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Biomedical subjects

J Bush

Publications and source records attributed to J Bush.

At least 19 recordsLinked to original sources
PubMed2006

Impacts of participating in confidential enquiry panels: a qualitative study.

OBJECTIVE: To describe the impacts of participating in confidential enquiry panels for the Confidential Enquiry into Stillbirths and Deaths in Infancy. DESIGN: Qualitative interview study. SETTING: The former northern health region of England. SAMPLE: Eighteen health professionals who had participated in at least one confidential enquiry panel. METHODS: Semistructured one-to-one interviews using purposive sampling; transcripts were analysed by identifying recurring themes. Data were organised and coded using NUD*IST. MAIN OUTCOME MEASURES: Views on the impacts of participation on clinical practice and views on the strengths and limitations of confidential enquiries. RESULTS: Participants valued attendance at panels as a learning experience that provoked reflection on their own clinical practice. Participants felt that taking part had a positive impact on their clinical thinking and practice by increasing their awareness of standards of care. These impacts occurred through both the detailed examination of cases and the interaction with colleagues from different disciplines and hospitals. Learning impacts were cascaded to colleagues through informal discussion and teaching. Concrete examples of changes in practice at the organisational level, stimulated by panel attendance, were reported. CONCLUSIONS: The confidential enquiry approach was supported not only as an effective way of assessing care but also as a valuable learning experience that motivated change in clinical practice. Local benefits of nationally coordinated confidential enquiries should be valued and supported in their future development. Wide multidisciplinary participation in enquiry panels coordinated through regional clinical networks should be promoted.

Committee Membership↗
PubMed2005

Endoanal magnetic resonance imaging of fistula-in-ano: a comparison of STIR with gadolinium-enhanced techniques.

PURPOSE: To compare a STIR sequence with gadolinium-enhanced techniques on endoanal magnetic resonance (MR) imaging of fistulas-in-ano by correlating the findings with those at surgery. MATERIAL AND METHODS: Twenty-two consecutive patients with clinical suspicion of perianal sepsis were studied using an endoanal coil followed immediately by a phased array coil. T1-weighted precontrast and postcontrast and STIR images in transverse and coronal planes were produced with each coil and analysed by noting the presence and site of a collection, primary track, the position of any internal opening, and subcutaneous or supralevator extension. An "expert" and also a "trainee" radiologist assessed the images. Operative findings were similarly recorded. The Fisher exact test was used to compare imaging with surgery. Interobserver variation was calculated using a kappa statistic. RESULTS: Of 22 patients with suspected fistulas, 8 were simple, 4 were complex, and 3 were superficial sinuses. Five had no anal pathology, 1 had anal excoriation, and 1 had a polyp. At surgery, 6 intersphincteric, 1 transsphincteric, 8 extrasphincteric, no supralevator collections, and 9 internal openings were noted. The overall sensitivity and specificity for detecting these were 75% and 64%, respectively, for STIR imaging, and 58.3% and 62.8% for gadolinium-enhanced imaging. There was good agreement between the "trainee" and the "expert" in the interpretation of images (kappa=0.7). CONCLUSION: A STIR sequence is more sensitive overall than gadolinium-enhanced techniques on endoanal magnetic resonance imaging of fistulas-in-ano because of increased sensitivity in detecting the internal opening. A combination of endoanal and phased array techniques using STIR imaging sequences is valuable preoperative assessment in both simple and complex cases.

Adult↗
PubMed2002

Cloning and expression of a lombricine kinase from an echiuroid worm: insights into structural correlates of substrate specificity.

Phosphagen kinases constitute a large family of enzymes catalyzing the reversible phosphorylation of guanidino acceptor compounds. These guanidino substrates differ substantially in size and chemical properties. In spite of the appearance of X-ray crystal structures for two members of this family, creatine kinase (CK) and arginine kinase (AK), the structural correlates of substrate specificity remain to be fully elucidated. We have determined the cDNA and deduced amino acid sequences for lombricine (guanidinethylphosphoserine) kinase (LK) from the echiuroid worm Urechis caupo and expressed the cDNA in Escherichia coli. The recombinant protein was purified by affinity chromatography and showed high capacity for phosphorylation of lombricine. Phosphagen kinases consist of a small, N-terminal domain and a much larger domain connected by a linker sequence. A key event in catalysis in CK and AK, and certainly all other phosphagen kinases, is a large conformational change involving involving a rotation of the two domains and the movement of two highly conserved flexible loops (one located in the small domain; the other located in the large domain of these enzymes) which clamp down on the substrates. Multiple sequence alignments of Urechis LK with the only other LK sequence available and CK, AK and glycocyamine kinase sequences, confirm the importance of the small flexible loop located in the N-terminal domain of phosphagen kinases as one component of the structural determinants of guanidine specificity. The role of the other flexible loop in the large domain in terms of substrate specificity remains questionable.

Amino Acid Sequence↗
PubMed2002

A prospective, case controlled study of the natural history of diabetic retinopathy and maculopathy after uncomplicated phacoemulsification cataract surgery in patients with type 2 diabetes.

AIM: To determine if uncomplicated phacoemulsification cataract surgery is associated with an accelerated rate of progression of diabetic retinopathy or maculopathy postoperatively. METHODS: A prospective trial of 50 type 2 diabetics undergoing monocular phacoemulsification cataract surgery by a single consultant surgeon. The grade of diabetic retinopathy and diabetic maculopathy in the operated and non-operated fellow eye was assessed preoperatively and for 12 months postoperatively. RESULTS: Overall, retinopathy progression was observed in 11 patients. In seven the retinopathy progressed in both eyes, in three it progressed in the operated eye alone, and in one it progressed in the fellow eye alone. Macular oedema was observed in 13 eyes postoperatively. Four had transient pseudophakic cystoid macular oedema and nine true diabetic maculopathy. Where maculopathy progressed it did so symmetrically in five patients, it progressed in the operated eye alone in four patients, and the fellow eye alone in two patients. There was no significant difference in the number of operated and fellow eyes whose retinopathy or maculopathy progressed postoperatively. In both the operated (OE) and non-operated (NoE) eyes retinopathy progression was associated with a higher mean HbA(1)C (OE p=0.003; NoE p=0.001) and insulin treatment (OE p=0.008, NoE p=0.04). CONCLUSION: Uncomplicated phacoemulsification cataract surgery does not cause acceleration of diabetic retinopathy postoperatively and any progression that is observed probably represents the natural history of the disease. Although macular oedema is common after cataract surgery it may follow a benign course and in many patients the development of clinically significant macular oedema postoperatively probably represents natural disease progression rather than being a direct effect of surgery.

Aged↗
PubMed2001

'Even the birds round here cough': stigma, air pollution and health in Teesside.

In this paper we explore how the presence of hazardous industry may affect the identity of a place and the people who live there. Drawing on Goffman's seminal work on stigma - together with recent debates on environmental and technological stigma - we extend the concepts of difference and spoiled identity from the individual to place. The paper is based on a qualitative study which explored public perceptions of the risks to health from air pollution in Teesside, a heavily industrialised area in north-east England. We did not set out to study stigma per se in this study, but emergent themes produced by grounded theory analysis highlighted the way in which the presence of technologies, air pollution, poor health and social exclusion may be used as 'discrediting' characteristics, to stigmatise one place, whilst confirming the usualness of another. We demonstrate place stigma as a complex, multiple and re-inforcing concept.

Adolescent↗
PubMed2001

Rab11-like GTPase associates with and regulates the structure and function of the contractile vacuole system in dictyostelium.

Screening of a cDNA library revealed the existence of a Dictyostelium cDNA encoding a protein 80% identical at the amino acid level to mammalian Rab11. Subcellular fractionation and immunofluorescence studies revealed that DdRab11 was exclusively associated with the ATPase proton pump-rich contractile vacuole membrane system, consisting of a reticular network and bladder-like vacuoles. Video microscopy of cells expressing GFP-DdRab11 revealed that this Rab was associated with contractile vacuolar bladders undergoing formation, fusion and expulsion of water. The association of DdRabll with contractile vacuole membranes was disrupted when cells were exposed to either hypo-osmotic conditions or an inhibitor of the ATPase proton pump. Cells that overexpressed a dominant negative form of DdRab11 were analyzed biochemically and microscopically to measure changes in the structure and function of the contractile vacuole system. Compared with wild-type cells, the dominant negative DdRab11-expressing cells contained a more extensive contractile vacuole network and abnormally enlarged contractile vacuole bladders, most likely the result of defects in membrane trafficking. In addition, the mutant cells enlarged, detached from surfaces and contained large vacuoles when exposed to water, suggesting a functional defect in osmotic regulation. No changes were observed in mutant cells in the rate of fluid phase internalization or release, suggesting the DdRab11-mediated membrane trafficking defects were not general in nature. Surprisingly, the rate of phagocytosis was increased in the dominant negative DdRab11-expressing cells when compared with control cells. Our results are consistent with a role for DdRab11 in regulating membrane traffic to maintain the normal morphology and function of the contractile vacuole.

Adenosine Triphosphatases↗
PubMed2000

Expansion of hematopoietic stem cells in vitro as a model system for human tissue engineering.

The authors have taken a new approach to finding optimal conditions for stimulating conservative division of single isolated CD34(+)lin(-) hematopoietic stem cell candidates from human umbilical cord blood. The approach required the design and development of a novel multi-well single cell combinatorial culture system. This system incorporates the use of a multi-well tissue culture plate in which each well receives a single hematopoietic stem cell candidate. During an experiment lasting several days to weeks, each cell-containing well is moved sequentially and serially to a microscopic imaging system. This movement is facilitated by computer control of a motorized stage and stabilization of the experiment in an environmentally controlled Biobox built on the microscopic stage. New image analysis software facilitates tracking of cell movement, recording the time of cell division, and immunophenotyping of multiple, individual, or recently doubled cells in real time by a robotically controlled pipetting station. The principles of single cell culture should help solve many problems in human hematopoietic stem cell expansion and may be applicable to a wide range of other systems of interest in tissue engineering.

Animals↗
PubMed2000

"It's just part of being a woman": cervical screening, the body and femininity.

This paper explores the importance of cervical screening discourses in framing women's perceptions of femininity. In-depth interviews with 35 women -- which focused on experiences of, and feelings about, cervical screening -- highlighted how medical discourses embedded within the cervical screening programme shape the feelings of normalcy and sense of obligation associated with having smear tests. With the introduction of the invitation based call and re-call programme in the UK, cervical screening has moved from an ad hoc system to a programme of mass surveillance and regulation of women's bodies. The paper highlights the ways in which cervical screening discourses were negotiated, accepted and resisted by the women interviewed. Possible theoretical explanations as to why cervical screening discourses have become important in framing femininity are discussed. The paper concludes by suggesting that the meaning and objective of mass screening programmes must be brought into question and reconsidered by feminists and those involved with the planning, implementation, research and use of screening services.

Adult↗
PubMed2000

Effect of maternal weight gain on infant birth weight.

OBJECTIVE: To ascertain whether increased weight gain during pregnancy resulted in higher birth weight infants. METHODS: A database was constructed from valid data of a sample of 159 healthy women between 19 to 37 years of age. The inclusion criteria were: maternal age of 19-37 years, term gestations (37-42 weeks), a baseline weight obtained at 0-15 weeks gestation, and a final weight obtained within 2 weeks of delivery. Weight gain was calculated by subtracting baseline weight from the final weight. A documented height enabled calculation of BMI. A negative screen for gestational diabetes was required. RESULTS: Women with lower first trimester BMI (< 25) had infants of lower birth weight than women of higher BMI (> 25). Women with lower gain (< 35 lbs) delivered smaller infants than women with higher gain (> 35 lbs). Women of higher BMI and higher gain delivered the largest infants (F = 5.37; p = 0.0015). Underweight women (BMI < 19) gained less weight than women of normal weight (BMI 19-25), who gained the most weight. Obese women (BMI > 29) gained the least weight (F = 6.26; p = 0.0005). CONCLUSION: The results confirmed that excessive maternal weight gain in pregnancy (> 35 lbs), does result in higher birth weight infants.

Adult↗
PubMed2000

The Internet as cure for inefficient office business processes.

Application service providers (ASPs) offer medical groups unprecedented efficiency in practice management via the Internet at low subscription rates. With online, real-time access to registration, scheduling, eligibility verification, claims processing and collection functions, medical groups can streamline workflow and better care for patients, while optimizing their reimbursement potential.

Contract Services↗
PubMed1999

A mutation that separates the RasG signals that regulate development and cytoskeletal function in Dictyostelium.

The expression of an activated RasG, RasG-G12T, in vegetative cells of Dictyostelium discoideium produced an alteration in cell morphology. Cells underwent a transition between an extensively flattened form that exhibited lateral membrane ruffling to a less flattened form that exhibited prominent dorsal membrane ruffling. These rasG-G12T transformants exhibited a redistribution of F-actin at the cell periphery and did not undergo the rapid contraction upon refeeding that is characteristic of wild-type cells. These results suggest a role for RasG in regulating cytoskeletal rearrangement in D. discoideum. We had shown previously that expression of rasG-G12T inhibited starvation induced aggregation (M. Khosla et al., 1996, Mol. Cell. Biol. 16, 4156-4162). rasG-G12T genes containing secondary mutations were transformed into cells to test whether the effects of rasG-G12T were transmitted through a single downstream effector. Cells expressing rasG-G12T/T35S or rasG-G12T/Y40C (secondary mutations within the effector domain) exhibited normal morphology and underwent normal aggregation, suggesting that signaling through the effector domain was required for both the morphological and the development changes induced by rasG-G12T. In contrast, cells expressing rasG-G12T/T45Q (a secondary mutation in the effector distal flanking domain) exhibited normal aggregation but a morphology indistinguishable from that of rasG-G12T transformants. This result suggests that RasG regulates developmental and cytoskeletal functions by direct interaction with more than one downstream effector.

Animals↗
PubMed1999

Expansion of hematopoietic stem cells in vitro as a model system for human tissue engineering.

The authors have taken a new approach to finding optimal conditions for stimulating conservative division of single isolated CD34 + lin hematopoietic stem cell candidates from human umbilical cord blood. The approach required the design and development of a novel multi-well single cell combinatorial culture system. This system incorporates the use of a multi-well tissue culture plate in which each well can receive a single hematopoietic stem cell candidate. Sequential movement of each cell-containing well to a microscopic imaging system, serially over a several-day to several-week experiment, is facilitated by computer control of a motorized stage and stabilization of the experiment in an environmentally controlled Bio-box built on the microscope stage. New image analysis software facilitates in the tracking of cell movement, recording of the time of cell division, and immunophenotyping of each of multiple individual or recently doubled cells in real time by a robotically controlled pipetting station. The principles of single cell culture should help solve many problems in human hematopoietic stem cell expansion and also may be applicable to a wide range of other systems of interest in tissue engineering.

Biotechnology↗
PubMed1998

Overexpression of a novel rho family GTPase, RacC, induces unusual actin-based structures and positively affects phagocytosis in Dictyostelium discoideum.

Rho family proteins have been implicated in regulating various cellular processes, including actin cytoskeleton organization, endocytosis, cell cycle, and gene expression. In this study, we analyzed the function of a novel Dictyostelium discoideum Rho family protein (RacC). A cell line was generated that conditionally overexpressed wild-type RacC three- to fourfold relative to endogenous RacC. Light and scanning electron microscopy indicated that the morphology of the RacC-overexpressing cells [RacC WT(+) cells] was significantly altered compared with control cells. In contrast to the cortical F-actin distribution normally observed, RacC WT(+) cells displayed unusual dorsal and peripheral F-actin-rich surface blebs (petalopodia, for flower-like). Furthermore, phagocytosis in the RacC WT(+) cells was induced threefold relative to control Ax2 cells, whereas fluid-phase pinocytosis was reduced threefold, primarily as the result of an inhibition of macropinocytosis. Efflux of fluid-phase markers was also reduced in the RacC WT(+) cells, suggesting that RacC may regulate postinternalization steps along the endolysosomal pathway. Treatment of cells with Wortmannin and LY294002 (phosphatidylinositol 3-kinase inhibitors) prevented the RacC-induced morphological changes but did not affect phagocytosis, suggesting that petalopodia are probably not required for RacC-induced phagocytosis. In contrast, inactivating diacylglycerol-binding motif-containing proteins by treating cells with the drug calphostin C completely inhibited phagocytosis in control and RacC WT(+) cells. These results suggest that RacC plays a role in actin cytoskeleton organization and phagocytosis in Dictyostelium.

Androstadienes↗
PubMed1998

Novel HLA-A and HLA-B alleles.

Nine novel HLA-A and HLA-B alleles are described: A*2609, A*6803, A*6806, B*1539, B*1540, B*2712, B*4103, B*5109, and B*5603. Most appear to have arisen by gene conversion events. B*5603 appears to have arisen by a reciprocal recombination event joining exon 2 of a B*55/ *56 allele with exon 3 of a B*15 allele. Serologically, the antigen encoded by this allele types with broad B22- and Bw6-specific alloantisera. Also unique, the antigen encoded by B*2712 does not react with B27-specific alloantisera but does react with Bw6-specific alloantisera.

Alleles↗
PubMed1997

Inactivation of two Dictyostelium discoideum genes, DdPIK1 and DdPIK2, encoding proteins related to mammalian phosphatidylinositide 3-kinases, results in defects in endocytosis, lysosome to postlysosome transport, and actin cytoskeleton organization.

Phosphatidylinositide 3-kinases (PI3-kinases) have been implicated in controlling cell proliferation, actin cytoskeleton organization, and the regulation of vesicle trafficking between intracellular organelles. There are at least three genes in Dictyostelium discoideum. DdPIK1, DdPIK2, and DdPIK3, encoding proteins most closely related to the mammalian 110-kD PI-3 kinase in amino acid sequence within the kinase domain. A mutant disrupted in DdPIK1 and DdPIK2 (delta ddpik1/ddpik2) grows slowly in liquid medium. Using FITC-dextran (FD) as a fluid phase marker, we determined that the mutant strain was impaired in pinocytosis but normal in phagocytosis of beads or bacteria. Microscopic and biochemical approaches indicated that the transport rate of fluid-phase from acidic lysosomes to non-acidic postlysosomal vacuoles was reduced in mutant cells resulting in a reduction in efflux of fluid phase. Mutant cells were also almost completely devoid of large postlysosomal vacuoles as determined by transmission EM. However, delta ddpik1/ddpik2 cells functioned normally in the regulation of other membrane traffic. For instance, radiolabel pulse-chase experiments indicated that the transport rates along the secretory pathway and the sorting efficiency of the lysosomal enzyme alpha-mannosidase were normal in the mutant strain. Furthermore, the contractile vacuole network of membranes (probably connected to the endosomal pathway by membrane traffic) was functionally and morphologically normal in mutant cells. Light microscopy revealed that delta ddpik1/ddpik2 cells appeared smaller and more irregularly shaped than wild-type cells; 1-3% of the mutant cells were also connected by a thin cytoplasmic bridge. Scanning EM indicated that the mutant cells contained numerous filopodia projecting laterally and vertically from the cell surface, and fluorescent microscopy indicated that these filopodia were enriched in F-actin which accumulated in a cortical pattern in control cells. Finally, delta ddpik1/ddpik2 cells responded and moved more rapidly towards cAMP. Together, these results suggest that Dictyostelium DdPIK1 and DdPIK2 gene products regulate multiple steps in the endosomal pathway, and function in the regulation of cell shape and movement perhaps through changes in actin organization.

Actins↗
PubMed1997

Evidence for a recycling role for Rab7 in regulating a late step in endocytosis and in retention of lysosomal enzymes in Dictyostelium discoideum.

The mammalian small molecular weight GTPase Rab7 (Ypt7 in yeast) has been implicated in regulating membrane traffic at postinternalization steps along the endosomal pathway. A cDNA encoding a protein 85% identical at the amino acid level to mammalian Rab7 has been cloned from Dictyostelium discoideum. Subcellular fractionation and immunofluorescence microscopy indicated that Rab7 was enriched in lysosomes, postlysosomes, and maturing phagosomes. Cell lines were generated that overexposed Rab7 wild-type (WT), Rab7 Q67L (constitutively active form), and Rab7 T22N (dominant negative form) proteins. The Rab7 T22N cell line internalized fluid phase markers and latex beads (phagocytosis) at one-third the rate of control cells, whereas Rab7 WT and Rab7 Q67L cell lines were normal in uptake rates but exocytosed fluid phase faster than control cells. In contrast, fluid phase markers resided in acidic compartments for longer periods of time and were more slowly exocytosed from Rab7 T22N cells as compared with control cells. Light microscopy indicated that Rab7-expressing cell lines contained morphologically altered endosomal compartments. Compared with control cells, Rab7 WT- and Rab7 Q67L-expressing cells contained a reduced number of vesicles, the size of postlysosomes (> 2.5 microns) and an increased number of smaller vesicles, many of which were nonacidic; in control cells, > 90% of the smaller vesicles were acidic. In contrast, Rab7 T22N cells contained an increased proportion of large acidic vesicles relative to nonacidic vesicles. Radiolabel pulse-chase experiments indicated that all of the cell lines processed and targeted lysosomal alpha-mannosidase normally, indicating the lack of a significant role for Rab7 in the targeting pathway; however, retention of mature lysosomal hydrolases was affected in Rab7 WT and Rab7 T22N cell lines. Contrary to the results observed for the fluid phase efflux experiments, Rab7 T22N cells oversecreted alpha-mannosidase, whereas Rab7 WT cells retained this hydrolase as compared with control cells. These data support a model that Rab7 may regulate retrograde transport of lysosomal enzymes and the V-type H(+)-ATPase from postlysosomes to lysosomes coupled with the efficient release of fluid phase from cells.

Amino Acid Sequence↗