Search PubMed⌕ Search

Biomedical subjects

B Richardson

Publications and source records attributed to B Richardson.

At least 37 records · Page 2Linked to original sources
PubMed2000

The TDS: a new device for comparing active and passive-guided touch.

A problem when comparing active and passive tactile perception of two-dimensional (2-D) stimuli is matching the active and passive tasks on all variables except the one of interest--active versus passive touch. A new computer-controlled device--the tactile display system (TDS)--has been developed to deal with this problem. The TDS tracks an "active" subject's fingertip movements during exploration of a raised line drawing and digitally records this spatio-temporal information. It then guides a passive participant's fingertip over the same path, matching for location and speed. Any difference in performance can thus be attributed to the different conditions (active versus passive) because other variables are held constant.

Blindness↗
PubMed2000

Impaired translational response and increased protein kinase PKR expression in T cells from lupus patients.

Activation of peripheral blood T cells results in a rapid and substantial rise in translation rates and proliferation, but proliferation in response to mitogen stimulation is impaired in systemic lupus erythematosus (SLE). We have investigated translation rates and initiation factor activities in T cells from SLE patients in response to activating signals. Activation by PMA plus ionomycin strongly increased protein synthesis in control T cells but not in T cells from SLE patients. The rate of protein synthesis is known to be strongly dependent on the activity of two eukaryotic translation initiation factors, eIF4E and eIF2alpha. We show that following stimulation, eIF4E expression and phosphorylation increased equivalently in control and SLE T cells. Expression of eIF4E interacting proteins - eIF4G, an inducer, and 4E-BP1 and 4E-BP2, two specific repressors of eIF4E function - and the phosphorylation level of 4E-BP1, were all identical in control and SLE T cells. In contrast, the protein kinase PKR, which is responsible for the phosphorylation and consequent inhibition of eIF2alpha activity, was specifically overexpressed in activated SLE T cells, correlating with an increase in eIF2alpha phosphorylation. Therefore, high expression of PKR and subsequent eIF2alpha phosphorylation is likely responsible, at least in part, for impaired translational and proliferative responses to mitogens in T cells from SLE patients.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Implementing home care in Canada: four critical elements.

While MacAdam proposes a "national approach to home care#8221; the obstacles to this are well known and substantial. They are the likely cost and the limitations of the federal government s role in healthcare. Building on MacAdam's assessment, this paper outlines four problems embedded in the various home-care service delivery models in Canada: the lack of factual client outcome information to support decision-making, the limited client choice of provider, the perverse incentive of fee for service and the bias against the for-profit provider. The paper proposes that the assessment, classification and measurement of outcomes for every recipient of home-care services be standardized using a proven assessment instrument, such as OASIS-B or MDS-HC, by healthcare professionals certified in its use. The resulting information would be captured in a regional database and available for analysis and research. CIHI would be contracted to manage a national database and to fund the training and certification of assessors. The paper proposes a new service delivery and funding model, utilizing standard client outcome information, different roles for regional health authorities and service providers, and a prospective payment mechanism replacing fee for service. A national home care program may be an elusive dream, but that shouldn't stop experimentation, evaluation and improvement.

Canada↗
PubMed2000

Mitogen-activated protein kinase activates human placental lactogen-B enhancer by an NF-IL6-dependent pathway.

Computer analysis of the human placental lactogen-B (hPL-B) enhancer reveals two putative binding sites for the transcription factor NF-IL6, but the role of NF-IL6 in the regulation of the enhancer is unknown. Using gel mobility shift and supershift assays, we demonstrated that NF-IL6 binds to both enhancer sites. Transient transfection studies indicated that the transcription factor NF-IL6 stimulates hPL-B enhancer activity by 4.4-fold in primary cultures of human trophoblast cells and by 32.0- and 8.4-fold in JAR and BeWo choriocarcinoma cells, respectively. Overexpression of MEK (mitogen-activated protein [MAP] kinase kinase), which is known to stimulate phosphorylation of NF-IL6, induced a 3.6-fold increase in hPL-B enhancer activity. The induction by MEK was completely inhibited by an expression plasmid for a dominant/negative mutant of NF-IL6 or by mutation of the NF-IL6 binding sites on the enhancer. PD98059, an inhibitor of MEK, inhibited hPL release from cultured trophoblast cells by about 50%. Taken together, these results indicate that MAP kinase stimulates the hPL-B enhancer by an NF-IL-6-dependent pathway.

CCAAT-Enhancer-Binding Proteins↗
PubMed2000

Medical faculty's views and experiences of parental leave: a collaborative study by the Gender Issues Committee, Council of Ontario Faculties of Medicine.

OBJECTIVES: To examine medical faculty's actual and ideal parental leave arrangements with the aim of informing policy decisions. Leave lengths, effect on career, financial arrangements, and availability of temporary replacements were explored. METHODS: All medical faculty (6387) in Ontario, Canada were surveyed by mail and asked about parental leave experiences since 1990. Responses of men and women were compared as were those of leave takers and the entire group. RESULTS: Thirty-two percent (n = 996) of the 3107 respondents were women and 68% (n = 2067) were men. Ninety-eight percent (n = 317) of new mothers had taken maternity leave, while only 21% (n = 159) of new fathers had. Both paid and unpaid leave was generally shorter than that allowed by law or identified as ideal. Parental leave had a somewhat negative effect on the careers of all faculty. Women were more worried than men about the effect of their absence on colleagues' work and more generous with ideal leave length and funding. Temporary replacement of leave takers was central to an effective leave policy. CONCLUSIONS: Institutional and academic culture may cause new parents to take suboptimal leave despite legislation allowing more. A change in the work environment is required for medicine to offer its teachers what it teaches--that infants benefit from nurturing, nursing, and stability early in life.

Attitude of Health Personnel↗
PubMed1999

Analysis of human peripheral blood T cells and single-cell-derived T cell clones uncovers extensive clonal CpG island methylation heterogeneity throughout the genome.

Methylation of cytosine residues in CpG dinucleotides is generally associated with silencing of gene expression. DNA methylation, as a somatic event, has the potential of diversifying gene expression in individual cells of the same lineage. There is little quantitative data available concerning the extent of methylation heterogeneity in individual cells across the genome. T cells from the peripheral blood can be grown as single-cell-derived clones and can be analyzed with respect to their DNA methylation patterns by restriction landmark genomic scanning. The use of the methylation-sensitive enzyme NotI to cut and end-label DNA fragments before their separation in two dimensions provides a quantitative assessment of methylation at NotI sites that characteristically occur in CpG islands. We have undertaken quantitative analysis of two-dimensional DNA patterns to determine the extent of methylation heterogeneity at NotI sites between peripheral blood single-cell-derived T cell clones from the same individual. A total of 1,068 NotI-tagged fragments were analyzed. A subset of 156 fragments exhibited marked methylation heterogeneity at NotI sites between clones. Their average intensity among clones correlated with their intensity in uncultured, whole-blood-derived T cells, indicating that the methylation heterogeneity observed in clones was largely attributable to methylation heterogeneity between the individual cells from which the clones were derived. We have cloned one fragment that exhibited variable NotI-site methylation between clones. This fragment contained a novel CpG island for a gene that we mapped to chromosome 4. The methylation status of the NotI site of this fragment correlated with expression of the corresponding gene. Our data suggest extensive diversity in vivo in the methylation and expression profiles of individual T cells at multiple unrelated loci across the genome.

Base Composition↗
PubMed1999

Intermittent umbilical cord occlusion in the ovine fetus near term: effects on behavioral state activity.

OBJECTIVE: The purpose of this study was to determine the effects on fetal behavioral state activity of intermittent umbilical cord occlusion resulting in repetitive severe short-term hypoxemia. STUDY DESIGN: Fifteen near-term fetal sheep (experimental group, n = 8; control group, n = 7) were studied during 4 days while behavioral and cardiovascular parameters were monitored. Each day after a 2-hour control period, cord occlusions were performed in the experimental group animals by complete inflation of an occluder cuff (duration, 90 seconds) every 30 minutes for 3 to 5 hours. Results are presented as group mean +/- SEM. RESULTS: During umbilical cord occlusions fetal arterial PO(2) (change of 12 mm Hg), oxygen saturation (change of 40%), and glucose concentration (change of 0.3 mmol/L) fell and PCO(2) (change of 7 mm Hg) rose, but all returned toward control values after release of occlusion. Fetal behavioral state activity was markedly disrupted by 90 seconds of cord occlusion, with animals showing an abrupt flattening of the electrocorticogram. In >90% of instances the first identifiable state after cord release was the high-voltage non-rapid-eye-movement state. There was no apparent change in this response through the 4 days of the study. For experimental group animals the mean percentages of time spent in low-voltage electrocortical state (from 53 +/- 2 to 36 +/- 2), electro-ocular state (from 45 +/- 3 to 28 +/- 3), and fetal breathing activity (22 +/- 4 to 12 +/- 3) were significantly decreased (P <.001) during occlusion hours with respect to nonocclusion hours. CONCLUSION: Intermittent umbilical cord occlusion with severe but limited hypoxemia and no cumulative acidosis in the near-term ovine fetus disrupts behavioral state activity, with a flattening of the electrocortical activity during occlusions and an overall decrease in the prominence of the low-voltage rapid-eye-movement state. If such insults are frequent and severe enough, they might have an effect on growth and development of the brain during the perinatal period.

Animals↗
PubMed1999

The ability of non-ergonomists in the health care setting to make manual handling risk assessments and implement changes.

The health care setting presents particular risks from manual handling and it is known that training in manual handling techniques is ineffective in reducing these risks when used as a stand-alone measure. The 'Manual Handling Operations Regulations 1992' requires employers to consider hazardous manual handling, advising the use of an ergonomics approach. However, it is not known how well-equipped non-ergonomists in the health care setting are to deal with this approach. Therefore, the ability of non-ergonomists to make manual handling risk assessments, with or without additional training, and to implement changes to the work environment was investigated. Twenty-five pairs of subjects from a broad cross section of departments in a busy teaching hospital were studied; training and a guide book were provided for one of each pair and the guide book only for the other. Subjects then independently prioritised three tasks in their department and undertook a full assessment of a specified task. All work was repeated by an ergonomist and the subjects' assessments were scored in comparison with the ergonomist. Each department was followed up after six months to assess progress with implementing recommendations. Trends in the data indicated that both groups appeared able to identify hazards though not necessarily to prioritise the tasks. The trained group tended to score better in assessments although wide variation existed within both groups and inter-group differences were not significant at the 5% level. Approximately half of staff assessments were considered 'adequate' to 'very good', in comparison with the ergonomist. Implementation of assessment recommendations ranged from nil to almost full compliance. Incomplete implementation seemed to be related to an apparent confusion in some departments over who was responsible for making changes, a lack of finances for changes and overstretched managers having other priorities.

Ergonomics↗
PubMed1999

Role of DNA methylation in the regulation of cell function.

The methylation of DNA helps stabilize chromatin in an inactive configuration and inhibits gene transcription. This mechanism of gene regulation is involved in essential genetic events including differentiation, genomic imprinting, and X chromosome inactivation. The alteration of methylation patterns can result in abnormal gene expression, with significant pathologic effects including carcinogenesis, autoimmunity, and some of the changes in gene expression associated with aging. The mechanisms establishing, maintaining, and modifying methylation patterns in normal and pathologic states are only now becoming understood, as are the mechanisms relating DNA methylation to gene expression and chromosome inactivation. Further characterization of these mechanisms holds promise for delaying or preventing the changes in methylation patterns that contribute to cancer, autoimmunity, and aging.

Animals↗
PubMed1999

Investigation of female survival benefit in metastatic melanoma.

Epidemiological studies show female survival benefit in advanced metastatic melanoma. In investigating a possible mechanism for this female survival benefit, we have previously reported that the female steroid 17beta-oestradiol significantly reduces invasion of a human melanoma cell line (A375-SM cells) and ocular melanoma cells through fibronectin. Neither cell type was found to possess oestrogen receptor-alpha. The aim of the current study was to obtain further information on the extent to which progression of cutaneous melanoma might be sex steroid sensitive by (a) examining the relationship between circulating sex steroids, sex hormone binding globulin and disease progression; (b) examining the relationship between sex steroid structure and the ability of steroids to reduce invasion of a melanoma cell line in vitro; and (c) examining the effects of sex steroids on proliferation of these cells in vitro. We report a significant reduction in circulating oestrone with disease progression in male but not female patients. Examining steroids for their ability to inhibit invasion of A375-SM cells through fibronectin in vitro, oestrogenic compounds (17beta-oestradiol and oestrone) were found to inhibit invasion; in this respect, oestrone was approximately 50 times more potent than 17beta-oestradiol; steroids lacking the benzene ring structure did not inhibit invasion, indeed dehydroepiandrosterone (DHEA) which acts as a precursor to androgenic steroids significantly enhanced invasion. Proliferation of A375-SM cells was unaffected by 17beta-oestradiol, oestrone or dihydrotestosterone when cells were cultured on plastic; in contrast, all three steroids induced modest proliferation of cells when grown on fibronectin with dihydrotestosterone the most mitogenic of the three steroids. These data are consistent with sex steroids playing a role in melanoma progression.

Adolescent↗
PubMed1999

Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya.

If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.

Adult↗
PubMed1999

Rapid method for screening dried blood samples on filter paper for human immunodeficiency virus type 1 DNA.

PCR is a highly sensitive method for the detection of human immunodeficiency virus type 1 (HIV-1) nucleic acids in blood mononuclear cells and plasma. However, blood separation techniques require extensive laboratory support systems and are difficult when a limited volume of blood is available, which is often the case for infants. The use of blood samples stored on filter paper has many advantages for the detection of perinatal HIV-1 infection, but current methods require extraction and purification of target DNA prior to PCR amplification. We report a highly sensitive and rapid method for the extraction and detection of HIV-1 DNA in infant blood samples stored on filter papers. Because this rapid protocol does not involve steps for the removal of potential inhibitors of the PCR, the highest sensitivity is achieved by testing the filter paper lysate in quadruplicate. Assays for HIV-1 DNA were done by using nested PCR techniques that amplify HIV-1 gag DNA from blood spot samples on filter paper and from corresponding viably frozen mononuclear cells separated from venous blood samples obtained from 111 infants born to HIV-1-seropositive mothers. PCR results with blood from filter papers showed 100% specificity (95% confidence internal [CI] 93.1 to 100%) and 96% (95% CI, 88.65 to 98.9%) and 88% (95% CI, 79.2 to 94.5%) sensitivity (for quadruplicate and duplicate tests, respectively) compared to PCR results with blood mononuclear cells. Moreover, this method could detect HIV-1 sequences of multiple subtypes.

Blood↗
PubMed1999

Pre-beta-HDL stimulates placental lactogen release from human trophoblast cells.

To examine whether pre-beta-high-density lipoprotein (HDL) may be involved in regulation of human placental lactogen (hPL) release, pre-beta-HDL was isolated from term pregnancy serum, and the effect of purified pre-beta-HDL on hPL release from trophoblast cells was examined after 1 h of exposure. Pre-beta-HDL stimulated a dose-dependent increase in hPL release with half-maximal stimulation at a dose of 300-400 microgram/ml, which is within the normal physiological range during pregnancy. Analysis of pre-beta-HDL and alpha-HDL in serum from pregnant women at different stages of gestation (determined by Western blot analysis) indicated that the pre-beta-HDL-to-alpha-HDL ratio increased linearly after the 10th week of gestation (r = 0.88, P < 0.001), reaching a maximum sixfold greater than that of nonpregnant women. The increase in serum pre-beta-HDL during pregnancy paralleled that of plasma hPL concentrations (r = 0.93, P < 0.001). Two-dimensional electrophoresis indicated that the increase in pre-beta-HDL was due primarily to an increase in pre-beta1-HDL and pre-beta2-HDL, two of the three forms of pre-beta-HDL present in blood. These results suggest a role for pre-beta-HDL in the regulation of hPL expression during pregnancy.

Cells, Cultured↗
PubMed1999

Environmentally induced autoimmune diseases: potential mechanisms.

Environmental and other xenobiotic agents can cause autoimmunity. Examples include drug-induced lupus, toxic oil syndrome, and contaminated l-tryptophan ingestion. Numerous mechanisms, based on (italic)in vitro(/italic) evidence and animal models, have been proposed to explain how xenobiotics induce or accelerate autoimmunity. The majority of these can be divided into three general categories. The first is those inhibiting the processes involved in establishing tolerance by deletion. Inhibiting deletion can result in the release of newly generated autoreactive cells into the periphery. The second mechanism is the modification of gene expression in the cells participating in the immune response, permitting lymphocytes to respond to signals normally insufficient to initiate a response or allowing the antigen-presenting cells to abnormally stimulate a response. Abnormal gene expression can thus disrupt tolerance maintained by suppression or anergy, permitting activation of autoreactive cells. The third is the modification of self-molecules such that they are recognized by the immune system as foreign. Examples illustrating these concepts are presented, and related mechanisms that have the potential to similarly affect the immune system are noted. Some mechanisms appear to be common to a variety of agents, and different mechanisms appear to produce similar diseases. However, evidence that any of these mechanisms are actually responsible for xenobiotic-induced human autoimmune disease is still largely lacking, and the potential for numerous and as yet unidentified mechanisms also exists.

Animals↗
PubMed1998

Differential regulation of translation and eIF4E phosphorylation during human thymocyte maturation.

Activation of peripheral blood T cells by cross-linking of CD3 results in a rapid and substantial rise in translation rates and proliferation, which coincides with an increase in the cap-binding protein, eIF4E activity. In contrast, immature CD4+ CD8+ double-positive (DP) thymocytes undergo apoptosis in response to anti-CD3 mAb. We have investigated translation initiation in the response of immature thymocytes to activating signals. Activation by anti-CD3 + anti-CD4 of immature CD4+ CD8+ DP thymocytes results in a rapid decrease in protein synthesis. In contrast, similar treatment of CD4+ or CD8+ single-positive (SP) thymocytes results in an increase in protein synthesis. The rate of protein synthesis is linked to the phosphorylation status of eIF4E. Following anti-CD3 + anti-CD4 stimulation, eIF4E phosphorylation strongly decreases in immature DP thymocytes, whereas it increases in mature SP thymocytes. The expression of 4E-BP2, a specific repressor of eIF4E function, is high in DP cells but decreases during maturation, raising the possibility of a role for 4E-BP2 in repressing eIF4E phosphorylation. These data provide evidence for differential regulation of the translational machinery during T cell development.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Fetal oxygen saturation and fractional extraction at birth and the relationship to measures of acidosis.

OBJECTIVE: We sought to determine umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population and their predictive value for measures of acidosis. STUDY DESIGN: The computerized perinatal database of St. Joseph's Health Centre, London, Ontario, was used to obtain the umbilical cord gases, pH, mode of delivery, gestational age at delivery, and nuchal cord status for all live-born infants >500 gm between January 1991 and December 1995 (n = 22,134). Oxygen saturation values were calculated from the umbilical cord PO2 and pH data with a previously derived empirical equation, the accuracy of which was rechecked with 100 consecutive cord blood samples where oxygen saturation values were both calculated and measured with a hemoximeter (r = 0.99, p = 0.001). Fractional oxygen extraction values were calculated from the umbilical cord oxygen saturation data. RESULTS: There were 18,250 "validated" paired umbilical vein and artery blood gas and pH results available for analysis after patient case exclusions for missing, unreliable, or "unphysiologic" data. For all validated patient cases, mean umbilical vein oxygen saturation was 63% +/- 16% (SD), mean umbilical artery oxygen saturation was 24% +/- 15%, and mean fractional oxygen extraction was 0.62 +/- 0.20, with all three of these parameters significantly affected by mode of delivery, gestational age at delivery, and nuchal cord status. Umbilical vein and artery oxygen saturation and fractional oxygen extraction values showed significant relationships with umbilical artery base excess, albeit weak (r = 0.18 to 0.22), and pH (r = 0.46), which were best described using cubic regression models. Receiver-operator characteristic curve statistics for the prediction of acidosis at birth were also significant for all three of these parameters but lower when predicting metabolic versus mixed acidosis. However, all showed a poor positive predictive value for significant acidosis at birth, whether metabolic or mixed and regardless of the cutoff values used. CONCLUSION: Umbilical cord oxygen saturation and fractional oxygen extraction values as measured at birth for a large tertiary hospital population indicate a decreased oxygen margin of safety for infants born postterm, by cesarean section after labor, and with a nuchal cord. However, these values have a limited relationship to measures of acidosis, which may have clinical implications for the usefulness of intrapartum pulse oximetry.

Acidosis↗