Biomedical subjects

J L Riley

Publications and source records attributed to J L Riley.

At least 37 records · Page 2Linked to original sources

PubMed1999

Constitutive cell surface association between CD4 and CCR5.

HIV-1 entry into cells involves formation of a complex between gp120 of the viral envelope glycoprotein (Env), a receptor (CD4), and a coreceptor. For most strains of HIV, this coreceptor is CCR5. Here, we provide evidence that CD4 is specifically associated with CCR5 in the absence of gp120 or any other receptor-specific ligand. The amount of CD4 coimmunoprecipitated with CCR5 was significantly higher than that with the other major HIV coreceptor, CXCR4, and in contrast to CXCR4 the CD4-CCR5 coimmunoprecipitation was not significantly increased by gp120. The CD4-CCR5 interaction probably takes place via the second extracellular loop of CCR5 and the first two domains of CD4. It can be inhibited by CCR5- and CD4-specific antibodies that interfere with HIV-1 infection, indicating a possible role in virus entry. These findings suggest a possible pathway of HIV-1 evolution and development of immunopathogenicity, a potential new target for antiretroviral drugs and a tool for development of vaccines based on Env-CD4-CCR5 complexes. The constitutive association of a seven-transmembrane-domain G protein-coupled receptor with another receptor also indicates new possibilities for cross-talk between cell surface receptors.

3T3 Cells↗

PubMed1999

Health care utilization by older adults in response to painful orofacial symptoms.

The purpose of this study was to determine which specific attributes of painful orofacial symptoms serve as predictors of health care utilization in a population based sample of elderly subjects. Furthermore, we documented patterns of health care utilization selection by type of health care provider. To our knowledge, these specific utilization patterns have never before been reported in the pain literature. Telephone interviews were conducted with a stratified random sample of 1636 community dwelling older (65+) north Floridians. A total of 5860 households were contacted and screened, with 75.3% participating to the point where their eligibility for the study could be determined. The percentage of subjects reporting health care utilization for a specific symptom ranged from 62 to 32%. One or more health care visits were reported by at least 50% of those reporting symptoms of toothache pain, facial pain, jaw joint pain and burning mouth in the past 12 months. These rates suggest that elderly individuals are willing and able to seek health care for painful orofacial symptoms. We found that pain intensity was the best predictor of whether an elderly individual utilized health care or not, which suggests that some pain intensity threshold may exist at which health care seeking behavior is initiated. The overall number of visits was not predicted by pain intensity but by other qualities more associated with time or level of dysfunction caused by the symptom. We also found that elderly adults, typically seek care for toothache from a dentist and from physicians for painful orofacial symptoms not associated with the teeth or mouth. These decisions regarding the selection of a health care professional may, in part, be a function of financial and insurance considerations, anatomical site and perception of the role of dentistry in orofacial care.

Aged↗

PubMed1999

Predicting treatment compliance following facial pain evaluation.

The purpose of this study was to document compliance to treatment follow-up for facial pain patients referred for outside services. In addition, we generated a multidimensional model of the psychosocial constructs associated with chronic pain to determine whether these factors were predictive of compliance across recommended therapy modalities or with an overall measure of compliance. These constructs included pain report, depressive symptoms, anxiety, cognitive coping strategies, and physical activity reduction. The sample consisted of 80 facial pain patients evaluated at a tertiary care, facial pain clinic at a large university medical center. Compliance ratings ranged from 93% to 50% and are consistent with the literature that indicates that compliance differs across treatment modality. Furthermore, compliance rates were lower for the more nontraditional facial pain treatments performed by physical therapists or psychologists. Depression was negatively associated with compliance to medication changes, therapeutic injections, and splint therapy, but not psychological counseling or physical therapy. Increased pain was only associated with physical therapy. Measures of psychological distress (depression and anxiety) and pain were predictive of the overall measure of compliance. These results suggest that psychological distress can be a barrier for positive patient outcomes through reduced treatment compliance.

Adaptation, Psychological↗

PubMed1999

Empirical test of the factor structure of the West Haven-Yale Multidimensional Pain Inventory.

OBJECTIVE: Although the West Haven-Yale Multidimensional Pain Inventory (MPI) is frequently used in clinical evaluation and research with chronic pain patients, few studies have reported item-level factor analyses. After performing such an analysis, Bernstein et al. (Spine 1995;20:956-63) reported lack of independence between the solicitous and distracting response scales in section II as well as the activities away from home and social activities scales in section III. They suggested that the combination of these scales would improve the internal structure of the MPI. The purpose of this study was to perform a confirmatory factor analysis testing whether the MPI would be improved by the consolidation of these scales. In addition, a third, empirical model was generated for comparison with the West Haven-Yale and Bernstein models. DESIGN: This study used exploratory and confirmatory factor analysis on two independent samples of chronic pain patients (n = 472 and n = 346) to test hypotheses regarding the factor structure of the MPI. RESULTS AND CONCLUSION: Principal axis factor analysis resulted in an empirical model that suggested that the primary psychometric problem of the MPI was lack of item-factor discrimination for several items. When the three models were tested using confirmatory factor analysis, improvement in model fit occurred when cross loading items were excluded. Nevertheless, the goodness of fit of original factor structure was adequate, suggesting it would be premature to suggest changes in this instrument.

Activities of Daily Living↗

PubMed1999

Empirical subgroups of the Coping Strategies Questionnaire-Revised: a multisample study.

OBJECTIVE: The purpose of this study was to examine the dimensions of coping, measured by the subscales of the new revised Coping Strategies Questionnaire (CSQ-R) using factor analysis, and to perform cluster analysis on these factors to explore the existence of distinct subgroups. No published studies have identifed subgroups of chronic pain patients based on the use of CSQ coping strategies. SOURCE: A sample of 419 chronic low back pain patients from a multidisciplinary pain rehabilitation clinic and a sample of 556 chronic pain patients of mixed pain etiology presenting for treatment at an anesthesia pain clinic were used to establish reliability of factors and clusters. RESULTS: Both samples yielded very similar two-factor solutions, with initial solutions accounting for 67.1% and 69.1% of the total variance. The factors were characterized as cognitive coping and distraction. Three homogeneous subgroups were then identified that consisted of a group high on cognitive coping, a group with low overall ratings of response CSQ-R items in general, and a group with frequent endorsement of catastrophizing and distraction-related items. CONCLUSION: This paper is the first to report empirically derived subgroups from scores on the CSQ or CSQ-R. In addition, the three clusters were significantly different across measures of pain, psychological distress, and levels of physical functioning, demonstrating validity for the clusters.

Adaptation, Psychological↗

PubMed1998

Development of an animal model for autotransfusion therapy: in vitro characterization and analysis of anti-CD3/CD28 expanded cells.

Previous studies have shown that in vitro culture of human CD4+ T cells with antibodies to CD3 and CD28 immobilized on beads induced an antiviral effect to HIV-1 infection. Herein, we have used CD4+ T cells from nonhuman primates to address issues critical for use of such cells for therapy and immune reconstitution of humans and nonhuman primates infected with HIV and simian immunovirus (SIV). These studies include definition of the kinetics of the antiviral effect, the relative stability of the acquired phenotype, and whether such activated and expanded CD4+ T cells retain their immune function. Results of our studies show that antiviral effect is induced rapidly following activation with anti-CD3/CD28-coated beads. Additionally, the antiviral effect is not stable in these cells and requires continuous culture with anti-CD3/CD28 beads. Removal of CD4+ T cells from anti-CD3/CD28 stimulation renders these cells susceptible to infection, demonstrating that the resistant phenotype is not stable in these cultures. However, anti-CD3/CD28 expanded CD4+ T cells do retain immune function. Thus, although these findings imply a note of caution for therapeutic strategies aimed at providing patients with virus-resistant CD4+ T cells, the present study suggests that transfusion of such cells with retained immune function may have immune restoration capability.

Animals↗

PubMed1998

Productive infection of neonatal CD8+ T lymphocytes by HIV-1.

CD8+ T lymphocytes confer significant but ultimately insufficient protection against HIV infection. Here we report that activated neonatal CD8+ T cells can be productively infected in vitro by macrophage-tropic (M-tropic) HIV-1 isolates, which are responsible for disease transmission, whereas they are resistant to T cell-tropic (T-tropic) HIV strains. Physiological activation of CD8-alpha/beta+ CD4- T cell receptor-alpha/beta+ neonatal T cells, including activation by allogeneic dendritic cells, induces the accumulation of CD4 messenger RNA and the expression of CD4 Ag on the cell surface. The large majority of anti-CD3/B7.1-activated cord blood CD8+ T cells coexpress CD4, the primary HIV receptor, as well as CCR5 and CXCR4, the coreceptors used by M- and T-tropic HIV-1 strains, respectively, to enter target cells. These findings are relevant to the rapid progression of neonatal HIV infection. Infection of primary HIV-specific CD8+ T cells may compromise their survival and thus significantly contribute to the failure of the immune system to control the infection. Furthermore, these results indicate a previously unsuspected level of plasticity in the neonatal immune system in the regulation of CD4 expression by costimulation.

CD4 Antigens↗

PubMed1998

CTLA-4 ligation delivers a unique signal to resting human CD4 T cells that inhibits interleukin-2 secretion but allows Bcl-X(L) induction.

We have assessed the functional effects of a panel of CTLA-4 mAbs on resting human CD4+ T cells. Our results demonstrate that some CTLA-4 mAbs can inhibit proliferative responses of resting CD4+ cells and cell cycle transition from G0 to G1. The inhibitory effects of CTLA-4 were evident within 4 h, at a time when cell surface CTLA-4 expression remained undetectable. Other CTLA-4 mAbs had no detectable inhibitory effects, indicating that binding of Ab to CTLA-4 alone is not sufficient to mediate down-regulation of T cell responses. Interestingly, while IL-2 production was shut off, inhibitory anti-CTLA-4 mAbs permitted induction and expression of the cell survival gene bcl-X(L). Consistent with this observation, cells remained viable and apoptosis was not detected after CTLA-4 ligation.

Abatacept↗

PubMed1998

The role of co-stimulation in regulation of chemokine receptor expression and HIV-1 infection in primary T lymphocytes.

Fusion and entry of the human immunodeficiency virus (HIV) into CD4(+) T lymphocytes requires expression of CD4 and a coreceptor. At least eight chemokine receptors can serve as coreceptors for HIV. Accumulating evidence indicates that multiple factors, including the state of cellular differentia- tion and activation, regulate the expression of alpha- and beta-chemokine receptors on lymphocytes. For example, binding of antibodies to the CD28 coreceptor can downregulate expression of beta-chemokine receptors, and this appears to have important consequences on the susceptibility of CD4(+) T lymphocytes to infection by HIV-1. In contrast, binding of the natural CD28 ligand B7 or antibodies to the CD28 homologue CTLA-4 can upregulate CCR5 expression, sug- gesting a reciprocal interaction between CD28 and CTLA-4 and the regulation of beta-chemokine receptor expression. Thus, the CD28/CTLA-4/B7 co-stimulation pathway is identi- fied as a potential novel target for the control of susceptibility to some strains of HIV-1 infection.

Abatacept↗

PubMed1998

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↗

PubMed1998

Orofacial pain symptom prevalence: selective sex differences in the elderly?

This study investigated sex differences in orofacial pain symptoms in a sample of elderly adults. Furthermore, differences across sex were tested on symptom continuity, overall duration, pain severity, activity reduction, and health care utilization, related to each specific symptom. Telephone interviews were conducted with a stratified random sample of community dwelling older (65+) north Floridians. A total of 5860 households were contacted and screened, with 75.3% participating to the point where their eligibility for the study could be determined. Of the remaining households, 1636 completed the interview. Of the total sample, 17.4% reported experiencing at least one of the four target orofacial pain symptoms (jaw joint pain, face pain, oral sores, burning mouth) during the past year, suggesting that orofacial pain symptoms are common in older adults. Our findings for prevalence of each specific symptom (jaw joint pain, 7.7%; face pain, 6.9%; oral sores, 6.4%; toothache, 12.0%; burning mouth, 1.7%) are similar to those estimated by the 1989 National Health Interview Survey, for the US adult population. Consistent with other epidemiological and clinical studies, we found that females were more likely to report jaw joint pain and face pain than males. In contrast to clinical studies, no differences were found on subjective ratings of pain severity, for any symptom. Differences across sex were most likely to be reported for jaw joint pain related variables, suggesting undetermined sex-uniqueness for these symptoms. In contrast to previous studies, older females tended to report lower levels of health care utilization than older males. This is the first study to our knowledge that reports orofacial symptom-specific sex differences among the elderly.

Adult↗

PubMed1998

Effects of physical and sexual abuse in facial pain: direct or mediated?

Research has identified a relationship between a history of physical and/or sexual abuse and a range of psychological, functional, and physical factors; however, the nature of this relationship has not been tested. We hypothesize two different mechanisms through which an abuse history could influence later life distress and dysfunction. A history of abuse could increase an individual's vulnerability to emotional distress or could increase an individual's tendency to attend, amplify, and over-interpret somatic symptoms. The purpose of this study was to test the influence of emotional distress and somatic focus on the relationship between a history of physical and/or sexual abuse and later chronic painrelated disability in patients with temporomandibular disorders. The subjects were 139 female patients evaluated at a facial pain clinic. Of the 139 subjects, 49% (n = 69) reported a history of physical and/or sexual abuse. Abused subjects reported significantly higher levels of anxiety, depression, and somatic symptoms than nonabused subjects. Path analysis with latent variables, using the LISREL-8 (Scientific Software International, Inc., Chicago, Illinois) statistical program was used to test the hypothesized relationships. When emotional distress and somatic focus were tested as mediators, the path coefficient from somatic focus to physical functioning was significant (beta = -0.38) while the path coefficient from negative emotion to physical functioning was not significant. These results favor somatization as the hypothesized mechanism over the emotional distress vulnerability hypotheses.

Adolescent↗

PubMed1998

Large-scale production of CD4+ T cells from HIV-1-infected donors after CD3/CD28 costimulation.

We describe a procedure for large-scale enrichment, growth, and harvesting CD4+ T cells. This method may be effective for HIV-1 immunotherapy, as the mode of stimulation, with anti-CD3 plus anti-CD28 coated beads (CD3/CD28 beads) induces a potent antiviral effect. PBMC were obtained by density gradient centrifugation of an apheresis product. Monocytes/macrophages were removed by incubating PBMC with beads coated with IgG. The cells were then magnetically depleted of B cells and CD8+ cells with mouse anti-CD20 and anti-CD8 MAbs and sheep antimouse coated beads. The remaining cells were >80% CD4+ and were transferred to gas-permeable bags containing CD3/CD28 beads and cultured in a closed system. After 14 days, the cell number increased an average of 37-fold, and cells were nearly 100% CD4+. Viral load, assessed by DNA PCR for HIV-1 gag, decreased >10-fold during culture in the absence of antiretroviral agents. Removal of CD3/CD28 beads from the cell suspension was accomplished by passing cells plus beads (3-30 x 10(9) cells in 2-12 L) over a MaxSep magnetic separator using gravity-driven flow. The cells were then concentrated to 300 ml in an automated centrifuge. This process allows safe and efficient growth of large numbers of CD4+ T cells from HIV-1+ donors.

Adoptive Transfer↗

PubMed1998

Validity of MMPI-2 profiles in chronic back pain patients: differences in path models of coping and somatization.

OBJECTIVE: To show clinical utility and empirical validity of Minnesota Multiphasic Personality Inventory-2 (MMPI-2) chronic pain patient subgroups by identification of differential multivariate relationships across groups. METHOD: This study used structural equation modeling to test cognitive coping strategies and somatization as mediator variables in path models with pain severity and depression used as exogenous (independent) variables and patient's activity level as the final endogenous (dependent) variable, across MMPI-2 profiles. RESULTS: Hierarchical cluster analysis, performed on a sample of 569 chronic low back patients, resulted in four cluster profiles identifiable as those found in previous work with the MMPI-2 (within normal limits, V-type, neurotic triad, and depressed-pathological). Somatization mediated the relationship between depression and activity level for the neurotic triad group but not the other three groups. A positive linear relationship was found between somatization and depression for the within normal limits, neurotic triad, and depressed-pathological groups, whereas their linear association was negative for the V-type group. Cognitive coping strategies mediated the relationship between depression and activity level for the within normal limits group. In addition, cognitive coping was predictive of activity level for the within normal limits, V-type, and neurotic triad groups but not for the depressed-pathological group. CONCLUSION: Consistent with previous cluster analytic studies, this study replicated four MMPI-2 cluster profile groups in chronic pain patients. These results have also shown that several multivariate relationships between variables are different across MMPI-2 groups, providing evidence for the validity for these MMPI-2 subgroups.

Adaptation, Psychological↗

PubMed1998

MHC class II gene silencing in trophoblast cells is caused by inhibition of CIITA expression.

PROBLEM: Major histocompatibility complex (MHC) class II molecule expression is specifically suppressed on fetal trophoblasts, even in response to interferon (IFN)-gamma, a potent inducer of MHC class II genes. The suppression of class II induction has been suggested to play a role in preventing rejection of the fetal allograft. The mechanism of this suppression is unknown. METHOD OF STUDY: Human trophoblast cell lines were examined for expression of MHC class II transcription factors and for activity of the IFN-gamma signaling pathway. Additionally, trophoblast cells were transfected with a vector expressing the class II transactivator, CIITA, and assayed for class II expression. RESULTS: The MHC class II transcription factors RFX and X2BP and the IFN-gamma signaling pathway components are expressed constitutively and are functional in trophoblasts. However, CIITA expression was absent in trophoblasts and could not be induced by IFN-gamma. Transfection of CIITA into trophoblast cells resulted in derepression of class II gene expression. CONCLUSIONS: The lack of induction of MHC class II genes in response to IFN-gamma in trophoblast cells is caused neither by the absence of factors that bind class II promoters, nor by a lesion in the IFN-gamma signaling pathway, but results from a specific inhibition of the CIITA gene.

Cell Line↗

PubMed1998

Naïve and memory CD4 T cells differ in their susceptibilities to human immunodeficiency virus type 1 infection following CD28 costimulation: implicatip6s for transmission and pathogenesis.

In vitro evidence suggests that memory CD4(+) cells are preferentially infected by human immunodeficiency virus type 1 (HIV-1), yet studies of HIV-1-infected individuals have failed to detect preferential memory cell depletion. To explore this paradox, we stimulated CD45RA+ CD4(+) (naïve) and CD45RO+ CD4(+) (memory) cells with antibodies to CD3 and CD28 and infected them with either CCR5-dependent (R5) or CXCR4-dependent (X4) HIV-1 isolates. Naïve CD4(+) cells supported less X4 HIV replication than their memory counterparts. However, naïve cells were susceptible to R5 viral infection, while memory cells remained resistant to infection and viral replication. As with the unseparated cells, mixing the naïve and memory cells prior to infection resulted in cells resistant to R5 infection and highly susceptible to X4 infection. While both naïve and memory CD4(+) subsets downregulated CCR5 expression in response to CD28 costimulation, only the memory cells produced high levels of the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta upon stimulation. Neutralization of these beta-chemokines rendered memory CD4(+) cells highly sensitive to infection with R5 HIV-1 isolates, indicating that downregulation of CCR5 is not sufficient to mediate complete protection from CCR5 strains of HIV-1. These results indicate that susceptibility to R5 HIV-1 isolates is determined not only by the level of CCR5 expression but also by the balance of CCR5 expression and beta-chemokine production. Furthermore, our results suggest a model of HIV-1 transmission and pathogenesis in which naïve rather than memory CD4(+) T cells serve as the targets for early rounds of HIV-1 replication.

ADP-ribosyl Cyclase↗

PubMed1997

Intrinsic resistance to T cell infection with HIV type 1 induced by CD28 costimulation.

When HIV-infected leukocytes are activated by the CD28 costimulatory receptor, HIV-1 is rapidly cleared from cultures, suggesting that costimulation can render T cells resistant to HIV-1 infection. In this study we tested the hypothesis that enhanced secretion of cytokines or chemokines could account for CD28-induced antiviral effects. In an acute infection system, resistance to infection with macrophage-tropic strains of HIV-1 was shown to be comprised of both soluble and cell-associated components. Induction of HIV-1 resistance was specific for CD28 costimulation, in that a variety of other accessory receptors, such as CD2, CD4, CD5, and MHC class I, failed to confer the antiviral resistance. The soluble component was secreted by both CD4 and CD8 T cells, was not unique to CD28 costimulation, and could be neutralized by removal of C-C chemokines (RANTES (regulated upon activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha and -1beta) from the culture supernatants of costimulated CD4 T cells. In contrast, CD28 stimulation of CD4 cells resulted in the specific induction of a pronounced intrinsic resistance to HIV-1 infection by macrophage tropic isolates of HIV-1.

CD28 Antigens↗

PubMed1997

Differential regulation of HIV-1 fusion cofactor expression by CD28 costimulation of CD4+ T cells.

Activation of CD4(+) T lymphocytes from human immunodeficiency virus-type 1 (HIV-1)-infected donors with immobilized antibodies to CD3 and CD28 induces a virus-resistant state. This effect is specific for macrophage-tropic HIV-1. Transcripts encoding CXCR4/Fusin, the fusion cofactor used by T cell line-tropic isolates, were abundant in CD3/CD28-stimulated cells, but transcripts encoding CCR5, the fusion cofactor used by macrophage-tropic viruses, were not detectable. Thus, CD3/CD28 costimulation induces an HIV-1-resistant phenotype similar to that seen in some highly exposed and HIV-uninfected individuals.

Antibodies, Monoclonal↗