PubMed Health⌕ Search

Biomedical subjects

M C Boerlijst

Publications and source records attributed to M C Boerlijst.

7 recordsLinked to original sources
PubMed2001

Carrier rate of zidovudine-resistant HIV-1: the impact of failing therapy on transmission of resistant strains.

OBJECTIVE: Because maintenance of treatment success in HIV-1 infection requires viruses to remain therapy sensitive in drug-naive seropositive persons, we looked at the primary infections caused by drug-resistant HIV-1 over time. Furthermore, to study the coverage rate of therapy and therapy failure in relation to the transmission of resistant viruses a mathematical model was developed. DESIGN: The reverse transcriptase and protease genes of viruses were analysed in newly infected people in the period 1990-1998 in the Amsterdam Cohort Study on HIV infection and AIDS in homosexual men. METHODS: The mathematical model was based on the coverage of drug regimens selecting zidovudine (ZDV) resistance, the lag time in which resistance is gained or lost, the death rate of people infected with resistant virus, and the replacement of resistance-selecting regimens by more potent treatments that substantially reduce viral load and mortality. RESULTS: Of 43 individuals with a primary HIV-infection, three (7%) harboured ZDV-resistant viruses. The first of the ZDV-resistant strains was transmitted in 1995, the last two in 1996. The build-up of ZDV resistance was described by the mathematical model indicating that the equilibrium level of resistance due to treatment depends only on the treatment rate and the outflow rate of patients with resistance virus. CONCLUSIONS: Our model indicates that the frequency of viral resistance in a population is determined largely by the number of individuals on insufficient or failing therapy and is influenced only modestly by secondary transmission of ZDV-resistant strains.

Anti-HIV Agents↗
PubMed1997

Evolution of genetic redundancy.

Genetic redundancy means that two or more genes are performing the same function and that inactivation of one of these genes has little or no effect on the biological phenotype. Redundancy seems to be widespread in genomes of higher organisms. Examples of apparently redundant genes come from numerous studies of developmental biology, immunology, neurobiology and the cell cycle. Yet there is a problem: genes encoding functional proteins must be under selection pressure. If a gene was truly redundant then it would not be protected against the accumulation of deleterious mutations. A widespread view is therefore that such redundancy cannot be evolutionarily stable. Here we develop a simple genetic model to analyse selection pressures acting on redundant genes. We present four cases that can explain why genetic redundancy is common. In three cases, redundancy is even evolutionarily stable. Our theory provides a framework for exploring the evolution of genetic organization.

Animals↗
PubMed1997

The logic of contrition.

A highly successful strategy for the Repeated Prisoner's Dilemma is Contrite Tit For Tat, which bases its decisions on the "standings" of the two players. This strategy is as good as Tit For Tat at invading populations of defectors, and much better at overcoming errors in implementation against players who are also using it. However, it is vulnerable to errors in perception. In this paper, we discuss the merits of Contrite Tit For Tat and compare it with other strategies, like Pavlov and the newly-introduced Remorse. We embed these strategies into an eight-dimensional space of stochastic strategies which we investigate by analytical means and numerical simulations. Finally, we show that if one replaces the conventions concerning the "standing" by other, even simpler conventions, one obtains an evolutionarily stable strategy (called Prudent Pavlov) which is immune against both mis-perception and mis-implementation.

Animals↗
PubMed1996

A new bell-shaped function for idiotypic interactions based on cross-linking.

Most recent models of the immune network are based upon a phenomenological log bell-shaped interaction function. This function depends on a single parameter, the "field," which is the sum of all ligand concentrations weighted by their respective affinities. The typical behavior of these models is dominated by percolation, a phenomenon in which a local stimulus spreads globally throughout the network. The usual reason for employing a log bell-shaped interaction function is that B cells are activated by cross-linking of their surface immunoglobulin receptors. Here we formally derive a new phenomenological log bell-shaped function from the chemistry of receptor cross-linking by bivalent ligand. Specifying how this new function depends on the ligand concentrations requires two fields: a binding field and a cross-linking field. When we compare the activation functions for ligand-receptor pairs with different affinities, the one-field and the two-field functions differ markedly. In the case of the one-field activation function, its graph is shifted to increasingly higher concentration as the affinity decreases but keeps its width and height. In the case of the two-field activation function, the graph of a low-affinity interaction is nested within the graphs of all higher-affinity interactions. We show that this difference in the relations among activation functions for different affinities radically changes the network behavior. In models that described B cell proliferation using the one-field activation function, network behavior was dominated by low-affinity interactions. Conversely, in our new model, the high-affinity interactions are the most significant. As a consequence, percolation is no longer the only typical network behavior.

Animals↗
PubMed1994

Diversity and virulence thresholds in AIDS.

We propose a model for the interaction between human immunodeficiency virus and the immune system. Two differential equations describe the interactions between one strain of virus and one clone of T lymphocytes. We use the model to generalize earlier results pertaining to the AIDS diversity threshold [Nowak, M. A., Anderson, R. M., McLean, A. R., Wolfs, T. F. W., Goudsmit, J. and May, R. M. (1991) Science 254, 963-969]. Our model has (i) a stable steady state corresponding to the "controlled" persistence of the virus and (ii) a region corresponding to AIDS. The separatrix between the two regimes is formed by the stable manifold of a saddle point. We define a dimensionless "virulence" parameter which combines the infectivity and antigenicity of a virus strain. We derive analytically two parameter conditions involving virulence. The first corresponds to a saddle-node bifurcation which causes AIDS due to the loss of the stable equilibrium. The second corresponds to a global bifurcation which causes AIDS due to a change in the basins of attraction. Incorporating diversity into the model, we derive a diversity threshold corresponding to the saddle-node bifurcation. In this threshold condition diversity and virulence have an equivalent effect. By studying the effect of diversity on the critical virulence that is required for a new mutant to cause AIDS, we again establish that diversity and virulence are equivalent parameters. Because in our model increasing diversity decreases the critical virulence, the strain that eventually causes AIDS need not be a virulent one.

Acquired Immunodeficiency Syndrome↗