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W A Moore

Publications and source records attributed to W A Moore.

10 recordsLinked to original sources

The effect of caloric restriction on lipofuscin accumulation in mouse brain with age.

Caloric restriction (CR), has been shown to extend average and maximum lifespan in rodents and other animals as well as to delay a wide variety of manifestations of aging. The purpose of this study was to further elucidate the relationship between lipofuscin (LF) accumulation and the aging process by examining the effect of lifelong CR on LF accumulation in brain cells. Specifically, 1) we include age groups of CR (CR1 approximately equal to 90 kcal/wk and CR2 approximately equal to 58 kcal/wk) and ad libidum fed (AL; approximately 120 kcal/wk) mice including groups at maximum lifespan; 2) CR was the major dietary manipulation; 3) LF was identified using EM; 4) LF was quantified by areal measurement; and 5) the results were analyzed by inferential statistics. We have found that 1) LF increased with age and 2) that animals in the CR2 group had significantly less overall LF in the perikarya of the granule cells of the dentate gyrus when compared to CR1 or AL animals at equivalent ages. In addition, CR2 mice at maximum lifespan (45 mo.) had slightly less LF than did CR1 or AL mice at their maximum lifespans (36 mo.). Our results clearly demonstrate that CR (at 52%, but not 25% of AL diet) retards the overall accumulation of LF with time and, further, suggest that LF accumulation is not simply a linear function of age.

Aging↗

Implications of increased intercellular variability of lipofuscin content with age in dentate gyrus granule cells in the mouse.

The purpose of this study was to further characterize lipofuscin (LF) accumulation with aging in brain cells, with a specific focus on the amount of intercellular variability of lipofuscin content within an apparently a homogenous population of dentate gyrus granule cells in the hippocampus of mice, as a function of age and caloric restriction (CR). Three age groups of CR and control mice including groups at maximum lifespan were studied. This study demonstrated that the intercellular variability of lipofuscin content was significantly greater in older mice and was significantly less in mice calorically restricted. Increased variability of metabolic function among cells with age, as measured by increased intercellular variability of lipofuscin content, may represent a definitive mechanism underlying the overall decreased efficiency of tissue and organ functioning that occurs with age. That this is so, is supported by the fact that CR, which has been shown to maintain the "youthful" state of many physiological functions, has been shown in this study to maintain the "youthful" state of low intercellular variability of lipofuscin content within a population of cells. LF accumulation may be a marker for the intrusion of entropy into cell metabolism.

Aging↗

Pattern sorting: a computer-controlled multidimensional sorting method using k-d trees.

Multidimensional binary trees provide a memory efficient and general method for computing sorting decisions in real time for a flow cytometer. Their fundamental advantage over conventional lookup table sorting techniques is that sort criteria in the full N-dimensional data space which cannot be described by projections onto two-dimensional parameter planes can be effectively implemented. This becomes particularly relevant when multidimensional analysis methods such as principal components or clustering are employed. We describe a prototype implementation of this method and point out other possible implementations.

Cluster Analysis↗

CD20 expression is increased on B lymphocytes from HIV-infected individuals.

In studies presented here, we show that expression of the pan B cell marker CD20 is markedly increased on B lymphocytes from HIV-infected individuals and that this increase tends to be greater in individuals with more advanced disease. By using multiparameter FACS analyses to quantitate surface density of CD20 and intracellular glutathione (GSH) levels simultaneously, we further show that the distribution of intracellular glutathione (GSH) levels in B cells of HIV-infected individuals is more heterogeneous than in uninfected controls. Finally, we show that the intracellular GSH levels correlate with CD20 expression on a per-cell basis in all infected individuals. These findings suggest that CD20 expression, which can be precisely measured, may prove to be a useful surrogate marker for monitoring HIV infection.

Antigens, CD↗

Experience in cell line testing.

For more than ten years Microbiological Associates, Inc. has provided testing services for cell lines, products and processes associated with the safety of recombinant biologics. The results of numerous cell line characterizations performed under the guidance of "Points to Consider" documents shed light on the incidence of contamination of production cell banks. The most common sources of compromise of production substrates are also identified. Findings from this short review, though necessarily general, permit attention to be focused on areas of cell line characterization where concern is warranted. Conversely, where an alternative technique of equal sensitivity to existing tests is available for specific cell substrates, these may be given consideration. The observations presented here support the overall safety of biopharmaceuticals produced from genetically engineered cell lines and the wisdom of a multifaceted approach to assure product safety.

Animals↗

Cytogenetic evaluation of di-(2-ethylhexyl)phthalate and its major metabolites in Fischer 344 rats.

Di-(2-ethylhexyl)phthalate (DEHP) and its two major metabolites, mono-(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (EH), were evaluated for their ability to induce chromosomal damage in male Fischer 344 rats after oral administration. Dose levels, the highest of which represents one-tenth of the five-day LD50, were based on a preliminary five-day dose-finding study for each test material. The dose levels selected were 5.0, 1.7, and 0.5 ml/kg/day for DEHP; 0.14, 0.05 and 0.01 ml/kg/day for MEHP; and 0.21, 0.07 and 0.02 ml/kg/day for EH. All test materials and vehicle control (corn oil) were administered by gavage for five consecutive days. A triethylenemelamine (TEM)-positive control group received a single intraperitoneal injection of 0.5 mg/kg TEM one day prior to sacrifice. Of the 50 metaphase bone marrow cells examined from each animal, no significant increase in chromatid and chromosome breaks or structural rearrangements were noted for DEHP, MEHP, and EH. In addition, the mitotic index, determined from 100 cells per animal, was unaffected by DEHP, MEHP, or EH. The results of this investigation indicate that DEHP, MEHP, and EH, at these dose levels, did not induce detectable chromosomal aberrations after oral administration.

Animals↗