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Biomedical subjects

D J Gordon

Publications and source records attributed to D J Gordon.

At least 19 recordsLinked to original sources
PubMed1992

Hydrogen peroxide lethality is associated with a decreased ability to maintain positive DNA supercoiling.

Hydrogen peroxide is more toxic to mammalian cells at 37 degrees C than 0 degree C at all concentrations studied. Histone-free nuclei (nucleoids) extracted from treated cells have a reduced ability to maintain positive DNA supercoiling, with the maximum effect at the higher temperature. Prior exposure of cells to sodium ascorbate at 0 degree C increased both toxicity and the inhibition of nuclear supercoil rewinding. After exposure at 0 degrees C, normal levels of supercoiling returned with both a fast and a slow component, kinetics characteristic of DNA single-strand break repair; the fast component was eliminated when cells were exposed at 37 degrees C due to in situ rejoining. At least a portion of the lethal lesions induced by hydrogen peroxide are DNA double-strand breaks (dsb) because the dsb repair-deficient mutant, xrs-5, is approximately two to three times more sensitive than wild-type cells over the initial portion of the survival curve. However, the increased toxicity found after exposure at 37 degrees C is observed equally in both cell lines, indicating that temperature-dependent cell killing is not directly linked to DNA dsb. It is suggested that cell killing at 37 degrees C is mediated through two linked processes. First, hydrogen peroxide may disrupt cation-stabilized nuclear supercoiling by direct ion oxidation. Second, as a part of the oxidation process, hydrogen peroxide will produce potentially cytotoxic free radicals close to the DNA-linked metal site, limited in extent only by the presence of chemicals capable of reducing metal ions prior to reoxidation.

Animals↗
PubMed1992

The addition of muscle to the lateral arm and radial forearm flaps for wound coverage.

There is good evidence of the benefit of transferring vascularized muscle into wounds that are contaminated or have been infected previously. This benefit particularly applies in cavities around bones and joints. We present two patients in whom the inclusion of a portion of muscle in the lateral arm and radial forearm flaps allowed the effective combination of good-quality skin cover with the properties of vascularized muscle.

Adult↗
PubMed1992

Comparison of allergic responses to dust mites in U.K. bakery workers and Swedish farmers.

The IgE RAST response to Dermatophagoides pteronyssinus and four storage mites (Lepidoglyphus destructor, Tyrophagus putrescentiae, Glycyphaghus domesticus, and Acarus siro) was examined in 251 U.K. bakery workers and compared with that previously found in 440 Swedish farmers. Storage mites are found commonly in stored hay and grain so both these groups potentially encounter them in their work. In neither group of workers was a positive RAST (greater than or equal to 0.35 PRU) to D. pteronyssinus correlated with a positive RAST to a single storage mite. As in the Swedish farmers, significant though not strong correlations were found in the U.K. bakers between positive RAST responses to G. domesticus and L. destructor and to T. putrescentiae and L. destructor (P less than 0.05). Homologous and heterologous RAST inhibition studies showed there was low cross-reactivity between storage mites and D. pteronyssinus. L. destructor showed the least inhibition by the other antigens, suggesting it possessed the fewest common allergens. The most important difference in the IgE responses between the two groups was the much higher response to D. pteronyssinus in the U.K. bakers, which was not found in the Swedish farmers whose highest IgE response was to L. destructor.

Agriculture↗
PubMed1992

Immune response to flour and dust mites in a United Kingdom bakery.

In a study of 279 United Kingdom bakery workers a high prevalence of immunological response to storage mites was found. To determine whether this was the consequence of exposure to storage mites in bakery work, a population of salt packing workers was examined as a comparison group not at occupational risk of exposure to storage mites. Forty two per cent of both groups were atopic (had a positive skin prick response greater than negative controls to D pteronyssinus, grass pollen, or cat fur by 2 mm or more) and 33% had an immediate skin prick test response to at least one of four storage mites (L destructor, G domesticus, T putrescentiae, A Siro). A higher percentage of the salt packing workers than the bakery workers had a positive radioallergosorbent test (RAST) (greater than or equal to 0.35 PRU) to D pteronyssinus and to the four storage mites. Logistic regression analysis identified atopy as the most significant variable for a positive skin test and RAST response to storage mites in both groups of workers. RAST inhibition was used to analyse extracted area and personal air samples. Analysis of static area samples for aeroallergen showed immunological identity with flour but L destructor was found in only one of seven exposed filters. The concentration of airborne flour was related to exposure rank of perceived dustiness and gravimetric measurement of total dust. Nineteen out of 32 filters from workers in jobs with higher dust exposure (rank >/=6) had a level of > 10 microgram/m(3) flour whereas this concentrations was exceeded in only one of 23 filters from workers in low dust exposure (< rank 6). It is concluded that storage mites are not of special significance in allergic responses in bakery workers. The development of immunological (and airway) responsiveness to inhaled flour dust is increased in those exposed to higher concentrations of airborne allergen, which appears to be predominantly flour and not storage mites.

Air Pollutants, Occupational↗
PubMed1992

Cost and health implications of cholesterol lowering.

BACKGROUND: A broad, scientific consensus supports the role of cholesterol as a risk factor for coronary heart disease and agrees that lowering cholesterol levels will reduce coronary heart disease incidence. Cost-effectiveness analysis is a potentially powerful method for measuring the benefits to be achieved by expenditures of health care dollars. METHODS AND RESULTS: The literature related to the effectiveness and cost-effectiveness of cholesterol lowering was reviewed. Application of cost-effectiveness methodology to the question of cholesterol reduction generally supports the use of population-wide educational programs and the aggressive use of cholesterol-lowering therapy for the secondary prevention of subsequent coronary events in persons with preexisting coronary heart disease. For primary prevention, however, therapy with medication has a favorable cost-effectiveness ratio only in identifiable high-risk persons, and the different costs of the various available medications should be taken into account. Therapy with medications, especially for primary prevention, would be more appealing if the price of the available medications were lower. CONCLUSIONS: High priority should be given to research that could validate these cost-effectiveness projections as well as to further studies of the elderly and women, in whom direct data on the precise costs, risks, and benefits of interventions to lower cholesterol remain sparse.

Anticholesteremic Agents↗
PubMed1991

Analysis of free radical damage within single cells using flow cytometry.

The data presented here illustrates the additional information that can be gained on single cell biological effects by using a method of damage estimation based on single cells. The experiments involving primarily free radical damage carried out using H2O2 and the radioprotectors cysteamine and WR 1065, both revealed data that could not have been obtained from a macroscopic study of free radical-DNA chemistry and analysis of reaction products. This serves to emphasise the difficulty in extrapolating both free radical based and other chemical reactions to effects seen in living systems.

Animals↗
PubMed1991

The effect of smoking on the development of allergic disease and specific immunological responses in a factory workforce exposed to humidifier contaminants.

The effects of smoking on the development of work related asthma and on the production of specific IgE and IgG antibodies to antigen from a contaminated humidifier are described for a sample of 258 workers from a printing factory. Current smoking was associated with low production of IgG antibody but with higher production of IgE antibody. No dose response for either antibody was found when numbers of cigarettes or pack-years smoked were considered. Work related asthma was detected in 12 workers by peak flow recordings. Six were current smokers and one was an ex-smoker. One subject with work related asthma had a high (and one a marginal) concentration of specific IgE to humidifier antigen.

Air Conditioning↗
PubMed1991

Neutron and cobalt-60 gamma irradiation produce similar changes in DNA supercoiling.

The effects of 60Co gamma-ray and d(20 MeV)Be neutron irradiation on DNA supercoiling have been studied using a nucleoid rewinding technique. Irradiation of viable CHO AA8 cells on ice with from 4 to 25 Gy of either radiation produced a similar resistance to rewinding of nuclear supercoils after treatment with ethidium bromide. The restitution from the effects of 12 Gy of either radiation was also similar, leaving no detectable residual damage. The discrepancy between these data and the reduced ability of neutrons to produce DNA breaks, as defined by the alkaline elution assay, is explained by the discontinuous deposition of dose associated with neutron irradiation. It is suggested from a microdosimetric analysis that the neutron radiation interacts with DNA at sites on average 5-10 times further apart than the interactions with gamma rays. The long DNA sequences which results after neutron irradiation are consequently eluted inefficiently during alkaline elution, giving a reported RBE of approximately 0.3. Restrictions in the rewinding of individual supercoils are not dependent on the interionization distance and thus give rise to an RBE of approximately 1. Furthermore, the complete removal of DNA damage, as measured by this technique, supports the hypothesis that neutron toxicity is associated with incorrect, not incomplete, rejoining of the DNA molecule.

Animals↗
PubMed1990

A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study.

In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from .453 to .496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is .815, an increase in the regression coefficient up to .556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination.

Adult↗
PubMed1990

Cellular radiosensitivity in V79 cells is linked to alterations in chromatin structure.

V79 cells grown as spheroids are more radioresistant than those grown as monolayers. Viable cells from spheroid culture contain restraints to ethidium bromide driven rewinding of DNA supercoils that are absent in monolayer cells. Spheroid cells also contain a DNA-protein matrix that is more resistant to detergent-induced degradation. The increase in structural integrity may be related to a 55-60 kD protein in the nucleoids of spheroid, but not monolayer cells. Spheroid cell radioresistance may therefore be related to a more stable chromatin platform for high fidelity repair of DNA damage.

Animals↗
PubMed1990

Role of circulating high-density lipoprotein and triglycerides in coronary artery disease: risk and prevention.

A substantial body of evidence suggests that circulating levels of high-density lipoprotein (HDL) and certain triglyceride-carrying lipoproteins may, like low-density lipoprotein (LDL), be important risk factors in the development of atherosclerotic coronary artery disease (CAD). Furthermore, both low HDL cholesterol and high triglyceride levels are frequently associated with other CAD risk factors, whose correction, often by hygienic means, may reduce CAD risk without fear of adverse side effects. However, the available evidence is not yet sufficiently coherent and compelling to justify guidelines (analogous to those for LDL cholesterol) for specific pharmacologic treatment of low plasma HDL cholesterol or moderately elevated plasma triglyceride levels to prevent CAD.

Coronary Disease↗
PubMed1990

The increase in radioresistance of Chinese hamster cells cultured as spheroids is correlated to changes in nuclear morphology.

Chinese hamster V79 cells grown as spheroids in roller culture are more radioresistant than those grown as monolayers. The supercoiled structure of chromatin, as salt-extracted nucleoids, has been examined using flow cytometry. Irradiated viable cells from spheroid culture contain restraints to supercoil relaxation that are absent in monolayer cells. Further analysis of the chromatin organization from each growth form shows that the radioresistant spheroid cells contain a DNA-protein matrix that is more resistant to detergent-induced degradation. The increase in structural integrity may be due to the retention of a 55-60 kDa protein that is apparent in the nucleoids of spheroid, but not monolayer cells. The increase in structural integrity of the spheroid cells may explain their greater radioresistance by providing a more stable platform for high-fidelity DNA damage repair.

Animals↗
PubMed1989

Treating high blood cholesterol in the older patient.

Although the general importance of treating high blood cholesterol to prevent coronary heart disease (CHD) is now widely accepted, its application to the older patient has not been well-defined. The association between total blood cholesterol levels and CHD morbidity and mortality weakens with age. However, because age itself is a major risk factor for CHD, treatment of hypercholesterolemia in the elderly may bring about a greater reduction in absolute risk than is obtained in younger persons. More research that directly addresses the benefits of the treatment of hypercholesterolemia in the elderly is needed.

Adult↗