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Biomedical subjects

A J Smith

Publications and source records attributed to A J Smith.

At least 37 records · Page 2Linked to original sources
PubMed2005

Faraday tilting of water-immersed granular beds.

Under low-frequency vertical vibration, a system of fine grains within a fluid is observed to tilt or to form piles, an effect studied by Faraday for grains in air. Here, we investigate the physical mechanisms behind Faraday tilting in a bed of vertically vibrated bronze spheres fully immersed in water. Experimental observations of surface tilting and bulk convection are compared with the results of molecular dynamics simulations in which the water is treated as an incompressible fluid. Our simulations reproduce the main features observed experimentally. Most tilt construction is shown to be due to horizontal fluid flow within the bed, principally occurring when the gap between the bed and the supporting platform is close to a maximum. Tilt destruction occurs by granular surface flow and in the bulk of the bed at times during each vibratory cycle close to and just later than bed impact. Destruction becomes more important for higher values of frequency and vibration amplitude, leading to lower tilt angles, partial tilting, or the symmetric domed geometry of Muchowski flow.

Journal Article↗
PubMed2005

Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy.

The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.

Animals↗
PubMed2005

Current patient perceptions on the menopause: a South African perspective.

OBJECTIVE: To evaluate current patient perspectives on the postmenopausal period in South Africa. METHODS: The study was conducted in a specialist private practice in Tygerberg, Cape Town, South Africa during 2004. All women with established postmenopausal status, seen over a period of 18 months, received a survey questionnaire by post. Of the 541 questionnaires that were posted, 421 were returned and 410 were used. Women gave written informed consent. RESULTS: The average age of the women was 60 years, with almost half (49%) greater than 10 years postmenopausal, and 78.5% were using hormonal therapy (HT). Of note is that 42% had been on HT for more than 10 years. The doctor was the most important source of information (87%), the most frequent reason for initiation of, and the second most frequent reason for discontinuation of therapy. The most important advantages of HT given were skeletal protection (85%) and treatment of vasomotor symptoms (70%), while development of breast cancer was given as the most prominent disadvantage (79%). CONCLUSION: This group of women was well informed regarding current indications and developments concerning HT. Despite their socioeconomic status, the doctor remained the key factor with regard to information and decision-making.

Adult↗
PubMed2005

A long-term study of the effects of diazinon on sleep, the electrocorticogram and cognitive behaviour in common marmosets.

The long-term sequelae of exposure to low doses of organophosphate compounds are ill defined, with effects variously reported on a range of indices of central nervous system functions such as sleep, cognitive performance and electroencephalogram (EEG). These indices were examined in common marmosets exposed to a range of doses of the organophosphorous sheep dip, diazinon. Cognitive performance was assessed by means of elements from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and radiotelemetry techniques were employed to monitor the electrocorticogram and sleep patterns. Data were collected for 12 months following intramuscular administration of a single dose of diazinon (10, 90 or 130 mg.kg (-1)) or vehicle. Although high levels of erythrocyte acetylcholinesterase (AChE) inhibition (up to 82%) and short-term changes in sleep patterns were seen, there was no evidence of biologically significant long-term changes in any measures. The effects of multiple exposures, impurities or mixtures of OP compounds remain to be investigated.

Acetylcholinesterase↗
PubMed2005

British Orthodontic Society, Chapman Prize Winner 2003. A novel in vitro culture model to investigate the reaction of the dentine-pulp complex to orthodontic force.

OBJECTIVE: To develop a novel mandible slice organ culture model to investigate the effects of externally applied force on the dentine-pulp complex. DESIGN: In vitro organ culture. SETTING: School of Dentistry, Birmingham, UK. MATERIALS AND METHODS: Transverse 2 mm thick sections were cut from the mandibles of five 28-day-old male Wistar rats. Serial sections were used for control and test pairs. Springs made from 0.016-inch and 0.019 x 0.025-inch stainless steel wires were used to apply a 50 g tensile or compressive force, respectively, to test specimens. Control and test specimens were cultured for 5 days in a humidified incubator with 5% CO(2) at 37 degrees C and processed for routine histological investigation. Nine more rats were used to provide control and compression test pairs where the pulps were extirpated after 3 days culture and total RNA isolated for gene expression analysis by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Histology showed the dental and supporting tissues maintained a healthy appearance in the control cultures after culture. Histomorphometric analysis revealed a 20-27% increase in pulp fibroblast density in test specimens compared with controls. Gene expression analyses revealed up-regulation in the test groups of PCNA, c-Myc, Collagen 1alpha, TGF-beta1 and alkaline phosphatase, whilst expression of osteocalcin was reduced. CONCLUSIONS: The results demonstrated that the present organ culture technique provides a valuable in vitro experimental model for studying the effects of externally applied forces. These forces stimulated a cellular response in the pulp chamber characterized by altered gene expression and proliferation of fibroblasts; the latter being unaffected by the nature of the force in terms of compression or tension.

Alkaline Phosphatase↗
PubMed2004

Use of polymer mats in series for sequential reactive barrier remediation of ammonium-contaminated groundwater: field evaluation.

A pilot-scale field trial was undertaken to evaluate the potential of in situ polymer mats (installed in series) as permeable reactive barriers within a treatment wall remediation system to induce sequential bioremediation of ammonium-contaminated groundwater. The treatment wall consisted of 10 m wide impermeable wings on either side of a 0.75 m wide permeable reactive zone flow-through box. Two polymer mats were positioned in the flow-through box. The upgradient polymer mat within the flow-through box was used to deliver oxygen to induce bacterial nitrification of the ammonium to nitrite/nitrate as the groundwater moved past. The downgradient polymer mat delivered ethanol to induce bacterial denitrification of the nitrite/nitrate to produce nitrogen gas. The field trial was carried out at a near-shore location. Initially the flow-through box was left open; however, this resulted in substantial groundwater mixing, which inhibited sequential remediation. Once the flow-through box was in-filled with gravel, groundwater mixing was reduced, achieving a greater than 90% reduction in total N. Estimated first-order half-lives for nitrification and denitrification rates were 1.2 and 0.4 d, respectively. Field nitrification half-lives were approximately an order of magnitude greater than rates determined in large-scale columns using soil and groundwater from the site, while denitrification half-lives were similar. The results of this pilot-scale field trial indicate that sequential bioremediation of ammonium-contaminated groundwater at field scale is feasible using in situ polymer mats as permeable reactive barriers, although hydraulic conditions can be complex in such barrier systems.

Biodegradation, Environmental↗
PubMed2004

Fluoride-induced changes to proteoglycan structure synthesised within the dentine-pulp complex in vitro.

Fluoride is known to influence mineralisation patterns within dentine, where alterations in the post-translational modification of proteoglycans (PG) have been proposed as an implicating factor. In light of recent studies elucidating changing PG profiles in the transition of predentine to mineralised dentine, this study investigates the influence of fluoride on the major PG populations (decorin, biglycan and versican) within the pulp, predentine and dentine. Tooth sections from rat incisors were cultured for 14 days in the presence 0, 1 and 6 mM sodium fluoride and the PG extracted from the pulp, predentine and dentine matrices. PG species and corresponding metabolites were identified by their immuno-reactivity to antibodies against decorin, biglycan and versican. Component glycosaminoglycan chains were characterised with respect to their nature, chain length and disaccharide composition. Levels of PG extracted from pulp and predentine were reduced, particularly for biglycan. Fluoride did not influence levels of decorin or versican within predentine or dentine, although the processing of these macromolecules within pulp and predentine was affected, particularly at higher fluoride concentrations. Levels of dermatan sulfate were reduced within pulp and predentine, although the effect was less pronounced for predentine. Fluoride reduced sulfation of glycosaminoglycan chains within pulp and predentine tissues, with a notable reduction in Deltadi6S evident. In all three tissues, glycosaminoglycan chain length was reduced. Considering the various roles for PG in the dentine-pulp complex, either directly or indirectly in the mineralisation process, changes in the synthesis, structure and processing of the different PG species within the pulp, predentine and dentine matrices provides a further molecular explanation for the altered mineralisation patterns witnessed during fluorosis.

Amino Acid Sequence↗
PubMed2004

Salicylidene salicylhydrazide, a selective inhibitor of beta 1-containing GABAA receptors.

1. A high-throughput assay utilizing the voltage/ion probe reader (VIPR) technology identified salicylidene salicylhydrazide (SCS) as being a potent selective inhibitor of alpha2beta1gamma1 GABA(A) receptors with a maximum inhibition of 56+/-5% and an IC(50) of 32 (23, 45) nm. 2. Evaluation of this compound using patch-clamp electrophysiological techniques demonstrated that the compound behaved in a manner selective for receptors containing the beta1 subunit (e.g. maximum inhibition of 68.1+/-2.7% and IC(50) value of 5.3 (4.4, 6.5) nm on alpha2beta1gamma1 receptors). The presence of a beta1 subunit was paramount for the inhibition with changes between alpha1 and alpha2, gamma1 and gamma2, and the presence of a subunit having little effect. 3. On all subtypes, SCS produced incomplete inhibition with the greatest level of inhibition at alpha1beta1gamma1 receptors (74.3+/-1.4%). SCS displayed no use or voltage dependence, suggesting that it does not bind within the channel region. Concentration - response curves to GABA in the presence of SCS revealed a reduction in the maximum response with no change in the EC(50) or Hill coefficient. In addition, SCS inhibited pentobarbitone-induced currents. 4. Threonine 255, located within transmembrane domain (TM) 1, and isoleucine 308, located extracellularly just prior to TM3, were required for inhibition by SCS. 5. SCS did not compete with the known allosteric modulators, picrotoxin, pregnenolone sulphate, dehydroepiandrosterone 3-sulphate, bicuculline, loreclezole or mefenamic acid. Neither was the inhibition by SCS influenced by the benzodiazepine site antagonist flumazenil. 6. In conclusion, SCS is unique in selectively inhibiting GABA(A) receptors containing the beta1 subunit via an allosteric mechanism. The importance of threonine 255 and isoleucine 308 within the beta1 subunit and the lack of interaction with a range of GABA(A) receptor modulators suggests that SCS is interacting at a previously unidentified site.

Amino Acid Sequence↗
PubMed2004

Improvement of neuronal visual responses in the superior colliculus in Prph2(Rd2/Rd2) mice following gene therapy.

Inherited retinal degenerations are a major cause of blindness for which there are currently no effective therapies. Significant progress concerning in vivo gene transfer has allowed retardation of degeneration or retinal functional improvement in different animal models. To date, there has been no evaluation of the impact of these treatments on higher visual function, a critical step for validating gene therapy treatment strategies. Here, we have used adeno-associated (AAV2)-mediated gene transfer of Prph2 in the Prph2(Rd2/Rd2) mouse model. We then assessed higher visual function by recording from central visually responsive neurons in the superior colliculus and improvements were correlated in individual animals with retinal function (ERG) and histological and biochemical changes. Although gene replacement therapy only partially restores photoreceptor morphology, it results in a 300% increase of the visual cycle protein rhodopsin, leading to retinal function improvement (250% increase of b-wave amplitude) and significantly higher central visual responses (166% increase at 24 cd/m(2)). These findings suggest that gene replacement therapy leading to even relatively modest structural improvement may result in improved central visual function.

Action Potentials↗
PubMed2004

Localization of MtuA, an LraI homologue in Streptococcus uberis.

AIMS: To determine the localization of MtuA, an LraI lipoprotein within Streptococcus uberis and assess whether the protein was able to induce an antibody response capable of growth inhibition. METHODS AND RESULTS: Immunoblots and ELISAs were performed on S. uberis cell fractions to localize the protein. The strongest reactivity was within the membrane-enriched fraction. Electron micrographs also showed labelling consistent with a location within the membrane. Specific antibodies from both rabbits and calves were unable to inhibit the growth of S. uberis in milk. In addition, MtuA was not detectable in a whole-cell ELISA and whole bacterial cells were unable to adsorb specific antibodies from antiserum raised against MtuA. CONCLUSIONS: The MtuA protein appears to be located within the cell membrane and is not on the bacterial surface and thus not available for interaction with potentially growth-inhibiting antibodies. SIGNIFICANCE AND IMPACT OF THE STUDY: Unlike PsaA of S. pneumoniae and MtsA of S. pyogenes, MtuA of S. uberis does not appear to be located at the cell surface. Therefore, in contrast to studies with other similar proteins, MtuA is unlikely to be a good vaccine candidate.

Animals↗
PubMed2003

Staphylococcus aureus in the oral cavity: a three-year retrospective analysis of clinical laboratory data.

OBJECTIVE: A retrospective analysis of laboratory data to investigate the isolation of Staphylococcus aureus from the oral cavity and facial area in specimens submitted to a regional diagnostic oral microbiology laboratory. METHODS: A hand search of laboratory records for a three-year period (1998-2000) was performed for specimens submitted to the regional diagnostic oral microbiology laboratory based at Glasgow Dental Hospital and School. Data were collected from forms where S. aureus was isolated. These data included demographics, referral source, specimen type, methicillin susceptibility and clinical details. RESULTS: For the period 1998-2000, there were 5,005 specimens submitted to the laboratory. S. aureus was isolated from 1,017 specimens, of which 967 (95%) were sensitive to methicillin (MSSA) and 50 (5%) were resistant to methicillin (MRSA). The 1,017 specimens were provided from 615 patients. MRSA was isolated from 37 (6%) of patients. There was an increasing incidence of S. aureus with age, particularly in the >70 years age group. The most common specimen from which MSSA was isolated was an oral rinse (38%) whilst for MRSA isolates this was a tongue swab (28%). The clinical condition most commonly reported for MSSA isolates was angular cheilitis (22%). Erythema, swelling, pain or burning of the oral mucosa was the clinical condition most commonly reported for MRSA isolates (16%). Patients from whom the MSSA isolates were recovered were most commonly (55%) seen in the oral medicine clinic at the dental hospital, whilst patients with MRSA were more commonly seen in primary care settings such as nursing homes, hospices and general dental practice (51%). CONCLUSION: In line with more recent surveys, this retrospective study suggests that S. aureus may be a more frequent isolate from the oral cavity than hitherto suspected. A small proportion of the S. aureus isolates were MRSA. There were insufficient data available to determine whether the S. aureus isolates were colonising or infecting the oral cavity. However, the role of S. aureus in several diseases of the oral mucosa merits further investigation.

Adolescent↗
PubMed2003

A DNA translocation motif in the bacterial transcription--repair coupling factor, Mfd.

The bacterial transcription-repair coupling factor, Mfd, is a superfamily II helicase that releases transcription elongation complexes stalled by DNA damage or other obstacles. Transcription complex displacement is an ATP-dependent reaction that is thought to involve DNA translocation without the strand separation associated with classical helicase activity. We have identified single amino acid substitutions within Mfd that disrupt the ability of Mfd to displace RNA polymerase but do not prevent ATP hydrolysis or binding to DNA. These substitutions, or deletion of the C-terminal 209 residues of Mfd, abrogate the ability of Mfd to increase the efficiency of roadblock repression in vivo. The substitutions fall in a region of Mfd that is homologous to the 'TRG' motif of RecG, a protein that catalyses ATP-dependent translocation of Holliday junctions. Our results define a translocation motif in Mfd and suggest that Mfd and RecG couple ATP hydrolysis to translocation of DNA in a similar manner.

Adenosine Triphosphate↗
PubMed2003

Prion diseases and dental treatment: principles and practice of patients with/suspected or at-risk of CJD: case reports.

The emergence of variant CJD (vCJD) in the last decade has heightened awareness of the need for rigorous infection control precautions in all healthcare environments. It has also raised particular problems in relation to the clinical management of patients who are either suffering from prion diseases or who are perceived as being 'at risk'. From the healthcare perspective CJD is of concern because at present it is an incurable, fatal disease and the causative agent, abnormal prion protein, is resistant to conventional inactivation procedures. Many healthcare workers are concerned about the risks of cross-infection when treating such patients. There are a number of guidelines for the management of CJD patients, though the information they provide sometimes appears contradictory and may require some interpretation in the clinical setting. This paper is based on real-life case scenarios and the advice given to dentists for the management of a group of patients with different manifestations of prion diseases.

Creutzfeldt-Jakob Syndrome↗
PubMed2003

The influence of fluoride exposure on dentin mineralization using an in vitro organ culture model.

This study aimed to characterize fluoride-induced alterations in dentin mineralization within a dentin-pulp organ culture system. Tooth sections derived from male Wistar rat incisors were cultured in Trowel-type culture for 14 days, in the presence of 0 mM, 1 mM, 3 mM and 6 mM sodium fluoride. Tooth sections were processed and analyzed for uptake of fluoride, its subsequent effect on dentin mineralization by tetracycline hydrochloride incorporation and mineral composition, expressed as calcium/phosphorous (Ca/P) ratios. Tetracycline hydrochloride incorporation was demonstrated to decrease with increased fluoride exposure, accompanied by significant increases in both Ca/P ratios and fluoride incorporation. These findings provide further evidence that the established alterations in dentin formation during fluorosis are a consequence of disruption to the mineralization process, and provide a model system with which to investigate further the potential role the extracellular matrix plays in inducing the apparent changes in mineral composition.

Animals↗
PubMed2003

Staphylococcal species in the oral cavity from patients in a regional burns unit.

The aim of this study was to perform a quantitative and qualitative analysis of oral carriage of staphylococci in a range of oral specimens from patients admitted to a regional burns unit. The study recruited 28 patients and reasons for admittance were: burns (46%), skin grafting (39%), lacerations (7%), scalding (4%) and necrotizing fasciitis (4%). No patient had smoke inhalation injuries or trauma to the oro-pharynx. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in oral specimens. For three patients only the wound and oral specimens were positive for MRSA. In one patient only the oral specimens were positive for MRSA. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in the oral specimens. In one patient only the oral specimens were positive for MSSA. Staphylococci could be recovered from the dental plaque, denture and toothbrush specimens with a mean count of 1.1 x 10(4)cfu/mL (range 20-5.3 x 10(4)), 5.4 x 10(3) (range 40-2.1 x 10(4)) and 264 cfu/mL (range 20-500), respectively. Both MSSA and MRSA could be recovered from these specimen types. In one patient only the toothbrush was positive for MRSA and all other oral specimens were negative. This study suggests that staphylococci are not infrequent colonizers of the oral cavity, and that this site may serve as a potential reservoir for transmission to other body sites.

Adolescent↗