PubMed Health⌕ Search

Biomedical subjects

Philip Smith

Publications and source records attributed to Philip Smith.

At least 19 recordsLinked to original sources
PubMed2006

The efficacy of acupuncture in the treatment of temporomandibular joint myofascial pain: a randomised controlled trial.

OBJECTIVES: To compare the effect of real acupuncture and sham acupuncture in the treatment of temporomandibulat joint myofascial pain, in order to establish the true efficacy of acupuncture. METHODS: A double blind randomised controlled trial conducted in the TMD Clinic, at the School of Dentistry, The University of Manchester. Twenty-seven patients were assigned to one of two treatment groups. Group 1 received real acupuncture treatment whilst Group 2 received a sham acupuncture intervention. Both the assessor and the patient were blinded regarding the group allocation. Baseline assessment of the outcome variables was made prior to the first treatment session, and was repeated following the last treatment. RESULTS: The results demonstrated that real acupuncture had a greater influence on clinical outcome measure of TMJ MP than those of sham acupuncture, and the majority of these reached a level of statistical significance. CONCLUSION: Acupuncture had a positive influence on the signs and symptoms of TMJ MP. In addition, this study provides evidence that the Park Sham Device was a credible acupuncture control method for trials involving facial acupoints.

Acupuncture Therapy↗
PubMed2005

Schistosoma mansoni secretes a chemokine binding protein with antiinflammatory activity.

The coevolution of humans and infectious agents has exerted selective pressure on the immune system to control potentially lethal infections. Correspondingly, pathogens have evolved with various strategies to modulate and circumvent the host's innate and adaptive immune response. Schistosoma species are helminth parasites with genes that have been selected to modulate the host to tolerate chronic worm infections, often for decades, without overt morbidity. The modulation of immunity by schistosomes has been shown to prevent a range of immune-mediated diseases, including allergies and autoimmunity. Individual immune-modulating schistosome molecules have, therefore, therapeutic potential as selective manipulators of the immune system to prevent unrelated diseases. Here we show that S. mansoni eggs secrete a protein into host tissues that binds certain chemokines and inhibits their interaction with host chemokine receptors and their biological activity. The purified recombinant S. mansoni chemokine binding protein (smCKBP) suppressed inflammation in several disease models. smCKBP is unrelated to host proteins and is the first described chemokine binding protein encoded by a pathogenic human parasite and may have potential as an antiinflammatory agent.

Animals↗
PubMed2005

Repression of interleukin-5 transcription by the glucocorticoid receptor targets GATA3 signaling and involves histone deacetylase recruitment.

Glucocorticoids are the mainstay of asthma therapy and mediate the repression of a number of cytokine genes, such as Interleukin (IL)-4, -5, -13, and granulocyte macrophage colony-stimulating factor (GM-CSF), which are central to the pathogenesis of asthmatic airway inflammation. The glucocorticoid receptor (GR) mediates repression by a number of diverse mechanisms. We have previously suggested that one such repressive activity is by direct binding of GR to elements within the GM-CSF enhancer that are recognized by the nuclear factor of activated T cells.activator protein 1 (NF-AT.AP-1) complex. We reasoned that, because many cytokine genes activated in asthma are transcriptionally regulated by the recruitment of this complex to DNA, their binding sites might provide a target for GR to mediate its repressive effects. Here, we show that transcriptional repression of the Interleukin-5 gene involves recruitment of GR to a DNA region located within the IL-5 proximal promoter, which is bound by NF-AT and AP-1 proteins. GR recruitment had a profound effect upon the activation capacity of GATA3, which has a binding site close to the NF-AT.AP-1 domain in both IL-5 and IL-13 promoters. Repression by GR involves co-repressor recruitment, because treatment of transfected cells with the deacetylase inhibitor trichostatin A caused a partial relief of repression. Additionally, repression could be augmented by co-transfection of cells with a histone deacetylase (HDAC1). These data suggest that the local recruitment of GR causes repression by inhibiting transcriptional activation by GATA3, a key tissue-specific determinant of expression of Th2 cytokines.

Binding Sites↗
PubMed2005

Reliability of recording static and dynamic occlusal contact marks using transparent acetate sheet.

STATEMENT OF PROBLEM: Inaccuracy in the transfer of information between clinician and technician regarding occlusal contacts can cause problems when fabricating indirect restorations, which can result in frustration for the dentist, technician, and patient. Few studies have considered the reproducibility of recording marked occlusal contacts. PURPOSE: This study aimed to test the reproducibility of a quick and simple means of recording marked occlusal contacts. MATERIAL AND METHODS: The static and dynamic occlusal contacts of 29 subjects, with no missing functional units, were marked using articulating paper. Three clinicians with varying clinical experience (3-10 years after graduation from dental school) were asked to independently record the marked occlusal contacts using a transparent acetate sheet. The results were analyzed for Kappa agreement. RESULTS: For the static occlusion, Kappa values of agreement between pairs of examiners were 0.88, 0.86, and 0.85, respectively, all indicating "almost perfect agreement." For the dynamic occlusion, the range of Kappa agreement between pairs of examiners produced a median of 0.91, 0.88, and 0.85, respectively, indicating almost perfect strength of agreement. CONCLUSIONS: The results suggest that marking occlusal contacts on a transparent acetate sheet provides a simple means of recording static and dynamic occlusal contacts with a high degree of reproducibility.

Acetates↗
PubMed2004

Helminth infection protects mice from anaphylaxis via IL-10-producing B cells.

Modulation of the immune system by infection with helminth parasites, including schistosomes, is proposed to reduce the levels of allergic responses in infected individuals. In this study we investigated whether experimental infection with Schistosoma mansoni could alter the susceptibility of mice to an extreme allergic response, anaphylaxis. We formally demonstrate that S. mansoni infection protects mice from an experimental model of systemic fatal anaphylaxis. The worm stage of infection is shown to mediate this protective effect. In vivo depletion studies demonstrated an imperative role for B cells and IL-10 in worm-mediated protection. Furthermore, worm infection of mice increases the frequency of IL-10-producing B cells compared with that in uninfected mice. However, transfer of B cells from worm-infected mice or in vitro worm-modulated B cells to sensitized recipients exacerbated anaphylaxis, which was attributed to the presence of elevated levels of IL-4-producing B cells. Worm-modulated, IL-10-producing B cells from IL-4-deficient, but not IL-5-, IL-9- or IL-13-deficient, mice conferred complete resistance to anaphylaxis when transferred to naive mice. Therefore, we have dissected a novel immunomodulatory mechanism induced by S. mansoni worms that is dependent on an IL-10-producing B cell population that can protect against allergic hypersensitivity. These data support a role for helminth immune modulation in the hygiene hypothesis and further illustrate the delicate balance between parasite induction of protective regulatory (IL-10) responses and detrimental (IL-4) allergic responses.

Adoptive Transfer↗
PubMed2004

Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages.

Infectious pathogens can selectively stimulate activation or suppression of T cells to facilitate their survival within humans. In this study we demonstrate that the trematode parasite Schistosoma mansoni has evolved with two distinct mechanisms to suppress T cell activation. During the initial 4- to 12-wk acute stages of a worm infection both CD4(+) and CD8(+) T cells are anergized. In contrast, infection with male and female worms induced T cell anergy at 4 wk, which was replaced after egg laying by T cell suppression via a known NO-dependent mechanism, that was detected for up to 40 wk after infection. Worm-induced anergy was mediated by splenic F4/80(+) macrophages (Mphi) via an IL-4-, IL-13-, IL-10-, TGF-beta-, and NO-independent, but cell contact-dependent, mechanism. F4/80(+) Mphi isolated from worm-infected mice were shown to induce anergy of naive T cells in vitro. Furthermore, naive Mphi exposed to live worms in vitro also induced anergy in naive T cells. Flow cytometry on in vivo and in vitro worm-modulated Mphi revealed that of the family of B7 costimulatory molecules, only programmed death ligand 1 (PD-L1) was selectively up-regulated. The addition of inhibitory mAb against PD-L1, but not PD-L2, to worm-modulated Mphi completely blocked the ability of these cells to anergize T cells. These data highlight a novel mechanism through which S. mansoni worms have usurped the natural function of PD-L1 to reduce T cell activation during early acute stages of infection before the subsequent emergence of egg-induced T cell suppression in the chronic stages of infection.

Animals↗
PubMed2004

Polysomnography performed in the unattended home versus the attended laboratory setting--Sleep Heart Health Study methodology.

STUDY OBJECTIVE: To compare polysomnographic recordings obtained in the home and laboratory setting. DESIGN AND SETTING: Multicenter study comparing unsupervised polysomnography performed in the participant's home with polysomnography supervised at an academic sleep disorders center, using a randomized sequence of study setting. Sleep Heart Health Study (SHHS) standardized polysomnographic recording and scoring techniques were used for both settings. PARTICIPANTS: 64 of 76 non-SHHS participants recruited from 7 SHHS field sites who had both a laboratory and home polysomnogram meeting acceptable quality criteria. MEASUREMENTS AND RESULTS: Median sleep duration was greater in the home than in the laboratory (375 vs 318 minutes, respectively, P < .0001) as was sleep efficiency (86% vs 82%, respectively, P < .0024). Very small, but significant increases in percentage of rapid eye movement sleep and decreases in stage 1 sleep were noted in the laboratory. Employing multiple definitions of respiratory disturbance index (RDI), median RDI was similar in both settings (for example, RDI with 3% desaturation: home 12.4, range 0.6-67; laboratory 9.5, range 0.1-93.4, P = .41). Quartile analysis of laboratory RDI showed moderate agreement with home RDI measurements. Based on the mean of laboratory and home RDI and using a cutpoint of 20, there was a biphasic distribution, with the RDI 3% above 20 being more common in the recordings performed in the laboratory than in the home and below 20 being more common in the recordings performed in the home than in the laboratory. These differences could not be attributed to quality of recording, age, sex, or body mass index. CONCLUSIONS: Using SHHS methodology, median RDI was similar in the unattended home and attended laboratory setting with differences of small magnitude in some sleep parameters. Differences in RDI between settings resulted in a rate of disease misclassification that is similar to repeated studies in the same setting.

Adult↗
PubMed2004

The impact of cognitive distortions, stress, and adherence on metabolic control in youths with type 1 diabetes.

PURPOSE: To investigate the role of cognitive distortions in the relationship between adherence behavior, diabetes-specific stress, general stress, and metabolic control. METHODS: Obtained questionnaire data, glucometer readings, and glycosylated hemoglobin (HbgA(1c)) assays from 143 youths (11-18 years old) with type 1 diabetes. Examined path model of relationships between cognitive distortions, stress, adherence behavior, and metabolic control. Data were analyzed using path analysis. RESULTS: Higher levels of negative cognitive distortions were associated with more stress (both diabetes-specific and general). Higher levels of general stress then led to less adherent behavior and subsequently poorer metabolic control (higher HbgA(1c)). More diabetes-specific stress also led to poorer metabolic control, as well as general stress. CONCLUSIONS: The findings indicate an indirect role of negative cognitive distortions in metabolic control. The current findings suggest that instead of the proposed direct link between cognitive distortions and adherence behavior, an indirect relationship may exist through stress.

Adolescent↗
PubMed2004

Tuberculosis prevention and control in long-term-care facilities for older adults.

In the United States, older adults comprise 22% of cases of tuberculous disease but only 12% of the population. Most cases of tuberculosis (TB) occur in community dwellers, but attack rates are highest among frail residents of long-term-care facilities. The detection and treatment of latent TB infection and TB disease can pose special challenges in older adults. Rapid recognition of possible disease, diagnosis, and implementation of airborne precautions are essential to prevent spread. It is the intent of this evidence-based guideline to assist healthcare providers in the prevention and control of TB, specifically in skilled nursing facilities for the elderly.

Aged↗
PubMed2004

Underimmunization among children: effects of vaccine safety concerns on immunization status.

OBJECTIVE: To examine the attitudes, beliefs, and behaviors of parents whose children were underimmunized with respect to > or =2 vaccines that have recently received negative attention, compared with parents whose children were fully immunized with respect to the recommended vaccines. DESIGN: Case-control study. SETTING: A sample of households that participated in the National Immunization Survey were recontacted in 2001. MAIN OUTCOME MEASURE: Vaccination status was assessed. Case subjects were underimmunized with respect to > or =2 of 3 vaccines (diphtheria-tetanus-pertussis or diphtheria-tetanus-acellular pertussis, hepatitis B, or measles-containing vaccines), and control subjects were fully immunized. RESULTS: The response rate was 52.1% (2315 of 4440 subjects). Compared with control households, case households were more likely to make 0 dollar to 30,000 dollars (adjusted odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.5-4.6) than at least 75,000 dollars, to have > or =2 providers (OR: 2.0; 95% CI: 1.3-3.1) than 1, and to have > or =4 children (OR: 3.1; 95% CI: 1.5-6.3) than 1 child. With control for demographic and medical care factors, case subjects were more likely than control subjects to not want a new infant to receive all shots (OR: 3.8; 95% CI: 1.5-9.8), to score vaccines as unsafe or somewhat safe (OR: 2.0; 95% CI: 1.2-3.4), and to ask the doctor or nurse not to give the child a vaccine for reasons other than illness (OR: 2.7; 95% CI: 1.2-6.1). Among case subjects, 14.8% of underimmunization was attributable to parental attitudes, beliefs, and behaviors. CONCLUSIONS: Attitudes, beliefs, and behaviors indicative of vaccine safety concerns contribute substantially to underimmunization in the United States. Although concerns were significantly more common among parents of underimmunized children, many parents of fully immunized children demonstrated similar attitudes, beliefs, and behaviors, suggesting a risk to the currently high vaccination levels. Efforts to maintain and improve immunization coverage need to target those with attitudes/beliefs/behaviors indicative of vaccine safety concerns, as well as those with socioeconomic and health care access problems.

Attitude to Health↗
PubMed2002

Characterization of signaling pathways activated by the interleukin 1 (IL-1) receptor homologue T1/ST2. A role for Jun N-terminal kinase in IL-4 induction.

T1/ST2 is a member of the interleukin (IL)-1 receptor superfamily, possessing three immunoglobulin domains extracellularly and a Toll/IL1R (TIR) domain intracellularly. The ligand for T1/ST2 is not known. T1/ST2 is expressed on Type 2 T helper (Th2) cells, and its role appears to be in the regulation of Th2 cell function. Here, we have investigated T1/ST2 signal transduction, using either transient overexpression of T1/ST2 or a cross-linking monoclonal antibody to activate cells. We demonstrate that T1/ST2 does not activate the transcription factor NF-kappaB when overexpressed in murine thymoma EL4 cells, or in the mast cell line P815 treated with the anti-T1/ST2 antibody. However, a chimera comprising the extracellular domain of the type 1 IL-1 receptor and the intracellular domain of T1/ST2 activates NF-kappaB both by overexpression and in response to IL-1. This artificial activation requires the IL1RAcP recruited via the extracellular portion (IL1R1) of the chimera. T1/ST2 is, however, able to activate the transcription factor activator protein-1 (AP-1), increase phosphorylation of c-Jun, and activate the MAP kinases c-Jun N-terminal kinase (JNK), p42/p44 and p38. Anti-T1/ST2 also induces the selective expression of IL-4 but not IFN-gamma in naive T cells. Importantly, this effect is blocked by prior treatment with the JNK inhibitor SP600125 confirming that JNK as a key effector in T1/ST2 signaling. The lack of effect on NF-kappaB when T1/ST2 is homodimerized identifies T1/ST2 as the first member of the IL-1 receptor superfamily so far studied that is apparently unable to activate NF-kappaB, consistent with evidence indicating the lack of a role for NF-kappaB in Th2 cell function.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Inhibition of type 1 cytokine-mediated inflammation by a soluble CD30 homologue encoded by ectromelia (mousepox) virus.

CD30 is up-regulated in several human diseases and viral infections but its role in immune regulation is poorly understood. Here, we report the expression of a functional soluble CD30 homologue, viral CD30 (vCD30), encoded by ectromelia (mousepox) virus, a poxvirus that causes a severe disease related to human smallpox. We show that vCD30 is a 12-kD secreted protein that not only binds CD30L with high affinity and prevents its interaction with CD30, but it also induces reverse signaling in cells expressing CD30L. vCD30 blocked the generation of interferon gamma-producing cells in vitro and was a potent inhibitor of T helper cell (Th)1- but not Th2-mediated inflammation in vivo. The finding of a CD30 homologue encoded by ectromelia virus suggests a role for CD30 in antiviral defense. Characterization of the immunological properties of vCD30 has uncovered a role of CD30-CD30L interactions in the generation of inflammatory responses.

Amino Acid Sequence↗
PubMed2002

IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13.

Functional redundancy is highly prevalent among the Th2 interleukins (IL)-4, IL-5, IL-9, and IL-13. To define the critical functions of these cytokines, we have generated a novel panel of compound Th2 cytokine-deficient mice (from single to quadruple cytokine knockouts). We find that these Th2 cytokines are not essential for fetal survival even during allogeneic pregnancy. Using intestinal parasite infection and a pulmonary granuloma model, we demonstrate cryptic roles for IL-4, IL-5, IL-9, and IL-13 in these responses. Significantly, although IL-5, IL-9, and IL-13 add to the speed and magnitude of the response, a threshold is reached at which IL-4 alone can activate all Th2 effector functions. These mice reveal distinct spatial, temporal, and hierarchical cytokine requirements in immune function.

Animals↗
PubMed2002

What influences family physicians' cancer screening decisions when practice guidelines are unclear or conflicting?

OBJECTIVES: To determine (a) the respondents' perceptions of 4 unclear or conflicting cancer screening guidelines: prostate-specific antigen (PSA) for men over 50, mammography for women 40-49, colorectal screening by fecal occult blood testing (FOBT), and colonoscopy for patients over 40; and (b) the influence of various factors on the decision to order these tests. STUDY DESIGN: National Canadian mail survey of randomly selected family physicians. POPULATION: Family physicians in active practice (n=565) selected from rural and urban family medicine sites in 5 provinces representing the main regions in Canada. OUTCOME MEASURED: Agreement with guideline statements, and decision to order screening test in 6 clinical vignettes. RESULTS: Of 565 surveys mailed, 351 (62.1%) were returned. Most respondents agreed with the Canadian Task Force recommendations, and most believed that various guidelines for 3 of the 4 screens were conflicting (PSA 86.6%; mammography 67.5%; FOBT 62.4%). Patient anxiety about cancer, patient expectations of being tested, and a positive family history of cancer increased the odds that the 4 tests would be ordered. A good quality patient-MD relationship decreased the odds of ordering a mammogram. Screening decisions were also significantly influenced by the respondents' beliefs about whether screening was recommended and whether screening could cause more harm than good. A physician's sensitivity to his or her colleagues' practice influenced screening decisions regarding PSA and mammography. CONCLUSIONS: These results suggest a conceptual framework for understanding the determinants of screening behavior when guidelines are unclear or conflicting.

Adult↗