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Biomedical subjects

J Sim

Publications and source records attributed to J Sim.

At least 19 recordsLinked to original sources
PubMed2002

Series of incidents of Listeria monocytogenes non-invasive febrile gastroenteritis involving ready-to-eat meats.

AIMS: A series of cases and outbreaks of febrile noninvasive gastrointestinal disease involving 31 identified cases was investigated in terms of the numbers and types of Listeria monocytogenes present in the suspect foods (ready-to-eat meats) and clinical samples from cases. METHODS AND RESULTS: Foods and faecal samples involved in the incidents were tested for the presence and number of L. monocytogenes. Isolates were typed by macrorestriction analysis using pulsed-field gel electrophoresis. The foods contained high levels of L. monocytogenes, in one case 1.8 x 10(7) g-1. Faecal samples contained L. monocytogenes for up to 15 d after the contaminated food was consumed. All isolates from the food and faecal samples were of serotype 1/2 and were indistinguishable from one another by macrorestriction typing. CONCLUSIONS: It is likely that the meats were contaminated either during their manufacture after they had been cooked or by underprocessing. The long shelf lives on these products would have allowed the contaminating L. monocytogenes to grow to the high numbers measured in this study, causing food poisoning as described. SIGNIFICANCE AND IMPACT OF THE STUDY: Outbreaks of febrile noninvasive listeriosis are relatively rare. This report adds ready-to-eat meats to the range of foods that have acted as vehicles for such outbreaks.

Bacterial Typing Techniques↗
PubMed2002

Viral hepatitis in South African healthcare workers at increased risk of occupational exposure to blood-borne viruses.

The prevalence of hepatitis A, B and C antibodies was measured in a group of healthcare workers (HCWs) at increased risk of occupational acquisition of blood-borne viruses (N=402) from a large, urban referral hospital in South Africa. The aims of this study were to determine the immunity of HCWs to these agents and to recommend policy for the protection of HCWs against occupational exposure to viral hepatitis in this country. Race, sex and age were shown to be important factors influencing the presence of hepatitis A (HAV) antibodies. Most black HCWs (96.2%) are protected from HAV infection. Females have significantly higher HAV antibodies compared with males and antibodies increase with increasing age. Hepatitis B antibodies (anti-HBs) were found in 30.6% of HCWs. Anti-HBs levels were significantly associated with a past history of HBV vaccination. However, only a small proportion of HCWs (21.2%) could remember ever being immunized against HBV. For those individuals that did receive HBV vaccination (N=83), the mean number of years since their last vaccine was 6.2 years (SD +/- 3.5). HCV antibodies were found in 1.8% of HCWs at increased risk of occupational exposure. It was not possible to define whether these infections were occupationally acquired but genotyping of the HCV (in two of seven cases) showed genotype 5, the predominant South African genotype. New recommendations for the prevention of viral hepatitis in HCWs in South Africa are made, including pre-employment screening for HAV based on self-selection criteria, universal anti-HBs screening with HBV booster vaccination. HCV recommendations are based on appropriate education of HCWs about this infection and its prevention and a standardized post-exposure testing protocol.

Adult↗
PubMed2001

Mutation of N304 to leucine in Streptomyces clavuligerus deacetoxycephalosporin C synthase creates an enzyme with increased penicillin analogue conversion.

Superimposition of deacetoxycephalosporin C synthase (DAOCS) and isopenicillin N synthase (IPNS) structures revealed that R74, R160, R266 and N304 are strategically located in the catalytic cavity of Streptomyces clavuligerus DAOCS (scDAOCS) and are crucial for orchestrating different substrates. Substitutions at these sites to a hydrophobic leucine residue were expected to stabilize the hydrophobic substrate bound state. Substantial improvements in the biotransformation of penicillin G, ampicillin and amoxicillin to their respective cephalosporin moieties were observed using the N304L mutant scDAOCS. Thus, our results have demonstrated the enhancement of scDAOCS activity via critical computational analysis and site-directed mutagenesis of endogenous ligands.

Amino Acid Substitution↗
PubMed2001

The effect of introduction of universal childhood hepatitis B immunization in South Africa on the prevalence of serologically negative hepatitis B virus infection and the selection of immune escape variants.

The effect of universal hepatitis B vaccination on the prevalence of serologically negative hepatitis B virus infection (HBV) and the emergence of HBsAg variants is unknown. We prospectively studied two different cohorts of 12--24 month old children in South Africa. They consisted of the unvaccinated children (n=459) born before the introduction of universal vaccination and the vaccinated children (n=1213) between 1 and 2 years after the introduction of the vaccination program. The frequency of detecting HBV DNA by PCR was reduced from 6.5% in unvaccinated children to 0.3% in vaccinated children (P<0.00001). There were no unique amino acid substitutions within the major hydrophilic region of the S sequence in both pre- and post-vaccination samples. Universal childhood vaccination reduced the frequency of serologically negative HBV infection and did not necessarily lead to selection of escape variants.

Amino Acid Sequence↗
PubMed2001

The invariant F283 and its strategic position in the hydrophobic cleft of Streptomyces jumonjinensis isopenicillin N synthase active site are functionally important.

Isopenicillin N synthase (IPNS) and related non-haem iron-binding enzymes including deacetoxycephalosporin C synthase (DAOCS) are proposed to have structurally similar active centers. Sequence alignment and computational structural analyses of predicted structures revealed 11 highly conserved hydrophobic amino acid residues in 134 IPNS-related enzymes form a contiguous hydrophobic patch in the IPNS active center, wherein F283 is strategically positioned. The investigation of single and double mutations at F283, adjacent (L284) and proximal sites (N285 and S216) of Streptomyces jumonjinensis IPNS advocate the explicit importance of the phenyl ring at position 283. A similarly placed phenylalanine (F264) in DAOCS was found to be also crucial for its enzyme activity.

Amino Acid Sequence↗
PubMed2001

Differential assembly of rat purinergic P2X7 receptor in immune cells of the brain and periphery.

ATP-gated P2X(7) purinoceptors are found in most immune cells of the periphery and the brain where their activation leads to multiple downstream events such as cell permeabilization, apoptosis, and/or cytokine release. P2X(7) receptors do not form heteromeric receptors with any of the other six P2X subunits, and it is not known what type of homomeric assemblies the P2X(7) subunit makes. We constructed and purified an ectodomain protein of the rat P2X(7) receptor (amino acids 60-323) and used this to generate a monoclonal antibody (Ab) with which to probe P2X(7) receptors in central and peripheral immune cells. In HEK cells expressing rat P2X(7) receptors, the Ab increased the maximum current evoked by BzATP by 3-8-fold with a 5-fold leftward shift in EC(50) concentration. This Ab recognized only a non-denatured, multimeric form of the receptor on blue native-PAGE but did not recognize the denatured form on SDS-PAGE. A C-terminal polyclonal P2X(7) Ab recognized both monomeric subunits on SDS-PAGE and a multimeric complex on blue native-PAGE in this heterologous expression system. With Western blotting using these two Abs, native P2X(7) receptors in peritoneal macrophage and bone marrow cells are shown to exist as a strongly bound multimeric complex, whereas P2X(7) receptors in brain glia and/or astrocytes appear to form only as monomeric subunits.

Animals↗
PubMed2001

Inhaled corticosteroids decrease vascularity of the bronchial mucosa in patients with asthma.

BACKGROUND: Increased vascularity in airway mucosa is a distinctive feature of airway remodelling in asthma. While corticosteroids have proved most effective in modifying airway inflammation, the effect of inhaled corticosteroids on increased airway mucosal vascularity in asthmatics has been little studied. OBJECTIVE: We examined the effect of inhaled corticosteroid on airway vascularity in bronchial biopsy specimens taken from asthmatic patients. SUBJECTS AND METHODS: We studied bronchial biopsies from 28 asthmatic patients before and after treatment with inhaled beclomethasone dipropionate (BDP) 800 microg/daily, or placebo, for 6 months in a double-blind manner. Biopsy specimens were evaluated for number of vessels and percentage of area occupied by vessels, using computerized image analysis after staining for type IV collagen in vessel walls. Specimens were also examined for extent of collagen III in the subepithelial basement membrane. In addition, we compared asthmatic specimens with biopsy specimens taken from non-asthmatic control subjects. RESULTS: There was a significant increase in number of vessels (P < 0.01) and percent vascularity (P < 0.001) in the submucosa of asthmatic patients compared with control subjects. After 6 months of treatment, we observed significant improvements in forced expiratory volume in 1 s (FEV1), FEV1% and airway responsiveness (P < 0.05, each) in the BDP treatment group compared with the placebo group. This was accompanied by significant decreases in both vessel number and percent vascularity in the airways of BDP-treated patients (P < 0.05, each). We also observed a significant correlation between change in percent vascularity and change in collagen III thickness in the BDP-treated patients (rs = 0.90, P < 0.001). Furthermore, the change in percent vascularity was inversely correlated with both FEV1 (rs = -0.49, P < 0.05) and airway responsiveness (rs = -0.36, P < 0.05). CONCLUSION: These findings suggest that inhaled corticosteroid treatment of asthma reduced airway wall vascularity during airway remodelling.

Adolescent↗
PubMed2001

Nurses' perceptions of physiotherapists as rehabilitation team members.

OBJECTIVE: To investigate nurses' perceptions of physiotherapists as members of the rehabilitation team. This study arose from the current emphasis that is placed on good multidisciplinary teamwork for effective rehabilitation and the awareness that different team members often have different perceptions of their respective roles within the team. DESIGN: Semi-structured interviews, the results of which were then subject to content analysis. SETTING AND SUBJECTS: Experienced rehabilitation nurses in two rehabilitation wards within a National Health Service Trust. RESULTS: Nurses perceived the role of physiotherapists as being concerned with mobility and movement, and valued the therapists' knowledge and skills in these areas. They felt, however, that physiotherapists had insufficient understanding of the demands and pressures of nursing practice and lacked recognition of the nurses' professional autonomy in decision-making in rehabilitation. Nurses viewed nursing and physiotherapy as two quite distinct and different roles within rehabilitation, despite some role overlap. Physiotherapy was perceived as specific and measurable, while nursing was perceived as generalized and undefined. These perceptions extended to their views on patient-staff interactions and organizational structures. Some of the differences, such as organizational structures, created barriers to rehabilitation. Others, such as physiotherapy expertise in mobility, were valued for their contribution to rehabilitation. Areas were identified where the two professions can assist each other in professional skills. CONCLUSION: Nurses valued the role and contribution of physiotherapists, but identified areas in which barriers existed to effective interprofessional working, particularly in relation to organizational factors and interprofessional relationships.

Adult↗
PubMed2000

'You'll never walk alone': CCTV surveillance, order and neo-liberal rule in Liverpool city centre.

This paper is concerned to chart the establishment and uses of CCTV within the location of Liverpool city centre. In doing this the paper seeks to contextualize CCTV within contemporary 'partnership' approaches to regeneration which are reshaping the material and discursive form of the city. Thus CCTV schemes along with other security initiatives are understood as social ordering strategies emanating from within locally powerful networks which are seeking to define and enact orderly regeneration projects. In focusing on the normative aspects of CCTV, the paper raises questions concerning the efficacy of understanding contemporary forms of 'social ordering practices' primarily in terms of technical rationalities while neglecting other, more material and ideological processes involved in the construction of social order.

Authoritarianism↗
PubMed2000

Ratings of perceived exertion in braille: validity and reliability in production mode.

OBJECTIVES: (a) To assess the validity and reliability of producing and reproducing a given exercise intensity during cycle ergometry using a braille version of Borg's standard 6-20 rating of perceived exertion (RPE) scale, and (b) to determine whether the exercise responses of blind participants, at a given produced RPE, were similar to those reported in recognised guidelines for sighted subjects. METHODS: Ten healthy registered blind volunteer participants (four women, six men; mean (SD) age 23.2 (9.0) years) performed an initial graded exercise cycle test to determine maximal heart rate (HRMAx) and maximal oxygen uptake (VO2MAX). Three trials of three exercise bouts at RPEs 9, 11, and 13 were then performed in random order on three separate days of the same week, with expired air and heart rate measured continuously. Each exercise bout was followed by 10 minutes of rest. The validity of the scale as a means of producing different exercise intensities was assessed using a two factor (RPE x trial) repeated measures analysis of variance. Intertrial reliability was assessed using intraclass correlation coefficients (ICC) and the bias +/-95% limits of agreement (95%LoA) procedure. RESULTS: Participants reported no difficulty in using the braille RPE scale. When asked to produce exercise intensities equating to RPE 9, 11, and 13, they elicited mean %VO2MAX values of 47%, 53%, and 63% respectively. Analysis of variance showed no significant differences in either %HRMAx or %VO2MAX between trials at each of the three RPEs, but there was a significant difference (p<0.001) in both %HRMAx and %VO2MAX between the three RPE levels. All pairwise comparisons of the three different RPEs were significantly different (p<0.016). The ICC between the second and third trial for %HRMAx was significant (p <0.05) for all three RPEs. Similarly for %VO2MAX, the ICC was significant for RPE 9 and 11 but not 13. The 95%LoA decreased for both %HRMAx and %VO2MAX with each successive trial. CONCLUSIONS: Blind participants were successful in using a braille RPE scale to differentiate exercise intensity on a cycle ergometer. In every trial at RPE 13, all participants achieved %HRMAX and %VO2MAX levels, which fell within the recommendedrange for developing cardiorespiratory fitness. Using %HRMAx as a judge of intertrial reliability, the participants were able to repeat similar exercise intensities after two trials at each of the three RPEs (9, 11,13). The same was true for RPE 9 and 11, when %VO2MAX was used as a judge, but further trials were required to achieve similar reliability at RPE 13. A braille RPE scale can be used by healthy blind people during cycle ergometry, with similar effect to the visual analogue scale recommended for use in healthy sighted people.

Adult↗
PubMed2000

Confidentiality within physiotherapy: perceptions and attitudes of clinical practitioners.

OBJECTIVES: This study examined the issue of confidentiality in relation to i) undergraduate curriculum content in physiotherapy, and ii) the awareness, experiences and attitudes of clinical physiotherapists. DESIGN: Postal survey of universities and focus group interviews with physiotherapists. SETTING: Twenty-five universities in the UK and Ireland and 44 therapists in five hospitals in southern England. RESULTS: The survey of universities indicated that legal and ethical aspects of confidentiality featured in virtually all preregistration courses that responded. However, whereas its inclusion was rated as extremely important, the degree of coverage of confidentiality varied considerably between courses. Within the focus groups, 35 informants recollected coverage of confidentiality in their preregistration education, and 12 in postregistration in-service training; in neither case was this coverage in great detail. Informants identified environmental factors and working practices as barriers to preserving confidentiality. Disclosure to others also gave rise to difficulties. Informants were only aware in general terms of the relevant sections of the Chartered Society of Physiotherapy's Rules of Professional Conduct. CONCLUSIONS: Aspects of hospital-based physiotherapy practice were seen to create specific problems in relation to confidentiality. More detailed sources of education and guidance on this issue appear to be required.

Adult↗
PubMed2000

Mutational evidence supporting the involvement of tripartite residues His183, Asp185, and His243 in Streptomyces clavuligerus deacetoxycephalosporin C synthase for catalysis.

Deacetoxycephalosporin C synthase (DAOCS) is a non-heme iron-binding and alpha-ketoglutarate dependent enzyme involved in catalyzing the biosynthesis of cephalosporins and cephamycins, antibiotics more potent than penicillins. In the crystal structure complex of Streptomyces clavuligerus DAOCS (scDAOCS), it was proposed that histidine-183, aspartate-185, and histidine-243 are putative iron-binding ligands. However, coordinates proposed for crystal structures of proteins may not definitely comply with catalysis. Hence, site-directed mutagenesis was done to replace each of these amino acid residues with leucine. The constructed expression vectors bearing the mutations were found to express the respective scDAOCS mutant enzymes at high levels in Escherichia coli BL21(DE3). Through enzymatic assays, it was shown that while the wildtype enzyme could convert penicillin to a more active cephalosporin, the substitution of the three proposed iron-binding sites of scDAOCS completely abolished the same activity in the respective mutant enzymes. Thus, these results clearly indicate that histidine-183, aspartate-185, and histidine-243 of scDAOCS are essential for the ring expansion activity.

Aspartic Acid↗
PubMed1999

Effect of AA-2414, a thromboxane A2 receptor antagonist, on airway inflammation in subjects with asthma.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways. The chemokines are potent chemoattractants for eosinophils and other types of cells associated with allergic inflammation. AA-2414, a new thromboxane A2 receptor antagonist, reduces bronchial hyperresponsiveness in asthmatic subjects, but its mechanism of action is unclear. OBJECTIVE: We tested the hypothesis that the beneficial effects of AA-2414 in asthma result from reduction in the number of inflammatory cells infiltrating the airway associated with inhibition of chemokine release. METHODS: We studied bronchial biopsy specimens from 31 asthmatic subjects before and after oral treatment with AA-2414 (80 mg/day) or matched placebo for 4 months in a double-blind manner. Biopsy specimens were examined by immunohistochemistry. Each subject recorded symptom score and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured before and after treatment. RESULTS: After treatment, significant improvements in symptom score (P <.05), PEF (P <.01), diurnal variation of PEF (P <.01), and bronchial responsiveness (P <.01) were observed in the AA-2414 group compared with the placebo group. These improvements were accompanied by a significant decrease in the number of submucosal EG2(+) eosinophils (P <.05). There was also a reduction in the number of cells expressing RANTES (P <.05) and macrophage inflammatory protein (MIP)-1alpha (P <.05) in the epithelium and of cells expressing monocyte chemotactic protein-3 (P <.01), RANTES (P <.05), MIP-1alpha (P <.01), and eotaxin (P <.01) in the submucosa in the AA-2414 treatment group. A significant correlation was found between the number of EG2(+) eosinophils and numbers of monocyte chemotactic protein-3(+) (rs = 0.52, P <.005), MIP-1alpha+ (rs = 0.34, P <.05), and eotaxin+ cells (r s = 0.47, P <.01) in the submucosa. There was a significant negative correlation between the increase in bronchial responsiveness and the change in number of submucosal EG2(+) cells (rs = -0.65, P <.001). CONCLUSIONS: These findings suggest that AA-2414 treatment of patients with asthma may inhibit activated eosinophil infiltration in part by modulating the expression of chemokines in bronchial tissues.

Adolescent↗
PubMed1999

Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma.

BACKGROUND: Bronchial asthma is characterized by airway wall remodeling. Matrix metalloproteinases (MMPs) are members of a family of proteolytic enzymes that degrade the extracellular matrix and that restrain the effects of their tissue inhibitors (TIMPs). Treatment with inhaled corticosteroids may prevent airway remodeling in asthma. However, the effects of corticosteroid treatment on MMPs and TIMPs in asthma are unknown. OBJECTIVE: We examined the effects of inhaled beclomethasone dipropionate (BDP) on the expression of MMP-9 and TIMP-1 and subepithelial collagen deposition in bronchial biopsy specimens from 30 subjects with asthma. METHODS: Inhaled BDP, 800 microg daily, or placebo was administered for 6 months in a double-blind, parallel-group study, and bronchial biopsies were performed before and after treatment. Biopsy specimens were examined for extent of collagen type III in the subepithelial basement membrane by means of immunohistochemistry, and expression of both epithelial and submucosal MMP-9 and TIMP-1 was quantitated. Numbers of inflammatory cells were also determined. RESULTS: We observed significant decreases in collagen type III deposition (P <.01) and the expression of submucosal MMP-9 (P <.01) and a significant increase in the expression of submucosal TIMP-1 (P <.05) in the BDP group. Significant correlations were found between the subepithelial collagen type III deposition and epithelial (r (s ) = 0.37, P <.05) and submucosal expression of MMP-9 (r (s ) = 0.47, P <.01). Additionally, the number of many inflammatory cells and myofibroblasts in airway mucosa were significantly decreased in the BDP group. CONCLUSION: Our findings suggest that corticosteroid treatment of asthma can reduce subepithelial collagen deposition by downregulation of MMP-9 expression and upregulation of TIMP-1 expression.

Administration, Inhalation↗
PubMed1999

Treatment options for regional musculoskeletal pain: what is the evidence?

Decisions about the best treatment options for patients with regional musculoskeletal pain must be made despite a lack of clear diagnostic criteria, an absence of robust outcome measures by which to assess response, and a paucity of evidence from high-quality randomized controlled trials. Although the randomized controlled trial is considered to be the 'gold standard' research design, it does not lend itself easily to the evaluation of all management strategies. This chapter explores these issues from a research perspective and reviews the various types of evidence available to help practitioners make informed decisions. The current evidence from systematic reviews in this area is summarized in the final part of the chapter.

Electric Stimulation Therapy↗