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Biomedical subjects

S Sharp

Publications and source records attributed to S Sharp.

At least 19 recordsLinked to original sources
PubMed2006

Accuracy of serum uric acid in predicting complications of pre-eclampsia: a systematic review.

BACKGROUND: Pre-eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre-eclampsia. OBJECTIVE: To determine the accuracy with which serum uric acid predicts maternal and fetal complications in women with pre-eclampsia. STUDY DESIGN: Systematic quantitative review of test accuracy studies. SEARCH STRATEGY: We conducted electronic searches in MEDLINE (1951-2004), EMBASE (1980-2004), the Cochrane Library (2004:4) and the MEDION database to identify relevant articles. A hand-search of selected specialist journals and reference lists of articles obtained was then carried out. There were no language restrictions for any of these searches. SELECTION CRITERIA: Two reviewers independently selected the articles in which the accuracy of serum uric acid was evaluated to predict maternal and fetal complications of pre-eclampsia. DATA COLLECTION AND ANALYSIS: Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standard. Summary likelihood ratios for positive (LR+) and negative LR(-) test results are generated for various threshold levels of uric acid. MAIN RESULTS: There were 18 primary articles that met the selection criteria, including a total of 3913 women and forty-one 2 x 2 tables. In women with pre-eclampsia, a positive test result of uric acid greater than or equal to a 350-micromol/l threshold predicted eclampsia with a pooled likelihood ratio (LR) of 2.1 (95% CI 1.4-3.5), while a negative test result had a pooled LR of 0.38 (95% CI 0.18-0.81). For severe hypertension as the outcome measure, the LRs were 1.7 (95% CI 1.3-2.2) and 0.49 (95% CI 0.38-0.64) for positive and negative test results, respectively, and for caesarean section the LRs were 2.4 (95% CI 1.3-4.7) and 0.39 (95% CI 0.20-0.76). For stillbirths and neonatal deaths the respective LRs were 1.5 (95% CI 0.91-2.6) and 0.51 (95% CI 0.20-1.3). For the prediction of small-for-gestational-age fetus, the pooled LRs were 1.3 (95% CI 1.1-1.7) and 0.60 (95% CI 0.43-0.83) for positive and negative results, respectively. AUTHOR'S CONCLUSION: Serum uric acid is a poor predictor of maternal and fetal complications in women with pre-eclampsia.

Biomarkers↗
PubMed2005

Determination of perchlorate in selected surface waters in the Great Lakes Basin by HPLC/MS/MS.

Surface water samples were collected from 55 sites in the Great Lakes Basin and analyzed for the presence of perchlorate using HPLC/MS/MS with an isotopically enriched internal standard. Sites included areas impacted by heavy industry, urbanization, agriculture and atmospheric deposition. Perchlorate was detected at several of the sites at concentrations close to the method detection limit (0.2 microg/l). Despite these low concentrations, its presence was confirmed by sample concentration and determination of the isotopic ratio of perchlorate. The presence of perchlorate at two of the sites was related to a fireworks display which had occurred prior to sampling. The other detections of perchlorate were in rivers/creeks draining watersheds which had high density livestock and crop farming activity. We suspect the two are related. To our knowledge, these are the first reported concentrations of perchlorate in Canadian surface waters.

Canada↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2004

Flux and instrumentation upgrade for the epithermal neutron beam facility at Washington State University.

An epithermal neutron beam facility for preclinical neutron capture therapy research has been constructed at the Washington State University TRIGA research reactor installation. Subsequent to a recent upgrade, this new facility offers a high-purity epithermal beam with intensity on the order of 1.2x10(9)n/cm(2)s. Key features include a fluoride-based design for the neutron filtering and moderating components as well as a novel collimator design that allows ease of assembly and disassembly of the beamline components.

Animals↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Bacterial Proteins↗
PubMed2002

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗
PubMed2001

Influence of culture system and medium enrichment on sulfotransferase and sulfatase expression in male rat hepatocyte cultures.

The expression of sulfotransferase and steroid sulfatase was studied in rat liver using the most promising culture models of hepatocytes, including monolayer culture with a pyruvate (30 mM) enriched medium, co-culture with rat epithelial cells from primitive biliary origin and collagengel sandwich culture. In the latter, addition of dexamethasone (1 microM) to the medium was examined. Phenol sulfotransferase enzymes (SULT1) were studied by measuring activities towards 4-methylphenol and estradiol, hydroxysteroid sulfotransferase (SULT2A) activity was determined towards dehydroepiandrosterone (DHEA). Microsomal steroid sulfatase activity was measured towards estrone sulfate. Western blot analysis was carried out using polyclonal antibodies raised against rat phenol sulfotransferase SULT1A1 (ASTIV), estrogen sulfotransferase SULT1E1 (EST) and hydroxysteroid sulfotransferase (HST). SULT2A activity towards DHEA was maintained at a high level during the whole culture time. In the co-culture it even reached the level of freshly isolated cells. Addition of pyruvate had no positive effect on the activity measured in monolayer cultures. High SULT1A1 activity towards 4-methylphenol was found in the co-culture system. In the monolayer culture, the activity initially decreased with 35% but was then kept at a constant level, while in the sandwich culture low activities were measured. For dexamethasone, an inducing effect on the various SULT activities could not be detected. Independently of the culture model used, the SULT1E1 activity towards estradiol decreased to 20% and 5% of the initial activity after four and seven days of culture, respectively. Microsomal steroid sulfatase activity was best maintained in collagengel sandwich cultures. During the first four days in culture it retained 73% of the initial activity, afterwards it decreased to 40% of the activity found in freshly isolated hepatocytes, irrespective of the culture conditions. High expectations exist for collagengel sandwich cultures, however, in our study the results were rather disappointing. Monolayer is a suitable culture model for short-term purposes. For long-term in vitro biotransformation studies, co-culture is preferred but is rather complex.

Albumins↗
PubMed2000

The BCSH guideline on addressograph labels: experience at a cardiothoracic unit and findings of a telephone survey.

In 1998 we implemented a BCSH recommendation that addressograph labels should not be used on blood transfusion specimen tubes. Over a 12-month period before the ban was introduced our laboratory received 5964 red cell transfusion requests, 182 (3.1%) of which contained an error in the identification details (ID) supplied on the request form and/or specimen. Three of these errors were of the 'wrong patient' type, i.e. the sample belonged to a different patient from the one whose ID appeared on the specimen tube and request form. Over the 12 months after the ban was introduced 511 (8. 1%) of 6326 requests contained a labelling error, an increase in error rate of 165%; no wrong-patient errors were identified, however. In a survey, seven (29.2%) of 24 transfusion laboratories in the UK accepted specimens labelled with addressograph stickers; in four of these cases a local blood transfusion committee had agreed that the BCSH guideline should not be followed. We believe the BCSH guideline is valid; its implementation, however, has major financial and workload implications, which probably explains why many hospitals apparently do not comply with it.

Blood Banks↗
PubMed1999

Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function.

The importance of estrogens in bone metabolism is illustrated by the accelerated bone loss and increase in osteoporotic fractures associated with postmenopausal estrogen deficiency. In this study, the expression and activity of the enzymes involved in estrogen metabolism in human osteoblastic cells were investigated in relation to differentiation of these cells. PCR reactions using mRNA from an in vitro differentiating human cell line (SV-HFO) were performed to assess mRNA expression of the enzymes aromatase, different subtypes of 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and steroid sulfatase. Aromatase, sulfatase, and 17beta-HSD type 2 and 4 were found to be expressed throughout differentiation. Expression of 17beta-HSD type 3, however, was relatively weak, except for early time points in differentiation. Type 1 17beta-HSD expression was not detected. Aromatase activity decreased during differentiation, as was demonstrated by the conversion of androstenedione (A) and testosterone (T) into estrone (E(1)) and estradiol (E(2)), respectively. The 17beta-HSD isozymes catalysing a reductive reaction convert androstenedione and estrone into testosterone and estradiol, respectively. Their activity declined with differentiation. Analysis of 17beta-HSD activity indicated both oxidative (E(2) to E(1); T to A) and reductive (E(1) to E(2); A to T) metabolism at all stages of osteoblast differentiation. Both activities declined as cells moved toward a differentiating mineralizing phenotype. However, the oxidative reaction was increasingly in favor of the reductive reaction at all times during differentiation. Sulfatase activity, as demonstrated by the conversion of estrone-sulfate into estrone, was constant during differentiation. In conclusion, we have demonstrated that all enzymes necessary for estrogen metabolism are expressed and biologically active in differentiating human osteoblasts. The activity of aromatase and 17beta-HSD was found to be dependent on the stage of cell differentiation. In addition, human osteoblasts effectively convert estradiol into estrone. The efficacy of osteoblasts to synthesize estradiol may determine the ultimate change in rate of bone turnover after menopause, as well as the development of osteoporosis. Moreover, the enzymes involved in the metabolism of estradiol may form a target for intervention.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Contrast agent neurotoxicity presenting as subarachnoid hemorrhage.

A patient developed signs, symptoms, and radiologic findings compatible with acute subarachnoid hemorrhage after receiving a large dose of heparin and intravascular contrast medium for coronary angiography and stent placement. Subsequent CT indicated the subarachnoid enhancement was due to contrast. Neurotoxicity from contrast agents is well-known, however this is an unusual report of toxicity mimicking subarachnoid hemorrhage clinically and radiologically.

Aged↗
PubMed1999

Randomised controlled trial of follow up care in general practice of patients with myocardial infarction and angina: final results of the Southampton heart integrated care project (SHIP). The SHIP Collaborative Group.

OBJECTIVE: To assess the effectiveness of a programme to coordinate and support follow up care in general practice after a hospital diagnosis of myocardial infarction or angina. DESIGN: Randomised controlled trial; stratified random allocation of practices to intervention and control groups. SETTING: All 67 practices in Southampton and south west Hampshire, England. SUBJECTS: 597 adult patients (422 with myocardial infarction and 175 with a new diagnosis of angina) who were recruited during hospital admission or attendance at a chest pain clinic between April 1995 and September 1996. INTERVENTION: Programme to coordinate preventive care led by specialist liaison nurses which sought to improve communication between hospital and general practice and to encourage general practice nurses to provide structured follow up. MAIN OUTCOME MEASURES: Serum total cholesterol concentration, blood pressure, distance walked in 6 minutes, confirmed smoking cessation, and body mass index measured at 1 year follow up. RESULTS: Of 559 surviving patients at 1 year, 502 (90%) were followed up. There was no significant difference between the intervention and control groups in smoking (cotinine validated quit rate 19% v 20%), lipid concentrations (serum total cholesterol 5.80 v 5.93 mmol/l), blood pressure (diastolic pressure 84 v 85 mm Hg), or fitness (distance walked in 6 minutes 443 v 433 m). Body mass index was slightly lower in the intervention group (27.4 v 28.2; P=0.08). CONCLUSIONS: Although the programme was effective in promoting follow up in general practice, it did not improve health outcome. Simply coordinating and supporting existing NHS care is insufficient. Ischaemic heart disease is a chronic condition which requires the same systematic approach to secondary prevention applied in other chronic conditions such as diabetes mellitus.

Angina Pectoris↗
PubMed1999

Kinetic properties of human dopamine sulfotransferase (SULT1A3) expressed in prokaryotic and eukaryotic systems: comparison with the recombinant enzyme purified from Escherichia coli.

Sulfation, catalyzed by members of the sulfotransferase enzyme family, is a major metabolic pathway which modulates the biological activity of numerous endogenous and xenobiotic chemicals. A number of these enzymes have been expressed in prokaryotic and eukaryotic systems to produce protein for biochemical and physical characterization. However, the effective use of heterologous expression systems to produce recombinant enzymes for such purposes depends upon the expressed protein faithfully representing the "native" protein. For human sulfotransferases, little attention has been paid to this despite the widespread use of recombinant enzymes. Here we have validated a number of heterologous expression systems for producing the human dopamine-metabolizing sulfotransferase SULT1A3, including Escherichia coli, Saccharomyces cerevisiae, COS-7, and V79 cells, by comparison of Km values of the recombinant enzyme in cell extracts with enzyme present in human platelets and with recombinant enzyme purified to homogeneity following E. coli expression. This is the first report of heterologous expression of a cytosolic sulfotransferase in yeast. Expression of SULT1A3 was achieved in all cell types, and the Km for dopamine under the conditions applied was approximately 1 microM in all heterologous systems studied, which compared favorably with the value determined with human platelets. We also determined the subunit and native molecular weights of the purified recombinant enzyme by SDS-PAGE, electrospray ionization mass spectrometry, dynamic light scattering, and sedimentation analysis. The enzyme purified following expression in E. coli existed as a homodimer with Mr approximately 68,000 as determined by light scattering and sedimentation analysis. Mass spectrometry revealed two species with experimentally determined masses of 34,272 and 34,348 which correspond to the native protein with either one or two 2-mercaptoethanol adducts. We conclude that the enzyme expressed in prokaryotic and eukaryotic heterologous systems, and also purified from E. coli, equates to that which is found in human tissue preparations.

Amino Acid Sequence↗
PubMed1998

Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases.

Sulfation and sulfate conjugate hydrolysis play an important role in metabolism, and are catalysed by members of the sulfotransferase and sulfatase enzyme super-families. In general, sulfation is a deactivating, detoxication pathway, but for some chemicals the sulfate conjugates are much more reactive than the parent compound. The range of compounds which are sulfated is enormous, yet we still understand relatively little of the function of this pathway. This review summarises current knowledge of the sulfation system and the enzymes involved, and illustrates how heterologous expression of sulfotransferases (SULTs) and sulfatases is aiding our appreciation of the properties of these important proteins. The role of sulfation in the bioactivation of procarcinogens and promutagens is discussed, and new data on the inhibition of the sulfotransferase(s) involved by common dietary components such as tea and coffee are presented. The genetic and environmental factors which are known to influence the activity and expression of human SULTs and sulfatases are also reviewed.

Amino Acid Sequence↗
PubMed1998

Microsomal steroid sulfatase: interactions with cytosolic steroid sulfotransferases.

Net sulfation of 4-methylumbelliferone in intact hepatocytes is regulated, in part, by substrate cycling between sulfotransferases (SULT) and arylsulfatases (ARS). Thus, ARS have the potential to influence rates of net sulfate conjugation of a variety of compounds in intact cells via interaction with SULT. Unlike ARSA and ARSB, which are lysosomal, steroid sulfate sulfatase (ARSC, also known as STS) is localized exclusively in the endoplasmic reticulum (ER). The present study was designed to assess the existence and extent of substrate cycling between steroids and their sulfate conjugates through ARSC and SULT, and also to initiate studies of the topology of the catalytic site of ARSC in the rat liver ER. Addition of rat liver microsomes to cytosol and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reduced rates of sulfation of dehydroepiandrosterone (DHEA) by SULT, and similarly hydrolysis of DHEA sulfate (DHEAS) was reduced when recombinant human hydroxysteroid SULT was added to rat liver microsomes in the presence of PAPS. There was no evidence for ARSC latency in the presence of detergent at either 4 or 37 degrees C, indicating that facilitated transport of steroid sulfates across the ER membrane may not be required for ARSC activity. The effect of proteases on ARSC activity in intact and disrupted microsomes was determined and compared with effects on components of the glucose-6-phosphatase system known to be localized on the lumenal and cytoplasmic surfaces of the ER. In contrast to the components of the glucose-6-phosphatase system, activity of ARSC in both intact and disrupted microsomes was substantially more resistant to protease inactivation. Our results indicate that substrate cycling of steroids and their sulfates does occur, and suggest that the active site of ARSC may be located within the ER membrane.

Animals↗