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Biomedical subjects

B Wilson

Publications and source records attributed to B Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Comparison of pocket-computer memory aids for people with brain injury.

Two styles of pocket computer memory aid were compared as support for people who had sustained non-progressive, closed-head brain injury. A purpose-designed interface provided a diary with auditory alarms, a notebook and links between diary entries and specific notepages. One computer had a physical keyboard, the other did not. Twelve adult volunteers were loaned each computer for 2 months, with a 1 month gap between, in counterbalanced order. It was found that all participants could use the memory aids, and most (83%) found them useful. Little customizing was needed, but amount of use varied widely. Predictors of usage included use of other reminding systems before joining the project, and speed in calculator addition which may reflect working memory. High users preferred the computer with a physical keyboard; low users made more entries with the palm-size computer. These data highlight the need to distinguish ability to use from willingness to use.

Activities of Daily Living↗
PubMed2001

Comorbidity of psychiatric and substance use disorders in late adolescence: a cluster analytic approach.

Cluster analysis was used to identify subgroups of youths with past-year substance and/or psychiatric disorders (N = 110, mean age 19.0 years). Data for this study came from a community-based, prospective longitudinal investigation of speech/language (S/L) impaired children and matched controls who participated in extensive diagnostic and psychosocial assessments at entry into the study at 5 years of age and again at follow-up. Clustering variables were based on five DSM diagnostic categories assessed at age 19with the University of Michigan Composite International Diagnostic Interview. Using Ward's method, the five binary variables were entered into a hierarchical cluster analysis. An iterative clustering method (K-means) was then used to refine the Ward solution. Finally, a series of analyses of variance (ANOVAs) were run to analyze group differences between clusters on measures of Global Assessment of Functioning (GAF), criminal involvement, anxiety and depressive symptomatology, and frequency of drug use and heavy drinking. The analysis yielded eight replicable cluster groups, which were labeled as follows: (a) anxious (20.9%); (b) anxious drinkers (5.5%); (c) depressed (16.4%); (d) depressed drug abusers (10%); (e) antisocial (16.4%); (f) antisocial drinkers (10%); (g) drug abusers (8.2%); (h) problem drinkers (12.7%). These groups were differentiated by external criteria, thus supporting the validity of our cluster solution. Cluster membership was associated with a history of S/L impairment: A large proportion of the depressed drug abusers and the antisocial cluster group had S/L impairment that was identified at age 5. Clarification of the developmental progress of the youths in these cluster groups can inform our approach to early intervention and treatment.

Adolescent↗
PubMed2001

Enhancing an appointment diary on a pocket computer for use by people after brain injury.

People with memory loss resulting from brain injury benefit from purpose-designed memory aids such as appointment diaries on pocket computers. The present study explores the effects of extending the range of memory aids and including games. For 2 months, 12 people who had sustained brain injury were loaned a pocket computer containing three purpose-designed memory aids: diary, notebook and to-do list. A month later they were given another computer with the same memory aids but a different method of text entry (physical keyboard or touch-screen keyboard). Machine order was counterbalanced across participants. Assessment was by interviews during the loan periods, rating scales, performance tests and computer log files. All participants could use the memory aids and ten people (83%) found them very useful. Correlations among the three memory aids were not significant, suggesting individual variation in how they were used. Games did not increase use of the memory aids, nor did loan of the preferred pocket computer (with physical keyboard). Significantly more diary entries were made by people who had previously used other memory aids, suggesting that a better understanding of how to use a range of memory aids could benefit some people with brain injury.

Appointments and Schedules↗
PubMed2001

Fourteen-year follow-up of speech/language-impaired and control children: psychiatric outcome.

OBJECTIVE: To examine the association between early childhood speech and language disorders and young adult psychiatric disorders. METHOD: In a longitudinal community study conducted in the Ottawa-Carleton region of Ontario, Canada, interviewers administered structured psychiatric interviews to age 19 participants who were originally identified as speech-impaired only, language-impaired, or nonimpaired at age 5. The first stage of the study took place in 1982 when participants were 5 years old, and the latest stage of the study took place between 1995 and 1997 when participants had a mean age of 19 years. This report examines the association between early childhood speech/language status and young adult psychiatric outcome. RESULTS: Children with early language impairment had significantly higher rates of anxiety disorder in young adulthood compared with nonimpaired children. The majority of participants with anxiety disorders had a diagnosis of social phobia. Trends were found toward associations between language impairment and overall and antisocial personality disorder rates. Males from the language-impaired group had significantly higher rates of antisocial personality disorder compared with males from the control group. Age of onset and comorbidity did not differ by speech/language status. The majority of participants with a disorder had more than one. CONCLUSIONS: Results support the association between early childhood speech and language functioning and young adult psychiatric disorder over a 14-year period. This association underscores the importance of effective and early interventions.

Adult↗
PubMed2001

Antiphospholipid antibodies and hemodialysis vascular access thrombosis.

Screening for the presence of APL for hemodialysis dependent individuals is yet another critical link where medical and nursing interventions will prolong vascular access survival and decrease morbidity. Because of the continuity they provide, hemodialysis nurses and advanced practice nurses are in excellent positions to identify individuals with persistent vascular thrombosis and make recommendations for further screening.

Antiphospholipid Syndrome↗
PubMed2000

Cloning and expression of MP13 gene from rat hippocampus, a new factor related to guanosine triphosphate regulation.

C-Fos and the Fos-related antigens (FRA) are induced by various stimuli. A novel 35-37 kDa FRA was induced much longer after the treatment using kainic acid (KA) and may be very important for neuronal survival after brain damage. To identify this long-term FRA, we have constructed a cDNA library derived from hippocampus after KA treatment and screened it with an antibody highly conserved M-peptide region of FRAs. One gene, MP13, was cloned with a 1662 bp open reading frame and coded for a 554-amino acid protein. MP13 has a leucine zipper region, a glutamine repeat region, and has high similarity to the activator of the small guanosine triphosphate (GTP)ase Rab5. Gel retardation analysis revealed that MP13 functions as a GTP regulation related factor.

Amino Acid Sequence↗
PubMed2000

Factors involved in the initial mutation of the fragile X CGG repeat as determined by sperm small pool PCR.

The fragile X syndrome is one of more than a dozen genetic diseases attributed to the amplification of a trinucleotide repeat. Despite the number of these disease loci, relatively little is known about the mechanism(s) that cause a stable allele to become unstable. Population and family studies of the fragile X CGG repeat have identified a number of factors that may play a role in repeat instability including the number of AGG interruptions, purity of the 3' and 5' end of the repeat and cis-acting factors as related to haplotype background. However, studies that assess whether these factors have an impact on the rate and magnitude of change of the repeat are lacking, mainly due to the lack of an appropriate model system. Therefore, in order to dissect the factors involved in the initial mutations of the CGG repeat, small pool (SP)-PCR was performed on DNA derived from sperm and blood from seven unaffected males whose repeat sizes range from 20 to 33. Using the SP-PCR-derived data, regression analyses suggested that components of the repeat structure such as the number of interruptions and purity of the 3' end of the repeat are important determinants of germline repeat instability. In contrast, elements other than repeat structure, such as haplotype background, seemed to have an impact on somatic repeat instability. The factors identified for either cell type, however, explained only a small portion of the variance, suggesting that other factors may be involved in this process.

Adult↗
PubMed2000

Immune modulatory effects of neural cell adhesion molecules on lipopolysaccharide-induced nitric oxide production by cultured glia.

Activation of glial cells often occurs at sites of neuronal injury or death and where there is disruption of communication between glia and neurons. We have previously reported that neurons exert an inhibitory influence on LPS-stimulated nitric oxide (NO) production in glial cells. We hypothesized that neural cell adhesion molecules (NCAM) might mediate this inhibitory effect, and this study was designed to elucidate the role of NCAM on lipopolysaccharide (LPS)-induced NO production. We found that soluble NCAMs reduced LPS-stimulated NO production by cultured glia. A monoclonal antibody that recognizes the third immunoglobulin (Ig) domain and can mimic the functions of NCAMs reduced LPS-stimulated NO production, whereas another antibody that binds to other regions of the NCAM did not modulate NO production. Using a 10-amino acid peptide from the third Ig domain of the NCAM, a peptide fragment within the region recognized by the NCAM antibody, mimics the effect of the molecule in reducing NO production. This study demonstrated that NCAMs could modulate LPS-stimulated NO production, most likely via interaction between NCAMs. These results suggest that neuron-glia interactions via NCAMs play an important role in regulating the activities of glial cells in the brain.

Adjuvants, Immunologic↗
PubMed2000

Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia.

Inflammation in the brain has been increasingly associated with the development of a number of neurological diseases. The hallmark of neuroinflammation is the activation of microglia, the resident brain immune cells. Injection of bacterial endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia nigra of adult rats produced neurodegeneration only in the substantia nigra. Although LPS appeared to impact upon mesencephalic neurons in general, an extensive loss of dopaminergic neurons was observed. Analysis of the abundance of microglia revealed that the substantia nigra had the highest density of microglia. When mixed neuron-glia cultures derived from the rat hippocampus, cortex, or mesencephalon were treated with LPS, mesencephalic cultures became sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose-dependent manner with the production of inflammatory factors and a loss of dopaminergic and other neurons. In contrast, hippocampal or cortical cultures remained insensitive to LPS treatment at concentrations as high as 10 microg/ml. Consistent with in vivo observations, mesencephalic cultures had fourfold to eightfold more microglia than cultures from other regions. The positive correlation between abundance of microglia and sensitivity to LPS-induced neurotoxicity was further supported by the observation that supplementation with enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data indicate that the region-specific differential susceptibility of neurons to LPS is attributable to differences in the number of microglia present within the system and may reflect levels of inflammation-related factors produced by these cells.

Animals↗
PubMed2000

Fragile X CGG repeat structures among African-Americans: identification of a novel factor responsible for repeat instability.

The cryptic CGG repeat responsible for the fragile X syndrome, located in the 5'-UTR of FMR1, is unique compared with the many other triplet repeat-causing diseases, making it ideal for identifying factors involved in repeat expansion that may be common to other triplet repeat diseases. To date, a number of factors have been identified which may influence repeat instability, including the number and position of interspersed AGGs, length of the 3' pure CGG repeat and haplotype background. However, nearly all such data were derived from studies of Caucasians. Using a large African-American population, we present the only comprehensive examination of factors associated with CGG repeat instability in a non-Caucasian population. Among Caucasians, susceptible alleles were thought to come from those in the intermediate repeat range (41-60 repeats); however, we find that susceptible alleles may come from a larger repeat pool (35-60 repeats) and are better defined by their pure CGG repeat and/or -presence of only one AGG interruption. These results demonstrate the existence of different susceptible alleles among world populations and may account for the similar prevalence of the fragile X syndrome in African-Americans compared with Caucasians despite the lower frequency of inter-mediate sized alleles in the African-American population. Finally, we show that repeat structures among unaffected African-Americans with the most frequent fragile X haplotype background are either pure or contain a single distal interruption. We propose that the lack of a proximal most interruption is a novel factor involved in CGG repeat instability.

5' Untranslated Regions↗
PubMed2000

Post-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Gö6976 in murine microglia.

Glia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated post-transcriptionally through the destabilization of iNOS mRNA by the indolocarbazole compound, Gö6976, in murine microglia. This Gö6976 effect is specific for iNOS since tumor necrosis factor alpha was unaffected by the compound. Interestingly, the post-transcriptional effects ascribed to Gö6976 were not observed with other inhibitors of protein kinase A, C (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect the iNOS/NO system at the transcriptional level. In the past, Gö6976 has been reported to be a rather specific inhibitor of PKC in vitro. Results from our experiments, through prolonged treatment with phorbol esters and with the various PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest that the Gö6976-mediated post-transcriptional regulation of iNOS gene expression and NO production in microglia is not mediated through its reputed effects on PKC activity. Since the effects of various neurotoxins and certain neurodegenerative diseases may be manifested through alterations in the iNOS/NO system, post-transcriptional control of this system may represent a novel strategy for therapeutic intervention.

Animals↗
PubMed2000

The indolocarbazole Gö6976 protects neurons from lipopolysaccharide/interferon-gamma-induced cytotoxicity in murine neuron/glia co-cultures.

The expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) after exposure to endotoxins has been implicated in immune-mediated neurotoxicity. The indolocarbazole compound Gö6976, which has been described as a selective protein kinase C (PKC) inhibitor in vitro, rescued neurons from lipopolysaccharide/interferon-gamma (LPS/IFNgamma)- or interleukin-1alpha/tumor necrosis alpha/IFNgamma (IL-1alpha/TNFalpha/IFNgamma)-induced cytotoxicity in murine primary neuron-glia co-cultures. Other compounds known to inhibit PKC, Ro31-8220, GF109203X, Gö7874, H7, staurosporine and H89, failed to rescue neurons from the LPS/IFNgamma-induced cytotoxicity. These results suggest that the neuroprotection by Gö6976 from the LPS/IFNgamma-induced neuronal cell death is not mediated through its reputed effects on PKC activity. The neuroprotection paralleled the inhibition of iNOS gene expression and NO production. However, further analyses correlating NO production with the extent of neurotoxicity suggested that additional mechanism(s) besides the inhibition of the iNOS/NO system may be responsible for the neuroprotective effects of Gö6976. An understanding of the mechanism underlying the neuroprotective effect of Gö6976 may provide key insights into potential interventions for immune-mediated neurodegenerative diseases.

Animals↗
PubMed2000

Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia.

Cerebral inflammation often originates in a region where neuronal death occurs and thereafter slowly spreads outward. This study aimed to elucidate the roles of neurons in modulating the production of inflammatory factors stimulated by the bacterial endotoxin lipopolysaccharide (LPS). Culturing neurons with mixed glia reduced nitrite and tumor necrosis factor-alpha (TNF-alpha) production compared to cultures with only mixed glia, and shifted the dose-response curve to the right. The decreased nitrite and TNF-alpha production were not due to the cytotoxicity of LPS. Immunocytochemical analysis of glia-neuron co-cultures revealed the morphological changes in the activated microglia. Culturing PC12 cells with rat mixed-glia also reduced nitrite production. The influence of neurons on glial inflammation was partly due to the cell-cell contacts between neurons and glia via neural cell adhesion molecules (NCAM) because NCAM significantly reduced LPS-stimulated nitrite production. These results demonstrate that neurons reduce the production of inflammatory factors by glia. Since cerebral inflammation is important in many neurological disorders, this study might provide insight about the role of glia-neuron interactions in inflammatory responses in the brain.

Animals↗
PubMed2000

Expression of angiogenic factor thymidine phosphorylase and angiogenesis in human atherosclerosis.

In atherosclerosis, leukocyte migration into the plaque is thought to occur across the endothelium of the arterial lumen. However, intraplaque microvessels have been noted. While the significance of, and stimuli for these are uncertain, it seems possible that they may represent a second portal of entry for leukocytes into the plaque. This study performed a basic characterization of intraplaque microvessels and tested the hypothesis that the novel angiogenic factor thymidine phosphorylase (TP) is expressed in atherosclerosis. Immunocytochemistry was performed on aortic and coronary plaques and morphometry on coronary plaques. In plaques from both sites, macrophages, foam cells, and giant cells were immunoreactive for the angiogenic factors TP and vascular endothelial growth factor. Venule-like intraplaque microvessels expressed endothelial leukocyte adhesion molecules HLA-DR and ICAM-1, in contrast to the endothelium overlying the plaque. In coronary plaques, there was a correlation between severity of stenosis and plaque microvascular density. These results are consistent with a role for plaque macrophage/foam cell TP in stimulating plaque angiogenesis. While attention has focused on dysfunction of the endothelium overlying the plaque, microvascular endothelium may also represent a portal of entry for leukocytes into established plaques.

Aorta↗
PubMed2000

The caudal canal in children: a study using magnetic resonance imaging.

The anatomy of the caudal (sacral extradural) space was studied in 41 children, using magnetic resonance imaging. The distance from the upper margin of the sacrococcygeal membrane to the dural sac, the length of the membrane and the maximum depth of the caudal space were each measured. Age, height, weight and body surface area were recorded and, using multiple linear regression (stepwise technique), equations predicting the length of the membrane and the distance between its upper margin and the lower limit of the dural sac were obtained. Wide variability limits the clinical usefulness of these equations. In all patients, the maximum depth of the caudal space was found to be at the upper margin of the sacrococcygeal membrane. No correlation was found between this maximum depth and the age, height, weight or body surface area of the child.

Adolescent↗
PubMed2000

Text entry on handheld computers by older users.

Small pocket computers offer great potential in workplaces where mobility is needed to collect data or access reference information while carrying out tasks such as maintenance or customer support. This paper reports on three studies examining the hypothesis that data entry by older workers is easier when the pocket computer has a physical keyboard, albeit a small one, rather than a touch-screen keyboard. Using a counter-balanced, within-subjects design the accuracy and speed with which adults over 55 years of age could make or modify short text entries was measured for both kinds of pocket computer. The keyboard computer was the Hewlett Packard 360LX (HP), but the touch-screen computers varied across studies (experiment 1: Apple Newton and PalmPilot; experiment 2: Philips Nino; experiment 3: Casio E10). All studies showed significant decrements in accuracy and speed when entering text via the touch-screen. Across studies, most participants preferred using the HP's small physical keyboard. Even after additional practice with the touch screen (experiments 2 and 3) many entries still contained errors. Experiment 3 showed that younger people were faster but not more accurate than older people at using the touch-screen keyboard. It is concluded that satisfactory text entry on palm-size computers awaits improvements to the touch-screen keyboard or alternative input methods such as handwriting or voice. Interface developments that assist older people typically benefit younger users too.

Aged↗