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Biomedical subjects

Peter Jung

Publications and source records attributed to Peter Jung.

17 recordsLinked to original sources
PubMed2006

Inducible microRNA expression by an all-in-one episomal vector system.

Here we describe an episomal, one-vector system which allows the generation of cell populations displaying homogenous, inducible gene inactivation by RNA interference in a one step procedure. A dual tet-repressor/activator system tightly controls a bi-directional promoter, which simultaneously drives expression of microRNAs and a fluorescent marker protein. We demonstrate the effectiveness of this vector by knockdown of p53 expression in a human cell line which resulted in the expected loss of G1-arrest after DNA damage. The generation of a cell pool homogenously expressing the ectopic microRNAs was achieved in 1 week without the need for viral infections. Induction of microRNA expression did not elicit an interferon response. Furthermore, the vector was adapted for convenient ligation-free transfer of microRNA cassettes from public libraries. This conditional knockdown-system should prove useful for many research and gene therapeutic applications.

Cell Line, Tumor↗
PubMed2006

Modeling the statistics of elementary calcium release events.

Elementary Ca(2+) signals, such as "Ca(2+) puffs", which arise from the release of Ca(2+) from endoplasmic reticulum through small clusters of inositol 1,4,5-trisphosphate receptors, are the building blocks for intracellular Ca(2+) signaling. The small number of release channels involved during a Ca(2+) puff renders the puffs stochastic, with distributed amplitudes, durations, and frequency, well characterized experimentally. We present a stochastic model that accurately describes simultaneously the statistical properties of the duration, amplitudes, frequencies, and spatial spread with a single set of parameters.

Calcium↗
PubMed2005

Anti-phase calcium oscillations in astrocytes via inositol (1, 4, 5)-trisphosphate regeneration.

Observations in cultured mouse astrocytes suggest anti-phase synchronization of cytosolic calcium concentrations in nearest neighbor cells that are coupled through gap junctions. A mathematical model is used to investigate physiologic conditions under which diffusion of the second messenger inositol (1, 4, 5)-trisphosphate (IP(3)) through gap junctions can facilitate synchronized anti-phase Ca(2+) oscillations. Our model predicts anti-phase oscillations in both cytosolic calcium and IP(3) concentrations if (a) the gap junction permeability is within a window of values and (b) IP(3) is regenerated in the astrocytes via, e.g. phospholipase C(delta). This result sheds new light on the current dispute on the mechanism of intercellular calcium signaling. It provides indirect evidence for a partially regenerative mechanism as the model excludes anti-phase synchrony in the absence of IP(3) regeneration.

Animals↗
PubMed2005

Stochastic simulation of neurofilament transport in axons: the "stop-and-go" hypothesis.

According to the "stop-and-go" hypothesis of slow axonal transport, cytoskeletal and cytosolic proteins are transported along axons at fast rates but the average velocity is slow because the movements are infrequent and bidirectional. To test whether this hypothesis can explain the kinetics of slow axonal transport in vivo, we have developed a stochastic model of neurofilament transport in axons. We propose that neurofilaments move in both anterograde and retrograde directions along cytoskeletal tracks, alternating between short bouts of rapid movement and short "on-track" pauses, and that they can also temporarily disengage from these tracks, resulting in more prolonged "off-track" pauses. We derive the kinetic parameters of the model from a detailed analysis of the moving and pausing behavior of single neurofilaments in axons of cultured neurons. We show that the model can match the shape, velocity, and spreading of the neurofilament transport waves obtained by radioisotopic pulse labeling in vivo. The model predicts that axonal neurofilaments spend approximately 8% of their time on track and approximately 97% of their time pausing during their journey along the axon.

Algorithms↗
PubMed2005

Axonal oscillations in developing mammalian nerve axons.

We study neuronal spike propagation in a developing myelinated axon in various stages of its development through detailed computational modeling. Recently, a form of bursting (axonal bursting), has been reported in axons in developing nerves in the absence of potassium channels. We present a computational study using a detailed model for a myelinated nerve in development to explore under what circumstances such an effect can be expected. It is shown that axonal oscillation may be caused by backfiring between the nodes of Ranvier or through backfiring from internodal sodium channels or by reducing the thickness of the myelin wrapping the axon between the nodes of Ranvier.

Action Potentials↗
PubMed2005

The effect of heat on tissue extensibility: a comparison of deep and superficial heating.

OBJECTIVE: To compare the effects of deep heating (shortwave diathermy [SWD]) and superficial heating (hydrocollator packs) on tissue extensibility. DESIGN: A double-blind, repeated-measures study. Possible effects of sex and intervention order were controlled. SETTING: A clinical laboratory. PARTICIPANTS: Twenty-four subjects with no neurologic or musculoskeletal pathologies affecting their lower limbs. INTERVENTIONS: Three intervention conditions: deep heating (SWD), superficial heating (hot packs), and no heating were applied in preallocated order to each subject at least 36 hours apart. MAIN OUTCOME MEASURES: Ankle dorsiflexion in weight bearing was measured by using an inclinometer to ascertain changes in the extensibility of the calf muscles and associated soft tissues. RESULTS: Deep heating increased the range of ankle dorsiflexion by 1.8 degrees +/-1.9 degrees . The change in ankle dorsiflexion after superficial and no heating was 0.7 degrees +/-1.5 degrees and -0.1 degrees +/-1.0 degrees , respectively. CONCLUSIONS: Deep heating, in the absence of stretching, increases tissue extensibility more than superficial heating or no heating. Superficial heating is more effective than no heating, but the difference was not statistically significant.

Adult↗
PubMed2005

Synaptic inhibition and pathologic hyperexcitability through enhanced neuron-astrocyte interaction: a modeling study.

Recently, upregulation of metabotropic glutamate receptors (mGluRs) on hippocampal astrocytes in epileptic tissues has become part of the etiology of epilepsy and suggests the involvement of astrocytes in the disease. Through computational modeling, we have shown in previous work that upregulated mGluRs on astrocytes can give rise to positive feedback in closed loop neuron-astrocyte circuits with epilepsy-type spontaneous neuronal spiking. In this paper we further quantify the necessary degree of upregulation of astrocytic mGluRs, relate it to recent clinical and experimental studies, and address through computational modeling the role of synaptic inhibition through interneurons in this form of hyperexcitability. We conclude that inhibitive circuitry cannot tame this form of hyperexcitability.

Animals↗
PubMed2004

Mechanism for neuronal spike generation by small and large ion channel clusters.

Neuronal action potentials are generated by clusters of ion channels between the Hillock and the first segment. If the clusters comprise a large number of sodium and potassium channels, action potentials are generated if the membrane potential exceeds a threshold of about -55 mV. Such behavior is well described by an excitable model such as, for example, the Hodgkin-Huxley equations. In this paper we show through stochastic modeling that if the size of the generating ion channel cluster is small, action potentials are generated regardless of whether the membrane potential is below or above the excitation threshold. Action potential generation is then determined by single-channel kinetics. We further show that this switch in generation mechanism manifests itself in peculiar statistical properties of the generated spike trains at small cluster sizes.

Action Potentials↗
PubMed2004

Dressed neurons: modeling neural-glial interactions.

Based on recent experimental data, we design a model for neuronal membrane potentials that incorporates the influence of the surrounding glia (dressed neurons). A neurotransmitter released into the synaptic cleft triggers a Ca(2+) response in nearby glial cells that spreads as a Ca(2+) wave and interacts with other synapses via the release of glutamate from astrocytes. We consider the simple case of a neuron-glia circuit that consists of a single neuron that triggers a Ca(2+) response in the glial cell which in turn feeds back into synapses of the same neuron. It is shown that persistent spiking can occur if the glutamate receptors on the astrocytes are overexpressed--a condition that has been reported from patients suffering from mesial-lobe epilepsy.

Animals↗
PubMed2003

Spontaneous oscillations of dressed neurons: a new mechanism for epilepsy?

Most modeling studies of neurons and neuronal networks are based on the assumption that the neurons are isolated from their normal environment. Based on recent experimental data we put forward a model for neurons that incorporates the influence of the surrounding glia (dressed neurons). We predict seizurelike spontaneous oscillations in the absence of stimuli for strong coupling between neurons and astrocytes. Consistent with our predictions, a signature of this enhanced crosstalk, over expression of glutamate receptors in astrocytes, has been observed specifically in epileptic tissue.

Astrocytes↗
PubMed2003

Use of intravenous immunoglobulin in children with stevens-johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the most severe cutaneous reactions that occur in children. Off-label use of human intravenous immunoglobulin (IVIG) has been reported in a number of autoimmune and cell-mediated blistering disorders of the skin, including severe cutaneous drug reactions. We review 28 previous reports in which IVIG was used in pediatric patients with SJS and toxic epidermal necrolysis and discuss our experience in 7 children with SJS, in whom no new blisters developed within 24 to 48 hours after IVIG administration and rapid recovery ensued. IVIG seems to be a useful and safe therapy for children with severe cutaneous drug reactions. Well-controlled, prospective, multicenter clinical trials are needed to determine optimal dosing guidelines and to compare the efficacy and safety of IVIG with other potentially effective modalities.

Adolescent↗
PubMed2002

Stochastic properties of Ca(2+) release of inositol 1,4,5-trisphosphate receptor clusters.

Intracellular Ca(2+) release is controlled by inositol 1,4,5-trisphosphate (IP(3)) receptors or ryanodine receptors. These receptors are typically distributed in clusters with several or tens of channels. The random opening and closing of these channels introduces stochasticity into the elementary calcium release mechanism. Stochastic release events have been experimentally observed in a variety of cell types and have been termed sparks and puffs. We put forward a stochastic version of the Li-Rinzel model (the deactivation binding process is described by a Markovian scheme) and a computationally more efficient Langevin approach to model the stochastic Ca(2+) oscillation of single clusters. Statistical properties such as Ca(2+) puff amplitudes, lifetimes, and interpuff intervals are studied with both models and compared with experimental observations. For clusters with tens of channels, a simply decaying amplitude distribution is typically observed at low IP(3) concentration, while a single peak distribution appears at high IP(3) concentration.

Biophysics↗
PubMed1995

Noise controlled spiral growth in excitable media.

We consider a two-dimensional pulse-coupled array of noisy threshold elements with a long-range interaction. For tight coupling, we observe the formation of spatio-temporal excitation waves, such as target and spiral waves. For weak coupling, we find noise sustained spiral growth, where the noise level controls the scale of the spiral. (c) 1995 American Institute of Physics.

Journal Article↗