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Biomedical subjects

A Thompson

Publications and source records attributed to A Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Characterization and localization of expression of an erythropoietin-induced gene, ERIC-1/TACC3, identified in erythroid precursor cells.

Gene expression profiles during erythropoietin (Epo)-induced differentiation of erythroid progenitor cells derived from the Friend virus anaemia (FVA) and phenylhydrazine (PHZ) murine models have been examined using differential display polymerase chain reaction (PCR). Ten cDNA fragments upregulated by Epo were isolated. The ribonuclease protection assay confirmed differential expression between Epo-stimulated and Epo-deprived cells for one of these, provisionally named ERIC-1. Sequencing of the full-length cDNA predicted a protein of 558 amino acids, 17 amino acids longer than mTACC3, the third member of a novel family of proteins that contain a coiled-coil domain. The human homologue, cloned using rapid amplification of cDNA ends (RACE)-PCR, encodes a larger protein of 838 amino acids that is identical to hTACC3. In addition to erythroid precursor cells, ERIC-1/TACC3 is expressed at high levels in the testes, at moderate levels in the thymus and peripheral leucocytes, and at lower levels in the spleen and intestinal tissue. Immunohistochemical analysis using an antibody to a GST fusion product of the C-terminus of hERIC-1/TACC3 revealed that it is localized to Sertoli cells in the human testes. Confocal microscopy demonstrated hERIC-1/TACC3 protein concentrated in the perinuclear vesicles of dermal microvascular endothelial cells. Although ERIC-1/TACC3 is expressed in a wide range of tissues, its upregulation by Epo in erythroid progenitors implies that it has a role in terminal erythropoiesis.

Amino Acid Sequence↗
PubMed2001

The use of renal scintigraphy in assessing the potential for recovery in the obstructed renal tract in children.

OBJECTIVE: To assess the value of renal scintigraphy with 99mTc-dimercaptosuccinic acid (DMSA) in predicting functional recovery after the surgical relief of obstructed kidneys in children. Patients and methods Forty-three children underwent surgery to relieve upper urinary tract obstruction; 37 had pelvi-ureteric junction obstruction and six had vesico-ureteric junction obstruction. The indication for surgery was a combination of an obstructed renogram with symptoms of either pain or pyelonephritis. Most children (41) had < 40% function on the affected side before surgery, with just two having hyperfunction (> 55%). In all patients intravenous urography before surgery showed hydronephrosis, and a micturating cystogram was used to exclude coexisting reflux in the presence of an associated megaureter. Diuretic renography (using 99mTc-mercaptoacetyl triglycine or 123I-hippuran) and DMSA scintigraphy were both carried out before surgery and the renography repeated 6 months afterward. RESULTS: The renographic drainage curves improved from obstructed to unobstructed or 'dilated unobstructed' on all postoperative studies. Regression analysis showed that preoperative DMSA scan was an excellent predictor of outcome (P < 0.001) whilst the preoperative renogram was a relatively poor predictor of the functional result. In four patients where the initial renographic function was < 10%, DMSA scintigraphy predicted correctly the capacity for recovery in three and the inability to improve in the fourth. Conclusion Before surgery, DMSA scintigraphy in children with upper urinary tract obstruction is a more useful estimate of probable long-term renal function than value from diuresis renography. If there is doubt about the desirability of reconstructive surgery, a DMSA scan may eliminate the need for more invasive methods of estimating recovery, e.g. a period of nephrostomy drainage.

Adolescent↗
PubMed2001

Spirituality and end-of-life care for an adolescent with AIDS.

AIDS is a life-threatening illness and, as is the case with all life-threatening illnesses, the spiritual beliefs of patients may influence their well being at the end of life. Patients' spiritual beliefs can offer comfort or be a source of distress. Health care professionals face ethical dilemmas, as they work with patients whose religious or spiritual idioms are incongruent with their own beliefs and traditions. The discussion in this case focuses on increasing health care professionals' sensitivity to the diverse spiritual needs of their patients. Guidelines are provided for assessment and interventions, as appropriate.

Acquired Immunodeficiency Syndrome↗
PubMed2001

The Multiple Sclerosis Impact Scale (MSIS-29): a new patient-based outcome measure.

Changes in health policy have underlined the importance of evidence-based clinical practice and rigorous evaluation of patient-based outcomes. As patient-based outcome measurement is particularly important in treatment trials of multiple sclerosis, a number of disease-specific instruments have been developed recently. One limitation of these instruments is that none was developed using the standard psychometric approach of reducing a large item pool generated from people with multiple sclerosis. Consequently, an outcome measure for clinical trials of multiple sclerosis that is disease specific and combines patient perspective with rigorous psychometric methods will complement existing instruments. The aim of this study was to develop such a measure. Standard psychometric methods were used. A pool of 129 questionnaire items was generated from interviews with 30 people with multiple sclerosis, expert opinion and literature review. The questionnaire was administered by postal survey to 1530 people selected randomly from the Multiple Sclerosis Society membership database. Redundant items and those with limited measurement properties were removed. The remaining items (n = 41) were grouped into scales using factor analysis, and then refined to form the Multiple Sclerosis Impact Scale (MSIS-29), an instrument measuring the physical (20 items) and psychological (nine items) impact of multiple sclerosis. Five psychometric properties of the MSIS-29 (data quality, scaling assumptions, acceptability, reliability and validity) were examined in a separate postal survey of 1250 Multiple Sclerosis Society members. A preliminary responsiveness study of the MSIS-29 was undertaken in 55 people admitted for rehabilitation and intravenous steroid treatment of relapses. The MSIS-29 satisfied all psychometric criteria. Data quality was excellent, missing data were low (maximum 3.9%), item test-re-test reliability was high (r = 0.65-0.90) and scale scores could be generated for >98% of respondents. Item descriptive statistics, item convergent and discriminant validity, and factor analysis indicated that it was legitimate to generate scores for MSIS-29 scales by summing items. MSIS-29 scales showed good variability, small floor and ceiling effects, high internal consistency (Cronbach's alpha <or=0.91) and high test-re-test reliability (intraclass correlation <or=0.87). Correlations with other measures and the analysis of group differences provided evidence that the MSIS-29 measures the physical and psychological impact of multiple sclerosis. Effect sizes (physical scale = 0.82, psychological scale = 0.66) demonstrated preliminary evidence of good responsiveness. These results indicate the MSIS-29 is a clinically useful and scientifically sound patient-based outcome measure of the impact of multiple sclerosis suitable for clinical trials and epidemiological studies.

Evidence-Based Medicine↗
PubMed2001

Location effects of a reporter gene on expression levels and on native protein synthesis in Lactococcus lactis and Saccharomyces cerevisiae.

The engineering of industrially important genetically modified organisms by the integration of heterologous genes into the chromosome is often the method of choice for several reasons concerned with long-term stability, homogeneous population distribution, and the enabling of selection without the addition of antibiotics. However, integration may disrupt endogenous gene expression, giving rise to increased levels of toxic metabolic byproducts or activating otherwise silent genes. The position of integration of a foreign gene in the chromosome can also influence its expression levels, and this effect will be of relevance in terms of optimizing protein production parameters. In this study, we determine how the random integration of a foreign reporter gene might affect expression levels and assess the use of proteome analysis to investigate possible effects on synthesis of endogenous proteins in two important food-relevant microorganisms, Saccharomyces cerevisiae and Lactococcus lactis. Eleven L. lactis integrants carrying the gusA gene were analyzed, and expression levels were found to vary by a factor of threefold in contrast to expression levels of lacZ in 18 S. cerevisiae integrants, which showed a 14-fold variation. Of relevance to industry is whether any changes in expression levels might occur as a consequence of storage of the modified strains. Here it is also shown that the above differences in expression levels were not significantly affected by storage of frozen cultures over a period of several months. Analysis of the protein composition of the yeast and lactococcal integrant strains by separation on one-dimensional (1D) and 2D gels showed no significant variations in position beyond those observed in control samples.

Bacterial Proteins↗
PubMed2001

The SF-36 in multiple sclerosis: why basic assumptions must be tested.

OBJECTIVES: To evaluate, in people with multiple sclerosis, two psychometric assumptions that must be satisfied for valid use of the medical outcomes study 36-item short form health survey (SF-36): the data are of high quality and, it is legitimate to generate scores for eight scales and two summary measures using the standard algorithms. METHODS: SF-36 data from 438 people representing the full range of multiple sclerosis were examined (mean age 48; 70% women). Data quality (per cent missing data and computable scale and summary scores) were determined, six scaling criteria were tested to determine the legitimacy of generating the eight SF-36 scale scores using Likert's method of summed ratings, and two scaling criteria were tested to determine the appropriateness of the standard SF-36 algorithms for weighting scale scores to generate two summary measures. RESULTS: Data quality was excellent except in the most disabled subgroup where missing responses reached a maximum of 16.5% and summary scores could only be computed for 72%. There was clear support for the generation of SF-36 scale scores. Item response distributions were symmetric, item mean scores and variances were equivalent, corrected item-total correlations were high (range 0.46-0.85) and similar, and definite scaling success rates exceeded 96%. Nevertheless, there were notable floor or ceiling effects in four of the eight scales. Assumptions for generating two SF-36 summary measures were only partially satisfied. Although principal components analysis suggested a two component model, these components explained less than 60% of the total variance in SF-36 scales, and less than 75% of the variance in five of the eight scales. Moreover, scale to component correlations did not support the use of scale weights derived from United States population data. CONCLUSIONS: When using the SF-36 as a health measure in multiple sclerosis summary scores should be reported with caution.

Activities of Daily Living↗
PubMed2001

Overexpression of cyclin D1 moderately increases ploidy in megakaryocytes.

BACKGROUND AND OBJECTIVES: Megakaryocytes undergo a unique cell cycle by which they replicate their complete genome many times in the absence of cytokinesis. In the search for regulators of the endomitotic cell cycle, we previously produced mice transgenic for cyclin D3 to identify this cyclin as able to enhance ploidy and to increase the number of differentiated cells in the megakaryocytic lineage. Of the D-type cyclins, cyclin D3 and to a much lesser extent cyclin D1, are present in megakaryocytes undergoing endomitosis and these cyclins are, respectively, markedly and moderately upregulated following exposure to the ploidy-promoting factor, Mpl-ligand. Our objective was to explore whether cyclin D1 can mimic the effect of cyclin D3 on ploidy in megakaryocytes. DESIGN AND METHODS: We generated transgenic mice overexpressing cyclin D1 in megakaryocytes and analyzed megakaryocyte ploidy, number and platelet levels in these mice and control mice. RESULTS: We show that transgenic mice in which cyclin D1 is overexpressed in megakaryocytes display higher ploidy level than the control mice, with no change in the number of differentiated cells of the megakaryocytic series, or in platelet level. INTERPRETATION AND CONCLUSIONS: Our models support a key role for D-type cyclins in the endomitotic cell cycle, and also indicate that although cyclin D3, from among the D cyclins, is unique in its high levels of expression in megakaryocytes, it is not unique in its ability to promote polyploidization.

Animals↗
PubMed2001

Primus (florasulam 50 G/L), a new triazolopyrimidine sulfonanilide herbicide to control broad-leaved weeds in maize when applied in early postemergence (1 to 6 leaf stage of maize). Preliminary results.

OBJECTIVE: PRIMUS was developed in maize in Belgium in 1999 and 2000 in the course of research into limiting or replacing the use of triazines in maize. One of the imperatives of this research was to find the lowest possible residue content (MRL). SELECTIVITY TEST: An application of florasulam, at the dose of 5 g of active substance (a.s.) at the 2 to 3 leaf stage of the maize was found to be selective on 132 (in 1999) and 126 (in 2000) varieties of maize. EFFICACY TEST: Florasulam was tested at doses of between 1 and 5 g a.s./hectare. The treatments were applied in early postemergence at the 3-5 leaf stage of the maize or in 2 separate applications: at the 1 leaf stage with a dose of 2 g a.s. florasulam at the 4 leaf stage with a dose of 2 g a.s. florasulam The herbicide was fully effective on the sensitive flora. A summary of the results is presented. A detailed weed spectrum is defined. PROGRAMMES: Herbicide programmes were developed on the basis of these findings. The results showed that the best partners for florasulam were triketones (sulcotrione and mesotrione) in very low doses. Sulcotrione was applied at doses of 75 to 150 g a.s./ha and mesotrione at 25 to 50 g a.s./ha. Triple mixes of florasulam + triketone + nicosulfuron in very low doses and 1 or 2 applications were also tested. The results were highly encouraging and this work should lead to practical recommendations. PHYTOTOXICITY: Phytotoxicity was observed on some occasions. The phytotoxicity results for the different figures seem, however, to depend more on the climate (difference between daytime and night-time temperatures just before and after the treatment) than on the products tested in the mixes. However, the florasulam + nicosulfuron (sulfonyl-urea antigrasses) may sometimes cause serious problems with selectivity. The phytotoxicity noted in the tests was usually short-lived (30 days). CONCLUSION: The results of the tests show that it is possible to consider replacing atrazine-based programmes with very low doses of modern herbicides applied at early stages of the maize. A mixture of active substances is vital. Repeated very low doses at the 1/2 and 4/5 leaf stages of the maize were found to be the most effective.

Cyclohexanones↗
PubMed2000

Double-helical dinuclear bis(dipyrromethene) complexes formed by self-assembly

Bis(dipyrromethene) ligands linked by an alkyl spacer between beta and beta' positions are shown to give helical dimers or monomers, dependent upon the length of the alkyl linker, upon complexation. Ligands consisting of methylene, ethylene, and propylene linkers -(CH(2))(n)()- (n = 1, 2, and 3) give helical dimers, while longer linking chains (n = 4, 5, or 6) give monomers or mixtures of dimers and monomers. X-ray crystal structures of the dimeric zinc complexes (n = 1, 2, and 3) reveal that the angles between dipyrromethene planes and the extent of helicity in the complexes differ as the length of the linker varies. The extent of helicity was assessed and found to be dependent upon the length and, specifically, the conformational preferences of the alkyl spacer unit. The presence of an ethylene linker gave complexes of greatest helicity. The use of a methylene spacer gave less helical structures upon complexation, while propylene spacers gave only slightly helical complexes. Our studies identify the crucial importance that the conformational preferences of the beta-beta' alkyl spacer group plays in the coordination algorithm of self-assembly to form dipyrromethene based complexes.

Journal Article↗
PubMed2000

X-ray crystallographic and (13)C NMR investigations of the effects of electron-withdrawing groups on a series of pyrroles

A series of pyrroles substituted with various electron-withdrawing groups (EWGs) on the N atom have been synthesized and full characterization including X-ray crystal structures obtained. Analysis of (13)C chemical shifts and X-ray crystal structures reveals that a trend between decreased aromaticity and the strength of the EWG exists. Experimental results regarding alternative mechanisms of nucleophilic substitution reactions can thus be rationalized.

Journal Article↗
PubMed2000

Amyloidogenicity and neurotoxicity of peptides corresponding to the helical regions of PrP(C).

An alpha-helical to beta-sheet conformational change in the prion protein, PrP(C), is believed to be causative in transmissible spongiform encephalopathies. Recent nuclear magnetic resonance structures of PrP(C) have identified three helical regions in the normal full-length protein. We have synthesised peptides corresponding to these helical regions (PrP144-154, helical region one; PrP178-193, helical region two; and PrP198-218, helical region three). Circular dichroism results show that the peptide corresponding to helical region one is unstructured, while peptides corresponding to the second and third helical regions have a high propensity to form beta-sheet structure in a pH-dependent manner in aqueous solutions. Peptides corresponding to the second helical region, PrP180-193 and PrP178-193, are the only ones that form amyloid by electron microscopy and congo red birefringence. PrP178-193 and the amyloidogenic Alzheimer's disease Abeta25-25 peptide were found to promote Cu (II)-induced lipid peroxidation and cytotoxicity in primary neuronal cultures, while PrP144-154, PrP198-218 and the nonamyloidogenic Abeta1-28 had no effect on Cu (II) toxicity. There was no increase in toxicity induced by PrP178-193 in cultures treated with Fe (II) or hydrogen peroxide, indicating a preferential modulatory effect on Cu (II) toxicity by PrP178-193. The data suggest that the PrP178-193 peptide has both structural and bioactive properties in common with Abeta25-35 and that the second putative helical region of PrP could be involved in modulation of Cu (II)-mediated toxicity in neurons during prion disease.

Amyloid beta-Peptides↗
PubMed2000

Cancer among people living in rural and remote Indigenous communities in Queensland.

OBJECTIVE: To describe the pattern of cancer among people living in rural and remote Indigenous communities in Queensland and to consider what implications the results have for cancer control. DESIGN AND SETTING: Descriptive analysis of data on incidence and mortality from the population-based Queensland Cancer Registry for the years 1982-1996. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates for different cancer sites. RESULTS: The pattern of cancer was different from that found in the Queensland population as a whole. Of all the cancer sites, cervical cancer showed the biggest difference: the age-standardised incidence was 4.7 times the State average (95% CI, 3.2-6.6) and the mortality rate was 13.4 times the State average (95% CI, 7.8-21.4). Rates of lung cancer and other smoking-related cancers, although not as high as those for cervical cancer, were also significantly higher than the Queensland average, while rates for prostate and colorectal cancer were significantly lower. CONCLUSION: The cancers that are over-represented among Indigenous people are amenable to preventive measures. The cancer burden among Indigenous people could be reduced by lowering the prevalence of smoking and improving participation in cervical cancer screening and follow-up of screening-detected abnormalities.

Adult↗
PubMed2000

Nuclear magnetic resonance studies of helical dipyrromethene-zinc complexes

[formula: see text] Analysis of helical chirality within dinuclear dipyrromethene-Zn(II) complexes has been achieved with the use of 1H NMR spectroscopy. The use of AgFOD and chiral lanthanide shift reagents gives fully resolved resonances attributable to two diastereomeric helical complexes.

Journal Article↗
PubMed2000

Ubiquitination of free cyclin D1 is independent of phosphorylation on threonine 286.

Cyclin D1 binds and regulates the activity of cyclin-dependent kinases (CDKs) 4 and 6. Phosphorylation of the retinoblastoma protein by cyclin D1.CDK4/6 complexes during the G(1) phase of the cell cycle promotes entry into S phase. Cyclin D1 protein is ubiquitinated and degraded by the 26 S proteasome. Previous studies have demonstrated that cyclin D1 ubiquitination is dependent on its phosphorylation by glycogen synthase kinase 3beta (GSK-3beta) on threonine 286 and that this phosphorylation event is greatly enhanced by binding to CDK4 (Diehl, J. A., Cheng, M. G., Roussel, M. F., and Sherr, C. J. (1998) Genes Dev. 12, 3499-3511). We now report an additional pathway for the ubiquitination of free cyclin D1 (unbound to CDKs). We show that, when unbound to CDK4, a cyclin D1-T286A mutant is ubiquitinated. Further, we show that a mutant of cyclin D1 that cannot bind to CDK4 (cyclin D1-KE) is also ubiquitinated in vivo. Our results demonstrate that free cyclin D1 is ubiquitinated independently of its phosphorylation on threonine 286 by GSK-3beta, suggesting that, as has been shown for cyclin E, distinct pathways of ubiquitination lead to the degradation of free and CDK-bound cyclin D1. The pathway responsible for ubiquitination of free cyclin D1 may be important in limiting the effects of cyclin D1 overexpression in a variety of cancers.

Animals↗
PubMed2000

Iloprost and cisaprost for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of the following agents:Prostaglandin analogues together with other agents proposed for the treatment of Raynaud's phenomenom (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: raynaud's or vasospasm, scleroderma or progressive systemic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing prostaglandin analogues versus placebo were eligible if they reported clinical outcomes within the start of therapy, and if the dropout rate was less than 35%. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios were calculated for all dichotomous outcomes and a weighted mean difference was calculated for all continuous outcomes. A fixed effects or random effects model was used if the data were homogeneous or heterogeneous, respectively. MAIN RESULTS: Seven randomized trials and 332 patients were included. Five of the seven trials were of parallel design. Five trials compared I.V. Iloprost and one trial studied p.o. Iloprost and another p.o. Cisaprost. Some trials were dose finding trials so various doses of Iloprost were used. Due to different efficacies of I.V. Iloprost, oral Iloprost and oral Cisaprost, the overall efficacy of these drugs was somewhat diluted. Intravenous Iloprost appears to be effective in the treatment of secondary Raynaud's phenomenon. REVIEWER'S CONCLUSIONS: Intravenous Iloprost is effective in the treatment of Raynaud's phenomenon secondary to scleroderma at decreasing the frequency and severity of attacks and preventing or healing digital ulcers. The effect seems to be prolonged after the intravenous infusion is given. Oral Iloprost may have less efficacy than intravenous Iloprost. However, Cisaprost has minimal or no efficacy when given orally for the treatment of Raynaud's phenomenon secondary to scleroderma.

Humans↗
PubMed2000

Ketanserin for Raynaud's phenomenon in progressive systemic sclerosis.

OBJECTIVES: To assess the effects and toxicity of the following agent: ketanserin versus placebo proposed for the treatment of Raynaud's phenomenon (RP) in scleroderma. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, and Medline up to 1996 using the Cochrane Collaboration search strategy developed by Dickersin et al.(1994). Key words included: Raynaud's or vasospasm, scleroderma or progressive systematic sclerosis or connective tissue disease or autoimmune disease. Current Contents were searched up to and including April 7, 1997. All bibliographies of articles retrieved were searched and key experts in the area were contacted for additional and unpublished data. The initial search strategy included all languages. SELECTION CRITERIA: All randomized controlled trials comparing ketanserin versus placebo were eligible if they reported clinical outcomes of interest. Trials with dropout rates greater than 35% were excluded. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two reviewers (DF, AT). Peto's odds ratios (OR) were calculated for all dichotomous outcomes, and a weighted mean difference (WMD) was carried out on all continuous outcomes. A fixed effects or random effects model were used if the data was homogeneous or heterogeneous, respectively. MAIN RESULTS: Three trials and 66 patients were included. The proportion improved was significantly better in the group on ketanserin with an odds ratio (OR) of 4.80 (95% CI 1.33, 17.37). However, when comparing ketanserin to placebo, the decrease in severity of RP attacks favoured placebo but this was not statistically significant. Side effects were significantly more common in the group using active treatment with an OR of 5.96 (95% CI 1.61, 22.06). Frequency of attacks did not change, but the duration of attacks decreased significantly in the ketanserin group. REVIEWER'S CONCLUSIONS: Ketanserin may have some efficacy in the treatment of Raynaud's phenomenon secondary to scleroderma. Overall, ketanserin is not significantly different from placebo for the treatment of Raynaud's phenomenon except for some decrease in the duration of attacks and more subjects improved on ketanserin compared to placebo. However, there were more side effects. It can be concluded that ketanserin treatment in Raynaud's phenomenon secondary to scleroderma is not clinically beneficial.

Humans↗