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Activation delay in healed myocardial infarction: a comparison between model and experiment.

Conduction delay in healed myocardial infarction, facilitating reentry, is frequently based on an increased path length the activation has to travel in a matrix of merging and diverging bundles that survive in the infarcted area. Additional delay occurs at sites where bundles bifurcate. The purpose of this study was to investigate conduction delay at sites where bundles bifurcate. A computer model was developed to simulate spread of activation in a two-dimensional sheet of excitable elements. A structure consisting of two isolated bundles merging into a single one was modeled. Extracellular electrograms calculated in the model were comparable to electrograms obtained in a superfused infarcted papillary muscle model. A zone of crowded isochrones or local conduction delay was found at the site where an isolated bundle bifurcated. The position of the isochrones in this area depended on the way activation times were determined. Lines of activation delay were mainly perpendicular to the fiber direction. In conclusion, the results have enabled us to better understand extracellular electrograms at pivoting points and show that activation sequences at a microscopic level can best be constructed on the basis of Laplacian signals.

Computer Simulation↗

Choroidal readaptation to gravity in rats after spaceflight and head-down tilt.

To determine when choroidal structures were restored after readaptation to Earth gravity or orthostatic position, fine structure and protein distribution were studied in rat choroid plexus dissected either 6 h [Space Life Sciences-2 (SLS-2) experiments] or 2 days [National Institutes of Health-Rodent 1 (NIH-R1) experiments] after a spaceflight, or 6 h after head-down tilt (HDT) experiments. Apical alterations were noted in choroidal cells from SLS-2 and HDT animals, confirming that weightlessness impaired choroidal structures and functions. However, the presence of small apical microvilli and kinocilia and the absence of vesicle accumulations showed that the apical organization began to be restored rapidly after landing. Very enlarged apical microvilli appeared after 2 days on Earth, suggesting increased choroidal activity. However, as distributions of ezrin and carbonic anhydrase II remained altered in both flight and suspended animals after readaptation to Earth gravity, it was concluded that choroidal structures and functions were not completely restored, even after 2 days in Earth's gravity.

Adaptation, Physiological↗

Unilateral lower limb suspension does not mimic bed rest or spaceflight effects on human muscle fiber function.

We used Ca2+-activated skinned muscle fibers to test the hypothesis that unilateral lower leg suspension (ULLS) alters cross-bridge mechanisms of muscle contraction. Soleus and gastrocnemius biopsies were obtained from eight subjects before ULLS, immediately after 12 days of ULLS (post-0 h), and after 6 h of reambulation (post-6 h). Post-0 h soleus fibers expressing type I myosin heavy chain (MHC) showed significant reductions in diameter, absolute and specific peak Ca2+-activated force, unloaded shortening velocity, and absolute and normalized peak power. Fibers obtained from the gastrocnemius were less affected by ULLS, particularly fibers expressing fast MHC isoforms. Post-6 h soleus fibers produced less absolute and specific peak force than did post-0 h fibers, suggesting that reambulation after ULLS induced cell damage. Like bed rest and spaceflight, ULLS primarily affects soleus over gastrocnemius fibers. However, in contrast to these other models, slow soleus fibers obtained after ULLS showed a decrease in unloaded shortening velocity and a greater reduction in specific force.

Adult↗

On the origin of the extracellular action potential waveform: A modeling study.

Although extracellular unit recording is typically used for the detection of spike occurrences, it also has the theoretical ability to report about what are typically considered intracellular features of the action potential. We address this theoretical ability by developing a model system that captures features of experimentally recorded simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons. We use the line source approximation method of Holt and Koch to model the extracellular action potential (EAP) voltage resulting from the spiking activity of individual neurons. We compare the simultaneous intracellular and extracellular recordings of CA1 pyramidal neurons recorded in vivo with model predictions for the same cells reconstructed and simulated with compartmental models. The model accurately reproduces both the waveform and the amplitude of the EAPs, although it was difficult to achieve simultaneous good matches on both the intracellular and extracellular waveforms. This suggests that accounting for the EAP waveform provides a considerable constraint on the overall model. The developed model explains how and why the waveform varies with electrode position relative to the recorded cell. Interestingly, each cell's dendritic morphology had very little impact on the EAP waveform. The model also demonstrates that the varied composition of ionic currents in different cells is reflected in the features of the EAP.

Action Potentials↗

Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.

The role of the ATP-sensitive K+ current (IK-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg2+ counteract this shortening. Under conditions of high [K+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low ( < 1%). However, the results of the model suggest that activation of IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.

Action Potentials↗

Modeling of cell signaling pathways in macrophages by semantic networks.

BACKGROUND: Substantial amounts of data on cell signaling, metabolic, gene regulatory and other biological pathways have been accumulated in literature and electronic databases. Conventionally, this information is stored in the form of pathway diagrams and can be characterized as highly "compartmental" (i.e. individual pathways are not connected into more general networks). Current approaches for representing pathways are limited in their capacity to model molecular interactions in their spatial and temporal context. Moreover, the critical knowledge of cause-effect relationships among signaling events is not reflected by most conventional approaches for manipulating pathways. RESULTS: We have applied a semantic network (SN) approach to develop and implement a model for cell signaling pathways. The semantic model has mapped biological concepts to a set of semantic agents and relationships, and characterized cell signaling events and their participants in the hierarchical and spatial context. In particular, the available information on the behaviors and interactions of the PI3K enzyme family has been integrated into the SN environment and a cell signaling network in human macrophages has been constructed. A SN-application has been developed to manipulate the locations and the states of molecules and to observe their actions under different biological scenarios. The approach allowed qualitative simulation of cell signaling events involving PI3Ks and identified pathways of molecular interactions that led to known cellular responses as well as other potential responses during bacterial invasions in macrophages. CONCLUSIONS: We concluded from our results that the semantic network is an effective method to model cell signaling pathways. The semantic model allows proper representation and integration of information on biological structures and their interactions at different levels. The reconstruction of the cell signaling network in the macrophage allowed detailed investigation of connections among various essential molecules and reflected the cause-effect relationships among signaling events. The simulation demonstrated the dynamics of the semantic network, where a change of states on a molecule can alter its function and potentially cause a chain-reaction effect in the system.

Computer Simulation↗

Digital superresolution and the generalized sampling theorem.

The technique of reconstructing a higher-resolution (HR) image of size MLxML by digitally processing LxL subpixel-shifted lower-resolution (LR) copies of it, each of size MxM, has now become well established. This particular digital superresolution problem is analyzed from the standpoint of the generalized sampling theorem. It is shown both theoretically and by computer simulation that the choice of regularly spaced subpixel shifts for the LR images tends to maximize the robustness and minimize the error of reconstruction of the HR image. In practice, since subpixel-level control of LR image shifts may be nearly impossible to achieve, however, a more likely scenario, which is also discussed, is one involving random subpixel shifts. It is shown that without reasonably tight bounds on the range of random shifts, the reconstruction is likely to fail in the presence of even small amounts of noise unless either reliable prior information or additional data are available.

Journal Article↗

Comparison of radiographic abnormalities of the sacroiliac joint in degenerative disease and ankylosing spondylitis.

Degenerative disease of the sacroiliac joint is common in middle-aged and elderly patients. Its radiographic features simulate those of ankylosing spondylitis. Interosseous space narrowing, subchondral sclerosis, and osteophytosis are apparent. Although intraarticular bony ankylosis is generally absent, anterior paraarticular bridging osteophytes resemble true osseous fusion of the joint cavity on frontal radiographs. Focal sclerosis in degenerative disease is most common on the superior and inferior margins of the articular cavity and can usually be differentiated from that accompanying ankylosing spondylitis and osteitis condensans ilii.

Adult↗

Effect of antiorthostatic suspension on interferon-alpha/beta production by the mouse.

Mice were suspended in a model that simulates weightlessness that occurs during prolonged space flight. After 1 and 2 weeks of suspension in an antiorthostatic (head-down tilt) position, the mice were challenged with polyriboinosinic-polyribocytidylic acid to induce interferon-alpha/beta. Interferon production was severely reduced in mice that had been suspended. When mice were allowed to recover in cages for a week following removal from suspension, they recovered their full interferon-production capacity. Mice suspended in an orthostatic (horizontal) position did not have their interferon production capabilities affected, which indicates that stress per se was not a major component in the effects of antiorthostatic suspension on interferon induction.

Animals↗

[A rare case of tumor-to-tumor metastasis: secondary deposits of pulmonary adenocarcinoma in a secretory meningioma].

OBJECTIVE: To report a rare case of tumour-to-tumour metastasis with differential diagnostic considerations. METHODS AND RESULTS: We report the operation of a Sylvian fissure secretory meningioma in a 48 year-old woman. The tumour was suspicious of a metastasis related to a pulmonary adenocarcinoma operated 4 months before. Histopathology confirmed metastatic adenocarcinoma in a secretory meningioma. CONCLUSIONS: Both secretory meningioma and tumour-to-tumour metastasis are rare, and to our knowledge this is the first report of such a rare coincidence. Secretory meningioma can simulate metastases both clinically (extensive oedema, space occupation, carcinoembryonic antigen secretion) and pathologically (secretory inclusions, positivity for cytokeratin 7 and carcinoembryonic antigen and negativity for vimentin), and therefore may cause a special differential diagnostic dilemma.

Adenocarcinoma↗

Cubby. A medical virtual environment based on multiscreen movement parallax.

In this paper a desktop virtual reality system named Cubby is described. Cubby is based on self-induced, head-coupled movement parallax on three orthogonal screens. It is argued that this system is better suited to medical practice than Immersive VR solutions or single screen Desktop VR systems. Whilst Cubby is currently limited to visualisation it opens up possibilities of direct instrumental manipulation and as such could prove useful as a medical simulator.

Computer Simulation↗

Increased and decreased expression of CD69 and CD23, respectively, in gravity-stressed lymphocytes.

BACKGROUND: Recent studies have shown that gravity-changing stress modulates expression levels of cell surface molecules on human lymphocytes. However, previous in vitro microgravity studies have been performed with lymphocytes treated with mitogenic agents. HYPOTHESIS: The aim of the study was to test if exposure of cells to gravity-changing stress alone alters the expression levels of cell surface molecules. Specifically, we examined whether the expression of activation markers is altered after exposure of lymphocytes to combinations of microgravity and hypergravity. METHODS: We used free-fall in parabolic flight for human subjects and a drop-shaft to expose peripheral blood mononuclear cells (PBMC) to gravity-changing stress. After such exposure, PBMC were isolated, and expression levels of CD69, CD23 and CD38 were estimated using three-color flow cytometry. RESULTS: Increased percentages of CD69-positive cells were observed with PBMC from 3 of 4 volunteers who undertook 10 parabolic flights. Exposure of blood to gravity-changing stress in the drop-shaft increased both ratios of CD69-positive cells and levels of CD69 expression on T and B cells. In contrast, the percentages of CD23-positive B cells was decreased. However, gravity-changing stress was not always followed by significant alteration in CD38 expression. CONCLUSIONS: Our findings suggest that CD69 and CD23 might be useful markers that are up- and down-regulated, respectively, after exposure of lymphocytes to gravity-changing stress.

ADP-ribosyl Cyclase↗

[Development of food rations for humans in extreme environments].

Adequacy of food rations to the human body demands was assessed in three series of investigations with 73 volunteers. The first series (n = 31) was arranged in various climatic-geographic areas (the Arctic, desert, high altitude, and the moderate climate of Russia). Each test continued for 12 days. Energy value of the food ration made up 3560 kilocalories. The second and third series (n = 12 and n = 30, respectively) were performed in a pressurized module with simulation of some extreme factors of space flight. Energy value of the food ration balanced in the content of staple nutrients varied between 2800 and 3500 kcal. Results of physical-hygienic studies suggest adequacy of the proposed food rations to volunteers' physiological demands for nutrients and energy in various extreme conditions.

Altitude↗

Acute nerve injury induces long-term potentiation of C-fiber evoked field potentials in spinal dorsal horn of intact rat.

Nerve injury produces a long lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperalgesia, an increase in response to noxious stimuli. The mechanism underlying the lasting abnormal pain is not well understood. Our previous works have shown that electrical tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber evoked field potentials in the spinal dorsal horn, which is considered as a synaptic model of pathological pain. In the present study we tested if nerve injury, which is proved to produce neuropathic pain, induced the spinal LTP in intact rats. C-fiber evoked field potentials in spinal dorsal horn produced by electrical stimulation (10-20 V, 0.5 ms, 1/min) of the sciatic nerve were recorded. For induction of LTP of C-fiber evoked field potentials, three types of noxious stimuli were applied. (1) Electrical tetanic stimulation (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals). (2) Transection of the sciatic nerve at 4-5 mm distal to the stimulation electrode. (3) Crushing the sciatic nerve with a forceps four times at 4-5 mm distal to stimulation electrode (from distal to proximal with 1 mm spacing at 10 s intervals), which simulated electrical tetanic stimulation. Acute nerve injury was made by either transection of the sciatic nerve at the distal to the stimulating electrode or crushing the sciatic nerve. We found that nerve injury by cutting or crushing the sciatic nerve produced LTP of C-fiber evoked field potentials lasting until the end of the experiments (3-9 h), and that pretreatment of the sciatic nerve with lidocaine 10 min prior to the nerve transectoin completely blocked LTP induced by nerve transection. The nerve transection-induced LTP was blocked by NMDA receptor antagonist AP5. LTP produced by nerve transection could not be further potentiated by electrical tetanic stimulation, while LTP induced by single electrical tetanic stimulation could be further potentiated by transection of the sciatic nerve. However, when LTP was saturated by several times of electrical tetanic stimulation, nerve transection did not affect the spinal LTP. We conclude that acute nerve injury induces LTP of C-fiber evoked field potentials in intact animals and that nerve transection is more powerful than electrical tetanic stimulation for induction of the spinal LTP. The results further support the notion that LTP of C-fiber evoked field potentials may underlie neuropathic pain.

Animals↗

The virtual terrorism response academy: training for high-risk, low-frequency threats.

The Virtual Terrorism Response Academy is a reusable virtual learning environment to prepare emergency responders to deal with high-risk, low-frequency events in general, terrorist attacks in particular. The principal learning strategy is a traditional one: apprenticeship. Trainees enter the Academy and travel through its halls, selecting different learning experiences under the guidance of instructors who are simultaneously master practitioners and master trainers. The mentors are real individuals who have been videotaped according to courseware designs; they are subsequently available at any time or location via broadband Internet or CD-ROM. The Academy features a Simulation Area where trainees are briefed on a given scenario, select appropriate resources (e.g., protective equipment and hazmat instruments), then enter a 3-dimensional space where they must deal with various situations. Simulations are done under the guidance of a master trainer who functions as a coach, asking questions, pointing out things, explaining his reasoning at various points in the simulation. This is followed by a debriefing and discussion of lessons that could be learned from the simulation and the trainee's decisions.

Computer Simulation↗

Computer simulation analysis of the effects of countermeasures for reentry orthostatic intolerance.

Fluid loading is a countermeasure currently in routine use to improve the g-tolerance of crewmembers during reentry and return of Shuttle flights. However, its effectiveness diminishes with mission duration. Countermeasures that will be effective on long-duration flights are needed and are presently under development. This paper discusses the application of computer simulation in the analysis of the effects of countermeasures for reentry orthostatic intolerance. The results suggest improvements upon the fluid loading countermeasure currently in use.

Blood Volume↗