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Biomedical subjects

D Grahn

Publications and source records attributed to D Grahn.

At least 37 records · Page 2Linked to original sources

Life shortening in mice exposed to fission neutrons and gamma rays. IV. Further studies with fractionated neutron exposures.

When mice were exposed to a total dose of 240 rad of fission neutrons divided into two, four, or six fractions given at 1-week intervals, more life shortening was observed than was seen after a single exposure. Maximum life shortening was observed with four fractions, although the value for six fractions was not significantly lower. Much of the augmentation effect was attributable to an increase in early deaths during the first 200-300 days after exposure, although differences persisted throughout the lifetime of the animals. The changes in life shortening were associated with changes in the distribution of causes of death; however, decrementation of the populations for any given specific cause of death failed to eliminate completely the differences in mean aftersurvival time.

Animals↗

Validity of urinary catheter specimen for diagnosis of urinary tract infection in the elderly.

Twenty elderly nursing home patients with long-term indwelling bladder catheters were studied to evaluate the validity of the microbiology of urine samples obtained from catheters that had not been changed for at least 30 days. Paired urine samples from "old" catheters and newly inserted catheters were compared for quantitative and qualitative microbiology. Urine microbiology for old catheters was highly sensitive but had poor specificity.

Aged↗

Life shortening in mice exposed to fission neutrons and gamma rays. V. Further studies with single low doses.

Data are presented on the mean after survival of female B6CF1 mice exposed to single doses of neutrons (1 to 40 rad) or gamma rays (22.5, 45, and 90 rad). For gamma-ray exposures and for neutron exposures up to 10 rad, the dose-response curves are indistinguishable from linear; higher neutron doses produce significant departures and linearity. Consequently, in these data, an upper limit of the relative biological effectiveness (RBE) exists for life shortening from all causes of death after single neutron exposures; this value is 15.0 +/- 5.1. The RBE depends on the cause of death, ranging from 2 to 5 for lymphoreticular tumors to 23-24 for lung tumors.

Animals↗

Genetic injury in hybrid male mice exposed to low doses of 60Co gamma-rays or fission neutrons. I. Response to single doses.

Young adult male B6CF1 mice were exposed to single whole body doses of fission neutrons or 60Co gamma rays. Postspermatogonial dominant lethal injury, incidence of reciprocal chromosome translocations induced in spermatogonia, incidence of abnormal epididymal sperm 4-6 weeks after exposure, and testis weight loss 3-6 weeks after exposure were all measured. Emphasis is on response to neutron doses between 1 and 40 rad, and gamma-ray doses between 22.5 and 145 rad, although more limited data from a 4-fold higher dose range were integrated into the analysis. Significant effects were seen at 1 and 2.5 rad of neutrons consistent with extrapolation from higher doses, with the exception of dominant lethal mutations, which occurred in significant excess of expectation. Dose-response functions were linear or linear-quadratic, depending upon end point, radiation quality, and dose range. For translocation frequencies, the D2 term was negative for neutron and positive for gamma-ray irradiations. RBE values varied with dose and end point. For testis weight loss and abnormal sperm over the full dose range, the RBEs were between 5 and 6. They were between 7 and 9 at lower doses (less than 10 rad) for translocations. RBEs for postimplantation and total dominant lethal rates were 5-6 above 10 rad and 10-14 below 10 rad. The RBEs for preimplant losses were between 15 and 25 above 10 rad and possibly higher below 10 rad, although the data are statistically "noisy". The tentative interpretations of unusual results at lowest doses involve variation in cell sensitivity, cell selection, probability of neutron traversal per cell, variance of magnitude of the energy deposition events, dose rate, and DNA repair.

Animals↗

Genetic risks associated with radiation exposures during space flight.

The genetic risks associated with manned space flight are judged to be of little significance to the general population. The risks may be significant to the irradiated individual, particularly if one focuses attention on the incidence of dominant and chromosomal mutations that are expressed in the first generation offspring. Even so, the risk is not increased to a great extent by the low linear energy transfer (LET) component of the space radiations. It is the presumed high LET component, neutrons especially, that would make the major contribution to the risk, because the relative biological effectiveness (RBE) values for this component, relative to low dose-rate photon irradiation, are between 10 and 40, depending upon the particular genetic effect and dose-rate comparison. The appropriate RBE value would probably be 20 or greater, so that even small neutron doses become magnified in their contribution. Under the assumed condition of protracted exposure to 8 rads of low LET radiation and 2 rads of high LET radiation, or from 48 to 88 rem, the individual's risk of transmitting a new dominant mutation that will be expressed in his immediate offspring is estimated to increase by at least 4% and as much as about 40%. The HZE-particle component is not expected to make a significant contribution to the total risk.

Aerospace Medicine↗

A demographic model for performing site-specific health risk projections.

An extension of an earlier life table model for estimating health risks in occupationally exposed workers is presented. The extension of the earlier methodology incorporates specific fertility assumptions and therefore produces a model that is able to perform health risk projections for populations living in or around sites that release agents with potentially adverse health consequences. Results show that fertility patterns are important for assessing risk, even for short-term projections. The interaction of initial age structure, competing risks from other causes of death, and fertility patterns are all important in determining future levels of excess mortality from various pollutants.

Actuarial Analysis↗

Morphologic and phenotypic analysis of an outcross line of blotchy mouse.

Blotchy is an X-linked recessive mutation at the "Mottled" locus in the mouse. The affected blotchy male (Blo/Y) mouse from an inbred genetic background demonstrates morphologic and physiologic abnormalities consistent with emphysema in adult life. Breeding of Blo/Y mice has been difficult because the inbred Blo/Y males are sterile. We report the successful development of a line of outbred Blo/Y male and Blo/Blo female nice by the controlled outcross mating of the inbred heterozygous Blo/+ female with the Argonne hybrid B6CF1 male mouse. The subsequent outcross Blo/Y progeny breed vigorously with the outcrossed Blo/+ female. The lungs of the outbred Blo/Blo female and inbred Blo/Y male mice demonstrate mild to moderate panacinar emphysema with a significant decrease in internal surface area (p less than 0.005) and an increase in mean linear intercept (p less than 0.005). In contrast, the lungs of the outbred Blo/Y is structurally normal. Despite the absence of emphysema-like changes in the outbred Blo/Y males, there were phenotypic features that suggest inherited abnormalities in connective tissue proteins including 1) high incidence of aortitis leading to premature death from aneurysmal rupture, and 2) significant decrease in the morphometrically determined parenchymal elastic fiber length in the lung (p less than 0.01). The outbred blotchy strain may be a useful experimental animal model in determining the pathogenesis of emphysema.

Animals↗

Interpretation of cytogenetic damage induced in the germ line of male mice exposed for over 1 year to 239Pu alpha particles, fission neutrons, or 60Co gamma rays.

The relative biological effectiveness (RBE) of 239Pu alpha particles, fission neutrons (0.85 MeV), and 60Co gamma rays has been evaluated for the induction of reciprocal chromosome translocations in spermatogonia and of chromosome/chromatid fragments and chromatid rearrangements in the primary spermatocyte of adult male B6CF1 mice. Age concurrency was maintained for both internal and external radiations which were delivered at about 1 rad/week for 239Pu (single intravenous dose of 10 microCi/kg), 0.67, 1.67, and 2.67 rad/week for neutrons, and 6.95, 17.4, and 32 rad/week for gamma rays for at least 60 weeks. In terms of frequency of translocations, the response to the alpha emitter was nonlinear (concave downward) with little dose-response predictability; to cumulative neutron exposures the response was linear, without evidence of a dose-rate effect; and to gamma radiation the responses were linear, and a significant dose-rate effect was seen. RBE estimates are variable. For translocations, the n/gamma ratio is between 10 and 24, depending upon weekly dose level, and the ratio is 1 or less for the alpha particle relative to the neutron. For fragments, the n/gamma ratio is 18 to 22, depending upon age factors, and alpha/n is 1.5. For chromatid rearrangements, n/gamma is 7 and alpha/n is essentially indeterminate, but much below one. The overall response to the alpha emitter is interpreted to be a complex function of (a) microdosimetric heterogeneity, (b) a nearly invariant deposition pattern in the gonad, (c) the high sensitivity of differentiating spermatogonia to cell killing, and (d) the capacity of stem cells in relatively radiation-free areas to progressively assume the major spermatogenic role.

Alpha Particles↗

Population characteristics and environmental factors that influence level and cause of mortality. A review.

Responsible evaluation of energy production effects on human health requires prior accounting for the socioeconomic, cultural, and climatic characteristics known to influence mortality rate and cause. Fifteen population characteristics and environmental variables (education, income, occupation, industrial mix, socioeconomic status, housing quality, climate, urban residence, geographic residence, internal migration, cigarette consumption, alcohol consumption, marital status, foreign birth or stock, and religious affiliation) and three age subgroups are discussed. An initial set of eight variables is indicated for mortality rate standardization, based on the reliability of their relationships with mortality. These eight variables are: education, occupation, industrial mix, urban residence, marital status, ethnic mix, and cigarette and alcohol consumption. Education and occupation are negatively related to mortality. Occupational exposure to toxicants (indicated by industrial mix), cigarette consumption, and alcohol consumption have positive linear relationships with various specific causes of mortality. Urban residence, marital status, and ethnicity have non-linear relationships with mortality and show consistent patterns for certain causes of death. In addition to these characteristics three age subgroups ( less than 1 year, 1-14 years, greater than or equal to 65 years) are discussed because of their relatively high or low rates compared to the rest of the population. A brief review of water and air pollution effects on mortality is included for completeness. Unique to this review is the quantitative summary (presented as an appendix) of the variables influencing adult mortality. It is a compilation of numerical relationships, derived either directly or indirectly from the published data, that support the choice of influencing variables.

Age Factors↗

Decreased lysyl oxidase activity in the aneurysm-prone, mottled mouse.

Inbred mice bearing certain alleles at the Mottled locus have defects in connective tissue which result in weakness of skin and of blood vessels. Previous studies have established that cross-links in collagen and elastin are decreased in these animals due to impaired formation of lysine-derived aldehydes. Lysyl oxidase activity in extracts of skin is markedly lower in those prepared from affected animals than control mice. An inhibitor of lysyl oxidase is present in equal amounts in affected and control skins and does not account for diminished activity found in affected animals.

Amino Acid Oxidoreductases↗

A sex-linked defect in the cross-linking of collagen and elastin associated with the mottled locus in mice.

A genetic abnormality in collagen and elastin cross-linking resembling experimental lathyrism has been identified in mice. The defect is an X-linked trait, attributed to the mottled locus which also influences coat color. The affected mice have aneurysms of the aorta and its branches, weak skin, and bone deformities in a spectrum of severity varying with the alleles at the mottled locus. A defect in the cross-linking of collagen was demonstrated in the skin of the affected animals by a marked increase in collagen extractability and a reduced proportion of cross-linked components in the extracted collagen. A decrease in lysine-derived aldehyde levels was found in both skin collagen and aortic elastin similar to that found in lathyritic tissue. Furthermore the in vitro formation of lysine-derived aldehyde was reduced. Thus the cause of the connective tissue abnormalities in these mice appears to be a defect in cross-link formation due to an impairment in aldehyde formation.

Animals↗