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Biomedical subjects

D Wray

Publications and source records attributed to D Wray.

At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed1994

Recent non-sterile inoculation injuries to dental professionals in the Lothian region of Scotland.

A retrospective study of inoculation injuries in dental practice was conducted by means of a questionnaire distributed to 310 dental practitioners in the Lothian region of Scotland. Recent injuries were independently classified by a hospital dentist, general dental practitioner and immunologist as constituting high, moderate or low risk of transmission to the dentist. A consultant physician in infectious diseases assessed the follow-up actions. The results indicate that non-sterile inoculation injuries are a common hazard of dental practice with 56% of respondents reporting at least one such injury within the last year. A total of 30% of reported injuries constituted a moderate or high risk of transmission to the dental practitioner. Action taken following such injuries was often considered to be inadequate. While many injuries could possibly be avoided by changes in surgery design, avoidance of other injuries would probably require fundamental changes in routine dental practice. While the incidence of such injuries is high, dental practice within the UK appears to be associated with a low risk of acquiring HIV infection by occupational exposure. The increasing awareness of the importance of other blood-borne viral infections makes this a continuing issue.

Blood-Borne Pathogens↗
PubMed1994

Passive transfer of seronegative myasthenia gravis to mice.

Muscle weakness in myasthenia gravis is due to autoantibody-induced loss of functional acetylcholine receptors (AChR). About 15% of myasthenia gravis patients, however, do not have detectable anti-AChR antibodies. To investigate the effect of their plasma immunoglobulins on neuromuscular transmission, mice were injected with plasma (and in some cases purified immunoglobulin G (IgG)) from 7 "seronegative" myasthenia gravis (SMG) patients, and neuromuscular transmission parameters were examined. When injected for 15 days, all patients' plasma caused reductions in miniature endplate potential amplitudes, while endplate potential quantal content was significantly reduced by plasma from 4 of the 7 patients. There were no changes in ACh-induced depolarization or single channel properties, and 125I-alpha-bungarotoxin binding studies showed no effect on AChR number, except in 1 case. Purified IgG injected for 3 days had similar effects to plasma injected for 15 days. Our findings confirm that SMG is autoantibody mediated and that there are pathogenic IgG antibodies. SMG appears to be a heterogeneous disorder and the target(s) for the antibodies may be diverse.

Acetylcholine↗
PubMed1994

Modulation by protein kinase A of a cloned rat brain potassium channel expressed in Xenopus oocytes.

A potassium channel from rat brain was expressed in Xenopus oocytes in order to study modulation of channel function by phosphorylation via protein kinase A. Application of 8-Br-cAMP to oocytes expressing the drk1 channel (with the first 139 amino acids of the N terminus deleted, delta Ndrk1) caused a voltage-independent elevation of current amplitude, which was not seen for endogenous currents or for wild-type full-length drk1 channel. This effect on delta Ndrk1 was blocked by pre-injection of oocytes with Walsh-peptide protein kinase A inhibitor, suggesting mediation via protein kinase A. The protein kinase inhibitor also reduced both delta Ndrk1 and full-length drk1 currents. Substitution of the serine residues by alanine at one or both of the two consensus protein kinase A phosphorylation sites on the C terminus (residues 440 and 492) of delta Ndrk1 resulted in a loss of function of the expressed channels. These results indicate that phosphorylation via protein kinase A modulates drk1 channel function and that both consensus phosphorylation sites seems to be essential for channels to function.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Appropriate and inappropriate prescribing of narcotics for ambulatory HIV-positive patients.

OBJECTIVE: To assess the appropriateness of narcotic-prescribing practices in an ambulatory clinic for patients infected with HIV. DESIGN, SETTING, AND PATIENTS: The medical records of 220 (190 HIV-positive) patients, seen in a clinic primarily designed for the long-term follow-up of ambulatory HIV-infected patients and located in an inner-city, public teaching hospital, were retrospectively reviewed to determine the prevalence and appropriateness of prescribing Drug Enforcement Administration schedule 2 narcotics. Appropriateness was based on published guidelines for the use of narcotics in the treatment of cancer patients. MEASUREMENTS AND MAIN RESULTS: The prevalence of narcotic use among the HIV-positive patients was 15%. Narcotics were prescribed for 38% of the patients who died, 33% of those with AIDS [Centers for Disease Control and Prevention (CDC) clinical class C], 4% of those with AIDS-related complex (ARC) (CDC clinical class B), and 5% of asymptomatic HIV-positive patients (CDC clinical class A). None of the HIV-negative patients seen in the clinic received narcotics. Narcotics were more likely to be prescribed for patients with AIDS than for patients with ARC (p < 0.001) or for HIV-positive patients (p < 0.001). For the three CDC clinical classes, there was no significant difference among the proportions of patients receiving narcotics inappropriately (p = 0.108). Among the risk groups, intravenous drug abusers were more likely to be prescribed narcotics inappropriately than were men who were homosexual (p < 0.001) or individuals who were heterosexual (p = 0.013); transfusion recipients were also more likely to be prescribed narcotics inappropriately than were homosexual men (p = 0.026) or heterosexual men or women (p = 0.032). Narcotics were more likely to be prescribed for patients with disseminated histoplasmosis (p = 0.022), Pneumocystis carinii pneumonia (p = 0.001), candidal esophagitis (p = 0.020), Kaposi's sarcoma (p < 0.001), or wasted appearance (p = 0.043). Inappropriate prescriptions were more likely to be given to patients with dementia (p = 0.005) or wasted appearance (p = 0.019). CONCLUSIONS: Physicians tend to prescribe narcotics inappropriately to patients known to have previously abused drugs and to those who appear wasted or have dementia. Physicians have a duty to prescribe narcotics appropriately as guided by recognized medical indications and the patients' views concerning their current medical needs.

AIDS-Related Complex↗
PubMed1994

Occupational risk and precautions related to HIV infection among dentists in the Lothian region of Scotland.

This retrospective study used a postal questionnaire to measure occupational risks and to assess infection control procedures among 310 dental practitioners. The study comprised general dental practices in the Lothian region of Scotland, Lothian Health Board Community Dental Service and Edinburgh Dental Hospital. Altogether, 217 dental practitioners responded by the due date giving recall of inoculation injuries within the previous 5 years and infection control measures employed. The study revealed that 191 practitioners (88%) had completed a course of hepatitis B vaccination but one-third of them had not been tested for post-vaccination antibody. In 1991, two thirds of dentists (66%: 137 of 207 respondents) wore the same pair of gloves, and 80% of dentists (142 of 177 respondents) wore the same mask, for dealing with more than one patient. The usual practice was to change gloves during sessions (44%: out of 71 dentists) and to change masks for each session or less often (75%: 73 out of 97 dentists). The proportion of dentists who never used gloves fell from 56% in 1981 to 1% in 1991. An autoclave was used for sterilisation by 85% of practitioners in 1991. Reported non-sterile inoculation injuries averaged 1.7 (S.D. = 3.2) injuries per dentist in the previous year with 56% of practitioners having had an injury. The average was 6.8 (S.D. = 15.9) injuries per dentist in the previous 5 years with 76% of practitioners having had an injury. Of recent non-sterile inoculation injuries described by dental practitioners, 30% constituted a moderate or high risk of transmission of infection to the practitioner (43 of 141 described injuries). Combined with HIV seroprevalance rates, probabilities of transmission and numbers of practising dentists, the mean reported number of non-sterile inoculation injuries in the previous 5 years may be used to provide estimates of expected numbers of dental practitioners occupationally infected with HIV in the previous 5 years. U.K. estimates were 0.004 dentists in Lothian region and 0.05 dentists in the Thames region occupationally infected with HIV in the previous five years. Non-sterile inoculation injuries appear to be a common hazard of dental practice. In any year, most dentists are exposed to the risk of blood-borne viral infection. Despite a high reported incidence of such injuries, dental practice within the U.K. appears to carry a low risk of acquiring HIV infection from occupational exposure.

Dentists↗
PubMed1994

Characterization of somatostatin receptors on human neuroblastoma tumors.

Neuroblastoma is the most common extracranial solid tumor of children. Neuroblastoma tumors derive from the neural crest and synthesize neurotransmitters including the neuropeptide somatostatin. This study was designed to characterize somatostatin receptors both in primary neuroblastoma tumors and in two neuroblastoma cell lines, SKNSH and IMR32. Somatostatin receptors were identified in 6 of 7 Stage I and II compared to 7 of 19 Stage III and IV tumors. Down-regulation of somatostatin receptor binding was observed in five tumors during disease progression. A lack of high affinity binding of somatostatin was identified as a poor prognostic indicator; negative binding correlated with advanced disease and death. Somatostatin receptor binding was observed in the IMR32 cell line, but not in the SKNSH cell line. IMR32 cells demonstrated a single class of high affinity binding sites for both somatostatin and a synthetic analogue, octreotide (Kd 0.16 +/- 0.05 nM and 0.89 +/- 0.23 nM, respectively). Somatostatin and octreotide inhibited both vasoactive intestinal peptide-mediated and forskolin-mediated cyclic AMP accumulation in IMR32 cells. Somatostatin and octreotide inhibition of signal transduction was attenuated by pretreatment of the cells with pertussis toxin. Octreotide inhibited proliferation of IMR32 cells by 70% in a 6-day culture. In contrast, octreotide did not exhibit high affinity binding in SKNSH cells and had no effect on cyclic AMP accumulation or on proliferation in SKNSH cells. Together, these data indicate that octreotide interacts with high affinity somatostatin receptors to modulate signal transduction and regulate proliferation in neuroblastoma cell lines. These data also suggest that somatostatin receptor expression may be an independent prognostic factor in primary neuroblastoma tumors.

Binding, Competitive↗
PubMed1993

Non-competitive antagonism of calcium by magnesium ions at the K(+)-depolarised mouse neuromuscular junction.

The effect of raising the external Ca2+ concentration on miniature end-plate potential (m.e.p.p.) frequency was measured in the K(+)-depolarised mouse phrenic nerve/hemidiaphragm preparation in the presence of a range of Mg2+ concentrations. With increasing external Mg2+, a plot of external Ca2+ concentration vs. m.e.p.p. frequency was shifted to the right and the maximum frequency attained was reduced. A Schild plot of the data gave a slope factor close to two. These data suggest a non-competitive antagonism of Ca2+ by Mg2+ under these conditions.

Animals↗
PubMed1993

Cross-linking of presynaptic calcium channels: a mechanism of action for Lambert-Eaton myasthenic syndrome antibodies at the mouse neuromuscular junction.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of neuromuscular transmission. Immunoglobulin G (IgG) autoantibodies act presynaptically to cause functional loss of Ca2+ channels by down-regulation. This in turn causes reduced release of acetylcholine in response to nerve stimulation (i.e. reduced quantal content). We show here that in vitro application of LEMS IgG for 24 h was as effective in causing reduced quantal content in mice as injecting animals with the antibody for 2 days. Furthermore, incubation with divalent (F(ab')2) fragments also significantly reduced quantal content. However, monovalent (Fab) fragments were without significant effect. No antibody or antibody fragment preparation affected spontaneous release. Whole LEMS IgG and F(ab')2 (but not Fab) fragments also inhibited K(+)-evoked 45Ca2+ flux in a small cell carcinoma cell line. These findings present functional evidence that LEMS IgG-induced down-regulation of nerve terminal Ca2+ channels arises due to antibody cross-linking of these channels.

Acetylcholine↗
PubMed1993

Current classifications of HIV-associated periodontal diseases.

The occurrence of unusual and severe forms of periodontal disease in HIV-infected individuals is well recognised. Several classification schemes have been proposed in an effort to associate periodontal deterioration with progressive stages of HIV infection and to determine aetiological factors in tissue destruction. No classification to date has proved entirely satisfactory. This paper reviews current classification schemes and suggests an alternative based upon the periodontal status of a cohort of HIV seropositive patients in Edinburgh. The proposed classification includes 'conventional', non-specific gingivitis and adult periodontitis such as occur in HIV seronegative individuals, but which may also be seen in seropositive subjects. However, conditions termed linear gingivitis and necrotising periodontitis may be pathognomonic for HIV infection. It is recommended that the term 'HIV-associated' be dropped in relation to periodontal disease.

Gingivitis↗