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S Bowman

Publications and source records attributed to S Bowman.

At least 19 recordsLinked to original sources
PubMed2003

Entering the post-genomic era of malaria research.

The sequencing of the genome of Plasmodium falciparum promises to revolutionize the way in which malaria research will be carried out. Beyond simple gene discovery, the genome sequence will facilitate the comprehensive determination of the parasite's gene expression during its developmental phases, pathology, and in response to environmental variables, such as drug treatment and host genetic background. This article reviews the current status of the P. falciparum genome sequencing project and the unique insights it has generated. We also summarize the application of bioinformatics and analytical tools that have been developed for functional genomics. The aim of these activities is the rational, information-based identification of new therapeutic strategies and targets, based on a thorough insight into the biology of Plasmodium spp.

Animals↗
PubMed2003

Association of damage with autoantibody profile, age, race, sex and disease duration in systemic lupus erythematosus.

OBJECTIVE: To determine if there is any association between autoantibody profile and damage in a cohort of patients with systemic lupus erythematosus (SLE). METHODS: A prospective cohort of SLE patients attending two SLE clinics in Birmingham was analysed. All patients fulfilled ARA criteria for SLE. Detailed clinical and serological information was recorded at each visit. Damage according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) was recorded 6-monthly and the last score in the year 2000 or prior to death was used in the analysis. Univariate analysis was performed with the chi(2) test, Fisher's exact test or univariate analysis of variance. Multivariate analysis was done with binary logistic regression. RESULTS: A total of 348 patients (326 females) were studied, comprising 208 Caucasians, 65 Afro-Caribbeans, 59 Asians, four Orientals and 12 others. There were 32 (9.2%) deaths and 156 (44.8%) patients had damage recorded during follow-up. The presence of damage showed no significant association with race, sex or anti-cardiolipin, anti-Ro, anti-La, anti-Sm, anti-RNP and anti-dsDNA antibodies. Only age, disease duration and other antibodies to extractable nuclear antigens (ENA) were found to be associated with the presence of damage. When individual organ damage was analysed, the only significant associations were of anti-Ro with ocular damage and of other anti-ENA antibodies (anti-Scl-70 and/or anti-Jo-1) with premature gonadal failure. Other autoantibodies were not predictive of damage in individual organs. CONCLUSIONS: Although autoantibodies are useful in diagnosis and predicting disease activity in SLE, they do not appear to be useful in predicting damage in SLE.

Adolescent↗
PubMed2003

Salivary gland expression of transforming growth factor beta isoforms in Sjogren's syndrome and benign lymphoepithelial lesions.

AIM: Transforming growth factor beta (TGF-beta) is involved in the control of autoimmune reactions, cell proliferation, and the accumulation of lymphocytes within organs. The aim of this study was to determine the expression of TGF-beta in salivary glands from patients with primary Sjogren's syndrome (SS) and benign lymphoepithelial lesions (BLEL) with emphasis on ductal epithelium. METHODS: Immunoperoxidase staining for TGF-beta isoforms and Ki67 antigen was performed on formalin fixed sections of labial glands from patients with primary SS (n = 15) and controls (n = 5) and parotid glands reported as BLEL (n = 5) or normal (n = 5). Ductal expression of TGF-beta was quantified by absorbance measurements using image analysis. The specificity of staining was confirmed by peptide blocking studies. RESULTS: All TGF-beta isoforms were detected within the cytoplasm of most lymphocytes, endothelial cells, and ducts in all specimens. Acinar expression was variable and weaker than that seen in ducts. Absorbance measurements revealed that the expression of all isoforms was greater in ducts within primary SS glands than in control glands. Ductal expression in control parotid glands was greater than that seen in BLEL glands, irrespective of the presence of adjacent lymphoid infiltrates. Comparisons between control specimens showed that ductal expression of all isoforms was highest in parotid glands, whereas no differences were detected between primary SS and BLEL glands. Ki67 positive lymphocytes and duct cells were mainly restricted to pathological specimens, with BLEL glands containing larger populations of positive cells than primary SS glands. CONCLUSION: These results demonstrate complex and variable changes in ductal expression of TGF-beta in primary SS and BLEL, which may be important in the control of lymphoid infiltration and the proliferation of lymphocytes and ductal epithelium.

Adolescent↗
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

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↗
PubMed2002

Macroradiography using conventional radiographic X-ray equipment.

Macroradiography is a radiographic imaging technique used to increase the size of the image relative to that of the object. Macroradiographic images suffer degradation due mainly to geometric unsharpness (U(g)). U(g) results from the finite size of the focal spot of the X-ray tube. Specialized equipment with a small effective focal spot size (Eff FSS) is generally used to perform macroradiography. The specialized nature of the equipment means macroradiographic examinations are not commonly undertaken. Macroradiographic examinations can also be performed on conventional radiographic equipment because the Eff FSS varies in the X-ray beam along the cathode-anode axis. Calculations and measurements of FSSs at different positions along the cathode-anode direction of the X-ray beam have been made. A simple technique of angling the X-ray tube 10 degrees towards the cathode reduces the Eff FSS in one dimension while still maintaining a vertical central ray. Reduced beam coverage results from this technique and an increase in radiographic exposure is required to compensate for the anode heel effect. Macroradiographic images of line pair phantoms and a hand-wrist phantom, at various tube angles, have been obtained to compare image detail.

Mathematics↗
PubMed2001

A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax.

The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600-1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.

Adult↗
PubMed2001

Gene discovery in Plasmodium chabaudi by genome survey sequencing.

The first genome survey sequencing of the rodent malaria parasite Plasmodium chabaudi is presented here. In 766 sequences, 131 putative gene sequences have been identified by sequence similarity database searches. Further, 7 potential gene families, four of which have not previously been described, were discovered. These genes may be important in understanding the biology of malaria, as well as offering potential new drug targets. We have also identified a number of candidate minisatellite sequences that could be helpful in genetic studies. Genome survey sequencing in P. chabaudi is a productive strategy in further developing this in vivo model of malaria, in the context of the malaria genome projects.

Amino Acid Sequence↗
PubMed2001

Assessment of the effect of fat-modified foods on diet quality in adults, 19 to 50 years, using data from the Continuing Survey of Food Intake by Individuals.

Fat-reduction strategies and the role of fat-modified foods in the US diet were assessed using a nationally representative survey: the 1996 US Department of Agriculture Continuing Survey of Food Intakes by Individuals. A sample of 878 men and 853 women was included. The sample was divided into low fat and high fat based on the Dietary Guideline's cutoff poin of 30% or less of energy from total fat. The survey sample was further stratified in nonusers, low-users or high-users of fat-modified foods. Approximately 10% of 7,000 foods were classified as fat-modified. There was a 400 to 500 kcal difference in energy intake of individuals consuming low-fat compared with high-fat diets. Adults who were users of fat-modified foods consumed more nutrient-dense diets, with higher intakes of vitamin A, folate, and iron. Not all fat-reduction strategies were equally effective in reducing fat and maintaining nutrient intake. Nonusers of fat-modified foods who consumed a low-fat diet tended to do so by substituting carbohydrate, in part from carbonated beverages, for fat. Both men and women consuming a low-fat diet had lower average BMIs; this difference between individuals consuming low-fat vs high-fat diets was significant for women who were high-users of fat-modified foods. The data suggest that a low-fat diet with high use of fat-modified foods may be one strategy for achieving adequate nutrient intake while maintaining weight in the desirable BMI range of 19 to 25.

Adolescent↗
PubMed2001

Academic models of clinical care for women: the National Centers of Excellence in Women's Health.

Between 1996 and 1999, 18 academic health centers were awarded the designation of National Center of Excellence (CoE) in Women's Health by the Office on Women's Health within the Department of Health and Human Services and were provided with seed monies to develop model clinical services for women. Although the model has evolved in various forms, core characteristics that each nationally designated CoE has adopted include comprehensive, women-friendly, women-focused, women-relevant, integrated, multidisciplinary care. The permanent success of these comprehensive clinical programs resides in the ability to garner support of leaders of the academic health centers who understand both the importance of multidisciplinary programs to the clinical care they provide women and the education they offer to the future providers of women's healthcare.

Academic Medical Centers↗
PubMed2000

Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter.

Bile salts are rapidly removed from the circulation by the liver-specific sodium/taurocholate cotransporter (SLC10A1). To understand factors controlling its liver-specific expression, we isolated human SLC10A1 from a YAC chromosomal clone. SLC10A1 spans approximately 23 kb distributed over five exons. The major transcription start site is at 299 bp, and a minor start site is at 395 bp from the translational start site. A 1.2-kb portion of the 5' flanking region was sequenced and shown to contain a number of liver-enriched elements, but no TATA box. Using secreted alkaline phosphatase reporter constructs liver-specific expression was examined. Transient transfection demonstrated that SLC10A1 promoter expression was selectively expressed eightfold in FAO and rat hepatocytes, while deletion mutants demonstrated liver-specific expression in a region extending from -5 to +198 bp, which contained putative sites for C/EBP and HNF3. Mutations of the C/EBP site resulted in loss of 77% of transcriptional activity. Cotransfection of C/EBP, but not other putative liver-enriched binding factors, increased SLC10A1 promoter activity. Electrophoretic mobility shift assays demonstrated specific protein-DNA interactions that involved C/EBPalpha and beta. These studies demonstrate that the TATA-less human SLC10A1 promoter exhibits liver-specific activity and its regulatory elements contain binding sites for C/EBP, which contributes specifically to its transcriptional regulation.

Amino Acid Sequence↗
PubMed2000

Assessing the impact of Plasmodium falciparum genome sequencing.

With the publication of the complete sequences for chromosomes 2 and 3 and the increasing availability of shotgun sequence covering most of its genome, Plasmodium falciparum biology is entering its post-genomic era. Analysis of the results generated to date has identified higher-order organisation of gene families involved in parasite pathology, provided information regarding the unique biology of this parasite and allowed the identification of potential chemotherapeutic drug targets. Continuing efforts to complete the P. falciparum genome and the availability of sequences from other protozoan parasites will facilitate a broader understanding of their biology, particularly with respect to their pathogenicity.

Animals↗
PubMed2000

Lupus patients with fatigue-is there a link with fibromyalgia syndrome?

OBJECTIVE: To determine whether fibromyalgia syndrome (FMS) was more common in patients with lupus who were complaining of fatigue. METHODS: We interviewed 216 patients attending two lupus clinics, all of whom fulfilled the revised American College of Rheumatology (ACR) criteria for lupus. The patients completed a questionnaire and were examined to determine the presence of fatigue and whether they fulfilled the ACR criteria for FMS. Disease activity was measured using the British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage score. Measurements of erythrocyte sedimentation rate, complement C3, lymphocyte count and DNA titre were also performed. RESULTS: Fifty per cent of our patients complained of fatigue, but only 10% of these patients fulfilled criteria for FMS. FMS did not correlate with any measure of disease activity although patients with FMS had lower mean DNA antibody titres and mean SLICC/ACR damage scores. CONCLUSION: A minority of lupus patients with fatigue fulfil the ACR criteria for FMS. Other possible factors leading to fatigue should be considered.

Adult↗
PubMed1999

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Animals↗
PubMed1999

Characterization of the mechanisms involved in the gender differences in hepatic taurocholate uptake.

Gender differences in the hepatic transport of organic anions is well established. Although uptake of many organic anions is greater in females, sodium-dependent taurocholate uptake is greater in hepatocytes from male rats. We examined the hypothesis that endogenous estrogens alter the number of sinusoidal bile acid transporters and/or decrease membrane lipid fluidity. The initial sodium-dependent uptake of [3H]taurocholate was 75% greater in hepatocytes from males than from either intact or oophorectomized females rats. Taurocholate maximal uptake was increased twofold (P < 0.03) without a significant change in the Michaelis-Menten constant. Sinusoidal membrane fractions were isolated from male and female rat livers with equal specific activities and enrichments of Na+-K+-ATPase. Males had a significant (P < 0.05) increase in cholesterol esters and phosphatidylethanolamine-to-phosphatidylcholine ratio. Fluorescence polarization indicated decreased lipid fluidity in females. In females, expression of the sodium-dependent taurocholate peptide (Ntcp) and mRNA were selectively decreased to 46 +/- 9 and 54 +/- 4% (P < 0.01), respectively, and the organic anion transporter peptide (Oatp) and Na+-K+-ATPase alpha-subunit were not significantly different. Nuclear run-on analysis indicated a 47% (P < 0.05) decrease in Ntcp transcription, without a significant change in Oatp. In conclusion, these studies demonstrated that decreased sodium-dependent bile salt uptake in female hepatocytes was due to decreased membrane lipid fluidity and a selective decrease in Ntcp.

Animals↗
PubMed1997

The nucleotide sequence of Saccharomyces cerevisiae chromosome IX.

Large-scale systematic sequencing has generally depended on the availability of an ordered library of large-insert bacterial or viral genomic clones for the organism under study. The generation of these large insert libraries, and the location of each clone on a genome map, is a laborious and time-consuming process. In an effort to overcome these problems, several groups have successfully demonstrated the viability of the whole-genome random 'shotgun' method in large-scale sequencing of both viruses and prokaryotes. Here we report the sequence of Saccharomyces cerevisiae chromosome IX, determined in part by a whole-chromosome 'shotgun', and describe the particular difficulties encountered in the random 'shotgun' sequencing of an entire eukaryotic chromosome. Analysis of this sequence shows that chromosome IX contains 221 open reading frames (ORFs), of which approximately 30% have been sequenced previously. This chromosome shows features typical of a small Saccharomyces cerevisiae chromosome.

Base Composition↗