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Biomedical subjects

D Wray

Publications and source records attributed to D Wray.

At least 37 records · Page 2Linked to original sources
PubMed1999

Functional and molecular aspects of voltage-gated K+ channel beta subunits.

Voltage-gated potassium channels (Kv) of the Shaker-related superfamily are assembled from membrane-integrated alpha subunits and auxiliary beta subunits. The beta subunits may increase Kv channel surface expression and/or confer A-type behavior to noninactivating Kv channels in heterologous expression systems. The interaction of Kv alpha and Kv beta subunits depends on the presence or absence of several domains including the amino-terminal N-type inactivating and NIP domains and the Kv alpha and Kv beta binding domains. Loss of function of Kv beta 1.1 subunits leads to a reduction of A-type Kv channel activity in hippocampal and striatal neurons of knock-out mice. This reduction may be correlated with altered cognition and motor control in the knock-out mice.

Alternative Splicing↗
PubMed1999

The effects of oxidizing and cysteine-reactive reagents on the inward rectifier potassium channels Kir2.3 and Kir1.1.

The inwardly rectifying potassium channel Kir2.3 possesses extracellular cysteine residues at positions 113, 140, and 145, as well as at position 79 near the outer membrane boundary. In this study, we have investigated the roles of these extracellular cysteine residues in mediating inhibition of the Kir2.3 channel by the cysteine-reactive reagents para-chloromercuribenzenesulphonate (PCMBS) and thimerosal, and the oxidizing agent hydrogen peroxide (H2O2). We have also compared the effects of these reagents with those on Kir1.1 channels (which do not possess cysteine residues equivalent to 140 and 79 in Kir2.3 channels). Mutant channels were made in which cysteine residues were mutated to serine by site-directed mutagenesis. Wild-type or mutant cRNA was injected into Xenopus oocytes and voltage-clamp recordings made 1-2 days later. Wild-type Kir2.3 currents were significantly inhibited by PCMBS, thimerosal and H2O2. Currents for mutants Kir2.3 C79S and C140S were also inhibited by PCMBS, thimerosal and H2O2. These mutations affected the time course of inhibition by all three reagents. For PCMBS, a slow component of inhibition was absent for the C79S mutation, and a fast component was absent for C140S. For the double mutation C79S/C140S, PCMBS no longer had any effect. For thimerosal, there was a slower time course for C140S, a faster time course for C79S, and a delayed onset for C79S/C140S. For H2O2, the main effect was a delayed onset for the double mutant. The reducing agent dithiothreitol (DTT) reversed the inhibition by both PCMBS and thimerosal of wild-type and mutant currents, but not the inhibition due to H2O2. Finally, wild-type Kir1.1 currents were not significantly inhibited by the applications of either PCMBS or thimerosal, while H2O2 produced small inhibition. The results taken together indicate that inhibition by the cysteine-reactive reagent PCMBS is mediated through cysteine residues 79 and 140 in Kir2.3 channels, with C79 mediating a slow component of inhibition and C140 a faster component, and that both residues are extracellularly exposed. The data indicate that these two cysteine residues are also main sites for inhibition by thimerosal and H2O2 but, unlike for PCMBS, an additional non-extracellular inhibitory site(s) must also be involved.

4-Chloromercuribenzenesulfonate↗
PubMed1999

Detection of serum antibodies against cytomegalovirus, varicella zoster virus and human herpesvirus 6 in patients with recurrent aphthous stomatitis.

There has recently been renewed interest in the possible role of viruses in recurrent aphthous stomatitis (RAS). In this study, sera from 22 patients with RAS, 24 patients with oral lichen planus (OLP) and 15 healthy controls were screened for IgG and IgM class antibodies to human cytomegalovirus (HCMV), varicella zoster virus (VZV) and human herpesvirus 6 (HHV-6). Commercially available ELISA and immunofluorescence kits were employed. There were no significant differences in the prevalence of IgG antibodies to HCMV, VZV or HHV-6 among the three patient groups. Similarly, there were no significant differences between the prevalence of HCMV and VZV IgM antibodies among RAS patients and controls. However, specific HHV-6 IgM was detected in 21 (95%) of the RAS patients and 17 (71%) of the lichen planus patients compared with 8 (53%) of the healthy controls. This difference between RAS patients and controls was statistically significant (P<0.01). These results do not support an aetiological role for HCMV or VZV in RAS but suggest possible involvement of HHV-6.

Adult↗
PubMed1998

A vision-based three-dimensional capture system for maxillofacial assessment and surgical planning.

We describe a vision-based three-dimensional facial data capture system designed for the planning of maxillofacial operations. We describe the system requirements and outline the methods used to develop a complete three-dimensional facial capture system. Our approach is based upon imaging the face using two stereo-pair sets of cameras. Scale-space-based stereo-matching is then used to recover correspondences between each of the captured stereo-pairs. Photogrammetric routines based on adjustment of bundles are used off-line to calibrate the system by imaging a single object that references all cameras to the same co-ordinate frame. This calibration scheme allows us to convert stereo correspondences to world points for each pair of cameras without the need for any subsequent fusion of data. Initial results show that we are able to capture key facial landmarks to within 0.5 mm.

Algorithms↗
PubMed1998

A comparison of fluconazole and itraconazole in the management of denture stomatitis: a pilot study.

OBJECTIVES: To compare fluconazole capsules (50 mg daily for 14 days) and itraconazole capsules (100 mg daily for 15 days) in the treatment of denture stomatitis, using objective clinical and mycological outcome measures. METHODS: Twenty complete denture wearers with denture stomatitis were enrolled. At baseline, palatal erythema was measured with an electro-optical instrument, a denture disc specimen was collected from the fitting surface of the denture for culture and an oral rinse and imprint cultures were collected for mycological culture. Ten patients received fluconazole capsules (50 mg daily for 14 days) and 10 received itraconazole capsules (100 mg daily for 15 days). Palatal erythema was reassessed and the microbiological specimens re-collected on day 14. RESULTS: The most common form of denture stomatitis seen in this group of patients was Newton's Type II. All patients responded to advice to leave their dentures out at night but there was a poor overall improvement in denture hygiene. There was an objective reduction in palatal erythema following treatment with both fluconazole and itraconazole. A wide range of yeasts were isolated from the mouths of all the denture stomatitis patients before treatment. C. albicans was the most common isolate. A mycological cure was achieved in only five of the 20 patients, one in the fluconazole group and four in the itraconazole group. A further eight patients in the fluconazole group and three in the itraconazole group had reduced yeast counts by the second visit. CONCLUSION: Fluconazole and itraconazole were of comparable efficacy in the treatment of denture stomatitis, on the basis of reduction in palatal erythema and mycological culture.

Adult↗
PubMed1998

A controlled study of gold contact hypersensitivity.

1203 patients attending for routine patch testing at 3 hospitals and 105 volunteers were tested with 0.5% and 0.05% gold sodium thiosulfate (GST). 38 patients (3.2%) and 5 volunteers (4.8%) had positive patch tests to GST. There were no significant differences between volunteers and patients with respect to age, sex, atopy or exposure to gold in dental restorations, jewellery or through occupation. There were no significant differences in prevalence of GST hypersensitivity in the 3 hospitals, or between patients and controls. This is the 1st controlled study of hypersensitivity to GST, and suggests that routine patch testing to gold is of limited clinical benefit.

Adolescent↗
PubMed1998

Update on oral lichen planus: etiopathogenesis and management.

Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways, an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other disorders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as with liver disease, have emerged. The management of lichen planus is still not totally satisfactory, and there is as yet no definitive treatment, but there have been advances in the control of the condition. There is no curative treatment available; immunomodulation, however, can control the condition. Based on the observed increased risk of malignant development, OLP patients should be offered regular follow-up examination from two to four times annually and asked to report any changes in their lesions and/or symptoms. Follow-up may be particularly important in patients with atrophic/ulcerative/erosive affections of the tongue, the gingiva, or the buccal mucosa. Much more research is required into the genetic and environmental aspects of lichen planus, into the premalignant potential, and into the possible associations with chronic liver, and other disorders. More clinical studies are required into the possible efficacy of immunomodulatory drugs such as pentoxifylline and thalidomide.

Adjuvants, Immunologic↗
PubMed1997

Search for human herpesvirus 6, human cytomegalovirus and varicella zoster virus DNA in recurrent aphthous stomatitis tissue.

In the present study, the involvement of human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV) and varicella zoster virus (VZV) in the aetiology of recurrent aphthous stomatitis (RAS) was investigated using the polymerase chain reaction (PCR). Biopsies from 21 RAS patients were analysed, and 20 oral lichen planus (OLP) and 13 normal biopsies were tested as controls. HHV-6-DNA was detected in six of the RAS samples whereas VZV-DNA and HCMV-DNA were not detected in any RAS samples. In the OLP samples, four biopsies were positive for HHV-6-DNA and two were positive for HCMV-DNA. One sample from this group was positive for both HHV-6-DNA and HCMV-DNA. VZV-DNA was not found in any RAS or OLP biopsies. No viral DNA was present in any normal control biopsies. These results do not support an aetiological role for HCMV and VZV in RAS, although the possible involvement of HHV-6 cannot be excluded.

Adult↗
PubMed1997

Search for Mycobacterium paratuberculosis DNA in orofacial granulomatosis and oral Crohn's disease tissue by polymerase chain reaction.

BACKGROUND: Although intestinal Crohn's disease has long been suspected to have a mycobacterial cause, possible mycobacterial involvement in orofacial granulomatosis (OFG) and oral lesions of Crohn's disease has not yet been investigated. AIMS: As the slow growing Mycobacterium paratuberculosis has been implicated in the aetiology of intestinal Crohn's disease, the potential involvement of this mycobacterial species in OFG and oral lesions of Crohn's disease was investigated. PATIENTS: To attempt detection of the organism in OFG and oral Crohn's disease tissue samples, a polymerase chain reaction (PCR) assay was used on archival formalin fixed, paraffin wax embedded oral tissue sections from 30 patients with OFG, seven with Crohn's disease, and 12 normal controls. METHODS: The PCR assay used was based on primers targeting the 5' region of the multicopy IS900 DNA insertion element of the M paratuberculosis genome. In order to achieve maximum sensitivity, two rounds of PCR were carried out and amplicons confirmed by Southern blot hybridisation to a digoxigenin labelled IS900 DNA probe. RESULTS: None of the OFG and oral lesions of Crohn's disease samples were positive for M paratuberculosis and all normal controls were also negative. CONCLUSIONS: These results suggest that M paratuberculosis may not be a major aetiological agent in OFG or oral Crohn's disease lesions, although the use of paraffin wax embedded tissue as opposed to fresh tissue as a sample source could underestimate the true prevalence of the organism.

Blotting, Southern↗
PubMed1997

A three-dimensional imaging system for archiving dental study casts: a preliminary report.

Dental study casts form an essential part of patient records for both diagnostic and medicolegal purposes. Storage of study casts poses major problems because of inconvenience and cost of mass storage. Various methods for recording and storage of study casts are discussed. A new biostereometric technique for digitally recording and storing dental casts, and using the recent advances in stereophotogrammetry, is presented. Archiving dental casts in a digital format would reduce problems of mass storage and provide new benefits such as duplication of casts and use in clinical and research studies.

Archives↗
PubMed1996

Relative potencies of metal ions on transmitter release at mouse motor nerve terminals.

1. The effects of a range of metal ions were systematically studied at the mouse neuromuscular junction in order to investigate the type of calcium channel present at the nerve terminal. 2. Endplate potentials and miniature endplate potentials were recorded from the phrenic nerve diaphragm muscle preparation with glass microelectrodes. 3. Endplate potential amplitudes and quantal contents were reduced by manganese (IC50 220 microM), cadmium (IC50 11 microM), cobalt (IC50 350 microM), and nickel (IC50 420 microM). Miniature endplate potentials were not affected by these ions at concentrations equal to the IC50s. Gadolinium did not reduce endplate potentials up to 100 microM. 4. Comparisons made with known channel types in neuroblastoma cell lines suggest that the calcium channels at the motor nerve terminal are different from those types studied in the cell lines, although most similarity is shown to the high-voltage activated calcium channel types.

Animals↗
PubMed1996

Three-dimensional modeling for modern diagnosis and planning in maxillofacial surgery.

The existing methods of recording the face in three dimensions are reviewed, and a new method for three-dimensional facial modeling is introduced. The technique utilizes two stereo pairs of videocameras, a stereo pair at each side of the patient's face. The system allows rapid capture of the face in three dimensions and precise measurement of anatomic landmarks. The system can be used to capture the facial image and a cephalogram almost simultaneously, allowing more accurate superimposition of soft and hard tissues. This precision will facilitate development of the surgical treatment plan. A computer program in the early stages of development will use the data generated by this biostereometric measurement system to predict soft tissue changes following orthognathic surgery.

Cephalometry↗
PubMed1995

Use of site-directed antibodies to probe the topography of the alpha 2 subunit of voltage-gated Ca2+ channels.

Polyclonal antibodies were raised against peptides corresponding to residues 1-15, 469-483 and 933-951 of the rabbit skeletal muscle L-type calcium channel alpha 2/delta primary translation product, for use as topological probes. Immunocytochemical comparison of the abilities of the antibodies to bind to the alpha 2 and delta subunits in intact and detergent-permeabilised rat dorsal root ganglion cells enabled the membrane orientation of these regions to be established. The resultant data indicate that the regions containing residues 1-15 and 469-483 of the alpha 2 subunit, and residues 1-17 of the delta subunit, are exposed on the extracellular surface of the membrane, findings consistent with a model that proposes alpha 2 to be entirely extracellular.

Amino Acid Sequence↗
PubMed1995

Comparison of periodontal disease in HIV seropositive subjects and controls (I). Clinical features.

The aims of this study were to investigate the prevalence and severity of periodontal diseases in HIV seropositive and assumed HIV seronegative individuals in the Edinburgh area. 29 HIV seropositive subjects were examined at baseline and at 3-monthly intervals. Attachment loss and dichotomous indicators of periodontal disease were recorded. 27 control subjects were seen at baseline only. Although there was no significant difference between the 2 groups in terms of mean attachment loss at baseline, HIV seropositive subjects had experienced more severe attachment loss localised to the lower incisor region. HIV seropositive subjects had a significantly higher mean % of sites exhibiting suppuration and redness. A distinct subgroup of 9 HIV seropositive subjects with widespread attachment loss was detected, which included those subjects with severely affected lower incisors. Site-specific attachment loss of > or = 3 mm was observed in only 20 sites out of 2814 sites in HIV+subjects observed longitudinally. The incidence of aggressive periodontal disease in this study was lower than anticipated, despite the inclusion of patients with advanced HIV infection or AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Changes in activation gating of IsK potassium currents brought about by mutations in the transmembrane sequence.

Expression of the rat kidney IsK protein in Xenopus oocytes produces slowly-activating potassium channel currents. We have investigated the relationship between structure and function of the single putative membrane-spanning domain using site-directed mutagenesis. Six mutants were constructed in which consecutive individual amino acids (53 to 58) of the transmembrane region were substituted by cysteine. Expression of four of these mutants in Xenopus oocytes resulted in currents which were similar to wild-type. However, for one mutant (position 55) activation curves were shifted in a hyperpolarising direction and for another mutant (position 58) activation curve were shifted in a depolarising direction. This suggests that the hydrophobic phenylalanine residues at positions 55 and 58 may play a critical role in IsK activation gating. This spacing of functional amino acids at every third residue may indicate an alpha-helical conformation for the membrane-spanning domain of IsK. Furthermore, these results also indicate that one face of the helix may represent a region of subunit association.

Amino Acid Sequence↗