Childhood immunisation in Rotorua.
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Child↗
Biomedical subjects
B Tsang
Publications and source records attributed to B Tsang.
Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells.
Excision repair cross complementation group 1 (ERCC-1) is a DNA repair gene that is essential for life, and it appears to be a marker gene for nucleotide excision repair activity. Overexpression of ERCC-1 during cisplatin-based chemotherapy is associated with clinical and cellular drug resistance. We therefore began to assess the influence of various pharmacological agents on the induction of ERCC-1 mRNA in A2780/CP70 human ovarian carcinoma cells. Cisplatin exposure in culture resulted in a 4- to 6-fold induction for the steady-state level of ERCC-1 mRNA in A2780/CP70 cells. ERCC-1 mRNA induction was concentration and time dependent. Cyclosporin A and herbimycin A, which suppress c-fos and c-jun gene expressions, respectively, blocked the cisplatin-induced increase in ERCC-1 mRNA. This effect of cyclosporin A or herbimycin A on the down-regulation of ERCC-1 correlates with enhanced cytotoxicity of cisplatin in this system. The products of c-fos and c-jun are components of the transcription factor AP-1 (activator protein 1). 12-O-Tetradecanoylphorbol 13-acetate (TPA), a known AP-1 agonist, induced ERCC-1 mRNA to the same extent as cisplatin, but did not synergize with cisplatin in this regard. The TPA effect was biphasic, with an initial increase during the first 1-6 hr, followed by decreasing mRNA levels at 24-72 hr. These data suggest that the effects of these pharmacological agents on ERCC-1 gene expression may be mediated through the modulation of AP-1 activities.
Benzoquinones↗
Phorbol ester exposure activates an AP-1-mediated increase in ERCC-1 messenger RNA expression in human ovarian tumor cells.
ERCC-1 is an essential gene in the nucleotide excision repair pathway, and may be essential for life. However, the mechanism of transcriptional activation and regulation of ERCC-1 gene expression is unclear. We therefore investigated the effect of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the ERCC-1 gene in A2780/CP70 human ovarian carcinoma cells. TPA induced a four- to sixfold increase in steady-state ERCC-1 messenger RNA (mRNA) levels that was time- and concentration-dependent. Nuclear run-on experiments demonstrated that the rate of transcription of ERCC-1 was approximately 2.8-fold higher in TPA-treated cells than in the controls. TPA stimulation of A2780/CP70 cells also resulted in a rapid but transient induction of c-jun and c-fos as determined by Northern and Western blot analyses, which peaked about 2 h before the peak in ERCC-1 expression. Electrophoretic mobility shift assays of nuclear extracts from TPA-treated cells revealed an increase in DNA-binding activity specific for the AP-1-like binding site in the 5'-flanking region of ERCC-1. c-Jun and c-Fos proteins were confirmed to be the components of the activated AP-1 complex by supershift analysis. The increase in AP-1 activity occurs immediately before the increase in ERCC-1 transcription. The increase in AP-1 DNA-binding activity and the increase in ERCC-1 mRNA expression were prevented by pretreatment with cycloheximide. These data suggest that AP-1 may contribute to the upregulation of ERCC-1 in response to TPA in human ovarian cancer cells.
Amanitins↗
Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells.
ERCC-1 is a critical gene within the nucleotide excision repair pathway, and cells without a functional ERCC-1 do not perform cisplatin-DNA adduct repair. We therefore investigated the cisplatin effect on ERCC-1 mRNA expression in vitro. In response to a 1-h cisplatin exposure, A2780/CP70 human ovarian cancer cells showed a 6-fold increase in steady-state level of ERCC-1 mRNA. This rise was attributable to increased transcription as measured by nuclear run-on assays and a 60% increase in ERCC-1 mRNA half-life. The increase in ERCC-1 mRNA was preceded by a 4-5-fold rise in mRNA expressions of c-fos and c-jun, a 14-fold increase in c-Jun protein phosphorylation, and an increase in in vitro nuclear extract binding activity to the AP-1-like site of ERCC-1. These data suggest that the induction of ERCC-1 expression in A2780/CP70 cells exposed to cisplatin results from two major factors: (a) an increase in the expression of transactivating factors that bind the AP-1-like site in the 5'-flanking region of ERCC-1 and (b) an increase in the level of c-Jun phosphorylation that enhances its transactivation property.
Amanitins↗
Vertical transmission of human immunodeficiency virus type 1: frequency and correlation of transmission (review).
Child bearing age women constitute the fastest growing subset of the human immunodeficiency virus (HIV) infected population. Consistent with this fact is the increasing number of HIV infected children. Vertical transmission from mother to child is the most common route of infection. Because of the nature of the virus, it is difficult to determine the timing of infection. There are three time periods during which infection can occur: prenatally, perinatally, or postnatally. Evidence for each is presented within this review.
Breast Feeding↗
Infection with the human immunodeficiency virus type 2: epidemiology and transmission (Review).
Human immunodeficiency virus type 2 (HIV-2) is known to be one of the agents that causes acquired immunodeficiency syndrome (AIDS). It has been present in West Africa since the 1960s and is currently epidemic there. Compared with human immunodeficiency virus type 1 (HIV-1), HIV-2 is genomically different. Furthermore, it is less prevalent worldwide than HIV-1. In West Africa, seropositive rates of HIV-2 are higher in urban versus rural communities, however, there are no gender differences. Sexual contact and vertical transmission are known modes of infectivity, though HIV-2 is less contagious than HIV-1.
Africa↗
Cisplatin and phorbol ester independently induce ERCC-1 protein in human ovarian carcinoma cells.
Nucleotide excision repair (NER) is the DNA repair pathway by which cisplatin-induced damage is removed from DNA in human cells. ERCC-1 is one of the essential proteins in NER, and is essential for life. Enhanced ERCC-1 expression has been associated with clinical and cellular resistance to cisplatin. We therefore carried out this study to investigate the effect of cisplatin on ERCC-1 protein expression in A2780/CP70 human ovarian cancer cells. Western blot analysis showed that ERCC-1 protein levels were increased to more than 3 times control after a 1 h cisplatin exposure to A2780/CP70 cells in culture. This increase was time- and concentration-dependent. The effect of cisplatin was maximal at 40 mM and peaked 24-48 h after exposure to the drug. These results extend our previous observations that ERCC-1 mRNA expression is induced by cisplatin in this system. TPA, a known AP-1 activator and tumor-promoting phorbol ester, also induced ERCC-1 protein to the same extent as cisplatin, but did not synergize with cisplatin in this regard. These findings suggest that ERCC-1 gene up-regulation in these cells can result through a DNA damage-response pathway, or through the induction of AP-1 activity, independent of the occurrence of DNA damage.
Antineoplastic Agents↗
Cerebral infarction in Noonan syndrome.
We report on an infant with severe Noonan syndrome, chylothoraces, and hepatosplenomegaly who suffered two episodes of cerebral infarction before age 6 months. No underlying cause for these events was found. The presentation is discussed in relationship to other reports of stroke in Noonan syndrome which have previously been associated with underlying vascular malformations.
Adult↗
Relationship between confabulation and measures of memory and executive function.
Confabulation has traditionally been attributed to a combination of memory impairment and executive dysfunction, but recent models propose that confabulation can result from executive dysfunction alone. One hundred and ten patients with diverse neurologic and psychiatric diagnoses were subdivided into high-, low-, and non-confabulator groups based upon the ratio of confabulations to total responses produced during story recall. Consistent with the combined deficit model, high-confabulators performed significantly worse than the low- and non-confabulators on measures of memory and measures of executive function that assess sustained attention, mental tracking, and set-shifting ability. However, there were no differences between groups on measures of problem-solving, concept formation, and verbal fluency, suggesting a dissociation in executive functions that contribute to confabulation.
Attention↗
Central angiotensin-induced water intake and salt appetite in the pig.
Single intracranial injections of the peptide analogues of angiotensin and the enzyme renin induced drinking of water and 1.8% NaCl solution in prepubertal female pigs maintained ad libitum on a sodium-free diet with unrestricted access to both fluids. Over the dose range 10(-12)-10(-9) mol angiotensin (AI), angiotensin II (AII), angiotensin III (AIII), and renin substrate (RS), the volumes of water and salt solution ingested were dose-dependent. As in other vertebrates, AII was the most potent and rapidly acting dipsogen. However, unlike in the rat, dog and pigeon, AIII was highly effective in stimulating both water intake and salt appetite, whereas AI and RS were relatively weak. Pretreatment of intracranial sites with 10(-9) mol of the AII competitive antagonist, Sar1-Ala8-angiotensin, had no effect on the volume of water or 1.8% NaCl ingested after 10(-10) mol AIII, suggesting that in the pig AIII can exert its dipsogenic effects without acting on central AII receptors. Single microinjections of 1 and 10 mU of renin also elicited dose-dependent drinking of water and 1.8% NaCl, but compared with the peptide analogues of angiotensin the responses had a longer latency and duration and were more variable between individual animals.
Angiotensins↗
The roles of calcium and cyclic AMP in cell proliferation.
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Animals↗
Effect of narcotic dependence and withdrawal on striatal dopamine-sensitive adenylate cyclase and synaptosomal cyclic AMP metabolism.
In rats rendered tolerant to the dependent on morphine, striatal cyclic AMP metabolism was significantly enhanced as reflected by elevated cyclic AMP levels and adenylate cyclase activity. Following withdrawal from morphine treatment, whereas the activity of straital adenylate cyclase was significantly reduced when compared to morphine-dependent rats, the drop in cyclic AMP was not significant. Although addition of dopamine (40 muM) stimulated equally well the striatal adenylate cyclase from control or morphine-dependent animals, the activity of dopamine-stimulated enzyme was blocked in animals undergoing withdrawal. The crude synaptosomal fraction of the whole brain obtained from morphine-dependent rats exhibited an even more pronounced increase in cyclic AMP which was accompanied by elevated adenylate cyclase and protein kinase activity. Naloxone administration suppressed this rise in cyclic AMP and reversed the morphine-stimulated increases in adenylate cyclase and protein kinase. Following the withdrawal of morphine treatment, alterations in cyclic AMP metabolism were similar to those noted for the morphine-naloxone group.
Adenylyl Cyclases↗