Biomedical subjects

B A Carnes

Publications and source records attributed to B A Carnes.

46 records · Page 3Linked to original sources

PubMed1986

Synergistic induction of altered hepatocyte foci by combined gamma radiation and diethylnitrosamine administered to neonatal rats.

To investigate mechanisms underlying the formation of carcinogen-induced altered hepatocyte foci, we histochemically examined the livers of 150-day-old rats that had been treated neonatally with single doses of gamma radiation (75, 150 or 300 rad, whole body) and i.p.-injected diethylnitrosamine (DEN, 0.15 mumol/g body wt) either separately or in combination. Three focus phenotypes, showing the elevated gamma-glutamyl transpeptidase [GG(+)] and/or the iron-exclusion [Fe(-)] histochemical marker(s) were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. DEN and gamma radiation each induced foci when given separately but total focus yield per cm3 of liver was more than 10-fold greater in DEN-treated than in irradiated rats and approximately 3-fold higher in females than in males. Combining the DEN and radiation treatments synergistically increased total focus yields for both sexes, although this response declined with increasing radiation dosage. For rats receiving DEN alone, the sex-dependent differential in total focus yield was due to the higher frequencies in females of the iron-excluding phenotypes [Fe(-) alone and Fe(-) + GG(+)]; the frequencies of foci showing only GG(+) were similar in both sexes. In contrast, the enhancement in total focus yield resulting from the combined DEN--radiation treatments was primarily a consequence of increases in the foci with GG(+) alone. The results suggest that (a) qualitatively different types of genetic damage (carcinogen-induced point mutations and radiation-induced rearrangements) may interact synergistically in the induction of phenotypically altered cells and (b) separate genetic loci are involved in the sex-mediated modulation of focus production and the synergistic enhancement of focus production by DEN--gamma radiation interactions.

Animals↗

PubMed1985

Protective effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid against induction of altered hepatocyte foci in rats treated once with gamma-radiation within one day after birth.

We have investigated the protective effects of S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR2721) on the induction by radiation of altered hepatocyte foci in 150-day-old Sprague-Dawley rats. WR2721 (100 micrograms/g of body weight) was administered to selected groups of neonatal animals 30 min prior to the administration of single doses of ionizing radiation (150 or 300 rads). Two focus phenotypes, described by the histochemical markers gamma-glutamyltranspeptidase and iron exclusion, were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. Although radiation was capable of inducing foci, induction was much more effective in female than in male rats. WR2721, however, reduced the frequencies of radiation-induced foci at both radiation doses, with the protective effect more readily apparent in female animals. The modulation of foci formation by WR2721 in the neonatal rat system suggests that this compound and related aminothiols may be useful probes for examining mechanisms of mutagenesis and carcinogenesis induced by radiation or chemicals.

Amifostine↗

PubMed1985

Neoplastic transformation is enhanced by multiple low doses of fission-spectrum neutrons.

The neoplastic transformation of C3H mouse 10T1/2 cells was measured induced by fission-spectrum neutrons delivered at a high dose rate in five fractions over 4 days. The transformation frequency was significantly enhanced over that due to single equivalent total doses. These new data, in the low dose region, demonstrate an increased transformation frequency by fractionated versus single exposures of high-dose-rate fission-spectrum neutrons; an increase equal to that observed with low-dose-rate fission-spectrum neutrons (i.e., 0.086 rad/min). Estimates of the dose modifying factor (DMF), based upon the ratio of the initial linear portions of the induction curves for high and for low dose rates, suggest the same DMF (approximately 7.8) for both five daily fractions of high-dose-rate neutrons and for low-dose-rate neutrons. However, when these results are compared to those following high-dose-rate 60Co gamma rays (100 rad/min), the relative biological effectiveness (RBE) for low-dose-rate fission-spectrum neutrons based upon slope ratios is 19.6; similarly, the RBE relative to five daily fractions of 60Co gamma rays is 78.8.

Animals↗

PubMed1984

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↗

PubMed1984

Characterization of histochemically detectable altered hepatocyte foci and their relationship to hepatic tumorigenesis in rats treated once with diethylnitrosamine or benzo(a)pyrene within one day after birth.

A new experimental system was used to examine the stages of chemically induced hepatic neoplasia in the rat. The treatment protocol involved the i.p. injection of a single dose of carcinogen [diethylnitrosamine or benzo(a)pyrene] into male and female rats within 1 day after birth, followed by dietary exposure to promoter (0.05% dietary phenobarbital) beginning at weaning. Rats were killed at intervals, and their livers were examined for tumors and for histochemically detectable foci of altered hepatocytes using six histochemical markers. Through serial frozen-sectioning techniques and computer-assisted image analysis, foci containing between one and six markers were identified, and their average diameters were calculated. The same complement of histochemical tests was applied to the primary hepatic tumors observed in this study. The principal findings were the following. (a) Both the diethylnitrosamine and benzo(a)pyrene treatments were tumorigenic and produced foci with similar phenotypic properties (numbers and identities of histochemical markers). (b) Foci relative growth rates and growth capacities (ranges of possible growth rates) were directly related to foci phenotypic complexity levels (numbers of markers per focus). (c) Individual foci were phenotypically stable; i.e., they neither gained nor lost markers. (d) A substantial fraction of the tumors observed in this study had fewer markers than the most complex foci. On the basis of these observations, we suggest that foci emerge as the result of a specific set of cellular changes solely inducible by carcinogenic stimuli, but the foci do not evolve through progressively more deviated forms into tumors. Instead, we postulate that tumorigenesis involves a separate transformation event that may occur in a susceptible fraction of foci subsequent to their induction or, alternatively, may occur at the time of exposure to carcinogen, in parallel with the carcinogen-mediated events leading to focus formation.

Aging↗

PubMed1984

Relationship of histochemically detectable altered hepatocyte foci to hepatic tumorigenesis.

A new experimental system was used to examine the stages of chemically induced hepatic neoplasia in the rat. The treatment protocol involved the intraperitoneal injection of a single non-necrogenic dose of carcinogen [N-nitrosodiethylamine (NDEA) or benzo[a]pyrene (BP)] into male and female rats within one day after birth, followed by dietary exposure to promoter (0.05% phenobarbital) from weaning. Rats were killed at intervals, and their livers were examined for tumours and for histochemically detectable foci of altered hepatocytes. Six histochemical markers were used. Through serial frozen-sectioning techniques and computer-assisted image analysis, foci containing between one and six markers were identified, and their average sizes were calculated. The same complement of histochemical tests was applied to the primary hepatic tumours observed in this study. The data showed that (1) the new treatment protocol was highly efficient in foci and tumour production; (2) growth rates and incidence levels of foci were directly related to hepatocarcinogenic effectiveness (NDEA greater than BP), whereas both carcinogens had similar effects on foci phenotypic properties; (3) after their formation, foci at a given level of phenotypic complexity did not become progressively more complex; (4) incidence levels of foci were sex-dependent (females greater than males), but growth rates of foci were the same for both sexes; (5) growth rates and growth capacities (ranges of possible growth rates) of foci were directly related to phenotypic complexity levels of foci; (6) frequencies and phenotypic complexities of foci were inversely related; the reverse was true for tumours, although 10% of the tumours were relatively simple (three markers or fewer); (7) marker frequency distribution patterns were completely different in foci and in tumours. From these observations, we suggest that the foci are not direct tumour progenitors but, instead, are manifestations of a mosaic of subtumorigenic effects of the carcinogenic stimulus on cellular functions associated with the control of cell division and phenotypic character. The observed foci and tumour characteristics suggest that these carcinogen-induced cellular changes define elements of the mechanism whereby a specific neoplastic transformation site is rendered more accessible to carcinogenic attack.

Aging↗

PubMed1983

Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration.

The effectiveness of N,N'-bis[2-hydroxybenzyl]-ethylene-diamine-N,N'-diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as 59Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the 59Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, we have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally to mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. We have demonstrated that HBED is superior to DF for removal of storage iron from liver parenchymal cells and that liposomes are useful carriers for iron chelators of low water solubility.

Animals↗

PubMedDate not supplied

A quantitative comparison of a percentile rule with a 2-fold rule for assessing mutagenicity in the Ames assay.

Using a model based on the bivariate normal density function, this paper compares the effectiveness of two commonly employed decision rules for assessing mutagenicity in the standard Ames Salmonella assay. The 2-fold method, which considers a compound significantly mutagenic if its mean number of revertants per plate at any dose is equal to or greater than twice the mean number of revertants per plate in the concurrent control, may be a poor indicator of significant mutagenesis. In the percentile method, the frequency of induced mutations for the test compound is tested against the 95th percentile of the accumulated historical data for the spontaneous mutation frequency. As judged by the higher probability of declaring a compound mutagenic that elevates the reversion rate above background, the percentile rule is more reliable than the 2-fold method.

Dose-Response Relationship, Drug↗

PubMedDate not supplied

A biologically motivated partitioning of mortality.

For over a century, actuaries and biologists working independently of each other have presented arguments for why total mortality needs to be partitioned into biologically meaningful subcomponents. These mortality partitions tended to overlook genetic diseases that are inherited because the partitions were motivated by a paradigm focused on aging. In this article, we combine and extend the concepts from these disciplines to develop a conceptual partitioning of total mortality into extrinsic and intrinsic causes of death. An extrinsic death is either caused or initiated by something that orginates outside the body of an individual, while an intrinsic death is either caused or initiated by processes that originate within the body. It is argued that extrinsic mortality has been a driving force in determining why we die when we do from intrinsic causes of death. This biologically motivated partitioning of mortality provides a useful perspective for researchers interested in comparative mortality analyses, the consequences of population aging, limits to human life expectancy, the progress made by the biomedical sciences against lethal diseases, and demographic models that predict the life expectancy of future populations.

Aging↗

PubMedDate not supplied

Caring for the professional caregiver: the application of Caplan's model of consultation in the era of HIV.

Nurses as well as other health-care professionals have been impacted by the current human immunodeficiency virus (HIV) epidemic. Issues related to virus transmission, voluntary testing, and professional requirements to provide care for those infected can trigger emotional as well as cognitive responses for all involved. The heavy emotional needs of patients and the regular confrontation of death increase the risk of burnout for those caring for the growing number of patients with acquired immunodeficiency syndrome. In an effort to retain and to recruit nurses who are willing to become involved in the care of those infected with the virus, it is imperative that nursing administration provide psychosocial support services for those nurses. This article describes the development and implementation of a psychosocial support program, based on Caplan's (1973) model of mental health consultation, for nursing staff impacted by the HIV epidemic. The program, established through a cooperative alliance between psychiatric/mental health clinical nurse specialists and nursing staff, has proved to be effective and efficient. It is recommended that other psychiatric/mental health nurses, including faculty, use the consultation model to improve the psychosocial support available to health-care professionals affected by the HIV epidemic.

Burnout, Professional↗