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Biomedical subjects

L Bass

Publications and source records attributed to L Bass.

At least 37 records · Page 2Linked to original sources
PubMed1990

Changes in language development among autistic and peer children in segregated and integrated preschool settings.

Five young children with autism enrolled in a segregated class, five other children with autism in an integrated class, and four normally developing peer children in the integrated class were compared for developmental changes in language ability as measured by the Preschool Language Scale before and after training. The results, based on Mann-Whitney U tests, showed that (a) all of the children as a group made better than normative progress in rate of language development, (b) the scores of the autistic children were significantly lower than the peers before and after treatment, and (c) there were no significant differences in changes in language ability between the autistic children in the segregated and integrated classes.

Autistic Disorder↗
PubMed1989

Gompertzian mortality derived from competition between cell-types: congenital, toxicologic and biometric determinants of longevity.

Gompertz-Makeham kinetics of population mortality is derived in terms of competition between hypothetical life-prolonging and life-shortening regulatory elements (cells) interacting in each organism by generalized Volterra-type competitive exclusion. The model is developed on two levels, the first applicable to homogeneous populations, and the second, a statistical generalization, applicable to inhomogeneous populations. It offers a natural classification of effects of exogeneous agents on longevity, including hormetic and paradoxical effects of toxic substances, thus relating to problems of risk assessment by extrapolation from high to low doses. Two applications, concerning the effects of radiation on mice and Drosophila imagos, respectively, are used to illustrate the flexibility of the model in the analysis and interpretation of observational data.

Animals↗
PubMed1989

Heterogeneity of membrane transport quantified by the analysis of a unidirectional flux transient of charged tracer.

A planar mosaic membrane consists of patches, each with a given area, diffusion coefficient, and mobility of charged tracer; a common electric field, constant in space and time, lies across all the patches. Given the properties of the patches, the transient of the total unidirectional flux (summed over the patches) is predictable. Here we deal with the inverse problem: Given only the observed transient of the total unidirectional flux (as defined experimentally by Ussing), the unknown transport heterogeneity of the mosaic membrane is to be analyzed. Results obtained previously for uncharged tracers are generalized to include effects of the field. In particular, the ratio of the arithmetic and harmonic means (both area-weighted) of the diffusion coefficients, evaluated over the membrane, is expressed in terms of only the observed transient and the field strength and is used to characterize the heterogeneity; and the unique exact solution of the inverse problem for two kinds of patches is recovered at any field strength. If the mosaic consists of n distinct kinds of patches, a sweep of the field strength from low to high values reveals (at most) n steplike shapes in the time course of the total unidirectional flux (normalized to its final steady value), which permit an approximate analysis of the heterogeneity by elementary means.

Biological Transport, Active↗
PubMed1989

Derecruitment in cat liver: extension of undistributed parallel tube model to effects of low hepatic blood flow on ethanol uptake.

Previous studies showed two deviations from the predictions of the undistributed parallel tube model for hepatic uptake of substrates: a small deviation at high flows and a large deviation at low flows. We have examined whether these deviations could be described by a single correction factor. In cats anesthetized with pentobarbital, a hepatic venous long-circuit technique with an extracorporeal reservoir was used to vary portal flow and hepatic venous pressure, and allow repeated sampling of arterial, portal, and hepatic venous blood without depletion of the cat's blood volume. Hepatic uptake of ethanol was measured over a wide range of blood flows and when intrahepatic pressure was increased at low flows. This uptake could be described by the parallel tube model with a correction for hepatic blood flow: Uptake = Vmax max.(1 - e-kF).c/(Km + c). In 22 cats, Vmax max = 90 +/- 5 mumols/(min.100 g liver), k = 0.021 +/- 0.0015 when flow (F) was in millilitres per minute per 100 g liver, and Km = 150 +/- 20 microM when c is the log mean sinusoidal concentration. (1 - e-kF) represents the proportion of sinusoids perfused and metabolically active. A dynamic interpretation of this proportion is related to intermittency (derecruitment) of sinusoidal flow. Half the sinusoids were perfused at a flow of 33 mL/(min.100 g liver) and the liver was essentially completely perfused (greater than 95%) at the normal flow of 150 mL/(min.100 g liver). Derecruitment was not changed by raising hepatic venous pressure, and it was not related to hepatic venous resistance.

Anesthesia↗
PubMed1989

Albumin enhances unidirectional fluxes of fatty acid across a lipid-water interface: theory and experiments.

The effect of albumin concentration on the unidirectional fluxes of [3H]oleate across a lipid-water interface was measured by using a new model system consisting of a lipid phase (n-decane) separated from a stirred buffer phase by a planar interface. Albumin (0.15 mM) enhanced the flux of oleate from the lipid phase more than 30-fold. A similar increase in the oleate flux into the lipid was seen when the aqueous oleate and albumin concentrations were increased while keeping the unbound oleate concentration fixed. The ratio of the unidirectional fluxes was constant over the range of albumin concentrations investigated (1-100 microM). Analysis using rigorous rate theory indicated that the permeability of the interfacial surface was flux-limiting at high albumin, whereas diffusion across the unstirred water layer was flux-limiting at low albumin. The observed kinetic patterns are similar to results previously reported in cellular transport systems and attributed to specialized mechanisms for cellular uptake from the albumin-bound pool.

Carrier Proteins↗
PubMed1988

Flux ratio theorems for nonlinear membrane transport under nonstationary conditions.

We extend flux ratio theorems concerning ratios of unidirectional flux transients passed (in complementary experiments) through a medium of spatially inhomogeneous transport properties pertaining to diffusion, migration and temporary trapping of the transported substance. Any nonlinearity in the transport equations leads to a breakdown of the Ussing flux ratio theorem pertaining to all times. An integrated flux ratio theorem is proved for the case when the nonlinearity is in the kinetics of trapping, as when trapping sites can be saturated. The new theorem is shown to fail when the nonlinearity is due to a concentration-dependence of the diffusion coefficient, as in facilitated transport. The nature of a nonlinearity in membrane transport can therefore be elucidated experimentally by the use of the integrated flux ratio.

Animals↗
PubMed1988

Clinical applicability of current pharmacokinetic models: splanchnic elimination of 5-fluorouracil in cancer patients.

What can be inferred from limited clinical data by using current models of hepatic elimination? We examined this question by analyzing previously published data on the steady-state uptake of the anticancer agent 5-fluorouracil (5-FU) in seven cancer patients in terms of the venous equilibration model, the undistributed and distributed forms of the sinusoidal perfusion model, and the convection-dispersion model. Because of appreciable extrasplanchnic removal of 5-FU, the value of the steady infusion rate was not used in our analysis. When the data from all patients were pooled by plotting the measured hepatic venous concentration against the measured hepatic arterial concentration, the high concentration data fell on a limiting straight line of slope 1, indicating that at high dose rates elimination of 5-FU in both the liver and gastrointestinal tract was close to saturation. The intercept of this line gave a model-independent estimate of Vmax/Q = 48.0 +/- 11.6 (SD) microM for the pooled data set, where Vmax is the maximum splanchnic elimination rate of 5-FU, and Q is the hepatic blood flow. The low concentration data points fell on a limiting straight line through the origin, from which model-dependent values of the Michaelis constant were determined. The venous equilibration model gave Km = 9.4 microM, while the undistributed sinusoidal perfusion model gave Km* = 26.5 microM. With these values of Km, both models fit the pooled data equally well. These methods were applied to analyses of the five individual data sets which contained sufficiently high concentration data points. The resulting mean values were Vmax/Q = 41.0 +/- 5.1 (sem) microM, Km = 8.4 +/- 1.3 microM and Km* = 23.2 +/- 3.2 microM. However, the splanchnic region is a highly heterogeneous organ system, for which an undistributed analysis provides no more than an upper bound on the Michaelis constant Km+ (Km+ less than or equal to Km*). A perfusion model distributed to represent total splanchnic elimination is developed in the Appendix. Using previous estimates of the degree of functional heterogeneity in the liver alone, this model yields Km+ values for individual patients which have a mean of 20.3 +/- 2.8 microM.

Fluorouracil↗
PubMed1987

On the relation between extended forms of the sinusoidal perfusion and of the convection-dispersion models of hepatic elimination.

Two models of hepatic elimination, the distributed sinusoidal perfusion model, and the convection-dispersion model, are extended and then compared for first order kinetics in the steady-state. The sinusoidal perfusion model is extended by the inclusion of intrahepatic sites of mixing between sinusoids. The degree of such mixing is estimated for taurocholate elimination by isolated perfused rat livers by a comparison of anatomical and kinetic estimates of uptake heterogeneity, using previously published data. The dispersion model is generalized by the inclusion of distributions of enzyme activity along the flow. Direct comparison of the two models in the limit in which the degree of dispersion is small, allows the flow-dependence of the dispersion coefficient to be determined, thereby greatly extending the explanatory power of the convection-dispersion model. Finally, the effect of intrahepatic mixing sites on uptake by Michaelis-Menten kinetics is quantified in terms of the distributed sinusoidal perfusion model, with results which may be applicable to capillary beds in general.

Animals↗
PubMed1987

Metabolites of 2-deoxyglucose in rat brain at 12-24 h: bounds on kinetic constants.

Activities of 2-deoxy-D-glucose and its metabolites in rat brain were examined at 12, 16, 20, and 24 h after intraperitoneal injection of 14C-labeled 2-deoxy-D-glucose. Plasma radioactivity was monitored for 2 h before each of these determinations. As proportion of total brain radioactivity, 2-deoxy-D-glucose decreased monotonically from the unexpectedly high value of 22% at 12 h to 11% at 24 h after injection, 2-deoxy-D-glucose 6-phosphate decreased monotonically from 69% at 12 h to 23% at 24 h, and unphosphorylated products (of high and low molecular weight) increased from 10% at 12 h to 64% at 24 h. The data were analyzed in terms of a four-compartment model. Secure lower and upper bounds on the rate constant, k4*, for the dephosphorylation of 2-deoxy-D-glucose 6-phosphate were established: k4* was at least 0.0158 +/- 0.0014 . min-1 and at most 0.0385 +/- 0.0037 . min-1. If k4* is constant in time, then appreciable dephosphorylation occurs within the 45-min experimental period commonly used in the standard 2-deoxy-D-glucose method for estimating local cerebral glucose utilization. The possibility that the effective k4* is lower at such early times is reviewed in the light of a reanalysis of previously published data. Implications of these results for the 2-deoxy-D-glucose method are discussed from the points of view of numerical analysis and capillary heterogeneity.

Animals↗
PubMed1986

Flux ratio theorems for nonstationary membrane transport with temporary capture of tracer.

It has been shown recently that the ratio of unidirectional tracer fluxes, passing in opposite directions through a membrane which has transport properties varying arbitrarily with the distance from a boundary, is independent of time from the very first appearance of the two outfluxes from the membrane. This surprising proposition has been proved for boundary conditions defining standard unidirectional fluxes, and then generalized to classes of time-dependent boundary conditions. The operational meaning of all the resulting theorems is that when any of them appear to be refuted experimentally, the presence of more than one parallel transport pathway (that is, of membrane heterogeneity transverse to the direction of transport) can be inferred and analyzed. Recent experimental data have been interpreted accordingly. However, the proofs of the theorems given so far have not taken into account the possibility of temporary capture of tracer at sites fixed in the membrane (including also entrances to microscopic culs-de-sac). The possible presence of such a process, which would not affect fluxes in the steady state, left a fundamental gap in the aforementioned inferences. It is shown here that all the theorems previously proved for the flux ratio under unsteady conditions remain valid when temporary capture of tracer is admitted, no matter how the rate of capture, and the probability distribution of residence times of tracer at capture sites, may depend on the distance from a membrane boundary. The validity of the aforementioned inferences from observed time-dependence of the flux ratio is thereby extended to a much wider class of membrane transport processes.

Biological Transport↗
PubMed1984

Asymptotic forms of tracer clearance curves: theory and applications of improved extrapolations.

Tracer clearance curves are conventionally extrapolated beyond times of observation by using monoexponential asymptotic forms. The inadequacy of the resulting predictions, especially as to the mean transit time and quantities derived from it, has been previously demonstrated experimentally. Here improvements in extrapolations and in the resulting predictions are derived theoretically and tested on previously published data, venous as well as externally recorded. First, secure lower bounds on the mean transit times are constructed, and shown to be much higher than conventional outright estimates for venous data (twice as high in some cases). Next, new asymptotic forms of tracer clearance curves from kinetically heterogeneous systems are derived; they are not monoexponential, but they are as robust, contain as few parameters and are as easily connected to data. It is shown theorectically that for real organs these new asymptotic forms should extrapolate and predict better than monoexponentials, and this is demonstrated on previously published venous data from perfused muscle. In particular, the resulting outright predictions of mean transit times are substantially better than the best lower bounds. Furthermore, a correction is derived to the standard estimate of the rate of regional cerebral blood flow. In an application to previously published data recorded externally, that correction reduces the estimated flow rate by 4%.

Animals↗
PubMed1983

Estimates and implications of co-operativity for enzyme kinetics in the intact liver: method of flow invariants.

For substrates rapidly equilibrated between blood and liver cells, steady-state co-operative enzyme kinetics determines combinations of inlet and outlet substrate concentrations which do not change with the rate of blood flow recirculating through an isolated perfused liver. The mathematical forms of these combinations (here called flow invariants) are different for each value of the Hill co-operativity constant which can therefore be estimated, on a set of intact perfused preparations, from that flow invariant which is stochastically least dependent on experimental changes in the flow rate. This estimate, made in a narrow range of substrate concentrations, is illustrated using previously published data on the phosphorylation of galactose by galactokinase in rat liver. Changes (if any) of hepatocellular Hill constants in liver disease could be of clinical interest. A conspicuous difference between effects of negative and positive cooperativity in the intact perfused organ is found: for negative (but not for positive) co-operativity, complete extraction of the substrate in a single pass through a shunt-free liver is predicted from Hill's equation for a specified range of finite input concentrations and flow rates. Substrates with negative co-operativity in vivo would therefore facilitate the quantification of intrahepatic shunts.

Animals↗
PubMed1983

Heterogeneity of splanchnic vascular transit times in man.

A new method of quantifying the heterogeneity of transit times through vascular beds, free from corrections for effects of recirculation, is applied to data of splanchnic transit times in eight normal subjects and three patients with cirrhosis and end-to-side portocaval shunts, as obtained by Bradley's method. There is proportionality between the heterogeneity, expressed as standard deviation and the mean transit time in the eight normal subjects. The heterogeneity of plasma transit times is not appreciably larger than that of red blood cells, despite the larger volume of distribution of plasma. This may suggest that the large vessels contribute substantially to the dispersions of vascular transits in the entire splanchnic system. Pearson Type III distribution is proposed for the frequency function of the splanchnic transit times, and the power of the pre-exponential factor is deduced for plasma and for red blood cells. It is found that the initial splanchnic transits are dominated by plasma, this may be due to sequestration of red cells in the spleen. The heterogeneity of transit times in normals is not appreciably different from that in patients with cirrhosis and portocaval shunt, which suggests that the extra heterogeneity of the cirrhotic liver is of the same order as the heterogeneity of the normal extrahepatic splanchnic organs. The method may be a useful tool to describe heterogeneity of vascular transits in other organs.

Adolescent↗