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Biomedical subjects

N L Anderson

Publications and source records attributed to N L Anderson.

At least 19 recordsLinked to original sources

Two-dimensional gel electrophoresis analysis of Syrian hamster embryo cells: morphological transformation is not cell type specific.

Studies were conducted to investigate the protein phenotype of normal and morphologically transformed Syrian hamster embryo (SHE) cells. Based upon two-dimensional gel protein phenotype analysis, we conclude that (i) SHE cells are a mixture of multiple cell types including mesenchymal and epithelial cells and (ii) several cell types present in the SHE cell population can be morphologically transformed by a variety of genotoxic and non-genotoxic carcinogens.

Animals

Covalent protein modifications and gene expression changes in rodent liver following administration of methapyrilene: a study using two-dimensional electrophoresis.

The effect of methapyrilene (MP), a mitochondrial proliferator and presumed nongenotoxic carcinogen, has been examined in rodent liver by means of high-resolution two-dimensional electrophoretic analysis of total proteins. Using this approach, we have discovered protein modifications in rat liver resulting from 1 week MP treatment that suggest the involvement of a reactive drug metabolite. The restriction of these molecular charge modifications to mitochondrial proteins indicates that such a reactive metabolite must be generated and confined within the mitochondrion. Quantitative changes in numerous nonmitochondrial proteins are also observed. Following a 4-week recovery period, almost all the 1-week treatment changes are reversed, reestablishing a protein pattern close to that of the controls. At the end of a 10-week exposure, the mitochondrial protein modifications are increased and are accompanied by a variety of quantitative protein changes indicative of a large shift in gene expression and/or cell type composition. When a 4-week untreated recovery period follows the 10-week treatment, small quantitative changes persist. In the mouse, where MP appears not to induce mitochondrial proliferation or tumorigenesis, 1 week treatment nevertheless produces mitochondrial protein changes in vivo consistent with attack by a reactive metabolite, but at a level substantially lower than that seen in the rat. Features of the mitochondrial protein modification indicate that it is covalent, does not involve cysteine or tryptophan, and results from binding of a negatively charged adduct. The possibility that the putative reactive metabolite could also attack mitochondrial (but not nuclear) DNA suggests that MP could be genotoxic in an unconventional way. Detection of protein modification by two-dimensional gel analysis appears to offer a general method for the detection and characterization of processes generating reactive metabolites.

Animals

A two-dimensional gel database of human plasma proteins.

An updated two-dimensional electrophoretic map of human plasma proteins is presented, together with a complete listing of the individual protein spots, their locations, size and isoelectric points relative to internal charge standards. Forty-nine polypeptide species are identified, many consisting of multiple spots differing in glycosylation or sequence (e.g., immunoglobulins). A further series of 35 as yet uncharacterized proteins is indicated.

Blood Proteins

A two-dimensional gel database of rat liver proteins useful in gene regulation and drug effects studies.

A standard two-dimensional (2-D) protein map of Fischer 344 rat liver (F344MST3) is presented, with a tabular listing of more than 1200 protein species. Sodium dodecyl sulfate (SDS) molecular mass and isoelectric point have been established, based on positions of numerous internal standards. This map has been used to connect and compare hundreds of 2-D gels of rat liver samples from a variety of studies, and forms the nucleus of an expanding database describing rat liver proteins and their regulation by various drugs and toxic agents. An example of such a study, involving regulation of cholesterol synthesis by cholesterol-lowering drugs and a high-cholesterol diet, is presented. Since the map has been obtained with a widely used and highly reproducible 2-D gel system (the Iso-Dalt system), it can be directly related to an expanding body of work in other laboratories.

Animals

The interactional dynamics of violence, Part I: An acute psychiatric ward.

The purpose of the following two articles is to shift the emphasis from a strictly patient-centered focus to an interaction-centered focus. Evidence from independent research projects in two different patient care settings demonstrates the interactional nature of violent behavior. One project was conducted on an acute adult psychiatric inpatient unit; the other project was conducted in a juvenile detention facility. Each of these articles describes one segment from two separate and independent parent research projects. Although these clinical research projects were conducted in two very different clinical facilities with very different patient populations, the researchers subsequently discovered common categories and themes regarding the issues of control and the interactional dynamics of violence in the two studies. Interactions between health care providers and patients in the acute psychiatric setting resembled the corresponding interactions in the juvenile detention setting. Both populations had been deprived of power, and all patients/adolescents had some restrictions on their freedom with few choices and opportunities to display positive conduct. Furthermore, the environment in each setting was structured according to the needs of the staff/caretakers, who assumed some degree of control over the individuals in the population being served. Labeling and control issues were identified in the findings from both studies. In the two articles that follow, the specific qualitative research methods used in each study are described. Common themes are discussed from each clinical perspective, using research data and case examples that exemplify the interactional basis of violent behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Attitude of Health Personnel

Pregnancy resolution decisions in juvenile detention.

A group of detained pregnant adolescents and expectant teenage fathers served as participants in a qualitative research project designed to describe how adolescents residing in a large metropolitan area juvenile detention facility make health- and pregnancy-related decisions. During the course of the study and clinical work with this population, it was found that although troubled and troublesome, these teenagers do not present as bleak and depressing a picture as might appear on the surface. Three primary themes emerged from the study findings: responsibility, reputation, and respect. These themes were bound to the important relationships in the teenagers' lives. The participants also presented some surprising strengths and resolutions for the future that psychiatric and liaison nurses working in the setting can use in program planning and clinical interventions.

Adolescent

Effects of toxic agents at the protein level: quantitative measurement of 213 mouse liver proteins following xenobiotic treatment.

By analyzing two-dimensional electrophoretic patterns of mouse liver proteins with a computerized image analysis system, we have observed quantitative changes in the abundance of more than 70 proteins in mice treated with various agents. Aroclor 1254, a mixture of polychlorinated biphenyls known to induce a broad spectrum of microsomal activity, induces the largest group of changes (60 proteins altered at p less than 0.001 significance). Phenobarbital produces a small set of characteristic changes that forms part of the much larger Aroclor 1254 effect. Ibuprofen treatment produces a phenobarbital-like pattern of change, with the addition of at least one protein change not observed with any of the other treatments. Cycloheximide and carbon tetrachloride each induces a different characteristic pattern of protein alteration. We have assigned most of the mouse liver proteins to a specific subcellular fraction, and it appears that the predominant class of proteins altered by each compound is present in the soluble phase, rather than in the microsomal fraction. The ability to survey large numbers of tissue proteins for involvement in pharmacologic and toxic effects may allow a more comprehensive understanding of the mechanisms of action in vivo and provide new markers of tissue damage.

Animals

Comparison of African trypanosomes of different antigenic phenotypes, subspecies and life cycle stages by two-dimensional gel electrophoresis.

High resolution two-dimensional polyacrylamide gel (2D gel) electrophoresis and autoradiography were used to analyze the protein gene products of African trypanosomes biosynthetically labelled with [35S]methionine. Using cloned populations of parasites it was found that: antigenically different bloodstream trypanosomes from the same serodeme differed only in their variant surface glycoproteins; Trypanosoma brucei, T.b. rhodesiense and T.b. gambiense subspecies could be distinguished on the basis of differences in expressed proteins; transformation from bloodstream trypomastigotes to procyclic epimastigote culture forms was accompanied by loss of variant surface glycoproteins and several other qualitative and quantitative changes in minor proteins. The results indicate that 2D gel analysis may allow improved classification of African trypanosomes (based on the observation of hundreds of protein markers) and may also provide a general technique for the identification of lifecycle stage specific markers.

Animals

Specific protein phosphorylation in human promyelocytic HL-60 leukemia cells susceptible or resistant to induction of cell differentiation by phorbol-12-myristate-13-acetate.

The pattern of protein phosphorylation induced by phorbol-12-myristate-13-acetate (PMA) was analyzed by two-dimensional gel electrophoresis in human HL-60 leukemia cells, which are susceptible to induction of cell differentiation by PMA, and in cells from an HL-60 cell variant designated R-94 that are resistant to such an induction. Protein phosphorylation was detected by observing either a rapid acid-directed charge shift of [35S]methionine-labeled protein or an increase in the amount of phosphate label in a 32P-labeled protein. The results indicated that PMA at 10(-7) M causes within 30 min after treatment the phosphorylation of at least ten different proteins in both the HL-60 and R-94 cells. Among these ten phosphorylated proteins, we identified a major cytoplasmic polypeptide (Mr approximately 64,000), a cytoskeletal protein (Mr approximately 56,000), a nonmuscle myosin light chain, and two proteins (Mr approximately 60,000 and 64,000) localized in or around the cell nucleus. Phosphoamino acid analysis of six of the ten phosphoproteins showed that they contain phosphoserine. None of these proteins contained phosphotyrosine or phosphothreonine. The R-94 cell variant was found to be capable of increased protein phosphorylation after PMA treatment; however, the level of phosphate incorporation reached only the level of the untreated HL-60 cells and thus fell far short of the level observed in the HL-60 cells after PMA treatment. It is suggested that the basis for the acquired resistance in R-94 cells towards induction of cell differentiation by PMA is a block in signal transmission involving phosphorylation of nuclear protein(s) following the binding of the inducer PMA to its receptor (protein kinase C).

Caenorhabditis elegans Proteins

Use of a pyrethrin larvicide to control Culicoides variipennis (Diptera: Ceratopogonidae) in an alkaline lake.

Laboratory bioassays with Culicoides variipennis larvae from Borax Lake, CA, indicated an LC90 of 16.8 ppb for pyrethrins at 23 degrees C. A field test in a pond adjoining the lake reduced adult C. variipennis emergence greater than 99% for over 30 days after treatment at a rate of 131 ppb pyrethrins. Further small scale field tests indicated that C. variipennis could be controlled in the lake at a rate of 701 g/ha pyrethrins applied as a peripheral treatment. The first lake treatment resulted in a 99.3% decrease in the density of C. variipennis larvae along the shoreline. Four treatments resulted in a 98.5% decrease from non-treatment years in the number of adult cumulative insect-days during May and June.

Animals