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Biomedical subjects

D J Gordon

Publications and source records attributed to D J Gordon.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Conformational changes in chromatin structure induced by the radioprotective aminothiol, WR 1065.

WR 1065, 2-[(minopropyl) amino] ethanethiol is an effective scavenger of free radicals. When present during irradiation it reduces cellular DNA damage as analysed by alkaline elution from filters. The same technique indicates that without irradiation, WR 1065 has no effect of DNA integrity. Using nucleoid analysis, where DNA damage is detected at the level of replicon clusters, WR 1065 distorts replicon supercoiling without breaking the DNA molecule. This confirmational change in nucleoid structure occurs with no detectable change in nucleoid protein content. It is proposed that perturbation of replicon supercoiling affects the process of normal DNA synthesis and strand break rejoining, allowing a longer time for the accurate repair of DNA damage.

Animals↗
PubMed1989

The use of flow cytometry in the detection of radiation- and chemically induced nuclear damage in human mononuclear cells.

Viable human mononuclear cells were treated with three known genotoxic agents, gamma radiation, bleomycin sulphate (BLM) and acetylaminofluorene (AAF). Following treatment, a high salt concentration buffer was used to disrupt the cells, releasing supercoiled DNA structures known as nucleoids. The nucleoids were treated with the fluorescent dye ethidium bromide, and exposed to a beam of laser light within a fluorescence activated cell sorter (FACS). Treatment of human mononuclear cells with the genotoxic agent BLM or with radiation prior to cell disruption and staining produced a dose-dependent increase in light scatter. However, treatment of human mononuclear cells with AAF, which requires metabolic activation, produced a dose response in light scatter that proved reversible and was not dependent on the formation of reactive metabolites. In the case of BLM and radiation, these changes in light scatter are interpreted as structural alterations in the nucleus partially induced by free radical attack, and thus provide an indication of the DNA damaging ability of the agent used. In contrast the reversible changes in light scatter seen with AAF may only indicate the ability of this agent to penetrate the genome. The significance of this reversible interaction with respect to genotoxicity is not known.

2-Acetylaminofluorene↗
PubMed1989

High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

Adult↗