Are older drivers' driving patterns during an on-road driving task representative of their real-world driving patterns?

OBJECTIVE: The current study investigated whether older drivers' driving patterns during a customized on-road driving task were representative of their real-world driving patterns. METHODS: Two hundred and eight participants (male: 68.80%; mean age = 81.52 years, SD = 3.37 years, range = 76.00-96.00 years) completed a customized on-road driving task that commenced from their home and was conducted in their own vehicle. Participants' real-world driving patterns for the preceding 4-month period were also collected via an in-car recording device (ICRD) that was installed in each participant's vehicle. RESULTS: During the 4-month period prior to completing the on-road driving task, participants' median real-world driving trip distance was 2.66 km (interquartile range [IQR] = 1.14-5.79 km) and their median on-road driving task trip distance was 4.41 km (IQR = 2.83-6.35 km). Most participants' on-road driving task trip distances were classified as representative of their real-world driving trip distances (95.2%, n = 198). CONCLUSIONS: These findings suggest that most older drivers were able to devise a driving route that was representative of their real-world driving trip distance. Future research will examine whether additional aspects of the on-road driving task (e.g., average speed, proportion of trips in different speed zones) are representative of participants' real-world driving patterns.

TGF-ß-mediated airway tolerance to allergens induced by peptide-based immunomodulatory mucosal vaccination.

We sought to modulate mucosal immune responses using neonatal vaccination to avert the development of allergic airways disease (AAD). Pulmonary pathology in AAD is driven by T helper (TH)2 cytokines, in particular interleukin (IL)4 and IL13, the expression and actions of which are regulated by the transcription factor STAT6. We developed a peptide homolog of STAT6, STAT6-IP. Neonatal mice given, intranasally, STAT6-IP, in an effort to modulate de novo airways immune responses, developed tolerance following subsequent allergen sensitization, with either ovalbumin or ragweed allergens, as demonstrated by reduced TH2 cytokines and specific immunoglobulin (Ig)E and the significant increases in the latency-associated peptide (LAP)(+) T-regulatory (Treg) cell subset and expression of transforming growth factor (TGF)-ß. This regulatory phenotype was transferrable by CD4(+) T cells or CD11c(+) dendritic cells (DCs) derived from STAT6-IP-vaccinated mice. Anti-TGF-ß treatment during allergen sensitization, however, re-established the pro-inflammatory TH2 response. Thus, neonatal STAT6-IP vaccination induces prospective TGF-ß-dependent tolerance to allergen and constitutes a novel highly effective immunomodulatory allergy prevention strategy.

Development and evaluation of a driving observation schedule (DOS) to study everyday driving performance of older drivers.

This paper describes the development and evaluation of an on-road procedure, the Driving Observation Schedule (DOS), for monitoring individual driving behavior. DOS was developed for use in the Candrive/Ozcandrive five-year prospective study of older drivers. Key features included observations in drivers' own vehicles, in familiar environments chosen by the driver, with start/end points at their own homes. Participants were 33 drivers aged 75+ years, who drove their selected route with observations recorded during intersection negotiation, lane-changing, merging, low speed maneuvers and maneuver-free driving. Driving behaviors were scored by a specialist occupational therapy driving assessor and another trained observer. Drivers also completed a post-drive survey about the acceptability of DOS. Vehicle position, speed, distance and specific roadways traveled were recorded by an in-vehicle device installed in the participant's vehicle; this device was also used to monitor participants' driving over several months, allowing comparison of DOS trips with their everyday driving. Inter-rater reliability and DOS feasibility, acceptability and ecological validity are reported here. On average, drivers completed the DOS trip in 30.48min (SD=7.99). Inter-rater reliability measures indicated strong agreement between the trained and the expert observers: intra-class correlations (ICC)=0.905, CI 95% 0.747-0.965, p<0.0001; Pearson product correlation, r (18)=.83, p<0.05. Standard error of the measurement (SEM), method error (ME) and coefficient of variation (CV) measures were consistently small (3.0, 2.9 & 3.3%, respectively). Most participants reported being 'completely at ease' (82%) with the driving task and 'highly familiar with the route' (97%). Vehicle data showed that DOS trips were similar to participants' everyday driving trips in roads used, roadway speed limits, drivers' average speed and speed limit compliance. In summary, preliminary findings suggest that DOS can be scored reliably, is of feasible duration, is acceptable to drivers and representative of everyday driving. Pending further research with a larger sample and other observers, DOS holds promise as a means of quantifying and monitoring changes in older drivers' performance in environments typical of their everyday driving.

Intravenous immunoglobulin attenuates airway hyperresponsiveness in a murine model of allergic asthma.

BACKGROUND: Intravenous immunoglobulin (IVIG) has potent anti-inflammatory and immune-modulating properties. IVIG has been utilized as a steroid-sparing agent in severe asthma, but the results of clinical trials have been conflicting. OBJECTIVE: To determine whether IVIG is able to attenuate bronchial reactivity, pulmonary inflammation and T cell function using a murine model of allergic airways disease. METHODS: BALB/c or C57BL/6 mice were sensitized to ovalbumin (OVA) or a phosphate-buffered saline control using local nasal sensitization, and then received five intranasal challenges on days 28-32 before sacrifice. Mice were treated intraperitoneally with either IVIG (1-2 g/kg) or equivalent human serum albumin 24 h before the first OVA challenge. Bronchial reactivity to methacholine was examined using the FlexiVent small animal ventilator. We evaluated pulmonary histology, mRNA from lung digests for T-helper type 2 (Th2)-related genes and bronchoalveolar lavage for cell counts and cytokines. Splenocytes were utilized to study OVA-induced cell proliferation, cytokine production and dendritic cell maturation. RESULTS: IVIG markedly attenuated the perivascular and peribronchial pulmonary inflammation, and decreased bronchial hyperresponsiveness to methacholine. IVIG treatment of splenocytes from sensitized animals diminished cellular proliferation to OVA, whereas IVIG treatment in vivo markedly attenuated OVA-driven splenocyte proliferation. This is accompanied by diminished IL-13 and TNF-α levels in splenocyte culture, decreased expression of Jagged-1, increased Delta-4 and decreased GATA-3 mRNA levels, signs that IVIG has suppressed the expected Th2 response that accompanies repeated allergen exposure. Increased regulatory T cells were found in draining pulmonary lymph nodes in IVIG-treated mice but not in controls. CONCLUSIONS AND CLINICAL RELEVANCE: IVIG was effective in ameliorating allergic airway disease in our model. IVIG may be a promising adjunct therapy requiring further study for patients with severe asthma.

Children with atopic histories exhibit impaired lipopolysaccharide-induced Toll-like receptor-4 signalling in peripheral monocytes.

BACKGROUND: The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll-like receptor (TLR)-4 on CD4(+) cells in nasal mucosa. OBJECTIVE: To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4(+) leucocytes. METHODS: Peripheral blood mononuclear cells from children (aged 2-18) and adults with or without a history of atopic conditions were cultured with/without IL-4 or LPS for up to 24 h. Expression of surface TLR-4, CD14, CD4, CD3, as well as of intracellular phosphorylated (p42/p44) ERK and p38 mitogen-activated protein kinase (MAPK) were assessed by flow cytometry. RESULTS: A history of atopy in children was associated with impaired LPS-induced TLR-4-dependent phosphorylation of (p42/44) ERK and p38 MAPK by CD4(+) monocytes. Decreased LPS signalling was reproduced by pre-incubation of control cells with recombinant IL-4. LPS stimulation also decreased TLR-4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4(+) T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non-atopic children, TLR-4 expression on monocytes of children with atopic histories decreased as a function of age. CONCLUSIONS: This study provides evidence for defective LPS recognition on circulating CD4(+) leucocytes of subjects with atopic histories compared with those from non-atopic children. CD4(+) TLR4(+) monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR-4-mediated innate immune function compared with non-atopic children.

B lymphocytes in inflammatory airway diseases.

B lymphocytes are key players in all facets of adaptive immune responses and are responsible for the production of IgE antibodies, initiators of allergic hypersensitivity reactions. Recent evidence indicates that B cells may be a crucial player in allergic and inflammatory airway pathology, directly populating upper and lower airway tissues. This review examines human and animal studies that directly demonstrated the presence of B lymphocytes in airway tissues and elaborates on their function as antibody-secreting cells, antigen-presenting cells and producers of inflammatory and regulatory cytokines. B lymphocytes appear to contribute to multiple facets of immune homeostasis in inflammatory diseases of the upper and lower airways.

Screening for motor deficits using the Pediatric Evaluation of Disability Inventory (PEDI) in children with language impairment.

OBJECTIVE: To evaluate the association between the Pediatric Evaluation of Disability Inventory (PEDI) motor and self-care domains with the Peabody Developmental Motor Scales-second edition (PDMS-2) gross motor and fine motor sub-scales. METHODS: Forty children (35-62 months) with primary language impairment (PLI) were recruited. The PEDI was completed at admission and the PDMS-2 was administered within 1 month by an OT, who was unaware of the PEDI results. RESULTS: Correlation between PEDI mobility and PDMS-2 gross motor domains was r = 0.23 (p = 0.15) and between PEDI self-care and PDMS-2 fine motor domains was r = 0.12 (p = 0.47). Associations between PEDI and PDMS-2 scores for age, gender and severity of language impairment sub-groups were poor-to-moderate. CONCLUSION: Findings indicate the PEDI is not sufficiently accurate to screen for motor deficits in children with PLI. More sensitive measures of motor performance are needed to detect subtle motor deficits in children with PLI.

The low prevalence of allergic disease in Eastern Europe: are risk factors consistent with the hygiene hypothesis?

BACKGROUND: The prevalence of allergic disease is known to be low in Eastern Europe. OBJECTIVE: To assess the association of suspected risk factors, including several closely linked to the hygiene hypothesis, with allergic symptoms and atopic sensitization in young school-aged children. METHODS: Observational study of 13 889 Belarusian children followed up at age 6.5 years in the Promotion of Breastfeeding Intervention Trial (PROBIT). Allergic symptoms and diseases were based on parental responses to the International Study of Asthma and Allergy in Childhood questionnaire, and prick tests to five common inhalant allergens were performed using standard methods. RESULTS: Significantly increased risks of wheezing and hayfever symptoms in the past 12 months, and of recurrent itchy rash were observed in boys, children with a positive first-degree family atopic history, and those who had received probiotics (especially as prophylaxis with antibiotic use). Pet ownership, contact with farm animals, the presence and number of younger and (especially) older siblings, and residency in rural areas of Western Belarus were associated with reduced risks. Maternal postnatal smoking was associated with wheezing and hayfever symptoms, while the duration of exclusive breastfeeding was not protective against any of the studied outcomes. The risk factors for allergic symptoms were similar in children with positive skin-prick tests to those in the overall cohort. CONCLUSION: Many of the risk and protective factors we identified are consistent with those reported in Western countries and with the hygiene hypothesis. Further research on dietary and other environmental and genetic factors is necessary to understand the low prevalence of allergic disease in Belarus and other Eastern European countries.

Efficient purification of eosinophils from human tissues: a comparative study.

BACKGROUND: Eosinophils are key effector cells in allergy and in other inflammatory diseases. Although they carry out their function in the tissues, no efficient method exists allowing for consistent purification of tissue eosinophils for culture. Rather, studies rely mainly on peripheral blood eosinophils. This study aimed to determine the most efficient protocol for purifying eosinophils from nasal polyp tissue. METHODS: Nasal polyps were obtained from patients undergoing surgical polypectomy. The polyps were minced and enzymatically digested. Surface receptor analysis was performed by flow cytometry. In order to obtain optimal purification, the nasal polyp cell suspension was subjected to two methods of purification: 1) positive magnetic selection of CCR3+cells, or 2) negative selection using CD3/CD14/CD16 magnetic beads. Enriched tissue eosinophils were cultured with or without IL-3, IL-5 or GM-CSF, and their survival was evaluated by flow cytometry. RESULTS: Tissue-derived eosinophils exhibited surface expression of NEC2, DNAM-1, NTBa, 2B4, and CD300a comparable to similarly prepared eosinophils obtained from the peripheral blood of the same patients. Positive selection consistently yielded eosinophils of high purity (>90%) with 63% viability. In contrast, negative selection yielded better viability (88%), reduced purity (66%), and could be utilized for in vitro activation experiments. CONCLUSION: Eosinophils can be purified from nasal polyps. Negative selection appears to be advantageous due to improved viability of the eosinophils, which may be cultured and activated in vitro. This methodology is an important advance in studying tissue eosinophils for further investigations on inflammatory tissue responses.

Actual vs. best practices for young children with cerebral palsy: a survey of paediatric occupational therapists and physical therapists in Quebec, Canada.

RATIONALE: Cerebral palsy (CP) constitutes a substantial portion of paediatric rehabilitation, yet little is known regarding actual occupational therapy (OT) and physical therapy (PT) practices. This study describes OT and PT practices for young children with CP in Quebec, Canada. METHODS: This was a cross-sectional survey. All eligible, consenting paediatric occupational therapists (OTs) and physical therapists (PTs) were interviewed using a structured telephone interview based on vignettes of two typical children with CP at two age points--18 months and 4 years. Reported practices were grouped according to the International Classification of Functioning, Disability and Health (ICF). RESULTS: 91.9% of PTs (n=62; 83.8% participation rate) and 67.1% of OTs (n=85; 91.4% participation rate) reported using at least one standardized paediatric assessment. OT and PT interventions focused primarily on impairments and primary function (such as gait function and activities of daily living). Both professions gave little attention to interventions related to play and recreation/leisure. Clinicians reported the need for more training and education specific to CP and to the use of research findings in clinical practice. CONCLUSION: Wide variations and gaps were identified in clinicians' responses suggesting the need for a basic standard of OT and PT management as well as strategies to encourage knowledge dissemination regarding current best practice.

Signal transducer and activator of transcription 6 down-regulates toll-like receptor-4 expression of a monocytic cell line.

BACKGROUND: Toll-like receptor 4 (TLR4), part of the bacterial lipopolysaccharide (LPS) receptor, is an important bridge between innate and adaptive immunity. Our previous studies have indicated reduced expression of TLR4 and reduced responsiveness to LPS in nasal mucosa of atopic adults compared with non-atopic adults. IL-4 and signal transducer and activator of transcription 6 (STAT6), which are increased in atopic patients, may have a role in modulating TLR4. OBJECTIVE: To examine direct effects of IL-4 and STAT6 on TLR4 expression of U-937 monocytic cells. METHODS: LPS responsiveness, under different conditions of U-937 cells was measured by nuclear factor (NF)-kappaB activation of transcription. TLR4 mRNA was quantified by real-time PCR and TLR4 surface expression was measured by flow cytometry. The promoter and 4.3 kb of the upstream region of TLR4 were cloned into a plasmid vector and transiently transfected into U-937 cells. Transfected cells were incubated with IL-4 and transcriptional activity was assayed by the luciferase assay. STAT6 was transfected to evaluate overexpression of this transcription factor. Cells were also incubated with Tyrphostin AG490 to inhibit tyrosine kinases. RESULTS: NF-kappaB activation by LPS was inhibited by IL-4 pre-incubation but not when IL-4 was added at the same time as LPS. TLR4 mRNA expression was inhibited by IL-4 as early as 6 h but the effect was lost by 24 h. Surface expression of TLR4 was inhibited by IL-4 at 12 and 24 h, but returned to baseline at 48 h. IL-4 inhibited activity of the TLR4 promoter as early as 6 h, but, like the mRNA, these effects were transient. STAT6 overexpression enhanced the inhibition of the TLR4 promoter and prolonged it. Inhibition of TLR4 by IL-4 was abolished by pre-incubation with the tyrosine kinase inhibitor Tyrphostin AG490. CONCLUSION: Our findings demonstrate that IL-4, through STAT6, can modulate TLR4 expression and suggests that Th2 cytokines can impact on the LPS responsiveness of cells.

The expression of stem cell factor and c-kit receptor in human asthmatic airways.

BACKGROUND: Asthmatic airways are characterized by infiltration with a variety of inflammatory cells such as mast cells and eosinophils. Stem cell factor (SCF) is an important activating and chemotactic factor for both mast cells and eosinophils. In addition, it is a critical growth and differentiation factor for mast cells. OBJECTIVES: To investigate the contribution of SCF to the pathogenesis of asthma, we examined the expression of SCF and its receptor c-kit in bronchial biopsies and bronchoalveolar lavage (BAL) specimens obtained from asthmatic subjects (n=13) and non-asthmatic control subjects (n=10). METHODS: SCF and c-kit were detected by in situ hybridization (ISH) and immunocytochemistry (ICC). In order to phenotype the cells expressing SCF and c-kit in asthmatic tissue and BAL cells, combined ISH and ICC were also performed. RESULTS: There was a significant difference (P<0.001) in the SCF mRNA expression in asthmatic airway epithelium (70.38+/-12.33% positive cells) compared with controls (12.7+/-17.21% positive cells). There was also a significant difference in subepithelial SCF-mRNA expression, being higher in asthmatics (P<0.001). A significant difference was also found in c-kit receptor mRNA expression in asthmatic biopsies both in epithelium (P<0.001) and subepithelium (P<0.05) compared with controls. ICC results were consistent with the ISH for both SCF and c-kit receptor from asthmatics and controls. The SCF and c-kit receptor mRNA and immunoreactivity in cells recovered from bronchial washing were also significantly higher in asthmatics compared with controls (P<0.05). While SCF expression was localized predominantly in the epithelial layer in bronchial biopsy tissues, alveolar macrophages were found to be the major source of SCF in bronchial washing from asthmatic subjects. CONCLUSION: The results of this study demonstrate the increased expression of SCF and its receptor, c-kit within human asthmatic airways, which suggests an important role of this cytokine in the pathophysiology of asthma.

Inhibition of IgE production in vitro by intact and fragmented intravenous immunoglobulin.

BACKGROUND: Intravenous immunoglobulin (IVIG) has been shown to suppress Ig production both in vivo and in vitro. We have previously found that IVIG inhibits IgE synthesis in human tonsillar B cells stimulated with IL-4 and anti-CD40 antibody. OBJECTIVE: The purpose of this study was to further clarify the mechanism behind the inhibition of IgE production by IVIG through comparing the effects of intact whole molecular IVIG and the F(ab')(2) or Fc fragments of IVIG. METHODS: Human B lymphocytes were purified from tonsils. Cell proliferation was measured by means of tritiated thymidine incorporation. IgE was determined by means of ELISA. Cell-cycle analysis was performed by using flow cytometry. RESULTS: Both intact and fractionated IVIG inhibited anti-CD40- and IL-4--stimulated IgE production in a dose-dependent manner. The maximal inhibition was achieved at 67 micromol/L (eg, 10, 6, and 4 mg/mL for intact IVIG, F[ab'](2), and Fc, respectively). The effect of F(ab')(2) was more pronounced than that of Fc at equimolar concentrations. Similarly, both intact and fragmented IVIG dose-dependently decreased tritiated thymidine incorporation. F(ab')(2) was also more potent than Fc in this effect. Heat-aggregated IVIG exhibited similar potency to regular IVIG in inhibiting B-cell proliferation. The inhibitory effects of IVIG were unlikely to have been caused by the induction of apoptosis because neither intact nor fractionated IVIG had a significant effect on cell-cycle parameters at the concentrations used. CONCLUSION: These data suggest that both F(ab')(2) and Fc portions contribute to the inhibition of in vitro IgE production by IVIG. The role of the F(ab')(2) portion is more important than that of the Fc portion.

Functional expression of IL-12 receptor by human eosinophils: IL-12 promotes eosinophil apoptosis.

In murine models of allergic inflammation, IL-12 has been shown to decrease tissue eosinophilia, but the underlying mechanisms are not known. We evaluated the expression of IL-12R and the effect of IL-12 on eosinophil survival. In situ hybridization demonstrated the presence of mRNA and immunoreactivity for IL-12Rbeta1 and -beta2 subunits in human peripheral blood eosinophils. Surface expression of IL-12Rbeta1 and -beta2 subunits on freshly isolated human eosinophils was optimally expressed after incubation with PMA. To determine the functional significance of IL-12R studies, we studied cell viability and apoptosis. Morphological analysis and propidium iodide staining for cell cycle demonstrated that recombinant human IL-12 increased in vitro human eosinophil apoptosis in a dose-dependent manner. Addition of IL-5 together with IL-12 abrogated eosinophil apoptosis, suggesting that IL-12 and IL-5 have antagonistic effects. Our findings provide evidence for a novel role for IL-12 in regulating eosinophil function by increasing eosinophil apoptosis.

IL-16 inhibits IL-5 production by antigen-stimulated T cells in atopic subjects.

BACKGROUND: We have previously shown increased expression of the CD4+ cell chemoattractant IL-16 at sites of airway allergic inflammation. Little is known about the significance of IL-16 in allergic inflammation and its role in allergen-driven T-cell cytokine responses. Because IL-16 interacts specifically with CD4+ T cells, we hypothesized that IL-16 released at sites of inflammation may modulate the pattern of cytokines produced by CD4+ T cells. OBJECTIVE: We investigated the effects of exogenous rhIL-16 on cytokine production of PBMCs from atopic and nonatopic subjects in response to antigen and PHA. METHODS: Primary cultures of freshly isolated PBMCs from ragweed-sensitive atopic subjects and nonatopic subjects were stimulated with ragweed or PHA in the presence or absence of rhIL-16. Supernatant levels of IL-4, IL-5, and IFN-gamma were determined by means of ELISA at different time points between 2 and 6 days. Effects of IL-16 on antigen-induced cellular proliferative responses were determined. RESULTS: No IL-4 protein was detected after antigen stimulation of PBMCs from atopic subjects, whereas significant levels of IL-5 were measured on day 6 (median, 534.9 pg/mL). IL-5 secretion was abolished in PBMC cultures depleted of CD4+ cells. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly reduced the amount of IL-5 released (median, 99.8 pg/mL; P <.001). Detectable levels of IFN-gamma (median, 53.3 pg/mL) were identified after antigen stimulation. The addition of rhIL-16 in antigen-stimulated PBMC cultures significantly increased IFN-gamma levels (median, 255.6 pg/mL; P <.05). Effects of rhIL-16 appear to be specific for antigen-stimulated PBMCs in atopic subjects because rhIL-16 did not alter IL-5 or IFN-gamma production in response to PHA nor did rhIL-16 alter cytokine production in nonatopic normal subjects. CONCLUSION: These studies suggest that IL-16 can play a role in regulating the production of cytokines seen in allergic states in response to antigen.

Use of the UFOV to evaluate and retrain visual attention skills in clients with stroke: a pilot study.

OBJECTIVE: The objective of this pilot study was to examine the use of a visual attention analyzer in the evaluation and retraining of useful field of view in clients with stroke. METHOD: Fifty-two clients with stroke referred to a driving evaluation service were evaluated with a visual attention analyzer referred to as the UFOV. The UFOV assesses three aspects of visual attention: processing speed, divided attention, and selective attention. Seven participants were retested to determine the test-retest reliability of the UFOV. Six participated in the development of a training protocol and in a 20-session visual attention retraining program. RESULTS: UFOV scores indicated substantial reduction in visual attention in clients after stroke, with older participants performing the most poorly. Test-retest reliability was moderate (ICC = .70). Mean UFOV scores improved significantly after retraining. CONCLUSION: Although UFOV scores indicated poor visual attention skills in clients with stroke, preliminary information suggests that UFOV scores significantly improve with training.

Activation via multiple signaling pathways induces down-regulation of platelet-activating factor receptors on human B lymphocytes.

Platelet-activating factor receptor (PAFR) has been identified in B cell lines and primary human B cells, but the regulation of PAFR during B cell activation has not been completely elucidated. In the present study, we have investigated the effects of B cell activation on PAFR binding parameters, PAFR mRNA and PAF-triggered intracellular calcium mobilization. The human B lymphoid cell line LA350 was shown to exhibit high levels of PAFR (48,550 +/- 4,310 sites/cell) as determined by radio-ligand binding assay with PAFR antagonist [3H]WEB2086. Treatment with phorbol 12,13-dibutyrate caused a biphasic reduction of PAFR binding. The early phase was inhibited by the protein kinase C inhibitor bisindolylmaleimide I (BIM), whereas the late phase was not blocked by BIM, protein tyrosine kinase inhibitor genistein, or the mitogen-activated protein kinase/extracellular signal-related kinase inhibitor PD98059. However, staurosporine, a broad-spectrum protein kinase inhibitor, completely inhibited the late phase down-regulation. Ionomycin also decreased [3H]WEB2086 binding sites, whereas the combination of PDB and ionomycin induced a greater reduction than either agent alone. Cross-linking of B cell receptor by anti-IgM Ab also induced down-regulation of PAFR, which was abolished by genistein or PD98059, but not by BIM or staurosporine. The decrease in surface PAFR number was closely paralleled by the reduction in PAFR mRNA both in LA350 cells and human tonsillar B cells, and was associated with decreased response to PAF indicated by decreased intracellular calcium mobilization. These data show that multiple signaling pathways are involved in down-regulating PAFR expression during B cell activation and development.

Visual testing for readiness to drive after stroke: a multicenter study.

OBJECTIVE: The purpose of this study was to determine the ability of a visual-perception assessment tool, the Motor-Free Visual Perception Test, to predict on-road driving outcome in subjects with stroke. DESIGN: This was a retrospective study of 269 individuals with stroke who completed visual-perception testing and an on-road driving evaluation. Driving evaluators from six evaluation sites in Canada and the United States participated. Visual-perception was assessed using the Motor-Free Visual Perception Test. Scores range from 0 to 36, with a higher score indicating better visual perception. A structured on-road driving evaluation was performed to determine fitness to drive. Based on driving behaviors, a pass or fail outcome was determined by the examiner. RESULTS: The results indicated that, using a score on the Motor-Free Visual Perception Test of < or =30 to indicate poor visual-perception and >30 to indicate good visual perception, the positive predictive value of the Motor-Free Visual Perception Test in identifying those who would fail the on-road test was 60.9% (n = 67/110). The corresponding negative predictive value was 64.2% (n = 102/159). Univariate logistic regression analyses revealed that older age, low Motor-Free Visual Perception Test scores and a right hemisphere lesion contributed significantly to identifying those who failed the on-road test. CONCLUSIONS: The predictive validity of the Motor-Free Visual Perception Test is not sufficiently high to warrant its use as the sole screening tool in identifying those who are unfit to undergo an on-road evaluation.