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Biomedical subjects

M Smyth

Publications and source records attributed to M Smyth.

At least 19 recordsLinked to original sources

Quantitative colorimetric measurement of residual antimicrobials in the urine of patients with suspected urinary tract infection.

A simple microtitre plate assay is used to detect antimicrobial activity in clinical urine specimens and its potential as a screening tool is assessed. The assay is based on a colorimetric substrate, p-nitrophenyl-beta-D-glucopyranoside, in combination with a Bacillus subtilis strain to detect antimicrobial residues. The assay identified antimicrobial activity in 31% of the 527 clinical urine samples tested. The majority of the samples (65%) came from the community, with the rest comprising hospital inpatients (19%) and out-patients (16%). The results demonstrated that there is an association between gender and the presence of inhibitory substances, as 40% of males and 27% of females tested positive. Just over two-fifths of hospital patients (46%) tested positive for inhibitory substances, compared to 26% of samples from community patients. Of the 306 samples that were culture-negative (<10(4) bacteria/mL), 42% were positive for inhibitory substances, compared with 17% among the remaining 221 samples. However, there was no evidence of an association between age and the presence of inhibitory substances. This study demonstrates that the bacteriostatic effect of the bacterial preservative boric acid is sufficient to upset the specificity of the assay. Furthermore, it has been suggested that antimicrobial activity can confuse the interpretation of culture results, as they have been found to play a major role in the occurrence of apparently sterile pyuria.

Adolescent↗

Identification of the pocket factors in a picornavirus.

Bovine enterovirus (BEV), along with other enteroviruses and the rhinoviruses, has a hydrophobic pocket within structural protein VP1. In the crystal structures of these viruses there is electron density commensurate with a non-protein molecule within the pocket. These molecules, termed pocket factors, have been shown to stabilise the capsid and their removal from the pocket is a necessary prerequisite to uncoating. The pocket factors have been proposed, from the electron densities and uncoating studies, to be short chain fatty acids. In order to identify the pocket factor of BEV, we have grown and purified the virus in an identical manner to that used for the crystal structure determination and have performed a lipophilic extraction. Palmitic acid, C(16:0), was the most abundant accounting for 40.8% by mass of the lipophilic extract (39.3 mol%). Myristic acid C(14:0), was next most abundant at 18.5% by mass (20.0 mol%). In addition, we have identified other fatty acids in smaller proportions. We have therefore shown that BEV contains saturated fatty acid pocket factors of varying chain length. We have also compared the profile of the fatty acyl chain composition of BEV with those for uninfected BHK-21 cell plasma membrane and endoplasmic reticulum extracts.

Animals↗

Bovine enterovirus as an oncolytic virus: foetal calf serum facilitates its infection of human cells.

Many viruses have been investigated for their oncolytic properties and potential use as therapeutic agents for cancer treatment. Most of these replication-competent viruses are human pathogens. We investigated the oncolytic properties of an animal virus which is non pathogenic for both its natural host and humans. Bovine enterovirus has previously been shown to exhibit a very wide tissue tropism for cell types in vitro. We compare the ability of bovine enterovirus to replicate in and to cause cytopathic effect in freshly isolated human monocytes and monocyte derived macrophages with the monocyte-like U937 tumour cell line. We also include the adherent ZR-75-1 human breast cancer cell line. We have also carried out infections of bovine enterovirus in the presence and in the absence of serum of bovine origin. Our study shows that the virus will replicate in and produce cytopathic effect in the U937 and ZR-75-1 cell types to the same extent as the cells (BHK-21) in which the virus is routinely propagated. We believe bovine enterovirus to be a worthwhile candidate for further study as an anti-tumour agent.

Animals↗

The role of size and binocular information in guiding reaching: insights from virtual reality and visual form agnosia III (of III).

Reaching out to grasp an object requires information about the size of the object and the distance between the object and the body. We used a virtual reality system with a control population and a patient with visual form agnosia (DF) in order to explore the use of binocular information and size cues in prehension. The experiments consisted of a perceptual matching task in addition to a prehension task. In the prehension task, control participants modified their reach distance in response to step changes in vergence in the absence of any clear reference for relative disparity. Their reach distance was unaffected by equivalent step changes in size, even though they used this information to modify grasp and showed a size bias in a distance matching task. Notably, DF showed the same pattern of results as the controls but was far more sensitive to step changes in vergence. This finding complements previous research suggesting that DF relies predominantly on vergence information when gauging target distance. The results from the perceptual matching tasks confirmed previous findings suggesting that DF is unable to make use of size information for perceptual matching, including distance comparisons. These data are discussed with regard to the properties of the pathways subserving the two visual cortical processing streams.

Agnosia↗

Selective posterior rhizotomy and intrathecal baclofen for the treatment of spasticity.

Spasticity occurs in children and adults due to a wide range of conditions, including cerebral palsy, head and spinal cord trauma, cerebrovascular accidents and multiple sclerosis. Multiple treatment options have been described, including medical and surgical treatments. Medical treatments include intramuscular botulinum A toxin, oral baclofen and supportive bracing. Surgical approaches include selective posterior rhizotomy, intrathecal baclofen and orthopedic procedures to address deformities. Many reports have been published on these different treatment options, but rarely has a comparison been made between them. Therefore, this review is aimed at comparing selective posterior rhizotomy and intrathecal baclofen injection for spasticity due to cerebral palsy, especially in children.

Baclofen↗

Cytomegalovirus MHC class I homologues and natural killer cells: an overview.

Viruses that establish a persistent infection with their host have evolved numerous strategies to evade the immune system. Consequently, they are useful tools to dissect the complex cellular processes that comprise the immune response. Rapid progress has been made in recent years in defining the role of cellular MHC class I molecules in regulating the response of natural killer (NK) cells. Concomitantly, the roles of the MHC class I homologues encoded by human and mouse cytomegaloviruses in evading or subverting NK cell responses has received considerable interest. This review discusses the results from a number of studies that have pursued the biological function of the viral MHC class I homologues. Based on the evidence from these studies, hypotheses for the possible role of these intriguing molecules are presented.

Animals↗

5-a-day Power Plus: process evaluation of a multicomponent elementary school program to increase fruit and vegetable consumption.

The 5-a-Day Power Plus program targeted multiethnic fourth- and fifth-grade students in 10 intervention and 10 control urban elementary schools in St. Paul, Minnesota, to increase fruit and vegetable consumption. The intervention included behavioral curricula in classrooms, parental involvement, school food service changes, and food industry support. Process evaluation was conducted by using surveys and classroom and lunchroom observations to assess the characteristics of teachers and food service staff, the degree the intervention was implemented as intended, and exteral factors that may have affected the program results. Results showed high levels of participation, dose, and fidelity for all of the intervention components, with the exception of parental involvement. The process evaluation findings help explain why the increase in fruit and vegetable consumption occurred mostly at school lunch and not at home. Future intervention research should focus on creating new and potent strategies for parental involvement and for increasing the appeal and availability of vegetables.

Child↗

The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses.

BACKGROUND: Coxsackievirus A9 (CAV9), a human pathogen causing symptoms ranging from common colds to fatal infections of the central nervous system, is an icosahedral single-stranded RNA virus that belongs to the genus Enterovirus of the family Picornaviridae. One of the four capsid proteins, VP1, includes the arginine-glycine-aspartate (RGD) motif within its C-terminal extension. This region binds to integrin alpha v beta 3, the only receptor for CAV9 to be conclusively identified to date. RESULTS: The crystal structure of CAV9 in complex with the antiviral compound WIN 51711 has been solved to 2.9 A resolution. The structures of the four capsid proteins, VP1 to VP4, resemble those of other picornaviruses. The antiviral compound is bound in the VP1 hydrophobic pocket, and it is possible that the pocket entrance contains a second WIN 51711 molecule. Continuous electron density for the VP1 N terminus provides a complete picture of the structure close to the fivefold axis. The VP1 C-terminal portion is on the outer surface of the virus and becomes disordered five-residues N-terminal to the RGD motif. CONCLUSIONS: The RGD motif is exposed and flexible in common with other known integrin ligands. Although CAV9 resembles coxsackie B viruses (CBVs), several substitutions in the areas implicated in CBV receptor attachment suggest it may recognise a different receptor. The structure along the fivefold axis provides new information on the uncoating mechanism of enteroviruses. CAV9 might bind a larger natural pocket factor than other picornaviruses, an observation of particular relevance to the design of new antiviral compounds.

Amino Acid Sequence↗

Pathways: a culturally appropriate obesity-prevention program for American Indian schoolchildren.

Pathways, a culturally appropriate obesity prevention study for third-, fourth-, and fifth-grade American Indian schoolchildren includes an intervention that promotes increased physical activity and healthful eating behaviors. The Pathways intervention, developed through a collaboration of universities and American Indian nations, schools, and families, focuses on individual, behavioral, and environmental factors and merges constructs from social learning theory with American Indian customs and practices. We describe the Pathways program developed during 3 y of feasibility testing in American Indian schools, with special emphasis on the activities developed for the third grade; review the theoretical and cultural underpinnings of the program; outline the construction process of the intervention; detail the curriculum and physical education components of the intervention; and summarize the formative assessment and the school food service and family components of the intervention.

Asian People↗

Divergent effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells.

We investigated the effects of paracetamol on reactive oxygen intermediate and reactive nitrogen intermediate production by U937 cells. Cells which had been treated with paracetamol (0.01 microM - 10 microM) exhibited a significant (p<0.001) increase in hydrogen peroxide production and a significant (p<0.001) increase in phorbol 12-myristate 13-acetate induced superoxide production. Conversely, paracetamol (0.01 microM - 10 microM) caused a significant (p<0.001) decrease in the amount of nitrite secreted into the culture medium. Our results indicate divergent effects of paracetamol on ROI and RNI production.

Acetaminophen↗

After an injury. What next?

BACKGROUND: The goal of treatment of sports injuries must be restoration of function to the greatest possible degree in the shortest possible time. Initially this will require first aid treatment to decrease swelling, congestion and muscle spasm but it is equally important to minimise deconditioning of the rest of the body. OBJECTIVE: This article summarises the approach to minimising the effects of an acute injury in an athlete and maximising the chances for a full return to sport without incurring further injuries. DISCUSSION: A good knowledge of anatomy is needed to make a specific diagnosis so a comprehensive treatment plan can be implemented. Treatment involves several options: immobilisation, NSAIDs, physiotherapy, surgery and rehabilitation. Rehabilitation, which should not wait until after the injury has healed, encompasses strength, flexibility, proprioception, endurance, motor relearning, aerobic fitness and sometimes counselling.

Anti-Inflammatory Agents, Non-Steroidal↗

Regulation of fibroblast-induced collagen gel contraction by interleukin-1beta.

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo. In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1beta (IL-1beta) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1beta induced a statistically significant inhibition of gel contraction in all fibroblast cell types (P<0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.

Adult↗

Changing fruit and vegetable consumption among children: the 5-a-Day Power Plus program in St. Paul, Minnesota.

OBJECTIVES: A randomized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach. METHODS: The intervention, conducted in 20 elementary schools in St. Paul, targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995. The intervention consisted of behavioral curricula in classrooms, parental involvement, school food service changes, and industry support and involvement. Lunchroom observations and 24-hour food recalls measured food consumption. Parent telephone surveys and a health behavior questionnaire measured psychosocial factors. RESULTS: The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption, lunchtime vegetable consumption among girls, and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables. CONCLUSIONS: Multicomponent school-based programs can increase fruit and vegetable consumption among children. Greater involvement of parents and more attention to increasing vegetable consumption, especially among boys, remain challenges in future intervention research.

Child↗

Detection of blood group antigens utilising immobilised antibodies and surface plasmon resonance.

Surface plasmon resonance (SPR) detection using the BIAcore biosensing system was employed for the detection of blood group-associated antigens (BGAA) on whole erythrocytes. The quantitative detection of erythrocytes was accomplished by covalently immobilising blood group-specific antibodies (IgM) to a dextran matrix and monitoring the cell binding response. Non-specific binding of erythrocytes to the IgM coated surface was not detected. Relatively mild regeneration conditions (20 mM NaOH) were employed to elute bound erythrocytes in order to preserve the activity of the immobilised antibody and allow the surface to be used repeatedly. Regeneration of the surface was particularly difficult when a high IgM immobilisation level was used and when the number of bound cells was high. Despite these considerations, a quantitative relationship between the cell binding response and erythrocyte concentration was confirmed. Erythrocyte preparations, diluted by a factor of ten as compared to physiological concentrations, were detectable. The occurrence of non-specific false positives appears to be minimal and allows the system to be used for blood typing. As a model study, the lectin concanavalin A (ConA) was covalently immobilised onto a hydrophilic dextran matrix and successfully used to support the capture of erythrocytes from suspension.

Antibodies, Monoclonal↗