scholarly journals Ca2+ Dependence of the Binomial Parameters p and n at the Mouse Neuromuscular Junction

2010 ◽  
Vol 103 (2) ◽  
pp. 659-666 ◽  
Author(s):  
Xueyong Wang ◽  
Martin J. Pinter ◽  
Mark M. Rich
Keyword(s):  
Neuromuscular Junction ◽  
Time Course ◽  
Quantal Release ◽  
Sequential Release ◽  
Vesicular Release ◽  
Wide Range ◽  
Compound Binomial ◽  
Graphical Technique ◽  
Binomial Statistics

The Ca2+ dependence of synaptic quantal release is generally thought to be restricted to probability of vesicular release. However, some studies have suggested that the number of release sites ( n) at the neuromuscular junction (NMJ) is also Ca2+ dependent. In this study, we recorded endplate currents over a wide range of extracellular Ca2+ concentrations and found the expected Ca2+ dependency of release. A graphical technique was used to estimate p (probability of release) and n using standard binomial assumptions. The results suggested n was Ca2+ dependent. The data were simulated using compound binomial statistics with variable n (Ca2+ dependent) or fixed n (Ca2+ independent). With fixed n, successful simulation of increasing Ca2+ required that p increase abruptly at some sites from very low to high values. Successful simulation with variable n required the introduction of previously silent release sites ( p = 0) with high values of p. Thus the success of both simulations required abrupt, large increases of p at a subset of release sites with initially low or zero p. Estimates of the time course of release obtained by deconvolving evoked endplate currents with average miniature endplate currents decreased slightly as Ca2+ increased, thus arguing against sequential release of multiple quanta at higher Ca2+ levels. Our results suggest that the apparent Ca2+ dependence of n at the NMJ can be explained by an underlying Ca2+ dependence of a spatially variable p such that p increases abruptly at a subset of sites as Ca2+ is increased.

scholarly journals Frequency of myelin oligodendrocyte glycoprotein antibodies in a large cohort of neurological patients

2021 ◽  
Vol 7 (2) ◽  
pp. 205521732110227
Author(s):  
Friederike Held ◽  
Sudhakar Reddy Kalluri ◽  
Achim Berthele ◽  
Ana-Katharina Klein ◽  
Markus Reindl ◽  
...  
Keyword(s):  
Time Course ◽  
Neurological Diseases ◽  
External Validation ◽  
Diagnostic Value ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Large Cohort ◽  
Wide Range ◽  
Neurological Patients ◽  
A Cell ◽  
Nosological Entity

Background Myelin oligodendrocyte glycoprotein (MOG) antibody disease (MOG-AD) is recognized as a distinct nosological entity. IgG antibodies against MOG (MOG-Ab) overlap with neuromyelitis optica spectrum disorders (NMOSD) phenotype in adults. However, an increasing number of clinical phenotypes have been reported to be associated with MOG-Ab. Objective To investigate the seroprevalence of MOG-Ab under consideration of demographics, disease entities and time course in a large cohort of unselected neurological patients. Methods Blood samples of 2.107 consecutive adult neurologic patients admitted to our department between 2016-2017 were tested for MOG-Ab using a cell-based assay. MOG-Ab persistence was analyzed in follow-up samples. External validation was performed in two independent laboratories. Results We found MOG-Ab in 25 of 2.107 (1.2%) patients. High antibody ratios were mostly associated with NMOSD and MOG-AD phenotype (5/25). Low ratios occurred in a wide range of neurological diseases, predominantly in other demyelinating CNS diseases (5/25) and stroke (6/25). MOG-Ab persistence over time was not confined to NMOSD and MOG-AD phenotype. Conclusion The present study demonstrates the occurrence of MOG-Ab in a wide range of neurological diseases. Only high MOG-Ab ratios were associated with a defined clinical phenotype, but low MOG-Ab ratios were not. The diagnostic value of low MOG-Ab is thus highly limited.

Measurement of pulmonary edema in intact dogs by transthoracic gamma-ray attenuation

1979 ◽  
Vol 47 (6) ◽  
pp. 1228-1233 ◽  
Author(s):  
D. S. Simon ◽  
J. F. Murray ◽  
N. C. Staub
Keyword(s):  
Pulmonary Edema ◽  
Time Course ◽  
Gamma Ray ◽  
High Sensitivity ◽  
Lung Edema ◽  
Lung Water ◽  
Vascular Congestion ◽  
Isolated Lung ◽  
Wide Range ◽  
Gamma Ray Attenuation

We evaluated the attenuation of the 122 keV gamma ray of cobalt-57 across the thorax of anesthetized dogs as a method for following the time course of lung water changes in acute pulmonary edema induced by either increased microvascular permeability or increased microvascular hydrostatic pressure. The gamma rays traversed the thorax centered on the seventh rib laterally where the lung mass in the beam path was greatest. Calibration measurements in isolated lung lobes demonstrated the high sensitivity and inherent accuracy of the method over a wide range of lung water contents. In control dogs reproducibility averaged +/-3%. Increased permeability edema led to large rapid increases in the transthoracic gamma ray attenuation (TGA), while increased pressure caused an immediate, modest increase in TGA (vascular congestion) followed by a slow further increase over 2 h. There was a fairly good correlation between the increase in extravascular lung water and the change in TGA. The method is simple, safe, and noninvasive and appears to be useful for following the time course of lung water accumulation in generalized lung edema in anesthetized animals.

scholarly journals "Creep currents" in single frog atrial cells may be generated by electrogenic Na/Ca exchange.

1986 ◽  
Vol 87 (6) ◽  
pp. 857-884 ◽  
Author(s):  
J R Hume ◽  
A Uehara
Keyword(s):  
Voltage Clamp ◽  
Time Course ◽  
Single Cells ◽  
Mechanical Activity ◽  
Common Mechanism ◽  
Mechanical Relaxation ◽  
Equilibrium Conditions ◽  
Atrial Cells ◽  
Current Voltage ◽  
Wide Range

The objective of these experiments was to test the hypothesis that the "creep currents" induced by Na loading of single frog atrial cells (Hume, J. R., and A. Uehara. 1986. Journal of General Physiology. 87:833) may be generated by an electrogenic Na/Ca exchanger. Creep currents induced by Na loading were examined over a wide range of membrane potentials. During depolarizing voltage-clamp pulses, outward creep currents were observed, followed by inward creep currents upon the return to the holding potential. During hyperpolarizing voltage-clamp pulses, creep currents of the opposite polarity were observed: inward creep currents were observed during the pulses, followed by outward creep currents upon the return to the holding potential. The current-voltage relations for inward and outward creep currents in response to depolarizing or hyperpolarizing voltage displacements away from the holding potential all intersect the voltage axis at a common potential, which indicates that inward and outward creep currents may have a common reversal potential under equilibrium conditions and may therefore be generated by a common mechanism. Measurements of inward creep currents confirm that voltage displacements away from the holding potential rapidly alter equilibrium conditions. Current-voltage relationships of inward creep currents after depolarizing voltage-clamp pulses are extremely labile and depend critically upon the amplitude and duration of outward creep currents elicited during preceding voltage-clamp pulses. An optical monitor of mechanical activity in single cells revealed (a) a similar voltage dependence for the outward creep currents induced by Na loading and tonic contraction, and (b) a close correlation between the time course of the decay of the inward creep current and the time course of mechanical relaxation. A mathematical model of electrogenic Na/Ca exchange (Mullins, L.J. 1979. Federation Proceedings. 35:2583; Noble, D. 1986. Cardiac Muscle. 171-200) can adequately account for many of the properties of creep currents. It is concluded that creep currents in single frog atrial cells may be attributed to the operation of an electrogenic Na/Ca exchange mechanism.

scholarly journals Metabolic aspects of the secretion of stored compounds from blood platelets. The effect of NaF at different pH on nucleotide metabolism and function of washed platelets

1981 ◽  
Vol 194 (1) ◽  
pp. 187-192 ◽  
Author(s):  
E H Mürer ◽  
K Davenport ◽  
E Siojo ◽  
H J Day
Keyword(s):  
Time Course ◽  
Adenine Nucleotides ◽  
Blood Platelets ◽  
Fluoride Concentration ◽  
Indirect Evidence ◽  
Inhibitory Effect ◽  
Nucleotide Metabolism ◽  
Wide Range ◽  
And Function ◽  
Special Circumstances

The purpose of this study was to investigate the response of human blood platelets to fluoride at different pH. The results were as follows. (1) Fluoride induced secretion faster and at a lower concentration when pH was lowered. (2) Platelets exposed to 2 mM-fluoride at 0 degrees C at pH 5.3 underwent secretion when first pH and then temperature was raised, although no secretion was seen at 2 mM-fluoride concentration in the absence of the preincubation at low pH. (3) The concentration of [14C]ATP in platelets decreased steeply in response to fluoride before induction of secretion. Addition of antimycin blocked or partly inhibited secretion. Fluoride thus exerts an inhibitory effect on platelet glycolysis before induction of secretion. (4) Fluoride accumulated in the platelet pellet by a time course that preceded secretion. The accumulation was faster and greater at pH 6 than at 7.4. These four points are taken as indirect evidence that fluoride has to penetrate to the interior of the platelet to induce secretion. The activation takes place over a wide range of acid pH in contrast with induction of platelet function via the outside of the plasma membrane. In addition evidence is presented that the salvage pathway may under special circumstances play an important role in the re-synthesis of platelet adenine nucleotides.

scholarly journals Ferritin is associated with the severity of lung involvement but not with worse prognosis in patients with COVID-19: data from two Italian COVID-19 Units.

2020 ◽  
Author(s):  
Francesco Carubbi ◽  
Lia Salvati ◽  
Alessia Alunno ◽  
Fabio Maggi ◽  
Erika Borghi ◽  
...  
Keyword(s):  
Ct Scan ◽  
Time Course ◽  
Mediastinal Lymph Node ◽  
Clinical Signs ◽  
Pulmonary Involvement ◽  
Imaging Data ◽  
Age And Gender ◽  
Disease Outcomes ◽  
Wide Range ◽  
And Gender

Abstract The coronavirus 2019 disease (COVID-19) is characterised by a heterogeneous clinical presentation, a complex pathophysiology and a wide range of imaging findings, depending on disease severity and time course. We conducted a retrospective evaluation of hospitalized patients with proven SARS-CoV-2 infection, clinical signs of COVID-19 and computed tomography (CT) scan-proven pulmonary involvement, in order to identify relationships between clinical, serological, imaging data and disease outcomes in patients with COVID-19. Clinical and serological records of patients admitted to two COVID-19 Units of the Abruzzo region in Italy with proven SARS-CoV-2 pulmonary involvement investigated with CT scan, assessed at the time of admission to the hospital, were retrospectively evaluated.Sixty-one patients (22 females and 39 males) of median age 65 years were enrolled. Fifty-six patients were discharged while death occurred in 5 patients. None of the lung abnormalities detected by CT was different between discharged and deceased patients. No differences were observed in the features and extent of pulmonary involvement according to age and gender. Logistic regression analysis with age and gender as covariates demonstrated that ferritin levels over the 25th percentile were associated with the involvement of all 5 pulmonary lobes (OR=14.5, 95% CI=2.3-90.9, p=0.004), the presence of septal thickening (OR=8.2, 95% CI=1.6-40.9, p=0.011) and the presence of mediastinal lymph node enlargement (OR=12.0, 95% CI=1.1-127.5, p=0.039) independently of age and gender.We demonstrated that ferritin levels over the 25th percentile are associated with a more severe pulmonary involvement, independently of age and gender and not associated with disease outcomes. The identification of reliable biomarkers in patients with COVID-19 may help guiding clinical decision, tailoring therapeutic approaches and ultimately improving the care and prognosis of patients with this disease.

scholarly journals High resolution AKT signaling in individual cells

2018 ◽  
Author(s):  
Sean M. Gross ◽  
Mark A. Dane ◽  
Elmar Bucher ◽  
Laura M. Heiser
Keyword(s):  
Single Cell ◽  
Intracellular Signaling ◽  
Time Course ◽  
Dynamic Range ◽  
Individual Cell ◽  
Akt Signaling ◽  
Live Cells ◽  
Theoretic Approach ◽  
Wide Range ◽  
Igf I

AbstractCells sense and respond to their environment by activating distinct intracellular signaling pathways, however an individual cell’s ability to faithfully transmit and discriminate environmental signals is thought to be limited. To assess the fidelity of signal transmission in the PI3K-AKT signaling pathway, we first developed an optimized genetically encoded sensor that had an increased dynamic range and reduced variation under basal conditions. We then used this reporter to track responses to varying doses of IGF-I in live cells and found that signaling responses from individual cells overlapped across a wide range of IGF-I doses, suggesting limited transmission accuracy. However, further analysis of individual cell traces revealed that responses were constant over time without stochastic fluctuations. We devised a new information theoretic approach to calculate the channel capacity using variance of the single cell time course data‐‐rather than population-level variance as has been previously used—and predicted that cells were capable of discriminating multiple growth factor doses. We validated these predictions by tracking individual cell responses to multiple IGF-I doses and found that cells can accurately distinguish at least four different IGF-I concentrations, as demonstrated by their distinct responses. Furthermore, we found a similar discriminatory ability to pathway inhibition, as assessed by responses to the PI3K inhibitor alpelisib. Our studies indicate that cells can faithfully transmit an IGF-I input into a down-stream signaling response and that heterogeneous responses result from variation in the input-output relation across the population. These observations reveal the importance of viewing each cell as having its own communication channel and underscore the importance of understanding responses at the single cell level.

On Respiration in the Dragonet Callionymus Lyra L

1968 ◽  
Vol 49 (3) ◽  
pp. 565-582
Author(s):  
G. M. HUGHES ◽  
SHUN-ICHI UMEZAWA
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Time Course ◽  
Water Pressure ◽  
Minute Volume ◽  
Individual Variations ◽  
Wide Range ◽  
The Relationship ◽  
Respiratory Rhythms ◽  
Normal Ventilation

1. The usefulness of a bottom-living fish, the dragonet (Callionymus lyra), in experiments on fish respiration is described. The position and nature of its opercular opening made it possible to determine directly the volume of water pumped over the gills and the PO2 of the mixed expired water. The normal ventilation volume for a 100 g. fish was about 30 c.c./min. 2. The relationship between cardiac and respiratory rhythms was investigated and showed a variety of ratios. The heart usually beats more than once during each respiratory cycle. Individual variations in the coupling between these rhythms was common and close couplings were observed in the absence of anaesthetic and at normal PO2s. 3. Changes in minute volume produced by altering the hydrostatic pressure across the respiratory system did not affect the heart rate. Percentage utilization fell at higher flow rates. Changes in flow per cm. of water pressure gradient was less with negative gradients than when the static pressure on the mouth side exceeded that in the opercular collecting chamber. 4. Oxygen consumption of the fish is directly related to the ambient PO2 over a wide range (30-120 mm. Hg). Sudden lowering of the PO2 in the inspired water leads to compensatory responses in which the minute volume is maintained or increased as a result of a rise in stroke volume and lowered respiratory frequency: there is also a marked bradycardia. During recovery the increased oxygen consumption of the fish resulted from a rise in utilization rather than a change in the respiratory rate or ventilation volume. 5. Analysis of the time course of the changes in heart rate and ventilation volume in experiments in which PO2 was changed supports the view that the receptors mediating bradycardia occur on the gills and respond directly to the change in PO2 rather than to the secondary increase in flow produced by the hypoxia.

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