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Biomedical subjects

T D Luckey

Publications and source records attributed to T D Luckey.

At least 19 recordsLinked to original sources

Nurture with ionizing radiation: a provocative hypothesis.

Whole body exposure to low-dose ionizing radiation appears to decrease overall cancer incidence. The data come from at least eight large studies of populations exposed to various forms of radioactive material and from more limited studies of occupational and environmental exposures to plutonium, radium, and radon. Earlier experiments in animals strongly support the protective effect that is apparent in humans. Also, experimental reports from invertebrates kept in radiation-deficient conditions suggest that ionizing radiation is essential for optimal growth and development. The combined evidence points to the presence of no-adverse-effect thresholds and of hormesis or beneficial effects at doses below those thresholds. Furthermore, according to the geological record, the high background radiation under which life first evolved has progressively attenuated up to the present. Thus it is intriguing to postulate that modern humans may live under conditions of partial deficiency of ionizing radiation; low doses of ionizing radiation may likely function as inducers of repair and detoxification mechanisms, much as low-level antigenic challenges are responsible for enhanced immune competence. This hypothesis runs contrary to the prevailing consensus of regulatory default assumptions, which negate the possibility of no-effect thresholds for agents that are carcinogenic at certain levels of exposure. Still, those are dogmatic policy assumptions without scientific or even empirical justification, whereas the hypothesis advanced here has consistent observational and experimental support. The implication is that a partial deficiency of ionizing radiation could be remedied by a safe supplementation, possibly through dietary means. Dose-response data from studies of nuclear workers and populations subjected to unusual exposures suggest that safe supplementation with about 0.4 cGy/mo would be beneficial and conservative.

Animals

Overview of gastrointestinal microecology.

In germ-free life many characteristics are not the consequence of living bacteria's metabolic activities but of bacteria acting as antigens. On the other hand, merely some bacteria species are able to activate the immune system. Noteworthy experimental results relate to inhibitory effects of dietary lactobacilli on intestinal carcinomas. Besides bacteria other components play a role within the very complex man-microbe ecosystem. Thus, protozoa, fungi, and viruses may be generally concerned with diseases in monogastric animals.

Animals

Ionizing radiation promotes protozoan reproduction.

This experiment was performed to determine whether ionizing radiation is essential for maximum growth rate in a ciliated protozoan. When extraneous ionizing radiation was reduced to 0.15 mrad/day, the reproduction rate of Tetrahymena pyriformis was significantly less (P less than 0.01) than it was at near ambient levels, 0.5 or 1.8 mrad/day. Significantly higher growth rates (P less than 0.01) were obtained when chronic radiation was increased. The data suggest that ionizing radiation is essential for optimum reproduction rate in this organism.

Background Radiation

[Immunostimulation in an animal model using intestinal bacteria preparations].

The treatment of mice with an injection preparation consisting of killed R-tribes of non-pathogenous E. coli caused an increase in microbicidic activities in the animal's blood and effects a significant protection against consecutive infections with Salmonella typhimurium. The enhancement of the animal' resistance capacity appears to be non-specific, and connected with the activity of leucocytes. Oral application of preparations of intestinal bacteria led to increased resistance against consecutive infections with Salmonella typhimurium and Haemophilus influenzae. Three different oral vaccines have been used: Streptococcus faecalis and E. coli, a viable vaccine of non-pathogenous Streptococcus faecalis and a viable vaccine of E. coli. The enhancement of the resistance can be attributed to an induction of the chemotactic efficiency of the animal neutrophilic cells. The chemotactic response of these cells seems to be enhanced. The mode of action of both the other oral vaccines remains obscure.

Adjuvants, Immunologic

Application of S. faecalis and E. coli oral vaccines in humans and animals.

Vaccines of non-pathogenic intestinal bacteria for oral administration have been used in the therapy of chronic and recurrent infections by the German Medical Association for Microbiological Therapy for over three decades. Three different oral bacterial vaccines were used in particular: 1. A sterile autolysate of non-pathogenic S. faecalis and E. coli; 2. a viable non-pathogenic S. faecalis vaccine, and; 3. a viable non-pathogenic E. coli vaccine. Clinical studies indicate the safety and efficacy of these bacterial products, and suggest the stimulation of immune activities and competitive capacities of S. faecalis and E. coli as mode of action. In animal experiments, orally administered intestinal bacterial vaccines enhance the resistance of mice against subsequent challenge with lethal doses of Salmonella typhimurium and Haemophilus influenzae. Mice were allowed access to a viable suspension of either S. faecalis or E. coli for at least 3 weeks. They were then challenged with either of the two unrelated pathogens. Both pre-treatment procedures conferred significant protection of the animals. The mechanism of this protective action appears to involve modification of white blood cell kinetics in the mice. The peritoneal resident cell population in mice is significantly increased by S. faecalis treatment.

Administration, Oral

Physiological benefits from low levels of ionizing radiation.

Extensive literature indicates that minute doses of ionizing radiation benefit animal growth and development, fecundity, health and longevity. Specific improvements appear in neurologic function, growth rate and survival of young, wound healing, immune competence, and resistance to infection, radiation morbidity, and tumor induction and growth. Decreased mortality from these debilitating factors results in increased average life span following exposure to minute doses of ionizing radiation. The above phenomena suggest the possibility that ionizing radiation may be essential for life. Limited data with protozoa suggest that reproduction rates decrease when they are maintained in subambient radiation environments. This may be interpreted to be a radiation deficiency. Evidence must now be obtained to determine whether or not ionizing radiation is essential for growth, development, nutrient utilization, fecundity, health and longevity of higher animals. Whether or not ionizing radiation is found to be essential for these physiologic functions, the evidence reviewed indicates that the optimal amount of this ubiquitous agent is imperceptibly above ambient levels.

Animals

In vitro induction of E-rosette formation in human bone marrow cells by the thymic proteins LSHr and LSHh.

Two thymic factors, LSHh and LSHr, were found to be active in the induction of E-rosette formation. In vitro incubation of human bone marrow cells, isolated by Ficoll gradient centrifugation, with subnanogram quantities of either of these LSH proteins increased the number of E-rosette-forming cells in the bone marrow cultures by a factor of two. Kidney extract and bovine serum albumin did not show significant activity when tested as controls. Commercial thymopoietin II peptide was found to be active in the assay at comparable concentrations. The data allow a comparison of LHS proteins with other preparations tested in this manner.

Bone Marrow

Biological activity of the pure thymus protein, LSHr.

LSHr, a protein from thymus, was shown to be a single pure peptide of 80,000 daltons by its migration in Sephadex G-150, SEDImentation velocity ultracentrifugation, both regular and SDS gel electrophoresis, and isoelectric focusing as a single symmetrical peak. It promoted the differentiation of T-lymphocytes in in vitro and in vivo tests. Human bone marrow cells showed differentiation in response to LSHr treatment to express a surface marker unique to T-cells following incubation with 10(-14) to 10(-9) M LSHr. Control proteins showed no effect. In preliminary experiments, administration of microgram quantities of LSHr to nude mice for 2-3 weeks induced development of T-cell function as determined by antibody response to a T-dependent antigen, and a response of spleen cells to T-cell mitogen.

Aged

pT, a new classification system for toxic compounds.

The use of pT, the reciprocal of the logarithm of the molar concentration of harmful compounds, allows a simple, quantitative expression of the potential for toxicity of a wide variety of compounds on a molar basis. Comparison of representative toxic compounds gives a valuable perspective on some chemical hazards shared by the biomedical community and society.

Animals

Quantification of two basic proteins related to a thymic hormone (LSH) and their occurrence in serum of normal and cancerous adults.

A quantitative assay for a thymic hormone (LSHr) was developed and utilized for biologic materials. The protein was isolated from tissue extracts or biologic fluids by precipitation with 20% (NH4)2SO4 and reprecipitation with 75% methanol with subsequent disc-electrophoresis on polyacrylamide gel. The proteins on the gel were stained with amido black. One of the two protein bands was readily identified with LSHr by its electrophoretic mobility and agar immunodiffusion tests. Comparison of the intensity of the protein bands obtained from biologic tissues with those of graded amounts of the pure LSHr allowed quantitative estimation. Another basic protein of the serum is found along with LSHr by the above fractionation procedure; it was tentatively named GEM 126 on the basis of its electrophoretic mobility. The total quantity of each of these serum basic proteins and their ratios to each other showed no correlation to any of 20 clinical and laboratory parameters in either healthy or cancerous adults. The lack of correlation between the quantity of serum protein presumed to be LSHr and cancer susceptibility suggests this thymic hormone is not deficient in patients with cancer. Treatment of female cancer patients with radiation and chemotherapy caused a decrease in serum GEM 126 when compared to healthy adults, and untreated or surgically treated cancer patients.

Adult

Feasibility studies in rats fed heavy metals as multiple nutrient markers.

The nitrates of five metals (cerium, terbium, ytterbium, lutetium, and iridium) were fed to rats to determine the feasibility of their use as nonabsorbed, multiple markers for recovery, passage, and indirect apparant digestibility studies. Fecal recovery of a single oral dose was completed within 72 hours. When the salts were mixed into the diet, 48-96 hours was required to establish a steady-state concentration of markers in feces. The diurnal variation of cerium in feces was found to be considerable when it was fed twice daily as a single dose prior to each feeding. When incorporated into the diet, negligible diurnal variation in fecal concentration was noted with lutetium, and small variation was seen with other metals. In nutrient apparent digestibility studies, good agreement was generally found between direct and indirect multiple marker methods. Experiments with a daily intake marker suggest that cerium was not satisfactory as a multiple marker in which neutron activation analysis was the method of determination.

Animal Nutritional Physiological Phenomena

Studies of nutritional safety of some heavy metals in mice.

Heavy metals have been proposed as nutrient markers to allow the accurate determination of the time of passage, nutrient intake, or apparent utilization of multiple nutrients. In order to evaluate possible toxic effects of scandium, chromium, lanthanum, samarium, europium, dysprosium, terbium, thulium, and ytterbium oxides, and barium sulfate upon growth, general development, reproduction, and lactation, mice were fed different levels of these compounds for three generations. The amount of elements fed were 0,110, 100, and 1000 times the use amount. The use amounts were (in ppm2.) : Sc, 0.12; Cr, 0.02; La.0.40;; Sm. 0.80; Eu, 0.036:TB, 1.20; Dy, 1.20; Tm. 0.08; Tb, 0.12; and Ba, 0.008. The use amount was one-fifth of the concentration required for activation analysis. Mortality and morbidity were negligible. No consistent growth rate changes were observed; however, different groups showed different growth rates during different generations. The number of mice born showed no significant differences amoung treatment groups. Survival, growth rate, hematology, morphological development, maturation, reproduction, and lactational performance were comparable in mice fed the different levels of 10 heavy metal oxides to those mice fed the basal diet.

Animals