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J O'Neill

Publications and source records attributed to J O'Neill.

At least 55 records · Page 3Linked to original sources
PubMed1999

Creating a hospital-community infrastructure: challenges and benefits.

With rising public expectations and demands for increased accountability, hospitals will be even more challenged by their local communities to implement strategies such as those developed at SMH to enable community participation that assists the hospital in serving its local population into the future. In response to unique health needs of its local community, SMH created an Inner City Health (ICH) Program in the early 1990s to provide comprehensive inpatient, ambulatory, and community outreach services. To build on its philosophy to reduce barriers to health for disadvantaged populations, the ICH Research Program, the only one of its kind in Canada, was also established. This paper will describe and explore the formalised infrastructure between SMH and the community; its evolution, as well as SMH's involvement with its community in context of the hospital's relationships with its Board of Directors, the Toronto teaching hospital system, media and advocacy groups. The role of ICH research in influencing evidence-based clinical practice, innovations in health science education and government policy will also be discussed as part of the SMH's hospital-community infrastructure.

Canada↗
PubMed1998

Effects of AF102B and tacrine on delayed match-to-sample in monkeys.

1. Object working memory, a function which declines in aging and dementia, was tested in young and aged pretrained monkeys using a delayed match-to-sample task. 2. During drug treatment, monkeys were given the m 1 muscarinic agonist AF102B (0.1-2.1 mg/kg i.m.), the cholinesterase inhibitor tacrine (0.5-2.0 mg/kg p.o.), or vehicle controls in a repeated measures design to assess putative cognitive enhancement. 3. Both agents improved task performance in both young and aged monkeys, AF102B yielding equivalent or greater, and less variable, improvement than tacrine. 4. AF102B may represent a low-toxicity alternative to tacrine for the treatment of age-related memory disorders.

Age Factors↗
PubMed1998

The effect of employment on quality of life and community integration after traumatic brain injury.

OBJECTIVES: To investigate the effect of employment on perceived quality of life (QOL), social integration, and home and leisure activities for individuals with traumatic brain injuries (TBIs). DESIGN: A number of demographic and injury-related variables (age at injury, time since injury, severity of injury, education, gender, preinjury household income, and marital status) were analyzed for their association first with employment and then with the QOL, social integration, and home and leisure activities. Any of these variables showing significant associations were then included along with level of employment in three final multivariate analyses of variance (MANOVAs), again predicting QOL, social integration, and home and leisure activities. SETTING: Urban, suburban, and rural New York state. PARTICIPANTS: 337 adults with TBI who resided in New York state and were between the ages of 18 and 65 years. MAIN OUTCOME MEASURES: The Craig Handicap Assessment Capacity Technique, the Bigelow Quality of Life Questionnaire, the Flanagan Scale of Needs (adapted), and a global QOL measure. RESULTS: Employment showed a strong and consistent relationship with perceived QOL, social integration within the community, and home and leisure activities. Part-time employment may have been superior to full-time employment for individuals with TBI: part-time workers had fewer unmet needs, were more socially integrated, and were more engaged in home activities than full-time workers. Loss of consciousness, as a measure of severity, was unexpectedly predictive of diminished sense of QOL for individuals with less severe injuries. CONCLUSIONS: Being employed contributes to one"s sense of well-being, social integration, and pursuit of leisure and home activities. Select advantages of working part-time for individuals with TBI were identified.

Adolescent↗
PubMed1998

Transcription factor Sp1 mediates cell-specific trans-activation of the human cytomegalovirus DNA polymerase gene promoter by immediate-early protein IE86 in glioblastoma U373MG cells.

Human cytomegalovirus (HCMV) gene expression is highly cell and tissue specific. Cell factor-mediated regulatory interactions are involved in regulating the restricted expression of the HCMV major immediate-early (IE) gene (J. F. Baskar, P. P. Smith, G. Nilaver, R. A. Jupp, S. Hoffmann, N. J. Peffer, D. J. Tenney, A. M. Colberg-Poley, P. Ghazal, and J. A. Nelson, 70:3207-3213, 1996). To gain an understanding of HCMV early gene activation, we studied the effect of each of the three major IE proteins, IE72, IE86, and IE55, on the HCMV DNA polymerase gene (pol; UL54) promoter. In transient-expression assays, the IE86 protein alone was able to transactivate the pol promoter, but IE72 and IE55 were not, in permissive U373MG cells. However, we were unable to detect IE86-mediated transactivation in nonpermissive HeLa or C33-A cells. Using electrophoretic mobility shift assays (EMSAs), we found that expression of the IE86 protein in U373MG cells resulted in specific binding of a DNA complex to an inverted-repeat element, IR1, of the pol promoter. Antibody supershifting and EMSA-Western blotting experiments further showed that IE86 and the cellular transcription factor Sp1 were components of the IR1 DNA-binding complex. Furthermore, we found that binding of DNA by Sp1 was dramatically increased in the presence of IE86. Interestingly, this IE86-induced DNA-binding activity of Sp1 was inhibited by a repressor activity presented in HeLa cells. In summary, our study suggests that a viral regulatory protein can modulate the DNA binding activity of a cellular transcription factor, resulting in cell-specific transactivation of viral genes.

Base Sequence↗
PubMed1997

Oncogene-dependent apoptosis in extracts from drug-resistant cells.

Many genotoxic agents kill tumor cells by inducing apoptosis; hence, mutations that suppress apoptosis produce resistance to chemotherapy. Although directly activating the apoptotic machinery may bypass these mutations, how to achieve this activation in cancer cells selectively is not clear. In this study, we show that the drug-resistant 293 cell line is unable to activate components of the apoptotic machinery-the ICE-like proteases (caspases)-following treatment with an anticancer drug. Remarkably, extracts from untreated cells spontaneously activate caspases and induce apoptosis in a cell-free system, indicating that drug-resistant cells have not only the apoptotic machinery but also its activator. Comparing extracts from cells with defined genetic differences, we show that this activator is generated by the adenovirus E1A oncogene and is absent from normal cells. We provide preliminary characterization of this oncogene generated activity (OGA) and show that partially purified OGA activates caspases when added to extracts from untransformed cells. We suggest that agents that link OGA to caspases in cells would kill tumor cells otherwise resistant to conventional cancer therapy. As this killing relies on an activity generated by an oncogene, the effect of these agents should be selective for transformed cells.

Adenosine Triphosphate↗
PubMed1997

Two-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p15 and 21q22.

Following a report of a linkage study that yielded evidence for a susceptibility locus for bipolar affective disorder on the long arm of chromosome 21, we studied 23 multiply affected pedigrees collected from Iceland and the UK, using the markers PFKL, D21S171, and D21S49. Counting only bipolar cases as affected, a two-point LOD of 1.28 was obtained using D21S171 (theta = 0.01, alpha = 0.35), with three Icelandic families producing LODs of 0.63, 0.62, and 1.74 (all at theta = 0.0). Affected sib pair analysis demonstrated increased allele sharing at D21S171 (P = 0.001) when unipolar cases were also considered affected. The same set of pedigrees had previously been typed for a tyrosine hydroxylase gene (TH) polymorphism at 11p15 and had shown some moderate evidence for linkage. When information from TH and the 21q markers was combined in a two-locus admixture analysis, an overall admixture LOD of 3.87 was obtained using the bipolar affection model. Thus the data are compatible with the hypothesis that a locus at or near TH influences susceptibility in some pedigrees, while a locus near D21S171 is active in others. Similar analyses in other datasets should be carried out to confirm or refute our tentative finding.

Bipolar Disorder↗
PubMed1997

The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

Animals↗
PubMed1997

Test of Xq26.3-28 linkage in bipolar and unipolar affective disorder in families selected for absence of male to male transmission.

BACKGROUND: There have been several reports of linkage between genetic markers on the X chromosome at Xq26.3-28 and bipolar affective disorder in family samples obtained from distinct ethnic and geographical origins. As part of a genome search in a series of 23 UK and Icelandic families, specifically selected for their large size and power to resolve the issue of linkage heterogeneity, we have tested the hypothesis that there is a locus for a genetic subtype of bipolar affective disorder which is linked to this region. METHOD: In families selected on the basis of absent male to male transmission for affective disorder, we performed two-point and FASTMAP multipoint linkage analyses with markers spanning the region between the genetic loci DXS102 and F8. RESULTS: We found negative lod scores for several models of affection status in families selected under stringent and relaxed criteria for the absence of male to male transmission. CONCLUSIONS: In the family sample we have obtained, our study provides no support for the presence of a locus increasing genetic susceptibility to bipolar affective disorder in this region of the X chromosome. It is likely that our finding reflects heterogeneity of linkage for bipolar and genetically related unipolar disorder that exists in specific ethnic populations. Alternatively the X-linked subtype of the disorder may have been present only in a few of our small families resulting in loss of power to detect the Xq26.3-28 linked subtype.

Genetic Linkage↗
PubMed1997

Sex of parent transmission effect in Tourette's syndrome: evidence for earlier age at onset in maternally transmitted cases suggests a genomic imprinting effect.

Parent of origin effects caused by genomic imprinting may influence the phenotypic expression of a number of heritable human disorders. To test this phenomenon in Tourette's syndrome (TS), we studied 437 first degree relatives systematically ascertained through 57 probands. We compared age at onset, age at diagnosis, and phenotypic expressions as observed in the diagnosis of TS, chronic motor tics, and obsessive compulsive behavior in the offspring of affected males with the offspring of affected females. Of the 437 subjects, 16.7% had matrilineal inheritance and 13.9% had patrilineal inheritance, as determined by family history methodology. Chi-square analysis of the different phenotypic expressions and sex of the transmitting parent failed to provide evidence of significant group differences. We found no significant differences in the age at diagnosis either. However, the maternally transmitted offspring showed a significantly earlier age at onset. This points to a parent of origin effect on the putative TS gene that could be explained by meiotic events or even intrauterine environmental influences. These findings may help explain the hitherto conflicting reports about the nature of genetic transmission in TS, and suggest a need to re-examine family data separately for maternally and paternally transmitted cases, taking into account the possible role of imprinting.

Age of Onset↗
PubMed1996

The Genome Sequence DataBase (GSDB): meeting the challenge of genomic sequencing.

The genome sequence database (GSDB) is a complete, publicly available relational database of DNA sequences and annotation maintained by the National Center for Genome Resources (NCGR) under a Cooperative Agreement with the US Department of Energy (DOE). GSDB provides direct, client- server access to the database for data contributions, community annotation and SQL queries. The GSDB Annotator, a multi-platform graphic user interface, is freely available. Automatically updated relational replicates of GSDB are also freely available.

Amino Acid Sequence↗
PubMed1996

Esophageal replacement using the colon: is it a good choice?

Thirty-eight children (2 months to 26 years of age) underwent esophageal replacement at our institution between 1962 and 1993. Twenty-four patients had esophageal atresia, with the replacement performed at a mean age of 17 months. The remaining patients (37%) had strictures and were older (mean, 7.4 years). Replacement procedures involved the right colon in 61% of cases and the transverse left colon in the others (39%). Sixty-three percent were placed substernally and 37% were done in transthoracic fashion. The average length of stay in the hospital was 34 days (range, 11 to 256 days.) Early complications (within 30 days) included cervical anastomotic leaks (11 patients; 29%) pneumonia (4), would infection (2), pneumothorax/hemothorax (3), wound dehiscence (1), prolonged ventilation (2), vocal cord paralysis (1), Horner's syndrome (1), pancreatitis (1), and perforated graft (1). Despite the incidence of early leaks, only two persisted long-term (more than 3 months). Other late complications included significant proximal strictures (5), and cologastric strictures developed in five patients. Seven cases were considered graft failures (18%), and all of these eventually require graft replacement. Additional problems included redundant graft requiring revision (4) and dumping syndrome (2). There were six cases of intestinal obstruction caused by adhesions. Four of these involved intrathoracic obstruction of the graft and two involved small bowel obstruction. There was only one death, which occurred late and was not related to the primary disease or procedure. Long-term follow-up data were available for 20 patients (53%). The follow-up period ranged from 1 to 33 years (mean, 12 years). Fourteen had excellent results after the initial interposition, being able to eat and function well without any further intervention. Seven patients (18%) have had poor results and 17 (45%) required additional procedures to obtain good functional results. In our experience, the colon continues to be a good option for esophageal replacement, but additional procedures frequently are necessary to optimize the functional outcome. Good results can be expected in the majority of cases, but late problems (ie, redundant colon and poor emptying) are not unusual, and careful follow-up is essential in the management of such patients.

Adolescent↗
PubMed1996

Hypertonic saline improves brain resuscitation in a pediatric model of head injury and hemorrhagic shock.

INTRODUCTION: Brain injury accompanied by hypovolemic shock is a frequent cause of death in multiply injured children. Hypertonic saline (HTS) has been shown to return hemodynamics to normal in adult models, without increasing intracranial pressure (ICP) as seen with crystalloids. To assess fluid resuscitation, the authors evaluated HTS versus lactated Ringer's solution (LR) with respect to hemodynamics and cerebrovascular hemoglobin oxygen saturation (Sco2) in anesthetized, head-injured, 1-month-old piglets. METHODS: Group 1 (n = 6) was studied for 3.5 hours after a cryogenic brain injury and no shock. Groups 2 and 3 had cryogenic brain injury followed by hemorrhagic shock, in which mean arterial pressure (MAP) was reduced to 40 to 50 mm Hg and maintained for 30 minutes. Group 2 (n = 5) was then resuscitated with 1 mL of 7.5% HTS per 1 mL of blood loss. Group 3 (n = 6) was resuscitated with 3 mL of LR per 1 mL of blood loss. Sco2 was determined by near-infrared spectroscopy in the injured region of the brain. All data were analyzed using analysis of variance with repeated measures. RESULTS: MAP, ICP, temperature, serum sodium, and cardiac output (CO) were similar in all groups during baseline and between groups 2 and 3 during shock. After resuscitation, MAP, CO, and core temperature were similar in all three groups, and serum sodium was increased in the HTS group (by 29%). Sco2 increased transiently after cryogenic injury in all groups, then gradually decreased to below baseline. After shock, Sco2 decreased precipitously in group 2 and 3. After resuscitation, Sco2 was different in the two resuscitation groups, increasing in the HTS group, above baseline values, but remaining below baseline values in the LR group (P < .002). ICP was lowered by HTS resuscitation and increased by LR resuscitation (P < .002) CONCLUSION: In our model of head injury and shock, resuscitation with either HTS or LR restored MAP and CO to control levels. However, during shock, the injured brain was severely deoxygenated, and administration of HTS restored cerebral oxygenation whereas LR did not, reflecting improved cerebral resuscitation by HTS without elevating ICP. The data suggest that HTS is a better resuscitation fluid than LR in head-injured children with hemorrhagic shock.

Animals↗
PubMed1996

Further tests for linkage of bipolar affective disorder to the tyrosine hydroxylase gene locus on chromosome 11p15 in a new series of multiplex British affective disorder pedigrees.

OBJECTIVE: This study was undertaken to confirm or refute previous reports that link bipolar affective disorder to polymorphic DNA markers at or near the gene for tyrosine hydroxylase. METHOD: A previous linkage analysis, which used a tetranucleotide repeat polymorphism at the tyrosine hydroxylase locus, of six Icelandic families was extended to include a new series of 17 multiply affected British families. RESULTS: Overall lod scores under the assumption of locus heterogeneity were between 1.20 and 1.40 at zero recombination with tyrosine hydroxylase, and these scores persisted across three affective disorder models. CONCLUSIONS: These results provide some support for linking affective disorder to this genetic region and suggest that additional linkage and association studies should be conducted to determine whether tyrosine hydroxylase or a nearby locus contributes to susceptibility to bipolar affective disorder in some families.

Alleles↗