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Biomedical subjects

N Bishop

Publications and source records attributed to N Bishop.

At least 19 recordsLinked to original sources
PubMed2002

The menstrual cycle and its effect on the immune status of female endurance runners.

Twenty highly trained, eumenorrhoeic female endurance runners were studied over three consecutive menstrual cycles. Average training distance per week, total years training and mood states were recorded throughout the three cycles. Salivary progesterone and menstrual cycle diaries were recorded over the first two cycles to identify luteal phase onset and the presence of any menstrual irregularities. Saliva samples were collected daily over the third cycle for analysis of immunoglobulin A (IgA) concentration and secretion and saliva flow rate. Two-way analysis of variance (ANOVA) revealed no significant differences in mood states across the phases of the menstrual cycle (P > 0.05). Training logs indicated that training did not alter throughout the 3 month study. One-way ANOVA revealed no significant differences in IgA concentration (P = 0.92), secretion rate (P = 0.84) or saliva flow rate (P = 0.95) across the phases of the menstrual cycle. Pearson's product-moment correlation revealed no relationship between IgA concentration and progesterone between the phases of the cycle (r = 0.39). We conclude that, in ovulatory female endurance runners whose physical and emotional stress are stable, IgA concentration is not significantly affected by fluctuations in progesterone during the menstrual cycle.

Adult↗
PubMed2000

TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes.

Class E vacuolar protein sorting (vps) proteins are required for appropriate sorting of receptors within the yeast endocytic pathway, and most probably function in the biogenesis of multivesicular bodies. We have identified the mammalian orthologue of Vps28p as a 221- amino acid cytosolic protein that interacts with TSG101/mammalian VPS23 to form part of a multiprotein complex. Co-immunoprecipitation and cross-linking experiments demonstrated that hVPS28 and TSG101 interact directly and that binding requires structural information within the conserved C-terminal portion of TSG101. TSG101 and hVPS28 are predominantly cytosolic. However, when endosomal vacuolization was induced by the expression of a dominant-negative mutant of another class E vps protein, human VPS4, a portion of both TSG101 and hVPS28 translocated to the surface of these vacuoles. We conclude that TSG101 and its interacting components are directly involved in endosomal sorting.

Adenosine Triphosphatases↗
PubMed2000

Variability within general practitioner prescribing over time.

AIMS: We have described intra-general practitioner (GP) prescribing variability over time in terms of volume, cost and average item cost of prescription items, within New Zealand general practice. METHODS: Longitudinal data over the financial years 1992-94 were studied for two GP samples. Prescription data for a regional sample of 305 GPs were obtained for the first six months (January to June) from the New Zealand pharmaceutical pricing office, Health Benefits Limited. Prescription data from a second national sample of 74 GPs were obtained from the PreMeC prescription analysis (PAS) database of GPs who had participated in three consecutive September to December prescription analyses. The coefficient of variation was used to measure the intra-GP variability over time in total prescription cost, volume of prescription items and average prescription item cost. RESULTS: The median intra-GP variability over time for the regional GP sample, based on reimbursement data, was 9% in total cost, 9% in total volume and 5% in average item cost. The median intra-GP variability in the national sample was very similar to the regional sample when based on reimbursement data, but when PAS data were used the variability was 16% in total cost, 17% in total volume and 8% average item cost. CONCLUSIONS: The year-on-year, intra-GP variability for cost was 9%, for volume 9-10% and for average item cost 5-6%. Pharmaceutical budget estimates should reflect year-to-year intra-GP prescribing variability of the order of 9%.

Drug Costs↗
PubMed2000

ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking.

The yeast vacuolar sorting protein Vps4p is an ATPase required for endosomal trafficking that couples membrane association to its ATPase cycle. To investigate the function of mammalian VPS4 in endosomal trafficking, we have transiently expressed wild-type or ATPase-defective human VPS4 (hVPS4) in cultured cells. Wild-type hVPS4 was cytosolic, whereas a substantial fraction of hVPS4 that was unable to either bind or hydrolyze ATP was localized to membranes, including those of specifically induced vacuoles. Vacuoles were exclusively endocytic in origin, and subsets of enlarged vacuoles stained with markers for each stage of the endocytic pathway. Sorting of receptors from the early endosome to the recycling compartment or to the trans-Golgi network was not significantly affected, and no mutant hVPS4 associated with these compartments. However, many hVPS4-induced vacuoles were substantially enriched in cholesterol relative to the endosomal compartments of untransfected cells, indicating that expression of mutant hVPS4 gives rise to a kinetic block in postendosomal cholesterol sorting. The phenotype described here is largely consistent with the defects in vacuolar sorting associated with class E vps mutants in yeast, and a role for mammalian VPS4 is discussed in this context.

ATPases Associated with Diverse Cellular Activitie↗
PubMed2000

Incidence of vertebral fractures in the first three months after orthotopic liver transplantation.

BACKGROUND AND OBJECTIVES: High rates of bone loss and increased fracture incidence have been reported in patients undergoing liver transplantation, mainly within the first post-operative year. The pathogenesis of post-transplantation bone disease has not been clearly established, but the high doses of glucocorticoids used for immunosuppression may contribute. The use of lower doses in recent years has been associated, in some studies, with lower rates of bone loss and decreased fracture incidence. The aim of this prospective study was to establish the incidence of vertebral fractures in the first 3 months in patients undergoing liver transplantation for chronic liver disease and to identify risk factors for fracture in these patients. DESIGN AND METHODS: Thirty-seven adults with end-stage liver disease were studied prospectively prior to and 3 months after liver transplantation. Vertebral fractures were assessed semi-quantitatively from lateral spine X-rays and bone mineral density measured using dual energy X-ray absorptiometry. RESULTS: Prior to transplantation, prevalent vertebral fractures were present in 13 patients (35%). New fractures developed after transplantation in 10 patients (27% of total) and were significantly more common in those with a prevalent vertebral fracture pre-operatively (P<0.02). Osteoporosis, defined as a bone mineral density T score below -2.5, was present in 39% of patients prior to transplantation, but bone mineral density was not helpful in predicting incident fracture, whether measured before or after transplantation. Over the 3-month study period, significant bone loss occurred in the femoral neck (P<0.05) but not the lumbar spine. CONCLUSIONS: Our results demonstrate a high incidence of vertebral fracture in the first 3 months after liver transplantation and indicate that prevalent vertebral fracture is an important risk factor for the subsequent development of fracture in these patients. Prevention of post-transplantation bone disease should focus both on optimizing bone mass prior to transplantation and preventing bone loss in the early post-operative period.

Absorptiometry, Photon↗
PubMed2000

Disassembly of membrane-associated NSF 20S complexes is slow relative to vesicle fusion and is Ca(2+)-independent.

N-ethylmaleimide-sensitive fusion protein (NSF) and its co-factor soluble NSF attachment protein (alpha)-SNAP) are essential components of the synaptic vesicle fusion machinery and form part of a structurally-conserved 20S protein complex. However, their precise function, relative to fusion itself, is not clear. Using a UV-activated cross-linking approach, we have measured the rate at which a single round of NSF-driven ATP hydrolysis leads to 20S complex disassembly within synaptic membranes. Although this rate is substantially faster than previous estimates of NSF-dependent ATP hydrolysis, it remains much lower than published rates for fusion of synaptic vesicles. Furthermore, the stability of 20S complexes is unaffected by Ca(2+) at concentrations that elicit rapid membrane fusion. We conclude that the ATPase activity of NSF does not contribute directly to vesicle fusion, but more likely plays an earlier role in the synaptic vesicle cycle.

Animals↗
PubMed1999

Human rabaptin-5 is selectively cleaved by caspase-3 during apoptosis.

We have previously shown that Xenopus rabaptin-5 is cleaved in apoptotic extracts, with a concomitant reduction in the ability of these extracts to support endosomal membrane fusion (Cosulich, S. C., Horiuchi, H., Zerial, M., Clarke, P. R., and Woodman, P. G. (1997) EMBO J. 16, 6182-6191). In this report we demonstrate that caspase-dependent cleavage is a conserved feature of rabaptin-5. Human rabaptin-5 is cleaved at two sites (HSLD(379) and DESD(438)) in apoptotic HeLa extracts. Cleavage is effected by caspase-3, since it is prevented when caspase-3 activity is either inhibited by Ac-DEVD-CHO or removed by immunodepletion. Moreover, an identical pattern of cleavage is observed using recombinant caspase-3. The action of caspase-3 is highly selective; neither caspase-2 nor caspase-7 are able to cleave recombinant or cytosolic rabaptin-5. Caspase-dependent cleavage of rabaptin-5 generates two physically separated coiled coil-forming domains, the C-terminal of which retains the ability to bind the Rab5 exchange factor rabex-5.

Base Sequence↗
PubMed1998

Interpretation of bone mineral density values in pediatric Crohn's disease.

Patients with Crohn's disease (CD) often have low bone mineral density (BMD) for their chronological age (CA). However, pediatric cases frequently have growth failure and delayed bone age (BA) and height age (HA). Do they really have the amount of osteoporosis as measured by BMD and calculated for their CA? The aim was to compare z-scores for BMD in relation to CA and z-scores corrected for BA or height age in pediatric patients. A group of 43 pediatric patients (mean age, 12 years; 14 girls, 29 boys) with CD in remission, prospectively had BMD (measured by dual energy x-ray absorptiometry) and BA. Abnormally low z-score for BMD (below 2 standard deviation [SD] for CA was found in 19 patients (44%). Among these, 9 patients (21% overall) had a BA of more than 2 SD lower than their CA and 12 had height age at least 2 years below CA. When the BMD z-score in these patients was corrected for their BA and height age, 6 of 9 and 8 of 12 patients had a normal BMD. In conclusion, when corrected for BA or CA delay, BMD was abnormal in 26 to 30% rather than 44% of cases. Correct assessment of BMD in Crohn's disease patients with bone age delay requires interpretation in terms of BA or HA, rather than CA.

Absorptiometry, Photon↗
PubMed1998

Formation and turnover of NSF- and SNAP-containing "fusion" complexes occur on undocked, clathrin-coated vesicle-derived membranes.

Specificity of vesicular transport is determined by pair-wise interaction between receptors (SNAP receptors or SNAREs) associated with a transport vesicle and its target membrane. Two additional factors, N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment protein (SNAP) are ubiquitous components of vesicular transport pathways. However, the precise role they play is not known. On the basis that NSF and SNAP can be recruited to preformed SNARE complexes, it has been proposed that NSF- and SNAP-containing complexes are formed after SNARE-dependent docking of transport vesicles. This would enable ATPase-dependent complex disassembly to be coupled directly to membrane fusion. Alternatively, binding and release of NSF/SNAP may occur before vesicle docking, and perhaps be involved in the activation of SNAREs. To gain more information about the point at which so-called 20S complexes form during the transport vesicle cycle, we have examined NSF/SNAP/SNARE complex turnover on clathrin-coated vesicle-derived membranes in situ. This has been achieved under conditions in which the extent of membrane docking can be precisely monitored. We demonstrate by UV-dependent cross-linking experiments, coupled to laser light-scattering analysis of membranes, that complexes containing NSF, SNAP, and SNAREs will form and dissociate on the surface of undocked transport vesicles.

Animals↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: I. Establishment of an in vitro system using the duck hepatitis B virus model.

Primary duck hepatocyte (PDH) cultures were established from ducklings congenitally infected with the duck hepatitis B virus (DHBV), plated onto feeder cell layers of irradiated human embryonic lung fibroblasts, and observed for 2 to 3 weeks. This system permitted the survival of the PDH in a differentiated form free of fibroblastic overgrowth for at least 3 weeks. The hepatocytes were shown to contain all the replicative DNA intermediates found during DHBV replication as well as the DHBV structural proteins PRE-S1, PRE-S2, and S of duck hepatitis B surface antigen (DHBsAg). The pool of supercoiled (SC) DHBV DNA increased dramatically from days 10 to 14 postplating. This PDH-feeder cell layer cell culture model provides a convenient system to study the effects of conventional inhibitors of DHBV replication and compounds targeted at the supercoiled form of DHBV DNA. This approach should allow the evaluation of a variety of strategies for treating chronic carriers of hepadnaviruses.

Animals↗
PubMed1990

Antiviral strategies in chronic hepatitis B virus infection: II. Inhibition of duck hepatitis B virus in vitro using conventional antiviral agents and supercoiled-DNA active compounds.

Primary duck hepatocyte (PDH) cultures, congenitally infected with the duck hepatitis B virus (DHBV), were grown on feeder cell layers of irradiated human embryonic lung fibroblasts and then exposed to a number of compounds with recognized or potential antiviral activity. These compounds included conventional antiviral agents, reverse transcriptase inhibitors, compounds with activity to supercoiled-DNA, and DNA-binding agents. Twenty-three compounds were evaluated, and 13 were found to inhibit significantly viral DNA replication. Seven of these compounds (ellipticine, amsacrine, coumermycin A1, Adriamycin, mitozantrone, chloroquine, and neocarzinostatin) acted at the level of viral SC DNA and significantly inhibited production of duck hepatitis B surface antigen (DHBsAg). Conventional agents that inhibited DHBV DNA replication included ganciclovir, acyclovir, bromovinyldeoxyuridine, ribavirin, phosphonoformate, and dideoxyadenosine. Except for dideoxyadenosine, these inhibitors of viral DNA synthesis did not significantly inhibit DHBsAg production. Two additional compounds, novobiocin and nalidixic acid, altered the pattern of viral DNA replication, especially the generation and processing of viral SC DNA, and also inhibited the production of DHBsAg. Several compounds acting at the level of viral SC DNA have now been identified and may offer potential for the management of chronic hepatitis B virus infection.

Animals↗
PubMed1989

High alkaline phosphatase activity and growth in preterm neonates.

In a study on 857 infants born preterm, high peak plasma alkaline phosphatase activity was independently related to slower growth rate in the neonatal period, and to a highly significant reduction in attained length at 9 months and 18 months post term. At 18 months the deficit in body length associated with peak neonatal plasma alkaline phosphase activity of 1200 IU/l or more was 1.6 cm (95% confidence interval 0.9 to 2.3 cm) after adjusting for confounding factors. The strength and magnitude of this association between high plasma alkaline phosphase activity and body length was greater than that for any other factor identified, including the infant's sex and the presence of fetal growth retardation. Data are presented that support the view that the high plasma alkaline phosphatase activity reflected early bone mineral substrate deficiency resulting in metabolic bone disease. We speculate that even silent early bone disease may interfere with the control of subsequent linear growth and emphasise the potential importance of providing preterm infants, especially those fed human milk, with adequate substrate for bone mineralisation.

Alkaline Phosphatase↗