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Biomedical subjects

E M Anderson

Publications and source records attributed to E M Anderson.

At least 19 recordsLinked to original sources

Gene profiling study of G3139- and Bcl-2-targeting siRNAs identifies a unique G3139 molecular signature.

G3139 is a phosphorothioate oligodeoxyribonucleotide that is targeted to the initiation codon region of the Bcl-2 mRNA, which downregulates Bcl-2 protein and mRNA expression via an antisense mechanism. In previous work, we have demonstrated that the phenotype observed in several prostate and melanoma cell lines after treatment with G3139 appears to be Bcl-2 independent. In contrast, downregulation of Bcl-2 expression by a small interfering RNA (siRNA) produced little or no phenotype change. In the present work, we performed an Agilent oligonucleotide microarray assay on mRNA isolated from PC3 prostate cancer cells that were treated with two different oligonucleotide gene-silencing reagents. G3139 and a Bcl-2-targeting siRNA both downregulate Bcl-2 expression, but via different mechanisms. A side-by-side comparative analysis showed that the expression profile generated by these molecules differs substantially. The study revealed upregulation of the expression of stress-inducible genes in PC3 cells at 1 and 3 days after a 5-h transfection with G3139 complexed with Lipofectamine 2000. In contrast, only a very diminished stress response was seen 1 and 3 days after a 24-h transfection of siRNA/Lipofectamine 2000 complexes. These results highlight the profound differences in off-target effects in cells treated with the phosphorothioate oligonucleotide G3139 and with an siRNA targeted to the same gene, and provide further evidence that the mechanism of action of G3139 is not related to Bcl-2 silencing.

Cell Line, Tumor↗

A survival analysis of clinically significant change in outpatient psychotherapy.

The number of sessions required to produce meaningful change has not been assessed adequately, in spite of its relevance to current clinical practice. Seventy-five clients attending outpatient therapy at a university-affiliated clinic were tracked on a weekly basis using the Outcome Questionnaire (Lambert et al., 1996) in order to determine the number of sessions required to attain clinically significant change (CS). Survival analysis indicated that the median time required to attain CS was 11 sessions. When current data were combined with those from an earlier investigation (Kadera, Lambert, and Andrews, 1996), it was found that clients with higher levels of distress took 8 more sessions to reach a 50% CS recovery level than clients entering with lower levels of distress. At a six-month follow-up, CS gains appeared to have been maintained. Other indices of change also were examined (reliable change, average change per session). The implications of these results for allocating mental-health benefits, such as the number of sessions provided through insurance, are discussed.

Adolescent↗

Engaging distortions: are we idealizing marriage?

The present study was an investigation of the premarital status of engagement in terms of relationship satisfaction and marital expectations using the Evaluation and Nurturing Relationship Issues, Communication and Happiness (ENRICH) Marital Satisfaction Scale (EMS) and its two subscales of Idealistic Distortion (ID) and Marital Satisfaction (MS) (D. G. Fournier, D. H. Olson, & J. M. Druckman, 1983). There were 104 students (23 men and 81 women), of which 15 were married, 19 were engaged, and 70 had extended dating relationships. On average, participants had been in the relationship for 3.8 years, and the mean age was 22 years. Results demonstrated that individuals engaged to be married had significantly higher idealistic distortion scores (M = 86.89) than did either married individuals (M = 56.67) or those in extended dating relationships (M = 61.19). Finally, a negative relation was found between length of relationships and marital satisfaction subscores. Results are discussed in light of factors contributing to such idealized thinking.

Adult↗

Status of nutrition labeling, health claims, and nutrient content claims for processed foods: 1997 Food Label and Package Survey.

The Food and Drug Administration (FDA) conducts studies of food labels as part of its ongoing monitoring of the nutritional status of the US population. In 1994 FDA nutrition labeling rules were implemented and in 1997 the Food Label and Package Survey characterized various aspects of the labeling of processed, packaged foods, including nutrition labeling, health claims, and nutrient content claims. For the survey, FDA selected a multistage, representative sample of food products from the SCAN-TRACK food sales database (AC Nielsen Co, Schaumburg, Ill). FDA identified 58 product groups and selected those product classes from the database that accounted for 80% of sales in each group. From each product class, FDA selected the 3 top-selling product brands and randomly selected follower brands. Based on label information from a final sample of 1,267 food products, FDA determined the percentage of products sold that bear Nutrition Facts labels, health claims, and nutrient content claims. The purpose of this article was to present FDA findings regarding the status of food labels 3 years after implementation of the nutrition labeling rules. Nutrition-labeled products accounted for an estimated 96.5% of the annual sales of processed, packaged foods. An additional 3.4% of products sold were exempt from labeling regulations. Nutrient content claims and health claims appeared on an estimated 39% and 4%, respectively, of the products sold. Dietitians and other health care professionals can use this survey information to identify food types with specific label information and to assist the US consumer in making more varied and healthful food choices in the marketplace.

Food Labeling↗

Concerns about allegations of child sexual abuse against teachers and the teaching environment.

OBJECTIVE: The major objective was to determine teachers' awareness of the potential for child abuse allegations against themselves and the effects on the teaching environment. METHOD: Of 3,000 questionnaires sent out to a random sample of New York state teachers, 515 were returned. The responding teachers were similar to New York state teachers in terms of gender, age, and racial/ethnic distribution. RESULTS: A large percent of the respondents (56%) were aware of false allegations made against a teacher in their school district. About a third (36.5%) expressed concern that a child abuse allegation could be made against them. In response to a vignette, forty-two (42%) advised a new teacher against being alone in a room with a student; 62% advised against casual touching; 70% advised against hugging or putting an arm around a student. Males more than female teachers, especially those teaching upper grades, advised against such contact. The more teachers expressed concern about abuse allegations against themselves, the more teachers advised against contact. CONCLUSIONS: Fear of abuse allegations are salient for teachers. Fears may cause teachers to limit contact with students with potentially adverse consequences for students and the teaching environment.

Adult↗

Does angiotensin play a role in human fetal erythropoiesis?

Angiotensin affects the growth of many cell types and there have been suggestions that it could influence cells which respond to erythropoietin. During first trimester, human fetal haematopoietic cells are exquisitely responsive to erythropoietin and we have assessed the potential for angiotensin to also influence the growth of these cell types in a standard culture system. The data obtained from these studies indicate that angiotensin does not influence fetal haematopoiesis over a range of concentrations.

Angiotensin II↗

Mutagenesis and comparative sequence analysis of a base triple joining the two domains of group I ribozymes.

Tertiary interactions are important in the higher-order folding of catalytic RNAs. Recently, a base triple, joining the two major domains of the catalytic core, was determined in group I introns from the cyanobacterium Anabaena PCC7120 and the eukaryote Tetrahymena thermophila. This base triple involves the fifth base pair of P4 and the fifth base of the single-stranded region J8/7. We made base pair and single-nucleotide substitutions in the fifth base pair of P4, a G-C in the wild-type Anabaena intron, and tested them for self-splicing activity. The results suggest a hydrogen bonding model in which only the C of the base pair interacts directly with the fifth base of J8/7. Comparative sequence analysis was used to determine the different combinations of base triples that occur in approximately 450 natural group I introns identified to date. About 94% of the base triples analyzed are compatible with the proposed hydrogen bonding model. Disrupting this base triple in the Tetrahymena intron resulted in the disappearance of splicing intermediates (intron 3' exon and 5' exon), even though the first step of splicing was not affected. Restoration of the base triple by a compensatory mutation reverted the intermediates to wild-type levels. These results suggest that disruption of the base triple increases the rate of the second step of splicing or of a conformational change preceding the second step. Repositioning of the base triple to form a new set of interactions may be required for the second step of splicing.

Anabaena↗

Factor structure of the Private Self-Consciousness Scale.

Several issues concerning the factors of the Private Self-Consciousness Scale (PRSC) of Fenigstein et al. (1975) are examined, including possible artifactuality and appropriate conceptualization. Findings confirm the existence of the 2 factors reported in previous research (Burnkrant & Page, 1984; Lennox, Welch, Wolfe, Zimmerman, & Dixon, 1987; Mittal & Balasubramanian, 1987; Piliavin & Charng, 1988) and suggest that these factors are substantive, not artifactual, in nature. One factor was found to be associated with mild levels of psychopathology, whereas the other was not. In addition to providing a clearer conception of the nature of these factors, our results may help to resolve apparently contradictory findings in the PRSC literature. Implications for research on self-focused attention are also discussed.

Factor Analysis, Statistical↗

In utero haematopoietic stem cell transplantation: current perspectives and future potential.

In utero transplantation (IUT) of haematopoietic cells is a new therapeutic option for families with increased risk of having a child with an inherited disorder. Immunological naiveté and the rapidly expanding haematopoietic system in the first trimester human fetus, make therapeutic intervention by IUT a real possibility for those disorders which can be diagnosed early in gestation. Fewer cells are required than in postnatal BMT and therapy can be offered before the pathological sequelae of a disorder become manifested. However, only a few cases of IUT have been performed in humans and it is imperative that consensus is reached quickly on issues such as cell numbers/cell types so that the benefits of this approach to treatment can be realised. This review presents the current status of IUT, the cases thus far recorded and offers a prospective view of developments in this rapidly expanding area.

Female↗

The effect of folate on the methotrexate/indomethacin interaction in a murine cancer cell line.

1. The effect of folate on the interaction between methotrexate (a folate analogue) and indomethacin has been examined in murine NC carcinoma cells. 2. Conditioning of NC cells to a physiological (20 nM) folate concentration after culture in a high folate concentration increased the response to methotrexate. The sensitivity of these conditioned cells to methotrexate related inversely to the folate concentration. 3. At 20 nM and 2 microM folate, indomethacin 1 micrograms ml-1 potentiated the cytotoxicity of methotrexate 4 and 8 ng ml-1 (both P < 0.03). 4. When NC cells were incubated with [3H]-methotrexate at 20 nM and 2 microM folate, there was a trend for increased tritium accumulation with indomethacin 0.36 micrograms ml-1 (1 microM; P < 0.01). 5. We conclude that the folate concentration can affect the sensitivity of NC cells to methotrexate, although the degree of potentiation of cytotoxicity by indomethacin remains similar.

Animals↗

Interaction between methotrexate and indomethacin on a human normal haemopoietic cell line.

1. The interaction between methotrexate and indomethacin has been examined, at a physiological folate concentration (20 nM), on a human normal lymphoblast-like cell line (RPMI 1788) in vitro. 2. Indomethacin (1 microgram ml-1) increased the reduction of lymphoblast growth caused by methotrexate (10-80 ng ml-1). 3. Indomethacin (0.1 and 1 microgram ml-1) potentiated the cytotoxicity of methotrexate (20 and 40 ng ml-1) after 4 days in culture. 4. Indomethacin (0.4 micrograms ml-1) reduced the accumulation of tritium in lymphoblasts incubated with [3H]-methotrexate after 30 min; therefore initial drug accumulation was not responsible for the potentiation seen after 4 days. 5. If indomethacin increases the killing of human cancer cells by methotrexate in vivo, with a smaller potentiation on lymphoblasts, this combination may be beneficial in treating human malignancy.

Adult↗

Long-term storage of human fetal haematopoietic progenitor cells and their subsequent reconstitution. Implications for in utero transplantation.

Haematopoietic progenitor cells were isolated from human fetal liver, obtained between 6 and 15 weeks gestation. After preparation of a single cell suspension, the cells were stored using a stepwise freezing protocol; taking the cells from room temperature through -70 degrees C to liquid nitrogen. Viability (trypan blue exclusion), morphology (Leishman stain), identification of cell type (flow cytometry) and growth characteristics in semi-solid culture medium were assessed using the fresh cell suspension. We were able to confirm that the predominant cells in human fetal liver up to about 15 weeks gestation are those of the erythroid lineage. It was established that viability in excess of 75% was required to ensure adequate growth in culture after frozen storage and it was deemed important to ensure morphological integrity of the cell preparations. The colonies formed in culture were observed to be producing haemoglobin between 7 and 9 days after initial seeding. We have determined that cells can be stored in liquid nitrogen for up to 2 years without loss of (1) viability, (2) morphological features and (3) ability to form colonies and produce haemoglobin in culture. These findings offer encouragement for the implementation of a cell bank to support an in utero transplantation programme.

Cell Separation↗

Advances in vertebral artery surgery at the skull base.

Between July 1975 and May 1985, 219 procedures were performed on the vertebral system; two were intracranial, 118 were at the skull base and 99 were at the neck base. Of the 108 patients operated on at the skull base, procedures were multiple in five and bilateral in two. Bypass to the vertebral artery between the transverse process of C1 and C2 was performed 91 times. The blood supply for the bypass was the common carotid (70), the external carotid (9), the internal carotid (9), the subclavian (3), and the occipital artery (3). Decompression was performed in three patients, segmental resection in seven, and ligation in two. The primary objective was to increase the flow capacity of the vertebral artery. This flow to the Circle of Willis supplies the forebrain and the hindbrain if the internal carotid artery is obstructed and the posterior communicating artery is patent, or it may supply only the hindbrain when no communication exists. The pathologic processes include atherosclerosis, thrombosis, dissection, compression, and vasospasm. The male:female ratio is 2:3. Long-term mortality is 19% for the male and 4.6% for the female. Hindbrain symptoms in the male predates cardiac symptoms by 2 to 4 years. Operative mortality and stroke rate is less than 3% combined. Long-term graft patency is 87%. Vertebral artery surgery at the skull base produces results superior to those following proximal segment reconstruction when measured by dynamic computerized tomographic scanning, neurofunctional testing, and symptom relief. Success following reconstruction depends on careful patient selection and surgical expertise. The techniques of reconstruction are well established and results have been durable for over a decade.

Journal Article↗