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S Scott

Publications and source records attributed to S Scott.

At least 109 records · Page 6Linked to original sources
PubMed1998

Bacterial SOS checkpoint protein SulA inhibits polymerization of purified FtsZ cell division protein.

Cell division of Escherichia coli is inhibited when the SulA protein is induced in response to DNA damage as part of the SOS checkpoint control system. The SulA protein interacts with the tubulin-like FtsZ division protein. We investigated the effects of purified SulA upon FtsZ. SulA protein inhibits the polymerization and the GTPase activity of FtsZ, while point mutant SulA proteins show little effect on either of these FtsZ activities. SulA did not inhibit the polymerization of purified FtsZ2 mutant protein, which was originally isolated as insensitive to SulA. These studies define polymerization assays for FtsZ which respond to an authentic cellular regulator. The observations presented here support the notion that polymerization of FtsZ is central to its cellular role and that direct, reversible inhibition of FtsZ polymerization by SulA may account for division inhibition.

Bacterial Proteins↗
PubMed1998

Can the effects of exercise on bone quality be detected using the CUBA clinical ultrasound system?

OBJECTIVES: To determine whether the CUBA clinical quantitative ultrasound bone analyser was able to distinguish variations in bone quality between groups categorised according to activity level. METHOD: Eighty one white women aged 32 to 89 completed a confidential questionnaire on general health, diet, and exercise participation and underwent ultrasound testing at the right calcaneus utilising a CUBA clinical ultrasound system. RESULTS: The results confirmed the inverse relationship between age and the ultrasound indicators of bone quality: broadband ultrasound attenuation (BUA) (r = -0.52) and velocity of sound (VOS) (r = -0.68). Subject height weakly but significantly correlated with BUA (r = 0.39) and VOS (r = 0.35), and subject weight only correlated significantly with BUA (r = 0.37). Activity level was significantly associated (p < 0.05) with the changes in ultrasound attenuation (BUA). The use of hormone replacement therapy or the contraceptive pill, a family history of osteoporosis, and gross indicators of calcium consumption did not yield significant results. CONCLUSION: Data obtained from the CUBA clinical system were sensitive enough to allow women to be classified into groups according to activity level. These data were within the range of "normal" ultrasound data and hence it is suggested that the machine has research as well as clinical value.

Adult↗
PubMed1998

Insulin potentiates platelet-derived growth factor action in vascular smooth muscle cells.

Correlative studies have indicated that hyperinsulinemia is present in many individuals with atherosclerosis. Insulin resistance has also been linked to cardiovascular disease. It has proved to be difficult to decipher whether hyperinsulinemia or insulin resistance plays the most important role in the pathogenesis of atherosclerosis and coronary artery disease. In this study, we demonstrate that insulin increases the amount of farnesylated p21Ras in vascular smooth muscle cells (VSMC), thereby augmenting the pool of cellular Ras available for activation by platelet-derived growth factor (PDGF). In VSMC incubated with insulin for 24 h, PDGF's influence on GTP-loading of Ras was significantly increased. Furthermore, in cells preincubated with insulin, PDGF increased thymidine incorporation by 96% as compared with a 44% increase in control cells (a 2-fold increment). Similarly, preincubation of VSMC with insulin increased the ability of PDGF to stimulate gene expression of vascular endothelial growth factor 5- to 8-fold. The potentiating influence of insulin on PDGF action was abrogated in the presence of a farnesyltransferase inhibitor. Thus, the detrimental influence of hyperinsulinemia on the arterial wall may be related to the ability of insulin to augment farnesyltransferase activity and provide greater amounts of farnesylated p21Ras for stimulation by various growth promoting agents.

Animals↗
PubMed1998

A new triple stain for Helicobacter pylori suitable for the autostainer: carbol fuchsin/Alcian blue/hematoxylin-eosin.

OBJECTIVE: To develop an inexpensive stain to simultaneously visualize gastric morphology and Helicobacter pylori. METHODS: Gastric biopsies were stained with Genta stain using manual methods, and with carbol fuchsin/Alcian blue/hematoxylin-eosin using an automatic slide stainer (Sakura DRS-601). Slides were then coded and interpreted by 2 pathologists. Helicobacter pylori was scored using a visual scale (0 [none] to 5 [maximum]). RESULTS: One hundred slides were scored; H pylori was present in 64%. Carbol fuchsin/Alcian blue/hematoxylin-eosin stain gave excellent demonstration of gastric morphology. All positive cases (score > or =2) were correctly interpreted. Thirty-six slides had a score of 1 (< or =2 bacteria per entire slide). Of these, 10 were scored negative by Genta stain and 12 were scored negative by the carbol fuchsin/Alcian blue/hematoxylin-eosin stain (P = not significant). Hematoxylin-eosin was significantly less accurate than either of the other 2 stains (P < .02). CONCLUSION: The carbol fuchsin/Alcian blue/hematoxylin-eosin (El-Zimaity) stain is an economical stain suitable for simultaneous visualization of H pylori infection and gastric morphology.

Alcian Blue↗
PubMed1997

Isolation of full-length ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype.

A gene mutated in the human genetic disorder ataxia-telangiectasia (A-T), ATM, was recently identified by positional cloning. ATM is a member of the phosphatidylinositol-3-kinase superfamily, some of which are protein kinases and appear to have important roles in cell cycle control and radiation signal transduction. We describe herein, to our knowledge, for the first time, the cloning of a full-length cDNA for ATM and correction of multiple aspects of the radio-sensitive phenotype of A-T cells by transfection with this cDNA. Overexpression of ATM cDNA in A-T cells enhanced the survival of these cells in response to radiation exposure, decreased radiation-induced chromosome aberrations, reduced radio-resistant DNA synthesis, and partially corrected defective cell cycle checkpoints and induction of stress-activated protein kinase. This correction of the defects in A-T cells provides further evidence of the multiplicity of effector functions of the ATM protein and suggests possible approaches to gene therapy.

Ataxia Telangiectasia↗
PubMed1997

MRC OX-2 defines a novel T cell costimulatory pathway.

T cell activation requires the engagement of the TCR as well as a second, costimulatory signal. In this study, we demonstrate that MRC OX-2 (OX-2) mediates a previously unrecognized T cell costimulatory signal leading to enhanced T cell proliferation. One extensively studied costimulatory pathway, the B7/CD28 pathway, delivers its signal when CD28 is engaged by either of two ligands, B7-1 or B7-2, expressed on APC. Recent data have suggested that an additional ligand may exist in this pathway. This possibility prompted us to search previously cloned genes with both structural and expression characteristics similar to B7-1 and B7-2. Our search yielded OX-2, a rat lymphocyte activation marker, as a promising candidate gene. We now report that Chinese hamster ovary cell transfectants expressing the OX-2 protein can costimulate murine CD4+ T cells to proliferate in an Ag-independent fashion using anti-CD3, as well as an Ag-dependent fashion using peptide. In contrast to B7-1-mediated costimulation, OX-2 does not result in detectable levels of IL-2, IL-4, or IFN-gamma. In addition, OX-2 transfectants do not bind the soluble receptor reagents of the B7/CD28 pathway (CD28-Ig and CTLA4Ig). Furthermore, OX-2 costimulation is not inhibited by CTLA4Ig, as is B7-1-mediated costimulation, but is readily inhibited with an anti-OX-2 mAb. Thus, OX-2 is a T cell costimulatory ligand that acts through a non-B7/CD28 pathway, which leads to functionally distinct consequences, as reflected by the resulting cytokine profile.

Amino Acid Sequence↗
PubMed1997

Effects of exercise on fatigue, aerobic fitness, and disease activity measures in persons with rheumatoid arthritis.

The effects of 12 weeks of low-impact aerobic exercise on fatigue, aerobic fitness, and disease activity were examined in a quasi-experimental time series study of 25 adults with rheumatoid arthritis (RA). Measures were obtained preintervention, midtreatment (after 6 weeks of exercise), end of treatment (after 12 weeks of exercise), and at a 15-week follow-up. ANOVAS for repeated measures showed that those subjects who participated more frequently reported decreased fatigue, while those who participated less frequently reported an increase in fatigue. All subjects, on average, showed increased aerobic fitness and increased right and left hand grip strength, decreased pain, and decreased walk time. There were no significant increases in joint count or sedimentation rate. Significant improvements in measures at the 15-week follow-up also were found. Findings indicate that persons with RA who participate in appropriate exercises may lessen fatigue levels and experience other positive effects without worsening their arthritis.

Adult↗
PubMed1997

Profiling the care needs of the population with dementia: a survey in central Scotland.

OBJECTIVE: To demonstrate a low-cost method of producing local information for dementia service planning. DESIGN: (1) Multiservice census. (2) Stratified random sample survey (stratified by setting) to assess needs. SETTING: All community and institutional settings in Forth Valley Health Board area. PARTICIPANTS: (1) People age 65 + defined by health and social care professionals as having 'problems of memory/confusion (as is caused by dementia)' (N = 2060). (2) As (1) excluding those with score < 2 on Levin's checklist and no relevant known diagnosis (N = 286). MAIN OUTCOME MEASURES: Coverage of population with dementia against EURODEM prevalence. Place of residence of sufferers. Level of care needs. MAIN RESULTS: Identified population, pro-rating for identifiable non-response, accounted for 78% of EURODEM prevalence. Assuming unidentified 22% to live at home, 45% of total population with dementia were in some form of institutional care. Survey demonstrated high levels of need in local population with dementia known to services. Assistance was required more than once a day with mobility by 48%, personal care by 60%, domestic tasks by 75% and because of behavioural problems by 57%. Assistance was required at night by 59% because of personal care needs and by 54% because of behaviour problems. CONCLUSIONS: The value of a broad-based survey 'snapshot' across the range of settings was confirmed. It can be accomplished relatively quickly and cheaply and complements information collected in other ways.

Aged↗
PubMed1997

The dynamics of measles epidemics.

The interepidemic interval (T) of measles in London from 1647 to 1837 evolved progressively from 5-yearly to 2-yearly by 1800. Measles mortality was significantly ( p<0.001) cross-correlated with the annual wheat prices, a good index of nutrition although at a 2-year lag. Epidemics correlated with low autumn temperatures (p<0. 001). A linearised model of the dynamics of epidemics shows that T is determined by the product of population (N) and susceptibility (beta) and that the system will settle at its steady state unless the epidemics are driven. It is suggested that (i) the progressive change in T was caused by a rise in population size (N) and an increased susceptibility (beta) related to malnutrition and (ii) epidemics were driven by oscillations in low autumn temperature (p<0. 001) and by cycles of susceptible young children produced by malnutrition during pregnancy.

Child↗
PubMed1997

Aggrecanase and metalloproteinase-specific aggrecan neo-epitopes are induced in the articular cartilage of mice with collagen II-induced arthritis.

OBJECTIVE: To analyze the roles of two classes of proteinases, 'aggrecanase', and matrix metalloproteinases (MMPs), in chondrodestruction during murine collagen-induced arthritis (CIA). METHODS: Generation of the 'aggrecanase' neo-epitope (NITEGE373), and the MMP neo-epitope (VDIPEN341) within aggrecan was studied by immunoperoxidase microscopy using specific anti-peptide antibodies in normal and stromelysin-1 (SLN-1) deficient knockout mice with CIA. RESULTS: High levels of NITEGE373 and VDIPEN341 neo-epitopes were observed in foci within CIA paw articular cartilage exhibiting depletion of glycosaminoglycans, in advance of significant cartilage erosion. The highest concentrations of NITEGE373 and VDIPEN341 labeling were observed and often co-distributed in the chondrocyte pericellular matrix, suggesting that stimulated chondrocytes can synthesize and/or activate both enzymes. Other regions of the cartilage frequently exhibited either NITEGE373 or VDIPEN341 labeling, but not both neo-epitopes simultaneously, suggesting that 'aggrecanase' and MMP cleavages of aggrecan may be generated independently. No detectable differences were observed in expression or distribution of either neo-epitope in SLN-1 knockout versus wild-type mice. In addition, in vitro digestion of joint sections with SLN-1 did not alter the expression of cartilage NITEGE373, while markedly increasing VDIPEN341 labeling. Peripheral nerves and brains of naive mice also exhibited intense anti-NITEGE373 labeling. CONCLUSIONS: These data indicate that NITEGE373 and VDIPEN341 aggrecan neo-epitopes are sensitive and specific markers of early joint pathology, and are consistent with the hypothesis that SLN-1 does not have 'aggrecanase' activity, and that 'aggrecanase' is distinct from the MMPs which cleave aggrecan at the MMP site.

Aggrecans↗
PubMed1997

Interacting factors affecting illegitimacy in preindustrial northern England.

Illegitimacy in a historic, single community at Penrith, Cumbria (1557-1812), has been studied using aggregative analysis, family reconstitution and time series analysis. This population was living under extreme conditions of hardship. Long, medium and short wavelength cycles in the rate of illegitimacy have been identified by time series analysis; each represents a different response to social and economic pressures. In a complex interaction of events, the peaks of the cycles in wheat prices were associated with rises in adult mortality which promoted an influx of migrants and a concomitant rise in illegitimacy. The association between immigration and illegitimacy was particularly noticeable after the mortality crises of the late sixteenth and early seventeenth centuries. Children of immigrant families also tended to produce illegitimate offspring. Native and immigrant families responded differently to extrinsic fluctuations, and variations in their reproductive behaviour were probably related to access to resources.

Emigration and Immigration↗
PubMed1997

Patient-reported problems associated with dysphonia.

In the UK there has been little assessment of the efficacy of therapy for patients with dysphonia. Current objective assessment methods (e.g. acoustical analysis) do not correlate well with patient symptoms. Existing subjective measures are based on clinical impression. To date, no measure has been based on the patient's experience and the aim of this study was to explore the difficulties that patients encounter as a consequence of their illness or disability. One hundred and thirty-three dysphonic patients completed an open-ended questionnaire where they were asked to make a list of the problems they experienced due to their voice disorder. Responses were categorized using the WHO International Classification of Impairments, Disabilities and Handicaps. A total number of 467 problems were listed: 60% impairments, 26% disabilities and 14% were handicap related. The six major impairments related to altered voice and throat symptoms. Although the majority of disabilities resulted from lack of projection and clarity, the most frequently reported was singing. Reported handicaps encompassed psychological, emotional and employment-related difficulties and effects on family and friends. People with dysphonia experience social, lifestyle and employment difficulties as a consequence of their voice disorder. Responses to the open-ended questionnaire have considerable practical applications in targeting more comprehensive treatment strategies.

Adolescent↗
PubMed1997

Noninvasive capnometry monitoring for respiratory status during pediatric seizures.

OBJECTIVE: To determine the reliability and clinical value of end-tidal CO2 by oral/nasal capnometry for monitoring pediatric patients presenting post ictal or with active seizures. DESIGN: Clinical, prospective, observational study. SETTING: University affiliated children's hospital. INTERVENTIONS: One hundred sixty-six patients (105 patients with active seizures, 61 post ictal patients) had end-tidal CO2 obtained by oral/nasal sidestream capnometry, and respiratory rates, oxygen saturation, and pulse rates recorded every 5 mins until 60 mins had elapsed. End-tidal CO2 values were compared with a capillary PCO2 and clinical observation. MEASUREMENTS AND MAIN RESULTS: The mean end-tidal CO2 reading was 43.0 +/- 11.8 torr [5.7 +/- 1.6 kPa] and the mean capillary PCO2 reading was 43.4 +/- 11.7 torr [5.7 +/- 1.6 kPa]. The correlation between end-tidal CO2 and capillary PCO2 was significant (r2 = .97; p < .0001). A relative average bias of 0.33 torr (0.04 kPa) with end-tidal CO2 lower than capillary PCO2 was established with 95% limits of agreement +/-4.2 torr (+/-0.6 kPa). Variability of difference scores was not related to range of mean scores (r2 = .00003), age (r2 = .0004), or respiratory rates (r2 = .0009). End-tidal CO2 (r2 = .22; p < .001) correlated better with respiratory rate changes when compared with oxygen saturation (r2 = .02; p = .01). CONCLUSIONS: Dependable end-tidal CO2 values can be obtained in pediatric seizure patients using an oral/nasal cannula capnometry circuit. Continuous end-tidal CO2 monitoring provides the clinician with a reliable assessment of pulmonary status that can assist with decisions to provide ventilatory support.

Adolescent↗
PubMed1997

Evidence that angiotensin II and lipoxygenase products activate c-Jun NH2-terminal kinase.

The effect of angiotensin II (Ang II) to activate c-Jun amino-terminal kinase (JNK) was studied in a Chinese hamster ovary fibroblast cell line overexpressing the rat vascular type-1a Ang II receptor (CHO-AT1a). Ang II treatment induced a time-dependent activation of JNK. Ang II (10(-7) mol/L) activated JNK activity, with a peak at 30 minutes (9.39 +/- 2.52-fold, n = 7, P < .02 versus control), which was maintained until 3 hours (2.7 +/- 0.65-fold, n = 3, P < .02 versus control). Ang II-induced JNK activation at 30 minutes was inhibited by a specific lipoxygenase (LO) pathway inhibitor, cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (1 mumol/L) by 87.5% (n = 4, P < .01 versus Ang II-induced JNK activity). The direct addition of 12-HETE also induced a time-dependent JNK activation. 12-HETE (10(-7) mol/L) activated JNK activity, with a peak at 10 minutes (3.43 +/- 0.87-fold, n = 6, P < .02 versus control), which remained elevated until 1 hour. These results suggest that the LO pathway is a mediator of Ang II-induced JNK activation. 15-HETE can also activate JNK at 5 minutes, but this activity was reduced at 30 minutes and could not be seen at 1 hour, indicating that the time course was different from that seen with 12-HETE. N-Acetylcysteine (NAC), an antioxidant, was used to perturb intracellular reactive oxygen intermediate (ROI) levels to assess the role of endogenous ROIs in regulating JNK activity. Pretreatment of cells with 500 mumol/L NAC for 1 hour attenuated approximately 50% of Aug II-induced JNK activation, suggesting that ROIs, at least partially, mediate Ang II-induced JNK activation. Furthermore, 12-HETE-induced JNK activation was reduced by approximately 90% by NAC. Finally, pertussis toxin completely blocked 12-HETE-induced JNK activation, suggesting that Gi-protein signaling participates in 12-HETE-induced effects. These results suggest that LO activation plays a role in mediating Ang II-induced JNK activation in part by altering the redox tone and Gi-protein signaling of cells.

Angiotensin II↗
PubMed1996

Oscillatory dynamics of smallpox and the impact of vaccination.

The evolution of smallpox epidemics in London, 1647-1893, was studied by time series analysis of deaths from the disease in the Bills of Mortality. The interepidemic interval (T) evolved progressively from 4 years to 2 years at 1800. The dynamics of epidemics during 1647-1800 are explicable in terms of the transmission of viral diseases which shows that (i) T is determined by the product of population size (N) and susceptibility (beta), (ii) T determines the mean age of catching the disease, (iii) the system will settle at its steady-state, endemic level unless the epidemics are driven. It is suggested that (i) the progressive change in T was initially caused by a rise in N and later by an increased beta related to malnutrition and (ii) the epidemics were driven by an oscillation in delta beta associated with seasonal dry conditions. The effects of variolation and vaccination became apparent after 1800: the endemic level fell progressively, the epidemics were reduced in amplitude and they were not driven. The dynamics of the disease can now be described by an SEIR model: severe outbreaks of smallpox are followed by decaying epidemics. Endemic smallpox mortality also interacts with the dynamics of the population so that a long wavelength oscillation (associated with recovery after the plague) and a 5/6 year (associated with immigration) oscillation are generated.

Disease Outbreaks↗
PubMed1996

I can do that.

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Humans↗