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M Bell

Publications and source records attributed to M Bell.

At least 73 records · Page 4Linked to original sources
PubMed1998

Conformation and ion-channeling activity of a 27-residue peptide modeled on the single-transmembrane segment of the IsK (minK) protein.

IsK (minK) protein, in concert with another channel protein KVLQT1, mediates a distinct, slowly activating, voltage-gated potassium current across certain mammalian cell membranes. Site-directed mutational studies have led to the proposal that the single transmembrane segment of IsK participates in the pore of the potassium channel [Takumi, T. (1993) News Physiol. Sci. 8, 175-178]. We present functional and structural studies of a short peptide (K27) with primary structure NH2-1KLEALYILMVLGFFGFFTLGIMLSYI27R-COOH, corresponding to the transmembrane segment of IsK (residues 42-68). When K27 was incorporated, at low concentrations, into phosphatidylethanolamine, black-lipid membranes, single-channel activity was observed, with no strong ion selectivity. IR measurements reveal the peptide has a predominantly helical conformation in the membrane. The atomic resolution structure of the helix has been established by high-resolution 1H NMR spectroscopy studies. These studies were carried out in a solvent comprising 86% v/v 1,1,1,3,3,3-hexafluoro-isopropanol-14% v/v water, in which the IR spectrum of the peptide was found to be very similar to that observed in the bilayer. The NMR studies have established that residues 1-3 are disordered, while residues 4-27 have an alpha-helical conformation, the helix being looser near the termini and more stable in the central region of the molecule. The length (2. 6 nm) of the hydrophobic segment of the helix, residues 7-23, matches the span of the hydrocarbon chains (2.3 +/- 0.25 nm) of fully hydrated bilayers of phosphatidylcholine lipid mixture from egg yolk. The side chains on the helix surface are predominantly hydrophobic, consistent with a transmembrane location of the helix. The ion-channeling activity is believed to stem from long-lived aggregates of these helices. The aggregation is mediated by the pi-pi stacking of phenylalanine aromatic rings of adjacent helices and favorable interactions of the opposing aliphatic-like side chains, such as leucine and methionine, with the lipid chains of the bilayer. This mechanism is in keeping with site-directed mutational studies which suggest that the transmembrane segment of IsK is an integral part of the pore of the potassium channel and has a similar disposition to that in the peptide model system.

Amino Acid Sequence↗
PubMed1998

Affect recognition in deficit syndrome schizophrenia.

This study has three aims: (1) to compare a deficit syndrome schizophrenia sample (n=19) with a non-deficit sample (n=50) on affect recognition; (2) to determine the association between individual deficit criteria and affect recognition performance in the deficit sample; and (3) to compare the deficit syndrome and negative syndrome samples with respect to affect recognition test performance. Results revealed that the deficit sample had significantly lower adjusted mean affect recognition scores than the non-deficit sample. In addition, 17 of the 19 subjects with deficit syndrome had impairments in affect recognition, whereas, non-deficit subjects were only slightly more likely to score in the impaired range than the unimpaired range. Within the deficit sample Diminished Sense of Purpose was the criterion most strongly associated with affect recognition impairment. Finally, a group of subjects classified as having prominent negative symptoms did not demonstrate the same pattern of impairment as shown by the deficit syndrome sample. The relationship between affect recognition, information processing and the deficit syndrome is discussed along with implications for classification in schizophrenia.

Adult↗
PubMed1998

Making sense of Census data: a components analysis of employment change among indigenous Australians.

"The 1996 Census count of indigenous Australians included a substantial number of individuals who were not recorded as indigenous by the previous census. This paper considers the implications of this for interpreting change in employment numbers. Two adjustments are made to employment change data. First, reverse survival of the 1996 population is applied to reconstruct 1991 employment figures. Second, administrative data are used to discount employment generated by participation in labour market programs. The effect is to substantially deflate the strong intercensal employment growth apparent from census counts with the conclusion that the rate of indigenous employment in the mainstream labour market has fallen."

Australia↗
PubMed1998

Understanding the 1996 census migration data.

"The Australian Census provides two approaches to measuring migration: indicators which distinguish movers from non-movers, and a geographic classification which identifies each person's usual residence on census night, and their usual address one year and five years previously. Although these data represent a rich source of information, they contain several traps for the unwary. We show that differences in the variables and classifications used can result in marked variations in the apparent intensity and patterns of migration. The questionnaire and processing methodology used in the 1996 Census also resulted in a number of inconsistencies between the migration indicators and the usual address information. We examine the magnitude and source of these anomalies, assess their implications and propose a partial solution."

Australia↗
PubMed1998

Antagonism of the IL-6 cytokine subfamily--a potential strategy for more effective therapy in rheumatoid arthritis.

Pro-inflammatory cytokines, some of which have the capacity to modulate cartilage and bone metabolism, are important mediators of the frequently sustained and destructive inflammation that characterises rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) have been studied extensively in this regard. That these proteins are important is no longer in doubt following the demonstration that the IL-1 receptor antagonist and neutralising antibodies directed against TNF alpha are clinically effective. Recent studies suggest that interleukin-6 (IL-6) and other members of the IL-6 cytokine subfamily are also potentially important cytokines in the pathogenesis of RA. The recognition of shared molecular subunits in the receptors for these cytokines raises the possibility that components of these receptors or their derivatives, either alone or in combination, may be useful for antagonising members of the IL-6 cytokine subfamily. Effective antagonism could be therapeutically beneficial in respect to attenuating inflammation and protecting critically important chondral and skeletal tissue. In this review the rationale and possible strategies for such antagonism are discussed.

Animals↗
PubMed1998

Low-dose theophylline increases urine output in diuretic-dependent critically ill children.

OBJECTIVE: Determine the effect of low-dose theophylline on urine output and the urinary adenosine: cAMP (cyclic adenosine monophosphate) excretion ratio (a measure of phosphodiesterase inhibition) in diuretic-dependent critically ill children. DESIGN: Observational clinical case series and animal laboratory experiment. SETTING: A university pediatric intensive care unit and a pharmacology research laboratory. PATIENTS: 10 consecutive oliguric patients treated with theophylline for diuresis. INTERVENTIONS: Urine output, fluid intake, diuretic dosages, and number of pressors (including dopamine) were monitored over the 24-h period prior to and the 24-h period immediately after theophylline was started. Hourly collections of urine were obtained at baseline and 1 and 3 h after theophylline was started and urinary excretion rates of adenosine and cAMP were measured and calculated. MEASUREMENTS AND RESULTS: Mean theophylline level in the children was 5.0 microg/ml. Urine output increased from 1.58 +/- 0.46 to 3.75 +/- 0.77 ml/kg per h (p = 0.008, paired t-test) after theophylline administration. There was no significant change in fluid intake, vasoactive agents, or dosages of other diuretics during the study periods. Intrarenal infusion of the IC50 concentration of isobutylmethylxanthine for phosphodiesterase activity resulted in a reduction of the adenosine: cAMP urinary excretion ratio in rats (p < 0.05). Low-dose theophylline had no effect on the adenosine: cAMP urinary excretion ratio in children. Concurrent therapy with dopamine was associated with an enhanced diuretic effect of theophylline (with dopamine, 1.30 +/- 0.30 to 5.07 +/- 0.77 ml/kg per h vs without dopamine, 1.77 +/- 0.76 to 2.86 +/- 1.08 ml/kg per h; p = 0.03, two-way ANOVA). There was no interaction between dopamine and low-dose theophylline on the urinary adenosine: cAMP excretion ratio (p = 0.56, two-way ANOVA). CONCLUSIONS: Theophylline increased urine output in diuretic-dependent critically ill children and the diuretic effect may have been potentiated by concurrent use of dopamine. Adenosine receptor antagonism may be a more likely mechanism for the diuretic effect of theophylline than phosphodiesterase inhibition.

Adenosine↗
PubMed1998

Candida albicans ALS3 and insights into the nature of the ALS gene family.

The ALS1 (agglutinin-like sequence) gene of Candida albicans encodes a protein similar to alpha-agglutinin, a cell-surface adhesion glycoprotein of Saccharomyces cerevisiae (Hoyer et al. 1995). A central domain of a tandemly repeated 108-bp sequence is found in the ALS1 coding region. This tandem-repeat motif hybridizes to multiple C. albicans genomic DNA fragments, indicating the possibility of other ALS1-like genes in C. albicans (Hoyer et al. 1995). To determine if these fragments constitute a gene family, tandem-repeat-hybridizing genomic fragments were isolated from a fosmid library by PCR screening using primers based on the consensus tandem-repeat sequence of ALS1 (Hoyer et al. 1995). One group of fosmids, designated ALS3, encodes a gene with 81% identity to ALS1. The sequences of ALS1 and ALS3 are most conserved in the tandem-repeat domain and in the region 5' of the tandem repeats. Northern-blot analysis using unique probes from the 3' end of each gene demonstrated that ALS1 expression varies, depending on which C. albicans strain is examined, and that ALS3 is hyphal-specific. Both genes are found in a variety of C. albicans and C. stellatoidea strains examined. The predicted Als1p and Als3p exhibit features suggesting that both are cell-surface glycoproteins. Southern blots probed with conserved sequences from the region 5' of the tandem repeats suggest that other ALS-like sequences are present in the C. albicans genome and that the ALS family may be larger than originally estimated.

Amino Acid Sequence↗
PubMed1998

In the queue for total joint replacement: patients' perspectives on waiting times. Ontario Hip and Knee Replacement Project Team.

We assessed patients on the waiting lists of a purposive sample of orthopaedic surgeons in Ontario, Canada, to determine patients' attitudes towards time waiting for hip or knee replacement. We focused on 148 patients who did not have a definite operative date, obtaining complete information on 124 (84%). Symptom severity was assessed with the Western Ontario/McMaster Osteoarthritis Index and a disease-specific standard gamble was used to elicit patients' overall utility for their arthritic state. Next, in a trade-off task, patients considered a hypothetical choice between a 1-month wait for a surgeon who could provide a 2% risk of post-operative mortality, or a 6-month wait for joint replacement with a 1% risk of post-operative mortality. Waiting times were then shifted systematically until the patient abandoned his/her initial choice, generating a conditional maximal acceptable wait time. Patients were divided in their attitudes, with 57% initially choosing a 6-month wait with a 1% mortality risk. The overall distribution of conditional maximum acceptable wait time scores ranged from 1 to 26 months, with a median of 7 months. Utility values were independently but weakly associated with patients' tolerance of waiting times (adjusted R-square = 0.059, P = 0.004). After splitting the sample along the median into subgroups with a relatively 'low' and 'high' tolerance for waiting, the subgroup with the apparently lower tolerance for waiting reported lower utility scores (z = 2.951; P = 0.004) and shorter times since their surgeon first advised them of the need for surgery (z = 3.014; P = 0.003). These results suggest that, in the establishment and monitoring of a queue management system for quality-of-life-enhancing surgery, patients' own perceptions of their overall symptomatic burden and ability to tolerate delayed relief should be considered along with information derived from clinical judgements and pre-weighted health status instruments.

Adult↗
PubMed1998

Developing nurse practitioners to develop practice: the experiences of nurses working on a nursing development unit.

AIM: To elicit nurses' accounts of their involvement with nursing research and their interpretations of the meaning of these projects for their practice. BACKGROUND: The links between research and practice development in health care are poorly understood and require further exploration in the light of the emerging research and development agenda within the National Health Service. METHODS: Semi-structured interviews were conducted with 15 qualified nurses working on a Nursing Development Unit. The interviews were tape recorded, transcribed and analysed thematically. FINDINGS: Data analysis identified two distinct groups--a core group of nurses actively engaged in the research projects and a peripheral group involved in data collection. The characteristics of the core group mirror the characteristics of those involved in nonresearch-based practice development activities. CONCLUSIONS: Engaging in research activities does not always result in the development of practice, however, there appears to be a link between practice development and critical thinking.

Attitude of Health Personnel↗
PubMed1998

Mechanism responsible for T-cell antigen receptor- and CD28- or interleukin 1 (IL-1) receptor-initiated regulation of IL-2 gene expression by NF-kappaB.

Initiation of the T-helper lymphocyte activation program is regulated through the T-cell receptor (TCR) and costimulatory receptors. Analysis of TCR and either anti-CD28- or interleukin 1 (IL-1)-mediated activation of the IL-2 promoter shows that costimulatory signals augment promoter activity through NF-kappaB sites. This study comparatively evaluates the mechanisms whereby signals initiated from the TCR and these two costimulatory receptors converge to synergistically increase NF-kappaB transcriptional activity. IL-1 alone stimulates an acute but transient NF-kappaB nuclear localization and a suboptimal NF-kappaB transcriptional response. In contrast, anti-CD3-anti-CD28 or anti-CD3-IL-1 synergistically stimulate prolonged NF-kappaB nuclear localization and NF-kappaB-mediated transcription. Both TCR- and costimulatory receptor-initiated synergistic NF-kappaB responses result from prolonging high rates of cytosolic IkappaB degradation during the second phase of the biphasic NF-kappaB nuclear localization. However, in contrast to previous reports, prolonged nuclear localization of NF-kappaB complexes is not necessarily associated with long-term depletion of IkappaBbeta. In response to either costimulus, c-Rel selectively translocated to the nucleus as a result of induced c-Rel expression and the continued production of c-Rel-IkappaBalpha complexes, which turn over rapidly due to the high rate of IkappaBalpha degradation in the cytosol during the second phase of the response. In contrast, IkappaBbeta is nearly completely degraded during the acute response to either IL-1 or anti-CD3-IL-1 while anti-CD3-anti-CD28 stimulates only a partial reduction (35 to 40%) in cytosolic IkappaBbeta. Cyclosporine (CsA), which inhibits stimulus-induced NF-kappaB transcriptional activity, selectively inhibits the stimulus-induced c-Rel nuclear localization and the rapid formation and degradation of c-Rel-IkappaBalpha complexes in the cytosol. CsA also inhibits both the prolonged, high rate of IkappaBalpha degradation and the lower level of IkappaBbeta turnover during the second phase of the activation response. Together, these results suggest a mechanism by which signals from the T-cell antigen receptor and either CD28 or IL-1 synergistically regulate IL-2 gene transcription by modulating NF-kappaB nuclear translocation.

Animals↗
PubMed1998

Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression.

We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4 and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2 secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF replacement studies. Inhibition using an IGF-II antibody showed that tumor cell-derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2 secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by IGFs, while no specific effect of insulin was detectable. The addition of 100 ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action. Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2 and -4 expression and leukemic cell growth. However, only slight differences in the IGF-I-R mRNA expression were seen for T- and B-cells compared with the differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus, although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4 expression in leukemic cells.

Base Sequence↗
PubMed1997

Positive and negative affect recognition in schizophrenia: a comparison with substance abuse and normal control subjects.

This study had three aims: to compare a schizophrenia sample (n = 50) with a substance abuse (n = 25) and normal sample (n = 81) on affect recognition; to compare differences in their performance between positive and negative affect recognition; and to introduce a new videotape method of stimulus presentation. Subjects were asked to identify the predominant affect depicted in 21 5-10-s vignettes containing three trials of seven affect states. Results demonstrate significant group differences: normal subjects scored in the normal or mild range, substance abuse (s/a) subjects scored in the mild and moderate ranges, and the schizophrenia sample scored predominantly in the moderate to severe ranges. Accuracies were 92.3% for the normal sample, 77.2 for the s/a sample and 64.8 for the schizophrenia sample. Response dispersions were 97.6% for the schizophrenia group, 69% for the s/a sample and 38% in the normal sample. A repeated measures ANOVA revealed a group by type of affect interaction with schizophrenia subjects showing far greater differential impairment on negative affect recognition. Difficulty of item did not contribute to this difference. Test-retest reliability at 5 months for this new method was r = 0.76, and stability of categorization was very high over 5 months (weighted kappa = 0.93). These affect recognition deficits in schizophrenia are discussed as they relate to lateralization of brain function, high EE families, social skills impairment and implications for rehabilitation services.

Adult↗
PubMed1997

Affect recognition in schizophrenia: a function of global impairment or a specific cognitive deficit.

To investigate cognitive variables related to affect recognition in schizophrenia, 63 subjects with DSM-III-R diagnoses of schizophrenia or schizoaffective disorder were administered a test battery which included the Bell-Lysaker Emotion Recognition Task (BLERT), Wisconsin Card Sorting Test (WCST), Wechsler Memory (WMS-R) and Adult Intelligence Scales (WAIS-R), Hopkins Verbal Learning Test, Gorham's Proverbs, and Continuous Performance Task (CPT). Coefficients revealed a moderate relationship between emotion recognition and WCST and CPT but no significant relationship with other test variables. Multiple regression analysis demonstrated that approximately one-third of the variance in BLERT scores could be explained by cognitive variables including the Digit Symbol Subtest, CPT, and Hopkins Verbal Learning Test. Other analyses demonstrated that subjects with moderate to severe affect recognition impairment had more perseverative errors, had fewer complete categories on the WCST and had more errors on the CPT. However, there were no significant differences on global measures of impairment such as WAIS-R IQs and Digit Symbol Substitution Test. The discussion focuses on deficits in affect recognition as a distinct feature which contributes to the heterogeneity of the disorder.

Adult↗
PubMed1997

Responsive gels formed by the spontaneous self-assembly of peptides into polymeric beta-sheet tapes.

Molecular self-assembly is becoming an increasingly popular route to new supramolecular structures and molecular materials. The inspiration for such structures is commonly derived from self-assembling systems in biology. Here we show that a biological motif, the peptide beta-sheet, can be exploited in designed oligopeptides that self-assemble into polymeric tapes and with potentially useful mechanical properties. We describe the construction of oligopeptides, rationally designed or based on segments of native proteins, that aggregate in suitable solvents into long, semi-flexible beta-sheet tapes. These become entangled even at low volume fractions to form gels whose viscoelastic properties can be controlled by chemical (pH) or physical (shear) influences. We suggest that it should be possible to engineer a wide range of properties in these gels by appropriate choice of the peptide primary structure.

Amino Acid Sequence↗
PubMed1997

Q fever vaccination in Queensland abattoirs.

Outbreaks of Q fever continue to be recorded in abattoirs despite a protective vaccine being available. All accredited abattoirs in Queensland were surveyed to ascertain the number that conducted Q fever vaccination programs. Only ten of the 30 abattoirs had vaccination programs. Vaccination programs were present at all abattoirs with more than 360 employees. Thirty-seven per cent of abattoir employees worked at abattoirs that did not have vaccination programs. Research is required into the attitudes and barriers to vaccination at smaller abattoirs so that vaccination coverage can be increased. Economic data, including litigation costs, should be considered in a cost-effectiveness study so that smaller abattoirs appreciate the benefits of implementing vaccination programs. The protocols for vaccination of new employees should be analysed for their capacity to provide appropriate worker coverage. Abattoir workers are a readily identifiable at-risk group who should be fully protected from this occupational disease. It is the responsibility of industry and health authorities to ensure all workers are appropriately protected.

Abattoirs↗
PubMed1997

An intergenerational program for persons with dementia using Montessori methods.

An intergenerational program bringing together older adults with dementia and preschool children in one-on-one interactions is described. Montessori activities, which have strong ties to physical and occupational therapy, as well as to theories of developmental and cognitive psychology, are used as the context for these interactions. Our experience indicates that older adults with dementia can still serve as effective mentors and teachers to children in an appropriately structured setting.

Aged↗