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J Eisinger

Publications and source records attributed to J Eisinger.

At least 19 recordsLinked to original sources

Distribution of non-heme porphyrin content of individual erythrocytes by fluorescence image cytometry and its application to lead poisoning.

The quantitation of the non-heme porphyrin content of circulating erythrocytes is an important tool in the screening, diagnosis, and management of lead disease, iron deficiency anemia, and certain porphyrias. Useful information about these pathological conditions may be obtained from the distribution of the non-heme porphyrin content of individual red blood cells. An image-based cytometry system was developed and used to determine the cellular distributions of zinc protoporphyrin (ZPP) in the erythrocytes of normal and lead-exposed human subjects. The fluorescence cytometry system described here lends itself to a wide range of statistical studies of cell populations, in which extrinsic fluorescent probes or antibodies may be used instead of porphyrin. Image-based cytometry appears to offer a number of important advantages over the more conventional flow cytometry systems, including greater sensitivity, applicability to a wider range of cellular parameters, and the ability to retain images of each cell used in the survey for subsequent examination. Pairs of absorption and fluorescence images of many fields of dispersed immobilized red cells were acquired by means of a program which controls the microscope stage, focussing, shutters, filter wheels, and a cooled, slow-scan CCD camera. The observed marked differences in the ZPP distributions of erythrocytes from donors with chronic and acute lead exposure are discussed in terms of the metabolism of internalized lead.

Algorithms

Modulation of lateral transport of membrane components by spatial variations in diffusivity and solubility.

The effect of spatially varying diffusivity and solubility on the efficiency of intramembrane transport is investigated by obtaining solutions to the generalized lateral diffusion equation in which both the diffusion coefficient, D(r), and the partition coefficient, K(r), are functions of position. The mean-time-to-capture by a sink, tc, of particles diffusing in a plane is obtained analytically for the case of a sink surrounded by gradients in D(r) and K(r) with radially symmetrical geometry. It is shown that for particles originating at random locations, tc is shortened dramatically, if in an annular region around the sink, D and K are significantly greater than in the remainder of the plane. Similarly, a viscous boundary layer surrounding a sink is demonstrated to represent a significant barrier for diffusing particles. To investigate more complex geometries, a finite difference numerical integration method is used and is shown to provide comparable results for tc with modest computational power. The same method is used to calculate the tc for particles originating at a source that is joined to the sink by a channel. The increase in the rate with which particles travel from a source to a sink when they are joined by a high diffusivity and/or solubility channel is illustrated by several numerical examples and by graphical representations that show the equilibrium particle density (and hence the effective particle flow) in the presence of different sink, source, and channel combinations. These results are discussed in terms of fluidity domains and other membrane heterogeneities.

Cell Membrane

Distribution of erythrocyte free porphyrin content in erythropoietic protoporphyria.

Erythrocytes of patients suffering from erythropoietic protoporphyria (EPP) contain high levels of unchelated protoporphyrin IX (PP) molecules when they enter circulation, and the leakage of PP that leaks from the circulating cells is responsible for the patients' cutaneous photosensitivity. The level of PP in EPP blood has long been used as an indicator of the severity of the disease and is useful in its management. The present study investigates what additional information may be obtained by determining the distribution of the PP content of individual EPP red cells. Absorption and fluorescence images of fields of the dispersed and immobilized red cells from nine patients with EPP were acquired under computer control by use of an inverted fluorescence microscope equipped with a cooled slow-scan charge-coupled device camera. The distribution functions of the fluorescence emitted by individual red blood cells (IRBC) were derived by a suitable image analysis program and were converted to the distributions of the cellular PP content by relating the average value of the distributions (Iav) to the PP level of packed cells, as determined by an extraction assay. The IRBC distributions show that a small percentage of the red cells is responsible for most of the PP fluorescence, and the distributions of IRBC/Iav for the nine patients with EPP were found to be very similar. This is consistent with the leakage rate during circulation being approximately proportional to the cells' PP content.

Erythrocyte Membrane

Living with lead.

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Environmental Pollutants

The orientational freedom of molecular probes. The orientation factor in intramolecular energy transfer.

The measurement of the efficiency of Förster long-range resonance energy transfer between donor (D) and acceptor (A) luminophores attached to the same macromolecular substrate can be used to estimate the D-A separation, R. If the D and A transition dipoles sample all orientations with respect to the substrate (the isotropic condition) in a time short compared with the transfer time (the dynamic averaging condition), the average orientation factor less than K2 greater than is 2/3. If the isotropic condition is not satisfied but the dynamic averaging condition is, upper and lower bounds for less than K2 greater than, and thus R, may be obtained from observed D and A depolarizations, and these limits may be further narrowed if the transfer depolarization is also known. This paper offers experimental protocols for obtaining this reorientational information and presents contour plots of less than K2 greater than min and less than K2 greater than max as functions of generally observable depolarizations. This permits an uncertainty to be assigned to the determined value of R. The details of the D and A reoreintational process need not be known, but the orientational distributions are assumed to have at least approximate axial symmetry with respect to a stationary substrate. Average depolarization factors are derived for various orientational distribution functions that demonstrate the effects of various mechanisms for reorientation of the luminophores. It is shown that in general the static averaging regime does not lend itself to determinations of R.

Energy Transfer

Central nervous system dysfunction due to lead exposure.

Central nervous system dysfunction was investigated in workers at a secondary lead smelter by means of performance tests. Correlations between test scores and zinc protoporphyrin levels, a biological indicator of lead toxicity, are statistically significant. This correlation should prove to be useful in current efforts to evaluate effects of lead exposure.

Adult

Hemoglobin, serum iron, and zinc protoporphyrin in lead-exposed workers.

In a previous study of secondary lead smelter workers (males), a significant prevalence of low hemoglobin levels (less than 14 g/100 ml) was found; a statistically significant negative correlation between hemoglobin and zinc protoporphyrin was also detected. In the present study serum iron (Fe) levels and total iron binding capacity (TIBC) were included in the investigation of 111 secondary lead smelter workers and 37 nonexposed controls. The distribution and mean values of serum iron and TIBC were found to be in the normal range in the lead exposed workers; there was no significant difference when compared to the control population. There was no significant correlation between blood lead or zinc protoporphyrin and serum iron, TIBC and Fe/TIBC. A statistically significant negative correlation between hemoglobin and blood lead levels was found; the correlation between hemoglobin and zinc protoporphyrin reached a much higher level of significance. The results support the view that anemia (low hemoglobin levels) in lead exposed male workers is related to the heme synthesis inhibiting effects of lead, as reflected by elevated zinc protoporphyrin levels, and is not due to iron deficiency.

Adult

[Dosage of ionized calcium in osteo-articular pathology].

The dosage of calcium ionized serum using a selective electrode, was performed in a series of controls and patients with osteo-articular diseases. Normal values were 43 mg/l between 20 and 50 years of age, and 41 mg/l after 60 years. The level of ionized calcium, when given as a percentage of total blood calcium, did not decrease with age (normal value : 44%). It was increased in hyper-parathyroidism, rhumatoid polyarthritis and lytic bone metastasis. It did not vary in Paget's disease, osteoporosis, osteomalacia, condensing metastasis, Kahler's disease and spasmophilia. The ionized calcium in definitely diminished in hypoparathyroidism.

Adolescent