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J Eilers

Publications and source records attributed to J Eilers.

At least 19 recordsLinked to original sources

Argus: a new instrument for the measurement of the stratospheric dynamical tracers, N2O and CH4.

We describe here a new instrument for the simultaneous, in situ measurement of the stratospheric tracer molecules, nitrous oxide (N2O) and methane (CH4). Argus is unique in its small size making it well suited for limited payload atmospheric research platforms. Argus employs second harmonic spectroscopy using tunable lead-salt diode lasers emitting in the mid-infrared. We first explain the Argus design philosophy followed by detailed descriptions of the instrument's optical, mechanical, and thermal sub-systems. Argus employs an in-flight calibration system providing real time calibrations and tightly constrained uncertainty estimates of the returned data. Data analysis is carried out using non-linear least-squares model fits to the acquired second harmonic spectra. A sampling of Argus data acquired on a recent stratospheric research campaign in the Arctic winter is presented.

Methane↗

GABA-mediated Ca2+ signalling in developing rat cerebellar Purkinje neurones.

1. Cellular responses to GABA(A) receptor activation were studied in developing cerebellar Purkinje neurones (PNs) in brain slices obtained from 2- to 22-day-old rats. Two-photon fluorescence imaging of fura-2-loaded cells and perforated-patch recordings were used to monitor intracellular Ca2+ transients and to estimate the reversal potential of GABA-induced currents, respectively. 2. During the 1st postnatal week, focal application of GABA or the GABA(A) receptor agonist muscimol evoked transient increases in [Ca2+]i in immature PNs. These Ca2+ transients were reversibly abolished by the GABA(A) receptor antagonist bicuculline and by Ni2+, a blocker of voltage-activated Ca2+ channels. 3. Perforated-patch recordings were used to measure the reversal potential of GABA-evoked currents (E(GABA)) at different stages of development. It was found that E(GABA) was about -44 mV at postnatal day 3 (P3), it shifted to gradually more negative values during the 1st week and finally equilibrated at -87 mV at around the end of the 2nd postnatal week. This transition was well described by a sigmoidal function. The largest change in E(GABA) was -7 mV x day(-1), which occurred at around P6. 4. The transition in GABA-mediated signalling occurs during a period in which striking changes in PN morphology and synaptic connectivity are known to take place. Since such changes were shown to be Ca2+ dependent, we propose that GABA-evoked Ca2+ signalling is one of the critical determinants for the normal development of cerebellar PNs.

Animals↗

Oral mucositis and the clinical and economic outcomes of hematopoietic stem-cell transplantation.

PURPOSE: To explore the relationship between oral mucositis and selected clinical and economic outcomes in blood and marrow transplant patients. PATIENTS AND METHODS: Subjects consisted of 92 transplant patients from eight centers who participated in a multinational pilot study of a new oral mucositis scoring system (Oral Mucositis Assessment Scale [OMAS]). In the pilot study, patients were evaluated for erythema and ulceration/pseudomembrane formation beginning on the first day of conditioning and continuing for 28 days. We examined the relationship between patients' peak OMAS scores and days with fever (body temperature > 38.0 degrees C), the occurrence of significant infection, days of total parenteral nutrition (TPN), and days of injectable narcotic therapy (all over 28 days), days in hospital (over 60 days), total hospital charges for the index admission, and vital status at 100 days. RESULTS: Patients' peak OMAS scores spanned the full range of possible values (0 to 5) and were significantly (P <.05) correlated with all of the outcomes of interest except days with fever (P =.21). In analyses controlling for type of graft (autologous v allogeneic) and study center, a 1-point increase in peak OMAS score was associated with (1) 1.0 additional day with fever (P <.01), (2) a 2.1-fold increase in risk of significant infection (P <.01), (3) 2.7 additional days of TPN (P <.0001), (4) 2.6 additional days of injectable narcotic therapy (P <.0001), (5) 2.6 additional days in hospital (P <.01), (6) $25,405 in additional hospital charges (P <.0001), and (7) a 3.9-fold increase in 100-day mortality risk (P <.01). Mean hospital charges were $42,749 higher among patients with evidence of ulceration compared with those without (P =.06). CONCLUSION: Oral mucositis is associated with significantly worse clinical and economic outcomes in blood and marrow transplantation.

Adult↗

NMDA receptor-mediated subthreshold Ca(2+) signals in spines of hippocampal neurons.

We have used rapid confocal microscopy to investigate the mechanism of Ca(2+) signals in individual dendritic spines of hippocampal CA1 pyramidal cells. The experiments focused on the signals that occur during single weak synaptic responses that were subthreshold for triggering postsynaptic action potentials. These Ca(2+) signals were not strongly affected by blocking the EPSPs with the AMPA receptor antagonist CNQX. The signals were also not strongly reduced by blocking T-type voltage-gated Ca(2+) channels (VGCCs) with Ni(2+) or by blocking a broad range of VGCCs with intracellular D890. The spine Ca(2+) signals were blocked by NMDA receptor channel (NMDAR) antagonist and had the voltage dependence characteristic of these channels. Neither ryanodine nor cyclopiazonic acid (CPA), substances known to deplete intracellular Ca(2+) stores, substantially reduced the amplitude of synaptically evoked Ca(2+) signals. CPA slowed the recovery phase of Ca(2+) signals in spines produced by synaptic stimulation or by backpropagating action potentials, suggesting a role of intracellular stores in Ca(2+) reuptake. Thus, we find that Ca(2+) release from intracellular stores is not required to produce spine Ca(2+) signals. We conclude that synaptic Ca(2+) signals in spines are primarily caused by Ca(2+) entry through NMDARs. Although these channels are largely blocked by Mg(2+) at voltages near the resting potential, they can nevertheless produce significant Ca(2+) elevation. The resulting Ca(2+) signals are an integral component of individual evoked or spontaneous synaptic events and may be important in the maintenance of synaptic function.

2-Amino-5-phosphonovalerate↗

Large-scale oscillatory calcium waves in the immature cortex.

Two-photon imaging of large neuronal networks in cortical slices of newborn rats revealed synchronized oscillations in intracellular Ca2+ concentration. These spontaneous Ca2+ waves usually started in the posterior cortex and propagated slowly (2.1 mm per second) toward its anterior end. Ca2+ waves were associated with field-potential changes and required activation of AMPA and NMDA receptors. Although GABAA receptors were not involved in wave initiation, the developmental transition of GABAergic transmission from depolarizing to hyperpolarizing (around postnatal day 7) stopped the oscillatory activity. Thus we identified a type of large-scale Ca2+ wave that may regulate long-distance wiring in the immature cortex.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Two-photon Na+ imaging in spines and fine dendrites of central neurons.

Dendritic spines are assumed to be the smallest units of neuronal integration. Because of their miniature size, however, many of their functional properties are still unclear. New insights in spine physiology have been provided by two-photon laser-scanning microscopy which allows fluorescence imaging with high spatial resolution and minimal photodamage. For example, two-photon imaging has been employed successfully for the measurement of activity-induced calcium transients in individual spines. Here, we describe the first application of two-photon imaging to measure Na+ transients in spines and dendrites of CA1 pyramidal neurons in hippocampal slices. Whole-cell patch-clamped neurons were loaded with the Na(+)-indicator dye SBFI (sodium-binding benzofuran-isophthalate). In situ calibration of SBFI fluorescence with ionophores enabled the determination of the actual magnitude of the [Na+]i changes. We found that back-propagating action potentials (APs) evoked Na+ transients throughout the proximal part of the dendritic tree and adjacent spines. The action-potential-induced [Na+]i transients reached values of 4 mM for a train of 20 APs and monotonically decayed with a time constant of several seconds. These results represent the first demonstration of activity-induced Na+ accumulation in spines. Our results demonstrate that two-photon Na+ imaging represents a powerful tool for extending our knowledge on Na+ signaling in fine cellular subcompartments.

Action Potentials↗

Intracranial stenoocclusive disease: double-detector helical CT angiography versus digital subtraction angiography.

BACKGROUND AND PURPOSE: To our knowledge, no large-scale studies comparing the accuracy of CT angiography (CTA) to intraarterial digital subtraction angiography (DSA) of intracranial stenosis have been reported. We attempted to determine the diagnostic value of intracranial CT angiography (CTA) of normal vasculature and variants as well as of stenoocclusive disease. METHODS: One-hundred and twelve patients underwent CTA and intraarterial angiography, and 2205 vascular segments were examined to ascertain presence, visibility, and degree of arterial stenoses (n = 105) as well as anatomic variants. Source, maximum intensity projection (MIP), and MIP-generated multiplanar reformatted (MPR) images were evaluated. RESULTS: All 55 anatomic variants were identified correctly. Visibility of small-vessel segments was increased from 75% to 83% by using source images. MPR was helpful in differentiating distal vertebral hypoplasia from stenosis and in overcoming artifacts. All 43 occlusive segments were graded correctly (sensitivity = 100%, predictive value = 93.4%) as follows: severely stenotic ([n = 23], sensitivity = 78%, predictive value = 81.8%); moderately stenotic ([n = 36], sensitivity = 61%, predictive value = 84.6%); and mildly stenotic ([n = 3], sensitivity = 66%, predictive value = 28%). Normal segments (n = 2100) had a sensitivity of 99.5%, and CTA evinced a specificity of 99% for detecting stenoocclusive disease. Approximately one-third of wrong assessments were related to the petrous segment of the carotid artery. CONCLUSION: CTA with double-detector technology and advanced postprocessing algorithms, including MPR, is about as reliable as MRA in depicting the vasculature of the anterior and posterior circulation and in grading intracranial stenoocclusive lesions, with the exception of the petrous segment of the carotid artery. CTA might be superior to MRA in the evaluation of poststenotic low-flow segments.

Angiography, Digital Subtraction↗

Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo.

NMDA receptors, a class of glutamate-gated cation channels with high Ca2+ conductance, mediate fast transmission and plasticity of central excitatory synapses. We show here that gene-targeted mice expressing NMDA receptors without the large intracellular C-terminal domain of any one of three NR2 subunits phenotypically resemble mice made deficient in that particular subunit. Mice expressing the NR2B subunit in a C-terminally truncated form (NR2B(deltaC/deltaC) mice) die perinatally. NR2A(deltaC/deltaC) mice are viable but exhibit impaired synaptic plasticity and contextual memory. These and NR2C(deltaC/deltaC) mice display deficits in motor coordination. C-terminal truncation of NR2 subunits does not interfere with the formation of gateable receptor channels that can be synaptically activated. Thus, the phenotypes of our mutants appear to reflect defective intracellular signaling.

Amino Acid Sequence↗

Factors influencing oral cavity status during high-dose antineoplastic therapy: a secondary data analysis.

PURPOSE/OBJECTIVES: To identify factors associated with oral cavity status in patients receiving high-dose antineoplastic therapy. DESIGN: Descriptive, correlational secondary analysis. SETTING: Midwestern university oncology special care unit. SAMPLE: 50 males and females, ages 15-69. METHODS: The Oral Assessment Guide (OAG) was used to assess oral cavity status every shift throughout hospitalization. Additional data were collected by chart audit. Correlations and Cox regression analysis were performed. MAIN RESEARCH VARIABLES: Oral cavity status, absolute granulocyte count, blood urea nitrogen (BUN), creatinine, mean OAG score during the preparative regimen (prep-OAG), age, and total body irradiation (TBI). FINDINGS: Elevated BUN and creatinine, higher prep-OAG, older age, and TBI were associated with higher OAG scores. Cox analysis revealed that TBI was predictive of an OAG score > or = 16, and an OAG score > or = 18 was predictive of death by day +20. CONCLUSIONS: Patients who receive TBI and chemotherapy in combination are most likely to experience severely compromised oral cavity status. Those who are older, have poorer oral status, and have decreased renal function are at increased risk. IMPLICATIONS FOR NURSING PRACTICE: High-risk patients must be identified early, and oral assessments and care must be given consistently to decrease morbidity and potential mortality.

Adolescent↗

The flaginserter: a simple device for automatically marking events in video recordings.

Dynamic imaging of cellular responses often involves the use of standard video components. While these components (cameras, monitors, etc.) are relatively inexpensive and easily available, there is the difficulty of integrating them into experimental set-ups. Especially for video recordings of fast signals that occur in neurobiological preparations (e.g. synaptic responses), there is a critical need for accurate synchronisation of video images with external events, such as extracellular stimulation or intracellular depolarising voltage steps. We developed a circuit that allows such events within the video sequence to be marked by means of a white flag that is inserted into the video image. Depending on the mode of insertion, the time resolution is better than 17 ms or better than 65 micros (i.e. a single video field or video line, respectively). The circuit has been shown to work reliable in combination with video-rate confocal imaging and patch-clamp recordings.

Animals↗

Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene.

Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear. To investigate the physiological role of a major endogenous calcium-binding protein, calbindin D28k (calbindin) in vivo, we have generated calbindin null mutant mice by gene targeting. Surprisingly, calbindin deficiency does not affect general parameters of development and behavior or the structure of the nervous system at the light microscopic level. Null mutants are, however, severely impaired in tests of motor coordination, suggesting functional deficits in cerebellar pathways. Purkinje neurons, the only efferent of the cerebellar cortex, and inferior olive neurons, the source of the climbing fiber afferent, have previously been shown to express calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging of Purkinje cells in cerebellar slices revealed marked changes of synaptically evoked postsynaptic calcium transients. Their fast, but not their slow, decay component had larger amplitudes in null mutant than in wild-type mice. We conclude that endogenous calbindin is of crucial importance for integrated nervous system function.

Animals↗

Dendritic signal integration.

Recent studies have identified various forms of active dendritic signals that may contribute to neuronal integration. One of the most remarkable findings is the demonstration of highly localized Ca2+ transients that are limited to small dendritic segments and even to single dendritic spines. In addition, through use of the powerful two-photon excitation imaging technique, it has been possible to reveal the existence of dendritic Ca2+ signals under in vivo conditions. Finally, active backpropagation of action potentials into dendrites has been shown to boost dendritic Ca2+ signals supralinearly and, thus, to contribute to the induction of long-term potentiation.

Animals↗

Axonal calcium entry during fast 'sodium' action potentials in rat cerebellar Purkinje neurones.

1. Using laser-scanning confocal microscopy, fast Ca2+ transients were recorded in individual not yet myelinated axons of Purkinje neurones in cerebellar slices from young rats. Axonal Ca2+ transients could be detected during a single action potential and had progressively larger amplitudes when the number of action potentials was increased. 2. Under voltage-clamp conditions, axonal Ca2+ transients were as large as those observed in dendrites and in the cell body. Axonal Ca2+ transients were completely blocked by 100 nM of the neurotoxin omega-agatoxin IVA, indicating that they were caused by Ca2+ entry through P-type voltage-gated Ca2+ channels. 3. In conclusion, our results demonstrate action potential-mediated Ca2+ entry through voltage-gated Ca2+ channels in axons of cerebellar Purkinje neurones. Experimental evidence indicates that the resulting transient Ca2+ accumulations regulate the frequency of action potentials travelling along the axon.

Action Potentials↗

Localized calcium signalling and neuronal integration in cerebellar Purkinje neurones.

The use of high resolution imaging techniques has revealed new forms of dendritic signal integration in neurones. In contrast to electrical signals that have a more widespread influence on the cell, brief Ca2+ transients resulting from synaptic activation are often restricted to a small part of the dendritic tree. In cerebellar Purkinje neurones, different levels of Ca2+ signalling have been observed that may involve the entire neurone or be spatially limited to fine dendritic structures. The Ca2+ signals accompanying subthreshold excitatory postsynaptic potentials resulting from stimulation of the excitatory parallel fibre input can be restricted to regions as small as a spiny dendrite or a single dendritic spine. With the recruitment of increasing numbers of inputs there is a summation of Ca2+ signals in highly restricted regions of the spiny dendrites that is independent of electrical summation at the soma. Of a number of potential sources that could provide the Ca2+ responsible for the postsynaptic changes, Ca2+ entry through voltage-gated Ca2+ channels has received the most support, although other sources like Ca2+ entry through ligand-gated channels and especially Ca2+ release from intracellular stores need to be considered.

Animals↗