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Biomedical subjects

H M Wallace

Publications and source records attributed to H M Wallace.

At least 19 recordsLinked to original sources
PubMed1998

Induction of spermidine/spermine N1-acetyltransferase in human cancer cells in response to increased production of reactive oxygen species.

Reactive oxygen species (ROS) are involved in a number of disease states where they are believed to be responsible for cellular damage. In this study we examined the effect of ROS generation on polyamine catabolism. Treatment of human breast cancer cells with either H2O2 or hyperoxia increased the activity of spermidine/spermine N1-acetyltransferase (SSAT). These increases occurred before any significant signs of cellular injury. Agents known to decrease the production of reactive oxygen species such as dimethylthiourea and o-phenanthroline prevented the increase in SSAT activity indicating ROS involvement in the induction process. These results suggest that induction of SSAT may be a protective response to oxidative stress in mammalian cells facilitating removal of polyamines from the cell to prevent their toxic accumulation.

Acetyltransferases↗
PubMed1998

Hyperoxia influences mRNA expression of cytokines in cultured human umbilical vein endothelial cells.

High concentrations of oxygen, indispensable for the treatment of severe hypoxemia from neonatal as well as adult respiratory distress syndrome, increase the risk of oxygen toxicity. Biochemical mechanisms are lipid peroxidation, protein sulfhydryl oxidation, enzyme inactivation, and DNA damage. Recent reports suggest that cytokines might be involved in free radical injury as well as in adaptive response to hyperoxic injury. However, actual signal transduction pathways involving cytokines have not yet been clarified. In this study we exposed cultured human umbilical vein endothelial cells (HUVECs) to either ambient air or 100% oxygen, and compared for the rate of DNA synthesis ([3H]thymidine uptake) at different time points up to 72 h. After exposing the cells to each treatment condition, we extracted RNA, constructed complementary DNA using reverse transcriptase, amplified the specific DNA segments of cytokines by polymerase chain reaction (PCR), and used the PCR products for gel electrophoresis to examine the bands which signified mRNA levels of corresponding cytokines. There was a significant decrease in the rate of DNA synthesis as early as 24 h. The mRNA expression of IL-1 beta and TNFa seemed less influenced by hyperoxia, while IL-8 and TGF beta showed marked increase in mRNA levels at 6 h of 100% oxygen exposure.

Cells, Cultured↗
PubMed1996

Hydrogen peroxide, but not superoxide, stimulates bone resorption in mouse calvariae.

Reactive oxygen species such as superoxide and hydrogen peroxide have been implicated as regulatory factors in the control of osteoclastic bone resorption. While superoxide radicals have been suggested to be the main bone resorbing species in organ culture and in vivo, hydrogen peroxide (H2O2) has recently been shown to activate isolated osteoclasts in vitro. In this study, we investigated the effects of hydrogen peroxide and superoxide on bone resorption in mouse calvarial organ cultures. Hydrogen peroxide stimulated bone resorption in a concentration-dependent manner in calvarial organ cultures with a maximal effect at 1 mumol/L (45Ca release; treated/control = 1.6 +/- 0.07; p < 0.001 from control). Bone resorption induced by H2O2 was significantly inhibited by catalase to 1.2 +/- 0.05; p < 0.02. In contrast, the combination of xanthine and xanthine oxidase, which generates superoxide anions, failed to stimulate bone resorption, except in the presence of superoxide dismutase (SOD), which resulted in a modest increase in bone resorption to a treated/control ratio of 1.2 +/- 0.05; p < 0.02. Analysis of calvarial bones which were exposed to H2O2 showed a significant increase in osteoclast numbers suggesting that H2O2 may be capable of stimulating osteoclast formation in addition to enhancing activity of mature osteoclasts. Our data are consistent with previous work, which has shown that H2O2 is a bone resorbing factor with effects on both osteoclast formation and in activity of mature osteoclasts. The experiments with SOD further suggest that the enhancement of bone resorption previously noted with superoxide generating systems may be due in part to generation of H2O2.

Analysis of Variance↗
PubMed1996

Maternity care for Hispanic women who cross to the United States side of the Mexico border.

Medical chart abstracts and interviews were conducted among 587 Hispanic women within the first 72 hours following childbirth in any of five hospitals in San Diego County in 1991-1992. Demographic and maternal/infant obstetrical outcome data from 83 women who admitted that they had crossed the US/ Mexico Border to receive reproductive health services were compared with data from women who did not cross the Border. Border crossers were younger, less conversant in English, and more financially vulnerable. Several barriers existed for women in both groups that prevented entering and remaining within prenatal care programmes. Outcome data were favorable despite these adverse risk factors.

Adolescent↗
PubMed1995

Accelerated gastric epithelial proliferation.

Gastric body mucosal proliferation was quantified and localised under conditions of increased gastrin drive using a variety of techniques. Rats were given omeprazole 400 mumol/kg/day by gavage and after 30 days mean serum gastrin rose 11-fold (p < 0.001). Total mucosal polyamines rose 220% from 15.9 to 50.9 nmol/mg protein (p < 0.001). This was associated with a 238% increase in crypt cell production rate from 0.541 to 1.83 crypt cells/h by vincristine metaphase arrest (p < 0.02). Using computer aided counting of proliferating cell nuclear antigen (PCNA) immunostained nuclei to assess epithelial proliferation in hypergastrinaemia rat stomach: mucus neck cell PCNA labelling was increased by 41% (p < 0.001) and gland cell PCNA labelling was increased by 222% (p < 0.001). PCNA/AgNOR (argyrophilic nuclear organiser regions) co-stained sections were used to assess proliferative activity in cycling and non-cycling cell populations. Data from these experiments suggest that, in addition to increasing the number of mucosal cells in cycle, cell life and cell cycle duration may be reduced in hypergastrinaemia.

Animals↗
PubMed1994

Regulation of spermidine/spermine N1-acetyltransferase in human tumour cells.

It seems therefore that the induction of N1-SAT has a number of facets: some stabilization of the enzyme protein; stabilization of mRNA; requirement for new protein and RNA synthesis; and a Ca(2+)-sensitive induction site. It may be there is a polyamine-analogue-binding/induction site as well as an induction site which binds agents such as doxorubicin and butyrate (Figure 3). At present it is not clear whether the polyamine analogues interact directly with the active site of N1-SAT and it will be interesting to determine the effect of site-specific mutagenesis on the inducibility of N1-SAT by both polyamine analogues and antitumour agents like doxorubicin. Alternatively, it may be that agents such as doxorubicin and butyrate alter the conformation of DNA and thus release polyamines from intracellular binding sites. This increase in intracellular polyamine content may then induce N1-SAT activity which in turn will activate polyamine efflux with the net result being a decrease in intracellular polyamine content and the rate of cell growth.

Acetyltransferases↗