PubMed Health⌕ Search

Biomedical subjects

A H Marcus

Publications and source records attributed to A H Marcus.

17 recordsLinked to original sources
PubMed2000

Dynamics of the mitochondrial reticulum in live cells using Fourier imaging correlation spectroscopy and digital video microscopy.

We report detailed studies of the dynamics of the mitochondrial reticulum in live cells using two independent experimental techniques: Fourier imaging correlation spectroscopy and digital video fluorescence microscopy. When both methods are used to study the same system, it is possible to directly compare measurements of preaveraged statistical dynamical quantities with their microscopic counterparts. This approach allows the underlying mechanism of the observed rates to be determined. Our results indicate that the dynamics of the reticulum structure is composed of two independent contributions, each important on very different time and length scales. During short time intervals (1-15 sec), local regions of the reticulum primarily undergo constrained thermally activated motion. During long time intervals (>15 sec), local regions of the reticulum undergo long-range "jump" motions that are associated with the action of cytoskeletal filaments. Although the frequency of the jumps depend on the physiological state of the cells, the average jump distance ( approximately 0.8 microm) is unaffected by metabolic activity. During short time intervals, the dynamics appear to be spatially heterogeneous, whereas the cumulative effect of the infrequent jumps leads to the appearance of diffusive motion in the limit of long time intervals.

Biophysical Phenomena↗
PubMed1998

The conceptual structure of the integrated exposure uptake biokinetic model for lead in children.

The integrated exposure uptake biokinetic model for lead in children was developed to provide plausible blood lead distributions corresponding to particular combinations of multimedia lead exposure. The model is based on a set of equations that convert lead exposure (expressed as micrograms per day) to blood lead concentration (expressed as micrograms per deciliter) by quantitatively mimicking the physiologic processes that determine blood lead concentration. The exposures from air, food, water, soil, and dust are modeled independently by several routes. Amounts of lead absorbed are modeled independently for air, food, water, and soil/dust, then combined as a single input to the blood plasma reservoir of the body. Lead in the blood plasma reservoir, which includes extracellular fluids, is mathematically allocated to all tissues of the body using age-specific biokinetic parameters. The model calculation provides the estimate for blood lead concentration for that age. This value is treated as the geometric mean of possible values for a single child, or the geometric mean of expected values for a population of children exposed to the same lead concentrations. The distribution of blood lead concentrations about this geometric mean is estimated using a geometric standard deviation, typically 1.6, derived from the analysis of well-conducted community blood studies.

Algorithms↗
PubMed1998

Some useful statistical methods for model validation.

Although formal hypothesis tests provide a convenient framework for displaying the statistical results of empirical comparisons, standard tests should not be used without consideration of underlying measurement error structure. As part of the validation process, predictions of individual blood lead concentrations from models with site-specific input parameters are often compared with blood lead concentrations measured in field studies that also report lead concentrations in environmental media (soil, dust, water, paint) as surrogates for exposure. Measurements of these environmental media are subject to several sources of variability, including temporal and spatial sampling, sample preparation and chemical analysis, and data entry or recording. Adjustments for measurement error must be made before statistical tests can be used to empirically compare environmental data with model predictions. This report illustrates the effect of measurement error correction using a real dataset of child blood lead concentrations for an undisclosed midwestern community. We illustrate both the apparent failure of some standard regression tests and the success of adjustment of such tests for measurement error using the SIMEX (simulation-extrapolation) procedure. This procedure adds simulated measurement error to model predictions and then subtracts the total measurement error, analogous to the method of standard additions used by analytical chemists.

Animals↗
PubMed1989

Nickel absorption and kinetics in human volunteers.

Mathematical modeling of the kinetics of nickel absorption, distribution, and elimination was performed in healthy human volunteers who ingested NiSO4 drinking water (Experiment 1) or added to food (Experiment 2). Nickel was analyzed by electrothermal atomic absorption spectrophotometry in serum, urine, and feces collected during 2 days before and 4 days after a specified NiSO4 dose (12 micrograms of nickel/kg, n = 4; 18 micrograms of nickel/kg, n = 4; or 50 micrograms of nickel/kg, n = 1). In Experiment 1, each of the subjects fasted 12 hr before and 3 hr after drinking one of the specified NiSO4 doses dissolved in water; in Experiment 2, the respective subjects fasted 12 hr before consuming a standard American breakfast that contained the identical dose of NiSO4 added to scrambled eggs. Kinetic analyses, using a compartmental model, provided excellent goodness-of-fit for paired data sets from all subjects. Absorbed nickel averaged 27 +/- 17% (mean +/- SD) of the dose ingested in water vs 0.7 +/- 0.4% of the same dose ingested in food (a 40-fold difference); rate constants for nickel absorption, transfer, and elimination were not significantly influenced by the oral vehicle. The elimination half-time for absorbed nickel averaged 28 +/- 9 hr. Renal clearance of nickel averaged 8.3 +/- 2.0 ml/min/1.73 m2 in Experiment 1 and 5.8 +/- 4.3 ml/min/1.73 m2 in Experiment 2. This study confirms that dietary constituents profoundly reduce the bioavailability of Ni2+ for alimentary absorption; approximately one-quarter of nickel ingested in drinking water after an over-night fast is absorbed from the human intestine and excreted in urine, compared with only 1% of nickel ingested in food. The compartmental model and kinetic parameters provided by this study will reduce the uncertainty of toxicologic risk assessments of human exposures to nickel in drinking water and food.

Adult↗
PubMed1987

Dose-response curves for erythrocyte protoporphyrin vs blood lead: effects of iron status.

An increase in erythrocyte protoporphyrin (EP) is one of the most useful indicators of adverse biological response to lead exposure. A nonlinear mathematical model relating EP to blood lead concentration (PbB) was fitted to data in a sample of 1677 U.S. children (ages 2-6 years) in the Second National Health and Nutrition Examination Survey (NHANES II). Iron status was defined by percentage transferrin saturation (PTS). The dose-response curves for EP vs PbB increased systematically with decreasing PTS, largely due to decrease of a parameter proportional to red cell lead-holding capacity with decreasing PTS.

Adult↗
PubMed1986

Sexual differences in the distribution and retention of organic and inorganic mercury in methyl mercury-treated rats.

At 56 days of age, male and female Long-Evans rats received 1 mumole of 203Hg-labeled methyl mercuric chloride per kilogram sc and total, organic, and inorganic mercury contents and concentrations in tissues were determined for up to 98 days postdosing. Whole body clearance of mercury was faster in females than in males, and females attained higher peak percentages of the methyl mercury dose in kidney and brain than did males. Females had significantly higher mean percentages of the mercury dose present in the kidney and brain as organic or total mercury and in brain as inorganic mercury than did males. Males had significantly higher mean percentages of the dose present as organic or total mercury in pelt and whole body than did females. When expressed on a concentration basis, the only significant sexual difference was in the higher average concentration of organic mercury in the kidneys of females. When expressed on a tissue content basis, significant male-female differences in the kinetics (sex X time interactions) of organic mercury retention were found in kidney, brain, skeletal muscle, pelt, and whole body. Significant sex X time interactions in the concentrations of organic mercury were found in kidney, skeletal muscle, and whole body. Kinetics of retention and concentration of inorganic Hg in the pelt differed significantly for males and females. Discordance in degree of statistical significance of differences in mercury contents and concentrations reflected in part differences in relative body composition of males and females. Integrated exposures of tissues of males and females to organic or inorganic mercury were determined by fitting multiexponential retention functions to retention data. Differences in integrated exposure were estimated by the female-to-male ratio of areas under retention curves. Reconstruction of whole body organic and inorganic mercury burdens from constituent tissues indicated that integrated exposures of males and females to inorganic mercury were equal but females had a lower integrated exposure to organic mercury. Integrated exposure of liver to either form of mercury was about equal in males and females. However, the integrated exposure of the brain of females to inorganic mercury was 2.19 times that of males suggesting a sexual difference in accumulation or retention of inorganic mercury in the nervous system. These sexual differences in distribution and retention of organic and inorganic mercury after methyl mercury exposure may underlie reported sexual differences in sensitivity to the toxic effects of methyl mercury.

Animals↗
PubMed1985

Multicompartment kinetic models for lead. I. Bone diffusion models for long-term retention.

The long-term retention of lead in bone poses a number of difficulties for the usual multicompartment models. The use of diffusion models based on exchange of lead between blood in canaliculi and the crystalline bone of the osteon allows a linear compartmental approximation suitable for statistical estimation of kinetic parameters in peripheral compartments. The model is applied to lead retention by beagle dogs.

Animals↗
PubMed1985

Multicompartment kinetic models for lead. II. Linear kinetics and variable absorption in humans without excessive lead exposures.

Multicompartment models with constant fractional transfer rates have been fitted to experimental data on lead metabolism in four subjects studied by M. B. Rabinowitz, G. W. Wetherill, and J. D. Kopple (Science 182, 725-727, 1973; Environ. Health Perspect. 7, 145-153, 1974; Arch. Environ. Health 31, 220-223, 1976; J. Clin. Invest. 58, 260-270, 1976; J. Lab. Clin. Med. 90, 238-248, 1977). Long-term retention is estimated for blood, soft tissue, cortical and trabecular bone pools, and for facial hair. The absorption of lead from diet is shown to change with time, but no evidence was found for other variable or nonlinear kinetic mechanisms of lead metabolism in humans without excessive lead exposure.

Diffusion↗
PubMed1985

Multicompartment kinetic model for lead. III. Lead in blood plasma and erythrocytes.

Multicompartment models have been fitted to experimental data on plasma lead and blood lead concentrations of subjects studied by P. E. deSilva (Brit. J. Ind. Med. 38, 209-217, 1981) and one subject studied by W.I. Manton and C.R. Malloy (Brit. J. Ind. Med. 40, 51-57, 1983). Nonlinear models for plasma lead vs blood lead in populations provide significantly better descriptions than does a linear model. Short-term kinetic data do not clearly resolve the precise nonlinear mechanism, however, Parameters of plasma and erythrocyte distribution in a single subject were significantly different on two occasions.

Erythrocytes↗
PubMed1983

Compartmental models for trace metals in mammals.

Kinetic models for the distribution and elimination of certain trace metals in mammals allow evaluation of metal burdens in critical target organs under time-variables exposure patterns, and thus may assist in formulating exposure standards. The linear compartmental model is described and some of its implications for conceptual models of trace metal metabolism are developed. The model is then applied to data on multiple doses of cadmium in mice. Many trace metals do not follow simple linear kinetic models because exposure to more than one metal simultaneously often results in synergistic effects.

Animals↗
PubMed1981

Ontogeny of the barley plant as related to mutation expression and detection of pollen mutations.

Clustering of mutant pollen grains in a population of normal pollen due to premeiotic mutational events complicates translating mutation frequencies into rates. Embryo ontogeny in barley will be described and used to illustrate the formation of such mutant clusters. The nature of the statistics for mutation frequency will be described from a study of the reversion frequencies of various waxy mutants in barley. Computer analysis by a "jackknife" method of the reversion frequencies of a waxy mutant treated with the mutagen sodium azide showed a significantly higher reversion frequency than untreated material. Problems of the computer analysis suggest a better experimental design for pollen mutation experiments. Preliminary work on computer modeling for pollen development and mutation will be described.

Computers↗
PubMed1979

First passage times as environmental safety indicators: carboxyhemoglobin from cigarette smoke.

The concentration of carbon monoxide in the blood of a cigarette smoker varies in response to the frequency and dose of CO delivered by the cigarettes he smokes and by the rate at which CO washes out of his blood. Moments of first passage times or exit times above a nominal threshold can be calculated using a stochastic differential equation that takes into account certain random variations in smoking intervals. CO doses, and washout rate. Almost any additional source of variation decreases in length of time a smoker may expect to smoke until a threshold value is exceeded. In particular the methodology proposed by Gori (1976) and Gori and Lynch (1978) for constant intervals, doses and rate may greatly overestimate the length of the "low-risk" interval for carbon monoxide concentration. One possible modification that may reduce CO hazards is to smoke less from each cigarette, even when this may be partially compensated by increased frequency of smoking.

Absorption↗