Biomedical subjects
Publications and source records attributed to B Mackey.
Pressure-damaged Escherichia coli O157 cells were more acid sensitive than native cells and were impaired in pH homeostasis. However differences in acid sensitivity were not related to differences in cytoplasmic pH (pH(i)). Cellular beta-galactosidase was more acid labile in damaged cells. Sensitization to acid may thus involve loss of protective or repair functions.
Apolipoprotein E (apoE) alleles determine the age-adjusted relative risk (epsilon4 > epsilon3) for Alzheimer's disease (AD). ApoE may affect AD pathogenesis by promoting deposition of the amyloid-beta (Abeta) peptide and its conversion to a fibrillar form. To determine the effect of apoE on Abeta deposition and AD pathology, we compared APP(V717F) transgenic (TG) mice expressing mouse, human, or no apoE (apoE(-/-)). A severe, plaque-associated neuritic dystrophy developed in APP(V717F) TG mice expressing mouse or human apoE. Though significant levels of Abeta deposition also occurred in APP(V717F) TG, apoE(-/-) mice, neuritic degeneration was virtually absent. Expression of apoE3 and apoE4 in APP(V717F) TG, apoE(-/-) mice resulted in fibrillar Abeta deposits and neuritic plaques by 15 months of age and substantially (>10-fold) more fibrillar deposits were observed in apoE4-expressing APP(V717F) TG mice. Our data demonstrate a critical and isoform-specific role for apoE in neuritic plaque formation, a pathological hallmark of AD.
The relationship between membrane damage and loss of viability following pressure treatment was examined in Escherichia coli strains C9490, H1071, and NCTC 8003. These strains showed high, medium, and low resistance to pressure, respectively, in stationary phase but similar resistance to pressure in exponential phase. Loss of membrane integrity was measured as loss of osmotic responsiveness or as increased uptake of the fluorescent dye propidium iodide. In exponential-phase cells, loss of viability was correlated with a permanent loss of membrane integrity in all strains, whereas in stationary-phase cells, a more complicated picture emerged in which cell membranes became leaky during pressure treatment but resealed to a greater or lesser extent following decompression. Strain H1071 displayed a very unusual pressure response in stationary phase in which survival decreased to a minimum at 300 MPa but then increased at 400 to 500 MPa before decreasing again. Membranes were unable to reseal after treatment at 300 MPa but could do so after treatment at higher pressures. Membrane damage in this strain was thus typical of exponential-phase cells under low-pressure conditions but of stationary-phase cells under higher-pressure conditions. Heat shock treatment of strain H1071 cells increased pressure resistance under low-pressure conditions and also allowed membrane damage to reseal. Growth in the presence of IPTG (isopropyl-beta-D-thiogalactopyranoside) increased resistance under high-pressure conditions. The mechanisms of inactivation may thus differ at high and low pressures. These studies support the view that membrane damage is an important event in the inactivation of bacteria by high pressure, but the nature of membrane damage and its relation to cell death may differ between species and phases of growth.
The epsilon4 allele of apolipoprotein E (ApoE) is an important genetic risk factor for Alzheimer's disease (AD). Increasing evidence suggests that this association may be linked to the ability of ApoE to interact with the amyloid-beta (Abeta) peptide and influence its concentration and structure. To determine the effect of ApoE on Abeta and other AD pathology in vivo, we used APPsw transgenic mice and ApoE knockout (-/-) mice to generate APPsw animals that carried two (ApoE +/+), one (ApoE +/-), or no copies (ApoE -/-) of the normal mouse ApoE gene. At 12 months of age, Abeta deposition was present in the cortex and hippocampus and was also prominent within leptomeningeal and cortical blood vessels of all APPsw ApoE +/+ mice. Importantly, although Abeta deposition still occurred in APPsw ApoE -/- mice, no fibrillar Abeta deposits were detected in the brain parenchyma or cerebrovasculature. There was also no neuritic degeneration associated with Abeta deposition in the absence of ApoE. These data demonstrate that ApoE facilitates the formation of both neuritic and cerebrovascular plaques, which are pathological hallmarks of AD and cerebral amyloid angiopathy.
Strains of Escherichia coli O157 isolated from patients with clinical cases of food-borne illness and other sources exhibited wide differences in resistance to high hydrostatic pressure. The most pressure-resistant strains were also more resistant to mild heat than other strains. Strain C9490, a representative pressure-resistant strain, was also more resistant to acid, oxidative, and osmotic stresses than the pressure-sensitive strain NCTC 12079. Most of these differences in resistance were observed only in stationary-phase cells, the only exception being acid resistance, where differences were also apparent in the exponential phase. Membrane damage in pressure-treated cells was revealed by increased uptake of the fluorescent dyes ethidium bromide and propidium iodide. When strains were exposed to the same pressure for different lengths of time, the pressure-sensitive strains took up stain sooner than the more resistant strain, which suggested that the differences in resistance may be related to susceptibility to membrane damage. Our results emphasize the importance of including stress-resistant strains of E. coli O157 when the efficacy of a novel or mild food preservation treatment is tested.
High concentrations of soil B are detrimental to crop productivity in certain arid and semiarid regions of the western United States. Production of tall fescue on B-affected soils may be a viable strategy to reduce and maintain soil B concentrations at nontoxic levels for most agronomic crops. A 2-year field experiment was conducted to study B uptake in tall fescue (Festuca arundinacea) Schreb. cv. Au Triumph grown in soil containing potentially toxic levels of native soil B. The soil B concentrations (water-extractable B greater than 5 mg B liter-1) did not affect the dry matter (DM) yield of tall fescue. Boron concentrations in shoot tissue for both years ranged from 88 to 121 mg B kg-1 DM. whereas in root tissue, concentrations ranged from 50 to 60 mg B kg-1 DM. For both years of the study, soil samples were taken at depth of 0-45 and 45-90 cm at the beginning and end of the designated growing season and analyzed for water-extractable B. Summary data from all cropped plots at the two soil depths indicated that the mean water-extractable B concentrations were reduced by 35% after 2 years in the tall fescue plots, whereas losses of extractable B from bare plots did not exceed 13% for both years. Tall fescue apparently can be used as a component in an overall strategy to lower extractable soil native B levels in irrigated agriculture soils and potentially reduce leaching of B into shallow ground water.
We examined the effects of energy restriction on immune response and also compared the effects of low fat (LF, 18.6 E%) and high fat (HF, 40.7 E%) diets during energy restriction on immunological parameters. Ten overweight women were fed the HF diet for 42 days (P1) to maintain their body weights. For the next 84 days (P2), the energy intake was reduced to 50% of the intake during P1 for all the women, five of them were fed the HF diet and the other five the LF diet. For the last 35 days of the study (P3), subjects remained on their respective diets, but the energy intake was increased to maintain BW to the level reached at the end of energy restriction. Serum concentrations of IgG, IgA, IgM, C3 and C4, numbers of lymphocytes and their subsets, blastogenesis of peripheral blood mononuclear cells cultured with phytohemagglutinin, concanavalin A and protein A were determined several times during the study. Delayed hypersensitivity skin (DHS) response to seven recall antigens was determined towards the end of each study period. None of the parameters studied were different between the HF and LF dietary groups. During energy restriction the subjects lost an average of 7 kg in the LF group and 9 kg in the HF group. Energy restriction caused a significant (P < 0.005) decrease in the serum concentration of IgG, IgA, C3, and the number of circulating natural killer (NK) cells. An increase in energy intake during P3 reversed some of the decreases caused by energy restriction, but the levels did not return to pre-restriction levels during these 35 days of refeeding adequate dietary energy. The numbers of circulating lymphocytes and their subsets with the exception of NK cells, serum levels of IgM and C4, and the DHS response monitored 48 h after the application of antigens were not affected by energy restriction. Health status of the women in our study did not seem to be compromised; however, it could be compromised under more drastic restrictions or with moderate restrictions in high risk subjects.
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A statewide survey of populations in proximity to blackbird roost sites to determine exposure to histoplasmosis from such sites has demonstrated that a site harboring Histoplasma capsulatum, even though undisturbed, adds significantly to the exposure rate of proximal populations. Disturbance of such a site increases the exposure rate dramatically with or without concurrent clinical cases of histoplasmosis.
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In a survey of California almonds, aflatoxin was found in 14% of 74 samples of unsorted, in-shell almonds as received by the processor in 1972, but it occurred at very low levels (below 20 parts per billion (ppb)) in 90% of the contaminated samples. The overall proportion of individual nuts contaminated was especially low and is estimated with 95% probability to have been in the range of 1 nut/55,300 nuts to 1 nut/14,700 nuts. Aflatoxin contamination is not restriced to any particular section of the almond-growing region of California. Commercial sorting procedures are effective in removing most aflatoxin-contaminated nutmeats, since none of 26 samples of processed, whole nutmeats contained aflatoxin. In contrast, 13 of 27 samples of diced almonds were contaminated, but nine of these 13 samples contained less than 20 ppb. Only one of 25 samples of sliced nutmeats contained aflatoxin (4 ppb). Thus, aflatoxin incidence in almonds varies greatly with the category of finished product. The apparent high incidence in diced nutmeats is probably due mostly to the more uniform distribution of aflatoxin occurring in this product (because of its small particle size) than that occurring in the other products. Sample size requirements for monitoring aflatoxin in almonds are discussed.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
What happens when women scientists are excluded from designing and conducting research? This paper discusses the importance of recruiting and retaining women as scientists. It explores the impact on science of discrimination, harassment, and retaliation against women scientists. The paper presents case examples suggesting that when women scientists' careers are stymied, research that could be beneficial to women may be devalued, delayed, or derailed.