Biomedical subjects

Martin J Lizak

Publications and source records attributed to Martin J Lizak.

9 recordsLinked to original sources

PubMed2006

MR assessment of changes of tumor in response to hyperbaric oxygen treatment.

Enhancement of image intensity, using the T1-weighted spoiled gradient-echo (SPGR) sequence, was measured in SCC tumor implanted in the flank of C3H mice while they were subjected to several types of oxygenation challenges inside a hyperbaric chamber designed and constructed to fit in an MRI resonator. The central portions of the tumor gave a positive enhancement, while the periphery showed signal reduction during both normobaric (NBO) and hyperbaric (HBO) oxygen challenges. In the contralateral normal leg, nearly 70% of the region showed a decrease in intensity, and the rest showed a positive enhancement. The positive signal enhancement was markedly greater under HBO compared to NBO. Calculated R1, R2, and M0 maps from multivariate fitting of images acquired by a multislice multiecho (MSME) sequence with variable TR before, during, and after HBO treatment confirm that the source of SPGR signal enhancement in the tumor is associated with shortening of T1.

Animals↗

PubMed2005

Study of ocular transport of drugs released from an intravitreal implant using magnetic resonance imaging.

Ensuring optimum delivery of therapeutic agents in the eye requires detailed information about the transport mechanisms and elimination pathways available. This knowledge can guide the development of new drug delivery devices. In this study, we investigated the movement of a drug surrogate, Gd-DTPA (Magnevist) released from a polymer-based implant in rabbit vitreous using T1-weighted magnetic resonance imaging (MRI). Intensity values in the MRI data were converted to concentration by comparison with calibration samples. Concentration profiles approaching pseudosteady state showed gradients from the implant toward the retinal surface, suggesting that diffusion was occurring into the retinal-choroidal-scleral (RCS) membrane. Gd-DTPA concentration varied from high values near the implant to lower values distal to the implant. Such regional concentration differences throughout the vitreous may have clinical significance when attempting to treat ubiquitous eye diseases using a single positional implant. We developed a finite element mathematical model of the rabbit eye and compared the MRI experimental concentration data with simulation concentration profiles. The model utilized a diffusion coefficient of Gd-DTPA in the vitreous of 2.8 x 10(-6) cm2 s(-1) and yielded a diffusion coefficient for Gd-DTPA through the simulated composite posterior membrane (representing the retina-choroidsclera membrane) of 6.0 x 10(-8) cm2 s(-1). Since the model membrane was 0.03-cm thick, this resulted in an effective membrane permeability of 2.0 x 10(-6) cm s(-1). Convective movement of Gd-DTPA was shown to have minimal effect on the concentration profiles since the Peclet number was 0.09 for this system.

Animals↗

PubMed2005

Syneretic response to incremental pressures in calf lenses.

PURPOSE: Syneretic response to pressure variation of 1 atm or more has been demonstrated previously in bovine and human lenses with nuclear magnetic resonance (NMR) relaxation measurements. This study is designed to prove that a similar response is observable in smaller pressure increments closer to the normal physiological range. METHODS: Excised calf eyes were enucleated, the lenses dissected out, and immersed in medium. The lenses were exposed to incremental pressures ranging from 1 to 3 atm. At each pressure increment, a series of T1-weighted and spin echo images were acquired. Each image was segmented into seven regions of interest and tabulated. Longitudinal (T1) and transverse (T2) relaxation times were calculated from numerical fits of the experimental values to a one-term exponential expression. RESULTS: The relaxation parameters were obtained from fitting the image intensities to exponential equations, which yielded a relaxation time T and a pre-exponential factor M. The relaxation times and the pre-exponential terms of both parameters displayed linear dependence on pressure. There was no evidence of a threshold for syneretic response. Both T1 and T2 relaxation times decreased with increasing pressure. The pre-exponential term M2 increased with pressure, whereas M1 decreased with pressure; however, the slope of the latter was statistically not significantly different from zero. CONCLUSIONS: Syneretic response to pressure in calf lenses as determined by NMR relaxation measurements proved to be linearly dependent on pressure over a wide range of hydrostatic pressures. There was no range where the syneretic response was absent. These two findings allow the conclusion that the phenomenon observed hitherto at large pressure changes in vitro could be operative in vivo under physiological pressure changes during accommodation.

Animals↗

PubMed2004

Considerations for setting up a small-animal imaging facility.

Imaging techniques allow for the conduct of noninvasive, in vivo longitudinal small-animal studies, but also require access to expensive and complex equipment, and personnel who are properly trained in their use. The authors describe their planning and staffing of the NIH Mouse Imaging Facility, and highlight important issues to consider when designing a similar facility.

Animals↗

PubMed2004

Controlled drug release from an ocular implant: an evaluation using dynamic three-dimensional magnetic resonance imaging.

PURPOSE: The ability of an episcleral implant at the equator of the eye to deliver drugs to the posterior segment was evaluated, using a sustained-release implant containing gadolinium-DTPA (Gd-DTPA). The movement of this drug surrogate was assessed with magnetic resonance imaging (MRI) in the rabbit eye. The results were compared with a similar implant placed in the vitreous cavity through a scleral incision at the equator. METHODS: Polymer-based implants releasing Gd-DTPA were manufactured and placed in the subconjunctival space on the episclera or in the vitreous cavity in live rabbit eyes (in vivo) and in freshly enucleated eyes (ex vivo). Release rates of implants in vitro were also determined. Dynamic three-dimensional MRI was performed using a 4.7-Tesla MRI system for 8 hours. MR images were developed and analyzed on computer. RESULTS: Episcleral implants in vivo delivered a mean total of 2.7 microg Gd-DTPA into the vitreous, representing only 0.12% of the total amount of compound released from the implant in vitro. No Gd-DTPA was detected in the posterior segment of the eye. Ex vivo, the Gd-DTPA concentration in the vitreous was 30 times higher. In vivo eyes with intravitreal implants placed at the equator delivered Gd-DTPA throughout the vitreous cavity and posterior segment. Compartmental analysis of the ocular drug distribution from an episcleral implant showed that the elimination rate constant of Gd-DTPA from the subconjunctival space into the episcleral veins and conjunctival lymphatics was 3-log units higher than the transport rate constant for Gd-DTPA movement into the vitreous. CONCLUSIONS: In vivo, episcleral implants at the equator of the eye did not deliver a significant amount of Gd-DTPA into the vitreous, and no compound was identified in the posterior segment. A 30-fold increase in vitreous Gd-DTPA concentration occurred in the enucleated eyes, suggesting that there are significant barriers to the movement of drugs from the episcleral space into the vitreous in vivo. Dynamic three-dimensional MRI using Gd-DTPA, and possibly other contrast agents, may be useful in understanding the spatial relationships of ocular drug distribution and clearance mechanisms in the eye.

Animals↗

PubMed2003

NADPH-dependent reductases and polyol formation in human leukemia cell lines.

Because of the limited availability of human tissues, leukemia cell lines are often utilized as the models for human leukocytes. In this study, we investigated the NADPH-dependent reductases and polyol pathway in commonly utilized human leukemia cell lines. The relative amounts of aldose and aldehyde reductases were estimated by separating two enzymes with chromatofocusing. The flux of glucose through the polyol pathway was examined by 19F-NMR using 3-fluoro-3-deoxy-D-glucose (3FG) as substrate. Sugar alcohol analysis was conducted by gas chromatography. In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low. Although lymphocytic cells also contained both aldose and aldehyde reductases, the levels of aldose reductase appeared to be higher in lymphocytic cells than myeolcytic cells. In two lymphocytic cells MOLT-4 and SKW6.4, aldose reductase is clearly dominant. When incubated in medium containing D-galactose, all cell lines quickly accumulated galactitol. There was correlation between galactitol levels and aldose reductase levels. The aldose reductase inhibitor FK 366 significantly reduced the formation of galactitol. 19F-NMR of the cells cultured with 3FG as substrate demonstrated the formation of 3-fluoro-3-dexoy-sorbitol in all the cell lines examined in this study. The relative amounts of sorbitol and fructose varied significantly among the cells. The data confirm that the polyol pathway is present in both myelocytic and lymphocytic leukemia cell lines. However, there is a large variation among the cell lines in the levels of enzymes and flux of glucose through the polyol pathway.

Chromatography, Gas↗

PubMed2003

Syneretic response of aging normal human lens to pressure.

PURPOSE: The study was designed to observe whether a reversible syneretic response to pressure is operative in normal human lenses and whether such a response demonstrates a uniform age dependence. METHODS: Seven sections (from the anterior outer cortex to the posterior outer cortex) of 10 human lenses were imaged at 2 atmospheres (atm) pressure and the T(1) (spin-lattice) and T(2) (spin-spin) relaxation data on each section were collected. The pressure was then released and NMR relaxographic data were collected under 1 atm. RESULTS: Both T(1) and T(2) relaxation times were at their minimum in the nuclear region and at their maximum at the two outer cortexes. With increasing pressure, T(2) relaxation times decreased. The pressure-dependent change in T(2) relaxation times decreased with age. Changes in T(1) relaxation times showed no consistent pressure or age dependence. The population index of T(2) relaxation, M(2), had a maximum in the nucleus and a minimum in the two cortexes. The population index of T(1) relaxation, M(1,) was minimal in the nucleus and maximal at the two cortexes. M(2) increased with increasing pressure, whereas M(1) did not show consistent pressure dependence. The percentage of change in M(2) (DeltaM(2)) showed a statistically significant increase with increasing age, whereas the %DeltaM(1) showed no significant age-dependent trend. CONCLUSIONS: The positional dependence of relaxation times and the population indexes indicated that spin-spin relaxation represents the behavior of the bound water and the spin-lattice relaxation that of total water. As pressure increases, the strength of hydrogen bonding as well as the amount of bound water increases. The pressure-induced change in the total water is minimal. Thus, the free water-to-bound water ratio decreases with increasing pressure, demonstrating a significant syneretic response. The extent of reversible syneretic response decreases with age and is actually reversed in older lenses. The implication is that the ability of the human lens to respond reversibly to pressure decreases with the decrease in accommodation, and, when the ability is lost altogether, an increase in free water, a possible source of cataract formation, may ensue.

Adult↗

PubMed2002

Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides.

OBJECTIVE: Bacterial DNA contains immunostimulatory CpG motifs that cause inflammation when injected into the knee joints of normal mice. We examined whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune responses prevent CpG-induced arthritis. METHODS: CpG, suppressive, and/or control ODN were injected into the knees of BALB/c mice. Joint swelling and inflammation were evaluated by physical measurement, by histologic analysis of joint tissue, and by magnetic resonance imaging. RESULTS: Immunostimulatory CpG DNA induced local arthritis, characterized by swelling of the knee joints, the presence of inflammatory cell infiltrates, the perivascular accumulation of mononuclear cells, and hyperplasia of the synovial lining. Administering suppressive (but not control) ODN reduced the manifestations and severity of arthritis up to 80%. CONCLUSION: Suppressive ODN may be useful for the prevention or treatment of arthritis induced by bacterial DNA.

Animals↗

PubMed2002

Relaxographic studies of aging normal human lenses.

Ten excised normal human lenses of various ages were studied. Seven sections of each lens, from anterior outer cortex to posterior outer cortex were imaged and the T(1) (spin-lattice) and T(2) (spin-spin) relaxation data on each section were collected. T(1) and T(2) relaxation were analysed by fitting pixel intensity to one term exponential expressions. Both T(1) and T(2) relaxation times showed minimal values in the nuclear region and maxima at the two outer cortexes. The pre-exponential terms of the fittings of both T(1) and T(2) relaxation,M(1) and M(2), were normalized in order to eliminate instrumental variations over a 2 year period. M(2) had a maximum in the nucleus and minima in the two cortexes. M(1) exhibited minimal value in the nucleus and maxima at the two cortexes. The positional dependence of T(2) relaxation times as well as that of M(2) indicated that they represent the behavior of the bound water in the lens. The positional dependence of M(1) suggests that this relaxation represents the total water that has a minimal value in the nucleus. The T(2) relaxation time decreases with increase in the age of the lens at each location. The slope of the change in T(2) relaxation time with age is greatest in the outer cortexes and diminishes as one proceeds to the nucleus. T(1) relaxation times and M(1) do not show significant change with age. This and the age dependence of the other relaxographic parameters imply that the aging of the lens involves major changes in its hydration properties that are more accentuated in the cortexes. The interpretation of these changes is in agreement with the syneretic theory of lens aging.

Adult↗