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Brian Cox

Publications and source records attributed to Brian Cox.

28 records · Page 2Linked to original sources
PubMed2003

Structure and function of the PWI motif: a novel nucleic acid-binding domain that facilitates pre-mRNA processing.

The PWI motif is a highly conserved domain of unknown function in the SRm160 splicing and 3'-end cleavage-stimulatory factor, as well as in several other known or putative pre-mRNA processing components. We show here that the PWI motif is a new type of RNA/DNA-binding domain that has an equal preference for single- and double-stranded nucleic acids. Deletion of the motif prevents SRm160 from binding RNA and stimulating 3'-end cleavage, and its substitution with a heterologous RNA-binding domain restores these functions. The NMR solution structure of the SRm160-PWI motif reveals a novel, four-helix bundle and represents the first example of an alpha-helical fold that can bind single-stranded (ss)RNA. Structure-guided mutagenesis indicates that the same surface is involved in RNA and DNA binding and requires the cooperative action of a highly conserved, adjacent basic region. Thus, the PWI motif is a novel type of nucleic acid-binding domain that likely has multiple important functions in pre-mRNA processing, including SRm160-dependent stimulation of 3'-end formation.

Amino Acid Motifs↗
PubMed2003

PRISM, a generic large scale proteomic investigation strategy for mammals.

We have developed a systematic analytical approach, termed PRISM (Proteomic Investigation Strategy for Mammals), that permits routine, large scale protein expression profiling of mammalian cells and tissues. PRISM combines subcellular fractionation, multidimensional liquid chromatography-tandem mass spectrometry-based protein shotgun sequencing, and two newly developed computer algorithms, STATQUEST and GOClust, as a means to rapidly identify, annotate, and categorize thousands of expressed mammalian proteins. The application of PRISM to adult mouse lung and liver resulted in the high confidence identification of over 2,100 unique proteins including more than 100 integral membrane proteins, 400 nuclear proteins, and 500 uncharacterized proteins, the largest proteome study carried out to date on this important model organism. Automated clustering of the identified proteins into Gene Ontology annotation groups allowed for streamlined analysis of the large data set, revealing interesting and physiologically relevant patterns of tissue and organelle specificity. PRISM therefore offers an effective platform for in-depth investigation of complex mammalian proteomes.

Animals↗
PubMed2003

Effects of lamotrigine and levetiracetam on seizure development in a rat amygdala kindling model.

In kindling models of epilepsy, the period during which repeated stimulation evokes intensifying seizures is attributed to an underlying epileptogenic process, and the point at which class 5 kindled seizures occur is considered the established epileptic state. Previous studies have indicated that a separation can occur between drug effects on these two components. For example, carbamazepine and phenytoin inhibit kindled seizures but have no effect on seizure development, whereas levetiracetam inhibits both components. We have investigated the profile of lamotrigine in the amygdala kindling model, including levetiracetam for comparison. As expected, both treatments dose-dependently inhibited class 5 kindled seizures. In a separate study, daily administration of either lamotrigine (20mgkg(-1) i.p.) or levetiracetam (50mgkg(-1) i.p.) demonstrated antiepileptogenic-like effects by blocking seizure development during the treatment period. Following cessation of drug treatment, further daily stimulation resulted in kindled seizure development, though there was a significant increase with both treatment groups, relative to the control group, in the total number of stimulations required to produce classes 3 and 5 seizures. In addition, prior levetiracetam treatment appeared to delay or prevent the expected increase in after-discharge duration (ADD). These results suggest that lamotrigine, like levetiracetam, possesses the ability to counteract kindling acquisition, which differentiates it from other drugs with sodium channel blocking activity.

Amygdala↗
PubMed2003

National audit of women with abnormal cervical smears in New Zealand.

OBJECTIVE: To evaluate the follow-up of women with abnormal cervical smears identified by the National Cervical Screening Programme (NCSP) in New Zealand. DESIGN: Survey and clinical audit. SETTING: The study took place in New Zealand. POPULATION: The population included women aged 20-69 years enrolled on the NCSP with first abnormal smear recorded in 1999. METHODS: Participants were interviewed, and clinical data collected from the NCSP-register, and from clinicians. MAIN OUTCOME MEASURES AND RESULTS: The overall response rate was 57%. The proportions of women whose initial assessment, treatment or follow-up fell outside recommended times were between 17 and 35%. Of women with high-grade smears, 72% underwent a treatment procedure. Of these, 91% were excision biopsies, 6% hysterectomies and 4% ablation procedures. Approximately 10% of women had persistent or recurrent abnormalities at 6 and 12 months after treatment. CONCLUSIONS: Overall, results were largely reassuring, but limited by the low response rate. Most women were managed within current clinical guidelines. Areas requiring improvement were identified, in particular in relation to longer than recommended waiting times for assessment and treatment.

Adult↗
PubMed2003

Analysis of the generation and segregation of propagons: entities that propagate the [PSI+] prion in yeast.

The propagation of the prion form of the yeast Sup35p protein, the so-called [PSI(+)] determinant, involves the generation and partition of a small number of particulate determinants that we propose calling "propagons." The numbers of propagons in [PSI(+)] cells can be inferred from the kinetics of elimination of [PSI(+)] during growth in the presence of a low concentration of guanidine hydrochloride (GdnHCl). Using this and an alternative method of counting the numbers of propagons, we demonstrate considerable clonal variation in the apparent numbers of propagons between different [PSI(+)] yeast strains, between different cultures of the same [PSI(+)] yeast strain, and between different cells of the same [PSI(+)] culture. We provide further evidence that propagon generation is blocked by growth in GdnHCl and that it is largely confined to the S phase of the cell cycle. In addition, we show that at low propagon number there is a bias toward retention of propagons in mother cells and that production of new propagons is very rapid when cells with depleted numbers of propagons are rescued into normal growth medium. The implications of our findings with respect to yeast prion propagation mechanisms are discussed.

Chromosome Segregation↗
PubMed2003

PSA testing and digital rectal examination in New Zealand.

OBJECTIVE: To investigate the use of digital rectal examination and prostate specific antigen (PSA) testing in a population-based sample of men in New Zealand. METHODS: A random selection of men aged 40-74 years, weighted by age, was chosen from the general electoral roll of New Zealand. Only men with a telephone who had been married at some time were eligible. Telephone interviews were conducted using a standard questionnaire. Crude and age-adjusted proportions were calculated. Logistic regression was used to explore associations between sociodemographic factors and digital rectal examination or PSA testing. RESULTS: Interviews were completed for 85% of the 1,486 eligible men and analyses were confined to the 1,225 European men. Many more men reported having a digital rectal examination (41%; 95% CI 33.8-48.2) than a PSA test (9%; 95% CI 4.2-14.2). Men in the lowest social class were significantly less likely to have had a digital rectal examination (OR 0.30; 95% CI 0.18-0.50) or PSA test (OR 0.25; 95% CI 0.11-0.60) compared with those in the highest social class. Men with vocational training or no post-school qualifications were approximately half as likely to report a digital rectal examination or a PSA test compared with men with degrees or diplomas. CONCLUSIONS: Although current New Zealand recommendations are that population screening for prostate cancer should not be introduced, many men are still having digital rectal examinations and PSA tests in the absence of symptoms. The frequency of PSA testing is considerably lower than in Australia and appears to be largely influenced by a man's social class.

Adult↗
PubMed2002

Human colorectal cancer cells efficiently conjugate the cyclopentenone prostaglandin, prostaglandin J(2), to glutathione.

Cyclopentenone prostaglandins (PGs), particularly those of the J-series, affect proliferation and differentiation in a number of cell lines. J-ring PGs have been shown to be ligands for the peroxisome proliferator-activated receptor (PPAR)-gamma and to modulate NF-kappaB-mediated gene transcription. We have previously reported that large quantities of eicosanoids, including PGJ(2), are produced by the human colorectal cancer cell line HCA-7 while lesser amounts of Delta(12)-PGJ(2) and 15-deoxy-Delta(12,14)-PGJ(2) are formed. In this and other cell lines, cyclopentenone PGs have been shown to increase cell proliferation, but factors that influence their formation and metabolism are poorly understood. Unlike other PGs, cyclopentenone PGs contain alpha,beta-unsaturated carbonyl groups that readily adduct various biomolecules such as glutathione (GSH) in vitro. We now report that in HCA-7 cells, PGJ(2) is largely metabolized by conjugation to GSH. Characterization of the adducts by liquid chromatography (LC)-mass spectrometry (MS) revealed two major metabolites consisting of (1) a novel GSH conjugate in which the carbonyl at C-11 of PGJ(2) is reduced and (2) intact PGJ(2) conjugated to GSH. Approximately 70% of the PGJ(2) added to HCA-7 cells was esterifed to GSH after 2 h of incubation, suggesting this pathway represents the major route of metabolic disposition of PGJ(2) in HCA-7 cells.

Antineoplastic Agents↗
PubMed2002

Vasectomy and risk of prostate cancer.

CONTEXT: Vasectomy is a common method of contraception, but concern exists about a reported association with risk of prostate cancer. OBJECTIVE: To examine whether vasectomy increases risk of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: National population-based case-control study of 923 new cases of prostate cancer among men aged 40 to 74 years from the New Zealand Cancer Registry who were on the general electoral roll. Controls (n = 1224) were randomly selected from the general electoral roll, with frequency matching to cases in 5-year age groups. Cases (3-15 months after diagnosis) and controls were interviewed by telephone between January 1997 and November 1999. MAIN OUTCOME MEASURES: Relative risk (RR) of prostate cancer for men who had had a vasectomy vs those who had not. RESULTS: There was no association between prostate cancer and vasectomy (RR, 0.92; 95% confidence interval [CI], 0.75-1.14) nor with time since vasectomy (RR, 0.92; 95% CI, 0.68-1.23 for > or = 25 years since vasectomy). Adjustment for social class, geographic region, religious affiliation, and a family history of prostate cancer did not affect these RRs. CONCLUSIONS: Vasectomy does not increase the risk of prostate cancer, even after 25 years or more.

Adult↗
PubMed2000

Smoking-related Cancers in Maori and non-Maori in New Zealand, 1974-1993: Fewer Bladder Cancers among Maori.

Smoking is, and long has been, more prevalent among Maori than non-Maori in New Zealand. Lung cancer, but not other smoking-related cancers, is known to be markedly more common among Maori than non-Maori. Incidence and mortality data from the New Zealand Cancer Registry for cancers of the mouth/pharynx, oesophagus, pancreas, larynx, kidney and bladder, as well as lung/pleura, during the period 1974 to 1993 were analysed by sex to determine whether the rates of each of these smoking-related cancers were higher in Maori than in non-Maori. Truncated (35-64 yr) age-standardized incidence rates for 1974-93 were significantly higher in Maori than non-Maori for cancers of the pancreas, lung/pleura and kidney (both sexes), mouth/pharynx and oesophagus (males only). There was no difference between the Maori and non-Maori rates for cancer of the larynx, and bladder cancer incidence was significantly lower in Maori than non-Maori. Mortality rates followed a similar pattern as those for incidence for cancers of the pancreas, larynx, lung/pleura and kidney (both sexes) and bladder (males only). The pattern predicted by the higher prevalence of smoking in Maori than non-Maori was borne out for all smoking-related cancers except bladder and laryngeal cancer. Under-enumeration through lower access to health services may have contributed to the lower than expected rates of bladder cancer in Maori, but a role for a genetically or lifestyle related protective effect is suggested.

Journal Article↗