Search PubMed⌕ Search

Biomedical subjects

E A Carlson

Publications and source records attributed to E A Carlson.

30 records · Page 2Linked to original sources

Factors for improved genetic counseling for retinoblastoma based on a survey of 55 families.

Of 55 families in which one or more patients with retinoblastoma were treated, five of these families involved more than one patient. The remaining 50 were sporadic cases. Two of the five familial cases involved collateral inheritance and three involved direct inheritance. Factors important for genetic counseling included the time of onset of first symptoms, the age of the father, the occurrence of a second primary tumor, unilateral vs bilateral involvement, and the cytogenetic analysis of the patient's chromosomes. Additionally, mutational mosaicism was considered as a cause for sporadic cases of retinoblastoma. Use of the risk figures derived from this study should provide more precise genetic counseling for parents, siblings, and patients with retinoblastoma.

Adolescent↗

Suppressive effects of benzo[a]pyrene upon fish immune function: evolutionarily conserved cellular mechanisms of immunotoxicity.

Knowledge gained through the use of alternative animal models has significantly enhanced our understanding of life at all levels of biological organization. The discipline of toxicology is under considerable pressure to develop such models due to increasing public concern regarding the experimental use of mammals. Studies in this laboratory have focused on the utility of a small laboratory fish model, the Japanese medaka (Oryzias latipes), to investigate immunotoxicological effects of benzo[a]pyrene (BaP). BaP is a ubiquitous environmental contaminant and known mammalian immunotoxicant. This laboratory has demonstrated that in vivo exposure of medaka to BaP (2-200 microg/g BW) significantly depresses both innate and humoral immunity. Further studies have indicated that BaP activates its own biotransformation pathway within medaka immune cells following both in vivo and in vitro exposure. In addition, reduction of BaP metabolism with alpha-naphthoflavone results in the reversal of BaP-induced suppression of antibody production in vitro. Inhibition of CYPlA-mediated metabolism within medaka immune cells also alleviates the immunotoxicity induced by benzo[a]pyrene-7,8-dihydrodiol, but not benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). This suggests that BPDE may be an ultimate immunotoxicant. Results from this study in medaka are in agreement with previously conducted rodent studies that indicated a role for immunotoxic BaP metabolites in BaP-induced suppression of humoral immunity.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

The Japanese medaka (Oryzias latipes) model: applicability for investigating the immunosuppressive effects of the aquatic pollutant benzo[a]pyrene (BaP).

Despite the fact that BaP is a carcinogen, mammalian immunosuppressant, and ubiquitous aquatic pollutant, knowledge regarding the effects of BaP on the immune system of fish is still lacking. To begin to fill this gap, studies were conducted in medaka to examine the effects and mechanisms by which BaP exposure might alter host immunocompetence. Fish, exposed by IP injection of BaP (2-600 microg/g BW), were examined after 48 h for effects upon immune function and CYP1A expression/activity. Benzo[a]pyrene, at a concentration below that which increased levels of CYPIA expression/activity (2 microg BaP/g BW) suppressed lymphocyte proliferation. Concentrations of BaP at 20 and 200 microg/g BW. suppressed antibody-forming cell (AFC) numbers, superoxide production, and host resistance against bacteria. In contrast, exposure to the low affinity aryl hydrocarbon receptor (AhR) agonist, benzo[e]pyrene (BeP), neither induced CYP1A expression nor altered immune function. Given the lack of immunosuppressive effects produced by BeP, and the fact that exposure to the AhR antagonist (and CYP1A inhibitor) alpha-naphthoflavone (ANF) ameliorated the suppressive effects of BaP upon AFC numbers, the AhR pathway (including CYP1A-mediated production of reactive BaP metabolites) appears important in mediating BaP-induced immunotoxicity in fish, as in mammals. In the past, the medaka has proven a successful model for assessing carcinogenic agents. These studies have demonstrated its utility for also determining the immunosuppressive effects of an important aquatic contaminant.

Animals↗

Age-related differences in the sensitivity of the fish immune response to a coplanar PCB.

Polychlorinated biphenyls (PCBs) are widespread environmental pollutants. Because of their persistence and bioaccumulation in aquatic organisms (among other factors), the biological impact of PCB exposure on resident fish populations is of particular concern. To assess the effect(s) of an environmentally relevant coplanar PCB congener on the fish immune response, juvenile and aged Japanese medaka (Oryzias latipes) were injected i.p. with either vehicle or PCB 126 (at 0.01 or 1.0 microg/g BW) and examined after 3 and 14 days. CYP1A protein levels, examined as an indicator of PCB exposure, were significantly increased (compared to controls) in all fish treated with the highest PCB dose. Kidney phagocyte superoxide (O2*-) production was examined to indicate effects upon innate immune function. After 14 days, unstimulated O2*- production by kidney phagocytes from juvenile and aged medaka treated with the highest PCB dose was significantly increased compared to controls. Stimulated O2*- production by aged PCB-treated fish was unaffected (compared to controls) at both post-exposure timepoints. However, phagocytes from PCB-treated juvenile medaka demonstrated reduced O2*- production at 3 days post-exposure and increased levels after 14 days (compared to controls). These results demonstrate the sensitivity of medaka phagocyte function for examining PCB-induced immunotoxicity.

Age Factors↗