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Biomedical subjects

N L Anderson

Publications and source records attributed to N L Anderson.

101 records · Page 6Linked to original sources
PubMedDate not supplied

A protein expression database for the molecular pharmacology of cancer.

In the last six years, the Developmental Therapeutics Program (DTP) of the US National Cancer Institute (NCI) has screened over 60,000 chemical compounds and a larger number of natural product extracts for their ability to inhibit growth of 60 different cancer cell lines representing different organs of origin. Whereas inhibition of the growth of one cancer cell type gives no information on drug specificity, the relative growth inhibitory activities against 60 different cells constitute patterns that encode detailed information on mechanisms of action and resistance (as reviewed in Boyd and Paull, Drug Devel. Res. 1995, 34, 19-109 and Weinstein et al., Science 1997, 275, 343-349). In order to correlate the patterns of activity with properties of the cells, we and other laboratories are characterizing the cells with respect to a large number of factors at the DNA, mRNA, and protein levels. As part of that effort, we have developed a two-dimensional gel electrophoresis (2-DE) protein expression database covering all 60 cell types (Buolamwini et al., submitted). Here we present analyses of the correlations among protein spots (i) in terms of their patterns of expression and (ii) in terms of their apparent relationships to the pharmacology of a set of 3989 screened compounds. The correlations tend to be stronger for the latter than for the former, suggesting that the spots have more robust signatures in terms of the pharmacology than in terms of expression levels. Links to pertinent databases and tools of analysis will be updated progressively at http:@www.nci.nih.gov/intra/lmp/jnwbio.htm and http:@epnwsl.ncifcrf.gov:2345/dis3d/dtp.++ +html.

Antineoplastic Agents↗
PubMedDate not supplied

Large-scale oligonucleotide synthesizers. I. Basic principles and system design.

The central problem in scaling up oligonucleotide synthesis is to expose each element of a large bed to the same conditions obtaining in very small ones, for the same intervals of time. Our analysis suggests that scale-up is chiefly limited by fluid path length through the bed. By using annular beds in zonal centrifuge rotors of unique design, with fluid flow controlled by combining centrifugal force with differences in physical density between reagents, reagent fronts may be kept exactly perpendicular to the direction of flow in each bed element. Under these conditions, bed volume may be increased by increasing rotor length and diameter. The rotor is lined with polypropylene or Teflon, and has a thick tempered glass end window. Transparent rotary valves of a unique design allow any of 47 reagents to be selected and the direction of flow through the rotor to be controlled. A photodiode spectrophotometer provides complete absorption spectra on fluid in the rotor inlet and outlet lines every 4 s, and a large balance weighs effluent from the synthesizer continuously. The entire operation is controlled by a work station, and steps may be programmed by time, absorbance, or reagent mass. Reagents are identified by spectra, and trityls are integrated on line. A detailed time-stamped log file provides a complete record of each synthesis.

Equipment Design↗
PubMedDate not supplied

A comparative study of mouse liver proteins arylated by reactive metabolites of acetaminophen and its nonhepatotoxic regioisomer, 3'-hydroxyacetanilide.

Acetaminophen (4'-hydroxyacetanilide), a widely used analgesic/antipyretic drug, is hepatotoxic in large doses, whereas the m-hydroxy isomer of acetaminophen, 3'-hydroxyacetanilide, is not hepatotoxic. Both are oxidized by mouse liver cytochromes P-450 to reactive metabolites that bind covalently to hepatic proteins. Because previous studies have shown that peak levels of liver protein adducts formed after the administration of each of these compounds to mice are nearly equivalent, and because liver protein adduct formation correlates with hepatotoxicity caused by acetaminophen in mice, we investigated the abundance and patterns of protein adducts formed by acetaminophen and its regioisomer for significant differences. Hepatotoxic doses of acetaminophen to mice significantly altered the abundances of several liver proteins 2 h after dosing as revealed by densitometric analysis of two-dimensional electrophoretic patterns of these proteins. The same analysis after the administration to mice of 3'-hydroxyacetanilide indicated that this nonhepatotoxic regioisomer of acetaminophen caused several similar changes in protein patterns, but also revealed some significant differences. Binding of radiolabeled acetaminophen and 3'-hydroxyacetanilide to hepatic proteins corroborated and extended these results. Two hours after the administration of 14C-labeled analogs of these two compounds to mice, at a time when their extent of total covalent binding to hepatic proteins is approximately equivalent, there are many similarities but also some differences in selectivity of proteins that are adducted, as revealed by both one-dimensional and two-dimensional gel electrophoresis followed by phosphorimage analysis of radiolabel bound to protein bands. Moreover, protein adducts formed from 3'-hydroxyacetanilide were found to be less stable than those formed from acetaminophen under the conditions of electrophoretic analysis. Furthermore, a comparison of radiodetection and immunodetection of protein adducts formed from acetaminophen with an antibody specific for acetaminophen protein adducts indicates that the antibody detects most of the same proteins that are radiolabeled and that the relative quantitative contribution of various adducts to the overall covalent binding of acetaminophen to proteins is approximately the same by both methods. Thus, 3'-hydroxyacetanilide should prove to be a useful tool to aid in the discrimination of hepatic acetaminophen protein adducts that may be critical or noncritical to survival of hepatocytes.

Acetaminophen↗
PubMedDate not supplied

Depressed adolescent mothers' perceptions of their own maternal role.

Although there is a growing body of research in the area of adolescent pregnancy and parenting, little is known about the more personal experiences of these teens. Ethnographic research methods were used in the present study with the goal of narrowing existing gaps in knowledge about the affective component of adolescent mothers' role attainment. The sample consisted of 15 voluntary informants who reported depressive symptoms during pregnancy or postpartum. The findings suggest that for some adolescent mothers the experience of motherhood may help them improve their previously self-destructive lives. Many adolescent mothers have engaged in impulsive high-risk activities prior to their pregnancies. Through the establishment of a maternal identity and simultaneous development of a strong sense of maternal protectiveness these young women are making realistic, future-oriented decisions that are motivating them to leave gang life, finish high school, go to college, and get vocational training. However, a subset of adolescent mothers who experience chronic depressive mood along with social isolation in the postpartum period may be at increased risk for development of problematic maternal behaviors.

Adolescent↗
PubMedDate not supplied

A public health nursing early intervention program for adolescent mothers: outcomes from pregnancy through 6 weeks postpartum.

BACKGROUND: Adolescent pregnancy and parenting remain a major public concern because of their impact on maternal-child health and on the social and economic well-being of the nation. Federal welfare reform legislation has created an urgent need for community-based nursing intervention programs to improve health and social outcomes for disadvantaged adolescent mothers and to promote their self-sufficiency. OBJECTIVE: To evaluate the effects of an early intervention program (EIP) that uses a public health nursing model on health and social outcomes of adolescent mothers and their children and on the quality of mother-child interaction. METHODS: Pregnant adolescents referred to a county health department were randomly assigned to an experimental (EIP) or control (traditional public health nursing [TPHN]) group. The sample included 121 adolescents from predominantly minority and impoverished backgrounds who were followed from pregnancy through 6 weeks postpartum. Intense and comprehensive home visitation by public health nurses and preparation-for-motherhood classes were provided to adolescents in the EIP. Health outcomes were determined on the basis of medical record data. Other measures included maternal self-report on selected behaviors, nurse interviews, and the Nursing Child Assessment Teaching Scale (NCATS). RESULTS: Early findings indicate reduced premature birth and low-birth-weight (LBW) rates for young mothers receiving both forms of public health nursing care. No significant differences between groups were found for infant birth weight or type of delivery. Infants in the EIP had significantly fewer total days of birth-related hospitalization and rehospitalization than those in the TPHN group during the first 6 weeks of life (chi2(1) = 6.41; p = 0.01). Adolescents in the EIP demonstrated significantly more positive educational outcomes (e.g., lower school dropout rates) than those in the TPHN group (chi2(1) = 6.76; p < 0.009). CONCLUSIONS: The early findings of this study demonstrate that pregnant adolescents benefit from both traditional and more intense public health nursing care in terms of prenatal and perinatal outcomes. The EIP was associated with decreased infant morbidity during the first 6 weeks of life and decreased maternal school dropout. Long-term outcomes for the EIP are being evaluated.

Adolescent↗
PubMedDate not supplied

An early intervention program for adolescent mothers: a nursing demonstration project.

OBJECTIVE: To improve health outcomes in a vulnerable population of adolescent mothers and their infants. DESIGN: Effects of an intensive early intervention program (EIP) are compared with those of traditional public health nursing (TPHN) care. SETTING: A large California county with urban and rural communities, an ethnically diverse population, and a high teen birth rate. PARTICIPANTS: One hundred twenty-one young mothers and their children from impoverished and predominantly minority backgrounds. INTERVENTIONS: During pregnancy and through 1 year postpartum, participants (n=63) in the EIP were provided with 4 prenatal classes and approximately 17 home visits by specially trained public health nurses. Interventions addressed health issues, sexuality and family planning, life skills, the maternal role, and social support systems. Participants in TPHN (n=58) received three home visits (for intake, prenatal care, and postpartum/well-baby care information). MAIN OUTCOME MEASURES: Antepartum, intrapartum, and newborn medical records; maternal responses to written questionnaires; and nurse interviews. RESULTS: Early program outcomes indicate reduced premature birth rates for both groups compared with national data on adolescent mothers, and fewer days of infant hospitalization during the first 6 weeks postpartum for the EIP participants. CONCLUSION: Public health nurse care (both traditional and intensive) significantly improved perinatal outcomes; the intensive intervention significantly reduced the number of infant hospitalization days.

Adolescent↗
PubMedDate not supplied

The manipulator reputation in juvenile detention: collective labeling in a total institution.

Adolescent manipulative behaviors are the focus of a combined field study and literature review. A taxonomy of manipulation generated within the setting of a large metropolitan juvenile detention facility is compared with literature sources and examined from the theoretical construct of a total institutional behavioral environment. Issues are raised which require consideration in planning nursing care for this and similar client populations.

Adolescent↗
PubMedDate not supplied

"Sometimes you don't feel ready to be an adult or a mom:" the experience of adolescent pregnancy.

PROBLEM: To obtain a description of pregnant adolescents' responses to the preparation for motherhood class curriculum. METHODS: The design of this study was based in the anthropological tradition of qualitative research, ethnography; N = 36. FINDINGS: Within one category identified in this study, maternal role, three primary themes emerged: responsibility, respect, and reparation. CONCLUSIONS: The findings of this study indicate that for some adolescents, pregnancy implies a desire and an opportunity to heal childhood wounds if relevant psychotherapeutic interventions can be provided. Nurses can identify pregnant teens who are already suffering with depression and encourage them to seek counseling prior to the birth of their baby before they are experiencing the added stressors inherent in new motherhood.

Adolescent↗
PubMedDate not supplied

Simultaneous measurement of hundreds of liver proteins: application in assessment of liver function.

Proteins implement most biological functions at the molecular level. As one might expect based on this fact, it appears that the altered functional states associated with toxic effects involve changes in the abundance or structure of proteins. Although numerous specific assays exist to measure changes in the abundance of individual proteins, practical limitations have prevented widespread use of multiple protein assays for the global characterization of toxicity. Recent developments in protein analytical technology are rapidly changing this picture. Two-dimensional gel electrophoresis, a technique capable of resolving and quantitating hundreds of proteins simultaneously, is becoming an automated, high-throughput tool. In parallel, techniques have been developed that allow the resulting deluge of protein measurements to be organized into a prototype Molecular Effects Database describing xenobiotic effects in rodent liver. This database can detect, classify, and characterize a broad range of liver toxicity mechanisms. It currently contains approximately 10 million protein measurements, including data on the liver effects of 43 compounds, with a further 50 compounds to be added in 1995. Observed effects range from very broad (sex steroids alter levels of 45% of all liver proteins) to very specific (e.g., hepatic hydroxymethyl glutaryl coenzyme A reductase inhibitors). Companion 2-dimensional databases describing rodent brain and kidney have been initiated, as have linkages to the genomic sequence databases. Assimilation of this approach into research and regulatory toxicology poses an interesting challenge--one that is likely to lead to a radically more sophisticated understanding of toxicity and its biological basis.

Animals↗