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Biomedical subjects

C D Myers

Publications and source records attributed to C D Myers.

At least 19 recordsLinked to original sources

Massage for mechanical neck disorders.

BACKGROUND: Mechanical neck disorders (MND) are common, disabling and costly. Massage is a commonly used modality for the treatment of neck pain. OBJECTIVES: To assess the effects of massage on pain, function, patient satisfaction and cost of care in adults with neck pain. To document adverse effects of treatment. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL databases were electronically searched, without language restriction, from their inception to September 2004 SELECTION CRITERIA: Studies using random or quasi-random assignment were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently conducted citation identification, study selection, data abstraction and methodological quality assessment. Using a random-effects model, we calculated the relative risk and standardized mean difference. MAIN RESULTS: Nineteen trials met the inclusion criteria. Overall, the methodological quality was low, with 12/19 assessed as low-quality studies. Trials could not be statistically pooled because of heterogeneity in treatment and control groups. Therefore, a levels-of-evidence approach was used to synthesize results. Assessment of the clinical applicability of the trials showed that the participant characteristics were well reported, but neither the descriptions of the massage intervention nor the credentials or experience of the massage professionals were well reported. Six trials examined massage as a stand-alone treatment. The results were inconsistent. Of the 14 trials that used massage as part of a multimodal intervention, none were designed such that the relative contribution of massage could be ascertained. Therefore, the role of massage in multimodal treatments remains unclear. AUTHORS' CONCLUSIONS: No recommendations for practice can be made at this time because the effectiveness of massage for neck pain remains uncertain. Pilot studies are needed to characterize massage treatment (frequency, duration, number of sessions, and massage technique) and establish the optimal treatment to be used in subsequent larger trials that examine the effect of massage as either a stand-alone treatment or part of a multimodal intervention. For multimodal interventions, factorial designs are needed to determine the relative contribution of massage. Future reports of trials should improve reporting of the concealment of allocation, blinding of outcome assessor, adverse events and massage characteristics. Standards of reporting for massage interventions, similar to CONSORT, are needed. Both short- and long-term follow-up are needed.

Humans↗

Gender role expectations of pain: relationship to sex differences in pain.

Empirical research supports the existence of sex differences in pain; yet these differences are poorly understood. Although biological mechanisms have been posited to explain variability, results of pain modeling manipulations suggest social learning may be a stronger influence on pain response. In this report we use the term sex to refer to the biological category of male or female. We use the term gender to refer to the socially acquired aspects of being male or female sometimes referred to as femininity and masculinity. This study investigated a new measure, the Gender Role Expectations of Pain questionnaire (GREP), which was designed to measure sex-related stereotypic attributions of pain sensitivity, endurance, and willingness to report pain. Subjects were 156 male and 235 female undergraduates at a southeastern university. Psychometric investigation of the questionnaire revealed a 5-factor solution that closely mirrored the theoretical construction of the items. Test-retest reliability was also shown for individual items on a separate sample of 28 subjects. Results supported hypotheses about gender role: both men and women rated men as less willing to report pain than women (F(1,389) = 336, P <.001); both men and women rated women more sensitive (F(1,389) = 9.5, P <.05) and less enduring of pain (F(1,389) = 65.7, P <.001) than men; and men rated their own endurance as higher than the typical man (F(1,389) = 65.7, P <.001). Sex accounted for 46% of the variance in willingness to report pain. Results suggest that the GREP distinguished between the socially learned reactions to pain for men and women. It is recommended that the influence of gender-related expectations for pain be assessed in all studies investigating human sex differences in pain.

Journal Article↗

Sex differences in negative emotional responses to chronic pain.

We proposed a sequential model of pain processing with pain intensity as stage 1, pain unpleasantness as stage 2, pain-related emotions (depression, anxiety, frustration, anger, fear) as stage 3, and overt behavioral expression of pain as stage 4. We tested hypotheses about relationships between sex and the first 3 stages of pain processing by conducting simultaneous regression analysis using LISREL-8 with data collected from 967 women and 680 men with chronic pain. We found the following results: (1) women reported higher pain-related frustration and fear; (2) frustration related most highly to pain intensity among women, as compared with anxiety and depression among men; (3) depression and frustration related most highly to usual and highest pain unpleasantness among women, as compared with frustration among men; and (4) contrary to expectations, pain-related emotions were more strongly related to pain for men. Consistent with the sequential model of pain processing, emotional response to pain was more closely related to pain unpleasantness than to pain intensity across sex. Anxiety and frustration were the emotions most highly related to pain. The current results highlight sex differences in the experience of chronic pain and the importance of assessing a range of emotions in patients with pain.

Journal Article↗

Sleep disturbance in orofacial pain patients: pain-related or emotional distress?

Associations between pain, depression, and sleep disturbance have been documented in several chronic pain patient samples. The current study assessed the prevalence and magnitude of sleep disturbance in a sample of 128 orofacial pain patients referred for clinical evaluation and tested linkages between sleep, depression, anxiety, and pain using cross-sectional and longitudinal data. Seventy-seven percent of the patients reported reduced sleep quantity since pain onset. In cross-sectional analyses, reduced sleep quantity was associated with depression and pain. Reduced sleep quality was associated with negative affect. Longitudinally, initial depression and pain predicted sleep at time two and initial pain predicted negative affect. Sleep did not predict pain. Results support the hypothesis that pain, rather than sleep disturbance, increases negative affect across time, whereas negative affect is more a cause of concurrent reduced sleep quality than is pain. The results highlight the importance of assessing for sleep disturbance in orofacial pain patients.

Adolescent↗

Factors predicting orofacial pain patient satisfaction with improvement.

AIMS: To determine psychosocial predictors of patients' ratings of satisfaction with improvement and subjective pain relief. This study also examined the underlying components of patient satisfaction with improvement, as assessed at follow-up. METHODS: The sample consisted of 107 chronic orofacial pain patients evaluated at a university-based orofacial pain clinic and referred for treatment with individualized treatment plans. Pain and psychosocial functioning were assessed with standard, reliable, validated self-report instruments administered at the initial evaluation. Follow-up data were collected via a telephone-administered structured interview 8 months after the initial evaluation. Regression methodology was used to determine prediction models for satisfaction with improvement and subjective pain relief. Patient ratings of the quality of the caregiver communication were used as a control variable in all analyses. RESULTS: Quality of caregiver communication predicted approximately 10 to 14% of the variance in outcomes in all models. Greater initial use of cognitive coping strategies and reduced depression predicted higher ratings of satisfaction with improvement and increased pain relief. When concurrent relationships among variables at the follow-up were examined, greater subjective pain relief since the evaluation, lower current pain, and higher ratings of overall mood were significant predictors of patient satisfaction with improvement. CONCLUSION: This study is one of the first to report that the use of certain cognitive coping strategies is associated with positive outcome for patients suffering from orofacial pain. These findings underscore the importance of individual differences on behavioral and psychosocial parameters in the prediction of patients' subjective evaluation of treatment outcome.

Activities of Daily Living↗

Dynamic control of deactivation gating by a soluble amino-terminal domain in HERG K(+) channels.

K(+) channels encoded by the human ether-à-go-go-related gene (HERG) are distinguished from most other voltage-gated K(+) channels by an unusually slow deactivation process that enables cardiac I(Kr), the corresponding current in ventricular cells, to contribute to the repolarization of the action potential. When the first 16 amino acids are deleted from the amino terminus of HERG, the deactivation rate is much faster (Wang, J., M.C. Trudeau, A.M. Zappia, and G.A. Robertson. 1998. J. Gen. Physiol. 112:637-647). In this study, we determined whether the first 16 amino acids comprise a functional domain capable of slowing deactivation. We also tested whether this "deactivation subdomain" slows deactivation directly by affecting channel open times or indirectly by a blocking mechanism. Using inside-out macropatches excised from Xenopus oocytes, we found that a peptide corresponding to the first 16 amino acids of HERG is sufficient to reconstitute slow deactivation to channels lacking the amino terminus. The peptide acts as a soluble domain in a rapid and readily reversible manner, reflecting a more dynamic regulation of deactivation than the slow modification observed in a previous study with a larger amino-terminal peptide fragment (Morais Cabral, J.H., A. Lee, S.L. Cohen, B.T. Chait, M. Li, and R. Mackinnon. 1998. Cell. 95:649-655). The slowing of deactivation by the peptide occurs in a dose-dependent manner, with a Hill coefficient that implies the cooperative action of at least three peptides per channel. Unlike internal TEA, which slows deactivation indirectly by blocking the channels, the peptide does not reduce current amplitude. Nor does the amino terminus interfere with the blocking effect of TEA, indicating that the amino terminus binding site is spatially distinct from the TEA binding site. Analysis of the single channel activity in cell-attached patches shows that the amino terminus significantly increases channel mean open time with no alteration of the mean closed time or the addition of nonconducting states expected from a pore block mechanism. We propose that the four amino-terminal deactivation subdomains of the tetrameric channel interact with binding sites uncovered by channel opening to specifically stabilize the open state and thus slow channel closing.

Animals↗

Multiple murine double minute gene 2 (MDM2) proteins are induced by ultraviolet light.

The mdm2 (murine double minute 2) oncogene encodes several proteins, the largest of which (p90) binds to and inactivates the p53 tumor suppressor protein. Multiple MDM2 proteins have been detected in tumors and in cell lines expressing high levels of mdm2 mRNAs. Here we show that one of these proteins (p76) is expressed, along with p90, in wild-type and p53-null mouse embryo fibroblasts, indicating that it may have an important physiological role in normal cells. Expression of this protein is induced, as is that of p90, by UV light in a p53-dependent manner. The p76 protein is synthesized via translational initiation at AUG codon 50 and thus lacks the N terminus of p90 and does not bind p53. In cells, p90 and p76 can be synthesized from mdm2 mRNAs transcribed from both the P1 (constitutive) and P2 (p53-responsive) promoters. Site-directed mutagenesis reveals that these RNAs give rise to p76 via internal initiation of translation. In addition, mdm2 mRNAs lacking exon 3 give rise to p76 exclusively, and such mRNAs are induced by p53 in response to UV light. These data indicate that p76 may be an important product of the mdm2 gene and a downstream effector of p53.

Animals↗

Sex differences in the perception of noxious experimental stimuli: a meta-analysis.

Fillingim and Maixner (Fillingim, R.B. and Maixner, W., Pain Forum, 4(4) (1995) 209-221) recently reviewed the body of literature examining possible sex differences in responses to experimentally induced noxious stimulation. Using a 'box score' methodology, they concluded the literature supports sex differences in response to noxious stimuli, with females displaying greater sensitivity. However, Berkley (Berkley, K.J., Pain Forum, 4(4) (1995) 225-227) suggested the failure of a number of studies to reach statistical significance suggests the effect may be small and of little practical significance. This study used meta-analytic methodology to provide quantitative evidence to address the question of the magnitude of these sex differences in response to experimentally induced pain. We found the effect size to range from large to moderate, depending on whether threshold or tolerance were measured and which method of stimulus administration was used. The values for pressure pain and electrical stimulation, for both threshold and tolerance measures, were the largest. For studies employing a threshold measure, the effect for thermal pain was smaller and more variable. The failures to reject the null hypothesis in a number of these studies appear to have been a function of lack of power from an insufficient number of subjects. Given the estimated effect size of 0.55 threshold or 0.57 for tolerance, 41 subjects per group are necessary to provide adequate power (0.70) to test for this difference. Of the 34 studies reviewed by Fillingim and Maixner, only seven were conducted with groups of this magnitude. The results of this study compels to caution authors to obtain adequate sample sizes and hope that this meta-analytic review can aid in the determination of sample size for future studies.

Female↗

Specific changes in rasGAP-associated 62 kilodalton protein during integrin mediated cell-substrate interaction.

A cascade of signal transduction events is initiated when cells make contact with each other or with a substrate. The nature of these signal transduction pathways is beginning to be elucidated. In particular, adhesive interactions between cells and their substrate, mediated by cell-surface integrins and extracellular matrix proteins, appears to activate the MAP kinase pathway. Here we show that in mouse fibroblasts and rat epithelial cells, tyrosine phosphorylation of a 62 kilodalton rasGAP-associated protein (GAPa-p62) is decreased upon cell-substrate interaction. Interaction between fibroblasts and various extracellular matrices such as fibronectin, vitronectin and collagen IV, but not laminin, results in tyrosine dephosphorylation of GAPa-p62. Cell-substrate mediated tyrosine dephosphorylation of GAPa-p62 is defective in transformed cell lines, suggesting a possible role for p62 in tumorigenic transformation. These studies suggest that in fibroblasts, and perhaps even in epithelial cells, the signal transduction pathway(s) triggered by different integrin engagement events converge on the rasGAP protein and alter the tyrosine phosphorylation and/or association of GAPa-p62.

3T3 Cells↗

The Coping Strategies Questionnaire: a large sample, item level factor analysis.

OBJECTIVE: The Coping Strategies Questionnaire (CSQ), a measure of coping in chronic pain patients, was subjected to item-level exploratory factor analysis. SUBJECTS: A sample of 965 chronic pain patients were used in the analysis. RESULTS: Principal components analysis using a varimax rotation procedure identified nine factors that accounted for 54.5% of the variance. Of these nine factors, the first five represent subscales of the original CSQ subscales. The catastrophizing subscale replicated with significant loadings for all six original items, and ignoring sensations replicated with five of six items. Factors representing reinterpreting pain sensations, coping self-statements, and diverting attention subscales also appeared. The items from the praying and hoping subscale split into separate praying and hoping factors (factors 6 and 8). When reliability coefficients were calculated, factors 7 through 9 had unacceptably low internal consistency and thus were not considered stable factors. Correlations between factors 1 through 6 and other measures of psychological and physical functioning were calculated in the construct validation portion of this study. Previously found relationships were replicated in that the correlations between CSQ factor scores and measures of pain, depression, and disability were in the same direction in this data set as those previously reported.

Adaptation, Psychological↗

Bias effects in three common self-report pain assessment measures.

OBJECTIVE: Past research has shown response biases to influence the accuracy of results from self-report measures. In pain assessment, where a percentage of patients have financial and other reasons to minimize or exaggerate psychological disturbance, it becomes especially important to identify the influence of response bias in self-report of adjustment. This study investigated the susceptibility of three commonly used self-report pain assessment measures to response bias. DESIGN: This study used a within-subjects (asymptomatic subjects) design with two experimental conditions and nonequivalent control group (chronic pain patients). SUBJECTS: Experimental group: 40 students enrolled in an occupational therapy program at a major southeastern United States university. CONTROL GROUP: 200 subjects referred to a multidisciplinary pain clinic at a major teaching hospital. MEASURES: Coping Strategies Questionnaire, Multidimensional Pain Inventory, and Pain Beliefs and Perceptions Inventory. RESULTS: With few exceptions, asymptomatic subjects scored significantly differently on these measures while portraying themselves as either coping well or coping poorly. In addition, when using the "coping poorly" response set, asymptomatic subjects reproduced scores similar to those of symptomatic chronic pain patients. CONCLUSION: The susceptibility to manipulation appeared constant across the three measures, a finding that highlighted the difficulties clinicians and researchers encounter in accurate interpretation of results from these measures in the absence of validity indicators. This study also emphasizes the ease with which subjects with sufficient motivation can present themselves in an untruthful and manipulative manner and can generate scores that are, on their own, difficult to distinguish from those of a group of typical chronic pain patients.

Adaptation, Psychological↗

Developmental genetic analysis of troponin T mutations in striated and nonstriated muscle cells of Caenorhabditis elegans.

We have been investigating a set of genes, collectively called mups, that are essential to striated body wall muscle cell positioning in Caenorhabditis elegans. Here we report our detailed characterization of the mup-2 locus, which encodes troponin T (TnT). Mutants for a heat-sensitive allele, called mup-2(e2346ts), and for a putative null, called mup-2(up1), are defective for embryonic body wall muscle cell contraction, sarcomere organization, and cell positioning. Characterizations of the heat-sensitive allele demonstrate that mutants are also defective for regulated muscle contraction in larval and adult body wall muscle, defective for function of the nonstriated oviduct myoepithelial sheath, and defective for epidermal morphogenesis. We cloned the mup-2 locus and its corresponding cDNA. The cDNA encodes a predicted 405-amino acid protein homologous to vertebrate and invertebrate TnT and includes an invertebrate-specific COOH-terminal tail. The mup-2 mutations lie within these cDNA sequences: mup-2(up1) is a termination codon near NH2 terminus (Glu94) and mup-2(e2346ts) is a termination codon in the COOH-terminal invertebrate-specific tail (Trp342). TnT is a muscle contractile protein that, in association with the thin filament proteins tropomyosin, troponin I and troponin C, regulates myosin-actin interaction in response to a rise in intracellular Ca2+. Our findings demonstrate multiple essential functions for TnT and provide a basis to investigate the in vivo functions and protein interactions of TnT in striated and nonstriated muscles.

Alleles↗

Role of B cell antigen processing and presentation in the humoral immune response.

In the 25 years since it was first indicated that lymphocyte subpopulations must interact during the generation of a humoral immune response, there has been an explosion of data on the molecular mechanism of this interaction. It has been demonstrated that T cells recognize a processed antigen fragment presented by a major histocompatibility complex molecule on the surface of an antigen-presenting cell. The minimal peptides required for T cell recognition of several proteins have been determined, the molecular genetics of many of the cell surface molecules involved have been defined, and the three-dimensional structure of the T cell receptor and the major histocompatibility antigens have been deduced. Several cell types have been found to act as antigen-presenting cells, although the roles of these populations in vivo remain unclear. However, it is clear that there must be a physical interaction between a B cell and a T cell before the B cell can respond to a T-dependent antigen. This interaction requires processing and presentation of the antigen by the B cell. Therefore this review focuses on antigen processing and presentation by resting B cells, one of the key steps in initiation of a humoral immune response.

Antibody Formation↗

Splenic B cells and antigen-specific B cells process anti-Ig in a similar manner.

B lymphocytes can process and present antigen to T cells. However, the fate of native antigen after its binding to specific B cells, i.e., the intracellular events involved in the processing and recycling of the antigenic fragments to the cell surface for antigen presentation, are not well understood. In the present study, we demonstrate that murine B cells degrade anti-Ig molecules bound to their surface and release acid soluble fragments into the supernatant. We also demonstrate that the kinetics of this process are identical for anti-mu, anti-delta, and anti-light chain antibodies, indicating that both surface IgM and surface IgD are equally effective in binding antigen and directing its processing. We also describe the effects of azide, chloroquine, and irradiation on this process. To extend these studies to the processing of specifically bound antigen, we demonstrate that highly purified trinitrophenyl antigen-binding cells degrade anti-Ig molecules with the same kinetics as unpurified splenic B cells. Thus, this purified population provides a suitable model system for the analysis of antigen degradation by antigen-specific cells.

Animals↗

The processing of antigen and anti-Ig by antigen-specific B cells.

B lymphocytes are very efficient antigen-presenting cells when they bear surface receptors for the antigen in question. However, there is very little known about the intracellular events occurring between the time B cells bind native antigen and present it in processed form to T cells. To analyze internalization and degradation of antigen versus anti-Ig or anti-MHC antibodies by B cells, we have used highly purified resting antigen-specific B lymphocytes that bind the hapten, trinitrophenyl. These cells were treated with [125I]-labeled trinitrophenylated antigens or with [125I]-labeled antibodies reactive with either cell surface immunoglobulin or major histocompatibility complex (MHC) (class I or class II) molecules. The fate of these proteins was followed by measuring the amount of acid soluble and insoluble radioactivity associated with the cells or released into the incubation medium. The cell-associated and released radioactivity was further analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Our results demonstrate that the kinetics of degradation of specific antigen into acid soluble fragments which are released into the culture medium closely parallel those with which B cells acquire the ability to specifically conjugate to carrier-specific T cells. In contrast, degradation of anti-Ig is more complete than the degradation of antigen but requires a longer period of time to reach completion. Furthermore, the initial release of soluble fragments of anti-Ig as compared to antigen into the culture medium is marginally slower. Finally, there is significant intracellular accumulation of degradation intermediates when anti-Ig is processed, but this is not the case with antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antigen-induced changes in phospholipid metabolism in antigen-binding B lymphocytes.

Previous studies have demonstrated a marked change in the metabolism of phospholipids (PL) after activation of resting B lymphocytes with anti-immunoglobulin (anti-Ig). In this study we examined PL metabolism in highly purified trinitrophenyl (TNP)-binding B cells after their activation with various forms of TNP-carrier protein. Such cells show similar changes in PL metabolism when stimulated with either antigen or anti-Ig, i.e., increased incorporation of 32PO4 into phosphatidic acid and phosphatidyl inositol (PI) but not phosphatidyl choline, phosphatidyl ethanolamine, or phosphatidyl serine. We have demonstrated that these responses to antigen are TNP-specific and dose-related between 1 and 50 micrograms/ml, producing up to a 2.5-fold stimulation of 32PO4 incorporation into PI. The PL response is also directly related to the density of TNP on the carrier and can be augmented by additional cross-linking of the carrier protein. These data suggest that cross-linking of surface Ig by antigen induces a change in PL metabolism as an early event in B cell activation.

Animals↗