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Biomedical subjects

W H Bossert

Publications and source records attributed to W H Bossert.

At least 19 recordsLinked to original sources
PubMed1999

The blood-stage dynamics of mixed Plasmodium malariae-Plasmodium falciparum infections.

We present the first mathematical model of the within-host dynamics of a mixed-species malaria infection in a human: the blood-stage population dynamics of a dual infection with Plasmodium malariae and Plasmodium falciparum. Our results reproduce several important features of such infections in nature, including the asymmetry of species asexual-form densities, inter-specific suppression through interactions with the human immune system, and seasonal alternations in species prevalence. Most importantly, our results suggest that an existing P. malariae infection can reduce the peak parasitemia of a subsequent P. falciparum superinfection by as much as 50%. This result integrates numerous empirical observations and supports the hypothesis that clinical outcomes of P. falciparum infections may be influenced by the presence of a congener.

Animals↗
PubMed1999

Multispecies Plasmodium infections of humans.

We analyzed point-prevalence data from 19 recent studies of human populations in which either Plasmodium ovale or Plasmodium vivax co-occur with Plasmodium falciparum and Plasmodium malariae. Although the only statistical interactions among, sympatric congeners are pairwise, the frequencies of mixed-species infections relative to standard hypotheses of species sampling independence show no strong relation to overall malaria prevalence. The striking difference between the P. falciparum-P. malariae-P. ovale and the P. falciparum-P. malariae-P. vivax data is that the first typically shows a statistical surplus of mixed-species infections and the second a deficit. This suggests that the number of Plasmodium species present in a human population may be less important in determining the frequencies of mixed-species infections than is the identity of those species.

Africa↗
PubMed1998

The optimal production of gametocytes by Plasmodium falciparum.

We use a simple model of the blood-stage infection dynamics of the malaria parasite Plasmodium falciparum to consider the adaptive significance of different rates of conversion from its pathogenic, asexual stages to its transmissible, sexual forms. We find that maximize transmissivity in single-strain infections are generally greater than the highest rates reported for in vitro cultures and are several times those for which the behavior of the model is consistent with clinical profiles of infection dynamics. When two strains that share a common immune agent coinfect a host through simultaneous inoculation or sequential superinfection, however, a strain with a lower, clinically-consistent value of the conversion rate inhibits the transmissivity of one with the higher value optimal for single-strain infection. Hence we suggest that "apparent" competition by way of a common immune response might be responsible for selection of the former.

Animals↗
PubMed1998

A target for intervention in Plasmodium falciparum infections.

We present a set of simple mathematical models to investigate interactions between malaria parasites and the human immune system and the differentiation of parasites from asexual, pathogenic into sexual, transmissible blood stages. Each model represents a different combination of empirically based hypotheses, and salient behaviors of each fit criteria developed from clinical data. In all models, however, higher gametocyte conversion rates result in lower peak asexual-form densities. Therefore, to the extent that asexual-form densities are associated with disease symptoms, interventions that stimulate gametocytogenesis should produce unexpected clinical benefits.

Animals↗
PubMed1997

The dynamics of Plasmodium falciparum blood-stage infection.

We develop a system of ordinary differential equations to model the dynamics of the blood-stages of the malaria parasite, Plasmodium falciparum. Variants of the model allow the study of a set of hypotheses about the interaction of the parasite with the host immune system, in particular with regard to the stimulation of the immune response and the regulation of the rate of conversion from the pathogenic, asexual to the transmissible, sexual blood stage. The values of several parameters of our models can be estimated from previous empirical work. Although the dynamics of the variants differ somewhat, in each variant some set of values of the three unconstrained parameters, different from one variant to the next, produces a range of behaviours quantitatively consistent with those reported from clinical studies. Some parameter values produce infections which quickly terminate, while others approach a chronic equilibrium level or produce oscillations, with repeated severe peaks separated by periods of undetectable parasitemia. We examine these and several other distinctions that might be used to assess model variants and focus further empirical research.

Animals↗
PubMed1997

Mixed-species Plasmodium infections of Anopheles (Diptera:Culicidae)

Mixed-pathogen infections of vectors rarely are considered in the epidemiological literature, although they may occur in nature. A review of published reports shows that many Anopheles species are capable of carrying sporozoites of > 1 Plasmodium species, of doing so simultaneously in field conditions, and of acquiring and transmitting these in experimental situations. Mixed-species infections in mosquito populations occur at frequencies greater than or equal to the product of the constituent species prevalences, whereas human populations have apparent mixed-species infections at frequencies less than or equal to their corresponding expected values. We present a model for the accumulation of parasite infections over the lifespan of a mosquito that explains this surplus of mixed-species infections. However, the expected frequencies of mixed infections on the basis of our model are greater than those found in nature, indicating that the sampling by mosquitoes of Plasmodium species from human malaria infections may not be random.

Age Factors↗
PubMed1997

Mixed-species Plasmodium infections of humans.

We analyzed point-prevalence data from 35 recent studies of human populations in which Plasmodium falciparum and one other Plasmodium species were the reported causes of malaria infections. For the P. falciparum-Plasmodium vivax pair, higher overall prevalence in a human population is associated with fewer mixed-species infections than expected on the basis of the product of individual species prevalences. This is not true for P. falciparum-Plasmodium malariae.

Animals↗
PubMed1984

Ventilatory response to chronic metabolic acidosis and alkalosis in the dog.

Systematic data are not available with regard to the anticipated appropriate responses of arterial PCO2 to primary alterations in plasma bicarbonate concentration. In the present study, we attempted to rigorously characterize the ventilatory response to chronic metabolic acid-base disturbances of graded severity in the dog. Animals with metabolic acidosis produced by prolonged HCl feeding and metabolic alkalosis of three different modes of generation, i.e., diuretics (ethacrynic acid or chlorothiazide), gastric drainage, and administration of deoxycorticosterone acetate (alone or in conjunction with oral sodium bicarbonate), were examined. The results indicate the existence of a significant and highly predictable ventilatory response to chronic metabolic acid-base disturbances. Moreover, the magnitude of the ventilatory response appears to be uniform throughout a wide spectrum of chronic metabolic acid-base disorders extending from severe metabolic acidosis to severe metabolic alkalosis; on average, arterial PCO2 is expected to change by 0.74 Torr for a 1-meq/l chronic change in plasma bicarbonate concentration of metabolic origin. Furthermore, the data suggest that the ventilatory response to chronic metabolic alkalosis is independent of the particular mode of generation.

Acidosis↗
PubMed1973

A definition of proximal and distal tubular compliance. Practical and theoretical implications.

Micropuncture studies were carried out in the rat to evaluate the in situ distensibility characteristics of the proximal and distal tubules under a variety of experimental conditions. In the first phase, we determined the response of tubular diameter (D) to changes in tubular pressure (P) induced by partially obstructing single tubules. The response observed under these conditions (i.e., when interstitial pressure is presumed to be constant) has been defined as the compliance of the tubule. Over the range of tubular pressures studied (10-35 mm Hg for the proximal tubule, 5-25 mm Hg for the distal tubule) the compliance characteristics of the proximal and distal tubule were found to be markedly different; the proximal tubular pressure-diameter relationship was linear, DeltaD/DeltaP = 0.45 mum/mm Hg, whereas the distal pressure-diameter relationship was curvilinear, DeltaD/DeltaP = c(-0.1xP+2.2). In the second phase we used the compliance data to construct a series of theoretical pressure-diameter curves that define the response of the tubule to increments in interstitial as well as intratubular pressure. These curves indicate that changes in distal diameter should provide a sensitive index of a rise in interstitial pressure under conditions in which the transtubular pressure gradient is increased by a small amount, but that proximal diameter should provide a more sensitive index of changes in interstitial pressure when the transtubular pressure gradient is increased by a large amount. In subsequent experiments in which furosemide was administered, we observed that the pressure-diameter relationships for both the proximal and distal tubule were indistinguishable from the compliance curves, a finding consistent with the interpretation that interstitial pressure was not appreciably changed from control. By contrast, when mannitol was administered, both proximal and distal tubular pressure-diameter relationships were significantly altered in a fashion consistent with a large increase in interstitial pressure. Neither with furosemide nor mannitol administration did it appear likely that significant changes in tubular compliance could account for the observed behavior of the tubule.Finally, we propose that a knowledge of tubular compliance will be useful in exploring the interrelationships between tubular and peritubular pressures, tubular anatomy, and transtubular ionic permeability. Recent studies linking changes in the geometry of lateral intercellular spaces of the tubule to changes in passive ion movement suggest that an investigation of such anatomical-functional correlates should be productive.

Animals↗
PubMed1967

Standing-gradient osmotic flow. A mechanism for coupling of water and solute transport in epithelia.

At the ultrastructural level, epithelia performing solute-linked water transport possess long, narrow channels open at one end and closed at the other, which may constitute the fluid transport route (e.g., lateral intercellular spaces, basal infoldings, intracellular canaliculi, and brush-border microvilli). Active solute transport into such folded structures would establish standing osmotic gradients, causing a progressive approach to osmotic equilibrium along the channel's length. The behavior of a simple standing-gradient flow system has therefore been analyzed mathematically because of its potential physiological significance. The osmolarity of the fluid emerging from the channel's open end depends upon five parameters: channel length, radius, and water permeability, and solute transport rate and diffusion coefficient. For ranges of values of these parameters encountered experimentally in epithelia, the emergent osmolarity is found by calculation to range from isotonic to a few times isotonic; i.e., the range encountered in epithelial absorbates and secretions. The transported fluid becomes more isotonic as channel radius or solute diffusion coefficient is decreased, or as channel length or water permeability is increased. Given appropriate parameters, a standing-gradient system can yield hypertonic fluids whose osmolarities are virtually independent of transport rate over a wide range, as in distal tubule and avian salt gland. The results suggest that water-to-solute coupling in epithelia is due to the ultrastructural geometry of the transport route.

Biological Transport, Active↗