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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

701 records · Page 39Linked to original sources
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Comparing the response surfaces of two cholinolytics when used in combination with physostigmine as a pretreatment against organophosphate challenge.

Physostigmine (PHY) is currently being evaluated as a potential pretreatment against nerve agent challenge. Although it might provide increased protection against nerve agent-induced incapacitation, it is nonetheless behaviorally toxic itself. Addition of a cholinolytic adjunct is expected to significantly reduce this behavioral toxicity. The efficacy of pretreatment regimens (PRG) (composed of PHY in combination with either scopolamine (SCP) or trihexyphenidyl (artane; ART] was evaluated in guinea pigs challenged with soman (98 ug/kg, sc; 3.5 LD50) to determine the dose of PHY and adjunct required for optimal efficacy as well as the better of the two adjuncts. Three different endpoints were measured on each animal: (1) whether or not the animal survived up to 24 hours post challenge, (2) severity of incapacitation, and (3) time to recovery. The survival data revealed no significant differences between the two adjuncts and PHY against soman, but the data suggests that a pretreatment combination of PHY and ART is likely to give a greater therapeutic index than one containing SCP. Furthermore, since ART is less toxic behaviorally, it would most likely be better tolerated as a pretreatment with PHY in non-agent exposed subjects. The findings in this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents. In conducting the work described in this report, the investigators adhered to the "Guide for the Care and Use of Laboratory Animals" as promulgated by the Committee on Revision of the Guide for Laboratory Animal Facilities and Care of the Institute of Laboratory Animal Resources, National Research Council.

Animals↗
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An evaluation of two animal models for dietary influences on reproductive toxicology.

Chronic protein deficiency (8 weeks) was examined in marmosets (Callithrix jacchus) and sub-acute (1 week) methionine- and choline-deprivation was investigated in F344 rats. The marmosets were considered to have become protein-deficient but there was no alteration in sperm morphology, either at the end of the diet or 5 weeks later. Weight loss was also observed in rats on the methionine- and choline-free diet and they had significantly decreased sperm counts 4 weeks after the end of treatment. However, there was no effect on sperm morphology, or on the proportion of cytosine residues that were methylated in the sperm DNA.

Animals↗
PubMedDate not supplied

A perspective on JEN.

Explore the source record for details and available documents.

Emergency Medicine↗
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The significance of the extracellular matrix in intracranial aneurysms.

To what extent might change sin the extracellular matrix proteins in intracranial aneurysms (IA) or parent artery (PA) wall contribute to enlargement? Using IA specimens obtained from the coroner's office, the wall structure by light (Trichrome and Actin stains) and immunofluorescent microscopy (IF) (collagen I and fibronectin) have been studied in 18 specimens. It is well known that IA only arise when there is a deficiency in the internal elastic membrane and some breakdown in the media. The results show a normal three layer structure of intima, media, (muscularis), and adventitia in the PA extending out into the neck of the aneurysm. Immunofluorescent stains (IS) show collagen I and fibronectin limited to the adventitia and muscularis, respectively, of the PA and control arteries. The enlarging IA wall shows almost complete loss of this architecture. By IF stain, collagen I and fibronectin are intermingled throughout the IA wall. It is postulated that loss of structure and the confining muscularis layer permit easier elastic enlargement from a more or less homogeneous wall structure.

Actins↗
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Market your expertise for the changing future of intravenous therapy.

Redirecting an i.v. team is a progressive approach to interdepartmental and community i.v. needs for the future viability of i.v. therapy. Cut backs and cost justification can be redirected to increase revenue. First the i.v. team should present a proposal to hospital management that includes statistics of i.v. team duties, cost justification by phlebitis and infection, and ways that revenue can be increased. Areas of expertise and needs in the department, hospital or agency, and community must be determined. The possibilities and feasibility of implementation should be researched and prioritized. These possibilities should then be planned, developed, and implemented according to the prioritized list.

Forecasting↗
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Plasmid DNA gene therapy: studies with the human interleukin-2 gene in tumor cells in vitro and in the murine B16 melanoma model in vivo.

The plasmid DNA vector pVCL-1102 containing the coding sequence for the human IL-2 gene was evaluated for expression in tumor cells in vitro and in vivo. In vitro transfection of murine B16 tumor cells with pVCL-1102 resulted in the expression of 36,000 IU (5.7 micrograms) of biologically active IL-2/10(6) cells/48 h. In vitro transfection of human tumor lines and primary cultures from human biopsies with pVCL-1102 resulted in the expression of 1,289 to 9345 IU of IL-2/10(6) cells/48 h and 30 to 794 IU of IL-2/10(6) cells/48 h, respectively. In vivo, direct intratumor injection of pVCL-1102 resulted in retention of intact plasmid DNA in the tumor tissue and IL-2 secretion by cell cultures derived from the injected tumors. Formulation of pVCL-1102 with the cationic lipid DMRIE/DOPE inhibited DNA degradation and enhanced in vivo transfection efficiency over plasmid DNA alone. Antitumor activity of the pVCL-1102/DMRIE/DOPE complex was evaluated in a B16 melanoma model in mice. An IL-2-specific effect could not be demonstrated in a subcutaneous model because the intratumor injection of plasmid DNA lacking the IL-2 coding sequence also resulted in a significant reduction in tumor volume. However, an IL-2-specific effect was observed when B16 cells were transfected in vitro prior to implantation into the mouse. Transient transfection of B16 cells with pVCL-1102 rendered the cells less tumorigenic in vivo and produced a significant reduction in tumor volume. These data demonstrate that a plasmid DNA expression vector can be used to deliver the IL-2 gene to tumor cells in vitro and in vivo, resulting in the expression of significant levels of IL-2 protein. These data also illustrate the need for the use of appropriate controls when evaluating the in vivo biological activity of plasmid DNA in murine tumor models.

Animals↗
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Immunotherapy of established tumors in mice by intratumoral injection of interleukin-2 plasmid DNA: induction of CD8+ T-cell immunity.

Intratumoral (i.t.) injection of a plasmid DNA vector encoding the murine interleukin-2 (IL-2) gene was used to treat established renal cell carcinoma (Renca) tumors in BALB/c mice. Tumor regression was observed in 60-90% of mice that were injected i.t. for 4 days with IL-2 plasmid DNA complexed with the cationic lipid DMRIE/DOPE ((+/-)-N-(2-hydroxyethyl)-N,N-dimethyl-2,3-bis(tetradecyloxy)-1-propa naminium bromide/dioleoylphosphatidylethanolamine). The mice remained tumor-free until the conclusion of the study, which was 4 months after tumor challenge. In a rechallenge experiment, mice that were rendered tumor-free for 6 months by IL-2 plasmid DNA treatment rejected a subsequent challenge of Renca cells but could not reject a challenge with the unrelated, syngeneic CT-26 tumor. Spleen cells from cured mice contained Renca-specific cytotoxic T lymphocytes, and adoptive transfer of mixed lymphocyte cultures into naive mice at 2 days after challenge with Renca cells prevented tumor growth. In vivo depletion of T-cell subsets at the time of i.t. injection with IL-2 plasmid DNA demonstrated that CD8+ T cells, but not CD4+ T cells, were the primary effectors of the antitumor response.

Animals↗