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Biomedical subjects

D L Preston

Publications and source records attributed to D L Preston.

At least 19 recordsLinked to original sources

Aging influences multiple incidices of oxidative stress in the aortic media of the Fischer 344/NNiaxBrown Norway/BiNia rat.

Here, we determine the influence of aging on multiple markers of oxidative stress in the aorta of adult (6-month), aged (30-month) and very aged (36-month) Fischer 344/NNiaHSdxBrown Norway/BiNia (F344/NxBN) rats. Compared to adults, increases in as determined by oxidation of hydroethidine (HE) to ethidium (Et) were increased 79.7+/-7.0% in 36-month aortae and this finding was highly correlated with increases in medal thickness (r=0.773, p<0.01) and total protein nitration (r=0.706, p<0.01) but not Ki67, a marker for cell proliferation. Regression analysis showed that increases in aortic superoxide anion (O.-2) with aging were significantly correlated with changes in the expression and/or regulation of proteins involved in metabolic (AMPK-alpha), signaling (mitogen activated protein kinases (MAPKs) along with c-Src), apoptotic (Bax, Bcl-2, Traf-2) and transcriptional (NF-kappaB) activities. These results suggest that the aging F344/NxBN aorta may be highly suited for unraveling the molecular events that lead to age-associated alterations in aortic oxidative stress.

AMP-Activated Protein Kinases↗

Thyroid abnormalities associated with protracted childhood exposure to 131I from atmospheric emissions from the Mayak weapons facility in Russia.

Between 1948 and 1960, the Mayak nuclear weapons facility in Ozyorsk, Russia discharged relatively high levels of radionuclides, primarily (131)I, into the atmosphere, resulting in appreciable exposure to the residents of Ozyorsk. To evaluate the association between thyroid diseases and childhood exposure to radioiodines, we screened 894 Ozyorsk residents born between 1952 and 1953. The study population was comprised of 581 exposed individuals living in Ozyorsk during the years of heaviest exposure and 313 nonexposed individuals who moved to Ozyorsk when radiation exposure from Mayak largely had ended. The screening protocol included a patient interview, palpation of the thyroid, cervical lymph nodes and salivary glands, an ultrasound examination, and measurement of fT4, TSH and TPOAb. Twenty-eight percent of the study group was diagnosed with a thyroid abnormality. The prevalence of nodular disease was significantly higher in the exposed group (20.7%) compared with the nonexposed (14.4%) group (relative risk = 1.4, 95% CI = 1.1; 1.9). Risks were larger for solitary nodules and for nodules > or = 10 mm in diameter. Expansion of the study to increase the number of persons screened as well as detailed dose estimation would offer an unique opportunity to evaluate thyroid disease in relation to chronic exposure to radioiodines during childhood.

Adolescent↗

High-pressure melting of MgSiO3.

The melting curve of MgSiO(3) perovskite has been determined by means of ab initio molecular dynamics complemented by effective pair potentials, and a new phenomenological model of melting. Using first principles ground state calculations, we find that the MgSiO(3) perovskite phase transforms into post perovskite at pressures above 100 GPa, in agreement with recent theoretical and experimental studies. We find that the melting curve of MgSiO(3), being very steep at pressures below 60 GPa, rapidly flattens on increasing pressure. The experimental controversy on the melting of the MgSiO(3) perovskite at high pressures is resolved, confirming the data by Zerr and Boehler.

Journal Article↗

The Techa River Cohort: study design and follow-up methods.

Residents living on the banks of the Techa River in the Southern Urals region of Russia were exposed to radioactive contamination from the Mayak plutonium production and separation facility that discharged liquid radioactive waste into this river. This paper describes the methods used to establish and follow the Extended Techa River Cohort (ETRC), which includes almost 30,000 people living along the Techa River who were exposed to a complex mixture of radionuclides, largely 90Sr and 137Cs. The system of regular follow-up allows ascertainment of vital status, cause of death and cancer incidence. With over 50 years of follow-up and over 50% deceased, the ETRC now provides a valuable opportunity to study a wide range of health effects, both early and late, associated with protracted internal and external radiation exposures. The wide range of doses allows analysis of the nature of the dose-response relationship based on internal comparisons. Other features of the cohort are the high proportion (40%) exposed under age 20, and the inclusion of both sexes. The limitations of the study include loss to follow-up due to difficulties in tracing some cohort members and migration and incomplete ascertainment of cause of death.

Adult↗

Protracted radiation exposure and cancer mortality in the Techa River Cohort.

In the 1950s many thousands of people living in rural villages on the Techa River received protracted internal and external exposures to ionizing radiation from the release of radioactive material from the Mayak plutonium production complex. The Extended Techa River Cohort includes 29,873 people born before 1950 who lived near the river sometime between 1950 and 1960. Vital status and cause of death are known for most cohort members. Individualized dose estimates have been computed using the Techa River Dosimetry System 2000. The analyses provide strong evidence of long-term carcinogenic effects of protracted low-dose-rate exposures; however, the risk estimates must be interpreted with caution because of uncertainties in the dose estimates. We provide preliminary radiation risk estimates for cancer mortality based on 1,842 solid cancer deaths (excluding bone cancer) and 61 deaths from leukemia. The excess relative risk per gray for solid cancer is 0.92 (95% CI 0.2; 1.7), while those for leukemia, including and excluding chronic lymphocytic leukemia, are 4.2 (CI 95% 1.2; 13) and 6.5 (CI 95% 1.8; 24), respectively. It is estimated that about 2.5% of the solid cancer deaths and 63% of the leukemia deaths are associated with the radiation exposure.

Cohort Studies↗

High-pressure melting of molybdenum.

The melting curve of the body-centered cubic (bcc) phase of Mo has been determined for a wide pressure range using both direct ab initio molecular dynamics simulations of melting as well as a phenomenological theory of melting. These two methods show very good agreement. The simulations are based on density functional theory within the generalized gradient approximation. Our calculated equation of state of bcc Mo is in excellent agreement with experimental data. However, our melting curve is substantially higher than the one determined in diamond anvil cell experiments up to a pressure of 100 GPa. An explanation is suggested for this discrepancy.

Journal Article↗

Lung cancer in Mayak workers.

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.

Adolescent↗

Dose response and temporal patterns of radiation-associated solid cancer risks.

Findings of the Life Span Study (LSS) cohort of atomic-bomb survivors are a primary source for quantitative risk estimates that underlie radiation protection. Because of the size and length of follow-up, the LSS provides considerable information on both the nature of the dose response and on how radiation-associated excess risks vary with age, age at exposure, sex, and other factors. Our current analyses extend the mortality follow-up by 7 y (through 1997) and add 8 y (through 1995) to the incidence follow-up. During the follow-up periods there have been a total of about 9,300 solid cancer deaths and almost 12,200 incident cases. As outlined in this presentation, while discussing issues related to the shape of the dose response and low dose risks in some detail, the new reports consider temporal patterns in greater detail than has been done previously. As we have reported, the LSS solid cancer dose response is well described by simple linear dose response over the 0 to 2 Sv range (with some leveling off at higher estimated doses). This remains the case with the extended follow-up. Although LSS is often referred to as a high dose study, about 75% of the 50,000 cohort members with doses in excess of 5 mSv have dose estimates in a range of direct interest for radiation protection (0-200 mSv). Analyses of data limited to this low dose range provide direct evidence of a significant solid cancer dose response with a risk per unit dose that is consistent with that seen for the full dose range. Previous LSS reports have focused on descriptions of the solid cancer excess risks in which the excess relative risk varies with age at exposure and sex. In addition to the age at exposure effects, our current analyses suggest excess relative risks also vary with age (at death or diagnosis). Excess relative risks are higher for those exposed earlier in life, with attained age-specific risks changing by about 20% per decade, but tend to decrease with increasing attained age, roughly in proportion to (1/attained-age)1.5, for any age at exposure. Despite the decreasing relative risk, excess rates have increased rapidly throughout the study period with some indication, especially for the incidence data, that attained-age-specific rates are higher for those exposed at younger ages. Simple comparisons of site-specific excess risks are used to illustrate how the interpretation of age-at-exposure effects on excess relative risks or excess rates is complicated by changes in baseline rates with birth cohort or time period.

Age Factors↗

Cancer mortality risk among workers at the Mayak nuclear complex.

At present, direct data on risk from protracted or fractionated radiation exposure at low dose rates have been limited largely to studies of populations exposed to low cumulative doses with resulting low statistical power. We evaluated the cancer risks associated with protracted exposure to external whole-body gamma radiation at high cumulative doses (the average dose is 0.8 Gy and the highest doses exceed 10 Gy) in Russian nuclear workers. Cancer deaths in a cohort of about 21,500 nuclear workers who began working at the Mayak complex between 1948 and 1972 were ascertained from death certificates and autopsy reports with follow-up through December 1997. Excess relative risk models were used to estimate solid cancer and leukemia risks associated with external gamma-radiation dose with adjustment for effects of plutonium exposures. Both solid cancer and leukemia death rates increased significantly with increasing gamma-ray dose (P < 0.001). Under a linear dose-response model, the excess relative risk for lung, liver and skeletal cancers as a group (668 deaths) adjusted for plutonium exposure is 0.30 per gray (P < 0.001) and 0.08 per gray (P < 0.001) for all other solid cancers (1062 deaths). The solid cancer dose-response functions appear to be nonlinear, with the excess risk estimates at doses of less than 3 Gy being about twice those predicted by the linear model. Plutonium exposure was associated with increased risks both for lung, liver and skeletal cancers (the sites of primary plutonium deposition) and for other solid cancers as a group. A significant dose response, with no indication of plutonium exposure effects, was found for leukemia. Excess risks for leukemia exhibited a significant dependence on the time since the dose was received. For doses received within 3 to 5 years of death the excess relative risk per gray was estimated to be about 7 (P < 0.001), but this risk was only 0.45 (P = 0.02) for doses received 5 to 45 years prior to death. External gamma-ray exposures significantly increased risks of both solid cancers and leukemia in this large cohort of men and women with occupational radiation exposures. Risks at doses of less than 1 Gy may be slightly lower than those seen for doses arising from acute exposures in the atomic bomb survivors. As dose estimates for the Mayak workers are improved, it should be possible to obtain more precise estimates of solid cancer and leukemia risks from protracted external radiation exposure in this cohort.

Adult↗

Dislocation-mediated melting: the one-component plasma limit.

The melting parameter Gamma(m) of a classical one-component plasma is estimated using a relation between the melting temperature, density, shear modulus, and a crystal coordination number that follows from our model of dislocation-mediated melting. We obtain gamma(m)=172+/-35, in good agreement with the results of numerous Monte Carlo calculations.

Journal Article↗

A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan).

OBJECTIVES: Laboratory and animal studies have shown a protective effect of green tea on cancer of different sites, but epidemiological evidence is limited and inconclusive. This prospective study in Japan examined the association between green tea consumption and cancer incidence. METHODS: Subjects were 38,540 people (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who responded to a mail survey carried out between 1979 and 1981. A self-administered questionnaire ascertained consumption frequency of green tea using precoded answers (never, once per day, twice to four times per day, and five or more times per day). Follow-up continued until 31 December 1994. The study analyzed solid cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined (4069); and cancer of specific sites with more than 100 cases, i.e. stomach (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122), lung (436), breast (281), and bladder (122). Poisson regression was used to allow for city, gender, age, radiation exposure, smoking status, alcohol drinking, body-mass index, education level, and calendar time. RESULTS: Green tea consumption was virtually unrelated to incidence of cancers under study. The relative risks of all cancers for those consuming green tea twice to four times per day and five or more times per day were 1.0 (95% confidence interval 0.91-1.1) and 0.98 (0.88-1.1), respectively, as compared with those consuming green tea once per day or less. CONCLUSION: Our findings do not provide evidence that regular green tea consumption is related to reduced cancer risks.

Aged↗

Impact of comparison group on cohort dose response regression: an example using risk estimation in atomic-bomb survivors.

Cohort-based dose-response analyses can be biased if based on a comparison group that is not comparable to the exposed persons with respect to uncontrolled factors related to disease incidence or mortality. When data exist over a range of doses including the very low dose region, internal regression standardized analyses based on the regression intercept derived from the exposed subcohort alone can provide risk estimates that are not subject to such comparison-group bias. In the Life Span Study cohort of atomic-bomb survivors, persons with dose estimates of zero comprise a broader geographic distribution than that of persons with non-zero dose estimates. Because there is geographic variation in mortality rates, the zero-dose persons might bias background rate estimates thereby affecting inference about radiation risk. This is illustrated using mortality due to all causes. Restricting the comparison group to certain geographically defined subcohorts resulted in as much as a 6% increase or 8% decrease in the risk estimate. This bias can be corrected using an SMR-type estimate in the regression model, allowing retention of the comparison group in the analysis if it is needed for stability or precision in estimating age, time, and sex effects. Consideration of heterogeneity in comparison groups is particularly important in dose-response studies focused on low doses at which the response may be comparable in magnitude to such heterogeneity.

Age Factors↗

Longevity of atomic-bomb survivors.

BACKGROUND: Conflicting claims have been made regarding biological and health consequences of exposure to low doses of radiation. Studies have suggested that certain low-dose exposed atomic-bomb survivors live longer than their peers. Earlier studies in other radiation-exposed populations demonstrated life shortening from mortality from cancer but lacked dosimetry and relied on comparison groups which may introduce bias because of lack of comparability. We have re-examined the effect of radiation on life expectancy in one cohort of survivors of the atomic bombings of Hiroshima and Nagasaki, Japan. METHODS: We did a prospective cohort study of 120,321 survivors. The study encompasses 45 years of mortality follow-up with radiation-dose estimates available for most cohort members. We calculated relative mortality rates and survival distribution using internal comparison (cohort-based estimation of background mortality). FINDINGS: Median life expectancy decreased with increasing radiation dose at a rate of about 1.3 years per Gy, but declined more rapidly at high doses. Median loss of life among cohort members with estimated doses below 1 Gy was about 2 months, but among the small number of cohort members with estimated doses of 1 Gy or more it was 2.6 years. Median loss of life among all individuals with greater-than-zero dose estimates was about 4 months. INTERPRETATION: These results are important in light of the recent finding that radiation significantly increases mortality rates for causes other than cancer. The results do not support claims that survivors exposed to certain doses of radiation live longer than comparable unexposed individuals. Because the cohort was intentionally constructed to contain a higher proportion of high-dose atomic-bomb survivors, average loss of life among all exposed atomic-bomb survivors would be less than the 4 months found for the study cohort.

Aged↗

Bladder-cancer incidence in relation to vegetable and fruit consumption: a prospective study of atomic-bomb survivors.

We examined the relation between consumption of 22 dietary items and subsequent bladder-cancer incidence in a cohort of atomic-bomb survivors in Japan. Subjects were 38,540 people (14,873 men and 23,667 women) who responded to a mail survey carried out between 1979 and 1981 and who had no known cancer diagnosed before the start of follow-up (1 January 1980 for men, 1 February 1981 for women). Consumption frequencies for 22 dietary items were ascertained with pre-coded answers. As of the end of 1993, there were 114 (83 men and 31 women) incident cases of bladder cancer among 450,326 person-years at risk. Statistical analysis was done using Poisson regression for grouped survival data Consumption of green-yellow vegetables and fruit were protectively associated with risk. Adjusted for gender, age, radiation exposure, smoking status, educational level, body-mass index and calendar time, the relative risk (RR) for those consuming green-yellow vegetables 2-4 times per week and almost everyday was 0.62 [95% confidence interval (CI) 0.39-0.98] and 0.54 (95% CI 0.30-0.94) respectively, as compared with those consuming once per week or less. The corresponding RR for fruit consumption was 0.50 (0.30-0.81) and 0.62 (0.39-0.99) respectively. Chicken consumption was unexpectedly associated with decreased risk, but additional adjustment for consumption did not change the relation of green-yellow vegetables or of fruit to risk. The consumption of the other dietary items, including meat and green tea, was not related to risk. The findings add to evidence that high consumption of vegetables and fruit are protective against bladder cancer.

Aged↗

Radiation-related cancer risks at low doses among atomic bomb survivors.

To clarify the information in the Radiation Effects Research Foundation data regarding cancer risks of low radiation doses, we focus on survivors with doses less than 0.5 Sv. For reasons indicated, we also restrict attention mainly to survivors within 3, 000 m of the hypocenter of the bombs. Analysis is of solid cancer incidence from 1958-1994, involving 7,000 cancer cases among 50,000 survivors in that dose and distance range. The results provide useful risk estimates for doses as low as 0.05-0.1 Sv, which are not overestimated by linear risk estimates computed from the wider dose ranges 0-2 Sv or 0-4 Sv. There is a statistically significant risk in the range 0-0.1 Sv, and an upper confidence limit on any possible threshold is computed as 0.06 Sv. It is indicated that modification of the neutron dose estimates currently under consideration would not markedly change the conclusions.

Age Factors↗