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PubMed1997

Comparison of the fixation of subcapital femoral neck osteotomies with absorbable self-reinforced poly-L-lactide lag-screws or metallic screws in sheep.

Seven subcapital femoral osteotomies of adult sheep were each fixed with two absorbable self-reinforced poly-L-lactide lag-screws, and seven other osteotomies were each fixed with two metallic cancellous bone screws. At 3 and 12 weeks, radiographs were taken and callus formation, displacement, and union were evaluated. At 12 weeks, the animals were killed and strength measurements were carried out. According to the radiographs, union was achieved in six of seven osteotomies in both groups, while after 3 weeks one fixation in both the group treated with absorbable screws and the group treated with metallic screws had failed. There were no statistical differences between the groups with respect to callus formation or displacement. Regarding the strength of the osteotomized bones, at 12 weeks there were no statistically significant differences in the load-carrying capacity between the bones fixed with self-reinforced poly-L-lactide screws and those fixed with metallic screws. These results showed that self-reinforced poly-L-lactide screws, which have been used successfully in fractures and osteotomies in cancellous bone, are strong enough to support this more demanding fixation of weight-bearing bones.

Animals↗
PubMed1998

Effects of injurious compression on matrix turnover around individual cells in calf articular cartilage explants.

The effects of mechanical injury on the metabolism of cartilage matrix are of interest for understanding the pathogenesis of osteoarthrosis and the development of strategies for cartilage repair. The purpose of the present study was to examine the effects of injury on matrix turnover in a calf articular cartilage explant system for which the effects of mechanical loading on cell activity and the cell-mediated pathways of matrix metabolism are already well characterized. New methods of quantitative autoradiography were used in combination with established biochemical and biomechanical techniques for the analysis of cell and matrix responses to acute mechanical injury, with particular attention to the processes of localized matrix turnover in the cell-associated matrices of individual chondrocytes. Matrix deposition and turnover around cells in control explants was spatially dependent, with the highest rates of proteoglycan deposition and turnover and the lowest rates of collagen deposition (as indicated by [3H]proline autoradiography) occurring in the pericellular matrix. Injurious compression was associated with (a) an abrupt decrease in the tensile load-carrying capacity of the collagen matrix, apparently associated with mechanical failure of the tissue, (b) a considerable but subtotal decrease in cell viability, marked by the emergence of an apparently inactive cell population interspersed within catabolically active but abnormally large cells, and (c) sustained, elevated rates of proteoglycan turnover, particularly in the cell-associated matrices of apparently viable cells, which involved the increased release of aggregating species in addition to a spectrum of degradation fragments that were also in controls. These results may represent an in vitro model for the responses of chondrocytes and the cartilage extracellular matrix to mechanical injury.

Animals↗
PubMed2006

Forces involved in lower limb lengthening: an in vivo biomechanical study.

Despite improvements in surgical techniques for limb-lengthening procedures, the complication rate remains high. Bone fixators must cope with the forces involved during treatment, providing sufficient strength to maintain integrity of the limb in the course of lengthening, while permitting some "micromotion" across the bone gap that could enhance healing during the final phase of bone consolidation. This study reports on the forces generated during limb lengthening in the distraction and consolidation phases. Forces were measured on 19 patients between 6 and 22 years of age with 10 femoral and 11 tibial lengthenings of 1 mm/day by means of a monotube external fixator, fitted diaphysially, and modified to measure tension and weight-bearing forces. Peak force measured during the lengthening period amounted to about 14 N/kg of body mass. Generally, distraction forces leveled off at between 8 and 10 N/kg of body mass. During the consolidation period, the average force carried by the fixator dropped from 55% initially to about 10% of the force transmitted to the ground, consistent with increased load carrying capacity of the bone as healing progressed. Studying the forces involved in limb lengthening is important to gain knowledge of the forces required to overcome the resistance offered by the tissues that bridge the osteotomy site, to understand the biology of distraction osteogenesis and histiogenesis across the regenerate over time, and to provide scientific guidelines for frame removal.

Adolescent↗
PubMed2000

Self-organization, scale and stability in a spatial predator-prey interaction.

Simple predator-prey models often predict extreme instability in interactions where the prey are depressed well below their carrying capacity. Although the behaviour of some laboratory systems conforms to this pattern, field and mesocosm studies generally show prolonged co-existence of prey and predator. Prominent among the possible causes of this discrepancy are the effects of spatial heterogeneity. In this paper we show that both discrete and continuous representations of the spatial Rosenzweig-McArthur model with immobile prey can be stabilized by self-organized prey heterogeneity. This concordance of behaviour closely parallels that which we have previously established in the context of invasion waves. We use the continuous model variant to calculate the characteristic spatial scales of the self-organized structures. The discrete variant forms the basis of a simulation study demonstrating the variety of stable structures and elucidating their relation to the history of the system. We note that all stable prey distributions take the form of a network of occupied patches separated by prey-free regions, and liken the process which generates such assemblages to the formation of a landscape mozaic.

Animals↗
PubMed2001

Perflubron emulsion reduces inflammation during extracorporeal circulation.

The recovery from cardiac surgery and cardiopulmonary bypass can be complicated by an acute inflammatory response. Circulating blood through an extracorporeal circuit (ECC) contributes to this complication. Perfluorocarbon-based blood substitutes (PFCs) are under investigation for use as a component of the ECC "prime" solution, because PFCs increase the oxygen-carrying capacity of the diluted blood. Some PFCs may provide the additional benefit of attenuating the ECC-induced inflammatory response. Earlier, we reported that perflubron emulsion (PFE, Alliance Pharmaceutical Corp.) reduced neutrophil (PMN) activation in vivo. However, the potential of PFE to reduce ECC-induced PMN activation has not been investigated. In this study, we used a small-scale ECC model to quantify the extent of PMN activation during circulation and to examine if PFE treatment attenuated PMN activation. ECC circuits were filled with a mixture of blood and Plasmalyte. Two groups were studied: an untreated group containing blood plus PlasmaLyte and a treated group in which some of the Plasmalyte was substituted with PFE (4.5 g/100 ml). Hematology and measures of whole blood PMN activation were made from blood samples taken periodically throughout the 120-min ECC circulation period. We found, for the untreated group, a significant decrease in the number of circulating PMNs and an increase in PMN activation with time. PMN activation was demonstrated as a significant increase in the expression of the PMN adhesion protein CD11b (P < 0.05) and an increase in PMN oxygen free radical production (reactive oxygen species (ROS)). After 120 min of circulation, the PMNs remained capable of a significant response to a second inflammatory stimulus, but PFE treatment significantly attenuated the fMLP-induced increase in PMN ROS at t = 120 min (P < 0.05). These results suggest that PFE may have dual utility in cardiac surgery, to increase oxygen delivery and to serve as an antiinflammatory agent.

Animals↗
PubMed1994

Dormancy, regression, and recurrence: towards a unifying theory of tumor growth control.

In several recent publications, mathematical models of autocrine-paracrine and autocrine-paracrine-endocrine controls of growth in both homogeneous and heterogeneous tumor populations were developed (Michelson & Leith, 1991, Bull. math. Biol. 53, 639-656; 1992a, Proc. Third Int. Conf. Comm. Control, pp. 481-490; 1992b, Bull, math. Biol. 55, 993-1011). For the homogeneous case, a generic tumor was modeled as a single, growing population using the Verhulst equation of logistic growth. The heterogeneous tumor was modeled as a pair of populations, one proliferating and one quiescent. Mitogenic signals were represented as modifications to the Malthusian growth parameters, and adaptational signals were represented as modifications to the logistic carrying capacities. Interactions between populations were represented by competitive feedback and transition rates. In this paper a theory of growth control is proposed to determine whether tumor dormancy, regression, and recurrence can be explained by a more unifying theory of signal processing. The models developed earlier form the basis for this analysis. Dormancy is described as an equilibrium state from which tumors may re-emerge if that equilibrium is disrupted. The types of disruption in signal processing needed to induce recurrence are discussed with respect to surgery and wound healing. Based on this theory, it appears that sort of feedback between the host's ability to support the proliferating cells (adaptational signal processing) and the transition rates into and out of the proliferating and quiescent compartments must exist. A paradigm based on the development of hypoxia in a spherical tumor is proposed as that link.

Cell Differentiation↗
PubMed1995

Population dynamics of feline immunodeficiency virus within cat populations.

A deterministic model was constructed for studying the circulation of Feline Immunodeficiency Virus (FIV), a feline retrovirus homologous to Human Immunodeficiency Virus (HIV), within populations of domestic cats. The model has been tested with data generated by a long-term study of several natural cat populations. Simulations and a study of stability show that once introduced, the retrovirus is maintained within the population, with a stable equilibrium stage reached by both numbers of susceptible and infected individuals. An estimation of parameters indicates that the transmission rate is low and depends on the structure of the population. In addition, FIV has a low impact on the population in that the total number of cats at equilibrium when this virus is present is almost always equal to the habitat carrying capacity in the absence of the virus. Those results, in agreement with other observations, suggest that FIV originally arose in the distant past.

Animals↗
PubMed1997

On the evolution of density dependent dispersal in a spatially structured population model.

A simple metapopulation lattice model of two competing phenotypes is presented, where one phenotype reacts more sensitively to overcrowding by migrating to neighbouring local habitats. The sensitivity is formulated by means of a threshold density of the subpopulations, above which dispersal is triggered off. If this threshold density is not very far from the local carrying capacity, an increased mobility provides benefits on the metapopulation level. At a surprisingly small difference between migrational triggering thresholds, the phenotype of larger mobility (or lower threshold) squeezes out the less mobile one from the whole system in a wide parameter range. Evolutionary considerations give an optimal threshold level for our model metapopulation.

Animals↗
PubMed1997

Molecular complementarity I: the complementarity theory of the origin and evolution of life.

We assert that molecular complementarity is much more widespread than is commonly acknowledged in biological systems, if not actually ubiquitous. It creates the coupling necessary for non-equilibrium systems to form. It stabilizes aggregates against degradation, thereby increasing concentrations to levels adequate to foster the formation of prebiotic systems and represents the earliest form in which natural selection was manifested. Complementarity confers on all interacting parts of such systems in formation carrying capacity. RNA or DNA are not, therefore, necessary to the emergence of life, but represent specialized forms of complementary molecules adapted specifically to information storage and transmission. Non-genetic information exists in metabolic functions and probably preceded genetic information historically. Complementarity also provides the basis for homeostasis and buffering of such systems not only in a chemical, but also in structural and temporal terms. It provides a mechanism for understanding how new, emergent properties can arise, and a basis for the self-organization of systems. We demonstrate that such aggregates can have properties not predictable from their individual components, thus providing a means for understanding how new functions emerge during evolution. Selection is for modules rather than individual components. The formation of functional sub-systems that can then be integrated as modules greatly increases the probability of the emergence of life. The result of such modular evolution alters the standard view of evolution from a tree or bush-like image to an integrated network composed of alternating periods of integration (as molecules and molecular aggregates merge) and divergence (as molecules and aggregates undergo variations). This provides a mechanism for evolution by punctuated equilibria. Molecular complementarity puts strict limits on variations, however, preventing evolution from being random. The evolutionary, physiological and embryological consequences of this view of life are outlined, and various models and experiments described that further characterize it.

Animals↗
PubMed2000

Resource competition in stage-structured populations.

Two models are made to account for the dynamics of a consumer-resource system in which the consumers are divided into juveniles and adults. The resource grows logistically and a type II functional response is assumed for consumers. Resource levels determine fecundity and maturation rates in one model, and mortality rates in the other. The analysis of the models shows that the condition for establishment of consumers is that the product of per capita fecundity rate and maturation rates is higher than the product of juvenile and adult per capita decay rates at a resource level equal to its carrying capacity. This result imposes a minimal abundance of resource able to maintain the consumers. A second result shows an equilibrium stage structure, with a small instability when juveniles and adults mean saturation constants are different. The implications of these results for community dynamics are discussed.

Age Factors↗
PubMed2000

Extinction risk of a density-dependent population estimated from a time series of population size.

Environmental threats, such as habitat size reduction or environmental pollution, may not cause immediate extinction of a population but shorten the expected time to extinction. We develop a method to estimate the mean time to extinction for a density-dependent population with environmental fluctuation. We first derive a formula for a stochastic differential equation model (canonical model) of a population with logistic growth with environmental and demographic stochasticities. We then study an approximate maximum likelihood (AML) estimate of three parameters (intrinsic growth rate r, carrying capacity K, and environmental stochasticity sigma(2)(e)) from a time series of population size. The AML estimate of r has a significant bias, but by adopting the Monte Carlo method, we can remove the bias very effectively (bias-corrected estimate). We can also determine the confidence interval of the parameter based on the Monte Carlo method. If the length of the time series is moderately long (with 40-50 data points), parameter estimation with the Monte Carlo sampling bias correction has a relatively small variance. However, if the time series is short (less than or equal to 10 data points), the estimate has a large variance and is not reliable. If we know the intrinsic growth rate r, however, the estimate of K and sigma(2)(e)and the mean extinction time T are reliable even if only a short time series is available. We illustrate the method using data for a freshwater fish, Japanese crucian carp (Carassius auratus subsp.) in Lake Biwa, in which the growth rate and environmental noise of crucian carp are estimated using fishery records.

Animals↗
PubMed2002

Restoration of a functional open reading frame by homologous recombination between two adenoviral vectors.

In this study, we examined the ability of adenoviral (Ad) vectors to undergo homologous recombination. The lacZ gene was divided between two parental, first-generation vectors such that neither encoded a functional product but both shared 494 bp in common. The open reading frame could only be restored by homologous recombination. We observed beta-galactosidase activity only upon co-infection of both parental vectors and after the onset of viral DNA replication, creating a delay in expression of 24-36 hours in HeLa cells. At peak efficiency, this recombination vector system resulted in beta-galactosidase activity levels 100x above background and just 18x less than a conventional, first-generation vector in HeLa cells. After recombination, the resultant progeny vector genomes containing reconstituted expression cassettes were devoid of all viral genes and contained two packaging signals. These progeny genomes were efficiently packaged, could be separated from their parental vectors based on their lighter buoyant densities in CsCl gradients, and were subsequently used as functional gene transfer vectors. This novel recombination vector system should be useful for transferring large transgenes (because the carrying capacity of two Ad vectors can be exploited) or expressing any cytotoxic or Ad replication inhibitory protein (because the parental vectors exhibit no background expression).

Adenoviridae↗
PubMed1996

Red blood cell spacing in rat coronary capillaries during the cardiac cycle.

Theoretical studies have demonstrated a pronounced effect of red blood cell (RBC) spacing on tissue oxygen supply. Our objective was to collect data regarding RBC spacing and related linear capillary hematocrit (Hct) in rat coronary capillaries, from two distinct locations within the capillary bed (proximal and distal portions), in the subendo- and midmyocardium, during systole and diastole. Hearts were rapidly frozen in situ, and tissue sections were stained in order to distinguish capillaries in proximal and distal portions of the capillary bed, as well as the RBCs within them. Morphometric data were compared according to capillary type, cardiac region, and cardiac phase. Distal portions of the capillary bed had a significantly greater capillary Hct (p < 0.001) and significantly lower RBC spacing values (P < 0.01), compared to proximal portions, irrespective of cardiac phase or region. There was a greater frequency of RBC spacing values equal to O microns in systole compared to diastole (P < 0.001) and a greater frequency of RBC spacing values greater than 40 microns in proximal portions of the capillary bed compared to distal portions (P < 0.001). These results suggest that intracapillary resistance to O2 transport is reduced, and O2 carrying capacity of the blood increased, in distal portions of the capillary bed, where PO2 in the blood is lower.

Animals↗
PubMed1996

Antidotal effect of dihydroxyacetone against cyanide toxicity in vivo.

Potassium cyanide (CN) intoxication in mice was found to be effectively antagonized by dihydroxyacetone (DHA), particularly if administered in combination with another CN antidote, sodium thiosulfate. Cyanide-induced convulsions were also prevented by DHA treatment, either alone or in combination with thiosulfate. Injection (i.p.) of DHA (2 g/kg) 2 min after or 10 min before CN (s.c.) increased LD50 values of CN(8.7 mg/kg) by factors of 2.1 and 3.0, respectively. Treatment with a combination of DHA and thiosulfate after CN increased the LD50 by a factor of 2.4. Pretreatment with a combination of DHA and thiosulfate (1 g/kg) increased the LD50 of CN to 83 mg/kg. Administration of alpha-ketoglutarate (2.0 g/kg), but not pyruvate, 2 min after CN increased the LD50 of CN by a factor of 1.6. Brain, heart and liver cytochrome oxidase activities were also measured following in vivo CN treatment with and without DHA. Pretreatment with DHA prevented the inhibition of cytochrome oxidase activity by CN and treatment with DHA after CN accelerated the recovery of cytochrome oxidase activity, especially in brain and heart homogenates. DHA is a physiological agent and, therefore, could prove to be a safe and effective antidote for CN, particularly in cases of fire smoke inhalation in which a combination of CN and carbon monoxide is present. In these cases the normally used antidote, sodium nitrite, to induce methemoglobin so as to trap the CN, is contraindicated because some of the oxygen-carrying capacity of the blood will have already been diminished by carbon monoxide.

Animals↗
PubMed1994

The effect of scale dependent processes on kin selection: mating and density regulation.

Kin selection models describe fitness determining interactions that occur within small clusters of individuals often referred to as trait groups (Wilson, 1975). Because each individual influences not only its own fitness, but also the fitness of other members of the trait group, kin selection has both inter- and intra-group components (Hamilton, 1975; Wade, 1980). The importance of intergroup selection depends on the magnitude of inter-group differences in fertility and on the amount of genetic variation among trait groups. Migration and density regulation are likely to be important determinants of productivity and variation. Existing models integrate density regulation and migration structure into kin selection theory by applying carrying capacities or migration rates to trait groups. This requires that dispersal and density regulation both operate at the spatial scale of trait groups and excludes many cases of biological interest. I present a model that allows interaction, density regulation, and dispersion to operate over distinct spatial scales. The results of existing models can be retrieved as special cases of the general framework developed here. This model indicates that the appropriate scale for studying kin selection is determined by the spatial area over which the population is regulated. In effect, only a fraction of the total inter-trait group variance is available to intergroup selection. Processes that generate genetic variation over spatial scales larger than the "regulation scale" cannot aid the evolution of altruism. The analysis of a specific mating/migration model indicates how the various components of variation are determined by biological parameters such as migration rate. These results have important implications for the study of relatedness in natural populations.

Animals↗
PubMed1996

Competition in a spatially heterogeneous environment: modelling the risk of spread of a genetically engineered population.

In recent years regulations have been developed to address the risks of releasing genetically engineered organisms into the natural environment. These risks are generally considered to be proportional to the exposure multiplied by the hazard. Exposure is, in part, determined by the spatial spread of the organisms, a component of risk suited to mathematical analysis. In this paper we exampine a mathematical model describing the spread of organisms introduced into a hetereogeneous environment, focusing on the risk of spread and plausibility of containment strategies. Two competing populations are assumed, one the natural species and the other an engineered species or strain, both of which move randomly in a spatially heterogenous environment consisting of alternating favourable and unfavourable patches. The classical Lotka-Volterra competition model with diffusion is used. Analyses of the possible spread and invasion of engineered organisms are thus reduced to finding periodic travelling wave solutions to the model equations. We focus on whether a very small number of engineered organisms can spatially invade a natural population. Initially we investigate the problem for spatially periodic diffusion coefficients and demonstrate that, under the right circumstances and a large enough unfavourable patch, invasion does not succeed. However, if spatially periodic carrying capacities are assumed along with spatially varying diffusion rates, the situation is far more complex. In this case containment of the engineered species is no longer only a simple function of the unfavourable patch length. By using perturbation solutions to the nonuniform steady states, approximate invasion conditions are obtained.

DNA, Recombinant↗
PubMed1996

Travelling Wave Solutions for the Spread of Farmers into a Region Occupied by Hunter-Gatherers

The geographical spread of an initially localized population of farmers into a region occupied by hunter-gatherers is modelled as a reaction-diffusion process in an infinite linear habitat. Hunter-gatherers who come in contact with farmers are converted at rate e. Growth of initial farmers, converted farmers, and hunter-gatherers is logistic with intrinsic rates rf, rc, and r h. The carrying capacities of all farmers (i.e., initial and converted farmers combined) and hunter-gatherers are K and L. Individuals migrate at random, where the diffusion constant, D, is the same for all three groups. Under the above assumptions, we deduce the conditions under which wavefronts of initial or converted farmers are generated. Numerical work suggests that a travelling wave solution of constant shape always exists, comprising an advancing wavefront of all farmers and a retreating wavefront of hunter-gatherers. Linear analysis in phase space suggests that the speed is given by 2(Drf)1/2 or 2[D(r c+eL)]1/2, whichever is greater. The composition of the expanding distribution of all farmers appears to depend on the relative magnitude of rf versus rc+eL and of eK versus rh. A wavefront of initial farmers is not generated if rf rh. On the other hand, a wavefront of initial farmers is generated if rf>rc+eL. In this case, the waveform is peaked with leading and trailing edges that converge to 0 if eK rh so that there is substantial displacement of the indigenous hunter-gatherers by the initial farmers.

Journal Article↗
PubMed1999

A mathematical model with a modified logistic approach for singly peaked population processes.

When a small number of individuals of a single species are confined in a closed space with a limited amount of indispensable resources, breeding may start initially under suitable conditions, and after peaking, the population should go extinct as the resources are exhausted. Starting with the logistic equation and assuming that the carrying capacity of the environment is a function of the amount of resources, a mathematical model describing such a pattern of population change is obtained. An application of this model to a typical set of population records, that of deer herds by V. B. Scheffer (1951, Sci. Monthly 73, 356-362) and E. C. O'Roke and F. N. Hamerstrom (1948, J. Wildlife Management 12, 78-86), yields estimates of the initial amount of indispensable food and its availability or nutritional efficiency which were previously unspecified.

Animals↗