Believing in and recognising healthcare excellence.
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Attitude of Health Personnel↗
Biomedical subjects
S Jackson
Publications and source records attributed to S Jackson.
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↗
Understanding social policy in Europe.
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Aged↗
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↗
Incidence and remission of lower urinary tract symptoms. Authors should have used standardised questionnaire.
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England↗
Re: race and differences in breast cancer survival in a managed care population.
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Black or African American↗
Plasma and salivary IgG subclasses in HIV type 1 infection: evidence of both transudation and local synthesis of IgG in parotid saliva.
In this study we measured the levels of plasma and salivary IgG subclasses in 81 HIV-1-infected individuals and 30 uninfected controls. Salivary IgG1 was increased in HIV-1-infected patients, while salivary IgG2 and IgG4 were decreased. Patients with high levels of plasma anti-HIV-1 IgG antibodies presented a higher CD4+ cell count and lower viral load. High levels of anti-HIV-1 IgG antibodies in plasma were also associated with high levels of anti-HIV-1 IgG antibodies in parotid saliva. In comparing the HIV-1 recognition patterns of salivary IgG with plasma IgG, we determined that plasma and salivary IgG antibodies had similarities as well as differences in their reactivity to HIV-1 antigens. The present study demonstrates that HIV-1 infection affects both plasma and salivary IgG and provides evidence that the origin of HIV-1-specific IgG antibodies in parotid saliva is primarily transudated from plasma; however, some local synthesis of IgG in parotid saliva also occurs.
Adolescent↗
Identification of differential methylation of the WT1 antisense regulatory region and relaxation of imprinting in Wilms' tumor.
Wilms' tumor (WT) is associated with loss of heterozygosity at chromosome 11p13, the site of the Wilms' tumor suppressor gene, WT1. Although the preferential loss of maternal alleles suggested that differential allelic expression of WT1 might occur, this has not been evident in normal fetal tissues or WTs. In this study, we show that the WT1 antisense regulatory region is differentially methylated, with Southern blot analysis of four loss of heterozygosity-negative WTs and their corresponding normal kidneys indicating that allelic methylation is lost in WTs. Reverse transcription-PCR expression analysis correlates methylation with monoallelic expression of the antisense WT1 transcript (WT1-AS) in normal kidney. However, WTs display hypomethylation and biallelic expression of WT1-AS. Our findings are consistent with imprinting of WT1-AS in normal kidney and the relaxation of imprinting in Wilms' tumorigenesis. This identifies the WT1 antisense regulatory region in intron 1 as a primary site for epigenetic deregulation at chromosome 11p13 in WTs.
Alleles↗
False positivity of enzyme-linked immunosorbent assay for measurement of secretory IgA antibodies directed at HIV type 1 antigens.
We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encountered in Western blot. Binding did not appear to be mediated by salivary proteins known to bind to IgA, including secretory component, amylase, lactoferrin, lysozyme, galactosyl transferase, or secretory leukocyte protease inhibitor, and was not influenced by blocking reagents or by changes in secondary anti-IgA antibodies. Although these findings will not likely impact on the use of saliva as a diagnostic fluid for HIV-1 infection (the HIV-1 response in saliva is mostly of the IgG isotype), they indicate that assessments of this secretion as an indicator of IgA mucosal immune responses to HIV-1 vaccines should be undertaken with caution.
Animals↗
Expression and function of PPARgamma in rat and human vascular smooth muscle cells.
BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) is activated by fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZDs). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell (VSMC) proliferation and migration in vitro and in postinjury intimal hyperplasia. METHODS AND RESULTS: Rat and human VSMCs express mRNA and nuclear receptors for PPARgamma1. Three PPARgamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPARgamma is upregulated in rat neointima at 7 days and 14 days after balloon injury and is also present in early human atheroma and precursor lesions. CONCLUSIONS: Pharmacological activation of PPARgamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.
3T3 Cells↗
Blood donation by healthy individuals with haemochromatosis.
AIM: To determine how many individuals with haemochromatosis undergoing therapeutic venesections in our department might be eligible for blood donation. METHODS: Patients with genetic haemochromatosis were assessed with respect to complications of their disorder, the presence of other medical conditions and their suitability to be blood donors. RESULTS: Of 74 patients, 53 have been tested and shown to be homozygous for the Cys282Tyr mutation, and 30 of these (40%) fulfilled criteria for blood donation. This group is having 409 units of blood removed annually or 13-units per individual that is currently discarded. Of these 30 patients, all (100%) were keen to be blood donors. CONCLUSION: It is timely to review the policy regarding use of this wasted blood for transfusion.
Blood Banks↗
E6 proteins from diverse cutaneous HPV types inhibit apoptosis in response to UV damage.
In addition to their role in anogenital cancer, human papillomaviruses (HPVs) are also involved in the development of a range of cutaneous lesions. HPV types 5 and 8 are associated with the development of skin cancers in individuals with Epidermodysplasia verruciformis (EV). A broad spectrum of HPV types are also commonly found in non-melanoma skin cancers in immunocompromised individuals, such as organ transplant recipients. The skin cancers in EV and immunocompromised patients occur predominantly at body sites exposed to ultra violet (UV) radiation, pointing to a key role for UV in their development. Here we show that the E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV damage. This occurs in both p53 null and wild type cells and does not require p53 degradation.
Apoptosis↗