Biomedical subjects

Eugene Demidenko

Publications and source records attributed to Eugene Demidenko.

28 records · Page 2Linked to original sources

PubMed2004

Statistical estimation of resistance/conductance by electrical impedance tomography measurements.

This paper is built upon the assumption that in electrical impedance tomography, vectors of voltages and currents are linearly dependent through a resistance matrix. This linear relationship was confirmed experimentally and may be derived analytically under certain assumptions regarding electrodes (Isaacson, 1991). Given measurement data consisting of voltages and currents, we treat this relationship as a linear statistical model. Thus, our goal is not to reconstruct the image but directly estimate its electromagnetic properties reflected in the resistance and/or conductance matrix using electrical impedance tomography (EIT) measurements of voltages and currents on the periphery of the body. Since no inverse problem is involved the algorithm for estimation merely reduces to one matrix inversion. We estimate the impedance resistance matrix using well established statistical inference techniques for linear regression models. We provide a comprehensive treatment for a two-dimensional homogeneous body of a circular shape, by which many concepts of electrical impedance tomography, such as width of electrodes, the difference between voltage-current and current-voltage systems are illustrated. Our theory may be applied to various tests including EIT hardware calibration and whether the medium is homogeneous. These tests are illustrated on phantom agar data.

Agar↗

PubMed2003

Spin traps: in vitro toxicity and stability of radical adducts.

We have evaluated the effects of DMPO, CMPO, EMPO, BMPO, and DEPMPO on functioning CHO cells and the stability of the radical adducts in the presence of cells. The potential toxic effects of the spin traps were measured by two estimates of cell viability (trypan blue exclusion and colony formation) and one of cell function (rate of oxygen consumption). We also studied the effects of the spin traps on colony formation in a second cell line, 9L tumor cells. Toxicity varied with the type of cell line and the parameter that was measured. In aqueous solutions the order of stability for all spin adducts was SO(3) > OH > CH(3), while in cell suspensions it was SO(3) > OH approximately CH(3). The radical adducts of the new spin traps have significantly increased stability as compared to DMPO. These results indicate that the new spin traps potentially offer increased stability of spin adducts in functioning cells. It also is clear that it is necessary to carry out appropriate studies of the stability and toxicity in the system that is to be studied for any particular use of these spin traps. It then should be feasible to select the spin trap(s) best suited for the proposed study.

Animals↗

PubMed2003

Power and sample size calculations for generalized regression models with covariate measurement error.

Covariate measurement error is often a feature of scientific data used for regression modelling. The consequences of such errors include a loss of power of tests of significance for the regression parameters corresponding to the true covariates. Power and sample size calculations that ignore covariate measurement error tend to overestimate power and underestimate the actual sample size required to achieve a desired power. In this paper we derive a novel measurement error corrected power function for generalized linear models using a generalized score test based on quasi-likelihood methods. Our power function is flexible in that it is adaptable to designs with a discrete or continuous scalar covariate (exposure) that can be measured with or without error, allows for additional confounding variables and applies to a broad class of generalized regression and measurement error models. A program is described that provides sample size or power for a continuous exposure with a normal measurement error model and a single normal confounder variable in logistic regression. We demonstrate the improved properties of our power calculations with simulations and numerical studies. An example is given from an ongoing study of cancer and exposure to arsenic as measured by toenail concentrations and tap water samples.

Arsenic↗

PubMed2003

Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity.

Photodynamic therapy (PDT) with verteporfin (lipid form of benzoporphyrin derivative,benzoporphyrin derivative monoacid ring A) was used to treat radiation-induced fibrosarcoma tumors before X-ray treatment. When verteporfin was injected 3 h before light irradiation, the tumor partial pressure of oxygen (pO(2)) rose from a pretreatment value of 2.8 +/- 1 to 15.2 +/- 6.9 mm Hg immediately after light application was complete (P = 0.048). When the optical irradiation was given 15 min after verteporfin injection, the tumor pO(2) decreased slightly after treatment [i.e., 6.8 +/- 1.6 mm Hg (pretreatment) versus 4.1 +/- 0.3 mm Hg (posttreatment)], whereas control tumor pO(2) did not change significantly. In vitro study of the cellular oxygen consumption rate before and after PDT treatment indicated that the consumption rate decreased linearly with delivered optical dose and quantitatively matched the loss of cell viability as measured by a mitochondrial tetrazolium assay. Doppler measurements show that red cell flux is still patent immediately after treatment, indicating that oxygen should still be delivered to the tumor. Computational simulations of the oxygen supply from the vessels and the consumption from mitochondrial activity confirmed that if oxygen consumption is decreased in the presence of unhindered blood flow, the tumor oxygenation should rise, and the hypoxic fraction of the tumor should decrease. Combination treatments with PDT delivered (100 J/cm(2) optical dose, with 1 mg/kg benzoporphyrin derivative monoacid ring A injected 3 h before treatment) after radiation treatment (10 Gy from 300 keV source) were compared with PDT delivered simultaneously with radiation. Tumor regrowth assay showed that the delays to reach double the tumor volume for PDT alone and radiation alone were 2.7 +/- 1.6 and 3.2 +/- 1.7 days, respectively. When radiation was given before PDT, the delay was 5.4 +/- 1.4 days, and when PDT was given at the same time as radiation, the delay was 8.1 +/- 1.5 days. This observation indicates that the combined effect in the latter case was greater than additive (P = 0.049).

Animals↗

PubMed2003

Plasma membrane cholesterol: a possible barrier to intracellular oxygen in normal and mutant CHO cells defective in cholesterol metabolism.

The effect of the cholesterol content of the plasma membrane on the intracellular concentration of oxygen in Chinese hamster ovary (CHO) cells and their mutants was investigated by EPR oximetry. Total and free cholesterol content was significantly higher in 25 RA CHO cells as compared to wild-type and M 19 CHO cells, with most of the free cholesterol in normal and mutant CHO cells located in the plasma membrane. The plasma membrane cholesterol content also was altered by various biochemical means, and the effect on the oxygen gradient was studied. Comparing the three cell lines, the gradient was larger with increased content of cholesterol in the plasma cell membrane. This result also is supported by an additional increase in the oxygen gradients with the incorporation of additional cholesterol in the plasma membrane and a decrease in the oxygen gradient when the cholesterol was depleted from the plasma membrane. The results indicate that the concentration of cholesterol in the plasma membrane can be an important factor for the magnitude of the oxygen gradient observed across the cell membrane.

Animals↗

PubMed2003

Oxygen consumption rates and oxygen concentration in molt-4 cells and their mtDNA depleted (rho0) mutants.

Respiratory deficient cell lines are being increasingly used to elucidate the role of mitochondria and to understand the pathophysiology of mitochondrial genetic disease. We have investigated the oxygen consumption rates and oxygen concentration in wild-type (WT) and mitochondrial DNA (mtDNA) depleted (rho(0)) Molt-4 cells. Wild-type Molt-4 cells have moderate oxygen consumption rates, which were significantly reduced in the rho(0) cells. PCMB (p-chloromercurobenzoate) inhibited the oxygen consumption rates in both WT and rho(0) cells, whereas potassium cyanide decreased the oxygen consumption rates only in WT Molt-4 cells. Menadione sodium bisulfite (MSB) increased the oxygen consumption rates in both cell lines, whereas CCCP (carbonyl cyanide m-chlorophenylhydrazone) stimulated the oxygen consumption rates only in WT Molt-4 cells. Superoxide radical adducts were observed in both WT and rho(0) cells when stimulated with MSB. The formation of this adduct was inhibited by PCMB but not by potassium cyanide. These results suggest that the reactive oxygen species (ROS) induced by MSB were at least in part produced via a mitochondrial independent pathway. An oxygen gradient between the extra- and intracellular compartments was observed in WT Molt-4 cells, which further increased when cells were stimulated by CCCP and MSB. The results are consistent with our earlier findings suggesting that such oxygen gradients may be a general phenomenon found in most or all cell systems under appropriate conditions.

Benzoates↗

PubMed2003

Magnetic resonance imaging studies of age-dependent responses to scaled focal brain injury in the piglet.

OBJECT: Whether the brain differs in its response to traumatic injury as a function of age remains unclear. To further investigate the age-dependent response of the brain to mechanical trauma, a cortical contusion model scaled for brain growth during maturation was used to study the evolution of injury over time as demonstrated on serial magnetic resonance (MR) imaging studies in piglets of different ages. METHODS: Sixteen Yorkshire piglets received scaled cortical contusions. Animals were either 5 days (six animals), 1 month (five animals), or 4 months (five animals) of age at injury. These ages correspond developmentally to human infants, toddlers, and early adolescents, respectively. Serial MR imaging examinations, including fluid-attenuated inversion-recovery and T1-, T2-, and diffusion-weighted sequences were performed at 24 hours, 1 week, and 1 month after injury. Lesions were quantified and expressed as a ratio of the lesion volume divided by the volume of the uninjured hemisphere for each animal and each MR sequencing. Differences in relative lesion volume among the varied ages at a single time point and in lesion volume over time at each age were compared. In addition, the relationship between age and evolution of injury were analyzed using a two-compartment mathematical model. Histological features were examined at 1 month postinjury. Despite comparable injury inputs, the youngest animals had lesions whose volumes peaked earlier and resolved more quickly than those in older animals. The intermediate-age piglets (toddler) had the most pronounced swelling of any age group, and the oldest piglets (adolescent) had the latest peak in lesion volume. CONCLUSIONS: Scaled cortical contusions in piglets demonstrated age-dependent differences in injury response, both in magnitude and time course. These observations may shed light on development-related trauma response in the gyrencephalic brain.

Age Factors↗

PubMed2003

The combination of a potent vitamin D3 analog, EB 1089, with ionizing radiation reduces tumor growth and induces apoptosis of MCF-7 breast tumor xenografts in nude mice.

PURPOSE: The purpose of this research was to evaluate theinfluence of the combination of the vitamin D(3) analogue EB 1089 with fractionated radiation on growth and apoptosis of MCF-7 tumor xenografts in athymic mice. EXPERIMENTAL DESIGN: Four to six-week-old ovariectomized mice were injected s.c. with MCF-7 tumor cells suspended in Matrigel. When tumors reached a size of approximately 150-200 mm(3), animals were exposed to EB 1089 (45 pmols/day) for 8 days, whereas mice that were to be irradiated in the absence of EB 1089 received solvent (Solutol HS15). After the termination of EB 1089 and solvent administration, tumors were irradiated (3 x 5 Gy) over a period of 3 days using a 300 KV Pantax Therapax irradiator. Tumor growth was monitored for 25-30 days after the last dose of irradiation in a double-blind manner; tumor cellularity was assessed by H&E and trichrome staining, cell proliferation by Ki-67 staining, and apoptosis by terminal deoxynucleotidyltransferase-mediated nick end labeling assay. Rates of tumor regression were assessed using a mixed effects statistical model. RESULTS: A significantly higher rate of decline in tumor volume (7.5% per day) was observed in mice exposed to radiation subsequent to EB 1089 compared with animals treated with radiation alone (5.6% per day). Final tumor volumes in animals irradiated after EB 1089 were approximately 50% lower than in the group that received radiation alone. Loss of cellularity, a marked reduction in the fraction of proliferating cells, and the promotion of apoptosis confirmed that the combination of EB 1089 with radiation was significantly more effective than radiation alone in blocking tumor cell growth and promoting tumor cell death. CONCLUSIONS: This work demonstrates that EB 1089 can improve local tumor control by fractionated radiation, in part through the promotion of apoptotic cell death.

Animals↗

PubMed2002

Changes in oxygenation of intracranial tumors with carbogen: a BOLD MRI and EPR oximetry study.

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.

Animals↗

PubMedDate not supplied

Life spans and senescent phenotypes in two strains of Zebrafish (Danio rerio).

Zebrafish have become a widely used model organism in developmental biology research. In order to initiate an experimental foundation for aging studies, we have determined some basic gerontological parameters for populations of outbred zebrafish, and the golden sparse strain. Outbred zebrafish manifested a mean life span of about 42 months, with the longest living individual surviving for 66 months. The golden sparse populations had a mean life span of 36 months and a maximum longevity of 58 months. Skeletal length at death increased with age, suggestive of indeterminate growth. A common age-related phenotype was spinal curvature. Radiographic analysis excluded bony changes as the cause of the spinal curvature, suggesting muscle abnormalities as a primary mechanism. These data and a growing abundance of related biological resources suggest that the zebrafish may be a compelling model organism for studies on aging.

Aging↗