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Biomedical subjects

G T Clark

Publications and source records attributed to G T Clark.

At least 19 recordsLinked to original sources

Lipidomic analysis of the molecular specificity of a cholinephosphotransferase in situ.

Dynamic lipidomics using ESI-MS (tandem electrospray ionization mass spectrometry) of 9-deuterated choline (choline-d(9)) incorporation into mammalian cell PtdCho (phosphatidylcholine) permits assessment of the molecular specificity of synthesis. Bulk cell PtdCho synthesis occurs in spatially distinct locations, using separate CPTs (1,2 diacylglycerol CDP:choline cholinephosphotransferases). We assessed whether in vitro molecular selectivity of DAG (diacylglycerol) incorporation between CPTs is manifest in situ, by monitoring choline-d(9) incorporation into PtdCho and lyso-PtdCho molecular species over 3 h in control cells and in CHO-K1 cells overexpressing hCEPT1. Compared with controls, the basal molecular species composition of hCEPT1 overexpressors was significantly enriched in arachidonate. This was not due to net accretion of cellular PtdCho arguing against effects of inadequate unsaturated PtdCho degradation or remodelling. Rather, time-course analyses of PtdCho and lyso-PtdCho pools showed that both arachidonate-containing DAG incorporation and turnover of PtdCho is increased in hCEPT1 overexpressors. Increased choline-d(9) incorporation into arachidonyl lyso-PtdCho shows that both phospholipase A(1)- and A(2)-mediated turnover is involved. Spatially distinct molecular specificity of DAG incorporation into cellular PtdCho at the level of hCEPT1 exists in situ.

Animals↗

The effect of eicosapentaenoic acid on rat lymphocyte proliferation depends upon its position in dietary triacylglycerols.

Animal and human studies have shown that greatly increasing the amount of fish oil [rich in long-chain (n-3) PUFA] in the diet can decrease lymphocyte functions. The effects of a more modest provision of long-chain (n-3) PUFA and whether eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6) have the same effects as one another are unclear. Whether the position of 20:5 or 22:6 in dietary triacylglycerols (TAG) influences their incorporation into immune cells and their subsequent functional effects is not known. In this study, male weanling rats were fed for 6 wk one of 9 diets that contained 178 g lipid/kg and that differed in the type of (n-3) PUFA and in the position of these in dietary TAG. The control diet contained 4.4 g alpha-linolenic acid (18:3)/100 g total fatty acids. In the other diets, 20:5 or 22:6 replaced a portion (50 or 100%) of 18:3, and were in the sn-2 or the sn-1(3) position of dietary TAG. There were significant dose-dependent increases in the proportion of 20:5 or 22:6 in spleen mononuclear cell phospholipids when 20:5 or 22:6 was fed. These increases were at the expense of arachidonic acid and were largely independent of the position of 20:5 or 22:6 in dietary TAG. Spleen lymphocyte proliferation increased dose dependently when 20:5 was fed in the sn-1(3) position of dietary TAG. There were no significant differences in interleukin-2, interferon-gamma or interleukin-10 production among spleen cells from rats fed the different diets. Prostaglandin E(2) production by spleen mononuclear cells was decreased by inclusion of either 20:5 or 22:6 in the diet in the sn-1(3) position. Thus, incorporation of 20:5 or 22:6 into spleen mononuclear cell phospholipids is not influenced by the position in dietary TAG. However, the pattern of incorporation may be influenced, and there are some differential functional effects of the position of long-chain (n-3) PUFA in dietary TAG. A moderate increase in the intake of 20:5 at the sn-1(3) position of dietary TAG increases lymphocyte proliferation.

Animals↗

Signal intensity changes in T2-weighted MR image of the human trapezius muscle upon cold pressor stimulation.

OBJECTIVE: The ability to measure hemodynamics of skeletal muscle proper is one of the major goals for muscle pain researchers. The aim of the present study was to evaluate the ability of signal intensity (SI) in T2-weighted trapezius muscle magnetic resonance imaging (MRI) to detect intramuscular hemodynamic changes during cold pressor stimulation (CPS). MATERIALS AND METHODS: Fifteen healthy volunteers (mean age, 25.9+/-2.1 years) participated in this study. T2-weighted MRI was acquired using a 1.5 tesla MR unit with a body array coil. The slice level was set perpendicular to the muscle long axis at the mid-point of the horizontal portion of the right trapezius muscle. Cold pressor stimulation (4 degrees C) was applied to each subject's right foot and ankle for 2 min. The SI changes were recorded continuously for 7 min before, 2 min during, and 6 min after withdrawal of cold pressor stimulation. Six of these subjects also underwent a mock-CPS trial. RESULTS: The mean SI level in T2-weighted trapezius muscle MRI significantly increased during CPS (P<0.0001, one way repeated measure ANOVA) and returned to the baseline level after cold pressor withdrawal. No statistically significant signal changes were observed across the mock-CPS trial subjects. These findings are identical to the cold pressor-induced hemodynamic changes documented in the trapezius muscle by near-infrared spectroscopy evaluation. CONCLUSIONS: SI measurement in T2-weighted trapezius muscle MRI is sufficiently sensitive to detect intramuscular hemodynamic changes during CPS.

Adult↗

The value of maximum jaw motion measurements for distinguishing between common temporomandibular disorder subgroups.

OBJECTIVE: The purpose of this study was to determine if mandibular motion measurements could be used to distinguish between common temporomandibular disorder (TMD) subgroups that were established on the basis of only clinical signs and symptoms. STUDY DESIGN: Patients were 41 consecutive TMD clinic patients (31 women and 10 men). These patients were divided into 6 typical TMD subgroups. The subgroups were patients with (1) arthromyalgia, (2) arthromyalgia with disk condyle incoordination, (3) disk condyle incoordination only, (4) osteoarthritis, (5) suspected disk displacement without reduction, or (6) other diagnoses. RESULTS: There were no subjects in the other-diagnosis subgroup and only 1 subject with suspected disk displacement without reduction who was dropped without further consideration. The data for mean age showed that the osteoarthritis subgroup (n = 12) was statistically older (17 years) than the disk-condyle-incoordination-only subgroup (n = 11). The mean age of the other 2 groups, arthromyalgia (n = 11) and arthromyalgia with disk condyle incoordination (n = 6), was between the osteoarthritis and the disk-condyle-incoordination-only subgroups. For the 4 TMD subgroups whose data were analyzed, the mean differences between similar jaw opening measurements ranged from 6 to 8 mm with a standard deviation of approximately 8 to 10 mm. The mean left lateral motions were 0.5 to 1.3 mm larger than observed on the right. The widest mean jaw opening (56 mm) occurred in the disk-condyle-incoordination-only group. These differences were not found to be statistically significant. CONCLUSION: Analysis of opening, lateral and protrusive jaw motion data showed these measurements could not reliably differentiate between patients with osteoarthritis, arthromyalgia, arthromyalgia with disk condyle incoordination and disk condyle incoordination only.

Adult↗

Electrospray ionisation mass spectrometric analysis of lipid restructuring in the carp (Cyprinus carpio L.) during cold acclimation.

Cold acclimation of carp from 30 degrees C to 10 degrees C causes a restructuring of liver microsomal phospholipids characterised by increased proportions of monounsaturated fatty acid in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). Here, we have used electrospray ionisation mass spectrometry (ESI-MS) to determine the patterns of alteration to individual molecular species compositions of PC, PE and phosphatidylinositol (PI) in response to gradually decreasing temperature. The results demonstrate that cold induces precise changes to a limited number of phospholipid species, and that these changes are distinct and different for each phospholipid class. The major change for PC was increased 16:1/22:6, but for PE the species that increased was 18:1/22:6. By contrast, the PI species that increased during cold acclimation were characterised by an sn-1 monounsaturated fatty acid in combination with arachidonoyl or eicosapentaenoyl fatty acid at the sn-2 position. Analysis of acyl distribution indicates that cold only caused the accumulation of monounsaturated fatty acids at the sn-1 and not at the sn-2 position of phospholipids. These results highlight the tight and restricted range of modifications that membranes make to their phospholipid composition in response to thermal stress.

Animals↗

Intramuscular haemodynamic responses to different durations of sustained extension in normal human masseter.

Ten healthy non-smoking males (mean age 24.3+/-0.8 years) with no history of chronic muscle pain or migraine participated in this study. Intramuscular total haemoglobin (Hb), an indicator of blood volume in the illuminated area, was measured with a non-invasive, near-infrared spectroscopic device. Each participant was told to maintain maximal mouth opening to extend the masseter muscle for 30, 60 or 120 s in random order. Data were continuously recorded from the right masseter 1 min before, at set times during and for 5 min after sustained muscle extension in each trial. Each trial was separated by a 10-min interval. Heart rate (HR) and blood pressure (BP) were also recorded. The mean normalized Hb decreased during muscle extension and rebound hyperaemia was observed after it in each trial (P=0.0001). Hb returned to baseline within 60 s. The magnitude of the decremental change during extension and of the incremental change in the rebound hyperaemia was not significantly different among the three trials (P=0.9071); neither were mean normalized HR and BP. These data suggest that sustained extension of the masseter produces a reduction in total intramuscular Hb during extension and a secondary increase in Hb following a return to the resting muscle's normal length.

Adult↗

Correlation of the near-infrared spectroscopy signals with signal intensity in T(2)-weighted magnetic resonance imaging of the human masseter muscle.

The purpose of this study was to compare and contrast blood volume changes transcutaneously measured using near-infrared (NIR) spectroscopy against water signal intensity changes taken from a transverse T(2)-weighted MR image of the masseter muscle in healthy human subjects before, during and after contraction. Eight healthy non-smoking males with no history of chronic muscle pain or vascular headaches participated (mean age: 23.9+/-0.6 years). The MRI data were gathered using a turbo spin echo sequence (TR: 2300 ms; TE: 90 ms; FOV: 188x300 mm; scanning time: 30 s; slice thickness: 10 mm) and the slice level was set at the mid-point between the origin and insertion of the masseter. Intramuscular haemoglobin (Hb) levels and water content of the right masseter muscle were continuously monitored for 2 min before, 30 s during and 15 min after a maximum voluntary clenching (MVC) task. Both the near-infrared and MRI data were baseline-corrected and normalized and mean levels were established and plotted. Plots of the data showed that both near-infrared-based total Hb and T(2)-weighted MRI-based signal-intensity levels clearly decreased during contraction and a clear post-contraction rebound response was evident after the contraction. The near-infrared data were found to be highly correlated with MRI-based signal-intensity data (Pearson's r=0.909, P<0.0001). In conclusion, these data provide powerful evidence that near-infrared data (total Hb), transcutaneously taken from the masseter muscle in humans, will reflect the intramuscular water signal intensity changes seen using a T(2)-weighted MRI imaging method.

Adult↗

The effect of altering jaw position on the transmission of vibration between the skull and teeth in humans.

The forces that develop in the human temporomandibular joint during function have never been directly measured, yet many patients exhibit excessive localized wear and tear of the joint, suggesting that at times these forces exceed tissue tolerance. The purpose here was to gain insight into vibration transmission between the cranium and mandible in healthy humans during variations of jaw position. In 13 normal healthy adult men (age 25-40 years) with normal dentitions, vibration (around 400 Hz, sine wave) was applied to the skull vertex and changes in the intensity of the vibration signal were measured using several small linear accelerometers cemented to the buccal surfaces of mandibular first molars and the labial surfaces of maxillary central incisors. The jaw was opened, protruded and moved laterally by the individual participant and vibration signal intensities were tested (lower first molar signal/upper incisor signal) for change at each mandibular position by ANOVA. The results showed the vibration signal changed significantly with opening and less so on protrusion and laterotrusion. The vibration signal during opening could be categorized into three types: (1) signal increased continuously with increased opening; (2) signal increased, then reached a plateau during last third of opening; (3) signal increased, then decreased when the individual moved from 40 mm to maximum opening. These findings show that as the jaw moves laterally, and especially as it opens, the magnitude of the vibration signal increases substantially compared with the near-closed position.

Acceleration↗

A vibratory stimulation-based inhibition system for nocturnal bruxism: a clinical report.

For the single subject tested to date, the bruxism-contingent vibratory-feedback system for occlusal appliances effectively inhibited bruxism without inducing substantial sleep disturbance. Whether the reduction in bruxism would continue if the device no longer provided feedback and whether the force levels applied are optimal to induce suppression remain to be determined.

Adult↗

An evidence-based assessment of occlusal adjustment as a treatment for temporomandibular disorders.

STATEMENT OF PROBLEM: Occlusal adjustment therapy has been advocated as a treatment modality for temporomandibular disorders. In contrast to this position, a panel at the 1996 National Institute of Health technology assessment conference on TMD indicated that no clinical trials demonstrate that occlusal adjustment is superior to noninvasive therapies. PURPOSE: This article summarizes the published experimental studies on occlusal adjustments and temporomandibular disorders. MATERIAL AND METHODS: Eleven research experiments involving 413 subjects with either bruxism (n = 59), temporomandibular disorders (n = 219), headaches and temporomandibular disorders (n = 91), or chronic cervical pain (n = 40) were selected for critical review from the English dental literature. RESULTS: Three experiments evaluated the relationship between occlusal adjustment and bruxism. Six experiments evaluated occlusal adjustment therapy as a treatment for patients with primary temporomandibular disorders. One experiment looked at occlusal adjustment effect on headache/temporomandibular disorder symptoms; another looked at its effect on chronic neck pain. Most of these experiments used a mock adjustment or a comparison treatment as the control condition in adults who had an existing nonacute general temporomandibular disorder. Overall, the data from these experiments did not demonstrate elevated therapeutic efficacy for occlusal adjustment over the control or the contrasting therapy. CONCLUSION: The experimental evidence reviewed was neither convincing nor powerful enough to support the performance of occlusal therapy as a general method for treating a nonacute temporomandibular disorder, bruxism, or headache.

Adult↗

A piezoelectric film-based intrasplint detection method for bruxism.

STATEMENT OF PROBLEM: An accurate, easy-to-use, long-term method other than EMG is needed to monitor bruxism. PURPOSE: This article presents pilot data on the reproducibility, validity, and utility of an intrasplint piezoelectric film method. MATERIAL AND METHODS: Simulated bruxism behaviors (steady-state and rhythmic clenching, grinding, and tapping) in 5 subjects were recorded with the use of both masseter EMG and an intrasplint piezoelectric film method. RESULTS: Correlation coefficients calculated for simulated bruxism event duration with the use of a masseter EMG or an intrasplint piezoelectric film method were 0.99 for tapping and steady-state clenching, 0.96 for rhythmic clenching, and 0.79 for grinding. CONCLUSION: Piezoelectric film has its limitations and does not faithfully capture sustained force magnitudes. However, for the target behaviors associated with bruxism (tooth grinding, clenching, and tapping), it appears to faithfully reproduce above-baseline events with durations statistically indistinguishable from those recorded with masseter EMG. Masseter EMG was poorest at detecting a simulated side-to-side grinding behavior.

Adult↗

A review of temporomandibular disorder diagnostic techniques.

The American Dental Association has approved several devices as aids in the diagnosis of temporomandibular disorders. Concerns remain, however, about their safety and effectiveness. This article reviews the validity and use of several instruments that claim to serve as aids in the detection of masticatory muscle pain, trismus, joint noises, and limitation of jaw motion. A review of data from 62 published articles indicated that, although commercial devices that measure jaw muscle tenderness, muscle activity levels, joint noises, and jaw motion are safe and can document these phenomena, cost-benefit analyses of these devices have not yet been conducted. Moreover, these devices have not been shown to have stand-alone diagnostic value and, when tested, they have demonstrated unacceptable sensitivity and specificity levels. None of the instruments reviewed in this article can be said to provide more than ancillary documentation.

Auscultation↗

Occlusal stabilization appliances. Evidence of their efficacy.

BACKGROUND: There is substantial controversy regarding the value of occlusal appliances for managing temporomandibular joint disorders. This article specifically assesses whether the evidence is sufficient to judge occlusal appliances as being efficacious for the management of localized masticatory myalgia, arthralgia or both. A major confounder is that few studies have measured or evaluated whether subjects had strong, ongoing parafunctional activity (such as clenching or grinding) and whether appliances influenced this behavior. LITERATURE REVIEWED: The authors evaluated four placebo-controlled studies, several randomized wait-list controlled studies and several random-assignment treatment-comparison studies. Data from the wait-list condition studies vs. those from the occlusal appliance condition studies consistently suggested that the latter treatment's effect on patient symptom level is far more than that of no treatment on a wait-list group's condition. In contrast, the studies on placebo-controlled vs. occlusal appliance studies yielded a mix of data: two showed a positive benefit of occlusal vs. nonoccluding appliances, and two showed a null effect or no difference. CONCLUSIONS: Considering all of the available data (pro and con), the authors conclude that the use of occlusal appliances in managing localized masticatory myalgia, arthralgia or both is sufficiently supported by evidence in the literature. CLINICAL IMPLICATIONS: The mechanism of action by which occlusal appliances affect localized myalgia and arthralgia probably is behavioral modification of jaw clenching. However, if the behavior continues unabated, even the best splint will not work.

Arthralgia↗

Education problems and Web-based teaching: how it impacts dental educators?

This article looks at six problems that vex educators and how web-based teaching might help solve them. These problems include: (1) limited access to educational content, (2) need for asynchronous access to educational content, (3) depth and diversity of educational content, (4) training in complex problem solving, (5) promotion of lifelong learning behaviors and (6) achieving excellence in education. The advantages and disadvantage of web-based educational content for each problem are discussed. The article suggests that when a poorly organized course with inaccurate and irrelevant content is placed online, it solves no problems. However some of the above issues can be partially or fully solved by hosting well-constructed teaching modules on the web. This article also reviews the literature investigating the efficacy of off-site education as compared to that provided on-site. The conclusion of this review is that teleconference-based and web-based delivery of educational content can be as effective as traditional classroom-based teaching assuming the technologic problems sometimes associated with delivering teaching content to off-site locations do not interfere in the learning process. A suggested hierarchy for rating and comparing e-learning concepts and methods is presented for consideration.

Computer-Assisted Instruction↗

Highly saturated endonuclear phosphatidylcholine is synthesized in situ and colocated with CDP-choline pathway enzymes.

Chromatin-associated phospholipids are well recognized. A report that catalytically active endonuclear CTP:choline-phosphate cytidylyltransferase alpha is necessary for cell survival questions whether endonuclear, CDP-choline pathway phosphatidylcholine synthesis may occur in situ. We report that chromatin from human IMR-32 neuroblastoma cells possesses such a biosynthetic pathway. First, membrane-free nuclei retain all three CDP-choline pathway enzymes in proportions comparable with the content of chromatin-associated phosphatidylcholine. Second, following supplementation of cells with deuterated choline and using electrospray ionization mass spectrometry, both the time course and molecular species labeling pattern of newly synthesized endonuclear and whole cell phosphatidylcholine revealed the operation of spatially separate, compositionally distinct biosynthetic routes. Specifically, endogenous and newly synthesized endonuclear phosphatidylcholine species are both characterized by a high degree of diacyl/alkylacyl chain saturation. This unusual species content and synthetic pattern (evident within 10 min of supplementation) are maintained through cell growth arrest by serum depletion and when proliferation is restored, suggesting that endonuclear disaturated phosphatidylcholine enrichment is essential and closely regulated. We propose that endonuclear phosphatidylcholine synthesis may regulate periodic nuclear accumulations of phosphatidylcholine-derived lipid second messengers. Furthermore, our estimates of saturated phosphatidylcholine nuclear volume occupancy of around 10% may imply a significant additional role in regulating chromatin structure.

Choline-Phosphate Cytidylyltransferase↗

Reliability, validity, and utility of various occlusal measurement methods and techniques.

STATEMENT OF PROBLEM: The controversy continues regarding the efficacy of several commercially available devices that are used as aids in the diagnosis of occlusal abnormalities. PURPOSE: This article reviews the reliability, validity, and utility of instruments that claim to detect occlusal interferences and abnormal vertical dimension of occlusion. MATERIAL AND METHODS: Data, opinions, and technical information from 37 published articles were reviewed. Evidence for method reliability, validity, and utility was assessed. RESULTS: Although occlusal contact detection devices can document the occlusal contact patterns on teeth, the basic in vivo testing of their reproducibility and validity has not been performed. Moreover, while EMG and jaw tracking systems can indeed measure jaw muscle activation and jaw position, no cost-benefit analysis of these devices has yet been conducted. One manufacturer suggests that these instruments be used in conjunction with an electrical muscle stimulation device to find a new resting jaw position that is more open vertically. This new, more open position has been inappropriately labeled as evidence of vertical dimension of occlusion over-closure. CONCLUSION: None of the instruments reviewed can be said to be more than ancillary documentation devices and they have been inadequately tested for reliability and validity. Moreover, because scientifically acceptable disease definitions are not available for these 2 conditions, the issue of over-diagnosing becomes a substantial concern.

Dental Occlusion↗

Biomechanical calculation of human TM joint loading with jaw opening.

A three-dimensional, static mathematical calculation of the stomatognathic system was done to predict total temporomandibular joint (TMJ) loading at different levels of jaw opening. The model assumed that muscle forces acting on the mandible could be simulated by a combination of contractile components (CCs) and elastic components (ECs) and that static equilibrium existed within the body of the mandible. The model also imposed the constraint that any generated joint reaction force would act on the centre of the condyle. The results of the model demonstrated that under all conditions of opening and for all values of the elastic modulus selected, the forces between the TMJ condyle and the articular eminence were compressive in nature. The compressive force magnitude increased from 2.7 to 27.6 N incrementally as the jaw opened from 10 to 40 mm. Overall data in this study indicated that the TMJ tissues undergo low levels of compression at open positions up to 40 mm. Finally, the condition of trismus (increased jaw closing activation with opening) was simulated, the joint reaction force at 20 mm opening increased from 7.7 to 64.9 N with only a 20% activation of the closers.

Adult↗

Topical medications for orofacial neuropathic pain: a review.

BACKGROUND: The authors discuss the local pharmacotherapy for chronic orofacial neuropathic pain disorders such as neuropathies, neuromas and neuralgias. METHODS: The authors conducted a systematic literature review on this topic. The focus of the review involved the two most commonly applied medications for neuropathic disorders--local anesthetics and capsaicin. Other compounds such as nonsteroidal anti-inflammatory drugs, sympathomimetic agents, anticonvulsants and N-methyl-D-aspartate receptor antagonists also were reviewed. The medication delivery and retention methods appropriate for oral and perioral disease and pain control are described in this article. RESULTS: There are an ever-increasing number of agents that can be used to help patients with neuropathic-based oral and perioral pain problems. Moreover, a clear advancement in the delivery of these medications is the development of a vehicle-carrier agent (pluronic lecithin organogel) that can penetrate the mucosa and cutaneous tissues and carry the active medication with it to the treatment site. The major caveat underlying these treatment strategies is that except for patient testimony and a few studies, there are limited empirical data on the efficacy of most of these new formulations, and additional research is clearly needed. CONCLUSIONS: Because of their rapid onset and low side-effect profile, topical medications offer a distinct advantage over systemic administration for those orofacial disorders that are regional, near the surface and chronic and that demonstrate some response such as pain relief to topical or subcutaneous anesthetics. CLINICAL IMPLICATIONS: Practicing dentists now have some new tools they can use to help manage patients who have a chronic nerve pain disorder in and around the mouth.

Administration, Topical↗