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1.  Crystal structure of Bacillus subtilis YckF: structural and functional evolution⋆ 
Journal of structural biology  2004;148(1):98-109.
The crystal structure of the YckF protein from Bacillus subtilis was determined with MAD phasing and refined at 1.95Å resolution. YckF forms a tight tetramer both in crystals and in solution. Conservation of such oligomerization in other phosphate sugar isomerases indicates that the crystallographically observed tetramer is physiologically relevant. The structure of YckF was compared to with its ortholog from Methanococcus jannaschii, MJ1247. Both of these proteins have phosphate hexulose isomerase activity, although neither of the organisms can utilize methane or methanol as source of energy and/or carbon. Extensive sequence and structural similarities with MJ1247 and with the isomerase domain of glucosamine-6-phosphate synthase from Escherichia coli allowed us to group residues contributing to substrate binding or catalysis. Few notable differences among these structures suggest possible cooperativity of the four active sites of the tetramer. Phylogenetic relationships between obligatory and facultative methylotrophs along with B. subtilis and E. coli provide clues about the possible evolution of genes as they loose their physiological importance.
PMCID: PMC2792015  PMID: 15363790
Protein structure initiative; Crystal structure; MAD phasing; Oligomerization; Tetramer; Putative active site; Catalytic Glu-152; Evolutionary pathway; Gene hybridization; Diminished physiological role
2.  Accident and emergency attendance rates: variation among patients from different general practices. 
As a consequence of the 1989 National Health Service review health authorities are likely to take a greater interest in patterns of use of secondary care services by patients of different general practitioners. Use of accident and emergency departments has been shown to predict subsequent use of other hospital services. If meaningful comparisons are to be made between practices it is important to identify factors other than variation in clinical practice which influence attendance at accident and emergency departments. A one in 20 sample of patients attending an accident and emergency department was studied. Patients were aggregated by general practice and by electoral ward of residence, and the influence of a range of variables was examined using multiple regression. For both groups of patients distance from an accident and emergency department was an important factor in the rate of attendance. It was possible to examine the effect of several socioeconomic variables in the analysis by electoral ward: these were not associated significantly with attendance rates. Similarly, in the analysis by practice, mean list size per partner could not explain variation in attendance rates. This study supports others which have indicated that distance from an accident and emergency department must be taken into account when interpreting attendance rates.
PMCID: PMC1371242  PMID: 2115351
3.  Aseptic meningitis associated with high dose intravenous immunoglobulin therapy. 
Two cases of aseptic meningitis occurred in temporal association with high dose intravenous immunoglobulin therapy to treat thrombocytopenia. In neither case was any other aetiological agent identified and both patients completely recovered within a few days. This phenomenon has been reported in only one previous paediatric case.
PMCID: PMC1014401  PMID: 2030359
4.  Salmonella in a chicken hatchery. 
The Ulster Medical Journal  1987;56(2):157-159.
PMCID: PMC2448232  PMID: 3328363
6.  Locations for renal services--patient satisfaction surveys. 
The Ulster Medical Journal  1998;67(2):110-114.
Renal services have been given priority in recent years in an attempt to align them with levels of provision in other European countries. A survey of patients receiving renal replacement therapy in the Northern Ireland Regional Centre, Belfast, was carried out to ascertain their views on services (survey I). After the establishment of a Northern Health and Social Services Board (NHSSB) sub-regional unit in 1995, the survey was repeated for patients attending the new unit (survey II). In survey I, 53% NHSSB patients responded. Travelling time to and from hospital was a major issue for the majority of patients, with 33% of haemodialysis patients receiving twice weekly treatment unwilling to attend more frequently, even if clinically advised to do so. In survey II, 60% of patients responded. Travel times to the sub-regional unit were significantly shorter and patients felt it provided a similar or better standard of service, compared with the regional centre. All the twice weekly haemodialysis patients would increase to thrice weekly if clinically advised to do so. The study underlines the importance of locating dialysis facilities closer to patients' homes.
PMCID: PMC2448983  PMID: 9885547
8.  Expanding access to coronary artery bypass surgery: who stands to gain? 
British Heart Journal  1995;73(2):129-133.
OBJECTIVE--To determine the perceptions of general practitioners (GPs) about the benefits of coronary artery bypass surgery, in terms of gains in life expectancy, for different groups of patients. DESIGN--A questionnaire survey of all GPs in Northern Ireland. SETTING--A survey conducted collaboratively by the departments of public health medicine in each of the four health boards in the province, serving a total population of 1.5 million. MAIN OUTCOME MEASURES--The median and mean gain in life expectancy perceived by groups of doctors for smoking and non-smoking male and female 55 year old patients. The percentage of 50 year old and 70 year old non-smoking patients considered likely to have their lives extended with bypass surgery. Differences were assessed using the Mann-Whitney U test for unpaired samples and the Wilcoxon signed rank tests for paired. RESULTS--541 GPs replied (response rate 56%). The median (and mean) perceived gain in life expectancy after cardiac surgery for non-smoking 55 year old subjects was 120 (104) months for men and 120 (112) months for women (z = 6.42; P < 0.0001; Wilcoxon signed rank test). For male and female smokers of the same age, the perceived gains were 48 (47) and 60 (52) months respectively (z = 6.72; P < 0.0001; Wilcoxon signed ranks test), both figures being significantly different than for non-smokers. The median (and mean) percentage of patients that the doctors considered would have their lives extended by bypass surgery was 70 (64) of every 100 "young" patients and 40 (42) of every 100 "old" patients, (z = 16.2; P < 0.0001). CONCLUSIONS--These results point to a significant overestimation of the benefits of coronary artery bypass surgery by GPs in Northern Ireland and to a need to develop guidelines for referral.
PMCID: PMC483778  PMID: 7696021
9.  Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography. 
The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.
PMCID: PMC485480  PMID: 7931375
10.  Is choice of general practitioner important for patients having coronary artery investigations? 
Quality in Health Care  1994;3(1):17-22.
OBJECTIVE--To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment. DESIGN--Postal questionnaire survey. SETTING--Collaborative survey by the departments of public health medicine in each of the four health boards in Northern Ireland, serving a total population of 1.5 million. SUBJECTS--All (962) GPs. MAIN MEASURES--The relation between GPs' referral decisions and patients' age, sex, employment status, home circumstances, smoking habits, and obesity. RESULTS--541 GPs replied (response rate 56%). Most were "neutral" towards a patient's sex (428, 79%), weight (331, 61%), smoking habit (302, 56%), employment status (431, 80%), and home circumstances (408, 75%) in making decisions about referral. In assigning priority for surgery most were neutral towards the patient's sex (459, 85%), employment status (378, 70%), and home circumstances (295, 55%). However, most GPs (518, 95%) said that younger patients were more likely to be referred, and a significant minority were less likely to refer patients who smoked (202, 37%) and obese patients (175, 32%) and more likely to refer employed patients (97, 18%) and those with dependents (117, 22%) (compared with patients with otherwise comparable clinical characteristics); these views paralleled the priority which GPs assigned these groups. The stated likelihood of referral of young patients was independent of the GPs' belief in ability to benefit from revascularisation, but propensity to refer and perception of benefit were significantly associated for all other patient characteristics. CONCLUSION--GPs' weighting of certain characteristics in reaching decisions about referral for angiography is not uniform and may contribute to unequal access to revascularisation services for certain patient groups.
PMCID: PMC1055177  PMID: 10136255
12.  Junior medical posts in the NHSSB: what the doctors think. 
The Ulster Medical Journal  1992;61(1):35-38.
This survey of house officers in the Northern Health and Social Services Board in Northern Ireland demonstrated that they have complaints not just about the number of hours they work. Thirty-nine per cent noted poor standards of food and/or accommodation. Many complained about doing routine "non-medical" work and thought that their working conditions would be improved by nurses having more responsibility for managing intravenous medication and the employment of phlebotomists. Doctors expressed concerns about a lack of career counselling and availability of training in research methods in their posts.
PMCID: PMC2448788  PMID: 1621300
13.  Perinatal mortality in Northern Ireland: where are we now? 
The Ulster Medical Journal  1989;58(1):40-45.
Perinatal mortality in Northern Ireland has been declining over the last 30 years, but the factors which may account for this fall have not been clearly delineated. Crude perinatal mortality figures yield very little insight into the problem, and meaningful management statistics are urgently required if service performance is to be reasonably assessed. This paper sets out the case for birth-weight standardisation and explores the utility of a broad diagnostic taxonomy of causes of death.
PMCID: PMC2448549  PMID: 2773170
14.  Surgeons' attitudes to some aspects of day case surgery 
The Ulster Medical Journal  1986;55(1):61-69.
The level of day case surgery is much lower in Northern Ireland than in England. A questionnaire was sent to all 55 consultant general surgeons in Northern Ireland to assess attitudes to this form of care and 51 (93%) replied. They were asked about the suitability of five procedures for day surgery. The three minor procedures of vasectomy, cystoscopy and gastroscopy were regarded as suitable or very suitable by 50 (98% of those who replied), 48 (94%) and 48 (94%) respectively. For the two intermediate procedures, 25 (49%) regarded the repair of inguinal hernia as suitable for day case surgery and 22 (43%) ligation of varicose veins. When asked about eight factors limiting their use of day surgery for inguinal hernia repair, the two most frequently rated as important were ‘home conditions’ and ‘level of provision of domiciliary care’ (both by 44 (86%) of the surgeons). Of factors which might promote their use of day surgery for this operation the two most important were ‘more efficient use of health service resources’ (71%) and the ‘ability to convalesce at home’ (67%). The problem of under-reporting of day cases and the importance of accurate statistics are considered.
PMCID: PMC2448102  PMID: 3739063
19.  Immunization with heat-killed Mycobacterium vaccae stimulates CD8+ cytotoxic T cells specific for macrophages infected with Mycobacterium tuberculosis. 
Infection and Immunity  1997;65(11):4525-4530.
Immune responses to Mycobacterium tuberculosis are analyzed in mice which have been immunized with Mycobacterium vaccae to examine novel ways of altering protective immunity against M. tuberculosis. The spleen cells of mice immunized with M. vaccae proliferate and secrete gamma interferon (IFN-gamma) in response to challenge with live M. tuberculosis in vitro. Immunization with M. vaccae results in the generation of CD8+ T cells which kill syngeneic macrophages infected with M. tuberculosis. These effector cytotoxic T cells (CTL) are detectable in the spleen at 2 weeks after immunization with M. vaccae but cannot be found in splenocytes 3 to 6 weeks postimmunization. However, M. tuberculosis-specific CTL are revealed following restimulation in vitro with heat-killed M. vaccae or M. tuberculosis, consistent with the activation of memory cells. These CD8+ T cells secrete IFN-gamma and enhance the production of interleukin 12 when cocultured with M. tuberculosis-infected macrophages. It is suggested that CD8+ T cells with a cytokine secretion profile of the Tc1 class may themselves maintain the dominance of a Th1-type cytokine response following immunization with M. vaccae. Heat-killed M. vaccae deserves attention as an alternative to attenuated live mycobacterial vaccines.
PMCID: PMC175650  PMID: 9353029
21.  Necrotising fasciitis. 
BMJ : British Medical Journal  1994;308(6942):1453-1454.
PMCID: PMC2540307  PMID: 8019275
23.  708 Common and 2010 rare DISC1 locus variants identified in 1542 subjects: analysis for association with psychiatric disorder and cognitive traits 
Molecular Psychiatry  2013;19(6):668-675.
A balanced t(1;11) translocation that transects the Disrupted in schizophrenia 1 (DISC1) gene shows genome-wide significant linkage for schizophrenia and recurrent major depressive disorder (rMDD) in a single large Scottish family, but genome-wide and exome sequencing-based association studies have not supported a role for DISC1 in psychiatric illness. To explore DISC1 in more detail, we sequenced 528 kb of the DISC1 locus in 653 cases and 889 controls. We report 2718 validated single-nucleotide polymorphisms (SNPs) of which 2010 have a minor allele frequency of <1%. Only 38% of these variants are reported in the 1000 Genomes Project European subset. This suggests that many DISC1 SNPs remain undiscovered and are essentially private. Rare coding variants identified exclusively in patients were found in likely functional protein domains. Significant region-wide association was observed between rs16856199 and rMDD (P=0.026, unadjusted P=6.3 × 10−5, OR=3.48). This was not replicated in additional recurrent major depression samples (replication P=0.11). Combined analysis of both the original and replication set supported the original association (P=0.0058, OR=1.46). Evidence for segregation of this variant with disease in families was limited to those of rMDD individuals referred from primary care. Burden analysis for coding and non-coding variants gave nominal associations with diagnosis and measures of mood and cognition. Together, these observations are likely to generalise to other candidate genes for major mental illness and may thus provide guidelines for the design of future studies.
PMCID: PMC4031635  PMID: 23732877
DISC1; recurrent major depressive disorder; sequencing
25.  Homologs of Mycobacterium leprae 18-kilodalton and Mycobacterium tuberculosis 19-kilodalton antigens in other mycobacteria. 
Infection and Immunity  1993;61(4):1509-1515.
Most of the antigens of Mycobacterium leprae and M. tuberculosis that have been identified are members of stress protein families, which are highly conserved throughout many diverse species. Of the M. leprae and M. tuberculosis antigens identified by monoclonal antibodies, all except the 18-kDa M. leprae antigen and the 19-kDa M. tuberculosis antigen are strongly cross-reaction between these two species and are coded within very similar genes. Studies of T cell reactivity against mycobacterial antigens have indicated that M. tuberculosis bears epitopes that are cross-reactive with the M. leprae 18-kDa antigen, but attempts to identify an 18-kDa antigen-like protein or protein coding sequence in M. tuberculosis have been unsuccessful. We have used a combination of low-stringency DNA hybridization and polymerase chain reaction techniques to identify, isolate, and sequence genes from M. avium and M. intracellulare that are very similar to the 18-kDa antigen gene of M. leprae and others that are homologs of the 19-kDa antigen gene of M. tuberculosis. Unlike M. leprae, which contains a single 18-kDa antigen gene, M. avium and M. intracellulare each have two 18-kDa antigen coding sequences. Although the M. leprae, M. avium, and M. intracellulare 18-kDa antigen genes are all very similar to one another, as are the M. tuberculosis, M. avium, and M. intracellulare 19-kDa antigen genes, we have been unable to detect any 18-kDa antigen-like coding sequences in DNA from M. tuberculosis.
PMCID: PMC281393  PMID: 8454357

Results 1-25 (28)