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M Scott

Publications and source records attributed to M Scott.

At least 19 recordsLinked to original sources
PubMed2004

The Hera database and its use in the characterization of endoplasmic reticulum proteins.

MOTIVATION: Information concerning endoplasmic reticulum (ER) proteins is widely dispersed and cannot be easily and rapidly processed by the biological community. We present a comprehensive database of human ER proteins, called Human ER Aperçu (Hera). The Hera database was constructed by exhaustively searching through public databases and the scientific literature for ER proteins. RESULTS: Hera was used for the analysis of characteristics common to all human ER proteins. Our results show that a high proportion of ER proteins (59%) have at least one transmembrane domain and display physical characteristics consistent with this observation. In addition, one-third of ER proteins contain known ER retrieval or retention signals and 70% of ER proteins contain a signal peptide or anchor. Finally, 85% of ER proteins contain at least one InterPro motif. The most abundant InterPro motifs in ER proteins represent many of the most well-characterized functions of the ER.

Amino Acid Motifs↗
PubMed2003

Right-hemisphere encephalopathy in elderly subjects with schizophrenia: evidence from neuropsychological and brain imaging studies.

RATIONALE: Cognitive impairment is a recognised feature of schizophrenia. Elderly patients with early-acquired schizophrenia are seriously affected, with a proportion of them showing clinically significant dementia, not accounted for by any recognized degenerative processes common in this age group, such as Alzheimer's disease. Progression of cognitive deficits is described in elderly institutionalised patients, but disputed amongst community dwelling subjects. The pattern of cognitive deficits in this age group is not yet clearly defined, although there is some evidence that it differs from that in Alzheimer's disease. There is little evidence of any underlying specific brain abnormality. OBJECTIVES: To characterize the neuropsychological deficits in elderly schizophrenia patients and distinguish them from those in Alzheimer's disease. To establish the presence of underlying structural brain abnormality using MRI. METHODS: Twenty-eight elderly schizophrenia patients with onset before the age of 45 years carried out neuropsychology tests. Twelve scored in the dementia range and were compared with 16 equally impaired patients with early Alzheimer's disease. Thirteen of the schizophrenia patients consented to brain MRI. The imaging data were analysed using a newly developed automated method of measuring CSF volume distributions and compared with data from 30 age-matched normal controls. RESULTS: The schizophrenia group was more impaired on visuo-spatial tasks than the Alzheimer's group but less impaired on corresponding verbal tasks, despite similar overall cognitive impairment. The MR scans revealed right-sided enlargement of ventral CSF spaces in the schizophrenia patients especially in the posterior third, and this correlated with their impaired performance on visuo-spatial tasks. CONCLUSIONS: The results suggest that right hemisphere impairment underlies the specific profile of cognitive impairment in elderly patients with schizophrenia.

Aged↗
PubMed2003

Field performance of transgenic tall fescue (Festuca arundinacea Schreb.) plants and their progenies.

Tall fescue (Festuca arundinacea Schreb.) is a hexaploid, outcrossing grass species widely used for forage and turf purposes. Transgenic tall fescue plants were generated by biolistic transformation of embryogenic cell suspension cultures that were derived from single genotypes of widely used cultivar Kentucky-31. Primary transgenics from two genotypes, their corresponding regenerants from the same genotypes and control seed-derived plants were transferred to the field and evaluated for 2 years. Progenies of these three classes of plants were obtained and evaluated together with seed-derived plants in a second field experiment. The agronomic characteristics evaluated were: heading date, anthesis date, height, growth habit, number of reproductive tillers, seed yield and biomass. The agronomic performance of the primary transgenics and regenerants was generally inferior to that of the seed-derived plants, with primary transgenics having fewer tillers and a lower seed yield. However, no major differences between the progenies of transgenics and the progenies of seed-derived plants were found for the agronomic traits evaluated. Primary transgenics and regenerants from the same genotype were more uniform than plants from seeds. Progenies of transgenics performed similarly to progenies of the regenerants. The addition of a selectable marker gene in the plant genome seems to have had little effect on the agronomic performance of the regenerated plants. No indication of weediness of the transgenic tall fescue plants was observed. Our results indicate that outcrossing grass plants generated through transgenic approaches can be incorporated into forage breeding programs.

Biolistics↗
PubMed2003

Effects of live attenuated and killed Salmonella vaccine on T-lymphocyte mediated immunity in laying hens.

The impact of live and killed Salmonella vaccines on cell-mediated immunity (CMI) was investigated in 18- and 32-week-old White Leghorn chickens, by assessing splenic lymphocyte proliferation, expression of IL-2 mRNA in concanavalin A (Con A) stimulated cells and flow cytometric analysis of cell subpopulations. Con A and Salmonella enteritidis (SE) flagella induced proliferation of splenocytes were enhanced in the 18- and 32-week-old chickens treated with live vaccine, compared to the corresponding control chickens. Among the killed vaccine treated birds, Con A-mediated response was higher in the 18-week-old chickens compared to the corresponding control birds. Increased proliferation was accompanied by increased CD4 and reduced CD8 and gammadelta T-lymphocytes in the 18-week-old live vaccine treated chickens. Relative expression of IL-2 mRNA in Con A-stimulated splenocytes from 18-week-old birds was not affected by vaccine treatment. Overall, live vaccine was more effective in increasing the lymphocyte proliferation to Con A as well as SE antigen. This enhanced CMI may prove beneficial in protecting chickens against SE infection.

Animals↗
PubMed2003

Competitive enzyme-linked immunoassay of monoclonal immunoglobulin G anti-D preparations.

The development of monoclonal immunoglobulin G (IgG) anti-D for prophylaxis necessitates estimation of their potency in terms of their red cell-binding ability, but it is unclear which quantification methodology is most suitable for this. The aim of this study was to assess 50 monoclonal anti-D from the 4th International Workshop for quantitative and qualitative binding to red cells in a competitive enzyme-linked immunoassay (EIA) in which varying amounts of monoclonal antibodies (MoAbs) and a constant amount of biotinylated monoclonal anti-D (BRAD-5) compete for red cell binding. The potencies of the MoAb were estimated against the International Reference Preparation (IRP) for anti-D Ig. Two MoAbs as supplied were insufficiently inhibitory of biotinylated BRAD-5 binding to be quantified; the potencies of the remainder ranged from 4 to 343 IU mL-1 and included 11 MoAbs showing dose-responses that were nonparallel to those of other MoAb and the IRP. Estimation of the concentration of antibody in the supernatants by radial immunodiffusion ranged from 0.5 to 61 micro g mL-1, giving specific activities of <1-24 IU micro g-1. The results show that competitive EIA is suitable for quantitating most monoclonal anti-D for development and quality control purposes, regardless of their D epitope reactivity.

Antibodies, Monoclonal↗
PubMed2003

Overwintering in Drosophila melanogaster: outdoor field cage experiments on clinal and laboratory selected populations help to elucidate traits under selection.

Insects can adapt to temperate environments by increasing levels of resistance to cold conditions over winter and/or altering reproductive patterns to focus reproduction in favourable conditions. In temperate areas, Drosophila melanogaster persists over winter at the adult stage. A previous experiment, conducted with flies kept in outdoor population cages in the temperate winter, indicated that temperate populations produced more eggs than did tropical populations following an abrupt increase in reproduction in late winter. In contrast, the tropical populations produced more eggs prior to the increase. Both patterns resulted in a higher net number of surviving offspring for temperate populations. Here we again examine the clinal pattern in reproduction using outdoor cages, this time held under tropical winter conditions. In this environment, surprisingly, egg production was higher and on average earlier in populations originating from temperate areas. However, mortality rates also increased with latitude of origin, and the relationship of lifetime egg production to latitude should therefore be measured. To test the role of altered pattern of egg production per se in the reproductive advantage of temperate populations in the temperate winter, we tested the performance of laboratory lines selected for altered reproductive patterns, under temperate winter conditions. Lines selected for high early fecundity exhibited this characteristic in the field cages and lines selected for late reproduction exhibited a relatively high fecundity in spring. The timing of the abrupt increase in egg production was identical in these sets of lines and occurred at the same time in recently collected populations, suggesting evolutionary conservation of the switch. These findings suggest that changes in early and late reproduction per se determine adaptation to temperate winter conditions, and illustrate how laboratory selection lines can be used to understand traits underlying adaptive shifts in field performance.

Adaptation, Physiological↗
PubMed2002

Section 1A: Rh serology. Coordinator's report.

One hundred forty-two Rh-specific monoclonal antibodies (Mabs) were evaluated by serology in 27 laboratories. Evaluators were asked to test each Mab at three dilutions in specified serological techniques against normal positive and normal negative phenotype cells, and any Rh variant cells that they had available. Raw data was submitted to the coordinator for overall analysis. Results were analysed by expressing the sum of reaction grades for each Mab with each variant cell as a percentage of the sum of reaction grades of that Mab with normal phenotype cells. Anti-D Mabs were sorted into 23 groups which had the same pattern of reactions with different partial D phenotype cells. Eighteen of these corresponded to previously defined patterns; five were new patterns. Combined with data from the previous workshop, this means that 30 different reaction patterns have been defined. A new nomenclature is introduced for numbering the epitopes. Reactions with new variants DNB, DNU and DAR indicated some further subsplits of these patterns. Reactions with Category Va cells indicated that there were five different types of Va cells that could be distinguished serologically with monoclonal antibodies. No patterns of reactivity corresponding to the epitope groups could be observed with the different types of weak D tested. Anti-E Mabs were sorted into 14 groups, and the E variant cells into seven groups.

Antibodies, Monoclonal↗
PubMed2002

Idiopathic slow transit constipation and megacolon are not associated with neurturin mutations.

Chronic idiopathic slow-transit constipation (ISTC) and idiopathic megacolon (IMC) are early-onset gastrointestinal motility disorders of unknown aetiology. The gene encoding the neurotrophic factor neurturin may be a candidate for these disorders, as neurturin-deficient mice have a similar enteric phenotype. In the present study, we tested this hypothesis. Genomic DNA from 26 cases of chronic idiopathic STC [with a family history of constipation in 15 (58%) and Hirschsprung's disease in two (8%)], and five cases of IMC [two familial (40%)] was screened by direct DNA sequencing using the fluorescent dideoxy terminator method. Results were compared with published sequence data and 24 control DNAs. Our results revealed several previously unreported common sequence polymorphisms, but overall frequencies were comparable between patients and controls. We conclude that mutation of neurturin is not a frequent cause of ISTC or IMC.

Adult↗
PubMed2002

The United Kingdom National External Quality Assessment Scheme (blood transfusion laboratory practice): trends in proficiency and practice between 1985 and 2000.

Proficiency in blood transfusion laboratory practice has improved over the last 15 years (1985-2000). Error rates for ABO grouping have fallen from 0 x 19 to 0 x 02% (P = 0 x 003). A similar trend is evident for antibody screening, with error rates for false negative antibody screens falling from 3 x 2 to 0 x 5% (P < 0 x 001), and for antibody identification, for sera containing a single alloantibody, with error rates falling from 8 x 8% to 0 x 9% over the last 10 years (P < 0 x 001). Proficiency in serological crossmatching to detect clinically significant non-ABO incompatibilities (other than Kidd), has also improved (P < 0 x 001). However, error rates for RhD grouping have not changed and there has been a recent decline in proficiency in detecting weak ABO incompatibilities and Kidd antibodies with heterozygous cells. Procedures for pretransfusion testing have also been rationalized over this time. The indirect antiglobulin test (IAT) is used in isolation by 73% of laboratories for antibody screening, and 10% rely on the direct room temperature (DRT), immediate spin (IS) crossmatch in the absence (current and/or historical) of clinically significant antibodies. Despite the improvements in error rates that have occurred alongside the rationalizations, there is still evidence of noncompliance with current published BCSH guidelines and manufacturers' instructions.

Antibodies↗
PubMed2002

Neurosteroids and glutamate toxicity in fibroblasts expressing human NMDA receptors.

We characterized glutamate receptor-mediated toxicity in mouse fibroblasts expressing the human NR1a/2A or NR1a/2B NMDA receptor. After induction of NMDA receptors, cells in both lines died over a 24 h time period. This toxicity was associated with a progressive increase in the glutamate content of the media. Cell death could be prevented by including either the non-competitive NMDA receptor antagonist ketamine or the competitive antagonist D,L-AP5. Cells expressing NR1a/2A receptors were maximally protected by 0.5 mM D,L -AP-5, while those expressing NR1a/2B receptors required 2 mM D,L -AP-5 for maximal protection. The neurosteroid pregnenolone sulfate, which negatively modulates NMDA receptor function, partially protected fibroblasts containing NR1a/2A or NR1a/2B NMDA receptor constructs. However, the neurosteroid pregnenolone sulfate, which has been reported to act as a positive allosteric modulator of the NMDA receptor, had no effect on the toxicity caused by endogenous glutamate. Our results on cells expressing human NMDA receptors suggest that certain neurosteroids may protect against NMDA induced toxicity while having low neurotoxic liabilities of their own.

Journal Article↗
PubMed2001

Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment.

NF-kappaB binding sites are present in the promoter regions of many acute phase and inflammatory response genes, suggesting that NF-kappaB plays an important role in the initiation of innate immune responses. However, targeted mutations of the various NF-kappaB family members have yet to identify members responsible for this critical role. RelA-deficient mice die on embryonic day 15 from TNF-alpha-induced liver degeneration. To investigate the importance of RelA in innate immunity, we genetically suppressed this embryonic lethality by breeding the RelA deficiency onto a TNFR type 1 (TNFR1)-deficient background. TNFR1/RelA-deficient mice were born healthy, but were susceptible to bacterial infections and bacteremia and died within a few weeks after birth. Hemopoiesis was intact in TNFR1/RelA-deficient newborns, but neutrophil emigration to alveoli during LPS-induced pneumonia was severely reduced relative to that in wild-type or TNFR1-deficient mice. In contrast, radiation chimeras reconstituted with RelA or TNFR1/RelA-deficient hemopoietic cells were healthy and demonstrated no defect in neutrophil emigration during LPS-induced pneumonia. Analysis of RNA harvested from the lungs of mice 4 h after LPS insufflation revealed that the induction of several genes important for neutrophil recruitment to the lung was significantly reduced in TNFR1/RelA-deficient mice relative to that in wild-type or TNFR1-deficient mice. These results suggest that TNFR1-independent activation of RelA is essential in cells of nonhemopoietic origin during the initiation of an innate immune response.

Animals↗
PubMed2001

UV induces nucleolar translocation of ING1 through two distinct nucleolar targeting sequences.

The ING1 candidate tumor suppressor is downregulated in a variety of primary tumors and established cancer cell lines. Blocking its expression experimentally promotes unregulated growth in vitro and in vivo, using cell and animal models. Alternative splicing products encode proteins that localize to the nucleus, inhibit cell cycle progression and affect apoptosis in different model systems. Here we show that ING1 proteins translocate to the nucleolus 12-48 h after UV-induced DNA damage. When a small 50 amino acid portion of ING1 was fused to green fluorescent protein, the fusion protein was efficiently targeted to the nucleolus, indicating that ING1 possesses an intrinsic nucleolar targeting sequence (NTS). We mapped this activity to two distinct 4 amino acid regions, which individually direct fused heterologous proteins to the nucleolus. Overexpression of ING1 induced apoptosis of primary fibroblasts in the presence and absence of UV exposure. In contrast, NTS mutants of ING1 that were not targeted to the nucleolus did not efficiently induce apoptosis when overexpressed and instead protected cells from UV-induced apoptosis. Taken together, these results indicate that UV induces ING1 to translocate to the nucleolus and that this translocation may facilitate apoptosis.

Amino Acid Sequence↗
PubMed2001

Segmental amplification of 11q23 region identified by fluorescence in situ hybridization in four patients with myeloid disorders: a review.

Four cases with a segmental amplification of 11q23 region were detected by FISH. The amplification was either contiguous amplification on chromosome 11, or multiple markers involving the 11q23 region. The markers were derivative chromosomes, or isochromosomes. Amplification of 11q23 region was associated with complex karyotypes at the time of diagnosis or following treatment in secondary leukemias. Three were AML cases belonging to either AML-M5a or AML-1 subtypes and one was a myeloproliferative disorder. These cases were resistant to treatment. Conventional cytogenetic analysis and fluorescence in situ hybridization (FISH) studies using MLL, 11 painting, or 11 centromere probes ascertained the segmental amplification. Since the patients did not respond to treatment the amplification of gene or genes that map to 11q23 may be responsible for the unfavorable prognosis. Hence, this type of amplifications could have clinical significance.

Acute Disease↗
PubMed2001

Treatment delays for patients with acute myocardial infarction within the Coromandel region of New Zealand.

AIM: To assess treatment delays incurred by Coromandel patients requiring thrombolytic therapy for acute myocardial infarction at Thames Hospital. METHODS: A chart search was undertaken at Thames Hospital to identify all patients admitted from July 1993 to July 1998 with a diagnosis of acute myocardial infarction who were treated with thrombolytic therapy. Times of pain onset, general practitioner (GP) assessment, transportation, hospital arrival and thrombolytic administration were noted. Additional information, when required, was obtained from the patient's GP or the St Johns Ambulance service. RESULTS: 153 patients were thrombolysed at Thames Hospital over this period, mean age 65.1 years, 36.6% in heart failure. The mean time from pain onset to GP contact was 157.2 minutes and varied from 63.2 minutes in Coromandel Township to 272.5 minutes in Pauanui. Delays from GP contact to thrombolysis were longer for patients living in outlying areas versus Thames and its environs, 169.4 +/- 45.9 versus 125.2 +/- 50.4 minutes (mean +/-SD) respectively, p<0.001. This contributed to a total delay from pain onset to thrombolysis of 316.7 +/- 145.8 minutes for patients in outlying areas versus 269.1 +/- 185.8 minutes for local patients (p=0.014). CONCLUSIONS: Delays in providing thrombolytic therapy for acute infarct patients reflect not only transport times but also delays in seeking initial medical assessment and hospital triage times. Transport times become particularly significant for those outside of Thames and its environs. Only with improved patient education and local delivery of thrombolytic therapy will these delays be adequately addressed.

Aged↗