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Biomedical subjects

R W Young

Publications and source records attributed to R W Young.

At least 19 recordsLinked to original sources
PubMed1997

Neutron RBEs for cytopenia and repopulation of stroma and hematopoietic stem cells: mathematical models of marrow cell kinetics.

The objectives of this study were to (a) extend previous bone-marrow cell kinetics models that have been published for ionizing photons to include neutron radiations, and (b) provide Relative Biological Effectiveness (RBE) values for time-specific cell killing (cytopenia) and compensatory cellular proliferation (repopulation in response to toxic injury) for neutron doses ranging from 0.01 to 4.5 Gy delivered uniformly over one minute, hour, day, week, and month. RBEs for cytopenia of a cell lineage were based on ratios of protocol-specific doses that determined the same cell population nadir, whereas the RBEs for repopulation of a lineage were based on the ratios of protocol-specific doses that corresponded to the same total number of cells killed over the radiation treatments, and which should be replaced for long-term survival of the animal. Time-dependent RBEs were computed for neutron exposures relative to the effect of 60Co gamma rays given as a prompt dose. By the use of these RBE factors, low or variable dose rates, dose fractionations given over long periods of time, and different protocols involving several radiation qualities can be converted realistically, and by standard convention, into an equivalent dose of a reference radiation comprised of x or gamma rays given either as a pulse or at any other reference dose rate for which risk information based on epidemiological or animal dose-response data are available. For stromal tissues irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 4.24 to 0.70 and RBEs for repopulation varied from a high of 6.88 to a low of 2.24. For hematopoietic stem cells irradiated by fission neutrons, time-dependent RBEs for cytopenia were computed to range from 5.02 to 0.22 and RBEs for repopulation varied from a high of 5.02 to a low of 1.98. RBEs based on tissue-kerma-free-in-air would be about twofold lower for isotropic cloud or rotational exposure geometries because marrow dose from isotropic neutron fields suffer factor-of-two greater attenuation than the gamma doses from gamma photons. For certain doses and dose rates, the RBE values computed for compensatory cellular proliferation clearly demonstrate the behavior that is commonly referred to as an inverse dose-rate effect, i.e., protraction of exposure may-under certain conditions-increase the magnitude of the dose response. Furthermore, because of non-linear rates for repair and repopulation, the highest RBEs are not necessarily found for the lowest doses nor the lowest RBEs always found at the highest doses.

Animals↗
PubMed1994

Bone marrow equivalent prompt dose from two common fallout scenarios.

A cell-kinetics model for radiation-induced myelopoiesis has been derived for mice, rats, dogs, sheep, swine, and burros. The model was extended to humans after extensive comparisons with molecular and cellular data from biological experiments and an assortment of predictive/validation tests on animal mortality, cell survival, and cellular repopulation following irradiations. One advantage of the model is that any complex pattern of protracted irradiation can be equated to its equivalent prompt dose. Severity of biological response depends upon target-organ dose, dose rate, and dose fractionation. Epidemiological and animal data are best suited for exposures given in brief periods of time. To use those data to assess risk from protracted human exposures, it is obligatory to model molecular repair and compensatory proliferation in terms of prompt dose. Although the model is somewhat complex both mathematically and biologically, this note describes simple numerical approximations for two common exposure scenarios. Both approximations are easily evaluated on a simple pocket calculator by a health physicist or emergency management officer.

Animals↗
PubMed1994

Dose-rate RBE factors for photons: hematopoietic syndrome in humans vs. stromal cell cytopenia.

Traditionally, dose-response modeling has been on a strict experiment-by-experiment basis. Such an approach greatly restricts understanding of complex biological systems affected by numerous confounding factors that individually vary from experiment to experiment. In contrast, work described in this manuscript relies on a new analytical process (that considers both pooled and experiment-specific considerations) that was used to jointly analyze the bone marrow cell kinetics from a large data base on six species of test animals irradiated by protracted schedules of ionizing photon radiations. From this approach, we have modeled how the human LD50 may vary with dose protraction and how the dose rate efficiency or RBE factors for x rays, 137Cs, and 60Co change for irradiations given at constant rate over one minute, hour, day, week, and month.

Animals↗
PubMed1994

The family of sunlight-related eye diseases.

Five ocular disorders, independent clinical entities affecting different parts of the eye with distinctive histopathological features, are part of the same family of eye diseases because they share the same causal factors, of which the most important is molecular damage produced by sunlight. This family of eye diseases includes the major sources of impaired vision and blindness in our society, age-related cataract and age-related macular degeneration. Pterygium, photokeratitis, and cancer of peri-ocular skin are also sunlight-related eye diseases. In each condition, solar radiation, oxygen, and heat, acting in combination, are the primary causal factors. Analysis of the action spectra indicates that only the high-energy radiation in the solar spectrum, particularly the ultraviolet (UV), is hazardous to the eye. The evidence in support of these conclusions is summarized. It indicates that the risk of all sunlight-related eye diseases can be diminished by use of eyewear that absorbs the high-energy constituents of solar radiation during exposure to sunlight.

Blindness↗
PubMed1993

Mathematical models of marrow cell kinetics: differential effects of protracted irradiations on stromal and stem cells in mice.

UNLABELLED: It is known that hematopoiesis is supported by bone-marrow stem cells, but those cells must seed and grow on a stromal microenvironment. Typically, studies have shown that a surviving fraction of about 30 hematopoietic stem cells (HSCs) (i.e., about 0.04%) correspond to the LD50, although other studies have shown that marrow can repopulate from a single viable cell under strong regiments of antibiotics and infusions of irradiated blood elements. PURPOSE: This paper describes comparisons between our results (from maximum-likelihood estimation techniques for cellular damage, repair, and compensatory repopulation) and published experimental data on marrow stromal cells. METHODS AND MATERIALS: After biophysical consideration of the rate constants that were derived by maximizing the likelihood function (a consideration necessary to extend the model to cell populations not indicated by the model as "critical" for recovery), the rate constants for cellular damage to stem cells are fitted to experimental data. Rate constants for repair and proliferation of stem cells are assigned based on published data on repair/proliferation half-times, and these assignments affect the evaluation of the rate constants for cellular damage. From the two models, that is one for "critical" cells (having radiosensitive and repopulation characteristics similar to stromal cells) and another for stem cells, effects on two cell populations of different radiosensitivities and repopulation rates can be demonstrated for complex schedules of protracted irradiations which could reduce either cell population below a critical need for marrow repopulation. RESULTS: Our analysis of animal mortality data has indicated that recovery of an animal from potentially lethal irradiation is dominantly regulated by cells with survival and repopulation characteristics similar to those of stroma cells. CONCLUSION: In contrast to the surviving fraction of hematopoietic stem cells, it appears that the probability of an animal's recovery is high if the "critical" population of cells is above 1% (our "best" maximum likelihood estimate, from mouse data, with the corresponding lower confidence bound at about 0.2%). Of course, a few stem cells--perhaps only one--must maintain a potential for repopulation of blood and marrow.

Animals↗
PubMed1993

The Charles F. Prentice Medal Award Lecture 1992: optometry and the preservation of visual health.

The discovery that sunlight is the primary causal factor in a family of serious eye diseases is doubly significant because it offers a simple, safe, and inexpensive means of preventing all of them simultaneously. The need for prevention is underscored by the terrible expense of sunlight-related eye diseases--$50 billion for cataract surgery in the U.S. during the past decade, plus the added cost to society of visual impairment and blindness. There is widespread scientific agreement that the use of eyewear with lenses that preferentially absorb the high-energy components of the solar spectrum, including 100% of UV radiation, will substantially reduce the risk of all sunlight-related eye diseases without interfering with visual function. A program to preserve visual health by such means can be based primarily on public education. Because the method of preventing these diseases is the use of appropriate eyewear, this unprecedented opportunity falls within the field of expertise of optometry.

Awards and Prizes↗
PubMed1993

A cell kinetics model of radiation-induced myelopoiesis: rate coefficient estimates for mouse, rat, sheep, swine, dog, and burro irradiated by photons.

Rate coefficients in the model of cell kinetics and mortality introduced by Jones et al. (Radiat. Res. 128, 258-266, 1991) are estimated using mortality data from 27 animal experiments. Adjustments are made for the six species and three nominal classes of gamma radiation represented in these studies. The model fits most of the mortality data quite well when the rate coefficient representing cellular proliferation is fitted to individual species and each of the other coefficients is given a single value across the entire data set. Results are qualitatively similar to those reported by Morris et al. (Radiat. Res. 128, 267-275, 1991) who estimated the rate coefficients from a limited number of mouse studies involving only 250 kVp X rays. As in the earlier study, estimates here lead to greater cell survival than is observed for marrow cells in the amplification division compartment.

Animals↗
PubMed1993

A cell-kinetics model for radiation-induced myelopoiesis.

A mathematical model of time-dependent cellular damage, repair, killing and repopulation of bone marrow following treatments with ionizing radiations is described. Effects from variable dose rates, multiple exposures, different radiation sources and arbitrary intervals between treatments can be modeled by ordinary differential equations. Of several unique features, the most unusual is that rate constants for injury, repair, killing and proliferation of cells are evaluated by likelihood analysis of animal mortality data. Results indicate that a relatively radioresistant pool of bone marrow cells mediates the proliferation of the hematopoietic stem cells. Applications include modeling of 1) myelopoietic integrity as a function of time and dose rate, 2) the whole-body survival curve (at any point in the treatment protocol) for cells critical to myelopoiesis, 3) a prompt dose equivalence from any completed portion of a therapeutic schedule and 4) potential gain from schedule changes during the course of the treatment.

Animals↗
PubMed1992

Estimation of median human lethal radiation dose computed from data on occupants of reinforced concrete structures in Nagasaki, Japan.

This paper presents an estimate of the median lethal dose for humans exposed to total-body irradiation and not subsequently treated for radiation sickness. The median lethal dose was estimated from calculated doses to young adults who were inside two reinforced concrete buildings that remained standing in Nagasaki after the atomic detonation. The individuals in this study, none of whom have previously had calculated doses, were identified from a detailed survey done previously. Radiation dose to the bone marrow, which was taken as the critical radiation site, was calculated for each individual by the Engineering Physics and Mathematics Division of the Oak Ridge National Laboratory using a new three-dimensional discrete-ordinates radiation transport code that was developed and validated for this study using the latest site geometry, radiation yield, and spectra data. The study cohort consisted of 75 individuals who either survived > 60 d or died between the second and 60th d postirradiation due to radiation injury, without burns or other serious injury. Median lethal dose estimates were calculated using both logarithmic (2.9 Gy) and linear (3.4 Gy) dose scales. Both calculations, which met statistical validity tests, support previous estimates of the median lethal dose based solely on human data, which cluster around 3 Gy.

Adult↗
PubMed1992

Sunlight and age-related eye disease.

Within 50 years, if current trends continue, 50 million elderly Americans will suffer visual impairment from macular degeneration or cataract. However, available evidence indicates that this impending crisis of visual health can be minimized by a simple, safe, inexpensive, and practical means of prevention. Cataract and macular degeneration are the ultimate consequences of normal aging, a lifelong process of deterioration. Three major causes of ocular deterioration have been identified: oxygen, heat, and solar radiation. Among these, the radiation hazard is readily accessible to human intervention. The lens is damaged by ultraviolet radiation in sunlight, whereas the retina can be harmed by high-energy visible radiation (the "violet and blue"). Use of sunglasses that block all ultraviolet radiation and severely attenuate high-energy visible radiation will slow the pace of ocular deterioration and delay the onset of age-related disease, thereby reducing its prevalence. A 20-year delay would practically eliminate these diseases as significant causes of visual impairment in the United States.

Age Factors↗
PubMed1992

Vitreoretinal surgical technique for transplanting retinal pigment epithelium in rabbit retina.

Transplantation of retinal pigment epithelial (RPE) cells has been proposed as a potential remedial procedure for previously untreatable retinal diseases. In this study, a vitreoretinal surgical technique was used to transplant pigmented RPE cells obtained from pigmented rabbits into the subretinal space of New Zealand White rabbits. At the time the animals were sacrificed, the retina was re-attached in all but 4 of the 24 experimental eyes. Histologically, by one week the transplanted RPE cells had formed a monolayer in patchy areas beneath the attached retina. By electron microscopy, RPE cells with prominent melanin granules were found attached to Bruch's membrane. Three weeks after transplantation, grafted RPE cells had formed apical microvilli and tight junctions with adjacent cells. The nucleus of the cells containing pigment had become oval, and their contact with Bruch's membrane appeared to be composed of bsal infoldings that were well formed. Our findings demonstrated the functional appearance of the transplanted RPE cells.

Animals↗
PubMed1991

Cellular retinoic acid-binding protein in rat lacrimal gland.

We employed a monoclonal antibody to cellular retinoic acid-binding protein (CRABP) to assess the presence and localization of this retinoid-binding protein in the lacrimal gland of the rat. Immunoblots of extracts of rat lacrimal gland showed specific immunostaining of lacrimal CRABP in the region 14-16 kDa. Sections of rat lacrimal glands that were stained with anti-CRABP antibodies showed reaction product in the cytoplasm of the acinar cells. Retinoic acid may play a role in maintaining the proper function of lacrimal gland cells.

Animals↗
PubMed1991

A mathematical model for radiation-induced myelopoiesis.

A model for damage, repair, killing, and repopulation of myelopoietic marrow is presented. Evaluation produces time and dose-rate profiles during and following any complex irradiation. Equations model variable dose rates, multiple exposures, different sources, and arbitrary intervals between treatments. If factors which dominate the control of biological processes can be demonstrated, an option is to set biological rate constants to experimentally determined values. Previously, knowledge did not permit identification of dominating biological processes and their temporal rates. But a unique feature of this study is that unspecified lesions for killing and injury of cells are evaluated from mortality data on the animal species of choice. "Unspecified" is used to indicate a condition of assumption-free modeling of molecular processes, whereby rate constants for cellular effects are simply computed directly from animal mortality data. Coefficients (estimated by maximum-likelihood methods for nonspecific processes) are compared with experimental values for specific processes. The model has many uses, including modeling of the myelopoietic potential as a function of time. Another option is to calculate the whole-body survival curve for cells that control myelopoiesis as a result of the treatment schedule. Also through simple extensions of the model, an extremely complex protocol can be identified with an equivalent prompt dose value--even for partial-body, fractionated exposures.

Animals↗
PubMed1991

Estimation of coefficients in a model of radiation-induced myelopoiesis from mortality data for mice following X-ray exposure.

The rate coefficients in the model of cell kinetics and mortality introduced by Jones et al. (Radiat. Res. 128, 258-266 (1991)) are estimated using mortality data from several mouse experiments. The evaluated model fits data from a large variety of prompt, protracted, and fractionated irradiations with 250-k Vp X rays with good fidelity. Although the maximum-likelihood estimates are not unique, all estimates lead to greater cell survival than that observed in in vitro experiments on nonterminally differentiated reproducing cells from the marrow.

Animals↗
PubMed1989

Symptomatology of acute radiation effects in humans after exposure to doses of 0.5-30 Gy.

This article distills from available data descriptions of typical human symptoms in reaction to prompt total-body ionizing radiation in the dose range 0.5 to 30 Gy midline body tissue. The symptoms are correlated with dose and time over the acute postexposure period of 6 wk. The purpose is to provide a symptomatology basis for assessing early functional impairment of individuals who may be involved in civil defense, emergency medical care and various military activities in the event of a nuclear attack. The dose range is divided into eight subranges associated with important pathophysiological events. For each subrange, signs and symptoms are designated including estimates of symptom onset, severity, duration and incidence.

Accidents↗