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Biomedical subjects

S Jackson

Publications and source records attributed to S Jackson.

At least 55 records · Page 3Linked to original sources

Telephone support group intervention for persons with hemophilia and HIV/AIDS and family caregivers.

The purpose of this pilot project was to test the feasibility of a telephone support group intervention for persons with hemophilia and HIV/AIDS and for their family caregivers. Their support needs were unique because they did not identify with predominant groups of persons with AIDS and were geographically dispersed from peers. The 12 week intervention involved separate telephone support groups for hemophiliacs and for family caregivers. The two groups, comprised of a predetermined maximum of six people, were co-led by a professional and a peer. The support group for family caregivers involved six people and the group for men with hemophilia included five people, including one peer facilitator and one professional facilitator in each group. The telephone support group discussions were taped, transcribed, and analyzed for prevalent themes. The peer and professional facilitators maintained weekly field notes. All participants reported that the telephone groups had a positive impact on meeting their support needs. They believed that they had benefitted from sharing information and that the support groups had decreased their feelings of isolation and loneliness. Participants, however, contended that the intervention should be longer than 12 weeks.

Adaptation, Psychological↗

Impact of parental consent and notification policies on the decisions of adolescents to be tested for HIV.

Restrictions have been placed on the ability of adolescents to obtain human immunodeficiency virus (HIV) testing independent of their parents. Although some states have given adolescents the right to consent to HIV testing independently, many states have remained silent on the issue or have compromised these rights by providing for parental consent or notification when adolescents seek testing. This article examines existing policies and explores whether policies that require adolescents to obtain parental consent, or that permit or mandate parental notification, may deter them from obtaining needed HIV testing.

Abortion, Legal↗

Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression.

The transactivation/transformation-domain associated protein (TRRAP) belongs to the Ataxia-telangiectasia mutated (ATM) super-family and has been identified as a cofactor for c-MYC-mediated oncogenic transformation. TRRAP and its yeast homolog (Tra1p) are components of histone acetyltransferase (HAT) complexes, SAGA (refs. 2,4,5), PCAF (ref. 3) and NuA4 (ref. 6), which are important for the regulation of transcription and cell cycle progression and also have a role in cell viability. Yet the biological function of this molecule and how it controls proliferation are still unclear. Here we show that null mutation of Trrap in mice results in peri-implantation lethality due to a blocked proliferation of blastocysts. We use an inducible Cre-loxP system to show that loss of Trrap blocks cell proliferation because of aberrant mitotic exit accompanied by cytokinesis failure and endoreduplication. Trrap-deficient cells fail to sustain mitotic arrest despite chromosome missegregation and disrupted spindles, and display compromised cdk1 activity. Trrap is therefore essential for early development and required for the mitotic checkpoint and normal cell cycle progression.

Adaptor Proteins, Signal Transducing↗

A team education project: an evaluation of a collaborative education and practice development in a continuing care unit for older people.

The team education project aims to improve the impact of education on practice. The principles of this approach are that all clinical disciplines are involved and education activities are based in the practice area. This project took place in a continuing care unit for older people and the design was negotiated with staff in the unit. Bereavement was identified as the focus for the project. An education programme which combined information giving with reflective workshops was implemented and evaluated. Emerging findings reflect the complex nature of loss and bereavement in the continuing care unit. Staff adopted the term 'living bereavement ' to describe the reactions to the ongoing losses experienced by those living, working and visiting a continuing care unit. A core group of staff used the groups to reflect on practice and expand their understanding. Although the staff reported the groups were successful, it has been difficult to demonstrate any change in practice. A psychoanalytic approach to analyzing the organizational behaviour offered useful explanations relating to the difficulties in attempting change.

Aged↗

Genetic analysis of the Drosophila Gs(alpha) gene.

One of the best understood signal transduction pathways activated by receptors containing seven transmembrane domains involves activation of heterotrimeric G-protein complexes containing Gs(alpha), the subsequent stimulation of adenylyl cyclase, production of cAMP, activation of protein kinase A (PKA), and the phosphorylation of substrates that control a wide variety of cellular responses. Here, we report the identification of "loss-of-function" mutations in the Drosophila Gs(alpha) gene (dgs). Seven mutants have been identified that are either complemented by transgenes representing the wild-type dgs gene or contain nucleotide sequence changes resulting in the production of altered Gs(alpha) protein. Examination of mutant alleles representing loss-of-Gs(alpha) function indicates that the phenotypes generated do not mimic those created by mutational elimination of PKA. These results are consistent with the conclusion reached in previous studies that activation of PKA, at least in these developmental contexts, does not depend on receptor-mediated increases in intracellular cAMP, in contrast to the predictions of models developed primarily on the basis of studies in cultured cells.

Adenylyl Cyclases↗

Case-control study of the health of those looked after by local authorities.

AIMS: To assess the health needs and provision of health care to school age children in local authority care. METHODS: A total of 142 children aged 5 to 16 in local authority care, and 119 controls matched by age and sex were studied. Main outcome measures were routine health care, physical, emotional, and behavioural health, health threatening and antisocial behaviour, and health promotion. RESULTS: Compared with children at home, those looked after by local authorities were significantly more likely to: experience changes in general practitioner; have incomplete immunisations; receive inadequate dental care; suffer from anxieties and difficulties in interpersonal relationships; wet the bed; smoke; use illegal drugs; and have been cautioned by police or charged with a criminal offence. They also tend to receive less health education. They were significantly more likely to have had a recent hearing or eye sight test, and reported significantly less physical ill health overall. CONCLUSIONS: The overall health care of children who have been established in care for more than six months is significantly worse than for those living in their own homes, particularly with regard to emotional and behavioural health, and health promotion. In contrast to uncontrolled observational studies we have not found evidence of problems with the physical health of these children.

Adolescent↗

Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a ligand-activated nuclear receptor expressed in all of the major cell types found in atherosclerotic lesions: monocytes/macrophages, endothelial cells, and smooth muscle cells. In vitro, PPARgamma ligands inhibit cell proliferation and migration, 2 processes critical for vascular lesion formation. In contrast to these putative antiatherogenic activities, PPARgamma has been shown in vitro to upregulate the CD36 scavenger receptor, which could promote foam cell formation. Thus, it is unclear what impact PPARgamma activation will have on the development and progression of atherosclerosis. This issue is important because thiazolidinediones, which are ligands for PPARgamma, have recently been approved for the treatment of type 2 diabetes, a state of accelerated atherosclerosis. We report herein that the PPARgamma ligand, troglitazone, inhibited lesion formation in male low density lipoprotein receptor-deficient mice fed either a high-fat diet, which also induces type 2 diabetes, or a high-fructose diet. Troglitazone decreased the accumulation of macrophages in intimal xanthomas, consistent with our in vitro observation that troglitazone and another thiazolidinedione, rosiglitazone, inhibited monocyte chemoattractant protein-1-directed transendothelial migration of monocytes. Although troglitazone had some beneficial effects on metabolic risk factors (in particular, a reduction of insulin levels in the diabetic model), none of the systemic cardiovascular risk factors was consistently improved in either model. These observations suggest that the inhibition of early atherosclerotic lesion formation by troglitazone may result, at least in part, from direct effects of PPARgamma activation in the artery wall.

Animals↗

Retinoids inhibit proliferation of human coronary smooth muscle cells by modulating cell cycle regulators.

Retinoids inhibit rat vascular smooth muscle cell (VSMC) proliferation in vitro and intimal hyperplasia in vivo. We examined the mechanism of the antiproliferative effect of retinoids on human coronary artery smooth muscle cells (human CASMCs). The RAR ligands all-trans-retinoic acid (atRA) and ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-propenyl]-benzoic acid (TTNPB); a pan-RXR/RAR agonist, 9-cis-retinoic acid (9cRA); and the RXR-selective ligand AGN4204 all inhibited DNA synthesis stimulated with platelet-derived growth factor and insulin (IC(50): TTNPB 63 nmol/L, atRA 120 nmol/L, AGN4204 460 nmol/L, 9cRA 1.5 micromol/L). All retinoids blocked cell cycle progression as determined by flow cytometry and inhibited retinoblastoma protein (Rb) phosphorylation. TTNPB, atRA, and AGN4204 inhibited the mitogenic induction of cyclin D1, whereas 9cRA had no effect. None of the retinoids affected the expression of CDK 2, 4, or 6 or cyclin E. All retinoids attenuated mitogen-induced downregulation of CDKI p27(Kip1), a major negative regulator of Rb phosphorylation, partly through stabilizing p27(Kip1) turnover. These data demonstrate that retinoids have antiproliferative activity by modulating G(1) --> S cell cycle regulators in human CASMCs through inhibition of Rb phosphorylation and elevation of p27(Kip1) levels.

Cell Cycle Proteins↗

Rheumatoid nodule of the nasal septum.

Necrotizing granulomatous nodules are a common feature in patients with rheumatoid disease, affecting 20 per cent of seropositive patients. Although most commonly found subcutaneously at points of pressure, these nodules may occur in the connective tissues elsewhere in the body. In the upper aerodigestive tract, nodules have been described in diverse locations, but commonly in the trachea, larynx and the ear. We present the first reported case of a rheumatoid nodule affecting the nasal septum.

Aged↗

Management of the neck in N0 squamous cell carcinoma of the oral cavity.

Mortality in treated squamous cell carcinoma of the oral cavity is most often owing to locoregional failure. In an attempt to improve survival, an aggressive approach to surgical management is often favoured. Although it is generally accepted that the N0 neck should be treated if the risk of micrometastatic disease exceeds 20%, there is little direct support in the literature for this position. A retrospective review of all patients presenting with T1-2, N0 squamous cell carcinoma of the oral cavity treated at the Cancer Control Agency of British Columbia from 1985 to 1994 was conducted. Patients were followed for a minimum of 5 years with documentation of patterns of recurrence and disease-specific survival relative to initial management. The decision regarding management of the neck was frequently made to accommodate treatment of the primary site or reconstructive strategies. Thirteen percent of patients with T1, N0 disease underwent prophylactic neck dissection. No significant difference in outcome was noted in this group. Thirty-three percent of patients with T2, N0 disease underwent prophylactic neck dissection. There was a trend toward improved 5-year survival and lower recurrence rates in the group whose necks were treated, but the difference was not found to be statistically significant. In conclusion, this review showed a trend toward increased survival with prophylactic treatment of the neck in T2, N0 squamous cell carcinoma of the oral cavity, but a larger study would be needed to show a statistically significant benefit.

Aged↗

Control of vascular cell proliferation and migration by PPAR-gamma: a new approach to the macrovascular complications of diabetes.

Compared with nondiabetic subjects, type 2 diabetic individuals are at an increased risk for coronary artery disease and coronary restenosis after angioplasty or stenting. Increased proliferation and migration of vascular smooth muscle cells (VSMCs) contribute importantly to the formation of both atherosclerotic and restenotic lesions. Therefore, pharmaceutical interventions targeting proteins that regulate VSMC growth or movement are a promising new approach to treat diabetes-associated cardiovascular disease. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear receptor superfamily that, when activated by thiazolidinedione (TZD) insulin sensitizers, regulates a host of target genes. All of the major cells in the vasculature express PPAR-gamma, including endothelial cells, VSMCs, and monocytes/macrophages. PPAR-gamma is present in intimal macrophages and VSMCs in early human atheromas. In an animal model of vascular injury; PPAR-gamma levels are substantially elevated in the neointima that forms after mechanical injury of the endothelium. Recent experimental studies provide evidence that PPAR-gamma may function to protect the vasculature from injury. Cell culture studies have shown that TZD PPAR-gamma ligands inhibit both the proliferation and migration of VSMCs. These antiatherogenic activities of PPAR-gamma may also occur in vivo, because TZDs inhibit lesion formation in several animal models. PPAR-gamma ligands may also protect the vasculature indirectly by normalizing metabolic abnormalities of the diabetic milieu that increase cardiovascular risk. Activation of PPAR-gamma, newly defined in vascular cells, may be a useful approach to protect the vasculature in diabetes.

Blood Vessels↗

Changes in electromyogram during upper limb muscle contraction induced by resistive loaded breathing in humans.

Expiratory only resistive loaded breathing (RL) reduces high energy electromyogram (EMG) power (EH) during an isometric contraction of a leg extensor muscle, but not an arm flexor. An interaction between afferent activity during expiratory RL and inspiratory non-loaded phases of breathing, which the contraction spanned, could have accounted for the reduced EH in these long contractions. Therefore this study tested the hypothesis that brief arm extensor muscle contractions (70% of maximal force), performed during a single phase of expiratory RL, would also exhibit reduced EH. Surprisingly, EH in triceps, but not biceps brachii was reduced significantly when the contraction was performed during inspiratory RL rather than expiratory RL. The results suggest that either (a) short and prolonged contractions or (b) motor drive to arm and leg extensors are affected differently by RL.

Adult↗

Role of Bak in UV-induced apoptosis in skin cancer and abrogation by HPV E6 proteins.

Ultraviolet B (UVB) damage is recognized as the most important etiological factor in the development of skin cancer. Human papillomaviruses (HPV) have also been implicated in the disease, although the mechanism of action of these viruses remains unknown. We present evidence here that Bak protein is involved in signaling apoptosis in the skin in response to UVB damage, and that cutaneous HPV E6 proteins target and abrogate Bak function by promoting its proteolytic degradation both in vitro and in regenerated epithelium. Additionally, HPV positive skin cancers had undetectable levels of Bak in contrast to HPV negative cancers, which expressed Bak. This study supports a link between the virus and UVB in the induction of HPV-associated skin cancer and reveals a survival mechanism of virally infected cells.

Apoptosis↗