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PubMed2002

A quantitative model for neutrophil response and delayed-type hypersensitivity reaction in rats orally inoculated with various doses of Salmonella Enteritidis.

Our aim was to investigate the quantitative relationship between inoculation doses and physiological responses to infection by Salmonella enterica serovar Enteritidis. Rats were orally inoculated with 10-10(9) c.f.u. of S. Enteritidis and monitored for 6 days. Neutrophil and delayed-type hypersensitivity (DTH) responses were assessed, and the spleens were analyzed for the pathogen. The experimental data were analyzed by a mathematical model for the host response to salmonella infection, which is based on the assumptions that: (i) the number of pathogens in the inoculum is Poisson distributed, (ii) any cell that is inoculated can multiply and form a clone to infect the animal, (iii) the probability of infection by any cell of the pathogen is independent of the number of cells ingested, and (iv) the magnitude of the immune response increases with dose, but eventually saturates to a maximum level. The probability of infection assessed by the DTH response is 7.5 x 10(-3)/c.f.u. of the inoculum (confidence interval 5.1 x 10(-5), 1.2 x 10(-2)). When five S. Enteritidis independently initiated the infection, the DTH response to the resulting clones of the salmonellae saturated to the maximum level. The probability of infection assessed by the neutrophil response is 3.4 x 10(-4)/c.f.u. (1.0 x 10(-4), 6.8 x 10(-4)). The response saturated when six S. Enteritidis independently initiated the infection. The probability of infection assessed by the analysis of spleens is 1.2 x 10(-3)/c.f.u. (4.1 x 10(-4), 2.6 x 10(-3)). We conclude that at low inocula, infections are initiated by very small numbers of bacteria. The magnitude of the immune responses is similar whether only a few or a larger number of bacteria initiated the infection.

Animals↗
PubMed1987

Absorption of protein via the intestinal wall. A quantitative model.

Intact, biological active insulin and pancreatic RNase can be absorbed from the intestinal lumen into the blood circulation. The absorption is dependent on the addition of bile acid (sodium cholate) and proteinase inhibitor. The quantitative absorption of insulin and pancreatic RNase has been demonstrated in an in situ model. The amount of insulin absorbed after 30 min from the ileum to the mesenteric vein was 0.025% of the initial amount. Sodium cholate (10 mg/ml) and 3000 KIU/ml aprotinin enhanced this absorption by 30 times. The amount of pancreatic RNase which was absorbed from the ileum to the blood was 0.002% of the initial amount during 30 min. Sodium cholate (10 mg/ml) and 3000 KIU/ml aprotinin increased the absorption by a factor of 200. No damage occurred to the intestine during the experimental procedures. The sieving characteristics of the intestinal wall were not altered by the presence of sodium cholate and proteinase inhibitor in the intestinal lumen. These results suggest that sodium cholate and proteinase inhibitors can facilitate the absorption of intact, biologically active proteins across the intestinal wall.

Animals↗
PubMed1989

Quantitative model of mononuclear phagocyte lineage proliferation in murine bone marrow.

An analysis and a synthesis of published and original experimental evidence have been performed with a view to providing a global qualitative and quantitative description of the proliferation of monocyte precursors in murine bone marrow. Two versions of a mathematical model are proposed. The first consists of two dividing generations of granulocyte-macrophage colony-forming cells (GM-CFC) and two dividing generations of macrophage colony-forming cells (M-CFC), differentiating into promonocytes (PM) and then into monocytes (MC). The second version consists of two generations of GM-CFC and three generations of M-CFC, followed by PM and MC. Both are compatible with experimental data, and further evidence is needed to elaborate a unique representation. The kinetic constants have been taken from published material whenever possible and estimated from available data and model kinetics in the case of unknown quantities. The models are applied to a pulse labeling assay, and calculated labeled subpopulations are compared with experimental values. Agreement is satisfactory for both versions in the case of MC, while a calculated PM labeling index falls more rapidly than the experimental values. However, inconsistency also exists between PM and MC experimental data.

Animals↗
PubMed2006

Quantitative model of Ras-phosphoinositide 3-kinase signalling cross-talk based on co-operative molecular assembly.

In growth-factor-stimulated signal transduction, cell-surface receptors recruit PI3Ks (phosphoinositide 3-kinases) and Ras-specific GEFs (guanine nucleotide-exchange factors) to the plasma membrane, where they produce 3'-phosphorylated phosphoinositide lipids and Ras-GTP respectively. As a direct example of pathway networking, Ras-GTP also recruits and activates PI3Ks. To refine the mechanism of Ras-PI3K cross-talk and analyse its quantitative implications, we offer a theoretical model describing the assembly of complexes involving receptors, PI3K and Ras-GTP. While the model poses the possibility that a ternary receptor-PI3K-Ras complex forms in two steps, it also encompasses the possibility that receptor-PI3K and Ras-PI3K interactions are competitive. In support of this analysis, experiments with platelet-derived growth factor-stimulated fibroblasts revealed that Ras apparently enhances the affinity of PI3K for receptors; in the context of the model, this suggests that a ternary complex does indeed form, with the second step greatly enhanced through membrane localization and possibly allosteric effects. The apparent contribution of Ras to PI3K activation depends strongly on the quantities and binding affinities of the interacting molecules, which vary across different cell types and stimuli, and thus the model could be used to predict conditions under which PI3K signalling is sensitive to interventions targeting Ras.

Animals↗
PubMed2001

Quantitative modeling of perception and production of time intervals.

The accurate perception/production of durations in the seconds and minutes range is important in a number of everyday activities, but the lack of direct experimental evidence on the neural circuits that could be involved has precluded the detailed elucidation of the underlying physiological mechanisms. We show, using a basic biophysical model of a timekeeping system and experimental data on time intervals produced or estimated under different conditions, that experimental values, variability, and distributions can be quantitatively explained in terms of a background synaptic activity such as that generated by attention. The model provides a plausible neural substrate for encoding time intervals, and the findings suggest how it may interplay at the single neuron level with the attentional system, to elaborate a subjective representation of the elapsing time.

Humans↗
PubMed1983

Mouse sciatic nerve regeneration through semipermeable tubes: a quantitative model.

The regeneration of transected mouse sciatic nerves using semipermeable acrylic copolymer tubes to enclose both stumps has been qualitatively assessed from 1 to 30 weeks post-operative. Quantitative morphometric analysis of electron micrograph montages of complete transverse sections of the segment regenerated between stumps has permitted determinations of the percents of total area occupied by the various tissue constituents--blood vessels, epineurium, perineurium, endoneurium, myelinated axon/Schwann cell units, and unmyelinated axon/Schwann cell units. Significant differences were found in the total cross-sectional area of segments regenerated through tubes of 1.0 mm versus 0.5 mm internal diameters. Segments regenerated with the distal stump inserted in the tube contained significantly greater percentages of neural units and were significantly larger at 8 weeks post-operative compared to segments regenerated for 9-10 weeks with the distal stump avulsed. The morphometric method permits rapid quantitation of sizeable electron micrograph montages which at 1300 X permit all types of tissue components, including the unmyelinated axons, to be visualized.

Acrylic Resins↗
PubMed1996

Logarithmic quantitation model using serum ferritin to estimate iron overload in secondary haemochromatosis.

Nineteen children and adolescents receiving repeated transfusions and subcutaneous desferrioxamine treatment were investigated in an attempt to quantitate iron overload non-invasively. Before patients were started on desferrioxamine individual relationships were correlated for 12 to 36 months between transfused iron, absorbed iron estimated gastrointestinally, and increasing serum ferritin concentrations. Patients with inflammation, increased liver enzymes, or haemolysis were excluded from analysis. The relationship between the variables could be described by a logarithmic regression curve (y = transfused iron [plus eventually gastrointestinally absorbed iron] = iron overload = a+b log [x = serum ferritin]) for each individual patient. All patients showed close correlation (R2) between x and y (median R2 of 0.909, 0.98, and 0.92 in thalassaemia, aplastic anaemia, and sickle cell anaemia patients, respectively). When started on desferrioxamine, current serum ferritin concentrations were used to derive the iron overload from each individual regression curve. The derived estimated iron overload ranged from 0.6 g to 31 g. Left ventricular dilatation was observed in three patients with beta thalassaemia and in one patient with aplastic anaemia with median iron overload of 20.7 (14.1-31.3) g and 24.0 g respectively. Hypothyroidism was found in four patients with beta thalassaemia and one patient with aplastic anaemia with iron overload between 14.7 (6.8 and 26.1) g and 15.1 g respectively. Human growth hormone deficiency was detected in three patients with beta thalassaemia with an iron overload of 4.2 (3.5-6.8) g; all three patients had excellent desferrioxamine compliance.

Adolescent↗
PubMed1988

A new quantitative model of total endolymph flow in the system of semicircular ducts.

1. A new concept of endolymph flow in the vertebrate vestibular system is presented. This approach describes quantitatively the flow in the entire system of three semicircular ducts interconnected by the utriculus and the crus commune. This approach is quite distinct from the classical theory in which the labyrinth is generally conceived to consist of three separate duct circuits. 2. The present approach shows the following set of distinct differences to the classical view: (a) In a labyrinth composed of three ducts perpendicular to each other the flow is non-zero in the other ducts when the labyrinth is rotated in the plane of a particular duct. (b) In a labyrinth with two equal ducts and with the duct planes under approximately 73 degrees the flow in one duct is zero when the rotation takes place in the plane of the other duct. Previous measurements of duct angles reflect this value surprisingly well. An obtuse or sharp angle between duct planes can lead to better performance of a particular labyrinth because the "external impulses" in the different ducts may amplify or compensate each other. (c) The behaviour of the flow in the entire labyrinth is a non-linear function of direction or rotation (cf. points (d), (e]. (d) Six time constants for the entire labyrinth can be distinguished (three long, three short); the flow in a particular duct is composed of six terms with these time constants. The composition of this flow and thus the relative importance of the terms depends on the positioning of the labyrinth with respect to the rotation vector. (e) The time constants also depend, for different labyrinths, on a shared influence of the dimensions of the ducts and the elastic properties of all three cupulae. (f) The forces in a particular duct depend also on the amount of motion the fluid will acquire in the other ducts. (g) The sensitivity of a particular duct depends also on the dimensions of the other parts in the vestibular system. 3. Equations for a system consisting of two ducts and for the classical single duct system are also given. Both systems are special cases of the three-duct system. The single duct equations are equivalent with equations given by Oman (1980) and Oman et al. (1987) which include the contribution of a wide utriculus. 4. The present theory of endolymph flow is mainly supported by the outcome of previously performed experiments concerning time constants and rotation of human subjects in different planes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Application of a quantitative model to differentiate benign from malignant breast lesions detected by dynamic, gadolinium-enhanced MRI.

Both benign and malignant breast lesions may exhibit intense contrast enhancement when imaged using gadolinium-enhanced MRI. We propose a quantitative approach for fitting dynamic signal intensity (SI) data that may distinguish benign from malignant lesions. We studied 78 lesions in 75 women (18 malignancies, 16 fibroadenomas, and 44 other benign breast lesions) to determine the potential of this model for decreasing false-positive MR results. Twenty-eight lesions showed no enhancement; all were benign. One lesion showed a complex pattern not amenable to region-of-interest analysis and was considered a false positive. SI versus time data for the remaining 49 lesions were fit to the proposed model. We found that one parameter, M, the normalized slope of the SI enhancement profile evaluated at half the maximal signal intensity, seemed to be highly correlated with malignancy and offered improved discrimination between malignant and benign lesions compared to a previously published two-point slope method.

Breast Diseases↗
PubMed2006

Angiogenesis inhibitors in a murine neuroblastoma model: quantitative assessment of intratumoral blood flow with contrast-enhanced gray-scale US.

PURPOSE: To quantify intratumoral ultrasonographic (US) contrast agent flow at gray-scale imaging as a measure of functional tumor vascularity in an orthotopic murine neuroblastoma model treated with angiogenesis inhibitors. MATERIALS AND METHODS: After Institutional Animal Care and Use Committee approval, retroperitoneal neuroblastomas were established in mice with unmodified NXS2 cells (n = 13) or with cells engineered to overexpress an angiogenesis inhibitor--either tissue inhibitor of matrix metalloproteinase-3 (n = 22) or a truncated soluble form of the vascular endothelial growth factor receptor-2 (truncated soluble fetal liver kinase-1; n = 13). When tumors were approximately 600 mm3, contrast material-enhanced gray-scale US was performed, and the imaging was recorded on cine clips. Regions of interest within tumors were analyzed off-line to determine postcontrast change in signal intensity (SI) from baseline to initial peak (deltaSI), rate of SI increase from baseline to initial peak (RSI), and contrast material washout. The Mann-Whitney test was used to evaluate potential differences in these US parameters between treatment groups. The mean intratumoral endothelial cell (CD34) and pericyte (smooth muscle actin [SMA]) counts at immunohistochemical analysis were also evaluated. Spearman correlation test was used to investigate the relation between US parameters and these histologic markers. RESULTS: The deltaSI and RSI were lower in tumors overexpressing an angiogenesis inhibitor than in control tumors (all P < .03). Contrast material washout did not differ between groups. For the entire cohort, the RSI correlated with the immunohistochemical assessment of tumor vascularity (SMA and CD34 counts) (P < .003). CONCLUSION: Quantification of intratumoral flow of a US contrast agent at gray-scale imaging shows promise for monitoring tumor vascular response to antiangiogenic therapy.

Albumins↗
PubMed1984

A quantitative model for the measurement of cerebral vascular extraction fraction in vivo following intravenous injection: simulation studies.

A mathematical method has been developed by which the cerebral vascular extraction fraction of flow- and diffusion-limited tracers injected intravenously can be measured quantitatively. Successive injections of three tracers are required: a test tracer such as 15O-labeled water; a completely diffusible tracer as a reference tracer and also as a flow tracer; and a tracer for cerebral blood volume (CBV). The arterial tracer concentration curves and total integrated head counts of the test and reference tracers, as well as CBF and CBV values, are required to calculate the extraction fraction. No calibration is required between the head counts and arterial curves. No decay correction of the head and arterial activity is required, because isotopic decay is explicitly included in the equation. The effect of nonextracted test tracer can be corrected. Simulation studies have shown that the calculated extraction fraction values are not sensitive to measurement error in CBF, CBV, partition coefficient, change in measurement time, or time shift effect between the arterial and head data. If there is mixing of two different tissues in the brain, the calculated extraction fraction values are close to the weighted mean values of extraction fraction by relative weight of the tissues. It is concluded that it is possible to apply this method to human studies with a positron emission tomograph scanner and to animal studies with external coincidence detectors.

Antipyrine↗
PubMed2005

A quantitative model for assessing community dynamics of pleistocene mammals.

Previous studies have suggested that species responded individualistically to the climate change of the last glaciation, expanding and contracting their ranges independently. Consequently, many researchers have concluded that community composition is plastic over time. Here I quantitatively assess changes in community composition over broad timescales and assess the effect of range shifts on community composition. Data on Pleistocene mammal assemblages from the FAUNMAP database were divided into four time periods (preglacial, full glacial, postglacial, and modern). Simulation analyses were designed to determine whether the degree of change in community composition is consistent with independent range shifts, given the distribution of range shifts observed. Results indicate that many of the communities examined in the United States were more similar through time than expected if individual range shifts were completely independent. However, in each time transition examined, there were areas of nonanalogue communities. I conducted sensitivity analyses to explore how the results were affected by the assumptions of the null model. Conclusions about changes in mammalian distributions and community composition are robust with respect to the assumptions of the model. Thus, whether because of biotic interactions or because of common environmental requirements, community structure through time is more complex than previously thought.

Animals↗
PubMed2004

Quantitative models of Pavlovian conditioning.

Over the last few years, research on learning and memory has become increasingly interdisciplinary. In the past, theories of learning, as a prerogative of psychologists, were generally formulated in purely verbal terms and evaluated exclusively at the behavioral level. At present, scientists are trying to build theories with a quantitative and biological flavor, seeking to embrace more complex behavioral phenomena. Pavlovian conditioning, one of the simplest and ubiquitous forms of learning, is especially suited for this multiple level analysis (i.e., quantitative, neurobiological, and behavioral), in part because of recent discoveries showing a correspondence between behavioral phenomena and associative properties at the cellular and systems levels, and in part because of its well established quantitative theoretical tradition. The present review, examines the mayor quantitative theories of Pavlovian conditioning and the phenomena to which they have been designed to account. In order to provide researchers from different disciplines with a simple guideline about the rationale of the different theoretical choices, all the models are described through a single formalism based on the neural network connectionist perspective.

Animals↗
PubMed1995

A quantitative model of autoimmune disease and T-cell vaccination: does more mean less?

According to a simple mathematical model, the activated effector T cells that cause an autoimmune disorder can also cure the disease if administered in large doses. This prediction has been tested in the nonobese diabetic (NOD) mouse model and demonstrates that administration of intermediate doses of a diabetogenic T-cell clone caused early hyperglycemia, whereas a higher dose cured the disease. As discussed here by Lee Segel and colleagues, the proposed application of T-cell vaccination to treat clinical disease obliges immunologists to consider the quantitative complexities of regulation.

Animals↗
PubMed2004

Quantitative modelling of interaction of propafenone with sodium channels in cardiac cells.

A mathematical model of the interaction of propafenone with cardiac sodium channels is based on experimental data that demonstrate use-dependent effects of the drug. The Clancy-Rudy model is applied to describe Na-channels in absence of the drug. The values of rate constants of the drug-receptor reaction are fitted to experimental data by iterative computer simulations using a genetic algorithm. The model suggests the following interpretation of available experimental results: First, drug molecules have access to the binding sites predominantly in the inactivated states. Secondly, the biphasic development of the block during depolarisation is consistent with a rapid increase due to drug binding in the fast inactivated state (rate constants k(on) = 645 micromol(-1) l s(-1), k(off) = 16.21 s(-1)) and a slow increase due to binding in the intermediate inactivated state (rate constants approximately 100-fold lower), followed by transition to the drug-occupied slow inactivated state (rate constants 0.784 and 0.921 s(-1)). Thirdly, the observed biphasic time course of recovery of I(Na) from block following restoration of the resting voltage results from simultaneous relief of block from the channels residing in the intermediate and slow inactivated states. Fourthly, the accumulation of blocked channels in the slow inactivated state is responsible for the observed use-dependent effects. Fifthly, when incorporated into a quantitative description of the electrical activity of a ventricular cell, the model predicts that propafenone (0.2 micromol l(-1)) effectively suppresses premature excitations, leaving the regular action potentials nearly unaffected.

Algorithms↗
PubMed2000

Quantitative model studies on the formation of aroma-active aldehydes and acids by strecker-type reactions.

Application of aroma extract dilution analysis on the volatiles formed by reacting glucose and L-phenylalanine (30 min, 100 degrees C) revealed the Strecker aldehyde, phenylacetaldehyde (PA), and, in addition, phenylacetic acid (PAA) as the two key odorants among the volatiles formed. Quantitative measurements on alpha-dicarbonyl formation revealed that the 3-deoxyosone and glyoxal were formed as the first prominent sugar degradation products, whereas 2-oxopropanal became predominant after approximately 4 h at 100 degrees C. Among the four alpha-dicarbonyls analyzed, 2-oxopropanal proved to be the most effective in generating PA as well as PAA from phenylalanine, but the reaction parameters significantly influenced the ratio of both odorants; for example, at pH 3.0 the ratio of PA to PAA was 3:1, whereas at pH 9.0 the ratio was 1:5. Furthermore, in the presence of oxygen and copper ions the formation of the acid was further increased. 3-Deoxyosone and glucosone were found to be effective precursors of phenylacetaldehyde, but neither was very effective in acid generation. On the basis of the results, a new oxygen-dependent formation pathway of the Strecker reaction is proposed.

Acetaldehyde↗