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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 307 records · Page 17Linked to original sources

A visuospatial "phonological loop" in working memory: evidence from American Sign Language.

In two experiments, the question of whether working memory could support an articulatory rehearsal loop in the visuospatial domain was investigated. Deaf subjects fluent in American Sign Language (ASL) were tested on immediate serial recall. In Experiment 1, with ASL stimuli, evidence was found for manual motoric coding (worse recall under articulatory suppression) and previous findings of ASL-based phonological coding (worse recall for phonologically similar lists) were replicated [corrected]. The two effects did not interact, suggesting separate components which both contribute to performance. Stimuli in Experiment 2 were namable pictures, which had to be recoded for ASL-based rehearsal to occur. Under these conditions, articulatory suppression eliminated the phonological similarity effect. Thus, an articulatory process seems to be used in translating pictures into a phonological code for memory maintenance. These results indicate a configuration of components similar to the phonological loop for speech, suggesting that working memory can develop a language-based rehearsal loop in the visuospatial modality.

Adolescent↗

MIST VR. A laparoscopic surgery procedures trainer and evaluator.

The key bimanual instrument tasks involved in laparoscopic surgery have been abstracted for use in a virtual reality surgical skills evaluator and trainer. The trainer uses two laparoscopic instruments mounted on a frame with position sensors which provide instrument movement data that is translated into interactive real time graphics on a PC (P133, 16 Mb RAM, graphics acceleration card). An accurately scaled operating volume of 10 cm3 is represented by a 3D cube on the computer screen. "Camera" position and size of target objects can be varied for different skill levels. Targets appear randomly within the operating volume according to the skill task and can be grasped and manipulated with the instruments. Accuracy and errors during the tasks and time to completion are logged. Mist VR has tutorial, training, examination, analysis and configuration modes. Six tasks have been selected and include combinations of instrument approach, target acquisition, target manipulation and placement, transfer between instruments, target contact with optional diathermy, and controlled instrument withdrawal/replacement. Tasks can be configured for varying degrees of difficulty and the configurations saved to a library for reuse. Specific task configurations can be assigned to individual students. In the examination mode the supervisor can select the tasks, repetitions and order and save to a specific file for that trainee. Progress can be assessed and there is the option for playback of the training session or examination. Data analyses permit overall, including task, and right or left hand performances to be quantified. Mist VR represents a significant advance over the subjective assessment of training performances with existing "plastic box" basic trainers.

Computer-Assisted Instruction↗

Extent of heterogeneity in mitochondrial DNA of European populations.

Variation in the mitochondrial DNA (mtDNA) control region as detected by sequence-specific oligonucleotide (SSO) probes is described for 595 individuals from six European or European-derived populations. Estimates of diversity for mtDNA types exceed 0.91 in all populations, while 50% of the 158 types which were observed occur only once. Of 68 shared types, most occur rarely (< 3% of the total population); only one type occurs at a frequency greater than 10%, and it is present at comparable frequencies in all six populations (18-29%). An analysis of molecular variance (AMOVA) incorporating genetic distances between types shows that 100% of the variation present in the total sample is attributable to within-population diversity, while there are essentially no between-population differences. Another AMOVA was performed for the first hypervariable region SSO sites only, which included this sample plus an additional 537 SSO types from mine more European populations that were inferred from published mtDNA control region sequence data. Similar results were obtained, with over 99% of the variation overall attributable to within-population differences, and less than 1% of the variation attributable to between-population differences. The Saami were the most different from other populations, which had been observed in an earlier study of nucleotide sequence data. Overall, there is no statistically significant heterogeneity for European populations (p > 0.001), and these groups are virtually indistinguishable with respect to mtDNA SSO types. These results demonstrate the utility of mtDNA typing for forensic investigations.

Analysis of Variance↗

Immunolocalisation of the prion protein (PrP) in the brains of sheep with scrapie.

Cheviot sheep from the Neuropathogenesis Unit flock were examined for PrP in brain sections using immunocytochemistry in order to aid scrapie diagnosis. Brains were collected from sheep which had been naturally or experimentally infected with scrapie and fixed in periodate-lysine-paraformaldehyde or in formalin. Immunolabelling was achieved using a monoclonal antibody (FH11) raised to the N-terminus of recombinant PrP protein. Several pre-treatments were studied in an effort to enhance PrP immunolabelling such as trypsin, formic acid and hydrated autoclaving. Trypsin was successful in highlighting PrP staining in formalin-fixed tissue. PrP staining was regularly observed in the dorsal vagus nucleus of the medulla oblongata and in the thalamus. Differences in the distribution and intensity of PrP immunostaining were apparent between the scrapie sources ME7 and SSBP/I.

Animals↗

Schistosomiasis in Lake Malawi.

BACKGROUND: In 1992 two US Peace Corps volunteers (PCVs) developed central nervous system schistosomiasis due to infection with Schistosoma haematobium following recreational water exposure at Cape Maclear on Lake Malawi, an African lake considered by many to be free of schistosomiasis. To determine the transmission potential and risk for aquiring schistosomiasis in Lake Malawi, a cross-sectional survey of resident expatriates and visitors to Malawi was done during March and April, 1993. METHODS: A volunteer cohort of expatriates and visitors representing a cross-section of Malawi's foregn population answered detailed questions about freshwater contact and provided blood specimens to determine the seroprevalence of S haematobium and S mansoni by ELISA and immunoblot analyses. A survey for vector snails was conducted along Lake Malawi's southwestern shore. FINDINGS: The study population of 955 included 305 US citizens and 650 non-US foreign nationals. 303 of the study population had serological evidence of current or past schistosome infection. Seroprevalence was 32% (141/440) among expatriates whose freshwater exposure was limited to Lake Malawi; S haematobium antibodies were found in 135 of 141 (96%) seropositive specimens. Risk of seropositivity increased with the number of freshwater exposures at Lake Malawi resorts. Although many resort areas in the southwestern lake region posed a significant risk, Cape Maclear was the location most strongly associated with seropositivity (OR 2.9, 95% Cl 1.6-5.1). Schistosome-infected Bulinus globosus, the snail vector of S haematobium in Malawi, were found at Cape Maclear and other locations along the lakeshore. INTERPRETATION: S haematobium infection is highly prevalent among expatriates and tourists in Malawi. Recreational water contact at popular resorts on Lake Malawi is the most likely source of infection. Transmission of schistosomiasis is occurring in Lake Malawi, a previously under-recognised site of transmission.

Adult↗

Age-dependent silencing of globin transgenes in the mouse.

Variegation of transgene expression, a heterocellular or mosaic pattern of expression seen in all mice in a given transgenic line, is a frequently observed but unexplained phenomenon. We have encountered variegation with globin transgenes; when lacZ expression is driven by globin control elements a proportion of erythrocytes express beta-galactosidase (beta-gal), while the remaining erythrocytes express none. The percentage of expressing cells is constant within each line (at any particular developmental stage), but varies between lines. Such variation may account for much of the line-to-line variability which has been reported in the expression of a transgene construct. We have now extended these observations by studying expression of several globin/lacZ transgenes with increasing age. Expression of beta-gal is variegated in all lines in adult mice, including those made with a beta-globin promoter and locus control region driving lacZ. The extent of variegation differs widely between lines, but in all lines there is a marked decline in the number of erythrocytes expressing beta-gal with increasing age. Progression of silencing continues long past the point at which globin switching is complete, suggesting that it is not related to this process. We observe that age-dependent silencing is most severe in high copy number animals. Increasing variegation of transgene expression with ageing of mice is likely to complicate interpretation of the developmental regulation of transgenes. We speculate that it reflects a general mechanism of epigenetic regulation.

Aging↗

Wortmannin-sensitive activation of p70s6k by endogenous and heterologously expressed Gi-coupled receptors.

In order to study the regulation of the ribosomal protein S6 kinase, p70s6k, by G protein-coupled receptors, Rat-1 fibroblasts were stably transfected with two versions of the alpha2 adrenergic receptor. Stimulation of clone 1C cells, which express 3.5 pmol/mg of protein of the human alpha2C10 receptor, with the alpha2 agonist UK 14304 led to a transient increase in p70s6k activity. UK 14304 also activated p70s6k in a clone expressing the porcine alpha2A receptor (400 fmol/mg of protein). Lysophosphatidic acid (LPA), acting through endogenous G protein-coupled receptors, also activated p70s6k in alpha2 receptor-transfected and in nontransfected cells. Activation of p70s6k by both UK 14304 and LPA was accompanied by increased phosphorylation of the protein. Rapamycin completely blocked the activation of p70s6k by both agents. Activation of p70s6k by UK 14304 and by LPA, but not by platelet-derived growth factor (PDGF), was blocked by preincubation of cells with pertussis toxin. Wortmannin, a selective inhibitor of phosphoinositide (PI) 3-OH kinase, prevented activation of p70s6k by UK 14304, LPA, and PDGF. These data indicate that p70s6k is regulatable by Gi-coupled receptor agonists in a pertussis toxin-sensitive fashion in Rat-1 fibroblasts and that activation of p70s6k by such agents appears to involve an isoform of PI 3-kinase.

Adrenergic alpha-Agonists↗

Surface-associated material from the bacterium Actinobacillus actinomycetemcomitans contains a peptide which, in contrast to lipopolysaccharide, directly stimulates fibroblast interleukin-6 gene transcription.

The oral commensal Gram-negative bacterium Actinobacillus actinomycetemcomitans is believed to be the causative organism of localized juvenile periodontitis, a disease in which there is rapid loss of alveolar bone supporting the teeth. Previously, we have reported that gentle saline extraction of this bacterium removed a loosely adherent proteinaceous fraction from the cell surface of the bacterium, which we have termed surface-associated material. This material contained potent bone-resorbing activity. We now report that surface-associated material is also a potent stimulator of cytokines, and in particular, interleukin-6 (IL-6) synthesis, while the lipopolysaccharide from this bacterium is only a weak stimulator of IL-6 synthesis by fibroblasts and monocytes. In contrast to enteric lipopolysaccharide (LPS), which induces fibroblast IL-1, IL-6 and tumour necrosis factor (TNF) alpha synthesis, surface-associated material stimulated gingival fibroblasts to synthesize only IL-6, with no induction of IL-1 or TNF (the normal inducers of IL-6 synthesis). Reverse transcriptase PCR also failed to detect mRNA for IL-1 or TNF in surface-associated-material-stimulated fibroblasts, although both mRNAs were present in Escherichia coli LPS-stimulated cells. Neutralizing antibodies to IL-1 and/or TNF or the natural IL-1 receptor antagonist (IL-1ra) inhibited enteric LPS-induced IL-6 synthesis, but did not inhibit surface-associated-material-induced synthesis. In addition, dexamethasone, which completely suppressed LPS-induced IL-6 synthesis, only inhibited surface-associated-material-induced IL-6 synthesis by 50%. This suggests that the active constituent in the surface-associated material stimulates IL-6 gene transcription by a transcriptional control mechanism distinct to that of E. coli LPS. The IL-6 stimulating activity of the surface-associated material is inhibited by both heat and trypsin, suggesting that it is proteinaceous. The activity has been isolated using anion-exchange, reverse-phase and size-exclusion HPLC. The active moiety is a peptide of molecular mass 2kDa which may be the product of a bacterial short open reading frame.

Aggregatibacter actinomycetemcomitans↗

In the black.

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Black or African American↗

Photodynamic effects of toluidine blue on human oral keratinocytes and fibroblasts and Streptococcus sanguis evaluated in vitro.

BACKGROUND AND OBJECTIVE: Some oral bacteria are susceptible to killing by red light after their sensitization with toluidine blue O (TBO). The photochemotherapy of periodontal disease in vivo would require a therapeutic window where bacteria could be killed without adjacent normal tissue damage. STUDY DESIGN/MATERIALS AND METHODS: The laser-induced effects of TBO on normal human gingival keratinocytes and fibroblasts have been studied in vitro. For the assessment of viability, the CellTiter 96TM AQueous Non-Radioactive Cell Proliferation Assay was used. RESULTS: TBO was cytotoxic at low concentrations (5.0 micrograms/ml). Sensitization of keratinocytes and fibroblasts with 2 and 5.0 micrograms/ml TBO, respectively, for 5 min and exposure to light from a 7.3 mW Helium/Neon (HeNe) laser for up to 2 min (0.876J) did not reduce cell viability. However, killing of Streptococcus sanguis was achieved following exposure to HeNe light for 75 sec (0.547J) in the presence of TBO at a concentration of 2.5 micrograms/ml. CONCLUSION: The development of a system for the lethal photosensitization of bacteria responsible for periodontal disease may be possible.

Dose-Response Relationship, Drug↗

Membrane exon sequences of the three Xenopus Ig classes explain the evolutionary origin of mammalian isotypes.

We have cloned and sequenced the genes corresponding to the membrane exons of the three immunoglobulin (Ig) heavy chain isotypes (mu, upsilon and chi) of Xenopus. Among membrane Ig (mIg) polypeptides, the transmembrane domain are the most highly conserved. The transmembrane and cytoplasmic domains of Xenopus mIgM are similar to the corresponding domains of all known vertebrate mIgM molecules, supporting the idea that amphibian mu gene is homologous, not just analogous, to the mu gene of higher vertebrates. The membrane forms of the two other Ig isotypes mIgX and mIgY exhibit the specific structure found in all Ig membrane exons, but are not homologous with any specific mammalian non-mu Ig isotype; they are most similar to Xenopus mIgM. Based on the conserved transmembrane domains of Xenopus mIgX, mIgY, we suggest that first the upsilon and later the chi genes arose by duplication from the original mu gene. The transmembrane and the 37-amino-acid-long cytoplasmic domains of Xenopus mIgY have conserved residues found in avian mIgY and mammalian mIgG and mIgE, suggesting that the modern isotypes might share a common ancestor with amphibian mIgY. However, while the sequence similarity between the membrane exons of avian mIgY and mammalian mIgG and IgE is striking, the overall similarity with Xenopus mIgY is very low. Thus, the genes giving rise to Xenopus mIgY and those eventually leading to avian mIgY and mammalian mIgG and mIgE must have diverged early in evolution, probably at the level of the primitive amphibians or before.

Amino Acid Sequence↗