Single neuron computation

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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

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

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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.

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

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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.

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

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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

Single-cell axotomy of cultured hippocampal neurons integrated in neuronal circuits.

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Gomis-Rüth, Susana; Stiess, Michael; Wierenga, Corette J; Meyn, Liane; Bradke, Frank

2014-05-01

An understanding of the molecular mechanisms of axon regeneration after injury is key for the development of potential therapies. Single-cell axotomy of dissociated neurons enables the study of the intrinsic regenerative capacities of injured axons. This protocol describes how to perform single-cell axotomy on dissociated hippocampal neurons containing synapses. Furthermore, to axotomize hippocampal neurons integrated in neuronal circuits, we describe how to set up coculture with a few fluorescently labeled neurons. This approach allows axotomy of single cells in a complex neuronal network and the observation of morphological and molecular changes during axon regeneration. Thus, single-cell axotomy of mature neurons is a valuable tool for gaining insights into cell intrinsic axon regeneration and the plasticity of neuronal polarity of mature neurons. Dissociation of the hippocampus and plating of hippocampal neurons takes ∼2 h. Neurons are then left to grow for 2 weeks, during which time they integrate into neuronal circuits. Subsequent axotomy takes 10 min per neuron and further imaging takes 10 min per neuron.

Results on a Binding Neuron Model and Their Implications for Modified Hourglass Model for Neuronal Network

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Viswanathan Arunachalam

2013-01-01

Full Text Available The classical models of single neuron like Hodgkin-Huxley point neuron or leaky integrate and fire neuron assume the influence of postsynaptic potentials to last till the neuron fires. Vidybida (2008 in a refreshing departure has proposed models for binding neurons in which the trace of an input is remembered only for a finite fixed period of time after which it is forgotten. The binding neurons conform to the behaviour of real neurons and are applicable in constructing fast recurrent networks for computer modeling. This paper develops explicitly several useful results for a binding neuron like the firing time distribution and other statistical characteristics. We also discuss the applicability of the developed results in constructing a modified hourglass network model in which there are interconnected neurons with excitatory as well as inhibitory inputs. Limited simulation results of the hourglass network are presented.

The ISI distribution of the stochastic Hodgkin-Huxley neuron.

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Rowat, Peter F; Greenwood, Priscilla E

2014-01-01

The simulation of ion-channel noise has an important role in computational neuroscience. In recent years several approximate methods of carrying out this simulation have been published, based on stochastic differential equations, and all giving slightly different results. The obvious, and essential, question is: which method is the most accurate and which is most computationally efficient? Here we make a contribution to the answer. We compare interspike interval histograms from simulated data using four different approximate stochastic differential equation (SDE) models of the stochastic Hodgkin-Huxley neuron, as well as the exact Markov chain model simulated by the Gillespie algorithm. One of the recent SDE models is the same as the Kurtz approximation first published in 1978. All the models considered give similar ISI histograms over a wide range of deterministic and stochastic input. Three features of these histograms are an initial peak, followed by one or more bumps, and then an exponential tail. We explore how these features depend on deterministic input and on level of channel noise, and explain the results using the stochastic dynamics of the model. We conclude with a rough ranking of the four SDE models with respect to the similarity of their ISI histograms to the histogram of the exact Markov chain model.

A chimeric path to neuronal synchronization

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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).

A chimeric path to neuronal synchronization

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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)

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)

Existence of multiple receptors in single neurons: responses of single bullfrog olfactory neurons to many cAMP-dependent and independent odorants.

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Kashiwayanagi, M; Shimano, K; Kurihara, K

1996-11-04

The responses of single bullfrog olfactory neurons to various odorants were measured with the whole-cell patch clamp which offers direct information on cellular events and with the ciliary recording technique to obtain stable quantitative data from many neurons. A large portion of single olfactory neurons (about 64% and 79% in the whole-cell recording and in the ciliary recording, respectively) responded to many odorants with quite diverse molecular structures, including both odorants previously indicated to be cAMP-dependent (increasing) and independent odorants. One odorant elicited a response in many cells; e.g. hedione and citralva elicited the response in 100% and 92% of total neurons examined with the ciliary recording technique. To confirm that a single neuron carries different receptors or transduction pathways, the cross-adaptation technique was applied to single neurons. Application of hedione to a single neuron after desensitization of the current in response to lyral or citralva induced an inward current with a similar magnitude to that applied alone. It was suggested that most single olfactory neurons carry multiple receptors and at least dual transduction pathways.

Chimera states in a Hodgkin-Huxley model of thermally sensitive neurons

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Glaze, Tera A.; Lewis, Scott; Bahar, Sonya

2016-08-01

Chimera states occur when identically coupled groups of nonlinear oscillators exhibit radically different dynamics, with one group exhibiting synchronized oscillations and the other desynchronized behavior. This dynamical phenomenon has recently been studied in computational models and demonstrated experimentally in mechanical, optical, and chemical systems. The theoretical basis of these states is currently under active investigation. Chimera behavior is of particular relevance in the context of neural synchronization, given the phenomenon of unihemispheric sleep and the recent observation of asymmetric sleep in human patients with sleep apnea. The similarity of neural chimera states to neural "bump" states, which have been suggested as a model for working memory and visual orientation tuning in the cortex, adds to their interest as objects of study. Chimera states have been demonstrated in the FitzHugh-Nagumo model of excitable cells and in the Hindmarsh-Rose neural model. Here, we demonstrate chimera states and chimera-like behaviors in a Hodgkin-Huxley-type model of thermally sensitive neurons both in a system with Abrams-Strogatz (mean field) coupling and in a system with Kuramoto (distance-dependent) coupling. We map the regions of parameter space for which chimera behavior occurs in each of the two coupling schemes.

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...

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

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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

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

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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.

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

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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.

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

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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.

Hodgkin lymphoma

Science.gov (United States)

Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

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

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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.

A path integral approach to the Hodgkin-Huxley model

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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.

Hodgkin lymphoma - children

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... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... Cancer Institute website. Childhood Hodgkin lymphoma treatment (PDQ) - health professional ...

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

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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.)

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

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

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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

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

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.

Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

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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

Increasing inhibitory input increases neuronal firing rate: why and when? Diffusion process cases

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Feng Jianfeng [COGS, Sussex University (United Kingdom)]. E-mail: jf218@cam.ac.uk; Wei Gang [Department of Mathematics, Hong Kong Baptist University, Hong Kong (China)]. E-mail gwei@math.hkbu.edu.hk

2001-09-21

Increasing inhibitory input to single neuronal models, such as the FitzHugh-Nagumo model and the Hodgkin-Huxley model, can sometimes increase their firing rates, a phenomenon which we term inhibition-boosted firing (IBF). Here we consider neuronal models with diffusion approximation inputs, i.e. they share the identical first- and second-order statistics of the corresponding Poisson process inputs. Using the integrate-and-fire model and the IF-FHN model, we explore theoretically how and when IBF can happen. For both models, it is shown that there is a critical input frequency at which the efferent firing rate is identical when the neuron receives purely excitatory inputs or exactly balanced inhibitory and excitatory inputs. When the input frequency is lower than the critical frequency, IBF occurs. (author)

Spiking neuron devices consisting of single-flux-quantum circuits

International Nuclear Information System (INIS)

Hirose, Tetsuya; Asai, Tetsuya; Amemiya, Yoshihito

2006-01-01

Single-flux-quantum (SFQ) circuits can be used for making spiking neuron devices, which are useful elements for constructing intelligent, brain-like computers. The device we propose is based on the leaky integrate-and-fire neuron (IFN) model and uses a SFQ pulse as an action signal or a spike of neurons. The operation of the neuron device is confirmed by computer simulator. It can operate with a short delay of 100 ps or less and is the highest-speed neuron device ever reported

Hodgkin's sygdom--et histologisk problem

DEFF Research Database (Denmark)

Lauritzen, A F; Specht, L; Nissen, N I

1989-01-01

Since the Rye classification of Hodgkin's disease, many lesions which resemble Hodgkin's disease microscopically have been described. The histological features of Hodgkin's disease, including the BNLI subclassification of nodular sclerosis, and the lesions which resemble Hodgkin's disease microsc...

Impact of Bounded Noise and Rewiring on the Formation and Instability of Spiral Waves in a Small-World Network of Hodgkin-Huxley Neurons.

Science.gov (United States)

Yao, Yuangen; Deng, Haiyou; Ma, Chengzhang; Yi, Ming; Ma, Jun

2017-01-01

Spiral waves are observed in the chemical, physical and biological systems, and the emergence of spiral waves in cardiac tissue is linked to some diseases such as heart ventricular fibrillation and epilepsy; thus it has importance in theoretical studies and potential medical applications. Noise is inevitable in neuronal systems and can change the electrical activities of neuron in different ways. Many previous theoretical studies about the impacts of noise on spiral waves focus an unbounded Gaussian noise and even colored noise. In this paper, the impacts of bounded noise and rewiring of network on the formation and instability of spiral waves are discussed in small-world (SW) network of Hodgkin-Huxley (HH) neurons through numerical simulations, and possible statistical analysis will be carried out. Firstly, we present SW network of HH neurons subjected to bounded noise. Then, it is numerically demonstrated that bounded noise with proper intensity σ, amplitude A, or frequency f can facilitate the formation of spiral waves when rewiring probability p is below certain thresholds. In other words, bounded noise-induced resonant behavior can occur in the SW network of neurons. In addition, rewiring probability p always impairs spiral waves, while spiral waves are confirmed to be robust for small p, thus shortcut-induced phase transition of spiral wave with the increase of p is induced. Furthermore, statistical factors of synchronization are calculated to discern the phase transition of spatial pattern, and it is confirmed that larger factor of synchronization is approached with increasing of rewiring probability p, and the stability of spiral wave is destroyed.

Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

Science.gov (United States)

Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

2017-02-04

Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.

Auditory-nerve single-neuron thresholds to electrical stimulation from scala tympani electrodes.

Science.gov (United States)

Parkins, C W; Colombo, J

1987-12-31

Single auditory-nerve neuron thresholds were studied in sensory-deafened squirrel monkeys to determine the effects of electrical stimulus shape and frequency on single-neuron thresholds. Frequency was separated into its components, pulse width and pulse rate, which were analyzed separately. Square and sinusoidal pulse shapes were compared. There were no or questionably significant threshold differences in charge per phase between sinusoidal and square pulses of the same pulse width. There was a small (less than 0.5 dB) but significant threshold advantage for 200 microseconds/phase pulses delivered at low pulse rates (156 pps) compared to higher pulse rates (625 pps and 2500 pps). Pulse width was demonstrated to be the prime determinant of single-neuron threshold, resulting in strength-duration curves similar to other mammalian myelinated neurons, but with longer chronaxies. The most efficient electrical stimulus pulse width to use for cochlear implant stimulation was determined to be 100 microseconds/phase. This pulse width delivers the lowest charge/phase at threshold. The single-neuron strength-duration curves were compared to strength-duration curves of a computer model based on the specific anatomy of auditory-nerve neurons. The membrane capacitance and resulting chronaxie of the model can be varied by altering the length of the unmyelinated termination of the neuron, representing the unmyelinated portion of the neuron between the habenula perforata and the hair cell. This unmyelinated segment of the auditory-nerve neuron may be subject to aminoglycoside damage. Simulating a 10 micron unmyelinated termination for this model neuron produces a strength-duration curve that closely fits the single-neuron data obtained from aminoglycoside deafened animals. Both the model and the single-neuron strength-duration curves differ significantly from behavioral threshold data obtained from monkeys and humans with cochlear implants. This discrepancy can best be explained by

Characteristics of lymphographic semiotics in children with Hodgkin's disease

International Nuclear Information System (INIS)

Baryshnikov, V.L.; Krivenko, Eh.V.; Minkh, N.V.

1984-01-01

Direct low lymphography was performed in 140 children aged 2.5 to 16 wheh Hodgkin's disease. Typical changes in the lymph nodes were found in 45 (32.14%) patient;. Symptoms of disordered drainage function of the nodes in children occur more frequently than in adults (in 71% of the cases observed). X.ray signs of the morphological changes in the lymph nodes that in combination with functional symptoms give 4 main symptomocomplexes which are characteristic of Hodgkin's disease in children are singled out

Gender differences in human single neuron responses to male emotional faces.

Science.gov (United States)

Newhoff, Morgan; Treiman, David M; Smith, Kris A; Steinmetz, Peter N

2015-01-01

Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions. This study included recordings of single-neuron activity of 14 (6 male) epileptic patients in four brain areas: amygdala (236 neurons), hippocampus (n = 270), anterior cingulate cortex (n = 256), and ventromedial prefrontal cortex (n = 174). Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions. Significant gender differences were found in the left amygdala, where 23% (n = 15∕66) of neurons in men were significantly affected by facial emotion, vs. 8% (n = 6∕76) of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.

Bistability induces episodic spike communication by inhibitory neurons in neuronal networks.

Science.gov (United States)

Kazantsev, V B; Asatryan, S Yu

2011-09-01

Bistability is one of the important features of nonlinear dynamical systems. In neurodynamics, bistability has been found in basic Hodgkin-Huxley equations describing the cell membrane dynamics. When the neuron is clamped near its threshold, the stable rest potential may coexist with the stable limit cycle describing periodic spiking. However, this effect is often neglected in network computations where the neurons are typically reduced to threshold firing units (e.g., integrate-and-fire models). We found that the bistability may induce spike communication by inhibitory coupled neurons in the spiking network. The communication is realized in the form of episodic discharges with synchronous (correlated) spikes during the episodes. A spiking phase map is constructed to describe the synchronization and to estimate basic spike phase locking modes.

Neuromorphic silicon neuron circuits

Directory of Open Access Journals (Sweden)

Giacomo eIndiveri

2011-05-01

Full Text Available Hardware implementations of spiking neurons can be extremely useful for a large variety of applications, ranging from high-speed modeling of large-scale neural systems to real-time behaving systems, to bidirectional brain-machine interfaces. The specific circuit solutions used to implement silicon neurons depend on the application requirements. In this paper we describe the most common building blocks and techniques used to implement these circuits, and present an overview of a wide range of neuromorphic silicon neurons, which implement different computational models, ranging from biophysically realistic and conductance based Hodgkin-Huxley models to bi-dimensional generalized adaptive Integrate and Fire models. We compare the different design methodologies used for each silicon neuron design described, and demonstrate their features with experimental results, measured from a wide range of fabricated VLSI chips.

Gender Differences in Human Single Neuron Responses to Male Emotional Faces

Directory of Open Access Journals (Sweden)

Morgan eNewhoff

2015-09-01

Full Text Available Well-documented differences in the psychology and behavior of men and women have spurred extensive exploration of gender's role within the brain, particularly regarding emotional processing. While neuroanatomical studies clearly show differences between the sexes, the functional effects of these differences are less understood. Neuroimaging studies have shown inconsistent locations and magnitudes of gender differences in brain hemodynamic responses to emotion. To better understand the neurophysiology of these gender differences, we analyzed recordings of single neuron activity in the human brain as subjects of both genders viewed emotional expressions.This study included recordings of single-neuron activity of 14 (6 male epileptic patients in four brain areas: amygdala (236 neurons, hippocampus (n=270, anterior cingulate cortex (n=256, and ventromedial prefrontal cortex (n=174. Neural activity was recorded while participants viewed a series of avatar male faces portraying positive, negative or neutral expressions.Significant gender differences were found in the left amygdala, where 23% (n=15/66 of neurons in men were significantly affected by facial emotion, versus 8% (n=6/76 of neurons in women. A Fisher's exact test comparing the two ratios found a highly significant difference between the two (p<0.01. These results show specific differences between genders at the single-neuron level in the human amygdala. These differences may reflect gender-based distinctions in evolved capacities for emotional processing and also demonstrate the importance of including subject gender as an independent factor in future studies of emotional processing by single neurons in the human amygdala.

Stages of Childhood Hodgkin Lymphoma

Science.gov (United States)

... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

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

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

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.

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.

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...

Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry.

Science.gov (United States)

Zhu, Hongying; Zou, Guichang; Wang, Ning; Zhuang, Meihui; Xiong, Wei; Huang, Guangming

2017-03-07

The use of single-cell assays has emerged as a cutting-edge technique during the past decade. Although single-cell mass spectrometry (MS) has recently achieved remarkable results, deep biological insights have not yet been obtained, probably because of various technical issues, including the unavoidable use of matrices, the inability to maintain cell viability, low throughput because of sample pretreatment, and the lack of recordings of cell physiological activities from the same cell. In this study, we describe a patch clamp/MS-based platform that enables the sensitive, rapid, and in situ chemical profiling of single living neurons. This approach integrates modified patch clamp technique and modified MS measurements to directly collect and detect nanoliter-scale samples from the cytoplasm of single neurons in mice brain slices. Abundant possible cytoplasmic constituents were detected in a single neuron at a relatively fast rate, and over 50 metabolites were identified in this study. The advantages of direct, rapid, and in situ sampling and analysis enabled us to measure the biological activities of the cytoplasmic constituents in a single neuron, including comparing neuron types by cytoplasmic chemical constituents; observing changes in constituent concentrations as the physiological conditions, such as age, vary; and identifying the metabolic pathways of small molecules.

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

143 patients with Hodgkin's disease stage III (65 PS III, 78 CS III) were treated with radiotherapy alone (33 patients), combination chemotherapy alone (56 patients), or radiotherapy plus combination chemotherapy (54 patients). They were followed till death or from 7 to 191 months. Prognostic fac...... regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease....

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

Discrimination of Communication Vocalizations by Single Neurons and Groups of Neurons in the Auditory Midbrain

OpenAIRE

Schneider, David M.; Woolley, Sarah M. N.

2010-01-01

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...

hamlet, a binary genetic switch between single- and multiple- dendrite neuron morphology.

Science.gov (United States)

Moore, Adrian W; Jan, Lily Yeh; Jan, Yuh Nung

2002-08-23

The dendritic morphology of neurons determines the number and type of inputs they receive. In the Drosophila peripheral nervous system (PNS), the external sensory (ES) neurons have a single nonbranched dendrite, whereas the lineally related multidendritic (MD) neurons have extensively branched dendritic arbors. We report that hamlet is a binary genetic switch between these contrasting morphological types. In hamlet mutants, ES neurons are converted to an MD fate, whereas ectopic hamlet expression in MD precursors results in transformation of MD neurons into ES neurons. Moreover, hamlet expression induced in MD neurons undergoing dendrite outgrowth drastically reduces arbor branching.

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

Hodgkin Lymphoma (For Kids)

Science.gov (United States)

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

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.

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.

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

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

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.

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.

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.

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Science.gov (United States)

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

Coding of vocalizations by single neurons in ventrolateral prefrontal cortex.

Science.gov (United States)

Plakke, Bethany; Diltz, Mark D; Romanski, Lizabeth M

2013-11-01

Neuronal activity in single prefrontal neurons has been correlated with behavioral responses, rules, task variables and stimulus features. In the non-human primate, neurons recorded in ventrolateral prefrontal cortex (VLPFC) have been found to respond to species-specific vocalizations. Previous studies have found multisensory neurons which respond to simultaneously presented faces and vocalizations in this region. Behavioral data suggests that face and vocal information are inextricably linked in animals and humans and therefore may also be tightly linked in the coding of communication calls in prefrontal neurons. In this study we therefore examined the role of VLPFC in encoding vocalization call type information. Specifically, we examined previously recorded single unit responses from the VLPFC in awake, behaving rhesus macaques in response to 3 types of species-specific vocalizations made by 3 individual callers. Analysis of responses by vocalization call type and caller identity showed that ∼19% of cells had a main effect of call type with fewer cells encoding caller. Classification performance of VLPFC neurons was ∼42% averaged across the population. When assessed at discrete time bins, classification performance reached 70 percent for coos in the first 300 ms and remained above chance for the duration of the response period, though performance was lower for other call types. In light of the sub-optimal classification performance of the majority of VLPFC neurons when only vocal information is present, and the recent evidence that most VLPFC neurons are multisensory, the potential enhancement of classification with the addition of accompanying face information is discussed and additional studies recommended. Behavioral and neuronal evidence has shown a considerable benefit in recognition and memory performance when faces and voices are presented simultaneously. In the natural environment both facial and vocalization information is present simultaneously and

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

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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.

Pulsed neural networks consisting of single-flux-quantum spiking neurons

International Nuclear Information System (INIS)

Hirose, T.; Asai, T.; Amemiya, Y.

2007-01-01

An inhibitory pulsed neural network was developed for brain-like information processing, by using single-flux-quantum (SFQ) circuits. It consists of spiking neuron devices that are coupled to each other through all-to-all inhibitory connections. The network selects neural activity. The operation of the neural network was confirmed by computer simulation. SFQ neuron devices can imitate the operation of the inhibition phenomenon of neural networks

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

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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

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

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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.

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.

Stimulus-response functions of single avian olfactory bulb neurones.

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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.

Stages of Adult Hodgkin Lymphoma

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... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

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

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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.

Hodgkin's Lymphoma of the Breast

African Journals Online (AJOL)

TNHJOURNALPH

RESULT. A tissue diagnosis of Hodgkin's lymphoma with typical ... It was the first cancer to be cured ... ultrasonography showed enlarged liver. The .... McMillan A, Horning S. Non-Hodgkins lymphoma of the Breast. Cancer. 2007;110:25-30. 5.

Biophysically realistic minimal model of dopamine neuron

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Oprisan, Sorinel

2008-03-01

We proposed and studied a new biophysically relevant computational model of dopaminergic neurons. Midbrain dopamine neurons are involved in motivation and the control of movement, and have been implicated in various pathologies such as Parkinson's disease, schizophrenia, and drug abuse. The model we developed is a single-compartment Hodgkin-Huxley (HH)-type parallel conductance membrane model. The model captures the essential mechanisms underlying the slow oscillatory potentials and plateau potential oscillations. The main currents involved are: 1) a voltage-dependent fast calcium current, 2) a small conductance potassium current that is modulated by the cytosolic concentration of calcium, and 3) a slow voltage-activated potassium current. We developed multidimensional bifurcation diagrams and extracted the effective domains of sustained oscillations. The model includes a calcium balance due to the fundamental importance of calcium influx as proved by simultaneous electrophysiological and calcium imaging procedure. Although there are significant evidences to suggest a partially electrogenic calcium pump, all previous models considered only elecrtogenic pumps. We investigated the effect of the electrogenic calcium pump on the bifurcation diagram of the model and compared our findings against the experimental results.

Hodgkin's disease in pregnancy

International Nuclear Information System (INIS)

Szelc, S.; Szeliga, E.

1993-01-01

Pregnancy outcome and its influence on the effect of the MOPP chemotherapy for 30 patients with Hodgkin's disease were analyzed. During the first 6 months after completing the treatment 305 of pregnancies were interrupted. Pregnancy during complete remission of Hodgkin's disease after combined treatment does not increase the risk of relapse and is not a risk to delivery and foetus. (author)

ATR alterations in Hodgkin's lymphoma

NARCIS (Netherlands)

Liu, Angen; Takakuwa, Tetsuya; Fujita, Shigeki; Luo, Wen-Juan; Tresnasari, Kristianti; Van den Berg, Anke; Poppema, Sibrand; Aozasa, Katsuyuki

Hodgkin's lymphoma (HL) is characterized by the presence of neoplastic Hodgkin and Reed-Sternberg cells (HRSC) in a background of inflammatory cells. Free radicals and oxidative stress generated in the inflammatory lesions could cause DNA damage, thus providing a basis for lymphomagenesis.

Controlling Chaos in Neuron Based on Lasalle Invariance Principle

International Nuclear Information System (INIS)

Wei Duqu; Qin Yinghua

2011-01-01

A new control law is proposed to asymptotically stabilize the chaotic neuron system based on LaSalle invariant principle. The control technique does not require analytical knowledge of the system dynamics and operates without an explicit knowledge of the desired steady-state position. The well-known modified Hodgkin-Huxley (MHH) and Hindmarsh-Rose (HR) model neurons are taken as examples to verify the implementation of our method. Simulation results show the proposed control law is effective. The outcome of this study is significant since it is helpful to understand the learning process of a human brain towards the information processing, memory and abnormal discharge of the brain neurons. (general)

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

International Nuclear Information System (INIS)

Yoshioka, Masahiko

2002-01-01

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

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

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Xie, Rou-Gang; Chu, Wen-Guang; Hu, San-Jue; Luo, Ceng

2018-01-01

Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG) neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih) revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics. PMID:29303989

Characterization of Different Types of Excitability in Large Somatosensory Neurons and Its Plastic Changes in Pathological Pain States

Directory of Open Access Journals (Sweden)

Rou-Gang Xie

2018-01-01

Full Text Available Sensory neuron types have been distinguished by distinct morphological and transcriptional characteristics. Excitability is the most fundamental functional feature of neurons. Mathematical models described by Hodgkin have revealed three types of neuronal excitability based on the relationship between firing frequency and applied current intensity. However, whether natural sensory neurons display different functional characteristics in terms of excitability and whether this excitability type undergoes plastic changes under pathological pain states have remained elusive. Here, by utilizing whole-cell patch clamp recordings, behavioral and pharmacological assays, we demonstrated that large dorsal root ganglion (DRG neurons can be classified into three classes and four subclasses based on their excitability patterns, which is similar to mathematical models raised by Hodgkin. Analysis of hyperpolarization-activated cation current (Ih revealed different magnitude of Ih in different excitability types of large DRG neurons, with higher Ih in Class 2-1 than that in Class 1, 2-2 and 3. This indicates a crucial role of Ih in the determination of excitability type of large DRG neurons. More importantly, this pattern of excitability displays plastic changes and transition under pathological pain states caused by peripheral nerve injury. This study sheds new light on the functional characteristics of large DRG neurons and extends functional classification of large DRG neurons by integration of transcriptomic and morphological characteristics.

A Neuron-Based Model of Sleep-Wake Cycles

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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.

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

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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.

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

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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.

General Information about Adult Hodgkin Lymphoma

Science.gov (United States)

... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

Automated quantification of neuronal networks and single-cell calcium dynamics using calcium imaging.

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Patel, Tapan P; Man, Karen; Firestein, Bonnie L; Meaney, David F

2015-03-30

Recent advances in genetically engineered calcium and membrane potential indicators provide the potential to estimate the activation dynamics of individual neurons within larger, mesoscale networks (100s-1000+neurons). However, a fully integrated automated workflow for the analysis and visualization of neural microcircuits from high speed fluorescence imaging data is lacking. Here we introduce FluoroSNNAP, Fluorescence Single Neuron and Network Analysis Package. FluoroSNNAP is an open-source, interactive software developed in MATLAB for automated quantification of numerous biologically relevant features of both the calcium dynamics of single-cells and network activity patterns. FluoroSNNAP integrates and improves upon existing tools for spike detection, synchronization analysis, and inference of functional connectivity, making it most useful to experimentalists with little or no programming knowledge. We apply FluoroSNNAP to characterize the activity patterns of neuronal microcircuits undergoing developmental maturation in vitro. Separately, we highlight the utility of single-cell analysis for phenotyping a mixed population of neurons expressing a human mutant variant of the microtubule associated protein tau and wild-type tau. We show the performance of semi-automated cell segmentation using spatiotemporal independent component analysis and significant improvement in detecting calcium transients using a template-based algorithm in comparison to peak-based or wavelet-based detection methods. Our software further enables automated analysis of microcircuits, which is an improvement over existing methods. We expect the dissemination of this software will facilitate a comprehensive analysis of neuronal networks, promoting the rapid interrogation of circuits in health and disease. Copyright © 2015. Published by Elsevier B.V.

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

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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

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

Behavioral and Single-Neuron Sensitivity to Millisecond Variations in Temporally Patterned Communication Signals.

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Baker, Christa A; Ma, Lisa; Casareale, Chelsea R; Carlson, Bruce A

2016-08-24

In many sensory pathways, central neurons serve as temporal filters for timing patterns in communication signals. However, how a population of neurons with diverse temporal filtering properties codes for natural variation in communication signals is unknown. Here we addressed this question in the weakly electric fish Brienomyrus brachyistius, which varies the time intervals between successive electric organ discharges to communicate. These fish produce an individually stereotyped signal called a scallop, which consists of a distinctive temporal pattern of ∼8-12 electric pulses. We manipulated the temporal structure of natural scallops during behavioral playback and in vivo electrophysiology experiments to probe the temporal sensitivity of scallop encoding and recognition. We found that presenting time-reversed, randomized, or jittered scallops increased behavioral response thresholds, demonstrating that fish's electric signaling behavior was sensitive to the precise temporal structure of scallops. Next, using in vivo intracellular recordings and discriminant function analysis, we found that the responses of interval-selective midbrain neurons were also sensitive to the precise temporal structure of scallops. Subthreshold changes in membrane potential recorded from single neurons discriminated natural scallops from time-reversed, randomized, and jittered sequences. Pooling the responses of multiple neurons improved the discriminability of natural sequences from temporally manipulated sequences. Finally, we found that single-neuron responses were sensitive to interindividual variation in scallop sequences, raising the question of whether fish may analyze scallop structure to gain information about the sender. Collectively, these results demonstrate that a population of interval-selective neurons can encode behaviorally relevant temporal patterns with millisecond precision. The timing patterns of action potentials, or spikes, play important roles in representing

Synaptic Plasticity and Spike Synchronisation in Neuronal Networks

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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.

Generation of Induced Neuronal Cells by the Single Reprogramming Factor ASCL1

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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.

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

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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.

Mode-locking behavior of Izhikevich neurons under periodic external forcing

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Farokhniaee, AmirAli; Large, Edward W.

2017-06-01

Many neurons in the auditory system of the brain must encode periodic signals. These neurons under periodic stimulation display rich dynamical states including mode locking and chaotic responses. Periodic stimuli such as sinusoidal waves and amplitude modulated sounds can lead to various forms of n :m mode-locked states, in which a neuron fires n action potentials per m cycles of the stimulus. Here, we study mode-locking in the Izhikevich neurons, a reduced model of the Hodgkin-Huxley neurons. The Izhikevich model is much simpler in terms of the dimension of the coupled nonlinear differential equations compared with other existing models, but excellent for generating the complex spiking patterns observed in real neurons. We obtained the regions of existence of the various mode-locked states on the frequency-amplitude plane, called Arnold tongues, for the Izhikevich neurons. Arnold tongue analysis provides useful insight into the organization of mode-locking behavior of neurons under periodic forcing. We find these tongues for both class-1 and class-2 excitable neurons in both deterministic and noisy regimes.

Inverse stochastic resonance in networks of spiking neurons.

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Uzuntarla, Muhammet; Barreto, Ernest; Torres, Joaquin J

2017-07-01

Inverse Stochastic Resonance (ISR) is a phenomenon in which the average spiking rate of a neuron exhibits a minimum with respect to noise. ISR has been studied in individual neurons, but here, we investigate ISR in scale-free networks, where the average spiking rate is calculated over the neuronal population. We use Hodgkin-Huxley model neurons with channel noise (i.e., stochastic gating variable dynamics), and the network connectivity is implemented via electrical or chemical connections (i.e., gap junctions or excitatory/inhibitory synapses). We find that the emergence of ISR depends on the interplay between each neuron's intrinsic dynamical structure, channel noise, and network inputs, where the latter in turn depend on network structure parameters. We observe that with weak gap junction or excitatory synaptic coupling, network heterogeneity and sparseness tend to favor the emergence of ISR. With inhibitory coupling, ISR is quite robust. We also identify dynamical mechanisms that underlie various features of this ISR behavior. Our results suggest possible ways of experimentally observing ISR in actual neuronal systems.

Canards Existence in FitzHugh-Nagumo and Hodgkin-Huxley Neuronal Models

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Jean-Marc Ginoux

2015-01-01

Full Text Available In a previous paper we have proposed a new method for proving the existence of “canard solutions” for three- and four-dimensional singularly perturbed systems with only one fast variable which improves the methods used until now. The aim of this work is to extend this method to the case of four-dimensional singularly perturbed systems with two slow and two fast variables. This method enables stating a unique generic condition for the existence of “canard solutions” for such four-dimensional singularly perturbed systems which is based on the stability of folded singularities (pseudo singular points in this case of the normalized slow dynamics deduced from a well-known property of linear algebra. This unique generic condition is identical to that provided in previous works. Application of this method to the famous coupled FitzHugh-Nagumo equations and to the Hodgkin-Huxley model enables showing the existence of “canard solutions” in such systems.

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...

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.

Hodgkin's Lymphoma

Science.gov (United States)

... People who have had illnesses caused by the Epstein-Barr virus, such as infectious mononucleosis, are more likely to develop Hodgkin's lymphoma than are people who haven't had Epstein-Barr infections. By Mayo Clinic Staff . Mayo Clinic Footer ...

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.

Intussuscepção em linfoma Não-Hodgkin Intussuception in Non-Hodgkin's lymphoma

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Alessandra O. Ehrhardt

2003-06-01

Full Text Available Intussusception in adults is a rare condition and it can occur as a gastric complication from non-Hodgkin's lymphoma. Such complications can be difficult to diagnose because of ill-defined symptoms. Methods of imaging such as abdominal X-rays, ultrasonography, tomography and colonoscopy are useful for its diagnosis. Here a female patient with non-Hodgkin's lymphoma that evolved to intussusception of bowels, the regression of which was achieved by clinical and chemotherapeutic treatment without surgical intervention.

Second cancers after treatment for Hodgkin's disease: A review

International Nuclear Information System (INIS)

Boivin, J.F.; Hutchison, G.B.

1984-01-01

The authors review several reports of series of patients with Hodgkin's disease among whom second primary cancers have been diagnosed after radiotherapy or chemotherapy or both for Hodgkin's disease. An analysis of these reports suggests that (a) chemotherapy is a strong risk factor for leukemia, and (b) in the absence of chemotherapy, leukemia shows little or no increased incidence over ''spontaneous'' rates. Seven drugs have been identified as being frequently used in treatment of Hodgkin's disease (nitrogen mustard, cyclophosphamide, chlorambucil, procarbazine, vinglastine, vincristine, and prednisone). A large proportion of the patients receiving chemotherapy for Hodgkin's disease are exposed to several drugs and quantitative estimates of the independent leukemogenic effects of these drugs have not yet been obtained. Most of the person-years' experience accrued in the published studies occurred in the first decade after treatment for Hodgkin's disease. Follow-up over longer intervals of time will be necessary before solid tumor risk after therapy for Hodgkin's disease can be evaluated

Human temporal cortical single neuron activity during working memory maintenance.

Science.gov (United States)

Zamora, Leona; Corina, David; Ojemann, George

2016-06-01

The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

Science.gov (United States)

Zamora, Leona; Corina, David; Ojemann, George

2016-01-01

The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

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.

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 from...... the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different...

MRI assessment of bone marrow involvement in Hodgkin disease and non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Tesoro Tess, J.D.; Balzarini, L.; Ceglia, E.; Petrillo, R.; Musumeci, R.

1990-01-01

In order to evaluate the possible role of MRI in detecting lymphomatous marrow involvement, a MRI examination was performed in newly diagnosed patients with Hodgkin's disease (HD) and nonHodgkin lymphoma (NHL). From this the authors concluded that MRI should not be used as a replacement for bone marrow biopsies in HD and NHL, but rather as a complementary tool utilizing the panoramic view offered by MRI which permit to disclose focal areas of bone involvement different from the sacrum, thus not valuable with routine biopsies. (author). 4 refs.; 1 tab

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

Internally generated preactivation of single neurons in human medial frontal cortex predicts volition

Science.gov (United States)

Fried, Itzhak; Mukamel, Roy; Kreiman, Gabriel

2011-01-01

Understanding how self-initiated behavior is encoded by neuronal circuits in the human brain remains elusive. We recorded the activity of 1019 neurons while twelve subjects performed self-initiated finger movement. We report progressive neuronal recruitment over ~1500 ms before subjects report making the decision to move. We observed progressive increase or decrease in neuronal firing rate, particularly in the supplementary motor area (SMA), as the reported time of decision was approached. A population of 256 SMA neurons is sufficient to predict in single trials the impending decision to move with accuracy greater than 80% already 700 ms prior to subjects’ awareness. Furthermore, we predict, with a precision of a few hundred ms, the actual time point of this voluntary decision to move. We implement a computational model whereby volition emerges once a change in internally generated firing rate of neuronal assemblies crosses a threshold. PMID:21315264

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

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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.

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...

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.

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.)

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.

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....

Single neurons in prefrontal cortex encode abstract rules.

Science.gov (United States)

Wallis, J D; Anderson, K C; Miller, E K

2001-06-21

The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on the prefrontal cortex (PFC) because its damage often results in difficulty in following rules. Here we explore its neural basis by recording from single neurons in the PFC of monkeys trained to use two abstract rules. They were required to indicate whether two successively presented pictures were the same or different depending on which rule was currently in effect. The monkeys performed this task with new pictures, thus showing that they had learned two general principles that could be applied to stimuli that they had not yet experienced. The most prevalent neuronal activity observed in the PFC reflected the coding of these abstract rules.

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.

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.

Ensembles of gustatory cortical neurons anticipate and discriminate between tastants in a single lick

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Jennifer R Stapleton

2007-10-01

Full Text Available The gustatory cortex (GC processes chemosensory and somatosensory information and is involved in learning and anticipation. Previously we found that a subpopulation of GC neurons responded to tastants in a single lick (Stapleton et al., 2006. Here we extend this investigation to determine if small ensembles of GC neurons, obtained while rats received blocks of tastants on a fixed ratio schedule (FR5, can discriminate between tastants and their concentrations after a single 50 µL delivery. In the FR5 schedule subjects received tastants every fifth (reinforced lick and the intervening licks were unreinforced. The ensemble firing patterns were analyzed with a Bayesian generalized linear model whose parameters included the firing rates and temporal patterns of the spike trains. We found that when both the temporal and rate parameters were included, 12 of 13 ensembles correctly identified single tastant deliveries. We also found that the activity during the unreinforced licks contained signals regarding the identity of the upcoming tastant, which suggests that GC neurons contain anticipatory information about the next tastant delivery. To support this finding we performed experiments in which tastant delivery was randomized within each block and found that the neural activity following the unreinforced licks did not predict the upcoming tastant. Collectively, these results suggest that after a single lick ensembles of GC neurons can discriminate between tastants, that they may utilize both temporal and rate information, and when the tastant delivery is repetitive ensembles contain information about the identity of the upcoming tastant delivery.

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.

Recording single neurons' action potentials from freely moving pigeons across three stages of learning.

Science.gov (United States)

Starosta, Sarah; Stüttgen, Maik C; Güntürkün, Onur

2014-06-02

While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.(1) for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.

Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease. Pneumonitis nach infradiaphragmaler Bestrahlung bei Morbus Hodgkin

Energy Technology Data Exchange (ETDEWEB)

Zierhut, D.; Flentje, M. (Radiologische Klinik, Heidelberg Univ. (Germany)); Kalle, A. von (Medizinische Poliklinik, Heidelberg Univ. (Germany)); Moeller, P. (Pathologisches Inst., Heidelberg Univ. (Germany))

1992-12-01

A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.).

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...

Optimal physiological structure of small neurons to guarantee stable information processing

Science.gov (United States)

Zeng, S. Y.; Zhang, Z. Z.; Wei, D. Q.; Luo, X. S.; Tang, W. Y.; Zeng, S. W.; Wang, R. F.

2013-02-01

Spike is the basic element for neuronal information processing and the spontaneous spiking frequency should be less than 1 Hz for stable information processing. If the neuronal membrane area is small, the frequency of neuronal spontaneous spiking caused by ion channel noise may be high. Therefore, it is important to suppress the deleterious spontaneous spiking of the small neurons. We find by simulation of stochastic neurons with Hodgkin-Huxley-type channels that the leakage system is critical and extremely efficient to suppress the spontaneous spiking and guarantee stable information processing of the small neurons. However, within the physiological limit the potassium system cannot do so. The suppression effect of the leakage system is super-exponential, but that of the potassium system is quasi-linear. With the minor physiological cost and the minimal consumption of metabolic energy, a slightly lower reversal potential and a relatively larger conductance of the leakage system give the optimal physiological structure to suppress the deleterious spontaneous spiking and guarantee stable information processing of small neurons, dendrites and axons.

Theoretical analysis of transcranial magneto-acoustical stimulation with Hodgkin–Huxley neuron model

Directory of Open Access Journals (Sweden)

Yi eYuan

2016-04-01

Full Text Available Transcranial magneto-acoustical stimulation (TMAS is a novel stimulation technology in which an ultrasonic wave within a magnetostatic field generates an electric current in an area of interest in the brain to modulate neuronal activities. As a key part of the neural network, neurons transmit information in the nervous system. However, the effect of TMAS on the neuronal firing rhythm remains unknown. To address this problem, we investigated the stimulatory mechanism of TMAS on neurons with a Hodgkin-Huxley neuron model. The simulation results indicate that the magnetostatic field intensity and ultrasonic power can affect the amplitude and interspike interval of neuronal action potential under continuous wave ultrasound. The simulation results also show that the ultrasonic power, duty cycle and repetition frequency can alter the firing rhythm of neural action potential under pulsed ultrasound. This study can help to reveal and explain the biological mechanism of TMAS and to provide a theoretical basis for TMAS in the treatment or rehabilitation of neuropsychiatric disorders.

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)

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.

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.

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...

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...

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

Effects of channel noise on firing coherence of small-world Hodgkin-Huxley neuronal networks

Science.gov (United States)

Sun, X. J.; Lei, J. Z.; Perc, M.; Lu, Q. S.; Lv, S. J.

2011-01-01

We investigate the effects of channel noise on firing coherence of Watts-Strogatz small-world networks consisting of biophysically realistic HH neurons having a fraction of blocked voltage-gated sodium and potassium ion channels embedded in their neuronal membranes. The intensity of channel noise is determined by the number of non-blocked ion channels, which depends on the fraction of working ion channels and the membrane patch size with the assumption of homogeneous ion channel density. We find that firing coherence of the neuronal network can be either enhanced or reduced depending on the source of channel noise. As shown in this paper, sodium channel noise reduces firing coherence of neuronal networks; in contrast, potassium channel noise enhances it. Furthermore, compared with potassium channel noise, sodium channel noise plays a dominant role in affecting firing coherence of the neuronal network. Moreover, we declare that the observed phenomena are independent of the rewiring probability.

Long-term memory in Aplysia modulates the total number of varicosities of single identified sensory neurons.

OpenAIRE

Bailey, C H; Chen, M

1988-01-01

The morphological consequences of long-term habituation and sensitization of the gill withdrawal reflex in Aplysia california were explored by examining the total number of presynaptic varicosities of single identified sensory neurons (a critical site of plasticity for the biochemical and biophysical changes that underlie both types of learning) in control and behaviorally trained animals. Sensory neurons from habituated animals had 35% fewer synaptic varicosities than did sensory neurons fro...

BigNeuron: Large-scale 3D Neuron Reconstruction from Optical Microscopy Images

OpenAIRE

Peng, Hanchuan; Hawrylycz, Michael; Roskams, Jane; Hill, Sean; Spruston, Nelson; Meijering, Erik; Ascoli, Giorgio A.

2015-01-01

textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and standardization to provide a community resource for automated reconstruction of dendritic and axonal morphology of single neurons. Understanding the structure of single neurons is critical for unde...

Multiplicative mixing of object identity and image attributes in single inferior temporal neurons.

Science.gov (United States)

Ratan Murty, N Apurva; Arun, S P

2018-04-03

Object recognition is challenging because the same object can produce vastly different images, mixing signals related to its identity with signals due to its image attributes, such as size, position, rotation, etc. Previous studies have shown that both signals are present in high-level visual areas, but precisely how they are combined has remained unclear. One possibility is that neurons might encode identity and attribute signals multiplicatively so that each can be efficiently decoded without interference from the other. Here, we show that, in high-level visual cortex, responses of single neurons can be explained better as a product rather than a sum of tuning for object identity and tuning for image attributes. This subtle effect in single neurons produced substantially better population decoding of object identity and image attributes in the neural population as a whole. This property was absent both in low-level vision models and in deep neural networks. It was also unique to invariances: when tested with two-part objects, neural responses were explained better as a sum than as a product of part tuning. Taken together, our results indicate that signals requiring separate decoding, such as object identity and image attributes, are combined multiplicatively in IT neurons, whereas signals that require integration (such as parts in an object) are combined additively. Copyright © 2018 the Author(s). Published by PNAS.

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

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....

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...

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

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

Acute nonlymphocytic leukemia: a delayed complication of Hodgkin's disease therapy: analysis of 109 cases

International Nuclear Information System (INIS)

Cadman, E.C.; Capizzi, R.L.; Bertino, J.R.

1977-01-01

The use of combined modality therapy (irradiation and combinations of drugs) in the treatment of Hodgkin's disease has produced a significant improvement in survival, during which most patients lead an active and productive life. The estimated 1% incidence of leukemia in treated Hodgkin's disease patients, however, is greater than would be expected in the general population. There is a vast amount of literature which indicates that alkylating agents, procarbazine and irradiation are leukemogenic and immunosuppressive in animals and man. It is then conceivable that the current intensive treatment programs which use these agents are promoting the development of acute non-lymphocytic leukemia (ANLL). This leukemia has occurred most often in patients whose Hodgkin's disease is poorly controlled and who have received more aggressive therapy. The latent period from the diagnosis of Hodgkin's disease to the diagnosis of leukemia is significantly shorter (p < 0.0005) in those patients who have received intensive and near maximal radiotherapy (total nodal irradiation), combination chemotherapy (MOPP or equivalent) or a sequential combination of the two modalities than similar patients who were threated with less than total nodal irradiation and or single agent chemotherapy. The following characteristic features have occurred with sufficient frequency to suggest that the subsequent leukemia is a distinct clinicopathological entity: pancytopenia, megaloblastoid marrow, nucleated red blood cells in the peripheral blood, random chromosomal aberrations of the bone marrow in most patients (94%), and refractoriness to antileukemia therapy (response rate 6.5%) with a very short survival

Hodgkin's disease part 1: pathology, staging, and management of early stage disease

International Nuclear Information System (INIS)

Mauch, Peter; Yahalom, Joachim

1995-01-01

Over the past 25 years there have been dramatic improvements in our understanding of the epidemiology, biology, natural history, and treatment of Hodgkins disease. Hodgkin's disease is one of the few cancers where both chemotherapy and radiation therapy have provided dramatic improvements in cure of this once uniformly fatal disease. Part 1 of the refresher course on Hodgkin's disease will include a review of: 1) New Findings in epidemiology, immunohistochemistry and molecular biology of the Reed-Sternberg cell including association with Epstein-Barr virus; 2) Review of pathology including discussions of NS 1 vs NS2, and nodular LP subclassifications; 3) Recommendations for staging including the role of staging laparotomy in Hodgkin's disease; 4) Standard techniques for commonly used radiation therapy fields for Hodgkin's disease and 5) Treatment of early stage Hodgkin's disease including an overview on recent and current clinical trials

Comparison of squamous cell carcinoma with non-Hodgkin's lymphoma of tonsillar region

International Nuclear Information System (INIS)

Tsukiyama, Iwao; Yamashita, Kohsuke; Kajiura, Yuuichi; Ogino, Takashi; Akine, Yasuyuki; Egawa, Sunao; Ono, Isamu

1987-01-01

A total of 98 patients with malignant tumors of the tonsil (Squamous cell carcinoma, 34 patients, Non-Hodgkin's lymphoma, 64 patients) werw treated with radiation therapy between 1962 and 1979 at the National Cancer Center Hospital. All were staged by the TNM system, using UICC Classification 1978. With regard to stage distribution, Stage III is most frequent (47.1 %) in squamous cell carcinoma, Stage IV is most frequent (48.4 %) in Non-Hodgkin's lymphoma. Much more advanced cases were included in Non-Hodgkin's lymphoma. Five year survival rate for patients with squamous cell carcinoma and Non-Hodgkin's lymphoma were 49 % and 62 %, respectively. 50 % survival months with squamous cell carcinoma and Non-Hodgkin's lymphoma were 58.7 months and 195.5 months, respectively. Better prognosis was observed in Non-Hodgkin's lymphoma than squamous cell cacinoma. (author)

Rheumatic manifestations at presentation of Hodgkin's disease and non-Hodgkin's malignant lymphoma. A national survey of one hundred forty-six patients

International Nuclear Information System (INIS)

Gaudin, P.; Rozand, Y.; Fauconnier, J.; Phelip, X.

1995-01-01

The authors report the findings of a national survey conducted at the request for the French Society for Rheumatology to list the rheumatic manifestations that can be inaugural in Hodgkin's disease on non-Hodgkin's malignant lymphoma. This was an exploratory, retrospective, descriptive study of 146 patients from 22 rheumatology departments. A number of clinical features (young male, nocturnal sweats, generalized pruritus, protracted fever, central or peripheral lymphadenopathy) and laboratory test abnormalities (evidence of severe inflammation) considerably increased the likelihood of Hodgkin's disease rather than malignant lymphoma. The diagnosis of bony involvement requires multidisciplinary studies of tumor specimens. (authors). 4 figs., 7 tabs., 71 refs

Pneumonitis following infradiaphragmatic irradiation in Hodgkin's disease

International Nuclear Information System (INIS)

Zierhut, D.; Flentje, M.; Kalle, A. von; Moeller, P.

1992-01-01

A case is reported on radiation pneumonitis in the left costodiaphragmatic sinus 6 weeks following combined chemo- and radiotherapy of Hodgkin's disease. Thoracotomy was performed in order to exclude a pulmonal relapse of Hodgkin's disease. Thereby the diagnosis of radiation pneumonitis was histologically proven. The development of pneumonitis after irradiation of the spleen may occur and has to be considered in the differential diagnosis of pulmonal affections. (orig.) [de

Hodgkin's lymphoma mimicking necrotizing pneumonia: case report

Energy Technology Data Exchange (ETDEWEB)

Park, Eun Ah; Lee, Hyun Ju; Im, Jung GI; Goo, Jin Mo; Lim, Kun Young; Lee, Chang Hyun [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2004-11-01

This study describes a case of pulmonary Hodgkin's lymphoma of the nodular sclerosing type presenting as a large cavitary mass with air-fluid levels. We also conduct a review of the previous articles on pulmonary Hodgkin's lymphoma.

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

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.

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.

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.

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.

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...

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

Value encoding in single neurons in the human amygdala during decision making.

Science.gov (United States)

Jenison, Rick L; Rangel, Antonio; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A

2011-01-05

A growing consensus suggests that the brain makes simple choices by assigning values to the stimuli under consideration and then comparing these values to make a decision. However, the network involved in computing the values has not yet been fully characterized. Here, we investigated whether the human amygdala plays a role in the computation of stimulus values at the time of decision making. We recorded single neuron activity from the amygdala of awake patients while they made simple purchase decisions over food items. We found 16 amygdala neurons, located primarily in the basolateral nucleus that responded linearly to the values assigned to individual items.

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

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.

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

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

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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.

Autaptic pacemaker mediated propagation of weak rhythmic activity across small-world neuronal networks

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Yilmaz, Ergin; Baysal, Veli; Ozer, Mahmut; Perc, Matjaž

2016-02-01

We study the effects of an autapse, which is mathematically described as a self-feedback loop, on the propagation of weak, localized pacemaker activity across a Newman-Watts small-world network consisting of stochastic Hodgkin-Huxley neurons. We consider that only the pacemaker neuron, which is stimulated by a subthreshold periodic signal, has an electrical autapse that is characterized by a coupling strength and a delay time. We focus on the impact of the coupling strength, the network structure, the properties of the weak periodic stimulus, and the properties of the autapse on the transmission of localized pacemaker activity. Obtained results indicate the existence of optimal channel noise intensity for the propagation of the localized rhythm. Under optimal conditions, the autapse can significantly improve the propagation of pacemaker activity, but only for a specific range of the autaptic coupling strength. Moreover, the autaptic delay time has to be equal to the intrinsic oscillation period of the Hodgkin-Huxley neuron or its integer multiples. We analyze the inter-spike interval histogram and show that the autapse enhances or suppresses the propagation of the localized rhythm by increasing or decreasing the phase locking between the spiking of the pacemaker neuron and the weak periodic signal. In particular, when the autaptic delay time is equal to the intrinsic period of oscillations an optimal phase locking takes place, resulting in a dominant time scale of the spiking activity. We also investigate the effects of the network structure and the coupling strength on the propagation of pacemaker activity. We find that there exist an optimal coupling strength and an optimal network structure that together warrant an optimal propagation of the localized rhythm.

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 ce...

Non-Hodgkin lymphoma - children

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... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Updated: January 27, 2016. Accessed June 3, 2016. American Society of Clinical ... Institute website. Childhood non-Hodgkin lymphoma treatment (PDQ) - health ...

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....

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

Apoptosis and radiosensitization of Hodgkin cells by proteasome inhibition

International Nuclear Information System (INIS)

Pajonk, Frank; Pajonk, Katja; McBride, William H.

2000-01-01

Purpose: Malignant cells from Hodgkin's disease have been reported to be defective in regulation of NF-κB activity. Ionizing radiation is known to activate NF-κB, and it has been suggested that this pathway may protect cells from apoptosis following exposure to radiation and other therapeutic agents. Defective NF-κB regulation in Hodgkin cells could therefore dictate the response of this disease to therapy, as well as be responsible for maintaining the malignant phenotype. The purpose of this study was to explore whether NF-κB activity could be modulated in Hodgkin cells and whether it determines the response of these cells to treatment with ionizing radiation and/or dexamethasone. Methods and Materials: Activation of NF-κB in cells is accomplished in large part by degradation of its inhibitor IκB through the 26s proteasome. HD-My-Z Hodgkin cells were treated with the proteasome inhibitor MG-132 or transduced with a dominant negative super-repressor IκBα. Clonogenic survival, apoptosis, proteasome activity, and NF-κB binding activity were monitored in response to ionizing radiation and/or dexamethasone treatment. Results: HD-My-Z Hodgkin cells had modest NF-κB levels but, unlike other cell types, did not decrease their level of constitutively active NF-κB in response to proteasome inhibition with MG-132. In contrast, transduction with a non-phosphorable IκBα construct abolished expression. MG-132 did, however, induce apoptosis in HD-My-Z cells and sensitized them to ionizing radiation. Dexamethasone treatment had no effect on NF-κB activity or clonogenic survival of Hodgkin cells, but protected them from irradiation. Conclusion: We conclude that inhibition of 26s proteasome activity can induce apoptosis in HD-My-Z Hodgkin cells and radiosensitize them, in spite of the fact that their constitutively active NF-κB levels are unaltered. The proteasome may be a promising new therapeutic target for intervention in this disease. In contrast, the use of

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

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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.

Towards a general theory of neural computation based on prediction by single neurons.

Directory of Open Access Journals (Sweden)

Christopher D Fiorillo

Full Text Available Although there has been tremendous progress in understanding the mechanics of the nervous system, there has not been a general theory of its computational function. Here I present a theory that relates the established biophysical properties of single generic neurons to principles of Bayesian probability theory, reinforcement learning and efficient coding. I suggest that this theory addresses the general computational problem facing the nervous system. Each neuron is proposed to mirror the function of the whole system in learning to predict aspects of the world related to future reward. According to the model, a typical neuron receives current information about the state of the world from a subset of its excitatory synaptic inputs, and prior information from its other inputs. Prior information would be contributed by synaptic inputs representing distinct regions of space, and by different types of non-synaptic, voltage-regulated channels representing distinct periods of the past. The neuron's membrane voltage is proposed to signal the difference between current and prior information ("prediction error" or "surprise". A neuron would apply a Hebbian plasticity rule to select those excitatory inputs that are the most closely correlated with reward but are the least predictable, since unpredictable inputs provide the neuron with the most "new" information about future reward. To minimize the error in its predictions and to respond only when excitation is "new and surprising," the neuron selects amongst its prior information sources through an anti-Hebbian rule. The unique inputs of a mature neuron would therefore result from learning about spatial and temporal patterns in its local environment, and by extension, the external world. Thus the theory describes how the structure of the mature nervous system could reflect the structure of the external world, and how the complexity and intelligence of the system might develop from a population of

Childhood Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

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In childhood Hodgkin lymphoma, current treatment uses risk-adapted, response-based paradigms to determine the length and intensity of treatment. Get detailed information about newly diagnosed and recurrent classical and nodular lymphocyte predominant Hodgkin lymphoma, including presentation, diagnosis and staging, prognosis, and treatment in this summary for clinicians.

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

Contribution of LFP dynamics to single-neuron spiking variability in motor cortex during movement execution

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Rule, Michael E.; Vargas-Irwin, Carlos; Donoghue, John P.; Truccolo, Wilson

2015-01-01

Understanding the sources of variability in single-neuron spiking responses is an important open problem for the theory of neural coding. This variability is thought to result primarily from spontaneous collective dynamics in neuronal networks. Here, we investigate how well collective dynamics reflected in motor cortex local field potentials (LFPs) can account for spiking variability during motor behavior. Neural activity was recorded via microelectrode arrays implanted in ventral and dorsal premotor and primary motor cortices of non-human primates performing naturalistic 3-D reaching and grasping actions. Point process models were used to quantify how well LFP features accounted for spiking variability not explained by the measured 3-D reach and grasp kinematics. LFP features included the instantaneous magnitude, phase and analytic-signal components of narrow band-pass filtered (δ,θ,α,β) LFPs, and analytic signal and amplitude envelope features in higher-frequency bands. Multiband LFP features predicted single-neuron spiking (1ms resolution) with substantial accuracy as assessed via ROC analysis. Notably, however, models including both LFP and kinematics features displayed marginal improvement over kinematics-only models. Furthermore, the small predictive information added by LFP features to kinematic models was redundant to information available in fast-timescale (spiking history. Overall, information in multiband LFP features, although predictive of single-neuron spiking during movement execution, was redundant to information available in movement parameters and spiking history. Our findings suggest that, during movement execution, collective dynamics reflected in motor cortex LFPs primarily relate to sensorimotor processes directly controlling movement output, adding little explanatory power to variability not accounted by movement parameters. PMID:26157365

Molecular hierarchy in neurons differentiated from mouse ES cells containing a single human chromosome 21.

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Wang, Chi Chiu; Kadota, Mitsutaka; Nishigaki, Ryuichi; Kazuki, Yasuhiro; Shirayoshi, Yasuaki; Rogers, Michael Scott; Gojobori, Takashi; Ikeo, Kazuho; Oshimura, Mitsuo

2004-02-06

Defects in neurogenesis and neuronal differentiation in the fetal brain of Down syndrome (DS) patients lead to the apparent neuropathological abnormalities and contribute to the phenotypic characters of mental retardation, and premature development of Alzheimer's disease, those being the most common phenotype in DS. In order to understand the molecular mechanism underlying the cause of phenotypic abnormalities in the DS brain, we have utilized an in vitro model of TT2F mouse embryonic stem cells containing a single human chromosome 21 (hChr21) to study neuron development and neuronal differentiation by microarray containing 15K developmentally expressed cDNAs. Defective neuronal differentiation in the presence of extra hChr21 manifested primarily the post-transcriptional and translational modification, such as Mrpl10, SNAPC3, Srprb, SF3a60 in the early neuronal stem cell stage, and Mrps18a, Eef1g, and Ubce8 in the late differentiated stage. Hierarchical clustering patterned specific expression of hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation, such as Syngr2, Dncic2, Eif3sf, and Peg3.

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

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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.

Pyrogen release in vitro by lymphoid tissues from patients with Hodgkin's disease.

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Bodel, P

1974-01-01

The mechanism of fever in patients with Hodgkin's disease was investigated by examining endogenous pyrogen production by blood, spleen, and lymph node cells incubated in vitro. Blood leucocytes from febrile or afebrile patients with Hodgkin's disease did not produce pyrogen spontaneously. Spleen cells, however, frequently released pyrogen during initial incubations, unlike spleen cells from patients with non-malignant diseases. Pyrogen production occurred from spleens without observed pathologic infiltrates of Hodgkin's disease. Lymph nodes involved with Hodgkin's disease produced pyrogen more frequently than did nodes involved with other diseases. Pyrogen production by tissue cells was prolonged, required protein synthesis, and in some cases was due to mononuclear cells; it did not correlate with fever in the patient. These studies demonstrate spontaneous production of endogenous pyrogen in vitro by lymphoid tissue cells from patients with Hodgkin's disease.

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.

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.

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

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...

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

Single-cell imaging of bioenergetic responses to neuronal excitotoxicity and oxygen and glucose deprivation.

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Connolly, Niamh M C; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen H M

2014-07-30

Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, and subsequent neuronal injury. We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contribution of effects of non-neuronal cells. Hence, we here characterized bioenergetics during transient excitotoxicity in rat and mouse primary neurons at the single-cell level using fluorescent sensors for intracellular glucose, ATP, and activation of the energy sensor AMP-activated protein kinase (AMPK). We identified ATP depletion and recovery to energetic homeostasis, along with AMPK activation, as surprisingly rapid and plastic responses in two excitotoxic injury paradigms. We observed rapid recovery of neuronal ATP levels also in the absence of extracellular glucose, or when glycolytic ATP production was inhibited, but found mitochondria to be critical for fast and complete energetic recovery. Using an injury model of oxygen and glucose deprivation, we identified a similarly rapid bioenergetics response, yet with incomplete ATP recovery and decreased AMPK activity. Interestingly, excitotoxicity also induced an accumulation of intracellular glucose, providing an additional source of energy during and after excitotoxicity-induced energy depletion. We identified this to originate from extracellular, AMPK-dependent glucose uptake and from intracellular glucose mobilization. Surprisingly, cells recovering their elevated glucose levels faster to baseline survived longer, indicating that the plasticity of neurons to adapt to bioenergetic challenges is a key indicator of neuronal viability. Copyright © 2014 the authors 0270-6474/14/3410192-14$15.00/0.

Primary Refractory and Relapsed Classical Hodgkin Lymphoma - Significance of Differential CD15 Expression in Hodgkin-Reed-Sternberg Cells

Directory of Open Access Journals (Sweden)

Daniel Benharroch, Shai Pilosof, Jacob Gopas, Itai Levi

2012-01-01

Full Text Available We recognized a few possible complications of classical Hodgkin lymphoma therapy in a cohort of 209 patients: 8 developed a primary refractory disease (primary progression, 36 showed an early relapse and 21 showed a late relapse. Sialyl-CD15 expression in Hodgkin-Reed-Sternberg cells was significantly more positive in primary refractory Hodgkin lymphoma, which confirms our previously published findings. Bcl-2 showed a significantly lower level of expression in primary refractory disease than in the other follow-up groups. This is in contrast with a previous finding of Bcl-2, associated with a poor prognosis in primary refractory illness. Another category of variables, old age and advanced stages, was significantly different in the various complications but this finding is probably to be expected. We could not demonstrate a difference between the sequels and the control group with regard to several clinical and immunohistochemical markers. Sialyl-CD15 and Bcl-2 expression, in contrast, were confirmed as prognostic factors, mainly of tumor progression into primary refractory disease.

Linfoma não-Hodgkin de órbita: relato de caso Non-Hodgkin orbital lymphoma: case report

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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.

Brentuximab Vedotin Treatment for Primary Refractory Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Hung-Bo Wu

2013-01-01

Full Text Available Up to 40% of patients with advanced Hodgkin lymphoma (HL become refractory or relapsed after current standard chemotherapy, among which primary refractory HL confers a particularly poor outcome. With intensive salvage chemotherapy and autologous stem cell transplantation, the long-term remission rate for these patients was only 30%, but more selective treatments with higher therapeutic index are needed. We report the experience of using a new anti-CD30 immunotoxin, brentuximab vedotin, in salvage treatment of a 30-year-old woman with primary refractory Hodgkin lymphoma. The patient presented with SVC syndrome due to the bulky mediastinal tumor and was confirmed to have classical Hodgkin lymphoma, nodular sclerosis type, stage IIIA. The tumor responded to induction chemotherapy transiently, but local progression was noted during subsequent cycles of treatment. Salvage radiotherapy to the mediastinal tumor, obtained no remission but was followed by rapid in-field progression and then lung metastasis. She declined stem cell transplantation and received salvage brentuximab vedotin (BV therapy, which induced dramatic shrinkage of tumor without significant side effects. Serial followup of PET/CT imaging confirmed a rapid and continuous complete remission for 12 months. Although durability of the remission needs further observation, this case illustrates the excellent efficacy of brentuximab vedotin in primary refractory Hodgkin lymphoma.

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

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

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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.

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

Assimilation of Biophysical Neuronal Dynamics in Neuromorphic VLSI.

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Wang, Jun; Breen, Daniel; Akinin, Abraham; Broccard, Frederic; Abarbanel, Henry D I; Cauwenberghs, Gert

2017-12-01

Representing the biophysics of neuronal dynamics and behavior offers a principled analysis-by-synthesis approach toward understanding mechanisms of nervous system functions. We report on a set of procedures assimilating and emulating neurobiological data on a neuromorphic very large scale integrated (VLSI) circuit. The analog VLSI chip, NeuroDyn, features 384 digitally programmable parameters specifying for 4 generalized Hodgkin-Huxley neurons coupled through 12 conductance-based chemical synapses. The parameters also describe reversal potentials, maximal conductances, and spline regressed kinetic functions for ion channel gating variables. In one set of experiments, we assimilated membrane potential recorded from one of the neurons on the chip to the model structure upon which NeuroDyn was designed using the known current input sequence. We arrived at the programmed parameters except for model errors due to analog imperfections in the chip fabrication. In a related set of experiments, we replicated songbird individual neuron dynamics on NeuroDyn by estimating and configuring parameters extracted using data assimilation from intracellular neural recordings. Faithful emulation of detailed biophysical neural dynamics will enable the use of NeuroDyn as a tool to probe electrical and molecular properties of functional neural circuits. Neuroscience applications include studying the relationship between molecular properties of neurons and the emergence of different spike patterns or different brain behaviors. Clinical applications include studying and predicting effects of neuromodulators or neurodegenerative diseases on ion channel kinetics.

Open questions in the management of nodular lymphocyte predominant hodgkin lymphoma.

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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.

PA03.13. Effect of triphaladi rasayana along with yoga therapy on low grade non hodgkins lymphoma and resistant intermediate and high grade non hodgkins lymphoma

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Soumya, MS Surya; Sarasa, TP

2013-01-01

Purpose: 1. To find out the effect of Thriphaladi Rasayana along with Yoga Therapy on low grade Non Hodgkins Lymphoma and resistant intermediate and high grade NonHodgkins Lymphoma. 2. To apply a less costly, less morbid, well accepted method of treatment on NHL. 3.To find a simple method to increase the immunity. 4.To try a drug which is easy to prepare? Method: Purposive sampling technique was used for the study. Sample of 30 patients age range 25 75 years with histologicaly proven NonHodgkins lymphoma, attending the M.O.I.O.P of the regional cancer centre during a period of 18 months. Groups1) Low grade NonHodgkins Lymphoma 2) Resistant intermediate &High grade NonHodgkins lymphoma (failed chemotherapy) were taken. Procedure : 2 groups were given Triphaladhi Rasayana (15 grams of powder with ghee and honey) twice dailymorning& at bed time with milk as anupana for period of 1month along with selected yoga asanas and niyama? Result: Symptoms included were fever, night sweats, weight loss, lymph nodes enlargement, splenomegaly, and hepatomegaly. In low grade symptom relief was noted in almost all cases. Lymph node changes notedLow grade5 2% (complete remission), 38% (partial remission), 10% (no change), intermediate35% (CR), 52% (PR) & 13% (NC), High grade67% (CR), 33%(PR). Hepatomegaly changes :ve in low grade92.86%, intermediate 90.9% & high grade100%. Splenomegaly changes :ve in low grade92.86%, intermediate72.72% & high grade80% Over all remission status of 30 patientscomplete remission30%, partial remission 30% & no change30%? Conclusion: Thriphaladirasayana along with Yoga therapy is very effective in Low grade NonHodgkins lymphoma and resistant intermediate and high grade Non hodgkins Lymphoma?

Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

International Nuclear Information System (INIS)

Champion, P.E.; Groshar, D.; Hooper, H.R.; Palmer, M.; Catz, Z.; Belch, A.; McEwan, A.

1992-01-01

67 Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management. (Author)

Modern Radiation Therapy for Hodgkin Lymphoma

DEFF Research Database (Denmark)

Specht, Lena; Yahalom, Joachim; Illidge, Tim

2014-01-01

Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced...... 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......, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom...

Hodgkin's disease of the prostate: a detailed case report

International Nuclear Information System (INIS)

Klotz, L.H.; Herr, H.W.

1986-01-01

Malignant lymphoma of the prostate is an unusual entity, and nonHodgkin's lymphoma constitutes most reported cases. We report a well documented case of Hodgkin's lymphoma, initially involving the gastrointestinal tract and spleen, which recurred in the prostate following initial remission with chemotherapy. Treatment with external beam radiotherapy resulted in a rapid complete response that has been sustained for 18 months

Single-cell analysis of peptide expression and electrophysiology of right parietal neurons involved in male copulation behavior of a simultaneous hermaphrodite.

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El Filali, Z; de Boer, P A C M; Pieneman, A W; de Lange, R P J; Jansen, R F; Ter Maat, A; van der Schors, R C; Li, K W; van Straalen, N M; Koene, J M

2015-12-01

Male copulation is a complex behavior that requires coordinated communication between the nervous system and the peripheral reproductive organs involved in mating. In hermaphroditic animals, such as the freshwater snail Lymnaea stagnalis, this complexity increases since the animal can behave both as male and female. The performance of the sexual role as a male is coordinated via a neuronal communication regulated by many peptidergic neurons, clustered in the cerebral and pedal ganglia and dispersed in the pleural and parietal ganglia. By combining single-cell matrix-assisted laser mass spectrometry with retrograde staining and electrophysiology, we analyzed neuropeptide expression of single neurons of the right parietal ganglion and their axonal projections into the penial nerve. Based on the neuropeptide profile of these neurons, we were able to reconstruct a chemical map of the right parietal ganglion revealing a striking correlation with the earlier electrophysiological and neuroanatomical studies. Neurons can be divided into two main groups: (i) neurons that express heptapeptides and (ii) neurons that do not. The neuronal projection of the different neurons into the penial nerve reveals a pattern where (spontaneous) activity is related to branching pattern. This heterogeneity in both neurochemical anatomy and branching pattern of the parietal neurons reflects the complexity of the peptidergic neurotransmission involved in the regulation of male mating behavior in this simultaneous hermaphrodite.

Environmental risk factors related to the development of canine non-Hodgkin's lymphoma Fatores de risco ambientais relacionados ao desenvolvimento do linfoma não Hodgkin canino

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Danielle Almeida Zanini

2013-01-01

Full Text Available This research aimed to investigate the possible risk factors associated with the development of canine non-Hodgkin's lymphoma. Owners of 83 dogs with non-Hodgkin's lymphoma and of 84 healthy dogs answered an epidemiological questionnaire. Dogs who lived outside of the house and within 100 meters of busy streets or avenues (defined as more than 50 vehicles per minute had a higher risk for developing the disease (OR: 3.1, 95% CI: 1.4-6.9, P=0.005. These results suggest that air pollution derived from vehicle traffic may be associated with the development of canine non-Hodgkin's lymphoma.Este trabalho teve como objetivo investigar os possíveis fatores de risco ambientais, associados com o desenvolvimento de linfoma não-Hodgkin nos cães. Um questionário epidemiológico foi aplicado aos proprietários de 83 cães com linfoma não-Hodgkin e 84 proprietários de cães saudáveis. Os cães que viviam permanentemente no lado de fora da casa e em torno de 100 metros de ruas movimentadas ou avenidas (mais de 50 veículos por minuto tiveram um maior risco de desenvolvimento da doença (OR: 3,1, IC 95%: 1,4-6,9, P=0,005. Esses resultados sugerem que a poluição do ar oriunda do tráfego veicular pode estar associada com o desenvolvimento de linfomas não-Hodgkin canino.

Association between simian virus 40 and non-Hodgkin lymphoma

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Vilchez, Regis A.; Madden, Charles R.; Kozinetz, Claudia A.; Halvorson, Steven J.; White, Zoe S.; Jorgensen, Jeffrey L.; Finch, Chris J.; Butel, Janet S.

2002-01-01

BACKGROUND: Non-Hodgkin lymphoma has increased in frequency over the past 30 years, and is a common cancer in HIV-1-infected patients. Although no definite risk factors have emerged, a viral cause has been postulated. Polyomaviruses are known to infect human beings and to induce tumours in laboratory animals. We aimed to identify which one of the three polyomaviruses able to infect human beings (simian virus 40 [SV40], JC virus, and BK virus) was associated with non-Hodgkin lymphoma. METHODS: We analysed systemic non-Hodgkin lymphoma from 76 HIV-1-infected and 78 HIV-1-uninfected patients, and non-malignant lymphoid samples from 79 HIV-1-positive and 107 HIV-1-negative patients without tumours; 54 colon and breast carcinoma samples served as cancer controls. We used PCR followed by Southern blot hybridisation and DNA sequence analysis to detect DNAs of polyomaviruses and herpesviruses. FINDINGS: Polyomavirus T antigen sequences, all of which were SV40-specific, were detected in 64 (42%) of 154 non-Hodgkin lymphomas, none of 186 non-malignant lymphoid samples, and none of 54 control cancers. This difference was similar for HIV-1-infected patients and HIV-1-uninfected patients alike. Few tumours were positive for both SV40 and Epstein-Barr virus. Human herpesvirus type 8 was not detected. SV40 sequences were found most frequently in diffuse large B-cell and follicular-type lymphomas. INTERPRETATION: SV40 is significantly associated with some types of non-Hodgkin lymphoma. These results add lymphomas to the types of human cancers associated with SV40.

Lymphocyte-predominant Hodgkin disease: a comprehensive overview.

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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.

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

Computer Modelling of Functional Aspects of Noise in Endogenously Oscillating Neurons

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Huber, M. T.; Dewald, M.; Voigt, K.; Braun, H. A.; Moss, F.

1998-03-01

Membrane potential oscillations are a widespread feature of neuronal activity. When such oscillations operate close to the spike-triggering threshold, noise can become an essential property of spike-generation. According to that, we developed a minimal Hodgkin-Huxley-type computer model which includes a noise term. This model accounts for experimental data from quite different cells ranging from mammalian cortical neurons to fish electroreceptors. With slight modifications of the parameters, the model's behavior can be tuned to bursting activity, which additionally allows it to mimick temperature encoding in peripheral cold receptors including transitions to apparently chaotic dynamics as indicated by methods for the detection of unstable periodic orbits. Under all conditions, cooperative effects between noise and nonlinear dynamics can be shown which, beyond stochastic resonance, might be of functional significance for stimulus encoding and neuromodulation.

Functional hyposplenia after splenic irradiation for Hodgkin's disease

International Nuclear Information System (INIS)

Coleman, C.N.; McDougall, I.R.; Dailey, M.O.; Ager, P.; Bush, S.; Kaplan, H.S.

1982-01-01

We previously reported a patients who developed fulminant pneumococcal sepsis 12 years after successful treatment for Hodgkin's disease, which included splenic irradiation. We have since evaluated splenic size and function in 25 patients who had received splenic irradiation 5 to 16 years previously either for Hodgkin's disease (n . 19) or non-Hodgkin's lymphoma (n . 6). Mean maximum splenic diameter as measured on a 99mTc-sulfur colloid liver-spleen scan was 6.2 cm in the irradiated group and 9.7 cm in a control group (p less than 0.001). The mean percentage of erythrocytes containing pits when observed with interference phase microscopy was 13.0% in the irradiated group, which was significantly different (p less than 0.001) from the levels found in each of the control groups: normal subjects, 0.9%; unstaged and untreated lymphoma patients, 0.6%; and patients after splenectomy, 33.7%. Patients who have had splenic irradiation should be considered at risk of developing overwhelming pneumococcal sepsis

Hodgkin's lymphoma arising in a case of mycosis fungoides: An unusual association

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Preeti Sharma

2018-01-01

Full Text Available Mycosis fungoides is a cutaneous T-cell lymphoma with a high risk for developing secondary malignancies, especially B-cell lymphoproliferative disorders. About 40 cases of Hodgkin's lymphoma associated with mycosis fungoides have been reported in literature till date. We report a case of a 35-year-old gentleman who presented with intensely itchy reddish lesions all over the body. Multiple skin biopsies taken from the lesions on scalp and back confirmed the clinical diagnosis of mycosis fungoides. While on treatment, he presented with multiple bilateral cervical, axillary and inguinal lymphadenopathy 9 years after the primary diagnosis of mycosis fungoides. Excision biopsy of a cervical lymph node revealed partial effacement of architecture by a tumor comprising polymorphous background. Histopathology and immunohistochemistry revealed a diagnosis of Hodgkin's lymphoma - nodular sclerosis subtype. The patient was started on chemotherapy for stage IV Hodgkin's lymphoma. Our case emphasizes the importance of keeping secondary Hodgkin's lymphoma in mind while dealing with a patient of mycosis fungoides. Our case immunohistochemically supports the distinct etiopathogenesis of Epstein–Barr virus-negative Hodgkin's lymphoma vis-à-vis cutaneous mycosis fungoides.

Nodal involvement in Hodgkin disease and non-Hodgkin lymphoma assessed by magnetic resonance

International Nuclear Information System (INIS)

Tesoro Tess, J.D.; Balzarini, L.; Ceglia, E.; Petrillo, R.; Musumeci, R.

1990-01-01

Magnetic Resonance Imaging (MRI) demonstrates a good capability in distinguishing nodal involvement in hodgkin disease and nonhodgkin lymphoma both in the chest and in the retroperitoneal areas the initial presentation of the disease. However CT and lymphangiography demonstrated comparable or superior values of accuracy and sensitivity. (H.W.) 4 refs.; 2 tabs

Co-release of glutamate and GABA from single vesicles in GABAergic neurons exogenously expressing VGLUT3

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Johannes eZimmermann

2015-09-01

Full Text Available The identity of the vesicle neurotransmitter transporter expressed by a neuron largely corresponds with the primary neurotransmitter that cell releases. However, the vesicular glutamate transporter subtype 3 (VGLUT3 is mainly expressed in non-glutamatergic neurons, including cholinergic, serotonergic, or GABAergic neurons. Though a functional role for glutamate release from these non-glutamatergic neurons has been demonstrated, the interplay between VGLUT3 and the neuron’s characteristic neurotransmitter transporter, particularly in the case of GABAergic neurons, at the synaptic and vesicular level is less clear. In this study, we explore how exogenous expression of VGLUT3 in striatal GABAergic neurons affects the packaging and release of glutamate and GABA in synaptic vesicles. We found that VGLUT3 expression in isolated, autaptic GABAergic neurons leads to action potential evoked release of glutamate. Under these conditions, glutamate and GABA could be packaged together in single vesicles release either spontaneously or asynchronously. However, the presence of glutamate in GABAergic vesicles did not affect uptake of GABA itself, suggesting a lack of synergy in vesicle filling for these transmitters. Finally, we found postsynaptic detection of glutamate released from GABAergic terminals difficult when bona fide glutamatergic synapses were present, suggesting that co-released glutamate cannot induce postsynaptic glutamate receptor clustering.

Expression of Epstein-Barr virus in Hodgkin lymphoma Specimens in IRAN.

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Laila Mozafari

2013-09-01

Full Text Available  Background &Objectives: The Epstein-Barr Virus (EBV( is related with various diseases including infectious mononucleosis, Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma and post-transplant lymphoprolifrative disorders. The aim of this study was to characterize the association between EBV and Hodgkin's lymphoma through EBERs in situ hybridization (EBER-ISH in Iranian patients.    Materials &Methods: In this study, 43 Hodgkin's lymphoma tissue samples were selected from formalin-fixed paraffin embedded blocks and analyzed by EBERs in situ hybridization. Data analyzed by SPSS16 statistical software, Fisher's exact test and Mantel-Haensel significant level 0.05.   Results: 43 Hodgkin's lymphoma patients were 29 (67% male samples and 14 (33% female samples. In 20 (47% samples Epstein-Barr virus was present. The positive cases included 13 samples  male and 7 samples female. Fisher's exact test showed statistically no significant difference between sex and subtypes. Age distribution of relation of Hodgkin's lymphoma and EBV virus were 75% (12 of 16 in the age group of 1-14 years,  22% (5 of 23 in the age group 15-49 years and 75% (3 of 4 in the age group over 49 years, respectively. Fisher's exact test showed statistically significant difference between 1-14 and 15-49 age group years (p-value: 0.003.   Conclusion: Results shown higher presence rate of Epstein-Barr virus in Hodgkin's lymphoma specimens  of children and older adult. This pattern is similar to other developing countries. 

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

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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

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.

Thyroid dysfunction after mantle irradiation of Hodgkin`s disease patients

Energy Technology Data Exchange (ETDEWEB)

Khoo, V.S.; Liew, K.H.; Crennan, E.C.; D`Costa, I.M. [Peter MacCallum Caner Institute, East Melbourne, VIC (Australia). Department of Radiation Oncology; Quong, G. [Austin and Repatriation Medical Centre, West Heidelberg, VIC (Australia). Department of Radiation Oncology

1998-02-01

Thyroid dysfunction can develop in patients with Hodgkin`s disease who are treated with mantle irradiation. During the period 1970-89, the records of 320 patients who received mantle irradiation and who had thyroid function tests (TFT) were retrospectively reviewed. The median age was 30 years (range, 7-69 years). The median mantle and thyroid dose was 36 Gy (range, 30-40 Gy) and 39.8 Gy (range, 32-65 Gy), respectively. Overall thyroid dysfunction was present in 39% of the patients. Clinical hypothyroidism was seen in 10% and biochemical hypothyroidism was noted in 25%. Hyperthyroidism was found in 4% of patients. Thyroid nodules had developed in six patients (2%), of which those in four patients were malignant. Age, sex, histological subtype, stage of disease, dose, Iymphangiogram and treatment with chemotherapy were not significant factors in the development of thyroid dysfunction. The narrow dose range prevented adequate analysis of dose effect. The results indicate that the incidence of thyroid abnormalities is high enough to warrant regular TFT assessment with pre-irradiation levels and follow-up testing for life because the development of abnormalities can occur many years later. Thyroid examination should form part of the routine follow-up examination and any abnormality should be promptly investigated. Copyright (1998) Blackwell Science Pty Ltd 32 refs., 3 tabs.

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.

Chaos control and synchronization of two neurons exposed to ELF external electric field

International Nuclear Information System (INIS)

Wang Jiang; Zhang Ting; Che Yanqiu

2007-01-01

Chaos control and synchronization of two unidirectional coupled neurons exposed to ELF electrical field via nonlinear control technique is investigated. Based on results of space-time characteristics of trans-membrane voltage, the variation of cell trans-membrane voltage exposed to extremely low frequency (ELF) electric field is analyzed. The dynamical behaviors of the modified Hodgkin-Huxley (HH) model are identified under the periodic ELF electric field using both analytical and numerical analysis. Then, using the results of the analysis, a nonlinear feedback linearization control scheme and a modified adaptive control strategy are designed to synchronize the two unidirectional coupled neurons and stabilize the chaotic trajectory of the slave system to desired periodic orbit of the master system. The simulation results demonstrated the efficiency of the proposed algorithms

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

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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.

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

Coexisting chaotic attractors in a single neuron model with adapting feedback synapse

International Nuclear Information System (INIS)

Li Chunguang; Chen Guanrong

2005-01-01

In this paper, we consider the nonlinear dynamical behavior of a single neuron model with adapting feedback synapse, and show that chaotic behaviors exist in this model. In some parameter domain, we observe two coexisting chaotic attractors, switching from the coexisting chaotic attractors to a connected chaotic attractor, and then switching back to the two coexisting chaotic attractors. We confirm the chaoticity by simulations with phase plots, waveform plots, and power spectra

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

Directory of Open Access Journals (Sweden)

Tristan Aumentado-Armstrong

2015-10-01

Full Text Available Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

Electrosensory Midbrain Neurons Display Feature Invariant Responses to Natural Communication Stimuli.

Science.gov (United States)

Aumentado-Armstrong, Tristan; Metzen, Michael G; Sproule, Michael K J; Chacron, Maurice J

2015-10-01

Neurons that respond selectively but in an invariant manner to a given feature of natural stimuli have been observed across species and systems. Such responses emerge in higher brain areas, thereby suggesting that they occur by integrating afferent input. However, the mechanisms by which such integration occurs are poorly understood. Here we show that midbrain electrosensory neurons can respond selectively and in an invariant manner to heterogeneity in behaviorally relevant stimulus waveforms. Such invariant responses were not seen in hindbrain electrosensory neurons providing afferent input to these midbrain neurons, suggesting that response invariance results from nonlinear integration of such input. To test this hypothesis, we built a model based on the Hodgkin-Huxley formalism that received realistic afferent input. We found that multiple combinations of parameter values could give rise to invariant responses matching those seen experimentally. Our model thus shows that there are multiple solutions towards achieving invariant responses and reveals how subthreshold membrane conductances help promote robust and invariant firing in response to heterogeneous stimulus waveforms associated with behaviorally relevant stimuli. We discuss the implications of our findings for the electrosensory and other systems.

The Effect of Single Pyramidal Neuron Firing Within Layer 2/3 and Layer 4 in Mouse V1.

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Meyer, Jochen F; Golshani, Peyman; Smirnakis, Stelios M

2018-01-01

The influence of cortical cell spiking activity on nearby cells has been studied extensively in vitro . Less is known, however, about the impact of single cell firing on local cortical networks in vivo . In a pioneering study, Kwan and Dan (Kwan and Dan, 2012) reported that in mouse layer 2/3 (L2/3), under anesthesia , stimulating a single pyramidal cell recruits ~2.1% of neighboring units. Here we employ two-photon calcium imaging in layer 2/3 of mouse V1, in conjunction with single-cell patch clamp stimulation in layer 2/3 or layer 4, to probe, in both the awake and lightly anesthetized states , how (i) activating single L2/3 pyramidal neurons recruits neighboring units within L2/3 and from layer 4 (L4) to L2/3, and whether (ii) activating single pyramidal neurons changes population activity in local circuit. To do this, it was essential to develop an algorithm capable of quantifying how sensitive the calcium signal is at detecting effectively recruited units ("followers"). This algorithm allowed us to estimate the chance of detecting a follower as a function of the probability that an epoch of stimulation elicits one extra action potential (AP) in the follower cell. Using this approach, we found only a small fraction (layer-2/3 or layer-4 pyramidal neurons produces few (<1% of local units) reliable single-cell followers in L2/3 of mouse area V1, either under light anesthesia or in quiet wakefulness: instead, single cell stimulation was found to elevate aggregate population activity in a weak but highly distributed fashion.

Correlated conductance parameters in leech heart motor neurons contribute to motor pattern formation.

Science.gov (United States)

Lamb, Damon G; Calabrese, Ronald L

2013-01-01

Neurons can have widely differing intrinsic membrane properties, in particular the density of specific conductances, but how these contribute to characteristic neuronal activity or pattern formation is not well understood. To explore the relationship between conductances, and in particular how they influence the activity of motor neurons in the well characterized leech heartbeat system, we developed a new multi-compartmental Hodgkin-Huxley style leech heart motor neuron model. To do so, we evolved a population of model instances, which differed in the density of specific conductances, capable of achieving specific output activity targets given an associated input pattern. We then examined the sensitivity of measures of output activity to conductances and how the model instances responded to hyperpolarizing current injections. We found that the strengths of many conductances, including those with differing dynamics, had strong partial correlations and that these relationships appeared to be linked by their influence on heart motor neuron activity. Conductances that had positive correlations opposed one another and had the opposite effects on activity metrics when perturbed whereas conductances that had negative correlations could compensate for one another and had similar effects on activity metrics.

Fertility and sexual function in female Hodgkin lymphoma survivors of reproductive age.

Science.gov (United States)

Eeltink, Corien M; Incrocci, Luca; Witte, Birgit I; Meurs, Saskia; Visser, Otto; Huijgens, Peter; Verdonck-de Leeuw, Irma M

2013-12-01

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. Young female Hodgkin lymphoma survivors are at risk of infertility and impaired sexual function. However, little is known about their awareness of infertility and its association with sexual functioning. A descriptive questionnaire survey. In this cross-sectional study, a survey was completed by female Hodgkin lymphoma survivors (40 years). Outcome measures included self-reported fertility status and sexual problems and the internationally validated Female Sexual Function Index. In total, 36 survivors were included (mean age 32 years, SD 4). Eighteen women (50%) thought themselves fertile. Eight survivors (22%) who perceived themselves as being infertile were more often treated with alkylator-based chemotherapy, and 63% reported sexual dysfunction. Ten survivors (28%) were not aware as to whether they were fertile or not; seven of these would like to have children. The reported fertility status was related to age and chemotherapy regimen. Regarding sexuality, 14 (39%) of the female Hodgkin lymphoma survivors reported one or more sexual problem and none reported recovery. Female sexual dysfunction according to the Female Sexual Function Index was reported by 11 (31%) survivors. Almost 30% of Hodgkin lymphoma survivors do not know whether they are fertile or not. Overall sexual dysfunction is common in Hodgkin lymphoma survivors and comparable to the general population. However, a lack of desire was significantly more often reported in female Hodgkin lymphoma survivors. To prevent assumed infertility and unintended childlessness by postponing parenthood in young female survivors, awareness of fertility status is needed. There is also a need to routinely assess sexual function and provide adequate interventions to improve arousal and lubrication problems. © 2013 John Wiley & Sons Ltd.

A study of single multiplicative neuron model with nonlinear filters for hourly wind speed prediction

International Nuclear Information System (INIS)

Wu, Xuedong; Zhu, Zhiyu; Su, Xunliang; Fan, Shaosheng; Du, Zhaoping; Chang, Yanchao; Zeng, Qingjun

2015-01-01

Wind speed prediction is one important methods to guarantee the wind energy integrated into the whole power system smoothly. However, wind power has a non–schedulable nature due to the strong stochastic nature and dynamic uncertainty nature of wind speed. Therefore, wind speed prediction is an indispensable requirement for power system operators. Two new approaches for hourly wind speed prediction are developed in this study by integrating the single multiplicative neuron model and the iterated nonlinear filters for updating the wind speed sequence accurately. In the presented methods, a nonlinear state–space model is first formed based on the single multiplicative neuron model and then the iterated nonlinear filters are employed to perform dynamic state estimation on wind speed sequence with stochastic uncertainty. The suggested approaches are demonstrated using three cases wind speed data and are compared with autoregressive moving average, artificial neural network, kernel ridge regression based residual active learning and single multiplicative neuron model methods. Three types of prediction errors, mean absolute error improvement ratio and running time are employed for different models’ performance comparison. Comparison results from Tables 1–3 indicate that the presented strategies have much better performance for hourly wind speed prediction than other technologies. - Highlights: • Developed two novel hybrid modeling methods for hourly wind speed prediction. • Uncertainty and fluctuations of wind speed can be better explained by novel methods. • Proposed strategies have online adaptive learning ability. • Proposed approaches have shown better performance compared with existed approaches. • Comparison and analysis of two proposed novel models for three cases are provided

General Information about Childhood Hodgkin Lymphoma

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... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... memory. Second cancers (new types of cancer). For female survivors of Hodgkin lymphoma, there is an increased ...

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.

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

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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.

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.

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

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

Non-Hodgkin's lymphoma - the role of radiation therapy

International Nuclear Information System (INIS)

Gospodarowicz, Mary K.

1995-01-01

Objective: To review the approach to the diagnosis, assessment, treatment and continuing management of patients with Non-Hodgkin's lymphoma with the emphasis on the role of radiation therapy in this group of diseases. The entity of 'Non-Hodgkin's Lymphoma' encompasses a diverse group of disorders involving almost any part of the body. This diversity bedevils any attempt to unify the approach to this disease on a rational basis. Nevertheless, some broad principles can be applied to almost any presentation of Non-Hodgkin's lymphoma. The approach to the management of Non-Hodgkin's lymphoma is based on the histologic type, localization and extent of disease and other disease and patient related prognostic factors. The accurate pathologic diagnosis of lymphoma has been greatly facilitated by availability of markers, molecular and genetic techniques. The newly proposed revised classification of lymphomas and its impact on these of RT will be discussed. Although the Ann Arbor staging classification has been shown to provide important prognostic information, other factors have equivalent, if not greater, influence on outcome in patients with Non-Hodgkin's lymphomas. The management of lymphomas is based primarily on the histologic type and extent of the disease including stage, tumour bulk, number of sites involved and location of the disease. The success of curative radiation therapy is contingent upon the presence of localized disease, normal tissue tolerance allowing the delivery of RT curative dose (30-35 Gy) and the tumour bulk. The current evidence suggests that locoregional RT for stage I and II low grade lymphoma results in approximately 50% prolonged (10-15 years) failure free rate and possible cure. Radiation alone is no longer used for intermediate and high grade lymphomas. The standard management of stage I and II intermediate grade large cell and mixed lymphomas is with doxorubicin based chemotherapy (e.g. CHOP) followed by involved field radiation. The

[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.

Novel insights in the pathogenesis of Hodgkin lymphoma : microenvironment, genetic landscape and regulation of HLA expression

NARCIS (Netherlands)

Liu, Yuxuan

2013-01-01

Gemuteerde genen spelen belangrijke rol in ontstaan Hodgkin lymfoom Het klassieke Hodgkin lymfoom (eerder bekend als ‘de ziekte van Hodgkin’) bestaat voor slechts een zeer klein deel uit tumorcellen en voor het overgrote deel uit normale immuuncellen. Die samenstelling maakt het Hodgkin lymfoom

Effects of radiochemotherapy and splenectomy on cellular immunity in long-term survivors of Hodgkin's disease and non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Steele, R.; Han, T.

1978-01-01

Thirty-six patients treated for Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) who had been in complete remission and off all therapy for greater than two years were examined for evidence of immunosuppression. All patients were found to have marked depression of their lymphocyte blastogenic response to phytohemagglutinin (PHA) and of their skin test responses. No abnormalities of serum protein or immunoglobulins were found. T cells were significantly lower than normal in patients who had had Hodgkin's disease, but not in those who had had NHL. B cells, on the other hand, were significantly elevated in both groups. Splenectomy elevated the total lymphocyte count, while those who had not had a splenectomy had lower than normal lymphocyte counts. B cells were elevated while T cells tended to be lower in both splenectomy and nonsplenectomy groups, though only in the nonsplenectomized patients did this reach statistical significance. The PHA response tended to be higher in patients with less advanced disease and less extensive treatment than in those with more advanced disease and more extensive treatment, although there was no statistically significant difference. Skin test response though, was shown to correlate well with both stage of disease at diagnosis and extent of treatment

Switching neuronal state: optimal stimuli revealed using a stochastically-seeded gradient algorithm.

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Chang, Joshua; Paydarfar, David

2014-12-01

Inducing a switch in neuronal state using energy optimal stimuli is relevant to a variety of problems in neuroscience. Analytical techniques from optimal control theory can identify such stimuli; however, solutions to the optimization problem using indirect variational approaches can be elusive in models that describe neuronal behavior. Here we develop and apply a direct gradient-based optimization algorithm to find stimulus waveforms that elicit a change in neuronal state while minimizing energy usage. We analyze standard models of neuronal behavior, the Hodgkin-Huxley and FitzHugh-Nagumo models, to show that the gradient-based algorithm: (1) enables automated exploration of a wide solution space, using stochastically generated initial waveforms that converge to multiple locally optimal solutions; and (2) finds optimal stimulus waveforms that achieve a physiological outcome condition, without a priori knowledge of the optimal terminal condition of all state variables. Analysis of biological systems using stochastically-seeded gradient methods can reveal salient dynamical mechanisms underlying the optimal control of system behavior. The gradient algorithm may also have practical applications in future work, for example, finding energy optimal waveforms for therapeutic neural stimulation that minimizes power usage and diminishes off-target effects and damage to neighboring tissue.

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.

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.

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.

Single-dose palonosetron for prevention of chemotherapy-induced nausea and vomiting in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy containing steroids: results of a phase II study from the Gruppo Italiano per lo Studio dei Linfomi (GISL).

Science.gov (United States)

Di Renzo, Nicola; Montanini, Antonella; Mannina, Donato; Dondi, Alessandra; Muci, Stefania; Mancuso, Salvatrice; De Paolis, M Rosaria; Plati, Caterina; Stelitano, Caterina; Patti, Catia; Olivieri, Attilio; Liardo, Eliana; Buda, Gabriele; Cantaffa, Renato; Federico, Massimo

2011-10-01

The control of nausea and vomiting induced by chemotherapy is paramount for overall treatment success in cancer patients. Antiemetic therapy during chemotherapy in lymphoma patients generally consists of anti-serotoninergic drugs and dexamethasone. The aim of this trial was to evaluate the efficacy of a single dose of palonosetron, a second-generation serotonin type 3 (5-HT(3)) receptor antagonist, in patients with aggressive non-Hodgkin's lymphoma receiving moderately emetogenic chemotherapy (MEC) containing steroids. Patients received a single intravenous bolus of palonosetron (0.25 mg) before administration of chemotherapy. Complete response (CR) defined as no vomiting and no rescue therapy during overall phase (0-120 h) was the primary endpoint. Complete control (CC) defined as CR and only mild nausea was a secondary endpoint. Eighty-six evaluable patients entered in the study. A CR was observed in 74 patients (86.0%) during the overall phase; the CR during the acute (0-24 h) and delayed (24-120 h) phases was 90.7% and 88.4%, respectively. CC was 89.5% during the acute and 84.9% during the delayed phase; the overall CC was 82.6%. This was the first trial, which demonstrated the efficacy of a single dose of palonosetron in control CINV in patients with aggressive non-Hodgkin's lymphoma receiving MEC regimen containing steroids.

Non-Hodgkin lymphoma in Romania: a single-centre experience.

Science.gov (United States)

Fetica, Bogdan; Achimas-Cadariu, Patriciu; Pop, Bogdan; Dima, Delia; Petrov, Ljubomir; Perry, Anamarija M; Nathwani, Bharat N; Müller-Hermelink, Hans K; Diebold, Jacques; MacLennan, Kenneth A; Fulop, Annamaria; Blaga, Mihaiela L; Coza, Daniela; Nicula, Florian Al; Irimie, Alexandru; Weisenburger, Dennis D

2017-06-01

Epidemiologic studies of non-Hodgkin lymphoma (NHL) in Eastern Europe are scarce in the literature. We report the experience of the "Ion Chiricuta" Institute of Oncology in Cluj-Napoca (IOCN), Romania, in the diagnosis and outcome of patients with NHL. We studied 184 consecutive NHL patients diagnosed in the Pathology Department of IOCN during the years 2004-2006. We also obtained epidemiological data from the Northwestern (NW) Cancer Registry. In the IOCN series, the most common lymphoma subtype was diffuse large B-cell lymphoma (43.5%), followed by the chronic lymphocytic leukaemia/small lymphocytic lymphoma (21.2%). T-cell lymphomas represented a small proportion (8.2%). The median age of the patients was 57 years, with a male-to-female ratio of 0.94. Patients with indolent B-cell lymphomas had the best overall survival, whereas those with mantle cell lymphoma had the worst survival. The NW Cancer Registry data showed that the occurrence of NHL in the NW region of Romania was higher in men [world age-standardized incidence rate/100 000 (ASR)-5.9; 95% CI 5.1-6.6] than in women (ASR-4.1; 95% CI 3.5-4.7) with age-standardized male-to-female ratio of 1.44 (p = 0.038). Chronic lymphocytic leukaemia/small lymphocytic lymphoma was the most common NHL in the NW region of Romania, accounting for 43% of all cases, followed by diffuse large B-cell lymphoma (36%). The 5-year, age-standardized cumulative relative survival for NHL in the County of Cluj in NW Romania, for the period of 2006-2010, was 51.4%, with 58.4% survival for men and 43.2% for women. Additional studies of NHL in Eastern Europe are needed. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

NeuronBank: a tool for cataloging neuronal circuitry

Directory of Open Access Journals (Sweden)

Paul S Katz

2010-04-01

Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

[Hodgkin and non-Hodgkin lymphoma of adolescents and young adults].

Science.gov (United States)

Garciaz, Sylvain; Coso, Diane; Brice, Pauline; Bouabdallah, Réda

2016-12-01

Lymphoma is one of the most frequent cancers in adolescent and young adults. Hodgkin Lymphoma is curable in more than 90% of cases. Recent pediatric and adults protocols aimed to decrease long term toxicities (mostly gonadic and cardiovascular) and secondary malignancies, reducing the use of alkylating agents and limiting radiation fields. Risk-adapted strategies, using positron emission tomography staging, are about to become a standard, both in adult and pediatric protocols. These approaches allow obtaining excellent results in adolescents with Hodgkin lymphoma. On the other hand, treatment of adolescents with diffuse large B-cell lymphoma raises some questions. Even through children have good outcomes when treated with risk-adapted strategies, adolescents who are between 15 and 18 years old seem to experience poorer survivals, whereas patients older than 18 years old have globally the same outcome than older adults. This category of patient needs a particular care, based on a tight coordination between adults and pediatric oncologists. Primary mediastinal lymphomas, a subtype of BLDCL frequent in young adult population, exhibits poorer outcomes in children or young adolescent population than in older ones. Taking together, B-cell lymphoma benefited from recent advances in immunotherapy (in particular with the extended utilization of rituximab) and metabolic response-adapted strategies. In conclusion, adolescent and young adult's lymphomas are very curable diseases but require a personalized management in onco-hematological units. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Association of Hodgkin's lymphoma with Epstein Barr virus infection

Directory of Open Access Journals (Sweden)

Elmir Čičkušić

2007-02-01

Full Text Available The role of Epstein Barr virus (EBV in the onset of Hodgkin's lymphoma has been a subject of ongoing research. However, confirmation of EBV oncogenic involvement was not possible due to the small number of neoplastic cells characteristic for this type of tumor. Presence of EBV infection in neoplastic and non-neoplastic cells was analyzed in 81 cases of Hodgkin's lymphoma. In neoplastic cells, using an immunohistochemical method, latent membrane protein 1 (LMP1 was found in 33,3% of cases, while in situ hybridization results demonstrated the presence of EBER RNA in 48,1% of the cases. EBER RNA was found in non-neoplastic lymphocytes in 38,3% of cases. EBV is most frequently associated with Hodgkin's lymphoma in the first and seventh decade of life, specifically the nodular sclerosis subtype. No apparent difference was observed in the association of Hodgkin's lymphoma with EBV between genders, or in relation to clinical stage of the disease and average age of the patient. However, association with childhood age is significantly greater in comparison to adults. EBV associated disease shows a significantly greater prevalence in T lymphocytes. Slightly more abundant are cytotoxic T lymphocytes, which are also more frequently in contact with Reed-Sternberg cells, although there is no difference in number and positioning of histiocytes. Variations between the data on the association of EBV with Hodgkin's lymphoma among studies from different parts of the world suggest that factors of age, gender, ethnic background and social status might present biological modifiers of EBV influence on the pathogenesis of this neoplasm. The differences in non-neoplastic infiltrate EBV+ and EBV- lymphoma indicate the effect of the virus on the immune interaction of tumor and host in this disease.

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

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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

Immuno phenotype of blood lymphocytes in radiation-associated Hodgkin's disease

International Nuclear Information System (INIS)

Butenko, A.K.

2000-01-01

Immuno phenotype of peripheral blood lymphocytes has been studied in Hodgkin's disease including patients exposed to radionuclides of the characteristic Chernobyl pattern. The group of patients under study has been characterized by decreasing T- and NK-cell immunity, such a decrease being more pronounced in radiation-associated Hodgkin's lymphoma. The data obtained as well as the evidence of Epstein-Barr virus activation could explain the aggressiveness of the disease in such patients and the difficulties in their treatment

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

Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia.

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Landgren, Ola; Engels, Eric A; Pfeiffer, Ruth M; Gridley, Gloria; Mellemkjaer, Lene; Olsen, Jørgen H; Kerstann, Kimberly F; Wheeler, William; Hemminki, Kari; Linet, Martha S; Goldin, Lynn R

2006-09-20

Personal history of autoimmune diseases is consistently associated with increased risk of non-Hodgkin lymphoma. In contrast, there are limited data on risk of Hodgkin lymphoma following autoimmune diseases and almost no data addressing whether there is a familial association between the conditions. Using population-based linked registry data from Sweden and Denmark, 32 separate autoimmune and related conditions were identified from hospital diagnoses in 7476 case subjects with Hodgkin lymphoma, 18,573 matched control subjects, and more than 86,000 first-degree relatives of case and control subjects. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risks for each condition using logistic regression and also applied multivariable hierarchical regression models. All P values are two-sided. We found statistically significantly increased risks of Hodgkin lymphoma associated with personal histories of several autoimmune conditions, including rheumatoid arthritis (OR = 2.7, 95% CI = 1.9 to 4.0), systemic lupus erythematosus (OR = 5.8, 95% CI = 2.2 to 15.1), sarcoidosis (OR = 14.1, 95% CI = 5.4 to 36.8), and immune thrombocytopenic purpura (OR = infinity, P = .002). A statistically significant increase in risk of Hodgkin lymphoma was associated with family histories of sarcoidosis (OR = 1.8, 95% CI = 1.01 to 3.1) and ulcerative colitis (OR = 1.6, 95% CI = 1.02 to 2.6). Personal or family history of certain autoimmune conditions was strongly associated with increased risk of Hodgkin lymphoma. The association between both personal and family histories of sarcoidosis and a statistically significantly increased risk of Hodgkin lymphoma suggests shared susceptibility for these conditions.

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

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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.

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

Computerised tomography in the staging of Hodgkin's disease and non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Vinnicombe, Sarah J.; Reznek, Rodney H.

2003-01-01

The last 25 years have seen major changes in the imaging investigation and subsequent management of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL); accurate staging is vital for prognostication and treatment in both, and particularly in HD. The choice of imaging modality for staging depends on its accuracy, impact on clinical decision-making, and availability. Modern CT scanners fulfil most of the desired criteria. The advent of CT scanning, along with the development of ever more effective chemotherapeutic regimens, has resulted in the virtual demise of bipedal lymphangiography (LAG) as a staging tool in patients with lymphoma. It has rendered superfluous a battery of other tests that were in routine use. This contribution reviews the evidence for the use of CT in preference to LAG. CT accurately depicts nodal enlargement above and below the diaphragm, has variable sensitivity for intra-abdominal visceral involvement and is generally outstanding in depicting the extent of disease, especially extranodal extension. Despite the advances in CT technology, there are still areas where CT performs less well (e.g. disease in normal-sized lymph nodes, splenic and bone marrow infiltration). The influence of technical factors, such as the use of intravenous contrast medium, is discussed. In some instances, CT is not the imaging modality of choice and the place of newer techniques such as MRI and endoscopic ultrasound will be reviewed. (orig.)

Ordering chaos and synchronization transitions by chemical delay and coupling on scale-free neuronal networks

International Nuclear Information System (INIS)

Gong Yubing; Xie Yanhang; Lin Xiu; Hao Yinghang; Ma Xiaoguang

2010-01-01

Research highlights: → Chemical delay and chemical coupling can tame chaotic bursting. → Chemical delay-induced transitions from bursting synchronization to intermittent multiple spiking synchronizations. → Chemical coupling-induced different types of delay-dependent firing transitions. - Abstract: Chemical synaptic connections are more common than electric ones in neurons, and information transmission delay is especially significant for the synapses of chemical type. In this paper, we report a phenomenon of ordering spatiotemporal chaos and synchronization transitions by the delays and coupling through chemical synapses of modified Hodgkin-Huxley (MHH) neurons on scale-free networks. As the delay τ is increased, the neurons exhibit transitions from bursting synchronization (BS) to intermittent multiple spiking synchronizations (SS). As the coupling g syn is increased, the neurons exhibit different types of firing transitions, depending on the values of τ. For a smaller τ, there are transitions from spatiotemporal chaotic bursting (SCB) to BS or SS; while for a larger τ, there are transitions from SCB to intermittent multiple SS. These findings show that the delays and coupling through chemical synapses can tame the chaotic firings and repeatedly enhance the firing synchronization of neurons, and hence could play important roles in the firing activity of the neurons on scale-free networks.

Nab-paclitaxel/Rituximab-coated Nanoparticle AR160 in Treating Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Science.gov (United States)

2018-04-17

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

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

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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.

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

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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.

Bone marrow in pediatric patients with Hodgkin's disease.

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Khan, Fauzia Shafi; Hasan, Rabiya Fayyaz

2012-01-01

Hodgkin's disease is a malignant process of lymphoreticular system that constitutes 6% of childhood cancers Accurate staging of lymphoma is the basis for rational therapeutic planning and assessment of the presence or absence of marrow involvement is a basic part of the staging evaluation. The objective of this study was to determine the incidence of marrow infiltration in paediatric patients with Hodgkin's disease and to ascertain its morphological spectrum in the marrow. The study included 85 paediatric patients with diagnosed Hodgkin's disease seen at The Children's Hospital/Institute of Child Health, Lahore, from January 2010 to December 2011, referred to haematology department for bone marrow biopsies. Ages ranged between two years to fourteen years with an average age of seven years, the male female ratio being 13:1. Mixed cellularity was the commonest histological type present in 66 (78%) cases. The presenting feature common in all cases was superficial lymphadenopathy followed by hepatomegaly in 17 (20%) cases and splenomegaly in 16 (19%). All the marrow aspirates were negative for infiltration. Trephine biopsies revealed marrow infiltration in 9 (10.5%). Five (56%) cases had bilateral while 4 (44%) had unilateral involvement. Pattern of infiltration was diffuse in 8 (89%) and focal in one (11%) trephines. Increased marrow fibrosis was present in eight (89%) cases. Diagnostic Reed Sternberg cells were identified in only one case and the mononuclear variants were present in six cases and atypical cells were present in two cases in these immunohistochemistry for CD15 and CD30 was performed which was positive. Granulomas in one and lymphoid aggregates were present in two trephine biopsies otherwise negative for Hodgkin's infiltration. Bone marrow infiltration was present in 10.5% cases, immunohistochemistry was used to confirm infiltration in two cases, the pattern of infiltration being diffuse in majority (89%).

Transition Dynamics of a Dentate Gyrus-CA3 Neuronal Network during Temporal Lobe Epilepsy.

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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.

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

Non-Coding RNAs in Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Anna Cordeiro

2017-05-01

Full Text Available MicroRNAs (miRNAs, small non-coding RNAs that regulate gene expression by binding to the 3’-UTR of their target genes, can act as oncogenes or tumor suppressors. Recently, other types of non-coding RNAs—piwiRNAs and long non-coding RNAs—have also been identified. Hodgkin lymphoma (HL is a B cell origin disease characterized by the presence of only 1% of tumor cells, known as Hodgkin and Reed-Stenberg (HRS cells, which interact with the microenvironment to evade apoptosis. Several studies have reported specific miRNA signatures that can differentiate HL lymph nodes from reactive lymph nodes, identify histologic groups within classical HL, and distinguish HRS cells from germinal center B cells. Moreover, some signatures are associated with survival or response to chemotherapy. Most of the miRNAs in the signatures regulate genes related to apoptosis, cell cycle arrest, or signaling pathways. Here we review findings on miRNAs in HL, as well as on other non-coding RNAs.

A Challenging Case of Primary Breast Hodgkin's Lymphoma.

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Zarnescu, Narcis Octavian; Iliesiu, Andreea; Procop, Alexandru; Tampa, Mircea; Matei, Clara; Sajin, Maria; Costache, Mariana; Dumitru, Adrian; Lazaroiu, Anca Mihaela

2015-03-01

Primary breast lymphoma (PBL) is a rare entity accounting for less than 1% of all breast malignancies. Diagnostic criteria for primary Hodgkin's lymphoma of the breast are: the presence of sufficient tissue for diagnosis, close interaction between mammary tissue and lymphomatous infiltrate and no evidence or prior diagnosis of widespread lymphoma. Our case illustrates an unusual presentation of Hodgkin's lymphoma of the breast: clinically as inflammatory breast cancer and core biopsy as granulomatous mastitis, the final diagnosis requiring surgical biopsy. Current information regarding this entity is scant, mainly build upon its rarity. In this paper we assess the clinical presentation, the step-by-step diagnosis, the treatment and the importance of immunohistochemistry in this uncommon condition.

MiR-17/106b seed family regulates p21 in Hodgkin's lymphoma

NARCIS (Netherlands)

Gibcus, Johan H.; Kroesen, Bart-Jan; Koster, Roelof; Halsema, Nancy; de Jong, Debora; de Jong, Steven; Poppema, Sibrand; Kluiver, Joost; Diepstra, Arjan; van den Berg, Anke

2011-01-01

Hodgkin's lymphoma (HL) is a B cell-derived lymphoma characterized by a minority of malignant Hodgkin Reed-Sternberg (HRS) cells that have lost their normal B cell phenotype. Alterations in the cell cycle and apoptosis pathways might contribute to their resistance to apoptosis and sustained cell

Phase Locking of Multiple Single Neurons to the Local Field Potential in Cat V1.

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Martin, Kevan A C; Schröder, Sylvia

2016-02-24

The local field potential (LFP) is thought to reflect a temporal reference for neuronal spiking, which may facilitate information coding and orchestrate the communication between neural populations. To explore this proposed role, we recorded the LFP and simultaneously the spike activity of one to three nearby neurons in V1 of anesthetized cats during the presentation of drifting sinusoidal gratings, binary dense noise stimuli, and natural movies. In all stimulus conditions and during spontaneous activity, the average LFP power at frequencies >20 Hz was higher when neurons were spiking versus not spiking. The spikes were weakly but significantly phase locked to all frequencies of the LFP. The average spike phase of the LFP was stable across high and low levels of LFP power, but the strength of phase locking at low frequencies (≤10 Hz) increased with increasing LFP power. In a next step, we studied how strong stimulus responses of single neurons are reflected in the LFP and the LFP-spike relationship. We found that LFP power was slightly increased and phase locking was slightly stronger during strong compared with weak stimulus-locked responses. In summary, the coupling strength between high frequencies of the LFP and spikes was not strongly modulated by LFP power, which is thought to reflect spiking synchrony, nor was it strongly influenced by how strongly the neuron was driven by the stimulus. Furthermore, a comparison between neighboring neurons showed no clustering of preferred LFP phase. We argue that hypotheses on the relevance of phase locking in their current form are inconsistent with our findings. Copyright © 2016 the authors 0270-6474/16/362494-09$15.00/0.

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

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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

[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.

Chronic Prurigo: An Unusual Presentation of Hodgkin Lymphoma

Directory of Open Access Journals (Sweden)

Shireen Dumont

2018-05-01

Full Text Available Background: Prurigo nodularis is a condition of unknown origin defined by papulonodular eruption and intense pruritus. Hodgkin lymphoma often presents nonspecific initial symptoms. An association between systemic malignancy and cutaneous manifestations has long been documented. We report a case of prurigo nodularis as a first presentation of Hodgkin lymphoma. Case: A 35-year-old woman presented with a 2-year history of pruritus. Previously diagnosed with bedbugs, the pruritus persisted even after insect eradication, with the appearance of papulonodular lesions consistent with chronic prurigo. The pruritus and the pain were refractory to all treatments. She had no past medical history or clinical, radiological, or laboratory findings. A lymphadenopathy was revealed 2 years after onset of the symptoms. Lymph node biopsy showed a nodular sclerosis Hodgkin lymphoma. The patient was initiated on chemotherapy and the skin lesions decreased. Conclusion: This case report of chronic prurigo as the first manifestation of a systemic malignancy reminds us of the importance of a systematic diagnostic approach to this kind of patients initially and throughout time, especially if the symptoms do not respond to treatment. Our case may question the role of imaging examinations in the management and follow-up of a persistent prurigo nodularis.

Fertility preservation after chemotherapy for Hodgkin lymphoma

NARCIS (Netherlands)

van der Kaaij, Marleen A. E.; van Echten-Arends, Jannie; Simons, Arnold H. M.; Kluin-Nelemans, Hanneke C.

2010-01-01

Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause

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

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

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Terao, Shin-ichi; Sobue, Gen; Higashi, Naoki; Takahashi, Masahiko; Suga, Hidemichi; Mitsuma, Terunori [Aichi Medical Univ., Nagakute (Japan)

1995-03-01

{sup 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).

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)

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.

Outcomes of allogeneic hematopoietic stem cell transplantation for lymphomas: a single-institution experience

Directory of Open Access Journals (Sweden)

Mira Romany Massoud

Full Text Available ABSTRACT Introduction: Allogeneic hematopoietic stem cell transplantation offers the opportunity for extended survival in patients with Hodgkin's and non-Hodgkin lymphomas who relapsed after, or were deemed ineligible for, autologous transplantation. This study reports the cumulative experience of a single center over the past 14 years aiming to define the impact of patient, disease, and transplant-related characteristics on outcomes. Methods: All patients with histologically confirmed diagnosis of Hodgkin's or non-Hodgkin lymphomas who received allogeneic transplantation from 2000 to 2014 were retrospectively studied. Results: Forty-one patients were reviewed: 10 (24% had Hodgkin's and 31 (76% had non-Hodgkin lymphomas. The median age was 50 years and 23 (56% were male. The majority of patients (68% had had a prior autologous transplantation. At the time of allogeneic transplantation, 18 (43% patients were in complete and seven (17% were in partial remission. Most (95% patients received reduced-intensity conditioning, 49% received matched sibling donor grafts, 24% matched-unrelated donor grafts, and 27% received double umbilical cord blood grafts. The 100-day treatment-related mortality rate was 12%. After a median duration of follow up of 17.1 months, the median progression-free and overall survival was 40.5 and 95.8 months, respectively. On multivariate analysis, patients who had active disease at the time of transplant had inferior survival. Conclusions: Allogeneic transplantation results extend survival in selected patients with relapsed/refractory Hodgkin's and non-Hodgkin lymphomas with low treatment-related mortality. Patients who have active disease at the time of allogeneic transplantation have poor outcomes.

Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.

Science.gov (United States)

Hook, Paul W; McClymont, Sarah A; Cannon, Gabrielle H; Law, William D; Morton, A Jennifer; Goff, Loyal A; McCallion, Andrew S

2018-03-01

Genetic variation modulating risk of sporadic Parkinson disease (PD) has been primarily explored through genome-wide association studies (GWASs). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal time points. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including genes with known PD associations and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1-null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Copyright © 2018 American Society of Human Genetics. All rights reserved.

Radiotherapy in non-Hodgkin lymphomas

International Nuclear Information System (INIS)

Faria, S.L.

1992-01-01

The treatment of non-Hodgkin lymphomas (NHL) is discussed. The use of radiotherapy, chemotherapy or both in a combined therapy is studied considering several aspects as age of the patients (adults vs children), size and extension of the lymphoma, stage of the disease. It is mentioned that more advanced cases and those with more aggressive histology need combined modality treatments or even just chemotherapy. (M.A.C.)

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...

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.

BigNeuron: Large-Scale 3D Neuron Reconstruction from Optical Microscopy Images

NARCIS (Netherlands)

H. Peng (Hanchuan); M. Hawrylycz (Michael); J. Roskams (Jane); S. Hill (Sean); N. Spruston (Nelson); E. Meijering (Erik); G.A. Ascoli (Giorgio A.)

2015-01-01

textabstractUnderstanding the structure of single neurons is critical for understanding how they function within neural circuits. BigNeuron is a new community effort that combines modern bioimaging informatics, recent leaps in labeling and microscopy, and the widely recognized need for openness and

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

Long-term pruritus as the initial and sole clinical manifestation of occult Hodgkin's disease.

Science.gov (United States)

Omidvari, Shapour H; Khojasteh, Habib Noorani; Mohammadianpanah, Mohammad; Monabati, Ahmad; Mosalaei, Ahmad; Ahmadloo, Niloofar

2004-06-01

Pruritus or itch is a frequent symptom of patients with Hodgkin's disease. It often occurs during the clinical course of the disease and rarely may precede the diagnosis of underlying disease. In this report, we present a 16-year-old patient who had history of generalized pruritus without any skin rash for 4 years before the diagnosis of Hodgkin's disease. Within that period, she had received symptom-oriented medications, with no significant effect. After the first cycle of chemotherapy, her pruritus resolved completely. This case suggests that long-term generalized pruritus may be indicative of a significant underlying problem like Hodgkin's disease.

Weak noise in neurons may powerfully inhibit the generation of repetitive spiking but not its propagation.

Directory of Open Access Journals (Sweden)

Henry C Tuckwell

2010-05-01

Full Text Available Many neurons have epochs in which they fire action potentials in an approximately periodic fashion. To see what effects noise of relatively small amplitude has on such repetitive activity we recently examined the response of the Hodgkin-Huxley (HH space-clamped system to such noise as the mean and variance of the applied current vary, near the bifurcation to periodic firing. This article is concerned with a more realistic neuron model which includes spatial extent. Employing the Hodgkin-Huxley partial differential equation system, the deterministic component of the input current is restricted to a small segment whereas the stochastic component extends over a region which may or may not overlap the deterministic component. For mean values below, near and above the critical values for repetitive spiking, the effects of weak noise of increasing strength is ascertained by simulation. As in the point model, small amplitude noise near the critical value dampens the spiking activity and leads to a minimum as noise level increases. This was the case for both additive noise and conductance-based noise. Uniform noise along the whole neuron is only marginally more effective in silencing the cell than noise which occurs near the region of excitation. In fact it is found that if signal and noise overlap in spatial extent, then weak noise may inhibit spiking. If, however, signal and noise are applied on disjoint intervals, then the noise has no effect on the spiking activity, no matter how large its region of application, though the trajectories are naturally altered slightly by noise. Such effects could not be discerned in a point model and are important for real neuron behavior. Interference with the spike train does nevertheless occur when the noise amplitude is larger, even when noise and signal do not overlap, being due to the instigation of secondary noise-induced wave phenomena rather than switching the system from one attractor (firing regularly to

A novel single neuron perceptron with universal approximation and XOR computation properties.

Science.gov (United States)

Lotfi, Ehsan; Akbarzadeh-T, M-R

2014-01-01

We propose a biologically motivated brain-inspired single neuron perceptron (SNP) with universal approximation and XOR computation properties. This computational model extends the input pattern and is based on the excitatory and inhibitory learning rules inspired from neural connections in the human brain's nervous system. The resulting architecture of SNP can be trained by supervised excitatory and inhibitory online learning rules. The main features of proposed single layer perceptron are universal approximation property and low computational complexity. The method is tested on 6 UCI (University of California, Irvine) pattern recognition and classification datasets. Various comparisons with multilayer perceptron (MLP) with gradient decent backpropagation (GDBP) learning algorithm indicate the superiority of the approach in terms of higher accuracy, lower time, and spatial complexity, as well as faster training. Hence, we believe the proposed approach can be generally applicable to various problems such as in pattern recognition and classification.

Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.

Science.gov (United States)

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-02-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.

Utility of LRF/Pokemon and NOTCH1 Protein Expression in the Distinction of Nodular Lymphocyte-Predominant Hodgkin Lymphoma and Classical Hodgkin Lymphoma

Science.gov (United States)

Bohn, Olga; Maeda, Takahiro; Filatov, Alexander; Lunardi, Andrea; Pandolfi, Pier Paolo; Teruya-Feldstein, Julie

2014-01-01

Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a protooncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch derepression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target. PMID:24326827

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.

A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma

NARCIS (Netherlands)

E. van den Neste (Eric); J.-L. André (Jean-Luc); Gastinne, T. (Thomas); A. Stamatoullas (Aspasia); C. Haioun (Corinne); Belhabri, A. (Amine); O. Reman (Oumédaly); O. Casasnovas (O.); H. Ghesquieres; G.E.G. Verhoef (Gregor); Claessen, M.-J. (Marie-José); H.A. Poirel (Hélène A); M.-C. Copin; Dubois, R. (Romain); P. Vandenberghe (Peter); Stoian, I.-A. (Ioanna-Andrea); Cottereau, A.S. (Anne S.); Bailly, S. (Sarah); L. Knoops (Laurent); F. Morschhauser (Frank)

2018-01-01

textabstractJAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in Hodgkin lymphoma. In this phase II study we

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)

Dynamic chromosomal rearrangements in Hodgkin's lymphoma are due to ongoing three-dimensional nuclear remodeling and breakage-bridge-fusion cycles.

Science.gov (United States)

Guffei, Amanda; Sarkar, Rahul; Klewes, Ludger; Righolt, Christiaan; Knecht, Hans; Mai, Sabine

2010-12-01

Hodgkin's lymphoma is characterized by the presence of mono-nucleated Hodgkin cells and bi- to multi-nucleated Reed-Sternberg cells. We have recently shown telomere dysfunction and aberrant synchronous/asynchronous cell divisions during the transition of Hodgkin cells to Reed-Sternberg cells.1 To determine whether overall changes in nuclear architecture affect genomic instability during the transition of Hodgkin cells to Reed-Sternberg cells, we investigated the nuclear organization of chromosomes in these cells. Three-dimensional fluorescent in situ hybridization revealed irregular nuclear positioning of individual chromosomes in Hodgkin cells and, more so, in Reed-Sternberg cells. We characterized an increasingly unequal distribution of chromosomes as mono-nucleated cells became multi-nucleated cells, some of which also contained chromosome-poor 'ghost' cell nuclei. Measurements of nuclear chromosome positions suggested chromosome overlaps in both types of cells. Spectral karyotyping then revealed both aneuploidy and complex chromosomal rearrangements: multiple breakage-bridge-fusion cycles were at the origin of the multiple rearranged chromosomes. This conclusion was challenged by super resolution three-dimensional structured illumination imaging of Hodgkin and Reed-Sternberg nuclei. Three-dimensional super resolution microscopy data documented inter-nuclear DNA bridges in multi-nucleated cells but not in mono-nucleated cells. These bridges consisted of chromatids and chromosomes shared by two Reed-Sternberg nuclei. The complexity of chromosomal rearrangements increased as Hodgkin cells developed into multi-nucleated cells, thus indicating tumor progression and evolution in Hodgkin's lymphoma, with Reed-Sternberg cells representing the highest complexity in chromosomal rearrangements in this disease. This is the first study to demonstrate nuclear remodeling and associated genomic instability leading to the generation of Reed-Sternberg cells of Hodgkin's lymphoma

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)

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)

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

International Nuclear Information System (INIS)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-01-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis

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

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

Hodgkin's disease following thorium dioxide angiography

Energy Technology Data Exchange (ETDEWEB)

Gotlieb, A I; Kirk, M E [McGill Univ., Montreal, Quebec (Canada). Dept. of Pathology; Hutchison, J L [Montreal General Hospital, Quebec (Canada)

1976-09-04

Hodgkin's disease occurred in a 53-year-old man who, 25 years previously, had undergone cerebral angiography, for which thorium dioxide suspension (Thorotrast) was used. Deposits of thorium dioxide were noted in reticuloendothelial cells in various locations. An association between thorium dioxide administration and the subsequent development of malignant tumours and neoplastic hematologic disorders has previously been reported.

Imaging of supradiaphragmatic manifestations of extranodal nonHodgkin's lymphoma

International Nuclear Information System (INIS)

Cohnen, M.; Saleh, A.; Engelbrecht, V.; Moedder, U.; Germing, U.

2002-01-01

Malignant lymphomas are differentiated into Hodgkin's and non-Hodgkin's-lymphoma (NHL). The following article discusses the imaging of extranodal NHL in supradiaphragmatic localizations. Lymphoma can affect nearly all tissues, and represent a rare entity as primary extranodal NHL. A secondary involvement of non-nodal tissue as consequence of a generalized lymphoproliferative disease is more common,and may be seen as well in HIV-positive patients defining AIDS. As extranodal lymphoma mimick the radiologic appearance of other malignant tumors, direct diagnosis without histologic analysis is often impossible. The article describes typical manifestations of lymphoma of the lungs, the head and neck area including the large glands, and rare localizations as the heart or the breast. (orig.) [de

Characterizing human stem cell-derived sensory neurons at the single-cell level reveals their ion channel expression and utility in pain research.

Science.gov (United States)

Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

2014-08-01

The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell-derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders.

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Nielsen, O; Pedersen, Niels Tinggaard

2002-01-01

-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53...... alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non......-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas...

Bi-directional astrocytic regulation of neuronal activity within a network

Directory of Open Access Journals (Sweden)

Susan Yu Gordleeva

2012-11-01

Full Text Available The concept of a tripartite synapse holds that astrocytes can affect both the pre- and postsynaptic compartments through the Ca2+-dependent release of gliotransmitters. Because astrocytic Ca2+ transients usually last for a few seconds, we assumed that astrocytic regulation of synaptic transmission may also occur on the scale of seconds. Here, we considered the basic physiological functions of tripartite synapses and investigated astrocytic regulation at the level of neural network activity. The firing dynamics of individual neurons in a spontaneous firing network was described by the Hodgkin-Huxley model. The neurons received excitatory synaptic input driven by the Poisson spike train with variable frequency. The mean field concentration of the released neurotransmitter was used to describe the presynaptic dynamics. The amplitudes of the excitatory postsynaptic currents (PSCs obeyed the gamma distribution law. In our model, astrocytes depressed the presynaptic release and enhanced the postsynaptic currents. As a result, low frequency synaptic input was suppressed while high frequency input was amplified. The analysis of the neuron spiking frequency as an indicator of network activity revealed that tripartite synaptic transmission dramatically changed the local network operation compared to bipartite synapses. Specifically, the astrocytes supported homeostatic regulation of the network activity by increasing or decreasing firing of the neurons. Thus, the astrocyte activation may modulate a transition of neural network into bistable regime of activity with two stable firing levels and spontaneous transitions between them.

Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

KAUST Repository

Jolivet, Renaud

2015-02-26

Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

Multi-timescale Modeling of Activity-Dependent Metabolic Coupling in the Neuron-Glia-Vasculature Ensemble

Science.gov (United States)

Jolivet, Renaud; Coggan, Jay S.; Allaman, Igor; Magistretti, Pierre J.

2015-01-01

Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell) can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS) are still debated. To address this question, we developed a detailed biophysical model of the brain’s metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV) ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging. PMID:25719367

Multi-timescale modeling of activity-dependent metabolic coupling in the neuron-glia-vasculature ensemble.

Directory of Open Access Journals (Sweden)

Renaud Jolivet

2015-02-01

Full Text Available Glucose is the main energy substrate in the adult brain under normal conditions. Accumulating evidence, however, indicates that lactate produced in astrocytes (a type of glial cell can also fuel neuronal activity. The quantitative aspects of this so-called astrocyte-neuron lactate shuttle (ANLS are still debated. To address this question, we developed a detailed biophysical model of the brain's metabolic interactions. Our model integrates three modeling approaches, the Buxton-Wang model of vascular dynamics, the Hodgkin-Huxley formulation of neuronal membrane excitability and a biophysical model of metabolic pathways. This approach provides a template for large-scale simulations of the neuron-glia-vasculature (NGV ensemble, and for the first time integrates the respective timescales at which energy metabolism and neuronal excitability occur. The model is constrained by relative neuronal and astrocytic oxygen and glucose utilization, by the concentration of metabolites at rest and by the temporal dynamics of NADH upon activation. These constraints produced four observations. First, a transfer of lactate from astrocytes to neurons emerged in response to activity. Second, constrained by activity-dependent NADH transients, neuronal oxidative metabolism increased first upon activation with a subsequent delayed astrocytic glycolysis increase. Third, the model correctly predicted the dynamics of extracellular lactate and oxygen as observed in vivo in rats. Fourth, the model correctly predicted the temporal dynamics of tissue lactate, of tissue glucose and oxygen consumption, and of the BOLD signal as reported in human studies. These findings not only support the ANLS hypothesis but also provide a quantitative mathematical description of the metabolic activation in neurons and glial cells, as well as of the macroscopic measurements obtained during brain imaging.

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...

Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

NARCIS (Netherlands)

Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

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

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

Effects of the network structure and coupling strength on the noise-induced response delay of a neuronal network

International Nuclear Information System (INIS)

Ozer, Mahmut; Uzuntarla, Muhammet

2008-01-01

The Hodgkin-Huxley (H-H) neuron model driven by stimuli just above threshold shows a noise-induced response delay with respect to time to the first spike for a certain range of noise strengths, an effect called 'noise delayed decay' (NDD). We study the response time of a network of coupled H-H neurons, and investigate how the NDD can be affected by the connection topology of the network and the coupling strength. We show that the NDD effect exists for weak and intermediate coupling strengths, whereas it disappears for strong coupling strength regardless of the connection topology. We also show that although the network structure has very little effect on the NDD for a weak coupling strength, the network structure plays a key role for an intermediate coupling strength by decreasing the NDD effect with the increasing number of random shortcuts, and thus provides an additional operating regime, that is absent in the regular network, in which the neurons may also exploit a spike time code

Linfoma no Hodgkin primario de mama, revisión de la literatura y presentación de un caso Primary non-Hodgkin breast lymphoma, literature review and a case a presentation

Directory of Open Access Journals (Sweden)

Caridad Verdecia Cañizares

2011-06-01

Full Text Available El linfoma no Hodgkin primario de la mama es una entidad poco frecuente en pediatría y representa el 0,4 al 0,5 % de todos los tumores mamarios malignos. Debido a que carecen de características propias, tanto clínicas, citológicas como ecográficas, resulta muy difícil establecer el diagnóstico preoperatorio. Se presenta el caso de un linfoma no Hodgkin primario de la mama en una paciente de 3 años que llegó en estadio avanzado de la enfermedad, y se subraya la importancia del tratamiento en un equipo multidisciplinario.The primary non-Hodgkin breast lymphoma is a not frequent entity in children and account for the 0,4 to 0,5% of the malignant breast tumors. Due to they lack of own clinical, cytological and echography features, it is very difficult to made the preoperative diagnosis. This is the case of a primary non-Hodgkin breast lymphoma in a patient aged 3 with an advanced stage of disease, emphasizing the significance of treatment in a multidisciplinary staff.

Single-Cell Detection of Secreted Aβ and sAPPα from Human IPSC-Derived Neurons and Astrocytes.

Science.gov (United States)

Liao, Mei-Chen; Muratore, Christina R; Gierahn, Todd M; Sullivan, Sarah E; Srikanth, Priya; De Jager, Philip L; Love, J Christopher; Young-Pearse, Tracy L

2016-02-03

Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining Aβ and sAPPα secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction. We have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid β (Aβ) and soluble amyloid precursor protein-alpha (sAPPα) and present novel findings that could not have been observed without a single-cell analytical platform. First, we

Localization of Hodgkin's disease and lymphomas by 67-gallium substraction scanning

Energy Technology Data Exchange (ETDEWEB)

Krolikiewicz, H; Maruyama, Y; Deland, F H; Beihn, R M; Hafner, T; Utley, J F

1977-01-01

/sup 67/Ga-subtraction scan was found to be useful and a promising new method for the pre-treatment evaluation of the patient with Hodgkin's disease or non-Hodgkin's lymphoma. The scan appeared to be most accurate in the neck, chest, and axillary regions. It appears to offer a means of increasing the accuracy of evaluating the abdomen, the para-aortic and pelvic regions. It may be a useful method for the follow-up to detect recurrences. It was an easily performed, safe, non-invasive test, well tolerated and accepted by patients.

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.

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

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

Characterizing Human Stem Cell–derived Sensory Neurons at the Single-cell Level Reveals Their Ion Channel Expression and Utility in Pain Research

Science.gov (United States)

Young, Gareth T; Gutteridge, Alex; Fox, Heather DE; Wilbrey, Anna L; Cao, Lishuang; Cho, Lily T; Brown, Adam R; Benn, Caroline L; Kammonen, Laura R; Friedman, Julia H; Bictash, Magda; Whiting, Paul; Bilsland, James G; Stevens, Edward B

2014-01-01

The generation of human sensory neurons by directed differentiation of pluripotent stem cells opens new opportunities for investigating the biology of pain. The inability to generate this cell type has meant that up until now their study has been reliant on the use of rodent models. Here, we use a combination of population and single-cell techniques to perform a detailed molecular, electrophysiological, and pharmacological phenotyping of sensory neurons derived from human embryonic stem cells. We describe the evolution of cell populations over 6 weeks of directed differentiation; a process that results in the generation of a largely homogeneous population of neurons that are both molecularly and functionally comparable to human sensory neurons derived from mature dorsal root ganglia. This work opens the prospect of using pluripotent stem-cell–derived sensory neurons to study human neuronal physiology and as in vitro models for drug discovery in pain and sensory disorders. PMID:24832007

Incidence of subclinical hypothyroidism in patients with Hodgkin lymphoma and non-Hodgkin requiring neck irradiation and/or mediastinum in the Hospital Mexico in the year 2009

International Nuclear Information System (INIS)

Monestel Umana, Rigoberto

2010-01-01

The treatment of lymphoma, both Hodgkin as non-Hodgkin, has had irradiation as part of management. The neck and/or mediastinum is irradiated and occurs, inevitably, partial or total irradiation of the thyroid gland. The evaluation that the effect may have on the function of the gland has been the purpose of this study. The risk of hypothyroidism in patients with Hodgkin lymphoma and non-Hodgkin should receive radiation therapy to the head, neck and/or mediastinum was studied. This has represented a first report of a follow-up study, of 2 years, analytical, longitudinal, observational, prospective. This is a first report of a follow-up study, of 2 years, analytical, longitudinal, observational, prospective. Design of cases, controls and a sample of 32 patients were studied; of these 31.25% have developed subclinical hypothyroidism. The subgroup with hypothyroidism was studied and an association was found between thyroid failure and dose, including the possibility of reversion of disorders. Association with the type of lymphoma and received chemotherapy was found, while with age, sex, lymphoma staging and dose received by the lymphoma is found without association. The onset of subclinical hypothyroidism generated by irradiation of the neck and/or mediastinum is associated with the radiation dose received by the thyroid. A relationship, unclear, has existed between the type of lymphoma and chemotherapy indicated as a treatment and should be explored further, a routine basis indicating the evaluation of the thyroid function in all these patients to avoid the development of unmonitored disorders. (author) [es

Role of neuronal activity in regulating the structure and function of auditory neurons

International Nuclear Information System (INIS)

Born, D.E.

1986-01-01

The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

Radioimmunotherapy of non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Batista Cuellar, Juan F.

2016-01-01

Non-Hodgkin lymphoma have a worse prognosis compared with other varieties of lymphoma and conventional therapy has specific onco higher incidence of unsatisfactory answers becoming more frequent recurrences of the disease. Radioimmunotherapy has proven to be an effective adjuvant therapy often in cases where conventional therapy this not proving effective. In this paper an exhibition of the current international state of the therapeutic and experiences and possibilities that exist in our environment to develop their use is done. (author)

Sleep Dependent Synaptic Down-Selection (II: Single Neuron Level Benefits for Matching, Selectivity, and Specificity

Directory of Open Access Journals (Sweden)

Atif eHashmi

2013-10-01

Full Text Available In a companion paper (Nere et al., this volume, we used computer simulations to show that a strategy of activity-dependent, on-line net synaptic potentiation during wake, followed by off-line synaptic depression during sleep, can provide a parsimonious account for several memory benefits of sleep at the systems level, including the consolidation of procedural and declarative memories, gist extraction, and integration of new with old memories. In this paper, we consider the theoretical benefits of this two-step process at the single neuron level and employ the theoretical notion of Matching between brain and environment to measure how this process increases the ability of the neuron to capture regularities in the environment and model them internally. We show that down-selection during sleep is beneficial for increasing or restoring Matching after learning, after integrating new with old memories, and after forgetting irrelevant material. By contrast, alternative schemes, such as additional potentiation in wake, potentiation in sleep, or synaptic renormalization in wake, decrease Matching. We also argue that, by selecting appropriate loops through the brain that tie feedforward synapses with feedback ones in the same dendritic domain, different subsets of neurons can learn to specialize for different contingencies and form sequences of nested perception-action loops. By potentiating such loops when interacting with the environment in wake, and depressing them when disconnected from the environment in sleep, neurons can learn to match the long-term statistical structure of the environment while avoiding spurious modes of functioning and catastrophic interference. Finally, such a two-step process has the additional benefit of desaturating the neuron's ability to learn and of maintaining cellular homeostasis. Thus, sleep-dependent synaptic renormalization offers a parsimonious account for both cellular and systems-level effects of sleep on learning

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

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

Top-down inputs enhance orientation selectivity in neurons of the primary visual cortex during perceptual learning.

Directory of Open Access Journals (Sweden)

Samat Moldakarimov

2014-08-01

Full Text Available Perceptual learning has been used to probe the mechanisms of cortical plasticity in the adult brain. Feedback projections are ubiquitous in the cortex, but little is known about their role in cortical plasticity. Here we explore the hypothesis that learning visual orientation discrimination involves learning-dependent plasticity of top-down feedback inputs from higher cortical areas, serving a different function from plasticity due to changes in recurrent connections within a cortical area. In a Hodgkin-Huxley-based spiking neural network model of visual cortex, we show that modulation of feedback inputs to V1 from higher cortical areas results in shunting inhibition in V1 neurons, which changes the response properties of V1 neurons. The orientation selectivity of V1 neurons is enhanced without changing orientation preference, preserving the topographic organizations in V1. These results provide new insights to the mechanisms of plasticity in the adult brain, reconciling apparently inconsistent experiments and providing a new hypothesis for a functional role of the feedback connections.

Results from radiant treatment in no Hodgkin's lymphomas of adults

International Nuclear Information System (INIS)

Alert, J.; Rodriguez, E.; Mesa, E.; Diaz, C.

1982-01-01

From 1973 to 1979, at the Institute of Oncology and Radiobiology, Havana City, 91 adults were irradiated because they underwent no Hodgkin's lymphomas at Stage I (located) and Stage II (regional extension) to whom radiant treatment was the basic therapeutic selection, with single or multiple fields and dose ranging between 3 500 and 4 000 rads-tumor, and some of them at Stage III, where primary treatment was chemotherapy. Present survival for all of them after 3 and 5 years is 55.7% and 54.7%, with 84.4% for patients at Stage I, 55.8% and 52.4% for Stage II and 33.8% for Stage III. Survival was similar for both sexes; in the same way ganglionar processes and those of extraganglionar localization presented no significant survival differences. Only to 7 patients (7.7%) modular forms were diagnosed. (author)

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).

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.

The effect of correlated neuronal firing and neuronal heterogeneity on population coding accuracy in guinea pig inferior colliculus.

Directory of Open Access Journals (Sweden)

Oran Zohar

Full Text Available It has been suggested that the considerable noise in single-cell responses to a stimulus can be overcome by pooling information from a large population. Theoretical studies indicated that correlations in trial-to-trial fluctuations in the responses of different neurons may limit the improvement due to pooling. Subsequent theoretical studies have suggested that inherent neuronal diversity, i.e., the heterogeneity of tuning curves and other response properties of neurons preferentially tuned to the same stimulus, can provide a means to overcome this limit. Here we study the effect of spike-count correlations and the inherent neuronal heterogeneity on the ability to extract information from large neural populations. We use electrophysiological data from the guinea pig Inferior-Colliculus to capture inherent neuronal heterogeneity and single cell statistics, and introduce response correlations artificially. To this end, we generate pseudo-population responses, based on single-cell recording of neurons responding to auditory stimuli with varying binaural correlations. Typically, when pseudo-populations are generated from single cell data, the responses within the population are statistically independent. As a result, the information content of the population will increase indefinitely with its size. In contrast, here we apply a simple algorithm that enables us to generate pseudo-population responses with variable spike-count correlations. This enables us to study the effect of neuronal correlations on the accuracy of conventional rate codes. We show that in a homogenous population, in the presence of even low-level correlations, information content is bounded. In contrast, utilizing a simple linear readout, that takes into account the natural heterogeneity, even of neurons preferentially tuned to the same stimulus, within the neural population, one can overcome the correlated noise and obtain a readout whose accuracy grows linearly with the size of

The role of gallium-67 in Hodgkin's disease

International Nuclear Information System (INIS)

Bogart, Jeffrey A.; Chung, T. Chung; Mariados, Neil F.

1996-01-01

Purpose/Objective: Although widely used, the value of gallium imaging in managing Hodgkin's lymphoma remains unclear. Methods: Retrospective review of gallium and treatment data in patients with Hodgkin's disease between January 1990 and July 1995. Results: Eighty-six of 101 patients had Ga-67 imaging. Stage was as follows: 1A-11 patients, 1B - 2, 2A - 27, 2B - 22, 3A - 10, 3B - 5, 4A - 3 and 4B - 6. Sixty-two patients had staging gallium scans and 15% of tumors were not gallium avid. Two patients were upstaged based on gallium scan. Five patients had positive laparotomy and all had negative abdominal gallium exams. Three studies had false positive lesions. Initial therapy was assessed with gallium in 61 patients and 45 had complete response. Tumor recurred in 36% ((10(28))) of patients gallium negative after 3-6 cycles of chemotherapy, with no recurrences in 17 patients gallium negative after radiotherapy or chemo radiation. Six of 7 patients with focal gallium uptake after chemotherapy received radiotherapy and all remain disease free. Seven patients had persistent or progressive gallium-avid tumor after chemotherapy correlating with clinical disease. Two patients had false positive exams after radiotherapy. Twenty-two patients had gallium scans at recurrence. One scan was (false) negative and in two cases, gallium imaging was the initial evidence of recurrent tumor. Conclusion: Ga-67 imaging may help confirm the presence of active Hodgkin's disease, but was unreliable in defining disease remission after chemotherapy in this study population. Prospective studies may help define the role of gallium scans

One nuclear calcium transient induced by a single burst of action potentials represents the minimum signal strength in activity-dependent transcription in hippocampal neurons.

Science.gov (United States)

Yu, Yan; Oberlaender, Kristin; Bengtson, C Peter; Bading, Hilmar

2017-07-01

Neurons undergo dramatic changes in their gene expression profiles in response to synaptic stimulation. The coupling of neuronal excitation to gene transcription is well studied and is mediated by signaling pathways activated by cytoplasmic and nuclear calcium transients. Despite this, the minimum synaptic activity required to induce gene expression remains unknown. To address this, we used cultured hippocampal neurons and cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH) that allows detection of nascent transcripts in the cell nucleus. We found that a single burst of action potentials, consisting of 24.4±5.1 action potentials during a 6.7±1.9s depolarization of 19.5±2.0mV causing a 9.3±0.9s somatic calcium transient, is sufficient to activate transcription of the immediate early gene arc (also known as Arg3.1). The total arc mRNA yield produced after a single burst-induced nuclear calcium transient was very small and, compared to unstimulated control neurons, did not lead to a significant increase in arc mRNA levels measured using quantitative reverse transcriptase PCR (qRT-PCR) of cell lysates. Significantly increased arc mRNA levels became detectable in hippocampal neurons that had undergone 5-8 consecutive burst-induced nuclear calcium transients at 0.05-0.15Hz. These results indicate that a single burst-induced nuclear calcium transient can activate gene expression and that transcription is rapidly shut off after synaptic stimulation has ceased. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

DEFF Research Database (Denmark)

Frederiksen, B.; Specht, L.; Henrichsen, J.

1989-01-01

Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antib......Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase...

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

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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.

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

Colored noise and memory effects on formal spiking neuron models

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da Silva, L. A.; Vilela, R. D.

2015-06-01

Simplified neuronal models capture the essence of the electrical activity of a generic neuron, besides being more interesting from the computational point of view when compared to higher-dimensional models such as the Hodgkin-Huxley one. In this work, we propose a generalized resonate-and-fire model described by a generalized Langevin equation that takes into account memory effects and colored noise. We perform a comprehensive numerical analysis to study the dynamics and the point process statistics of the proposed model, highlighting interesting new features such as (i) nonmonotonic behavior (emergence of peak structures, enhanced by the choice of colored noise characteristic time scale) of the coefficient of variation (CV) as a function of memory characteristic time scale, (ii) colored noise-induced shift in the CV, and (iii) emergence and suppression of multimodality in the interspike interval (ISI) distribution due to memory-induced subthreshold oscillations. Moreover, in the noise-induced spike regime, we study how memory and colored noise affect the coherence resonance (CR) phenomenon. We found that for sufficiently long memory, not only is CR suppressed but also the minimum of the CV-versus-noise intensity curve that characterizes the presence of CR may be replaced by a maximum. The aforementioned features allow to interpret the interplay between memory and colored noise as an effective control mechanism to neuronal variability. Since both variability and nontrivial temporal patterns in the ISI distribution are ubiquitous in biological cells, we hope the present model can be useful in modeling real aspects of neurons.

Axillary Hodgkin's disease in manual workers.

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Andrieu, J M; Weh, H J; Teillet, F; Asselain, B

1979-01-01

Between 1965 and 1974, 16 patients were clinically staged as having unique axillary localizations of Hodgkin's disease. Sex ratio (4.3), mean age (40.8 years) and professional occupations (12 out of the 16 patients were engaged in manual work) were significantly different from that of all patients observed during the same period. These facts lead us to suppose the existence of a link between manual work and initial axillary localizations.

Breast conserving surgery in locoregional treatment of breast carcinoma after Hodgkin lymphoma

International Nuclear Information System (INIS)

Haberer, S.; Le Scodan, R.; Kirova, Y.M.; Moisson, P.; Campana, F.; Fourquet, A.; Bollet, M.A.; Belin, L.; Savignoni, A.; Stevens, D.; Decaudin, D.; Pierga, J.Y.; Reyal, F.

2012-01-01

Purpose. - To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. Patients and methods. - Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. Results. - Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). Conclusions. - Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position. (authors)

The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management.

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Hawkes, Eliza A; Wotherspoon, Andrew; Cunningham, David

2012-03-01

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

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

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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

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

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Sadra Sadeh

2015-01-01

Full Text Available 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

Clinical, Molecular, and Environmental Risk Factors for Hodgkin Lymphoma

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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.

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....

Symptomatic coronary artery disease after mantle irradiation for Hodgkin's disease

International Nuclear Information System (INIS)

King, Vernon; Constine, Louis S.; Clark, Douglas; Schwartz, Ronald G.; Muhs, Ann G.; Henzler, Margaret; Hutson, Alan; Rubin, Philip

1996-01-01

Purpose: a) To assess the age-related incidence of morbid cardiac events including cardiac death (CD), nonfatal myocardial infarction (MI), and angina pectoris (AP) in all patients treated for Hodgkin's disease at a single institution; b) to examine the prevalence of cardiac risk factors and presence of coronary artery disease (CAD) in affected patients. Methods and materials: 475 patients were treated for Hodgkin's disease in our institution between 1954 and 1989. The status of 97% of the cohort was established either by patient visit and examination in 1992-1993, personal telephone contact, or documentation of death. The 326 of these patients who had mantle irradiation (RT) and survived 3 years formed the study population. Patients who experienced AP, MI, or CD secondary to CAD were assessed for the presence of specific cardiac risk factors. Cardiac catheterization and necropsy data were reviewed to determine the presence and degree of coronary artery stenosis. Results: Eighteen of 326 patients (5.5%) have had a morbid cardiac event directly related to CAD. Seven patients had CD. Seven patients experienced nonfatal MI, and four patients had AP. The mean interval from RT to morbid cardiac event was 13.1 years (range: 4.4-27.0), and the mean age at the time of the event was 39.4 years (range: 24-65). Four of these patients had morbid cardiac events between ages 24-29 years. Based on US statistics of CD secondary to MI, the relative risk of CD for the treated group was 2.8 (3.1 for males and 1.8 for females). Remarkably, no difference was found in the risk of experiencing a morbid cardiac endpoint in patients stratified by either decile of age at which RT was given, or by duration of follow-up. Only one patient experiencing an event (AP) had received an anthracycline. The mean RT dose to the central cardiac volume for the affected patients was 44.3 Gy (range: 35-60.4). Autopsy or catheterization data were available on 15 patients and revealed 90-100% stenosis of at

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

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Montijn, Jorrit Steven; Klink, P Christaan; van Wezel, Richard J A

2012-01-01

Divisive normalization models of covert attention commonly use spike rate modulations 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 in gamma-band frequencies (25-100 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 multi-level hierarchical structure and a time dimension; allowing the simulation of a recently reported backward progression of attentional effects along the visual cortical hierarchy. A simple cascade of normalization models simulating different cortical areas is shown to cause signal degradation and a loss of stimulus discriminability over time. To negate this degradation and ensure stable neuronal stimulus representations, we incorporate a kind of oscillatory phase entrainment into our model that has previously been 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 and predicts a latency effect on neuronal responses as a result of cued attention.

Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics.

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Andreas Sagner

2018-02-01

Full Text Available During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.

Hodgkin's lymphoma-related vanishing bile duct syndrome: A case report and literature review

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Kiong-Ming Wong

2013-11-01

Full Text Available We report the case of a 38-year-old man who developed vanishing bile duct syndrome in association with Hodgkin's lymphoma. He was noted to have cervical lymphadenopathy and marked elevation of total serum bilirubin at diagnosis. He achieved complete remission with normalization of serum bilirubin after eight courses of Adriamycin, bleomycin, vinblastine, and dacarbazine chemotherapy followed with autologous hematopoietic cell transplantation. Consecutive liver biopsies performed at diagnosis and at the stage of complete remission revealed the disappearance and regeneration of interlobular bile ducts, respectively. Our case provides pathological evidence that Hodgkin's lymphoma-related vanishing bile duct syndrome is a reversible bile duct injury disease. Bilirubin is a reliable serum marker to monitor the treatment response of these cases. The mechanism to develop hyperbilirubinemia with vanishing bile duct in such a case of Hodgkin's lymphoma remains to be studied. A literature review was carried out.

The what and where of adding channel noise to the Hodgkin-Huxley equations.

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Joshua H Goldwyn

2011-11-01

Full Text Available Conductance-based equations for electrically active cells form one of the most widely studied mathematical frameworks in computational biology. This framework, as expressed through a set of differential equations by Hodgkin and Huxley, synthesizes the impact of ionic currents on a cell's voltage--and the highly nonlinear impact of that voltage back on the currents themselves--into the rapid push and pull of the action potential. Later studies confirmed that these cellular dynamics are orchestrated by individual ion channels, whose conformational changes regulate the conductance of each ionic current. Thus, kinetic equations familiar from physical chemistry are the natural setting for describing conductances; for small-to-moderate numbers of channels, these will predict fluctuations in conductances and stochasticity in the resulting action potentials. At first glance, the kinetic equations provide a far more complex (and higher-dimensional description than the original Hodgkin-Huxley equations or their counterparts. This has prompted more than a decade of efforts to capture channel fluctuations with noise terms added to the equations of Hodgkin-Huxley type. Many of these approaches, while intuitively appealing, produce quantitative errors when compared to kinetic equations; others, as only very recently demonstrated, are both accurate and relatively simple. We review what works, what doesn't, and why, seeking to build a bridge to well-established results for the deterministic equations of Hodgkin-Huxley type as well as to more modern models of ion channel dynamics. As such, we hope that this review will speed emerging studies of how channel noise modulates electrophysiological dynamics and function. We supply user-friendly MATLAB simulation code of these stochastic versions of the Hodgkin-Huxley equations on the ModelDB website (accession number 138950 and http://www.amath.washington.edu/~etsb/tutorials.html.

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

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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

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.

2015-01-01

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. SIGNIFICANCE STATEMENT 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

Primary non-Hodgkin lymphoma of skeletal muscle: imaging findings

International Nuclear Information System (INIS)

Zhou Liangping; Peng Weijun; Tang Feng; Mao Jian; Yang Wentao

2006-01-01

Objective: To analyze the imaging manifestations of primary non-Hodgkin lymphoma of skeletal muscle and improve the recognition of this rare disease. Methods: Five cases of primary non- Hodgkin lymphoma of skeletal muscle proved pathologically underwent imaging exam, including MRI and CT in 3 cases, only MRI in 1 case, only CT in 1 case, X-ray in 2 cases and bone scintigraphy in 2 cases. Results: Diffuse enlargements of involved muscle with presentation of overall configuration were observed in all five cases. All 4 cases manifested as homogeneous soft masses, which is isoattenuating to normal muscle on unenhanced CT images. After intravenous injection of contrast media, the masses enhanced homogeneously and slightly (2 cases) or moderately (1 case) on CT images. The lesions were homogenous and had isointense or slightly low signal intensity compared with that of uninvolved muscle on T 1 -weighted images and high signal intensity on T 2 -weighted images. After intravenous injection of contrast media, all 2 cases enhanced homogeneously and moderately with the enhanced signal intensity of involved muscle greatly higher than that of uninvolved muscle on MR images. Two cases of X-ray plain showed no destruction of bone and 2 cases of bone scintigraphy exams showed increased radiotracer uptake of involved muscle with no infiltration of bone marrow. Conclusion: There are several characteristics on the imaging of primary non-Hodgkin lymphoma of skeletal muscle. MRI is the optimal imaging method for the diagnosis of this disease. (authors)

Encoding of Spatial Attention by Primate Prefrontal Cortex Neuronal Ensembles

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Treue, Stefan

2018-01-01

Abstract Single neurons in the primate lateral prefrontal cortex (LPFC) encode information about the allocation of visual attention and the features of visual stimuli. However, how this compares to the performance of neuronal ensembles at encoding the same information is poorly understood. Here, we recorded the responses of neuronal ensembles in the LPFC of two macaque monkeys while they performed a task that required attending to one of two moving random dot patterns positioned in different hemifields and ignoring the other pattern. We found single units selective for the location of the attended stimulus as well as for its motion direction. To determine the coding of both variables in the population of recorded units, we used a linear classifier and progressively built neuronal ensembles by iteratively adding units according to their individual performance (best single units), or by iteratively adding units based on their contribution to the ensemble performance (best ensemble). For both methods, ensembles of relatively small sizes (n decoding performance relative to individual single units. However, the decoder reached similar performance using fewer neurons with the best ensemble building method compared with the best single units method. Our results indicate that neuronal ensembles within the LPFC encode more information about the attended spatial and nonspatial features of visual stimuli than individual neurons. They further suggest that efficient coding of attention can be achieved by relatively small neuronal ensembles characterized by a certain relationship between signal and noise correlation structures. PMID:29568798

3D Reconstruction and Standardization of the Rat Vibrissal Cortex for Precise Registration of Single Neuron Morphology

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Egger, Robert; Narayanan, Rajeevan T.; Helmstaedter, Moritz; de Kock, Christiaan P. J.; Oberlaender, Marcel

2012-01-01

The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain. PMID:23284282

Pure state consciousness and its local reduction to neuronal space

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Duggins, A. J.

2013-01-01

The single neuronal state can be represented as a vector in a complex space, spanned by an orthonormal basis of integer spike counts. In this model a scalar element of experience is associated with the instantaneous firing rate of a single sensory neuron over repeated stimulus presentations. Here the model is extended to composite neural systems that are tensor products of single neuronal vector spaces. Depiction of the mental state as a vector on this tensor product space is intended to capture the unity of consciousness. The density operator is introduced as its local reduction to the single neuron level, from which the firing rate can again be derived as the objective correlate of a subjective element. However, the relational structure of perceptual experience only emerges when the non-local mental state is considered. A metric of phenomenal proximity between neuronal elements of experience is proposed, based on the cross-correlation function of neurophysiology, but constrained by the association of theoretical extremes of correlation/anticorrelation in inseparable 2-neuron states with identical and opponent elements respectively.

Linfoma No Hodgkin Primario de Mama: Reporte de un Caso.

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H. Gámez Oliva

2016-01-01

Full Text Available El linfoma no Hodgkin primario de la mama es una patología poco frecuente, constituye menos del 0,5% de todos los tumores mamarios malignos, debido a que carecen de características propias, tanto clínicas, mamográficas como ultrasonográficas. Es difícil el diagnóstico preoperatorio, la citología mediante BAAF tiene mejor rendimiento que el estudio con material congelado ya que este último tiende a confundirse con el carcinoma. En la actualidad se prefiere el tratamiento con quimioterapia tanto para el tratamiento local como para el regional. Presentamos el caso de un linfoma no Hodgkin primario de la mama en una paciente de 72 años.

Diagnosis and Treatment of Hodgkin's Lymphoma: At Times a Challenge

International Nuclear Information System (INIS)

Abbasi, N.Z.; Zahur, Z.; Khan, A.A.; Sheikh, A.S.; Memon, K.H.; Ali, F.; Din, M.J.

2013-01-01

Hodgkin's lymphoma has been traditionally defined as a hematopoietic neoplasm composed of diagnostic Reed-Sternberg cells. More than 70% of the cases involve cervical or supraclavicular lymph nodes. Isolated sub-diaphragmatic lymphadenopathy or organ involvement is rare. We present the case of Hodgkin's lymphoma in a 51 years old female, who presented with obstructive jaundice and lymphadenopathy, empirically treated previously as a case of tuberculosis. Chemotherapy with modified ABVD protocol was given with dose modification according to LFT's. Her liver functions returned to normal levels after the first cycle. The main purpose of reporting the case is to stress definitive diagnosis of the disease before initiating treatment and the modified chemotherapy regimen used in this infrequent presentation of the disease. (author)

Single-trial estimation of stimulus and spike-history effects on time-varying ensemble spiking activity of multiple neurons: a simulation study

International Nuclear Information System (INIS)

Shimazaki, Hideaki

2013-01-01

Neurons in cortical circuits exhibit coordinated spiking activity, and can produce correlated synchronous spikes during behavior and cognition. We recently developed a method for estimating the dynamics of correlated ensemble activity by combining a model of simultaneous neuronal interactions (e.g., a spin-glass model) with a state-space method (Shimazaki et al. 2012 PLoS Comput Biol 8 e1002385). This method allows us to estimate stimulus-evoked dynamics of neuronal interactions which is reproducible in repeated trials under identical experimental conditions. However, the method may not be suitable for detecting stimulus responses if the neuronal dynamics exhibits significant variability across trials. In addition, the previous model does not include effects of past spiking activity of the neurons on the current state of ensemble activity. In this study, we develop a parametric method for simultaneously estimating the stimulus and spike-history effects on the ensemble activity from single-trial data even if the neurons exhibit dynamics that is largely unrelated to these effects. For this goal, we model ensemble neuronal activity as a latent process and include the stimulus and spike-history effects as exogenous inputs to the latent process. We develop an expectation-maximization algorithm that simultaneously achieves estimation of the latent process, stimulus responses, and spike-history effects. The proposed method is useful to analyze an interaction of internal cortical states and sensory evoked activity

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

Relationship of intratumoural protein expression patterns to age and Epstein-Barr virus status in classical Hodgkin lymphoma

DEFF Research Database (Denmark)

Ludvigsen, Maja; Kamper, Peter; Hamilton-Dutoit, Stephen Jacques

2015-01-01

In Western countries, the age distribution of Hodgkin lymphoma (HL) follows a characteristic bimodal curve showing an early and a late peak at approximately 35 and 70 yr, respectively. Furthermore, the presence of latent Epstein-Barr virus (EBV) genome in the Hodgkin Reed-Sternberg cells...

Transplante de células-tronco hematopoéticas em linfoma Hodgkin Stem cell transplantation in Hodgkin lymphoma

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Rosane I. Bittencourt

2010-05-01

Full Text Available O linfoma Hodgkin(LH é uma malignidade hematológica que conta com um armamentário terapêutico selecionado de acordo com o estadiamento e a classificação prognóstica de cada doente. A sobrevida dos pacientes tratados para o LH clássico vem aumentando significativamente, com taxas de cura entre 80%-85%. Entretanto, 20%-25% são refratários aos tratamentos iniciais e cerca de 30% recaem após ter alcançado resposta completa. Os pacientes considerados com falha à terapia de primeira linha ainda têm uma segunda chance de cura se apresentarem quimiossensibilidade aos esquemas de salvamento, seguido por uma das modalidades de transplante de células-tronco hematopoéticas (TCTH. O TCTH autólogo representa uma estratégia atrativa para os pacientes com LH que falham ao tratamento convencional de primeira linha. Os resultados em termos de sobrevidas livre de doença e global são superiores aos esquemas de salvamento com quimioterapia convencional. Este procedimento tem finalidade curativa para 50% dos pacientes em segunda remissão quimiossensíveis e pode levar a remissões duráveis naqueles com mais de duas linhas de terapia. Atualmente, o TCTH alogênico, basicamente com condicionamento de intensidade reduzida (RIC, está indicado em pacientes com recaída precoce após o TCTH autólogo ou em pacientes bastante jovens com refratariedade a mais de duas linhas de tratamento convencional.Hodgkin's Lymphoma is a hematologic malignancy with a wide range of therapeutic options that must be chosen according to the stage and the prognostic classification of each patient. The overall survival of patients treated for classic Hodgkin's Lymphoma is increasing significantly, with current cure rates being between 80% and 85%. Nevertheless, 20% to 25% are refractory to the initial treatment and about 30% relapse after having reached a complete response. Patients that have failed standard therapy still have a second chance of cure if they present

Measurement of Levels of Ebstein-Barr Virus Antibodies in Patients with Hodgkins Lymphoma and Comparison with Normal Population

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M Mortazavi-zadeh

2004-07-01

Full Text Available Introduction: Hodgkins lymphoma is a unique malignancy with unknown etiology .Curability and prognosis of Hodgkin,s disease (HD depends on quickly early diagnosis .One of hypothesis proposed for the cause of this disease is Epstein- Barr virus infection and its activity in HD patients . Material and Methods:This case- control study was performed to determine the type and titers of antibodies against EBV capsid Antigens (Anti VCA IgM & IgG in HD patients as compared to the general population and its relation to age , sex , and subtype of Hodgkin. Thus, a fifty- person group of Hodgkin disease patients as the case group and a fifty – person group from the general population with the same age and sex characteristics as the control group were studied. Result: There was no significant difference for mean titer of IgM between two age ranges in each group of case and control. Also, there was statistically no significant difference between case and control groups ( P.Value=0.558 .Most of the patients as well as non affected persons had negative IgM titers. Regarding IgG, there was statistically no significant difference between case and control groups for being either negative or positive, and most persons (92% of each group and were positive for IgG, but mean titer of IgG was 2.87 mmol/lit in case group and 1.50 mmol/lit in control group , and this difference between two groups was statistically significant (Pvalue = 0.0001 . Conclusion: High titer of Anti-VCA IgG in Hodgkin disease patients compared to general population as seen in this study can explain over activity of EBV in Hodgkin's disease patients and the probable role of EBV in establishment and/or activity of the disease.

[Effect of pulse magnetic field on distribution of neuronal action potential].

Science.gov (United States)

Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

2014-08-25

The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

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

Mucosal bridges of the upper esophagus after radiotherapy for Hodgkin's disease

Energy Technology Data Exchange (ETDEWEB)

Papazian, A.; Capron, J.P.; Ducroix, J.P.; Dupas, J.L.; Quenum, C.; Besson, P.

1983-05-01

A 47-yr-old man developed dysphagia 4 yr after mediastinal radiotherapy for Hodgkin's disease. X-ray series, fiberoptic endoscopy, and computerized transverse tomography showed mucosal bridges in the upper esophagus. Histologically, these bridges were constituted from normal epithelium overlying a chronic inflammatory lamina propria, without evidence of Hodgkin's disease recurrence or of squamous cell carcinoma. Swallowing was improved by endoscopic electrocoagulation and Eder-Puestow dilatations. Several arguments favor the hypothesis that these mucosal bridges were the late sequelae of radiation esophagitis.

Fertility in female survivors of Hodgkin's lymphoma

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Irene Biasoli

2012-01-01

Full Text Available Currently, Hodgkin's lymphoma is one of the most curable types of cancer. Patients are often young and so the long-term morbidities of treatment have become of increasing concern. Among these, infertility is one of the most challenging consequences for patients in reproductive age. Premature ovarian failure in premenopausal women is a serious long-term sequel of the toxicity of chemotherapy. The main consequence of this syndrome is infertility, but women also present other symptoms related to estrogen deprivation. Different rates of impaired gonadal function are reported, depending on the patient's age, stage of disease, dose and intensity of chemotherapy and the use of radiation therapy. The most established strategy in female infertility is cryopreservation of embryos after in vitro fertilization. Additionally, the use of oral contraceptives or gonadotropinreleasing hormone analogs (GnRH-a during treatment is under study. This review will provide a general overview of the main studies conducted to evaluate the infertility rate among female Hodgkin's lymphoma survivors and risk factors associated to treatment, different end-point definitions for evaluating fertility and also a brief description of the available strategies for fertility preservation.

The Limited Utility of Multiunit Data in Differentiating Neuronal Population Activity.

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Corey J Keller

Full Text Available To date, single neuron recordings remain the gold standard for monitoring the activity of neuronal populations. Since obtaining single neuron recordings is not always possible, high frequency or 'multiunit activity' (MUA is often used as a surrogate. Although MUA recordings allow one to monitor the activity of a large number of neurons, they do not allow identification of specific neuronal subtypes, the knowledge of which is often critical for understanding electrophysiological processes. Here, we explored whether prior knowledge of the single unit waveform of specific neuron types is sufficient to permit the use of MUA to monitor and distinguish differential activity of individual neuron types. We used an experimental and modeling approach to determine if components of the MUA can monitor medium spiny neurons (MSNs and fast-spiking interneurons (FSIs in the mouse dorsal striatum. We demonstrate that when well-isolated spikes are recorded, the MUA at frequencies greater than 100Hz is correlated with single unit spiking, highly dependent on the waveform of each neuron type, and accurately reflects the timing and spectral signature of each neuron. However, in the absence of well-isolated spikes (the norm in most MUA recordings, the MUA did not typically contain sufficient information to permit accurate prediction of the respective population activity of MSNs and FSIs. Thus, even under ideal conditions for the MUA to reliably predict the moment-to-moment activity of specific local neuronal ensembles, knowledge of the spike waveform of the underlying neuronal populations is necessary, but not sufficient.

Evoking prescribed spike times in stochastic neurons

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Doose, Jens; Lindner, Benjamin

2017-09-01

Single cell stimulation in vivo is a powerful tool to investigate the properties of single neurons and their functionality in neural networks. We present a method to determine a cell-specific stimulus that reliably evokes a prescribed spike train with high temporal precision of action potentials. We test the performance of this stimulus in simulations for two different stochastic neuron models. For a broad range of parameters and a neuron firing with intermediate firing rates (20-40 Hz) the reliability in evoking the prescribed spike train is close to its theoretical maximum that is mainly determined by the level of intrinsic noise.

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

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Barton, Michael; Boyages, John; Crennan, Elizabeth; Davis, Sidney; Fisher, Richard J; Hook, Carolyn; Johnson, Neva; Joseph, David; Liew, Kuen H; Morgan, Graeme; O' Brien, Peter; Pendlebury, Sue; Pratt, Gary; Quong, George; Thornton, Deborah; Walker, Quenten; Wallington, Margaret; Trotter, Grant

1995-01-15

Purpose: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. Methods and Materials: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. Results: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year acturial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. Conclusions: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity.

IgG4-related disease simulating Hodgkin lymphoma in a child

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D. Eric Ewing, MD

2016-06-01

Full Text Available Immunoglobulin (Ig G4-related disease is a recently described syndrome characterized by mass forming lymphoplasmacytic tissue infiltration and elevated serum IgG4 concentrations usually affecting middle-aged or older individuals. Lymphadenopathy is frequently observed and is sometimes the first or only manifestation of the disease. We report a case of IgG4-related disease mimicking Hodgkin lymphoma in a 13-year-old girl. The patient presented with progressive unilateral cervical lymphadenopathy of several months duration. Biopsy showed follicular hyperplasia with progressive transformation of germinal centers. Interfollicular areas were expanded by small lymphocytes, histiocytes, eosinophils and fibrosis with occasional CD30 positive cells initially concerning for interfollicular Hodgkin lymphoma. Immunohistochemical analysis revealed an intrafollicular plasmacytosis with an IgG4-positive/IgG-positive plasma cell ratio of 50% supporting a diagnosis of IgG4-related lymphadenopathy, progressively transformed germinal centers type. Laboratory studies were supportive with elevated serum IgG4 (178 mg/dL and IgE (30.40 kU/L levels along with an elevated serum IgG4/IgG ratio (0.16. Very few cases of IgG4-related disease have been described in children. Within this age group, there is considerable clinical overlap between IgG4-related disease associated lymphadenopathy and Hodgkin lymphoma. In addition, lymphadenopathy secondary to IgG4-related disease demonstrates substantial histologic diversity with the potential to simulate the inflammatory background and fibrosis of Hodgkin lymphoma. The importance of accurate diagnosis is underscored by the prognostic implications considering the marked response of the syndrome to steroid therapy. In addition, appropriate follow up is critical to monitor for relapse and additional organ involvement.

Radiation therapy for early stage Hodgkin's disease: Australasian patterns of care

International Nuclear Information System (INIS)

Barton, Michael; Boyages, John; Crennan, Elizabeth; Davis, Sidney; Fisher, Richard J.; Hook, Carolyn; Johnson, Neva; Joseph, David; Liew, Kuen H.; Morgan, Graeme; O'Brien, Peter; Pendlebury, Sue; Pratt, Gary; Quong, George; Thornton, Deborah; Walker, Quenten; Wallington, Margaret; Trotter, Grant

1995-01-01

Purpose: Analysis of treatment outcome for Stage I-IIA supradiaphragmatic Hodgkin's disease treated solely by irradiation in Australia and New Zealand. Methods and Materials: Patients with supradiaphragmatic Hodgkin's disease only who were treated by irradiation alone with curative intent between 1969 to 1988 were retrospectively reviewed. Ten radiation oncology departments in Australia and New Zealand contributed patient data to the study. Patient, tumor, and treatment variables were recorded. Disease-free interval, survival, and complications were analyzed. Results: Eight hundred and twenty patients were reviewed. The median age was 29 years. There were 437 men and 383 women. The distribution of 310 clinically staged patients was 170 stage IA, 5 IB, and 135 IIA. Five hundred and ten patients received laparotomies, and pathologic staging was as follows: IA 214, IB 13, IIA 283. The 10-year acturial disease-free rate was 69% and overall survival rate was 79%. Increasing age, male sex, higher number of involved sites, the use of involved field irradiation, no staging laparotomy, and earlier year of treatment were significantly associated with an increased risk of relapse and lower survival. Actuarial 10-year survival following recurrence was 48%. Acute complications requiring interruption to treatment occurred in 46 patients (6%), but < 1% had their treatment permanently suspended. Actuarial complication rates at 10 years were: cardiac 2%, pulmonary 3% and thyroid 5%. There were 44 second malignancies including 10 non-Hodgkin's lymphomas, 3 leukemias, 7 lung, and 6 breast cancers. Mean delay to the development of a second cancer was 6 years. The 10-year actuarial rate of second malignancy was 5%. Conclusions: The Australasian experience of early stage Hodgkin's disease is consistent with the results in the published literature and confirms that irradiation produces a high cure rate with minimal toxicity

Dumbbell-shaped Hodgkin's disease with cauda equina compression mimicking a herniated inter-vertebral disc, a case report.

Science.gov (United States)

Liao, Jen-Chung; Fu, Tsai-Sheng; Chen, Wen-Jer; Jung, Shih-Ming

2007-01-01

Hodgkin's disease may involve the spine as a setting of the advanced disease. An initial manifestation of Hodgkin's disease in spine is extremely rare and the major involved sites usually are the thoracic or cervical spine. The mechanisms of pathogenesis for the formation of an epidural mass during Hodgkin's disease are hematogenous dissemination from nodal sites or local infiltration of lymphomatous tissue. We document here a case of a 16 year-old boy who suffered from incomplete voiding due to dumbbell-shaped retroperitoneal Hodgkin's disease with cauda equina compression. He was successfully managed using surgery and adjuvant chemotherapy. Although lymphadenomatous tissue responds well to radiotherapy and chemotherapy, the role of surgery in this case was to achieve immediate nerve tissue decompression and to obtain an adequate specimen for pathological diagnosis. Magnetic resonance imaging (MRI) is a non-invasive and helpful tool when detecting spinal and paraspinal lesions and we emphasize that spinal MRI should be performed without delay if there is persistent back pain or sciatica.

Nuclear medicine and lymphoma: the role of the FDG PET in non Hodgkin's lymphoma in children

International Nuclear Information System (INIS)

Montravers, F.; Kerrou, K.; Gutman, F.; Grahek, D.; Talbot, J.N.

2006-01-01

As for adult population, FDG PET is recognized as an efficient tool for staging, adaptation of therapy and follow-up of Hodgkin's disease in children. The interpretation of PET needs however to take into account some specificities of imaging as the frequent brown fat activation and the physiologic thymic uptake. The role of FDG PET in non Hodgkin's lymphoma (NHL) in children is less established. Although LNH are more frequent than Hodgkin 's lymphoma in children, FDG PET is rarely performed at diagnosis, probably due to the therapeutic emergency of these aggressive pediatric forms. During follow-up, FDG PET has been however shown to be useful, especially for the characterization of residual masses. (authors)

Editorial perspective--advances in B-cell non-Hodgkin's lymphoma

NARCIS (Netherlands)

Hagenbeek, A.; Bischof Delaloye, A.

2003-01-01

Radioimmunotherapy (RIT) represents an exciting new therapeutic option for the treatment of B-cell non-Hodgkin's lymphoma (NHL), emerging at a time when significant advances have been made in NHL classification, molecular genetics and treatment. Despite recent treatment advances, including the use

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group

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G. Santini

2004-05-01

Full Text Available The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky, were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5% achieved complete remission and 4 (4.3% partial remission. Three patients (3.2% were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9%, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126. Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

Sperm quality before treatment in patients with early stage Hodgkin's lymphoma enrolled in EORTC-GELA Lymphoma Group trials.

NARCIS (Netherlands)

Kaaij, M.A. van der; Heutte, N.; Echten-Arends, J. van; Raemaekers, J.M.M.; Carde, P.; Noordijk, E.M.; Ferme, C.; Thomas, J.; Eghbali, H.; Brice, P.; Bonmati, C.; Henry-Amar, M.; Kluin-Nelemans, H.C.

2009-01-01

BACKGROUND: Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin's lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin's

Sperm quality before treatment in patients with early stage Hodgkin's lymphoma enrolled in EORTC-GELA Lymphoma Group trials

NARCIS (Netherlands)

van der Kaalj, Marleen A. E.; Heutte, Natacha; van Echten-Arends, Jannie; Raemaekers, John M. M.; Carde, Patrice; Noordijk, Evert M.; Ferme, Christophe; Thomas, Jose; Eghbali, Houchingue; Brice, Pauline; Bonmati, Caroline; Henry-Amar, Michel; Kluin-Nelemans, Hanneke C.

2009-01-01

Background Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin's lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin's

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

Thyroid cancer following radiotherapy for Hodgkin's disease: a case report and review of the literature

International Nuclear Information System (INIS)

Moroff, S.V.; Fuks, J.Z.

1986-01-01

Improved survival resulting from advances in therapy in patients with Hodgkin's disease is associated with long-term morbidity, including the potential for the development of a second solid malignancy. We report a 44-year-old man with an unusually aggressive course of thyroid carcinoma 15 years after treatment for Hodgkin's disease. In a review of the English-language literature, we found 21 cases of thyroid cancer following radiotherapy for Hodgkin's disease, with latency periods ranging from 6 to 48 years. The development of secondary thyroid cancer after high-dose neck irradiation may be related to hypothyroidism, itself a complication of radiotherapy. Thyroid function should be measured at least once a year in all patients given neck irradiation, with initiation of thyroid hormone replacement if there is evidence of sustained hypothyroidism

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

Gastrointestinal cancer after treatment of Hodgkin's disease

International Nuclear Information System (INIS)

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

1997-01-01

Purpose: This study aimed to quantify the risk of gastrointestinal cancer following Hodgkin's disease treatment according to age at treatment, type of treatment, and anatomic sites. Methods and Materials: Cases were identified from the records of 2,441 patients treated for Hodgkin's disease between 1961 and 1994. Follow-up averaged 10.9 years, representing 26,590 person-years of observation. Relative risks (RR) for gastrointestinal cancer incidence and mortality were computed by comparison with expected annualized rates for a general population matched for age, sex, and race. Results: Gastrointestinal cancers developed in 25 patients. The incidence RR was 2.5 [95% confidence interval (CI), 1.5-3.5] and mortality RR was 3.8 (CI, 2.4-4.7). Sites associated with significantly increased risks included the stomach [RR 7.3 (CI, 3.4-13.8)], small intestine [RR 11.6 (CI, 1.9-38.3)], and pancreas [RR 3.5 (CI, 1.1-8.5)]. Risk was significantly elevated after combined modality therapy, RR 3.9 (CI, 2.2-5.6). The risk after radiotherapy alone was 2.0 (CI, 1.0-3.4), not a statistically significant elevation. The RR for gastrointestinal cancer was greatest after treatment at young age and decreased with advancing age. It was significantly elevated within 10 years after treatment [RR 2.0 (CI, 1.1-3.5)] and increased further after 20 years [RR 6.1 (CI, 2.5-12.7)]. Risk assessed by attained age paralleled risk according to age at treatment. Fifteen cases of gastrointestinal cancers arose within the irradiation fields. Conclusion: Patients treated for Hodgkin's disease are at modestly increased risk for secondary gastrointestinal cancer, especially after combined modality therapy and treatment at a young age. Risk was highest more than 20 years after treatment, but was significantly elevated within 10 years. Gastrointestinal sites with increased risk included the stomach, pancreas, and small intestine

Emulating the electrical activity of the neuron using a silicon oxide RRAM cell

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Adnan eMehonic

2016-02-01

Full Text Available In recent years, formidable effort has been devoted to exploring the potential of Resistive RAM (RRAM devices to model key features of biological synapses. This is done to strengthen the link between neuro-computing architectures and neuroscience, bearing in mind the extremely low power consumption and immense parallelism of biological systems. Here we demonstrate the feasibility of using the RRAM cell to go further and to model aspects of the electrical activity of the neuron. We focus on the specific operational procedures required for the generation of controlled voltage transients, which resemble spike-like responses. Further, we demonstrate that RRAM devices are capable of integrating input current pulses over time to produce thresholded voltage transients. We show that the frequency of the output transients can be controlled by the input signal, and we relate recent models of the redox-based nanoionic resistive memory cell to two common neuronal models, the Hodgkin-Huxley (HH conductance model and the leaky integrate-and-fire model. We employ a simplified circuit model to phenomenologically describe voltage transient generation.

Emulating the Electrical Activity of the Neuron Using a Silicon Oxide RRAM Cell

Science.gov (United States)

Mehonic, Adnan; Kenyon, Anthony J.

2016-01-01

In recent years, formidable effort has been devoted to exploring the potential of Resistive RAM (RRAM) devices to model key features of biological synapses. This is done to strengthen the link between neuro-computing architectures and neuroscience, bearing in mind the extremely low power consumption and immense parallelism of biological systems. Here we demonstrate the feasibility of using the RRAM cell to go further and to model aspects of the electrical activity of the neuron. We focus on the specific operational procedures required for the generation of controlled voltage transients, which resemble spike-like responses. Further, we demonstrate that RRAM devices are capable of integrating input current pulses over time to produce thresholded voltage transients. We show that the frequency of the output transients can be controlled by the input signal, and we relate recent models of the redox-based nanoionic resistive memory cell to two common neuronal models, the Hodgkin-Huxley (HH) conductance model and the leaky integrate-and-fire model. We employ a simplified circuit model to phenomenologically describe voltage transient generation. PMID:26941598

Increased risk of breast cancer in splenectomized patients undergoing radiation therapy for Hodgkin's disease

International Nuclear Information System (INIS)

Chung, Chung T.; Bogart, Jeffrey A.; Adams, James F.; Sagerman, Robert H.; Numann, Patricia J.; Tassiopoulos, Apostolos; Duggan, David B.

1997-01-01

Purpose: Second malignancies have been reported among patients who were treated by radiation therapy or chemotherapy alone or in combination. Studies have implied an increased risk of breast cancer in women who received radiotherapy as part of their treatment for Hodgkin's disease. This review was performed to determine if there is an association between splenectomy and subsequent breast cancer. Methods and Materials: One hundred and thirty-six female patients with histologically proven Hodgkin's disease were seen in the Division of Radiation Oncology between 1962 and 1985. All patients received mantle or mediastinal irradiation as part of their therapy. The risk of breast cancer was assessed and multiple linear regression analysis was performed on the following variables: patient age, stage, dose and extent of radiation field, time after completing radiation therapy, splenectomy, and chemotheraphy. Results: Breast cancer was observed in 11 of 74 splenectomized patients and in none of 62 patients not splenectomized. The mean follow-up was 13 years in splenectomized patients and 16 years, 7 months in nonsplenectomized patients. Nine patients developed invasive breast cancer and two developed ductal carcinoma in situ. Splenectomy was the only variable independently associated with an increased risk of breast cancer (p < 0.005) in multiple linear regression analysis; age, latency, and splenectomy considered together were also associated with an increased risk of breast cancer (p < 0.01). Conclusion: Our data show an increased risk of breast cancer in splenectomized patients who had treatment for Hodgkin's disease. A multiinstitutional survey may better define the influence of splenectomy relative to developing breast cancer in patients treated for Hodgkin's disease. The risk of breast cancer should be considered when recommending staging laparotomy, and we recommend close follow-up examination including routine mammograms for female patients successfully treated for

Risk assessment in the management of newly diagnosed classical Hodgkin lymphoma.

Science.gov (United States)

Connors, Joseph M

2015-03-12

Treatment of Hodgkin lymphoma is associated with 2 major types of risk: that the treatment may fail to cure the disease or that the treatment will prove unacceptably toxic. Careful assessment of the amount of the lymphoma (tumor burden), its behavior (extent of invasion or specific organ compromise), and host related factors (age; coincident systemic infection; and organ dysfunction, especially hematopoietic, cardiac, or pulmonary) is essential to optimize outcome. Elaborately assembled prognostic scoring systems, such as the International Prognostic Factors Project score, have lost their accuracy and value as increasingly effective chemotherapy and supportive care have been developed. Identification of specific biomarkers derived from sophisticated exploration of Hodgkin lymphoma biology is bringing promise of further improvement in targeted therapy in which effectiveness is increased at the same time off-target toxicity is diminished. Parallel developments in functional imaging are providing additional potential to evaluate the efficacy of treatment while it is being delivered, allowing dynamic assessment of risk during chemotherapy and adaptation of the therapy in real time. Risk assessment in Hodgkin lymphoma is continuously evolving, promising ever greater precision and clinical relevance. This article explores the past usefulness and the emerging potential of risk assessment for this imminently curable malignancy. © 2015 by The American Society of Hematology.

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)

Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

Science.gov (United States)

Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

2017-08-01

Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common

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)

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

2018-05-01

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 (organization. [Figure not available: see fulltext.

Enfermedad de Hodgkin: nuevos conceptos clínico-patológicos Hodgkin´s disease: new clinico-pathologic features

Directory of Open Access Journals (Sweden)

José René Mesa Cuervo

2000-04-01

Full Text Available La enfermedad de Hodgkin, considerada una neoplasia linfoide, se clasifica en 5 grupos a partir de la conferencia de Rye en 1966. La variedad esclerosis nodular es la más frecuente, afecta generalmente regiones supradiafragmáticas y se divide en 2 grados, con características morfológicas y pronósticas diferentes. El grado II, de mal pronóstico, exige formas de tratamiento más agresivas. La celularidad mixta suele tener mayor diseminación de la enfermedad y junto a la esclerosis nodular, se catalogan como formas clásicas de la enfermedad, con positividad para los marcadores inmunofenotípicos CD15 y CD30. El predominio linfocítico se considera un linfoma de células del centro germinal y emerge como entidad clínicopatológica diferente. La depleción linfocítica se diagnostica con baja frecuencia y tiene un pronóstico desfavorable. El diagnóstico diferencial con linfomas no hodgkinianos no siempre es posible y actualmente se señala que la delimitación entre ambos tipos de linfomas no está bien definida. El grupo no clasificado tiende a desaparecerHodgkin´s disease, considered a lymphoid neoplasia, is classified in 5 groups, since Rye Conference in 1960. Nodular sclerosis variety is commonest, generally involve supradiaphragmatic regions and is divided in two grades with distinct morphologic ant prognostic features. Grade II of badly prognosis demand a more aggresive treatment. Mixed cellularity ussualy has a greater disease spreading level and joined with nodular sclerosis, are classified as classic forms of disease, positive to immunophenotypical markers, CD15 and CD30. Lymphocytic predominance is to be considered as a cell lymphoma of germinal center and emerge as a distinct clinico-pathologic entity with a unfavourable prognosis. Differential diagnosis in non-Hodgkin´s lymphomas, unusually is possible and at present, delimitation between both types of lymphoma, es not well defined. Non classified group have a tendency to

NeuronMetrics: software for semi-automated processing of cultured neuron images.

Science.gov (United States)

Narro, Martha L; Yang, Fan; Kraft, Robert; Wenk, Carola; Efrat, Alon; Restifo, Linda L

2007-03-23

Using primary cell culture to screen for changes in neuronal morphology requires specialized analysis software. We developed NeuronMetrics for semi-automated, quantitative analysis of two-dimensional (2D) images of fluorescently labeled cultured neurons. It skeletonizes the neuron image using two complementary image-processing techniques, capturing fine terminal neurites with high fidelity. An algorithm was devised to span wide gaps in the skeleton. NeuronMetrics uses a novel strategy based on geometric features called faces to extract a branch number estimate from complex arbors with numerous neurite-to-neurite contacts, without creating a precise, contact-free representation of the neurite arbor. It estimates total neurite length, branch number, primary neurite number, territory (the area of the convex polygon bounding the skeleton and cell body), and Polarity Index (a measure of neuronal polarity). These parameters provide fundamental information about the size and shape of neurite arbors, which are critical factors for neuronal function. NeuronMetrics streamlines optional manual tasks such as removing noise, isolating the largest primary neurite, and correcting length for self-fasciculating neurites. Numeric data are output in a single text file, readily imported into other applications for further analysis. Written as modules for ImageJ, NeuronMetrics provides practical analysis tools that are easy to use and support batch processing. Depending on the need for manual intervention, processing time for a batch of approximately 60 2D images is 1.0-2.5 h, from a folder of images to a table of numeric data. NeuronMetrics' output accelerates the quantitative detection of mutations and chemical compounds that alter neurite morphology in vitro, and will contribute to the use of cultured neurons for drug discovery.

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.

Internally generated preactivation of single neurons in human medial frontal cortex predicts volition

OpenAIRE

Fried, Itzhak; Mukamel, Roy; Kreiman, Gabriel

2011-01-01

Understanding how self-initiated behavior is encoded by neuronal circuits in the human brain remains elusive. We recorded the activity of 1019 neurons while twelve subjects performed self-initiated finger movement. We report progressive neuronal recruitment over ∼1500 ms before subjects report making the decision to move. We observed progressive increase or decrease in neuronal firing rate, particularly in the supplementary motor area (SMA), as the reported time of decision was approached. A ...

Single-neuron correlates of subjective vision in the human medial temporal lobe

OpenAIRE

Kreiman, Gabriel; Fried, Itzhak; Koch, Christof

2002-01-01

Visual information from the environment is transformed into perceptual sensations through several stages of neuronal processing. Flash suppression constitutes a striking example in which the same retinal input can give rise to two different conscious visual percepts. We directly recorded the responses of individual neurons during flash suppression in the human amygdala, entorhinal cortex, hippocampus, and parahippocampal gyrus, allowing us to explore the neuronal responses in untrained subjec...

Impact of adaptation currents on synchronization of coupled exponential integrate-and-fire neurons.

Directory of Open Access Journals (Sweden)

Josef Ladenbauer

Full Text Available The ability of spiking neurons to synchronize their activity in a network depends on the response behavior of these neurons as quantified by the phase response curve (PRC and on coupling properties. The PRC characterizes the effects of transient inputs on spike timing and can be measured experimentally. Here we use the adaptive exponential integrate-and-fire (aEIF neuron model to determine how subthreshold and spike-triggered slow adaptation currents shape the PRC. Based on that, we predict how synchrony and phase locked states of coupled neurons change in presence of synaptic delays and unequal coupling strengths. We find that increased subthreshold adaptation currents cause a transition of the PRC from only phase advances to phase advances and delays in response to excitatory perturbations. Increased spike-triggered adaptation currents on the other hand predominantly skew the PRC to the right. Both adaptation induced changes of the PRC are modulated by spike frequency, being more prominent at lower frequencies. Applying phase reduction theory, we show that subthreshold adaptation stabilizes synchrony for pairs of coupled excitatory neurons, while spike-triggered adaptation causes locking with a small phase difference, as long as synaptic heterogeneities are negligible. For inhibitory pairs synchrony is stable and robust against conduction delays, and adaptation can mediate bistability of in-phase and anti-phase locking. We further demonstrate that stable synchrony and bistable in/anti-phase locking of pairs carry over to synchronization and clustering of larger networks. The effects of adaptation in aEIF neurons on PRCs and network dynamics qualitatively reflect those of biophysical adaptation currents in detailed Hodgkin-Huxley-based neurons, which underscores the utility of the aEIF model for investigating the dynamical behavior of networks. Our results suggest neuronal spike frequency adaptation as a mechanism synchronizing low frequency

Non-Hodgkin's lymphoma of the sphenoid sinus presenting as isolated oculomotor nerve palsy

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Huh Ji

2007-08-01

Full Text Available Abstract Background Solitary involvement of the sphenoid sinus has rarely been reported in non-Hodgkin's lymphoma. Isolated oculomotor nerve palsy is uncommon as an initial presentation of malignant tumors of the sphenoid sinus. Case presentation A 53-year-old woman presented with a three-month history of headache and diplopia. Neurological examination revealed complete left oculomotor nerve palsy. Magnetic Resonance Imaging (MRI demonstrated a homogenous soft-tissue lesion occupying the left sphenoid sinus and invading the left cavernous sinus. The patient underwent transsphenoidal biopsy and the lesion was histologically diagnosed as non-Hodgkin's lymphoma, diffuse large B-cell type. Tumor cells were positive for CD20 and negative for CD3. Following six cycles of chemotherapy, the left oculomotor nerve palsy that had been previously observed was completely resolved. There was no enhancing lesion noted on follow-up MRI. Conclusion It is important to recognize that non-Hodgkin's lymphoma of the sphenoid sinus can present with isolated oculomotor nerve palsy, although it is extremely rare. The cranial nerve deficits can resolve dramatically after chemotherapy.

Breast cancer following treatment for Hodgkin's disease: the need for screening in a young population

International Nuclear Information System (INIS)

O'Brien, P.C.

1995-01-01

Several recent publications have highlighted the issue of an increased risk of breast cancer in women treated with radiotherapy, chemotherapy, or combined modality therapy for Hodgkin's disease. The risk is greatest in women 30 years or younger at the time of treatment. In the Australasian Radiation Oncology Lymphoma Group database, 60% of women fell into this age category. This article reviews the available data pertaining to induction of breast cancer by radiotherapy for Hodgkin's disease. Breast examination should now be an integral part of the long term follow up for these women. There is also a case for the use of screening mammography. Any breast mass developing subsequent to treatment for Hodgkin's disease should be regarded with a high index of clinical suspicion and, accordingly, biopsies should be performed in the majority of cases, even when mammography is negative. 30 refs., 3 tabs

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.)

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...... origin. In particular, we allow for the noise to be of arbitrary intensity. The optimal control problem is solved using dynamic programming when the controller has access to the voltage (closed-loop control), and using a maximum principle for the transition density when the controller only has access...... 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...

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.

Development of Graves' disease following radiation therapy in Hodgkin's disease

International Nuclear Information System (INIS)

Loeffler, J.S.; Tarbell, N.J.; Garber, J.R.; Mauch, P.

1988-01-01

Radiation-related thyroid dysfunction is a common occurrence in patients with Hodgkin's disease treated with mantle field radiation. Although chemical and clinical hypothyroidism are most commonly seen, Graves' disease has also been described. We have examined the records of 437 surgically staged patients who received mantle field irradiation between April 1969 and December 1980 to ascertain the frequency of manifestations of Graves' disease. Within this group, seven patients developed hyperthyroidism accompanied by ophthalmic findings typical of those seen in Graves' disease. The actuarial risk of developing Graves' disease at 10 years following mantle irradiation for Hodgkin's disease was 3.3% in female patients and 1% in male patients in this study. The observed/expected ratios were 5.9 and 5.1 for female and male patients, respectively. This observed risk significantly exceeded that seen in the general population

Non-Hodgkin lymphoma presenting as bilateral tonsillar hypertrophy: case report.

LENUS (Irish Health Repository)

Khan, Sardar U

2012-02-01

We describe the case of a 57-year-old man who was referred to us with persistent sore throat, dysphagia, and enlarged tonsils. He had not responded to earlier treatment with antibiotic therapy and other routine measures. In view of the persistent nature of the patient\\'s symptoms and the tonsillar hypertrophy, we decided to perform a tonsillectomy and to send the excised specimens for pathologic analysis. Histologic evaluation identified non-Hodgkin lymphoma in both tonsils. The patient was treated with postoperative chemo- and radiotherapy, and he was free of symptoms during 18 months of follow-up. To the best of our knowledge, only 4 cases of bilateral non-Hodgkin lymphoma of the tonsils have been reported in the English-language literature. We also discuss the importance of histologic analysis of excised tonsil tissue in selected cases.

CFTR mediates noradrenaline-induced ATP efflux from DRG neurons.

Science.gov (United States)

Kanno, Takeshi; Nishizaki, Tomoyuki

2011-09-24

In our earlier study, noradrenaline (NA) stimulated ATP release from dorsal root ganglion (DRG) neurons as mediated via β(3) adrenoceptors linked to G(s) protein involving protein kinase A (PKA) activation, to cause allodynia. The present study was conducted to understand how ATP is released from DRG neurons. In an outside-out patch-clamp configuration from acutely dissociated rat DRG neurons, single-channel currents, sensitive to the P2X receptor inhibitor PPADS, were evoked by approaching the patch-electrode tip close to a neuron, indicating that ATP is released from DRG neurons, to activate P2X receptor. NA increased the frequency of the single-channel events, but such NA effect was not found for DRG neurons transfected with the siRNA to silence the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the immunocytochemical study using acutely dissociated rat DRG cells, CFTR was expressed in neurons alone, but not satellite cells, fibroblasts, or Schwann cells. It is concluded from these results that CFTR mediates NA-induced ATP efflux from DRG neurons as an ATP channel.

Linfoma não Hodgkin gástrico Gastric non-Hodgkin Lymphoma

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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.

Adult Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Adult Hodgkin lymphoma (HL) can be cured in over 75% of new cases with combination chemotherapy and/or radiation therapy. Subtypes include classical HL (nodular sclerosis mixed-cellularity, lymphocyte depletion, and lymphocyte-rich) and nodular lymphocyte–predominant HL. Get comprehensive information on HL and treatment in this clinician summary.

From Knights Corner to Landing: a Case Study Based on a Hodgkin-Huxley Neuron Simulator

OpenAIRE

George Chatzikonstantis; Diego Jiménez; Esteban Meneses; Christos Strydis; Harry Sidiropoulos; Dimitrios Soudris

2017-01-01

Brain modeling has been presenting significant challenges to the world of high-performance computing (HPC) over the years. The field of computational neuroscience has been developing a demand for physiologically plausible neuron models, that feature increased complexity and thus, require greater computational power. We explore Intel’s newest generation of Xeon Phi computing platforms, named Knights Landing (KNL), as a way to match the need for processing power and as an upgrade over the previ...

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.

On the number of preganglionic neurones driving human postganglionic sympathetic neurones: a comparison of modelling and empirical data

Directory of Open Access Journals (Sweden)

Vaughan G Macefield

2011-12-01

Full Text Available Postganglionic sympathetic axons in awake healthy human subjects, regardless of their identity as muscle vasoconstrictor, cutaneous vasoconstrictor or sudomotor neurones, discharge with a low firing probability (~30%, generate low firing rates (~0.5 Hz and typically fire only once per cardiac interval. The purpose of the present study was to use modelling of spike trains in an attempt to define the number of preganglionic neurones that drive an individual postganglionic neurone. Artificial spike trains were generated in 1-3 preganglionic neurones converging onto a single postganglionic neurone. Each preganglionic input fired with a mean interval distribution of either 1000, 1500, 2000, 2500 or 3000 ms and the standard deviation varied between 0.5, 1.0 and 2.0 x the mean interval; the discharge frequency of each preganglionic neurone exhibited positive skewness and kurtosis. Of the 45 patterns examined, the mean discharge properties of the postganglionic neurone could only be explained by it being driven by, on average, two preganglionic neurones firing with a mean interspike interval of 2500 ms and SD of 5000 ms. The mean firing rate resulting from this pattern was 0.22 Hz, comparable to that of spontaneously active muscle vasoconstrictor neurones in healthy subjects (0.40 Hz. Likewise, the distribution of the number of spikes per cardiac interval was similar between the modelled and actual data: 0 spikes (69.5 vs 66.6 %, 1 spike (25.6 vs 21.2 %, 2 spikes (4.3 vs 6.4 %, 3 spikes (0.5 vs 1.7 % and 4 spikes (0.1 vs 0.7 %. Although some features of the firing patterns could be explained by the postganglionic neurone being driven by a single preganglionic neurone, none of the emulated firing patterns generated by the firing of three preganglionic neurones matched the discharge of the real neurones. These modelling data indicate that, on average, human postganglionic sympathetic neurones are driven by two preganglionic inputs.

High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

Science.gov (United States)

Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

2016-01-01

Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

Second acute leukemia and other malignancies following treatment for Hodgkin's disease

International Nuclear Information System (INIS)

Valagussa, P.; Santoro, A.; Fossati-Bellani, F.; Banfi, A.; Bonadonna, G.

1986-01-01

The records of 1329 patients with Hodgkin's disease admitted from 1965 to 1982 were analyzed to assess the relative frequency of second neoplasms. Within a median follow-up of 9.5 years, a total of 68 new cancers were documented. Nineteen cases of acute nonlymphocytic leukemia, 6 cases of non-Hodgkin's lymphomas, and 43 cases with different types of solid tumors were identified. The overall risk of non-Hodgkin's lymphoma was 1.3% +/- 0.6% and of solid tumors was 8.3% +/- 1.5% when basal cell carcinomas were included and 6.7% +/- 1.4% when basal cell carcinomas were excluded. No cases of leukemia were documented in patients treated with radiation therapy only. The 12-year estimate of leukemia by treatment was as follows: chemotherapy only 1.4% +/- 2.3%; radiation plus MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) 10.2% +/- 5.2%; radiation plus ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine) 0; and radiation plus other drug regimens 4.8% +/- 1.6%. The risk of leukemia was particularly high (15.5% +/- 7.4%) in patients who received salvage MOPP after radiation failure. A positive association was also noted between increasing age and risk of second malignancies, especially leukemia. The incidence of second neoplasms can be markedly decreased by deleting from potentially curative therapy certain drugs such as alkylating agents, procarbazine, and nitrosourea derivatives

A case of Hodgkin`s disease presenting a cardiac tamponade during treatment developed a pancytopenia after cessation of chemotherapy

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Ohta, Shigeru; Iwami, Mika; Narita, Tsutomu; Higashino, Katsumi; Suzuki, Atsushi; Taga, Takashi; Shimada, Morimi [Shiga Univ. of Medical Science, Otsu (Japan)

1998-10-01

There had been many reports about cardiac complications of patients with Hodgkin`s disease (HD) after cessation of treatment in Europe and the United States. However, cases of HD accompanied with these complications were extremely rare in Japan. We report a case with HD that developed a cardiac tamponade during the clinical course of chemotherapy and showed a pancytopenia after cessation of chemotherapy. The case was a 14 year-old boy with HD (nodular sclerosis) of anterior upper mediastinum origin. He received modified MOPP therapy and irradiation to the semimantle field and to the mediastinum. The total dose of radiation was 36.3 Gy. He suddenly developed a chest pain, chest discomfort, and dyspnea during the sixth course of chemotherapy. He was diagnosed to have a cardiac tamponade by thoracentesis. The symptoms were improved by continuous transcutaneous drainage. The invasion of HD into the effusion was not detected by cytology, and the chemotherapy was completed after one course. However, he gradually developed a macrocytic anemia and finally developed a pancytopenia. The bone marrow specimen revealed a hypoplasia without evidence of pathological cells. The karyotype of marrow derived cells was normal. With oxymetholone administration, the pancytopenia has improved in four months. He has now been doing well for five years after the cessation of therapy. (author)

O papel da Fludarabina no tratamento dos linfomas não Hodgkin de baixo grau de malignidade The role of Fludarabine in the treatment of low-grade non-Hodgkin's lymphomas

Directory of Open Access Journals (Sweden)

Gino Santini

2001-09-01

Full Text Available Dentro das perspectivas futuras do tratamento dos linfomas não Hodgkin (LMH está aquela de melhorar os resultados com os denominados linfomas de baixo grau de malignidade. Dentro do estado-da-arte atual, este grupo de linfomas pode ser considerado incurável. Desde o observar-e-esperar até o transplante alogênico de medula óssea, muitas dúvidas existem e devem ser esclarecidas. O objetivo desta revisão é de apresentar e discutir a utilização da Fludarabina , isolada ou associada à antraciclínicos e alquilantes no tratamento dos linfomas não Hodgkin de baixo grau de malignidade (LBG.Concerning to the perspective of low-grade non-Hodgkin's lymphoma remains the challenge to find the best treatment improving the objective responses and the possibility of cure . Low-grade lymphoma may be currently considered a group of incurable diseases. From watch-and-wait until allogeneic bone marrow transplantation, many doubts exist and should be clarify. The aim of this article is to present and to discuss the role of Fludarabine, alone or in combination with anthracyclines and/or cyclophosphamide, in the treatment of low-grade lymphomas.

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.

Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

International Nuclear Information System (INIS)

Henkenberens, Christoph; Christiansen, Hans; Franzke, Anke; Raab, Peter; Oschlies, Ilske; Klapper, Wolfram

2014-01-01

Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I E A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [de

Recurrence of non-Hodgkin's lymphoma isolated to the right masticator and left psoas muscles

International Nuclear Information System (INIS)

Connor, S.E.J.; Chavda, S.V.; West, R.

2000-01-01

We present the clinical and magnetic resonance imaging findings of a patient who, following treatment for pancreatic non-Hodgkin's lymphoma (NHL), relapsed with apparently isolated involvement of the right masticator space and left psoas muscles. Non-Hodgkin's lymphoma arising from the masticator space muscles is very rare. In addition, simultaneous lymphomatous involvement of multiple discrete skeletal muscle sites, in the absence of disease elsewhere, has previously only been reported in the limb or limb girdle muscles. Lymphoma should be considered as a cause of isolated enlarged skeletal muscles, even when involving such distant sites. (orig.)

Partiële in plaats van complete splenectomie bij kinderen voor pathologische stadiëring van de ziekte van Hodgkin

NARCIS (Netherlands)

Hoekstra, H J; Tamminga, R Y; Timens, W

1993-01-01

OBJECTIVE: Evaluation of partial splenectomy in children for pathological staging of Hodgkin's disease. DESIGN: Prospective clinical study. PLACE: University Hospital Groningen. METHOD: From 1982 to 1988, 12 children with Hodgkin's disease underwent partial splenectomy during laparotomy for

Adult Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Non-Hodgkin lymphomas (NHL) include indolent types (follicular lymphoma, Waldenstrom macroglobulinemia, and MALT) and aggressive types (diffuse large cell, Burkitt, and mantle cell). Treatment and prognosis depend on the specific type. Get comprehensive information on NHL classification and treatment in this clinician summary.

Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study.

Science.gov (United States)

Etter, John Lewis; Cannioto, Rikki; Soh, Kah Teong; Alquassim, Emad; Almohanna, Hani; Dunbar, Zachary; Joseph, Janine M; Balderman, Sophia; Hernandez-Ilizaliturri, Francisco; Moysich, Kirsten B

2018-03-27

Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82). The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Simultaneous Primary Hodgkin's Lymphoma of the Sigmoid Colon and Papillary Thyroid Carcinoma in an HIV-Positive Patient.

Science.gov (United States)

Liszewski, Walter; Sittig, Mark; Kandil, Emad; Van Sickels, Nicholas; Safah, Hana

2015-01-01

Primary Hodgkin's lymphoma of the colon is a rare phenomenon previously only reported in patients with chronic diverticulitis or inflammatory bowel disease. Herein we report a case of primary Hodgkin's lymphoma of the sigmoid colon in an HIV-positive patient without a history of inflammatory bowel disease or chronic diverticulitis that was later complicated by the discovery of concurrent papillary thyroid carcinoma.

Synchronous perforation of non-Hodgkin's lymphoma of the small intestine and colon: a case report

Directory of Open Access Journals (Sweden)

Baidoun Fadi

2011-02-01

Full Text Available Abstract Introduction Primary non-Hodgkin's lymphoma of the small and large bowel presenting as a perforated viscus entity with peritonitis is extremely rare. A thorough literature review did not reveal any cases where primary lymphoma of the jejunum presented with perforation and peritonitis synchronously with primary lymphoma of the descending colon. Case presentation This report concerns a 64-year-old Caucasian woman admitted with severe abdominal pain and fever. An emergency laparotomy revealed a large mass with perforation in the proximal jejunum with intense mesenteric thickening and lymphadenopathy. The descending colon was edematous and covered with fibrinous exudate. Histopathological examination of the resected segment of jejunum revealed a T cell non-Hodgkin's lymphoma. On post-operative day 10, a computed tomography scan of our patient's abdomen and pelvis showed leakage of contrast into the pelvis. Re-exploration revealed perforation of the descending colon. The histopathology of the resected colon also showed T cell non-Hodgkin's lymphoma. Her post-operative course was complicated by acute renal and respiratory failure. The patient died on post-operative day 21. Conclusions Lymphoma of the small intestine has been reported to have a poor prognosis. The synchronous occurrence of lesions in the small intestine or colon is unusual, and impacts the prognosis adversely. Early diagnosis and treatment are important to improve the prognosis of bowel perforation in patients with non-Hodgkin's lymphoma.

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

T-Cell Traffic Jam in Hodgkin's Lymphoma: Pathogenetic and Therapeutic Implications

Directory of Open Access Journals (Sweden)

Claudio Fozza

2011-01-01

Full Text Available In hematologic malignancies, the microenvironment is often characterized by nonneoplastic cells with peculiar phenotypic and functional features. This is particularly true in Hodgkin's lymphoma (HL, in which T lymphocytes surrounding Hodgkin's Reed-Sternberg cells are essentially polarized towards a memory T-helper type 2 phenotype. In this paper we will first evaluate the main processes modulating T-cell recruitment towards the lymph node microenvironment in HL, especially focusing on the role played by cytokines. We will then consider the most relevant mechanisms of immune escape exerted by neoplastic cells in order to evade antitumor immunity. The potential pathogenetic and prognostic impact of regulatory T cells in such a context will be also described. We will finally overview some of the strategies of cellular immunotherapy applied in patients with HL.

Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

Science.gov (United States)

Bierer, Julie Arenberg; Faulkner, Kathleen F

2010-04-01

The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a

Report of a case of Hodgkin's nodular sclerosis disease

International Nuclear Information System (INIS)

Canizares, Claudio; Araujo, Ivan; Flores, Marlon; Guerrero, Patricia; Sanchez, Mayra

2004-01-01

We report a case of Hodgkin's nodular sclerosis disease that presents moderate anemia and lymph node enlargement with a massive infiltrate to the bone marrow. It is rare for these patients to develop such an infiltrate, which give a bad prognosis. The treatment recommended in stage I is Radiotherapy and chemotherapy. (The author)

Diversity in antibody-based approaches to non-Hodgkin lymphoma

NARCIS (Netherlands)

Maloney, David; Morschhauser, Franck; Linden, Ola; Hagenbeek, Anton; Gisselbrecht, Christian

2010-01-01

Non-Hodgkin lymphoma (NHL) remains one of the most common cancers in the US, with survival dependent on the type and stage of disease. B-cell lymphomas account for similar to 85% of all cases of NHL, and are commonly treated with chemotherapy, or monoclonal antibodies (mAbs) that t arget CD20

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood non-Hodgkin lymphoma has different types including Burkitt, diffuse large B-cell, primary mediastinal B-cell, lymphoblastic, and anaplastic large cell lymphoma. Get information about the risk factors, symptoms, tests to diagnose, staging, and treatment of all types of newly diagnosed and recurrent NHL and lymphoproliferative disease in this expert-reviewed summary.

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 ...

Sister chromatid cohesion defects are associated with chromosome instability in Hodgkin lymphoma cells

International Nuclear Information System (INIS)

Sajesh, Babu V; Lichtensztejn, Zelda; McManus, Kirk J

2013-01-01

Chromosome instability manifests as an abnormal chromosome complement and is a pathogenic event in cancer. Although a correlation between abnormal chromosome numbers and cancer exist, the underlying mechanisms that cause chromosome instability are poorly understood. Recent data suggests that aberrant sister chromatid cohesion causes chromosome instability and thus contributes to the development of cancer. Cohesion normally functions by tethering nascently synthesized chromatids together to prevent premature segregation and thus chromosome instability. Although the prevalence of aberrant cohesion has been reported for some solid tumors, its prevalence within liquid tumors is unknown. Consequently, the current study was undertaken to evaluate aberrant cohesion within Hodgkin lymphoma, a lymphoid malignancy that frequently exhibits chromosome instability. Using established cytogenetic techniques, the prevalence of chromosome instability and aberrant cohesion was examined within mitotic spreads generated from five commonly employed Hodgkin lymphoma cell lines (L-1236, KM-H2, L-428, L-540 and HDLM-2) and a lymphocyte control. Indirect immunofluorescence and Western blot analyses were performed to evaluate the localization and expression of six critical proteins involved in the regulation of sister chromatid cohesion. We first confirmed that all five Hodgkin lymphoma cell lines exhibited chromosome instability relative to the lymphocyte control. We then determined that each Hodgkin lymphoma cell line exhibited cohesion defects that were subsequently classified into mild, moderate or severe categories. Surprisingly, ~50% of the mitotic spreads generated from L-540 and HDLM-2 harbored cohesion defects. To gain mechanistic insight into the underlying cause of the aberrant cohesion we examined the localization and expression of six critical proteins involved in cohesion. Although all proteins produced the expected nuclear localization pattern, striking differences in RAD21

Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma and chronic inflammatory conditions in Uganda: implications for disease risk and characteristics.

Science.gov (United States)

Orem, Jackson; Sandin, Sven; Mbidde, Edward; Mangen, Fred Wabwire; Middeldorp, Jaap; Weiderpass, Elisabete

2014-10-01

Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda. © 2014 Wiley Periodicals, Inc.

Single-Cell Imaging of Bioenergetic Responses to Neuronal Excitotoxicity and Oxygen and Glucose Deprivation

OpenAIRE

Connolly, Niamh M; Düssmann, Heiko; Anilkumar, Ujval; Huber, Heinrich J; Prehn, Jochen HM

2014-01-01

Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It is characterized by overactivation of glutamate receptors, leading to excessive Ca2+/Na+ influx into neurons, energetic stress, and subsequent neuronal injury.We and others have previously investigated neuronal populations to study how bioenergetic parameters determine neuronal injury; however, such experiments are often confounded by population-based heterogeneity and the contributio...

Impact of cardiovascular counseling and screening in Hodgkin lymphoma survivors

NARCIS (Netherlands)

Daniëls, L.A.; Krol, S.D.G.; de Graaf, M.A.; Scholte, A.J.H.A.; van 't Veer, M.B.; Putter, H.; de Roos, A.; Schalij, M.J.; van de Poll-Franse, L.; Creutzberg, C.L.

2014-01-01

Purpose Cardiovascular disease (CVD) is the most common nonmalignant cause of death in Hodgkin lymphoma (HL) survivors, especially after mediastinal irradiation. The role of screening for CVD in HL survivors is unclear, but confrontation with risks of CVD may have a negative influence on

Fertility in female survivors of hodgkin's lymphoma.

OpenAIRE

Biasoli, I.; Falorio, S.; Luminari, S.; Spector, N.; Federico, M.

2012-01-01

Currently, Hodgkin's lymphoma is one of the most curable types of cancer. Patients are often young and so the long-term morbidities of treatment have become of increasing concern. Among these, infertility is one of the most challenging consequences for patients in reproductive age. Premature ovarian failure in premenopausal women is a serious long-term sequel of the toxicity of chemotherapy. The main consequence of this syndrome is infertility, but women also present other symptoms related to...

Management of relapsed/refractory classical Hodgkin lymphoma in transplant-ineligible patients.

Science.gov (United States)

Mehta-Shah, Neha; Bartlett, Nancy L

2018-04-12

Addition of brentuximab vedotin, a CD30-targeted antibody-drug conjugate, and the programmed death 1 (PD-1) inhibitors nivolumab and pembrolizumab to the armamentarium for transplant-ineligible relapsed/refractory classical Hodgkin lymphoma has resulted in improved outcomes, including the potential for cure in a small minority of patients. For patients who have failed prior transplant or are unsuitable for dose-intense approaches based on age or comorbidities, an individualized approach with sequential use of single agents such as brentuximab vedotin, PD-1 inhibitors, everolimus, lenalidomide, or conventional agents such as gemcitabine or vinorelbine may result in prolonged survival with a minimal or modest effect on quality of life. Participation in clinical trials evaluating new approaches such as combination immune checkpoint inhibition, novel antibody-drug conjugates, or cellular therapies such as Epstein-Barr virus-directed cytotoxic T lymphocytes and chimeric antigen receptor T cells offer additional options for eligible patients. © 2018 by The American Society of Hematology.

Primary gastric Hodgkin's lymphoma: favourable outcome following multi-agent chemotherapy without surgical intervention.

LENUS (Irish Health Repository)

Quintyne, K I

2011-02-01

The authors report the case of a 51-year-old man who presented with left-sided abdominal pain and weight loss associated with drenching night sweats. Preliminary blood tests yielded no specific cause for his symptoms, but abdominal ultrasound revealed multiple hepatic lesions and peripancreatic lymphadenopathy. Further imaging, including positron emission tomography (PET)\\/CT, revealed fludeoxyglucose 18F (FDG) avid uptake within lymphadenopathy above and below the diaphragm and also noted gastric thickening. Diagnosis was established with gastric biopsy and revealed gastric Hodgkin\\'s lymphoma. He was started on and tolerated multi-agent chemotherapy. Repeated PET\\/CT and gastric biopsy showed complete metabolic and pathologic response to treatment.

Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Henkenberens, Christoph; Christiansen, Hans [Medizinische Hochschule Hannover, Klinik fuer Strahlentherapie und Spezielle Onkologie, Hannover (Germany); Franzke, Anke [Medizinische Hochschule Hannover, Klinik fuer Haematologie, Haemostaseologie, Onkologie und Stammzelltransplantation, Hannover (Germany); Raab, Peter [Medizinische Hochschule Hannover, Institut fuer Diagnostische und Interventionelle Neuroradiologie, Hannover (Germany); Oschlies, Ilske; Klapper, Wolfram [Universitaetsklinikum Schleswig-Holstein, Institut fuer Pathologie, Sektion Haematopathologie, Kiel (Germany)

2014-09-15

Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I{sub E}A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [German] Retrospektive und prospektive Kohortenstudien deuten daraufhin, dass eine Beteiligung des zentralen Nervensystems (ZNS) in etwa bei 0,5 % der Patienten mit fortgeschrittenem Hodgkin-Lymphom auftritt. Die isoliert primaer intrakranielle Manifestation des Hodgkin-Lymphoms ist extrem selten, mit wenigen bisher bekannten Faellen. Wenig ist auch ueber die optimale

Treatment of patients with minimal stage IIIA Hodgkin's disease

International Nuclear Information System (INIS)

Powlis, W.D.; Mauch, P.; Goffman, T.; Goodman, R.L.

1987-01-01

Treatment recommendations for patients with upper abdominal Stage IIIA Hodgkin's (III1A) disease have varied widely. The current study reports on a combined institutional retrospective review of 85 patients with surgically staged III1A Hodgkin's disease. Twenty-two patients received combined modality therapy (CMT), 36 patients were treated initially with total nodal irradiation (TNI), and 27 with mantle and para-aortic radiotherapy (MPA). Patients treated with CMT had an actuarial 8-year freedom from relapse (FFR) of 96% as compared to a FFR of 51% in TNI treated patients (p = 0.002), and a FFR of 54% in MPA treated patients (p = 0.004). Of the 11 relapses in MPA treated patients, 7 had a component of their failure in the untreated pelvic or inguinal nodes. The patients treated with CMT had an 8-year actuarial survival of 100% as compared to 79% in TNI treated patients (p = 0.055) and 78% in patients treated with MPA (p = 0.025). Histology and the number of splenic nodules were the most important prognostic variables. Patients with MC/LD histology and greater than or equal to 5 splenic nodules have a high risk of relapse (10/13) when treated with radiation alone (TNI or MPA). We recommend CMT for this group of patients. Patients with NS/LP histology and 1-4 splenic nodules represent a favorable subset of Stage III1A patients. Only 4/21 patients have relapsed and all 21 patients are currently alive without disease regardless of treatment. We currently feel that patients with Stage III1A Hodgkin's disease with NS/LP histology and splenic disease limited to 1-4 nodules are good candidates for MPA as an alternative to TNI or CMT

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.

Dynamics and Synchronization of Noise Perturbed Ensembles of Periodically Activated neuron Cells

DEFF Research Database (Denmark)

Belykh, V. N.; Pankratova, Evgeniya; Mosekilde, Erik

2008-01-01

The role of noise for a single neuron and for an ensemble of mutually coupled neurons is investigated. For a single element we show that an increase in noise intensity in the regime of irregular. ring enhances the coherence of the neuronal response. For this regime of spiking a study...... based on the connection graph stability method and through numerical simulation....

Firing dynamics of an autaptic neuron

International Nuclear Information System (INIS)

Wang Heng-Tong; Chen Yong

2015-01-01

Autapses are synapses that connect a neuron to itself in the nervous system. Previously, both experimental and theoretical studies have demonstrated that autaptic connections in the nervous system have a significant physiological function. Autapses in nature provide self-delayed feedback, thus introducing an additional timescale to neuronal activities and causing many dynamic behaviors in neurons. Recently, theoretical studies have revealed that an autapse provides a control option for adjusting the response of a neuron: e.g., an autaptic connection can cause the electrical activities of the Hindmarsh–Rose neuron to switch between quiescent, periodic, and chaotic firing patterns; an autapse can enhance or suppress the mode-locking status of a neuron injected with sinusoidal current; and the firing frequency and interspike interval distributions of the response spike train can also be modified by the autapse. In this paper, we review recent studies that showed how an autapse affects the response of a single neuron. (topical review)

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.

Neuronal growth on L- and D-cysteine self-assembled monolayers reveals neuronal chiral sensitivity.

Science.gov (United States)

Baranes, Koby; Moshe, Hagay; Alon, Noa; Schwartz, Shmulik; Shefi, Orit

2014-05-21

Studying the interaction between neuronal cells and chiral molecules is fundamental for the design of novel biomaterials and drugs. Chirality influences all biological processes that involve intermolecular interaction. One common method used to study cellular interactions with different enantiomeric targets is the use of chiral surfaces. Based on previous studies that demonstrated the importance of cysteine in the nervous system, we studied the effect of L- and D-cysteine on single neuronal growth. L-Cysteine, which normally functions as a neuromodulator or a neuroprotective antioxidant, causes damage at elevated levels, which may occur post trauma. In this study, we grew adult neurons in culture enriched with L- and D-cysteine as free compounds or as self-assembled monolayers of chiral surfaces and examined the effect on the neuronal morphology and adhesion. Notably, we have found that exposure to the L-cysteine enantiomer inhibited, and even prevented, neuronal attachment more severely than exposure to the D-cysteine enantiomer. Atop the L-cysteine surfaces, neuronal growth was reduced and degenerated. Since the cysteine molecules were attached to the surface via the thiol groups, the neuronal membrane was exposed to the molecular chiral site. Thus, our results have demonstrated high neuronal chiral sensitivity, revealing chiral surfaces as indirect regulators of neuronal cells and providing a reference for studying chiral drugs.

Radiological study of two disseminated maligant non-Hodgkin lymphomas affecting only the bones in children

International Nuclear Information System (INIS)

Vanel, D; Rebibo, G.; Tamman, S.; Bayle, C.; Hartmann, O.

1982-01-01

Malignant non-Hodgkin lymphomas are a neoplastic proliferation of lymphoid cells whose clinical manifestations are extremely variable. All tissues can be affected. There may be localization in lymphoid organs (Waldeyer's ring, spleen, digestive tract), other localizations (lungs, pleura, liver, bone marrow, central nervous system) and unusual localizations. Although bone marrow is often affected, bone involvement is very rare in the early stages of the disease. This report concerns the radiological study of two disseminated malignant non-Hodgkin lymphomas affecting only the bone in children. (orig.)

Risk for valvular heart disease after treatment for hodgkin lymphoma

NARCIS (Netherlands)

D.J. Cutter (David J.); M. Schaapveld (Michael); S. Darby (S.); M. Hauptmann; F.A. Van Nimwegen (Frederika A.); A.D.G. Krol (Augustinus); C.P.M. Janus (Cécile P.M.); F.E. van Leeuwen (F.); B.M.P. Aleman (Berthe)

2015-01-01

textabstractBackground: Hodgkin lymphoma (HL) survivors are at increased risk for developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response. Methods: A case-control study was nested in a cohort of 1852 five-year HL survivors diagnosed at ages

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease

DEFF Research Database (Denmark)

Specht, L.; Horwich, A.; Ashley, S.

1994-01-01

patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology......PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681...

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.

When long-range zero-lag synchronization is feasible in cortical networks

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Atthaphon eViriyopase

2012-07-01

Full Text Available Many studies have reported long-range synchronization of neuronal activity between brain areas, in particular in the gamma-band with frequencies in the range of 40-80 Hz. Several studies have reported synchrony with zero phase lag, which is remarkable considering the synaptic and conduction delays inherent in the connections between distant brain areas. This result has led to many speculations about the possible functional role of zero-lag synchrony, e.g., for neuronal communication in attention, memory and feature binding. However, recent studies using recordings of single-unit activity and local field potentials report that neuronal synchronization occurs with non-zero phase lags. This raises the questions whether zero-lag synchrony can occur in the brain and, if so, under which conditions.We used analytical methods and computer simulations to investigate which connectivity between neuronal populations allows or prohibits zero-lag synchrony. We did so for a model where two oscillators interact via a relay oscillator. Analytical results and computer simulations were obtained for both type I Mirollo-Strogatz neurons and type II Hodgkin-Huxley neurons. We have investigated the dynamics of the model for various types of synaptic coupling and importantly considered the potential impact of Spike-Timing Dependent Plasticity (STDP and its learning window. We confirm previous results that zero-lag synchrony can be achieved in this configuration. This is much easier to achieve with Hodgkin-Huxley neurons, which have a biphasic phase response curve, than for type I neurons. STDP facilitates zero-lag synchrony as it adjusts the synaptic strengths such that zero-lag synchrony is feasible for a much larger range of parameters than without STDP.

Temporal-pattern recognition by single neurons in a sensory pathway devoted to social communication behavior.

Science.gov (United States)

Carlson, Bruce A

2009-07-29

Sensory systems often encode stimulus information into the temporal pattern of action potential activity. However, little is known about how the information contained within these patterns is extracted by postsynaptic neurons. Similar to temporal coding by sensory neurons, social information in mormyrid fish is encoded into the temporal patterning of an electric organ discharge. In the current study, sensitivity to temporal patterns of electrosensory stimuli was found to arise within the midbrain posterior exterolateral nucleus (ELp). Whole-cell patch recordings from ELp neurons in vivo revealed three patterns of interpulse interval (IPI) tuning: low-pass neurons tuned to long intervals, high-pass neurons tuned to short intervals, and bandpass neurons tuned to intermediate intervals. Many neurons within each class also responded preferentially to either increasing or decreasing IPIs. Playback of electric signaling patterns recorded from freely behaving fish revealed that the IPI and direction tuning of ELp neurons resulted in selective responses to particular social communication displays characterized by distinct IPI patterns. The postsynaptic potential responses of many neurons indicated a combination of excitatory and inhibitory synaptic input, and the IPI tuning of ELp neurons was directly related to rate-dependent changes in the direction and amplitude of postsynaptic potentials. These results suggest that differences in the dynamics of short-term synaptic plasticity in excitatory and inhibitory pathways may tune central sensory neurons to particular temporal patterns of presynaptic activity. This may represent a general mechanism for the processing of behaviorally relevant stimulus information encoded into temporal patterns of activity by sensory neurons.

Lymph node non-Hodgkin's lymphoma incidentally discovered during a nephrectomy for renal cell carcinoma.

Science.gov (United States)

Fernandez-Pello, Sergio; Rodriguez Villamil, Luis; Gonzalez Rodriguez, Ivan; Venta, Victoria; Cuervo, Javier; Menéndez, Carmen Luz

2013-06-16

We report the case of a left laparoscopic nephroureterectomy with the incidental discovery of a non-Hodgkin's lymphoma in one of the lymph nodes of the renal hilum. A laparoscopic nephroureterectomy was decided on for a 64-year-old man. Renal cell carcinoma in the kidney and one lymph node of the renal hilum with non-Hodgkin's lymphoma was found. Chemotherapy was not started for the lymphoma discovery. There are no signs of relapse after two years of follow up. Coexistence in the same patient is an extremely rare condition. We review the literature about this issue to clarify this association.

Decision-making in the management of adult classical Hodgkin's lymphoma: determining the optimal treatment.

Science.gov (United States)

Mounier, Nicolas; Nicolas, Mounier; Gisselbrecht, Christian; Christian, Gisselbrecht

2015-04-01

This review discusses promising new approaches in classical Hodgkin's lymphoma that have been recently evaluated. There is a focus on the fluorodeoxyglucose PET scanning that is now considered crucial for staging and treatment evaluation, including interim evaluation after two cycles. An up-front treatment strategy is discussed, with the place of radiation therapy and the difficult choice of chemotherapy intensity emphasized. Indications for frail patients are also reviewed, particularly elderly or HIV-positive patients. Emerging data on the antibody drug conjugate brentuximab vedotin and its future potential in the transplantation framework for relapsed/refractory Hodgkin's lymphoma is also discussed.

67Ga imaging in Hodgkin's disease

International Nuclear Information System (INIS)

Huys, J.; Schelstraete, K.; Simons, M.

1982-01-01

In order to answer the question if 67 Ga imaging has a practical utility for the management of the patient with Hodgkin's disease, 108 scans performed on 60 patients were reviewed. When used during the initial staging of the disease or during restaging because of recurrences, 67 Ga imaging-at least in our experience-gave many false negative results in the cervical, axillary and inguinal areas, whereas the majority of true positive scans was found at the mediastinal level (including the lower mediastinum), and also in the lung parenchyma and the upper epigastric regions. Because of its lack of sensitivity, 67 Ga imaging cannot replace other staging procedures, but nevertheless is a valuable adjunctive test, as it can identify tumor localization that may have remained undetected by other methods. Fifty-four scans were performed to monitor treatment with radiation therapy or chemotherapeutic agents. Disappearance or decreases of 67 Ga uptake after treatment usually corresponded to a disappearance or regression of the tumor as ascertained by other methods. When the treatment was shown to be ineffective, 67 Ga uptake persisted or even became more prominent. When during follow-up, a new concentration of 67 Ga appeared at the original location or elsewhere, a relapse was extremely likely. However, one must be aware of false positive images. In our material, no correlation was found between the intensity of the 67 Ga uptake and the histological subtypes of Hodgkin's disease. Neither did we observe any relation to the blood sedimentation rate or serum iron levels

Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma

Directory of Open Access Journals (Sweden)

Oncale MB

2017-02-01

Full Text Available Melody B Oncale, Hossein Maymani, Loretta J Nastoupil Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: Immunotherapy is a rapidly evolving therapeutic option in the treatment of lymphoma. Neoplastic cells evade immune recognition through the programmed death (PD-1/PD-ligand immune checkpoint pathway. Several novel agents have been developed to restore the immune system’s ability to recognize and destroy cancer cells. Nivolumab and pembrolizumab are two anti-PD-1 antibodies that have demonstrated success in the treatment of refractory Hodgkin lymphoma. Harnessing the immune system’s ability to target neoplastic cells, ideally without the use of cytotoxic chemotherapeutic agents, is one way in which these novel agents are changing the therapeutic landscape in the treatment of lymphomas. Here, we review the emerging data regarding checkpoint inhibitors in the management of Hodgkin lymphoma, the unique adverse effects encountered with the use of these agents, and a practical approach to the management of these adverse effects. Additionally, we discuss upcoming trials that will further assess the promising future developments of checkpoint inhibition in the treatment of not only Hodgkin lymphoma but also other B cell lymphomas and myeloma. These agents offer immense promise of a future where many lymphomas can be treated without the toxic effects of chemotherapeutic agents. Keywords: Hodgkin lymphoma, programmed death-1, nivolumab, pembrolizumab, lymphoma

Influence of more extensive radiotherapy and adjuvant chemotherapy on long-term outcome of early-stage Hodgkin's disease: a meta-analysis of 23 randomized trials involving 3,888 patients. International Hodgkin's Disease Collaborative Group

DEFF Research Database (Denmark)

Specht, L.; Gray, R.G.; Clarke, M.J.

1998-01-01

PURPOSE: To assess the effect of more extensive radiotherapy and of adjuvant combination chemotherapy on long-term outcome of early-stage Hodgkin's disease. METHODS: In a collaborative worldwide systematic overview, individual patient data were centrally reviewed on 1,974 patients in eight.......7%; P counterbalanced by a nonsignificant excess of deaths from other...... causes (12.4% v 10.0% 10-year risk). CONCLUSION: More extensive radiotherapy fields or the addition of chemotherapy to radiotherapy in the initial treatment of early-stage Hodgkin's disease had a large effect on disease control, but only a small effect on overall survival. Recurrences could be prevented...

Immuno- and chemotherapy in the treatment of non-Hodgkins lymphomas

International Nuclear Information System (INIS)

Dwilewicz-Trojaczek, J.; Charlinski, G.

2009-01-01

Non-Hodgkin's lymphomas is a heterogeneous group of neoplasms. The lymphomas have various origins: from B and T cells. REAL/WHO classification system of NHL subdivided these diseases into lymphoma from precursor and peripheral lymphocytes. Clinical course may be: very aggressive and aggressive (generally - curable disease); and indolent lymphoma (generally - curable disease). The treatment of each subtype NHL is different, correct diagnosis is critically important. In the treatment of aggressive NHL are used combined chemotherapy, the addition of monoclonal antibody has greatly increased its efficacy. There are several therapeutic strategies to treat indolent NHL. The treatment of asymptomatic indolent lymphoma offers no benefit, and these patients may be observed. Once symptomatic, front-line therapy consist of single agent or combination chemotherapy, often combined with monoclonal antibody. The monoclonal antibodies have revolutionized the treatment of NHL. Monoclonal antibody fixes the antigen on the membrane o f the lymphoma cells. Monoclonal antibodies there are unconjugated, used alone or combined with chemotherapy (immunochemotherapy) or combined with immunotoxins or radionuclides (radioimmunotherapy). This is the progress in the treatment of lymphoma. (authors)

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

DEFF Research Database (Denmark)

Barrington, Sally F; Qian, Wendi; Somer, Edward J

2010-01-01

To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries.......To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries....

Non-Hodgkin's lymphoma presenting as a primary bladder tumor: a case report

Directory of Open Access Journals (Sweden)

Molinos-Castro Sonia

2010-04-01

Full Text Available Abstract Introduction Primary lymphoma of the bladder represents 0.2% of all bladder malignancies. Secondary involvement of the bladder by malignant lymphoma occurs in 10% to 50% of cases. Most lymphomas of the bladder are non-Hodgkin's lymphomas of the B-cell type, with preponderance among women. The impact of positron emission tomography (PET on tumor staging has recently become very important due to its use in the study of diagnosis extension and individual therapy design. Case presentation We report the case of a 79-year-old Caucasian man with intermittent haematuria as the presenting symptom of non-Hodgkin's lymphoma of the bladder. He was first diagnosed with primary lymphoma of the bladder using the current staging method, but a positron emission tomography study subsequently revealed that he instead had a secondary involvement of the bladder. Conclusion The staging of non-Hodgkin's lymphomas, which is useful in order to plan accurate therapy, has been changing since the introduction of positron emission tomography scanning. Primary lymphomas of the bladder, although very rare, may be even more uncommon when this imaging technique is used to assess the extension of the disease. Although the interpretation of this technique has some limitations that should be taken into account, the extensive use of positron emission tomography should nonetheless help improve the diagnosis of this disease.

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.

Childhood leukaemia and non-Hodgkin's lymphoma near large rural construction sites, with a comparison with Sellafield nuclear site

International Nuclear Information System (INIS)

Kinlen, L.J.; Dickson, M.; Stiller, C.A.

1995-01-01

The objective was to determine whether population mixing produced by large, non-nuclear construction projects in rural areas is associated with an increase in childhood leukaemia and non-Hodgkin's lymphoma. A study was undertaken of the incidence of leukaemia and non-Hodgkin's lymphoma among children living near large construction projects in Britain since 1945, situated more than 20 km from a population centre, involving a workforce of more than 1000, and built over three or more calendar years. A 37% excess of leukaemia and non-Hodgkin's lymphoma at 0-14 years of age was recorded during construction and the following calendar year. The excesses were greater at times when construction workers and operating staff overlapped (72%), particularly in areas of relatively high social class. For several sites the excesses were similar to or greater than that near the nuclear site of Sellafield (67%), which is distinctive in its large workforce with many construction workers. Seascale, near Sellafield, with a ninefold increase had an unusually high proportion of residents in social class I. The findings support the infection hypothesis and reinforce the view that the excess of childhood leukaemia and non-Hodgkin's lymphoma near Sellafield has a similar explanation. (author)

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.

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

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

DEFF Research Database (Denmark)

Hjalgrim, H; Askling, J; Sørensen, P

2000-01-01

15-34 years was 3.49 (95% CI = 2.46-4.81; n = 37), which was statistically significantly higher than the SIR for any other age group (P: for difference =.001). CONCLUSION: The increased risk of Hodgkin's disease after the occurrence of infectious mononucleosis appears to be a specific phenomenon....

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

Science.gov (United States)

... Reporting & Auditing Grant Transfer Grant Closeout Contracts & Small Business Training Cancer Training at NCI (Intramural) Resources for ... memory. Second cancers (new types of cancer). For female survivors of Hodgkin lymphoma, there is an increased ...

Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

Science.gov (United States)

2017-04-17

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle 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 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; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease

International Nuclear Information System (INIS)

Joensuu, H.

1989-01-01

Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease

Primary Bilateral Non-Hodgkin's Lymphoma of the Adrenal Gland: A Case Report

Directory of Open Access Journals (Sweden)

Ahmed Amine Bouchikhi

2012-01-01

Full Text Available Primary bilateral non-Hodgkin's lymphoma (NHL of the adrenal gland is a very rare entity. Indeed less than 60 cases have been reported in the literature. Hence, we report a case of high-grade lymphoma of both adrenal glands that was found in a young patient of 32 years of age. The patient was admitted in the emergency department of our hospital with a profile of hemorrhagic shock. After stabilization, the imaging investigations demonstrated large bilateral adrenal masses. The CT-scan guided biopsy of both adrenal glands allowed the diagnosis of primary bilateral adrenal NHL. The patient died after the first chemotherapy session. The presence of bilateral adrenal masses associated with a rapid increase of volume should raise the diagnosis of primary adrenal non-Hodgkin's lymphoma.

Fast calcium transients translate the distribution and conduction of neural activity in different regions of a single sensory neuron.

Science.gov (United States)

Purali, Nuhan

2017-09-01

In the present study, cytosolic calcium concentration changes were recorded in response to various forms of excitations, using the fluorescent calcium indicator dye OG-BAPTA1 together with the current or voltage clamp methods in stretch receptor neurons of crayfish. A single action potential evoked a rise in the resting calcium level in the axon and axonal hillock, whereas an impulse train or a large saturating current injection would be required to evoke an equivalent response in the dendrite region. Under voltage clamp conditions, amplitude differences between axon and dendrite responses vanished completely. The fast activation time and the modulation of the response by extracellular calcium concentration changes indicated that the evoked calcium transients might be mediated by calcium entry into the cytosol through a voltage-gated calcium channel. The decay of the responses was slow and sensitive to extracellular sodium and calcium concentrations as well as exposure to 1-10 mM NiCl 2 and 10-500 µM lanthanum. Thus, a sodium calcium exchanger and a calcium ATPase might be responsible for calcium extrusion from the cytosol. Present results indicate that the calcium indicator OG-BAPTA1 might be an efficient but indirect way of monitoring regional membrane potential differences in a single neuron.

A Hybrid Fuzzy Time Series Approach Based on Fuzzy Clustering and Artificial Neural Network with Single Multiplicative Neuron Model