ORCID Profile
0000-0002-7467-7933
Current Organisations
The University of Auckland
,
Brainwave Trust Aotearoa
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Publisher: Informa UK Limited
Date: 19-11-2021
Publisher: Wiley
Date: 29-04-2016
DOI: 10.1111/ALL.12909
Abstract: Vitamin D has immune-modulating effects. We determined whether vitamin D supplementation during pregnancy and infancy prevents aeroallergen sensitization and primary care respiratory illness presentations. A randomized, double-blind, placebo-controlled parallel-group trial. We assigned pregnant women, from 27-week gestation to birth, and then their infants, from birth to 6 months, to placebo or one of two dosages of daily oral vitamin D. Woman/infant pairs were randomized to: placebo lacebo, 1000 IU/400 IU or 2000 IU/800 IU. When the children were 18 months old, we measured serum-specific IgE antibodies and identified acute primary care visits described by the doctor to be due to a cold, otitis media, an upper respiratory infection, croup, asthma, bronchitis, bronchiolitis, a wheezy lower respiratory infection or fever and cough. Specific IgE was measured on 185 of 260 (71%) enrolled children. The proportion of children sensitized differed by study group for four mite antigens: Dermatophagoides farinae (Der-f1, Der-f2) and Dermatophagoides pteronyssinus (Der-p1, Der-p2). With results presented for placebo, lower dose, and higher dose vitamin D, respectively (all P < 0.05): Der-f1 (18%, 10%, 2%), Der-f2 (14%, 3%, 2%), Der-p1 (19%, 14%, 3%) and Der-p2 (12%, 2%, 3%). There were study group differences in the proportion of children with primary care visits described by the doctor as being for asthma (11%, 0%, 4%, P = 0.002), but not for the other respiratory diagnoses. Vitamin D supplementation during pregnancy and infancy reduces the proportion of children sensitized to mites at age 18 months. Preliminary data indicate a possible effect on primary care visits where asthma is diagnosed.
Publisher: Elsevier BV
Date: 05-1998
DOI: 10.1016/S0167-4781(98)00035-9
Abstract: The murine Unp gene encodes a ubiquitin-specific protease, a member of a family of enzymes that includes the product of the human tre-2 oncogene. The Unp gene has previously been mapped to chromosome 9. We have cloned in bacteriophage a 50 kilobase region of chromosome 9 containing the Unp gene, and have determined the nucleotide sequence of the gene. The gene has 22 exons, distributed over 47.4 kb. A processed ribosomal S2 pseudogene was identified in the third intron of the Unp gene. Expression of Unp is driven by a GC-rich, 'housekeeping' type promoter.
Publisher: Springer Science and Business Media LLC
Date: 05-02-2015
Publisher: Wiley
Date: 02-2005
DOI: 10.1111/J.1365-2990.2004.00604.X
Abstract: The ubiquitin-proteasome system (UPS) is a central component in the cellular defence against potentially toxic protein aggregates. UPS dysfunction is linked to the pathogenesis of both sporadic and inherited neurodegenerative diseases, including dominantly inherited familial amyotrophic lateral sclerosis (fALS). To investigate the role of the UPS in fALS pathogenesis, transgenic mice expressing mutant G9 3A Cu,Zn superoxide dismutase (SOD1) were crossed with transgenic mice expressing epitope tagged, wild-type or dominant-negative mutant ubiquitin (Ub(K48R)). RNase protection assays were used to confirm expression of the Ub transgenes in spinal cord and ubiquitin transgene levels were estimated to account for 9-12% of total ubiquitin. Mice expressing the G9 3A transgene exhibited neurological symptoms and histopathological changes typical of this model irrespective of ubiquitin transgene status. Impaired rotarod performance was observed in all G9 3A transgenics by 7 weeks of age irrespective of ubiquitin genotype. The presence of wild-type or mutant ubiquitin transgenes resulted in a small but significant delay in the onset of clinical symptoms and mild acceleration of disease progression, without influencing overall survival. These data suggest that relatively small changes in ubiquitin expression can influence the development of neurodegenerative disease and are consistent with a neuroprotective role for the UPS.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.VACCINE.2016.01.048
Abstract: Most women decide about infant immunisation during pregnancy. However, we have limited knowledge of the immunisation intentions of their partners. We aimed to describe what pregnant women and their partners intended for their future child's immunisations, and to identify associations between parental intentions and the subsequent timeliness of infant immunisation. We recruited a cohort of pregnant New Zealand (NZ) women expecting to deliver between April 2009 and March 2010. The cohort included 11% of births in NZ during the recruitment period and was generalisable to the national birth cohort. We completed antenatal interviews independently with mothers and partners. We determined immunisation receipt from the National Immunisation Register and defined timely immunisation as receiving all vaccines (scheduled at 6-weeks, 3- and 5-months) within 30 days of their due date. We described independent associations of immunisation intentions with timeliness using adjusted odds ratios (OR) and 95% confidence intervals (CI). Of 6172 women, 5014 (81%) intended full immunisation, 245 (4%) partial immunisation, 140 (2%) no immunisation and 773 (13%) were undecided. Of 4152 partners, 2942 (71%) intended full immunisation, 208 (5%) partial immunisation, 83 (2%) no immunisation and 921 (22%) were undecided. Agreement between mothers and partners was moderate (Kappa=0.42). Timely immunisation occurred in 70% of infants. Independent of their partner's intentions, infants of pregnant women who decided upon full immunisation were more likely to be immunised on time (OR=7.65, 95% CI: 4.87-12.18). Independent of the future mother's intentions, infants of partners who had decided upon full immunisations were more likely to be immunised on time (OR=3.33, 95% CI: 2.29-4.84). During pregnancy, most future parents intend to fully immunise their child however, more partners than mothers remain undecided about immunisation. Both future mothers' and future fathers' intentions are independently associated with the timeliness of their infant's immunisations.
Publisher: Elsevier BV
Date: 12-1997
Publisher: Springer Science and Business Media LLC
Date: 06-09-2001
Abstract: The murine Unp gene encodes a widely expressed ubiquitin-specific protease. The predicted sequence of the UNP protein features motifs common to viral oncoproteins through which these proteins interact with the retinoblastoma gene product pRb, as well as the related 'pocket proteins' p107 and p130. We have explored the possibility that UNP interacts with pocket proteins, and report here that such associations can be detected in vitro and in cells. Associations of UNP and pocket proteins are sensitive to site-directed mutations in a manner directly analogous to those documented in viral oncoproteins. We conclude that within cells UNP does physically associate with pRb, and can also associate with p107 and p130.
Publisher: Wiley
Date: 10-05-2007
Publisher: Elsevier BV
Date: 09-2000
DOI: 10.1016/S0167-4838(00)00134-5
Abstract: The ubiquitin-specific proteases (Ubps) are a family of largely dissimilar enzymes with two major conserved sequence regions, containing either a conserved cysteine residue or two conserved histidine residues, respectively. The murine Unp oncoprotein and its human homologue, Unph, both contain regions similar to the conserved Cys and His boxes common to all the Ubps. In this study we show that Unp and Unph are active deubiquitinating enzymes, being able to cleave ubiquitin from both natural and engineered linear ubiquitin-protein fusions, including the polyubiquitin precursor. Mutation of the conserved Unp Cys and His residues abolishes this activity, and identifies the likely His residue in the catalytic triad. Unp is tumorigenic when overexpressed in mice, leading to the suggestion that Unp may play a role in the regulation of ubiquitin-dependent protein degradation. We have demonstrated here that the high-level expression of Unp in yeast does not disrupt the degradation of the N-end rule substrate Tyr-beta-galactosidase (betagal), the non-N-end rule substrate ubiquitin-Pro-betagal, or the degradation of abnormal, canavanine-containing proteins. These data suggest that Unp is not a general modulator of ubiquitin-dependent proteolysis. However, Unp may have a role in the regulation of the degradation of a specific, as yet undescribed, substrate(s).
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CANLET.2010.01.025
Abstract: The ubiquitin-proteasome system (UPS) and autophagy provide major cellular pathways for protein degradation. Since the p53 pathway controls autophagy, we investigated whether p53 regulates UPS in ovarian tumour cell lines. A reporter cell line (SKOV3-EGFPu) was established to measure UPS function against a constant genetic background. Transient expression of either wild type or mutant p53 in SKOV3-EGFPu cells reduced UPS activity as compared to vector control. These results, together with those from endogenous p53 expression in seven ovarian cancer cell lines, suggest that expression of both wild-type and mutant p53 protein impairs UPS function. Thus, p53 expression may regulate protein homeostasis by down-regulating UPS function in response to cellular stress.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.NUT.2021.111560
Abstract: This study aimed to examine the relationship between dietary practices and sleep in young children. In this study, 2-y-old children (n = 6327) and their mothers were enrolled at birth and during pregnancy, respectively. The study obtained maternal demographic, health, and lifestyle data during late pregnancy. Parents reported the 2-y-old child's dietary practices on a food frequency questionnaire, as well as sleep duration and night-waking frequency. Measures of dietary intake quantified servings per day for each food group (grouped as low/moderate/high intake). Sleep measures were as inadequate sleep when <11 h sleep in a 24-h period and increased night waking when waking ≥2 times per night. Multivariable logistic regression analyses examined associations between toddler diet and sleep, which were described using adjusted odds ratios (ORs) and 95% confidence intervals. In this study, 2-y-old children (n = 6288) slept for a mean of 12.3 hours (standard deviation: ±1.5 hours) over a 24-h period, with 734 children (12%) getting <11 h of sleep in 24 h. Increased night waking occurred in 1063 children (17%). Compared with low intake, high soft drink/snack/fast food intake was associated with inadequate sleep (OR: 1.37) and increased night waking (OR: 1.34). High milk/cheese/yoghurt intake (OR: 1.55) was associated with increased odds of night waking, but moderate (OR: 0.81) or high (OR: 0.78) vegetable intake was associated with decreased odds of night waking. Exposure to screens (OR: 1.28) and heavy maternal cigarette smoking (OR: 2.20) were also associated with inadequate sleep and increased night waking, respectively. At age 2 y, higher consumption of soft drinks/snacks/fast foods is associated with shorter, more disrupted sleep. Conversely, higher vegetable consumption is associated with less disrupted sleep. Dietary modifications may improve toddlers' sleep.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2012
DOI: 10.1007/S10637-011-9744-Z
Abstract: The human tumour suppressor protein p53 is mutated in nearly half of human tumours and most mutant proteins have single amino acid changes. Several drugs including the quinazoline derivative 1 (CP-31398) have been reported to restore p53 activity in mutant cells. The side chain of 1 contains a styryl linkage that compromises its stability and we wished to explore the activity of analogues containing more stable side chains. Reactivation of p53 function was measured by flow cytometry as the ability to potentiate radiation-induced G(1)-phase cell cycle arrest and by western blotting to determine expression of p21(WAF1). DNA binding was measured by competition with ethidium and preliminary pharmacological and xenograft studies were carried out. Screening of analogues for potentiation of radiation-induced G(1)-phase cell cycle arrest using NZOV11, an ovarian tumour cell line containing a p53(R248Q) mutation, demonstrated that the (2-benzofuranyl)-quinazoline derivative 5 was among the most active of the analogues. Compound 5 showed similar effects in several other p53 mutant human tumour cell lines but not in a p53 null cell line. 5 also potentiated p21(WAF1) expression induced by radiation. DNA binding affinity was measured and found to correlate with p53 reactivation activity. Plasma concentrations of 5 in mice were sufficient to suggest in vivo activity and a small induced tumour growth delay (7 days) of NZM4 melanoma xenografts was observed. Compound 5 restores p53-like function to a human tumour cells lines expressing a variety of mutant p53 proteins, thus providing a basis for the design of further new drugs.
No related grants have been discovered for Catherine Gilchrist.