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C Moyes

Publications and source records attributed to C Moyes.

17 recordsLinked to original sources
PubMed1998

N-acetyl transferase 1: two polymorphisms in coding sequence identified in colorectal cancer patients.

Increased cancer risk has been associated with functional polymorphisms that occur within the genes coding for the N-acetyltransferase enzymes NAT1 and NAT2. We detected two NAT1 polymorphisms in colorectal cancer patients by heteroduplex analysis. DNA sequencing revealed the wild-type sequence (NAT1*4) and two single base substitutions at adjacent positions 999 bp (C to T, NAT1*14) and 1000 bp (G to A, NAT1*15) of the gene, changing Arg187 to a stop codon and Arg187 to Gln respectively. NAT1 alleles NAT1*4 (0.98) and NAT1*15 (0.02) were present at a similar frequency in patients with colorectal cancer (n=260) and in a Scottish control group (n=323). The third allele, NAT1*14, was present only in the colorectal cancer group at a frequency of 0.006. NAT1 genotype NAT1*4/ NAT1*15 was significantly less frequent in individuals that had a slow NAT2 genotype. This was observed in both cancer and control groups and suggests that this association was unrelated to cancer risk. We conclude that polymorphisms within the coding region of the NAT1 gene are infrequent and do not appear to have an independent association with colorectal cancer risk. However, the relationship between NAT1 and NAT2 polymorphisms appears non-random, suggesting a linkage between these enzymes.

Acetyltransferases↗
PubMed1998

Direct detection of eae-positive bacteria in human and veterinary colorectal specimens by PCR.

A PCR test based on the amplification of an eae-specific sequence was designed and evaluated for its ability to directly detect homologous sequences in enteropathogenic Escherichia coli and Citrobacter spp. (amplification of eae open reading frame, 178 bp) in sections of the intestines of humans and animals with colonic lesions. Positive PCR results were observed with eae-positive reference strains of E. coli and Citrobacter rodentium (Citrobacter freundii biotype 4280). Known eae-negative reference strains of E. coli and other laboratory strains of enteric bacteria were negative by the amplification test. The sensitivity of the PCR for detection of eae-positive E. coli and C. rodentium was between 1 and 2 CFU. To detect these sequences directly from sections of fixed colon from human and veterinary sources, PCR conditions were modified by the addition of 0.1 mM 8-methoxypsoralen to eliminate extraneous bacterial DNA from the PCR amplification cocktail without added template. Sections of colon from three pigs experimentally affected with colon lesions due to enteropathogenic (attaching and effacing) E. coli were PCR positive for bacterial eae genome. Sections from control animals were negative. Sections of colon from one of 18 biopsies from confirmed AIDS patients and from 22 of 35 colorectal cancer patients were PCR positive for bacterial eae genome. The PCR test was a simple and quick method of detecting bacterial eae genome in human and veterinary clinical specimens. This method may remove the need for initial culture and detection of the gene by DNA probing from potential associated lesions. The clear relationship of bacteria containing the eae gene with colonic lesions in the pigs and mice indicates that a similar relationship is possible for human patients having similar lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Regulation of muscle mitochondrial design.

Mitochondria are responsible for the generation of ATP to fuel muscle contraction. Hypermetabolic stresses imposed upon muscles can lead to mitochondrial proliferation, but the resulting mitochondria greatly resemble their progenitors. During the mitochondrial biogenesis that accompanies phenotypic adaptation, the stoichiometric relationships between functional elements are preserved through shared sensitivities of respiratory genes to specific transcription factors. Although the properties of muscle mitochondria are generally thought to be highly conserved across species, there are many examples of mitochondrial differences between muscle types, species and developmental states and even within single cells. In this review, we discuss (1) the nature and regulation of gene families that allow coordinated expression of genes for mitochondrial products and (2) the regulatory mechanisms by which mitochondrial differences can arise over physiological and evolutionary time.

Journal Article↗
PubMed1997

Characterization of the intracellular signalling pathways that underlie growth-factor-stimulated glucose transport in Xenopus oocytes: evidence for ras- and rho-dependent pathways of phosphatidylinositol 3-kinase activation.

The stimulation of glucose transport is one of the early cellular responses to growth factors and is essential for cell proliferation, yet the molecular processes that underlie this response are poorly defined. The aim of this study was to characterize the role of the low-molecular-mass G-proteins, Ras and Rho, and their downstream targets, Raf protein kinase and phosphatidylinositol 3-kinase, in the regulation of glucose transport in Xenopus oocytes by two distinct growth-factor receptors: the insulin-like growth factor I (IGF-I) tyrosine kinase receptor and the heterotrimeric G-protein-coupled lysophosphatidic acid (LPA) receptor. Microinjection of a neutralizing anti-Ras antibody partially blocked IGF-I-stimulated deoxyglucose uptake but was without effect on LPA-stimulated deoxyglucose uptake. In contrast, microinjection of the C3 coenzyme of botulinum toxin, which selectively ADP-ribosylates and inactivates Rho, inhibited LPA-stimulated, but not IGF-I-stimulated, deoxyglucose uptake. Similarly, LPA- but not IGF-I-stimulated deoxyglucose uptake was attenuated in oocytes expressing a dominant negative rho construct. Cells expressing a dominant negative mutant of Raf protein kinase exhibited markedly reduced sensitivity to both LPA and IGF-I, consistent with a role for endogenous Raf in glucose uptake by both growth factors. Furthermore, expression of a constitutively activated form of raf-1 resulted in a growth-factor-independent increase in deoxyglucose uptake. Measurements of phosphatidylinositol 3-kinase activity in microinjected cells support the hypothesis that the IGF-I receptor stimulates glucose transport by a Ras-dependent activation of phosphatidylinositol 3-kinase, whereas the G-protein-coupled LPA receptor controls this response by a pathway that involves Rho-dependent activation of a distinct phosphatidylinositol 3-kinase. Thus we provide evidence for clear differences in the signalling pathways that control glucose transport by G-protein-coupled and tyrosine kinase growth-factor receptors. Furthermore this is the first demonstration that active Rho is involved in the signalling pathways that regulate glucose uptake in response to some growth factors.

Animals↗
PubMed1997

Measles control.

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Humans↗
PubMed1997

N-acetyltransferase 2 genotype in colorectal cancer and selective gene retention in cancers with chromosome 8p deletions.

BACKGROUND: Genetic polymorphisms in N-acetyltransferase (NAT2) can change the normally fast acetylation of substrates to slow acetylation, and have been associated with the development of some cancers. The NAT2 locus may also suffer dysregulation during cancer progression, as the gene resides on chromosome 8p22, a region which is frequently deleted in colorectal cancer. SUBJECTS AND METHODS: A polymerase chain reaction based method was used to determine NAT2 genotype in 275 patients with colon cancer and 343 normal control DNAs. Within the cancer group, 65 cases known to contain deletions in chromosome 8p were examined for loss of heterozygosity at the NAT2 locus. RESULTS: Overall, there was no statistical difference in frequency or distribution of NAT2 alleles and genotype between colon cancer and control groups. There was a significant association between the slow acetylation genotype and early age of onset. NAT2 genotype did not vary with other clinical features of colon cancer, which included Dukes's stage, site of tumour, and sex. Of 48 informative cases, only three (6%) showed loss of heterozygosity, indicating that the NAT2 locus is not commonly deleted in colorectal cancer. This suggests that NAT2 is retained during the process of allele loss possibly because of its proximity to a gene necessary for cell viability. CONCLUSIONS: NAT2 does not play a major role in colorectal cancer risk, but may influence risk in some age groups. The nature of the loss of heterozygosity at the chromosome 8p site is complex and is worthy of further study.

Acetylation↗
PubMed1996

Lysophosphatidic acid stimulates glucose transport in Xenopus oocytes via a phosphatidylinositol 3'-kinase with distinct properties.

Lysophosphatidic acid (LPA) stimulated the transport of deoxyglucose into oocytes isolated from Xenopus laevis. This stimulation was accounted for entirely by an increase in the Vmax for transport. Various LPAs with different acyl groups in the sn-1 position and phosphatidic acid stimulated deoxyglucose (deGlc) transport in these cells with a rank order potency of 1-oleoyl-LPA > 1-palmitoyl-LPA > phosphatidic acid = 1-stearoyl-LPA > 1-myristoyl-LPA. The phosphatidylinositol 3'-kinase inhibitor LY294002 completely blocked LPA-stimulated deoxyglucose uptake (IC50 approximately 2 microM). In marked contrast, wortmannin, which can completely block both insulin-like growth factor-I (IGF-I)-stimulated deGlc uptake in oocytes and phosphatidylinositol 3'-kinase activation at concentrations as low as 20 nM [Gould, Jess, Andrews, Herbst, Plevin and Gibbs (1994) J. Biol. Chem. 269, 26622-26625], was a relatively poor inhibitor of LPA-stimulated deGlc transport, even at concentrations as high as 100 nM. We further show that LPA stimulates phosphatidylinositol 3'-kinase activity(s) that can phosphorylate both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate, and that this stimulation is inhibited by LY294002 but is relatively insensitive to wortmannin, again in marked contrast to IGF-I-stimulated phosphatidylinositol 3'-kinase activity. Antibodies against the p85 regulatory subunit of phosphatidylinositol 3'-kinase or antiphosphotyrosine antibodies immunoprecipitated IGF-I-stimulated but not LPA-stimulated phosphatidylinositol 3'-kinase activity. We conclude that LPA stimulates glucose uptake in Xenopus oocytes by a mechanism that may involve activation of a form of phosphatidylinositol 3'-kinase that is distinguished from other isoforms by its resistance to wortmannin and by its substrate specificity. Since the LPA-activated form of phosphatidylinositol 3'-kinase is pharmacologically and immunologically distinct from that which is involved in IGF-I-stimulated glucose transport in these cells, we suggest that distinct isoforms of this enzyme are able to function with the same biological effect, at least in the regulation of sugar transport.

Androstadienes↗
PubMed1994

Risk factors for asthma symptoms in Kawerau children.

AIMS: To study risk factors for asthma prevalence in Kawerau children aged 8-13 years. METHODS: Questionnaires on asthma symptoms and risk factors were completed in 1992 by parents of 708 Kawerau schoolchildren aged 8-13 years, a response rate of 82.0%; for a subgroup of children, stored serum samples from a 1984 survey were also analysed. RESULTS: The overall prevalence of current wheeze (21.3%) was similar to that observed in other New Zealand surveys. The prevalence of current wheeze was elevated in males (odds ratio (OR) = 1.7, 95% CI 1.2-2.5), in those who had been passively exposed to cigarette smoke from the primary caregiver (OR = 1.4, 95% CI 1.0-2.1), in those who had had pets in the home at age 0-5 years (OR = 1.9, 95% CI 1.2-2.9) and in those with one or more birth parents with asthma (OR = 2.1, 95% CI 1.4-3.1); current wheeze was less common in those with older children living in the same household (for 2 or more older children in the same household, OR = 0.5, 95% CI 0.2-1.0). In a small nested case-control study it was found that current wheeze was more common in those with high levels of IgE (OR = 6.4, 95% CI 1.3-36.4) or low levels of selenium (OR = 3.1, 95% CI 0.9-11.8) in stored serum collected 8 years previously. There was no difference in the proportions with current wheeze, or with diagnosed asthma between Maori and European children, but Maori children were more likely to have current frequent nocturnal wheeze (OR = 2.2, 95% CI 1.0-5.1), current severe wheeze (OR = 1.8, 95% CI 0.8-3.7) or to have been admitted to hospital with asthma (OR = 2.4, 95% CI 1.2-4.8). Passive exposure to tobacco smoke was more common among Maori children, but this only partially accounted for the greater asthma severity in Maori children, and the lower prescribing of prophylactic medications in this group may also have contributed. CONCLUSIONS: Multiple factors were associated with asthma symptoms in children in this age-group, including a family history of asthma, male gender, environmental tobacco smoke, environmental allergen exposure, atopy, and low selenium status. Further studies are required to assess the relative contributions of these factors to the prevalence of asthma in New Zealand.

Adolescent↗
PubMed1988

Hepatitis B virus: the importance of age at infection.

Recent studies have demonstrated the importance of age at infection with hepatitis B virus (HBV). Age affects whether the infection is self-limited or results in the chronic carrier state, the severity of the acute infection, and the incidence of various sequelae of the chronic carrier state. In particular, although the acute infection is more severe in adults, infections in infants and preschool children carry much greater risks of chronic carriage which increases the risk of primary hepatocellular carcinoma and cirrhosis later in life. This has two important implications for areas where HBV is endemic. First, more impact can be gained by vaccinating infants and preschool children than by vaccinating healthy adults. Second, if funds are limited, greater impact will be gained by immunising a larger number of children with low doses of vaccine so that they are protected during the early years of life when the risk of chronic carriage is highest, rather than using the standard dose in a smaller number of children even though protection may be longer lasting with standard doses. These two considerations provide the basis for an efficient strategy for control in communities or countries where HBV is endemic or hyperendemic.

Adolescent↗
PubMed1988

Immunogenicity of a recombinant yeast-derived hepatitis B vaccine (Engerix B) in children.

Eighty-one children seronegative for markers of hepatitis B virus infection aged 0-10 years received 10 micrograms of a yeast-based hepatitis B vaccine (Engerix B) at 0, 1, and 6 months. Eighty subjects responded with a geometric mean titre of 7640 IU/L one month after the third dose. All seroconverters produced high level of antibodies regardless of age, race, or sex. It is concluded that Engerix B used in the dose and schedule described is highly immunogenic.

Antigens↗
PubMed1987

Immunogenicity of low doses of hepatitis B vaccine in children: a study in 650 New Zealand children.

Six hundred and fifty New Zealand children from 2-12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma-derived hepatitis B vaccine (H-B-Vax), at 0, 1, and 6 months, and tested 2-3 months later for antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti-HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti-HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 2-4-year-olds than in older children. This study demonstrated that a satisfactory anti-HBs response was obtained using one-fifth of the recommended doses of hepatitis B vaccine.

Child↗