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S Leach

Publications and source records attributed to S Leach.

At least 19 recordsLinked to original sources
PubMed2002

Electronic poster presentations in BAPEN--a controlled evaluation.

INTRODUCTION: We sought to compare the quality of e-poster and traditional poster communications. METHODS: At the 2001 BAPEN congress, ten presenters were invited to supplement their poster by submitting its title and contents electronically. On projection, the submissions appeared as a poster. During chaired rounds, presenters 'talked to' the projection as if it were a traditional poster. They 'clicked' onto individual tables or figures to enlarge to full screen. A further 'click' returned the screen to poster format. Delegates attending two e-poster sessions, and a control group attending two simultaneous traditional poster rounds, responded to a questionnaire, on a scale 0--4, to statements which related: to the ability to (1) hear and (2) see well, (3) the posters'clarity and attractiveness, (4) whether the format of the session captured their interest and (5) encouraged discussion. Delegates also responded on how e-posters should be used in future meetings. Comparison was made using chi2 for trend. RESULTS: Questionnaires were returned from attendees at e-poster (27) and traditional (25) poster rounds. For all questions, the trend was in favour of e-posters with significant differences seen for 'seeing' (P= 0.009), 'interest capture' (P< 0.007) and 'encouragement of discussion' (P<0.05). Thirty-two vs one delegates thought that e-posters should be used in future, 28 vs 4 delegates thought that e-posters and traditional posters should be used together, but most(23 vs 8) thought that traditional posters should not be completely replaced. CONCLUSIONS: E-posters enable detailed search of a computer-based database of presentations, and viewing of the full content of all posters. Post-conference collaboration is enhanced by facilitating e-mail contact. E-posters should be used in tandem with traditional posters to improve the delivery of original communications.

Audiovisual Aids↗
PubMed2001

Transmission potential of smallpox in contemporary populations.

Despite eradication, smallpox still presents a risk to public health whilst laboratory stocks of virus remain. One factor crucial to any assessment of this risk is R0, the average number of secondary cases infected by each primary case. However, recently applied estimates have varied too widely (R0 from 1.5 to >20) to be of practical use, and often appear to disregard contingent factors such as socio-economic conditions and herd immunity. Here we use epidemic modelling to show a more consistent derivation of R0. In isolated pre-twentieth century populations with negligible herd immunity, the numbers of cases initially rose exponentially, with an R0 between 3.5 and 6. Before outbreak controls were applied, smallpox also demonstrated similar levels of transmission in 30 sporadic outbreaks in twentieth century Europe, taking into account pre-existing vaccination levels (about 50%) and the role of hospitals in doubling early transmission. Should smallpox recur, such estimates of transmission potential (R0 from 3.5 to 6) predict a reasonably rapid epidemic rise before the implementation of public health interventions, because little residual herd immunity exists now that vaccination has ceased.

Disease Outbreaks↗
PubMed2001

Molecular cloning of a third member of the potassium-dependent sodium-calcium exchanger gene family, NCKX3.

We describe here the identification and characterization of a novel member of the family of K(+)-dependent Na(+)/Ca(2+) exchangers, NCKX3 (gene SLC24A3). Human NCKX3 encodes a protein of 644 amino acids that displayed a high level of sequence identity to the other family members, rod NCKX1 and cone/neuronal NCKX2, in the hydrophobic regions surrounding the "alpha -repeat" sequences thought to form the ion-binding pocket for transport. Outside of these regions NCKX3 showed no significant identity to other known proteins. As anticipated from this sequence similarity, NCKX3 displayed K(+)-dependent Na(+)/Ca(2+) exchanger activity when assayed in heterologous expression systems, using digital imaging of fura-2 fluorescence, electrophysiology, or radioactive (45)Ca(2+) uptake. The N-terminal region of NCKX3, although not essential for expression, increased functional activity at least 10-fold and may represent a cleavable signal sequence. NCKX3 transcripts were most abundant in brain, with highest levels found in selected thalamic nuclei, in hippocampal CA1 neurons, and in layer IV of the cerebral cortex. Many other tissues also expressed NCKX3 at lower levels, especially aorta, uterus, and intestine, which are rich in smooth muscle. The discovery of NCKX3 thus expands the K(+)-dependent Na(+)/Ca(2+) exchanger family and suggests this class of transporter has a more widespread role in cellular Ca(2+) handling than previously appreciated.

Animals↗
PubMed2001

Neural activation during frequency-memory performance.

Lesion studies have demonstrated that frequency memory, or memory for the frequency of occurrence, is associated with prefrontal and not temporal lobe lesions. This study examined neural activation during performance on a frequency-memory-judgment task and a recognition-memory task, both using words. Relative to a control task, the authors observed peaks of activation during frequency-memory performance in the left ventrolateral prefrontal cortex (BA 45) and other areas typically associated with working memory (dorsolateral prefrontal cortex, posterior parietal cortex). Recognition performance was associated with activation in the same left ventrolateral prefrontal location as was observed with frequency memory. When comparing activation during frequency memory with activation during recognition memory, the authors found a suppression of activation in the hippocampus bilaterally during frequency memory. This study supports a neuroanatomical distinction between frequency and recognition memory.

Adult↗
PubMed2000

Reactions of e(-)(aq), CO(2)(*)(-), HO(*), O(2)(*)(-) and O(2)((1)delta(g)) with a dendro[60]fullerene and C(60)[C(COOH)(2)](n) (n = 2-6).

Using pulse radiolysis and laser flash photolysis, we have investigated the reactions of the deleterious species, e(-)(aq), HO&z.rad;, O(2)(*)(-) and O(2)((1)Delta(g)) with 10 water-soluble cyclopropyl-fused C(60) derivatives including a mono-adduct dendro[60]fullerene (d) and C(60) derivatives based on C(60)[C(COOH)(2)](n=2-6), some of which are known to be neuroprotective in vivo. The rate constants for reactions of e(-)(aq) and HO&z.rad; lie in the range 0.5-3.3 x 10(10) M(-1) s(-1). The d and bis-adduct monoanion radicals display sharp absorption peaks around 1000 nm (epsilon = 7 000-11 500 M(-1) cm(-1)); the anions of the tris-, tetra-, and penta-adduct derivatives have broader, weaker absorptions. The monohydroxylated radicals have their most intense absorption maxima around 390-440 nm (epsilon = 1000-3000 M(-1) cm(-1)). The anion and hydroxylated radical absorption spectra display a blue-shift as the number of addends increases. The radical anions react with oxygen (k approximately 10(7)-10(9) M(-1) s(-1)). The reaction of O(2)(*)(-) with the C(60) derivatives does not occur via an electron transfer. The rate constants for singlet oxygen reaction with the dendrofullerene and eee-derivative in D(2)O at pH 7.4 are k approximately 7 x 10(7) and approximately 2 x 10(7) M(-1) s(-1) respectively, in contrast to approximately 1.2 x 10(5) M(-1) s(-1) for the reaction with C(60) in C(6)D(6). The large acceleration of the rates for electron reduction and singlet oxygen reactions in water is due to a solvophobic process.

Carbon↗
PubMed2000

Verbal working memory and solvent exposure: a positron emission tomography study.

Neuropsychological studies have documented frontal dysfunction in patients with a history of exposure to organic solvents. The deficits typically observed in these patients appear to be related to working memory (WM). This study used [15O] water positron emission tomography (PET) to examine the pattern of neural activation during verbal working memory in patients with a history of exposure to solvents. Six individuals with solvent exposure were compared with 6 age- and education-matched controls. On the 2 WM tasks examined with PET, with equivalent task performance, participants with solvent exposure demonstrated frontal peaks that were atypical for the tasks, whereas the posterior peaks were typical for the tasks. The results support frontal dysfunction and compensatory use within anterior regions of the WM system in patients with solvent exposure.

Brain↗
PubMed2000

Localized reversible frameshift mutation in the flhA gene confers phase variability to flagellin gene expression in Campylobacter coli.

Phase variation of flagellin gene expression in Campylobacter coli UA585 was correlated with high-frequency, reversible insertion and deletion frameshift mutations in a short homopolymeric tract of thymine residues located in the N-terminal coding region of the flhA gene. Mutation-based phase variation in flhA may generate functional diversity in the host and environment.

Bacterial Proteins↗
PubMed2000

Alternatively spliced isoforms of the rat eye sodium/calcium+potassium exchanger NCKX1.

We have investigated the structure, function, and expression of the rat eye sodium/calcium+potassium exchanger NCKX1. The sequence of independent rat NCKX1 clones and the analysis of rat eye mRNA by RT-PCR revealed a region of alternative splicing that comprised four exons and encoded a stretch of 113 amino acids near the beginning of the large cytosolic loop. In comparison with other NCKX1 molecules and the rat NCKX2 protein, rat NCKX1 was highly conserved within the hydrophobic regions but was quite divergent in the two large hydrophilic loops. The only exception was the region of the cytosolic loop encoded by the second alternatively spliced exon, which was approximately 60% identical. Similar to bovine, but different from human, rat NCKX1 possessed an acidic motif that was repeated 14 times in the cytoplasmic loop. Analysis of NCKX1 expression in different rat tissues by Northern blot revealed a very high level of expression of a 7-kb transcript in the eye but also lower levels of transcripts of various lengths in other tissues. The recombinant rat NCKX1 protein was tagged in the extracellular loop with the FLAG epitope and expressed in HEK-293 cells. Surface delivery and potassium-dependent sodium/calcium exchange activity were observed for each spliced variant.

Alternative Splicing↗
PubMed2000

Neural activation during performance of number-letter sequencing.

Recent advances in neuroimaging have enabled researchers to establish relatively specific areas of the brain that are involved in working memory. In this positron emission tomography study we examined the pattern of neural activation associated with performance on number-letter sequencing, a purported measure of working memory included in the new Wechsler scales for memory and intelligence. After controlling for basic audition, verbalization, and attention, areas of activation were observed in the orbital frontal lobe, dorsolateral prefrontal cortex, and posterior parietal cortex. This is highly consistent with reports from the literature on activation patterns associated with working memory. More activation peaks were observed in the right hemisphere, suggesting the participants utilized visualization of the verbal information. Consistent with task conceptualization, this study provides support for number-letter sequencing as a task involving working memory.

Adult↗
PubMed1999

A role for the hepatobiliary system in IgE-mediated intestinal inflammation in the rat.

BACKGROUND: For many years the central focus of research into gastrointestinal hypersensitivity reactions has been the mast cell population of the intestinal lamina propria. Since bile is known to deliver immunological mediators to the gastrointestinal tract, the possibility arises that extra-intestinal populations of mast cells may also contribute to IgE-mediated intestinal damage. OBJECTIVES: To characterize hepatic mast cells in the rat and to investigate the role of the hepatobiliary system in a model of IgE-mediated reactivity to dietary antigen. METHODS: Wistar rats were passively sensitized with monoclonal antidinitrophenyl (DNP) IgE antibodies, and were later challenged orogastrically with DNP-HSA. Additional animals were sensitized, then bile duct-cannulated prior to antigen challenge. At various time points, liver and intestinal samples were collected for histological examination, and bile was collected and assayed for histamine and TNFalpha. RESULTS: Hepatic mast cells display a mucosal mast cell-like phenotype, and are closely associated with the vessels of the portal triads. Orogastric antigen challenge led to a rapid and significant decline (P<0.0001) in detectable mast cells as a result of anaphylactic degranulation. The median number of granulated mast cells associated with each portal triad in liver sections declined from six per portal triad to one per portal triad post-antigen challenge. After 15 min, biliary histamine concentrations rose above background levels (P<0.01). TNFalpha was also detectable in the majority (4/6) of bile samples within 15 min of challenge. Histological examination of the gastrointestinal mucosa revealed disruption to the villous epithelium ranging from oedematous changes to gross destruction. Such damage was not seen in animals in which bile had been externally drained. CONCLUSION: The data indicate that biliary products are major contributors to the gastrointestinal damage arising from IgE-mediated hypersensitivity reactions in the rat, and such hypersensitivity reactions may involve a population of mast cells which reside in the liver.

Animals↗
PubMed1999

Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer.

Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Analysis of coccal cell formation by Campylobacter jejuni using continuous culture techniques, and the importance of oxidative stress.

Campylobacter jejuni is an important human gastrointestinal pathogen. In hostile environments it may adapt its physiology to prolong survival, potentially including the adoption of a viable, non-culturable form and a change to coccal cell morphology. By independently controlling the individual parameters of continuous cultures of Camp. jejuni (e.g. pH, nutrient limitation, growth rate, etc.), coccal cell formation was shown to be elicited only be high oxygen tension in conjunction with reduced carbon concentration. Electron microscopy revealed degradative changes in these cells. This occurred as a transient response over 48 h coincident with a large reduction in maximum growth rate and viable count. Kinetic analysis of the biomass reduction of the cultures demonstrated that significant underlying growth was maintained, with the subsequent selection of a more oxygen-resistant population of cells and reversion to spiral morphology. Coccal cells appear to be predominantly a degenerate form of Camp. jejuni resulting from oxidative damage. While some of these coccal cells may recover, the more interesting population of cells is probably that which retains, or regains, spiral morphology during adaptation to oxidative stress.

Campylobacter jejuni↗
PubMed1998

Functional characterization of alternatively spliced human SERCA3 transcripts.

The sarcoplasmic (or endoplasmic) reticulum Ca2+-ATPase (SERCA)-3 has been implicated in the possible dysregulation of Ca2+ homeostasis that accompanies the pathology of hypertension and diabetes. We report the molecular cloning of two alternatively spliced transcripts from the human SERCA3 gene, ATP2A3, that encode proteins that differ at their carboxy termini by 36 amino acids. SERCA3 transcripts were most abundantly expressed in lymphoid tissues, intestine, pancreas, and prostate. The two human SERCA3 proteins encoded by alternatively spliced transcripts were recognized by the monoclonal antibody PL/IM430 and demonstrated Ca2+ uptake and ATPase activity with an apparent Ca2+ affinity 0.5 pCa unit lower than that of other SERCA gene products. The subcellular distribution of SERCA3 protein was indistinguishable from that of SERCA2b, with expression in the nuclear envelope and in the endoplasmic reticulum throughout the cell. Two variant SERCA3 constructs, huS3-I and huS3-II, were isolated that encode proteins with three amino acid differences: Ala-673 (in huS3-I) substituted for Thr (in huS3-II), Ile-817 substituted for Met, and an insertion of Glu-994. huS3-I displayed a 10-fold lower capacity to transport Ca2+ than huS3-II.

Alternative Splicing↗
PubMed1997

Changes with growth rate in the membrane lipid composition of and amino acid utilization by continuous cultures of Campylobacter jejuni.

Methods and media (defined and complex) are described which permit studies designed to determine the influence of single environmental factors on the survival and virulence of Campylobacter jejuni. The effect of growth rate on selected physiological traits (amino acid utilization, membrane lipid composition, motility, cell morphology) was studied in continuous culture. In both media, growth was at the expense of amino acid (serine, aspartate, glutamate and proline) catabolism. Slow growth in the complex medium shifted amino acid utilization from more (serine and aspartate) to less preferred substrates (glutamate, proline and possibly amino acids from the proteolysis of peptones). Low growth rates promoted the conversion of unsaturated 11-octadecenoic acid substituted phosphatidyl ethanolamines to corresponding 11-methylene substituted species, a feature correlated with stationary phase and exposure to environmental stress in other organisms. During continuous growth, cells lost motility although they still possessed flagella. Slow growth resulted in longer cells. Future studies will investigate the independent effects of nutrient stress and growth rate on the virulence and persistence of cells.

Acetates↗
PubMed1997

Degradation of Altosid XR briquets under field conditions in Minnesota.

Incomplete degradation of control products and subsequent carryover of active ingredient to the next year are operational concerns for control agencies. Altosid XR briquets were weighed before and after 6-18 months of exposure in temporary wetlands to determine the rate of physical degradation of the briquets. Degradation rate was influenced mainly by the number of days a briquet remained under water. The average briquet degraded to 19% of its weight within 150 days of immersion and was completely degraded after 1.5 yr under water. The active ingredient (methoprene) content of briquets declined faster among those exposed to air and more slowly among those that were immersed.

Biodegradation, Environmental↗
PubMed1996

Twenty-four hour urinary nitrate excretion in 48 populations from 30 countries: an ECP-INTERSALT collaborative study.

BACKGROUND: There is considerable interest in the possible role of nitrate in gastric carcinogenesis, but little information on nitrate intake around the world. This is the first study to give comprehensive standardised data on nitrate excretion as a marker of intake, using 48 worldwide population samples. METHODS: Urinary nitrate excretion has been shown to be a valid measure of nitrate intake in people under 50. This report presents data on 24-hour urinary nitrate excretion from urine collections obtained in the INTERSALT study, based on random samples of men and women aged 20-49 from each of 48 population samples in 30 countries. RESULTS: There was large variation in urinary nitrate excretion both within and between samples; within-sample (individual) distributions tended to be skewed towards higher values. Median values of the samples ranged from 0.42 mmol/day (Labrador, Canada) to 3.52 (Beijing, People's Republic of China) in men and 0.44 mmol/day (Colombia) to 3.44 (Beijing) in women. Overall, median values were higher in men than women by 11% on average (higher in men in 37 of 48 population samples). Comparison by geographical region of median values for men and women combined showed relatively low values in the samples in North America and Northern Europe (range 0.46-0.88 mmol/day), slightly higher values in Western Europe and Africa (0.68-1.11), and intermediate to high values in Southern Europe, Eastern and Central Europe and India (0.86-2.47). The highest median values were found in the Far Eastern samples (up to 3.48). Median values in the Central and South American samples ranged from 0.48 mmol/day (Colombia) to 1.37 (Xingu Indians of Brazil, and Argentina). CONCLUSIONS: For the first time, these data give standardized information on urinary nitrate excretion from different geographical regions of the world, and provide a basis for the further exploration of the role of nitrate in the aetiology of disease in human populations.

Adult↗
PubMed1993

Schizophrenia-associated chromosome 11q21 translocation: identification of flanking markers and development of chromosome 11q fragment hybrids as cloning and mapping resources.

Genetic linkage, molecular analysis, and in situ hybridization have identified TYR and D11S388 as markers flanking the chromosome 11 breakpoint in a large pedigree where a balanced translocation, t(1;11)(q43;q21), segregates with schizophrenia and related affective disorders. Somatic cell hybrids, separating the two translocation chromosomes from each other and from the normal homologues, have been produced with the aid of immunomagnetic sorting for chromosome 1- and chromosome 11-encoded cell-surface antigens. The genes for two of these antigens map on either side of the 11q breakpoint. Immunomagnetic bead sorting was also used to isolate two stable X-irradiation hybrids for each cell-surface antigen. Each hybrid carries only chromosome 11 fragments. Translocation and X-irradiation hybrids were analyzed, mainly by PCR, for the presence of 19 chromosome 11 and 4 chromosome 1 markers. Ten newly designed primers are reported. The X-irradiation hybrids were also studied cytogenetically, for human DNA content, by in situ Cot1 DNA hybridization and by painting the Alu-PCR products from these four lines back onto normal human metaphases. The generation of the translocation hybrids and of the chromosome 11q fragment hybrids is a necessary preliminary to determining whether a schizophrenia-predisposition gene SCZD2 is encoded at this site.

Animals↗