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Biomedical subjects

C Holroyd

Publications and source records attributed to C Holroyd.

13 recordsLinked to original sources
PubMed2005

Mortality experience of male workers at a UK tin smelter.

BACKGROUND: Between 1937 and 1991, Capper Pass and Sons Limited operated a tin smelter complex in North Humberside, UK, at which employees were potentially exposed to a number of substances, including lead, arsenic, cadmium and natural series radionuclides. Decommissioning and site clearance continued until 1995. Between 1967 and 1995 the company was a subsidiary of Rio Tinto plc. AIMS: The aim was to identify any significant excess, or deficits, in mortality among former employees that might be attributable to factors associated with occupation. METHODS: We defined a cohort of 1462 males who had been employed for at least 12 months between 1/11/1967 and 28/7/1995, followed-up through to 31/12/2001. The mortality of the cohort was compared against that expected for both national and regional populations. RESULTS: Mortality from all causes and all cancers did not differ from that expected. Mortality from ischaemic heart disease showed a deficit and mortality from lung cancer showed a statistically significant excess. Mortality from smoking related diseases other than lung cancer showed a non-significant deficit. CONCLUSIONS: The pattern of lung cancer mortality is consistent with the hypothesis that the risk of lung cancer has been enhanced by occupational exposure to one or more carcinogens, the effect of which diminishes with time since exposure. The deficit in ischaemic heart disease may be attributed to a protective effect from manual labour. The results provide no evidence for attribution of other excess or deficits in mortality to factors associated with employment.

Adult↗
PubMed2001

Protein translocation machineries of peroxisomes.

Targeting of peroxisomal matrix and membrane proteins is performed by distinct transport machineries and requires the concerted action of at least 23 peroxins. Cargo recognition takes place in the cytosol and the multiple binding sites for peroxisomal signal sequence receptors at the peroxisomal membrane reflect the existence of an import cascade where the cargo-loaded receptors successively interact with different components of the import machinery. These interactions are likely to trigger conformational changes of the proteins within the import cascade which are required for the consecutive steps of peroxisomal protein import: docking, translocation, cargo release and receptor recycling.

Animals↗
PubMed2001

The use of the fluorescein disappearance test in the management of childhood epiphora.

PURPOSE. The fluorescein disappearance test (FDT) is reported to be an objective measure of lacrimal outflow in congenital non-canalisation of the nasolacrimal system. We introduced FDT into our evaluation of children with epiphora to investigate its sensitivity/specificity with regard to symptoms in a prospective study. We also examined the FDT against findings at syringing and probing (S&P) and persistence or resolution of symptoms on follow-up. METHODS. Over a period of 16 months, 88 consecutive children (median age 12 months; range 2.5-192) with epiphora were reviewed and FDT measured at 5 and 10 minutes; 66 FDT were evaluated for inter-observer variation in a masked fashion. S&P were scheduled on the basis of symptoms, abnormal FDT and age "1 year. Normal FDT prompted review. Younger children were observed for natural history and possible resolution with repeat FDT. Equivocal symptoms and normal FDT initiated discharge and telephone review. RESULTS. Inter-observer correlation coefficient = 0.86. Sensitivity/specificity of FDT was 76/76% at 5 minutes and 63/89% at 10 minutes, respectively. In patients under 1 year of age undergoing follow-up (29 patients; 38 eyes) FDT at 10 minutes correctly predicted persistence of symptoms in 65% and resolution in 66% of eyes (follow-up 3-14 months; mean 6); 23 patients (mean age 27 months; range 12-72) underwent S&P with positive surgical findings in 20 (87%). On review, symptoms had improved in 64% eyes (20/31). CONCLUSION. FDT at 5 minutes is an objective measure of symptoms with high inter-observer agreement and agreement with surgical findings. FDT read at 10 minutes may be useful to indicate the persistence or resolution of symptoms and guide patient management.

Journal Article↗
PubMed2000

A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function.

Sets of SNARE proteins mediate membrane fusion by assembling into core complexes. Multiple SNAREs are thought to function in different intracellular trafficking steps but it is often unclear which of the SNAREs cooperate in individual fusion reactions. We report that syntaxin 7, syntaxin 8, vti1b and endobrevin/VAMP-8 form a complex that functions in the fusion of late endosomes. Antibodies specific for each protein coprecipitate the complex, inhibit homotypic fusion of late endosomes in vitro and retard delivery of endocytosed epidermal growth factor to lysosomes. The purified proteins form core complexes with biochemical and biophysical properties remarkably similar to the neuronal core complex, although each of the four proteins carries a transmembrane domain and three have independently folded N-terminal domains. Substitution experiments, sequence and structural comparisons revealed that each protein occupies a unique position in the complex, with syntaxin 7 corresponding to syntaxin 1, and vti1b and syntaxin 8 corresponding to the N- and C-terminal domains of SNAP-25, respectively. We conclude that the structure of core complexes and their molecular mechanism in membrane fusion is highly conserved between distant SNAREs.

Amino Acid Sequence↗
PubMed2000

The R-SNARE endobrevin/VAMP-8 mediates homotypic fusion of early endosomes and late endosomes.

Endobrevin/VAMP-8 is an R-SNARE localized to endosomes, but it is unknown in which intracellular fusion step it operates. Using subcellular fractionation and quantitative immunogold electron microscopy, we found that endobrevin/VAMP-8 is present on all membranes known to communicate with early endosomes, including the plasma membrane, clathrin-coated pits, late endosomes, and membranes of the trans-Golgi network. Affinity-purified antibodies that block the ability of endobrevin/VAMP-8 to form SNARE core complexes potently inhibit homotypic fusion of both early and late endosomes in vitro. Fab fragments were as active as intact immunoglobulin Gs. Recombinant endobrevin/VAMP-8 inhibited both fusion reactions with similar potency. We conclude that endobrevin/VAMP-8 operates as an R-SNARE in the homotypic fusion of early and late endosomes.

Animals↗
PubMed1999

Fusion of endosomes involved in synaptic vesicle recycling.

Recycling of vesicles of the regulated secretory pathway presumably involves passage through an early endosomal compartment as an intermediate step. To learn more about the involvement of endosomes in the recycling of synaptic and secretory vesicles we studied in vitro fusion of early endosomes derived from pheochromocytoma (PC12) cells. Fusion was not affected by cleavage of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins synaptobrevin and syntaxin 1 that operate at the exocytotic limb of the pathway. Furthermore, fusion was inhibited by the fast Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid but not by the slow Ca(2+) chelator EGTA. Endosome fusion was restored by the addition of Ca(2+) with an optimum at a free Ca(2+) concentration of 0.3 x 10(-6) M. Other divalent cations did not substitute for Ca(2+). A membrane-permeant EGTA derivative caused inhibition of fusion, which was reversed by addition of Ca(2+). We conclude that the fusion of early endosomes participating in the recycling of synaptic and neurosecretory vesicles is mediated by a set of SNAREs distinct from those involved in exocytosis and requires the local release of Ca(2+) from the endosomal interior.

Animals↗
PubMed1995

Forms of early walking.

Children in the first weeks of independent locomotion display a wide variety of walking forms. The walking forms differ in mechanical strategy and concern with balance. Three extreme walking forms are presented: the Twister, who uses trunk twist, the Faller, who uses gravity, and the Stepper, who remains balanced as much as possible. Each walking form is presented as a "d-space", a mathematical format combining continuous and discrete aspects, developed to express the sequence and pattern of a movement without the inappropriate precision of a physical trajectory. The three d-spaces represent analyses of three extreme modes of early walking. They are used to generate the variety of early walking forms and to predict mixtures of mechanical strategies as children mature and converge to more similar walking forms over the first few months of independent locomotion.

Biomechanical Phenomena↗
PubMed1993

Differential expression of cyclic AMP-dependent protein kinase isozymes in normal human melanocytes and malignant melanomas.

Analysis of cyclic AMP-dependent protein kinase catalytic (C) and regulatory (R) subunits in normal human melanocytes and malignant melanomas demonstrated molar excess of regulatory over catalytic subunit in both cell types. Overall, greater catalytic activity, as a measure of C subunit, and cyclic AMP binding activity, as a measure of R subunit, were detected in metastatic compared to primary melanomas compared to normal human melanocytes. The protein kinase-specific R subunits, expressed in both melanocytes and malignant melanomas, were identified as RI-alpha and RII-alpha. Differences were noted for the ratios of RI/RII and RI holoenzyme/free RI subunit among different melanomas.

Base Sequence↗
PubMed1975

Tape/slide programmes for independent study. Methods of presentation to students.

Programmed audio tape/slide presentations have been presented to students by a variety of methods, (a) individual or pairs of students using automatic equipment in study booths; (b) students using simple portable equipment in or out of the learning centre; (c) groups of students in which discussion was encouraged; and (d) groups of students in which the student answered the questions individually without discussion. Each method has its advantages and disadvantages. With the exception of the groups without discussion, all were popular and chosen by a significant number of students as the method of choice. Automatic equipment in study booths was the most popular single method though the use of simple portable equipment had particular advantages. The majority of students prefer to have access to more than one method of presentation and attempts should be made to provide the learner with a variety of opportunities. The use of individual learning materials by groups of students should be further explored.

Attitude↗