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Biomedical subjects

E J Hall

Publications and source records attributed to E J Hall.

At least 163 records · Page 9Linked to original sources
PubMed1990

Enhanced intestinal permeability to 51Cr-labeled EDTA in dogs with small intestinal disease.

Intestinal permeability in dogs with small intestinal disease was measured by quantitation of 24-hour urinary excretion of 51Cr-labeled EDTA following intragastric administration. Permeability was high in dogs with a variety of naturally acquired small intestinal diseases including wheat-sensitive enteropathy of Irish Setters, small intestinal bacterial over-growth, and giardiasis, and permeability was decreased after successful treatment. These findings indicate that the assessment of intestinal permeability may be a useful technique for detecting small intestinal disease and for monitoring the efficacy of treatment in dogs.

Animals↗
PubMed1990

The relative biological effectiveness of photon radiation from encapsulated iodine-125, assessed in cells of human origin: I. Normal diploid fibroblasts.

The relative biological effectiveness (RBE) of photon radiation from encapsulated Iodine-125 "seed" sources has not previously been investigated in human cells. The RBE of 125I photons relative to 137Cs gamma rays was examined in normal diploid human fibroblasts derived from lung and skin. The cells were irradiated in plateau phase using a specially designed incubator-irradiator which permitted simultaneous 125I and 137Cs irradiation. The cells were irradiated at various dose rates ranging from 7 to 70 cGy/hr. Dosimetry was performed using Monte Carlo computer calculations to simulate the 125I irradiations and the exposure-standardization measurements made by the U.S. National Bureau of Standards which are the basis for the specified strengths of 125I seeds. Simulation of the exposure standardization measurements revealed systematic errors due to the unrecognized presence of low-energy fluorescence X rays. The specified activity of the type of seeds used for this study (high-activity, no radiographic marker) was found to be too high by more than 10%. The RBE of 125I assessed with both lung fibroblast lines was found to be 1.2 and was 1.3 for the skin fibroblasts. The RBE did not change over the range of dose rates tested. In fact, for both 125I and 137Cs, the dose response curves did not change with dose rate over the range tested, implying full repair of sublethal damage at dose rates below 70 cGy/hr in these non-dividing cells.

Brachytherapy↗
PubMed1990

The inverse dose-rate effect for oncogenic transformation by neutrons and charged particles: a plausible interpretation consistent with published data.

The enhancement of oncogenic transformation in the C3H10T1/2 system by protraction of a high-LET irradiation has been widely reported. Prima facie, the results are inconsistent in that some but not all experiments have shown an enhancement. That the reported data follow a clear pattern is shown, and a model whose predictions are quantitatively consistent with these trends is discussed. The model, developed from that originally suggested by Rossi and Kellerer (1986), postulates that cells are especially sensitive to radiation during some period of their cycle. A sensitive period of about 1 h is shown to yield predictions consistent with all available data. If the suggested model is realistic and applicable to human cells in vivo, little enhancement would be expected for high-LET radiations such as from radon daughters or HZE cosmic rays, though an effect might be expected from trapped protons on astronauts in earth orbit. For fission neutrons a time-dependent factor of N = 2 in the formula for dose equivalent (H = DQN) might be appropriate for very low dose rates, if a quality factor Q = 10 were applied. If Q was taken as 20, then a value of N = 1 would probably be adequate.

Animals↗
PubMed1990

Modulating factors in the expression of radiation-induced oncogenic transformation.

Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitative are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression of transformation. Densely ionizing alpha-particles, similar to those emitted by radon daughters, are highly effective in inducing transformations and appear to interact in a supra-additive fashion with asbestos fibers. The activation of a known dominant oncogene has not yet been demonstrated in radiation-induced oncogenic transformation. The most likely mechanism for radiation activation of an oncogene would be via the production of a chromosomal translocation. Radiation also efficiently induces deletions and may thus lead to the loss of a suppressor gene.

Animals↗
PubMed1990

Development of wheat-sensitive enteropathy in Irish Setters: biochemical changes.

Biochemical changes in the small intestine during development of naturally acquired wheat-sensitive enteropathy of Irish Setters were investigated. To distinguish primary biochemical abnormalities from secondary effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were sequentially obtained between weaning and 1 year of age; specific activity and reorientating sucrose density-gradient distribution of organelle marker enzymes were determined. Major primary biochemical abnormalities were not detected in affected progeny. In affected dogs fed wheat, there was a selective, but secondary, loss of the brush border alkaline phosphatase and aminopeptidase N activities. This loss was associated with the development of partial villus atrophy, but represented a specific effect of dietary wheat on the brush border, not merely a nonspecific effect of mucosal damage, because other brush border enzymes, including disaccharidases, were not similarly affected. Increased soluble activities of lysosomal and peroxisomal marker enzymes late in the disease process may represent alterations in these 2 organelles as a secondary consequence of mucosal damage.

Alkaline Phosphatase↗
PubMed1990

Studies with bifunctional bioreductive drugs. I. In vitro oncogenic transforming potential.

The oncogenic transforming potential of a series of bioreductive drugs including RSU-1069 and its various alkyl-substituted derivatives, RB-7040, RB-88716, RSU-1164, and RB-88712, has been compared using the C3H 10T1/2 cell system. While the aziridine moiety at the terminal end of the side chain confers greater cytotoxicity to both the 2-nitroimidazole (RSU-1069) and the 5-nitrofuran (RB-88716), it also increases the oncogenic transforming potential of the drugs correspondingly. By substituting the aziridine ring with methyl groups, the cytotoxicity and oncogenicity of these bioreductive drugs decrease in a way that is proportional to the degree of methylation. A clear structure-activity relationship can be demonstrated from these methyl-substituted derivatives such that a tetramethyl-substituent (RB-7040) is much less cytotoxic and oncogenic than a dimethyl-substituent (RSU-1164). RB-7040, which has in vitro and in vivo sensitizing efficiency comparable to the parental compound RSU-1069, is roughly tenfold less cytotoxic and, at concentrations that achieve an in vitro enhancement ratio of 2.9, induces a transforming frequency that is indistinguishable from the spontaneous rate.

Animals↗
PubMed1990

Studies with bifunctional bioreductive drugs. II. Cytotoxicity assayed with A-549 lung carcinoma cells of human origin.

A lung carcinoma cell line of human origin (A-549) cultured in vitro was used to investigate the cytotoxic effect of a range of bifunctional bioreductive drugs. The drugs tested consisted of nitroimidazoles or nitrofurans with terminal aziridine rings on the side chain and are designated RSU-1069, RSU-1164, RB-7040, RB-88716, and RB-88712. Measurements of the cytotoxicity in air demonstrated that methyl and alkyl addition to the aziridine ring reduced cell killing with progressive substitution of the alkylating moiety. A comparison was made of cytotoxicity in air and hypoxia with cells exposed to drugs for a 4-h period. A direct comparison of the aerobic and hypoxic cytotoxicity of RSU-1069 in human (A-549) and rodent cells (V-79-379A) yielded similar results. The cytotoxicity factors, defined to be the ratio of drug concentrations under aerobic and hypoxic conditions which result in 10% cell survival, were found to be 40, 25, 18, and 8, respectively, for the four agents RSU-1069, RSU-1164, RB-88712, and RB-88716 tested in A-549 cells. It has been suggested that under aerobic conditions the aziridine ring is primarily responsible for aerobic toxicity, whereas under hypoxic conditions, the aziridine moiety combined with a reduced 2-nitro moiety produces a bifunctional agent (I. J. Stratford et al., Br. J. Cancer 53, 339-344, 1986).

Antineoplastic Agents↗
PubMed1990

The effects of the temporal distribution of dose on oncogenic transformation by neutrons and charged particles of intermediate LET.

The effects of dose rate and dose fractionation on high-LET radiation-induced oncogenic transformation of C3H 10T1/2 cells were examined. Cells were irradiated with graded doses of 5.9-MeV monoenergetic neutrons administered either in single acute exposures (30 mGy/min) or extended over an 8-h period at low dose rates (from 0.21 to 1 mGy/min). Although cell survival studies showed no difference in effect with a change in radiation delivery rate, enhancement of oncogenic transformation occurred when the dose rate was reduced. When the neutron dose was divided into three fractions over 8 h, the biological effect was intermediate between that for the acute and that for the low-dose-rate exposures. Further irradiations were made using deuterons with an LET of 40 keV/microns. The dose-mean lineal energy was comparable to that measured for the 5.9-MeV monoenergetic neutrons. An inverse dose-rate/fractionation effect for the induction of transformation by high-LET deuterons was observed when the time between each of three fractions for a 0.3-Gy total dose was at least 45 min. No further enhancement was seen for longer dose fractionations, suggesting that very long protracted exposures of high-LET radiation would produce no additional enhancement.

Animals↗
PubMed1990

Development of wheat-sensitive enteropathy in Irish Setters: morphologic changes.

Morphologic changes in the small intestine were investigated during development of naturally acquired wheat-sensitive enteropathy in Irish Setters. To distinguish underlying morphologic abnormalities from nonspecific effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were taken sequentially between 4 months and 1 year of age. At 4 months of age, there were no differences in villus height, comparing the 3 groups, but increased numbers of intraepithelial lymphocytes and goblet cells were already present in biopsy specimens from the affected Irish Setters fed wheat. Dietary wheat resulted in a progressive reduction in villus height in the jejunum of affected Irish Setters from 6 months onward. Underlying morphologic abnormalities were not found, and the characteristic morphologic changes of this enteropathy were secondary to the presence of dietary wheat. However, development of partial villus atrophy was preceded by increased numbers of intraepithelial lymphocytes and goblet cells.

Age Factors↗
PubMed1989

Oncogenic transforming potential of nitroimidazole radiosensitizers.

The oncogenic transforming potentials of a number of hypoxic cell radiosensitizers have been compared including misonidazole, SR-2508, Ro-03-8799, and RSU-1069, using the C3H 10T1/2 cell system. While the dual function bioreductive 2-nitroimidazole RSU-1069 is a particularly potent hypoxic cell radiosensitizer, both in vitro and in vivo, it is also more cytotoxic and has a considerably higher oncogenic transforming potential than the other nitroimidazoles tested. In combination with radiation, RSU-1069 produces a supra-additive transforming response in C3H 10T1/2 cells. For all the other sensitizers tested, the number of transformants produced by drug and radiation combined are simply additive. RB-6145, an analog of RSU-1069 with an equivalent sensitizing efficiency, is substantially less toxic and much less oncogenic than RSU-1069. At doses that produce similar in vitro enhancement ratios, RB-6145 is no more oncogenic than misonidazole and produces an additive transforming incidence in combination with radiation. RB-6145 appears to be a promising substitute for RSU-1069 for future clinical application(s) as a hypoxic cell sensitizer.

Animals↗
PubMed1989

Changes in biological effectiveness of the neutron beam at Clatterbridge (62 MeV p on Be) measured with cells in vitro.

Chinese hamster V79 cells have been used to assess changes in RBE of the p(62)Be neutron beam at the Clatterbridge Hospital with depth in a phantom and with use of a hydrogenous filter. The cells were exposed at depths of 2 and 12 cm and at a depth of 2 cm with a hydrogenous filter. Two groups of experimenters each conducted two experiments. The ratios of relative biological effectiveness (RBE) at a depth of 12 cm to that at 2 cm were found by the two groups to be 0.99 +/- 0.04 and 0.96 +/- 0.02 (standard errors). The effect of a polythene filter 4.5 cm thick was measured at a depth of 2 cm and the ratio of RBE with and without the filter was found by both groups to be 0.99 +/- 0.02. All the experiments suggest that there may be small effects of beam hardening by depth and filtration but these results are in marked contrast with those obtained using an in vivo system.

Animals↗
PubMed1989

Assessment of canine intestinal permeability, using 51Cr-labeled ethylenediaminetetraacetate.

The 51Cr-labeled EDTA was validated as a suitable permeability probe in dogs for measurement of passive, unmediated diffusion across intestinal mucosa via intercellular pathways. The 51Cr-labeled EDTA was stable in aqueous solution and did not bind to biologic tissue and fluids. After incubation of 51Cr-labeled EDTA in isolated jejunal loops, analytic subcellular fractionation of jejunal mucosa on reorientating sucrose-density gradients was performed, and no association of 51Cr-labeled EDTA with particulate intracellular organelles was detected. Intravenously administered 51Cr-labeled EDTA was rapidly and completely excreted in urine. Intestinal permeability to 51Cr-labeled EDTA after oral administration was assessed in healthy dogs. The percentage of the administered dose of 51Cr-labeled EDTA excreted in the urine in 24 hours ranged from 2.3 to 17.6% (median, 13%).

Animals↗