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Biomedical subjects

E Robertson

Publications and source records attributed to E Robertson.

At least 19 recordsLinked to original sources
PubMed2007

Structure and function of latency-associated nuclear antigen.

Latency-associated nuclear antigen (LANA) encoded by open reading frame 73 (ORF73) is the major latent protein expressed in all forms of KSHV-associated malignancies. LANA is a large (222-234 kDa) nuclear protein that interacts with various cellular as well as viral proteins. LANA has been classified as an oncogenic protein as it dysregulates various cellular pathways including tumor suppressor pathways associated with pRb and p53 and can transform primary rat embryo fibroblasts in cooperation with the cellular oncogene Hras. It associates with GSK-3beta, an important modulator of Wnt signaling pathway leading to the accumulation of cytoplasmic beta-catenin, which upregulates Tcf/Lef regulated genes after entering into the nucleus. LANA also blocks the expression of RTA, the reactivation transcriptional activator, which is critical for the latency to lytic switch, and thus helps in maintaining viral latency. LANA tethers the viral episomal DNA to the host chromosomes by directly binding to its cognate binding sequence within the TR region of the genome through its C terminus and to the nucleosomes through the N terminus of the molecule. Tethering to the host chromosomes helps in efficient partitioning of the viral episomes in the dividing cells. Disruptions of LANA expression led to reduction in the episomal copies of the viral DNA, supporting its role in persistence of the viral DNA. The functions known so far suggest that LANA is a key player in KSHV-mediated pathogenesis.

Animals↗
PubMed2004

Efficacy and tolerability of levetiracetam in patients with therapy-resistant epilepsy and learning disabilities.

INTRODUCTION: The purpose was to evaluate the effects of levetiracetam (LEV) in routine therapy in learning disabled patients with therapy-resistant epilepsy. METHODS: In an open observational add-on study design, 46 patients (residents of the Bethel Epilepsy Centre) with severe therapy-resistant epilepsy and different degrees of learning disabilities, who were treated with LEV between its introduction in Autumn 2000 and February 2002, were evaluated retrospectively. Information on monthly seizure frequencies, seizure severity and psychiatric status was extracted from the current patient case records. A 3 months baseline and a 3 months LEV treatment period (after 3 months of titration) were compared. Responders were defined as having a 50% reduction in seizure frequency and being evaluated as good or very good in an ad hoc global clinical efficacy scale. When only one criterion was positive, a careful individual decision was made based on the impact on the patients' daily activities. RESULTS: The responder rate was 41.3% (34.8 for 50% seizure reduction). It was higher in focal and multifocal epilepsy as compared to symptomatic generalised epilepsy/Lennox Gastaut Syndrome (P<0.05). Antiepileptic response occurred in doses between 500 and 4000 mg/day. Changes in seizure severity were rare. Nine patients experienced positive psychotropic effects (mostly improved vigilance and mood); six of these patients had antiepileptic effects as well. Twelve patients had adverse effects, mostly mild; in three cases, however, more severe effects led to discontinuation. CONCLUSIONS: LEV is an effective and generally well-tolerated drug for this patient group, especially in focal and multifocal epilepsy.

Adolescent↗
PubMed2003

No association between two polymorphisms at the 5HT2A gene and bipolar affective puerperal psychosis.

OBJECTIVE: To examine whether variation at two common polymorphisms, T102C and -1438AG, of the serotonin 2A gene (5HT2A) are involved in the puerperal triggering mechanism of bipolar affective puerperal psychosis. METHOD: A total of 242 parous women diagnosed with bipolar disorder were genotyped for the two polymorphisms. Of these, 165 women had experienced a manic or psychotic episode, according to DSM-IV criteria, within 6 weeks of childbirth (the puerperal psychosis group). The comparison group comprised of 77 parous women who had not experienced psychiatric disturbance following childbirth. RESULTS: No significant differences between genotype or allelic frequencies were found between the two groups for either polymorphism. CONCLUSION: The results indicate that variation at two common polymorphisms of the 5HT2A gene does not appear to play a major role in the development of bipolar affective puerperal psychosis.

Adult↗
PubMed2003

Impact of country of birth on hospital admission for women of childbearing age in Sweden: a five year follow up study.

STUDY OBJECTIVE: This study examines whether morbidity, defined as the first psychiatric hospital admission and the first somatic hospital admission, differs among subgroups of foreign born and second generation (that is, native born with at least one parent born abroad) women compared with Swedish born women (that is, with both parents native born) after adjusting for sociodemographic factors. DESIGN SETTING: In this follow up study the population consisted of 1 452 944 women, of whom 369 771 have an immigrant background (including second generation immigrants), aged 20-45 years. The population of 31 December 1993 was followed up to 31 December 1998. Differences in risk (hazard ratio) between different groups of immigrant women were estimated, adjusting for age, marital status, number of children, and disposable income. MAIN RESULTS: All four groups of foreign born women had higher age adjusted risks (HRs varied from 1.44 to 1.67) for a first psychiatric hospital admission than Swedish born women. The risk decreased only marginally when the sociodemographic factors were taken into consideration. Additionally, second generation women also had a higher age adjusted risk (HR = 1.42; CI = 1.37 to 1.48) than Swedish born women. The risk decreased only slightly in the main effect model. However, on analysing country of birth and first somatic hospital admissions, only non-European refugee women showed an increased age adjusted risk (HR = 1.26; CI = 1.24 to 1.29), which remained after adjusting for sociodemographic factors. CONCLUSIONS: Foreign born and second generation women of childbearing age had a higher risk than Swedish born women for a first psychiatric hospital admission. However, only non-European refugees were at higher risk of somatic hospital admissions.

Adult↗
PubMed2001

Molecular genetic approaches to puerperal psychosis.

Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of puerperal psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.

Bipolar Disorder↗
PubMed2000

Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1).

A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and puerperal psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of puerperal psychosis are manifestations of an affective disorder diathesis with a puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and puerperal psychosis at two known polymorphisms within the estrogen receptor alpha gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the puerperal trigger, but due to the small numbers of puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in puerperal psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850-853, 2000.

Adult↗
PubMed2000

Variation at the serotonin transporter gene influences susceptibility to bipolar affective puerperal psychosis.

Up to half of parous females with bipolar disorder (manic depression) develop an episode of severe psychiatric disturbance, usually called puerperal psychosis, within a few days of giving birth. We report significant evidence (p<0.003) that variation at the serotonin transporter gene exerts a substantial (odds ratio=4) and important (population attributable fraction=69%) influence on susceptibility to such episodes.

Adult↗
PubMed2000

A study of barriers to the engagement of significant others in adult addiction treatment.

Using the focus group methodology, this study identified personal and structural barriers to the engagement of significant others in an outpatient addictions treatment program. Twenty-eight significant others (family members, other kin, and friends) associated with 21 patients participated in one of three focus group sessions. The cut-and-paste technique was used to analyze the narrative data. Improving communication and reconnecting patients with a supportive community were forms of support identified. Patients' willingness to accept support and therapists' invitation to involve significant others in the treatment were identified as necessary precursors to their initial involvement. Providing educational and therapeutic support to significant others were endorsed as important elements in maintaining their involvement. Offering a diversity of therapeutic services beyond standard office hours, providing home visits and child care were viewed as facilitators for their involvement. It became apparent that support providers tended to resent having their own needs ignored. Feelings of isolation, fatalism, loneliness, ignorance, and fear were expressed by significant others. Theoretical and practical implications of the findings are discussed.

Adult↗
PubMed2000

Tumour necrosis factor alpha and bipolar affective puerperal psychosis.

The macrophage theory of depression proposes that an excessive secretion of monocyte/macrophage cytokines causes symptoms of depression. It has been suggested that changes in immune function that accompany pregnancy and childbirth could contribute to the affective symptoms suffered by many puerperal women. Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that has been implicated in inflammatory infections and immune diseases. Production of TNFalpha has been shown to be regulated by oestrogen, which suggests it as a potential candidate for susceptibility to post-partum mood disorders. Several polymorphisms have been identified in the TNFalpha gene. The -308 promoter polymorphism has been associated with elevated production of TNFalpha and has been found to influence the neurological outcome of various infections. In a case-control association study, we have examined the frequency of this polymorphism in groups of parous DSM-IV Bipolar females with (N = 116) and without (N = 56) puerperal psychosis, and a female non-psychiatric comparison group (N = 72). We provided no support for the hypothesis that this polymorphism influences susceptibility to bipolar disorder, or acts as a trigger for puerperal psychosis. However, variation at other polymorphisms within TNFalpha or in other oestrogen-regulated genes involved in immune function remain interesting candidates for study in post-partum mood disorders.

Adult↗
PubMed2000

Intracellular forms of human NOTCH1 functionally activate essential Epstein-Barr virus major latent promoters in the Burkitt's lymphoma BJAB cell line but repress these promoters in Jurkat cells.

We have demonstrated that intracellular forms of NOTCH1 transactivate two major Epstein-Barr virus (EBV) latent promoters, the LMP1 and Cp1 promoters in an EBV-negative B-cell line, BJAB. Truncated intracellular NOTCH1 associated with the nuclear membrane (DeltaE) transactivates the LMP1 promoter fivefold; however, the intranucleus localized form of NOTCH1 (ICN) transactivates this promoter approximately twofold in chloroamphenicol acetyltransferase (CAT) reporter assays in BJAB cells. Additionally, DeltaE activated the major Cp1 promoter 12-fold, whereas the ICN form of NOTCH1 activates at only about half that level when compared to that of DeltaE membrane-bound NOTCH1. This result differs from previously observed data, where intracellular NOTCH1 bound to the nuclear membrane, DeltaE, and nucleus-localized NOTCH1, ICN, all had similar levels of activation in 293 cells. This suggests distinct transcriptional activities in different cell types. Moreover, in Jurkat cells, a T-cell line, intranucleus localized NOTCH1 molecules demonstrated a repressive activity against the two EBV major latent promoters. Only DeltaE activated the Cp1 and LMP1 promoters at a level slightly above background, whereas intranucleus localized NOTCH1 ICN, or the form of NOTCH1 lacking the ankyrin repeats, DeltaE(TAR), surprisingly resulted in the repression of these promoters in Jurkat cells. Similarly, another truncated form of NOTCH1, referred to as ICNW, which contains the tryptophan residue W(1767) within one of the RBP-Jkappa interacting domains, repressed the LMP1 promoter approximately twofold. Further analysis of the truncated NOTCH1 molecules on the LMP1 promoter element, lacking the two RBP-Jkappa binding sites, suggests that repression in Jurkat cells may be affected by the presence of the two RBP-Jkappa binding sites. These studies indicate that intracellular NOTCH1 can activate the EBV major latent promoters in BJAB cells. However, in Jurkat cells, intracellular truncated forms of NOTCH1 lacking the RBP-Jkappa binding sites repress these EBV latent promoters. Only the membrane-bound form of NOTCH1, DeltaE, activated the EBV major latent promoters in Jurkat cells, albeit at a lower level than that seen in BJAB cells. Our data suggest that EBNA2 and truncated intracellular nuclear localized forms of NOTCH1 may be functionally similar in their interactions with RBP-Jkappa; however, these molecules may have distinctly different transcriptional partners in BJAB and Jurkat cells. Moreover, these truncated NOTCH1 molecules may not represent the normal processed forms of NOTCH1 in cells and may exhibit dominant negative phenotypes in the absence of the required posttranslational modifications. Further investigations are necessary to determine the similarity and differences occurring with intracellular NOTCH1 in other B- and T-cell lines.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Perceptions of care and services by the clients and families: a personal experience.

This study was initiated in response to a provincial mental health policy emphasizing the primacy of the person and the hospital's decision to adopt total quality management. The objective of the project was to learn more about how clients and families viewed the care and services received during a psychiatric admission. Their perceptions were elicited through seven focus groups including multiple admission (3) clients and families of single and multiple admission clients (2 each). Group sessions were tape-recorded, transcribed and analysed for themes. Three major themes were identified: quantity and quality of care, individuality and partnership. Both positive and negative comments were made within each of these themes, but two major areas for improvement were continuity of care and the environment. The findings are being used to change practices within the Department of Psychiatry.

Adult↗
PubMed1998

Patterns of drug use among nonmetropolitan and rural adults.

This article examines illegal drug use among adults living in nonmetropolitan and rural areas of the United States using data from the National Household Survey on Drug Abuse. Subjects were classified into three categories by residence: nonmetropolitan-urban, metropolitan-rural, and nonmetropolitan-rural. Respondents indicate about 10% of adults were current users of marijuana or other illegal drugs. Discriminant analysis was used to examine differences among groups of individuals classified as current users, past users, and nonusers. For both marijuana and other illegal drugs, the variables that accounted most for group differences were age, marital, status, employment status, occupation, and income. Only minor differences in drug use were exhibited across the three residential categories. It is recommended that future research on the rural and nonmetropolitan adult population incorporate both structural level measures of socioeconomic and demographic characteristics of localities, and individual level measures of peer influence, work stress, family factors, and psychosocial characteristics.

Adult↗
PubMed1996

Physiotherapy in knee osteoarthrosis: effect on pain and walking.

Patients with knee osteoarthrosis are often referred for physiotherapy and many different types of treatment are given. The value of many of these treatments has been questioned. This study was intended to evaluate the effect of commonly used physiotherapy treatments in a training programme on patients with medial knee osteoarthrosis, scheduled for surgery. The results from this study also provide useful data for further evaluation of different physiotherapy treatments to this patient group. Thirty-four patients were randomised to physiotherapy three times a week for 5 weeks and the other 34 received no treatment. The training programme is described in detail. The patients were evaluated by clinical examination, step test, gait analysis and isokinetic measurements of thigh muscle strength before and after treatment. The patients in the treatment group experienced a feeling of overall improvement in the knee and the ability to descend steps improved when compared to the control group. There were no significant differences in gait, range of motion or isokinetic measurements of muscle strength between the groups. We conclude that physiotherapy as given here made our patients feel better and their ability to descend stairs improved. These improvements are beneficial to the patients and support the positive effects of exercises and activity. Whilst the objective improvements were small, suggesting that this treatment may not be justified, patients in the treatment group believed that they were improved.

Aged↗