studies were nested in cohorts of five-year survivors of first primary Hodgkin lymphoma (HL), testicular cancer...... (TC) or cervical cancer (CX) from seven countries. Detailed data were abstracted from patient records and radiation doses were reconstructed to the site of the stomach cancer for cases and to the corresponding sites for matched controls. Among 327 cases and 678 controls, mean doses to the stomach were...... 15.3 Gy, 24.7 Gy and 1.9 Gy, respectively, for Hodgkin lymphoma, testicular cancer and cervical cancer survivors, with an overall mean dose of 10.3 Gy. Risk increased with increasing radiation dose to the stomach cancer site (P

  11. Malignant mesothelioma after radiation treatment for Hodgkin lymphoma

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Burgers, Jacobus A; Baas, Paul

    2009-01-01

    Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the disease may be associated with radiation exposure. Recently, increased risks for second primary mesothelioma after radiation for lymphoma have been reported. Because...... these findings are based on small numbers of patients, they need to be confirmed. We examined mesothelioma risk in 2567 5-year survivors of Hodgkin lymphoma. The risk was almost 30-fold increased in Hodgkin lymphoma patients treated with irradiation compared with the general population. Although histology...... and survival of the mesothelioma cases were comparable with cases from the general population, asbestos exposure and the proportion of males were lower than expected. The evidence for radiotherapy as cause for mesothelioma independent of exposure to asbestos is expanding, and the diagnosis of mesothelioma...

  12. Renal and perirenal non-Hodgkin's lymphoma: CT findings

    International Nuclear Information System (INIS)

    Lee, Seon Kyu; Kim, Seung Hyup; Lee, Goo; Choi, Byeung In; Han, Man Chung

    1992-01-01

    CT findings of 19 kidneys in 12 patients with renal and perirenal non-Hodgkin's lymphoma were retrospectively reviewed to determine distinguishing characteristic and specific findings. CT manifestation of the renal and perirenal lymphoma included multiple nodules in five kidneys(26.3%), trans-capsular infiltration in three kidneys(15.8%), trans-sinus infiltration in nine kidneys(47.4%) and diffuse infiltration in two kidneys(10.5%). Perirenal changes were thickening of the renal fascia in ten kidneys(52.6%) and crescent lesion of low attenuation in the subcapsular area in five kidneys(26.3%) Retroperitoneal lymphadenopathy was evident in eleven patient(57.9%). Renal calyceal dilatation without renal pelvic dilatation(selective calycelal dilatation) was noted in three kidneys. Familiarity with these CT findings of renal and perirenal lymphoma may be helpful in the diagnosis and management of patient with non-Hodgkin's lymphoma

  13. Calcifications in mediastinal lymphoma after radiation therapy of Hodgkin's disease

    International Nuclear Information System (INIS)

    Frank, P.; Menges, V.

    1976-01-01

    One case of calcifications in mediastinal lymphoma after radiation therapy of Hodgkin's disease is reported. The incidence of these calcifications is remarkably low. They are mostly localized in the anterior mediastinum showing a characteristical pattern which is initially stippled, later confluent and coral-shaped. An open interval after radiation therapy is typical for this phenomenon. The cause of the calcifications is discussed. (orig.) [de

  14. [Presentation of a case of cervical actinomycosis versus Hodgkin lymphoma].

    Science.gov (United States)

    Viscasillas Pallás, G; Cisa Lluís, E; Cruellas Taischik, F; Doménech Juan, I; Dicenta Sousa, M

    2005-01-01

    Actinomycosis is an unfrequent bacterian infection, that affects 50% of the cases in the cervical facial region. The evolution and clinical, anatomopathologic radiologic characteristic, and its presentation bring us to suspect another type of more frequent pathology: the neoplastic, that make very difficult its diagnosis. We present the case of a young patient affected by a cervical tumoration initially oriented as Hodgkin lymphoma that finally was diagnosed as cervical actinomycosis and treated with penicillin.

  15. Optimization of treatment of children with 3 stage Hodgkin's disease

    International Nuclear Information System (INIS)

    Kobikov, S.Kh.

    1989-01-01

    147 children younger than 15 years suffering from the 3rd stage of Hodgkins children is performed using gamma therapeutic Rocus type devices and betatron (B5M-25) and linear accelerator (LUEh-25) of 15-27.5 MeV energy electrons. Immediate and delayed treatment results are evaluated. Unfavourable clinical factors effecting the recurrence frequency are revealed. Inconsistence of supporting chemotherapy in the reduction of the number of recurrents is confirmed

  16. Vitiligo at the sites of irradiation in a patient with Hodgkin's disease

    Energy Technology Data Exchange (ETDEWEB)

    Pajonk, F.; Weissenberger, C.; Witucki, G.; Henke, M. [Radiological Univ. Clinic, Freiburg (Germany). Dept. of Radiation Therapy

    2002-03-01

    Background: Vitiligo is one of the most common skin disorders. However, the etiology of vitiligo is still unknown. Current hypotheses discuss autoimmune, autotoxic and neuronal mechanisms. Here we report the case of radiation-induced depigmentation of the skin of a patient with Hodgkin's disease and 25-year history of vitiligo. Patient and Method: We compared possible differences in skin color, skin moisture, microcirculation and skin elasticity between normal skin and skin exhibiting persistent depigmentation in a 37-year-old patient 40 months after completion of external beam radiotherapy. Results: Colormetrically we found a dose-dependent decrease of the red/green and yellow/blue saturation combined with an overall increase in brightness in depigmented skin when compared with normal skin. This was in agreement with a loss of melanocytes in vitiligo. Depigmentation was complete in areas receiving 40 Gy. Areas which received 30 Gy showed depigmentation only if the skin dose was increased by the loss of depth of the build-up dose region in areas with direct contact with the irradiation table. We could not show any change in skin moisture, microcirculation or skin elasticity. Conclusions: Complete radiation-induced depigmentation of skin from patients suffering from vitiligo is a side effect of radiation therapy. Patients should be informed about this side effect by the radiooncologist. Preventing the loss of depth of the build-up dose region might improve the cosmetic results of radiation therapy in patients with history of vitiligo. (orig.)

  17. [No Hodgkin Linfoma diagnosis with intra-atrial infiltration].

    Science.gov (United States)

    Alcocer Gamba, Marco Antonio; León González, Salvador; Castro Montes, Eliodoro; Loarca Piña, Luis Martín; Lugo Gavidia, Leslie Marisol; García Hernández, Enrique; González Galindo, Ulises; Paredes Serrano, Miguel Isaías

    2012-09-01

    Cardiac tumors are rare entities in clinical practice, with an incidence of 0.05%. Approximately 75% are benign and 25% malignant. Among these, Lymphomas are uncommon, representing about 0.25%. The non-Hodgkin lymphomas can occur in extranodal tissues in 20% of the cases and 80% of these non-Hodgkin lymphomas are composed of diffuse B cells. The extranodal presentation is most frequent in young adults, with a high degree of malignancy and rapid growth. It can present with primary infiltration of various organs; cardiac involvement occurs in 20 to 28% of cases, usually located in the right chambers and with nonspecific symptoms, depending on the location and extent of the tumor. The diagnostic test in these cases is undoubtedly the biopsy of the lymph node or the affected tissue. We present the case of non-Hodgkin disease of diffuse large cells, with right intra-atrial involvement in a 23-year-old-female patient, who presented with progressive dyspnea. A transesophageal echocardiography was performed and an intra-atrial tumor mass was detected. A biopsy was performed, by femoral venous catheterization, allowing the establishment of the histopathological diagnosis and treatment. At a one year follow up, the patient shows complete remission.

  18. Primary non-Hodgkin's lymphoma of the mediastinum

    International Nuclear Information System (INIS)

    Levitt, L.J.; Aisenberg, A.C.; Harris, N.L.; Linggood, R.M.; Poppema, S.

    1982-01-01

    Non-Hodgkin's lymphoma localized to the mediastinum and adjacent structures occurred in 12 of 215 (6%) non-Hodgkin's lymphoma patients seen at the Massachusetts General Hospital between 1975 and 1979. Lymphangiography, radionuclide scanning and whole body computerized tomography were used to exclude patients with extrathoracic disease at presentation. Eleven of the 12 patients presented with extensive contiguous extranodal disease (Stage II/sub E/) with involvement of either the pericardium, sternum, chest wall, pulmonary parenchyma or, in four cases, with superior venacaval obstruction. Diffuse large cell lymphoma (eight cases) and diffuse poorly differentiated lymphocytic lymphoma (four cases) were the prevalent histologic subtypes; no instances of lymphoblastic lymphoma without extra-thoracic spread were encountered. None of four lymphomas studied could be characterized as either B- or T-cell tumors utilizing conventional surface marker techniques. Ten of the 12 patients achieved complete remissions, either after treatment with combination chemotherapy alone (three patients) or after both chemotherapy and mediastinal irradiation (seven patients). Two of these ten have subsequently relapsed, but median survival has not been reached after a mean period of observation of 28 months. Primary nonlymphoblastic non-Hodgkin's lymphoma of the mediastinum is more common than previously realized, displays aggressive contiguous spread within the chest and responds well to combination chemotherapy with or without adjuvant mediastinal irradiation

  19. [Predictive value of Hodgkin's lymphoma tumor burden in present].

    Science.gov (United States)

    Kulyova, S A; Karitsky, A P

    2014-01-01

    Today approximately 70% of patients with Hodgkin lymphoma can be cured with the combined-modality therapy. Tumor burden, the importance of which was demonstrated 15 years ago for the first time, is a powerful prognostic factor. Data of literature of representations on predictive value of Hodgkin's lymphoma tumor burden are shown in the article. The difficult immunological relations between tumor cells and reactive ones lead to development of the main symptoms. Nevertheless, the collective sign of tumor burden shows the greatest influence on survival and on probability of resistance, which relative risk can be predicted on this variable and treatment program. Patients with bulky disease need escalated therapy with high-dose chemotherapy. Integration into predictive models of the variable will change an expected contribution of clinical and laboratory parameters in the regression analyses constructed on patients with Hodgkin's lymphoma. Today the role of diagnostic functional methods, in particular a positron emission tomography, for metabolic active measurement is conducted which allows excluding a reactive component.

  20. KIR genotype distribution among Lebanese patients with Hodgkin's lymphoma.

    Science.gov (United States)

    Hoteit, Rouba; Abboud, Miguel; Bazarbachi, Ali; Salem, Ziad; Shammaa, Dina; Zaatari, Ghazi; Mahfouz, Rami

    2015-06-01

    In addition to their important role in fighting infection, natural killer cells are cytotoxic to cancer cells. Studies demonstrated that some KIR genes were responsible for the reduction of the risk of Hodgkin's lymphoma (HL) while others were associated with an increased risk of HL. The aim of this study is to assess KIR genotypic distribution in Lebanese patients with Hodgkin's lymphoma. KIR genotype was analyzed in 41 HL patients and 120 healthy Lebanese individuals using the KIR Genotyping SSP kit. No significant association between HL and any KIR gene was found. Among HL patients, the AA, AB, and BB genotype frequencies were, respectively, 41.46%, 43.9% and 14.63% with an A:B ratio of 1.73:1. As for the controls, the AA, AB, and BB genotype frequencies were, respectively, 39.17%, 50%, and 10.83% with an A:B ratio of 1.79:1. In this first study from the Mediterranean region, KIR genotype does not seem to be associated with Hodgkin's lymphoma. Further clinical and translational research is needed to rule out the protective or predisposing role of KIR genes in this important clinical entity.

  1. Risk of Hodgkin's disease and other cancers after infectious mononucleosis

    DEFF Research Database (Denmark)

    Hjalgrim, H; Askling, J; Sørensen, P

    2000-01-01

    followed for cancer occurrence. The ratio of observed-to-expected numbers of cancers (standardized incidence ratio [SIR]) served as a measure of the relative risk for cancer. SIRs of Hodgkin's disease in different subsets of patients were compared with the use of Poisson regression analysis. All...... statistical tests including the trend tests were two-sided. RESULTS: A total of 1381 cancers were observed during 689 619 person-years of follow-up among 38 562 infectious mononucleosis patients (SIR = 1. 03; 95% confidence interval [CI] = 0.98-1.09). Apart from Hodgkin's disease (SIR = 2.55; 95% CI = 1.......87-3.40; n = 46), only skin cancers (SIR = 1.27; 95% CI = 1.13-1.43; n = 291) occurred in statistically significant excess. In contrast, the SIR for lung cancer was reduced (SIR = 0.71; 95% CI = 0.58-0.86; n = 102). The SIR for Hodgkin's disease remained elevated for up to two decades after the occurrence...

  2. Power-Law Dynamics of Membrane Conductances Increase Spiking Diversity in a Hodgkin-Huxley Model.

    Science.gov (United States)

    Teka, Wondimu; Stockton, David; Santamaria, Fidel

    2016-03-01

    We studied the effects of non-Markovian power-law voltage dependent conductances on the generation of action potentials and spiking patterns in a Hodgkin-Huxley model. To implement slow-adapting power-law dynamics of the gating variables of the potassium, n, and sodium, m and h, conductances we used fractional derivatives of order η≤1. The fractional derivatives were used to solve the kinetic equations of each gate. We systematically classified the properties of each gate as a function of η. We then tested if the full model could generate action potentials with the different power-law behaving gates. Finally, we studied the patterns of action potential that emerged in each case. Our results show the model produces a wide range of action potential shapes and spiking patterns in response to constant current stimulation as a function of η. In comparison with the classical model, the action potential shapes for power-law behaving potassium conductance (n gate) showed a longer peak and shallow hyperpolarization; for power-law activation of the sodium conductance (m gate), the action potentials had a sharp rise time; and for power-law inactivation of the sodium conductance (h gate) the spikes had wider peak that for low values of η replicated pituitary- and cardiac-type action potentials. With all physiological parameters fixed a wide range of spiking patterns emerged as a function of the value of the constant input current and η, such as square wave bursting, mixed mode oscillations, and pseudo-plateau potentials. Our analyses show that the intrinsic memory trace of the fractional derivative provides a negative feedback mechanism between the voltage trace and the activity of the power-law behaving gate variable. As a consequence, power-law behaving conductances result in an increase in the number of spiking patterns a neuron can generate and, we propose, expand the computational capacity of the neuron.

  3. Shaping Neuronal Network Activity by Presynaptic Mechanisms.

    Directory of Open Access Journals (Sweden)

    Ayal Lavi

    2015-09-01

    Full Text Available Neuronal microcircuits generate oscillatory activity, which has been linked to basic functions such as sleep, learning and sensorimotor gating. Although synaptic release processes are well known for their ability to shape the interaction between neurons in microcircuits, most computational models do not simulate the synaptic transmission process directly and hence cannot explain how changes in synaptic parameters alter neuronal network activity. In this paper, we present a novel neuronal network model that incorporates presynaptic release mechanisms, such as vesicle pool dynamics and calcium-dependent release probability, to model the spontaneous activity of neuronal networks. The model, which is based on modified leaky integrate-and-fire neurons, generates spontaneous network activity patterns, which are similar to experimental data and robust under changes in the model's primary gain parameters such as excitatory postsynaptic potential and connectivity ratio. Furthermore, it reliably recreates experimental findings and provides mechanistic explanations for data obtained from microelectrode array recordings, such as network burst termination and the effects of pharmacological and genetic manipulations. The model demonstrates how elevated asynchronous release, but not spontaneous release, synchronizes neuronal network activity and reveals that asynchronous release enhances utilization of the recycling vesicle pool to induce the network effect. The model further predicts a positive correlation between vesicle priming at the single-neuron level and burst frequency at the network level; this prediction is supported by experimental findings. Thus, the model is utilized to reveal how synaptic release processes at the neuronal level govern activity patterns and synchronization at the network level.

  4. Linfoma não-Hodgkin de órbita: relato de caso Non-Hodgkin orbital lymphoma: case report

    Directory of Open Access Journals (Sweden)

    Cristiane do Prado Silva

    2008-04-01

    Full Text Available O objetivo é relatar manifestação incomum de linfoma não-Hodgkin de órbita. Paciente masculino, de 75 anos, se apresentou com queixa de lacrimejamento crônico bilateral. Havia feito dacriocistorrinostomia endonasal à direita e à esquerda por duas vezes, sem sucesso. Ao exame, massas de consistência fibroelástica, em topografia das "bolsas" de gordura das pálpebras inferiores e proptose axial. O paciente negava outros sintomas ou sinais sistêmicos. Hemograma sem alteração, hormônios tireoidianos normais. A tomografia computadorizada mostrava infiltrado difuso na órbita e proptose axial. Biópsia de gordura orbitária e de medula óssea diagnosticaram linfoma não-Hodgkin. O paciente foi tratado com quimioterapia, sendo em seguida submetido à cirurgia da via lacrimal bilateral, com resolução do quadro. A doença sistêmica que exigia diagnóstico e tratamento adequados para que se tivesse bom prognóstico estava mascarada pelo quadro de epífora bilateral.The purpose is to report an unusual case of orbital non-Hodgkin lymphoma. A 75-year-old man presented with bilateral chronic epiphora complaint and inferior eyelid tumors, axial proptosis, without previous systemic manifestation. The patient was submitted to bilateral endonasal dacryocystorhinostomy twice and the epiphora complaint persisted. The inferior eyelid and bone marrow biopsy revealed non-Hodgkin lymphoma. The patient was treated with systemic chemotherapy and dacryocystorhinostomy with good resolution. The precise diagnosis and the treatment were very important to reach a good resolution of the bilateral epiphora complaint.

  5. Checkpoint inhibitors and radiation treatment in Hodgkin's lymphoma. New study concepts of the German Hodgkin Study Group

    International Nuclear Information System (INIS)

    Baues, C.; Semrau, R.; Marnitz, S.; Gaipl, U.S.; Broeckelmann, P.J.; Engert, A.; Rosenbrock, J.

    2017-01-01

    Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients. Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin's lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts. Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials. The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL. (orig.) [de

  6. FDG PET for therapy monitoring in Hodgkin and non-Hodgkin lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Barrington, Sally F. [St. Thomas' Hospital, PET Imaging Centre, King' s College London and Guy' s, King' s Health Partners, London (United Kingdom); Kluge, Regine [University Hospital of Leipzig, Department of Nuclear Medicine, Leipzig (Germany)

    2017-08-15

    PET using {sup 18}F-FDG for treatment monitoring in patients with lymphoma is one of the most well-developed clinical applications. PET/CT is nowadays used during treatment to assess chemosensitivity, with response-adapted therapy given according to 'interim' PET in clinical practice to adults and children with Hodgkin lymphoma. PET is also used to assess remission from disease and to predict prognosis in the pretransplant setting. Mature data have been reported for the common subtypes of aggressive B-cell lymphomas, with more recent data also supporting the use of PET for response assessment in T-cell lymphomas. The Deauville five-point scale incorporating the Deauville criteria (DC) is recommended for response assessment in international guidelines. FDG uptake is graded in relation to the reference regions of normal mediastinum and liver. The DC have been validated in most lymphoma subtypes. The DC permit the threshold for adequate or inadequate response to be adapted according to the clinical context or research question. It is important for PET readers to understand how the DC have been applied in response-adapted trials for correct interpretation and discussion with the multidisciplinary team. Quantitative methods to perform PET in standardized ways have also been developed which may further improve response assessment including a quantitative extension to the DC (qPET). This may have advantages in providing a continuous scale to refine the threshold for adequate/inadequate response in specific clinical situations or treatment optimization in trials. qPET is also less observer-dependent and limits the problem of optical misinterpretation due to the influence of background activity. (orig.)

  7. Yttrium-90 ibritumomab tiuxetan in the treatment of non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    McKinney MS

    2014-08-01

    Full Text Available Matthew S McKinney, Anne W Beaven Division of Hematologic Malignancies, Department of Medicine, Duke University Medical Center, Durham, NC, USA Abstract: Most cases of indolent non-Hodgkin lymphoma (NHL are incurable with standard chemoimmunotherapy approaches, and patients with relapsed/refractory disease have progressively shorter remissions and short survival with subsequent chemotherapy regimens. This may potentially be overcome with diversification of treatment strategies to include other modalities including radiotherapy, small molecule signaling transduction inhibitors, or high-dose chemotherapy with stem cell support. Yttrium-90 ibritumomab tiuxetan (Zevalin® is a novel treatment entity for indolent NHL. A radiolabeled antibody conjugate, it consists of a murine anti-CD20 antibody linked to a chelator molecule, tiuxetan, which is bound to radioactive yttrium. Yttrium-90 ibritumomab tiuxetan is approved for use as consolidation after initial treatment of follicular lymphoma as well as single-agent therapy in relapsed/refractory B-cell NHL. Responses are seen even in patients refractory to conventional cytotoxic chemotherapy and rituximab in both indolent and aggressive NHL subtypes. Recent clinical studies have also shown that yttrium-90 ibritumomab tiuxetan has significant activity when combined with novel targeted small molecular inhibitors as well as in autologous and allogeneic transplantation regimens. Here we review the biology underlying the efficacy of yttrium-90 ibritumomab tiuxetan in NHL and present an overview of the clinical experience with this agent in NHL. Finally, we discuss the current role of yttrium-90 ibritumomab tiuxetan in the armamentarium of treatments for NHL and possibilities for incorporating it into future NHL treatment algorithms. Keywords: non-Hodgkin lymphoma, indolent, CD20, radioimmunotherapy, ibritumomab tiuxetan

  8. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  9. NBLAST: Rapid, Sensitive Comparison of Neuronal Structure and Construction of Neuron Family Databases.

    Science.gov (United States)

    Costa, Marta; Manton, James D; Ostrovsky, Aaron D; Prohaska, Steffen; Jefferis, Gregory S X E

    2016-07-20

    Neural circuit mapping is generating datasets of tens of thousands of labeled neurons. New computational tools are needed to search and organize these data. We present NBLAST, a sensitive and rapid algorithm, for measuring pairwise neuronal similarity. NBLAST considers both position and local geometry, decomposing neurons into short segments; matched segments are scored using a probabilistic scoring matrix defined by statistics of matches and non-matches. We validated NBLAST on a published dataset of 16,129 single Drosophila neurons. NBLAST can distinguish neuronal types down to the finest level (single identified neurons) without a priori information. Cluster analysis of extensively studied neuronal classes identified new types and unreported topographical features. Fully automated clustering organized the validation dataset into 1,052 clusters, many of which map onto previously described neuronal types. NBLAST supports additional query types, including searching neurons against transgene expression patterns. Finally, we show that NBLAST is effective with data from other invertebrates and zebrafish. VIDEO ABSTRACT. Copyright © 2016 MRC Laboratory of Molecular Biology. Published by Elsevier Inc. All rights reserved.

  10. A COMPUTATIONAL MODEL OF MOTOR NEURON DEGENERATION

    Science.gov (United States)

    Le Masson, Gwendal; Przedborski, Serge; Abbott, L.F.

    2014-01-01

    SUMMARY To explore the link between bioenergetics and motor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP production and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeostasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fasciculation-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fasciculation, and differential vulnerability of motor neuron subpopulations. PMID:25088365

  11. Fertility and sexual function in female Hodgkin lymphoma survivors of reproductive age

    NARCIS (Netherlands)

    Eeltink, C.M.; Incrocci, L.; Witte, B.I.; Meurs, S.; Visser, O.; Huijgens, P.C.; de Leeuw, I.M.

    2013-01-01

    Aims and objectives: To assess the perceived fertility status and to determine the association between perceived fertility status and sexual function, as reported by young female Hodgkin lymphoma survivors. Background: Young female Hodgkin lymphoma survivors are at risk of infertility and impaired

  12. Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma)

    NARCIS (Netherlands)

    Rudiger, T; Jaffe, ES; Delsol, G; deWolf-Peeters, C; Gascoyne, RD; Georgii, A; Harris, NL; Kadin, ME; MacLennan, KA; Poppema, S; Stein, H; Weiss, LE; Muller-Hermelink, HK

    1998-01-01

    Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare

  13. Thyroid carcinoma induced by irradiation for Hodgkin's disease. Report of a case.

    Science.gov (United States)

    Weshler, Z; Krasnokuki, D; Peshin, Y; Biran, S

    1978-01-01

    In a 22-year-old male, who had been irradiated 16 years previously for Hodgkin's disease, a radiation-induced thyroid carcinoma developed. This was the only case with such development in a group of 207 cases with Hodgkin's disease who were treated by irradiation including the thyroid gland.

  14. The Case for Combined-Modality Therapy for Limited-Stage Hodgkin's Disease

    OpenAIRE

    Hill-Kayser, Christine E.; Plastaras, John P.; Tochner, Zelig; Glatstein, Eli

    2012-01-01

    Results of the Hodgkin's Disease.6 trial are critically examined in light of the advances in radiation therapy techniques that have occurred since it was initiated. The ultimate findings of the HD.6 trial do not close the case for combined-modality treatment of limited-stage Hodgkin's disease.

  15. Synchronous development of breast cancer and chest wall fibrosarcoma after previous mantle radiation for Hodgkin's disease

    International Nuclear Information System (INIS)

    Patlas, Michael; McCready, David; Kulkarni, Supriya; Dill-Macky, Marcus J.

    2005-01-01

    Survivors of Hodgkin's disease are at increased risk of developing a second malignant neoplasm, including breast carcinoma and sarcoma. We report the first case of synchronous development of chest wall fibrosarcoma and breast carcinoma after mantle radiotherapy for Hodgkin's disease. Mammographic, sonographic and MR features are demonstrated. (orig.)

  16. Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

    Science.gov (United States)

    Zhang, Liyuan; Fan, Denggui; Wang, Qingyun

    2017-01-01

    In temporal lobe epilepsy (TLE), the variation of chemical receptor expression underlies the basis of neural network activity shifts, resulting in neuronal hyperexcitability and epileptiform discharges. However, dynamical mechanisms involved in the transitions of TLE are not fully understood, because of the neuronal diversity and the indeterminacy of network connection. Hence, based on Hodgkin-Huxley (HH) type neurons and Pinsky-Rinzel (PR) type neurons coupling with glutamatergic and GABAergic synaptic connections respectively, we propose a computational framework which contains dentate gyrus (DG) region and CA3 region. By regulating the concentration range of N-methyl-D-aspartate-type glutamate receptor (NMDAR), we demonstrate the pyramidal neuron can generate transitions from interictal to seizure discharges. This suggests that enhanced endogenous activity of NMDAR contributes to excitability in pyramidal neuron. Moreover, we conclude that excitatory discharges in CA3 region vary considerably on account of the excitatory currents produced by the excitatory pyramidal neuron. Interestingly, by changing the backprojection connection, we find that glutamatergic type backprojection can promote the dominant frequency of firings and further motivate excitatory counterpropagation from CA3 region to DG region. However, GABAergic type backprojection can reduce firing rate and block morbid counterpropagation, which may be factored into the terminations of TLE. In addition, neuronal diversity dominated network shows weak correlation with different backprojections. Our modeling and simulation studies provide new insights into the mechanisms of seizures generation and connectionism in local hippocampus, along with the synaptic mechanisms of this disease.

  17. Synaptic glutamate release by postnatal rat serotonergic neurons in microculture.

    Science.gov (United States)

    Johnson, M D

    1994-02-01

    Serotonergic neurons are thought to play a role in depression and obsessive compulsive disorder. However, their functional transmitter repertoire is incompletely known. To investigate this repertoire, intracellular recordings were obtained from 132 cytochemically identified rat mesopontine serotonergic neurons that had re-established synapses in microcultures. Approximately 60% of the neurons evoked excitatory glutamatergic potentials in themselves or in target neurons. Glutamatergic transmission was frequently observed in microcultures containing a solitary serotonergic neuron. Evidence for co-release of serotonin and glutamate from single raphe neurons was also obtained. However, evidence for gamma-aminobutyric acid release by serotonergic neurons was observed in only two cases. These findings indicate that many cultured serotonergic neurons form glutamatergic synapses and may explain several observations in slices and in vivo.

  18. What the training of a neuronal network optimizes.

    Science.gov (United States)

    Tabor, Zbisław

    2007-09-01

    In the study a model of training of neuronal networks built of integrate-and-fire neurons is investigated. Neurons are assembled into complex networks of Watts-Strogatz type. Every neuronal network contains a single receptor neuron. The receptor neuron, stimulated by an external signal, evokes spikes in equal time intervals. The spikes generated by the receptor neuron induce subsequent activity of a whole network. The depolarization signals, traveling the network, modify synaptic couplings according to a kick-and-delay rule, whose process is termed "training." It is shown that the training decreases the mean length of paths along which a depolarization signal is transmitted from the receptor neuron. Consequently, the training also decreases the reaction time and the energy expense necessary for the network to react to the external stimulus. It is shown that the initial distribution of synaptic couplings crucially determines the performance of trained networks.

  19. Single versus Serial Measurements of Neuron-Specific Enolase and Prediction of Poor Neurological Outcome in Persistently Unconscious Patients after Out-Of-Hospital Cardiac Arrest - A TTM-Trial Substudy.

    Directory of Open Access Journals (Sweden)

    Sebastian Wiberg

    Full Text Available Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA. This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population.This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTM-trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and follow-up was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score of 3 to 5.A total of 685 (73% patients participated in the study. At day three after OHCA 63 (9% patients had died and 473 (69% patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002. Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83.NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations of serial NSE measurements may

  20. Potential and techniques of radiotherapy in the treatment of Non-Hodgkin lymphomas of low malignancy

    International Nuclear Information System (INIS)

    Onckels, T.

    1982-01-01

    This paper deals with the therapy (in particular: radiotherapy) of malignant Non-Hodgkin lymphomas. The problems caused by Non-Hodgkin lymphomas, their behavioural differences as compared with Hodgkin lymphomas are shown. Some methodical fundamentals of radiotherapy are explained and their importance for a successful radiotherapy is made clear, taking into consideration the peculiarities of the Non-Hodgkin lymphomas. It is being tried in the paper to survey the results of the therapy described in the literature with special regard to radiotherapy, with the background of the two currently relevant clinical classifications of Non-Hodgkin lymphomas, the Rappaport classification and the Kiel classification. Referring to the author's own group of patients the possibilities of radiotherapy alone or in combination with a chemotherapy in the various stages of the disease and thus the indication of radiotherapy are discussed. (orig.) [de

  1. Role of routine imaging in detecting recurrent lymphoma; a review of 258 patients with relapsed aggressive non-Hodgkin and Hodgkin lymphoma

    DEFF Research Database (Denmark)

    El-Galaly, Tarec Christoffer; Mylam, Karen Juul; Bøgsted, Martin

    2014-01-01

    After first-line therapy, patients with Hodgkin and aggressive non-Hodgkin lymphomas are followed closely for early signs of relapse. The current follow-up practice with frequent use of surveillance imaging is highly controversial and warrants a critical evaluation. Therefore a retrospective...... multicenter study of relapsed Hodgkin and aggressive non-Hodgkin lymphomas (nodal T-cell and diffuse large B-cell lymphomas) was conducted. All included patients had been diagnosed during the period 2002-2011 and relapsed after achieving complete remission on first-line therapy. Characteristics and outcome...... of imaging-detected relapses were compared to other relapses. A total of 258 patients with recurrent lymphoma were included in the study. Relapse investigations were initiated outside preplanned visits in 52% of the patients. Relapse detection could be attributed to patient-reported symptoms alone...

  2. Mechanisms of Idelalisib-Associated Diarrhea in Patients With Relapsed Chronic Lymphocytic Leukemia, Indolent Non-hodgkin Lymphoma, or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2017-10-11

    Absence of Signs or Symptoms; B-Cell Non-Hodgkin Lymphoma; Digestive System Signs and Symptoms; Indolent Adult Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Indolent Adult Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma

  3. Prospective Coding by Spiking Neurons.

    Directory of Open Access Journals (Sweden)

    Johanni Brea

    2016-06-01

    Full Text Available Animals learn to make predictions, such as associating the sound of a bell with upcoming feeding or predicting a movement that a motor command is eliciting. How predictions are realized on the neuronal level and what plasticity rule underlies their learning is not well understood. Here we propose a biologically plausible synaptic plasticity rule to learn predictions on a single neuron level on a timescale of seconds. The learning rule allows a spiking two-compartment neuron to match its current firing rate to its own expected future discounted firing rate. For instance, if an originally neutral event is repeatedly followed by an event that elevates the firing rate of a neuron, the originally neutral event will eventually also elevate the neuron's firing rate. The plasticity rule is a form of spike timing dependent plasticity in which a presynaptic spike followed by a postsynaptic spike leads to potentiation. Even if the plasticity window has a width of 20 milliseconds, associations on the time scale of seconds can be learned. We illustrate prospective coding with three examples: learning to predict a time varying input, learning to predict the next stimulus in a delayed paired-associate task and learning with a recurrent network to reproduce a temporally compressed version of a sequence. We discuss the potential role of the learning mechanism in classical trace conditioning. In the special case that the signal to be predicted encodes reward, the neuron learns to predict the discounted future reward and learning is closely related to the temporal difference learning algorithm TD(λ.

  4. Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

    2010-01-01

    Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

  5. NEURON and Python

    OpenAIRE

    Michael Hines; Andrew P Davison; Eilif Muller

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because ...

  6. Teaching and learning the Hodgkin-Huxley model based on software developed in NEURON’s programming language hoc

    Science.gov (United States)

    2013-01-01

    Background We present a software tool called SENB, which allows the geometric and biophysical neuronal properties in a simple computational model of a Hodgkin-Huxley (HH) axon to be changed. The aim of this work is to develop a didactic and easy-to-use computational tool in the NEURON simulation environment, which allows graphical visualization of both the passive and active conduction parameters and the geometric characteristics of a cylindrical axon with HH properties. Results The SENB software offers several advantages for teaching and learning electrophysiology. First, SENB offers ease and flexibility in determining the number of stimuli. Second, SENB allows immediate and simultaneous visualization, in the same window and time frame, of the evolution of the electrophysiological variables. Third, SENB calculates parameters such as time and space constants, stimuli frequency, cellular area and volume, sodium and potassium equilibrium potentials, and propagation velocity of the action potentials. Furthermore, it allows the user to see all this information immediately in the main window. Finally, with just one click SENB can save an image of the main window as evidence. Conclusions The SENB software is didactic and versatile, and can be used to improve and facilitate the teaching and learning of the underlying mechanisms in the electrical activity of an axon using the biophysical properties of the squid giant axon. PMID:23675833

  7. Challenges and perspectives in the immunotherapy of Hodgkin lymphoma.

    Science.gov (United States)

    Michot, Jean-Marie; Lazarovici, Julien; Ghez, David; Danu, Alina; Fermé, Christophe; Bigorgne, Amélie; Ribrag, Vincent; Marabelle, Aurélien; Aspeslagh, Sandrine

    2017-11-01

    Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects. Immunotherapy is a promising new treatment option for Hodgkin lymphoma, and anti- programmed death-1 (PD1) agents have produced striking results in patients with relapsed or refractory disease. The microenvironment of Hodgkin lymphoma appears to be unique in the field of human disease: the malignant Reed-Sternberg cells only constitute 1% of the cells in the lymphoma, but they are surrounded by an extensive immune infiltrate. Reed-Sternberg cells exhibit 9p24.1/PD-L1/PD-L2 copy number alterations and genetic rearrangements associated with programmed cell death ligand 1/ ligand 2 (PD-L1/2) overexpression, together with major histocompatibility complex-I (MHC-I) and major histocompatibility complex-II (MHC-II) downregulation (which may facilitate the tumour's immune evasion). Although HL may be a situation in which defective immune surveillance is restored by anti-PD1 therapy, it challenges our current explanation of how anti-PD1 agents work because MHC-I expression is required for CD8-T-cell-mediated tumour antigen recognition. Here, we review recent attempts to understand the defects in immune recognition in HL and to design an optimal evidence-based treatment for combination with anti-PD1. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Nasal non-hodgkin's lymphoma : CT findings

    Energy Technology Data Exchange (ETDEWEB)

    No, Tae Youn; Baek, Ho Gil; Won, Jong Bu; Park, Sung Ho; Park, O Bong; Baik, Seung Kug; Shin, Mi Jung; Kim, Bong Ki; Choi, Han Yong [Wallace Memorial Baptist Hospital, Pusan (Korea, Republic of)

    1997-05-01

    To describe the characteristics of CT findings in nasal lymphoma. We retrospectively reviewed CT findings and pathologic findings of eight patients (six males and two females) aged between 24 and 68 years with pathologically-proven nasal lymphoma. We analyzed mass location, laterality, size, margin, mass effect, adjacent bony change and contrast enhancement pattern. All eight cases were non-Hodgkin's lymphoma, intermediate grade, diffuse large cell type. Seven cases were B-cell type and one was T-cell. In all cases, tumors were located in the medial wall of the inferior turbinate. In four cases, they were also found in the anterior ethmoidal sinus, and in one case, in the nasal septum. The mean size of the main mass was 3.3cm. In seven cases, tumors were unilateral (one on the right; six on the left), and in the remaining case, bilateral. In six cases tumor margin was smooth and in two cases focal nodularity was seen. In two cases there was no bony change, and in four, there was mucosal thickening along the nasal septum; in one of these four, minimal bony erosion was also found. In the other two cases, bony destruction was seen, and tumors were very large(7cm in diameter) or bilterally located. In three cases, the nasal septum was displaced by the mass. In all cases with bony change, the nasal septum was involved. All tumors were homogeneously well enhanced after IV contrast administration. The main CT findings of nasal non-Hodgkin's lymphoma were smooth margin, unilateral location (mainly in the medial wall of the inferior turbinate and growing to the medial side without bony destruction) mucosal thickening along the nasal septum and clear homogeneous enhancement after IV contrast administration. These characteristics will help diagnosis, help deter-mine the appropriate region for radiation and other appropriate therapy, and facilitate prognosis in patients with nasal non-Hodgkin's lymphoma.

  9. NON-HODGKIN'S LYMPHOMAS OF FEMALE REPRODUCTIVE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. V. Babkina

    2008-01-01

    Full Text Available Non-Hodgkin's lymphomas are extremely rare among all tumors of female reproductive system. Diagnostic mistakes and inadequate therapeu- tic tactics in these diseases are results of usual absence of alertness of gynecologists. The aims are to analyze reasons of diagnostic mistakes in patients with non-Hodgkin's lymphomas of female reproductive system and to discover definitive clinical and morphological characteristics of female reproductive system lymphoid tumors. During the period between 1989 and 2006, 305 cases of primary extranodal non-Hodgkin's lym- phomas were detected; female reproductive system was affected in 7% of patients (totally 40 patients, which were included in investigated group. In the whole analyzed group of women (n=40, median age 43 yrs, range 17-84 yrs, patients with primary lesion of female reproductive system had median age of 40 yrs and with secondary involvement - 46 yrs. Most of patients were fertile (60%, n=24. Such tumors was localized in breast in 40% of cases (n=16, in ovaries - 20% (n=8, in uterine corpus - 12,5% (n=5, in uterine cervix - 15% (n=6, and in vagina - remaining 12,5% (n=5. Average time from diagnosis to beginning of the treatment was 7,5 months. As a result, the onset of specific therapy was delayed in 65% cases (n=26 and 50% (n=20 underwent unneeded surgery. Diagnostic mistakes lead to inadequate treatment. Extranodal non-Hodgkin’s lymphomas of female reproductive system, both primary and secondary, are rare pathology. Primary lesion is more typical for older women, sec- ondary is mainly affecting younger women (in reproductive period. Chemotherapy response and prognosis are better in primary cases.

  10. Prevalence of menstrual cycles and outcome of 50 pregnancies after high-dose chemotherapy and auto-SCT in non-Hodgkin and Hodgkin lymphoma patients younger than 40 years.

    Science.gov (United States)

    Akhtar, S; Youssef, I; Soudy, H; Elhassan, T A M; Rauf, S M; Maghfoor, I

    2015-12-01

    Data are limited regarding the prevalence of menstrual cycles and pregnancies after high-dose chemotherapy (HDC) and auto-stem cell transplantation (SCT). Female patients who underwent HDC auto-SCT for non-Hodgkin and Hodgkin lymphoma (1997-2012) were reviewed. The selection criteria were as follows: (1) alive without disease 12 and 24 months after auto-SCT for menstrual cycles and pregnancy, respectively, (2) age SCT, and (3) no primary infertility. One-hundred and seventy-six females underwent single auto-SCT. Eighty-nine were eligible for menstrual cycles and pregnancy analysis. Median age at auto-SCT was 25 years (14-40 years), at pregnancy 27 years (20-37 years), median follow-up 65 months (range 24-190). Regular menstrual-cycles resumed in 56/89 patients (63%). Increasing age (P=0.02) and number of prior chemotherapy cycles (P=0.02) are associated with higher risk of amenorrhea. Forty patients tried to get pregnant, 26 (65%) became pregnant 50 times: 43 (86%) live birth, 7 (14%) miscarriage and 2/50 had birth defects. Twenty-four patients practiced breastfeeding (median duration 4 months (1-24 months)). Enough breast milk production was reported 62.5% vs 100% in those patients who did or did not receive above the diaphragm radiation therapy, respectively, (P=0.066). Our data highlights significantly higher than perceived incidence of menstrual cycle resumption, successful pregnancies and breastfeeding after HDC auto-SCT.

  11. Lymphogranuloma venereum and non-Hodgkin lymphoma: a case report

    Directory of Open Access Journals (Sweden)

    Mauro Romero Leal Passos

    2012-06-01

    Full Text Available Lymphogranuloma venereum (LGV is an uncommon, contagious, sexually transmitted disease (STD. We report a case of a 17-year-old teenager who presented with a 2-month-old ulcerous vegetant lesion in the right inguinal region. The patient was diagnosed with LGV and received erythromycin treatment. Three months after treatment, he presented with a new ulcerous lesion, very similar to the previous one, in the right supraclavicular region. He was diagnosed with a diffuse large B-cell non-Hodgkin lymphoma. Both diseases are rare in Rio de Janeiro City, Brazil, and physicians should not neglect the possibility of STDs in such cases.

  12. Changing patterns of Hodgkin lymphoma incidence in Singapore

    DEFF Research Database (Denmark)

    Hjalgrim, H.; Seow, A.; Rostgaard, K.

    2008-01-01

    rates increased annually by 7.0% (95% confidence interval 3.4%-10.7%) and 3.4% (0.1%-6.8%), respectively, in men and by 13.7% (9.1%-18.6%) and 12.2% (7.8-16.8%), respectively, in women between 1968 and 2004. However, the incidence peak remained considerably lower than what can be observed in young......A bimodal age-specific incidence pattern with a relatively high proportion of cases occurring in adolescents and young adults is a hallmark of Hodgkin lymphoma (HL) epidemiology in Western industrialized countries. The young adult incidence peak is believed to reflect the association between HL...

  13. Rituximab induced hypoglycemia in non-Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    Lali V

    2006-12-01

    Full Text Available Abstract Background Hypoglycemia is a vary rare toxicity of rituximab. The exact mechanism of rituximab induced hypoglycemia is not clear. Case presentation A 50 year old female presented with a left tonsillar non Hodgkin's lymphoma and was started on R-CHOP chemotherapy. Twenty four hours after the first rituximab infusion, she developed hypoglycemia which was managed by IV glucose infusion. Conclusion Hypoglycemia following rituximab administration is rare. Possibilities of hypoglycemia should be kept in mind in patients developing symptoms like fatigue, restlessness, and sweating while on rituximab therapy.

  14. Autologous stem cell transplantation in the treatment of Hodgkin's disease

    Directory of Open Access Journals (Sweden)

    Tarabar Olivera

    2009-01-01

    Full Text Available Background/Aim. High-dose chemotherapy with autologous stem cell transplantacion (ASCT has shown to produce long-term disease-free survival in patients with chemotherapysensitive Hodgkin disease. The aim of the study was to evaluate efficacy of ASCT in the treatment of Hodgkin's disease. Methods. Between May 1997 and September 2008, 34 patients with Hodgkin's disease in median age of 25 (range 16-60 years, underwent ASCT. Autologous SCT were performed as consolidation therapy in one poor-risk patients with complete response (CR and in 10 patients in partial remission (PR after induction chemotherapy (32.5%, for chemosensitive relapse (CSR 1 and CSR 2 in 47% patients and in 20.5% patients with chemoresistant disease (CRD. All except one patient were in stage III/IV, extranodal site of disease had 24 patients and bulky disease had l0 patients. All the patients received a uniform preparatory regimen (BEAM. Results. An overall response was achieved in 30 of 32 evaluated patients, with 62.5% in CR and 31.25% in PR. After applying radiotherapy, two patients with PR after ASCT reached CR. Median follow-up was 15.5 months (range 3-133 months. The probability of overall survival (OS and progression-free survival (PFS at a 3-year period for all patients was 51.9 % and 48.9%, respectively. For 22 patients in CR after ASCT, a 3-year DFS was 66.5%. Estimates of 2.5-year survival were 14.3%, 61.9% and 100% for CRD, CSR and for patients with CR/PR, respectively (p < 0.01. However, when patients undergoing consolidation were analyzed separately from those in CSR, no significant difference in OS and PFS was observed according to the disease status at ASCT. In univariate analysis for OS, PFS i DFS, extranodal site of disease and disease bulk had no predictive value. Twelve patients died. The main cause of death was Hodgkin's disease. Transplant-related mortality was 3.1%. One patient with CRD developed secondary acute myeloid leukemia and died 28 months after the

  15. Combined modality treatment is the treatment of choice for stage I/IE intermediate and high grade non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Maazen, R.W.M. van der; Noordijk, E.M.; Thomas, J.; Raemaekers, J.M.M.; Meerwaldt, J.H.

    1998-01-01

    Background and purpose: In a retrospective study, the efficacy of radiotherapy alone was compared with combined modality treatment in patients with stage I/IE non-Hodgkin's lymphoma (NHL). Patients and methods: Between 1980 and 1994, 296 patients with stage I/IE non-Hodgkin's lymphoma of intermediate or high grade malignancy (according to the Working Formulation) were treated in four different institutions. All patients were included except patients that presented with NHLs localized in the central nervous system, testis or skin. Two hundred two patients were treated with radiation therapy alone and 94 patients were treated with combined modality treatment. Results: Increasing age and radiation as a single treatment (versus combined modality treatment) were highly significant adverse prognostic factors by multivariate analysis. The actuarial 10-year rates for progression-free and overall survival were 83 and 70%, respectively, for the patients treated with combined modality treatment and 47 and 43%, respectively, for the patients treated with radiation therapy alone. Conclusion: Combined modality treatment is the treatment of choice for patients with stage I/IE intermediate and high grade non-Hodgkin's lymphomas. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  16. A Decade of Comparative Dose Planning Studies for Early-Stage Hodgkin Lymphoma: What Can We Learn?

    Energy Technology Data Exchange (ETDEWEB)

    Maraldo, Maja V., E-mail: dra.maraldo@gmail.com [Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Specht, Lena [Department of Oncology, Section of Radiotherapy, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark); Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen (Denmark)

    2014-12-01

    During the past 4 decades, the treatment of Hodgkin lymphoma has changed dramatically, and combined modality treatment is now considered the standard of care for patients with early-stage disease. However, the risk of late effects has led to concerns regarding the use of radiation therapy, especially in young patients with a long life expectancy. In this study, we review the current evidence for modern radiation therapy planning and delivery techniques in the treatment of early-stage Hodgkin lymphoma with a focus on a reduced delivered dose, a reduced irradiated volume, and a more conformal dose distribution. Although studies are difficult to compare because of differences in field technique, prescribed dose, target volumes, patient population, and reported dosimetric and plan evaluation parameters, modern radiation therapy significantly reduces exposure to normal tissues and thereby the estimated risk of late effects. However, there is no such thing as a single best modern delivery technique when multiple organs at risk are considered simultaneously because of the heterogeneity in patient anatomy and disease location, and the choice of radiation therapy technique should be made individually for each patient.

  17. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)

    Science.gov (United States)

    Morris, S W; Naeve, C; Mathew, P; James, P L; Kirstein, M N; Cui, X; Witte, D P

    1997-05-08

    Anaplastic Lymphoma Kinase (ALK) was originally identified as a member of the insulin receptor subfamily of receptor tyrosine kinases that acquires transforming capability when truncated and fused to nucleophosmin (NPM) in the t(2;5) chromosomal rearrangement associated with non-Hodgkin's lymphoma, but further insights into its normal structure and function are lacking. Here, we characterize a full-length normal human ALK cDNA and its product, and determine the pattern of expression of its murine homologue in embryonic and adult tissues as a first step toward the functional assessment of the receptor. Analysis of the 6226 bp ALK cDNA identified an open reading frame encoding a 1620-amino acid (aa) protein of predicted mass approximately 177 kDa that is most closely related to leukocyte tyrosine kinase (LTK), the two exhibiting 57% aa identity and 71% similarity over their region of overlap. Biochemical analysis demonstrated that the approximately 177 kDa ALK polypeptide core undergoes co-translational N-linked glycosylation, emerging in its mature form as a 200 kDa single chain receptor. Surface labeling studies indicated that the 200 kDa glycoprotein is exposed at the cell membrane, consistent with the prediction that ALK serves as the receptor for an unidentified ligand(s). In situ hybridization studies revealed Alk expression beginning on embryonic day 11 and persisting into the neonatal and adult periods of development. Alk transcripts were confined to the nervous system and included several thalamic and hypothalamic nuclei; the trigeminal, facial, and acoustic cranial ganglia; the anterior horns of the spinal cord in the region of the developing motor neurons; the sympathetic chain; and the ganglion cells of the gut. Thus, ALK is a novel orphan receptor tyrosine kinase that appears to play an important role in the normal development and function of the nervous system.

  18. Effect of trimethylcolchicinic acid methyl ether d-tartrate (TMCA) on Hodgkin's and non-Hodgkin's lymphoma.

    Science.gov (United States)

    Stolinsky, D C; Jacobs, E M; Irwin, L E; Pajak, T F; Bateman, J R

    1976-01-01

    Trimethylcolchicinic acid methyl ether d-tartrate (TMCA; NSC-36351) was administered daily by mouth to 71 patients with malignant lymphomas. Partical (greater than 50%) responses were observed in eleven of 37 patients with Hodgkin's disesse, two of 22 patients with lymphocytic lymphoma, and one of two patients with mixed cell lymphoma. One complete and three partial responses were noted in nine patients with histiocytic lymphoma. Responses lasted from one to 91+ months (median: four months) and occurred in patients whose disease was resistant to alkylating agents, vinblastine, vincristine, procarbazine, prednisone or BCNU. Toxic effects included leukopenia, thrombocytopenia, nausea, diarrhea, stomatitis, alopecia and dermatitis.

  19. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma

    Science.gov (United States)

    Chang, Ellen T.; Ambinder, Richard F.; Lennette, Evelyne T.; Rubertone, Mark V.; Mann, Risa B.; Borowitz, Michael; Weir, Edward G.; Abbondanzo, Susan L.; Mueller, Nancy E.

    2012-01-01

    An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma. PMID:22972983

  20. [Stevens-Johnson syndrome and Hodgkin's disease: A fortuitous association or paraneoplastic syndrome?].

    Science.gov (United States)

    Schoeffler, A; Levy, E; Weinborn, M; Cuny, J-F; Schmutz, J-L; Barbaud, A; Cribier, B; Bursztejn, A-C

    2014-02-01

    Hodgkin's disease has been associated with a variety of cutaneous symptoms. We report two cases of Stevens-Johnson syndrome (SJS) associated with Hodgkin's disease. Case 1: a 22-year-old man was hospitalized for a second erythematous vesicular eruption with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He also developed enlarged cervical lymph nodes that revealed Hodgkin's disease. The latter diagnosis was followed by two recurrent rashes. Treatment consisted of systemic chemotherapy. Complete remission was obtained with no signs of cutaneous recurrence after 24 months of regular follow-up. Case 2: a 29-year-old man was admitted for a generalized erythematous and bullous rash with intense mucosal involvement. Histopathological examination confirmed the diagnosis of Stevens-Johnson syndrome. He then developed muco-cutaneous icterus that was secondary to Hodgkin's disease. Under specific hematologic treatment, no cutaneous relapse was noticed. These cases illustrate the rare association of SSJ revealing Hodgkin's disease. In these cases, no evidence was found of infectious disease or drug-induced cutaneous effects. Only one case of toxic epidermal necrolysis associated with Hodgkin's disease had previously been reported. The link between both diseases may be immunosuppression induced by Hodgkin's disease, which could favor infection inducing SJS or secretion by tumor cells granulysin, a mediator responsible for damage to keratinocytes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. MRI diagnosis of renal involvement in children with non Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    Zeng Xiangting; Lin Daiying; Lin Shixu; Wu Xianheng; Zheng Yue

    2004-01-01

    Objective: To understand the various MRI manifestations of renal involvement of non Hodgkin's lymphoma (NHL) in children. Methods: MRI findings and characteristics in 11 cases confirmed by pathology with NHL renal involvement were retrospectively analyzed and the differential diagnosis was discussed. the positive rates of renal involvement in all lymphomas in children were also investigated. Results: In 11 cases NHL, 1 case had single mass in one kidney; 8 cases showed multiple nodules in both kidneys; 1 case which the two kidneys were widespread gradually had only single mass in one kidney; 1 case which the kidneys' cortex penetrated incrassation had no typical mass. All cases had encroached on abdominal viscera in various degrees. All focuses showed low or gently high signal on T 1 WI and low signal on T 2 WI, which had no putrescence in the center section. Conclusion: The MRI signs of renal involvement of NHL in children have certain characteristics. It is accurate to display the renal involvement of NHL by MRI scan. MRI is very valuable for the clinical staging and for the evaluation of therapeutic effects in NHL

  2. Matrix-dependent local retention of secretory vesicle cargo in cortical neurons

    NARCIS (Netherlands)

    de Wit, J.; Toonen, R.F.G.; Verhage, M.

    2009-01-01

    Neurons secrete many diffusible signals from synaptic and other secretory vesicles. We characterized secretion of guidance cues, neuropeptides, neurotrophins, and proteases from single secretory vesicles using pHluorin-tagged cargo in cortical neurons. Stimulation triggered transient and persistent

  3. Radiotherapy for mediastinal non-Hodgkin's lymphoma in children

    International Nuclear Information System (INIS)

    Masaki, Hidekazu

    1985-01-01

    Mediastinal non-Hodgkin's lymphoma in children is known to have an adverse prognosis, that is called ''lymphoblatic lymphoma''. Recently, chemotherapy for leukemia using multiple agents has been applied for non-Hodgkin's lymphoma in children, and this has improved relapse-free survival. Radiotherapy has been employed in order to reduce local recurrence. Two children received whole thoracic irradiation (10 Gy) who had mediastinal mass with malignant pleural effusion, then control of the effusion was achieved. Thereafter, radiation field was decreased in size to mantle field, and main tumor was treated to 30 Gy. In the course of treatment, mediastinal tumor was disappeared. Thereafter, radiation field was decreased in size to mantle field, and main tumor was treated to 30 Gy. In the course of treatment, mediastinal tumor was disappeared. For one child with only a mediastinal mass, mantle field was employed. He was treated to 30 Gy with chemotherapy. but he had CNS relapse. CNS prophylaxis is of considerable importance in this lymphoma according to the protocol of leukemia. (author)

  4. Skeletal manifestation of Non-Hodgkin's lymphoma in pediatric patients

    International Nuclear Information System (INIS)

    Rosenthal, H.; Galanski, M.; Kolb, R.; Gratz, K.F.; Reiter, A.

    2000-01-01

    Purpose. Skeletal manifestation of Non-Hodgkin's lymphoma is rare in pediatric patients. Objective of the study was to determine imaging features, before and after treatment, and to correlate these features with clinical outcome. Methods. A retrospective analysis of 1246 patients from two therapy studies (NHL-BMF-90 and 95) was performed. Imaging studies of 63 patients with bone involvement of lymphoma were reevaluated. Results. Incidence of initial bone involvement in Non-Hodgkin's lymphoma was 6.8%. Distribution was best assessed by bone scan, MRI revealed larger areas of marrow involvement and detected additional lesions. Sites of prediliction were long bones of the lower extremities with epiphyseal involvement in 39%. Residual signal alterations in MRI after successful therapy remained in 71%. Osteonecrosis after therapy was a common finding. Clinical outcome war not correlated to the presence of bone involvement. Conclusions. Since clinical outcome is not effected by bone involvement in childhood NHL, value of screening may be limited. Knowledge of imaging characteristics is mandatory for initial evaluation of primary osseous lymphomas and symptomatic lesions as well as for therapy controlls. (orig.) [de

  5. Current Issues in Histology, Biology and Prognosis of Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Marjanović Goran

    2017-06-01

    Full Text Available High risk Hodgkin lymphoma patients may occasionally have borderline characteristics similar to gray zone lymphomas and T-cell/histiocyte rich B cell lymphomas. These entities require different and more aggressive treatment modalities. Aggressive behavior is often associated with disturbances caused by Epstein Barr virus, or immune evasion caused by overexpression of check point inhibitors PDL-1 and PDL-2 coupled with the lack of expression of Class I and II MHC molecules. Galectin-1, TARC, sCD163 and other surrogate markers of immunosuppression in Hodgkin lymphoma may be useful for the assessment of treatment response. The improvements in lymphoma management diminished the importance of prognostic factors unified in the International Prognostic Scoring system, reducing them from 7 to 3 factors that remained relevant. Interim PET analysis is the only method able to identify resistant patients while chemotherapy is ongoing, thus enabling adjustment of treatment according to the treatment response. Efforts for stratification of patients according to disease histology, biology, microenvironment, clinical scoring systems and PET scan are ongoing. Current breakthroughs have set strong background for novel therapies with monoclonal antibodies and check point inhibitors that will result in improvement of management of high risk patients.

  6. [Lymph node tuberculosis as primary manifestation of Hodgkin's disease].

    Science.gov (United States)

    Audebert, Franz; Schneidewind, Arne; Hartmann, Pia; Kullmann, Frank; Schölmerich, Jürgen

    2006-06-15

    A 63-year-old female patient was admitted to the authors' hospital for further diagnostic work-up for suspected reactivation of a previously successfully treated lymph node tuberculosis, which had been diagnosed 1 year prior to the current admission. The clinical signs consisted of worsening of the patient's general condition, negacervical lymphadenopathy, night sweats, dyspnea, and superficial inflammation of the right mamma. A contrast-enhanced CT scan of the neck, thorax and abdomen revealed a generalized enlargement of the cervical, axillar, mediastinal and retroperitoneal lymph nodes, multiple intrapulmonary nodular lesions with a diameter of up to 6 mm, and a substantial right-sided pleural effusion. Under the assumption of reactivation of a lymph node tuberculosis, the patient was initially treated with an extended tuberculostatic therapy. Because of disease progression another lymph node biopsy was performed revealing Hodgkin's disease of mixed-cellularity type with a partly histiocytic necrotizing, partly tuberculoid reaction. The biopsy was negative for acid-fast bacilli. Thereupon initiated chemotherapy according to the ABVD protocol led to a rapid amelioration of the clinical symptoms. In the clinical setting of suspected or confirmed lymph node tuberculosis malignant lymphoma should always be considered. This consideration is particular important since Hodgkin's disease is typically associated with a cellular immunosuppression predisposing the subject to tuberculosis.

  7. CT findings in AIDS-related non-Hodgkin lymphoma

    International Nuclear Information System (INIS)

    Raval, J.K.; Boswell, W.D. Jr.; Gill, P.S.; Levine, A.M.; Halls, J.M.

    1987-01-01

    Patients with AIDS have an increased incidence of non-Hodgkin lymphoma. The authors report body CT findings at initial presentation in 30 AIDS patients, all of whom had AIDS-related non-Hodgkin lymphoma. In the authors' series, the lymphomas were typically bulky masses. Extranodal involvement was very common and seen in 16 of 30 (53%) of patients with the following distribution: rectal seven of 30 (masses), bowel excluding rectum four of 30 (multiple focal masses), liver three of 30 (multiple focal masses), adrenal two of 30 (focal masses), pericardium two of 30 (diffuse thickening with effusion), chest two of 30 (focal masses), and bone one of 30 (focal mass). One patient had multiple focal splenic lesions. Twenty-three of 30 (77%) patients had stage III or IV disease. Histologically, the lymphomas were of intermediate or high grade and were all of B-cell origin. B-cell lymphomas are seen with an increased frequency in patients with AIDS and very commonly have extranodal involvement. Because of the high preponderance of stage III or IV disease, it is important to scan all nonpalpable lymph node-bearing areas. Due to the multiplicity of causes for lymphadenopathy in AIDS patients, CT-guided biopsy may be useful in confirming diagnosis

  8. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.

    Science.gov (United States)

    Liu, W Robert; Shipp, Margaret A

    2017-11-23

    Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade. © 2017 by The American Society of Hematology.

  9. Clinical prognostic factors in non-Hodgkin's lymphomas

    International Nuclear Information System (INIS)

    Joensuu, H.

    1986-01-01

    Hospital records of 201 consecutive and histologically diagnosed non-Hodgkin's lymphoma patients were retrospectively analysed in an effort to determine the clinical prognostic factors affecting survival. The uncorrected five-year survival was 45%, and when corrected for other causes of death than lymphoma 48%. Response to the primary treatment, stage of the disease at diagnosis, occurrence of B-symptoms and age were strongly correlated to the final outcome. B-symptoms had negative effect on survival during the first year after the diagnosis, but not afterwards. Survival decreased with advancing age except in children, who had as poor survival as patients over 60 years of age. The primary site, sex or occurrence of extranodal lymphoma (43%) did not have influence on survival. Patients with a positive bone marrow aspiration biopsy did not have less favourable survival than other patients with stage IV lymphoma. Patients with a positive bipedal lymphangiogram had similar prognosis as those with a negative one. It is concluded that the most important prognostic factors other than histology in non-Hodgkin's lymphomas are response to the primary treatment, stage, age and occurrence of B-symptoms. (orig.) [de

  10. Radiation therapy in clinical stage I and II Hodgkin's disease

    International Nuclear Information System (INIS)

    Gospodarowicz, M.K.; Sutcliffe, S.B.; Bergsagel, D.E.; Chua, T.

    1992-01-01

    A review of the Princess Margaret Hospital (Toronto, Canada) experience over the last 20 years in treating clinically staged patients with stage I and II Hodgkin's disease was performed to analyse the impact of patient selection and extended field radiation on relapse and survival. Of the 878 patients with stage I and II Hodgkin's disease, 521 with clinical stages I and II received radiation alone as the initial treatment. The actuarial survival for all stage I and II patients was 85.1% at 5 years and 76.2% at 10 years, and for clinically stages patients treated with radiation alone, 87.2 and 77.6%, respectively. The relapse-free rate (RFR) for all clinical stage I and II patients treated with radiotherapy (RT) alone was 70.1% at 5 years and 65.8% at 10 years. Significant prognostic factors for RFR and survival included age, stage and histology. In addition, the extent of radiation was identified as an independent prognostic factor for survival as well as for relapse. (Author)

  11. MRI appearance of primary non-Hodgkin's lymphoma of bone

    International Nuclear Information System (INIS)

    Hermann, G.; Abdelwahab, I.F.; Klein, M.J.; Kenan, S.

    1997-01-01

    Objective. To evaluate the signal characteristics of primary non-Hodgkin's lymphoma of bone on MRI. Designs and patients. Ten patients with primary non-Hodgkin's lymphoma of bone were included in the study. T1- and T2-weighted imaging was performed. The signal intensity of the lesions was compared with that of the surrounding muscle. Results. The results of the MRI were compared with the histological findings. In the majority of cases (5/10) the lesion involved the femur. In one case each the tibia, humerus, ileum, sacrum, and skull, respectively, were affected. A soft tissue mass was present in four cases. In nine of ten cases on T1-weighted imaging the lesion was hypointense. On T2-weighted imaging seven of ten lesions were hypointense compared with muscle, one isointense and, in two cases, part of the lesion showed slightly hyperintense signal. In all ten cases the signal pattern appeared inhomogeneous. Pathological examination showed extensive fibrosis in the majority of cases. Conclusion. According to our results there is decreased signal intensity of bone marrow on both T1- and T2-weighted imaging, unlike other primary round cell tumors of bone. Because the diagnoses were established with small tissue biopsies, the reason for these findings is speculative. (orig.)

  12. Dcc regulates asymmetric outgrowth of forebrain neurons in zebrafish.

    Directory of Open Access Journals (Sweden)

    Jingxia Gao

    Full Text Available The guidance receptor DCC (deleted in colorectal cancer ortholog UNC-40 regulates neuronal asymmetry development in Caenorhabditis elegans, but it is not known whether DCC plays a role in the specification of neuronal polarity in vertebrates. To examine the roles of DCC in neuronal asymmetry regulation in vertebrates, we studied zebrafish anterior dorsal telencephalon (ADt neuronal axons. We generated transgenic zebrafish animals expressing the photo-convertible fluorescent protein Kaede in ADt neurons and then photo-converted Kaede to label specifically the ADt neuron axons. We found that ADt axons normally project ventrally. Knock down of Dcc function by injecting antisense morpholino oligonucleotides caused the ADt neurons to project axons dorsally. To examine the axon projection pattern of individual ADt neurons, we labeled single ADt neurons using a forebrain-specific promoter to drive fluorescent protein expression. We found that individual ADt neurons projected axons dorsally or formed multiple processes after morpholino knock down of Dcc function. We further found that knock down of the Dcc ligand, Netrin1, also caused ADt neurons to project axons dorsally. Knockdown of Neogenin1, a guidance receptor closely related to Dcc, enhanced the formation of aberrant dorsal axons in embryos injected with Dcc morpholino. These experiments provide the first evidence that Dcc regulates polarized axon initiation and asymmetric outgrowth of forebrain neurons in vertebrates.

  13. Pembrolizumab and Ibrutinib in Treating Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-01-25

    B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Mediastinal Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Lymphoplasmacytic Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Waldenstrom Macroglobulinemia; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Lymphoplasmacytic Lymphoma; Refractory Mantle Cell Lymphoma

  14. Lenalidomide and Blinatumomab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

    Science.gov (United States)

    2018-04-19

    CD19 Positive; Mediastinal Lymphoma; Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Recurrent Diffuse Large B-Cell 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 Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Small Lymphocytic Lymphoma

  15. Disseminated primary non-Hodgkin's lymphoma of bone : a case report

    International Nuclear Information System (INIS)

    Park, Hee Jin; Lee, Sung Moon; Lee, Hee Jung; Kim, Jung Sik; Kim, Hong

    2000-01-01

    Primary lymphoma of bone is uncommon and disseminated non-Hodgkin's lymphoma is extremely rare. The authors report a case of primary non-Hodgkin's lymphoma of bone involving the whole skeleton without evidence of involvement of lymph nodes or other tissue. Radiographic examination demonstrated moth-eaten or permeative bone destruction with endosteal scalloping. The MRI revealed hypointense bone marrow to fat on T2 weighted images before treatment. Bone marrow biopsy and subsegment immunohistochemical studies demonstrated the presence of non-Hodgkin's lymphoma, T-cell type. The patient underwent standard chemotherapy and showed marked resolution, clinically and radiologically. (author)

  16. Primary Hodgkin lymphoma located in the base of the tongue (a case report)

    International Nuclear Information System (INIS)

    Zalesska-Krecicka, M.; Zatonski, T.; Fraczek, M.; Krecicki, T.; Wolowiec, D.; Gisterek, I.

    2006-01-01

    Primary extranodal location of Hodgkin lymphoma is uncommon. We present a case of a woman with isolated Hodgkin disease localized in the base of the tongue, detected accidentally and treated successfully by total resection and local irradiation. Primary location of Hodgkin lymphoma (HL) in the non lymphoid tissue is very uncommon, and the primary involvement of the tongue has not been described so far. We present a case of a woman with isolated HL localized in the base of the tongue, detected accidentally by the laryngological examination performed because of choking. (authors)

  17. Rewiring of neuronal networks during synaptic silencing.

    Science.gov (United States)

    Wrosch, Jana Katharina; Einem, Vicky von; Breininger, Katharina; Dahlmanns, Marc; Maier, Andreas; Kornhuber, Johannes; Groemer, Teja Wolfgang

    2017-09-15

    Analyzing the connectivity of neuronal networks, based on functional brain imaging data, has yielded new insight into brain circuitry, bringing functional and effective networks into the focus of interest for understanding complex neurological and psychiatric disorders. However, the analysis of network changes, based on the activity of individual neurons, is hindered by the lack of suitable meaningful and reproducible methodologies. Here, we used calcium imaging, statistical spike time analysis and a powerful classification model to reconstruct effective networks of primary rat hippocampal neurons in vitro. This method enables the calculation of network parameters, such as propagation probability, path length, and clustering behavior through the measurement of synaptic activity at the single-cell level, thus providing a fuller understanding of how changes at single synapses translate to an entire population of neurons. We demonstrate that our methodology can detect the known effects of drug-induced neuronal inactivity and can be used to investigate the extensive rewiring processes affecting population-wide connectivity patterns after periods of induced neuronal inactivity.

  18. Mechanical Dissociation of Retinal Neurons with Vibration

    Science.gov (United States)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  19. FDG-PET/CT predicts outcome in patients with aggressive non-Hodgkin's lymphoma and Hodgkin's disease.

    Science.gov (United States)

    Querellou, Solène; Valette, Frédéric; Bodet-Milin, Caroline; Oudoux, Aurore; Carlier, Thomas; Harousseau, Jean-Luc; Chatal, Jean-François; Couturier, Olivier

    2006-11-01

    Early therapy response assessment with metabolic imaging is potentially useful to determine prognosis in aggressive lymphoma and, thus, can guide first-line therapy. Forty-eight patients with aggressive lymphoma [24 Hodgkin's disease (HD); 24 non-Hodgkin's lymphoma (NHL)] underwent fluoro-deoxyglucose positron emission tomography (FDG-PET) before chemotherapy (PET1) and at mid-treatment (PET2). Therapeutic response was evaluated using conventional methods at mid-treatment. PET2 results were related to event-free survival (EFS) and overall survival (OS) using Kaplan-Meier analyses. PET1 was positive in all patients. PET2 was negative in 38 patients (18 NHL-20 HD) and positive in 10 (6 NHL-4 HD). Of the PET-negative patients, 61 and 65% achieved complete remission, and only 50 and 25% of PET-positive patients, respectively, for NHL and HD, achieved complete remission. Significant associations were found between PET2 and EFS (p = 0.0006) and OS (p = 0.04) for NHL, and EFS (p < 0.0001) for HD (but not for OS, because no HD patient died). FDG-PET at mid-treatment can predict the outcome of patients with aggressive lymphoma and should be a useful tool to modify an ineffective therapy.

  20. Statistics of Visual Responses to Image Object Stimuli from Primate AIT Neurons to DNN Neurons.

    Science.gov (United States)

    Dong, Qiulei; Wang, Hong; Hu, Zhanyi

    2018-02-01

    Under the goal-driven paradigm, Yamins et al. ( 2014 ; Yamins & DiCarlo, 2016 ) have shown that by optimizing only the final eight-way categorization performance of a four-layer hierarchical network, not only can its top output layer quantitatively predict IT neuron responses but its penultimate layer can also automatically predict V4 neuron responses. Currently, deep neural networks (DNNs) in the field of computer vision have reached image object categorization performance comparable to that of human beings on ImageNet, a data set that contains 1.3 million training images of 1000 categories. We explore whether the DNN neurons (units in DNNs) possess image object representational statistics similar to monkey IT neurons, particularly when the network becomes deeper and the number of image categories becomes larger, using VGG19, a typical and widely used deep network of 19 layers in the computer vision field. Following Lehky, Kiani, Esteky, and Tanaka ( 2011 , 2014 ), where the response statistics of 674 IT neurons to 806 image stimuli are analyzed using three measures (kurtosis, Pareto tail index, and intrinsic dimensionality), we investigate the three issues in this letter using the same three measures: (1) the similarities and differences of the neural response statistics between VGG19 and primate IT cortex, (2) the variation trends of the response statistics of VGG19 neurons at different layers from low to high, and (3) the variation trends of the response statistics of VGG19 neurons when the numbers of stimuli and neurons increase. We find that the response statistics on both single-neuron selectivity and population sparseness of VGG19 neurons are fundamentally different from those of IT neurons in most cases; by increasing the number of neurons in different layers and the number of stimuli, the response statistics of neurons at different layers from low to high do not substantially change; and the estimated intrinsic dimensionality values at the low

  1. Automatically tracking neurons in a moving and deforming brain.

    Science.gov (United States)

    Nguyen, Jeffrey P; Linder, Ashley N; Plummer, George S; Shaevitz, Joshua W; Leifer, Andrew M

    2017-05-01

    Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

  2. Automatically tracking neurons in a moving and deforming brain.

    Directory of Open Access Journals (Sweden)

    Jeffrey P Nguyen

    2017-05-01

    Full Text Available Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.

  3. Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

    Science.gov (United States)

    2018-04-10

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/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 and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  4. Corticospinal mirror neurons

    OpenAIRE

    Kraskov, A.; Philipp, R.; Waldert, S.; Vigneswaran, G.; Quallo, M. M.; Lemon, R. N.

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like p...

  5. Hodgkin's disease. Prognostic value of 67-Gallium whole body scan

    International Nuclear Information System (INIS)

    Hervas, I.; Bello, P.; Gonzalez-Cabezas, P.; Flores, D.; Torres, I.; Perez-Velasco, R.; Mateo, A.; Lopez-Tendero, P.; Segura, A.

    2002-01-01

    Aim: Evaluation of the response to therapy is important in the clinical management of lymphoma. Gallium 67 scintigraphy has been considered a good technique for monitoring response after treatment of patients with Hodgkin's disease. The aim of this study is to assess the clinical impact of gallium 67 scintigraphy before and after treatment and to compare the overall survival between the patients whose gallium studies after treatment were negative and those whose studies did not become negative. Methods: We have studied 75 patients (41 women, 35 men) with histological diagnosis confirmed Hodgkin's disease controlled by the Department of Oncology of our Hospital. All the patients underwent 67Ga scintigraphy at the moment of the diagnosis (basal study) and in the case that basal study was positive (abnormal hyper-uptake focus) we performed follow-up studies after the treatment. We have calculate the overall survival between the patients whose studies after treatment were negative (first group) and those whose studies did not become negative (second group) and between patients whose studies were negative at diagnosis (third group). Gallium scintigraphy were performed 48-120 hours after the injection of 185-296 MBq (6-8 mCi) of 67Ga citrate. The statistic analysis used to compare the overall survival of the three groups was chi-square test with Yate's correction. Results: Gallium scintigraphy was positive at diagnosis in 47 patients (62,6%). In 39 of them we could perform the follow up study after the treatment. The follow up study was negative in 31 patients while in 8 patients the gallium scintigraphy remained positive after treatment. With a median follow-up of 8 years: In the first group (basal study positive and negative after treatment) the median overall survival was not reached (96% of patients remained alive). In the second group (basal study positive and positive after treatment) the median overall survival was 29 months (3 patients remained alive (37,5%)). In

  6. Hodgkin's lymphoma presenting with markedly elevated IgE: a case report

    Directory of Open Access Journals (Sweden)

    Ellis Anne K

    2009-12-01

    Full Text Available Abstract Background Markedly elevated IgE as a manifestation of a lymphoproliferative disorder has been only rarely reported. Case Presentation We present the case of a 22 year old female referred to the adult Allergy & Clinical Immunology clinic for an extremely elevated IgE level, eventually diagnosed with Hodgkin's lymphoma. She had no history of atopy, recurrent infections, eczema or periodontal disease; stool was negative for ova & parasites. Chest X-ray revealed large bilateral anterior mediastinal masses that demonstrated prominent uptake on gallium scan. Mediastinal lymph node biopsy was consistent with Hodgkin's lymphoma, nodular sclerosing subtype, grade I/II. Conclusion Although uncommon, markedly elevated IgE may be a manifestation of a malignant process, most notably both Hodgkin's and Non-Hodgkin's lymphomas. This diagnosis should be considered in evaluating an otherwise unexplained elevation of IgE.

  7. Affluence and Private Health Insurance Influence Treatment and Survival in Non-Hodgkin's Lymphoma.

    LENUS (Irish Health Repository)

    Comber, Harry

    2016-12-01

    The aim of this study was to investigate inequalities in survival for non-Hodgkin\\'s lymphoma (NHL), distinguishing between direct and indirect effects of patient, social and process-of-care factors.

  8. Expression of SDF1 receptors in the patients with Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    farhad Shahsavar

    2014-09-01

    Conclusion: The results of this study showed that RDC1 could be a marker for diagnosis of Hodgkin lymphoma. However, further studies using larger sample sizes and more accurate techniques are needed to confirm these results.

  9. Nuclear medicine and non Hodgkin malignant lymphomas; Medecine nucleaire et lymphomes malins non hodgkiniens

    Energy Technology Data Exchange (ETDEWEB)

    Solary, E.; Chatal, J.F. [Institut National de la Sante et de la Recherche Medicale, INSERM U517- IFR 100, 21- Dijon (France); Institut National de la Sante et de la Recherche Medicale, INSERM U- IFR 26, 44 - Nantes (France)

    2002-10-01

    The radioimmunotherapy of non Hodgkin lymphoma is a new step in the clinical development of the internal radiotherapy in nuclear medicine. It opens the door to the more difficult and still uncertain application to solid tumors. (N.C.)

  10. Acute myelomonocytic leukemia following splenectomy in a patient with long-standing Hodgkin disease

    International Nuclear Information System (INIS)

    Rosenbloom, B.E.; Klein, E.J.; Uszler, J.M.; Ellis, R.; Block, J.B.; Tanaka, K.R.

    1978-01-01

    The association of acute nonlymphocytic leukemia with Hodgkin disease has been recorded in more than 100 instances. In most of these cases the patient has had long-standing Hodgkin disease and radiotherapy has been carried out. The combination of previous radiotherapy and chemotherapy appears to further increase the risk of leukemia developing. In a patient under our care with Hodgkin disease acute myelomonocytic leukemia developed following splenectomy for hypersplenism. The onset of acute leukemia immediately following splenectomy in a patient with Hodgkin disease has not previously been noted. In addition, because the patient's usual bone marrow sampling sites were hypoplastic, we utilized an 111 In-chloride bone marrow scan to find a site that was accessible for aspiration

  11. Dynamics of immune indices in patients with Hodgkin's disease following splenectomy and radiation therapy

    International Nuclear Information System (INIS)

    Ankudinov, V.A.; Aslyaev, L.A.; Khvorostenko, M.I.; Krugovov, B.A.; Kosse, V.A.

    1981-01-01

    The effect of splenectomy and radiation therapy on immunoreactivity in patients with Hodgkin's disease is studied. It is established that splenectomy and laparatomy are advisable prior to radiation therapy [ru

  12. Changes over the course of time in histological subclassification of Hodgkin's disease in Denmark

    DEFF Research Database (Denmark)

    Lauritzen, A.F.; Specht, Lena; Nissen, N.I.

    1991-01-01

    subclassification according to the BNLI proposals. Two cases (0.4%) were reclassified as not being Hodgkin's disease, and 489 cases (99.6%) were reclassified as Hodgkin's disease in the subgroups: LP 7.5% (16.7%), NS 65.1% (54.7%), MC 21.9% (26.4%) and LD 1.2% (1.2%) (the numerals in brackets state the original...

  13. Correlation between apoptosis, proliferation and bcl-2 expression in malignant non-Hodgkin's lymphoma

    Science.gov (United States)

    Kiberu, S W; Pringle, J H; Sobolewski, S; Murphy, P; Lauder, I

    1996-01-01

    Aim—To investigate whether clinical features of non-Hodgkin's lymphomas, at the time of first biopsy, correlate with studies of cell proliferation and cell death as well as with the level of bcl-2 expression. Methods—Bcl-2 expression, determined by immunocytochemistry, was compared with cell proliferation, measured using in situ hybridisation for histone mRNA, and cell death by apoptosis, measured using in situ end labelling for DNA cleavage. Results—Histone mRNA staining gave a labelling index of 30% of cells for reactive germinal centres, 5.2-13.5% of cells for low grade non-Hodgkin's lymphoma and 12.1-50.5% of cells for high grade non-Hodgkin's lymphoma. In situ end labelling gave a labelling index of 5.0-10.0% of cells for reactive germinal centres, 1.0-3.7% of cells for low grade non-Hodgkin's lymphoma and 4.7-13.5% of cells for high grade non-Hodgkin's lymphoma. There was a positive correlation between apoptotic index and proliferation index. More cases of low grade than high grade non-Hodgkin's lymphoma expressed bcl-2. There was no correlation between apoptotic index and bcl-2 expression for high grade non-Hodgkin's lymphoma. Conclusions—The molecular mechanisms controlling cell proliferation and death in non-Hodgkin's lymphoma are complex, probably involving a range of genes, including bcl-2. A better understanding of resistance to cell death is needed if the clinical goal of tailoring cancer treatment to individual tumours is to be achieved. Images PMID:16696087

  14. Chemotherapy alone versus chemotherapy plus radiotherapy for early stage Hodgkin lymphoma

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed Ahmed; Skoetz, Nicole

    2011-01-01

    BACKGROUND: Combined modality treatment (CMT) consisting of chemotherapy followed by localised radiotherapy is standard treatment for patients with early stage Hodgkin lymphoma (HL). However, due to long term adverse effects such as secondary malignancies, the role of radiotherapy has been...... questioned recently and some clinical study groups advocate chemotherapy only for this indication. OBJECTIVES: We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing chemotherapy alone with CMT in patients with early stage Hodgkin lymphoma with respect...

  15. Health of children born to women after radiation and chemotherapy for Hodgkin's lymphoma

    Directory of Open Access Journals (Sweden)

    A. A. Danilenko

    2014-01-01

    Full Text Available Presents data of the health of 411 children (I generation and 23 children (II generation born to 340 women received chemotherapy or radiotherapy due to Hodgkin’s lymphoma. Most children were born healthy. Congenital pathology were registered in 19 (14.6 % childrenof I generation and 1 (4.3 % – of II generation. In 3 children of I generation Hodgkin,s lymphoma was diagnosed.

  16. Non-Hodgkin s Lymphoma Presenting as an Endobronchial Polypoid Mass: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Han, Ji Yeon; Lee, Ki Nam; Roh, Mee Sook; Kim, Woo Jung [Dong-A University College of Medicine, Busan (Korea, Republic of)

    2011-02-15

    Non-Hodgkins lymphoma seldom, if ever, involves the tracheobronchial tree, and it manifests as a diffuse infiltrating pattern with clinically apparent systemic lymphoma. Endobronchial involvement presenting as an endobronchial polypoid mass is far rarer. We report here on a case of diffuse large B-cell non-Hodgkin lymphoma that presented as an endobronchial polypopid mass obstructing the central bronchi and this led to lobar atelectasis

  17. Role of Radiation Therapy in the Treatment of Hodgkin Lymphoma.

    Science.gov (United States)

    Gonzalez, Victor J

    2017-06-01

    Radiation therapy has historically been the pillar of curative treatment for Hodgkin lymphoma (HL). With improved efficacy of systemic therapy and the ever-increasing recognition of treatment-related morbidity in long-term survivors, the role of radiotherapy has evolved significantly. Modern combined modality therapy (CMT) with multi-agent chemotherapy followed by involved site radiation therapy (ISRT) to initially involved sites of disease remains the gold standard for the majority of patients with HL. Reduction of long-term treatment-related toxicity has become the major driver in clinical trial design for early-stage HL while improved disease-specific survival remains the goal in patients with more advanced and unfavorable disease. This review will address the data supporting the use of radiotherapy in HL as well as specific methods for reducing late toxicity from radiotherapy.

  18. Minimizing Late Effects for Patients With Mediastinal Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Aznar, Marianne C.; Maraldo, Maja V.; Schut, Deborah A.

    2015-01-01

    PURPOSE: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer. We investigated the risk for the development of CD and secondary lung, breast, and thyroid cancer after radiation therapy (RT) delivered with deep inspiration breath......-hold (DIBH) compared with free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT). The aim of this study was to determine which treatment modality best reduced the combined risk of life-threatening late effects in patients with mediastinal HL. METHODS AND MATERIALS......: Twenty-two patients with early-stage mediastinal HL were eligible for the study. Treatment plans were calculated with both 3DCRT and IMRT on both DIBH and FB planning computed tomographic scans. We reported the estimated dose to the heart, lung, female breasts, and thyroid and calculated the estimated...

  19. Breast cancer risk in female survivors of Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    De Bruin, Marie L; Sparidans, Judith; van't Veer, Mars B

    2009-01-01

    PURPOSE: We assessed the long-term risk of breast cancer (BC) after treatment for Hodgkin's lymphoma (HL). We focused on the volume of breast tissue exposed to radiation and the influence of gonadotoxic chemotherapy (CT). PATIENTS AND METHODS: We performed a cohort study among 1,122 female 5-year......%). The relative risk remained high after prolonged follow-up (> 30 years after treatment: SIR, 9.5; 95% CI, 4.9 to 16.6). Mantle field irradiation (involving the axillary, mediastinal, and neck nodes) was associated with a 2.7-fold increased risk (95% CI, 1.1 to 6.9) compared with similarly dosed (36 to 44 Gy......) mediastinal irradiation alone. Women with >or= 20 years of intact ovarian function after radiotherapy at young ages (

  20. Thrombotic complications in children with non-Hodgkin lymphoma

    Directory of Open Access Journals (Sweden)

    N. V. Lipay

    2013-01-01

    Full Text Available Our study was aimed at identifying of risk factors of venous thrombosis (VT in children with non-Hodgkin lymphomas. VT episodes were registered in 13 of 174 children treated (7.5 %. Possible impact of morphological type, initial mediastinal involvement, gender, age and use of L-asparaginase as a risk factor of thrombosis development were analyzed. Using multivariate analysis primary mediastinal tumor (OR = 4.73 [CI: 1.42–17.10] and patient age older than 13 years (OR = 4.3 [CI: 1.19–20.28 were identified as prognostic factors of thrombosis development (р < 0,05.