Search PubMed⌕ Search

Biomedical subjects

J A Jacquez

Publications and source records attributed to J A Jacquez.

At least 19 recordsLinked to original sources
PubMed1992

Theory of production rate calculations in steady and non-steady states and its application to glucose metabolism.

I present a review and synthesis of the basic theory, steady state, and non-steady state for the calculation of metabolite production rates for systems that have a central well-mixed compartment that is the site of tracer input and sampling. The theory is then applied to the calculation of glucose production. If the only inputs are into the central compartment, an experimental design that involves varying tracer infusion rates to maintain constant specific activity in the central compartment and the same constant specific activity in the peripheral compartments allows calculation of the endogenous production. That holds even if the models are unidentifiable. The correct equation and Steele's pool fraction approximation reduce to the same result for this experimental design. However, that does not justify the use of Steele's equation when there are deviations from the exact experimental design. When the specific activity in the central compartment is not constant, model-dependent correction terms to Steele's equation are needed.

Animals↗
PubMed1991

Assessing risk factors for transmission of infection.

Commonly used measures of effect, such as risk ratios and odds ratios, may be quite biased when used to assess the effect of factors that alter transmission risks given exposure to infected individuals. This is demonstrated in a simulation model involving a higher-risk behavior and a lower-risk behavior affecting the sexual transmission of human immunodeficiency virus. The bias arises because population contact patterns between higher-risk and lower-risk persons change their relative probabilities of exposure to an infected individual as an epidemic progresses. The assessment of contact patterns is thus central to risk assessment for contagious diseases. A new formulation of selective mixing presented here, together with a structured mixing specification of the social settings of contact, provides a theoretic framework for the investigation of contact pattern determinants.

Bias↗
PubMed1991

Reproduction numbers and thresholds in stochastic epidemic models. I. Homogeneous populations.

We compare threshold results for the deterministic and stochastic versions of the homogeneous SI model with recruitment, death due to the disease, a background death rate, and transmission rate beta cXY/N. If an infective is introduced into a population of susceptibles, the basic reproduction number, R0, plays a fundamental role for both, though the threshold results differ somewhat. For the deterministic model, no epidemic can occur if R0 less than or equal to 1 and an epidemic occurs if R0 greater than 1. For the stochastic model we find that on average, no epidemic will occur if R0 less than or equal to 1. If R0 greater than 1, there is a finite probability, but less than 1, that an epidemic will develop and eventuate in an endemic quasi-equilibrium. However, there is also a finite probability of extinction of the infection, and the probability of extinction decreases as R0 increases above 1.

Computer Simulation↗
PubMed1990

The effects of population structure on the spread of the HIV infection.

A model for the spread of human immunodeficiency virus (HIV) in a population of male homosexuals is presented. The population is divided into five groups on the basis of degree of sexual activity. Within each group, the individuals are classified as 1) susceptible; 2) infective; or 3) removed because of a lack of sexual activity associated with advanced acquired immunodeficiency disease (AIDS). The infective individuals are further subdivided into four stages of infection. Analyses of the model address two questions with regard to the spread of HIV: (1) What is the effect of level of sexual activity on an individual's risk for infection, and (2) What is the effect that assumptions about mixing between groups have on both individual risk and transmission throughout a population? Results from analyses using a number of different parameter estimates show that increased levels of sexual activity increase the likelihood that an individual will become infected. In addition, the initial spread of the disease is markedly affected by variation in the amount of contact among individuals from different subpopulations. The steady-state incidence of the disease is not markedly affected by variation in the contact patterns, but the size of the steady-state population and therefore the proportion of infected individuals in the population does vary significantly with changes in the degree of mixing among subpopulations. These results show clearly the sensitivity of model outcomes to variation in the patterns of contact among individuals and the need for better data on such interactions to aid in understanding and predicting the spread of HIV.

HIV Infections↗
PubMed1990

Parameter estimation: local identifiability of parameters.

For biological systems one often cannot set up experiments to measure all of the state variables. If only a subset of the state variables can be measured, it is possible that some of the system parameters cannot influence the measured state variables or that they do so in combinations that do not define the parameters' effects separately. Such parameters are unidentifiable and are in theory unestimable. Given a model of the system, linear or nonlinear, and initial estimates of the values of all parameters, we exhibit a simple theory and describe a program for checking the local identifiability of the parameters at the initial estimates for given experiments on the model. The program, IDENT, is available from the authors.

Animals↗
PubMed1989

A resource facility for kinetic analysis: modeling using the SAAM computer programs.

Kinetic analysis and integrated system modeling have contributed significantly to understanding the physiology and pathophysiology of metabolic systems in humans and animals. Many experimental biologists are aware of the usefulness of these techniques and recognize that kinetic modeling requires special expertise. The Resource Facility for Kinetic Analysis (RFKA) provides this expertise through: (1) development and application of modeling technology for biomedical problems, and (2) development of computer-based kinetic modeling methodologies concentrating on the computer program Simulation, Analysis, and Modeling (SAAM) and its conversational version, CONversational SAAM (CONSAM). The RFKA offers consultation to the biomedical community in the use of modeling to analyze kinetic data and trains individuals in using this technology for biomedical research. Early versions of SAAM were widely applied in solving dosimetry problems; many users, however, are not familiar with recent improvements to the software. The purpose of this paper is to acquaint biomedical researchers in the dosimetry field with RFKA, which, together with the joint National Cancer Institute-National Heart, Lung and Blood Institute project, is overseeing SAAM development and applications. In addition, RFKA provides many service activities to the SAAM user community that are relevant to solving dosimetry problems.

Animals↗
PubMed1979

Studies on the turnover of proteins of the rat erythrocyte membrane.

The membrane proteins of erythrocytes were labeled by injecting L-[14C]-leucine and later L-[3H]leucine into rats, the two injections being 31 days apart. Control animals received the two isotopic forms of L-leucine simultaneously. Deviations in labeling ratio from control patterns were found on sodium dodecyl sulfate-polyacrylamide gel electrophorograms in restricted regions suggestive of turnover or loss of a few small proteins from the membrane between the 31 days. Most of the ghost proteins show no turnover.

Animals↗
PubMed1978

Comparison using central core model of renal medulla of the rabbit and rat.

The studies presented here use a central core model of the renal medulla, the details of which have been given elsewhere (Foster et al., Mathematical Biosci. 32: 307-335, 337-360, 1976). The central core model of the rabbit medulla predicts concentration gradients and volume flow rates in line with what is known for the rabbit. The handling of urea, however, is not consistent with the scheme proposed by Kokko and Rector (Kidney Intern. 2: 214-233, 1972). Moreover, the low concentration of urea predicted for the urine suggests an absence in the model of some form of mediated transport for urea in the inner medulla. The central core model of the rat medulla failed to predict results consistent with what is known about the rat. Substitution of the rabbit thermodynamic parameters into the model for the rat resulted in predictions that more closely resembled what one might expect, but were not entirely satisfactory. The implication is that there may be an interspecies difference in the concentration machinery between the rabbit and rat.

Animals↗
PubMed1978

Differential labeling of components in human erythrocyte membranes associated with the transport of glucose.

The irreversible inhibition of glucose transport by 1-fluoro-2,4-dinitrobenzene (FDNB) has been used to identify membrane proteins possibly associated with glucose transport in human erythrocytes. D-Glucose was shown to enhance significantly the rate of FDNB inhibition of transport when present during the reaction, whereas cytochalasin B (CB) and D-maltose retarded this FDNB inhibition of transport. This modulation of the inhibition reaction formed basis for a double isotopic differential labeling technique using [14C]- and [3H] FDNB followed by SDS-polyacrylamide gel electrophoresis to distinguish transport-associated polypeptides from bulk membrane dinitrophenylated proteins. Reactions in the presence of CB or maltose revealed the presence of a differentially labeled polypeptide(s), with a molecular weight of approximately 60,000-65,000 daltons. This effect could in part be reversed in the presence of D-glucose but not L-glucose. Reactions in the presence of D-glucose resulted in two regions of differential labeling. One region was around 200,000 daltons and the other corresponded to a 90,000-dalton band. Extraction of membrane proteins with p-chloromercuribenzene sulfonate resulted in no loss of the 60,000-dalton peak, indicating that this labeled polypeptide(s) was firmly anchored in the hydrophobic core of the membrane. These results indicate that as many as three membrane polypeptides are differentially labeled by FDNB under conditions strongly associated with the inhibition of the glucose transport system and may be involved in the regulation of glucose transport.

Biological Transport, Active↗
PubMed1976

An analysis of the adequacy of the asymmetric carrier model for sugar transport.

In 1972, Lieb, W. R. and Stein, W. D. (Biochim, Biophys. Acta 265, 187-207) in their review of sugar transport in human erythrocytes concluded that the conventional two-state carrier model was inconsistent with the experimental data available at that time. Since then, other papers have appeared which question the validity of the model. In this paper, we give a brief derivation of the equations describing the two-state carrier model, and analyze the predictions of the model in the classical experiments, i.e. zero-trans, infinite-cis, and equilibrium exchange. We show that the estimate of the half saturation constant of 2.8 mM for glucose at the inner face of the human red cell membrane for the infinite-cis procedure reported by Hankin, B.L., Liev, W.R. and Stein, W.D ((1972) Biochim. Biophys. Acta 288, 114-126) is unreliable. We note that all of the other experimental findings are consistent with the asymmetric carrier model.

Biological Transport, Active↗
PubMed1976

The action of a binary nonionic detergent on a kidney membrane fraction.

The disruption of a kidney cortex microsomal membrane preparation by a binary, nonionic detergent, was followed by using as markers, the changes in total protein content, and (Na+, K+)-ATPase in a supernatant fraction. Both markers responded similarly to changes in pH, microsome concentration and detergent concentration, but responded differently for time-dependent studies. The (Na+, K+)-ATPase activity was increased 2.2-fold (76.1 mumoles Pi/mg protein/h, 95% ouabain-sensitive) by a single detergent treatment and 3.5-fold (92% ouabain-sensitive) by a sequential detergent treatment. Changes in the critical micelle concentration (cmc) were observed for varying detergent and protein concentrations, which suggest interactions of monomeric detergent with the membrane. The peak of (Na+, K+)-ATPase activity occurred above the cmc which suggests the participation of micelles in releasing the enzyme from the membranes. Hill plots of the protein released as the detergent concentration was varied showed a change in the slope near the cmc indicating a four-fold increase in the binding of detergent to membranes as the detergent concentration is increased above the cmc. These results suggest that the disruption of membranes by detergent involves the binding of detergent monomers to the membrane followed by the formation of co-micelles of the detergent with segments of the membrane to complete the separation process.

Adenosine Triphosphatases↗
PubMed1975

One-way fluxes of alpha-aminoisobutyric acid in Ehrlich ascites tumor cells. Trans effects and effects of sodium and potassium.

One-way fluxes in the steady state and one-way influxes at zero intracellular concentrations were measured for alpha-aminoisobutyric acid (AIB) in Ehrlich ascites tumor cells at 32 degrees C. The one-way fulxes show trans effects in the concentration of AIB and are dependent on sodium levels. The one-way fluxes for initial influx and for the steady state were fitted with the equations derived for the frequently used two-state carrier model. Estimates of the parameters of these equations were obtained with use of nonlinear least squares. These gave relatively good fits of the flux data and the data on steady-state distribution ratios. The two-state carrier model predicted a trans inhibition of one-way influx and a trans stimulation of one-way efflux. The former phenomenon has been demonstrated for AIB transport in Ehrlich ascites cells and there is evidence, through less firm, for the latter.

Aminoisobutyric Acids↗
PubMed1975

Neutral amino acid transport pathways in uptake of L-thyroxine by Ehrlich ascites cells.

Neutral amino acid pathways were investigated as possible mediators of L-thyroxine (T4) entry into ascites cells. 14C-Labeled T4, alpha-aminoisobutyric acid (AIB), L-phenylalanine (Phe), and cycloleucine (cLeu) uptakes were measured at initial extracellular amino acid concentrations of 1 muM in a modified Krebs-Ringer phosphate buffer, pH 7.4. T4 uptake was markedly slower than that of AIB, Phe, or cLeu over a 25-min period. T4 uptake was neither competitively stimulated nor inhibited by either AIB or Phe when these latter amino acids were varied over the concentration range 1.0 x 10(-6) to 1.0 x 10(-2) M. Preloading cells with 30 mM L-methionine did not enhance the uptake of T4. TJ efflux from preloaded cells was not affected by either AIB or Phe in the extracellular fluid (ECF). The uptakes of AIB, Phe, and cLeu were markedly altered by replacement of ECF Na+ with choline+, whereas T4 uptake was unchanged. It was concluded that neural amino acid transport pathways (specifically A, L, ASC, and beta) do not participate in the transmembrane transfer of L-thyroxine into Ehrlich ascites cells.

Amino Acids↗