The Relationship between the Formation of Urea and Argininosuccinate in a Patient with Argininosuccinic Aciduria Studied with Labelled Precursors

1974 ◽  
Vol 46 (6) ◽  
pp. 715-727
Author(s):  
C. W. Crane ◽  
F. A. Jenner ◽  
R. J. Pollitt

1. The time-course of urinary excretion of [15N]urea and [15N]argininosuccinate or [15N]arginine after an oral dose of [15N]ammonium lactate has been followed in patients with argininosuccinic aciduria and cystine-lysinuria respectively. The labelled argininosuccinate and arginine appeared more slowly than expected on simple precursor-product models. 2. In the patient with argininosuccinic aciduria, simultaneous ingestion of [15N]-ammonium lactate and [carbamoyl-14C]citrulline gave very different ratios of labelling with the two isotopes for urinary urea and argininosuccinate. Urinary argininosuccinate had not been in equilibrium with the urea precursor in this patient, but the plasma [14C]citrulline bore a reasonable precursor-product relationship to the urinary [14C]argininosuccinate. 3. Intravenous [guanidino-14C]arginine given to the patient with argininosuccinic aciduria resulted in a much higher degree of labelling of the plasma globulins than the albumin. This is consistent with a considerable turnover of hepatic arginine, as would be expected with a functioning Krebs-Henseleit urea cycle. 4. These results can be explained with a compartmentation model in which most of the urea is synthesized in the liver, but most of the urinary argininosuccinate is peripheral in origin.

1997 ◽  
Vol 77 (1) ◽  
pp. 405-420 ◽  
Author(s):  
Kelvin E. Jones ◽  
Parveen Bawa

Jones, Kelvin E. and Parveen Bawa. Computer simulation of the responses of human motoneurons to composite 1A EPSPS: effects of background firing rate. J. Neurophysiol. 77: 405–420, 1997. Two compartmental models of spinal alpha motoneurons were constructed to explore the relationship between background firing rate and response to an excitatory input. The results of these simulations were compared with previous results obtained from human motoneurons and discussed in relation to the current model for repetitively firing human motoneurons. The morphologies and cable parameters of the models were based on two type-identified cat motoneurons previously reported in the literature. Each model included five voltage-dependent channels that were modeled using Hodgkin-Huxley formalism. These included fast Na+ and K+ channels in the initial segment and fast Na+ and K+ channels as well as a slow K+ channel in the soma compartment. The density and rate factors for the slow K+ channel were varied until the models could reproduce single spike AHP parameters for type-identified motoneurons in the cat. Excitatory synaptic conductances were distributed along the equivalent dendrites with the same density described for la synapses from muscle spindles to type-identified cat motoneurons. Simultaneous activation of all synapses on the dendrite resulted in a large compound excitatory postsynaptic potential (EPSP). Brief depolarizing pulses injected into a compartment of the equivalent dendrite resulted in pulse potentials (PPs), which resembled the compound EPSPs. The effects of compound EPSPs and PPs on firing probability of the two motoneuron models were examined during rhythmic firing. Peristimulus time histograms, constructed between the stimulus and the spikes of the model motoneuron, showed excitatory peaks whose integrated time course approximated the time course of the underlying EPSP or PP as has been shown in cat motoneurons. The excitatory peaks were quantified in terms of response probability, and the relationship between background firing rate and response probability was explored. As in real human motoneurons, the models exhibited an inverse relationship between response probability and background firing rate. The biophysical properties responsible for the relationship between response probability and firing rate included the shapes of the membrane voltage trajectories between spikes and nonlinear changes in PP amplitude during the interspike interval at different firing rates. The results from these simulations suggest that the relationship between response probability and background firing rate is an intrinsic feature of motoneurons. The similarity of the results from the models, which were based on the properties of cat motoneurons, and those from human motoneurons suggests that the biophysical properties governing rhythmic firing in human motoneurons are similar to those of the cat.


2013 ◽  
Vol 112 (1-3) ◽  
pp. 49-55 ◽  
Author(s):  
Tao Ma ◽  
Kaidong Deng ◽  
Chenggang Jiang ◽  
Yan Tu ◽  
Naifeng Zhang ◽  
...  

2002 ◽  
Vol 82 (10) ◽  
pp. 1000-1008 ◽  
Author(s):  
Patrick Segers ◽  
Jean-Paul Belgrado ◽  
Andre Leduc ◽  
Olivier Leduc ◽  
Pascal Verdonck

Abstract Background and Purpose. Pneumatic compression devices, used as part of the therapeutic strategy for lymphatic drainage, often have cuffs with multiple chambers that are inflated sequentially. The purpose of this study was to investigate (1) the relationship between cuff chamber pressure (Pchamber) and the pressure on the cuff-skin interface (Pinterface) and (2) the mechanical interaction of cuff chambers and consequences for device control. Subjects and Methods. In this study, we used 3 cylindrical (60-, 80-, and 100-mm-diameter) model limbs and 1 ellipsoidal model of the arm to test a commercially available pressure controller using “target pressures,” indicated by the controller, of 30, 60, 80, and 100 mm Hg. We studied the time course of Pchamber and Pinterface during the inflation sequence and the effect of local curvature on Pinterface. Results. Our data indicated that, overall, Pinterface is of the same order of magnitude as Pchamber. There was some effect of model diameter and shape, with the smaller curvatures yielding the highest Pinterface. Cuff chamber interaction led to Pchamber and Pinterface values in the most distal (first inflated) chamber that were up to 80% higher than the target pressure. For the 80-mm cylindrical model, for instance, pressure in this chamber reached 54, 98, 121, and 141 mm Hg, respectively, instead of the 30, 60, 80, and 100 mm Hg indicated by the controller. Discussion and Conclusion. The discrepancy between the target pressure, indicated by the controller, and the pressure measured inside the cuff chambers undermines the therapeutic control and efficacy of the pneumatic compression devices. Because the measured pressures were far beyond the pressure level indicated by the controller, it is recommended that pneumatic compression devices be used at much lower target pressures (<30 mm Hg) than those applied in clinical practice.


Author(s):  
LeRoy E. Taylor ◽  
Mark R. Henderson

Abstract This paper describes the roles of features and abstraction mechanisms in the mechanical design process, mechanical designs, and product models of mechanical designs. It also describes the relationship between functions and features in mechanical design. It is our experience that many research efforts exist in the areas of design and product modeling and, further, that these efforts must be cataloged and compared. To this end, this paper culminates with the presentation of a multi-dimensional abstraction space which provides a unique framework for (a) comparing mechanical engineering design research efforts, (b) relating conceptual objects used in the life cycle of mechanical products, and (c) defining a product modeling space.


1976 ◽  
Vol 86 (1) ◽  
pp. 83-91 ◽  
Author(s):  
M. A. Scaife ◽  
D. Jones

SUMMARYLettuce obeys the Shinozaki–Kira relationship in which the reciprocal of plant weight is linearly related to plant density. The intercept (a) represents the reciprocal of the weight of an isolated plant and the slope (b) represents the reciprocal of yield/unit area at high densities (the ‘ceiling yield’). This work examines the time course of (a) and (b) in an ‘ideal environment’ in which water and nutrients are non-limiting, and the light/temperature regime is constant.Two pot experiments are described: the first showed that the growth of isolated lettuces follows a logistic expression, which can therefore be substituted for a–1 in the Shinozaki-Kira equation. It was then hypothesized that b–1, the ‘ceiling yield’ would be constant over time. This was confirmed by the second experiment, giving the equationw–1t = w–10 e1–kt × w–1max × bd,in which wt is mean plant weight at time t, w0 and wmax are the initial and final weights of isolated plants, k is the early relative growth rate of such plants, b–1 is the constant ceiling yield, and d is the plant density.Two examples of the use of the equation are given: one shows how it predicts the interaction between seed size and plant density within a species (subterranean clover): the other illustrates how it can be used to explain why lettuce growth appears to be log-linear against time whereas cereal growth is more nearly just linear.


1992 ◽  
Vol 287 (3) ◽  
pp. 813-820 ◽  
Author(s):  
A Geissler ◽  
K Kanamori ◽  
B D Ross

1. Isolated rat liver was perfused with 10 mM-15NH4Cl, 5 mM-lactate and 1 mM-ornithine, or with 3 mM-[15N]alanine and 1 mM-ornithine, in haemoglobin-free medium. The liver was physiologically stable for over 3 h and synthesized urea at the rate of 1.15 mumol.min-1.g of liver-1 (15NH4(+)-perfused) or 0.41 mumol.min-1.g-1 ([15N]alanine-perfused). 2. The perfused liver was continuously monitored by 15N n.m.r. spectroscopy at 20.27 MHz for 15N. Well-resolved 15N resonances of precursors and intermediates of the urea cycle, present at tissue concentrations of 0.2-3.0 mumol/g, were observed from the intact liver in 5-40 min of acquisition. Key metabolites in liver extract and the final perfusion medium were analysed by n.m.r. and by biochemical assays to determine fractional 15N enrichment and the total 15N recovery. 3. In 15NH4(+)-perfused liver (n = 6), 15N incorporation into glutamate and alanine (1.0-1.3 mumol/g), as well as progressive formation of [15N2]urea, was observed during the first 2 h of perfusion. In the second and third hour, hepatic concentrations of [omega-15N]citrulline and [omega, omega'-15N]argininosuccinate increased to n.m.r.-detectable levels (0.3-0.9 mumol/g). The [15N]aspartate pool was large in the absence of added ornithine, but on its addition was rapidly incorporated into argininosuccinate (n = 3). 4. In [15N]alanine-perfused liver, major metabolites were [15N]glutamate, [gamma-15N]glutamine and [15N]urea. Urea-cycle intermediates were undetectable. 5. The results suggest that, in intact liver provided with excess ammonia, low concentrations of cytosolic argininosuccinate synthetase and argininosuccinate lyase limited the rate of metabolite flux in the urea cycle. By contrast, in alanine-perfused liver at a physiological rate of urea synthesis, mitochondrial carbamoylphosphate synthetase was rate-limiting. 6. The potential utility of 15N n.m.r. for study of metabolite channelling through urea-cycle enzymes in intact liver is discussed.


1992 ◽  
Vol 263 (2) ◽  
pp. E400-E415 ◽  
Author(s):  
A. Mari

A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two-compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis.


2004 ◽  
Vol 287 (3) ◽  
pp. C594-C602 ◽  
Author(s):  
Christopher M. Rembold ◽  
Robert L. Wardle ◽  
Christopher J. Wingard ◽  
Timothy W. Batts ◽  
Elaine F. Etter ◽  
...  

Serine 19 phosphorylation of the myosin regulatory light chain (MRLC) appears to be the primary determinant of smooth muscle force development. The relationship between MRLC phosphorylation and force is nonlinear, showing that phosphorylation is not a simple switch regulating the number of cycling cross bridges. We reexamined the MRLC phosphorylation-force relationship in slow, tonic swine carotid media; fast, phasic rabbit urinary bladder detrusor; and very fast, tonic rat anococcygeus. We found a sigmoidal dependence of force on MRLC phosphorylation in all three tissues with a threshold for force development of ∼0.15 mol Pi/mol MRLC. This behavior suggests that force is regulated in a highly cooperative manner. We then determined whether a model that employs both the latch-bridge hypothesis and cooperative activation could reproduce the relationship between Ser19-MRLC phosphorylation and force without the need for a second regulatory system. We based this model on skeletal muscle in which attached cross bridges cooperatively activate thin filaments to facilitate cross-bridge attachment. We found that such a model describes both the steady-state and time-course relationship between Ser19-MRLC phosphorylation and force. The model required both cooperative activation and latch-bridge formation to predict force. The best fit of the model occurred when binding of a cross bridge cooperatively activated seven myosin binding sites on the thin filament. This result suggests cooperative mechanisms analogous to skeletal muscle that will require testing.


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