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Biomedical subjects

J N Wardell

Publications and source records attributed to J N Wardell.

7 recordsLinked to original sources

Genetic engineering of hybridoma glutamine metabolism.

The murine hybridoma PQXB1/2 cannot be adapted to grow in culture media containing < 0.5 mM glutamine. Transformants selected following electroporation of PQXB1/2 cells with vectors containing a Chinese hamster glutamine synthetase (GS) cDNA under the control of the SV40 early promoter also failed to grow in the absence of glutamine in the culture medium. PQXB1/2 cells have, however, been transformed to glutamine independence following electroporation with a vector containing this glutamine synthetase cDNA under the control of the human cytomegalovirus immediate early promoter. In these cells, sufficient active glutamine synthetase was expressed from one vector per cell to enable growth in glutamine-free media. The specific activity of glutamine synthetase in two transformed cell lines producing parental levels of antibody was increased by 128 and 152%, respectively (0.57 and 0.63 mumol min-1 per 10(6) cells in transformants compared with parental levels of 0.25 mumol min-1 per 10(6) cells). This reprogramming of glutamine synthetase expression and glutamine metabolism is important for developing strategies to deal with ammonia toxicity and the production of cell lines with improved metabolic processes.

Animals↗

Effect of chronic maternal drug addiction on placental drug metabolism.

Microsomes were prepared from the term placentas of 5 drug-dependent and 4 normal (control) mothers and from the livers of 3 normal fetuses (gestational age = 22-24 weeks) to determine if chronic maternal drug addiction can induce metabolic pathways in the placenta which are utilized in the biotransformation of drugs of abuse. Using as model substrates aminopyrine for demethylation, aniline for hydroxylation, and bilirubin for conjugation, we observed little to none of substrate biotransformation in both drug-dependent and control placentas. Similarly, such enzymatic activity in the fetal liver was also low. We conclude that chronic maternal addiction does not induce metabolic pathways in the placenta for the biotransformation of drugs of abuse.

Biotransformation↗

Surface-associated growth.

In natural ecosystems, microbial activity is often associated with the presence of a surface, particularly in low-nutrient environments. The chemostat allows the study of such low-nutrient environments together with the precise control of other growth parameters. By using this system, enrichment cultures with inocula from two different river sources have been made. A more diverse community attached itself to surfaces placed in the chemostat when the cultures were carbon-limited than when the limiting nutrient was nitrogen. Further studies on a pseudomonad isolated from the carbon-limited enrichment cultures have shown that surface-associated organisms grow at approximately twice the rate of the same organism in the free surrounding medium. A hypothesis to explain this phenomenon based on the chemiosmotic theory is discussed.

Bacteria↗

Relationship of neonatal withdrawal to maternal methadone dose.

Neonatal withdrawal is described for a sample of 70 infants born to addicted women treated with methadone and comprehensive prenatal care. Although symptoms were manifested by over 90% of the infants, those born to women receiving near-term average doses of less than or equal to 20 mg/day had significantly less symptomatology, weight loss, and need for pharmacologic treatment than those of mothers still on higher doses. Reduction of methadone dose levels during the last 6 weeks of pregnancy to less than or equal to 20 mg/day appears to reduce the severity of neonatal withdrawal.

Female↗

Neonatal outcome following methadone exposure in utero.

To examine the relationship between maternal methadone exposure and neonatal head circumference and abstinence syndrome, we examined the records of 172 opiate-addicted gravidas enrolled in a methadone maintenance program in an urban hospital over a 2-year period. Higher doses of methadone in the third trimester were associated with increased head circumference reflecting both increased gestational duration and improved overall growth. Neonatal withdrawal was positively correlated with gestational age at delivery and race, with nonblack infants exhibiting higher neonatal abstinence scores than blacks following adjustment for maternal dose and gestational age at delivery. Selection of optimal methadone dosage is a complex problem in which the favorable neurobehavioral outcome associated with increased growth and gestational age must be weighed against the risks associated with more severe neonatal withdrawal. Our findings of improved overall fetal growth and gestational duration associated with higher methadone doses suggest that more liberal methadone dosing in pregnancy may improve long-term neonatal outcome.

Black or African American↗