bluuebunny/crossref_metadata_2025 huggingface dataset:
MATHEMATICAL MODELLING OF CELLULAR RESPONSES TO EXTERNAL SIGNALS
Authors: HOLZHÜTTER HERMANN-GEORG , QUEDENAU JÖRN
Published: November 2004

An empirical mathematical model is proposed to describe the response (growth rate, metabolic activity etc.) of a cell population to various intensities of an external signal (hormone, antibody, pharmacon etc.). The model is based on the assumption that the signal causes the target system to pass consecutively through i=1, …, N distinct population states having response coefficients Ri. Describing the interaction of the system with the signal according to the rules of chemical kinetics by two phenomenological parameters (k - sensitivity, n - cooperativity index) one arrives at a series expansion for Ri which is linear in the Ri’s but nonlinear with respect to k and n (“R-decomposition”). The pattern of expansion coefficients Ri is characteristic of a given signal and can be used to reveal similarities in the responses of the cell population to various signals. A user-friendly microcomputer program has been developed to fit the model equation to experimental data by means of constraint nonlinear regression analysis and to determine all characteristic curve parameters (number and location of extremal values, inflection points etc.). The robustness and benefit of the model is demonstrated by applications to various types of “exotic” dose-reponse-curves obtained from a neutral-red assay of fibroblasts. Similarities between response curves are studied.
CONTROL THEORY OF CELL METABOLISM: TOWARDS MORE REALISTIC “NON-IDEAL” SYSTEMS
Authors: KHOLODENKO B.N. , CASCANTE M. , MOLENAAR D. , DEMIN O.V. , VAN DER GUGTEN A.A. , WESTERHOFF H.V.
Published: November 2004

Metabolic Control Analyses have led to significant advances in understanding the control of cell metabolism. However, the classical theory does not address all complex cases of the organization of cellular metabolism. Here the control theory is extended to include (i) pathways with high enzyme concentrations and moiety conservation and (ii) metabolic channelling in general. The new theory descends the microlevel of elemental steps into the reaction cycle of the enzymes and turns back to the macrolevel of complete enzyme reactions. We showed how the elemental control coefficients are related to the traditional flux control coefficients of the enzymes. We derived what the sums of the enzyme control coefficients are equal to in various non-ideal cell pathways.
PARAMETER OPTIMIZATION OF MEMBRANE CARRIER MODELS — AN APPROACH USING EVOLUTIONARY STRATEGIES
Authors: LENZ JÜRGEN
Published: November 2004

Membrane carries (symporters) performing active transport of solutes are molecular machines which transduce the energy stored in the electrochemical gradient of certain ions into osmotical work. Evolutionary strategies have been used to find optimal catalytic states of different kinetic models of membrane carriers. The analysis shows that in many cases there are several nearly optimal solutions to a given quality function. In general, this is because dissociation constants compensate for rate constants and because the maxima of the quality functions are usually flat with respect to at least some parameters. The number of solutions increases with increasing model complexity. The advantage of kinetic complexity with respect to protein evolution is discussed. Symmetric solutions frequently appear even under asymmetric conditions in the environment. An attempt is made to compare the results of the theoretical analysis with experimental data of the rabbit intestinal Na +/glucose-symporter.
DYNAMIC ASPECTS OF CASCADE-TYPE METABOLIC REGULATION
Authors: MOLENAAR DOUWE , KHOLODENKO BORIS N. , VAN HEESWIJK WALLY C. , WESTERHOFF HANS V.
Published: November 2004

Cascade-type regulation, where certain enzymes in response to physiological signals modify the activity of other enzymes by covalent modification, is found in many organisms. We study the covalent regulation of glutamine synthetase which is involved in ammonia fixation in the bacterium Escherichia coli. In this paper we pose the question whether this type of regulation of glutamine synthetase has, under certain growth conditions an advantage over other types of regulation, e.g., allosteric regulation. We propose that the relatively slow dynamics of cascade-type regulation has an evolutionary advantage under conditions of fluctuating ammonia concentrations.
CONTROL ANALYSIS OF METABOLIC SYSTEMS CONSISTING OF UNI- AND/OR MULTIFUNCTIONAL UNITS: APPLICATION TO MODULAR SYSTEMS AND SLIPPING ENZYMES
Authors: SCHUSTER STEFAN , KAHN DANIEL , WESTERHOFF HANS V.
Published: November 2004

We present a quantitative method based on Metabolic Control Analysis that makes possible to subdivide large metabolic systems into modules and to integrate the information concerning the flux response of these modules so as to yield understanding of the control structure in terms of the mutual regulation of the modules. This work generalizes previous analyses of overall control properties in that it considers multiple fluxes to connect the modules and reaction networks of any complexity. The approach is applied to slipping enzymes.
MODELLING SYNERGISTIC EFFECTS OF TWO TOXIC AGENTS IN THE HONEYBEE
Authors: CHALVET-MONFRAY KARINE , BELZUNCES LUC P. , COLIN MARC E. , FLÉCHÉ CÉCILE , SABATIER PHILIPPE
Published: November 2004

In previous experiments, a synergistic lethal effect on the honeybee has been demonstrated with two toxic agents: deltamethrin and prochloraz. The toxic agents were applied simultaneously or sequentially. Deltamethrin is metabolized by esterase and by cytochrome P-450-dependent monooxygenase. Prochloraz is a potent competitive inhibitor of cytochrome P-450. An attractive hypothesis explaining this synergic toxicity is that the persistence of deltamethrin is due to inhibition of the oxidative metabolism of deltamethrin by prochloraz. We tested this hypothesis using a mathematical model. A compartmental model in continuous time was constructed to represent this synergy by analyzing the degradation of toxic agents. This pharmacokinetic model was based on differential equations, using numerical resolution and Runge-Kutta’s integration method. When applied to a mixture of toxic agents, this model implies that the cumulative mortality of both compounds might be delayed compared to the mortality from treatment with toxic agents used separately. The hypothesis of metabolic synergy is compatible with experimental data only if the half-life of deltamethrin is short. The data from the model and the experimental data, diverged when deltamethrin was administered before prochloraz, which suggests that the phenomenon is more complex than expected.
MODELLING FOOD PREFERENCES AND VIABILITY CONSTRAINTS
Authors: KASTNER-MARESCH ALOIS , KŘIVAN VLASTIMIL
Published: November 2004

Differential inclusions arising in population biology are analysed and a numerical approach to solve the corresponding initial value problems is proposed. These differential inclusions originate from optimal myopic strategies and from projecting differential equations onto a viability set. We show that such differential inclusions may piecewise be considered either as ordinary differential equations or as differential-algebraic equations with Index 2. The numerical method is based on this observation. Simulations for one population of predators feeding on two populations of prey and for a system of two competing populations whose growth is constrained by a limited resource are given.
AN ABSTRACT DIFFERENTIAL EQUATION ARISING FROM CELL POPULATION DYNAMICS
Authors: ARINO OVIDE , SÁNCHEZ EVA
Published: November 2004

We provide an analysis of the stability and bifurcation properties of the solutions of an abstract differential nonlinear equation arising from cell population dynamics. The work surveyed here stems from a remark we made with respect to these equations: that it is possible to associate to any of them a delay differential equation on an infinite dimensional vector space. Perturbation theory for nonlinear equations similar to the one known for delay differential equations on finite dimensional spaces could possibly yield the same results as for those equations.
CHEMOSTAT EQUATIONS FOR A PREDATOR-PREY CHAIN WITH DELAYED NUTRIENT RECYCLING
Authors: BERETTA E. , FERGOLA P. , TENNERIELLO C.
Published: November 2004

The problem of the equilibrium stability for the chemostat equation is considered in the special case of a biotic species feeding on one limiting nutrient and predated by another biotic species. Both the biotic species through the decomposition process can return with delay to the chemostat fraction of dead biomass as new nutrient. The delay kernels of nutrient recycling are assumed to be general L2(0, +∞) non-negative functions which admit up to second order finite moments.

Two approaches are adopted: the first one applies when both the biotic species have a self-regulating term in their evolution equations and can be worked out without linearizing the equations. This approach does not require any further constraint on delay kernels, whereas it introduces constraints on the remaining parameters of the model. The second approach applies to the linearized equations when the predator self-regulating term is set equal to zero. In this case the stability condition requires a constraint on the average time delays in the recycling processes. Both the approaches are performed by constructing suitable Krasovskii-Lyapunov functionals for the related functional retarded differential equations.
ROGUING AND REPLANTING IN ORCHARDS: SOME PRELIMINARY RESULTS
Authors: VAN DEN BOSCH FRANK , DE ROOS ANDRÉ M.
Published: November 2004

Roguing and replanting is a widely accepted control strategy of infectious diseases with limited reproduction capacity in orchards. Little is known about the effects of this type of management on the dynamics of the infectious disease. In this paper we analyze a model for the dynamics of a S-I-R type epidemic under roguing and replanting. The model is structured with respect to the number of infections on a tree. Trees are assumed to be rogued, and replaced by uninfected trees, when the number of infections on the tree reaches a threshold value, L max . It is shown that increasing L max can lead to large amplitude periodic fluctuations in the infectious disease and the number of trees rogued per year. We compare the L max which leads to periodic solutions, with the final value, L∞, theorem of the classical Kermak and McKendrick model. It is shown that the non-trivial steady state is stable if L max L∞. A biological interpretation of this result is given.
POSSIBILITY OF REVERSIBLE CHEMO-MECHANICAL COUPLING IN CARDIAC MUSCLE: A BOND GRAPH APPROACH
Authors: LEFÈVRE JACQUES
Published: November 2004

Current models of cardiac dynamics include a time-varying spring generating the pumping power. They ignore therefore the chemo-mechanical process of transduction. We present a new model, based on the bond graph notion of a two-port capacity which represents this transduction and is compatible with the dynamic spring idea. In addition to showing the power of bond graphs, our model suggests that the transduction is reversible and length-dependent.
A MATHEMATICAL MODEL OF ANEURYSM OF CIRCLE OF WILLIS
Authors: NIETO J. J. , TORRES A.
Published: November 2004

We introduce a new mathematical model of aneurysm of the circle of Willis. It is an ordinary differential equation of second order that regulates the velocity of blood flow inside the aneurysm. By using some recent methods of nonlinear analysis, we prove the existence of solutions with some qualitative properties that give information on the causes of rupture of the aneurysm.
THE RELEVANCE OF SPATIAL STATISTICS ON THE STATISTICAL MODEL BUILDING FOR CORONARY HEART DISEASE
Authors: VASCONCELOS RITA
Published: November 2004

For a long time, it has been widely acknowledged that putting data on a map underlines important features, and helps in the understanding and interpretation of the real world. Recent and extensive developments of spatial statistics and of geostatistics show the growing importance of this field.

Our aim was to help physicians to interpret a very large database on heart diseases (acute myocardial infarction and angina pectoris) on the Madeira Islands. Besides standard techniques, such as loglinear models fitting, we decided to explore the spatial aspect of the question, and to bring in to the analysis recent advances in exploratory and robust data analysis. We show the relevance of spatial statistics on the detection of "hidden" variables.
EPIDEMIC REACTION-DIFFUSION SYSTEM WITH CROSS-DIFFUSION: MODELING AND NUMERICAL SOLUTION
Authors: CAPASSO V. , DI LIDDO A. , NOTARNICOLA F. , RUSSO L.
Published: November 2004

Reaction-diffusion systems with cross-diffusion are analyzed here for modeling the population dynamics of epidemic systems. In this paper specific attention is devoted to the numerical analysis and simulation of such systems to show that, far from possible pathologies, the qualitative behaviour of the systems may well interpret the dynamics of real systems.
MATHEMATICAL MODELS FOR HIV TRANSMISSION IN GROUPS OF INJECTING DRUG USERS VIA SHARED DRUG EQUIPMENT
Authors: CAPASSO VINCENZO , SICURELLO FRANCESCO , VILLA MARCO
Published: November 2004

In many western countries, including Italy, sharing drug injection equipment is one of the main causes of HIV/AIDS spread. In this paper we propose an extension of the classical one population and multiple population mathematical models for the spread of HIV, by providing explicit expressions for the force of infection in terms of a stochastic model for the behaviour of individuals in a friendship group with respect to needle sharing.

For the single population model we provide a threshold theorem in terms of the basic reproductive ratio. The extension to the multiple population case is discussed in terms of mixing matrices. The qualitative behaviour for different choices of such matrices is shown by computer simulations.
MODELLING THE FELINE IMMUNODEFICIENCY VIRUS WITHIN POPULATIONS OF DOMESTIC CATS (Felis catus)
Authors: COURCHAMP F. , PONTIER D. , ARTOIS M.
Published: November 2004

We attempt to model the circulation of the Feline Immunodeficiency Virus (FIV), a retrovirus analogous to the HIV, within populations of domestic cats. Domestic cats exhibit different patterns of population dynamics, social behaviour and reproductive strategies. In fact, cats can be either solitary or living in large social groups, with many intermediate states.

The aim of the presented model is to provide a conceptualization of the mechanisms of FIV spreading rather than to be a predictive tool. As one of our goals is to integrate easily new informations when available, and to remain simple and close to the biological reality, parameters, such as sex, age classes and dispersion, have been incorporated successively. This model can also be adapted to different types of cat populations by simple changes, as it could be to other host populations. A study of the stability of the model has been done. Based on available data, values of two parameters has been estimated: the carrying capacity and the transmission rate. Results are in good accordance with biological data.
ECOLOGICAL MODELS OF MICROPARASITIC DISEASES: THE IMPORTANCE OF RECOVERY AND IMMUNITY
Authors: NORMAN RACHEL , BEGON MICHAEL , BOWERS ROGER G.
Published: November 2004

In order to understand, in terms of the epidemiology of a disease, the consequences of having a population which can recover from the disease back to a state of susceptibility and the additional effects of recovery to immunity, we have formulated and compared a series of models; each includes a biological feature known to occur in a real host-pathogen system. For example, vertical transmission of the disease or free living infective stages of the pathogen. Taken together, these models, in general, follow predictable patterns of behaviour. There are exceptions, but these can be explained in terms of some sort of density dependence or time delay written into the framework of the model.
LOOKING FOR A COMMON STRUCTURE IN STANDARD S-I-R EPIDEMIC MODELS
Authors: PICARD PHILIPPE , LEFÈVRE CLAUDE
Published: November 2004

In classical S-I-R stochastic epidemic models, the formulae giving the distribution of the final size of the epidemic are very robust from one model to the other. This shows that these models, even if they may look different, share a common structure. In the present paper we prove that all the associated final size laws may be expressed in terms of parameters qk, where qk represents the probability that any given set of k susceptibles does not get infected from any given infective. Some consequences and methods of study for S-I-R models in general follow from this characteristic.
A COMPARTMENTAL MODEL OF ENDOSYMBIOSIS
Authors: DUCHATEAU-NGUYEN GUILLEMETTE , WEISBUCH GÉRARD , PELITI LUCA
Published: November 2004

In a previous paper we showed that emergence of mutualism is made possible by selective recognition processes which allow the host to discriminate true symbionts from commensalists. In hydra/algae associations, algae are first ingested in the apex of digestive cells and then migrate to their basis. Both processes are selective.We extend here the previous differential model to a compartmental model and study the role of the two selection processes.
PHYLLOTAXIS: OPEN AND CLOSED SYSTEMS
Authors: BARABÉ DENIS
Published: November 2004

The inflorescence of Symplocarpus foetidus constitutes good material to analyse the biological processes and physical constraints involved in the development of plants. During the development of the inflorescence, two morphogenetic periods can be distinguished (i) before and (ii) during and after the development of floral parts. In the first period, when the floral primordia appear, the phyllotactic system could be explained by global processes at the inflorescence level. In the second period, the development of floral parts produces patterns which can be explained by local processes at the floral level. In this analysis the author defines the concepts of open system and closed system in phyllotaxis. In a closed system (e.g. spadix) the elements are arranged on a continuous and closed surface. In an open system (e.g. shoot apex) the elements appear on a surface periodically renewed and are removed from each other by the intercalary growth.
CORNEAL EPITHELIAL WOUND HEALING
Authors: DALE PAUL D. , SHERRATT JONATHAN A. , MAINI PHILIP K.
Published: November 2004

We propose a reaction-diffusion model of the mechanisms involved in the healing of corneal surface wounds. The model focuses on the stimulus for increased mitotic and migratory activity, specifically the role of epidermal growth factor. We determine an analytic approximation for the speed of travelling wave solutions of the model in terms of the parameters and verify the results numerically. By comparing the predicted speed with experimentally measured healing rates, we conclude that serum-derived factors can alone account for the overall features of the healing process, but that the supply of growth factors by the tear film, in the absence of serum-derived factors, is not sufficient to give the observed healing rate. Numerical solutions of the model equations also confirm the importance of both migration and mitosis for effective wound healing. By modifying the model, we obtain an analytic prediction for the healing rate of corneal surface wounds when epidermal growth factor is applied topically to the wound.
RESOLVING THE CHEMOTACTIC WAVE PARADOX: A MATHEMATICAL MODEL FOR CHEMOTAXIS OF DICTYOSTELIUM AMOEBAE
Authors: HÖFER T. , MAINI P. K. , SHERRATT J. A. , CHAPLAIN M. A. J. , MURRAY J. D.
Published: November 2004

The slime mould Dictyostelium discoideum is a widely studied paradigm for biological pattern formation. To provide an explanation for the apparently paradoxical behaviour of Dictyostelium amoebae in the symmetric chemoattractant waves which govern their aggregation, we extend the standard model for chemotaxis of a cell population by explicitly considering adaptation of the chemotactic signalling pathway. In the limiting cases of very fast and very slow adaptation kinetics the model equations reduce to the standard model which predicts cell movement opposite to the observed direction. Adaptation on an intermediate timescale, however, provides cells with a "short-term memory" of experienced chemoattractant concentrations which can fully account for the experimental observation of cell translocation opposite to the direction of propagation of the chemoattractant waves.
HIERARCHICAL MODELS FOR SPATIAL PATTERN FORMATION IN BIOLOGY
Authors: MAINI P. K.
Published: November 2004

We review some recent work investigating a hierarchy of patterning processes in which a reaction-diffusion model forms the top level. In one such hierarchy, it is assumed that the boundary is differentiated, and it is shown that this can greatly enhance the robustness of the patterns subsequently formed by the reaction-diffusion model. In the second, a spatial heterogeneity in background environment is first set-up by a simple gradient model. The resulting patterns produced by the reaction-diffusion system may be isolated to specific parts of the domain. The application of such hierarchical models to skeletal patterning in the tetrapod limb is considered.
A MECHANOCHEMICAL MODEL FOR ADULT DERMAL WOUND CONTRACTION
Authors: OLSEN L. , SHERRATT J. A. , MAINI P. K.
Published: November 2004

We propose a deterministic mathematical model to describe the biomechanics and cell biology of wound contraction, a ubiquitous feature in the normal healing of adult dermal excisional wounds. Our aim is to use the model to obtain a greater understanding of the mechanisms involved in wound contraction and in clinically important healing pathologies such as fibrocontractive diseases.

The model consists of two cell types — fibroblasts aand myofibroblasts, a generic chemical growth factor and a viscoelastic extracellular matrix (which includes type I collagen). The essential processes of cell motility, proliferation, differentiation and mechanical interaction with the matrix are modelled from experimental data. A novel aspect of this approach is the inclusion of two cell types.

The model is shown not only to simulate normal wound contraction (in good agreement with experimental data), but also to yield valuable insight into the fundamental mechanisms involved and the pathogenesis of fibrocontractive diseases, and makes experimentally testable predictions of the effects of varying biological parameters. Two important results are that collagen remodelling is more intrinsic to scar formation than to wound contraction and that dynamic gradients in the cell and matrix densities are the driving force for wound contraction.
A MODEL OF TYPE I COLLAGEN FIBRILLOGENESIS BASED ON DIFFUSION LIMITED AGGREGATION
Authors: PARKINSON JOHN , KADLER KARL E. , BRASS ANDY
Published: November 2004

The development of shape and form is intrinsic to the structure and function of many biological macromolecules including tubulin, actin and collagen. Type I collagen is a major structural protein in the body, providing mechanical strength for tissues such as bone and skin. It is present in the form of fibrils which display a regular banding pattern known as D-periodicity (where D = 67 nm). Type I collagen is a long rod-like molecule (300 nm ×1.5 nm) consisting of a triple helix formed from three polypeptide chains. In vivo and in vitro studies have shown that collagen molecules self-assemble in a regular D-staggered array to form striated fibrils. Further studies have shown that the process, termed fibrillogenesis, is entropy driven. A model based on diffusion limited aggregation was used to investigate the properties of rod self-assembly. This simple model reproduced several experimentally observed features of collagen fibril morphology including a linear mass/unit length profile and a preference for tip growth.
MATHEMATICAL MODELLING OF THE MECHANISM OF VERTEBRATE SOMITIC SEGMENTATION
Authors: POLEZHAEV A. A.
Published: November 2004

A mathematical model for the mechanism of periodic pattern formation in the process of somitogenesis is proposed. It is assumed that metameric arrangement first appears before somite formation at the stage of transition of mesodermal into presomitic cells. It is assumed that the transition occurs in a certain phase of the mitotic cycle and that it can be suppressed due to excretion of some transition inhibitor by presomitic cells. The model demonstrates that periodicity can appear as a result of interaction of the wave of somitogenic cell determination with the mitotic cycles of mesodermal cells. It is shown that the model naturally explains synchrony in the somite formation and the results of heat shock experiments.
MODELING A SMALL NEURONAL NETWORK: THE LOBSTER CARDIAC GANGLION
Authors: AV-RON EVYATAR
Published: November 2004

The lobster cardiac ganglion is a nine cell network that stimulates the lobster heart. The individual neurons are modeled by a simple biophysical bursting model. The neurons are then connected to form the network. Theoretical experiments examine the role of individual cells and network connectivity, in bringing about the network behavior.
MATHEMATICAL MODELLING OF ACUTE PAIN
Authors: BRITTON N. F. , SKEVINGTON S. M. , CHAPLAIN M. A. J.
Published: November 2004

It is an idea going back to Descartes and further, and held by most scientists until at least around the turn of the century, that the body has a hard-wired pain system where the instantaneous intensity of the stimulus at a particular point determines the pain felt there. This idea is incorrect in at least four respects. In this paper we model a more modern theory of pain and compare the results of the model with experimental data. The strengths and weaknesses of the model are pointed out and it is concluded that the model is a good one for acute, but not for chronic, pain.
GENETIC INTERPRETATION OF DISCRETE HEREDITY I: FINITE SET THEORY ORDERS GENES IN SMALL POPULATION
Authors: GILLOIS MICHEL
Published: November 2004

E. Mayr [55] emphasizes that population genetic theories regard a population as a bag full of colored beans. Such a simplified way of thinking is misleading. M. Gillois [19,20] introduces finite set theory in population genetic theories. Consequently he orders genes in small population and he develops new concepts as "identity situations", "constraint situations" and "generalized genotypes".

This paper presents these new concepts which shall be used in order to study dynamics of genes in small populations. These results are basic for deterministic models. Contrary to stochastic models, deterministic models are fully in accordance to the physical fate of genes through individual meiosis and mating.
MODELLING AUDITORY NEURONES WITH HODGKIN AND HUXLEY EQUATIONS — Application to Amplitude Modulation Processing
Authors: LORENZI C. , BERTHOMMIER F.
Published: November 2004

Physiological recordings have shown that stellate cells in the ventral cochlear nucleus (VCN) enhance amplitude modulation (AM) information, relative to their auditory nerve (AN) inputs. Modelling spike-discharge properties of VCN neurones implies to take into account the stochastic aspect of AN fibres firings and the fine temporal aspects of the neural integration occurring at the level of the VCN. These two aspects can be simulated using respectively independent Poisson point processes and a digital integration of Hodgkin and Huxley equations. We determine the response transfer functions to AM, using sinusoidally AM white noises. The resulting modulation transfer functions (MTF) based on spike count is all-pass while the computed MTF based on modulation gain is low-pass at low intensity and bandpass at high intensity. These results are closely compatible with real data and confirm that AM encoding is performed by good response synchrony at preferential AM rates. A detailed study of the nonlinear MTF also predicts two secondary preferential frequencies harmonically related to the primary one. We finally examine the model MTF in the presence of a continuous wideband background noise. AM coding performed by the stellate cell model is robust as simulations show enhanced selectivity in the presence of significant levels of wideband background noise.
SHAPING NEURONAL DENDRITES: INTERPLAY OF TOPOLOGICAL AND METRICAL PARAMETERS
Authors: SCHIERWAGEN ANDREAS K. , VAN PELT JAAP
Published: November 2004

The functional role of a neuron within a network is influenced by the geometry of its dendrites. In the present study we have used a new model of dendritic arborization to analyze how metrical and topological parameters interact to shape a certain dendritic tree. One of the specific questions addressed is how to change topological variability in a systematic way while preserving the metrical features. The second problem concerns the effect of topology on the relationship between dendritic size and the distribution of dendritic surface area with radial distance from soma. The simulation results reproduce features of dendritic architecture found in neocortical pyramidal cells and cat superior colliculus neurons.
Integrated actions of transforming growth factor-β1 and connective tissue growth factor in renal fibrosis
Authors: Qi W. , Twigg S. , Chen X. , Polhill T. S. , Poronnik P. , Gilbert R. E. , Pollock C. A.
Published: November 2004

Matrix accumulation in the renal tubulointerstitium is predictive of a progressive decline in renal function. Transforming growth factor-β1 (TGF-β1) and, more recently, connective tissue growth factor (CTGF) are recognized to play key roles in mediating the fibrogenic response, independently of the primary renal insult. Further definition of the independent and interrelated effects of CTGF and TGF-β1 is critical for the development of effective antifibrotic strategies. CTGF (20 ng/ml) induced fibronectin and collagen IV secretion in primary cultures of human proximal tubule cells (PTC) and cortical fibroblasts (CF) compared with control values ( P < 0.005 in all cases). This effect was inhibited by neutralizing antibodies to either TGF-β or to the TGF-β type II receptor (TβRII). TGF-β1 induced a greater increase in fibronectin and collagen IV secretion in both PTC ( P < 0.01) and CF ( P < 0.01) compared with that observed with CTGF alone. The combination of TGF-β1 and CTGF was additive in their effects on both PTC and CF fibronectin and collagen IV secretion. TGF-β1 (2 ng/ml) stimulated CTGF mRNA expression within 30 min, which was sustained for up to 24 h, with a consequent increase in CTGF protein ( P < 0.05), whereas CTGF had no effect on TGF-β1 mRNA or protein expression. TGF-β1 (2 ng/ml) induced phosphorylated (p)Smad-2 within 15 min, which was sustained for up to 24 h. CTGF had a delayed effect on increasing pSmad-2 expression, which was evident at 24 h. In conclusion, this study has demonstrated the key dependence of the fibrogenic actions of CTGF on TGF-β. It has further uniquely demonstrated that CTGF requires TGF-β, signaling through the TβRII in both PTCs and CFs, to exert its fibrogenic response in this in vitro model.
Effect of Amine/Sodium Fluoride Rinsing on Toothbrush Abrasion of Softened Enamel in situ
Authors: Lussi A. , Jaeggi T. , Gerber C. , Megert B.
Published: November 2004

The aim of this study was to test the effect of fluoride rinsing on the prevention of toothbrush abrasion of softened enamel in situ. For softening, the samples were immersed in 0.1 M citric acid (pH 3.5) for 3 min. Eight test subjects had to make 5 runs in which 4 slabs per run were attached to intraoral appliances. They were as follows: (1) no softening, no fluoride rinsing (control 1); (2) softening, no fluoride rinsing (control 2); (3) softening, rinsing in situ with a sodium/amine fluoride rinsing solution (250 ppm F) for 30 s; (4) rinsing in situ with the sodium/amine fluoride rinsing solution (250 ppm F) for 30 s, softening; (5) softening, rinsing in situ with an experimental amine fluoride-containing rinsing solution (250 ppm F) for 30 s. After exposure for 60 min to the oral milieu, the volunteers brushed the samples for 30 s with toothpaste and the loss of tooth substance was determined. For each test person, the secretion rate of resting and paraffin-stimulated saliva, buffering capacity and pH were measured. Toothbrush abrasion in situ was not significantly lower using the fluoride rinsing solutions before or after softening the enamel compared to no rinsing (p > 0.05). Multiple linear regression analyses revealed that 57% of the variation in toothbrush abrasion could be attributed to the severity of softening (p < 0.001) and the pH of stimulated saliva (p < 0.001). It was concluded that a single rinse for 30 s had no statistically significant effect on the prevention of toothbrush abrasion of softened enamel.
High-Dose Mycophenolate Mofetil in the Treatment of Posttransplant Glomerular Disease in the Allograft: A Case Series
Authors: Wu Jean , Jaar Bernard G. , Briggs William A. , Choi Michael J. , Kraus Edward S. , Racusen Lorraine C. , Atta Mohamed G. , Samaniego Milagros D.
Published: November 2004

Background: Glomerular disease is an important cause of allograft loss. Treatment regimens for posttransplant glomerular disease are not well defined. Several reports have demonstrated that mycophenolate mofetil (MMF) is effective in treating native kidney glomerular disease. The effects of MMF are dose related. Therefore, we hypothesized that high-dose MMF (3 g/day) would be effective in treating glomerular disease in the allograft, minimizing the need for intravenous steroids and/or cyclophosphamide. This case series describes the results of the use of high-dose MMF in 6 patients. Methods: High-dose MMF (3 g/day) was used to treat biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, proliferative lupus nephritis, and perinuclear antineutrophil cytoplasmic antibodies glomerulonephritis) in 6 renal transplant recipients. Patients were offered this treatment if they had failed or did not tolerate standard treatment regimens. Remission was defined by a decrease or stabilization of serum creatinine, decrease in proteinuria and, where applicable, improvement in immunological markers of disease. Results: All 6 patients had disease remission after starting MMF with the most common side effect being leukopenia, which responded to dose reduction. Conclusions: High-dose MMF may be an effective agent in treating glomerular disease in the allograft.
Color Doppler Ultrasound in Renal Transplant: Role of Resistive Index versus Renal Cortical Ratio in the Evaluation of Renal Transplant Diseases
Authors: Drudi Francesco M. , Pretagostini Renzo , Padula Simona , Donnetti Massimo , Giovagnorio Francesco , Mendicino Palma , Marchetti Federico , Ricci Paolo , Passariello Roberto
Published: November 2004

Background/Aims: Ultrasound (US) and color Doppler are not sensitive enough to detect anomalies in cortical perfusion, which is affected in most graft dysfunctions. The renal cortical ratio (RCR) is a variation in the resistive index (RI) values from the renal artery to cortical vessels, expressed in percent. The aim of this study was to compare the RI and RCR in the differentiation of normal and pathological grafts, to assess the positive predictive value of RCR and show that RCR enables earlier diagnosis than RI. Methods: Based on clinical, biochemical and histological examinations, 494 renal allografts were divided into 3 groups (normal grafts, acute and chronic pathologies). All patients underwent US color Doppler. RI was measured and RCR calculated. Follow-up confirmed the initial division in groups. Statistical significance was calculated using the two-tailed Student’s t test. The positive predictive value was calculated for each group. Results: 24 h after transplant, RCR differentiated normal grafts from acute dysfunctions despite confusing biochemical values and clinical symptoms. In chronic patients, RCR variations occurred later but always before the serum creatinine level increased. Conclusion: RCR presented a higher positive predictive value than RI. RCR curves were already altered in the early stages of transplant pathologies. RCR calculation is easy and makes a significant contribution towards a correct early diagnosis.
Significance of Acute versus Chronic Troponin T Elevation in Dialysis Patients
Authors: Ie Eric H.Y. , Klootwijk Peter J. , Weimar Willem , Zietse Robert
Published: November 2004

Introduction: Cardiac troponin T (cTnT) is often elevated in hemodialysis (HD) patients without acute coronary syndrome (ACS). The aim was to assess the predictive value for mortality of pre-dialysis cTnT in asymptomatic patients. If patients became symptomatic during follow-up, cTnT was followed to assess its diagnostic value for ACS. Methods: Forty-nine asymptomatic HD patients were included: 30 patients with a history of cardiovascular disease (CV+) and 19 without (CV–). In 11 patients cTnT, myoglobin and creatine kinase (CK) were measured before and during HD. During ACS, cTnT was followed until recovery. A cTnT of ≧0.03 µg/l was considered elevated. Follow-up was 2 years. Results: cTnT was elevated in 82% (40/49). More CV+ patients had an elevated cTnT (28/30) than CV– patients (12/19; p = 0.02). There was no change in cTnT, myoglobin and CK during HD. During ACS, cTnT increased above baseline, and tended to return to baseline after recovery. Mortality was 33% (16/49). Patients with elevated cTnT had a higher mortality rate (16/40) than patients with negative cTnT (0/9; p = 0.02). Conclusions: Elevated cTnT levels in asymptomatic HD patients are not caused by acute myocardial injury or by HD itself. They may be related to chronic myocardial damage and decreased clearance, and are of prognostic value. During ACS, however, a cTnT rise above the individual baseline is diagnostic of acute myocardial injury.
Prospects for Engineering the Urinary Tract
Authors: Koh Chester J. , Atala Anthony
Published: November 2004

Congenital abnormalities and acquired disorders can lead to organ damage or loss within the urinary tract. For reconstructive purposes, tissue engineering efforts are currently underway for virtually every type of tissue and organ within the urinary tract. Tissue engineering incorporates the fields of cell transplantation, materials science, and engineering for the purpose of creating functional replacement tissue, and requires personnel who have mastered the techniques of cell harvest, culture, expansion and transplantation, as well as polymer design. Major advances in the areas of stem cell biology, tissue engineering, and therapeutic cloning (nuclear transfer) techniques have made it possible to combine these technologies to create the comprehensive scientific field of regenerative medicine.
Safety of Long-Term Administration of Bisphosphonates in Elderly Cancer Patients
Authors: Tralongo Paolo , Repetto Lazzaro , Di Mari Anna , Mauceri Gaetano , Bollina Roberto , Ferrau’ Francesco , Conti Gianfranco
Published: November 2004

Background: To evaluate the effectiveness and tolerability of the long-term treatment bone metastases with pamidronate in older patients. Materials and Methods: Twenty-two ambulatory patients aged 70 or older were included in the study. The median age was 73 (range 70–77). Ten patients (46%) were affected by breast carcinoma, 7 (32%) by prostate carcinoma and 5 (22%) by multiple myeloma. Nine (40%) patients presented co-morbidity. All of the patients presented at least one metastatic lytic bone lesion measuring 1 cm or more in diameter; the median lesion number was 2 (range 1–4). Hormonal therapy or chemotherapy regimen, were allowed as clinically required. Patients were treated with a fixed dose of sodium pamidronate, 90 mg in 3 h infusion every 4 weeks. Results: Partial response was shown in 6 (28%) patients, stable disease in 11 (50%), and progression (PD) in 5 (22%). 2 out of 5 patients with PD presented skeletal-related events (SREs) such as bone fracture. The median treatment duration was 19 months. The treatment was well tolerated; in 5 patients (23%) a GI fever was observed, in 3 patients (18%) G1 nausea, and in 3 patients (14) G1 diarrhea. Two cases (9%) of acute renal insufficiency (creatinine 1.7 and 1.6 mg/dl), and 3 cases (14%) of hypocalcemia (7.6, 7.5 and 7.8 mg/dl) were also registered. The renal dysfunction was reversible and without consequence. Conclusion: Our experience suggests that the bisphosphonates long-term administration is useful and did not cause significant side effects in elderly subjects. Low-grade pyrexia, nausea/vomiting, acute/reversible renal dysfunction and hypo-calcemia were the most frequent side effects reported. However, they were of low grade and in most cases, did not require dose modifications and/or hospitalization.
The Outcome of Coronary Artery Bypass Grafting Surgery among Patients Hospitalized with Acute Coronary Syndrome: The Euro Heart Survey of Acute Coronary Syndrome Experience
Authors: Solodky Alejandro , Behar Solomon , Boyko Valentina , Battler Alexander , Hasdai David
Published: November 2004

Aim: To determine the frequency and outcomes of coronary artery bypass graft (CABG) surgery in patients with a wide spectrum of acute coronary syndromes (ACS). Methods and Results: We prospectively enrolled 10,484 ACS patients from 103 hospitals in 25 countries across Europe and the Mediterranean basin. Of the 10,204 patients with complete data, 460 (4.5%) underwent CABG while in hospital; 3.4% had ST elevation ACS, 5.4% had non-ST elevation ACS, and 4.4% had undetermined ECG ACS (p = 0.001 for non-ST elevation ACS vs. others). In general, patients who underwent CABG were more likely to be males, to have diabetes mellitus, hyperlipidemia, a positive family history of premature coronary disease, and prior angina pectoris, but had less often prior heart failure. While in hospital, all CABG patients underwent coronary angiography and 15.2% also underwent percutaneous revascularization, as compared with 51.3 and 33.1% in the remaining patients, respectively. The in-hospital mortality was 3.7% for ACS patients who underwent CABG and 4.8% for non-CABG ACS patients (p = nonsignificant) with an adjusted odds ratio of in-hospital death for CABG patients of 1.00 (95% CI 0.59–1.61). Conclusions: Approximately 4.5% of ACS patients underwent CABG during their initial hospitalization, with a greater likelihood among non-ST elevation ACS patients. Of the CABG patients, 15.2% also underwent percutaneous revascularization. The outcome of CABG patients was as good as non-CABG patients, indicating that CABG remains an effective and safe means to achieve revascularization among ACS patients in current clinical practice.
Clinical, Biochemical and Morphologic Diagnostic Markers in an Infant Male Pseudohermaphrodite Patient with Compound Heterozygous Mutations (G115D/R246W) in SRD5A2 Gene
Authors: Fernández-Cancio Mónica , Rodó Joan , Andaluz Pilar , Martínez de Osaba María Jesús , Rodríguez-Hierro Francisco , Esteban Cristina , Carrascosa Antonio , Audí Laura
Published: November 2004

A patient with male pseudohermaphroditism and clinical diagnosis of partial androgen insensitivity in the neonatal period was studied at pubertal age for a molecular diagnosis. Hormone studies were conducted at baseline and under hCG stimulation for testosterone and dihydrotestosterone determinations at 2 months of age. Gonadectomy was performed at 4 months. At the age of 13 years genital skin fibroblasts were studied for androgen binding and 5α-reductase activity and peripheral blood DNA was available for androgen receptor (AR) and 5α-reductase (SRD5A2) gene analysis. Exons 1–8 of AR gene and exons 1–5 of SRD5A2 gene were sequenced. AR gene coding sequences were normal. SRD5A2 gene analysis revealed two heterozygote mutations (G115D and R246W), with the mother carrying the G115D and the father the R246W mutations. The compound heterozygote mutations in SRD5A2 gene explained an extremely low 5α-reductase enzyme activity in genital skin fibroblasts. Revision of hormonal data from the neonatal period revealed an increased testosterone-to-dihydrotestosterone ratio at the end of an hCG stimulation test, which concurred with the molecular diagnosis. Testis morphology at 4 months of age was normal. Clinical and biochemical differential diagnosis between partial androgen insensitivity syndrome and 5α-reductase enzyme deficiency is difficult in the neonatal period and before puberty. Our results show that in our patient the testosterone-to-dihydrotestosterone ratio would have adequately orientated the diagnosis. The two mutations in SRD5A2 gene have been described in patients of different lineages, though not in combination to date. Testis morphology showed that, during early infancy, the 5α-reductase deficiency may not have affected interstitial or tubular development.
Endocrine and Cognitive Effects of Short-Time Soybean Consumption in Women
Authors: Celec Peter , Ostatníková Daniela , Cagánová Marieta , Žuchová Svetlana , Hodosy Július , Putz Zdeněk , Bernadič Marián , Kúdela Matúš
Published: November 2004

Background: Soy phytoestrogens are known to influence the hormonal status acting as partial estrogen agonists. Soy-derived food supplements are advised for hormone replacement therapy, prevention of atherosclerosis, age-related cognitive decline and even hormone-dependent cancer, although results from clinical studies are controversial. Whether increased soybean intake can affect the endocrine status and cognitive abilities is largely unknown. Aim: To observe the effects of 1 week of increased soybean intake on sex hormone levels and spatial cognitive abilities in women. Subjects and Methods: 16 young healthy female volunteers were asked to eat 900 g of soybeans within 1 week. Salivary testosterone (T), free and total plasma T, salivary and plasma estradiol (E) were measured by radioimmunoassay before and after the study period. Mental rotation (MR) and spatial visualization (SV) psychological tests were done at the days of sampling. Results: Soybean intake increased total plasma T levels (p < 0.02) while decreasing salivary T (p < 0.01) and not altering free plasma T levels. Salivary and plasma E levels were not changed. The results of MR and SV tests were improved after the study period. Conclusion: Short-time increased soybean intake alters the level of total plasma and salivary T and improves spatial cognition in women. Whether this effect is mediated by modulation of estrogen receptors, changes in sex hormone-binding globulin production or changes in activity of steroid-competent enzymes needs further study.
Design, Baseline Characteristics and Carotid Intima-Media Thickness Reproducibility in the PARC Study
Authors: Touboul P.J. , Vicaut E. , Labreuche J. , Belliard J.P. , Cohen S. , Kownator S. , Pithois-Merli I.
Published: November 2004

Background: Intima-media thickness (IMT) is associated with an increased risk of cardiovascular and cerebral ischemic events, but its correlation with the absolute cardiovascular risk is not known in large populations. The Paroi Artérielle et Risque Cardiovasculaire (PARC) Study is an epidemiological study designed to correlate conventional assessment of cardiovascular risk with the mean IMT of the common carotid. Methods: In the PARC study, 6,416 subjects were enrolled, including 80.7% subjects with cardiovascular risk factors and 19.3% without. A specific methodology was designed to harmonize the acquisition and processing of data at the 283 centers. Interreader agreement on image quality and IMT measurement of the common carotid artery (CCAIMT) was assessed from a random sample of 10% of the PARC study population. Results: The intraclass correlation coefficient was 0.98 (95% CI 0.966–0.985), and the accuracy was high (standard deviation of the error measurement: 0.0185 mm). Conclusions: The reproducibility of the measurements assessed by means of the intraclass correlation coefficient and the accuracy of the CCAIMT measurement obtained in the PARC Study demonstrate the feasibility of large multicenter studies of IMT measurement.