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Biomedical subjects

G Jackson

Publications and source records attributed to G Jackson.

At least 37 records · Page 2Linked to original sources

Identification of developmentally regulated genes in the somatic cells of the mouse testis using serial analysis of gene expression.

To identify genes developmentally regulated in the somatic cells of the testis, serial analysis of gene expression (SAGE) has been used to generate gene expression profiles from these cells in the fetal and adult mouse. To avoid germ cell transcripts, a fetal SAGE library was generated from germ cell-free fetal Wv/Wv mice, and an adult SAGE library was generated from adult testes depleted of germ cells with busulfan. The combined SAGE libraries contained 147570 tags identifying 12976 unique transcripts. Of these transcripts, 3607 were present in only the fetal library and 3941 were present in only the adult library. Most of the abundant differentially expressed tags in the adult testis library were from characterized genes, whereas 3' rapid amplification of complementary ends was required to identify most differentially expressed tags in the fetal library. These fetal tags were mostly associated with uncharacterized UniGene clusters. These data provide a comprehensive and quantitative analysis of gene expression in the somatic cells of the fetal and adult testis (including unknown transcripts) and identify genes differentially expressed in these cells during testis development. These differentially regulated genes are likely to provide insight into mechanisms regulating testis function both during development and in the adult animal.

Animals↗

Modelling oral malodour in a longitudinal study.

The aim of this study was to develop an in vitro model of the tongue microflora in order to assess anti-malodour compounds before clinical evaluation. Biofilms, derived from the tongue microflora, were grown in a constant depth film fermentor (CDFF) with nutrients supplied in the form of mucin- and serum-containing artificial saliva. Differential agars and a halimeter were used to determine the bacterial microflora and production of volatile sulphur compounds (VSCs), respectively. The resulting biofilms had a bacterial population which contained, on average, 29% streptococci, 48% Gram-negative anaerobes and 2.5% with an H2S-producing phenotype. When the biofilms were pulsed with either chlorhexidine or zinc acetate there was a reduction in the number of H2S-producing bacteria, however these counts subsequently recovered as pulsing continued. The generation of VSCs was correlated to the viable counts of the H2S-producing bacteria. By pulsing with anti-malodour compounds over time we observed a reduction in the quantity of VSCs produced and a change in the composition of the plaque to one which contained fewer H2S-producing bacteria.

Anti-Infective Agents, Local↗

Neisseria elongata endocarditis: case report and literature review.

We describe a case of infective endocarditis due to Neisseria elongata, and review the literature. N. elongata is a constituent of the normal oral flora and a rare cause of infective endocarditis. Unfamiliarity with the organism and its rod-shaped morphology may lead to a delay in microbiological diagnosis. Although the organism is relatively sensitive to antibiotics, our experience in the management of the described case and a review of previous reports suggest that antibiotic therapy alone may not be sufficient. It is likely that patients with N. elongata endocarditis will require surgery.

Anti-Bacterial Agents↗

Effects of elevated carbon dioxide concentration on growth and nitrogen fixation in Alnus glutinosa in a long-term field experiment.

Nitrogen-fixing plant species may respond more positively to elevated atmospheric carbon dioxide concentrations ([CO2]) than other species because of their ability to maintain a high internal nutrient supply. A key factor in the growth response of trees to elevated [CO2] is the availability of nitrogen, although how elevated [CO2] influences the rate of N2-fixation of nodulated trees growing under field conditions is unclear. To elucidate this relationship, we measured total biomass, relative growth rate, net assimilation rate (NAR), leaf area and net photosynthetic rate of N2-fixing Alnus glutinosa (L.) Gaertn. (common alder) trees grown for 3 years in open-top chambers in the presence of either ambient or elevated atmospheric [CO2] and two soil N regimes: full nutrient solution or no fertilizer. Nitrogen fixation by Frankia spp. in the root nodules of unfertilized trees was assessed by the acetylene reduction method. We hypothesized that unfertilized trees would show similar positive growth and physiological responses to elevated [CO2] as the fertilized trees. Growth in elevated [CO2] stimulated (relative) net photosynthesis and (absolute) total biomass accumulation. Relative total biomass increased, and leaf nitrogen remained stable, only during the first year of the experiment. Toward the end of the experiment, signs of photosynthetic acclimation occurred, i.e., down-regulation of the photosynthetic apparatus. Relative growth rate was not significantly affected by elevated [CO2] because although NAR was increased, the effect on relative growth rate was negated by a reduction in leaf area ratio. Neither leaf area nor leaf P concentration was affected by growth in elevated [CO2]. Nodule mass increased on roots of unfertilized trees exposed to elevated [CO2] compared with fertilized trees exposed to ambient [CO2]. There was also a biologically significant, although not statistically significant, stimulation of nitrogenase activity in nodules exposed to elevated [CO2]. Root nodules of trees exposed to elevated [CO2] were smaller and more evenly spaced than root nodules of trees exposed to ambient [CO2]. The lack of an interaction between nutrient and [CO2] effects on growth, biomass and photosynthesis indicates that the unfertilized trees maintained similar CO2-induced growth and photosynthetic enhancements as the fertilized trees. This implies that alder trees growing in natural conditions, which are often limited by soil N availability, should nevertheless benefit from increasing atmospheric [CO2].

Alnus↗

Biologic therapies for juvenile arthritis.

A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or block culpable molecules and so promote or inhibit cellular activity or proliferation. Of these agents, cytokine antagonists have shown greatest promise, and early clinical studies of tumour necrosis factor (TNF) blockade have identified dramatic clinical benefit in many children with JIA. However, as will also be discussed, overlap of pathways within a complex immune system makes clinical response unpredictable and raises additional ethical and administrative concerns.

Adolescent↗

Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator.

Erectile dysfunction (ED) is a common condition and studies predict that it will become even more common in the future. There is increasing evidence to suggest that it is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. The common pathological process is at the level of the endothelium, and cardiovascular risk factor control may be the key to preventing ED. Many men with established cardiovascular disease have ED. Specific guidelines for the management of ED in these patients have been produced by an expert panel. Cardiovascular risk stratification is an important initial step in managing such patients. In cardiac patients considered to have low cardiovascular risk, the management of ED can be safe and effective.

Blood Pressure↗

Adrenocorticotropic hormone directly stimulates testosterone production by the fetal and neonatal mouse testis.

Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in regulation of fetal Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor [melanocortin type 2 receptor (Mc2r)] was identified within this fetal-specific group. Subsequent real-time PCR studies confirmed that Mc2r was expressed in the fetal testis at 100-fold higher levels than in the adult testis. Incubation of fetal or neonatal testes with ACTH in vitro stimulated testosterone production more than 10-fold, although ACTH had no effect on testes from animals aged 20 d or older. The steroidogenic response of fetal and neonatal testes to a maximally stimulating dose of human chorionic gonadotropin was similar to the response shown to ACTH. The ED(50) for ACTH, measured in isolated fetal and neonatal testicular cells, was 5 x 10(-10) M and the lowest dose of ACTH eliciting a response was 2 x 10(-11) M. Circulating ACTH levels in fetal mice were around 8 x 10(-11) M. Neither alpha-MSH nor gamma-MSH had any effect on androgen production in vitro at any age. Fetal testosterone levels were normal in mice that lack circulating ACTH (proopiomelanocortin-null) indicating that ACTH is not essential for fetal Leydig cell function. Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation.

Adrenocorticotropic Hormone↗

Erectile dysfunction: cardiovascular risk and the role of the cardiologist.

Erectile dysfunction (ED) shares the same risk factors as coronary artery disease, so the level of occult cardiovascular risk in men with ED was assessed. A total of 174 men presenting with ED underwent cardiac risk stratification according to the Princeton Consensus Guidelines. Thirty per cent were stratified as intermediate/high cardiovascular risk and had ED treatment deferred until further cardiological assessment; 37% had abnormal lipid profiles; 24% had elevated HbA1C/glucose levels; 17% had uncontrolled hypertension; and 6% were suspected of having significant angina. ED is associated with a high incidence of occult cardiovascular disease. We suggest that cardiologists can significantly contribute to the management of ED.

Adult↗

Making PROGRESS in stable patients post stroke or transient ischaemic attack: implications for general practice.

Stroke is a major cause of morbidity and mortality. Those who survive have a one in six chance of a further stroke in the ensuing five years. The perindopril protection against recurrent stroke study (PROGRESS) is the first specific trial to address whether blood pressure lowering in hypertensive or non-hypertensive patients with a history of stroke or transient ischaemic attack (TIA) would reduce subsequent cerebrovascular and cardiovascular events. Results show that treatment based on perindopril significantly reduces stroke (28%), cardiovascular events (26%) and heart failure (26%). Stable patients post stroke should be considered for perindopril, and indapamide if possible, along with other evidence based risk reduction treatments (e.g. aspirin, statins). Therapy can be initiated and monitored either from hospital outpatients or general practice or both in co-operation.

Aged↗

Use of real-time PCR to measure Epstein-Barr virus genomes in whole blood.

The measurement of the Epstein-Barr viral load in peripheral blood has been recognised as an important way of monitoring the response to treatment in patients with Epstein-Barr virus (EBV)-related malignancies. In particular, EBV load in transplant recipients can be used as a predictive parameter for Post-transplant Lymphoproliferative Disorder (PTLD). The aim was to develop a rapid and reliable PCR protocol for the quantification of the cell-associated EBV genome. Real-time PCR using TaqMan methodology was established. This technique was applied to determine the EBV load in various study groups including healthy controls, transplant recipients, patients on haemodialysis, and patients with infectious mononucleosis. The baseline level of EBV genomes in the immunosuppressed renal transplant recipients was significantly different from that in the healthy controls.

DNA, Viral↗

Scedosporium apiospermum in chronic granulomatous disease treated with an HLA matched bone marrow transplant.

A patient with chronic granulomatous disease who was being treated with steroids was diagnosed with a soft tissue Scedosporium apiospermum infection. Despite extensive treatment with antifungals progression to involve solid tissue (bone) occurred. Treatment required an HLA matched bone marrow transplant, which led to complete clearance of the fungal infection, although the patient subsequently died.

Adolescent↗

The detection of apoptosis in a human in vitro skin explant assay for graft versus host reactions.

AIMS: Keratinocyte apoptosis is a major pathogenic mechanism in dermal complications, such as graft versus host disease (GVHD), after allogeneic bone marrow transplantation. However, the mechanisms by which recipient target cells undergo apoptosis in GVHD are still unclear, but may result from DNA damage caused by chemotherapeutic agents and/or by direct cytokine action. The basis of this investigation was to correlate keratinocyte apoptosis with (1) the severity of graft versus host reactions (GVHR) in vitro and (2) the clinical grade (0--III) of GVHD. METHODS: Skin sections generated from an in vitro skin explant model for detecting experimental or clinically relevant GVHR were investigated for the detection of apoptotic nuclei using the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) technique. This investigation also aimed to establish whether the TUNEL assay could be used as an additional, predictive method for the severity of GVHD before transplantation in potential patient/donor pairs given standard GVHD prophylaxis (cyclosporin A and methotrexate). RESULTS: By comparing mean values of apoptosis for each GVHR grade in a cohort of 83 retrospective skin sections it was shown that as the severity of GVHR increased there was a parallel increase in the percentage of apoptotic cells (p < 0.0001). However, the correlation between clinical GVHD grade II--III and overall keratinocyte apoptosis (> 2.6%) did not reach this degree of significance (chi(2): 4.2; degrees of freedom, 1; p = 0.04; Fisher's exact test: p = 0.06). CONCLUSIONS: The detection of apoptosis correlated with degree of GVHR using an in vitro assay and a higher degree of apoptosis tended to correlate with more severe GVHD. Further studies in a larger cohort of patients, using other methods to detect apoptosis in conjunction with the TUNEL assay, may give additional insight into the complex immunopathophysiology of GVHD.

Apoptosis↗

Factors associated with cardiac rehabilitation attendance: a systematic review of the literature.

BACKGROUND: Many eligible patients fail to attend cardiac rehabilitation courses. OBJECTIVE: To undertake a systematic literature review of studies that have investigated factors associated with cardiac rehabilitation attendance. METHODS: Literature published between 1978 and 2001 was searched using the MEDLINE, PSYCINFO and CINAHL computerized databases. Studies were sought that examined course attendance in eligible patient samples. Studies had to include at least one baseline predictor variable. RESULTS: Fifteen studies were identified and predictor variables were usually categorized as sociodemographic, medical and psychological. Nonattenders are more likely to be older, to have lower income/greater deprivation, to deny the severity of their illness; they are less likely to believe they can influence its outcome or to perceive that their physician recommends cardiac rehabilitation. Job status, gender and health concerns play an indirect role in attendance behaviour. Comparison of results between studies could be influenced by different case-mix, measurement instruments and country of origin. CONCLUSION: A number of factors predict cardiac rehabilitation attendance and some of these are potentially modifiable.

Adult↗

Sildenafil for primary pulmonary hypertension: short and long-term symptomatic benefit.

We report two cases of primary pulmonary hypertension (PPH) who benefited from oral sildenafil therapy. Both demonstrated a substantial improvement in exercise ability, which has been sustained at 3 and 6 months. Sildenafil acting as a phosphodiesterase 5 inhibitor may have an important role to play in the management of PPH and we believe further study to be of importance.

Administration, Oral↗

Viagra on the internet: unsafe sexual practice.

The vast majority of men who experience some form of erectile dysfunction (ED) do not seek medical advice, mainly due to embarrassment and social stigma. They often prefer to seek unorthodox and covert methods of treatment. Unprescribed medication for ED is dangerous because of the strong association between ED and coronary heart disease. Published guidelines already exist for the management of patients presenting with sexual dysfunction and cardiovascular risks. In this case report we highlight that ED itself is a risk factor for occult CHD and illustrate the need for careful medical assessment and adherence to published guidelines for the management of ED.

Adult↗

A systematic approach to erectile dysfunction in the cardiovascular patient: a Consensus Statement--update 2002.

Sexual activity is no more stressful to the heart when compared with a number of other natural daily activities, e.g. walking one mile on the level in 20 minutes. The cardiac risk of sexual activity in patients diagnosed with cardiovascular disease is minimal in properly assessed and advised patients. Erectile dysfunction (ED) is extremely common, affecting over half of men aged 40-70 years, and increases in frequency with age. ED and cardiovascular disease share many of the same risk factors and commonly coexist. ED in the otherwise asymptomatic man may be a marker for underlying coronary artery disease. ED in the diagnosed cardiovascular patient should be identified by routine questioning in general practice. Modern therapies can restore a sexual relationship in the majority of patients with ED and can lead to a substantial improvement in quality of life. The majority of patients assessed to be at low or intermediate cardiac risk, as defined later in this paper, can be effectively managed in primary care. Primary care treatment for ED in patients defined as high risk can be initiated following a specialist opinion and/or confirmation that the patient's cardiovascular condition is stabilised. There is no evidence that currently licensed treatments for ED add to the overall cardiovascular risk in patients with or without diagnosed cardiovascular disease. If one form of therapy is not effective, follow-up will identify the need for alternative approaches. The pro-active management of ED in the cardiovascular patient provides an ideal and effective opportunity to address other cardiovascular risk factors and improve treatment outcomes.

Activities of Daily Living↗